Vania Zhao '25

Overcoming Mortality: A Denial of Death & Dying

BY VANIA ZHAO '25

Cover Image: On the left is the general immune response that leads to wheal formation – the characteristic symptom of chronic urticaria. With cholinergic urticaria, increases in body temperature lead to this immune response through multiple mechanisms. On the right is the ribbon for chronic urticaria awareness.

Image Source: Wikimedia Commons Introduction From the moment of birth, the dying process begins. Through religion, science, philosophy, spirituality, and other means, humans have long attempted to understand, rationalize, and confront the inevitability of death. In our pursuit to find meaning in life despite the certainty of death, our inquisitive nature demands a way to transcend death. As we grow and deal with aging and the loss of those around us, the promise of eternal life beckons us to ask the forbidden question: what if death is not inevitable? What if we could escape the grasps of death entirely and live forever?

This essay will be a comprehensive exploration of immortality in the modern world through four pillars. The first part of this article will define and explain literal and symbolic immortality through various anthropological lenses, including models proposed by Robert Jay Lifton, Arnold van Gennep, and Robert Hertz, as well as through a spiritual and higher-existential lens. The second part will examine the possibility and feasibility of immortality by examining forms of immortality that exist with nature and the human body. The third part will outline hypothetical methods and models for immortality through modern medicine and technology and examine those methods through the anthropological, philosophical, ontological, and theological lens introduced in the second pillar. The fourth part will explore the implications of immortality for society, examining whether immortality is something that is desired in the modern day; it will also tackle questions in a future where immortality is possible, such as: Will the wealth gap widen? Would only a few social elites be able to afford immortality? How would the demographic look? How will education, religion etc. shift with this development? These questions are explored through the anthropological work of Antonio Sandu, who examines the posthuman/ transhuman world, as well as through hypothetical worlds through fiction.

What Is Immortality? While there are many forms of immortality, at its core, it is a continuation of life beyond the claws of death. Immortality can essentially be boiled down to two categories: literal immortality and symbolic immortality. Literal immortality is simple to define. It is achieved when an individual transgresses the limits of natural life and lives forever, retaining their consciousness beyond death accompanied by their physical bodies.

Many modern technologies aim to accomplish this. Meanwhile, symbolic immortality, according to Harvard psychiatrist Robert J. Lifton, MD, is to find a connection beyond the scope of individual life, often through concepts, imagery, or symbols to create meaning and significance to experience (Lifton, 1991). Lifton further splits symbolic immortality into five modes: biological, creative, theological, natural, and experimental (Lifton, 1991).

The Five Modes of Symbolic Immortality

Lifton’s modes of symbolic immortality provide a framework to compartmentalize the various forms of immortality created as a socio-cultural, psychological construct to cope with the inevitability of death, as well as the great unknown that lies beyond death. Biological immortality is the idea that one continues to live through their offspring– a generational continuation as well as the passing down of reproductive cells and DNA. Creative immortality consists of human influences that persist throughout the centuries, such as pieces of literature, art, and knowledge that extends to the greater human “flow” beyond the self. Theological immortality often constitutes a central immortal figure that has attained eternal life and perpetuates the idea of an immortal soul, offering immortality through spiritual belief under specific conditions. One can also find immortality through nature. As nature is cyclical and continuous, returning to nature upon death signifies an eventual renewal through the Earth. Finally, experimental immortality, or transcendence, is a psychological state of an ecstatic sense of timelessness, which can be found through stimulating activities or induced through substances. Symbolic immortality allows humans to form an explanation for the afterlife, as well as face the reality of death by believing that life doesn’t just end. The reassurance of a legacy, of some part of the self-persisting for eternity, offers a sense of solace in life (Lifton, 1991). While Lifton’s framework provides a helpful categorization of symbolic immortality, to further understand immortality (specifically literal immortality), it is necessary to examine the concept through additional anthropological frameworks and ethnographic methodology. Since it is impossible to conduct an ethnographic study on immortals because, to public knowledge, none exist. Immortality can be viewed as a complete deconstruction of death and mourning by eliminating the factor of death completely, combatting death anxiety. We can cross-examine literal immortality with rites of death to identify points of deviance and its significance. The first model, introduced by Arnold van Gennep (1991), a Belgian ethnographer, analyzes death and mourning rites through a tripartite structure of separation, liminality (a transitional state), and incorporation. Robert Hertz, a French sociologist, builds upon van Gennep’s works and examines rites through the soul, the body, and the mourners (1991). For starters, literal immortality completely rejects separation as the soul is bound eternally to the body, and neither experiences death (Lifton, 1991; Hertz, 1991). In contrast, for symbolic immortality, the soul is the only actor that does not experience death, while the body is corrigible and the corpse impure (Lifton, 1991; Hertz, 1991). By this logic, immortality denies all impurities of the earthly vessel, and becomes a form of perfection and purity. In contrast, if complete separation allows for purity, then since immortals never experience this separation, they can be seen as permanently impure. The inability to die also creates a complicated relationship with the mourner: one is never mourned and always the mourner.

Moreover, immortality rejects liminality. Van Gannep (1991) describes liminality as existing in a state of neither-nor. Immortality imposes, instead, a state of permanence. Immortals are never dead and always alive. It is black and white; they do not enter the gray area between life and death. Immortality signifies a stagnation of the natural cycle of life; there is no destruction, so there is no transition. Finally, as the immortal is never changing, there is no need for incorporation into anything at all, as one has never departed from their initial state. From these lenses, the search, and obsession, of immortality is driven by the denial of death completely and allows one to exist in a state of permanence, which is only seen in divinity. However, analysis of immortality through these models are in relation to death, and under the assumption that one has achieved immortality. The process of becoming immortal, or “transhuman” (a term used by anthropologists and futurists alike to describe the posthuman condition after life-prolonging procedures

Image 1: Time and Antiquity. Image Source: Pixabay

"...immortality rejects liminality... Immortality imposes, instead, a state of permanence"

"...symbolic and literal immortality serve as mental touchstones for humans to cope with the imminence and finality of death..."

or immortality), sees different relationships between these rites and actors, which will be explored further in the introduction of methods of immortality later in the essay (Sandu, 2015).

Immortality and Spirituality

Notions of both symbolic and literal immortality serve as mental touchstones for humans to cope with the imminence and finality of death. Thus, it is unsurprising that immortality is deeply ingrained within religion, philosophy, ontology and theology. While within each religion, there are nuances on the exact belief of immortality, there are overarching themes and similarities that can be derived. For instance, in symbolic theological immortality, the immortal soul is a key concept. This can be represented as eternal existence after death in a spiritual location such as heaven or hell, central to Christian ideas, or as reincarnation in Eastern religions such as Hinduism, Jainism, and Buddhism (Nagaraj, 2013), which take a more philosophical approach in comprehending the soul. Where in Western religions, the separation of the body of the soul is an irreversible process, in Eastern religions the soul can take on the form of flesh again, or as animals, plants, or spirits. There is no finality in the separation of the soul from the earthly body. In fact, one’s deeds can carry over to future lives in the forms of Karma, the results of your deeds, or yuan fen, a Chinese belief of relationships and connections formed in past lives that must be realized in the present. Aspects of one’s consciousness can also be transferred. Though not identical to the current life, consciousness throughout lives is part of a continuum or “stream” (Nagaraj, 2013), which calls into question whether the differences are enough to consider it the same self or being, on whether the human condition changes its ontological status (Sandu, 2015).

However, humans are not satisfied with attaining immortality through death. Thus, many seek immortality to prolong their current identity of self and transcend the human condition. Sandu attributes the “the Kantian category of synthesis, and also from the religious experience of humanity” (2015) as philosophical and theological separators of humanity and divinity. In many religions, deities possess immortality, omnipotence, and omniscience. Immortality is a staple in divinity, and a current impossibility for humans, thus it is no surprise that it is something that humanity is fascinated with. By defining the limitations of human beings, the distinctions of humanity and divinity through “anthropological characteristics” (Sandu, 2015), there is context for the efforts that humanity takes to overcome these limitations. However, connecting back the purity and impurity of the body and the quest for immortality, it can be seen as a gift just as a punishment, as is the case with the Gilgamesh Odyssey, the myth of the wandering Jew, the story of Ivan Turbinca (Sandu, 2015). Immortality is first portrayed as a desirable goal worthy to be sought after, but upon obtaining it becomes an eternal curse as an exile from the essence of being human. There are many nuances and complexities of immortality, but first, we must explore the question: is immortality possible?

Is Immortality Possible?

While it has been established that humans can feasibly become immortality symbolically, the question of whether a human can live forever literally has yet to be answered. Without factoring accidental death or death due to such as murders, the primary agent of death is aging and disease. There are many theories on why humans age: the shortening of telomeres (repetitive protective DNA sequence at the end of chromosomes, without which cells can no longer divide successfully), and genetic instability is often pinpointed as one of the leading causes of aging. Another is the deterioration of cellular functions (Max Planck Institute, n.d). Throughout history, humans have continuously pursued immortality despite their race, religion, or ethnicity. Immortality is an anthropological constant uniting all of humanity (Sandu, 2015). Clearly, it is an important mission for humanity. Thus, seeing that it is possible inspires humans for further discovery, and there are many instances of immortality in nature, and even within the human body that is driving research to further technologies. While immortality is not yet possible, research in these areas have already improved the quality of life through advances in medicine, curing diseases that were otherwise deadly or debilitating.

Immortality in Nature

It is important to examine the available forms of immortality as they offer us a clue on what is possible and how we can apply these insights to humans. Science looks to these instances for clues to significantly extend our lifespan, slow down the effects of aging, or to stop aging completely. The following three cases of immortality in nature offer us a glimpse of the secret to eternal life. According to the Australian Academy of Science, Turritopsis dohrnii, a type of jellyfish, has been dubbed the only biologically immortal species on earth. These jellyfish have the unique ability to switch back and forth between life stages depending on the situation. In events of

injury, starvation, or imminent death, a mature Turritopsis dohrnii reverts into a blob of tissue, which then changes back into the sexually immature polyp phase of life (Berthold, 2021).

The Hydra viridissima is a tubular shaped species with a tentacle-ringed mouth and adhesive feet that resembles the jellyfish in the polyp stage. Unlike the jellyfish, Hydra is immortal on a cellular level. Hydras have infinitely self-renewing stem cells, which is due to FoxO genes. These genes regulate the longevity of cells. When researchers suppressed FoxO genes, Hydra showed decreased ability to regenerate as well as signs of aging. Thus, it can be concluded that these genes are clearly paramount to their immortality (Berthold, 2021). The jellyfish and the Hydra have achieved biological and cellular immortality, but there is another form of immortality that can be found in nature– genetic immortality. Lobsters have an endless supply of telomerase, which continuously generate telomeres and maintain their healthy DNA. However, Lobsters can still die, and they do so frequently. They are still susceptible to disease, predation (especially by humans), and exhaustion of growing new shells (Berthold, 2021).

Immortality in Humans

While immortality can be found throughout nature, it can also be found closer to us. Immortality exists within our own bodies in many forms. One of the most perplexing and prominent forms is the case of cancer cells. While scientists are unsure of how regular somatic cells can grow into immortal cancer cells, a leading theory is that cells stabilize their telomeres through the actions of telomerase continuously proliferate and achieve immortality (Weinberg, 2014). The infinite capability of cancer cells to divide and proliferate poses a great threat to humanity, and it is, according to the CDC, the second leading cause of death after heart disease. However, in an ironic sense, one of the primary causes of death for humans could be the breakthrough to help humans achieve immortal life. As seen by the aforementioned instances of immortality, it can be concluded that immortality is indeed possible on a biological, cellular, and genetic basis, and can exist within humans. Based on these discoveries, humans are aiming to develop several methods of immortality on these different levels.

Methods of Artificial Immortality

Immortality for humans currently exists in the realm of science-fiction. However, there are several fields of research that are dedicated to prolonging of human life. Currently, there are five main methods of artificial immortality under development which include cryonics, genetic editing, cellular repair, intelligence digitization, and cyborgism. These methods can be understood through both a scientific and anthropological lens for a more holistic approach.

Cryonics

Unlike the other methods of immortality, it is important to note that cryonics does not directly allow for infinite life. Instead, cryonics aims to freeze someone just before or immediately after they pass away to preserve their body and mind until science is advanced enough to bring the person back, cure their disease or further extend their life. Cryonics is currently the only viable option of all the methods, and thus it is necessary to examine the practice, as well as its implications. The process of begins with the death of the patient. The technician must cool the body immediately in an ice bath to prevent degeneration. Blood is drained and replaced with cryoprotectant agents, as blood can freeze and form ice crystals. Finally, the body is placed in liquid nitrogen to preserve tissues and organs until its eventual revival. Currently, 165 patients have undergone the process, with over 2000 living people signed up for services that the

Image 2: Jellyfish, some of which are biologically immortal Image Source: Pixabay

Image 3: Cryonics Chamber Rendering Image Source: Pixabay

Image 4: Genes viewed under a microscope with rendering Image Source: Pixabay Cryonics Institute offers (Lawrie, 2018), who believe in the Institute’s mission to give current humans with a chance of either a second chance to live or immortal life for when the technology is available. As it is uncertain if cryonics will be successful, it can essentially be viewed as a new form of burial, suspending an individual in an indefinite liminal state of being neither fully alive nor dead. The body, specifically the brain, is seen as an important vehicle in the definition of personhood and houses one’s consciousness. Consciousness, through the ontological lens, is stored on a molecular level. However, cryonics is currently a more symbolic form of immortality, as it eases the patient’s death anxiety through the belief that one day technology will advance to the point that a. they can successfully be unfrozen and b. a cure exists for their disease or that immortality is available. In line with van Gennep’s ideas, since the stage of liminality due to being frozen could last for decades or centuries, in the process of incorporation, one would need to be accustomed to potentially an entirely different world, where everyone they knew, and love are already dead, and they are no aspect of the culture, technology, or society have any resemblance at all with the time they were from.

Genetic Editing

Evident from the lobsters’ longevity or cancer cells, the key to immortality may lie within our genetics. Scientists have long attempted to map out the human genome and advance technologies in genetic editing in hopes of eliminating diseases and eventually prolong life indefinitely. The most promising technology for genetic editing currently is the CRISPR/ CAD9 technique. In 2017, American researchers successfully edited the genome of an embryo using this technique, and thus the proposition of modifying the genome to produce more telomerase has become more of a possibility. However, simply increasing telomerase in humans is risky as it is associated with several types of cancers (Djojosubroto, 2003). Furthermore, genetic editing is extremely controversial as it brings into questions of ethics and morality, which will be further explored later in the essay. The question of whether a modified individual is still the same person is also called into question, opening philosophical debates about personhood and self.

Cellular Repair

Self-renewing stem cells, like those of the Hydra, is another promising area of research regarding artificial immortality for humans. Stem cell research has long dominated the medical field for various purposes as these cells can perform an array of tasks. For starters, the human embryonic stem cells are immortal. These cells do not age, they can proliferate indefinitely, and create any tissue of the organism (Mummery, 2014). Thus, not only do stem cells offer the promise of eternal life, but they also have the potential to heal disease and injury. Cellular repair transforms the body into a state of permanence, and its regenerative capabilities brings humanity closer to divinity through the sense of omnipotence. Cellular repairs further immortality by allowing invulnerability, which may be key to retaining quality of life for immortals. Both genetic editing and cellular repair places an emphasis on the body over the mind, and do not consider whether the human mind is capable of functioning beyond the lifespan in terms of memory or emotions. Thus, in both cases, the body is suspended in permanence, and one’s soul is eternally tied to the body. Again, this is an instance that rejects the separation of body and soul, and after incorporation into the state of immortality after undergoing the procedures, the notion of liminality will be rejected in favor of permanence.

Intelligence Digitization

Intelligence digitization is fundamentally different from immortality. Instead of creating an immortal body, the transfer of consciousness sustains an immortal mind. It is bringing symbolic immortality into the digital world. It celebrates and implements the separation of the body and the mind, in the lens of van Gennep and Hertz. Intelligence digitization is contingent upon notions of consciousness, and whether it is something that can exist without the body and be transferred into a computer. It raises philosophical questions on whether a digitized duplicate of a consciousness could be considered the same as the original consciousness. Questions about self are also raised in response to this method. In Buddhism, the transfer of consciousness is mentioned in the Tibetan philosophy under the Dhrong Jug technique (Sandu, 2015). It assumes that consciousness is a form of energy instead of a physical form, in the ontological sense, and perpetuates the idea of an immortal consciousness. Virtual immortality also allows the transcendence of omniscience and spatial limitation. As one exists in a digital space, they are no longer constricted by the physical realm, another staple of the divine. Intelligence digitization may be the technology to truly push humanity into an altered form of ontology, as previously mentioned forms do not allow omniscience and spatial limitations, and only overcomes biological limitations of humanity. Already, we have seen shifts of people to mourn in the digital space, finding more meaning and a more lasting legacy compared to traditional forms. Creative symbolic immortality is exercised without the limits of physical objects, which are subjected to destruction and deterioration (Bennet, 2015).

Cyborgs

A cyborg is a human/machine hybrid. Proposed theories for cyborg immortality include replacing faulty human parts with machines or placing the human consciousness into an artificial body. In her article for the Society of Cultural Anthropology, Cassandra Hartblay (2022) notes cyborg implementation as the ultimate destruction the notion that “natural and the technological are distinct spheres” by blurring boundaries between human/tool, human/animal, animal/ machine, body/mind, and physical/nonphysica. In terms of anthropological lenses that have been mentioned in this essay, it blurs the boundary between literal and symbolic immortality, as well as the body, mind, and soul. She mentions ethnographic consciousness, and how much our

Image 5: Cells under microscope with rendering Image Source: Pixabay

"Intelligence digitization is fundamentally different from immortality."

"...the final question remains: do people want to be immortal?"

Image 6: Human-AI interaction Image Source: Pixabay tools and objects become a part of us. A modernday analogy would be prosthetics. Cyborgism, in essence, is turning our entire body into an extension. It is the most complete overcoming of human limitation by destroying the body and replacing it with machines, including the brain by potentially implementing the consciousness as a chip or data in the machine body. Humans will be able to live in both a physical and digital world through cyborgism, a feature no other method will be able to accomplish (Hartblay, 2022).

The Implications of Immortality

Some of the world’s brightest minds are working fervently for breakthroughs in technologies revolving around immortality. Upon examining the roots of immortality, examples of immortality in nature, as well as developing methods for immortality, the final question remains: do people want to be immortal? The Pew Research Center had the same inquiry and published their finding through their article “Living to 120 and Beyond: Americans’ Views on Aging, Medical Advances and Radical Life Extension”. According to their data on whether Americans are willing to undergo life-prolonging treatment, such as the five methods of artificial immortality, most U.S. adults (56%) say no, but roughly two-thirds (68%) think that most other people would (Pew Research Center, 2022). From the data, it is evident that while most people currently will not undergo these procedures, they assume that others around them would. This assumption roots from the historical and cultural yearning for immortality, as mentioned earlier in the essay, that the average person would want to live beyond the human lifespan. However, as seen by the data, on the individual level, it is not a choice that most people would make currently. Perhaps it is because these technologies are immature. Additionally, there is always a reluctance, and skepticism, to accept new forms of developments until they are popularized and normalized for implementation into society. An example of this would be the internet, computers, or even vaccines. In fact, many people do not follow updates of new developments in the life prolonging field, and thus do not even know about available options. Another reluctance is the thought of losing loved ones if they do not opt for immortality, strained natural resources and wealth due to overpopulation, or the thought of artificial immortality as fundamentally unnatural. It could also be due to the eternal punishments that have been illustrated by lore throughout history.

Immortality and Transhumanism in a Knowledge-Based Society for Elites

While immortality is neither a currently viable nor widely sought after by the public, it is still worth thinking about what immortality would imply for our society when it becomes a possibility. There are two instances: the first is that immortality is exclusive, and the second is that immortality is accessible to all. In his article, “The Anthropology of Immortality and the Crisis of Posthuman Conscious,” Antonio Sandu examines the transhuman and posthuman condition in the pursuit of divinity, as well as its implications for society. For starters, Sandu posits that, in the anthropological lens, immortality does not transition humans from the current condition to a superhuman condition, instead, it is “similar to the supposed biological evolution of anthropoid primates towards the human state” (Sandu, 2015). It is important to note that the future, a “knowledge-based society (KBS)” of “intelligent evolution”, is not one chosen by natural selection, but instead artificial selection, driving humanity into a “existential singularity of a demiurgic nature” (Sandu, 2015). The methods introduced by this essay will be some of those driving factors for artificial selection, and those who can afford or have access to those services will be favored by that selection.

In a knowledge-based society, Sandu (2015) notes that due to transparency in knowledge, traditional social structures would be replaced

by network convergence, in which there will be both a social and anthropological paradigm. The idea is that when we can attain immortality, we would be in a post-singularity era. Not only would the human condition improve, but technology also targets the economy, society, and cultural developments through institutional design (Sandu, 2015). But what would this mean to people on an individual level? In the event of a virtual non-biological immortality, instead of susceptibility to biological threats, humans will instead be vulnerable to informational viruses. Issues of storage and data corruption also exist. Furthermore, immortality could result in the loss of personal identity, life motivation and even the will to survive (Sandu, 2015), whereas longevity is a tangible and desirable good. He insinuates that indefinite lifespan will diminish the purpose of life, as we will have infinite time and therefore no sense of urgency or innovation.

Like any new technology, initially, it will only be available to selected elites. From the price point to scarcity, immortality will not be a procedure just anybody can afford. In the thought-experiment of a post-immortality world, we will see a more defined pyramid structure of lifespan, with the elite on top as the demographic. Although this pyramid exists today, with the introduction of immortality, it will only widen the gap between the wealthy and the poor. Inequality would increase in all aspects of society. Due to longer lifespans, or indefinite lifespans, the wealthy will be able to amass more wealth, solidifying generational wealth, while the poor will be trapped in a more restrictive cycle of poverty, with less time and opportunities to create their wealth. In other words, those with power will only get more powerful, and those without will only fall further behind.

In fact, humans and transhumans would become distinct species (Sandu, 2015). Politically, in the declaration of independence, there is a line that quotes, “all men are created equal”. However, with advanced life-prolonging procedures that fundamentally either alter our biology, genetics, and consciousness, that statement no longer holds true, or will be highly questioned and obsolete. The new transhuman population will have “biological superiority”. Influence, and soft power of control systems developed by Joseph Nye in the international relations theory, will alter the structure of capital, leading to strict class systems with low social and economic mobility (Sandu, 2015), as the analysis in the previous paragraph illustrates. Sandu goes further and proposes the potential for “techno-slavery” or even classical forms of slavery despite the initial illusion of maintained democracy. Sandu then identifies two outcomes: the rebellion of the oppressed or space colonization, which will physically separate the two types of humans (Sandu, 2015). In the second case, humanity would have diverged into two different species completely irrelevant from one another and separated by physical space. The transhumans would appear like gods to the regular humans and would either abolish religion completely or become gods of a new religion. Ethics can be called into question to further analyze the state of society in a transhuman world. As technology for improving lifespan and genetics exist, the same could be done to decrease lifespan or remove genetic information for the normal humans, which are created to serve the transhumans (Sandu, 2015). This builds upon the risks introduced in the genetic engineering section of the paper. For instance, removing the human tendency for aggression or self-actualization, or other traits that prompt rebellion or disobedience, Sandu (2015) uses Nietzsche’s idea of slave mortality as herd mortality, showcasing that humans would be reduced to subhuman states engineered to serve the elite few with technologies that allow for those elite few to have an immortal rule, and that is truly a terrifying thought.

Equal Access Immortality

In the event that immortality is accessible to all, Sandu (2015) refers to John Harris’s idea that human reproduction would completely end. Thus, humanity trades biological symbolic immortality for biological literal immortality. The world would be composed entirely of the same people, without any new additions to society due to overpopulation if allowed. It would likely be ingrained into law, and anyone who attempts to reproduce would likely be eliminated. The world, in a sense, would become static. There will be little movement between social classes. There will be no incentive for change or innovation. If only immortality is guaranteed, then the quality of life will not be able to be guaranteed for all. Those who do not lead privileged lives will continue to suffer for all of eternity. If neither aging nor disease is an issue, that could potentially allow a maintenance of a decent quality of life. However, if solving these issues require additional technologies that do not come included with immortality, the poor will suffer additionally– life will be no better than death. Although hypotheticals of the future seek bleak, that is only in the event of abuse of power, corruption, and greed. Sandu and other experts maintain "...humanity trades biological symbolic immortality for biological literal immortality."

Image 7: Human connection and biology Image Source: Pixabay

an air of optimism and hopes that global ethics centered on social responsibility with respect for human rights and ethical principle in science will create sustainable, human-centered technology that improve the quality of life for everyone will prolonging lifespans before reaching technologies that allow for some form of immortality (Sandu, 2015). This allows responsibility in ensuring that dystopian-like futures do not come into actuality with the development and eventual implementation of immortality and other lifeprolonging technologies and maintaining the basis that all humans are equal and deserve equal rights and quality of life.

Netflix’s show Love, Death + Robots, volume 2, episode 3, presents a fictional world in which there is equal-access immortality and the ban of reproduction. The episode follows Detective Briggs, someone in charge of eliminating “unregistered offspring”. The detective has PTSD from killing children for his job, and the episode features the hunt of an unregistered offspring. In this world, immortality has diminished the meaning of life, which has also been explored in this essay, and there is no sense of wonder. However, when Detective Briggs discovers the newborn and her mother, he observes the two and marvels at the child’s curiosity opposed to his own numbness. As he previously imagined having children with his lover, he decides to spare the two, but as he is leaving another officer arrives and hears the cries of the baby. The two have no choice but to confront one another and shoot each other. In his final moments, Detective Briggs seems to have recovered the essence of being human again and dies feeling truly alive. Although fictional, the episode illustrates the human aspect of a future stripped of generational continuance in a manner that spurs a reevaluation of what it means to be human for the viewer, and the value of our legacy. It is ironic that in the moment of his death, Detective Briggs truly feels alive since he has lived for centuries and has already seen and experienced everything that could be experienced, except death and parenthood. While humans will always want more, and the promise of eternal life will always beckon us, the episode of Love, Death + Robots reminds us to appreciate our loved ones, as well as the ability to experience and wonder due to our mortality.

Conclusion

After examining symbolic and literal immortality through the lens of Hertz, van Gennep, and Lifton, as well as through other lenses such as philosophical, religious, theological, or ontological, exploring existing forms of immortality within nature and the human body, presenting technologies for immortality under development and analyzing them through various lenses, and finally diving into the implication of immortality for society through Sandu and hypothetical worlds through fiction, we now have a more holistic understanding of immortality dissected through different perspectives and lenses. As death, disease and aging is inevitable for everyone, it is important to examine the possibility of overcoming those limitations. Ian Pearson, a futurist who tracks and predicts development across of technology, society, and business, estimates that immortality will be attainable as soon as 2050, which means that we are at the dawn of what many call the “transhumanist” movement, and many of us will see immortality become an option in our lifetimes. Already, we are seeing a shift in that more people are accepting cryonics, which is a transition into other forms of immortality. In a self-perpetuating cycle, confidence in breakthroughs in related technologies, such as the various methods of artificial immortality, also increases those who would choose cryonics.

All in all, we must ask ourselves the big question, framed through bioanthropology: Are we indeed headed for the next stage of human evolution (Sandu, 2015)? In a rapidly changing world of technological innovation, how will we, as individuals, as a community, shape our present to secure a peaceful future for all? How will we adhere to our ethics and values in an increasingly complex world, in which traditional society and culture shifts to center around knowledge and data? From examining symbolic and literal immortality, to existing forms of immortality of various animals and cancer cells, proposed methods of immortality through different technologies, and the implications of immortality for our society, this article merely presents the tip of the iceberg in discussing a knowledge-based society, in which immortality is merely one aspect of a nuanced, unimaginable world. Although the possibilities are endless, it is, nonetheless, important to plant a seed of higher existential thinking in these matters as slowly, but surely, the future comes into actuality.

Works Cited

Bennett, J., & Huberman, J. (2015). From monuments to megapixels: Death, memory, and symbolic immortality in the contemporary United States. Anthropological Theory, 15(3), 338–357. https://doi.org/10.1177/1463499615575943

Berthold, E. (2021, May 24). The animals that can live forever. Curious. Retrieved April 27, 2022, from https://www.science.org.au/curious/earthenvironment/animals-can-live-forever

Djojosubroto, M. W., Choi, Y. S., Lee, H. W., & Rudolph, K. L. (2003). Telomeres and telomerase in aging, regeneration and cancer. Molecules and cells, 15(2), 164–175.

Hartblay, C. (n.d.). Cyborg. Society for Cultural Anthropology. Retrieved April 27, 2022, from https://culanth.org/fieldsights/cyborg

Hertz, R. Lifton R. J. Robben, A. C. G. M. (Ed.). van Gennep A . (1991). Death, mourning, and burial : A cross-cultural reader. John Wiley & Sons, Incorporated.

How and why do we age. MPI - Biology of ageing. (n.d.). Retrieved April 27, 2022, from https:// www.age.mpg.de/healthy-ageing/how-and-whydo-we-age

Lawrie, E. (2018, March 20). Are 'cryonic technicians' the key to immortality? BBC News. Retrieved April 28, 2022, from https://www.bbc. Living to 120 and beyond: Americans' views on aging, medical advances and Radical Life Extension. Pew Research Center's Religion & Public Life Project. (2022, April 15). Retrieved April 27, 2022, from https://www.pewforum. org/2013/08/06/living-to-120-and-beyondamericans-views-on-aging-medical-advancesand-radical-life-extension/.

Mummery C. (2004). Stem cell research: immortality or a healthy old age?. European journal of endocrinology, 151 Suppl 3, U7–U12. https://doi.org/10.1530/eje.0.151u007

Nagaraj, A. K., Nanjegowda, R. B., & Purushothama, S. M. (2013). The mystery of reincarnation. Indian journal of psychiatry, 55(Suppl 2), S171–S176. https://doi.org/10.4103/0019-5545.105519 (Retraction published Indian J Psychiatry. 2015 Oct-Dec;57(4):439)

Netflix. (2019). Love, Death + Robots. Retrieved from https://www.netflix.com/title/80174608.

Sandu, A. (2015). The anthropology of immortality and the crisis of posthuman conscience. Journal for the Study of Religions and Ideologies, 14(40), 3-26.

Weinberg, R. A. (2014). The Biology of Cancer. Garland Science.

Investigating the Annual Influenza Vaccine

STAFF WRITERS: FRANKIE CARR ‘22, LAUREN FERRIDGE ‘23, JULIETTE COURTINE ‘24, HAYDEN BARRY ‘25, VARUN LINGADAL ‘23, ABIGAIL FISHER ‘23 TEAM LEADS: MADELEINE BROWN ’22, KRISTAL WONG ‘22

Cover Image: Physicians recommend yearly vaccine for influenza. Patients should consult with their healthcare provider before inoculation.

Source: CDC

Introduction

Influenza is a highly contagious respiratory illness that may cause serious complications in individuals with weakened or compromised immune systems such as children and the elderly, and for people with certain health conditions (CDC, 2021c). Luckily, modern medicine has developed a way to curb the serious complications of the flu: vaccination. However, the fact that there are multiple strains of the flu that can each give rise to infection in humans, coupled with high within-strain mutation rate, contribute to the need for yearly “booster” inoculations to protect humans from a year’s predicted most prominent and most dangerous strands. Powerful antivirals such as Tamiflu can alleviate symptoms and speed up recovery. It is also important to note that an influenza virus was responsible for the previous global pandemic, given the moniker “the 1918 Spanish Flu,” and much can be compared between the latter pandemic and the current COVID-19 pandemic.

According to the US CDC, there were an estimated 35 million cases of flu-related instances and 20,000 flu-related deaths in the 2019-2020 flu season (CDC, 2021f). This paper will discuss the influenza virus and its pathology. It will also outline outlining the history of influenza, highlighting notable strains, epidemics, and pandemics. A large component of the piece will be dedicated to understanding current vaccine technology and dissecting the need for an annual vaccine.

Biology and Pathology of the Virus

The flu is caused by a family of viruses known as the influenza viruses. There are four kinds of influenza viruses: Alphainfluenzavirus (influenza A virus or IAV), Betainfluenzavirus (influenza B virus or IBV), Gammainfluenzavirus (influenza C virus or ICV), and Deltainfluenzavirus (influenza D virus or IDV), defined by their unique host specificities, the symptoms they trigger, and mutation rates (Asha & Kumar, 2019; Krammer et al., 2018; Sautto et al., 2018). All four types of viruses can infect humans. IAV is the cause of many of the past pandemics, including the aforementioned 1918 Spanish Flu (Asha & Kumar, 2019; Sederdahl & Williams, 2020). Meanwhile, IBV and ICV infections are rarer, with both disproportionately infecting children

(IBV has contributed to some of the seasonal epidemics of the past). IDV was not discovered until 2011 and thus there is ongoing research into its effects, although it is known that it can infect humans and can spread to them from cattle and swine populations (Asha & Kumar, 2019).

All of these viruses have a negative sense, singlestranded RNA genome. This means that once the virus has docked to a target cell and injected its genetic material into the host, its genome must be copied by an RNA polymerase, producing the positive strand which can then be transcribed into mRNA (and eventually translated into the viral proteins). These genomes are also segmented into eight smaller fragments, which can be thought as mini chromosomes of sort, with each segment coding for different protein(s). This segmentation allows for the rearrangement and combination of the genomes of different influenza viruses (of the same A, B, C, or D type) that are infecting the same host cell. Additionally, pieces of homologous fragments from different viruses can recombine into one new fragment, with sections from both parents. These processes of rearrangement and recombination are the origin of many zoonotic strains of influenza, and they are often referred to collectively as the “antigenic shift” (Asha & Kumar, 2019; Sederdahl & Williams, 2020). Antigenic shift is also responsible for another well-known feature of influenza: the large number of variable strains.

IAV strains are often labelled in the format of “H1N1” (the “swine flu” responsible for the 2009 pandemic) (Krammer et al., 2018). But what does this format stand for? There are two main proteins that vary between different flu strains: haemagglutinin (HA) and neuraminidase (NA). HA proteins coat the outside of the viral capsules (~500 molecules per virion) and are responsible for viral docking and entry into the target cell via binding to sialic acid in the cell’s membrane. For this reason, HA is a popular target for most vaccines. There are two groups of HA proteins with a total of 18 known varieties (labelled as H1, H2, etc) (Madsen & Cox, 2020). NA proteins are also present on the external face of the viral capsule (about ¼ to 1/5 as common as HA) and serve to cleave those same sialic acid molecules to release virions into the body once HA has allowed the virus entry to the cell and it has co-opted the cell’s machinery to build new virions. More research is being done to mobilize vaccination technologies against NA. There are 11 varieties of NA, labelled in the same way as HA varieties (N1, N2, etc). Rearrangement of these various HA and NA genes (for example, an H1N1 virus intermixing with an H18N11 virus to produce H1N1, H1N11, H18N1, and H18N11 virions) leads to the different IAV strains that are known to cause massive pandemics. Since these proteins are on the surface of the viruses, they make the perfect targets for the immune response and, thus, vaccines. The rearrangement mentioned above along with the fact that the different HA and NA proteins are different enough means that we require different vaccines for each strain. Additionally, differences in these proteins lead to variable transmissibility (the rate of spread of the virus from individual to individual) and virulence (the danger a virus poses to an individual; a measure of the symptoms caused by the virus) (Sautto et al., 2018; Webby & Sandbulte, 2008).

In addition to the specificity of HA, influenza viruses also have two evolution mechanisms driving antigenic diversity that further increase complexity and chance of new strain emergence. These two mechanisms are antigenic drift and antigenic shift (Webby & Sandbulte, 2008). Antigenic drift is the main reason for needing frequent updates of flu vaccines. It is the mechanism where amino acid changes occur that change binding sites of the HA, thus escaping recognition by antibodies and creating a new antigenic variant (Ziegler et al., 2018). This erases any immunity or memory developed from

Image 1: Tamiflu Image Source: Wikimedia Commons

"...influenza viruses also have two evolution mechanisms driving antigenic diversity that further increase complexity and chance of a new strain emergence."

previous vaccination. The second phenomenon, antigenic shift, is the virus’s ability to exchange or recombine gene segments between two different influenza strains within one host: simultaneously infecting and replicating within that host. This genetic reassortment generally occurs in a nonhuman host, but recombination of two strains enables the new virus to ‘hop’ from the animal reservoir to humans—where it unleashes a new flu strain on naïve human immune systems (Ziegler et al., 2018). Examples of animal reservoirs are birds or pigs, which have become namesakes for certain epidemics or pandemics such as the “swine flu” and the “avian flu”.

In the United States, flu season—the time period when flu cases begin to rise—occurs roughly between October and May (CDC, 2021). The timing of flu season is thought to be the result of a multitude of factors including an influx of people indoors, lack of vitamin D, as well as changes in humidity as temperatures begin to drop (Lowen, 2007). As the flu is estimated to be responsible for as many as 52,000 deaths and millions of hospitalizations in the United States alone per year, proper treatment is a necessity.

Most cases of the flu resolve without medical intervention, but antiviral drugs are available to relieve severe symptoms and prevent spread of infection. Currently, there are four FDA approved antiviral drugs for the flu: Rapivab, Relenza, Tamiflu, and Xofluza (FDA, 2021). Rapivab, Relenza, and Tamiflu are neuraminidase inhibitors. Neuraminidase is an enzyme that cleaves sialic acid—a carbohydrate on the surface of cells. In the context of the flu virus, this cleavage promotes the release of new viral particles. Neuraminidase inhibitors mimic sialic acid but cannot be cleaved by Neuraminidase, suppressing the virus (Palese, 1976). On the other hand, Xofluza prevents the flu virus from replicating by blocking viral transcription (Eisfeld, 2019). Although effective, antiviral drugs are reactive measures and are not considered the first line of defense against the flu virus. The most effective method at preventing the transmission of the flu is the flu vaccine.

