PULSE VOLUME 7, ISSUE 3. SPRING 2021.
SHAPING OUR FUTURE
from the editor-in-chief Dear Reader,
As our community starts to reopen, we begin to welcome back old experiences yet new opportunities. We hope that during this time and with an upcoming summer, our PULSE Spring Issue can provide a refreshing gaze of what is currently shaping our future. I am delighted to introduce this quarter’s issue that captures the innovations, drugs, and healthcare in our society. The issue includes a glance at the American healthcare system to the exploration of antidepressants. Not only that but incorporated are interesting articles ranging from the Mozart effect to Zoonotic diseases. Our partnered contributors additionally provide essential tips related to MCAT critical reading skills and effective note taking. I would like to acknowledge the writers, editors, and partners for their contributions and express my appreciation for their efforts this quarter. It is a pleasure serving as the Editor in Chief and I look forward to making PULSE even more successful over the next quarter. Please enjoy the read! With Regards, Sophia Cao
editors EJ Beck Sophia Carino Ashley Chen Riley Hurr (managing editor) Emory Kim Marissa McCollum Teresa Nam Helen Wei
pulse - spring 2021
writers
Deniz Eracar Meagan Johnson Areeha Khalid Jack Osborn Chloe Palumbo Sanjana Rao Rachel Zhang
production Sophia Cao Katrina Schmitt (cover designer)
other contributors MCAT-prep.com Kaplan Test Prep The Princeton Review
CONTENTS EDUCATION HOW TO BUILD MCAT CRITICAL READING SKILLS EFFECTIVE NOTE TAKING FOR THE MCAT KAPLAN MCAT PRACTICE PROBLEM
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POLICY DIVERSITY IN STEM: JOURNEY TO THE COVID-19 VACCINE THE AMERICAN HEALTHCARE SYSTEM
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RESEARCH THE MOZART (SCHMOZART) EFFECT THE SAFE COCOON OF CATATONIA METFORMIN: THE UNSUNG HERO DRUG DO ANTIDEPRESSANTS WORK?
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CURRENT EVENTS A HISTORY OF ZOONOTIC DISEASES: DON'T BLAME THE BAT
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HOW TO BUILD MCAT® CRITICAL READING SKILLS From Chemistry to CARS, the MCAT requires excellent critical reading skills. To improve your ability to read and glean information from a passage, you need to practice. Be critical when you read the content and watch for vague areas or holes in the science passages that aren't explained clearly.
READ ACTIVELY Take control of the passage. Don't let the passage control you. • • • • • •
Highlight key words and phrases. Link and predict major themes. Take notes on your scratch paper. Translate the main idea of each paragraph into your own words. Remember that information about new topics will be woven throughout the passage. You may need to piece together information from several paragraphs and a figure to get the whole picture. For CARS passages, summarize the main point and tone of the whole passage before attacking the questions.
ACTIVE READING WITH STUDY GROUPS If you have a study group you are working with, take turns asking and answering the questions below. Having to explain something to someone else not only solidifies your own knowledge, but helps you see where you might be weak. • • • • • •
What was this passage about? What was the conclusion or main point? Was there a paragraph that was mostly background? What information was found in each paragraph? Why was that paragraph there? What extra information could I have pulled out of the passage? What inferences or conclusions could I make? If something unique was explained or mentioned, what might be its purpose? Were there any comparisons in the passage?
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EDUCATION
• • • •
Were there paragraphs or figures that seemed useless (science passages only)? Are there any holes in the story (science passages only)? What am I not being told (science passages only)? Can I summarize the purpose and/or results of the experiment in a few sentences (science passages only)?
OUTSIDE READING FOR CARS Feeling nervous about what you might encounter in the CARS section? Some students don’t have as much experience reading texts from the social sciences and humanities. Try active reading and annotation with some of the sources below. Make sure to choose articles that are written at a fairly high level (that is, not a simple news article or movie review).
Periodicals • • • • • • •
The New Yorker Atlantic Monthly The Economist The American Scholar Legal Affairs Harper’s Foreign Affairs
Books • • • • • • • •
Welleck, Rene and Warren, Austin (1955), Theory of Literature Campbell, Joseph (1949), The Hero with a Thousand Faces Durant, Will (1935), The Story of Civilization Lakoff, George and Johnson, Mark (1980), Metaphors We Live By Panofsky, Erwin (1955), Meaning in the Visual Arts Bronowski, Jacob (1962), The Western Intellectual Tradition Sontag, Susan (1983), A Susan Sontag Reader Stanovich, Keith (2009), How to Think Straight About Psychology
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Online Sources If you find that you have more difficulty doing passages online than on paper, make sure to do as much of your outside reading as possible online. Many of the periodicals listed allow some degree of free online access. There are also two websites that provide non-copyright material for free: • •
Project Gutenberg (Gutenberg.org) Authorama (Authorama.com)
Make sure to choose non-fiction texts that are at a fairly high level of difficulty (that is, at MCAT CARS level). Here are some appropriate texts that will give you practice with reading challenging passage material on a computer screen: • • • • • •
Plato, The Republic Friedrich Wilhelm Nietzsche, Beyond Good and Evil Henry David Thoreau, Walden Edward Gibbon, The History of the Decline and Fall of the Roman Empire Ludwig Wittgenstein, Tractatus Logico-Philosophicus Adam Smith, An Inquiry into the Nature and Causes of the Wealth of Nations
For more Med School Advice, visit Princetonreview.com/med-school-advice.
Prepping for the MCAT this year? The Princeton Review’s most popular MCAT prep courses are starting now! Visit PrincetonReview.com/MCAT to learn more. 800-273-8439 | PrincetonReview.com | 800-2REVIEW MCAT is a registered trademark of the Association of American Medical Colleges. The Princeton Review is not affiliated with Princeton University.
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EDUCATION
EFFECTIVE NOTE TAKING FOR THE MCAT That's right, effectively studying for the MCAT requires more than just reading through pages and pages of review books. Like every other important exam you have taken, acing the MCAT will require that you study actively. This means that you must adapt your study habits according to your character, circumstances, and your ability to cope with multiple priorities. Perhaps you prefer to compile notes on every topic in order to feel confident that you have everything covered. If so, you can save time by developing your own abbreviation systems, acronyms, or mnemonics thereby increasing your understanding of important topics and making those topics easier to memorize (for example, have a look at our Free MCAT Biochemistry summary and mnemonics). With this technique, you should always leave space to add comments or additional notes during future study sessions. Furthermore, keep in mind that studying actively does not mean taking notes just to take them. On the contrary, those MCAT notes will only help you if you take the time to study them. Now, some premed students may consider it a waste of time to take notes and that is fine because you know best what kind of learner you are. If that is the case, then studying actively for you may mean reviewing flashcards (Science review apps for iPhone and Android) You can even create your own or see others using ANKI MCAT! Here are some tips:
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Gather only the most important points or equations/ formulas on a specific topic. Write down each point or equation on a notecard or post-it.
Did I fully understand what the questions were asking?
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3 5 4 5
Convert textbook content or general notes
into summary notes and review your summary notes from the start every weekend.
Consider multimedia: for example, you can read your summary notes into a smartphone MP3 app and then listen daily when you are engaging in physical activity or using transportation, etc.
