The Stethoscoop Fall 2016

Fall 2016

The

StethoSCOOP

The StethoSCOOP Edi tor-i n-Chi ef:

Zach Kassi r

Head of Graphi c Desi gn:

Courtney Stevens

Outreach Coordi nator:

Jonah Klapholz

Treasurer:

Gabri ella Alexandrou

Edi tors:

Ak i la Venk ataram any, Alex Gordon, Jonah Klapholz, Zach Kassi r

Wri ters:

Ak i la Venk ataram any, Alex Gordon, Dani el Szabo, Edw ard Ni renberg, Eli zabeth Gonzalez, Gabri ella Alexandrou , Ibraheem Rehm an, Jonah Klapholz, Kevi n Hui , Klaudi o Haxhi llari , Sophi a Phi , Uche Ezeh

Table of Contents The Bi ology of Happi ness and Why It?s Hard to Fi nd Joy Today

4

Increasi ng M aternal M ortali ty Rates i n the Uni ted States

6

The War Agai nst the Stochasti c: Pursui ng a Vacci ne Agai nst HIV

8

Wai ti ng for Care: the Drawback s of the Canadi an Healthcare System

10

Contemplati ng Di etary Supplements

12

Aducanumab: New Treatment for M ank i nd?s M ost Infamous Neurologi cal Di sease

14

How M edi cali zati on i s Changi ng Our Percepti on of the ?Ill?

16

Controversi al Cutti ng: The CRISPR-Cas System i n Sci ence and M edi ci ne

18

The Role of NSAIDs i n Healthcare

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M ale Reproducti ve Potenti al and Phthalates: A Potenti al Danger from Everywhere?

22

Genomi c Decodi ng of Superbugs

24

IBM Watson: The Future of M edi cal Di agnosi s and Treatment

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References

29

The Bi ology of Happi ness and Why It?s Hard to Fi nd Joy Today

By Eli zabeth Gonzalez

Most us probably know what happiness is.

We have all experienced happiness at some point in time, whether it was early morning on Christmas day as a child or receiving a grade above the mean on an exam today. We certainly know happiness when we feel it. Regardless, happiness can be best defined as a state of well being where individuals don?t feel an urge to change their state (Lemonick, 2005). Which makes sense. When we are happy, we want to stay happy. We will do almost anything to retain these feelings of joy. But why has it become so much harder to be happy today?

Happiness is associated with the prefrontal cortex, a region of the cerebral cortex that covers the front part of the frontal lobe. This specific part of the brain is involved with complex cognitive behavior. In particular, it?s involved in simulating experiences in your head before you try them out in real life (Gilbert, 2001). By imagining both past and present scenarios, we can obtain pleasure.

Another key component of the biology of our happiness is dopamine. Dopamine is a neurotransmitter that helps control the brain?s reward and pleasure enters. Specifically, this chemical factor is important in aspects of happiness associated with moving towards a goal (Lemonick, 2005). People normally associate feeling good when they think of happiness, but a big part of being happy is also about looking forward to something.

This brings us to the complicated part about happiness: we want zero pain and maximum pleasure and, obviously, this state is not possible.

There exists what is known as the Hedonic treadmill, which explains that emotional responses to a pleasant stimulus weakens or completely ceases if that stimulus remains constant (Kovác, 2012). Even if we wanted maximum pleasure, one certain factor could not keep us happy for long. In addition to wanting this state, we have what are known as metaneeds. Metaneed is a term for any higher need for an individual, such as truth, beauty, perfection, justice, order, playfulness, and meaningfulness. So besides wanting no pain and all pleasure, we want these additional factors in our lives to be completely satisfied.

We also think happiness is something to be attained. We believe that have to continually be doing things in order to succeed and, therefore, achieve happiness. Being these task-oriented individuals, we are constantly trying to improve ourselves. This characteristic leads to multitasking.

Although intended to help us complete tasks,

multitasking actually keeps us from doing anything well. It harms not only our performance but also our well being, leading to higher anxiety and depression levels. Psychologists at Harvard University conducted a study with 5,000 people and among these people, only 50% of adults reported that they spent their time in the present moment (Seppälä, 2016). That means we are mentally checked out about half the time. We are sacrificing the present in hopes of a happier future.

By believing that we can achieve happiness eventually, we are delaying the happiness we could have now. We believe in the payoff we will receive when we finally complete that certain task we have been working on. But what happens if we don?t succeed? There is something called impact bias that makes us believe that different outcomes are more different than they actually are (Gilbert, 2001). In this case, we believe that succeeding will make us much happier than if we didn?t succeed.

But this is not the case. This is actually a tendency for the prefrontal cortex to work badly. In reality, not succeeding has a far less impact on our happiness than we expect it to have.

To help with this, we have what can be referred to as our psychological immune system.

Essentially, this allows us to find a way to be happy with the outcome we are left with. For instance, the happiness of lottery winners and paraplegics was compared a year after their life-changing events occurred. After that year, both categories reported being equally happy with their lives (Gilbert, 2001). Going back to thinking that happiness is a goal to be attained, happiness is equally as likely to be generated on its own. We believe, however, that generated is not as real as natural happiness. Both synthetic and natural happiness are just as enduring. The only difference between the two is that happiness is synthetic when we don?t get what we want and natural when we do get what we want.

Essentially, succeeding is only one way of many ways that we can be happy.

So what makes us happy? It has been found that being in the present makes us more productive, which in turn makes us much happier and successful. We tend to enjoy the activity when we are completely in tune with what we are doing, regardless of what particular activity we are engaging in (Seppälä, 2016). In this sense, we are fully experiencing what is going on around us. By taking each task one step at the time, we can experience living in the moment. And ultimately, parts of that moment will bring us happiness.

5

Increasi ng M aternal M ortali ty Rates i n the Uni ted States

By Gabri ella Alexandrou

The United States is home to some of the world?s most exceptional hospitals. People from all over the world travel to the Massachusetts General Hospital or the Mayo Clinic to receive innovative treatments for life-threatening conditions. This is why it is so difficult to explain the astonishing increase in the death of mothers after childbirth.

Some would easily assume that maternal death around the world has fallen as medical care has improved; and they would be right, save for the glaring exception that is the United States.

Forty-nine states (excluding California) and the District of Columbia saw their maternal mortality ratios increase from 18.8 to 23.8 deaths per 100,000 live births between 2003 and 2014 (7).

Texas saw the greatest increase, with the amount of women dying after birth more than doubling from 17.7 to 35.8 between 2000-2014.

The surge in maternal mortality, especially in Texas, cannot be attributed to a single cause. Elise Turner, an associate professor of nursing at Mississippi's Belhaven University, believes that obesity is a ?tremendous piece of the problem? since ?the body is already stressed by obesity and the other accompanying diseases, such as

hypertension, diabetes and things that accompany that and then you put the demands of pregnancy on top of that and it's just very difficult? (4). It is widely known that the obesity rate in the United States has been increasing in the past several years.