History of Influenza - Present Day

The most severe pandemic prior to the current COVID-19 pandemic was the 1918 influenza pandemic, which was caused by an H1N1 virus (History of 1918 Flu Pandemic, 2019). The pandemic occurred during World War I, and the first cases in the United States were detected at an army encampment in March of 1918. A second wave of the flu emerged at a naval facility outside of Boston in September. The second wave was highly fatal, accounting for the majority of pandemic deaths and killing an estimated 195,000 Americans during the month of October alone (1918 Pandemic Influenza Historic Timeline, 2019). A third wave of flu emerged in the winter and spring of 1919 before the pandemic subsided. In total, the 1918 pandemic caused at least 50 million deaths worldwide (~675,000 in the United States) and infected 500 million people, representing nearly a ⅓ of the world’s population at the time (1918 Pandemic Influenza Historic Timeline, 2019).

A new influenza, caused by influenza A (H2N2), emerged in East Asia in February of 1957 and originated in China (1957-1958 Pandemic (H2N2 Virus), 2019). This provided the first opportunity to investigate the spread of influenza in a laboratory setting, though resources for surveillance were more limited compared to today (Kilbourne, 2006). The pandemic caused an estimated 1.1 million deaths worldwide, though it was generally considered to be less severe both than the Spanish Flu and the Russian Flu, which came after (Rogers, 2019). The 1968 pandemic, first discovered in Hong Kong, was also caused by an influenza A virus, H3N2. It caused approximately 100 million deaths worldwide and 100,000 deaths in the United States (1968 Pandemic (H3N2 Virus), 2019). This pandemic was later followed by the “Russian Flu” in 1977, which marked the return of an H1N1 virus.

More recently, around 2009, a novel influenza A virus, (H1N1)pdm09, emerged in the United States and quickly spread to the rest of the world. Between April 2009 and April 2010, the CDC estimated that this virus infected over 60 million people in the United States, killing between 151,700 and 575,400 people worldwide in that same time period. The pandemic primarily impacted children and young and middle-aged adults, but the impact was still less than that of previous pandemics (CDC, 2019).

Influenza Vaccine Vaccines Overview

The term vaccine is derived from the Latin word vaccinae, meaning cow. This is because the first vaccine was created by Edward Jenner, a British scientist and surgeon during the late 1700s, when he began trying to prevent patients from getting infected with the smallpox by giving them a case of the less-deadly cowpox. Until that time, doctors had been deliberately infecting patients with smallpox (by injecting it under the skin) to allow them to build up immunity to the disease to prevent severe infection; Jenner’s attempt was the first to create a safer way to build up natural

immunity (Baxby, 1999).

The goal of any vaccine is to allow the body to safely learn what a certain pathogen “looks like” and build an adaptive immune response to it. The role of B cells is to produce antibodies to bind to the target pathogen and memory B cells to mobilize a quicker response upon a subsequent infection. In addition, T cells work to destroy cells infected with it the virus or signal other immune cells to mount an effective response. By artificially stimulating adaptive immunity, rather than stimulation via infection by a pathogen, is referred to as vaccination. This word alludes to Jenner and his work with cowpox; Jenner has been hailed one of the fathers of germ theory (Pasteur, 1881). Vaccines can be prophylactic (or preventive, meaning that they prepare the body to fight off an infection that might occur later) or therapeutic (meaning that they teach the immune system what to fight when the body might already be infected, as is the case with the rabies vaccine (CDC, 2021) or the cancer vaccines that are being developed (Guo et al., 2013).

There are many kinds of vaccines, and they come in many different forms: some use attenuated/ weakened versions of a pathogen, dead/ inactivated versions of a pathogen, pieces of a pathogen, or some sort of carrier for genetic material to cause the host’s cells to produce the pieces of the pathogen that the immune system should target. Additionally, some vaccination protocols require different numbers of treatments/injections (CDC, 2018). Nonetheless, vaccines have truly revolutionized modern medicine, saved countless lives, and have helped nearly eradicate many diseases that plagued us for so long, including Polio (WHO, 2021).

History of Influenza Vaccination

The history of influenza vaccination has a rather recent start; it wasn't until 1933 that the virus was first isolated. English scientists Wilson Smith, Sir Christopher Andrews, and Sir Patrick Laidlaw isolated influenza A virus from nasal secretions of infected patients and successfully infected ferrets (Hannoun, 2013; Barberis et. al, 2016). In 1936, American virologist and epidemiologist Thomas Francis Junior successfully isolated influenza B virus (Hall, CDC). In the same year, Macfarlane Burnet successfully grew influenza virus on the chorio-allantoid membrane of embryonated hen eggs (Barberic et. al, 2016). Following this, in 1936, the first neutralized antibodies generated by human influenza virus infection were isolated (Barberis et. al, 2016). During the 1930s, there were several further developments, including the inactivation of the virus by formalin and virus purification through high-speed centrifugation (Barberis et. al, 2016). These led to the creation of early forms of influenza vaccine, and the first clinical trials were conducted in the mid-1930s. In 1938, Jonas Salk and Thomas Francis Junior managed to protect US military forces with influenza vaccines, research that would culminate in Salk’s development of the polio vaccine in 1952 (Barberis et. al, 2016).

The 1940s saw the first widespread vaccine with the objectives of protecting against disease and achieving high vaccination rates to ensure protection in unvaccinated people. The first vaccine was an inactivated, monovalent vaccine. Studies between 1942 and 1945 led to the discovery of influenza mismatch, a phenomenon that arises when the vaccine does not provide protection against the influenza strain that is widely circulating and causing the current seasonal epidemic (Barberis et. al, 2016). Thus, in 1944 and 1945, a bivalent vaccine was manufactured and widely distributed that contained influenza A and B strains inactivated with a formalin (aqueous formaldehyde)

Image 2: CDC Ad for 2021 National Influenza Vaccination Week (NIVW) December 5th – 11th, 2021.

Image Source: CDC

"Climate change is particularly devastating for the 100 million people, or 2% of the world’s population, who are homeless."

"The production of fluc vaccines is essentially a yearround process and involves a variety of global and domestic parties."

treatment (Hannoun, 2013). Wendell Meredith Stanley, an American biochemist, developed a detailed preparation and purification of influenza virus vaccine that was produced using embryonated hen eggs (Hannoun, 2013). These improvements in production, strain selection, and safety led to improved performance of the influenza vaccine.

In the 1950s, following pandemics and the discovery of new influenza strains, the World Health Organization (WHO) created a system to conduct surveillance to observe, predict, and monitor flu strains to prevent virus mismatch (Barberis et. al, 2016). The discovery of new subtypes required vaccines to cover new and different strains depending on the relative prevalence of influenza subtypes. In 1968, trivalent inactivated vaccines were first developed to provide increased coverage, and split/subunit vaccines helped decrease the risk of adverse reactions, particularly in children (Barberis et. al, 2016). Split/subunit vaccinations consist of viruses that are degraded into viral particles using detergents (O’Gorman et. al, 2015). These split vaccines can elicit a potent immune response in previously exposed individuals with increased safety and lower rates of adverse reaction (O’Gorman et. al, 2015).

The major downside of split vaccines was that they were seen to be less immunogenic than whole virus vaccines - that is, they do not prompt as large of an immune response. Thus, in the 1970s, genetic reassortment of influenza vaccines enabled vaccine strains to grow faster in embryonated hen eggs (Barberis et. al, 2016). Subunit vaccines soon followed, containing only the surface antigens of the influenza virus, hemagglutinin (HA) and neuraminidase (NA). Surveillance systems such as that created by WHO monitor circulating strains and their respective HA NA variants to ensure adequate vaccine coverage (Barberis et. al, 2016). Today, research has shifted to better predicting strains of influenza that could be circulating, developing a universal influenza vaccine that could protect against all influenza virus strains regardless of antigenic drift, and identifying sustainable ways to rapidly meet the global demand for influenza vaccines particularly when facing a global pandemic (Barberis et. al, 2016).

Production and Manufacturing of Different Vaccines

The production of flu vaccines is essentially a yearround process and involves a variety of global and domestic parties. The World Health Organization (WHO) hosts two annual meetings with relevant advisory groups – such as the FDA and vaccine manufacturers – to review important influenza data. This includes the results of flu samples collected by the CDC year-round and other laboratory data which is used to determine what strains of flu may be circulating or most serious (CDC, 2021). WHO makes a recommendation about what viral strains to include in the flu vaccine, but ultimately, the governing medical body of each country – which is the FDA in the United States – will make the final decision about what strains to protect against (WHO, 2022). In 2022, the first of these annual meetings was held in late February, although vaccine manufactures may have begun growing strains for vaccines as early as January. It may seem shocking that this year’s flu vaccine is already being produced, but the CDC estimates that it takes nearly six months to produce enough flu vaccine for the general population. All flu vaccine production is handled by private manufacturers in the United States (CDC, 2021).

There are four main types of flu vaccines, and they are manufactured in two different ways. The Quadrivalent flu vaccine is the primary formulation which uses inactivated viruses and protects against two type A strain flu viruses and two type B strain flu viruses. Different administration methods and formulations of the Quadrivalent vaccine can be administered to anyone six months or older. The Jet Injector is a method of administering the Quadrivalent flu vaccine which uses a high-pressured stream of liquid powered by compressed gas or springs. The Jet Injector can be administered on people between the ages of 18 and 64. The High-Dose Quadrivalent vaccine is for those 65 years or older. It contains four times more of the antigen than the regular Quadrivalent vaccine, which is what builds protection against the virus. The Adjuvanted vaccine is also for those 65 years or older and includes an adjuvant, which increases the immune response to the vaccine. Therefore, less vaccine is needed per dose for the same effect and more vaccines can be made using less resources (CDC, 2021).

These vaccines can be produced either through a cell-based process or a recombinant process. In the cell-based process, candidate vaccine viruses are injected into mammalian cells, allowed to incubate so the candidate vaccine viruses multiply. Then, the candidate vaccine viruses are extracted and refined, and used in the vaccine. Because these vaccines are produced using mammalian cells, they have shown greater protection against

the virus. The cells used to create the vaccine can also be frozen and stockpiled so, in case of a pandemic, vaccine production can be jump started. Recombinant vaccines involve genetically modifying a virus to deliver the “instructions” for producing the flu antigen into a cell where it is then grown, collected, and purified. For all vaccines, anyone outside of the FDA-approved age range or who has had severe reactions to the vaccine or any of its ingredients should not get the vaccine. The CDC does not recommend any one vaccine over another (CDC, 2021).

The nasal spray vaccine is also known as the Live Attenuated influenza vaccine (LAIV). It is an egg-based flu vaccine, which means it is produced first by candidate vaccine viruses (CVVs). The CVVS are injected into fertilized eggs and allowed to incubate for several days so the CVVs can replicate. The fluid containing the CVVs is then extracted from the eggs and the viruses are weakened, allowing for use in the nasal spray vaccine. The LAIV is administered from a health provider via mist. Half the dose is sprayed into one nostril, and the other half into the other (Immunization Action Coalition, 2021). The nasal spray vaccine is effective for most nonpregnant people between the ages of 2 and 50 (CDC, 2021). Those with weakened immune systems, who have had a severe allergic reaction to a past flu vaccine, children receiving aspirin- or salicylate-containing medications, people with cochlear implants, those with an active cerebrospinal fluid leak, and those without a spleen should not receive LAIV. One should also take precaution when receiving the LAIV if they are ill. The nasal spray flu vaccine is as effective as inactivated flu vaccines for most strains; however it is slightly less effective against the H1N1 strain (CDC, 2021). While the nasal spray vaccine increases vaccination costs, it is very effective in reducing the amount of healthcare necessary for flu-related illnesses (Tarride et al., 2012). Tracking and Surveillance To know which vaccine to produce, vaccine strain patterns of emergence, virulence, and severity must all be tracked. Many actors contribute to this effort. On a global scale, the Global Influenza Surveillance and Response System (GISRS) is coordinated by the World Health Organization (WHO) and endorsed by many national governments. GISRS fosters global confidence and trust and is an example of success of commitment to a global public health model. Its mission is to function as a “global mechanism of surveillance, preparedness and response for seasonal, pandemic, and zoonotic influenza; global platform for monitoring influenza epidemiology and disease; and a global alert for novel influenza viruses and other respiratory pathogens” (Global Influenza Surveillance and Response System (GISRS), n.d.).

The GISRS was founded in 1952 and was adopted by the Pandemic Influenza Preparedness Framework (PIP Framework) in 2011. These actions acknowledge the importance of surveillance in preparing for influenza strain emergences. The GISRS is a complex network that tests clinical samples, reports the positive results to the WHO, and provides influenza viruses to WHO Collaboration Centers (Ziegler et al., 2018). Today, it is comprised of 150 established laboratories, 142 National Influenza Centers, 6 WHO Collaborating Centers, 4 Essential Regulatory Laboratories, and 13 H5 Reference Laboratories (Ziegler et al., 2018) in 114 countries representing 91% of the world’s population (Broor et al., 2020). The GISRS network is a platform for systematic testing for RSV (respiratory virus) associated with respiratory illnesses and disciplined global reporting (Broor et al., 2020).

On a domestic level, the Center for Disease Control (CDC), the Food and Drug Administration (FDA) and the Surgeon General are all important actors in the United States’

Image 3: Figure 3: The flu vaccine Image Source: Wikimedia Commons

effort to prepare for and adapt to each flu season. The broad CDC goals are to “monitor and assess influenza virus and illness, .. support surveillance and response capacity, improve vaccine … interventions, and … enhance prevention and control policies” (CDC, 2020). Additionally, the CDC is the leading body that informs healthcare providers and public about influenza updates, and prevention and control measures. They connect with businesses, schools, and communities to help plan for flu threats (CDC, 2020).

The FDA is responsible for ensuring that the supply of flu vaccines and flu antiviral drugs is safe and effective (Commissioner, 2020b). They are also crucially involved in ensuring supply and distribution of the flu vaccine. They work to certify and approve new vaccines and treatments are safe for the public and conduct roll out and distribution efforts. Since engaging in flu vaccine efforts is a year-round effort, the FDA collaborates with the CDC and WHO to first identify and select the focused most likely strain for the upcoming season, produce materials for new vaccines in labs, and ensure new vaccines meet appropriate safety and efficacy standards (Commissioner, 2020a).

Lastly, the surgeon general is the “chief medical doctor and health educator” for the (Definition of Surgeon General - NCI Dictionary of Cancer Terms - National Cancer Institute, 2011). They are tasked with communicating scientific information to the American public on how to improve health and lower risk of infection. The Surgeon General can issue health warnings on consumer products, vaccines, or current health risks such as the flu and flu vaccine (“Surgeon General of the United States,” 2021).

As demonstrated, there are many actors, on the global, national, and community levels, that mobilize ahead of each flu season. Prediction of upcoming strains, accurate vaccines, and effective communication with the public will ensure public health safety and minimize incidence of flu infection, mortality, and morbidity.

Barriers to Vaccination

Vaccinations are sometimes classified as one of the greatest achievements of public health (Larson 2014), yet in recent decades the phrase “vaccine hesitancy” has also become more commonplace. More than ever before, globalization plays a key role in allowing people all over the world to share their concerns regarding vaccine safety, and the conversation is made additionally complex by an expansion in vaccination options (Larson 2014). Previously the delineation was between “pro-” and “anti-” vaccination; yet, this language was deemed polarizing and unproductive and therefore shifted to describing the newer term of vaccine hesitancy. The World Health Organization Strategic Advisory Group of Experts on Immunization (WHO SAGE) defines vaccine hesitancy as “the acceptance of vaccines on a continuum between demand and no demand ranging from accepting all vaccines to accepting no vaccine” (Schmid 2017). Due to the rising numbers of people who identify within this broad category, research on the topic has also expanded. Studies including data from countries across the world have shown that there are multiple influences which carry varying importance to certain communities, depending on the values of the culture and the vaccine being discussed. For example, in Greece, the education of one’s siblings and father was found to be an important marker for determining one’s hesitancy, whereas in Nigeria, the approval or disapproval of parental guardians was a deciding factor (Larson 2014).

It is worth noting that across risk groups, barriers for seasonal and pandemic influenza vaccination were similar in content and reported frequency (Schmid 2017). WHO SAGE has developed a model for categorizing these different factors. Specifically, the individual/social and contextual levels contain valuable information that will be discussed in this paper. It should be noted that the following research is based on countries in WHO regions, primarily Western samples. On the micro-level, there have been individual/social psychological and physical barriers identified.

The main psychological barriers include utility, subjective norm, and attitude, among others. The utility barrier is a comparison of the vaccine’s proposed benefits (including protection from disease and herd immunity) versus the possible risks (including vaccine-adverse events, contracting the disease, and even anticipated regret of not receiving the vaccine) (Schmid 2017). The subjective norm barrier identified that when social pressure to receive the vaccine is high, so is the uptake of vaccination, and attitude research showed that every risk group had lower vaccination uptake if the vaccine was not believed to be trusted or effective, therefore making it a major psychological barrier (Schmid 2017). The main contextual physical barriers to influenza vaccination were cues to action and previous healthcare system interaction. A lack of cues to action (i.e., medical professionals or relatives recommending vaccination) and previous interactions with one’s healthcare system such as through yearly check-ups were strongly correlated with less vaccine uptake. Interestingly,

Image 4: Inoculation with an annual flu vaccination may proves beneficial to a spectra of age groups. It is most beneficial amongst high-risk groups such as children, students, and the elderly. Image Source: CDC

access barriers such as political, geographical, or economic issues, or reliability of vaccination supply were not identified as a physical barrier to vaccination in this research (Schmid 2017).

Furthermore, socioeconomic status (SES) and level of knowledge were identified as major contextual barriers (Larson 2014). For the SES barrier, low SES was identified in multiple countries as being a barrier, yet the factors for why it was an obstacle varied. For example, in the United States, low SES was linked to trust issues with healthcare providers, whereas in Nigeria, it was primarily linked to low education (Larson 2014). Level of knowledge was also an important barrier because it was identified that in all risk groups as well as in the public, vaccination uptake decreased if knowledge concerning influenza and the vaccine was low (Schmid 2017). One can determine from this research that there are a variety of barriers leading to influenza vaccine hesitancy, but they are connected to different factors across countries and there is no “universal algorithm” with which to assess them all (Larson 2014). Further research should examine countries outside WHO regions with greater diversity in barriers, thereby creating a more comprehensive understanding of influenza vaccine hesitancy.

Why do we need a new flu vaccine each year?

Seasonal influenza causes 290,000 to 650,000 respiratory deaths each year (Madsen & Cox, 2020). This number increases when a novel influenza virus strain emerges and which the humans are immunologically naïve to. However, vaccination plays an important role in reducing this number. Seasonal flu vaccines are produced every year. Annual vaccines are based on predictions on which strain will be most prevalent that year. As mentioned earlier, influenza vaccines in the United States are “quadrivalent” and provide protection against two influenza A strains H1N1 and H3N2 and two influenza B strains (CDC, 2021). But despite the quadrivalent coverage, a new vaccine is still required every year. There are two main reasons for this; first, a person’s immune protection from vaccination declines over time so annual vaccines will promote protection, and second, flu viruses are constantly changing, and a different strain is dominant each year, so a different vaccine is necessary each flu cycle (CDC, 2021).

The rapid evolution of influenza and the ease with which it increases its antigenic diversity are the barriers that necessitate annual flu vaccines. While it would be ideal to have a universal and one-time flu vaccine, scientist must first identify other drawbacks of the current flu vaccine campaign. The main issues are that vaccines target variable proteins and time is needed to update vaccines. Consequently, it takes about 6-7 months to produce each seasonal flu vaccine (Webby & Sandbulte, 2008), which means predictions must occur months out of vaccine implementation. Predictions so far in advance can be inaccurate, risking the development of a vaccine that does not defend against the dominant strain.

Conclusion

The benefits of the flu vaccine are impressive, and its development has saved countless lives— particularly among those in high-risk groups such as children or the elderly. While flu season still poses serious health risks, widespread vaccine use as well as antiviral treatments have significantly reduced the number of deaths and prevented serious flu pandemics from sweeping the globe again. As the world continues to grapple with the COVID-19 pandemic, it is easy to draw parallels between the path of influenza and COVID. Notably, COVID-19 variants have increased the need for multiple vaccines and booster shots much like the annual flu vaccine. Most importantly, however, flu and COVID vaccines remain at the forefront of the world’s battle against these pandemics. "...flu viruses are constantly changing, and a different strain is dominant each year, so a different vaccine is necessary each flu cycle."

Asha, K., & Kumar, B. (2019). Emerging Influenza D Virus Threat: What We Know so Far! Journal of Clinical Medicine, 8(2), 192. https://doi. org/10.3390/jcm8020192

Baxby, D. (1999). Edward Jenner’s Inquiry; a bicentenary analysis. Vaccine, 17(4), 301–307. https://doi.org/10.1016/S0264-410X(98)00207-2 Bouvier, N. M., & Palese, P. (2008). The Biology of Influenza Viruses. Vaccine, 26(Suppl 4), D49–D53.

Broor, S., Campbell, H., Hirve, S., Hague, S., Jackson, S., Moen, A., Nair, H., Palekar, R., Rajatonirina, S., Smith, P. G., Venter, M., Wairagkar, N., Zambon, M., Ziegler, T., & Zhang, W. (2020). Leveraging the Global Influenza Surveillance and Response System for global respiratory syncytial virus surveillance— Opportunities and challenges. Influenza and Other Respiratory Viruses, 14(6), 622–629. https://doi.org/10.1111/irv.12672

CDC. (2019a, January 22). 1957-1958 Pandemic (H2N2 virus). CDC. https://www.cdc.gov/flu/ pandemic-resources/1957-1958-pandemic.html

CDC. (2019b, January 22). 1968 Pandemic (H3N2 virus) | Pandemic Influenza (Flu) | CDC. https:// www.cdc.gov/flu/pandemic-resources/1968pandemic.html

CDC. (2019c, April 18). 1918 Pandemic Influenza Historic Timeline. CDC. https://www.cdc.gov/ flu/pandemic-resources/1918-commemoration/ pandemic-timeline-1918.htm

CDC. (2019d, April 18). History of 1918 Flu Pandemic. CDC. https://www.cdc.gov/flu/ pandemic-resources/pandemic-timeline-1930and-beyond.htm

CDC. (2019e, June 11). 2009 H1N1 Pandemic. Centers for Disease Control and Prevention. https://www.cdc.gov/flu/pandemicresources/2009-h1n1-pandemic.html

CDC. (2020, December 9). What CDC Does. Centers for Disease Control and Prevention. https://www.cdc.gov/flu/pandemicresources/1918-commemoration/what-cdc-does. htm

CDC. (2021a, April 9). Rabies Vaccine Information Statement. https://www.cdc.gov/ CDC. (2021b, August 17). Understanding How Vaccines Work. https://www.cdc.gov/vaccines/ hcp/conversations/understanding-vacc-work. html

CDC. (2021c, August 26). Key Facts About Seasonal Flu Vaccine. Centers for Disease Control and Prevention. https://www.cdc.gov/ flu/prevent/keyfacts.htm

CDC. (2021d, October 4). Estimated Flu-Related Illnesses, Medical visits, Hospitalizations, and Deaths in the United States—2019–2020 Flu Season | CDC. https://www.cdc.gov/flu/about/ burden/2019-2020.html

Commissioner, O. of the. (2020a). FDA’s Critical Role in Ensuring Supply of Influenza Vaccine. FDA. https://www.fda.gov/consumers/ consumer-updates/fdas-critical-role-ensuringsupply-influenza-vaccine

Commissioner, O. of the. (2020b). Seasonal Flu (Influenza) and the FDA. FDA. https://www.fda. gov/news-events/public-health-focus/seasonalflu-influenza-and-fda

Dharmapalan, D. (2020). Influenza. The Indian Journal of Pediatrics, 87(10), 828–832. https:// doi.org/10.1007/s12098-020-03214-1 Harding, A., & Heaton, N. (2018). Efforts to Improve the Seasonal Influenza Vaccine. Vaccines, 6(2), 19. https://doi.org/10.3390/ vaccines6020019

Kalil, A. C., & Thomas, P. G. (2019). Influenza virus-related critical illness: Pathophysiology and epidemiology. Critical Care, 23, 258. https://doi. org/10.1186/s13054-019-2539-x

Keshavarz, M., Mirzaei, H., Salemi, M., Momeni, F., Mousavi, M. J., Sadeghalvad, M., Arjeini, Y., Solaymani-Mohammadi, F., Sadri Nahand, J., Namdari, H., Mokhtari-Azad, T., & Rezaei, F. (2019). Influenza vaccine: Where are we and where do we go? Reviews in Medical Virology, 29(1), e2014. https://doi.org/10.1002/rmv.2014 Kilbourne, E. D. (2006). Influenza Pandemics of the 20th Century. Emerging Infectious Diseases, 12(1), 9–14. https://doi.org/10.3201/ eid1201.051254

Krammer, F., Smith, G. J. D., Fouchier, R. A. M., Peiris, M., Kedzierska, K., Doherty, P. C., Palese, P., Shaw, M. L., Treanor, J., Webster, R. G., & García-Sastre, A. (2018). Influenza. Nature

Reviews Disease Primers, 4(1), 1–21. https://doi. org/10.1038/s41572-018-0002-y Kumar, A., Meldgaard, T. S., & Bertholet, S. (2018). Novel Platforms for the Development of a Universal Influenza Vaccine. Frontiers in Immunology, 9, 600. https://doi.org/10.3389/ fimmu.2018.00600

Leuba, S. I., Yaesoubi, R., Antillon, M., Cohen, T., & Zimmer, C. (2020). Tracking and predicting U.S. influenza activity with a real-time surveillance network. PLoS Computational Biology, 16(11), e1008180. https://doi.org/10.1371/journal. pcbi.1008180

Lewnard, J., & Cobey, S. (2018). Immune History and Influenza Vaccine Effectiveness. Vaccines, 6(2), 28. https://doi.org/10.3390/vaccines6020028 Madsen, A., & Cox, R. J. (2020). Prospects and Challenges in the Development of Universal Influenza Vaccines. Vaccines, 8(3), E361. https:// doi.org/10.3390/vaccines8030361

Melief, C. J. M., van Hall, T., Arens, R., Ossendorp, F., & van der Burg, S. H. (2015). Therapeutic cancer vaccines. The Journal of Clinical Investigation, 125(9), 3401–3412. https://doi. org/10.1172/JCI80009

National Cancer Institute. (2011, February 2). Definition of Surgeon General—NCI Dictionary of Cancer Terms (nciglobal,ncienterprise) [NciAppModulePage]. https://www.cancer.gov/ publications/dictionaries/cancer-terms/def/ surgeon-general

Pasteur, L. (1881). Translation of “An Address On The Germ Theory.” The Lancet, 118(3024), 271–272. https://doi.org/10.1016/S01406736(02)35739-8

Paules, C. I., Marston, H. D., Eisinger, R. W., Baltimore, D., & Fauci, A. S. (2017). The Pathway to a Universal Influenza Vaccine. Immunity, 47(4), 599–603. https://doi.org/10.1016/j. immuni.2017.09.007

Rogers, K. (n.d.). 1957 Flu Pandemic. Britannica. Retrieved December 4, 2021, from https://www. britannica.com/event/1957-flu-pandemic

Sautto, G. A., Kirchenbaum, G. A., & Ross, T. M. (2018). Towards a universal influenza vaccine: Different approaches for one goal. Virology Journal, 15(1), 17. https://doi.org/10.1186/ s12985-017-0918-y

Schmid, P., Rauber, D., Betsch, C., Lidolt, G., & Denker, M.-L. (2017). Barriers of Influenza Vaccination Intention and Behavior – A Systematic Review of Influenza Vaccine Hesitancy, 2005 – 2016. PLOS ONE, 12(1), e0170550. https://doi. org/10.1371/journal.pone.0170550 Sederdahl, B. K., & Williams, J. V. (2020). Epidemiology and Clinical Characteristics of Influenza C Virus. Viruses, 12(1), 89. https://doi. org/10.3390/v12010089

Webby, R. J., & Sandbulte, M. R. (2008). Influenza vaccines. Frontiers in Bioscience: A Journal and Virtual Library, 13, 4912–4924. https://doi. org/10.2741/3050

WHO. (2021, April 22). Counting the impact of vaccines. https://www.who.int/news-room/ feature-stories/detail/counting-the-impact-ofvaccines

WHO. (2022, February 21). WHO Consultation on the Composition of Influenza Virus Vaccines for Use in the 2022-23 Northern Hemisphere Influenza Season. https://www. who.int/news-room/events/detail/2022/02/21/ default-calendar/who-consultation-on-thecomposition-of-influenza-virus-vaccines-foruse-in-the-2022-23-northern-hemisphereinfluenza-season

World Health Organization. (n.d.). Global Influenza Surveillance and Response System (GISRS). Retrieved October 14, 2021, from https://www.who.int/initiatives/globalinfluenza-surveillance-and-response-system Ziegler, T., Mamahit, A., & Cox, N. J. (2018). 65 years of influenza surveillance by a World Health Organization‐coordinated global network. Influenza and Other Respiratory Viruses, 12(5), 558–565. https://doi.org/10.1111/irv.12570 a

Innovations in Cancer Treatment

STAFF WRITERS: TYLER CHEN ‘24, VICTORIA FAUSTIN ‘23, VAISHNAVI KATRAGADDA ‘24, ASHNA KUMAR ‘24, ARSHDEEP DHANOA ‘24, SARAH BERMAN ‘25, STEPHEN ADJEI ‘25, CAROLINE CONWAY ’24, SOYEON (SOPHIE) CHO ‘24, JENNIFER DO-DAI ‘25, SHOAIB JAMIL ‘25, CALLIE MOODY ‘24

TEAM LEADS: AYUSHYA AJMANI ’24, SREEKAR KASTURI ’24, ANAHITA KODALI ‘23

Cover Image: Histological slide of cancerous breast tissue that has been stained with H&E and magnified to 200x. The pink “riverways” are normal connective tissue, and the blue is cancer cells. Image Source: Wikipedia Commons

Sociocultural Overview of Cancer

Racial and Ethnic Disparities in Cancer Treatments

Racial and ethnic disparities persist within the United States. Unfortunately, these disparities have the potential to detrimentally influence healthcare accessibility and the quality of medical care. Cancer treatment is no exception. According to a 2002 study published in the Journal of the National Cancer Institute, there are two dimensions of treatment that can contribute to racial disparities in cancer treatment outcomes: racial differences in treatment efficacy and the failure to provide suitable care (Shavers & Brown, 2002). Although the authors found limited evidence surrounding racial/ethnic differences in treatment efficacy amongst patients with similar disease stage, grade, and comorbidities, it was overwhelmingly reported that racial disparities significantly prevailed in cancer treatment itself (i.e. the receipt of definitive primary therapy, adjuvant therapy, conservative surgery, followups etc.). Uppal et al. (2017) evaluated similar racial/ ethnic disparities in guideline-based care in regards to locally advanced cervical cancer and their relationship to hospital case volume. After the completion of their retrospective cohort study, it was determined that racial and ethnic disparities in the delivery of guideline-based care are the highest in high-volume hospitals (Uppal et al., 2017). Graboyes et al. reported a similar phenomenon in their 2018 study, in which they investigated racial and ethnic disparities in travel for head and neck cancer treatment and the impact of travel distance on survival. Long distance travel for healthcare was not only often associated with treatment at academic and highvolume hospitals, but also improved primary patient outcomes on multivariable analysis (as compared to short distance travel). Black and Hispanic patients with Medicaid insurance who had nonsurgical treatment were determined to be

less likely to travel long distances for treatment, thereby negatively influencing their potential quality of care and overall likelihood of improved primary outcome (Graboyes et al, 2018).

Data collected by Yedjou et al. (2017) mirrors this finding, as they found that cancer mortality was higher for both Black men and women compared to White men and women, with Black individuals having a disproportionate 33% higher risk of dying of cancer than White individuals. While it is imperative to note that this outcome is likely influenced by innumerable multi-faceted factors (including lifestyle, environment, age, genetics, family history, personal health history, and diet) it is also necessary to consider the negative consequences of racial/ethnic disparities in medicine. These racially and ethnically-driven inequalities can be attributed to a large number of clinical and non-clinical risk factors, ranging from lack of medical coverage and barriers to early detection and screening to more advanced stages of disease at diagnosis amongst minorities and unequal access to improvements in cancer treatment.

Understanding these risk factors may offer a potential explanation for the widely observed differences in cancer treatment and survival between people of color and white individuals. Over time, it has become increasingly apparent that equality in cancer treatment can yield significantly better cancer outcomes, and it is crucial that we, as a society, develop new strategies to address this ubiquitous issue, promoting cancer prevention, improving survival rate, and ultimately improving the health outcomes for racial and ethnic minorities.

Socioeconomic Disparities

While some disparities in cancer treatment have been decreasing in the past few decades, socioeconomic inequities are unfortunately widening. This effect is clear on both large and small scales, with the world’s poorest countries experiencing mortality rates two times higher than their richer counterparts for some cancer types. Even on an individual or countylevel, health disadvantages and access to less effective treatments result in a disproportionate burden of cancer deaths upon those of a lower socioeconomic status (SES). Reducing these disparities and healthcare disadvantages by improving access to treatments could actually result in a decrease of up to one third of cancer deaths in Americans aged 25 to 74 (Siegel et al., 2019).

The skewed distribution of cancer deaths along socioeconomic lines is directly attributable to disparities in treatment, as studies have continuously shown that those of lower SES are often treated with less aggressive or less advanced treatment options. Many of the disparities based on SES have actually been increasing for preventable cancers, as treatments vary greatly between patients of varied SES (Siegel et al., 2019). Men who live in areas of lower SES, for example, were less likely to have been treated with prostatectomy or radiation than men from higher SES areas, despite these being the most effective treatments. Instead, those of lower SES were given hormone therapy. These less effective treatments often mean higher mortality among individuals of lower SES (Byers et al., 2008).

An interesting case study exemplifying these disparities can be found in studying breast cancer. Women from areas of lower SES with localized breast cancer were more likely to undergo mastectomy than those from higher SES areas. Patients of lower SES who received lumpectomies, surgical operations to remove lumps from the breast, were often less likely to have initial radiotherapy following these procedures. For breast cancers that were estrogen/ progesterone receptor-positive, patients from lower SES areas were also less likely to receive antiestrogen therapy (Byers et al., 2008). After breast-conserving surgery, women who were poor or near poor were also less likely to receive sentinel lymph node biopsies and radiation and were less likely to receive any sort of axillary surgery. Interestingly, with treatments like aromatase inhibitors, there were no significant differences in usage based on SES; however, the more effective aromatase inhibitors were often reserved for patients of higher SES (Dreyer et al., 2017). As these more effective and aggressive therapies are often used solely for patients of higher SES, patients of lower SES suffer greater mortality rates. Necessary proper access to treatment is regardless of SES (Siegel et al., 2019).

Gender- and Sexuality-Based Disparities in Cancer Treatment

Some disparities in cancer treatment lie along lines of sex, gender, or sexual orientation. The sex an individual is assigned at birth can play a biological role in one’s susceptibility to cancer. For instance, one study on genetic components of lung cancer determined that about 1160 genes in smoking patients with lung cancer had expression patterns that consistently varied according to the patients’ sexes. This is particularly interesting given that female smokers tend to exhibit higher immune responses than males and that among individuals who have never smoked, females are more likely than males to develop lung cancer (Davuluri et al., 2021). "Women from areas of lower SES... were more likely to undergo mastectomy than those from higher SES areas."

"LGBTQ+ status can influence their cancer treatment, largely due to social stigmas acting as barriers to adequate care."

There is troubling evidence that women tend to be treated suboptimally. For example, women with head and neck squamous cell carcinoma (HNSCC) are less likely to receive chemoradiotherapy than men with the same condition, and women with HNSCC tend to be underrepresented in chemotherapy clinical trials (Benchetrit et al., 2019). In cases of renal cancer (cancer in the lining of kidney tubules), women are more likely to undergo procedures removing a small, localized renal mass and a large portion of normal tissue around it (a procedure called radical excision), while men are more likely to undergo partial excision, or the removal of only part of a renal mass. This is concerning because women are actually more likely to have benign growths and are also more likely to have multiple diseases simultaneously, meaning minimizing surgical complications is more of a concern (O’Malley et al., 2013).

This is not to say that gender bias in cancer treatment always favors men. In fact, in the case of breast cancer, men are at a disadvantage and are consistently diagnosed with more advanced stages, resulting in a need for more aggressive and expensive treatments from the moment of diagnosis. Furthermore, women tend to outlive men when comparing lifespan from the time of breast cancer diagnosis, although breast cancer mortality rates are generally comparable across genders (Nemchek, 2018). Nemchek (2018) proposes that the late diagnosis of breast cancer in men might result from less robust educational programs and might therefore be partially addressed by using breast cancer awareness resources targeted toward women to educate men about their risk.

LGBTQ+ status can influence their cancer treatment, largely due to social stigmas acting as barriers to adequate care. For instance, queer, lesbian, and bisexual women are less likely than heterosexual women to regularly see a physician and get screened for breast and gynecologic cancer due to social stigmas within the .doctors office Furthermore, women from communities of marginalized sexual orientations are more likely to be dissatisfied with health care professionals during cancer treatment. More than half of trans individuals report negative health care experiences, and they are consequently substantially less likely to seek emergency care. Additionally, gender-affirming hormones and/ or surgery can increase a patient’s cancer risk, making it all the more alarming that many patients receiving such treatments do not get screened for cancer as regularly as cisgender patients (Bryson et al., 2020). Overall, while there are biological effects of sex on cancer risk that require further investigation, evidence suggests that social structures related to gender and sexuality contribute to disparities in cancer treatment, so these social norms must be addressed in order to ensure equitability in cancer treatment and, by extension, in quality of life.