Remember, learning the techniques of effective note-taking is easy, but actually applying them takes a lot of motivation and self-discipline. So, assess exactly what you would like to achieve from your MCAT studying and how willing you are to work for that excellent MCAT score.
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EDUCATION
Kaplan MCAT PRACTICE PROBLEM QUESTION Some enzymes require the presence of a nonprotein molecule to behave catalytically. An enzyme devoid of this molecule is called a(n):
A. holoenzyme B. apoenzyme C. coenzyme D. zymoenzyme
THINK YOU’RE READY FOR TEST DAY? Find out with this fun and FREE way to tackle practice MCAT questions from Kaplan Test Prep. Register to receive one sample question a day for the next three months. You’ll get: • A new MCAT-style question each day to test your knowledge and skills • Complete explanations and expert strategies with every question • Compete against your friends to see who’s really ready for test day To get started go to: https://www.kaptest.com/mcat/mcat-practice/free-mcat-practice-question-a-day
B. An enzyme devoid of its necessary cofactor is called an apoenyzme and is catalytically inactive. ANSWER spring 2021 || 7
DIVERSITY IN STEM: JOURNEY TO THE COVID-19 VACCINE By
Areeha Khalid Emory Kim
From the credit of Rosalind Franklin’s work on DNA structure going to James Watson and Francis Crick to the extraction of Henrietta Lacks’ “immortal” HeLa cells without her knowledge or consent, women and minorities have been historically exploited without credit to their role in advancing scientific research. Yet, their contributions have been vital to the progression of medical technology as the COVID-19 pandemic has clearly demonstrated.
The Technology Behind the Vaccines The leading COVID-19 vaccines used today in the U.S. are the Pfizer and Moderna vaccines, both of which are mRNA vaccines based on the work of Dr. Katalin Kariko, a sixty-six year-old scientist and Hungarian immigrant to the U.S. Dr. Kariko, who has been working with mRNA since 1989, was inspired by the idea of designing and injecting mRNA into a cell, thereby inducing that cell to make any protein of her choosing. Her work was novel at a time when the mRNA field barely existed, causing it to remain overlooked. A field barely existed, causing it to remain overlooked.
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Throughout her career, Dr. Kariko bounced between universities and labs, unable to receive grants or tenured positions for her work and never earning more than $60,000 in a year. After finding herself again without a lab or funds for research in 1997, Dr. Kariko met Dr. Drew Weissman at the University of Pennsylvania. During a quick conversation over the copy machine, she convinced him to let her join his lab to work on a vaccine for HIV. Beginning in 2005, Dr. Kariko and Dr. Weissman discovered that adding a molecule called pseudouridine to mRNA allowed it to be able to alter cellular function without eliciting an attack by an individual’s immune system. This technology was eventually picked up by BioNTech (which partnered with Pfizer) in Germany and Moderna in the U.S. for work on coronavirus vaccines. When the COVID-19 pandemic began, Dr. Kariko’s methods were used by both companies to target a “spike protein” located on the COVID-19 vaccine surface. The first successful results of the Pfizer-BioNTech vaccine came back on November 8, 2020, and Dr. Kariko and Dr. Weissman received the vaccination just a few weeks later on December 18th. Without
Dr. Kariko’s lifelong devotion to mRNA research in the face of repeated lack of support from the universities she was a part of, the development of the COVID-19 vaccine may have taken much longer, costing countless human lives in the process.
The Making of the Vaccines Moreover, Dr. Kariko’s work is not the only example of women and minorities in STEM coming together to combat the COVID19 pandemic. Both the Pfizer and Moderna vaccines were developed using Dr. Kariko’s technology by teams of diverse scientists. Dr. Ugur Sahin and Dr. Özlem Türeci, a pair of Turkish immigrants to Germany, are physicians, scientists, and the founders of BioNTech, the company behind the Pfizer vaccine. Dr. Sahin and Dr. Türeci are a married couple who began their work on mRNA nearly twenty years ago in search of novel therapies to treat cancer by targeting specific antigens located in tumor cells. In 2018, Dr. Sahin spoke at a conference in Berlin about how he believed mRNA technology could be vital in case of a global pandemic. Just two years later, BioNTech and
POLICY
Pfizer partnered to do just that - with Dr. Sahin and Dr. Türeci’s team developing twenty potential candidates for the COVID-19 vaccine by March 2020, and the clinical trials for the selected version coming back with a 95% success rate in November. Much like the U.S., immigration continues to be a subject of heated debate in Germany, with far-right groups strictly in opposition. Dr. Sahin and Dr. Türeci’s success has prompted a call for globalization and removing the barriers for STEM research and careers. Like Dr. Sahin and Dr. Türeci, Dr. Kizzmekia Corbett, a Black woman and immunologist at National Institutes of Health (NIH) in Maryland, is sparking conversations about diversity and inclusivity in medical research due to her work on the Moderna COVID-19 vaccine. Dr. Corbett,
who is just thirty-four, worked with a team of scientists to develop and complete Phase I clinical trials for the Moderna vaccine in just ten months. As Dr. Anthony Fauci, the head of the National Institute of Allergy and Infectious Diseases at the NIH, put it, "The vaccine you are going to be taking was developed by an African American woman and that is just a fact.” Even with the Moderna vaccine completed and being administered to thousands daily, Dr. Corbett’s work has not finished. She continues to support marginalized communities by spreading awareness on the safety and importance of getting vaccinated, especially to those most at risk by the pandemic: Black, Native American, and Latino communities. The high risks in these communities are supported by statistics. For example, the CDC reports that
46% of Black adults in the U.S., as opposed to 30% of white adults, do not wish to get the COVID-19 vaccine. This is due to fear of side effects due to the speed with which it was developed, and a general distrust of the healthcare system due to a longstanding history of exploitative medical practices, such as the infamous Tuskegee syphilis study. To combat these health disparities, Dr. Corbett actively uses her Twitter account, @KizzyPhD, and speaks at events targeting communities of color in accessible locations, such as at churches. Her philosophy is to teach science in a digestible way that is understandable to her audience. In her words, “Churches often need to have something scientifically broken down for them by someone who also believes in God.” Through her thorough explana-
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Dr. Kizzmekia Corbett
Dr. Katalin Kariko
Dr. UGUR SAHIN
tions of the way the vaccine works and why people should get vaccinated, Dr. Corbett is taking the first step in stopping the history of gatekeeping scientific knowledge from the general public through inaccessibility and unnecessarily complicated jargon.