Data collected between 2009 and 2010 shows that 31.9% of women aged 20-39 were obese (2).

Currently, more than half of the women in the U.S. who become pregnant are above a healthy weight (2). A woman who is overweight or obese when she gets pregnant has an increased chance of having gestational diabetes or hypertension, the rates of which have been slowly increasing over the past two decades. In Utah, the number of births with gestational diabetes increased 164 percent since 1990, rising from 1.4 percent of all births to 3.7 percent of births in 2010, and Utah has one of the lowest gestational diabetes rates in the country.

In other states up to six percent of children are born to mothers suffering from gestational diabetes (3).

According to the Centers for Disease Control and Prevention ?early initiation of prenatal care by pregnant women, and continuous monitoring of pregnancy by health providers, are key to 6

preventing pregnancy-related complications and death? (6). The organization Planned Parenthood offers gynecological exams, which include breast exams and Pap smears, and weight and urine tests for pregnant women. In 2011, Texas? Republican lawmakers sharply reduced spending on women?s health care in an effort to eliminate government funding of Planned Parenthood (1). This is only one example of a pattern of cutting or failing to increase spending on reproductive healthcare programs because because of an ideological opposition to abortion among conservative lawmakers.

When lawmakers attempt to reduce federal funding to organizations like Planned Parenthood, pregnant women feel the consequences. PP and groups like it provide pre and post-natal care to women without easy access to it. For displaced patients, it can be difficult to find another provider either due to their location or finances(8).

On a larger scale, the American healthcare system does not work well enough to prevent pregnancy-related deaths. The Affordable Care Act made health insurance more available in 2010, but millions of families still cannot afford the care they

need. Dr. Michael Brodman, chairman of the Department of Obstetrics, Gynecology and Reproductive Science at the Mount Sinai Health System, and his group of 50 OB/GYN physicians found that New York had one of the highest maternal mortality rates in the country, and from that they found that this was due to the wide disparity of healthcare offered throughout the state.

Dr. Brodman stated, "If you're in Sweden, everybody gets treated the same way. If you are in New York City, you get treated one way. If you're in Buffalo, you get treated another way and if you're in Missouri, you get treated another way.? In 2015, Sweden boasted a mortality ratio of 3 maternal deaths out of 100,000 live births.

The United States is the richest country in the world and yet ranks at 30 out of 31 for the fewest maternal mortality deaths out of all the industrialized countries, only beating Mexico (7).

Clearly steps need to be taken to reduce the prevalence of these deaths. Analyzing treatment for mothers with poor health and increasing, rather than cutting funds to organizations like Planned Parenthood could be important first steps in reducing maternal mortality rates.

The War Agai nst the Stochasti c: Pursui ng a Vacci ne Agai nst HIV

By Edw ard Ni renberg

It?s odd to think that inaccuracy could translate into power, but stochastic error is precisely what makes HIV so potent and devastating. Between the pathogenesis and immune evasion, HIV stands as a constant source of unease for both the medical community, and for lay people alike. There is no cure, and antiretroviral therapy, while effective, is renowned for its unpleasantness.

Thus, the recent developments in a vaccine for the virus hold a potential to relieve humanity of this scourge, as the unique pathogenesis of the virus makes natural immunity impossible to establish.

HIV is a retrovirus and lentivirus, meaning it has an RNA genome that uses reverse transcriptase to convert to DNA and a long incubation period.

Globally, HIV-1 is more prevalent than HIV-2, and subtypes of the viruses are highly polymorphic (Brooks, 2016, p 639.). HIV relies on CD4 and CCR5 for cell entry (SDF-1 for lymphocyte-tropic forms) (Brooks et al, 2016). The coreceptor is necessary for the virus?s second membrane to fuse with the cell membrane, thereby forcing its contents into the cytoplasm.

The virus exploits the functionality of the immune system to destroy it. Professional antigen presenting cells (APCs) facilitate its dissemination.

Initially, the virus is M-tropic (replicates inside macrophages) and then progresses to a T-tropic (replicates inside T cells) phenotype. At the stage of being T-tropic, the virus stops replicating inside macrophages. Eventually, most T cells are killed,

but a fraction survives, adopting a memory phenotype, serving as a viral reservoir. The depletion of T helper cells is precisely what makes the virus so deadly (Brooks et al, 2016). When the innate immune system fails, the adaptive immune system must purge the infection. This is, however, almost impossible to do without the aid of T helper cells. T helper cells stimulate B cells to produce antibodies, and guide the polarization of the immune response. Furthermore, they create positive feedback loops that produce more of the same type of T helper cell, further promoting effectiveness. If this mechanism is disrupted, producing an effective adaptive immune response becomes virtually impossible (Brooks et al, 2016).

Even if the immune system detects the virus in time and kills infected cells, nothing changes.

Because of the error-prone nature of reverse transcriptase, the antigens on the virus that the immune system targets begin to change, and pathogenesis progresses until the state of T cell depletion occurs, making patients vulnerable to even minor infections.

Management of HIV is done through antiretroviral therapy. Many work by inhibiting viral proteases, which are essential for viral replication. Other drugs work by blocking viral entry into the cells. Integrase inhibitors prevent HIV DNA integration into chromosomes. While these cocktails have proven effective in dramatically reducing viral loads and promoting

patient survival, none have ever cured HIV-1 infection. Furthermore, as with any infectious disease, drug resistance can result, which is especially frequent in perinatally infected patients (Brooks, 2016, p. 652). PrEP is useful for preventing HIV transmission in individuals who have partners with the virus, which works by inhibiting reverse transcriptase, and is 98% effective (PrEP, 2016).

Vaccination seems like the most practical solution to HIV. However, vaccine creation is profoundly challenging, especially for a virus.

Viruses are smaller than bacteria, and have fewer epitopes (a region of the virus that the immune system can specifically recognize, typically an amino acid sequence), which makes them less immunogenic. Furthermore, HIV is particularly prone to mutation, so the vaccine has to target a constant region on the virus, one that isn?t prone to mutation. Another challenge with the virus is that it is not expressed in all infected cells. Thus, the immune system might overlook it. A major part of vaccine discovery has to do with finding an appropriate animal model, and for HIV the only one is chimpanzees, which, do not develop immunodeficiency from the virusonly viremia and antibodies.

In constructing a vaccine, the goal is to produce broadly-neutralizing antibodies (BnAbs): antibodies that will recognize the pathogen in as many strains as possible and mark it for destruction. A recent paper by Bruel et al in Nature Communications proposes antibodies that target the CD4-binding site, the glycans/V3 and V1/V2 loops on gp120, or the gp41 moiety. The results are quite promising. The goal is to use antibody-dependent cytotoxicity (ADCC) to destroy infected cells (Timothy, B. et al., 2015, p. 2) The strategy was to employ antibodies that would target the latent viral reservoir. The antibodies discussed in the paper work by NK cell recruitment, which are members of the innate immune system that sense altered expression of MHC class 1 and KARs that signal them to destroy infected cells (Janeway, 2012, p.