Immunology Overview

To begin to understand the theory behind different cancer treatments, it’s important to recognize the human body’s defense mechanisms against cancerous cells and tumors. Cancer immunoediting is the primary process in which the immune system deals with tumors. It consists of three overarching stages: elimination, equilibrium, and evasion. Each corresponds to the relative level of immunogenicity, or the ability to provoke an immune response, of the tumor cells in question (Dunn et al., 2004). Elimination, also known as cancer immunosurveillance, occurs at the beginning of tumor formation, and is the stage in which the body’s immune system has the strongest response in attacking tumor cells. This elaborate immune response can be characterized into four separate phases as well.

The first phase in the elimination aspect of cancer immunoediting involves initiating anti-tumor immune response. At this point, the individual’s immune system becomes alerted of the growing tumor. This occurs partly because the growing tumor disrupts the surrounding normal tissue because of the cancer cells’ stromal remodeling – a series of changes in the basic physiology of the tumor cells induced by angiogenesis, or the formation of new blood vessels, and surrounding tissue invasion that occur to ensure consistent tumor development (Hanahan & Weinberg, 2000). From here, proinflammatory molecules produced from the stromal remodeling process and chemokines released from the tumor cells attract the attention of cells in the innate immune system, leading to the immediate immune response (Dunn et al., 2004). Cells such as natural killer cells, killer T cells, dendritic cells, macrophages, γδ-cells, and others converge on the site and begin recognizing some of the tumor cells. There are many different proposed mechanisms of recognition of the tumor cells for each of these immune system cells, but regardless, what follows recognition is the production of Interferon-γ, which promotes the second stage of elimination.

The production of Interferon-γ by infiltrative lymphocytes in the first phase of elimination

has several downstream effects that define the second stage of elimination. The first effect is the increased production of the chemokines CXCL9, CXCL-10, and CXCL-10 within the tumor cells in response to higher levels of Interferon-γ, leading to more cells in the innate immune system to converge on the tumor site (Dunn et al., 2004). This in turn leads to a higher production of Interferon-γ, and the positive feedback loop ensues. A similar positive feedback loop is also seen through the increased production of Interleukin-12 from the higher production of Interferon-γ, which thus stimulates tumorinvasive natural killer cells to produce more Interferon-γ, and so on and so forth (HodgeDufour et al., 1997). Additionally, higher levels of Interferon- γ lead to higher levels of anti-tumor processes as well. Several Interferon-γ dependent processes have antiproliferative, proapoptotic, and/or angiostatic effects – all of which promote tumor death (Coughlin et al., 1998). In addition to these direct tumoricidal Interferon-γ dependent processes, Interferon-γ-activated macrophages and natural killer cells can also kill tumor cells through TRAIL (TNF-Related Apoptosis Inducing Ligand) related processes and perforindependent processes, respectively (Dunn et al., 2004). The resulting dead tumor cells serve as a plentiful source of tumor antigen for the immune system, leading to the next phase of elimination.

In the third stage, the tumor antigen supply leads the way for tumor-specific adaptive immune responses. Immature dendritic cells that first arrive at the tumor site via the initial immune response then become activated either by interacting with cytokines produced in the ongoing innate immune response, or by interacting with tumorinfiltrating natural killer cells (Gerosa et al., 2002). From here, the activated dendritic cells consume the tumor antigen, and then migrate to the draining lymph node, leading to the activation of naïve tumor-specific Th1 CD4+ T cells, which then leads to the development of tumor-specific CD8+ cytotoxic T cells due to the cross-presentations of tumor antigen peptides on the MHC class I molecules on the dendritic cells (Dunn et al., 2002). This development of adaptive immunity gives way to the fourth step of elimination, which should theoretically lead to the elimination of the tumor. In the fourth stage, the tumor-specific CD4+ and CD8+ T cells move towards the tumor site, helping kill the tumor cells. Theoretically speaking, the host should have the capacity to eliminate all tumor cells at this point, but less immunogenic tumor cells may evade this final adaptive immune response, progressing into the equilibrium stage. During the equilibrium stage, the back-andforth between increasing selective pressure of the adaptive response and the Interferon-γdependent processes and the tumor cells that withstood the initial immune response continues (Dunn et al., 2002). During this time, the remaining tumor cells are unstable and undergo many genetic mutations in hopes of withstanding the continuously improving immune response. As within the elimination phase, the equilibrium phase is characterized by Darwinian selection, in which the most “fit” tumor cells withstanding the immune response will continue to replicate (Kim et al., 2007). This period of dynamic equilibrium is the longest phase (lasting for years), as tumor cells continue to improve while the immune system adapts. However, those tumor cells that do manage to improve and withstand the immune attack will emerge out of the equilibrium phase and into the last phase: escape.

In the escape phase, tumor cells that have been selected for throughout the elimination and equilibrium phases can now exist and grow within a normal immune system and can thus grow in an uncontrollable manner. There likely were a series of different genetic and epigenetic changes within these selected tumor cells that allow them to circumvent the innate and/or the adaptive immune response to grow progressively. Several of the immunoevasive strategies resulting from mutations during the equilibrium phase have likely accumulated to produce a tumor cell capable of malignancy against a powerful immune environment (Dunn et al., 2002). One of these strategies is the development of immunosuppressive cytokines or the use of immunosuppressive mechanisms involving T cells – directly impeding the development of anti-tumor immune responses (Khong & Restifo, 2002). Additionally, other methods of escape include changes that occur directly on the tumor level. Some of these changes reduce the level of tumor recognition by effector T cells. These changes include loss of antigen expression, loss of MHC components, shedding of NKG2D ligands, and increased insensitivity to Interferon-γ (Dunn et al., 2002). Other methods include ways for tumor cells to evade immune destruction mechanisms, such as having defects in the traditional death-receptor signaling pathways or being able to express anti apoptotic signals. Either way, at this point, the tumor cells have developed a resistance to the immune system and can proliferate and grow uncontrollably without intervention. At this point, cancer can be clinically diagnosed.

"...the tumor cells have developed a resistance to the immune system and can proliferate and grow uncontrollably without intervention. At this point, cancer can be clinically diagnosed."

Figure 1: MRI scans of breast cancer before and after treatment. Using modern imaging techniques, the initial lesions highlighted with the yellow arrows were able to lapse upon the 14 month treatment of breast cancer.

Image Source: Wikimedia Commons

Different Stages of Cancer

Upon diagnosing a patient with cancer, doctors use a staging system to classify the extent to which the cancer has grown and how far it has spread from its original cells. This system consists of Stages 0-4, which will be described throughout this section. There are different methods to classify what stage a tumor is in, including imaging techniques (MRI, CT, x-ray), surgery, and biopsy. Using this standardized staging system helps doctors determine a patient’s prognosis at diagnosis as well as determine a treatment plan, including possible clinical trials the patient may be eligible for. Both the American Cancer Society (ACS) and the National Cancer Institute (NCI) state that the stage determined at diagnosis is retained throughout treatment, even if the cancer progresses and spreads further, allowing researchers to track statistics such as the prevalence of specific stages of cancer at diagnosis and patient outcomes as well as compare the effectiveness of treatments in a research study. However, many oncologists will often describe cancers based on its current state of progression.

During Stage 0, the cancer has yet to develop or spread. A small group of abnormal cells, or dysplasia, are localized at their initial location, not yet forming a tumor. This state where the cells display abnormal growth but are not yet invasive into other tissues or organs is also known as carcinoma in situ (CIS). The NIH does not classify this non-invasive stage as cancer because while these cells have the potential to develop into cancer, not all cases of CIS will progress into cancer. At this early stage, it is often difficult to detect these abnormal cells as CIS will usually not be visible on internal organ scans due to its small size. Cancers with more visible presentation such as skin cancer or that are screened for more often like breast or cervical cancer may be detected during Stage 0. An early diagnosis generally implies a good prognosis, as doctors can eliminate the threat of cancer before the abnormal cells progress and metastasize.

Generally, the higher the stage number, the larger the tumor is and the more the cancer has metastasized across adjacent regions of the body or the body as a whole. This classification of the anatomical extent of cancer spread is dependent upon the TNM system of staging (Cancer Staging, n.d.). The “T” category describes the extent of the tumor’s size, depth of invasion, or invasion of different structures. The “N” category indicates the absence or extent of metastasis of regional lymph nodes. Finally, the “M” category explains if there is a presence of distant metastasis (Brierley et al., 2016). The combination of TNM categories at the time of diagnosis constitutes the clinical TNM (cTNM) and analysis of the tumor biopsy comprises a pathological TNM (pTNM). The cTNM determines the overall approach to treatment, while the pTNM guides the possibility of different adjuvant therapies (Brierley et al., 2016).

Stage 1 of cancer manifests differently depending on the type of cancer in question. For example, in stomach cancer, Stage I is split in subset stages. Stage 1A entails that the cancer has not yet grown past the submucosa of the gastric wall; Stage IB means the cancer has not yet grown past the muscle layer of the stomach, and it may have spread into 1 or 2 neighboring lymph nodes (Stomach Cancer: Stage 1, n.d.). As such, the most effective treatment would be surgery, possibly followed by adjuvant therapy with chemotherapy. Compared to stomach cancer, breast cancer manifests differently. Stage 1A of breast cancer means that the cancerous tumor is <2cm in diameter and has not spread outside the breast; Stage IB entails a tumor that is still <2cm in diameter, and few cancerous cells are found in nearby lymph nodes (Breast Cancer: Stage 1, n.d.). Though manifested differently in their respective bodily regions, Stage 1 of cancer entails localized tumor formation with minimal possibility of spreading malignant cells to adjacent regions.

Stage 2 cancer signifies that the cancer is growing, but the cancer cells are contained within the initial site and have not fully spread to other sites (National Health Service, 2018). Within each type of cancer, the symptoms for this stage are more specific and can be divided into substages. For example, in Stage 2 breast cancer, the cancer is growing and contained in the breast or only within the nearby lymph nodes (National Breast Cancer, 2020). Stage 2A for breast cancer is determined by the cancer having spread to the lymph nodes paired with no tumor or a tumor less than 2cm wide, or the cancer not having spread to the lymph nodes paired with a tumor 2-5cm wide. Stage 2B is more advanced and diagnosed

by the cancer having spread to the lymph nodes and a tumor 2-5cm wide, or the cancer not having spread to the lymph nodes and a tumor 5cm wide. Similarly, for colon cancer, stage 2A occurs when the cancer is contained within the muscle layer of the colon and the serosa, or the outer lining of organs in the chest, and stage 2B occurs when the cancer has spread to the visceral peritoneum, which covers the surface of the abdominal organs (National Cancer Institute “Stage II Colorectal Cancer”, 2020; Merkel et al., 2001). Finally, stage 2C occurs when the cancer is starting to spread to different organs. These examples demonstrate that the sub-stages within stage 2 are determined by specific indicators of the degree to which the cancer has spread to other regions or developed larger tumors.

Stage 3 cancer is often defined as having spread around the local area and/or distant lymph nodes, but not yet metastasizing in distant tissues. Many patients are diagnosed at this state. Generally, 3 substates are defined slightly differently based on the cancer type. In lung cancer, state 3A means the cancer is on one side of body only. This state has approximately a 36% chance of 5-year survival (Willow). State 3B indicates that the cancer has spread to both sides of the body and has a 26% chance of 5-year survival. State 3C describes that the cancer has spread throughout the chest, often accompanied by a persistent or changed cough, trouble breathing, and chest pain. This state has approximately a 1% chance of 5-year survival (Willow).

Stage 4 cancer is referred to as metastatic cancer, because it means that the cancer has spread from the origin to various distant parts in the body. When a cancer metastasizes to a different part of the body, it is defined by the original location. For example, if breast cancer were to metastasize to the brain, it is still considered breast cancer instead of brain cancer. Many Stage 4 cancers have subcategories, such as Stage 4A or Stage 4B, which indicate the degree to which the cancer has spread throughout the body. The 5-year survival rate for people with breast cancer, for example, that has spread to distant areas of the body is 28%. On the other hand, the 5-year survival rate for mesothelioma that has spread to distant areas is 7%.

Current Treatments

Current treatments for cancer fall into two major categories: chemotherapy and surgery. Chemotherapy began as monotherapy drugs that targeted single types of cancer and only lasted for a limited amount of time (Pearson et al., 1949). However, starting with choriocarcinoma in 1958, the combination of multiple drugs increased the effectiveness of chemotherapy as a standard treatment for cancer, since different drugs can target different phases of the cancer cell’s cycles (Li et al., 1958; Einhorn & Donohue, 1977). Currently, chemotherapy is used to treat patients with advanced types of cancer such as choriocarcinoma, lymphoma, acute leukemia, and more.

Surgery, which aims to remove the tumer, emerged in the 20th century for solid tumors such as sarcomas, carcinomas, and lymphomas (Arruebo et al., 2011; National Cancer Institute “Solid Tumor”, 2020). Heading into the 21st century, non-invasive techniques in addition to the more invasive Halstedian techniques were invented, allowing for more conservative surgery techniques to remove tumors and minimizing functional damage on organs (Arruebo et al., 2011; Phillips et al., 1992).

Radiation therapy, or radiotherapy, began from Marie Curie’s discoveries and developed techniques such as linac radiotherapy, which specifically concentrates X-rays to the site, and computed tomography (CT) guided radiotherapy, which reduce toxic effects on the body by concentrating radiation on the CT-generated 3-dimensional reconstructions of tumors (Arruebo et al., 2011; Hall, 2006). Furthermore, image-guided radiation therapy (IGRT) and image-guided adaptive radiation therapy (IGART) use 4-dimensional video reconstructions of tumor movements as patients breathe or move around (Timmerman & Xing, 2009).

Chemotherapy

Utilizing chemical agents to interact with cancer cells, chemotherapy is a distinct approach to cancer treatment. The practice itself has existed for thousands of years: chemotherapy can be traced back to the ancient Egyptians who combined barley, pigs’ ears, and other chemical agents to treat gastric and uterine cancers (“Introduction to Chemotherapy”, n.d.). Nonetheless, the application of chemical agents as robust forms of cancer treatment emerged following the research conducted by German chemist Paul Ehrlich in the early 20th century (DeVita & Chu, 2008). Burgeoning forms of chemotherapy subsequently began to rival the dominant forms of cancer treatment at that time—namely surgery and radiation therapy. "...chemotherapy can be traced back to the ancient Egyptians..."

Figure 2: Diagram of chemotherapy treatment on cancerous cells. After the cancerous cells are surrounded by the chemotherapy drug, electrical impulses open the cell surface so that the drug can center. Upon the cell closing, the drug is trapped inside the cell. The drug damages the DNA inside of the nucleus of these cells and prevents them from dividing and growing. Image Source: Wikimedia Commons

"Studies specific to COVID-19 in patients have found that the median age of infected patients is around 56 years..."

In the early decades following Ehrlich’s research, chemotherapy was generally restricted to model development. Chemical drug discovery faced immense limitations in this stage: the vast repertoire of known chemicals had to be gleaned for suitable drug candidates, and the accessibility to clinical facilities to handle these chemicals had to be addressed (DeVita & Chu, 2008). Trials and tribulations to find substantive modeling systems lasted until the early 1940s when the first discoveries were made. A study of vesicant war gases employed by armies during World War II, such as sulfur mustard and nitrogen mustard, revealed that exposed soldiers demonstrated markedly less bone marrow and lymph nodes. Scientists in the U.S. experimented with nitrogen mustard gas on mice bearing transplanted lymphoid tumors, and signs of remission convinced them to experiment on humans. Unfortunately, the investigation resulted in temporary and incomplete cancer remission on human patients (DeVita & Chu, 2008). Various institutions and academic physicians thereafter became harsh critics of chemotherapy ever functioning as a viable cancer treatment beyond palliative care.

Breakthroughs in the 1960s brought chemotherapy to the forefront of cancer treatment discussions. Combination therapy, the idea of simultaneously administering a variety of drugs, tremendously improved patient outcomes from chemotherapy (Shewach & Kuchta, 2009). Cancer cells are themselves composed of mutated DNA that contribute to their aberrations from the normal cell cycle; thus, each chemical drug used for chemotherapy is only one or few genetic mutations away from becoming obsolete. Employing a combination of different chemicals at once requires that cancer cells must undergo several different mutations to prove resistant—overall decreasing the likelihood of resistance and increasing the efficacy of the chemotherapy (Shewach & Kuchta, 2009). Moreover, chemotherapy is a viable option for adjuvant therapy. Primary treatment, usually surgery, is followed by a secondary form of therapy to mitigate chances of cancer cell survival (Definition of Adjuvant Therapy, 2011).

A thematic setback to chemotherapy is the rather low specificity with which drugs can differentiate between cancerous and normal cells. Despite being comprised of mutated DNA, the genetic and metabolic framework of cancerous cells are identical to those of their non-cancerous counterparts. Novel chemotherapeutics such as angiogenesis inhibitors could address this critical challenge (DeVita & Chu, 2008). Chemotherapy as a form of cancer treatment has only burgeoned in the last half a century. The treatment demonstrates great promise in effectively reducing the lives claimed by all forms of cancer.

Surgery

Surgical resection of tumors is the oldest oncological treatment and is regarded as one of the most successful (Wyld et al., 2014; Singhal, 2016). However, while surgery is effective and can often completely eliminate a cancer as well as alleviate patient symptoms, there are many studies suggesting that surgery is perhaps not as effective as it needs to be (Chen et al., 2019). Some data has shown that surgery may lead to greater metastatic seeding of tumor cells. Surgical stress may also lead to inflammation, immunosuppression, and risk of ischemia or reperfusion injury, all of which may lead to increased tumor metastasis risk. Animal studies have demonstrated that surgery-induced stress results in malignant cancer growth. The body's response to surgery may also lead to an environment favorable for tumor metastasis, as the body releases increased cytokines and experiences a shift in immune cell populations. Specifically, regulatory T cells increase post-operatively and helper T cells and cytotoxic T cells decrease, allowing neoplastic cells to survive in varying degrees. Clinical trials have also shown that circulating and disseminated tumor cells increased after surgery in a variety of cancer types, including gastric, colorectal, and breast. Furthermore, anesthesia itself may lead

to greater cancer incidence. Some inhalational anesthetics, like isoflurane, have been shown to accelerate tumor progression. Renal cell carcinoma tumor cells, for example, migrate more rapidly after being exposed to 2% isoflurane. Intravenous anesthetics also pose problems, with compounds like ketamine reducing the activity of natural killer cells and doubling the survival and metastasis rate of cancers like lung cancers (Chen et al., 2019).

Another problem with surgical treatment is the risk of cancer recurrence. Depending on the tumor type, recurrence rates range between 8 and 50% across the US, especially since some tumors are difficult to cleanly resect. However, technological advancements in fluorescence are decreasing this issue. Previously, surgeons had to rely solely on visual inspection and finger palpation to decide which cells needed to be resected, leading to many cases where tumors became recurrent. By fluorescently labeling cells, the decisions made intraoperatively are made easier, allowing surgeons to find all tumor cells, including those that metastasized.

Several possible fluorescent contrast agents are being studied in trials now, such as EC17 and aminolevulinic acid, both of which are agents that are delivered systemically and accumulate in tumor cells. Other agents that target tumors specifically, whether through having an increased permeability in the tumor environment or targeting tumor cells through receptor-mediated binding, would work as well. Improved detection technology is also required, of course, to find the fluorescently labeled cells during a procedure. Some studies done with aminolevulinic acid fluorescence during malignant glioma resections have proven successful, with control surgeries having higher residual tumor volumes when performed solely under white light. Another study looking at the effectiveness of fluorescence during hepatic resection found that using NIR fluorescence allowed superficially located lesions to be found in five out of forty patients. These procedures using fluorescence are safe, as they do not expose patients to dangerously high levels of ionizing light. However, more research still needs to be done prior to the clinical approval of this method (Singhal, 2016). Eventually, using multimodal treatments without surgery might result in the best outcome for the patient; in the meantime, medical professionals rely on improvements in surgical techniques (Wyld et al., 2014).

Effect of Advancements in Imaging techniques to identify Cancer

Imaging techniques are extremely important for cancer detection. Not only can medically imaging aid physicians and radiologists in determining early treatment options for patients with cancer by exam, but it can also help radiologists detect other anomalies within the body. With the digitalization of medical scans through technologies such as the Picture Archiving and Communication System (PACS), medical imaging became much more convenient. Storing medical images and scans as digital representation helps prevent theft and ensures scans are organized and viewable by multiple physicians at once. However, digitalization and storage of medical scans have seen great improvement with the adoption of big data analytics.

The increased availability of large data sets to hospitals has increased the predictive power of hospitals. By representing characteristics of the population using large data sets including medical scans and electronic health records, hospitals can recommend treatments that are tailored to the individual needs of the patient. Analyzing and assessing large datasets can also provide other information and answers to questions such as the effectiveness of a program. These advancements have helped optimize workflows and have potential to reduce false positive rates in cancer detection.

Big Data acquisition has many important benefits to both medical imaging and the medical field in general. By collecting larger volumes of data, physicians and radiologists can develop and use programs that predict characteristics of their patient population more accurately by analyzing pre-existing datasets. For example, machine learning models can detect cancers in MRI Images through Stochastic Object Models (SOM). Specifically, a SOM can detect object variability or noise in an MRI scan if given a training data set of experimental data. According to a 2020 research project led by Professor Hua Li of the University of Illinois,

Figure 3: Illustration of the removal of cancerous tissue from the breast during the 1900’s. Since many modern techniques for fluorescently labeling the malignant cells weren’t present in the 20th century, surgeries performed were often invasive and scarring. Image Source: Wikimedia Commons

another machine learning model, the Generative Adversarial Network (GAN) can synthesize fake but extremely realistic MRI images and other medical images. Professor Li and her team have developed a new type of generative adversarial network (GAN) architecture called ProAmGAN with the sole purpose of creating realistic MRI images by comparing its images to real training data that does not contain noise. This enables hospitals to use ProAmGAN’s experimental data to be used to train SOMs to detect levels of noisy and randomized measurement data in real MRI objects, which will help doctors and radiologists distinguish cancers easier and reduce false positives.

Additionally, big data analysis can also help radiologists access information quickly and reliably. According to a 2019 study, despite the adoption of filmless radiology methods, access to information from imaging workflows must still be improved. In rare cases, radiology scans can be misplaced or remain received by physicians and medical practitioners for long periods of time. This can delay diagnoses and care for patients who need it most. As big data analytic methods make it easier to manage large volumes of data, hospitals gain the ability to provide large volumes of information to specific stakeholders in real time, resulting in immense benefits. Knowing exactly when important information will be available can not only optimize radiology workflows, but also allow documentation and reporting to be managed instantly. The previously mentioned study introduces a realtime web dashboard for radiologists. Named Pipeline, the dashboard relies on multi-sourced message streams to display imaging exam results in real time. Advancements such as these allow radiologists to improve radiology exams, where data can commonly be misplaced and remain unreported for long periods of time.

New Treatments

The passage of time brings novel research and innovation to various fields of study, and the effects of this phenomenon are equally apparent in the treatment of cancer. From adopting new techniques and oncological approaches to revisiting former medical methodologies with a fresh perspective, the current modality of cancer treatment is constantly evolving.

In fact, Khan et al. (2021) investigated flavonoids and their potential use and benefit in cancer treatment and clinical prospects. Flavonoids are a class of polyphenolic secondary metabolites found in plants, and in vitro and vivo studies show the potential of flavonoid nanoformulations, especially quercetin, naringenin, apigenin, catechins and fisetin, in the prevention and treatment of several types of cancer (Khan et al., 2021). While the use of flavonoids may offer new insights in the field of drug discovery, more research is still required, particularly investigating flavonoid safety and tumor site-specific action.

Many scientists now turn to a different practice: repurposing various pharmaceuticals and treatment alternatives to treat cancer. A primary example of this can be seen in La-Beck et al.’s 2021 study that explored the repurpose of amino-bisphosphonate by liposome formulation for a new role in cancer treatment. Aminobisphosphonates have been commercially available for over four decades and are generally used for the treatment of osteoporosis, Paget’s disease, hypercalcemia of malignancy, and bone metastases derived from various cancer types (La-Beck et al., 2021). While there is hesitancy to repurpose these pharmaceuticals due to their lack of patentability and low product cost, the team demonstrated the promise of this treatment option. Pegylated liposomal alendronate may be an attractive and promising immunotherapeutic agent, passively targeting and accumulating in tumors, having proven biocompatibility of the liposome carrier, and exhibiting preclinical anticancer efficacy (La Beck et al., 2021).

Similar repurposing with other drugs has been investigated by Aggarwal et. Al (2021), who examined this practice in the context of breast cancer treatment. Drugs such as alkylating agents, anthracyclines, antimetabolite, CDK4/6 inhibitor, aromatase inhibitor, mTOR inhibitor and mitotic inhibitors have been repositioned and successfully used in breast cancer treatment during the last decade. In their review, Aggarwal et al. (2021) suggest that a comprehensive approach of selecting the most appropriate geneprotein-pathway-target-drug modeling (via system biology and bioinformatics) has high potential in providing efficient, safer, and costeffective chemotherapeutics for breast cancer treatment of varying stages.

Frandsen et al. (2020) considered a different novel treatment approach known as calcium electroporation. This is a practice by which high calcium concentrations are introduced into cells by electroporation. Electroporation is a method that uses an electrical pulse to create temporary pores in cell membranes through which substances can pass into cells. Not only has

calcium electroporation has been shown to be a safe and efficient anti-cancer treatment in clinical studies with cutaneous metastases and recurrent head and neck cancer, but the treatment itself is also inexpensive and efficient, generally lacking side effects (Frandsen et al., 2020). It has been suggested that calcium electroporation could potentially be used on a wide-scale-basis for tumors of all types. Cancer treatment research is an ongoing area of investigation with no clear solution in sight. Yet, as society inches closer in research and discovery, unique and specialized treatment for cancer patients is no longer unfathomable.

Immunotherapy

Two prominent immunotherapy approaches have emerged during the past few decades: checkpoint blockades and direct tumor targeting (Waldman). Checkpoint blockades offer a promising avenue for mediating immune responses. Checkpoint blockades function by regulating downstream immune responses to block cytotoxic T lymphocyte activity. The most established checkpoints are programmed cell death protein 1 (PD1) and Cytotoxic T lymphocyte antigen (CTLA 4) that operate within the tumor microenvironment (Waldman, 20). PD1 mediates apoptosis and CTLA4 regulates T-cells as immunosuppressives (Waldman, 20). To target this pathway, researchers have identified monoclonal antibodies (mAb) to block this pathway (Topalian, 16). It is important to note that checkpoint blockades have varying efficacy based on cancer line and cancer type. In addition, research has found that tumors can still upregulate PD1 ligands and cause autoimmune loss (Topalian, 16).

Another field within immuno-oncology includes targeting tumor-associated macrophages (TAMs) within the tumor microenvironment (TME) (Ngambenjawong, 17). TAMs regulate transcription factors including interferons and cytokines to induce a pro-inflammatory response and function as the first line of defense for the immune system (Ngambenjawong, 17). TAMs have varying effects that are contingent on the macrophage; some increase definition of tumors, whereas others may stimulate tumors (Ngambenjawong, 17). Some promising macrophage therapeutic candidates have the ability to penetrate tumors, switching them from a cold, static state to a hot state.

Antibody conjugates are another method to target cancer cells expressing TAMs (Huang, 20). Antibodies can be used to physically block ligand-receptor interactions and stop signaling cascades (Huang, 20). Antibodies are classified by their heavy, constant region. There are five groups of antibodies: IgG, IgM, IgA, IgD, and IgE (Huang, 20). Antibodies also have a light, variable chain that binds to antigens, called the antigenbinding fragments (Fab) and the fragment crystallizable (Fc) region. The Fc receptor can be modified to prolong the half-life of the antibody, keeping it viable within the body for longer. Wild type antibodies are generally monospecific and symmetric with two identical sides, but can be engineered to be bispecific to bind to two different antigens (Huang, 20).

An emerging candidate for tumor targeting includes using bispecific antibodies (BsAbs) (Shim, 20). BsAbs engage two different targets within a signaling cascade, creating a more powerful upstream regulatory response. There are over 100+ BsAb conjugated formats. They generally consist of two or more antibody fragments held with a peptide linker, disulfide bonds, and non-covalent interactions.

Gene Therapy

Due to the toxicity of chemotherapy, new cancer treatment approaches have emerged in recent decades, including gene therapy. Gene therapy consists of a variety of treatment possibilities including immunotherapy, oncolytic virotherapy and gene transfer. Immunotherapy aids the immune system in fighting tumor cells through relying on the administration of genetically modified T cells, drugs that block immune checkpoints and therefore strengthen immune response, treatment vaccines, monoclonal antibodies that target tumor cells, or immune system modulators which also contribute to a more robust immune response. However, issues can arise in this form of treatment when immune cells mistakenly target healthy cells and cause further damage. While immunotherapy can treat several types of cancers, it is not as widely used as radiation therapy or chemotherapy. This treatment option still needs to be further studied to predict what patients’ responses to immunotherapy might be and combat possible resistance to treatment. Oncolytic virotherapy utilizes viruses which are known to invade host cells and replicate its own DNA using the host cell’s machinery. In this case, the virus would be targeting and invading cancer cells to induce apoptosis, which is particularly useful for metastatic cancers that have started to spread throughout the body. The viruses used in oncolytic virotherapy are

"...as society inches closer in research and discovery, unique and specialized treatment for cancer patients is no longer unfathomable."

"Risk factors for cancer can be 1) modifiable which are lifestyle-dependent or 2) unmodifiable which are genetic."

intended to remain harmless to the healthy cells of the body. The strains of viruses chosen to infect tumors typically possess an inherent ability to target cancer cells like adenovirus and reovirus. Unfortunately, immune response complicates the successful administration of this form of therapy as the immune system could target and destroy these foreign particles before it has the chance to induce death in cancer cells. Moreover, the method of gene transfer introduces novel genes into tumor cells through vectors like viruses and plasmids, to either induce apoptosis or slow tumor progression. The treatment combinations are incredibly diverse as scientists have tried using a number of genes and vectors to administer this form of therapy. The foreign genes introduced into the cancer cells could have apoptotic, antiangiogenesis (preventing the formation of blood vessels innervating tumor cells), or cellular stasis functionalities, all of which contribute to working against tumor growth.

Drug-Free Treatments

Recent studies have scientifically validated the use of herbs from traditional Chinese medicine to ameliorate cancer side-effects and treat tumors, including beta-elemene, a compound found in traditional Chinese cancer drugs (Zhai, 19). Scientists concluded that beta-elemene decreases abdominal pain, amenorrhea, congestive cardiac failure, constipation, and stomach pain (Zhai, 19). It was also discovered to upregulate p53 in ovarian cancer cells (and other signaling pathways that are non-functional in tumor cells) (Zhai, 19). beta-elemene also inhibited cell proliferation, halted the cell cycle, and induced cell apoptosis, indicating therapeutic potential beyond usage as a holistic therapy to reduce cancer symptoms (Zhai, 19).

Acupuncture is another form of traditional Chinese medicine validated to reduce side effects. Researchers treated mice models engrafted with osteosarcoma tumors with acupuncture to determine the effects on tumor growth and overall health (Xu, 20). Data indicated decreased body weight loss and stunted tumor growth and size (Xu, 20). Assays also detected an increase in NK cells in treated groups of mice, indicating that acupuncture stimulated an immune response to the engrafted tumors as NK cells are recruited to fight tumors (Xu, 20).

Other non-Western forms of medicine were also found to inhibit tumor growth. Researchers focusing on Ayurveda found a consistent way to recreate Indian holistic cancer treatments by combining traditional techniques with cuttingedge science. Researchers created a standardized version of an herb and gold tincture called “Swarna Bhasma” by using nanotech to produce gold nanoparticles and phytochemicals from herbs (Koobchandani, 20). Their mixture was validated to decrease tumor size in vivo. In mice models, the tumor volume of treated sample five weeks post-treatment was roughly 0.04 cm3, versus untreated with tumors averaging 0.08 cm3.

Lifestyle and Cancer Risk

Risk factors for cancer can be 1) modifiable which are lifestyle-dependent or 2) unmodifiable, which are genetic. Some of these modifiable factors include behavior, physical activity, use of drugs, sexual habits, and reproductive health. Smoking is a behavior that increases one’s risk of developing lung, bladder, kidney, pancreas, cervix, mouth, esophagus, and throat cancer. With physical activity, such as exercise, one can decrease the risk of developing cancer because it would help ensure that they are maintaining a healthy weight. Concerning skin cancer, one could decrease their risk by protecting their skin perhaps by staying out of the sun too much, especially during 11 AM and 3 PM, which are common peak hours of ultraviolet exposure. One could also avoid sunbeds, tanning lamps, wear sunscreen with an SPF of 30 or higher, and wear protective clothing such as long sleeve tops and long pants. In terms of reproductive cancers, the practice of safer sex (use of condoms and knowing partner sex history) could help prevent men and women from getting the Human Papilloma Virus (HPV), which increases women’s likelihoods of getting vaginal cancer and cervical cancer and increases the risk of anal and oral cancers for both men and women. One way a woman can reduce the risk of getting cervical cancer is by scheduling yearly pap smears; both men and women can also receive the HPV vaccine, which protect against the most common HPV types. The National Advisory Committee on Immunization (NACI) recommends the vaccine for females and males ages 9 to 26; however, the vaccine may also be given to women ages 27 to 45 who didn't get the vaccine when they were younger. Alcohol abuse has been shown to increase the chances of one developing liver cancer; however, drinking abnormal amounts of alcohol (more than a glass a day) could increase the chance of developing breast cancer since it leads to extra estrogen levels in the body.

In contrast to modifiable risks, breast cancer and ovarian cancer present an example of

unmodifiable risk. This is since one cannot control whether they inherit a mutated gene. Specifically, the BRCA-1 gene that is found on chromosome 17, this gene provides instructions for making a protein that acts as a tumor suppressor. Women that have one copy of a mutated BRCA-1 gene are more likely to get breast cancer & ovarian cancer if their 2nd BRCA-1 gene on their other 17th chromosome becomes mutated. Also, men can get breast cancer if they inherit a mutated copy of the BRCA-1 gene and then experience a mutation over the course of their lifetime on their 2nd 17th chromosome. Mastectomies and ovariectomies are lifestyle changes that could be implemented to decrease the risk of cancer cells developing in the breast or in the ovaries. Cancer development in such tissues could be quite hazardous since they pose the potential of metastasizing to other tissues in the body. In terms of decreasing the risk of colon cancer, one could get yearly colonoscopy screenings to detect the presence of abnormal lesions.

Magnitude of Cancer (Statistics)

Cancer is the second most common cause of death in the United States of America, surpassed only by heart disease. This is true even though cancer rates have been steadily declining after reaching a peak in 1991. A lot of this decline—31% total to be precise—has been attributed to preventative measures. Campaigns to reduce cigarette usage have played an especially important role in reducing the rates of lung cancer, which is the second-most prevalent cancer in America. In 2022, the American Cancer Society estimates that around 1.9 million more cancer cases will be diagnosed and an estimated 600,000 people will die from cancer this year. This estimate reflects a leveling-off of cancer estimates, as in 2020, it was estimated that 1.8 million more cancer cases will be diagnosed and there will be 606,520 more cancer deaths. Additionally, it is not known whether the COVID-19 pandemic will have a significant impact on the number of cancer cases diagnosed, though it is known that, in 2020, COVID-19 hampered cancer diagnosis rates. It is also not known whether COVID-19 will cause misattributions in cancer deaths, though it is known in the United Kingdom, at least, that COVID-19 has exacerbated deaths in cancer patients, which may lead to higher reports of cancer deaths in the United States, due to comorbidity. This effect is likely to be overrepresented in Black and Hispanic Americans. These groups hold a disproportionate amount of cancer cases and cancer deaths in specific areas. This is seen in the example of breast cancer—the most diagnosed form of cancer— in which cancer rates for White women are 100 times more common than in White men; these rates are only 70 times more common in Black women than Black men. While breast cancer diagnosis is more common in White women than Black women, Black women have a 40% higher death rate due to breast cancer than White women. Thus, during the COVID-19 pandemic, in which Black Americans are 2 times more likely to die of COVID-19 than White Americans, it is expected that cancer rates and deaths in 2021 will have a disproportionate impact on Hispanic/ Latino groups and African Americans.