Diversity in Stem: A Goal for a PostPandemic World Dr. Kariko, Dr. Sahin, Dr. Türeci, and Dr. Corbett are trailblazers in both the fight to stop the spread of COVID-19 and the fight to make spaces for minorities in healthcare and medical research. The stories of these scientists are powerful examples of the outcomes of a lifetime’s worth of dedicated research despite working
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Dr. Ozlem Tureci
within a system not designed for people like them to succeed, and a vision to the way the world should be. “CNBC Exclusive: CNBC Transcript: BioNTech CEO Dr. Ugur Sahin Speaks with CNBC's ‘Squawk Box’ Today.” CNBC. CNBC, January 11, 2021. https://www.cnbc.com/2021/01/11/ cnbc-exclusive-cnbc-transcript-biontech-ceodr-ugur-sahin-speaks-with-cnbcs-squawk-boxtoday.html. Gelles, David. “The Husband-and-Wife Team Behind the Leading Vaccine to Solve Covid19.” The New York Times. The New York Times, November 10, 2020. https://www. nytimes.com/2020/11/10/business/biontechcovid-vaccine.html. Jha, Ashish K. Twitter Post. December 12, 2020, 8:44 pm. https://twitter.com/ashishkjha/status/ 1337951468561829893?lang=en. Kolata, Gina. “Kati Kariko Helped Shield the World From the Coronavirus.” The New York Times. The New York Times, April 8, 2021. https://www.nytimes.com/2021/04/08/health/ coronavirus-mrna-kariko.html. Nguyen, Kimberly H. “COVID-19 Vaccination Intent, Perceptions, and Reasons for Not Vaccinating Among Groups Prioritized for Early Vaccination — United States, September and December 2020.” CDC Morbidity and Mortality Weekly Report, February 12, 2021.
Oltermann, Phillip. “Uğur Şahin and Özlem Türeci: German 'Dream Team' behind Vaccine.” The Guardian. Guardian News and Media, November 10, 2020. https:// www.theguardian.com/world/2020/nov/10/ ugur-sahin-and-ozlem-tureci-german-dreamteam-behind-vaccine. Roberts, Joanna. “Q&A: BioNTech Vaccine Is Only 'MRNA 1.0'. This Is Just the Beginning, Say Co-Founders.” Horizon, April 8, 2021. https://horizon-magazine.eu/article/ qa-biontech-vaccine-only-mrna-10-justbeginning-say-co-founders.html. Subbaraman, Nidhi. “This COVID-Vaccine Designer Is Tackling Vaccine Hesitancy - in Churches and on Twitter.” Nature News. Nature Publishing Group, February 11, 2021. https:// www.nature.com/articles/d41586-021-00338-y. “University of Pennsylvania MRNA Biology Pioneers Receive COVID-19 Vaccine Enabled by Their Foundational Research.” Penn Medicine. Accessed May 14, 2021. https://www. pennmedicine.org/news/news-releases/2020/ december/penn-mrna-biology-pioneersreceive-covid19-vaccine-enabled-by-theirfoundational-research.
POLICY
THE AMERICAN HEALTHCARE SYSTEM EXCESSIVE EXPENSE AND SOME SOLUTIONS By
Rachel Zhang EJ Beck
It’s often best to do some thorough research before buying a new car. What kind of mileage are you looking for? What price range? What color? How large is the car? There are many different factors and careful considerations which can influence your final decision. When it comes to a person’s health, whether it be experiencing pain or a circumstance of life and death, you simply can’t afford yourself the same flexibility. While being rushed to the nearest hospital, placed in an emergency room as an uninsured patient, or undergoing life-saving surgery, the monetary cost or quality of care is not under your control. In short, any person requiring urgent or necessary healthcare has low market power with a limited capacity for price negotiation. The United States spent $3 trillion or $11,582 per person on healthcare as of 2019, a number that far exceeded the spending of any other industrial nation. Unfor-
tunately, American healthcare quality and accessibility rankings are not reflective of this high budgetary spending. America has lower life expectancies and higher rates of chronic disease, obesity, and suicide compared to other nations of comparable spending. With no uniform system and no universal coverage, uninsured Americans and those requiring out of pocket procedures often experience financial hardship and extensive stress due to their costly medical expenses.
Expensive Healthcare The reasons for these high expenses, and a brief explanation of the various complexities of American healthcare are as follows: I. The American healthcare system consists of a very wide range of insurance companies, both private and public, as well as
various pharmaceuticals, hospitals, and other parties involved in healthcare pricings and negotiations. Medicare or Medicaid are forms of public insurance which cover very many people. These companies can afford to negotiate for lower prices from hospitals and pharmacies because losing the business of a large insurance company such as Medicare or Medicaid means losing a massive number of profitable patients. Nevertheless, there are also several hundred private insurance companies, each covering a smaller number of people. The costs for care when negotiated by these companies is much higher as hospitals and pharmacies have the capacity to demand a higher price. In the case of an uninsured patient, healthcare providers have ultimate control over an unregulated, unnegotiated cost. The complexities of such a varied system and lack of universal coverage contribute to these higher expenses and inacces-
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sibility. II. With so many insurance companies and cross-negotiation, a significant portion of healthcare expenses are administrative tasks. There are various insurance companies, plans, coverage, deductibles, copays, etc., each of which require sophisticated systems for management and regulation. Compounding bills and added complexity make the system even more expensive to manage as America continues to pour an increasing portion of healthcare spending into administrative management. III. Healthcare in America is also motivated by an interest in avoiding impending lawsuits, which is a legitimate concern for many physicians and hospitals. As a result, American healthcare involves the practice of defensive, preventative medicine; there are more orders for MRIs, CAT scans, and expensive procedures as a precautionary measure. Physicians and hospitals order these aforementioned scans to prevent lawsuits; patients approve of these
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scans as they improve quality of care; and medical technology companies profit off the earnings of using their machinery. While such precautions are understandable, they support the economic interests of parties involved, inducing a self-inflating healthcare system. IV. As time goes on, less government regulation has resulted in more powerful healthcare providers, including hospitals and pharmaceuticals, which have monopolized the market and effectively control medicinal prices. These inflated prices continue to result in higher company profits and more inaccessibility. While the aforementioned explanations are not an exhaustive list, they do demonstrate some of the inefficiencies within our current healthcare system. Pricing by insurance companies, administrative overspending, defensive medicine, and limited regulation have contributed to the monetization of healthcare as a privilege rather than a right.
Some Solutions Nevertheless, there are still several various ideas, although some conflict one another, which illustrate promising attempts and progressions towards favorable systemic improvements. • In March of 2010, President Barack Obama passed the Affordable Care Act (Obamacare), which increased access to Medicaid and improved the accessibility and affordability of American healthcare. However, those who oppose this act also recognized higher insurance company premiums, increased taxes, and the incentivization of businesses into hiring less employees to avoid covering healthcare. • Medicare for All is a single-payer system ensuring health care access for all promoted by Bernie Sanders in his 2020 presidential campaign. Still, while a single-payer system
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•
in which the government standardizes a price for each medical treatment might work well in theory, there remains the danger that influential private providers could increase these standards to much higher prices, creating a larger scale of inaccessibility. America’s variety in insurance companies, hospitals, and pharmaceuticals increases incentive for research and improved quality of care due to the potential profit. The diversification and technology of American healthcare through the private sector serves those who can afford care very well. To maintain these benefits of our current system, some researchers are considering the network in Germany. With a government-regulated network of private insurers, both nonprofit and for-profit companies are able to
achieve societally-desired healthcare provisions through insurance-company generated “sickness funds.” Germany's success in maintaining a comprehensive healthcare system while minimizing costs provide a promising example for future American policies to emulate. Despite these complexities and expensive concerns, there are aspects of American healthcare such as the diversified coverage, developed technology, and abundant resources which are very desirable. Through further research and succeeding developments, America’s healthcare system has salvageable aspects and high potential for improvement. “Affordable Care Act (ACA).” Healthcare.gov. U.S. Centers for Medicare & Medicaid Service, 2021. https://www.healthcare.gov/glossary/ affordable-care-act/. Boyle, Michael. “6 Reasons Healthcare Is So Expensive in the U.S.” Investopedia. Investopedia, Apr 27, 2021. https:// www.investopedia.com/articles/ personal-finance/080615/6-reasons-healthcareso-expensive-us.asp.