112-115). The antibodies are of the IgG1 isotype, which are the most abundant isotype in sera, making them a useful choice for targeting in a vaccine. Many antibodies successfully prevented transfer of the virus between cells (Timothy, B. et al., 2015, p. 2). Despite this progress, there is still the matter of eliciting these antibodies, which is where most of the issues arise. Vaccines have adjuvants that promote immunogenicity, but alum

Figure SEQ Figure \* ARABIC 1 HIV viral structure and genome (Brooks, 2016, p. 641)

is the only one approved for human use, and it is not as effective as certain other adjuvants (Janeway, 2012, p.721). Use of native antigen trimers on the virus as epitopes is garnering attention (Steichen et al, 2016, p.1). Steichen et al designed a method to target B cell precursors directly to produce bnAbs (2016, p.1). As we make new discoveries about possible sites on the virus useful for vaccination, the attainment of a vaccine seems more feasible, but BnAbs have existed since 1992 (Mascola and Hayes, 2013). HIV is clearly smart, but we are becoming smarter.

HIV is as fascinating as it is deadly. If we want to see global eradication of AIDS, a vaccine is the only path that can lead us there. Despite the challenges, it seems that we are closer than ever to cornering this blight that has eluded us for decades, and that is truly exciting. BnAbs have been identified. Methodology to induce them in vivo is being designed. Work remains to be done, but it seems we are closer than ever.

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Wai ti ng for Care: The Draw back s of the Canadi an Healthcare System

By Alex Gordon

Many consider access to healthcare to be an important metric of a nation?s prosperity. In recent years, the Canadian healthcare system has received much praise for its ability to ensure widespread access to care. Additionally, Canadians enjoy mostly free healthcare, which is in direct contrast to the models of other countries such as the United States. While these aspects of Canadian healthcare appear to be ideal, it is not a perfect system and has its own unique set of complications and criticisms, perhaps the greatest of which is the notoriously long wait times.

The Canadian healthcare system is funded through the collection of taxes. Private physicians provide the majority of services, but the government dictates the fees for a given service.

The disproportionately low number of doctors in Canada is often attributed to this price determination. Additionally, publicly funded hospitals are responsible for providing hospital services. Most medical services are covered under this system, with the exception of many non-essential services such as cosmetic surgery and some elective surgery. For example, the circumcision of newborns, unless medically required, is not covered. While the range of services covered is quite considerable, Canadians (except the elderly) need to pay for medications, dental care, and eye care out of pocket or with private insurance. Still, the range of services offered free of charge to Canadians is quite considerable, especially when compared to healthcare in the United States.

While the Canadian healthcare system has many positive aspects, these are offset by the long wait times to receive services. Generally, life-threatening emergency cases may be treated immediately, but non-urgent patients may wait several weeks or months for care. According to a study by the Fraser Institute, a Canadian public policy group, the median wait time to see a specialist physician after receiving a referral from a general practitioner was 18.3 weeks in 2015.

While long wait times may not be problematic in every case, it certainly is in the case of serious illnesses, such as cancer. The Fraser Institute also found that patients waiting for radiation oncology treatment experience a median wait time of 4.1 weeks. Though this is less than the median wait time to receive any specialized treatment, it is a long enough time to impact patient outcomes; even treatments for non-emergency cases, such as cancer patients, are much more effective when introduced early in the

progression of a disease. Additionally, even simple diagnostic scans have long wait times; Canadians can wait a median of 4.0 weeks for a computed tomography (CT) scan or 10.4 weeks for a magnetic resonance imaging (MRI) scan. These wait times can greatly delay the start of a patient?s treatment.

Interestingly, there are many who defend the Canadian healthcare system, claiming that the wait times are not entirely detrimental and that in some cases, they can reduce the risks of morbidity and mortality. For example, waiting lists allow higher risk patients to receive treatments before other patients, and prioritizing these patients can improve overall patient outcomes. Additionally, some believe that the time between referrals and operations allow doctors and patients to better assess whether the operations are truly necessary.

Lastly, many have argued that the universally long wait times have reduced the healthcare discrimination against low-income and uninsured patients, who often experience delays in receiving care in countries like the United States.

One consequence of the wait times in Canada is that some patients are seeking treatment at private medical centers, paying out of pocket for services that would normally be free at public hospitals. In a sense, these patients have paid for their services twice; in addition to the fees, they have paid into the healthcare system through their taxes. Still, this may be the best option for patients who cannot risk waiting for availabilities at public hospitals. This has been the subject of much controversy as of late because the Canadian government has threatened to fine or shut down some of these hospitals. According to the Canada Health Act, which contains the guidelines for the Canadian healthcare system, it is actually illegal for hospitals and doctors to charge fees for otherwise covered services; however, some private hospitals have been successful in court, arguing that ?the prohibition on obtaining private health insurance is not constitutional where the public system fails to deliver reasonable services.?

Like any other system of healthcare, the Canadian healthcare system has its advantages and disadvantages. Essentially, these benefits and drawbacks can be boiled down to a tradeoff between more universal access to care and wait times to receive care. Ideally, all Canadians would be able to efficiently receive services from the system they are required to fund. Hopefully, Canadian reformers will be able to reduce wait times while maintaining the accessibility of care.

11

Contemplati ng Di etary Supplements

By Klaudi o Haxhi llari

Dietary supplements are exactly what the name implies; they are additions to your diet in the form of vitamins, minerals and herbs. According to the National Institute of Health (2011), the majority of adults in the United States consume one or more dietary supplements regularly. Since supplements are frequently used, it is important to understand when it is necessary to consume them.

Often times, supplements are viewed as a risk-free alternative to prescription drugs; however, this is not usually the case. While supplements can have great health benefits, they also can have a varying range of side effects, occasionally with great severity. Additionally, like prescription medication, supplements can have serious precautions and interactions with other medication.

It is estimated that in 2007-2010, only 23% of all supplements were used at the recommendation of a health care provider (Bailey, Gahche, Miller, Thomas and Dwyer, 2013). This is likely because supplements are readily available at drug and retail stores without the need of approval or a prescription from a doctor. Sometimes people take supplements because they are encouraged to do so by someone close, such as a friend. While some

may experience benefits from a supplement, it does not mean that taking a particular supplement will be beneficial for everyone. There are a variety of reasons why a supplement may help you based on your body chemistry and your own nutritional deficiencies. If you are not deficient in that in which you are supplementing in, then it may not provide a benefit. Instead, it can end up harming you due to potential side effects.

If you have symptoms of a disease or disorder, you should consult your physician. Supplements should never be used based on your individual decision on how to cure a condition. For example, supplement companies may heavily advertise and claim that if you have a certain problem, you may see improvement with a particular supplement.

However, in many cases, the supplement may not be strong enough, which can lead to the progression of a disease or a decreased quality of life if you do not receive prescription medication with the correct strength to help you.