References

Acosta AM, Garg S, Pham H, et al. Racial and Ethnic Disparities in Rates of COVID-19–Associated Hospitalization, Intensive Care Unit Admission, and In-Hospital Death in the United States From March 2020 to February 2021. JAMA Netw Open Aggarwal, S., Verma, S. S., Aggarwal, S., & Gupta, S. C. (2021, January). Drug repurposing for breast cancer therapy: Old weapon for new battle. In Seminars in cancer biology (Vol. 68, pp. 8-20). Academic Press. American Cancer Society. Cancer Facts & Figures 2020. Atlanta: American Cancer Society; 2020. American Cancer Society. Facts & Figures 2021. American Cancer Society. Atlanta, Ga. 2021. Arruebo, Manuel, et al. “Assessment of the Evolution of Cancer Treatment Therapies.” Cancers, vol. 3, no. 3, 2011, pp. 3279–3330., https://doi.org/10.3390/cancers3033279. Benchetrit, Liliya, et al. “Gender Disparities in Head and Neck Cancer Chemotherapy Clinical Trials Participation and Treatment.” Oral Oncology, vol. 94, 2019, pp. 32–40., https://doi. org/10.1016/j.oraloncology.2019.05.009. Breast Cancer: Stage 1. (n.d.). Cancer Research UK. Retrieved October 23, 2021, from https:// www.cancerresearchuk.org/about-cancer/breastcancer/stages-types-grades/number-stages/ stage-1 Brierley, J., Gospodarowicz, M., & O'Sullivan, B. (2016). The principles of cancer staging. Ecancermedicalscience, 10, ed61. https://doi. org/10.3332/ecancer.2016.ed61 Bryson, Mary K., et al. “Awkward Choreographies from Cancer's Margins: Incommensurabilities of Biographical and Biomedical Knowledge in Sexual and/or Gender Minority Cancer Patients’ Treatment.” Journal of Medical Humanities, vol. 41, no. 3, 2018, pp. 341–361., https://doi. org/10.1007/s10912-018-9542-0. Burns, J. L., Hasting, D., Gichoya, J. W., McKibben, B., Shea, L., & Frank, M. (2020). Just in Time Radiology Decision Support Using

Real-time Data Feeds. Journal of Digital Imaging, 33(1), 137–142. https://doi.org/10.1007/s10278019-00268-2 Cancer Staging. (n.d.). Retrieved October 23, 2021, from https://www.cancer.org/treatment/ understanding-your-diagnosis/staging.html Cancer staging. National Cancer Institute. (n.d.). Retrieved October 22, 2021, from https://www. cancer.gov/about-cancer/diagnosis-staging/ staging. Coughlin, C. M., Salhany, K. E., Gee, M. S., LaTemple, D. C., Kotenko, S., Ma, X., Gri, G., Wysocka, M., Kim, J. E., Liu, L., Liao, F., Farber, J. M., Pestka, S., Trinchieri, G., & Lee, W. M. F. (1998). Tumor Cell Responses to IFNγ Affect Tumorigenicity and Response to IL-12 Therapy and Antiangiogenesis. Immunity, 9(1), 25–34. https://doi.org/10.1016/S1074-7613(00)80585-3 Davuluri, Sravanthi, et al. “The Molecular Basis of Gender Disparities in Smoking Lung Cancer Patients.” Life Sciences, vol. 267, 15 Feb. 2021. https://doi.org/10.1016/j.lfs.2020.118927. Definition of Adjuvant Therapy, NCI Dictionary of Cancer Terms (2011). National Cancer Institute. Retrieved from https://www.cancer. gov/publications/dictionaries/cancer-terms/def/ adjuvant-therapy. DeVita, Vincent T., and Edward Chu. “A History of Cancer Chemotherapy.” Cancer Research, vol. 68, no. 21, 30 Nov. 2008, pp. 8643–8653., https:// doi.org/10.1158/0008-5472.can-07-6611. Dunn, G. P., Old, L. J., & Schreiber, R. D. (2004). The Three Es of Cancer Immunoediting. Annual Review of Immunology, 22(1), 329–360. https://doi.org/10.1146/annurev. immunol.22.012703.104803 EINHORN, LAWRENCE H. “CisDiamminedichloroplatinum, Vinblastine, and Bleomycin Combination Chemotherapy in Disseminated Testicular Cancer.” Annals of Internal Medicine, vol. 87, no. 3, 1977, p. 293., https://doi.org/10.7326/0003-4819-87-3-293. Frandsen, S. K., Vissing, M., & Gehl, J. (2020). A comprehensive review of calcium electroporation—A novel cancer treatment modality. Cancers, 12(2), 290. Gerosa, F., Baldani-Guerra, B., Nisii, C., Marchesini, V., Carra, G., & Trinchieri, G. (2002). Reciprocal Activating Interaction between Natural Killer Cells and Dendritic Cells. Journal of Experimental Medicine, 195(3), 327–333. https://doi.org/10.1084/jem.20010938 Graboyes, E. M., Ellis, M. A., Li, H., Kaczmar, J. M., Sharma, A. K., Lentsch, E. J., ... & Hughes Halbert, C. (2018). Racial and ethnic disparities in travel for head and neck cancer treatment and the impact of travel distance on survival. Cancer, 124(15), 3181-3191. Hall, Eric J. “Intensity-Modulated Radiation Therapy, Protons, and the Risk of Second Cancers.” International Journal of Radiation Oncology*Biology*Physics, vol. 65, no. 1, 2006, pp. 1–7., https://doi.org/10.1016/j. ijrobp.2006.01.027. Hanahan, D., & Weinberg, R. A. (2000). The Hallmarks of Cancer. Cell, 100(1), 57–70. https:// doi.org/10.1016/S0092-8674(00)81683-9 Hodge-Dufour, J., Noble, P. W., Horton, M. R., Bao, C., Wysoka, M., Burdick, M. D., Strieter, R. M., Trinchieri, G., & Puré, E. (1997). Induction of IL-12 and chemokines by hyaluronan requires adhesion-dependent priming of resident but not elicited macrophages. The Journal of Immunology, 159(5), 2492–2500. Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). Lifetime Risk (Percent) of Being Diagnosed with Cancer by Site and Race/ Ethnicity; Males, 18 SEER Areas, 2012-2014SEER Cancer Statistics Review, 1975-2014, National Cancer Institute. Bethesda, MD Huang, Shuyu, Sander M. J. van Duijnhoven, Alice J. A. M. Sijts, and Andrea van Elsas. “Bispecific Antibodies Targeting Dual TumorAssociated Antigens in Cancer Therapy.” Journal of Cancer Research and Clinical Oncology 146, no. 12 (December 2020): 3111–22. https://doi. org/10.1007/s00432-020-03404-6. “Introduction to Chemotherapy” (n.d.). National Cancer Institute: SEER Training Modules. Retrieved October 22, 2021, from https://training. seer.cancer.gov/treatment/chemotherapy/. Jain S and Gradishar WJ. Chapter 61: Male Breast Cancer. In: Harris JR, Lippman ME, Morrow M, Osborne CK, eds. Diseases of the Breast. 5th ed. Philadelphia, Pa: Lippincott-Williams & Wilkins; 2014. Kazeminia, S., Baur, C., Kuijper, A., van Ginneken, B., Navab, N., Albarqouni, S., & Mukhopadhyay, A. (2020). GANs for medical image analysis. Artificial Intelligence in Medicine, 109, 101938. https://doi.org/10.1016/j.artmed.2020.101938 Khan, H., Ullah, H., Martorell, M., Valdes, S. E., Belwal, T., Tejada, S., ... & Kamal, M. A. (2021, February). Flavonoids nanoparticles in cancer: Treatment, prevention and clinical prospects. In Seminars in cancer biology (Vol. 69, pp. 200211). Academic Press. Khong, H. T., & Restifo, N. P. (2002). Natural selection of tumor variants in the generation of “tumor escape” phenotypes. Nature Immunology, 3(11), 999–1005. https://doi.org/10.1038/ni1102999 Khoobchandani, Menka, Kavita K Katti, Alice Raphael Karikachery, Velaphi C Thipe,

Deepak Srisrimal, Darsha Kumar Dhurvas Mohandoss, Rashmi Dhurvas Darshakumar, Chintamani M Joshi, and Kattesh V Katti. “New Approaches in Breast Cancer Therapy Through Green Nanotechnology and Nano-Ayurvedic Medicine – Pre-Clinical and Pilot Human Clinical Investigations.” International Journal of Nanomedicine Volume 15 (January 2020): 181–97. https://doi.org/10.2147/IJN.S219042. Kim, R., Emi, M., & Tanabe, K. (2007). Cancer immunoediting from immune surveillance to immune escape. Immunology, 121(1), 1–14. https://doi.org/10.1111/j.13652567.2007.02587.x Kuiler, E. W. (2015). Big Data Adoption in the Health Care Domain: Challenges and Perspectives. Journal of the Washington Academy of Sciences, 101(3), 11–22. La-Beck, N. M., Liu, X., Shmeeda, H., Shudde, C., & Gabizon, A. A. (2021, January). Repurposing amino-bisphosphonates by liposome formulation for a new role in cancer treatment. In Seminars in cancer biology (Vol. 68, pp. 175-185). Academic Press. Li, Min Chiu, et al. “Therapy of Choriocarcinoma and Related Trophoblastic Tumors with Folic Acid and Purine Antagonists.” New England Journal of Medicine, vol. 259, no. 2, 1958, pp. 66–74., https://doi.org/10.1056/nejm195807102590204. Maringe, Camille et al. The Lancet Oncology, Volume 21, Issue 8, 1023 - 1034 Markham, Merry Jennifer, et al. “Clinical Cancer Advances 2020: Annual Report on Progress against Cancer from the American Society of Clinical Oncology.” Journal of Clinical Oncology, vol. 38, no. 10, 2020, p. 1081., https://doi. org/10.1200/jco.19.03141. National Breast Cancer Foundation. “Stage 2 (II) and Stage 2A (IIA) Breast Cancer Overview.” National Breast Cancer Foundation, 17 Feb. 2022, https://www.nationalbreastcancer.org/breastcancer-stage-2. Ngambenjawong, Chayanon, Heather H. Gustafson, and Suzie H. Pun. “Progress in Tumor-Associated Macrophage (TAM)Targeted Therapeutics.” Advanced Drug Delivery Reviews 114 (May 2017): 206–21. https://doi. org/10.1016/j.addr.2017.04.010. NIH. “NCI Dictionary of Cancer Terms.” National Cancer Institute, https://www.cancer. gov/publications/dictionaries/cancer-terms/def/ solid-tumor. NIH. “NCI Dictionary of Cancer Terms.” National Cancer Institute, https://www.cancer. gov/publications/dictionaries/cancer-terms/def/ stage-ii-colorectal-cancer. O'Malley, Rebecca L., et al. “Gender Disparity in Kidney Cancer Treatment: Women Are More Likely to Undergo Radical Excision of a Localized Renal Mass.” Urology, vol. 82, no. 5, 2013, pp. 1065–1070., https://doi.org/10.1016/j. urology.2013.06.060. Pearson, O. H., et al. “ACTH- and CortisoneInduced Regression of Lymphoid Tumors in Man.A Preliminary Report.” Cancer, vol. 2, no. 6, 1949, pp. 943–945., https://doi. org/10.1002/1097-0142(194911)2:6<943::aidcncr2820020602>3.0.co;2-p. Phillips, E H. “Laparoscopic Colectomy.” SpringerReference, Dec. 1992, https://doi. org/10.1007/springerreference_108991. “Radiation Therapy for Cancer.” National Cancer Institute, https://www.cancer.gov/ about-cancer/treatment/types/radiationtherapy#:~:text=Radiation%20therapy%20 (also%20called%20radiotherapy,your%20 teeth%20or%20broken%20bones. Shavers, V. L., & Brown, M. L. (2002). Racial and ethnic disparities in the receipt of cancer treatment. Journal of the National Cancer Institute, 94(5), 334-357. Shewach, D. S., & Kuchta, R. D. (2009). Introduction to cancer chemotherapeutics. Chemical reviews, 109(7), 2859–2861. https:// doi.org/10.1021/cr900208x Shim, Hyunbo. “Bispecific Antibodies and Antibody–Drug Conjugates for Cancer Therapy: Technological Considerations.” Biomolecules 10, no. 3 (February 26, 2020): 360. https://doi. org/10.3390/biom10030360. “Side Effects of Radiation Therapy.” Cancer. Net, 23 Sept. 2020, https://www.cancer.net/ navigating-cancer-care/how-cancer-treated/ radiation-therapy/side-effects-radiation-therapy. Siegel, RL, Miller, KD, Fuchs, H, Jemal, A. Cancer Statistics, 2021. CA Cancer J Clin. 2021: 71: 7- 33. Stage 0 Treatment Options. breastcancer.org. (2021, July 29). Retrieved October 22, 2021, from https://www.breastcancer.org/treatment/ planning/cancer_stage/stage_0. Stages of Cancer. Cancer Research UK. (2021, May 7). Retrieved October 22, 2021, from https:// www.cancerresearchuk.org/about-cancer/whatis-cancer/stages-of-cancer. Stomach Cancer: Stage 1. (n.d.). Cancer Research UK. Retrieved October 23, 2021, from https:// www.cancerresearchuk.org/about-cancer/ stomach-cancer/stages/stage-1 Strickland, N. H. (2000). Current topic: PACS (picture archiving and communication systems): filmless radiology. Archives of Disease in Childhood, 83(1), 82–86. https://doi. org/10.1136/adc.83.1.82 Sun HF, et al. Clinicopathological characteristics and survival outcomes of male breast cancer according to race: A SEER population-based

study. Topalian, Suzanne L., Janis M. Taube, Robert A. Anders, and Drew M. Pardoll. “MechanismDriven Biomarkers to Guide Immune Checkpoint Blockade in Cancer Therapy.” Nature Reviews Cancer 16, no. 5 (May 2016): 275–87. https://doi. org/10.1038/nrc.2016.36. “Types of Radiation Therapy: How They Work and What to Expect.” Medical News Today, MediLexicon International, https://www. medicalnewstoday.com/articles/types-ofradiation-therapy. Uppal, S., Chapman, C., Spencer, R. J., Jolly, S., Maturen, K., Rauh-Hain, J. A., ... & Rice, L. W. (2017). Association of hospital volume with racial and ethnic disparities in locally advanced cervical cancer treatment. Obstetrics & Gynecology, 129(2), 295-304. Waldman, Alex D., Jill M. Fritz, and Michael J. Lenardo. “A Guide to Cancer Immunotherapy: From T Cell Basic Science to Clinical Practice.” Nature Reviews Immunology 20, no. 11 (November 2020): 651–68. https://doi. org/10.1038/s41577-020-0306-5. “What Do Cancer Stages and Grades Mean?” NHS Choices, NHS, https://www.nhs.uk/ common-health-questions/operations-tests-andprocedures/what-do-cancer-stages-and-gradesmean/. Willow, Jon Anne. “Stage 3 Lung Cancer: Prognosis, Life Expectancy, Treatment, and More.” Healthline, Healthline Media, 3 Aug. 2020, https://www.healthline.com/health/lungcancer/stage-3-symptoms-outlook#takeaway. Xu, Xiaoru, Xiangru Feng, Min He, Zepeng Zhang, Jiajia Wang, Haiyu Zhu, Tie Li, Fuchun Wang, Mengmeng Sun, and Zhihong Wang. “The Effect of Acupuncture on Tumor Growth and Gut Microbiota in Mice Inoculated with Osteosarcoma Cells.” Chinese Medicine 15, no. 1 (December 2020): 33. https://doi.org/10.1186/ s13020-020-00315-z. Yedjou, C. G., Tchounwou, P. B., Payton, M., Miele, L., Fonseca, D. D., Lowe, L., & Alo, R. A. (2017). Assessing the racial and ethnic disparities in breast cancer mortality in the United States. International journal of environmental research and public health, 14(5), 486. Zhai, Bingtao, Nana Zhang, Xuemeng Han, Qiujie Li, Mingming Zhang, Xiaying Chen, Guohua Li, et al. “Molecular Targets of β-Elemene, a Herbal Extract Used in Traditional Chinese Medicine, and Its Potential Role in Cancer Therapy: A Review.” Biomedicine & Pharmacotherapy 114 (June 2019): 108812. https://doi.org/10.1016/j. biopha.2019.108812. Zhou, W., Bhadra, S., Brooks, F. J., Li, H., & Anastasio, M. A. (2020). Progressively-Growing AmbientGANs for learning stochastic object models from imaging measurements. In F. W. Samuelson & S. Taylor-Phillips (Eds.), Medical Imaging 2020: Image Perception, Observer Performance, and Technology Assessment (p. 24). SPIE. https://doi.org/10.1117/12.2549610

Food Justice and the Impacts of Food Insecurity on Health

STAFF WRITERS: MD MUBTASEEM AHNAF ARONNO ‘24, ALLISON PITTMAN ‘25, SUMMER HARGRAVE ‘25, FRANCISCA FADAIRO '25, STEPHEN ADJEI '25, SOYEON (SOPHIE) CHO ‘24, MAY JIN '25, YIHAN (ELAINE) PU ‘25, ANDREW BARRY ‘24, ROHAN MENEZES '23, SHUXUAN (ELIZABETH) LI ‘25, JENNY OH ‘25, SARAH CHACKO ‘23, ERICA SIMON ‘25

TEAM LED BY: AKSHETA KANUGANTI ‘24, ANAHITA KODALI ‘23

Cover Image: Food is at the core of our health.

Image Source: Wikimedia Commons

Introduction:

What is food justice? How is the food that we eat related to our health? Food justice is the act of making good quality, healthy, and fresh foods available to people of all socio-economic backgrounds, race, and genders. Food justice is a response to the food insecurities that plague largely low-income households. Food insecurity refers to uncertainty or total lack of supply of quality healthy foods needed for an active and healthy lifestyle (FAO, 2003). The concept of food justice involves changing the damaged and damaging system that directly results in under-availability of healthy food in minority societies. Much of this underavailability is due to lack of affordability, and cultural preferences that have been shaped by a low economic status. Food as a result has taken up different meanings for different groups including African-American, Hispanic, and other people of color. Although food is usually considered to be a substance that can counter hunger, food is meant to be any edible substance that provides the essential nutrients for the body to function and carry out metabolic activities properly.

The food we eat has a direct impact on our functionality and overall health. Americans, especially racial minorities and low socioeconomic groups, suffer from many foodrelated diseases such as obesity, type 2 diabetes, cardiovascular, liver, and kidney disease, cancer and Alzheimer’s disease. All of these diseases are within the top 12 leading causes of death as of 2020, increasing the importance of food justice (NVSS, 2022). Furthermore, half of all American adults (117 million people) are living with at least one preventable disease, such as dental disease, experienced as a direct result of food insecurity (“Food Related Diseases,” n.d.). Black and Hispanic communities are further targeted by fast food chains as they encourage consumption of mainly unhealthy foods in advertisements on Spanish-language or African-American targeted TV channels (Malkan, 2021). Hispanic and Black children see on average more fast-food ads than their white peers. This excess advertisement of fast-food restaurants is likely due to the higher proportion of fast-food restaurants in Black and Hispanic neighborhoods, further highlighting the food justice problem: Hispanic and Black racial communities do not have as much access to healthier food options (Malkan, 2021). Food justice is necessary for these communities to dismantle the systemic racism in the United States. Healthier food options do not only improve

residents’ health, but new research shows that it can provide new occupations, increase wages, and stimulate overall local economic activity, thereby empowering people of color.

This article aims to bring to light the inequalities of access to healthy food based on characteristics such as race, economic status, geographical location, and gender that shouldn’t hinder quality food availability in this current global economy. This article will also highlight the physical and mental health issues related to food insecurity and show the importance for food justice in America.

In this paper, “healthy food” is considered to be minimally processed food, including fruits, vegetables, whole grains, healthy fats, and healthy sources of protein. On the other hand, “low quality food” is highly processed foods such as sugarsweetened beverages, foods with high saturated and trans fats, refined sugars, and highly processed snack foods (“The Best Diet”). Additionally, “empty calories” are food and drinks that provide high energy but low nutritional value. There are generally two categories of empty calories: added sugars and solid fats (Reedy & Krebs-Smith, 2010). Added sugars are simple carbohydrates: monosaccharides and disaccharides (Kent, 2016). Examples of foods rich in added sugars include soft drinks, cookies, and candy bars high in glycemic index and where sugar is added during processing or preparation; the glycemic index is a way that doctors and researchers can quantify how much eating a certain food increases blood sugar. Solid fats are also called saturated fats. They are solid at room temperature and found in meat and dairy products such as bacon and butter.

COVID-19’s effects on food insecurity in the US COVID-19 has drastically exacerbated existing food insecurity in the United States. Before the pandemic, “1 in 9 households in the United States were food insecure” (Leddy et al., 2020). However, according to Feeding America's Map the Meal Gap’s (MMG) annual projection of local and national-level food insecurity, the number of food-insecure Americans increased from 17 million in 2018 to 54 million in 2020. The number of food-secure children increased from 7 to 18 million (Gundersen et al., 2020). Rising unemployment, economic shutdowns, and the implementation of social-distancing policies prompted by COVID-19’s arrival in early 2020 have all contributed to rising household stress, healthcare interruptions, and inflation on food prices, perpetuating food insecurity rates and short and long-term poor health outcomes Food insecurity has adverse health effects by increasing family stressors, provoking highrisk behaviors such as unprotected sex and low medication adherence, and triggering severe inflammation. COVID-19 further worsens these issues, increasing anxiety about job security and family wellbeing, the prevalence of the aforementioned high-risk behaviors, and mechanisms that boost inflammation levels, including fat uptake and chronic-disease causing inflammatory markers such as C-reactive protein (11, 91), IL-6, and TNF receptor 1 (90). Furthermore, overburdened healthcare facilities often do not have the resources to attend to patients negatively impacted by these health implications due to large influxes of COVID-19 cases, which disproportionately impacts those who are food insecure during the pandemic (Leddy et al., 2020).

COVID-19 also exacerbates food insecurity “in the context of pre-existing economic disparities” by revealing flaws in the existing US food system (Leddy et al., 2020). The shutdown of grocery stores, farmers’ markets, food banks, and restaurants has elevated demand for at-home food preparation and created a stress on grocery stores and charitable feeding organizations. Much of the food grown for restaurant consumption has gone to waste and the quantity of food available in grocery stores has plummeted, as millions of Americans compete for available foods. Households relying on food banks also experience heightened food insecurity, as stayat-home orders strain the system by increasing food demands, disrupting the food supply chain, and producing a shortage in volunteer workers. In addition, unemployment and subsequent income loss have left many without the financial means to purchase enough food or compensate for the drastic increase in food prices because of the pandemic, and school shutdowns negatively impacted 30 million children who depend on the National School Lunch program to access low-cost or free meals (“COVID-19”). Those more vulnerable to COVID-19, such as those with pre-existing conditions or those that are immunocompromised, “may be unwilling or unable to access food due to fear of viral exposure, further driving food insecurity” (Leddy et al., 2020).

The widening of food insecurity caused by the COVID-19 pandemic and its subsequent economic and health crises has garnered little attention. The increased stress placed on the US food system and households “poses a serious threat to the nutritional health of millions [of Americans]” (Fitzpatrick et al., 2021). Therefore,

"COVID-19 also exacerbates food insecurty 'in the context of pre-existing economic disparities' by revealing flaws in the existing US food system (Leddy et al., 2020)"

Image 1: This image displays several facts and statistics about food insecurity in the United States. Though a high percentage of individuals in the US are consistently food secure, 14.6 of the US population (or 49.1 million people) live in households that are food insecure.

Image Source: Wikimedia Commons

it is essential that solutions are found to remedy current social disparities to mitigate effects on food insecurity from similar future dilemmas to the COVID-19 pandemic.

Inequities in food access: Race

The relationship between race and food inequity is complex and is influenced by social and economic disadvantages against people of color. Structural racism limits people of colors’ access to equal education, employment and social representation, resulting in consequences that may contribute to food insecurity. Statistical analysis modeled by Trends in food insecurity by race and ethnicity (see fig. 1) reveals that, in comparison to White and non-Hispanic households, a greater percent of Black and Hispanic households experience food insecurity. Particularly, the percent of Black and Hispanic households who experienced food insecurity during the Great Recession was approximately double the percent of white households. With the COVID-19 crisis, “rates of food insecurity among Black households with children are [reported to be] nearly twice as high [as compared to their white counterparts]” (Schanzenbach & Pitts, 2020). Institutional racism, interknit with political, social, economic, and legal elements of the United States, is one underlying cause of food insecurity.

Racial discrimination in education and employment opportunities have been identified as significant factors that engender social and economic consequences which ultimately could result in food insecurity. Systemic racism infiltrates the current education system, negatively

impacting students’ learning experience and beyond. Although marks of racism are more subtle in contemporary high education systems as compared to the past, modern education policies are nevertheless influenced by the history of racism.

Given the inextricable link between education and socioeconomic status, students from families with higher income are more likely to have access to greater educational resources, allowing for students to perform better on standardized tests that factor into institutions’ admission of applicants into higher-education programs. Specifically, standardized tests have been argued to “perpetuate false notions of meritocracy and mask existing systemic inequities in educational opportunity [as] a proxy for socioeconomic status, rather than a measure of academic ability” (Museus & Parker, 2015). Coupled with stereotypes that some students of color are not capable of performing as well as their peers, standardized tests and other educational measures may serve as factors that limit such populations’ access to quality education. Education is closely linked to employment opportunities, as higher-paying occupations often require higher educational backgrounds. Students of color with limited access to higher ranking institutions are less likely to be employed to high-paying jobs, contributing to restraints and inequities in food access. This perpetuating feedback loop negatively impacts a significant share of families of color and their ability to obtain sustained access to food.

Solutions have been identified in efforts to address the impact of structural racism on food insecurity. The federal government can expand and increase access to federal income support benefits for families; systems such as the Earned Income Tax Credit (EITC) and the Child Tax Credit provide financial credit for low- and moderate-income working people, adding to the incomes of families of color who are more likely to work in low-paid occupations (Odoms-Young, 2018). According to the 2018 Current Population Survey data conducted by CBPP, while 9% of white women have received credit from the EITC system, 21% of Latina and Black women – greater than twice the share of white women – have benefitted from the program (Marr & Huang, 2019). Programs that offer broader access to employment opportunities for people of color can also serve as solutions to combat the economic consequences of structural racism on food insecurity. By race, whites constituted the majority of the labor force at 78 percent (in 2018) while Blacks and Asians constituted, respectively, 13 percent and 6 percent (“Labor force characteristics,” 2019). To tackle the persistent issue of food inequity across race, the fundamental root of structural racism must be addressed with a human rights approach: once again, we make clear that all forms of discrimination, based on racial or socioeconomic factors, must be eliminated. Relevant efforts will require political measures and programmatic strategies to be carefully devised to promote effective equity in food access.

Economic status

The scarcity of healthy food in low-income communities is overshadowed by the more affordable unhealthy food option. It is not unheard of that “people experiencing food insecurity often consume a nutrient-poor diet, which may contribute to the development of obesity, heart disease, hypertension, diabetes, and other chronic diseases” (Murthy, 2016). In low-income areas, the most frequently eaten foods are cheap fast foods or monotropic meals - meals consisting of just eating one food, such as potatoes- that do not meet the body’s nutritional requirements. The paradox of food insecurity and obesity is perpetuated by socioeconomic disparities as “diets with greater nutrient density are more expensive than less-healthy calorically dense diets”(Levy et al, 2012). Since the 1950s, the fast-food trend has flourished with food production companies producing and distributing unhealthy foods at lower cost, thereby capitalizing on communities that can only afford such goods. In this way, unhealthy foods have become more common and accessible, leading to unhealthy lifestyles and health consequences. Moreover, in low-income areas, Yale researchers have recently found that there are not only significantly less healthy food options, but the produce tends to be lower in quality (it is less fresh and dirtier) (YaleNews). Those who cannot afford to live in higher income areas have fewer options to eat healthier, exacerbating the food justice problem. Therefore, the economic status of low- income earners directly impacts the quality of food they consume.

A culture around unhealthy eating—that has been built in a subtle systemic manner unknown to affected minority populations— is an additional point to consider in the food choices. The subtle systemic manner refers to purposeful focus on the minority population in marketing unhealthy food in America (Vlasits, 2016). A 9-month longitudinal study of food choices among minority and low-income individuals found that two interventions–

"The scarcity of healthy food in lowincome communities is overshadowed by the more affordable unhealthy food option"

"A household's geographic location is a significant predictor of healthy food access..."

“point-of-purchase color-coded food labeling and choice architecture” –improved healthy choices equally among employees from all racial/ ethnic and socioeconomic backgrounds” (Levy et al, 2012). The significance of this study is that interventions are effective ways of curtailing unhealthy food consumption and increasing healthy food choices. The point-of-purchase color-coded food labeling refers to a system of using colors (red, yellow, green) to differentiate healthy and unhealthy food: green being the healthiest and red the unhealthiest. The effect of this intervention was a psychological response to the colors, where customers avoided red which commonly signifies danger and yielding to green labeled foods. This intervention demonstrates that simpler consumer communication is needed to facilitate healthier food choices in low-income communities. Choice architecture is also a psychological play that involves arranging the store (where the observation occurred) in such a way that “green” foods are more accessible than the red foods. It also showed a significant change in food choices across all people. This shows that if healthy food is available, people are willing to buy it; however, shaping certain areas so a higher portion of food sources are unhealthy takes away the access to food, creating food injustice. This can be perceived as a systemic injustice like redlining but in the form of targeting by fast food chains. Instead of stereotyping certain areas based on income and predicting that unhealthy, but affordable, food would sell better, food justice aims to create equity in food access, regardless of income.

Geographical barriers to healthy food access

A household’s geographical location is a significant predictor of healthy food access, particularly in concert with a locale’s average socioeconomic status. One major issue indicated by prior research is that low-income neighborhoods, which are primarily urban, have less than half as many supermarkets as highincome neighborhoods on average (Moore and Diez-Roux, 2006). This disparity presents an issue for food justice as supermarkets are often able to provide a much larger selection of food products, including healthier options, and at a lower price than smaller alternatives, such as groceries and convenience stores (Powell et al., 2007; Walker et al., 2010). The difference may be partly due to the shift of wealthy households with higher purchasing power to suburbs, widening the physical distance between richer and poorer neighborhoods, and creating an incentive for larger stores to migrate with the former group (Morland et al., 2002; Treuhaft and Karpyn, 2010). The average nutritional quality of food products is lower, and prices higher, in neighborhoods with a lower median income (Hendrickson et al., 2006).

This geographical issue is particularly impactful given that lower median income is correlated with higher time requirements for child-rearing and employment, and lower rates of private vehicle ownership (Cotterill and Franklin, 1995; Morland et al., 2002). In combination with a lack of supermarkets, this leads to the increased exposure to high-calorie unhealthy food options in relatively prevalent convenience stores and fast-food restaurants, causing unhealthy eating habits (Morland et al., 2002; Walker et al., 2010). Therefore, income, time and mobility constraints limit neighborhood residents to purchasing less nutritious food available in their own area, turning these locales into food deserts (Morland et al., 2002; Walker et al., 2010). While food deserts have often been defined as primarily urban, rural areas have similarly low healthy food access due to income, time, and mobility issues, especially compared to suburban communities (Treuhaft and Karpyn, 2010).

The racial composition of neighborhoods has also been found to be a significant geographic indicator of healthy food access, even when controlling for economic status (Powell et al., 2007). This inequality is especially severe for Black Americans. In Detroit, Michigan, for example, the most impoverished white neighborhoods are on average over a mile closer to the nearest supermarket than the most impoverished Black neighborhoods (Zenk et al., 2005). An analysis of neighborhoods across multiple states found that majority nonwhite and racially mixed neighborhoods had less than half as many supermarkets (on average) as majority White neighborhoods (Moore and Diez Roux, 2011). For majority-Black neighborhoods, that proportion drops to a fourth (Morland et al., 2022). These healthy food access issues may be associated with disproportionate rates of morbidities and obesity in minority communities (Deaton and Lubotsky, 2003; Paeratakul et al., 2002). One potential reason for racial disparities in heathy food access is the modern impacts of historical racial segregation in residential areas, concentrating minority populations in lowresource areas, with limited economic activity and opportunities, and therefore limited healthy food access (Gee and Payne-Sturges, 2004; Bower et al., 2014).

Geographical location

The tropics, situated around the equator, boast a perpetual exposure to the sun and a season of heavy rainfall. It is precisely these climate conditions that make the area ripe as an agricultural playground. Inhabitants of tropical regions are much more dependent on the agrarian industry (in comparison to the manufacturing industry), specifically on crops for both local consumption, export, and their economic livelihoods. While local family farms produce around 80% of food globally, these same farmers suffer the most from malnutrition and food insecurity. Furthermore, the need to meet the global demand of crop production has resulted in wide-scale unsustainable agricultural practices, which in turn further endangers food security by land degradation (Rashid, 2018).

The country of Madagascar serves as a prime example for the exacerbating effect of unsustainable farming practices on food security in tropical, low-income countries. Herrera et al. investigated the challenges of food security in northeast Madagascar and the impact of agricultural practices that heighten food stress. In this evaluation, the authors linked increasing land size with the decreased agricultural productivity, highlighting the “inefficiencies of input use on larger fields, especially when they are in fragmented parcels” (Herrera et al., 2021). These inefficient farming techniques often degrade the soil and water of the field, consequently reducing future crop yield and the nutritional value of the obtained harvest. Also, the use of fertilizers introduces contaminants to local water streams, inflaming the water scarcity crisis plaguing the area. These agricultural practices are incompatible with the ever-growing global demand for food, considering the 70% global increase in agricultural productivity needed by 2050 as estimated by the Food and Agriculture Organization of the United Nations (“Making agriculture more sustainable and productive,” n.d.). The introduction of sustainable farming practices in these areas are a necessity in the interest of local and global food security.

Gender

Access to food is also divided by gender; globally, women are more likely than men to be food insecure, this difference becoming more intense in certain populations (Broussard, 2019). In the United States in 2020, the rate of food insecurity for single-mother households was 27.7%, compared to 16.3% for single-father households, and the national average food insecurity is 10.5% (Coleman-Jensen et al., 2021). This inequality can be attributed in part to the gender wage gap. According to an analysis done by the Pew Research Center, women earned 84% of their male counterparts’ salaries in 2020 (Barroso & Brown, 2021). This lower income correlates to less spending money available for meals, forcing women to either purchase less food or choose the less expensive- and often unhealthier- option. Further, pregnant women face even more stress due to greater physical and nutritional needs along with a potential lack of pay during maternity leave (Ivers & Cullen, 2011). For impoverished families, this temporary lack of income limits access to food for the entire family. Another worrisome consequence is the health of the baby, as approximately 17 million children are born underweight annually as a result of inadequate nutrition of their mothers before and during pregnancy (Sachs & Patel-Campillo, 2014). Thus, food insecurity’s disproportionate effect on women extends beyond gender to intersect with economic concerns and the wellbeing of the entire family.

Food Culture

Food culture is defined as the attitudes, beliefs and practices that surround the production and consumption of food; it is shaped by upbringing and incorporates elements of a person’s ethnicity, cultural heritage, and religion. Cultural components of behavior have significant impacts on patterns of eating, drinking, and social interactions–all of which contribute to health. One’s food habits and subsequent diet is a combination of sociodemographic

Image 2: This is a map of food desert locations in Chicago. Food deserts are regions in which inhabitants do not have easy access to healthy food (like from a supermarket). The white pentagons with carts in them represent grocery stores, and areas that are shaded with blue lines are food deserts. The darker red an area is, the more impoverished it is. From the graph, many grocery stores fall in low poverty areas, and in line with this, the darkest red areas – which have the highest rates of poverty – are also food deserts.

Image Source: Wikimedia Commons

"...globally, women are more likely than men to be food insecure..."

"To ensure successful health education programs...it is important to identify local cultural practices and beliefs, as well as the local food culture."

characteristics, health and lifestyle, food beliefs and attitudes, food preferences, dietary environment, and food availability. These food habits have large influences on the health disparities observed between societies. Studying the food behaviors that lead to such disparities can help explain why some groups seem to have a predisposition to certain health issues.

Diet is a cultural and social construct. It can impact one’s predisposition to certain health issues. Particularly, cultural-religious beliefs have shown how religion can have both a positive and negative impact on health. Religions often have health and dietary “rules;” for example, Judaism does not permit the consumption of pork. These “food taboos”—or prohibited foods—have both good and bad health implications. For example, a population of Seventh-Day Adventists in the United States in the 1980s was found to have low mortality, cancer, and diabetes (Phillips et al., 1980). This was a result of their low animal intake—Seventh-Day Adventists are lacto-ovovegetarians, which means that they are vegetarians that avoid alcohol. Another example comes from Ohio, where a group of Old Order Amish were found to have lower rates of hypertension, smoking, alcohol consumption, and stress in comparison to the non-Amish rural Ohio residents (Fuchs et al., 1990). However, obesity was extremely prevalent for this population, as the Amish see food and eating as very important. This, coupled with decreased physical activity and other factors contribute to the high incidence of obesity and related issues seen within the population. These examples demonstrate the unbreakable link between religion and health. Food is an important part of many religious cultures; because of this, it is important that health professionals seek to understand how various religious and cultural practices influence health outcomes, especially those that result from diet.

Similar to religion, ethnicity and socioeconomic status shape food culture, which in turn shapes the health of individuals within a population. Diet-related diseases are more prevalent among lower-income and minority groups, which is why it is important to study these groups to reduce these health disparities. In a study conducted in north central Florida, researchers aimed to explore how culture and community impact the nutritional attitudes, food choices, and dietary intake in a select group of African Americans. Among the individuals studied, there was a perception that “eating healthfully” meant giving up part of their cultural heritage and trying to conform to the dominant culture (James, 2010). The results highlighted how the social and cultural symbolism to eating healthy foods was a barrier to this specific population, which subsequently impacted the dietary habits of the individuals studied. Similar work is being done in Nebraska by Georgia Jones, an Associate Professor and Extension Food Specialist at the University of Nebraska-Lincoln. Jones specializes in food literacy and is working with multiple populations of Native Americans to determine how they can establish native food traditions in healthy ways. Historically, Native American populations have suffered from a high incidence of diabetes as they have over time, due to genetic mutations from ancestors, have more sugar in their blood. This could be due to Native Americans historically not having as much access to sources of glucose. Therefore, their bodies have evolved to hold onto glucose in their blood. In fact, as Jones said in an interview, “it's almost a rite of passage to have diabetes if you're Native American…It's kind of presumed that you're sooner or later going to get it” (Tan, 2012). This mindset indicates a mindset shared by many minority groups––that there is nothing that can be done about their predisposition to certain health conditions. However, a healthier diet with diabetes in mind could help Native Americans mediate their pre-diabetes more effectively. Increasing the amount of access to unhealthy food could only exacerbate the risk of diabetes for Native Americans. Hence, the need to connect cultural traditions with healthy eating cannot be ignored. Through increased and more thorough research, we can diminish the risk that food behavior poses to individuals in developing disease. To ensure successful health education programs, especially in relation to diet and a group’s culture surrounding food, it is important to identify local cultural practices and beliefs, as well as the local food culture.

