The Interdisciplinary Journal of Health, Ethics, & Policy

TUFTSCOPE THE INTERDISCIPLINARY JOURNAL OF HEALTH, ETHICS, & POLICY

A DISCUSSION WITH LYDIA X. Z. BROWN: DISABILITY JUSTICE POTENTIAL FOR WORLD’S FIRST HUMAN HEAD TRANSPLANT d 23AndMe: AT-HOME GENETIC Fall 2017 • Volume 17 Issue I TESTING JOURNAL HISTORY EDITORIAL BOARD INSIDE THIS ISSUE Since 2001, TuftScope: The Interdisciplinary Journal of Health, Ethics, & Policy has provided an academic forum for discus- Editor-in-Chief TuftScope | Fall 2017 • Volume 17, Issue I sion of pertinent healthcare and biosocial issues in today’s Neeki Parsa world. The journal addresses different aspects of health- LETTER FROM THE EDITOR care, bioethics, public health, policy, and active citizen- Managing Editor Moving Forward...... 5 ship. It is operated and edited by undergraduate students of Tufts University and is advised by an Editorial Board Michael Seleman Neeki Parsa composed of Tufts undergraduates and faculty. Today the journal is one of the few peer-reviewed, undergraduate- Senior Financial Officer Ursula Biba NEWS BRIEFS published journals in the country. Selections From Our News Analysis Blog...... 6 Faculty Advisors TuftScope Staff PUBLISHER AND PRINTER Harry Bernheim, PhD TuftScope is published by the TuftScope Journal organiza- Alexander Queen, PhD FEATURE INTERVIEW tion at Tufts University. The journal is printed by Puritan A Discussion with Lydia X. Z. Brown ...... 8 Press, NH (http://www.puritanpress.com). Junior Financial Officer Michael Seleman Akari Miki

COPYRIGHT TUFTSCOPE 2016 News & Analysis Editor BOOK REVIEW TuftScope is an open-access journal distributed under the Ted Midthun A Book Review of Mark Wolynn’s It Didn’t Start with You...... 12 terms of the Creative Commons Attribution License, which Neeki Parsa permits use, distribution, and reproduction in any medium, Research Highlights Editor provided the original author and source are credited. The Kurtis Chien-Young statements of authors within this journal do not reflect the ORIGINAL ARTICLES views or opinions of TuftScope Journal or Tufts University. New Media Editor Robots? Surgery? Robotic Surgery?...... 14 Leili Najmabadi Sachin Vallamkonda SUBMISSIONS INFORMATION Submissions on health, ethics, and policy topics from stu- Executive Manuscript & Layout Editors Smartphone App Interventions for Depression ...... 16 dents, faculty, and individuals are welcome. For more infor- David Park Kurtis Chien-Young mation please email [email protected]. Clair Li Antipsychotics in Nursing Homes...... 18 Acquisitions Editor Allison Kannam SUBSCRIPTIONS TO TUFTSCOPE Nikita Chaubal Subscriptions to the print edition of TuftScope may be obtained by emailing [email protected]. Lead Copy Editor The Plugged-In Physician...... 19 Jamie Tebeau Nikita Chaubal COVER IMAGE Copy Editors The cover image was created originally and independently Why Won’t People Eat Their Vegetables?...... 22 Rebecca Moragne by TuftScope. Cover image was obtained from the American Jesie Fu Helen Mizrach Museum of Natural History, and modified and designed by Annie Altman-Merino Clair Li and David Park, Manuscript and Layout Editors. Getting A Head: FEATURED STAFF The World’s First Human Head Transplant ...... 24 FUNDING Jacqueline Katz Helen Mizrach TuftScope is funded by grants from the Tufts Community Grace Materne Union Senate. Sidharth Anand Planarian Went to Space, Got Two Heads...... 27 Allison Kannam Annie Phan Katie Campbell CONTACT US Mohamad Hamze Email: [email protected] Alexander Pan Website: TuftScope.squarespace.com Address: Available on back cover. ISSN: 1534-7397

2 TuftScope | Fall 2017 • Volume 17, Issue I Fall 2017 • Volume 17, Issue I | TuftScope 3 INSIDE THIS ISSUE LETTER FROM THE EDITOR TuftScope | Fall 2017 • Volume 17, Issue I Moving Forward

Dear Reader, 23AndMe: At-Home Genetic Testing...... 30 Each year, the field of medicine adapts to the human body’s complexity with increasing depth and breadth; As Jamie Tebeau medical technology advances, the means by which healthcare providers apply their knowledge gradually follows suit. Healthcare moves forward by getting better acquainted with the science of the human body, but also by paying The Potential of Bexarotene and Irisin...... 32 attention to how the body interacts with its environment, both socially and physically. In this issue of TuftScope, Daniel Kaltman you will read articles that attempt to address health from three vantage points; The science of the human body and new interventions to rectify its circumstantial chemical malfunction, the social existence of the human and how we The Artificial Pancreas: A Personal Narrative ...... 34 interact with the field of medicine itself, and lastly, the importance of our physical surroundings as it pertains to our Machlan Sawden physical and mental health.

A Controversial Step Toward Life...... 36 When TuftScope published its first volume in 2001, America’s sociomedical landcape looked very different from its current manifestation. As Lydia X. Z. Brown illustrates in this volume’s Feature Interview, the history of disability Rebecca Moragne justice in America is a troubling one. In recent years, due to efforts by disability activists and organizers, the way we think about disability in the mainstream is set to gradually change, as we listen to narratives that complicate defini- The Case of the Icelandic Horse Epidemic...... 38 tions that are easy to take for granted as straight-forward. We can see the importance of physician-patient relation- Ted Midthun ships not only in these macro-consequences, but also in the seemingly small features of interaction. In her piece on the impact of internet self-diagnoses on the physician-patient relationship, Nikita Chaubal addresses the impor- A Type One Diabetes Vaccine...... 41 tance of adapting to technological changes that affect the way we interact with one another, especially in medicine. Julia Greco In an integration of a personal narrative, Machlan Sawden discusses the current state of, and concerns around the impending artificial pancreas. With the personal nature of the article, Sawden simultaneously explains the science of the artificial pancreas while reminding us how interventions designed to prolong life are often applied to patients’ daily lives in a rather invasive way. These articles illustrate the inextricable nature of human social existence and medicine.