Edwards, Erica & Lauren Dunn. “Is Germany's health care system a model for the U.S.?” NBC News. NBC News, Jun 30, 2019. https://www. nbcnews.com/health/health-news/germany-shealth-care-system-model-u-s-n1024491. Eisenberg, Richard. “What Broke American Health Care And How To Fix It.” Forbes. Forbes, Oct 25, 2019. https://www.forbes. com/sites/nextavenue/2019/10/25/ what-broke-american-health-care-and-how-tofix-it/?sh=5020ec4147ed. Hohman, Maura. “Why is healthcare so expensive in the United States?” Today. Today, Sep 22, 2020. https://www.today.com/tmrw/ why-healthcare-so-expensive-unitedstates-t192119. Ibarra, Ana. “Paying too much for health insurance? New subsidies announced.” CalMatters. CalMatters, Apr 14, 2021. https:// calmatters.org/health/2021/04/healthinsurance-subsidies/. Sanchez, Helamen. “Understanding the Healthcare Debate.” BYU Political Review. BYU Political Review, Feb 04, 2020. https://politicalreview. byu.edu/2020/02/04/understanding-thehealthcare-debate/. “The U.S. Health Care System: An International Perspective.” Department for Professional Employees. AFL-CIO, Aug 15, 2016. https:// www.dpeaflcio.org/factsheets/the-us-healthcare-system-an-international-perspective. Tikkanen, Roosa & Abrams, Melinda. “U.S. Health Care from a Global Perspective, 2019: Higher Spending, Worse Outcomes?” The Commonwealth Fund. The Commonwealth Fund, Jan 30, 2020. https://www. commonwealthfund.org/publications/ issue-briefs/2020/jan/us-health-care-globalperspective-2019.
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THE MOZART (SCHMOZART) EFFECT By
Chloe Palumbo Helen Wei
The “smart-baby” product industry has grown tremendously over the past few decades, gaining profound momentum grounded in the belief that classical music helps boost intelligence in infants–a phenomenon more commonly known as the Mozart effect. Whether in the form of CDs, interactive toys, or television programs, the societal obsession with distilling the wondrous powers of Mozart to augment intelligence in infants has captivated society for decades. But how accurate is the so-called Mozart effect and is there a scientific basis for this phenomenon? The term Mozart effect stems from a study conducted in 1993 by Rauscher and colleagues in which 36 college students listened to either 10 minutes of
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Mozart’s piano sonata, 10 minutes of silence, or 10 minutes of a monotonous voice prior to taking a spatial reasoning task–a test which measures one’s ability to conceive and alter three-dimensional relationships of objects in space over time. After the exam, the subjects’ spatiotemporal task scores were recorded across experimental groups and compared. Rauscher and colleagues found that participants who listened to Mozart’s piano sonata performed significantly better on the spatial reasoning relative to those who listened to a non-musical stimulus or silence, however, such improvements persisted for only 10-15 minutes after listening. From this, Rauscher et al. concluded that there was some short-term correlation between spatiotemporal task
score and listening to Mozart’s piano sonata. Shortly after the Rauscher et al. findings were published, the press eagerly jumped at the opportunity to spread the word to the public. However, amidst the public frenzy, loads of generalizations ensued and Rauscher et al.’s findings became progressively more distorted as the American public became entranced by the notion that listening to Mozart makes you smarter. The modest study conducted on young adults that measured spatiotemporal task score was suddenly transformed into the generalization that children who listened to classical music from a younger age could achieve higher SAT scores and IQs. The public’s fervent conviction that listening to Mozart helps boost
RESEARCH
intelligence during child development gave rise to the “smart-baby” industry of today that promotes products which promise to augment a child’s intelligence through classical music. After the empirical findings by Rauscher et al. were published, numerous studies attempted to replicate the results. However, still to this day, no studies have succeeded in replicating the magnitude of the effects found by Rauscher and colleagues. In fact, one of the largest and most comprehensive studies conducted by Pietschnig et al. found only a small increase in spatial task performance score for subjects who listened to Mozart’s piano sonata relative to subjects exposed to a non-musical stimulus or no musical stimulus at all. However, Pietschnig et al. found that the same magnitude of difference in spatial task performance score was observed when subjects were presented with some other musical stimulus, thereby producing a negligible difference between the two musical conditions. Additionally, Pietschnig et al. found evidence of publication bias in the Rauscher et al. study, thus emphasizing that there is little substantial evidence that listening to Mozart’s
piano sonata boosts spatiotemporal task performance. Although listening to Mozart may not make you smarter, these follow-up results provide some interesting insight into the relationship between listening to music and brain stimulation. Even in Pietschnig et al. study, subjects scored higher on spatial reasoning tasks after listening to some musical stimulus. Scientists speculate that any music the brain deems to be engaging is sufficient to stimulate the brain. In fact, one study conducted by Burdette et al. used fMRI to scan 21 subjects as they listened to a variety of music genres that they liked and disliked. Burdette et al. found that brain connectivity was most heavily influenced by the listener’s preferences rather than the specific type of music. Specifically, they found elevated brain connectivity in brain circuits concerned with focused internal thought, empathy, self-awareness, as well as memory and social emotion consolidation when subjects listened to their preferred music. While the precise neural mechanisms that underlie the process of listening to music are still yet to be elucidated, scientists are aware that listening to music is a highly active neural
process that has a plethora of benefits on the brain. Whether it is a tool to increase an infant's intelligence, music is no doubt a highly effective form of brain stimulation with massive potential particularly in the clinical environment. “Keep Your Brain Young with Music.” Johns Hopkins Medicine. Accessed May 15, 2021. https://www.hopkinsmedicine.org/health/ wellness-and-prevention/keep-your-brainyoung-with-music. Music And The Brain. n.d. Newatlas. https:// newatlas.com/science/eeg-study-music-chillsbrain-evolution/. “Music Has Powerful (and Visible) Effects on the Brain.” ScienceDaily. ScienceDaily, April 12, 2017. https://www.sciencedaily.com/ releases/2017/04/170412181341.htm. Pietschnig, Jakob|Voracek. “Mozart EffectShmozart Effect: A Meta-Analysis.” Intelligence. Elsevier. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. Tel: 877-839-7126; Tel: 407-345-4020; Fax: 407-363-1354; e-mail: usjcs@elsevier.com; Web site: http://www. elsevier.com, November 30, 2009. https://eric. ed.gov/?id=EJ882611. The Mozart Effect. Latin American Post. Accessed May 14, 2021. https://latinamericanpost. com/26947-myth-or-reality-the-mozart-effect. “The Powerful Effect of Music On the Brain.” The Powerful Effect of Music on the Brain, February 1, 2018. https://www.thetabernaclechoir.org/ articles/the-powerful-effect-of-music-on-thebrain.html. Spiegel, Alix. “'Mozart Effect' Was Just What We Wanted To Hear.” NPR. NPR, June 28, 2010. https://www.npr.org/templates/story/story. php?storyId=128104580. Weinberger, Norman M. “Music And The Brain.” Scientific American. Scientific American, September 1, 2006. https://www. scientificamerican.com/article/music-and-thebrain-2006-09/.