Physical Disease and Food Insecurity: Obesity

According to the CDC, in 2021, 42.5% of U.S. adults aged 20 and over are obese, including 9.0% with severe obesity, and 31.1% who are classified as overweight. These percentages have seen a stark increase in the past fifty years; in 1960, an estimated 31.5% of U.S. adults aged 20 and over were overweight (Sprankle, 2021). This can be attributed, in part, to the increase in fast food availability across the nation. Today, it is more common for both parents in a household to work, which means that there is less time to prepare food at home. Therefore, fast food has become a tempting option.

Fast food is a growing part of the American diet. The convenience it poses to busy Americans makes it more attractive than a home cooked meal. However, fast food is full of calories without any nutritional benefit (empty calories), which puts its consumers at risk for weight gain and obesity. Due to environmental injustices, the increasing trend of fast food disproportionately affects low-income and minority groups.

Environmental justice is defined as “fair treatment and meaningful involvement of all people regardless of race, ethnicity, income, national origin, or educational level in the development, implementation, and enforcement of environmental laws, regulations, and policies” (Hilmers et al., 2012). The concept of environmental injustice can be applied to food access across socioeconomic and ethnic groups. Higher obesity rates among low-income and minority populations are linked to a higher density of fast-food outlets in traditionally lowincome and minority neighborhoods––this promotes unhealthy eating habits.

The data researchers have collected on this issue presents concerning patterns. For example, Hispanic, African American, and low-income populations lived in regions with higher densities of convenience stores and fast-food restaurants (Hilmers et al., 2012). These findings correspond with the statistics, as the percentage of calories consumed from fast food in non-Hispanic Black adults was 21.1%, compared to 14.6% and 14.5% in non-Hispanic white and Hispanic adults, respectively. Similarly, in the youngest age group studied in a census (aged 20-39), there was a statistically significant decrease in the percentage of calories consumed from fast food with increasing income level (Fryar and Ervin, 2013). As demonstrated, accessibility is a key determinant of fast-food consumption; in order to reduce the prevalence of obesity in low-income and minority communities, there needs to be a reduction of fast food availability in certain neighborhoods. Ideally, this will result in a reduction in the obesity prevalence in such groups.

Diabetes

Diabetes is a health condition associated with disordered glucose metabolism. Research consistently demonstrates the relationship between food quality and diabetes; the association of empty calories and type 2 diabetes is particularly robust. Based on current understanding, type 2 diabetes usually develops over time due to a high concentration of blood sugar in the body, which damages the pancreas and impacts its ability to maintain glucose levels (Willett et al., 2002). It is a common condition that affects 17 million individuals in the U.S and has been increasing in prevalence over the past decades alongside the obesity epidemic (Schulze et al., 2004).

As the consumption of added sugars grew in both adults and children across the U.S, research on the link between simple carbohydrates and type 2 diabetes gained focus. A study by Schulze et al. (2004) found that high consumption of sugary beverages such as sugar-sweetened soft drinks and fruit punches is associated with weight gain and greater risk for type 2 diabetes. In another study by Willett et al. (2002), researchers calculated the glycemic load by multiplying the amount of carbohydrate with its glycemic index; this allows researchers to measure the rise in blood sugar due to the number of carbohydrates in a meal. They found that women in the highest 20 percent for glycemic load had almost double the risk for developing diabetes than did women in the lowest 20 percent for glycemic load. This study also identified that, in patients with diabetes, consuming foods with low glycemic index improved control of their glucose levels (Willett et al., 2002).

There are several pathways by which simple carbohydrates might increase the risk for type 2 diabetes. Schulze et al. (2004) proposed that

Image 3: Obesity is typical defined via BMI. This chart shows the various categories of BMI one can fall into.

Image Source: Wikimedia Commons

Image 4: Vascular disease is strongly linked to issues with food accessibility. Image Source: Wikimedia Commons sugary drinks are high in fructose, which raises blood sugar levels. Similarly, Willett et al. (2002) suggested that carbohydrates high in the glycemic index increase blood glucose and insulin demand. As a result of high blood sugar, beta cells in the pancreas, which control the synthesis and secretion of insulin, have to work harder and are more susceptible to damage; exhaustion of beta cells could lead to glucose intolerance and diabetes (Willett et al., 2002). In addition, sugary snacks and drinks may contribute to obesity, a risk factor for type 2 diabetes due to its link with insulin resistance (Willett et al., 2002), by preventing people from feeling full despite consuming high energy, which leads to subsequent energy intake (Schulze et al., 2004).

While many studies confirm the connection between simple carbohydrates and type 2 diabetes, the link between saturated fat and diabetes remains uncertain. One study found that increased proportions of saturated fatty acid in plasma correlate with an increased risk for developing this chronic condition (ARIC Study Investigators, 2003). However, dietary studies presented mixed results. Micha and Mozaffarian (2010) found that there is an independent relationship between the consumption of saturated fatty acids and diabetes – however, the risk for diabetes decreased with the consumption of monounsaturated fatty acids (healthy fat from plant foods) (Micha & Mozaffarian, 2010). A study by van Dam et al. (2002) also showed that saturated fat consumption was only associated with a higher risk of type 2 diabetes without adjustment for body mass index.

Therefore, evidence suggests that, of the two categories of empty calories, added sugars have a stronger association with the development of type 2 diabetes which may be attributed to their direct effect on blood sugar levels and their link to obesity. At the same time, more research is needed to determine the association between solid fat and diabetes.

Vascular disease

The term vascular disease is used as an umbrella term to describe many diseases involving the narrowing and stiffening of blood vessels, such as peripheral vascular disease, stroke, and aortic aneurysm. Vascular diseases and disorders are not restricted to just the blood vessels. Blood disorders such as sickle cell disorder, where deformed blood cells become adhesive and stick to the inner lining of blood vessels and platelets, disrupt blood flow by causing blockage within the vessels (Ofori-Acquah, 2020). Vascular diseases are burdensome to the US population and the healthcare industry; As of 2015, vascular diseases affect over 30 million people and generate healthcare costs of up to $100 billion annually (Clavijo, 2015).

Several studies have also suggested that food insecurity may be directly correlated with vascular disease and poor cardiovascular health. For example, a study by the USDA concluded that the prevalence of cardiovascular diseases was six times higher for individuals with low food security. At the same time, those individuals were 2.36 times more at risk of having 10-year cardiovascular disease risk and were more likely to die due to CVD. Low income is an essential factor in this correlation. According to the study, low-income individuals may suffer from limited

transportation access and food insecurity and find CVD treatments financially burdensome, increasing their likelihood of remaining food insecure. The same study claims that food insecurity is associated with the intake of sugar, processed foods, and other unhealthy meals. These dieting patterns contribute to early vascular changes in children, such as higher BMIs and accumulation of body fat, contributing to cardiovascular mortality (Chang et al., 2022).

Chang et. al's study demonstrates that the behavioral changes, stress levels, and nutritional quality associated with food insecurity contribute to CVD development and the increased risk of death from CVD (Chang et al., 2022). This relationship locks those affected in a vicious cycle of unfortunate circumstances: As CVD treatment becomes financially burdensome for low-income individuals, the individuals may turn to unhealthy dieting options due to their affordability, which directly contribute to cardiovascular disease and mortality (Chang et al., 2022).

Building on this analysis, Chang et. al's study lists sociodemographic factors used to determine which demographics struggling with food insecurity are more likely to develop cardiovascular complications. One such factor is race and ethnicity. The study cites "socioeconomic inequality, educational disparities, and bias… in healthcare" as factors that leave under-represented racial groups more at risk of cardiovascular complications. For example, according to a 2020 study by K. Cooksey, Hispanic and Black individuals are more likely to live in places with more unhealthy food options. Food insecurity was also linked to obesity among food-insecure Black and Hispanic individuals, which represented 46.1% and 35.7% of the sample population, respectively (Chang et al., 2022).

Furthermore, a 2017 study headed by Seth Berkowitz sought to identify a correlation between food insecurity and Atherosclerotic Cardiovascular Diseases (ASCVD). Like Chang, Berkowitz suggests that food insecurity is most associated with health behaviors and factors contributing to expensive medical treatment and poor health. The Berkowitz study used the National Health Interview Survey data to measure food insecurity with 10 question surveys over 30 days. Certain individuals with ASCVD identified their prior coronary artery diseases or recent strokes. The association between food insecurity among those with ASCVD and a composite score of sociodemographic characteristics was measured using Stata SE v 16.0. Berkowitz's results showed that 14.6% of individuals with ASCVD reported food insecurity, whereas only 9.1% of individuals without reported food insecurity (Berkowitz et al., 2017). Furthermore, Berkowitz et al. report the highest risk sociodemographic factors as follows: 65 years or older; Black or Hispanic; lowincome; female; separate marital status; and no health insurance.

Among those displaying only 1 of these characteristics, only 2.2% were food-insecure, whereas those showing anywhere from 2-6 of these characteristics reported 6.4 – 53.7% food insecurity (Berkowitz et al., 2017). Indeed, like Chang et al.’s study, Berkowitz et al. infer that food insecurity shows a solid correlation to cardiovascular disease and mortality. Those suffering from food insecurity may not display optimum dieting practices or have enough income to change their lifestyles. This leads to a critical conclusion: High healthcare expenses for treatment for vascular diseases contribute to prolonged food insecurity for specific groups. These studies display how important it is to tackle barriers preventing specific demographics from obtaining proper nutrition and paying for medical treatment.

Cancer

Food insecurity and one’s diet can be further correlated to increased likelihood of cancer, particularly breast, prostate, pancreatic and colorectal cancer. These forms of cancer can be influenced by dietary habits such as consuming processed and red meats. Red meats include beef, pork, veal, and lamb, while processed meats are but not limited to ham, hotdogs, bacon, and beef jerky (CTCA, 2021). There are growing sings of a correlation between increased consumption of red meat and processed meat and colorectal cancer.

Attention has in the past thirty years been continuously called upon the rise of cancer in younger, less fit groups. The New England Journal of Medicine advised for the age of screening for colorectal cancer (CRC) to be lowered to 45 based on studies done from 1974 to 2013. They’ve noticed a 1.0-2.4% rise per year in colon cancer cases in the 20-39 age group over this time period. As for rectal cancer cases, an even steeper margin of growth of 3.2% a year has been recorded for the 20-29 age group (Dyer, 2018). This significant increase in cases is why the American Cancer Society is urging younger screening, as this trend will most likely follow this generation into their older years.

"Given the link between nutrition and oral health, it is not surprising tha tfood insecurity plays a major role in the development of dental caries."

Several studies have attempted to answer the question of what is causing this rise in CRC cases and have begun researching the relationship between CRC and processed and red meat. Processed meat has already been labeled as a Group 1 carcinogen, placing it on the same level as alcohol and smoking as a probable risk for inducing cancer. Meanwhile, red meat has been placed in Group 2A, which should still be advisable for caution (Dyer, 2018). A 2017 on-going study in Germany took two groups of people (upwards of two thousand in each) with family history of CRC, one with CRC and one control, and conducted research on the diets of both. They examined the various mutations in the CRC group, looking for trends in the mutations that could reveal a correlation. They found insufficient data to determine if processed and red meats caused a specific mutation, though they claimed that they found an association of meat intake and CRC with a confidence interval of 95% (Carr et al., 2017). The report does note that due to the small sample size, the data is more helpful as a stepping stone for larger work.

The next year, another study in France by NutriNet-Santé included a baseline of 104,980 participants who did not have cancer. Their diets, as well as physical shape and activity, were monitored over a five-year span. In that span, 2228 were diagnosed with cancer, 153 cases being CRC. The other two significant cancers noted in the study were breast (739) and prostate (281). The study found that ultra-processed fats had a correlation to increased risk in all cancers. The study concluded that a 10% increase in processed food consumption was associated with a 12% increase in risk of all cancers (Fiolet et al., 2018). Such data further proves why meat consumption continues to be a high-level carcinogenic risk.

Dental disease

To maintain oral health, the human body requires daily nourishment in the form of a balanced diet containing appropriate amounts of all nutrients. Malnutrition (over and undernutrition) can severely compromise oral health and cause dental diseases such as dental caries, periodontal diseases, diseases of the oral mucosa, oral cancer, and infectious diseases. Among them, dental caries, or tooth decay, is the most prevalent disease worldwide and the most common pediatric disease in the United States (Chi, 2014). According to a recent survey by the global oral health data bank, the prevalence of dental caries varies in the range of 49% to 83% (Rathee, 2021). According to the CDC, from 2015 to 2018, the prevalence of untreated tooth decay in the United States was 13.2% for children aged 5 to 19 years and 25.9% for adults aged 20 to 44 years (FastStats, 2022).

A chronic infectious, transmissible disease, dental caries results from cariogenic bacteria, primarily Streptococcus mutans, in the dental plaque (Rathee, 2021). These bacteria anaerobically metabolize dietary sugars to produce lactic and other acids (Gondivkar et al., 2019). The formation of acid in the mouth reduces the oxygen coefficient, making conditions more anaerobic and favorable for cariogenic bacteria (Rathee, 2021). This increases the rate and progression of dental caries. Over time, the acid dissolves the calcified tissue – enamel and dentin – in the tooth, forming cavities. According to studies, this irreversible demineralization of teeth occurs at a pH of 5.5 and below (Rathee, 2021).

Dental caries is a multifactorial disease: it depends on the interaction between various factors, including the presence of fermentable sugar, host factors, and the presence of cariogenic microbial flora (Rathee, 2021). Plaque and dietary factors are interdependent upon each other in the causation of dental caries (Rathee, 2021). A diet rich in processed sugar provides the substrate for cariogenic bacteria in the mouth to flourish and generate enamel-demineralizing acids. Previous studies have found that frequent consumption of carbohydrates in the form of simple sugars such as sucrose increases the risk of dental caries (Gondivkar et al. 2019; Moynihan, 2004). Furthermore, Rugg-Gunn et al. and Burt et al. have found significant association between caries progression and dietary sugar intake in their longitudinal studies (Rugg-Gunn et al., 1984; Burt et al., 1998). The host acts simply as a platform for the interaction of plaque and diet (Usha, 2009).

Given the link between nutrition and oral health, it is not surprising that food insecurity plays a major role in the development of dental caries. According to a cross-sectional analysis of US National Health and Nutrition Examination Survey (NHANES) data from 2007 and 2008 conducted by Chi et al., children from low or very low food security households had significantly higher untreated caries prevalence than children with full food security (2014). Food-insecurity often forces parents or caregivers from low socioeconomic status (SES)-households to make food-purchasing decisions optimized for quantity rather than quality (Chi et al., 2014). For example, they may have no choice but to buy sugar-

sweetened beverages such as Coca-Cola or Pepsi which are cheap and easily accessible. However, these drinks have a high sugar content which significantly increases the risk of dental caries. Additionally, food-insecure households usually live in rural areas or poor neighborhoods where there is a lack of quality food stores (Tungare, 2021; Chi et al., 2014). Purchasing options in these so-called “food deserts” are often limited to convenience stores and fast-food restaurants. Therefore, these households only have access to processed foods, snacks, and sugar-sweetened beverages which are high-energy, nutrient-poor, fatty, and sugary. This deprives children of fresh, nutritiously dense food such as vegetables and fruits, complex carbohydrates, non-processed proteins, and dairy products.

In addition to dental caries prevalence in children, food insecurity is also linked with prevalence of dental diseases in adults. Last year, Bahanan et al. performed a cross-sectional analysis of the NHANES 2011-2012 and 2013-2014 data. The study, which included 10,723 adults, aged 18 and above, found that food-insecure adults had 1.2 times higher odds of having untreated dental caries than fully food-secure adults (Bahanan et al., 2021). This finding agrees with previous studies which investigated the harmful effects of food insecurity on self-reported oral health. For example, an analysis of NHANES 2011-2012 data by Wiener et al. found that adults with low food security were 58% more likely to report unmet dental care need as compared to adults with full food security (2018). This may be because foodinsecure individuals are more likely to consume a poor-quality diet deficient in fruits, vegetables, dairy products, vitamins, and minerals. Furthermore, food-insecure individuals tend to consume large amounts of energy dense food (e.g., burgers, hot dogs, etc.) and to adopt bad eating habits to cope with food deficiencies. As explained before, a diet rich in fermentable carbohydrates such as sucrose significantly increases the risk of developing dental caries.

Dental diseases such as dental caries negatively impact self-confidence and overall quality of life (Govindkar, 2019). Furthermore, compromised oral health can alter food choices and negatively impact food intake leading to suboptimal nutritional status. According to an analysis of the NHANES 2005-2008 data by Zhu and Hollis, teeth loss in adults is associated with lower diet quality and reduced energy intake (2014). This may partly explain the significant association between tooth loss and risk of chronic systemic diseases shown by previous studies (Zhu, 2019). Therefore, recognizing and managing oral health conditions is crucial in order to improve the health as well as the quality of life of affected individuals. However, this can only be done when food inequality is reduced by making healthy, nutritious food affordable and accessible to poor neighborhoods.

Mental Health and Food Insecurity:

Diet and mental health are linked in complex ways with physical health as a prominent mediator. It is commonly known that a healthy diet, positive mental health, and physical wellbeing are often correlated, but the underlying factors are often difficult to parse out. A "good quality diet" usually consists of healthy fats, fruits and vegetables, and high-fiber foods, and a healthy diet increases physical health via numerous biological pathways (Firth et al.). The most prominent factors of good physical health are typical levels of insulin sensitivity, lowered risk of heart diseases, and having a weight that corresponds to one's activity demands. These biological factors can drive individuals to have a

Image Source: Pixabay

"high intake of fruit, vegetables, whole grain, fish, olive oil, low-fat dairy and antioxidants and low intakes of animal foods" (Li et al). Healthy dietary patterns are associated with a reduced risk of depression by several meta-analyses (Li et al., Molendijk et al.). In addition, mentally healthy individuals often experience fewer cravings and put themselves in situations with healthier foods, such as home-cooked meals rather than fast foods. These findings demonstrate the various ways that positive diet and mental health are mediated by physical health.

The reverse trend is true in that an unhealthy diet covaries with the onset of depression symptoms. Multiple factors contribute to this correlation, including glycemic load, immune response activation, and the gut microbiome. First, having an excess of processed carbohydrates ultimately results in counter-regulatory secretions of cortisol and adrenaline. An overload of these hormones is one of the causes of depression in the long term (Firth et al.). Secondly, the immune system has been proposed as a possible pathway in which an unhealthy diet results in mood disorders via the inflammatory response. People with a Western diet (regular fast food consumption) and people with mood disorders both report heightened inflammatory symptoms, although causality has yet to be established (Yuan et al.). Lastly, the gut microbiome is tightly linked with the nervous system. The gut contains microbial metabolites, which often travel into various regions of the brain via the bloodstream. Abnormal regulation of the microbiota-gut-brain axis is one of the major predictors of major depressive disorder (Ortega et al.). These aforementioned factors exemplify pathways in which mental health disorders and unhealthy eating behavior are associated with each other.

Along with depression, research also links food insecurity to generalized anxiety and other anxiety disorders. According to a study conducted by the Journal of Hunger & Environmental Nutrition, those experiencing greater fear and generalized anxiety symptoms, such as families with children who must worry about having to keep more than themselves fed, experience elevated levels of food insecurity (Fitzpatrick et al., 2021). This correlation is further exacerbated by fears surrounding COVID-19. Anxiety over food shortages during times of stay-at-home orders and shutdowns has further increased uncertainties about access to food, perpetuating household food insecurity. The association between food insecurity and anxiety is particularly prevalent among women, which is evident in research carried out by the United States Department of Agriculture that measured food security in households in 2018. Respondents were asked about “anxiety related to the household food supply, running out of food, providing inadequately nutritious food, and substitutions or restrictions in food consumption by adults and/or children in the household due to lack of financial resources” (Maynard et al., 2018). Results indicated that food insecurity and self-reported anxiety/poor mental health were positively correlated in US women.

The “experience of food insecurity itself is characterized by worry and anxiety about the household food supply” (Maynard et al., 2018). The worry over access to food in low-income or struggling households represents a stressor that leads to periods of generalized anxiety or chronic stress. This development in turn generates a negative household or individual relationship with food due to constant uncertainty about food availability or affordability. According to responses collected through a survey by Health Equity, adults with high food security experience anxiety surrounding food insecurity due to “fear of the unknown,” and “are [living] week by week … [avoiding] asking for help … falling through the cracks, invisible to a system suddenly flooded by the needs of people it already recognizes as needing help” (Woflson et al., 2021).

Not only is the prevalence of food insecurity linked to anxiety disorders harmful to adults, but it can also be detrimental to children living in these households. Child health and behavioral development are susceptible to the household risk for food insecurity, and parental anxiety over food accessibility can pose a negative influence on children (Lauren et al., 2021). Food insecurity and eating disorders intersect at many levels. Higher levels of eating disorders, especially binge eating disorder (BED) and bulimia nervosa, are associated with food insecurity in adults. Studies have found that irregular food access results in an irregular trend of food intake: this trend is emphasized in part due to some food aid programs, such as the U.S. Supplemental Nutrition Assistance Program (SNAP). SNAP benefits are provided once a month, which are often used soon after reception and “exhausted before the end of the month.” Such fluctuations in food availability result in food restriction, in turn creating a tendency to binge-eat in the absence of food restriction (Hazzard et al., 2020).

Additionally, a survey conducted in 2018 found that altered eating patterns associated with food insecurity were consistent with the diagnostic criteria (as outlined in the DSM5) for binge eating disorder, including loss of control, recurrent episodes, and psychopathology (Rasmusson et al., 2018). Such eating patterns, in line with characteristics of BED or bulimia nervosa, often result in obesity or changes in body weight. Higher levels of food insecurity are associated with higher levels of weight self-stigma and dietary restraint along with binge eating and other eating disorder pathology (Becker et al., 2017). These trends of negative body image echo trends of high-calorie food consumption and obesity that also accompany food insecurity.

Eating disorders are a concern not only because of their ties to mental health, but because of their additional physical health implications. Both bulimia and binge eating disorder increase a person’s risk for type II diabetes as well as obesity (Raevuori et al., 2014). Bulimia nervosa, in particular, can lead to diverse medical complications because of purging behavior (Mehler & Rylander, 2015). Thus, food insecurity has diverse and adverse effects on both mental and physical health, characterized by its relation to eating behavior.

Conclusion:

The food that we eat is at the core of our health, both physical and mental. Eating foods that are rich in nutrients promotes good health and better quality of life; conversely, consistently eating foods that are high in saturated fats and that have low nutritional value can result in diabetes, obesity, dental disease, and various cancers. Despite this clear link, disparities persist in access to good food, with people of color, women, those in lower socioeconomic classes, and those in certain geographic regions having lower access to good food. This results in a disproportionate burden of food-related disease in these regions and for these people. Additionally, lack of access to food can promote mental health issues, which further can result in poor diets. Centering food justice in public health efforts will be key in addressing these issues in the coming years. References: Alkerwi, A., Vernier, C., Sauvageot, N., Crichton, G. E., & Elias, M. F. (2015). Demographic and socioeconomic disparity in nutrition: Application of a novel Correlated Component Regression approach. BMJ Open, 5(5), e006814–e006814. https://doi.org/10.1136/bmjopen-2014-006814 Am, Barroso, a, & Brown, A. (n.d.). Gender pay gap in U.S. held steady in 2020. Pew Research Center. Retrieved February 6, 2022, from https:// www.pewresearch.org/fact-tank/2021/05/25/ gender-pay-gap-facts/ ARIC Study Investigators, Wang, L., Folsom, A. R., Zheng, Z.-J., Pankow, J. S., & Eckfeldt, J. H. (2003). Plasma fatty acid composition and incidence of diabetes in middle-aged adults: The Atherosclerosis Risk in Communities (ARIC) Study. The American Journal of Clinical Nutrition, 78(1), 91–98. https://doi.org/10.1093/ ajcn/78.1.91 Asfaw, A. (2011). Does consumption of processed foods explain disparities in the body weight of individuals? The case of Guatemala. Health Economics, 20(2), 184–195. https://doi. org/10.1002/hec.1579 Bahanan, L., Singhal, A., Zhao, Y., Scott, T., & Kaye, E. (2021). The association between food insecurity and dental caries among U.S. adults: Data from the National Health and Nutrition Examination survey. Community Dentistry and Oral Epidemiology, 49(5), 464–470. https://doi. org/10.1111/cdoe.12622 Barroso, A., & Brown, A. (n.d.). Gender pay gap in U.S. held steady in 2020. Pew Research Center. Retrieved February 7, 2022, from https://www. pewresearch.org/fact-tank/2021/05/25/genderpay-gap-facts/ Becker, C. B., Middlemass, K., Taylor, B., Johnson, C., & Gomez, F. (2017). Food insecurity and eating disorder pathology. International Journal of Eating Disorders, 50(9), 1031–1040. https:// doi.org/10.1002/eat.22735 Berkowitz, S. A., Berkowitz, T. S. Z., Meigs, J. B., & Wexler, D. J. (2017). Trends in food insecurity for adults with cardiometabolic disease in the United States: 2005-2012. PLOS ONE, 12(6), e0179172. https://doi.org/10.1371/journal.pone.0179172 Black and Hispanic youth unfairly targeted by fast food TV ads. (2021, July 2). https://www. medicalnewstoday.com/articles/fast-foodsequity-problem-Black-and-Hispanic-youthunfairly-targeted-by-ads Boston, 677 Huntington Avenue, & Ma 02115 +1495-1000. (2013, November 20). The Best Diet: Quality Counts. The Nutrition Source. https:// www.hsph.harvard.edu/nutritionsource/healthyweight/best-diet-quality-counts/ Bower, K. M., Thorpe, R. J., Rohde, C., & Gaskin, "The food that we eat is at the core of our health, both physical and mental."

D. J. (2014). The intersection of neighborhood racial segregation, poverty, and urbanicity and its impact on food store availability in the United States. Preventive Medicine, 58, 33–39. https:// doi.org/10.1016/j.ypmed.2013.10.010 Broussard, N. H. (2019). What explains gender differences in food insecurity? Food Policy, 83, 180–194. https://doi.org/10.1016/j. foodpol.2019.01.003 Burt, B. A., Eklund, S. A., Morgan, K. J., Larkin, F. E., Guire, K. E., Brown, L. O., & Weintraub, J. A. (1988). The Effects of Sugars Intake and Frequency of Ingestion on Dental Caries Increment in a Three-year Longitudinal Study. Journal of Dental Research, 67(11), 1422–1429. https://doi.org/10.1177/00220345880670111201 Canella, D. S., Levy, R. B., Martins, A. P. B., Claro, R. M., Moubarac, J.-C., Baraldi, L. G., Cannon, G., & Monteiro, C. A. (2014). Ultra-Processed Food Products and Obesity in Brazilian Households (2008–2009). PLoS ONE, 9(3), e92752. https:// doi.org/10.1371/journal.pone.0092752 Carr, P. R., Jansen, L., Bienert, S., Roth, W., Herpel, E., Kloor, M., Bläker, H., Chang-Claude, J., Brenner, H., & Hoffmeister, M. (2017). Associations of red and processed meat intake with major molecular pathological features of colorectal cancer. European Journal of Epidemiology, 32(5), 409–418. Chang, R., Javed, Z., Taha, M., Yahya, T., ValeroElizondo, J., Brandt, E. J., Cainzos-Achirica, M., Mahajan, S., Ali, H.-J., & Nasir, K. (2021). Food insecurity and cardiovascular disease: Current trends and future directions. American Journal of Preventive Cardiology, 9, 100303. https://doi. org/10.1016/j.ajpc.2021.100303 Chi, D. L., Masterson, E. E., Carle, A. C., Mancl, L. A., & Coldwell, S. E. (2014). Socioeconomic Status, Food Security, and Dental Caries in US Children: Mediation Analyses of Data From the National Health and Nutrition Examination Survey, 2007–2008. American Journal of Public Health, 104(5), 860–864. https://doi.org/10.2105/ AJPH.2013.301699 Clavijo, L. C. (2015). Vascular Disease. Cardiology Clinics, 33(1), ix. https://doi.org/10.1016/j. ccl.2014.10.001 Coleman-Jensen, Rabbitt, Gregory, & Singh. (2021). Household Food Security in the United States in 2020 (ERR-298). U.S. Department of Agriculture Economic Research Service. Communications, N. W. (n.d.). COVID-19 Pandemic Exacerbated Food Insecurity, Especially in Families with Children. Retrieved February 7, 2022, from http://www.nyu.edu/content/nyu/en/ about/news-publications/news/2021/september/ pandemic-food-insecurity Cotterill, R., Franklin, A., Cotterill, R., & Franklin, A. (1995). The Urban Grocery Store Gap. https:// doi.org/10.22004/AG.ECON.161547 COVID-19 Pandemic Exacerbated Food Insecurity, Especially in Families with Children. (n.d.). Retrieved February 4, 2022, from http:// www.nyu.edu/content/nyu/en/about/newspublications/news/2021/september/pandemicfood-insecurity Deaton, A., & Lubotsky, D. (2003). Mortality, inequality and race in American cities and states. Social Science & Medicine, 56(6), 1139–1153. https://doi.org/10.1016/S0277-9536(02)00115-6 Dyer, O. (2018). Colorectal cancer: US guidelines urge screening from age 45 as incidence soars in younger adults. BMJ: British Medical Journal, 361. https://www.jstor.org/stable/26959760 Fast food rush fueling America’s obesity issue. (n.d.). Altoonamirror.Com. Retrieved February 7, 2022, from https://www.altoonamirror.com/ opinion/letters-to-the-editor/2021/04/fast-foodrush-fueling-americas-obesity-issue/ FastStats—Oral and Dental Health. (n.d.). Retrieved February 20, 2022, from https://www. cdc.gov/nchs/fastats/dental.htm Fiolet, T., Srour, B., Sellem, L., Kesse-Guyot, E., Alles, B., Mejean, C., Deschasaux, M., Fassier, P., Latino-Martel, P., Beslay, M., Hercberg, S., Lavalette, C., Monteiro, C. A., Julia, C., & Touvier, M. (2018). Consumption of ultra-processed foods and cancer risk: Results from NutriNet-Santé prospective cohort. BMJ: British Medical Journal, 360. https://www.jstor.org/stable/26958943 Firth, J., Gangwisch, J. E., Borsini, A., Wootton, R. E., & Mayer, E. A. (2020). Food and mood: How do diet and nutrition affect mental wellbeing? BMJ, m2382. https://doi.org/10.1136/bmj.m2382 Fitzpatrick, K. M., Harris, C., Drawve, G., & Willis, D. E. (2021). Assessing Food Insecurity Among US Adults During the COVID-19 Pandemic. Journal of Hunger & Environmental Nutrition, 16(1), 1–18. https://doi.org/10.1080/1 9320248.2020.1830221 Food Culture and its impact on our communities. (2020, April 12). https://theworldskitchens.com/ food-culture-and-its-importance/ Food Insecurity: A Public Health Issue. (2016). Public Health Reports, 131(5), 655–657. https:// doi.org/10.1177/0033354916664154 Food-Related Diseases. (n.d.). U.S. Right to Know. Retrieved February 7, 2022, from https:// usrtk.org/food-related-diseases/ Fryer, C. D., & Ervin, R. B. (2013). Caloric intake from fast food among adults: United States, 20072010. NCHS Data Brief, 114, 1–8. Garbacz, M. (n.d.). Strategic Discussions for Nebraska: Opportunities for Nebraska—Food Scarcity. 79. Gee, G. C., & Payne-Sturges, D. C. (2004).

Environmental Health Disparities: A Framework Integrating Psychosocial and Environmental Concepts. Environmental Health Perspectives, 112(17), 1645–1653. https://doi.org/10.1289/ ehp.7074 Glennie, C., & Alkon, A. H. (2018). Food justice: Cultivating the field. Environmental Research Letters, 13(7), 073003. https://doi. org/10.1088/1748-9326/aac4b2 Gondivkar, S. M., Gadbail, A. R., Gondivkar, R. S., Sarode, S. C., Sarode, G. S., Patil, S., & Awan, K. H. (2019). Nutrition and oral health. Disease-aMonth, 65(6), 147–154. https://doi.org/10.1016/j. disamonth.2018.09.009 Gundersen, C., Hake, M., Dewey, A., & Engelhard, E. (2020). Food Insecurity during COVID-19. Applied Economic Perspectives and Policy, 43(1), 153–161. https://doi.org/10.1002/aepp.13100 Hawk, T. T. (2017). Trends in Prices of Fresh vs. Ultra-Processed foods: Analyses of Seattle-King County Prices from 2004-16. [University of Washington]. http://hdl.handle.net/1773/38669 Hazzard, V. M., Loth, K. A., Hooper, L., & Becker, C. B. (2020). Food Insecurity and Eating Disorders: A Review of Emerging Evidence. Current Psychiatry Reports, 22(12), 74. https:// doi.org/10.1007/s11920-020-01200-0 Healthy foods scarce in poor neighborhoods, Yale researchers find. (2008, September 10). YaleNews. https://news.yale.edu/2008/09/10/ healthy-foods-scarce-poor-neighborhoods-yaleresearchers-find Hendrickson, D., Smith, C., & Eikenberry, N. (2006). Fruit and vegetable access in four lowincome food deserts communities in Minnesota. Agriculture and Human Values, 23(3), 371–383. https://doi.org/10.1007/s10460-006-9002-8 Herrera, J. P., Rabezara, J. Y., Ravelomanantsoa, N. A. F., Metz, M., France, C., Owens, A., Pender, M., Nunn, C. L., & Kramer, R. A. (2021). Food insecurity related to agricultural practices and household characteristics in rural communities of northeast Madagascar. Food Security, 13(6), 1393–1405. https://doi.org/10.1007/s12571-02101179-3 Hilmers, A., Hilmers, D. C., & Dave, J. (2012). Neighborhood Disparities in Access to Healthy Foods and Their Effects on Environmental Justice. American Journal of Public Health, 102(9), 1644–1654. https://doi.org/10.2105/AJPH.2012.300865 Ipr-rapid-research-reports-pulse-hh-data-9-july2020-by-race-ethnicity.pdf. (n.d.). Retrieved February 7, 2022, from https://www.ipr. northwestern.edu/documents/reports/ipr-rapidresearch-reports-pulse-hh-data-9-july-2020-byrace-ethnicity.pdf Ivers, L., & Cullen, K. (2011). Food insecurity: Special considerations for women. The American Journal of Clinical Nutrition, 94(6), 1740S-1744S. https://doi.org/10.3945/ajcn.111.012617 James, D. (2004). Factors influencing food choices, dietary intake, and nutritionrelated attitudes among African Americans: Application of a culturally sensitive model. Ethnicity & Health, 9(4), 349–367. https://doi. org/10.1080/1355785042000285375 Kent, M. (2016). Sugar. In Food and Fitness: A Dictionary of Diet and Exercise. Oxford University Press. https://www.oxfordreference.com/ view/10.1093/acref/9780191803239.001.0001/ acref-9780191803239-e-1651 Labor force characteristics by race and ethnicity, 2018: BLS Reports: U.S. Bureau of Labor Statistics. (n.d.). Retrieved February 7, 2022, from https://www.bls.gov/opub/reports/raceand-ethnicity/2018/home.htm Lauren, B. N., Silver, E. R., Faye, A. S., Rogers, A. M., Woo-Baidal, J. A., Ozanne, E. M., & Hur, C. (2021). Predictors of households at risk for food insecurity in the United States during the COVID-19 pandemic. Public Health Nutrition, 24(12), 3929–3936. https://doi.org/10.1017/ S1368980021000355 Leddy, A. M., Weiser, S. D., Palar, K., & Seligman, H. (2020). A conceptual model for understanding the rapid COVID-19–related increase in food insecurity and its impact on health and healthcare. The American Journal of Clinical Nutrition, 112(5), 1162–1169. https:// doi.org/10.1093/ajcn/nqaa226 Levy, D. E., Riis, J., Sonnenberg, L. M., Barraclough, S. J., & Thorndike, A. N. (2012). Food Choices of Minority and Low-Income Employees. American Journal of Preventive Medicine, 43(3), 240–248. https://doi.org/10.1016/j.amepre.2012.05.004 Levy, R. B., Rauber, F., Chang, K., Louzada, M. L. da C., Monteiro, C. A., Millett, C., & Vamos, E. P. (2021). Ultra-processed food consumption and type 2 diabetes incidence: A prospective cohort study. Clinical Nutrition, 40(5), 3608–3614. https://doi.org/10.1016/j.clnu.2020.12.018 Li, Y., Lv, M.-R., Wei, Y.-J., Sun, L., Zhang, J.-X., Zhang, H.-G., & Li, B. (2017). Dietary patterns and depression risk: A meta-analysis. Psychiatry Research, 253, 373–382. https://doi. org/10.1016/j.psychres.2017.04.020 Lin, T. K., Teymourian, Y., & Tursini, M. S. (2018). The effect of sugar and processed food imports on the prevalence of overweight and obesity in 172 countries. Globalization and Health, 14(1), 35. https://doi.org/10.1186/s12992-018-0344-y Louzada, M. L. da C., Baraldi, L. G., Steele, E. M., Martins, A. P. B., Canella, D. S., Moubarac, J.-C., Levy, R. B., Cannon, G., Afshin, A., Imamura, F., Mozaffarian, D., & Monteiro, C. A. (2015). Consumption of ultra-processed foods

and obesity in Brazilian adolescents and adults. Preventive Medicine, 81, 9–15. https://doi. org/10.1016/j.ypmed.2015.07.018 Machado, P. P., Steele, E. M., Levy, R. B., da Costa Louzada, M. L., Rangan, A., Woods, J., Gill, T., Scrinis, G., & Monteiro, C. A. (2020). Ultra-processed food consumption and obesity in the Australian adult population. Nutrition & Diabetes, 10(1), 39. https://doi.org/10.1038/ s41387-020-00141-0 Maynard, M., Andrade, L., Packull-McCormick, S., Perlman, C. M., Leos-Toro, C., & Kirkpatrick, S. I. (2018). Food Insecurity and Mental Health among Females in High-Income Countries. International Journal of Environmental Research and Public Health, 15(7), 1424. https://doi. org/10.3390/ijerph15071424 Mehler, P. S., & Rylander, M. (2015). Bulimia Nervosa – medical complications. Journal of Eating Disorders, 3(1), 12. https://doi. org/10.1186/s40337-015-0044-4 Mendonça, R. de D., Pimenta, A. M., Gea, A., de la Fuente-Arrillaga, C., Martinez-Gonzalez, M. A., Lopes, A. C. S., & Bes-Rastrollo, M. (2016). Ultraprocessed food consumption and risk of overweight and obesity: The University of Navarra Follow-Up (SUN) cohort study. The American Journal of Clinical Nutrition, 104(5), 1433–1440. https://doi.org/10.3945/ajcn.116.135004 Micha, R., & Mozaffarian, D. (2010). Saturated Fat and Cardiometabolic Risk Factors, Coronary Heart Disease, Stroke, and Diabetes: A Fresh Look at the Evidence. Lipids, 45(10), 893–905. https://doi.org/10.1007/s11745-010-3393-4 Minten, B., & Reardon, T. (2008). Food Prices, Quality, and Quality’s Pricing in Supermarkets versus Traditional Markets in Developing Countries *. Review of Agricultural Economics, 30(3), 480–490. https://doi.org/10.1111/j.14679353.2008.00422.x Molendijk, M., Molero, P., Ortuño SánchezPedreño, F., Van der Does, W., & Angel MartínezGonzález, M. (2018). Diet quality and depression risk: A systematic review and dose-response meta-analysis of prospective studies. Journal of Affective Disorders, 226, 346–354. https://doi. org/10.1016/j.jad.2017.09.022 Moore, L. V., & Diez Roux, A. V. (2006). Associations of Neighborhood Characteristics With the Location and Type of Food Stores. American Journal of Public Health, 96(2), 325–331. https://doi.org/10.2105/AJPH.2004.058040 Morland, K., Wing, S., Diez Roux, A., & Poole, C. (2002). Neighborhood characteristics associated with the location of food stores and food service places. American Journal of Preventive Medicine, 22(1), 23–29. https://doi.org/10.1016/S07493797(01)00403-2 Moynihan, P., & Petersen, P. E. (2004). Diet, nutrition and the prevention of dental diseases. Public Health Nutrition, 7(1a), 201–226. https:// doi.org/10.1079/PHN2003589 Museus, S. D., Ledesma, M. C., & Parker, T. L. (2015). Racism and Racial Equity in Higher Education: Racism and Racial Equity in Higher Education. ASHE Higher Education Report, 42(1), 1–112. https://doi.org/10.1002/aehe.20067 NVSS - Mortality Data. (2022, February 9). https://www.cdc.gov/nchs/nvss/deaths.htm Odoms-Young, A., & Bruce, M. A. (2018). Examining the Impact of Structural Racism on Food Insecurity: Implications for Addressing Racial/Ethnic Disparities. Family & Community Health, 41(S2), S3–S6. https://doi.org/10.1097/ FCH.0000000000000183 Ofori-Acquah, S. F. (2020). Sickle cell disease as a vascular disorder. Expert Review of Hematology, 13(6), 645–653. https://doi.org/10.1080/1747408 6.2020.1758555 Ortega, M. A., Alvarez-Mon, M. A., GarcíaMontero, C., Fraile-Martinez, O., Guijarro, L. G., Lahera, G., Monserrat, J., Valls, P., Mora, F., Rodríguez-Jiménez, R., Quintero, J., & ÁlvarezMon, M. (2022). Gut Microbiota Metabolites in Major Depressive Disorder—Deep Insights into Their Pathophysiological Role and Potential Translational Applications. Metabolites, 12(1), 50. https://doi.org/10.3390/metabo12010050 Paeratakul, S., Lovejoy, J., Ryan, D., & Bray, G. (2002). The relation of gender, race and socioeconomic status to obesity and obesity comorbidities in a sample of US adults. International Journal of Obesity, 26(9), 1205–1210. https://doi.org/10.1038/sj.ijo.0802026 Piperata, B. A., & Dufour, D. L. (2021). Food Insecurity, Nutritional Inequality, and Maternal–Child Health: A Role for Biocultural Scholarship in Filling Knowledge Gaps. Annual Review of Anthropology, 50(1), 75–92. https://doi. org/10.1146/annurev-anthro-101819-110317 Poti, J. M., Braga, B., & Qin, B. (2017). Ultraprocessed Food Intake and Obesity: What Really Matters for Health—Processing or Nutrient Content? Current Obesity Reports, 6(4), 420–431. https://doi.org/10.1007/s13679-017-0285-4 Powell, L. M., Slater, S., Mirtcheva, D., Bao, Y., & Chaloupka, F. J. (2007). Food store availability and neighborhood characteristics in the United States. Preventive Medicine, 44(3), 189–195. https://doi.org/10.1016/j.ypmed.2006.08.008 Raevuori, A., Suokas, J., Haukka, J., Gissler, M., Linna, M., Grainger, M., & Suvisaari, J. (2014). Highly increased risk of type 2 diabetes in patients with binge eating disorder and bulimia nervosa. International Journal of Eating Disorders, 48(6), 555–562. https://doi.org/10.1002/eat.22334