As it pertains to physical health and medical science, in recent years we have come closer than ever to complet- Visit TuftScope online at ing the world’s first human head transplant, developed means to offer personalized gene sequencing as it has come TuftScope.squarespace.com to fruition in 23AndMe, and found a potential vaccine for type 1 diabetes. In this issue, TuftScope’s writing staff for references, prior issues, and addresses these developments. In their articles, they ask how much research has been done, what limitations the science news from our editors existing research has, and what research still needs to be done to more holistically understand the relevant issues. and contributors. To engage with the notion of the human body’s interaction with its environment, Ted Midthun and Jesie Fu discuss behaviors and circumstances that exacerbate poor health outcomes; These behaviors can range from not paying Cover image: In this issue, TuftScope explores enough attention to the origins of disease, to inadequate vegetable intake. With expanding resources and a growing several intersections of health and social justice. population of scientists and doctors, questions are being asked and answered at a record rate. In this issue of TuftS- Cover art designed by Clair Li and David Park. cope, you will get a snapshot of some of these questions and a few of their answers.

My hope for a path forward is that our questions get more complicated, and that we encounter more moral conundrums as we venture into clarifying the human body and how to best take care of it. If our questions about the human body were ever simple, we likely would not have seen the progress we are in the midst of observing today. As these questions grow more complicated, they more accurately reflect the complexity of what it means to be a human, and feel okay. Get published! Contact us at Sincerely, Neeki Parsa Editor-in-Chief [email protected] They/Them/Theirs

4 TuftScope | Fall 2017 • Volume 17, Issue I Fall 2017 • Volume 17, Issue I | TuftScope 5 NEWS BRIEFS New Insight into the Impact of Neanderthal DNA on the Modern Human Katie Campbell Selections From Our News Analysis Blog pproximately 100,000 years ago, humans began mi- Several Neanderthal alleles were observed to play a role in Agrating out of Africa to Eurasia where they interbred skin and hair appearance. Some of these alleles are involved Acquired by Ted Midthun, News & Analysis Editor with Neanderthals. Today, about 2% of non-African, human in lighter skin or hair color, while others are involved in DNA is left over from the Neanderthals. Over the past few darker shades. The authors of the study concluded that this Considering Genetic Code for Blood Thinner Dosage years, numerous studies have explored the relationship be- suggests that Neanderthals may have varied in appearance as tween these Neanderthal genes and modern diseases. Pre- much as today’s humans. Jacqueline Katz vious research had shown that skin and hair characteristics The team was especially interested in characteristics im- might be related to Neanderthal DNA, but a study published pacted by sun exposure (such as skin and hair pigmentation, arfarin, most commonly referred to as Coumadin, but this difference is statistically significant. In a more conse- this week in the American Journal of Human Genetics per- mood, and sleeping patterns), because the Neanderthals Whas been used for decades to prevent the formation of quential way, this study shows practical use for genetic test- formed by a team of German geneticists has concluded that were already adapted to the lower levels of radiation present blood clots, often recommended to patients recovering from ing, and sets a precedent for future experimental methods. these genes also contribute to phenotypic characteristics like in Europe when the humans arrived. They speculate that Ne- hip or knee replacement surgery. And for decades, doctors Ohio State University Wexner Medical Center now have skin tone, hair color, and even smoking status. anderthal alleles have persisted in our DNA because of the have prescribed this blood thinner based on clinical factors evidence that support these loose claims. The research- The research was performed using data obtained in the evolutionary advantage and diversification they contributed including age, height, weight, gender, and race. It is the preva- ers analyzed the different levels of cytokines, indicators of UK Biobank pilot study, which consists of genetic data and to the interbred gene pool, and continue to persist in main- lence of the drug that prompted researchers to take another immune responses, in 80 pregnant patients' carrying either information about physical appearance, diet, sun exposure, taining gene variation in human genes today. look: “Over the last 10 years, warfarin has led to more med- male or female fetuses. When blood samples containing cyto- behavior, and disease for more than 112,000 participants. ication-related emergency room visits among older adults kines were exposed to bacteria, the researchers determined a 1 than any other drug.” greater inflammatory response in the blood samples of female Diet and Exercise Improve Blood Flow to the Brain for Patients with Type 2 Diabetes Recently, the Journal of the American Medical Associa- fetuses than those of male fetuses. This increased inflammation came out with a new warfarin study. The study conveys tion explains why pregnant patients carrying female fetuses Allison Kannam that working from a patient’s genetic profile along with other experience increased symptoms of achiness and fatigue. This ew findings from a 10-year-long study suggest that term behavior changes in their lives to improve management known clinical factors to determine the optimal dosage of discovery enables pregnant women and obstetricians to find NType 2 diabetics who reduce their caloric intake and of their diabetes. In the first comparison group, participants blood thinner vastly reduced the risk of major bleeding and, ways to alleviate such heightened symptoms. However, there increase physical activity may experience increased blood aimed to consume 1200 