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THE SAFE COCOON OF CATATONIA By
Meagan Johnson Teresa Nam
Nine-year-old Sophie fled the USSR with her family about six years ago. After her parents were raped, kidnapped, and subsequently beaten by a Russian mafia, Sophie's parents decided to seek asylum in Sweden. Months after making the 3,000-mile move to Sweden, their dream of safety and freedom was quickly bulldozed-the Swedish Migration Board failed to see why Sophie and her family deserved to remain in the country. Immediately after receiving the devastating news, Sophie succumbed to a mysterious illness: a comatose-like state without any apparent biological or medical
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reason. This illness would soon be diagnosed as Uppgivenhetssyndrom, or resignation syndrome. Lying prone, being fed through a tube, and wholly detached from their adolescent worlds seems like a rare phenomenon for a child as young as nine. However, Sophie's story is just one of a few hundred. Uppgivenhetssyndrom—unlike cancer or ischemic heart conditions---fails to transverse borders as every case lies in Sweden. First identified in the late 1990s, researchers coined "Uppgivenhetssydrom" as a long-standing disorder plaguing psychologically traumatized migrant children
amid a lengthy migration process. Symptoms included gradual withdrawal from the world around them: a profoundly depressive state. This stupor soon prompts paralysis, a lack of speech, and a failure to respond to any stimuli. After months or even years of being in a coma, remission is marked by a return to normal functioning. The child, without any signs of brain damage, wakes up as if they took a nap. Although symptoms resembling Uppgivenhetssydrom can be found in the medical literature (a similar phenomenon was observed in Nazi concentration camps), no hypoth-
RESEARCH
esis has been provided to account for its geographical magnitude. This could suggest that Uppgivenhetssydrom is culture-bound; that cultural expectations and beliefs influence symptom expression. "I think it is a form of protection, this coma they are in," says Dr. Elisabeth Hultcrantz, a physician with the Doctors of the World Sweden. Over the years, Dr. Hulcrantz has treated more than forty children with diagnosed Uppgivenhetssyndrom; often, providing pro bono consultations and treatments for families all across Sweden. Being one of the few physicians eager and willing to treat this mysterious illness, Hultcrantz defines Uppgivenhetssydrom as a condition "where the body and soul dissociate." Despite the patient recovering within months or years, there is no apparent biomedical cure. However, one proven remedy exists--the restored hope in their family's safety and well-being. The reasons for this illness are often chalked up to be malingering syndrome or Munchausen by proxy--both discriminately blaming the parents for their child's illness. But as Dr. Hultcrantz expounds, "When I explain to the parents what has happened, I tell them the world has been so terrible…they have gone into
themselves and disconnected the conscious part of their brain." A large majority of healthcare professionals are confident trauma and dread were two critical factors in understanding this mysterious illness as many of the affected children have reportedly witnessed extreme acts of violence executed upon themselves and their parents. Notably, one child was forced to watch their family friend being tortured and shot at point-blank range after being found guilty of owning a Wi-Fi company. Despite these accounts of severe trauma, right-wing politicians, xenophobic individuals, and even a few physicians believe the children are entirely faking their symptoms. The children are deemed "bratty" and "unruly"; this is simply a con to manipulate the immigration system into remaining in Sweden or a means for a young child to act out their favorite fairytale stories. On popular Swedish conservative websites, where conspiracy theorists frequent, an archive of podcasts and blog posts concerned with Uppgivenhetssydrom dominate the political arena. One podcast, in particular, infamously known as Weekend Warrior, attempts to persuade its viewers that these apathetic children are paid actors on behalf of the parents and further claims that pro-immi-
gration activists are "suckers." This questioning attitude to this tragedy affects the medical response and treatment for these children--making a case for anti-deportation laws and advocating for cultural sensitivity. While this investigation into Uppgivenhetssydrom details the horrific conditions forced on emotionally scarred children, this phenomenon also exposes gaps where human rights have unequivocally failed. With growing political and nuclear tensions growing worldwide, we have to ask ourselves: How long until this syndrome reaches the rest of the world? If slipping into a coma is synonymous with the safety of a cocoon, how dire are our children's lives? Although Sweden has been deemed the most "refugee-friendly" country in all of Europe, overburdened welfare systems compounded by scarce public resources exacerbate the fear that Sweden will soon turn away vulnerable families. As over 163,000 people applied for asylum in Sweden in 2015, the country took in more refugees per capita than any other country in the continent. The Swedish Migration Board is "the authority that considers applications from people who want to take up permanent residence in Sweden, come
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for a visit, seek protection from prosecution or become Swedish citizens." The Swedish Migration Board saw that many of those affected by this phenomenon were at risk for deportation, thus granting their parents' residency permits. However, there are many loopholes in the immigration policy established by this governmental agency. With such vague phrasing in their policy, members of the board began defining what was proper suffering to be granted refuge. Eventually, the Swedish Migration Board established a new diagnostic to categorize symptoms of Uppgivenhetssydrom. Under this new diagnostic, refugees had to prove that circumstances in their home country were particularly distressing or severe injury would result in their return. Not surprisingly, governmental officials in Sweden began seeing Uppgivenhetssydrom as too obviously political. Conservatives felt the issue of Uppgivenhetssyndrom was a massive con, while progressives
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felt Sweden was on the verge of a moral collapse. All the while, from the outside, Sweden looked like a humanitarian utopia. At its core, this debate goes back to the Foucauldian language of biopower and biological citizenship. Defining biopower as a political technology to manage and support human flourishing, Foucault further explains biological citizenship as the forms of belongings, rights, and demands for access to care that each citizen holds. The salient word being citizen. Objectors overlook the structural violence faced by children like nine-year-old Sophie. Instead, they fear that somewhat scarce resources will be diverted to foreigners--a typical side effect of growing nationalism. Although there is no discernible solution to preventing trauma-induced Uppgivenhetssyndrom, one thing we can extrapolate from the mysterious illness is that biopower and biological citizenship may not be coterminous. So, what happens
when making claims on the state to better one's life fails? With over sixty children set to be diagnosed with Uppgivenhetssyndrom this year alone, soon, they will slip into the safe cocoon that is catatonia. Aviv, R., Talbot, M., Sorkin, A. D., Collins, L., & Mnookin, S. (n.d.). The Trauma of Facing Deportation. Retrieved from https://www. newyorker.com/magazine/2017/04/03/ the-trauma-of-facing-deportation Sallin, K., Lagercrantz, H., Evers, K., Engström, I., Hjern, A., & Petrovic, P. (2016, January 29). Resignation Syndrome: Catatonia? CultureBound? Retrieved from https://www.ncbi.nlm. nih.gov/pmc/articles/PMC4731541/ Sweden's Mystery Illness: Resignation Syndrome. (2018, February 20). Retrieved April 29, 2021, from https://doctorsoftheworld.org/ blog/swedens-mystery-illness-resignationsyndrome/ Resignation Syndrome: A New Conversation. (2019, October 29). Retrieved April 29, 2021, from https://www.europenowjournal. org/2019/10/28/resignation-syndrome-a-newconversation/ Brink, S. (2017, March 30). Oscar-Nommed Film Looks At 'Resignation Syndrome.' What Exactly Is It? Retrieved April 29, 2021, from https://www.npr.org/sections/ goatsandsoda/2017/03/30/521958505/ only-in-sweden-hundreds-of-refugee-childrengave-up-on-life Photo (1): 170403_r29648-1200x780-1490288448_ custom-bc670a050fc62b4df8ede1845063a4e55 89f5ba6.jpg Photo (2): https://portfolium1. cloudimg.io/fit/960x540/c000000/ https://cdn.portfolium.com/