St. John?s wort is a common supplement that people use to help combat depression and is an example of a supplement with potential side effects that has been shown to be very similar to the

antidepressant medication, f luoxetine (Hoban, Byard, and Musgrave, 2015). This dispels the myth that all supplements are risk free. Also St. John?s Wort, like other antidepressant medications, increases serotonin in the body so there is an important precaution to not take other SSRIs with it. This is to ensure that users do not end up with serotonin syndrome which results from taking two drugs that increase serotonin levels simultaneously and can have effects ranging from diarrhea to seizures. This is one example, out of many, that supplements can have potentially harmful side effects and where the precautions must be taken seriously.

Another hazard with using supplements to self-treat conditions is that supplements are not regulated in the same way that drugs are.

Supplements do not have to pass equivalent safety and effectiveness requirements as medications in order to be approved for treatment. As the American Cancer Society (2015) describes, ?drugs are considered unsafe until proven safe? while ?dietary supplements are considered safe until proven unsafe.? This allows for supplements that are hazardous and not well-studied to be placed on the market.

There is strong evidence to show that some supplements do not contain the chemicals that they claim and instead contain fillers. In 2015, the New York State Attorney General?s Office found that the majority of the store branded supplements did not contain the ingredients listed and instead used various fillers and other ingredients that could be dangerous to people with food allergies (Cease and Desist Notification, 2015). Additionally, prior research showed that about a third of supplements that were tested contained fillers instead of their listed ingredients (Newmaster et al., 2013). This is a waste of money for consumers and can

potentially be unsafe. If one supplement container included the correct ingredients and the next container purchased did not, a condition may abruptly reappear and go untreated for some time.

Supplements are also not always of the same quality because of limited regulations. Storage plays a critical role in some supplements and this is not always taken care of effectively. For instance, the common supplement, fish oil, is known to provide great benefits to heart and brain health.

However, this only applies if the fish oil capsules have been stored in optimal conditions. Fish oil can become rancid from oxidation when exposed to excessive air, heat or light. If rancid fish oil is ingested, the free radicals from oxidation can end up harming your body.

Supplements should also not be taken in place of food that contains necessary vitamins and minerals for your body. They should only be taken if it is not possible for you to take the recommended amount through the food available to you. For example, new research shows that people who took calcium supplements were 22 percent more likely to develop plaque in their arteries (Anderson et al., 2016). This increased risk does not occur when calcium is ingested through food.

As noted earlier, supplements can have interactions with other medications, cause moderate to severe side effects, and call for important precautions. They can range in quality and even validity of ingredients. Since supplements do not usually require a prescription, it leaves you the freedom to discuss whether a particular supplement is right for you with your doctor. Due to the side effects that taking a supplement may have, it is strongly encouraged that you always take the opportunity to discuss with your doctor whether a particular supplement is right for you.

13

Aducanumab: New Treatm ent for Mank i nd?s Most Infam ous Neurologi cal Di sease

By Jonah Klapholz

Alzheimer?s disease is the most common form of dementia, a host of neurological diseases characterized by the atrophy of select parts of the cerebral cortex and subcortical structures in the brain. The most observable sign of the disease is cognitive decline. As their brains deteriorate, patients forget fundamental aspects of themselves and descend into alternate realities. For most of its history since its discovery in 1906, Alzheimer?s has been mysterious. Doctors and scientists devoted decades to searching for a mechanism, only to

emerge in disappointment. Progress towards clarifying the mechanistic aspects of Alzheimer?s on a molecular level has only occurred only in the last 40 years. The first Alzheimer?s drug trial did not occur until 1987.

Researches had no understanding of any genetic link to Alzheimer?s until 1993, when they identified APO-E4, a gene that raises susceptibility to Alzheimer?s. And the FDA did not put Alzheimer?s drugs on the market until 1993 (The Alzheimer?s Association).

Discoveries in Alzheimer?s research have become more abundant throughout the last 40 years and have looked increasingly at how the disease operates at the molecular level. The first and one of the most important discoveries regarding the molecular mechanism was in 1984, when researchers found that Alzheimer?s patients had abnormally high concentrations of a protein called Beta-amyloid in their brains. Further insight led researchers to discover that Beta-amyloid accumulation is an essential component in the development of Alzheimer?s disease. Proteins gather together outside neurons in various cortical regions and form insoluble fibers resistant to enzymatic degradation. As the disease progresses, the fibers accumulate into plaques that create neurofibrillary tangles, choking neurons and preventing them from communicating with one another. Plaque buildup eventually blocks nutrient uptake in neurons, causing them to atrophy and die (Rambaran, Serpell 112-113). Neuronal death creates the characteristic cognitive deficits associated with Alzheimer?s disease.

While many medications designed to target Beta-amyloid accumulation have entered the market since 1993, none are curative. However, although researchers have yet to reverse the disease, in September 2016 it was reported that there may be a way to slow it down. In a large-scale placebo-controlled study funded by Biogen, a biotechnology company that specializes in neurodegenerative diseases, researchers found that the antibody aducanumab significantly reduces the amount of Beta-amyloid plaque buildup in Alzheimer?s patients (Sevigny et al. 50).

All drugs aimed at Beta-amyloid removal have shown little success until Jeff Sevigny and his colleagues published their study in Nature. The 165 patients who received aducanumab as part of the study showed significantly less cognitive decline over time in comparison to untreated Alzheimer?s patients. Moreover, PET imaging revealed significant reduction in Beta-amyloid across multiple treatment groups, varying by dosage. At the highest dose of 10 milligrams per kilogram of body weight, patients became Beta-amyloid free after twelve months. This led

researchers to assume that the drug slowed cognitive decline by almost 70 percent (Sevigny et al. 52).

A f lurry of positive media attention followed the study?s release. Andrew Pollack of the New York Times described the trial as, ?Reviving the hopes for an approach to therapy that until now has experienced repeated failures? (Pollack). However, the optimism surrounding the study overshadowed some of its shortcomings (Adams). For example, the Sevigny et al. study only involved patients in the early stages of the disease and produced no data on late-stage Alzheimer?s patients who cannot live without aid (Sevigny et al. 50). This suggests that the drug would only be effective in certain types of Alzheimer?s patients. Moreover, the study did not actually measure the cognitive abilities of the patients, but rather Beta-amyloid destruction (Adams). Additionally, the drug presented side effects in many of the patients in the study.

Aducanumab caused localized areas of swelling in the brains of participants who had a preexisting genetic risk for developing Alzheimer?s. Dr. Thomas Wisniewski, a neurology professor at NYU Langone Medical Center stated, ?Most clinicians would find that unacceptable.?

Thirty-five percent of the high-dose patients dropped out of the study because they experienced swelling at lethal levels (Pollack).

Biogen, the manufacturer of aducanumab, has downplayed the severity of the drug?s side effects.