to 1800 calories per day and exercise on the other side, the formation of blood clots. The study was is more research needed to determine the specific maternal flow to the brain. Many individuals with type 2 diabetes are 175 minutes per week and had frequent follow ups for sev- conducted on 1,600 individuals age 65 and older undergoing hormones and other inflammatory factors in the placenta overweight or obese, and while improving diet and exercise eral years. In the control group, participants completed Dia- hip or knee replacement surgery. Patients were separated ran- that simulate the extensive immune reaction. Although this is widely recognized as a method to reduce many of diabetes’ betes Support and Education classes. At the completion of domly into two groups. The first group received warfarin dos- knowledge of increased inflammatory response in pregnant negative effects, its impact on cognition and the brain is not Look AHEAD, 321 participants received an MRI brain scan. ing based on purely clinical factors, and the second group’s patients with female fetuses is important, the immune sys- well-known. Researchers aimed to establish a clearer link The intervention group showed greater blood flow to the dose was based on these factors in addition to information tem should be boosted or placated with caution. The babies’ between these interventions and blood flow to the brain giv- brain, and the researchers believed their findings were most extracted from each patient’s genetic code. and pregnant patient’s health and well-being are the priority. en that type 2 diabetes affects circulation and reduced brain applicable to overweight rather than obese individuals. The While fifteen percent of the patients whose dosages were An optimally functioning immune system is necessary, even circulation can influence decision-making and cognition. Look AHEAD study also incorporated cognitive tests, and calculated through the traditional metric experienced at least despite the resulting inflammatory symptoms. As always, Recently, researchers investigated data from an existing researchers noted that participants who had poorer perfor- one adverse effect, a mere eleven percent of patients whose health care providers recommend daily exercise and a well- 10-year study called Action for Health in Diabetes (Look mance on these tests showed greater blood flow to the brain, warfarin dosing was guided by genetic testing saw unfavor- balanced diet to alleviate inflammation and strengthen the AHEAD) in which participants learned to implement long- indicating how the brain may respond to cognitive decline. able effects. A margin of four percent may seem meaningless, immune system. A Recent Zika Outbreak Could the Annual Flu Shot See Big Changes? Sidharth Anand Grace Materne 2016 Zika outbreak in Ecuador has been shown by a quitoes had a more suitable breeding ground, allowing the Anew study to be promoted by a more pronounced El spread of these disease. This was then exacerbated by a 7.8 s the winter season approaches, many will line up to re- lography, a high-resolution imaging technique. The data Niño phenomenon (2014-2016) and a disastrous earthquake magnitude earthquake, which destroyed many sanitation Aceive their influenza shot without thinking twice. How- indicates that while inside the chicken eggs, the H3N2 sub- in Manabi, Ecuador in April 2016. The Zika virus, carried facilities, major infrastructure and municipal amenities, ever, recent studies suggest an overwhelming need for more types mutates the protein L194P on the hemaglutinin glyco- by mosquitoes, causes mild symptoms like rashes and head- including access to drinking water. Thus, water circum- in-depth flu vaccine research. Traditionally, flu vaccines protein (HA). This mutation results in the human immune aches, but can also lead to a variety of symptoms including stantially had to be harvested from rainwater, and was often are manufactured by injecting the virus into chicken eggs system being less effective in recognizing the virus. Thus, if a microcephaly, or smaller head size at birth resulting from an infested by mosquito larvae, helping the virus spread. The and allowing for replication; The virus found in the fluid of vaccine for the H3N2 subtype contains the mutated protein, affected gestator. Both the earthquake and the pronounced leader of the study, Cecilia Sorensen, from the University of the eggs can then be isolated and used in vaccines. A recent it will be unsuccessful in establishing immunity against this El Niño events came together to increase temperatures and Colorado at Boulder says that natural disasters help create study examining the H3N2 subtype of influenza found that strain of influenza. Current research is investigating alter- rainfall, while destroying infrastructure throughout the a perfect hotbed for disease. Thus, the combined actions of when replicating inside the chicken eggs, the influenza virus natives to the chicken-egg test method and instead looking province. This helped bring disease-carrying mosquitoes the El Niño and the earthquake may pose relevance in other must adapt and mutate in order to grow in the new environ- at the possibility of mammalian cells and recombinant HA in closer contact with humans, increasing the outbreak of areas recently afflicted by a disaster, including Mexico with ment. protein vaccines. Research into alternatives to the aforemen- the disease. El Niño is a weather phenomenon which often the recent earthquake and the southern US as well as the In the case of the H3N2 subtype, the mutations during tioned method would hopefully facilitate the discovery of a plagues equatorial regions of the planet, increasing water hurricanes in the Caribbean. The next steps are to now look replication are causing vaccines to be only 33% effective. To type of vaccine with a higher than the thirty three percent temperatures, and thus the temperature on land, while infor patterns with disasters and create health-oriented recov- further study the mutation, researchers used X-ray crystal- success rate. creasing rainfall. As Ecuador got hotter and wetter, mos- ery plans before the disaster hits.