Rasmusson, G., Lydecker, J. A., Coffino, J. A., White, M. A., & Grilo, C. M. (2018). Household Food Insecurity is Associated with Binge-Eating Disorder and Obesity. International Journal of Eating Disorders, 52(1), 28–35. https://doi. org/10.1002/eat.22990 Reardon, T., Timmer, C. P., Barrett, C. B., & Berdegué, J. (2003). The Rise of Supermarkets in Africa, Asia, and Latin America. American Journal of Agricultural Economics, 85(5), 1140–1146. https://doi.org/10.1111/j.00925853.2003.00520.x Reedy, J., & Krebs-Smith, S. M. (2010). Dietary Sources of Energy, Solid Fats, and Added Sugars among Children and Adolescents in the United States. Journal of the American Dietetic Association, 110(10), 1477–1484. https://doi. org/10.1016/j.jada.2010.07.010 Religious Dietary Restrictions: Essential Quick Reference Guide | Thrive! (2018, January 24). Thrive Meetings and Events. https:// thrivemeetings.com/2018/01/religious-dietaryrestrictions-guide/ Rugg-Gunn, A. J., Hackett, A. F., Appleton, D. R., Jenkins, G. N., & Eastoe, J. E. (1984). Relationship between dietary habits and caries increment assessed over two years in 405 English adolescent school children. Archives of Oral Biology, 29(12), 983–992. https://doi.org/10.1016/00039969(84)90145-6 Sachs, C., & Patel-Campillo, A. (2014). Feminist Food Justice: Crafting a New Vision. Feminist Studies, 40(2), 396–410. https://doi.org/10.1353/ fem.2014.0008 Schulze, M. B. (2004). Sugar-Sweetened Beverages, Weight Gain, and Incidence of Type 2 Diabetes in Young and Middle-Aged Women. JAMA, 292(8), 927. https://doi.org/10.1001/ jama.292.8.927 Servello, A. (2016, June 21). The growing diet divide between rich and poor in America. STAT. https://www.statnews.com/2016/06/21/growingdiet-divide/ Shatenstein, B., & Ghadirian, P. (1998). Influences on diet, health behaviours and their outcome in select ethnocultural and religious groups. Nutrition, 14(2), 223–230. https://doi. org/10.1016/S0899-9007(97)00425-5 Srour, B., Fezeu, L. K., Kesse-Guyot, E., Allès, B., Debras, C., Druesne-Pecollo, N., Chazelas, E., Deschasaux, M., Hercberg, S., Galan, P., Monteiro, C. A., Julia, C., & Touvier, M. (2020). Ultraprocessed Food Consumption and Risk of Type 2 Diabetes Among Participants of the NutriNet-Santé Prospective Cohort. JAMA Internal Medicine, 180(2), 283. https://doi. org/10.1001/jamainternmed.2019.5942 Sustainable agricultural growth in the tropics | The Tropical Agriculture Platform (TAP) | Продовольственная и сельскохозяйственная организация Объединенных Наций | Tropical Agriculture Platform (TAP) | Food and Agriculture Organization of the United Nations. (n.d.). Retrieved February 7, 2022, from https:// www.fao.org/in-action/tropical-agricultureplatform/background/sustainable-agriculturalgrowth-in-the-tropics/ru/ The main consequences of non-sustainable farming. (n.d.). Challenge Advisory. Retrieved February 7, 2022, from https://www.challenge. org/knowledgeitems/the-main-consequencesof-non-sustainable-farming/ van Dam, R. M., Willett, W. C., Rimm, E. B., Stampfer, M. J., & Hu, F. B. (2002). Dietary Fat and Meat Intake in Relation to Risk of Type 2 Diabetes in Men. Diabetes Care, 25(3), 417–424. https://doi.org/10.2337/diacare.25.3.417 Walker, R. E., Keane, C. R., & Burke, J. G. (2010). Disparities and access to healthy food in the United States: A review of food deserts literature. Health & Place, 16(5), 876–884. https://doi. org/10.1016/j.healthplace.2010.04.013 What foods and drinks are linked to cancer? (2018, December 20). Cancer Treatment Centers of America. https://www.cancercenter.com/ community/blog/2017/10/what-foods-anddrinks-are-linked-to-cancer Willett, W., Manson, J., & Liu, S. (2002). Glycemic index, glycemic load, and risk of type 2 diabetes. The American Journal of Clinical Nutrition, 76(1), 274S-280S. https://doi.org/10.1093/ ajcn/76.1.274S Wolfson, J. A., Garcia, T., & Leung, C. W. (2021). Food Insecurity Is Associated with Depression, Anxiety, and Stress: Evidence from the Early Days of the COVID-19 Pandemic in the United States. Health Equity, 5(1), 64–71. https://doi. org/10.1089/heq.2020.0059 Women of Color Especially Benefit From Working Family Tax Credits. (n.d.). Center on Budget and Policy Priorities. Retrieved February 7, 2022, from https://www.cbpp.org/research/ federal-tax/women-of-color-especially-benefitfrom-working-family-tax-credits Y4671e.pdf. (n.d.). Retrieved February 7, 2022, from https://www.fao.org/3/y4671e/y4671e.pdf Yang et al. - PolicyLink is a national research and action insti.pdf. (n.d.). Retrieved February 21, 2022, from http://thefoodtrust.org/uploads/ media_items/grocerygap.original.pdf Yang, L., Beebe, R., & Sadowski, B. (n.d.). PolicyLink is a national research and action institute advancing economic and social equity by Lifting Up What Works®. 44.

Yuan, N., Chen, Y., Xia, Y., Dai, J., & Liu, C. (2019). Inflammation-related biomarkers in major psychiatric disorders: A cross-disorder assessment of reproducibility and specificity in 43 meta-analyses. Translational Psychiatry, 9(1), 233. https://doi.org/10.1038/s41398-019-0570-y Zenk, S. N., Schulz, A. J., Israel, B. A., James, S. A., Bao, S., & Wilson, M. L. (2005). Neighborhood Racial Composition, Neighborhood Poverty, and the Spatial Accessibility of Supermarkets in Metropolitan Detroit. American Journal of Public Health, 95(4), 660–667. https://doi.org/10.2105/ AJPH.2004.042150 Zhu, Y., & Hollis, J. H. (2014). Tooth loss and its association with dietary intake and diet quality in American adults. Journal of Dentistry, 42(11), 1428–1435. https://doi.org/10.1016/j. jdent.2014.08.012

An Excavation of the American Healthcare

STAFF WRITERS: PATRICK HERRIN ‘25, BRIDGET MCNALLY ‘24, ABENEZER SHEBERU ‘24, MARYANNE BARASA ‘25, ALLISON PITTMAN ‘25, JULIETTE COURTINE ‘24, JULIAN FRANCO JR. ’24, ANDREW BARRY ‘24, ELIZABETH LI ’25, NATHAN THOMPSON ‘25

TEAM LEAD: ANAHITA KODALI ‘23

Cover Image Source: Pixabay

Introduction:

Healthcare costs - What does the American government spend so much money on? In 2020, the United States government spent $4.1 trillion dollars on healthcare, a sharp 9.7 percent increase from 2019 spending and a 14.3 percent increase from 2018 (Centers for Medicare & Medicaid Services, 2021). While this marked increase is due in part to the federal allocation of funds to alleviate the fallout of the COVID-19 pandemic, there was also a sustained upsurge in healthcare spending as a percent of American Gross Domestic Product (GDP) from 13.3 percent in 2000 to 19.7 percent in 2020 (“U.S. National Health Expenditure as percent of GDP,” 2022); GDP measures the monetary value of the final version of various goods and services produced by a country in a specific time. When compared to other OECD (Organization for Economic Cooperation and Development) countries, the nature of U.S. healthcare spending renders the nation an outlier. In 2016, U.S. per capita healthcare spending ($9,892 that year) exceeded that of second place Switzerland by 25 percent, Canada by 108 percent, and the OECD median by a whopping 145 percent (“U.S. Health Care Spending Highest Among Developed Countries,” 2019). So, where does all the money go? The National Health Expenditure Accounts (NHEA) breaks down health expenditures in the U.S. into the following ten categories, listed in descending order of percent of total expenditures: Hospital Care; Physician and Clinical Services; Retail Prescription Drugs; Health, Residential, and Personal Care Services; Nursing Care Facilities and Continuing Care Retirement Communities; Dental Services; Home Health Care; Other Professional Services (including services provided by occupational therapists, speech therapists, chiropractors, and private-duty nurses); Other Non-durable Medical Products (which covers retail sales of non-prescription drugs); and Durable Medical Equipment (which covers retail sales of ophthalmic products like glasses and contacts as well as hearing aids, wheelchairs, and rental of medical equipment) (“Historical”, 2021). While U.S. healthcare funds are distributed widely over the various types of services or products that are necessary for a fully functioning healthcare system, one question remains to be answered: does this increased spending translate to increased efficacy? Unfortunately, this does not seem to be the case. Research shows that there were only 7.9 nurses and 2.6 active physicians per 1,000 U.S. population in 2015, while the OECD medians were 9.9 and 3.2, respectively. That same year, OECD countries boasted a median of 3.4

hospital beds per 1,000 population, whereas the U.S. had a mere 2.5 (“U.S. Health Care Spending Highest Among Developed Countries,” 2019). These disparities reflect a difference in medical resource pricing. The services and products which constitute the infrastructure of the healthcare system, as listed above, on average cost more in the United States than they do in other OECD countries. The most salient example is the sheer price of inpatient and outpatient care, entailing payments to hospitals and physicians, which currently accounts for roughly 51 percent of total U.S. healthcare spending (Cox & Kurani, 2020). Hospital procedures and physician salaries are more expensive in the U.S., driving up the price of the largest proportion of the American healthcare economy (“U.S. National Health Expenditure as percent of GDP,” 2022). All told, the discrepancy of spending in this sector alone accounts for 76.4 percent of the difference in U.S. healthcare spending compared to other OECD countries in 2018. Similarly, prescription drug prices are highly inflated in the U.S., contributing roughly 10 percent to the difference in healthcare spending that same year (Cox & Kurani, 2020).

Where does the money come from?

Given that healthcare spending is a large portion of The United States’ budget, it is important to discern where these funds come from and who supports this spending. There is a dual-pronged approach to funding health spending. The first and increasingly primary source is the portion of federal taxes that are collected through income taxes (“United State Tax Revenues”, 2019). These sources are variable, depending on which administration is in office – throughout the years, taxation rates have varied depending on the wealth and productivity of Americans. Thus, federal income tax is largely dependent on the state of the overall economy. A second source of funding is through private means and large insurance companies that reimburse or facilitate health expenditures (WHO Health Financing, 2017). While this is not a direct source of government funds, it can reimburse government spending on medical resources. Together, federal taxes and private capital contribute to hundreds of billions, approaching trillions, of dollars that fund the government and its health spending needs.

History: Historical reforms in American healthcare in the 1980s

Leading up to 1980, the U.S had been on par with other nations in healthcare spending per capita with respect to life expectancy. Although it is assumed that higher spending should coincide with a larger life expectancy, the U.S did not have a strong positive correlation compared to other countries. Since then, there has been a notable change in the U.S trajectory as we have spent significantly more than other nations with a minimal change in life expectancy (Frakt, 2018). A closer look into laws, acts, and amendments passed throughout the decade attributed to this increase in spending.

During the onset of the 1980s, Medicaid expanded and raised the nation’s budget on healthcare expenses. The Boren Amendment of 1980 made it essential for nursing homes to be paid at “reasonable and adequate” rates by the states. This amendment was eventually repealed in 1997 due to state Medicaid officials’ concerns over its high cost (Wiener and Stevenson, 1998). In 1981, Omnibus Budget Reconciliation Act (OBRA 81) was passed and required states to provide additional Medicaid payments to hospitals with high rates of low-income patients who are old, blind, disabled, or a family member with dependent children. Furthermore, it repealed the requirement that state Medicaid programs pay hospital rates equivalent to those paid by the federal Medicare program (Library of Congress, 1981).

The Consolidated Omnibus Budget Reconciliation Act of 1985 (COBRA) is a law passed by Congress and signed by President Ronald Reagan. It dealt primarily with providing some workers and their family members, who lose health benefits upon the loss of a job, the right to choose to continue group health benefits provided by their health plan for limited periods of time under certain instances. These circumstances involve a voluntary or involuntary job loss, reduction in the hours worked, transition between jobs, death, divorce, and other life events (U.S. Department of Labor). The following year, OBRA 86 provided state Medicaid with options to cover infants, young children, and pregnant women up to 100% of the poverty level regardless of whether they receive public assistance (The Henry J. Kaiser Family Foundation). The 1988 Medicare Catastrophic Coverage Act (MCCA) expanded Medicare coverage to widend benefits for the elderly and disabled. After a strong negative reaction, the MCCA was repealed the following year, retracting these major provisions (Kagan, 2021). "Given that healthcare spending is a large portion of the United States' budget, it is important to discern where these funds come from and who supports this funding."

Figure 1: Percent share of GDP spent on healthcare in 2009. America spends significantly more money on healthcare than other OECD countries around the world.

Image Source: Flickr Content Source: OECD Health Data 2009

With these reforms, life expectancy still did not increase as rapidly as the rate of U.S expenses on healthcare. Some outlying factors could include the lack of competition within the American health system and possible inflation (Frakt, 2018).

Historical reforms in American healthcare in 1990s

By the time President Clinton took office in 1993, National Health Expenditures (NHE) had been increasing by 10-14 percent annually for decades. NHE is a measure of the total amount the U.S. spends on “health care goods and services, public health activities, government administration, the net cost of health insurance, and investment related to health care” (Centers for Medicare and Medicaid Services [CMS], 2021). In 1990, NHE accounted for 12.1 percent of the U.S. GDP, a 7.1 percent increase over the last 30 years. This increase was largely associated with the development of expensive medical technologies and restrictions on Health Maintenance Organizations, which provide healthcare through provider networks for a fee (Moseley, 2008). Clinton and others were concerned about the effects this increase was having on American citizens and the economy. During his first week in office, President Clinton created the White House Task Force on Health Reform, the first major organized attempt to mend the American Healthcare System since Lyndon Johnson’s administration in 1965 (Kaiser Family Foundation [KFF], 2011). After the appointment of First Lady Hillary Clinton to Chair of the Task Force, it set to work to create a proposal for comprehensive reform of the American Healthcare System (Clinton Digital Library, n.d.). Ten months after his inauguration, Clinton’s administration introduced the Health Security Bill. If passed, it would have modified the public-private system that we know today. Every citizen would be required to enroll in the health plan, through which all employers would be obligated to pay 80 percent of their employees’ health coverage (Clinton Digital Library, n.d.). It would be required to have a “Health Security Card” ensuring access to care. Despite increased government oversight, Americans would still have been able to choose between private insurance plans, fostering competition between private insurers. This “managed competition” model combined with universal coverage was thought to appease both liberals and conservatives in Congress (Oberlander, 2007). Small businesses and individuals without a separate employer would be subsidized by the government. The plan was also appealing because it avoided major new taxes and left Medicare intact.

Despite the bipartisan allure the plan offered and the predicted benefits it promised, the bill ultimately failed to pass. Critics cited its length, complexity, and increase of government control over healthcare as bases for opposition (Oberlander, 2007). While the bill failed in 1994, many of its central ideas were repurposed in the successful Affordable Care Act.

This failure did not mean that the 1990s did not see successful healthcare reform. In 1997, the State Children's Health Insurance Program (S-CHIP) was enacted as part of the Balanced Budget Act (KFF, 2011). To qualify for Medicaid, families needed to have extremely low income. S-CHIP provided grants to states for low-income children who did not quite qualify for Medicaid

to be covered. The eligibility requirements for disabled Americans were also changed to increase coverage. Finally, arguably the most important reform of the 1990s was the passage of the Health Insurance Portability and Accountability Act (HIPAA) in 1996. HIPAA had been a part of the Health Security Act, and it prevents insurance companies from using pre-existing conditions in determining coverage (Manchikanti et al., 2017). HIPAA is also the authority on medical privacy and encourages longer-term coverage through tax benefits (KFF, 2011). While the 1990s did not see the level of reform that many Americans had hoped, policymakers created established a framework for future healthcare legislation was created, and the passage of S-CHIP and HIPAA provided muchneeded protection for millions of Americans.

Stakeholders of American Healthcare: The patients

Patients are critical stakeholders of the American healthcare system, yet the system supposedly designed to serve them has many flaws that have contributed to the health inequities that we see in the United States today. To illustrate the issue, consider a state in the United States with more than 21 hospitals available for open heart surgery, three of which can perform transplants; the state also has more MRI machines than in all of Canada and a large population of specialists. At first glance, these numbers may seem to suggest a thriving, well-funded healthcare system. Yet the reality is bleak— at the same time these numbers were recorded for the state of Colorado, more than 50 percent of those hospital beds were empty, 21 percent of women were giving birth without sufficient prenatal care, and roughly 450,000 citizens were uninsured (with another 400,000 uninsured residents on top of that) (Lamm, 1994). The fundamental goal of any healthcare system is to preserve and promote the continued health of a target population, but this objective is compromised if the system maintains inequality at an institutional level. The scenario described above is not an isolated occurrence. At its most basic level, the American healthcare system is not structured to serve its patient stakeholders equitably.

Primary contributors to this inequality are the ideologies and legislation of the United States’ political system. Since 1965 when Medicaid and Medicare were enacted, the American healthcare system has seen no substantial Congressional legislation promoting universal healthcare or expansion in coverage with the important exception of the Affordable Care Act in 2010. On the contrary, a large portion of legislation in the United States in the past 30 years has been looking to reduce and even terminate healthcare programs, especially those that support the health of migrants, dependent children, and the working poor (Putsch & Pololi, 2004). Furthermore, an individualized (and usually racialized) ideology has permeated the healthcare system through political channels, leading to general population perceptions that those patients who cannot afford insurance are responsible for their situations and should not be supported by the insured population. This thinking is reflected in healthcare financing for patients. Health insurance in the United States is balanced so that the public sector addresses mutual aid needs and private health insurance aims for actuarial fairness (meaning that they strive for adequate and fair premiums for business), leading to higher-risk populations being neglected (Putsch & Pololi, 2004). Furthermore, this ideology has permeated institutional practices and clinical decisions. Under the guise of business and marketing concerns, institutions can choose to locate facilities in suburban areas distant from low-income populations, and clinicians have been documented to describe low income, low intelligence, or otherwise less favorable patients in negative terminology (George & Dundes, 1978). The individual and institutionalized inequality of patients in the American healthcare system is exacerbated by a tradition of research that, remarkably, lacked patient input. Today, patient stakeholder input has begun to be prioritized (with one notable advancement being the founding of the Patient-Centered Outcomes Research Institute [PCORI] in 2010), allowing the healthcare system to gain important insights into primary stakeholder values and expectations (Fleurence et al., 2013). This is a positive indicator that the healthcare system is beginning to prioritize patients, although due to discriminatory biases, it is clear there are larger structural changes that must take place for the United States to achieve equitable patient care.

The physicians When considering how the American healthcare system works and where it needs to be reformed, it can be easy to forget one of the most vital features: physicians. Physicians are the cornerstone of healthcare. After completing an odyssey of education, observation, and training, they strive to both keep people healthy and treat people’s illnesses. Physicians must maintain a vast and intricate understanding of the human body and the injuries and diseases that afflict it, often while specializing in a specific subfield. At

"Patients are critical stakeholders of the American healthcare system, yet the system supposedly designed to serve them has many flaws that have contributed to the health inequities we see..."

"One of the best ways to help physicians maximize the quality of care they give is by directly involving them in workplace culture shifts."

the same time, they must be skilled in interacting with administration, colleagues, and, most importantly, patients. Not only is the road to practicing medicine long and laborious, practicing medicine can be stressful and exhausting. Even before the added dangers and workload resulting from the COVID-19 pandemic, physicians were facing significant levels of stress and burnout (Yates, 2020). Part of this issue involves a lack of help; a severe shortage of doctors is developing, and it is projected that there will be a shortage of between 37,800 and 124,000 physicians by 2034 (Association of American Medical Colleges [AAMC], 2021). Without physicians, let alone those who are not stressed our burnt out, the American healthcare system is in deep trouble. However, there are changes we can make to the system that will make life easier for physicians and in turn improve the quality of their care. Immediately after medical school, physicians-intraining are faced with some of the most difficult years of their career: residency. Residency is a crucial part of training to become a doctor, as students get hundreds of hours of direct clinical experience. Before becoming a doctor, it is important to be immersed in the complex world of medicine without taking on undue responsibility. However, residency is a grueling period that subjects students to long hours, sleep deprivation, and a lack of time off. Because residency lasts three to seven years, it is not something that students can merely “stick out”; they must adjust to the stressful and exhausting routine. Sleep deprivation and chronic overworking decreases productivity and the quality of care that residents can provide. By reducing residents’ shift lengths, increasing their supervision by physicians, and limiting their caseload based on experience, residents would not feel the burden of an unhealthy work-life balances much and would improve the quality of their care. This would save billions of dollars in preventable medical errors by residents (Institute of Medicine, 2009).

One of the best ways to help physicians maximize the quality of care they give is by directly involving them in workplace culture shifts. Participatory organization allows physicians to collaboratively identify workload overloads, unnecessary time sinks, areas that need more independent control, and communication issues (Weigl, 2013). Even if the physician shortage continues, the current system can be modified to maximize the number of patients physicians can see. For example, Telehealth visits, popularized during the COVID-19 pandemic, decrease wait times for patients and are often sufficient for the physician to make an informed decision and communicate it to the patient (Mangiofico, 2018). Telehealth also improves access to care, by allowing doctors to reach underserved rural and low-population areas more easily. Other methods of decreasing workload include increasing the number of physician assistants and minimizing unnecessary training requirements (Berg, 2022). Improvements can also be made in how physicians are compensated. While the current system does not favor low-income patients, it also does not fairly reimburse physicians for the quality of work they perform or for the relative burden of their workload. Right now, physicians are compensated on a fee-for-service basis, meaning they are paid based on the quantity of services that they perform, rather than the quality (i.e. the appropriateness of the services and the outcomes) (Pearl, 2015). This system becomes problematic because it rewards healthcare providers with more physicians. Complex operations and medical equipment are expensive, both for the provider and the patient. When a hospital has more resources, it can afford to use those resources and will choose to do so more often, even if less invasive, cheaper options may be available. By switching to a “pay-for-value” system of compensation, physicians would be rewarded for positive outcomes and aptness of their care instead of simply how much care they provide. This system would benefit both physicians and patients.

The payers

As the name suggests, the payers in in healthcare are the stakeholders that actually pay for a health service. They are responsible for processing eligibility, enrollment, claims, and payments for all of the patients that utilize their service. Examples of payers include insurance companies and government entities like the Centers for Medicare and Medicaid in the United States (“What Is the Difference Between Payers and Providers?”, 2019). There are several things that payers want in healthcare systems. Both the government and private insurers want shorter hospitalization times, shorter delays, shorter wait times, and quick returns to work for patients who are employed (Registry Stakeholders, n.d.). In essence, payers are invested in having more efficient healthcare systems.

The policymakers

Another stakeholder in the American Healthcare Industry are policymakers. They are essentially public health agencies and regulators with various jobs that create and maintain the healthcare system our nation uses today (Lübbeke et al.,

2019). It is through the framework they establish that healthcare is provided and accessible to the country’s citizens (Connecting Health Information Systems for Better Health, 2014). Policymakers undertake ample tasks to help uphold our current healthcare system. They gather and analyze information given to them directly from regional, national, and international patients, providers, and payers to assess and critique health technology and policy nationwide (Lübbeke et al., 2019). The results and outcomes produced by hospitals around the nation are compared to the benchmarks that these health policymakers set (Connecting Health Information Systems for Better Health, 2014). Furthermore, they often go further than just outcomes and assess the equipment used for the care. For example, they supervise implant systems and make sure that the nationally manufactured and the imported products used have met certain standards and specifications so that they are safe and reliable for public usage (Lübbeke et al., 2019). Policymakers also answer crucial questions like who is eligible to receive care, what care services are provided, how services are paid for, whether the services are being delivered well and are accessible, and others (Connecting Health Information Systems for Better Health, 2014). Providers and payers operate within the boundaries that the policymakers lay out. These boundaries aim to maximize health and increase the number of good, non-complicated patient outcomes within the country’s financial and resource constraints. Sources of private health insurance can be described as a patchwork of privately owned systems and programs that offer private insurance plans to their clients. This includes, but is not limited to, subsidized plans by employers, individually procured private plans outside of employment, coverage through TRICARE and other less regulated private plans that pay for one specific type of service or provide coverage in case of an emergency such as dental insurance, accident coverage or any other miscellaneous coverage for emergency hospital visits. The Health Insurance Organization formally refers to private health insurance as health insurance plans marketed by the private health insurance industry, as opposed to government-run insurance programs such Medicare and Medicaid (“What is private health insurance?” 2022). For years, private sources of American healthcare have remained the most prevalent in most American households. This is evident from the most recent report by the Centers for Disease Control and Prevention (CDC), which shows that in the months JanuaryJuly of 2021, 66.3 percent of adults (aged 18-64) were most likely to receive health care services under a private program (Cohen et al., n.d.). Additionally, the US Census Bureau released data that further concur with this report and provides analysis showing that in 2020, of the subtypes of private health insurance coverage, employmentbased insurance was the most common, covering 54.4 percent of the population for part of or the entire calendar year while 10.5 percent relied on direct purchase. (“Health insurance coverage in the United States”, 2021).

The federal Health Insurance Marketplace, which is also called the "Marketplace" or "Exchange," is

Image 2: Patients and physicians are two of the most important stakeholders in the American healthcare system. Image Source: Pixabay

"66.2 percent of adults (aged 18-64) were most likely to receive health care services under a private program (Cohen et al, n.d)."

Sources of American Healthcare: Private

"Numerous studies have found that ketamine is a promising alternative to traditional antidepressants due to its ability to rapidly onset, be effective, and yield lasting impacts."

Image 3:Ayahuasca, one of the oldest used psychedelics that is part of the culture of many indigenous populations scattered throughout South America, is commonly ingested through tea made from the boiling of the leaves.

Image Source: Wikimedia Commons the website where individuals can browse various health care plans available under the Affordable Care Act, commonly known as "Obamacare," as well as compare them, and purchase health insurance. (Loftsgordon, 2021)

TRICARE is a military health care program for active duty and retired members of the uniformed services, their families, and survivors. (Health Insurance Glossary, 2021)

Private sources of health insurance are regulated by the government where States primarily regulate health insurance by setting standards for when and on what terms a state-licensed health insurer must accept an applicant. Federal laws also regulate health insurance, including ERISA (Employee Retirement Income Security Act of 1974) and HIPAA (The Health Insurance Portability and Accountability Act of 1996). ERISA establishes national standards for employer- and union-sponsored health plan (Understanding Health Insurance). HIPAA required the creation of national standards to protect sensitive patient health information from being disclosed without the patient's consent or knowledge (Health Insurance Portability and Accountability Act of 1996, 2018).

Medicare:

Medicare is a federal health program managed by the Centers for Medicare and Medicaid Services (CMS). It provides health coverage regardless of income if you are 65 or older, or if you have a disability and are under 65 years of age (Medicare Rights Center, n.d.). Alternatively, individuals who have been diagnosed with Lou Gehrig’s (ALS) disease or an end-stage renal disease are immediately eligible as well (SAMHSA Soar, n.d.).

The benefits of Medicare are categorized into four different parts. They each provide different coverage at similar prices. Part A covers inpatient care (SAMHSA Soar). One (or one’s spouse) must have paid Medicare taxes for at least ten years to qualify (McWhinney, 2022). Part B covers items like lab work, wheelchairs, outpatient care, etc. Part C uses private Medicare-approved agencies to provide Medicare Advantage Plans (i.e. Health Maintenance Organization or Preferred Provider Organization) (SAMHSA Soar, n.d.). Part C additionally offers vision, hearing, and dental coverage (McWhinney, 2022). Part D covers prescription drugs; however, participants typically pay for Part D out-of-pocket. Typically, Medicare costs vary from plan to plan. In 2022, the cost for Part A premium per month is $499 (McWhinney, 2022). The Part A hospital inpatient deductible and coinsurance for each benefit period is $1,556. The Part B premium is $170.10, and its deductible and coinsurance are $233. For Part C and D, prices vary by plan considering these plans allow you to use private agencies (McWhinney, 2022).

Medicaid

Medicaid is a national and state-level program that helps fund health-related necessities for low-income residents of the United States. It was put in place as part of the Affordable Care Act, providing free health insurance to 74 million low-income and disabled people (Coleman, 2021). Medicaid and Medicare can be combined if one satisfies the requirements of being both low-income and elderly, respectively (FAQs Category, n.d.). Before Medicaid's enactment on the federal level, smaller state Medicaid programs only covered children, some parents, and women who are both low-income and pregnant (Gottlieb & Shepard, 2017). Medicaid was one of the first programs of its kind that provided such expansive coverage on a national level (“Status of State Medicaid Expansion Decisions,” 2022). The program brings numerous benefits at the federal level, and states may also opt-in to optional benefits. Mandatory benefits include hospital services at both the impatient and outpatient level, health services at the physician's office and at home, birth center services, x-rays, and transportation to medical care (Mandatory & Optional Medicaid Benefits, n.d.). States may choose among a selection of optional services such as Speech, hearing and language disorder services, prescription glasses, prosthetics, and physical therapy (Mandatory & Optional Medicaid Benefits, n.d.).

While Medicaid has a variety of intended benefits, it has also brought certain tradeoffs with no clear ways to resolve such issues. For example, while one of Medicaid's purposes is to reduce last-minute ER visits, emergency room use has increased by 40 percent for people who enter the program. Moreover, doctor's office visits increased by 50 percent, hospitalizations by 30 percent, and prescription drug use by 15 percent (Gottlieb & Shepard, 2017). These increases could reflect potential exploitation of the system, but they could also represent an increased awareness for self-care from a population that could not afford to do so previously. Due to pressures to repeal the Affordable Care Act, the government has reduced spendings for Medicaid by an estimated $800 billion (Gottlieb & Shepard, 2017).

Inequities in Health due to Lack of Insurance: Inequities in patient outcomes: insured versus

uninsured

One of the difficulties in evaluating the discrepancies between those with health insurance and those without is that the utilization of resources will vary for the two groups. Those who aren’t insured will be more reluctant to use resources due to the cost, so much of the data must be adjusted when analyzed. Even after adjustment, there are still stark differences between groups with insurance and their non-insured counterparts. Two 2012 studies completed at the Harvard Chan School found that health care insurance could prevent tens of thousands of premature deaths (Powell, 2019). This is reflected in the life expectancy of people with higher income (who are more likely to afford health care insurance), which has been 12 years longer than that of lower income people since 1940 (Bosworth et al., 2016)

Premature deaths caused by inferior healthcare are mostly seen in ages beyond twenty-five and are likely explained by a lack of access to preventative care. As years of poor health care pile up, adverse health effects begin to manifest themselves by age twenty-five and above (McWilliams, 2009). However, those with health insurance will be provided with higher quality resources, as well as be able to seek them out more consistently, resulting in lower rates of premature deaths. The National Library of Medicine conducted a study that found, among other healthcare inequality issues, that rates of influenza vaccination, cholesterol testing, mammography, and diagnosed hypertension rose in ranges of 5-10 percent in people above 65 compared to those below (McWilliams, 2009). Near-elderly adults who had lost their insurance were 82 percent more likely to report a decline in their own health than those who kept their private insurance (McWilliams, 2009). Outside of general care, recent studies have found that uninsured adults who are dealing with hypertension have significantly worse adjusted rates of blood pressure control (McWilliams, 2009). As it stands, patients without health care will continue to have an increase in medical concerns accompanied by a decrease in quality medical assistance to those who are privately insured.