RESEARCH
METFORMIN: THE UNSUNG HERO DRUG By
Jack Osborn Marissa McCollum
Metformin is a commonly prescribed drug used to treat high blood sugar most commonly in diabetic patients as an antihyperglycemic biguanide, referring to a class of drugs used to treat type 2 diabetes. These drugs function by decreasing hepatic glucose primarily by inhibiting the body’s metabolic process of producing sugar, known as gluconeogenesis. While the drug has been widely distributed for over two decades as a diabetic drug, having received FDA approval in October of 1998, only recently has evidence provided support for the use and implementation of the drug to both improve insulin sensitivity and limit carcinogenesis in otherwise healthy individuals. Thus, the drug shows new potential in delivering anti-cancer benefits that can be of use to everyone in society. Today, the drug is largely distributed as 1,1-dimethylbiguanide hydrochloride and has recently been shown to function
though previously undescribed mechanisms, including pathways that may offer overarching benefits to health. Beyond its capacity for diabetes treatment, increasing data has come to light surrounding metformin’s implications in regulating and improving gut health. More than one third of all Americans suffer from metabolic syndrome, an overarching disease state used to describe a series of inflammatory conditions such as elevated blood sugar, high blood pressure, and gut dysbiosis; the gut microbiome has been shown to play a crucial role in metabolic syndrome pathogenesis. Due to metformin’s therapeutic capacity to boost gut health, the drug shows promise in improving an otherwise healthy individual’s metabolic state, critical to longevity and a healthy life. Type 2 diabetes is characterized in its simplest terms as an inability or resistance to release insulin
in response to carbohydrates, resulting in elevating blood sugar. Insulin, a hormone normally released by the pancreas, serves to allow glucose to pass from blood into cells for use in metabolism. Since its initial administration, metformin has been shown to chronically improve insulin sensitivity and thereby mitigate a diabetic’s fasting blood sugar levels. Specifically, metformin both directly and indirectly upregulates the AMPK pathway, an essential control system of many cellular processes, including glucose production in the liver (see Figure I). In a cell treated with metformin, cellular respiration is suppressed, and glucose biosynthesis (gluconeogenesis) is inhibited. Metformin also indirectly mediates several other metabolic pathways that increase insulin sensitivity, resulting in lower overall blood sugar and healthier metabolism of consumed sugars. Importantly, metformin does not
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actually promote insulin release, which could cause compensatory low blood sugar, making it the preferred treatment for type 2 diabetes. In addition to its direct role in diabetes treatment, metformin also plays a crucial role in weight loss by inhibiting Insulin-like Growth Factor receptor signaling, a pathway similar to that of insulin. Unlike other diabetic drugs that specifically protect beta islet cells of the pancreas that release insulin in response to sugar, metformin plays a more widespread role in maintaining metabolic health. Additionally, the drug has been shown to decrease fasting insulin levels in patients with cognitive impairment and aberrant glucose metabolism. As both hypoglycemia and hyperglycemia are implicated in cognitive dysfunction, metformin’s potential use therein lies in improving cognition in diabetic individuals. Thus, metformin’s wide-ranging direct impact on a multitude of biochemical pathways, some of which remain undescribed, make therapeutic benefits possible not
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only for diabetic patients but also for otherwise healthy adults looking to improve their health and potentially lose weight without dangerous consequences. Today metformin remains somewhat understudied from the viewpoint of its anticancer and profound anti-inflammatory properties— both relevant and salient benefits. One elucidated mechanism surrounding its anti-cancer potential has been discovered through a series of protein phosphorylation cascades. Since the drug activates the AMPK pathway, leading to mTOR signaling inhibition, protein synthesis is altered, thereby hindering aberrant cell proliferation associated with cancer cells. The drug also suppresses oxidative phosphorylation, a process that can inadvertently generate reactive oxygen species (ROS); through inhibition of mitochondrial complex I (see Figure I), ROS production is hindered, further reducing DNA damage and limiting the extent through which cancer can develop. Furthermore, leukemia has been
well-characterized by mTOR pathway activation; metformin has been shown to inhibit the AKT/mTOR signaling pathway, creating a potential therapeutic approach for combating blood cancers, in addition to a series of cancers proliferated by the broader biochemical pathways. Regarding its anti-inflammatory properties, which alone have suppressive cancer capabilities, metformin has been shown to increase activity of brown fat, adipose tissue critical to generating body heat, thereby suppressing fat storage and increasing metabolic efficiency. As a result, especially in chronic use of the drug, metformin is capable of reducing fatty acid uptake and increasing cellular thermogenesis (heat generation), increasing resting metabolic rates, and thereby promoting weight loss, especially when coupled with exercise. Lastly, since the gut microbiome has been implicated in regulating metabolic health via production of short chain fatty acids critical to the immune system, metformin’s ability to regulate gut microbiota has been shown to vitally increase
RESEARCH the presence of short-chain fatty acid-producing bacteria, improving gut health. Taken together, by targeting a series of complicated but individually critical pathways often dysregulated through poor health, metformin presents significant hope as a therapeutic drug in not only harnessing but also improving health as a society at large. While metformin’s numerous benefits largely outweigh its costs, as with any drug, the costs must be considered before an individual is prescribed the drug. Prior to prescription, physicians evaluate the drug’s potential to cause more serious—albeit rare—side effects including lactic acidosis, which can occur if significant amounts of the drug accumulate in the blood, most often due to dehydration and kidney issues. Additionally, the drug can reduce absorption of vitamin B12 through chronic use, requiring metformin patients to supplement their diet with B12 intake. If patients are anemic, metformin must be supplemented with a series of vitamins to ensure that the drug does not exacerbate
deficiencies already present in the body. Some concerns stem from distribution rather than the drug itself: the FDA recommended that some metformin distributors producing an extended release version of the drug remove their tablets from the market in May of 2020 due to concerning levels of carcinogens. Even taking into account the negative associations and dangers of the drug, metformin holds astounding promise in unlocking a multitude of biological targets critical to longevity, including cancer, gut microbiome inflammatory pathways and even lipid metabolism pathways. While the future of the drug is not fully clear, looking back on the drug in years to come, the drug will assuredly continue to reveal benefits beyond its capacity to treat diabetes, akin to a miracle drug. Barros Metlova, Victoria. “Metformin: the Diabetes Drug Restoring Cognition?” Longevity Technology, March 16, 2021. https://www. longevity.technology/metformin-the-diabetesdrug-restoring-cognition/.