The study that it funded was only successful for only certain Alzheimer?s patients, and results remain controversial. Biogen, like Pfizer, Johnson & Johnson, AstraZeneca, and other pharmaceutical companies before it, has poured billions into Alzheimer?s research to yield controversial or disappointing results. And Alzheimer?s is on the rise. It will continue to increase in prevalence as the largest American generation ever ages.

Biogen?s moderately successful study may not come close to solving this problem, but it shows that researchers are beginning to tackle Alzheimer?s at the molecular level. While aducanumab represents a baby step, as the American population ages, the progress of Alzheimer?s research make remains to be seen.

15

How M edi cali zati on i s Changi ng Our Percepti on of The ?Ill?

By Sophi a Shi

The proliferation of scientific and technological advances in the past few decades has brought about a surge in the authority of the medical field in our lives. As a result of the creation of new medical labels and changing thresholds for diseases, an increasing number of regular human issues are becoming recognized as medical conditions in need of treatment. This phenomenon, known as medicalization, has changed the way people view those newly labeled as diseased.

The simple act of referring to bad breath as halitosis or low sexual arousal as sexual dysfunction distorts perceptions of a person with the condition. A study conducted to assess these differences found that students believe that a recently medicalized disease is more severe and rarer when it is called by its medicalized name rather than its common name (Young, Norman, & Humphreys, 2008). This unconscious shift in perception has not only caused more people with these medicalized disorders to see themselves as in a more critical state and make them more likely to seek out treatment, but has also had numerous side effects on how the public views them.

One of the primary arguments for the benefits of medicalization is its role in reducing stigma

towards those with certain disorders. The reasoning is that increasing the public?s understanding of various human issues through a biological explanation should reduce negative attitudes and misconceptions about those conditions. For instance, in the past, those who experienced symptoms of sexual dysfunction often carried a feeling of embarrassment due to very minimal discussion about the medical basis of the condition.

However, once sexual dysfunction became recognized as a disease and drugs like Viagra came out on the market, sexual dysfunction has become commonplace in society and has less stigma associated with it (Conrad & Leiter, 2004).

While creating medicalized diseases has decreased stigma in some cases, other studies have found the opposite effect to be true when looking at other conditions (Payton & Thoits, 2011; Buchman, Borgelt, Whiteley, & Illes, 2012). One particularly significant decision in the debate over medicalization was the labeling of obesity as a disease by the American Medical Association in 2013. There was significant backlash over this statement by many people with obesity who felt like the decision represented the public shaming fat people based on their bodies (Goldberg, 2014).

The act of categorizing people with disorders may increase perceptions of differences between people,

and thus result in adverse attitudes and stereotyping (Corrigan, 2007). Therefore, by labeling someone as medically ill, society may be widening the door for stigma to be at play.

The greatest stigma, perhaps, is inf licted on those with mental disorders. Many studies have shown that the public is more inclined to feel someone is dangerous if labeled with a mental illness (Kavaale, Haslam, & Gottdiener, 2013). The Diagnostic and Statistical Manual for mental disorders has been expanding their classifications of diseases with each new edition, leading to more and more people being identified as mentally ill.

The increase in awareness of new mental illnesses has been important in reducing the amount of blame and responsibility placed on subjects who are not fully in control of their actions because of a serious mental disorder (Kavaale et al., 2013). This effect, however, can be taken advantage of when people use a medical label as an excuse for unruly behaviors and fail to take responsibility for their wrongdoings such as in the case of crime. In 2008, a museum historian who had stolen important historical letters tried to use bipolar disorder in an insanity plea (Akasie, 2008). However, the court

did not accept his plea stating that he could not use bipolar disorder as an excuse for not knowing right from wrong (Akasie, 2008). This demonstrates some concerns with expanding the definitions of mental illnesses to encompass too broad a range of disruptive actions.

In fact, the concept of medicalization established in the 1960s and 70s was first used to criticize the body of thought that most delinquent behavior had psychological causes and required a similar form of treatment as used to treat mental patients (Poitras, 2012; Conrad & Schneider, 1992). Today, medicalization is used far more broadly to describe a variety of human conditions turned medical and the phenomenon continues to grow without any foreseeable endpoint.

Understanding its effect on how we perceive those with medicalized diseases is crucial not only for the recovery of those with actual disorders, but also for the public to be more aware of the negative impacts medical labels can have on our treatment of such individuals. While medicalization is not inherently good or bad, it will continue to have significant impacts on our society that we must be aware of in this increasingly medical world.

17

Controversi al Cutti ng: The CRISPR-Cas System i n Sci ence and Medi ci ne

By Ak i la Venk ataram any

Genetic engineering is one of the most popular fields of research in today?s day and age, promising life-changing advancements in the sciences. Most of the interest in genetic engineering surrounds stem cell research and medicine, where scientists are looking to fight the battle against cancers, genetic diseases, and antibiotic resistance. The discovery of the CRISPR-Cas system is revolutionizing the way researchers approach genome editing, and it promise to change the future of both research and medicine.

The CRISPR-Cas system is not an invention by any means; prokaryotes have used this as part of their adaptive immune system long before its discovery. CRISPRs, or clustered regularly interspaced short palindromic repeats, all have the same genetic sequence. When an invading virus enters the bacterium, segments of its DNA are

inserted amongst the CRISPR regions. Creation of CRISPR RNAs via transcription allows the RNAs to act as signaling molecules for the bacteria to begin destroying the virus. When another virus molecule attacks, the Cas enzymes, which are nucleases essential for CRISPR function, act alongside the CRISPR RNA and search for viral DNA in the cell. The RNA, once it encounters viral DNA, attaches tightly and causes the Cas enzyme to destroy the virus before it can cause damage to the bacterium1. This evolved method confers strong immunity and protects these small organisms from a variety of pathogens.

Because the CRISPR system essentially allows for targeted gene recognition in bacteria, scientists have harnessed its power for genomic editing. Jennifer Doudna and Emmanuelle Charpentier, along with other key researchers, discovered that RNA molecules can program the

Cas9 endonucleases to cleave specific nucleic acid sites. The CRISPR-Cas9 system can therefore be used as an editing tool to precisely change a genome in any organism. If scientists design the appropriate RNA molecule to match the specific DNA they are targeting, the gene sequence can be silenced or even edited. Since mutations and gene edits are often random or the result of errors in the DNA, the CRISPR-Cas9 system allows researchers to simulate these events and study the effects of gene malfunctions.

The discovery of CRISPR-Cas9 has changed the way researchers approach medicine and curing genetic diseases. By using the editing mechanism to remove parts of the genome or insert the appropriate DNA sequence that codes for defects or mutant genes, symptoms of diseases could be reversed. In October 2016, researchers at University of California, Berkeley, UC San Francisco Benioff Children?s Hospital Oakland Research Institute, and the University of Utah School of Medicine showed that CRISPR-Cas9 could correct the Sickle Cell mutation that causes Sickle Cell Disease. They synthesized RNA and a DNA oligonucleotide donor to replace the mutation in CD34+ hematopoietic stem/progenitors. As a result, the cells produced less sickle cell hemoglobin and more normal hemoglobin. Since Sickle Cell Disease is caused by a single mutation, this research promises an efficient cure and hope for researchers to consider this approach for other blood disorders with a single mutation.