References for all TuftScope articles can be found at TuftScope.squarespace.com 6 TuftScope | Fall 2017 • Volume 17, Issue I Fall 2017 • Volume 17, Issue I | TuftScope 7 was created as a way of deciding which bod- FEATURE INTERVIEW ies were disposable. In 1927, the United States Supreme Court decided in a case called Buck v. A Discussion with Lydia X. Z. Brown about Disability Justice Bell that it was not only not a violation of consti- tutional rights, but in the public interest, to invol- Michael Seleman untarily sterilize a white woman with intellectual disabilities, who was said to be one of three generations of people of intellectual disabilities. This was during the heyday of eugenics, which was Lydia X. Z. Brown is a disabled social justice educator currently teaching a course at Tufts University’s ExCol- mainstream science of white supremacy, anti- lege entitled, Rethinking Disability: From Public Policy to Social Movements. Currently, they are a third- Semitism, and intense ableism. That decision has year student at Northeastern University School of Law, and serve as Chair of the Massachusetts Developmental never been overturned. The chief justice Oliver Disabilities Council. Earlier this year, Brown published an anthology entitled All the Weight of Our Dreams, Wendell Holmes who wrote the decision said, with the Autism Women's Network. “Three generations of imbeciles are enough.” The following discussion sought to gain more insight into Lydia’s work with disability justice, and the field’s In 1938, just 11 years after that, Congress parameters, history, and direction. passed the Fair Labor Standards Act, which has a section called Section 14(c). Section 14(c) permits disabled people to be paid less than mini- [Photo: Lydia Brown, a young East Asian person wearing a navy blue suit and retro-patterned necktie, smiling. They are giving a talk for the mum wage, called commensurate wage. Today Colorado Trust in Denver, Colorado, February, 2017. Photo credit Rachel Mondragon.] for-profit companies, nonprofits, and government agencies can all pay disabled people cents per hour for menial labor and they call it opportu- Tell me about yourself briefly, and what you do. For those who don’t know about what disability rights nity. There are people that are still fighting to keep are, or how they manifest, can you speak a little about My name is Lydia Brown. I am currently a third-year law that law on the books. That means that disabled the violence and discrimination that exists towards student at Northeastern, and I’m also teaching here at the people fall into one of many categories of people those with disabilities? ExCollege for the second year. I teach the course on disabil- who have legal documentation (so are legally ity policy and social movements. For almost nine years, I’ve First, I want to make a distinction between disability considered allowed to work in the United States) been heavily involved in disability activism and community rights and disability justice. The work that I do is grounded who are allowed to be paid less than minimum organizing. My background has involved policy advocacy, in a framework of disability justice, which I define as the art wage: certain young workers, certain agricultural grassroots organizing, cultural activism and existing weirdly and practice of honoring the whole body and mind. Other rural workers, incarcerated workers and disabled on the margins of academia. Most recently, I was very proud people define it differently in disability justice work. Ki’tay workers- and of course all of these categories may this year to have published, with the Autism Women’s Net- Davidson defined it as act of love. Mia Mingus defines it as overlap. That’s the limitation of the law. work, the first-ever anthology entirely by autistic people of finding home or moving from access to wholeness. Talila You can have these laws on the books, like we color and other racialized autistic people, featuring over Lewis defines it as honoring the whole humanity of every have the Americans with Disabilities Act right sixty people living in seven different countries. It’s calledAll person. Shaine Neumeier defines it as not leaving anybody now, passed in 1990. It was signed under law by the Weight of Our Dreams, and I am one of the three editors. behind. Patty Berne outlines 10 principles to define it, which George H.W. Bush, then it was strengthened with It was a project that I’d first envisioned in 2014. include leadership of the most impacted, intersectional the ADA Amendments Act of 2008. Right now, I’ve also just completed a two year term in the Massa- practice, anti-capitalism, and anti-oppression as part of what it’s under attack. In Congress there’s a bipartisan [Photo: Lydia Brown, a young East Asian person, giving a short talk at the Disability Intersectional- chusetts state government as the chairperson of our state’s disability justice is. And in all those ways of understanding effort to pass a bill called House Resolution 620, ity Summit in Boston, Massachusetts, November 2016. They are gesturing with both hands. Their Developmental Disabilities Council. Generally, my work what disability justice is, it comes down to this: Disabil- sponsored by both Democrats and Republicans. t-shirt says "The Whole Damn System Is Guilty As Hell" with the logo of the power fist. They are over the past nine years has focused on violence and abuse, ity justice is a set of practices as well as a set of beliefs and People considered conservative and people con- also wearing a nametag that says "Lydia X.Z. Brown, they/them," and a color communication badge especially where the state is involved, either directly or in principles. It is about creating a society in which all people, sidered progressives are supporting a law called showing green. Photo credit: Kelsey Kent.] some manner by acquiescence or complicity, against dis- regardless of their bodies or minds and how they function the ADA Education and Reform Act, which is a vast majority of the time, the ADA is not being enforced, it is abled people- especially multiply-marginalized disabled or hear or what they look like, are actually affirmatively val- bland, non-threatening name disguising what it’s actually not being followed. Disabled people are literally dying across people, like disabled people of color and queer and trans ued and honored as worthy of love and care. That’s a very about- stripping away the enforcement rights of the ADA. the country because the ADA is not even being enforced. disabled people. That violence unfolds in schools, disability radically different approach than disability rights. Disabil- HR 620 would diminish the ability of disabled people to pur- And right now, it’s under attack. institutions like nursing homes, group homes, and psychiat- ity rights says that the way to solve issues affecting disabled sue acts of social exclusion done by businesses and compa- ric wards; and at the hands of police or in prisons. That’s a people is through fighting for equality, through changing the nies that often have millions of dollars to make their build- snapshot of the work I’ve been doing since 2009. law, through passing and enforcing non-discrimination laws ings accessible to people of disabilities but refused to do so Currently, I’m a writer, I’m a speaker, I’m an educator, so that we have more legal opportunities to not be discrimi- because it’s inconvenient, because it might cost them a little I’m an organizer, and I do whatever I can to support people nated against in employment, higher education, in housing. bit of money. They’re trying to ramrod this bill through Con- individually as well as more broadly through work that I All of those things are very important as they affect parts of gress right now, under the theory that there are people sup- hope ultimately leads to changes that will create more just people’s lives. But it’s also very limited framework because posedly bringing these frivolous “drive-by” ADA lawsuits to and equitable society to live in. Some of the work that I do, disability rights relies on the idea that law is somehow going make a quick buck. Because if you say allegedly that some- you can read about if you look for it online. Other work that to save us, and it’s not. one has an inaccessible entrance to their building, you might I’ve done, I don’t really talk about publicly, but I do a lot of Law was created as a tool of violence and control. Law automatically get several thousand dollars. Well that’s not direct support work too. happening. There are maybe some handful of very unscru- Interviewee contact: For more information about Lydia X.Z. Brown, Author contact: Michael Seleman is a Junior at Tufts University. their public speaking, and past work, see their website http://www. pulous lawyers who are doing that in the country but the Address correspondence to [email protected]. autistichoya.net.