Who has access to insurance? Disparities on racial/ethnic lines

Data shows that racial and ethnic minority groups in our nation experience higher rates of illness from a wide range of health conditions such as diabetes, hypertension, obesity, asthma, and heart disease compared to the majority people groups (CDC, 2021). Furthermore, numerous projects over the years have shown that racial/ethnic minority groups have disproportionately higher morbidity rates than their white counterparts (Bridges, 2018). More specifically, the life expectancy of non-Hispanic/Black Americans is four years lower (CDC, 2021). Many factors likely contribute to this, but a major contributor to this problem is the lower quality of care that minority groups on average receive from their providers. It isn’t only implicit biases that are at play here. Undocumented immigrants along with documented immigrants who have been in the country for less than five years are not eligible for public health insurance. There is an evident twotiered health care system that disproportionately affects racial/ethnic minority groups in the United States (Bridges, 2018). The problem lies both within individuals and the system we live in. Regardless of whether the negative bias towards minority groups from providers is implicit or not, its eradication must be encouraged. There must be conversations surrounding these topics, especially considering how such conversations could have tangible effects on the minority healthcare experience.

Who has access to insurance? Disparities on economic lines

In the United States, economic status poses perhaps the largest barrier to health insurance access; for many Americans, the cost of healthcare is simply too high. According to the 2019 National Health Interview Survey, the largest proportion (73.3 percent) of uninsured U.S. citizens reported being uninsured because coverage was not affordable. Despite the implementation of the Affordable Care Act (ACA) reducing the total of uninsured American citizens by 20 million in 2016, the following years saw another uptick in the percentage of the population who did not receive health coverage. Family income proves to be a large indicator of who is insured and who is not: over 80 percent of uninsured citizens lived 400 or more percent below the poverty line in 2019, and those 200 or more percent below were at the highest risk for being uninsured (Tolbert et al., 2020). Similarly, 72.5 percent of nonelderly, uninsured workers report that their employer does not offer them coverage, or the cost of the coverage they do offer is too steep (Tolbert et al., 2020). Insurance prices are outpacing wage growth, rendering those below 200 percent of the poverty line the most likely to be uninsured (Tolbert et al., 2020). Not only does one’s socioeconomic status itself determine eligibility or likelihood to obtain health insurance, but pairing one’s income status with eligibility for government subsidized aid, specifically Medicaid through the ACA and Marketplace subsidies, has also produced a sizeable coverage gap. In other

"Though the American government spends trillions of dollars on healthcare every year...health outcomes in American are not significantly better (and often worse) than comparably developed nations."

words, those who make too much to be covered by Medicaid and yet not enough to receive tax credits through ACA Marketplace reside in this “gap” where government aid for insurance is inaccessible and the cost of private health insurance is too steep (Garfied, et al., 2021). In those states which have not expanded coverage programs under the Biden administration, it is estimated that this “coverage gap” accounts for over 2 million low-income adults that are uninsured (Garfied, et al., 2021).

Who has access to insurance? Gender Disparities

Disparities in accessing health insurance spread across gender lines as well. Historically, men have been more likely to be uninsured than women; however, women are more likely to be enrolled in public health insurance coverage, while men are more likely to have coverage through an employer. This difference leads to a whole host of problems; most notably, it becomes more difficult for women to access necessary healthcare services under their insurance plans.

For the past twenty years, men have lagged behind women in health insurance coverage. As of 2020, 10.5 percent of women in the United States were uninsured, as compared to 13.4 percent of men who were uninsured at this time (Kaiser Family Foundation, 2022). According to a 2015 census, this gap is primarily among working-aged individuals; the gap shrinks with increasing age. Among both sexes, the uninsured rate peaks at age 26, the age where children are no longer covered under their parents’ health insurance policies, and then falls as individuals approach their mid-60s, wherein the uninsured rate sharply drops for individuals 65+ (United States Census, 2015).

While women are more likely than men to be insured, men are more likely to be on private (employer) insurance plans. In 2020, 61.5 percent of men were on their employer’s health insurance plans, as compared to 61.4 percent of women (Kaiser Family Foundation, 2022). While this difference may not seem significant, it significantly impacts woman who are on Medicare and Medicaid or other public insurance coverage mechanisms. 18.5 percent of women reported to be on public insurance in 2020, while only 15.1 percent of men reported themselves as being covered by a public insurance provider (Kaiser Family Foundation, 2022). However, these public insurance plans often make it difficult for women to access necessary care, because insurance companies associate the female gender with more health issues, complications, and interactions with the healthcare system. For many insurance providers, being a woman is a “preexisting condition” that they can charge higher prices for (The Commonwealth Fund, 2017). Because of this, women pay more, on average, for health insurance than do their male counterparts. For example, in 2013, the U.S. Government Accountability Office found that individualmarket plans in 38 states charged a nonsmoking 30-year-old single woman a higher premium than her male counterpart (The Commonwealth Fund, 2017). These prices make it increasingly difficult for women to attain and pay for health insurance plans; many women have even found that providers exclude necessary health services related to reproductive health––such as breast and colon cancer screenings, contraceptives, and preventative care––from their plans.

Finally, the gender disparity in attaining appropriate health insurance interacts with insurance disparities along racial, ethnic, and geographical lines. Women who identify as Latina and/or Black are more likely to be uninsured than are women who identify as white. From a geographical lens, women reported higher uninsured rates in states such as Texas (25 percent uninsured) and Florida (17 percent uninsured), as compared to much lower uninsured rates in California and New York. These states reported uninsured rates of 10 percent and 5 percent, respectively (The Commonwealth Fund, 2017). The 2010 Affordable Care Act (ACA) allowed both men and women to make strides in their health insurance coverage; after the ACA was passed, women’s uninsured rates decreased 9 percent (The Commonwealth Fund, 2017). Men experienced a similar drop in uninsured rates because of the ACA.

Conclusion

America’s healthcare system is incredibly complex and can be difficult to navigate. Though the American government spends trillions of dollars on healthcare every year – vastly more than most of its peer governments around the world – health outcomes in America are not significantly better (and often worse) than comparably developed nations. There are deep disparities across racial, economic, and gender lines that crosscut which Americans have access to insurance and therefore which Americans can afford healthcare. By better targeting the root causes of disparities in medicine at the legislative and individual levels, healthcare can become more accessible to all Americans, regardless of background.

References

5 critical actions to take now to improve physician

well-being | American Medical Association. (n.d.). Retrieved April 25, 2022, from https:// www.ama-assn.org/practice-management/ physician-health/5-critical-actions-take-nowimprove-physician-well-being AAMC Report Reinforces Mounting Physician Shortage. (n.d.). AAMC. Retrieved April 25, 2022, from https://www.aamc.org/news-insights/pressreleases/aamc-report-reinforces-mountingphysician-shortage ACA Helped Women Gain Insurance and Ability to Get Care. (n.d.). Retrieved April 25, 2022, from https://www.commonwealthfund. org/publications/issue-briefs/2017/aug/howaffordable-care-act-has-helped-women-gaininsurance-and Apr 19, P. & 2022. (2022, April 19). Status of State Medicaid Expansion Decisions: Interactive Map. KFF. https://www.kff.org/medicaid/issue-brief/ status-of-state-medicaid-expansion-decisionsinteractive-map/ Becker, T., & Babey, S. H. (n.d.). Persistent Gap: Gender Disparities in Health Insurance and Access to Care in California. 9. Blendon, R. J., Brodie, M., & Benson, J. (1995). What Happened to Americans’ Support for the Clinton Health Plan? Health Affairs, 14(2), 7–23. https://doi.org/10.1377/hlthaff.14.2.7 Bureau, U. C. (n.d.). Another Difference Between the Sexes – Health Insurance Coverage. The United States Census Bureau. Retrieved April 25, 2022, from https://www.census.gov/newsroom/ blogs/random-samplings/2015/09/anotherdifference-between-the-sexes-health-insurancecoverage-3.html CDC. (2021, November 24). Racism and Health. Centers for Disease Control and Prevention. https://www.cdc.gov/healthequity/racismdisparities/index.html Coleman, J. (2021, June 21). Medicaid enrollment reaches high of 74M Americans during pandemic [Text]. The Hill. https://thehill.com/policy/ healthcare/559428-medicaid-enrollmentreaches-high-of-74m-americans-duringpandemic/ Differences between Medicare and Medicaid— Medicare Interactive. (n.d.). Retrieved April 25, 2022, from https://www.medicareinteractive. org/get-answers/medicare-basics/medicarecoverage-overview/differences-betweenmedicare-and-medicaid Evidence on the Value of Medicaid | Econofact. (2017, July 2). https://econofact.org/evidence-onthe-value-of-medicaid FAQs Category: Medicare and Medicaid. (n.d.). HHS.Gov. Retrieved April 25, 2022, from https:// www.hhs.gov/answers/medicare-and-medicaid/ index.html Garfield, R., Jan 21, A. D. P., & 2021. (2021, January 21). The Coverage Gap: Uninsured Poor Adults in States that Do Not Expand Medicaid. KFF. https://www.kff.org/medicaid/issue-brief/ the-coverage-gap-uninsured-poor-adults-instates-that-do-not-expand-medicaid/ Gender and Insurance Costs. (n.d.). Investopedia. Retrieved April 25, 2022, from https://www. investopedia.com/gender-and-insurancecosts-5114126 Hartman, M., Martin, A. B., Washington, B., Catlin, A., & The National Health Expenditure Accounts Team. (2022a). National Health Care Spending In 2020: Growth Driven By Federal Spending In Response To The COVID-19 Pandemic: National Health Expenditures study examines US health care spending in 2020. Health Affairs, 41(1), 13–25. https://doi.org/10.1377/ hlthaff.2021.01763 Health financing. (n.d.). Retrieved April 25, 2022, from https://www.who.int/health-topics/healthfinancing Health Insurance Coverage of Men 19-64 (CPS) | KFF. (n.d.). Retrieved April 25, 2022, from https://www.kff.org/other/state-indicator/ health-insurance-coverage-of-men-19-64-cps/?c urrentTimeframe=0&sortModel=%7B%22colId %22:%22Location%22,%22sort%22:%22asc%22 %7D How the Patient-Centered Outcomes Research Institute is engaging patients and others in shaping its research agenda—PubMed. (n.d.). Retrieved April 25, 2022, from https://pubmed. ncbi.nlm.nih.gov/23381533/ Iii, G. B. M. (2008). The U.S. Health Care NonSystem, 1908-2008. AMA Journal of Ethics, 10(5), 324–331. https://doi.org/10.1001/virtualm entor.2008.10.5.mhst1-0805 Implicit Bias and Racial Disparities in Health Care. (n.d.). Retrieved April 25, 2022, from https://www.americanbar.org/groups/crsj/ publications/human_rights_magazine_home/ the-state-of-healthcare-in-the-united-states/ racial-disparities-in-health-care/ Key Facts about the Uninsured Population | KFF. (n.d.). Retrieved April 25, 2022, from https:// www.kff.org/uninsured/issue-brief/key-factsabout-the-uninsured-population/ Learning from Failure in Health Care Reform | NEJM. (n.d.). Retrieved April 25, 2022, from https://www.nejm.org/doi/full/10.1056/ nejmp078201 Leveraging interoperability standards to link patient, P., & Network, J. L. (2014). 3. Introducing the Key Stakeholders: Patients, Providers, Payors, and Policymakers (the Four P’s). https://jln1. pressbooks.com/chapter/3-introducing-the-keystakeholders-patients-providers-payors-andpolicymakers-the-four-ps/

Reform. Pain Physician, 4. Mandatory & Optional Medicaid Benefits | Medicaid. (n.d.). Retrieved April 25, 2022, from https://www.medicaid.gov/medicaid/benefits/ mandatory-optional-medicaid-benefits/index. html McWilliams, J. M. (2009). Health consequences of uninsurance among adults in the United States: Recent evidence and implications. The Milbank Quarterly, 87(2), 443–494. https://doi. org/10.1111/j.1468-0009.2009.00564.x Medicaid and Medicare: An Overview | SOAR Works! (n.d.). Retrieved April 25, 2022, from https://soarworks.samhsa.gov/article/medicaidand-medicare-overview Medicare vs. Medicaid: What’s the Difference? (n.d.). Investopedia. Retrieved April 25, 2022, from https://www.investopedia.com/articles/ pf/07/medicare-vs-medicaid.asp Medicine (US), I. of. (2009). Improving the Nation’s Health Care System. In Informing the Future: Critical Issues in Health: Fifth Edition. National Academies Press (US). https://www. ncbi.nlm.nih.gov/books/NBK219839/ Merzel, C. (2000). Gender differences in health care access indicators in an urban, low-income community. American Journal of Public Health, 90(6), 909–916. Physician Shortage Requires Multi-Prong Solution. (n.d.). Retrieved April 25, 2022, from https://www.ajmc.com/view/physician-shortagerequires-multiprong-solution Physician Stress and Burnout—ScienceDirect. (n.d.). Retrieved April 25, 2022, from https:// www.sciencedirect.com/science/article/pii/ S0002934319307570?via%3Dihub Putsch, R. W., & Pololi, L. (2004). Distributive Justice in American Healthcare: Institutions, Power, and the Equitable Care of Patients. THE AMERICAN JOURNAL OF MANAGED CARE, 10, 9. Registry stakeholders—PMC. (n.d.). Retrieved April 25, 2022, from https://www.ncbi.nlm.nih. gov/pmc/articles/PMC6549107/ The costs of inequality: Money = quality health care = longer life – Harvard Gazette. (n.d.). Retrieved April 25, 2022, from https://news. harvard.edu/gazette/story/2016/02/moneyquality-health-care-longer-life/ The effects of improving hospital physicians working conditions on patient care: A prospective, controlled intervention study | BMC Health Services Research | Full Text. (n.d.). Retrieved April 25, 2022, from https:// bmchealthservres.biomedcentral.com/ articles/10.1186/1472-6963-13-401 The ethics of excess. - Free Online Library. (n.d.). Retrieved April 25, 2022, from https://www.thefreelibrary.com/ The+ethics+of+excess-a016029057 The Gomer: A Figure of American Hospital Folk Speech on JSTOR. (n.d.). Retrieved April 25, 2022, from https://www.jstor.org/stable/539575? origin=crossref&seq=1 Three Ways to Transform American Health Care. (n.d.). Stanford Graduate School of Business. Retrieved April 25, 2022, from https://www.gsb. stanford.edu/insights/three-ways-transformamerican-healthcare Understanding and Addressing Racial Disparities in Health Care—PMC. (n.d.). Retrieved April 25, 2022, from https://www.ncbi.nlm.nih.gov/pmc/ articles/PMC4194634/ Universal Heatlh Care. (n.d.). The Balance. Retrieved April 25, 2022, from https://www. thebalance.com/universal-health-care-4156211 U.S. Health Care Spending Highest Among Developed Countries | Johns Hopkins. (n.d.). Retrieved April 25, 2022, from https:// publichealth.jhu.edu/2019/us-health-carespending-highest-among-developed-countries U.S. health spending as share of GDP 19602020. (n.d.). Statista. Retrieved April 25, 2022, from https://www.statista.com/statistics/184968/ us-health-expenditure-as-percent-of-gdpsince-1960/ What drives health spending in the U.S. compared to other countries. (n.d.). Peterson-KFF Health System Tracker. Retrieved April 25, 2022, from https://www.healthsystemtracker.org/brief/whatdrives-health-spending-in-the-u-s-comparedto-other-countries/ What growing life expectancy gaps mean for the promise of Social Security. (n.d.). Retrieved April 25, 2022, from https://www.brookings. edu/research/what-growing-life-expectancygaps-mean-for-the-promise-of-socialsecurity/#recent/ What Is the Difference Between Payers and Providers? (2019, September 25). Signature Performance. https://www. signatureperformance.com/understanding-thedifference-between-payers-and-providers/ Writer, A. P. H. S. (2016, February 22). The costs of inequality: Money = quality health care = longer life. Harvard Gazette. https://news.harvard.edu/ gazette/story/2016/02/money-quality-healthcare-longer-life/ Zhang, B. P. B., Gary Burtless, and Kan. (2016, February 12). What growing life expectancy gaps mean for the promise of Social Security. Brookings. https://www.brookings.edu/research/ what-growing-life-expectancy-gaps-mean-forthe-promise-of-social-security/

Assisted Reproductive Technology: An Overview

STAFF WRITIERS: MADELEINE CARR '24, ISABELLE KOCHER '22, SUMMER HARGRAVE '25, ELIZABETH LI '25, CAROLINE CONWAY '24

TEAM LEAD: ADITI GUPTA '23

Cover Image: Four Cell-Stage Human Embryos after in-vitro fertilization

Image Source: Wikimedia Commons

Introduction to ART (assisted reproductive technology)

On July 25, 1978, Louise Brown was born at Royal Oldham Hospital in the United Kingdom to her biological mother and father, Lesley and John Brown. This birth marked the dawn of a new age of assistive reproductive technology (ART). After attempting to procreate naturally for nine years without success, Lesley underwent a laparoscopic procedure during her natural ovulation to have an oocyte (more commonly known as an egg) removed. After the oocyte was removed from Lesley’s body, it was fertilized by John’s sperm in a lab. After a few days, a doctor placed an 8-cell stage embryo inside Lesley’s uterine cavity (Kamel, 2013). As of 2022, Louise Brown is 43 years old and is married with two children of her own. The incredible story of Louise Brown’s birth in 1978 was only the beginning of modern ART usage.

In 1992, the Centers for Disease Control and Prevention (CDC) defined ART to be “all fertility treatments in which either eggs or embryos are handled” (“Assisted…,” 2022). Over the years, technology has changed, advanced, and multiplied, ushering in a new age of human reproduction. Some examples of ART include In Vitro Fertilization (IVF), Intrauterine Insemination (IUI), and Gamete Intrafallopian Transfer (GIFT). Based on the CDC’s 2019 Fertility Clinic Success Rates Report, 2.1% of all infants born in the US are conceived via ART (2021). In the last decade, ART use has more than doubled (“Assisted…,” 2022). The growing use of this technology has allowed millions who have struggled with infertility – which affects 1 in 5 heterosexual women aged 15 to 49 years old – the opportunity to start a family ( “Infertility,” 2022).

Major Types of ART

A. In Vitro Fertilization (IVF)

IVF is by far the most common type of ART (“Assisted…”, 2022). According to the CDC, IVF is a procedure in which a woman’s eggs are removed from her body, and these eggs are fertilized in vitro, or in lab cultures. Once fertilization has occurred, the embryos are transferred back into a woman’s uterus (“Assisted…”, 2022). The success rates for IVF vary for each patient, most notably by age. For example, according to the Society for Assisted Reproductive Technology (SART), the chance that a single cycle of IVF will result in a live singleton birth is 51.0% for women under the

age of 35, 38.3% for women between 35-37 years, and just 25.1% for women aged 38-40 years old (SART, 2019).

B. Surrogacy

In addition to in vitro fertilization (IVF), another major type of ART is surrogacy. The term “surrogate” is derived from the Latin word “subrogare,” meaning “to substitute” (Patel et al., 2018). In the context of an ART, this is essentially what a surrogate does: substitute. There are two main types of surrogacies: traditional and gestational. Traditional surrogacy involves artificial insemination of a surrogate mother with the sperm of the intended father, making the surrogate is the biological mother of the child. On the other hand, gestational surrogacy occurs when an embryo, which contains the genetic makeup of both intended parents, is inserted into the surrogate uterus (Patel et al., 2018).

A salient risk associated with the surrogate process is multiple order pregnancy, which occurs when more than one embryo is inserted into the uterus and can result in twins (Patel et al. 2018). In recent years, more clinics are following single embryo transfers to reduce this risk. Additionally, as shown by Foster’s study (1987), surrogates may experience potential psychological trauma when having to cede the child upon birth (Patel et al., 2018). In addition to physical and emotional risks, there are religious, ethical and socioeconomic concerns associated with surrogacy as an ART, which will be discussed later in this paper. Despite its successful utilization, surrogacy has become one of the most controversial forms of ART to date and must be considered alongside its inherent complexities.

C. Others: GIFT/ZIFT/IUI

Two additional types of ART are gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT), both modified versions of IVF. Like standard IVF, GIFT and ZIFT both require treatment with female sex hormones (like estridinol and progesterone) to assist implantation and prevent miscarriage. GIFT and ZIFT are often used by intended mothers with fallopian tube problems, as the gamete or zygote, respectively, are inserted in the oviducts below the point of blockage or concern (Jones & Lopez, 2014). After these techniques were developed in the 1980s, they became popularized since they do not require complex IVF culture systems or expertise, allowing for increased accessibility in clinics. They also appear to offer better results than IVF, perhaps because fertilization occurs in a natural system within the reproductive tract (Ankeny, 2017). With GIFT, fertilization occurs in vivo in the fallopian tube rather than during incubation in a lab. An incision is made in the abdomen and the gametes (egg and sperm) are inserted into the fallopian tubes (Ankeny, 2017). If successful, the fertilized egg (zygote) will travel to the uterus and pregnancy will occur.

The ZIFT method is slightly different, where the fertilization of the egg with sperm occurs in vitro in a laboratory. Then, the fertilized zygotes are placed in the fallopian tubes and can travel down the oviduct before implantation (Jones & Lopez, 2014). Though the success rates of GIFT and ZIFT are comparable to IVF, these techniques are not widely used (Jones & Lopez, 2014).

In addition to the aforementioned types of ART, Intrauterine Insemination (IUI) is yet another option. In IUI, the sperm is placed in the uterine cavity during ovulation and does not necessarily require treatment with additional hormones. However, IUI has not been shown to be significantly effective in increasing conception rates (Human Reproduction, 2009). More research is necessary for IUI as a successful mechanism of ART.

Use of ART over time

The first accomplishment in the field of assisted reproduction occurred in 1779, when Italian priest and physiologist Lazzaro Spallanzani confirmed, through artificial insemination in dogs, that embryo development is the result of fusion between the egg and the sperm (Bozzini et al., 2016). This marked a key period of changing perceptions surrounding human reproduction and intercourse. Spallanzani established that sperm could be frozen and preserved, leading to advancements in ART in the animal industry and, several years later, human medicine. Eleven years after Spallanzani’s innovation, the first successful case of intrauterine insemination in a human took place (Sharma et al., 2018). In the late 1800s, the medical field experienced a mass transition from intrauterine insemination to in vitro fertilization (IVF). By the end of the 19th century, Cambridge professor Walter Heape reported the first case of embryo transfer in rabbits, and almost a century later, Robert G. Edwards and Patrick Steptoe performed the first successful IVF in Leslie Brown, leading to the birth of the world’s first test tube baby in 1978 (Steptoe & Edwards, 1978). However, while demand for ARTs has surged, success rates “remain stagnant with less than one in five IVF treatment cycles resulting in a live

"...the chance that a single IVF cycle will result in a live singleton birth is 51% for women under the age of 35...(SART , 2019)."

"For the patient, the single biggest risk factor is multiple pregancies from IVF..."

Image 1: Figure 1: Preterm Birth and Low Birth Incidence among ART infants from the CDC’s 2019 ART National Summary Report Image Source: CDC ("Assisted, 2022). birth” (“Sex, Science”, 2017). According to the Society for Assisted Reproductive Technologies (SART), the proportion of cycles with no reported outcome surged from 2005 to 2010, contributing to misleadingly high ART success rates (“2019 Assisted”, 2022). In addition, fertility clinics that accept a higher percentage of couples with previously unsuccessful IVFs are more likely to experience lower success rates, further contributing to the stagnant trend (“Reported IVF”, 2013).

ART and associated risk factors

Like all medical procedures and interventions, ART carries certain risks. For the patient, the single biggest risk factor is multiple pregnancies from IVF, which has many consequences (Morgan, 2017). The patient can develop high blood pressure and preeclampsia—damage to the kidney or other organs (“Preeclampsia,” 2022). Preeclampsia can lead to symptoms including kidney problems, weight gain, and headaches. Individuals pregnant via ART are also at an increased risk for needing a cesarean section, which is more common in ART-related pregnancies that feature multiple pregnancies, placental abnormalities, and/or congenital fetal anomalies (Morgan, 2017). Moreover, there is a slight increase in the likelihood of severe pregnancy complications and maternal mortality, occurring in 1 in 200 (0.5%) of patients who conceive via ART (Martin et al., 2016).

ARTs also has various risk factors for the offspring. Two of the most prominent side effects are low birth weight and prematurity, both of which again may be a result of multiple pregnancies. For patients who gave birth to twins after IVF, compared to those with two singletons, there were dramatic increases of extremely low birth weight and preterm birth (Rebar, 2013). In addition to low birth weight and prematurity, ART has been shown to increase the risk of placental abnormalities, such as when the placenta separates from the uterine wall in advance (Cochrane et al., 2020).

ART and accessibility

While ART is hardly a new technology, it remains inaccessible for a significant portion of the global population. In 2000, a mere 45 of the World Health Organization’s 191 members offered IVF services in their nations, and this group was primarily comprised of wealthy Western nations (Collins, 2002). These numbers have since seen drastic growth, as a 2010 evaluation by the International Federation of Fertility Societies identified IVF clinics in over half the world’s countries with Japan, India, and the United States offering the most clinics (Inhorn & Patrizio, 2015). However, there are clear patterns of regional disparities in the distribution of ART services. For instance, while Asia, the Middle East, and Latin America have relatively high ART service offerings, many sub-Saharan African nations lack robust ART resources as represented by the number of clinics; (Jones et al., 2011). This regional disadvantage is particularly problematic because sub-Saharan African nations have especially high rates of secondary infertility–the inability to become pregnant again following another pregnancy. Secondary infertility results from pregnancy-related infections of the reproductive tract, which often result from unsafe

abortions or substandard maternity care. More than 85% of infertile women in sub-Saharan African nations have been diagnosed due to an infection, while this rate is only 33% for women on a global scale (Mascarenhas et al., 2012). Over 10% of reproductive-aged women in sub-Saharan Africa are estimated to be secondarily infertile. Secondary infertility is also represented in high concentrations in South Asia, East Asia, Central Asia, the Pacific, and Central and Eastern Europe. These patterns of secondary infertility exasperate the insufficiency of ART services in sub-Saharan Africa.

However, even when ART services are available, this does not guarantee treatment, as only roughly half of infertile couples actively seek infertility care (Boivin et al., 2007). In some situations, such as those in Iraq and Syria in 2003 and 2011, major political conflicts like war can prevent access to care (Inhorn, 2012). Even once removed from a war zone, refugees may continue to face difficulties in accessing ART services depending on the restrictions of the countries in which they seek asylum. In France, for instance, undocumented immigrants or immigrants without a regular French residence will not receive coverage for ART services, which may ultimately serve as a barrier to care (Schüller, 2021).

Undocumented French immigrants are not alone in facing financial hurdles on the path to ART care. Generally, medical coverage of ART services is poor. This is especially true of IVF, which is expensive and mostly restricted to the private medical sector because few governments agree to subsidize the treatment in national health insurance policies. Currently, the average cost of just one IVF cycle in the United States is between $12,000-17,000, posing a significant financial burden to individuals pursuing ART (State Laws…, 2021); and when the chance of a successful singleton birth varies from 25-50% per cycle, the costs associated with multiple cycles can be prohibitively expensive. This expense may prevent some infertile individuals from undergoing even a single IVF treatment, while others may feel that a “catastrophic expenditure,” or a one-time charge amounting to more than 40% of annual non-food expenses, is worth the risk (Dyer & Patel, 2012). Such risk-taking especially applies to poor infertile couples and women, particularly those living in countries lacking ART resources. Additionally, although it is often a financial stretch for such patients to afford a single ART cycle, it is common for three or more cycles to pass before live birth is achieved. This financial burden is not alleviated by external philanthropic organizations because aside from the World Health Organization, few such institutions consider infertility care in developing countries to be a priority in healthcare (Ombelet, 2011). In response to financial difficulties, clinicians have attempted to provide low-cost IVF (LCIVF) with simplified culture methods that do not require complex incubators and rely on cheap, common chemicals. These services are provided to the countries that most need ART services, but in cases where LCIVF is unavailable, infertile individuals might be driven to seek cross-border reproductive care. Further research is needed to comprehensively assess the long-term safety and efficacy of LCIVF (Inhorn & Patrizio, 2015).

In addition to financial barriers, couples and individuals experiencing infertility may face obstacles to ART care based on their relationship or sexual situation. For example, Law 40 in Italy (which has since been amended but not abolished) only allowed “stable” heterosexual couples access to ARTs, though legal marriage was not a requirement, and explicitly excluded single or homosexual individuals (Rao, 2013). This pattern of preference for heteronormativity was also reflected in the outcomes of Australian antidiscrimination cases from the 1990s. In these cases, a female-identifying plaintiff was more likely to receive a favorable ruling regarding access to ART if her circumstances conformed to the heterosexual nuclear family structure (Statham, 2000). Similarly, in Czechia, legislation hinders access to ART treatment depending on the relationship or sexual condition of infertile couples and individuals. Czech lesbian couples are unable to access ART without conforming to heteronormative expectations, as the father of the child must be declared unknown or the sperm donor at the time of birth, carrying significant implications for parental rights. Czech gay men and couples do not have the option of conforming to the conventions of this system and must seek ART treatment with a surrogate mother in another country. These restrictions reflect the exclusive initial purpose of Czech ART to treat infertile heterosexual couples. Transgender individuals also face challenges in accessing ART care, as Czech law requires surgical elimination of one’s reproductive function prior to an official gender change. As a result, trans individuals who seek ART treatment pre-surgery or who seek to cryopreserve their eggs or sperm are only recognized based on their functional reproductive parts. For instance, a male-tofemale woman with a lesbian partner would be " In response to financial difficulties, clinicians have attempted to provide low-cost IVF (LCIVF) with simplified culture methods that do not require complex incubators and rely on cheap, common chemicals."

"... Truly equiable ART care requies an expansion of affordable treatment options and the mitigation of discriminatory policies surrounding ART."

treated as a man, and her relationship would be considered heterosexual for the purposes of ART (Hašková & Sloboda, 2018). While these examples come from Czechia, the problem of heteronormativity is pervasive and affects ARTseeking couples worldwide, as do expectations of conformity to a gender binary.

Finally, ART-seeking individuals with pre-existing medical conditions have been historically likely to encounter barriers to care. The medical condition most frequently cited as justification for denying ART access is HIV infection, even though since 2002, the American Society for Reproductive Medicine has held that requested reproductive assistance is required unless practitioners can demonstrate an inability to safely treat HIVpositive patients (Coleman, 2002). Even in cases where ART treatment is officially offered to patients with HIV, these offers may be hollow. For instance, one 2010 study on ART centers in the U.K. and in Denmark found that while 30% of included fertility clinics intended to treat HIVpositive patients, a far lower percentage was set up to provide such treatment (Nicopoullos et al., 2010). This policy-care discrepancy was further demonstrated when a 2001 study found that 72% of included ART clinics had policies in place for treating HIV-positive individuals, but only 39% had actually treated such patients in the last year (Apoola et al., 2001). Discrimination based on HIV status remains an issue for patients seeking ART care, as about 33% of HIV-positive patients in Western/Southern Europe and 40% of patients in Central/Eastern Europe reported HIV-related discrimination (Nöstlinger et al., 2014). Non-HIV disabilities are also cited as causes of ART denial, and this form of discrimination has a significant historical basis in the United States. In the early 1900s, many states had involuntary sterilization laws targeting several categories of people, including those with disabilities, to prevent these groups from having children. This precedent of forced sterilization is still federally legal today because of the 1927 Supreme Court case Buck v. Bell, which upheld the involuntary sterilization of a white woman with alleged “feeble-mindedness.” These sterilization laws were passed in the context of the eugenics movement, which sought to shape the genetic makeup of humanity by limiting reproduction to “desirable” groups, and this mindset also motivated the denial of fertility treatment for groups with mental or physical disabilities. In addition to HIV, severe lupus, uncontrolled diabetes, and uncontrolled hypertension have been cited as justifications for the denial of ART treatment. Furthermore, a 1987 study found that 79% of practitioners considered serious risk of transmission of a genetic disorder sufficient cause to deny patients ART treatment (Coleman, 2002). Overall, historically, ART resources often fail to meet demand, and even in cases when they do, financial or discriminatory barriers can prevent infertile individuals and their partners from accessing care.

Conclusion

ART is a landmark development in fertility science and has vastly broadened the opportunities to create a family for millions of individuals. Since 1987, over one million children have been born via ART in the United States alone (Centers…, 2017). Despite the scientific marvel of aiding millions of individuals – including single parents, LGBT individuals/couples, and biologically older women – to have offspring, success rates in fertility treatment have stagnated since the 90s. Compounding matters, when the current average cost of one IVF cycle is between $12,000 and $17,000, individuals seeking ART often struggle to afford such financially intensive treatments, many of which are not covered by insurance (State Laws…, 2021).

In addition to low ART success rates and financial barriers to treatment, many discriminatory medical practices remain entrenched in the field of fertility treatment. Individuals with preexisting medical conditions or those who defy society’s sexuality and gender conventions may be denied care or struggle to find facilities equipped to treat them. Additionally, current ART clinic numbers do not match infertility-driven demand, especially in sub-Saharan African countries. Truly equitable ART care requires an expansion of affordable treatment options and the mitigation of discriminatory policies surrounding ART.

Finally, the emotional burden of struggling with infertility coupled with the financial, temporal, and physical challenges associated with ART create considerable pregnancy-related stress, which has been found to negatively impact maternal and fetal health (Conde et al, 2010). Thus, considerable scientific and policy work should be done to improve ART success rates, increase accessibility to expensive and physically demanding ART treatments, and alleviate the stress associated with ART. In writing this review, it is the authors’ hopes to encourage intersectional work in fertility research and public policy to make ART more equitable for all.

Ankeny, R. A. (2017). Reproductive ethics: New Reproductive Technologies. International Encyclopedia of Public Health, 297–300. https:// doi.org/10.1016/b978-0-12-803678-5.00377-5 Apoola, A., tenHof, J., & Allan, P. S. (2001). Access to infertility investigations and treatment in couples infected with HIV: Questionnaire survey. BMJ, 323(7324), 1285. https://doi.org/10.1136/ bmj.323.7324.1285

Boivin, J., Bunting, L., Collins, J. A., & Nygren, K. G. (2007). International estimates of infertility prevalence and treatment-seeking: Potential need and demand for infertility medical care. Human Reproduction, 22(6), 1506–1512. https://doi. org/10.1093/humrep/dem046

Bozzini, G., Seveso, M., Bono, P., De Francesco, O., Mandressi, A., & Taverna, G. (2016). FRII03 Lazzaro Spallanzani (1729-1799): The First Successful Artificial Insemination Experiments. Journal of Urology, 195(4S). https://doi. org/10.1016/j.juro.2016.02.2924

Bozzini, G., Seveso, M., Bono, P., De Francesco, O., Mandressi, A., & Taverna, G. (2016). FRII03 Lazzaro Spallanzani (1729-1799): The First Successful Artificial Insemination Experiments. Journal of Urology, 195(4S). https://doi. org/10.1016/j.juro.2016.02.2924

Centers for Disease Control and Prevention, American Society for Reproductive Medicine, Society for Assisted Reproductive Technology (2017). 2015 Assisted Reproductive Technology National Summary Report. Atlanta (GA): US Dept of Health and Human Services.

Centers for Disease Control and Prevention. (2022, March 3). Infertility | Reproductive Health | CDC. https://www.cdc.gov/reproductivehealth/ infertility/index.htm

Centers for Disease Control and Prevention (2021). 2019 Assisted Reproductive Technology Fertility Clinic and National Summary Report. US Dept of Health and Human Services.

Centers for Disease Control and Prevention. (2022, March 17). Art success rates. Centers for Disease Control and Prevention. Retrieved April 26, 2022, from https://www.cdc.gov/art/artdata/ index.html#:~:text=Although%20the%20use%20 of%20ART,year%20are%20conceived%20 using%20ART. Cochrane, E., Pando, C., Kirschen, G. W., Soucier, D., Fuchs, A., & Garry, D. J. (2020). Assisted reproductive technologies (ART) and placental abnormalities. Journal of Perinatal Medicine, 48(8), 825–828. https://doi.org/10.1515/jpm2020-0141

Coleman, C. H. (2002). Conceiving Harm: Disability Discrimination in Assisted Reproductive Technologies. UCLA Law Review, 50(1), 17–68.

Collins, J. A. (2002). An international survey of the health economics of IVF and ICSI. Human Reproduction Update, 8(3), 265–277. https://doi. org/10.1093/humupd/8.3.265

Conde, A., Figueiredo, B., Tendais, I., Teixeira, C., Costa, R., Pacheco, A., Rodrigues, M. C., & Nogueira, R. (2010). Mother's anxiety and depression and associated risk factors during early pregnancy: effects on fetal growth and activity at 20-22 weeks of gestation. Journal of psychosomatic obstetrics and gynaecology, 31(2), 70–82. https:// doi.org/10.3109/01674821003681464

Dyer, S. J., & Patel, M. (2012). The economic impact of infertility on women in developing countries a systematic review. Facts, Views & Vision in ObGyn, 4(2), 102–109.

Hašková, H., & Sloboda, Z. (2018). Negotiating Access to Assisted Reproduction Technologies in a Post-Socialist Heteronormative Context. Journal of International Women’s Studies, 20(1), 53.

Inhorn, M. C. (2012). The New Arab Man: Emergent Masculinities, Technologies, and Islam in the Middle East. Princeton University Press. http://hdl.handle.net/2027/heb.34138

Inhorn, M. C., & Patrizio, P. (2015). Infertility around the globe: New thinking on gender, reproductive technologies and global movements in the 21st century. Human Reproduction Update, 21(4), 411–426. https://doi.org/10.1093/ humupd/dmv016

Intrauterine insemination. (2009). Human Reproduction Update, 15(3), 265–277. https:// doi.org/10.1093/humupd/dmp003

IVF by the Numbers—Penn Medicine. (2018). Penn Medicine. https://www.pennmedicine.org/ updates/blogs/fertility-blog/2018/march/ivf-bythe-numbers

Jones, H. W., Cooke, I., Kempers, R., Brinsden, P., & Saunders, D. (2011). International Federation of Fertility Societies Surveillance 2010: Preface. Fertility and Sterility, 95(2), 491. https://doi. org/10.1016/j.fertnstert.2010.08.011

Jones, R. E., & Lopez, K. H. (2014). Infertility. Human Reproductive Biology, 283–299. https:// doi.org/10.1016/b978-0-12-382184-3.00015-5 Kamel R. M. (2013). Assisted reproductive technology after the birth of Louise Brown. Journal of reproduction & infertility, 14(3), 96–109.