“Drug Approval Package.” Glucophage (Metformin Hydrochloride) NDA# 020357/S010. U.S. Food & Drug Administration , July 1, 2005. https:// www.accessdata.fda.gov/drugsatfda_docs/ nda/98/020357s010.cfm#:~:text=Approval%20 Date%3A%2010%2F22%2F1998. Festi, Davide, Ramona Schiumerini, Leonardo Henry Eusebi, Giovanni Marasco, Martina Taddia, and Antonio Colecchia. “Gut Microbiota and Metabolic Syndrome.” World journal of gastroenterology. Baishideng Publishing Group Inc, November 21, 2014. https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC4239493/. Kadanoff, Marcia, and Timothy Hay. “Everything You Always Wanted to Know About Metformin, But Were Afraid to Ask.” diaTribe Learn, March 18, 2021. https://diatribe.org/ everything-you-always-wanted-know-aboutmetformin-were-afraid-ask. Lv, Ziquan, and Yajie Guo. “Metformin and Its Benefits for Various Diseases.” Frontiers in endocrinology. Frontiers Media S.A., April 16, 2020. https://www.ncbi.nlm.nih.gov/pmc/ articles/PMC7212476/. Rena, Graham, D Grahame Hardie, and Ewan R Pearson. “The Mechanisms of Action of Metformin.” Diabetologia. Springer Berlin Heidelberg, August 3, 2017. https://www.ncbi. nlm.nih.gov/pmc/articles/PMC5552828/. Spiering, Martin J. “The Mystery of Metformin.” Journal of Biological Chemistry 294, no. 17 (April 26, 2019): 6689–91. https://doi. org/10.1074/jbc.cl119.008628. Xu, Dan, Jacquita S AFfandi, Timothy Yap, and Christopher M Reid. Metformin Use beyond Diabetes: Reducing Cardiovascular Events in the Healthy Elderly. Journal of Gerontology & Geriatric Medicine, June 30, 2020. https:// www.heraldopenaccess.us/openaccess/ metformin-use-beyond-diabetes-reducingcardiovascular-events-in-the-healthy-elderly.
Burgess, Lana. “Stopping Metformin: Side Effects, Risks, and How to Stop Safely.” Medical News Today. MediLexicon International, June 17, 2020. https://www.medicalnewstoday.com/ articles/323128.
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DO ANTIDEPRESSANTS WORK? A REVIEW FOCUSING ON PUBLICATION BIAS, THE PLACEBO EFFECT AND TRAIL DESIGNS By
Deniz Eracar Sophia Carino
“Do antidepressants really work?” It might seem like we have a definitive answer for this question, yet this question is commonly and repeatedly addressed by researchers and pharmaceutical companies across the United States as the country continues to have the highest rate of antidepressant use compared to any other nation in the world. Despite the extensive research conducted on developing new and “improved” antidepressants, the plethora of peer-reviewed research articles on antidepressants, and the fact that these medications are being used by a large percentage of the population, there is still an ongoing debate around their efficacy. While many literatures may suggest that antidepressants are effective and life-changing, their harms might outweigh benefits in the long run or their short term benefits may be more modest than we think. To understand the basis of these arguments and the skepti-
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cism surrounding the efficiency of antidepressant treatments, it is necessary to look back to the advancements in antidepressant research conducted over the past decades and the published research articles supporting these advancements, which is the approach that Turner et al. took in their 2008 meta-analysis. One main argument that might partially explain the conflicting views on these drugs is publication bias (or the “file drawer effect”), which refers to our intentions to selectively publish studies showing positive results over those showing neutral or negative results. In line with this idea, Turner et al. analyzed US Food and Drug Administration’s (FDA) registry and results database, in which drug companies are required to register all trials that they are planning to use to support their application for marketing approval or change in labelling, for antidepressant trials registered between the years 1987 and 2004. Their meta-analysis revealed that whether the studies
were published and how their results were reported if they were published were heavily dependent on their outcomes. For example, out of the 74 studies that the research group included in their data analysis, 38 were deemed positive by the FDA, and out of these 38 studies 37 were published. The remaining 36 studies were either categorized as negative or questionable and only 3 studies out of these were published as not positive, whereas the remaining 33 were either unpublished (22 studies) or published in a way that deemed the results of the study positive, which conflicted with the FDA’s conclusion. Overall, this makes the “positive” studies 12 times more likely to be published than the negative or inconclusive studies and implies a strong publication bias towards the publication of positive results. In addition to making the evidence that we base our medical decisions on biased, the “cherry-picking” of study outcomes may also make these decisions non-optimal and create
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a public view on antidepressants that is misrepresentative of the actual study results: the “negative” and “neutral” studies that never make it past being buried in a drawer may reveal a much different picture about antidepressants than the selectively positive published literature. Apart from whether we publish results of a study or how we mask a study’s results, how we choose participants for a study is also important when we are making claims about efficiency. For example, one meta analysis by Kirsch et al. suggests that the efficacy of antidepressants might depend on the severity level of the depression itself. To reach this conclusion, the researchers obtained full datasets from all clinical trials submitted to the FDA in support of the licensing of four new-generation antidepressants. The obtained data was assessed using meta-analytic techniques to analyze the effects of initial severity on self-report improvement scores of the patients. This revealed that drug-placebo
differences increased as a function of initial severity: whereas there was almost no difference observed for patients who had moderate levels of depression, the drugs resulted in a relatively small difference for patients with very severe depression and could only reach “clinical significance” (assessed by conventional criteria), for patients who were placed at the upper end of the severely depressed category. Lastly, we have to consider the placebo effect, and more specifically whether an increase in the placebo effect over the years may have contributed to our perception of the increased efficacy of the antidepressant drugs. In their research report, Khan et al. started their discussion by stating that more than fifteen years ago, the high failure rate of antidepressants clinical trials was attributed to the increasing magnitude of the placebo response. This finding, reported by Wash et al., has paved the way for meta-analytic reviews of antidepressant trials, psychotropic trials, and trials focused on patient-level data for
major depressive disorder, which all support that the placebo response has continued to grow between 1987-2013. To contribute to this debate, Khan et al. accessed the US Food and Drug Administration’s reviews for 85 clinical trials approved between the years 1987 and 2013 conducted on a total of 23109 patients. By grouping the trials into pre-2000 and post-2000 ones and controlling for possible confounding variables such as changes in trial design, the research team was able to calculate and compare the magnitude of placebo and antidepressant responses, antidepressant-placebo differences as well as the effect sizes and success rates of the clinical trials that took place during the 15 years time period. Their analysis was not only able to confirm their proposed hypothesis that the magnitude of the placebo response has continued to increase during the 15 year time period (the percentage symptom reduction for pre-2000 clinical trials was noted to be 29.8% whereas the percentage symptom
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reduction for trials after 2000 was noted to be 36.2%), but they were also able to replicate the findings of the original study by Wash et al. They reached the conclusion that the pattern of increase in placebo response noted by Wash et al. in 2001 has continued. Overall, the meta-analytic approaches taken by different research groups focusing on different aspects of the efficacy of antidepressants have proven that the question “Do antidepressants
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work?” might be more multifaceted than it seems. Whereas it is evident that antidepressants may not be as effective as published research portrays them to be due to publication bias, other factors such as the placebo effect and who the clinical research trials are designed for should also be taken into consideration. Carroll, A. E. (2018, March 12). Do Antidepressants Work? The New York Times. https:// www.nytimes.com/2018/03/12/upshot/ do-antidepressants-work.html.