8 TuftScope | Fall 2017 • Volume 17, Issue I Fall 2017 • Volume 17, Issue I | TuftScope 9 either better or worse, it's just literally different, observably it means to incorporate disability justice into kinship struc- FEATURE INTERVIEW so. tures, into sexual intimacy, and basically literally everything; Acknowledging that, that disability is contextually cre- and what it means to build that from the ground up. That's A Discussion with Lydia X. Z. Brown, continued ated, it is defined differently from community to community, where much of the real work is. from context to context, as much as it’s also a lived reality in Michael Seleman the body and mind of a person who is disabled, requires a What would you say to someone reading your work and more nuanced way of thinking than just saying there's only wanting to figure out a way to get involved in a small a medical or social model. It requires an entire shift into rec- capacity? How would they do that? So how does the violence actually play out in places like risk of being targeted for state violence. But we don’t nor- ognizing the the powerful role that society and culture have schools or prisons or nursing homes? mally talk about those stories because they’re inconvenient. Ask yourself, if you're involved with anything, if you are in constructing disability while also recognizing, honoring, Any institution, a place where people are under control When the white disability community talks about issues involved with, say, an HIV advocacy group, ask, are we talk- and making space for the lived, bodily, mental reality of how and surveillance, is a place ripe for abuse. There’s a power with police, they’ll really talk about cases in which a white ing about disability? Are we bringing a disability analysis my brain works. It's not just some made up thing that some- differential between the people that run it and have control disabled person has been targeted, because it certainly hap- into this? (Some people with HIV identify as disabled and one decided to create a label for; my brain works the way it and the people that are put in it, often for their own good or pens. But they are ignoring the fact that the most dangerous some do not.) But are we considering how ableism affects works. And if you're not autistic, then my brain and your worse for the public good as is usually the case with prisons intersection is to live at the nexus of race and disability. the work that we are doing? If you are part of a group that brain do not function the same way. That's simply a reality, and large-scale disability institutions. In schools, 94% - 96% provides direct services to people seeking abortions, ask, are our brains just don’t function the same way. of developmentally disabled students report severe bullying. How is the medical model of illness inadequate as it per- we considering disability? Are we considering how ableism tains to disability justice? might affect our work and what we've already been doing? In 2009, the U.S. Government Accountability Office released Since you started working in the field, do you feel If you are planning a party for your frat house, ask yourself, a report on restraint and seclusion. Note that restraint means Many people who do a “disability 101” will tell you there's that there are some areas in which you have seen honestly, is the party that we're planning taking into account anything from belting a student down to a table, physically two ways to think about disability. There's a medical model improvement? holding down a student, or shoving drugs down a student’s and a social model. The medical model, as they will define that maybe some people that we might be inviting and want throat to make them compliant, and seclusion means soli- it, says that the problem is the brain or body of the disabled There is a lot more public work being done within com- to come can't climb the fucking stairs at our fucking frat tary confinement, but in schools. Restraint and seclusion are person, and the solution to that problem is to fix the brain or munities of color and within white disabled communi- house to get into the party? Because we sure as hell should disproportionately applied to disabled kids. The ACLU has body through medical or psychiatric intervention that may ties at the nexus of race and disability and that's awesome. not be having drunken members of our frat carry him up the found that restraint, seclusion, and other forms of school rehabilitate, treat, potentially cure, prevent, and eliminate. There's a new organization, founded a year ago, the Har- stairs, that’s liability waiting to happen. No matter what it is, pushout and disproportionate discipline, through out-of- The social model, in contrast to that, says that the problem riet Tubman Collective, which is an all-Black organization asking, what about disability? school suspensions and expulsions, are disproportionately is not the brain or body of the disabled person but rather of deaf and disabled cultural workers, activists, attorneys, Because the reality is, even if you're not disabled, some- applied specifically to Black and Brown kids who also have the problem is society. The problem is when you've designed advocates, and artists. There is renewed public support for one you know in that group you're part of, the advocacy disabilities. And the GAO report found these restraints and a building that only has stairs to get into it. The problem is groups like Sins Invalid, based in the San Francisco area, group, the services group, your social group, is disabled, seclusions lead to thousands of severe injuries and even when you've designed an education system that assumes that which is a performance and disability justice collective. This whether or not they've told you or whether or not they would deaths per year. being able to read and write is a marker of intelligence and is centered around queer and trans disabled people of color. identify with that specific terminology. The more deliberate In Massachusetts, where we are right now, about an therefore value. The problem is designing an economic sys- There's been a lot of public discussion, spurred on by work you are in anything that you're doing, considering how does hour’s drive away in good traffic from Tufts University, tem that assumes that being able to work 40 hours a week like that of Vilissa Thompson, a Black disabled activist who disability impact this, how has ableism affected the way I've there’s an institution called the Judge Rotenberg Center in means that you're a valuable person and therefore deserve created the hashtag #DisabilityTooWhite and is an amazing done this before, and what can I do to be intentional about Canton, which is the only place in the entire country where access to health care and housing. That's the problem, the activist based out in North Carolina, and of Alice Wong, an actually caring, not just about mere access but about mean- disabled children, youth, and adults, including mid-aged society, and the solution to the problem is to fix society by Asian disabled activist based out of the Bay, and leads a lot ingful access, that's an important thing to be doing. and older adults, are subjected to painful electric shock as a changing it, by changing the standards and values that we of discussions on #CripTheVote and #CripLit and curates form of punishment. They are forced to wear a heavy back- use to design and structure everything from our buildings to the Disability Visibility Project. We have Victoria Rodríguez Is there anything else that you would like to say to pack with electrodes coming out of it that are taped to their our economic system. Roldán at the National LGBTQ Task Force, one of the lead- the TuftScope audience about the topic or about your arms, chests, and legs. And if they do anything staff dislike, I think, as do most people in disability justice work, not ing LGBTQ organizations, who is an out and proud psychi- course? whether it’s swearing, getting out of their seats without per- rights, that that bifurcation is inadequate because it doesn't atrically disabled, Latina trans woman who created the Dis- Don’t ever use euphemistic terms like “differently abled” mission, closing their eyes in the hallway, taking somebody’s account for the lived realities of actual disabled people's ability Justice Project within the Task Force. And all of that or “handicapable”; it's not cute and it's not funny. We're dis- hand, hitting somebody, or hitting themselves, then sud- bodies. It doesn't account for the fact that if you have chronic work is good. abled. It's not a bad thing to say the word. denly, they will receive a shock. It's like a dog shock-collar pain or chronic fatigue, no amount of accommodations and I don't think that by itself any one person's hashtag or And stop using disability as an example of a bad health but on humans and worse, because JRC invented their own universal design makes that go away. Further, accepting that some nonprofit creating something is automatically going to outcome. It's not. Disability is a way of existing in the world device in 1988 called a graduated electronic decelerator reality doesn't mean having to buy into the dehumanizing solve all these problems but there are a lot of people out there and a disabled person is not necessarily or inherently suf- (GED), which was deliberately designed to be more pain- idea that there's something inherently broken with your doing revolutionary work. Some of them have been doing fering or having a bad quality of life simply because they're ful and powerful than a police taser. And it’s 100% legal. In body. It just means that how your body functions is not the it long before even I was born and are still doing it and just disabled. fact, a judge has to sign off on it, every time it’s used. The same way as someone who's not labeled disabled. It means haven't been recognized more broadly for a lot of reasons: Finally, the class I teach is awesome, in large part due to United Nations has condemned it repeatedly, might I add. that maybe somethings are actively worse for you or impos- racism, ableism, anti-queerness. Honestly, intense classism the enormous amount of labor (emotional, intellectual, and Every single session in the Massachusetts legislature, a bill is sible for you than for someone who doesn't have that par- and the elitism of academia have been many contributing otherwise) that every student puts into it, and you should introduced to ban this practice, and every single session it’s ticular condition. But it also might mean that some things factors to why some amazing people have not received rec- definitely take it if Tufts offers it in the future. defeated. The bill has never gone through. are better for you, that some things, the way that your body ognition for their work. But most importantly, there's a lot Somewhere between 70-80% of all people who are incar- or your brain works, function better or more ideally or more of work being done within disabled communities to address cerated and 70-80% of all people who are killed by police are efficiently than someone who doesn't have that condition. cultural problems by designing the kind of world and com- deaf or disabled, according to estimates from HEARD, which That also may mean that there are aspects to it where your munities that we want to have. We’re mapping out what it References for all TuftScope articles can be found at means that if you are an Indigenous or Black person and you body simply functions in a noticeably different way than means to take accountability for abuse; what it means to TuftScope.squarespace.com also are deaf or disabled, you are at an extraordinarily high someone who doesn't have the same condition. But it's not create actually accessible spaces, housing, and events; what