Martin, A. S., Monsour, M., Kissin, D. M., Jamieson, D. J., Callaghan, W. M., & Boulet, S. L. (2016). Trends in Severe Maternal Morbidity After Assisted Reproductive Technology in the United States, 2008–2012. Obstetrics & Gynecology, 127(1), 59–66. https://doi. org/10.1097/AOG.0000000000001197

Mascarenhas, M. N., Flaxman, S. R., Boerma, T., Vanderpoel, S., & Stevens, G. A. (2012). National, Regional, and Global Trends in Infertility Prevalence Since 1990: A Systematic Analysis of 277 Health Surveys. PLoS Medicine, 9(12), 1–12. https://doi.org/10.1371/journal.pmed.1001356

Morgan, J. (2017, June 13). Part One: Assisted reproductive technologies and maternal risk | Your Pregnancy Matters. UT Southwestern Medical Center. http://utswmed.org/medblog/ part-one-art-risk/

Mother’s anxiety and depression and associated risk factors during early pregnancy: Effects on fetal growth and activity at 20-22 weeks of gestation—PubMed. (n.d.). Retrieved April 24, 2022, from https://pubmed.ncbi.nlm.nih. gov/20236029/

National Summary Report. (n.d.). Society for Assisted Reproductive Technology. Retrieved June 15, 2022, from https://www.sartcorsonline. com/rptCSR_PublicMultYear.aspx

Nicopoullos, J. D. M., Almeida, P., Vourliotis, M., Goulding, R., & Gilling-Smith, C. (2010). A decade of sperm washing: Clinical correlates of successful insemination outcome. Human Reproduction, 25(8), 1869–1876. https://doi. org/10.1093/humrep/deq134

Nöstlinger, C., Rojas Castro, D., Platteau, T., Dias, S., & Le Gall, J. (2014). HIV-Related Discrimination in European Health Care Settings. AIDS Patient Care and STDs, 28(3), 155–161. https://doi.org/10.1089/apc.2013.0247 Ombelet, W. (2011). Global access to infertility care in developing countries: A case of human rights, equity and social justice. Facts, Views & Vision in ObGyn, 3(4), 257–266.

Patel, N. H., Jadeja, Y. D., Bhadarka, H. K., Patel, M. N., Patel, N. H., & Sodagar, N. R. (2018). Insight into Different Aspects of Surrogacy Practices. Journal of human reproductive sciences, 11(3), 212–218. https://doi.org/10.4103/ jhrs.JHRS_138_17

Preeclampsia—Symptoms and causes. (2022). Mayo Clinic. https://www.mayoclinic.org/ diseases-conditions/preeclampsia/symptomscauses/syc-20355745

Rao, R. (2013). Hierarchies of Discrimination in Baby Making? A Response to Professor Carroll. Indiana Law Journal, 88(4), 1217–1221.

Rebar, R. W. (2013). What are the risks of the assisted reproductive technologies (ART) and how can they be minimized? Reproductive Medicine and Biology, 12(4), 151–158. https:// doi.org/10.1007/s12522-013-0156-y

Reported IVF Success Rates Can Be Misleading: Study. (2013, July 4). Reuters. https://www. reuters.com/article/us-reported-ivf-successrates-can-be-mis-idUKBRE9630L320130704

Reported IVF success rates can be misleading: Study. (2013, July 4). Reuters. https://www. reuters.com/article/us-reported-ivf-successrates-can-be-mis-idUKBRE9630L320130704

Schuller, C. (2021). L’AMP pour tous ? Autour d’une discrimination méconnue : l’exclusion des personnes « sans-papiers » de l’accès à la médecine de la reproduction. Sciences sociales et sante, 39(2), 79–101.

Sex, Science and Society After 40 Years of IVF. (2017, November 10). The University of Newcastle, Australia. https://www.newcastle.edu. au/newsroom/featured/sex,-science-and-societyafter-40-years-of-ivf

Sex, Science and Society after 40 years of IVF. (2017, November 10). The University of Newcastle, Australia. https://www.newcastle.edu. au/newsroom/featured/sex,-science-and-societyafter-40-years-of-ivf

Sharma, R. S., Saxena, R., & Singh, R. (2018). Infertility & Assisted Reproduction: A Historical

& Modern Scientific Perspective. The Indian Journal of Medical Research, 148(Suppl), S10–S14. https://doi.org/10.4103/ijmr.IJMR_636_18 Sharma, R. S., Saxena, R., & Singh, R. (2018). Infertility & assisted reproduction: A historical & modern scientific perspective. The Indian Journal of Medical Research, 148(Suppl 1), S10–S14. https://doi.org/10.4103/ijmr.IJMR_636_18

State Laws Related to Insurance Coverage for Infertility Treatment. (2021). National Conference of State Legislatures. https://www. ncsl.org/research/health/insurance-coverage-forinfertility-laws.aspx

Statham, B. (2000). (Re)producing Lesbian Infertility—Discrimination in Access to Assisted Reproductive Technology. Griffith Law Review, 9(1), 112–155.

Steptoe, P. C., & Edwards, R. G. (1978). Birth After the Reimplantation of a Human Embryo. The Lancet, 312(8085), 366. https://doi.org/10.1016/ S0140-6736(78)92957-4

Steptoe, P. C., & Edwards, R. G. (1978). Birth After the Reimplantation of a Human Embryo. The Lancet, 312(8085), 366. https://doi.org/10.1016/ S0140-6736(78)92957-4

Physician Burnout During the COVID-19 Pandemic

STAFF WRITERS: VAISHNAVI KATRAGADDA ‘24, JULIETTE COURTINE ‘24, CECELIA PLASS ‘25, AYUSHYA AJMANI ‘24, SOYEON (SOPHIE) CHO ‘24, JENNIFER DO-DAI ‘25, VALENTINA FERNANDEZ ’24, ASH CHINTA ‘24, KEVIN STAUNTON ‘24, ZARA KIGER ‘25

TEAM LED BY: DANIEL CHO ‘22, DINA RABADI ’22, ANAHITA KODALI ‘23

Cover Image Source: Pixabay

Introduction

Physician burnout originates from general burnout, which is defined as a psychological syndrome caused by chronic occupational stress combined with a lack of resources for individuals (Freudenberger, 1974). Physician burnout can also be defined as emotional exhaustion, depersonalization, and lack of purpose for physicians in the clinical field (Maslach et al., 1996). Physicians find themselves unable to interact and empathize with patients and their emotions because of emotional exhaustion. For depersonalization, clinicians treat patients not as individual human beings, but as a series of tasks to be treated. Lack of purpose, or sense of accomplishment, as a physician prevents them from fully appreciating clinical or other work-related outcomes, as they instead focus on their own ineffectiveness as a hindrance in the workplace. Physician burnout, similar to other types of burnout, may resemble phenomena such as depression in terms of emotional exhaustion. However, the decrease in sense of personal accomplishment and depersonalization do not have strong correlations to depression or other psychological issues (Leiter and Durup, 1994; Wurm et al., 2016). Physician burnout can be analogized to a continued depletion of “energy accounts” (Drummond, 2015). In this analogy, physicians withdraw energy from different “energy accounts” in and out of their workplace. The physical energy account allows physicians to physically carry out tasks for patients, through adequate nutrition, exercise, and rest. The emotional energy account is used to maintain healthy interpersonal relationships with patients as well as family and friends. The spiritual energy account motivates physicians with their purpose for continuing their clinical work. However, as physicians constantly withdraw energy without refilling their accounts through rest, their energy accounts become depleted. This accumulation of energy depletion causes physician burnout and the resulting consequences, ranging from a lack of personal accomplishment in physicians’ work, lack of efficacy in clinical practice to instability in healthcare systems (Drummond, 2015; West et al., 2018). Thus, physician burnout is negatively impacting individual physicians, patients, and healthcare organizations. This review will explain the description and neuroscience of physician burnout, as well as the syndrome in the context of COVID-19. The review will then evaluate steps to be taken to address this syndrome and positively

The current Covid-19 pandemic has posed a challenge to physicians everywhere, especially given the surge of cases of the Omicron variant. As of now, Omicron accounts for around 95% of the United States cases (Sohn, 2022). Despite this high surge, a study of around 70,000 Covid-19 cases conducted at Kaiser Permanente in Southern California found that infections with the Omicron variant were associated with substantially reduced risk of death and shorter durations of hospital stay (Lewnard et al, 2022). The chance of hospitalization is about 50% lower for patients infected with omicron compared to the delta variant. However, Omicron is between two and four times more contagious than Delta, creating a large spike in cases that is continuing to overwhelm healthcare systems (Sohn, 2022). While Omicron is milder in severity, the patient load continues to overwhelm hospitals leading to long wait times and severe consequences for both physicians and patients. As the COVID-19 pandemic has uniquely overloaded the US healthcare system, the pandemic provides an important framework to analyze how physician burnout may manifest.

Describing Physician Burnout

With an increased number of physicians reporting “emotionally exhaustive feelings from the work environment” over the past decade, the importance of understanding burnout at its root has become increasingly imperative (Patel et al., 2019). For many physicians, burnout tends to affect them in different ways due to the sheer factors that contribute to it. While there is no standardized way to label the different types of burnout, there are different metrics by which physician burnout can be better understood. As proposed under the Maslach Burnout Inventory in the late 80’s, these metrics include emotional exhaustion, depersonalization, and low personal accomplishment (Maslach et al., 1997). The metrics are used to assess various aspects of the burnout process and syndrome seen in a wide range of human services professionals. Over the past few decades, the MBI has become the most used tool to assess physician burnout; US health policy discussions surrounding the burnout crisis in medicine have largely been centered around the MBI. The inventory is split into the three component scales, with each one measuring a unique metric of burnout listed above. The inventory uses a 7 level frequency, with 0 being “never” and 6 being “daily” (Jackson, 2018).

When looking at the extremes of the MBI scale, it is clear how a physician can experience different outcomes within burnout. A physician reporting the highest scores on the 9-item emotional exhaustion survey would likely report feeling drained from work, used up at the end of the workday, frustrated from their job, and that they are being worked too hard at the workplace more than once weekly. Meanwhile, a high score on the 5-item depersonalization inventory would mean that a physician likely feels that work is hardening their emotions, treats patients as objects, does not care about work, and thinks patients are blaming them too easily. Finally, under the 8-item personal accomplishment questionnaire, a low score would mean that a physician is not able to create a relaxed atmosphere with patients, fails to address problems effectively, reports feeling lethargic, and is not able to accomplish goals in the workplace (Brady et al., 2020).

While these extremes are not the case for most physicians, they also do not paint the reality for most physician outcomes. Since rarely any physician experiences burnout in a onedimensional sense, the syndrome gets further complicated by the intersection of emotional exhaustion, depersonalization, and low personal accomplishment.

Trends in Physician Burnout

Physician burnout, though becoming especially prominent in recent years, was a serious systemic problem even before the outbreak of Covid-19. In the words of Gary Price M.D., president of the Physicians Foundation, “a bad situation has gotten worse” (Gliadkovskaya, 2021).

Three years ago, 42% of 15,000 US physicians already exhibited symptoms of burnout (Yates, 2020). There are multiple reasons for this; the advent of clerical processes such as electronic health record-keeping has forced physicians to spend more time on cumbersome paperwork in recent years (Gliadkovskaya, 2021; Alpert, 2019), and the workload of occupations in healthcare has always been high. One physician’s account describes how she “dread[ed] going to work” and even got into a car accident on account of driving after a 24 hour-shift (Ranjbar, 2018), while another physician describes how his work demands felt like a “cruel and unusual punishment” (Alpert, 2019). The situation is likely worse for physicians who are part of minority groups due to the additional barriers that they already face.

The stress levels that physicians face can even become lethally overwhelming. Before the beginning of the pandemic, there was a high suicide rate among physicians, with “roughly one doctor dying a day” (Gliadkovskaya, 2021).

"...42% of 15,000 US physicians already exhibited symptoms of burnout (Yates, 2020)."

Image Source: Wikimedia Commons

"...chronic stress... impact[s] brain architecture and function"

Despite this, very few sought mental healthcare due to the stigma still associated with it, or out of fear of being seen as incompetent (Gliadkovskaya, 2021). Given the generally demanding nature of their profession with the added and long-term complications of the pandemic, it is clear that physician burnout is something that must be addressed quickly.

The Neuroscience of Stress

One of the main pathways by which chronic stress contributes to bodily dysfunctions is through its impact on brain architecture and function. Specifically, stress disrupts the normal function of the adrenal glands, causing a high level of glucocorticoid release, which has been associated with a reduction in neurogenesis (de Celis et al., 2016). The adrenal gland and the brain have a very tight and intricate relationship; their cooperation is crucial for a properly functioning stress response (de Celis et al., 2016). The two distinct tissues that make up the adrenal gland (the cortex and medulla) each release hormones that help maintain homeostasis. The adrenal cortex predominantly produces steroid hormones, including glucocorticoids, whereas the adrenal medulla mostly secretes catecholamines, such as epinephrine and norepinephrine (de Celis et al., 2016). It is worth noting that despite their diverging functions, many medullacortex communication pathways are critical for regulation.

The adrenocortical glucocorticoids have been extensively studied and are strong mediators of brain function. Stress hormones as such have been linked with growth-inhibiting effects, which largely explains the connection between reduced neurogenesis and depression. In addition, animal studies suggest that stress alters synaptic plasticity, particularly affecting the firing properties of hippocampal neurons, which play a role in memory and learning (Kim et al., 2015). In both human and animal studies, stress has been found to change the morphology of neurons and decrease the volume of the hippocampus (Kim et al., 2015). Specifically, stress overly activates glucocorticoids (part of stress response), and these have been found to suppress cell proliferation and promote cell death (McConkey et al., 1989).

Clearly, the impact of stress on the brain is multifaceted. The functional connection between stress, brain function, and adrenal function is undeniable and, to tie it to a broader context, certainly impact to physician burnout. Today, physicians experience unprecedented amounts of stress and distress, but the the line between burnout and major depression (which likely function through overlapping mechanisms) remains unclear (Yates, 2020).

The biological response to stress leads to a signaling cascade pathway that releases stress hormones. When the amygdala, the part of the brain responsible for emotional processing, receives a signal from one of the body’s sensory organs such as the ears and eyes that it interprets as stress or danger, a distress signal is sent to the hypothalamus. Located in the brain, the hypothalamus gland maintains homeostasis within the body by connecting the nervous system with the endocrine system. The first part of the response occurs through the sympathetic nervous system. Upon activation, a signal is sent to the adrenal glands through the autonomic nerves from the hypothalamus. This signal causes the adrenal medulla to release epinephrine and norepinephrine into the bloodstream, leading to various physiological responses including

heightened heart rate and blood pressure, enhanced senses due to excess oxygen sent to the brain, and increased energy levels because of released glucose and other temporarily stored fats. However, repeated activation of this sympathetic pathway leads to headaches, tear on arteries, and blood clotting. These effects can increase risk for diseases such as coronary heart disease and hypertension.

The second part of this pathway involves activation of the HPA axis (a feedback system consisting of hypothalamus, pituitary gland, and adrenal glands). After the release of epinephrine and subsequent decrease in epinephrine levels, the hypothalamus triggers a cascading pathway if danger is still sensed starting with the release of corticotropin-releasing hormone (CRH) to the pituitary gland. CRH stimulates the pituitary gland to release adrenocorticotropic hormone (ACTH) to the adrenal glands which in turn stimulates the release of cortisol into the bloodstream. Cortisol is responsible for freeing up glucose stored in the liver so that the body is energized to deal with the stressor. When levels in the bloodstream are high, cortisol can inhibit the release of the production of CRH or ACTH, which results in decreased cortisol levels thus serving as a negative feedback loop. Cortisol is a glucocorticoid, which has been linked to reduced immune system function by suppressing T-cell proliferation, weakening the cytotoxicity of natural killer cells, and limiting growth and maturation of lymphocytes.

The relationship between cortisol and burnout is not completely understood. Some studies have found that burnout is associated with more cortisol, while others have found that burnout is associated with less cortisol (Morera et al., 2020). Thus, it is likely that the impacts of burnout on cortisol will be variable and appear on a spectrum – both high and low cortisol present unique complications to individual’s immune systems, meaning that the biology of burnout will likely result differently across physician populations.

Compassion Fatigue

Compassion fatigue (CF) is a unique form of burnout that is a combination of both institutional and individual factors affecting a physician’s work-life balance. CF has been characterized as an occupational hazard, in which physician exhaustion, depersonalization, and feelings of reduced personal accomplishment impact a physician’s ability to provide care (Babineau et al., 2019). During the COVID-19 pandemic, 40% of surveyed physicians indicate CF, reporting they felt that their work was not properly rewarded or appreciated by the institutions they served (Kase et al., 2021). Many of these feelings are even characteristic of secondary post-traumatic stress syndrome (Babineau et al., 2019). Because CF is not sustainable, it leads to increased physician turnover and greatly decreases the quality of care patients receive as hospital function itself is impacted. Among the physicians that choose to stay, there are increased cases of medical error. Studies on patients with diabetes, hypertension, and other chronic illnesses have even shown that patients are much more likely to adhere to care recommendations when their providers have a higher job satisfaction (Babineau et al., 2019). The biggest drivers of CF are extreme job demands, a lack of resources to provide proper care, a hospital’s culture and values, a lack of control or flexibility over schedule, and minimal social support or community at work. Early on in the pandemic, many physicians saw that they were unable to properly treat patients, resulting in constant emotional tolls that put intesne pressure on providers (Babineau et al., 2019). These personal factors are only increased by stressors involved with the pandemic, such as socioeconomic inequalities, stress of unemployment, limited support services, and worries about family exposure through the provider. A recent survey showed that out of 499 physicians surveyed, nearly all agreed that they felt some source of stress impacting their job satisfaction, whether that was family health, economic uncertainty, or having an uncertain future (Kase et al., 2021). With the pandemic also requiring increased hours and the fact that physicians no longer set their own hours due to working in a corporate setting leads to many providers working 5060 hours per week. This increased work is often not compensated, and instead, enforces a feeling of increased productivity and emotional capacity upon physicians that leads to increased malpractice suits. Interestingly, changes such as the shift patients using the internet to selfdiagnose has contributed to an expectation that physicians will perform at near perfect levels, adding pressure on physicians (Babineau et al., 2019). CF affects physicians as well, with the associated symptoms leading to increased anger, deficits in a physician’s attention span, and increased illnesses. However, studies have indicated institutional and individual effective ways in which this can be reduced. Institutional changes include providing more autonomy for providers to choose their schedules, implementing a culture around self"CF has been characterized as an occupational hazard, in which physician exhaustion, depersonalization, and feelings of reduced personal accomplishment impact a physicians' ability to provide care (Babinaeu et al, 2019)."

"One of the best ways to help physicians maximize the quality of care they give is by directly involving them in workplace culture shifts."

care, promoting effective work-life balance techniques, increasing rewards, and providing peer support networks (Babineau et al., 2019). This is especially important, as many surveys done on physicians indicated that those that had higher levels of CF were those that also agreed that self-care was not a priority (Kase et al., 2021). Individual changes shown to have long term benefits include mindfulness, which increases compassion for others and self by activating neurological pathways associated with empathy. Cognitive behavioral therapy has been effective as well, showing decreased symptomatology of CF. Communication classes addressing patientphysician interaction have shown that the associated decrease in BO and CF had longlasting effects up to three months, with physicians realizing that their practice is more humanistic (Babineau et al., 2019). Thus, implementing these procedures can drastically decrease rates of CF among physicians as they practice self-care and increased empathy on a more sustainable level.

Uniqueness of COVID-19

The COVID-19 pandemic is partly the product of modern society’s pace of life. The pandemic has spread faster and has been more deadly than past pandemics due to globalization, urbanization, and global warming.

COVID-19 is not associated with the highest case fatality rate compared with other emerging viral diseases such as SARS and Ebola, but the combination of a high reproduction number, superspreading events and a globally immunologically naïve population has led to the highest global number of deaths in the past 20 decade compared to any other pandemic (Smith, 2021).

The recent spike in human-to-human interactions and closer living quarters makes respiratory viruses more transmissible. For instance, modern air travel becomes a vector of travel for the virus, similar to how an animal would zoonotically transmit the virus. A virus that starts off as an epidemic can quickly transform into a pandemic if proper protocol is not immediately implemented. COVID-19 is defined as a pandemic because of its rapid global spread (Pitlik, 2020). However, the outbreak was considered an epidemic when it first started in Wuhan, China since it was within a specific community. Other recent pandemics include SARS, Ebola, Measles, Zika, HIV, and H1N1 Influenza.

Pandemics are emotionally overwhelming for all members of society, but especially for health care personnel (HCP). Not only are physicians and nurses risking their own lives working on the front lines, but they also risk transmitting highly contagious diseases to their co-workers, friends, and family members. This places a great deal of stress on those who work in healthcare settings. However, this is not the only thing HCP worries about. In fact, a unique set of stressors can be associated with COVID-19. Death anxiety, guilt of prioritizing certain patients over others, the uncertainties surrounding novel outbreak, public resistance to preventative policy (i.e vaccines and mask mandates), overall obsessive thoughts, and “superhuman expectations” all plague the mind of a physician amidst a time of crisis. Similar psychological reactions were experienced among HCP during the 2003 SARS pandemic (Lai et al., 2019). Similarly, the 2016 SARS epidemic in Hong Kong presented 68% facing high stress levels in a participant setting of 652 health care workers in one hospital (Chigwedere et al., 2021). Continuing the pandemic trajectory, a hospital in The United States of 657 HCP presented 57% PTSD symptoms, 48% depressive symptoms, and 33% anxiety symptoms during the 2020 COVID-19 pandemic (Chigwedere et al., 2021). The COVID-19 pandemic differs from past pandemics because of its magnitude and severity. However, physicians should be aware that in regard to any public health crisis, it is “common” to feel the emotional and physical stressors. In a complex study done by the BioMed Central Journal over the last 17 years, “results [of psychological symptoms] were consistent with over 90,000 physicians surveyed during and after seven different infectious disease outbreaks (SARS, H7N9, H5N1, MERS, Ebola, COVID-19) in 57 countries” (Fiest 2021). Physician burnout has been an issue throughout past pandemics but has been brought into a sharper focus by the COVID-19 pandemic.

The COVID-19 pandemic has led to an extensive negative impact on healthcare systems across the globe, including massive shortages recorded in healthcare personnel (HCP) and hospital and physician equipment. As March 2020 approached, the Centers for Disease Control's (CDC) National Healthcare Safety Network (NHSN) recognized the need to collect and report hospital statistics relevant for the pandemic to inform surveillance on the situation as it progressed (Wu et al., 2021). Their initial categories included: patient counts, bed occupancies, and mechanical ventilators in use, all to be reported on a voluntary basis. Within a month, two additional categories were added: HCP and healthcare supplies (i.e., personal

protective equipment (PPE)). The NHSN collected data from 4,535 hospitals regarding COVID-19 patients, finding that in April 2020 there was the highest percentage of inpatient beds occupied by COVID-19 patients and nearly a quarter of their reporting hospitals had more than 76% of their ventilators in-use for COVID-19 patients (Wu et al., 2021). That same month (with data being collected through July), NHSN collected data from 2,349 hospitals regarding staffing levels, of which 29% reported HCP shortages. The categories the NHSN reported (listed in order of the number of hospitals impacted) include: nurses, respiratory therapists, environmental services staff, physicians, and temporary workers (Wu et al., 2021). Additionally, 3,145 hospitals reported critically low supply levels: 11% reported having no on-hand supplies for at least 1 day. The categories for this report (listed in order of the number of hospitals impacted) include: eyes protection (i.e., face shields or goggles), single-use gowns, ventilator supplies, N95 respirators, surgical masks, and gloves (Wu et al., 2021). These data are not wholly surprising, due to the US being the largest importer of face masks, eye protection, and medical gloves in the world (Cohen et al., 2020). These personnel and equipment are integral for a well-functioning and safe hospital environment, two features made even more critical during a global pandemic. The importance of identifying the causes and solutions to these shortages is therefore more pressing than ever before.

Interestingly, according to NHSN data, HCP and supply shortages occurred in hospitals seemingly with little correlation to the burden of COVID-19 patients the hospital was experiencing. Researchers speculate possible explanations to include baseline reserve shortages, HCP or HCP family members need due to exposures, or supply chain issues (Wu et al., 2021). Further research into the shortage issue reveals deep-rooted structural issues which were aggravated by the spike in demands resulting from the pandemic. These include faulty hospital operating system costing models and the federal government’s failure to maintain and distribute established reserves of PPE coupled with interrupted global supply chains of PPE (Cohen et al., 2021). Possible solutions offered by researchers include modifying hospital costing models by removing the cost-minimization associated with PPE purchases, bolstering government maintenance and ability to dispense reserves, and supporting long term ambitions to reduce US reliance on imported hospital supplies (Cohen et al., 2020). Although these solutions provide a goal to work towards, the reality remains grim as COVID-19 cases surge across the nation and shortages remain a prominent issue. The US Drug & Food Administration (FDA) reports that there are ongoing medical device shortages, including dialysis-related products, PPE, Testing Supplies and Equipment, and ventilation-related products (FDA, 2022). Lack of proper equipment, as well as shortages in HCP, contribute to a strained and perilous workplace for many physicians across the nation, thereby contributing to physician burnout.

Alleviating Physician Burnout

In terms of addressing and preventing burnout across healthcare workers, many pathways to limit stress in the workplace may be effective. Mindfulness, small group discussions, and other individual-focused stress management techniques tend to significantly reduce absolute burnout, emotional exhaustion, and depersonalization. Additionally, duty hour

Image 2: COVID-19 has presented several unique challenges for physicians, contributing to increased levels of burnout.

Image Source: Pixabay

"66.2 percent of adults (aged 18-64) were most likely to receive health care services under a private program (Cohen et al, n.d)."

limitations, or setting minimum rest periods and maximum work periods, and other structural interventions also seem to reduce stress and burnout (West et al., 2016). Similarly, attempting to improve workplace culture has also been shown to limit stress effectively. Encouraging communication while promoting teamwork and giving healthcare workers a sense of agency over their work-life balance can do wonders in preventing burnout (Panagioti et al. 2017). Other methods in reducing healthcare workers’ stress can come in the way of targeting the bureaucracy of medicine, as reducing the amount of paperwork required of clinics and hospitals and/or streamlining a process for nonphysicians to complete documentation could alleviate some of the burden. Forgoing misbegotten regulations by state licensing boards and unnecessary requirements of insurance companies are also easy targets to lower the strain on hospitals’ shoulders (Shanafelt et al. 2017). Multiple groups have also committed themselves to the fight against physician burnout. The American Medical Association (AMA) has created the Joy in MedicineTM Recognition Program to recognize and honor healthcare organizations for their dedication to reducing stress and burnout in the workplace to encourage others to do the same (Berg, 2019). The Physicians Foundation also launched their Vital Signs campaign in 2019, which is designed to provide resources to manage mental health crises and burnout to prevent physician suicide (The Physicians Foundation 2019).

References

Analysis_of_covid_19_data_and_preparing_ for_the_future__part_2_.pdf. (n.d.). Retrieved May 18, 2022, from https://fshrmps.org/images/ downloads/2021_Conference_/analysis_ of_covid_19_data_and_preparing_for_the_ future__part_2_.pdf

Babineau, T., Thomas, A., & Wu, V. (2019). Physician Burnout and Compassion Fatigue: Individual and Institutional Response to an Emerging Crisis. Current Treatment Options in Pediatrics, 5(1), 1–10. https://doi.org/10.1007/ s40746-019-00146-7

Berg, S. (2019, September 21). AMA honors 22 organizations’ commitment to cutting doctor burnout. American Medical Association. https:// www.ama-assn.org/practice-management/ sustainability/ama-honors-22-organizationscommitment-cutting-doctor-burnout

Biological Stress Response—An overview | ScienceDirect Topics. (n.d.). Retrieved May 18, 2022, from https://www-sciencedirect-com. dartmouth.idm.oclc.org/topics/psychology/ biological-stress-response

Brady, K. J. S., Ni, P., Sheldrick, R. C., Trockel, M. T., Shanafelt, T. D., Rowe, S. G., Schneider, J. I., & Kazis, L. E. (2020). Describing the emotional exhaustion, depersonalization, and low personal accomplishment symptoms associated with Maslach Burnout Inventory subscale scores in US physicians: An item response theory analysis. Journal of Patient-Reported Outcomes, 4, 42. https://doi.org/10.1186/s41687-020-00204-x

Chigwedere, O. C., Sadath, A., Kabir, Z., & Arensman, E. (2021). The Impact of Epidemics and Pandemics on the Mental Health of Healthcare Workers: A Systematic Review. International Journal of Environmental Research and Public Health, 18(13), 6695. https://doi. org/10.3390/ijerph18136695

Clinical outcomes among patients infected with Omicron (B.1.1.529) SARS-CoV-2 variant in southern California | medRxiv. (n.d.). Retrieved May 18, 2022, from https://www.medrxiv.org/co ntent/10.1101/2022.01.11.22269045v1

Cohen, J., & Rodgers, Y. van der M. (2020a). Contributing factors to personal protective equipment shortages during the COVID-19 pandemic. Preventive Medicine, 141, 106263. https://doi.org/10.1016/j.ypmed.2020.106263

Cohen, J., & Rodgers, Y. van der M. (2020b). Contributing factors to personal protective equipment shortages during the COVID-19 pandemic. Preventive Medicine, 141, 106263. https://doi.org/10.1016/j.ypmed.2020.106263

COVID-19 in comparison with other emerging viral diseases: Risk of geographic spread via travel—PubMed. (n.d.). Retrieved May 18, 2022, from https://pubmed.ncbi.nlm.nih. gov/33517914/

de Celis, M. F. R., Bornstein, S. R., AndroutsellisTheotokis, A., Andoniadou, C. L., Licinio, J., Wong, M.-L., & Ehrhart-Bornstein, M. (2016). Erratum: The effects of stress on brain and adrenal stem cells. Molecular Psychiatry, 21(5), 722–722. https://doi.org/10.1038/mp.2016.26

Drummond, D. (2015). Physician Burnout: Its Origin, Symptoms, and Five Main Causes. Family Practice Management, 22(5), 42–47.

Fiest, K. M., Parsons Leigh, J., Krewulak, K. D., Plotnikoff, K. M., Kemp, L. G., Ng-Kamstra,

J., & Stelfox, H. T. (2021). Experiences and management of physician psychological symptoms during infectious disease outbreaks: A rapid review. BMC Psychiatry, 21, 91. https://doi. org/10.1186/s12888-021-03090-9

Freudenberger, H. J. (1974). Staff Burn-Out. Journal of Social Issues, 30(1), 159–165. https:// doi.org/10.1111/j.1540-4560.1974.tb00706.x

Gliadkovskaya, A. (2021, August 10). New survey finds COVID-19 is taking a significant toll on physicians. Fierce Healthcare. https://www. fiercehealthcare.com/practices/new-surveyfinds-significant-toll-covid-19-physicians

Health, C. for D. and R. (2022). Medical Device Shortages During the COVID-19 Public Health Emergency. FDA. https://www.fda.gov/medicaldevices/coronavirus-covid-19-and-medicaldevices/medical-device-shortages-during-covid19-public-health-emergency

Kase, S. M., Gribben, J. L., Guttmann, K. F., Waldman, E. D., & Weintraub, A. S. (2022). Compassion fatigue, burnout, and compassion satisfaction in pediatric subspecialists during the SARS-CoV-2 pandemic. Pediatric Research, 91(1), 143–148. https://doi.org/10.1038/s41390021-01635-y

Kim, E. J., Pellman, B., & Kim, J. J. (2015). Stress effects on the hippocampus: A critical review. Learning & Memory, 22(9), 411–416. https://doi. org/10.1101/lm.037291.114

Lai, J., Ma, S., Wang, Y., Cai, Z., Hu, J., Wei, N., Wu, J., Du, H., Chen, T., Li, R., Tan, H., Kang, L., Yao, L., Huang, M., Wang, H., Wang, G., Liu, Z., & Hu, S. (2020). Factors Associated With Mental Health Outcomes Among Health Care Workers Exposed to Coronavirus Disease 2019. JAMA Network Open, 3(3), e203976. https://doi. org/10.1001/jamanetworkopen.2020.3976

Leiter, M. P., & Durup, J. (1994). The discriminant validity of burnout and depression: A confirmatory factor analytic study. Anxiety, Stress, & Coping, 7(4), 357–373. https://doi. org/10.1080/10615809408249357

Maslach, C., Jackson, S. E., & Leiter, M. P. (1997). Maslach Burnout Inventory: Third edition. In Evaluating stress: A book of resources (pp. 191–218). Scarecrow Education.

May 18, & Fedinick, 2015 Kristi Pullen. (n.d.). Getting to know the HPA axis. NRDC. Retrieved May 18, 2022, from https://www.nrdc.org/ McConkey, D. J., Nicotera, P., Hartzell, P., Bellomo, G., Wyllie, A. H., & Orrenius, S. (1989). Glucocorticoids activate a suicide process in thymocytes through an elevation of cytosolic Ca2+ concentration. Archives of Biochemistry and Biophysics, 269(1), 365–370. https://doi. org/10.1016/0003-9861(89)90119-7

Medical Device Shortages During the COVID-19 Public Health Emergency | FDA. (n.d.). Retrieved May 18, 2022, from https://www.fda. gov/medical-devices/coronavirus-covid-19and-medical-devices/medical-device-shortagesduring-covid-19-public-health-emergency

Morera, L. P., Gallea, J. I., Trógolo, M. A., Guido, M. E., & Medrano, L. A. (2020). From Work WellBeing to Burnout: A Hypothetical Phase Model. Frontiers in Neuroscience, 14. https://www. frontiersin.org/article/10.3389/fnins.2020.00360

New survey finds COVID-19 is taking a significant toll on physicians | Fierce Healthcare. (n.d.). Retrieved May 18, 2022, from https://www. fiercehealthcare.com/practices/new-surveyfinds-significant-toll-covid-19-physicians

Panagioti, M., Panagopoulou, E., Bower, P., Lewith, G., Kontopantelis, E., Chew-Graham, C., Dawson, S., van Marwijk, H., Geraghty, K., & Esmail, A. (2017). Controlled Interventions to Reduce Burnout in Physicians: A Systematic Review and Meta-analysis. JAMA Internal Medicine, 177(2), 195–205. https://doi. org/10.1001/jamainternmed.2016.7674

Patel, R. S., Sekhri, S., Bhimanadham, N. N., Imran, S., & Hossain, S. (2019). A Review on Strategies to Manage Physician Burnout. Cureus, 11(6), e4805. https://doi.org/10.7759/ cureus.4805

Pitlik, S. D. (2020). COVID-19 Compared to Other Pandemic Diseases. Rambam Maimonides Medical Journal, 11(3), e0027. https://doi. org/10.5041/RMMJ.10418

Ranjbar, N., & Ricker, M. (2019). Burn Bright I: Reflections on the Burnout Epidemic (Part One of a Two-Part Series). The American Journal of Medicine, 132(3), 272–275. https://doi. org/10.1016/j.amjmed.2018.09.036

Shanafelt, T. D., Dyrbye, L. N., & West, C. P. (2017). Addressing Physician Burnout: The Way Forward. JAMA, 317(9), 901–902. https://doi. org/10.1001/jama.2017.0076

"Though the American government spends trillions of dollars on healthcare every year...health outcomes in American are not significantly better (and often worse) than comparably developed nations."

Sohn, E. (2022). How the COVID-19 pandemic might age us. Nature, 601(7893), S5–S7. https:// doi.org/10.1038/d41586-022-00071-0

The Physicians Foundation Launches Campaign to Help Prevent Physician Suicide. (2019, September 17). The Physicians Foundation. https://physiciansfoundation.org/press-releases/ the-physicians-foundation-launches-campaignto-help-prevent-physician-suicide/

West, C. P., Dyrbye, L. N., & Shanafelt, T. D. (2018). Physician burnout: Contributors, consequences and solutions. Journal of Internal Medicine, 283(6), 516–529. https://doi.org/10.1111/ joim.12752

Wu, H., Soe, M. M., Konnor, R., Dantes, R., Haass, K., Dudeck, M. A., Gross, C., Leaptrot, D., Sapiano, M. R. P., Allen-Bridson, K., Wattenmaker, L., Peterson, K., Lemoine, K., Tejedor, S. C., Edwards, J. R., Pollock, D., Benin, A. L., & Network, for the N. H. S. (2021). Hospital capacities and shortages of healthcare resources among US hospitals during the coronavirus disease 2019 (COVID-19) pandemic, National Healthcare Safety Network (NHSN), March 27–July 14, 2020. Infection Control & Hospital Epidemiology, 1–4. https://doi.org/10.1017/ ice.2021.280

Wurm, W., Vogel, K., Holl, A., Ebner, C., Bayer, D., Mörkl, S., Szilagyi, I.-S., Hotter, E., Kapfhammer, H.-P., & Hofmann, P. (2016). DepressionBurnout Overlap in Physicians. PLOS ONE, 11(3), e0149913. https://doi.org/10.1371/journal. pone.0149913

Yates, S. W. (2020). Physician Stress and Burnout. The American Journal of Medicine, 133(2), 160–164. https://doi.org/10.1016/j. amjmed.2019.08.034

DARTMOUTH UNDERGRADUATE JOURNAL OF SCIENCE Hinman Box 6225 Dartmouth College Hanover, NH 03755 USA

http://dujs.dartmouth.edu

dujs@dartmouth.edu