The ethics of using CRISPR-Cas9 in genomic editing is more controversial surrounding the use of human embryos to edit the human genome.

Jinjiu Huang at Sun Yat-sen University in Guangzhou led a team of scientists in a contentious study using non-viable embryos. They attempted to correct the gene that encodes ?-thalassemia, a fatal blood disorder, using CRISPR-Cas9. In the 71 embryos that they tested, only 54 were viable for testing, and 28 out of these had the gene successfully corrected. Along with the lackluster result, the CRISPR editing mechanism introduced new mutations into the embryos, the effects of which would be unknown until the embryos developed further. This prompted the research group to halt their studies until the technique can be fully perfected. The scientific community is hesitant to encourage this type of this research; in

fact, both Nature and Science, perhaps the two most respected scientific journals in the entire research community, previously rejected the paper detailing Huang?s results due to the ethical backlash. If these prestigious journals refuse to acknowledge research surrounding CRISPR-Cas9 in humans, scientists doing this type of research may find extremely limited support, thereby slowing any progress for its use in medicine.

Several summits and discussions with scientific authorities from the United States, Britain, and China took place in December 2015 to figure out how to best proceed in CRISPR-Cas9 research involving human embryos. These researchers reached the conclusion that while CRISPR-Cas9 research is important in furthering knowledge about gene editing, it poses serious ethical risks that must be taken into account.

Somatic cells, which do not reproduce into the next generation of cells, are better options to study this system. Furthermore, any medical treatments that result can be rigorously regulated, and the recipient of the treatment can weigh the pros and cons before receiving it. However, using germline cells, those that would be replicated for the next generation of cells, without elucidating the many risks involved would be irresponsible. For example, generating embryos with heritable genetic changes could have irreversible consequences in evolution. Based on these points, the researchers agreed that an ongoing international forum is necessary to create appropriate regulations for this research and also to publicize any concerns. This forum has been making decisions on studying CRISPR-Cas9 since its inception; in February 2016, with the permission of this committee, British researchers have begun studies with CRISPR-Cas9 and human embryos, but they now have to destroy the embryos after seven days. Regulation of the CRISPR-Cas9 studies shows the trepidation researchers have with exploring the limits, or lack thereof, with gene editing.

The use of CRISPR to target specific genes has a strong future in science; the power to edit a genome has never been as easy or accessible.

However, the ethics of using this for human research is still debatable. Whether or not the science community, along with the entire human population, will readily accept genomic editing research is yet to be seen.

19

The Role of NSAIDs i n Healthcare

By Kevi n Hui

Drugs and medicine usage are becoming more and more prevalent among general populations in the United States. According to the National Health and Nutrition Examination Survey in 2012, prescription drug use in US adults increased to 59%, compared to 51% in 20001.

These numbers do not even take into consideration the vast number of over-the-counter drugs that are available. Among the list of OTC drugs, NSAIDs, or nonsteroidal anti-inflammatory drugs, remain the most widely-used within the American population. Some of the most well-known drugs, aspirin and ibuprofen, are classified as NSAIDs and have become ubiquitous as the "cure all" as an analgesic, with approximately 43 million US adults (19%) claiming to be regular users of aspirin2.

Besides over-the-counter use, NSAIDs also play a critical role in the hospital setting, as pain relief is one of the most important factors considered in patient care. Despite this, a growing body clinical research studies into the full long-term effects of NSAIDs are not all positive, and it provides a much more balanced observation into their effectiveness and drawbacks. The results gathered from these continued studies allow us as consumers to developed a much more unbiased opinion towards

these "cure all" drugs.

The potential risks linked to NSAIDs occur from how the drugs interact with the body. The primary process through which NSAIDs work is by inhibiting the enzymes that produce prostaglandins, called COX-1 and COX-2.

Currently, there are two types of NSAIDs. Earlier developed NSAIDs target both enzymes, while some newer forms of NSAIDs, called coxibs, selectively target the COX-2 enzyme3. Though ultimately these two forms generate the same response, slight differences can create various side effects and risks from each form.

Within the United States alone, over 30 different NSAID compounds have been marketed to the public. The large number of compounds reflect that longstanding tradition of NSAID usage in the United States, with each newer compound seeking to improve efficacy while simultaneously limiting the side effects of the drug. But with every improved iteration, the associated side effects are a continued issue in the United States, with treatment using NSAID drugs causing 50,000 to 100,000 excess hospitalization cases each year5. One of the biggest drawbacks towards the use of NSAID drugs

are the potential complications they can cause to the gastrointestinal (GI) tract. A 2011 study performed by the Spanish National Health System showed that approximately 74% of patients with osteoarthritis with elevated risk for GI related side effects were receiving NSAIDs6. Because NSAIDs act as a weak acid within the body, they are particularly damaging to the mucosal lining of the stomach, where they can cause epithelial damage.

This can lead to bleeding and ulcers, which is one of the most common drug related side-effect in the United States7. This is particularly true for patients who are admitted due to GI complications, which poses an issue for hospitals that rely greatly on NSAIDs as the main source of pain relief for their patients, leading to inappropriate prescription of NSAIDs. Furthermore, along with GI complications, many studies also point towards the potential increased risk of cardiovascular issues. This is particularly true for patients who have previous histories of cardiovascular disease and may be prescribed NSAIDs for pain relief. According to a clinical research study in 2006, in a population of patients who have previously had a heart attack, any usage of NSAIDs increased their chances of mortality and rehospitalization8. The focus of these risks seem to be isolated in coxib NSAIDs

only. The product of COX-2 enzymes are responsible for platelet aggregation, vasoconstriction, and vascular proliferation9. By inhibiting these processes, patients are more susceptible to "exaggerated thrombotic response", which exacerbates previous presence of cardiovascular disease10. Fortunately, NSAIDs that demonstrated a drastic increase in these cardiovascular adverse events have been withdrawn from the market. Overall, these studies provide insight into NSAIDs that must be considered by physicians and patients alike when considering various outlets of treatment.

Despite the potential negative side effects, NSAIDs remain one of the most popular form of pain relief drugs on the market. Their efficacy towards pain management has made them one of the most commonly used drugs in the world11.

Many extensive marketing campaigns made by major drug companies have only accelerated this process, with NSAIDs account for nearly $10 billion in worldwide sales12. But ultimately, we as consumers need to decide whether or not to utilize NSAIDs. With the omnipresence of NSAIDs in both over-the-counter and in hospitals, knowing all the risks associated with their use allows us as consumers to make the most educated decisions for our treatment.

21

M ale Reproducti ve Potenti al and Phthalates: A Potenti al Danger from Everyw here?

By Ibraheem Rehm an

Female infertility is not only a commonly known issue, but it is also extensively researched.