10 TuftScope | Fall 2017 • Volume 17, Issue I Fall 2017 • Volume 17, Issue I | TuftScope 11 or emotionally (for those who cannot rekindle their relationships to their families), ability to fully complete these exercises BOOK REVIEW can be limited. Such a limitation renders the book, as is the case for almost all self-help books, helpful for indi- NEWS BRIEF viduals with an accommodating set of life circumstances. It Didn’t Start with You Furthermore For those who prefer to thoroughly The First Lethal and Transmissible Avian Virus understand the principal mechanisms to healthcare inter- Akari Miki Book by Mark Wolynn ventions before giving them whole-hearted credence, the book may not meet expectations. Because the majority Reviewed by Neeki Parsa n 2013, a previously unknown avian virus, H7N9, of his book engages with the clinical application of these Ibegan infecting poultry in China, and by late July ideas, his engagement with trauma psychology and epi- 2017, 1,600 people had contracted the virus. Of the genetic processes are relatively surface-level. For the infected people, 40 percent died, prompting research- Reviewed Book Information: reader with a background in biology, the book’s ephem- ers at the University of Wisconsin-Madison School It Didn’t Start with You eral discussion of the genetic mechanisms may be insuf- of Veterinary Medicine to immediately begin inves- By Mark Wolynn ficiently exhaustive, especially given the relative novelty tigation. According to the principal investigator, Pro- Published by Viking Press of epigenetic inheritance as a field. The clinical examples fessor Yoshihiro Kawaoka, this is the first case of an included in the latter half of the book at times call for a avian virus that is lethal and transmissible between N HIS THREE PART BOOK ENTITLED CONTENTS animals. It Didn’t Start with You, author Mark Wolynn takes art one of It Didn’t Start with You engages with the reapplication of the pertinent epigenetic mechanisms. His team received a sample of the H7N9 from a the reader through his approach to alleviating what Pfoundational logic to Wolynn’s approach, drawing on When Wolynn cites a former client whose grandmother Ihis book comes to describe as “inherited family trauma”. Sigmund Freud and Carl Jung to clarify the role of the was estranged from her family, he does not revisit the deceased patient and performed genomic analysis on As the founder and director of “The Family Constella- unconscious mind in our everyday words and behaviors, underlying science he purports drives the inheritance of it. Their most significant finding was that the virus tion Institute,” Wolynn’s clinical practice and educational and then on known cellular biological phenomena that this trauma from grandmother to grandchild. Especially had two different populations: one that was vulner- shed light on how the human body can make epigenetic workshops seek to acquaint his clients and readership for his more abstract examples, clarifying the potential able to Tamiflu, a common flu drug, and another that changes over the course of our lives, particularly as adap- was resistant. This observation suggested that after with a psychological outlook and methodology for allevi- for traumas to endure generations through epigenetic ating distress, for which those who suffer from depression, tations to trauma. He describes how historically, people infecting the patient, the virus was accumulating mu- research would clarify the full picture of inherited trauma. anxiety, or PTSD often don’t have language to describe. have inherited their parents’ adaptations to traumatic tations, improving its resistance to the drug. Wolynn starts his book with his own path to healing, life situations; at times, children of the victims of human The chapters engaging with these topics are successful in The next step was to determine whether H7N9 is beginning with his being diagnosed with central serous rights abuses can display elevated cortisol levels despite establishing a basic foundation for the interventions out- transmissible among ferrets, the most accurate ani- 1 retinopathy, an illness of the retina which, in its chronic not having ever personally experienced the trauma. lined in the rest of the book, but the depth of their respec- mal model for studying human infections. Each ex- form, can lead to legal blindness. Distraught with the lack The next two parts of his book outline specific prac- tive fields warrant novels on their own. perimental trial consisted of two ferrets, a healthy one of options the American medical system offered, he left tices to help readers locate their own “Core Complaints” and one that was deliberately infected with H7N9. through an analysis of their “Core Language.” The term his family and business to seek alternative care abroad. CONCLUSION Each ferret was placed in two adjacent cages with a In his exploration of non-specific medicines, which he “Core Complaint” refers to the concerns that are the It Didn’t Start with You can serve as an introduction barrier in between them that allowed the passage of characterizes primarily by their differences to conven- most pressing, salient, and repetitive in one’s own life. respiratory droplets. All of the previously healthy fer- tional Western medicine, he fails to find a solution that An individual’s “Core Language” are the words that they to a healing philosophy that has helped many who have curbs his atrophied vision and worsening depression. His use to describe the complaint. The book provides written entered Wolynn’s practice and have applied the exercises rets became infected, and the deliberately infected outlook on his path to healing only shifts when a spiri- exercises so readers can begin to broach these questions in his book to their lives. While valid complaints have ferrets as well as the ferrets to which they transmit- tual mentor tells him to “go home and call [his] mother on their own. The exercises try to help readers become arisen pertaining to the circumstantial impracticality ted the virus died, confirming the lethality and infec- and father.”1 In a realization that his own life story and acquainted with their own family history, and the ways of some of the practices he puts forward in the book, It tiousness of the virus. existence was inextricable from those of his own parents such a history may have influenced their present-day Didn’t Start with You succeeds as a self-help book for cli- Professor Kawaoka predicts that H7N9 will con- and his relationship to them, he returns home to see his anxieties and fears. Peppered throughout these chapters ents with access to these avenues of healing and are com- tinue to accumulate mutations that enhance their mother. He describes his formerly tenuous relationship pathogenicity and transmissibility, a phenomenon are anecdotes from his own patients, and their stories of patible with this style of mental healthcare intervention. with her and the shift that accommodated its rekindling; success through unearthing their own core complaints. known as gain-of-function. Prior to this study, he “For the first time I could remember, I was able to let In this way, as he tackles the abstract nature of unseen published a commentary that emphasizes the im- myself receive my parents’ love and care—not in the way trauma, he routinely returns to narratives that reinforce portance of research on gain-of-function of viruses 1 I had once expected it, but in the way they could give it.” their significance. Thus, these latter two-thirds of the References for these articles can be found at in transmissibility, drug resistance, pathogenicity, After his return home, the story promptly moves back to book serve as a self-help guide to tackling anxieties that TuftScope.squarespace.com and ability to replicate, because it would facilitate the the current health of his eye, as he reports that his vision could be related to ancestral trauma that isn’t immediately development of pre-pandemic vaccines and antiviral has restored to 20/20, and implicitly attributes this to his apparent as relevant to personal healing. drugs. As gain-of-function studies get underway, the journey in familial healing as it relates to his body’s over- best measure for global public health is to improve all well-being. This anecdote exemplifies much of what LIMITATIONS close surveillance on the circulating virus. the rest of the book puts forward: solutions to seemingly central tenet to finding relief for familial trauma is unsolvable or enigmatic physical or emotional distress. Acommunicating with one’s family and exhuming the He gives these solutions a possible scientific foundation, experiences and lives of their ancestors. For those who and then extends the phenomenon to overall wellness, have limited access to their family, either practically (for but without tying back to an underlying mechanism. those who have not met or cannot locate their families),