Khan, Arif, Kaysee Fahl Mar, Jim Faucett, Shirin Khan Schilling, and Walter A. Brown. "Has the rising placebo response impacted antidepressant clinical trial outcome? Data from the US Food and Drug Administration 1987‐2013." World Psychiatry 16, no. 2 (2017): 181-192. Turner, Erick H., Annette M. Matthews, Eftihia Linardatos, Robert A. Tell, and Robert Rosenthal. "Selective publication of antidepressant trials and its influence on apparent efficacy." New England Journal of Medicine 358, no. 3 (2008): 252-260. Kirsch, Irving, Brett J. Deacon, Tania B. HuedoMedina, Alan Scoboria, Thomas J. Moore, and Blair T. Johnson. "Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration." PLoS Med 5, no. 2 (2008): e45.
CURRENT EVENTS
A HISTORY OF ZOONOTIC DISEASES: DON'T BLAME THE BAT By
Sanjana Rao Ashley Chen
It’s almost 100% likely that you know or know of someone who has been infected by a zoonotic disease. Zoonotic diseases have taken the lives of upwards of 33 million people since 1981 and are estimated to infect a billion people every year. Yet, what are zoonotic diseases? Zoonoses include any disease caused by a pathogen that originated in animals and ‘spilled over’ into humans. SARS, Malaria, HIV, Rabies, and most recently, COVID19, all fall under this category—as do most of the pandemics within the last century. The lethality and virulence of zoonotic diseases have mostly been attributed to two causes: natural selection within the animal host, and the novel nature of animal borne diseases. Our immune systems and gastrointestinal tracts are responsible for fighting off and excreting most of the pathogens that attempt to interrupt our daily lives. However, when they see a pathogen that they’ve never encountered before, especially one that can successfully replicate
within a human host, it must ‘catch up’ with the virus and quickly produce an immune response against it. This novel nature provides some explanation for how zoonotic diseases spread and evolve into pandemics so rapidly. Unfortunately, there are also limitations; it does not explain why they’re so hard to treat. This may be due to natural selection within the animal itself, as well as within the human host. The host and the pathogen are theorized to be locked in an evolutionary arms race of sorts, both adapting to the responses of the other. As the host is often at a disadvantage, especially if the pathogen is a virus (and can thus adapt quicker), a pandemic is often hard to eradicate. The critical point is when the animal virus or pathogen gains the ability to replicate/ reproduce in the first human host (patient zero). This is termed the spillover point. While there are multiple theories, there has yet to be a conclusive story addressing the origin of COVID-19. However, we do know
how SARS, its closely related coronavirus cousin, came to be. SARS, or severe acute respiratory syndrome, was first seen in China in 2002, where it quickly spread to other countries via travelers to Vietnam, Singapore, and Hong Kong. It was highly virulent and spread by airborne transmission amongst doctors treating affected patients, neighboring hotel rooms, and even within housing estates. It caused pneumonia-like symptoms. It had a short incubation time and a high fatality rate, both of which may have contributed to the ease (relative to COVID-19) of eradication despite the lack of effective vaccines. Mid-2003, researchers found traces of a similar coronavirus in palm civets, which were sold at a market in Guangdong, where the first patient was from; however, these results only pertained to a few civets (most civets had no antibodies to the virus), making it unlikely that they were the source of the disease. Researchers then surveyed 45 species, ultimately finding traces of coronavirus precursors in only
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3 of them: bats. Further research narrowed down the source to horseshoe bats — suggesting that the civets served solely as an amplifier host (a host which is not necessarily affected by the disease but allows it to reproduce/replicate to high levels) for the disease, while these bats served as the true reservoir. Bats serve as the reservoir for
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many lethal illnesses in humans (such as rabies and Ebola) and are responsible for more zoonotic diseases than any other taxonomic order. In addition, diseases originating in bats, on average, have a higher fatality rate than other zoonotic diseases. This is possibly due to their high body temperature (due to their elevated metabolism which supports their ability to fly)
and powerful immune systems. Bats can over-activate the interferon alpha (an inflammatory cytokine associated with immune response) pathway, causing very high inflammation levels — too high for a human and most pathogens to survive. As a result, most pathogens do not survive in bats and those that do are often highly virulent and lethal if they spill
CURRENT EVENTS
over into humans. This is due to the same evolutionary arms race argument outlined above. So how can we prevent the next global pandemic? The probability of a spillover happening increases whenever animals and humans interact in close proximity for extended periods of time. Examples of this include livestock rearing (the highly fatal Hendra virus came from horse breeding in Australia), hunting (lyme disease is spread by deer ticks), and pests such as mosquitos and fleas (Malaria and the bubonic plague). Often, virulent zoonoses spill over from ‘exotic’ species that humans do not usually interact with, such as in wild flavor/animal markets, unusual pets (parrots and q-fever), or rituals that involve wild animals or their bodily fluids. It can be tempting to disassociate the origin and blame regarding zoonoses from the western world (as seen with the persecution of Asian-Americans following the
COVID-19 outbreak), considering most of the examples discussed take place elsewhere. However, this overlooks one of the most insidious causes of spillovers: habitat destruction. Zoonotic spillovers are becoming more common, and this is likely due to deforestation and destruction of ecosystems, which in turn force animals like bats in closer proximity to humans. These activities are often practiced by large western corporations in developing nations. Around 33% of the world’s bat species are classified as threatened or endangered, and COVID-19 associated bat persecution has further damaged these fragile populations. The blame associated with the advent of these virulent pathogens rests entirely with us, and this persecution only increases the probability of another spillover event occurring. To prevent the next global pandemic, habitat restoration and ecosystem protection are essential, as is the implementation of
stricter guidelines and legislation surrounding the safe handling of animals and animal products. Science News. 2021. Close relatives of the coronavirus may have been in bats for decades. [online] Available at: <https://www. sciencenews.org/article/covid-19-coronavirusevolution-close-relatives-bats> [Accessed 15 May 2021]. Science. 2017. What are zoonotic diseases?. [online] Available at: <https://www. nationalgeographic.com/science/article/ how-do-animals-pass-dangerous-zoonoticdiseases-to-humans-zoonoses-coronavirus> [Accessed 15 May 2021]. [3] Cdc.gov. 2006. SARS | Home | Severe Acute Respiratory Syndrome | SARS-CoV Disease | CDC. [online] Available at: <https://www.cdc. gov/sars/index.html> [Accessed 15 May 2021]. [4] Rocha, R. et al. (2021), Bat conservation and zoonotic disease risk: a research agenda to prevent misguided persecution in the aftermath of COVID‐19. Anim Conserv. https://doi. org/10.1111/acv.12636 [5] Medicalnewstoday.com. 2021. Why are infections from animals so dangerous to humans?. [online] Available at: <https:// www.medicalnewstoday.com/articles/ zoonotic-diseases-why-are-infections-fromanimals-so-dangerous-to-humans#Animalvirus-vs.-the-human-immune-system> [Accessed 15 May 2021]. [6] Quammen, D. (2012) Spillover: Animal Infections and the Next Human Pandemic. W.W. Norton & Company, Inc.: New York. ISBN: (Hardcover) 978-0393066807
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ulse p THE PRE-MEDICAL STUDENTS’ ASSOCIATION the university of chicago FACEBOOK /uchicagopmsa WEBSITE pmsa.uchicago.edu