Did you know that 1 in 8 couples in the world experience fertility issues? There are more than 1 billion couples in the world, which means that about 125 million people cannot conceive a child.

Furthermore, almost 40% of the infertility cases are due to male factors, not female factors.

However, male infertility and its causes are a less researched area compared to female infertility.

Recent research has shed some light on some environmental and lifestyle associated factors that can possibly lead to reduced male reproductive ability by negatively affecting sperm quality or the balance of key hormones in the body.

Environmental factors include Endocrine Disrupting Chemicals (EDCs), molecules such as Bisphenol A, Alkylphenols, certain pesticides, and phthalates. Lifestyle associated factors include obesity, tobacco smoking, alcohol addiction, substance abuse, stress, excessive heat and possibly even the electromagnetic radiation from your cell phones!

This article could not possibly explore all of these factors, so it will focus on phthalates, a type of EDC. We must keep in mind that this is just one factor and that a multifactorial approach would give a better depiction of the full extent of the damage on male fertility, but since phthalates are so prevalent it is worthwhile to focus on them.

Phthalates are esters of phthalic acid and belong to a group of chemicals known as peroxisome proliferators (PPs) [1, 2]. They act through Peroxisome Proliferator-Activated Receptors (PPAR), which are transcription regulators of key genes [1, 3, 4]. These genes are responsible for the synthesis of proteins which are essential in the development of the male reproductive system and production of testosterone [5]. Phthalates act through PPAR?s to cause hypospadias, cryptorchidism, a decrease in Anogenital distance, degradation of the testes or hepatocyte proliferation [1, 3, 7].

The commercial use of phthalates is to plasticize, or soften plastics such as Polyvinyl Chloride (PVC) [3]. Phthalates are highly prevalent in many commonly used objects such as gelling agents, lubricants, credit cards, food containers, notebooks, paper clips, tape, many types of clothing, cosmetics, nail polish, shampoo, children?s toys, and pacifiers [6]. It is impossible to go even one hour without in some way coming in contact with phthalates. Phthalates are not covalently bonded to plastics, and can easily enter the environment causing impairment to the male

reproductive system [1, 7]. Furthermore, they can easily enter the human body through respiration or dermal absorption [8]. There are several types of phthalates, some of which include DEHP, DINP, DBP, and Finasteride. Most metabolites are biologically more active than their diester phthalate counterparts [9]. Some phthalates have destructive effects on the male body; whereas others pass through the body without causing any significant harm. The relationship between phthalates and male reproductive health has been controversial [10]. Nevertheless, many clinical conditions are caused by Phthalates disrupting the physiological function of the male reproductive system by hindering the development of the testes or the male reproductive tract [1].

Phthalates therefore have the potential to impair fertility and reduce the quality of sperm.

According to the World Health Organization (WHO), semen analysis consists of sperm count, sperm concentration, sperm motility, sperm morphology, and semen volume. Although the exact mechanism of how phthalates cause their effects is still being studied, a large number of research studies have shown that certain phthalates can affect these parameters.

Phthalates are very common in the lives of most individuals, regardless of one?s gender, location, or age [17, 18]. Not only is it impossible to hide from phthalates, but it is also very easy for them to enter our bodies. Many animal studies have shown that phthalates cause higher occurrences of reproductive developmental anomalies [12, 14].

However, most of these studies were conducted on rats, whose physiology cannot be exactly compared to humans. A number of studies on humans have shown that phthalates can cause reproductive diseases, but also decrease sperm quality [9, 11, 13, 15, 16]. At the same time, a few human studies report that phthalates had no significant effect on the male reproductive system. However, these articles show that phthalates are generally a threat to male reproductive health around the world, but results have been inconsistent.

In conclusion, people, especially pregnant women, should avoid phthalates as much as possible because of the dangers of in utero exposure, men should be aware of the possible adverse effects EDC?s can have on their reproductive ability, and factories that use phthalates should try to find an alternative source.

This is easier said than done but it would be for a cause of great importance. After all, from a purely evolutionary perspective, reproduction and survival into future generations is the purpose of life.

23

Genomi c Decodi ng of Superbugs

By Dani el Szabo A pathogen with no treatment options. This nightmare is a real concern in the medical community. It is clear that pathogenic resistance to commonly prescribed treatments is increasing. An incomplete elimination of the pathogen, the disease causing agent, due to ineffective treatment concentration in the body affords the bug proliferation of its more resistant forms. Scientists must work within small time frames to produce treatments that replace their ineffective predecessors. While physicians have a variety of treatments available for most bugs, there are a few that have achieved total resistance to all, and their numbers are growing. Existing methods, such as new drug discovery, for limiting the spread of multi-drug resistance (MDR) are inadequate. The scientific community must develop and incorporate other technologies in this fight. One promising development is the real-time decoding of pathogen genetic material, which yields valuable information on how to effectively combat it.

The idea of processing pathogen genomes to

identify weaknesses is not new. In fact, the first complete decoding for a bug was completed in 1995, over twenty years ago. Whole genome sequencing (WGS) is a procedure in which an organism?s entire DNA is cut into readable pieces and are all run through a sequencer, capable of organizing the information into a readable sequence. The output is registered into a larger database. The complete sequencing of a bug?s genetic information is an enormous task though, which prevented its widespread use until better technologies developed. The focus shifted to alternative treatment strategies, such as drug development. Drug development companies refine their effective drug search with uncovered genetic vulnerabilities, but the bugs change too rapidly for their treatments to stay effective for long.

Discoveries are being outpaced by resistance, so there is a need for change. With the improvement of methods and technologies for real-time, WGS of pathogens is a promising countermeasure outside of drug development. WGS used to take weeks and several thousands of dollars. According to The

Guardian (2014), it now takes less than a day, and costs less than $125. Advances in WGS makes participation in the database tenable for labs, a requirement for a current, effective database. The comparison between individual results and the database provides the doctor important information related to the patient?s care and reduces transmission chance in outbreaks.

Diagnosing a patient with a specific illness is challenging, but knowing what medication to prescribe is nearly impossible. A single bacteria or virus can present drug resistances that are unique to each infected person. Currently, doctors prescribe a concoction of drugs to eliminate the pathogen, with the hope that it is susceptible to at least one. This method promotes resistance to all of the prescribed drugs, including in the body?s non-pathogenic bacteria or viruses.

Additionally, ingesting several antibiotics damages the bacteria important to your body in processes like digestion. An advantage of a real-time, WGS is that it can tell physicians what resistances the disease-causing agent has. The DNA processed from the bugs includes even plasmid DNA, circular strands of DNA that confer bacteria their resistances. The amino acid sequence collected from the patient is compared to a library of genes that are responsible for drug resistance. If the sample sequence matches a sequence in the database, the pathogen has the associated resistance. Based on those results, the physicians will prescribe only effective drugs, limiting exposure and resistance to the other drugs.

In outbreaks of a pathogen, an essential first step is to determine its path of transmission. If a pathogen?s pathway can be tracked, sources of future transmission can be located and isolated.