Author contact: Neeki Parsa is a Senior at Tufts University. Image source: https://pixabay.com/en/dna-double-helix-genome-human-30518/ Author correspondence to [email protected]

12 TuftScope | Fall 2017 • Volume 17, Issue I Fall 2017 • Volume 17, Issue I | TuftScope 13 blood loss and pain along with less apparent scarring.2 More- INSIGHT over, these aspects usually can result in shorter hospitalization time and faster recovery period. A 2013 FDA-funded survey Robots? Surgery? Robotic Surgery? of surgeons across the country using the da Vinci Surgical System reports “fewer patient complications and shorter hos- Sachin Vallamkonda pital stays as a benefit of surgery with the system.” Similarly, a 2014 study published in the Journal of Urology discusses N THE 2005 MOVIE STAR WARS: EPISODE III command allowing for some of the first solo-surgeon laparo- hospital outcomes for laparoscopic nephrectomy – a mini- 7 Revenge of the Sith, a renowned scene ensues where a scopic procedures. mally invasive technique – versus open partial nephrectomy team of robots operates on the injured Anakin Skywalker In 1998, Computer Motion created Zeus, which had on patients with kidney cancer. 9,10 The paper states that “[a]t a Ias they construct him into the infamous Darth Vader. Robots more surgical robotic arms.7 The Zeus console was much population level, the patients with kidney cancer treated with performing complex operations may seem like science fic- more advanced and also held potential for telerobotics, the laparoscopic partial nephrectomy experienced a shorter and tion, but, in 1991, the Probot system almost autonomously ability for a surgeon to conduct surgery on a patient at a dis- less intense hospitalization, supporting the benefits of lapa- Image Source: Intiutive Surgical 1 achieved a surgical prostate procedure. tance away using a console system and surgical robot. With roscopy.”10 Although, the same study also did stress the need utilizes.13 The Mayo Clinic staff defines Zeus, the first robot-assisted heart for more studies on the proper application and adoption of Technological advances in the field of health have also led robotic surgery as a machine system “These robotic arms and in- bypass surgery in the United States this technique based on the risk of potential complications. to the growing prominence of a new field in today’s world: with which physicians perform sur- and first robot-assisted coronary strument tips have high preci- Alongside the benefit of minimally invasive procedures, medical technology. Alongside the many medical technology gery with augmented precision and artery bypass grafting surgery in robotic surgery holds other useful advantages. For instance, companies budding and prospering across the country, many control compared to conventional sion and the ability to detect Canada were accomplished. In 2001, the da Vinci Surgical System is the only surgical machine from younger generations are attracted to this promising new mechanisms of open surgery. Both Dr. Jacques Marescaux in New York that allows the surgeon to operate while seated in a one of discipline. For example, the Center for Research, Engineer- the Mayo Clinic and NYU Langone and correct a surgeon’s acci- performed a cholecystectomy – the several ergonomically beneficial positions.6 This small but ing, Science and Technology program in the Paradise Val- Health’s Robotic Surgery Center procedure to remove the gall bladder significant improvement allows for less surgeon fatigue dur- ley High School system bestows young students to explore emphasize the capacity of robotic dental minor hand tremors.” – on a patient in a hospital in Stras- ing operation.6 The 3D video and high-definition imaging 14 6,7 Abrazo Arrowhead Campus’ da Vinci Surgical System. They surgery to perform operations in a bourg, France. This was achieved on the da Vinci machine is also advantageous, allowing the 2,3 not only complete tasks on the machine but also learn about minimally invasive way. Robotic surgery includes every- using the teleprescence surgery with the Zeus machine. surgeon to utilize deft magnification and depth perception the presence of engineering and technology in the medical thing from robot arm assistant to a more holistic robotic During this time, Intuitive Surgical designed the famous features. Furthermore, the da Vinci system has EndoWrist field. surgical console system. One of the most widely used robot- da Vinci Surgical System. In 2003, Intuitive Surgical bought instruments that mimic the hand effectively.6 These robotic 6,7 At the beginning of 2017, the FDA approved Intuitive assisted surgery systems is Intuitive Surgical’s da Vinci Sur- Computer Motion, thus discontinuing the Zeus machine. arms and instrument tips have high precision and the ability Surgical’s newest da Vinci model: the da Vinci X Surgical Sys- gical System. The NYU Langone Health Robotic Surgery This da Vinci machine comprised of a console system for the to detect and correct a surgeon’s accidental minor hand trem- tem.15 A Nasdaq article by Zachs Equity Research explains Center recognizes it as “the world’s most advanced surgical surgeon and four robotic arms attached to a cart beside the ors. The da Vinci Si Surgical System edition now has a dual 3 3 how “worldwide da Vinci procedure volumes grew approxi- ro b ot .” Today, robot-assisted surgery is accruing popularity patient. This machine had more degrees of freedom than console feature allows an assistant surgeon to also operate in mately 18% year over year in the first quarter of 2017, thanks in medical centers and hospitals around the globe. the Zeus, enhanced 3D imaging, and instruments that better the surgery.6 6 to stellar performances in the U.S. general surgery and world- mimicked the human hand. With FDA approval, the da Vinci wide urologic procedures.”15 With cost-efficient and clinically HISTORY OF ROBOTIC SURGERY Surgical System became the first surgical robot approved for ROBOTIC SURGERY IN THE WORLD OF TODAY 7 safe procedures, the da Vinci Surgical System and similar he world’s first surgical robot was the Arthrobot cre- general laparoscopic surgery in the United States. he most commonly-used surgical robot system today robot-assisted surgical systems are likely to grow and prosper Tated by researchers at the University of British Columbia Today, Intuitive Surgical counts over three million sur- Tis the da Vinci Surgical System. Millions of minimally in coming years. and Vancouver General Hospital and used for the first time gical procedures that have been accomplished using the da invasive surgical procedures have taken place around the 4,5 8 Robotic surgery is thriving today. According to a recent in 1983. It assisted with positioning patients undergoing Vinci Surgical System. There have also been over ten thou- world thanks to its system. In fact, Intuitive Surgical has a 16 4 article by Allied Market Research, in the next five years, orthopedic surgery via voice command. In 1985, the PUMA, sand publications in clinical journals regarding the surgery da Vinci Surgeon Locator website where anyone online can 8 the global market for robotic surgery systems is expected to or Programmable Universal Manipulation Arm, was cre- with the da Vinci system. find surgeons who use the da Vinci Surgical System in their 7 secure $20.5 billion. This market segment was also apparently ated at the industrial robotics company Unimation. It was nearby area.11 An October 2017 Independent Online (IOL) “the highest revenue-generating segment, accounting for a robotic arm that situated the needle employed for brain WHY ROBOTIC SURGERY article describes how patient preference for robotic surgery in 7 nearly half of the market share in 2015.” biopsy. he aforementioned three decades have led to remark- regards to certain procedures has led to the closing of about The future of robot-assisted surgical systems promises Minimally invasive surgery also began to gain popular- Table breakthroughs in not only science and technology twenty-five percent of prostate cancer units since 2010.12 The new and exciting advancements. There are many compa- ity during this era when in 1987 a French physician used a but also medicine and healthcare. Quite significantly, these many advantages and efficiency of robotic surgery has led nies besides Intuitive Surgical investing and pursuing in new laparoscopic procedure for a cholecystectomy – a feat never developments entail improvements in the health and comfort many hospitals to purchase robot-assisted surgical systems. developments in the field of robot-assisted surgical machines. accomplished until then. Researchers at the Imperial Col- of the patient. One challenge of robot-assisted surgery present today is These enterprises include companies such as Titan Medi- lege of London soon developed the Probot for prostate sur- One specific aspect of modern robotic surgery that con- its complex system. To succesfully operate these systems, sur- 8,6 cal with their SPORT Surgical System, Accury with their gery in 1988. A later 1997 study concluded that the Probot stitutes its own myriad of benefits would be the advantage of geons must take training courses to become acquainted with Cyberknife System, Medrobotics with their Flex Robotic Sys- had “shown itself capable of performing prostate resections minimally invasive procedures. In contrast to conventional their functioning. The FDA-funded survey mentioned also tem, and more.17 in humans with an accuracy comparable with a human sur- open surgery techniques, minimally invasive surgery work noted that the surgeons spoken with attested that “learning 1 These novel developments continue to contribute g e on .” The ROBODOC from Integrated Surgical Systems fol- to accomplish the operation by inserting the surgical instru- how to use the da Vinci Surgical System is the biggest chal- 7 immensely to the fields of biomedical science and healthcare. lowed in 1992 used for orthopedic surgery. ments fitted to long thin poles through a small incision or lenge because of the device’s complex user-interface.”9 These Perhaps soon, a surgical machine like the da Vinci system will In 1994, the NASA-funded company Computer Motion several small incisions on the patient. With smaller and fewer advancements therefore also affect the breadth of medical be commonplace in your local hospital’s operating room. designed Automated Endoscopic System for Optimal Posi- incisions being made, the patient experiences decreased training. One example of this expansion of medical educa- 7 tioning (AESOP). AESOP was useful for holding and position is shown by the Abrazo Arrowhead Campus hospital in tioning the camera with stability during a wide variety of Arizona that has been training student surgeons with the da References for this article can be found at surgical operations. Later versions of the AESOP had voice Author contact: Sachin Vallamkonda is a [year] at Tufts University. Address correspondance to [email protected] Vinci Xi Surgical System that the hospital’s operation room TuftScope.squarespace.com