Normally, the ?family tree?, a vertical web illustrating the pathogen?s transmission, is created by interviewing the infected people about their actions leading up to and after the infection.

Relying on their statements results in inaccuracy, an issue that can be eliminated by rapid genome sequencing. In a whole genome there can be billions of bases, and in every generation a number of them will mutate, described as the background mutation rate.

Frequently, the mutation has no effect on the organism and is inherited by its progeny. A pathogen in a new host retains the same characteristic mutations from the one in the previous host. If their whole sequences are compared, they will be identified as closely related, and an accurate ?family tree? can be constructed. In 2013, the United States government adopted WGS to track and control Listeria monocytogenes (Lm), a foodborne illness, in real-time.

Microbiology labs now submit Lm genotypes from patients to a national database, where they are cataloged and compared. The number of solved outbreaks has increased dramatically: two outbreaks in pre-WGS year, five in WGS year one, and nine in year two (Jackson et. al, 2016). WGS is now being implemented for other pathogens.

The world anguishes about increasing drug resistances leading to superbugs. It is essential that we explore all avenues for combating this trend, a process that we, as emerging scientists, will contribute to significantly. Whole Genome Sequencing may become an invaluable tool at our disposal. It can be used to inform physicians of unique pathogen traits, and suggest treatments. Genotypic variation can be excellent for tracking outbreaks to their source. The WGS procedure carries promise, but its future is unknown. The pathogens are winning the fight, but the war is up to us.

25

IBM Watson: The Future of Medi cal Di agnosi s and Treatm ent

By Uche Ezeh

Some diseases and illnesses can be difficult to define and characterize precisely, making their diagnoses challenging. Consider diseases in which the symptoms are not immediately apparent, let alone understood. This can result in ineffective treatments. But, today?s science and technology is making it possible to reach a more accurate and comprehensive diagnosis. IBM is at the forefront of this pursuit, trying to design a system that combines human intelligence with technology to answer any query. IBM?s supercomputer Deep Blue is famous for defeating world chess champion Gary Kasparov and IBM?s Watson wowed the world 5 years ago with its 1st place victory against former Jeopardy winners, Brad Rutter and Ken Jennings. While these accomplishments have been a big leap forward in the development of cognitive

computing systems, people in the artificial intelligence community are ready to make an even greater leap by bringing this technology to the field of health care and medicine. The cognitive prowess of Watson has been appealing to clinicians and analysts because ?Watson [can] give physicians rapid clinical decision support at the point of care?

[1], which could be revolutionary.

The medical community sees AI technology as being instrumental in diagnosing patients and providing better treatment options. IBM executives argue that Watson is unique in ?that it can read and make sense of unstructured data, such as a doctor?s notes about a patient. The more data Watson reads, the more it learns, so its recommendations get better over time? [2]. This ability could potentially 26

lead to better treatment advice, especially in a field like oncology where there still is a lack of clarity and uncertainty when it comes to the understanding of cancers, especially rare cancers.

Memorial Sloan Kettering in New York City has teamed up with IBM in order to train Watson Oncology ?to interpret cancer patients? clinical information and identify individualized, evidence-based treatment options that leverage our specialists? decades of experience and research? [3]. Clinicians and analysts at

Memorial Sloan Kettering hope to capitalize on IBM?s ability to consolidate clinical research information, that would normally take years to compile, and ultimately ?integrate the latest published research with decades of longitudinal data? [and] help physicians synthesize available information, and improve patient care? [3].

Watson Oncology has already been integrated into hospitals in other regions of the world. A recent article, ?Watson goes to Asia:

Hospitals use supercomputer for cancer treatment,? revealed how Watson is being used in hospitals in Asia helping oncologists provide better treatments for their patients. Dr. Amit Rauthan, an oncologist at Manipal Hospital in the southern Indian city of Bangalore, described in the article how Waston has been of use when diagnosing and drawing up treatment plans for his patients. And while Watson frequently reaffirms his diagnoses and treatment therapies, Watson does sometimes recommend a different course of treatment. For example, Dr. Rauthan recommended chemotherapy for one of his patients who had stage 2 colon cancer.

However, Watson suggested he continue observation of the patient, rather than immediately starting him/her on chemotherapy [4]. In this case, Dr. Rathaun sided with Watson?s recommendation.

While Dr. Rauthan doesn?t disclose whether the alternative treatment was more effective, he did reassure that at the end of the day he is the person that ultimately decides what?s best for his patients.

Watson?s diagnostic capabilities are even more beneficial in regions of the world that don?t have access to the plethora of medical literature. In 2015, cancer was reported as being leading cause of death in China. Rural residents are more likely to have difficulties in accessing health care services and thus Dr. Kyu Rhee, chief health officer for IBM Watson Health, believes that Watson technology can help reduce cancer incidence and mortality estimates by increasing access to cancer care for people living those areas of the country. In addition, Dr. Qunwei Chen, an oncologist in eastern China, believes that IBM?s Watson can also be beneficial for Chinese hospitals in the small towns since usually aren?t able to attend conferences about new technologies and treatment procedures [4].

IBM?s Watson technology has also been helpful in diagnosing and providing treatment advice for other types of diseases. For example, Boston University and IBM are collaborating to help in the diagnosis and treatment of pediatric diseases. Watson is being trained on a rare form of

kidney disease called steroid-resistant nephrotic syndrome (SRNS), in which children die even before diagnosis [5]. Doctors have been unable to understand what causes genetic defects leading to the disease, but ?interpretation of sequencing results can be a labor-intensive process? [and] analysis may not always yield a definitive causative variant [5].? Christopher Walsh, MD, PhD, director of the Division of Genetics and Genomics at Boston Children?s Hospital, acknowledges the challenges of undiagnosed illnesses, but expresses optimism in Watson?s aiding to ?diagnose and cure these rare diseases so [they] can uncover all relevant insights from the patient?s clinical history, DNA data, supporting evidence and population health data? [5].

AI systems have shown great potential and capabilities, and some have become commonplace, such as GPS, Siri, Facebook?s facial recognition software, and especially Google?s search engine [6]. And in recent years, we have seen the emergence of even more profoundly capable systems of AI systems. Google and Tesla are designing self-automated cars, which are shown to be less accident prone than those driven by humans. Even though IBM Watson may possess the necessary algorithms to propose appropriate treatment plan and more accurate diagnosis, the author of the article ?Can An Algorithm Diagnose Better Than A Doctor?? argues that diagnosing is an art and ?the way the patient walks, speaks, smells, or thinks are all important to the final diagnosis? [7]. It is important to remember that the final decision still comes down to the doctor. While there is doubt that such technology can ever replace a doctor, there is certainly confidence that the doctor?s use of this technology will help in assessing all diagnostic factors to ensure that the patient receives the best care possible. No matter what direction current developments go within the field of medicine, technology cannot replace or mimic the human ability to provide unconditional positive regard and empathic understanding towards patients.

28

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