14 TuftScope | Fall 2017 • Volume 17, Issue I Fall 2017 • Volume 17, Issue I | TuftScope 15 INSIGHT Smartphone App Interventions for Depression Kurtis Chien-Young

AJOR DEPRESSIVE DISORDER, CONVEN- in “inactive” control groups received no treatment, and par- tionalized as depression, is a mood disorder in ticipants in “active” control groups received some sort of sup- which a person suffers from major depressive epi- plementary intervention in addition to the use of a mental sodes.M1 Episodes are often characterized by low mood, loss of health app.3 These interventions ranged from interpersonal pleasure, fatigue, difficulty concentrating, and a number of therapy to the use of miscellaneous smartphone apps, and other symptoms.1 Each year, approximately 6.7% of adults in were administered in order to limit the time and attention the United States experience at least one major depressive epi- the participant could invest into the mental health app being sode.2 The disorder places a heavy burden on each individual studied.3 affected, but successful treatment options exist. Traditionally, Utilization of mental health apps was found to have a depression is treated by either medication, psychotherapy, or positive effect on lowering depressive symptoms among par- a combination of the two.1 Brain stimulation by electrocon- ticipants.3 Certain conditions seemed to adjust the effective- vulsive therapy is also an option if medication and therapy ness of the intervention. For example, standalone apps with are ineffective.1 However, the current treatment methods can comprehensive treatment methods provided better results prove inaccessible for some people struggling with depres- than apps meant to pair with other forms of treatment.3 Apps sion. Certain insurance policies may not cover mental health that required only brief periods of attention were more effec- Image Source: http://images.shape.mdpcdn.com/sites/shape.com/files/depression-apps-fb.jpg services, and those without coverage may face steep costs tive, likely due to the attrition rate of lengthier app interven- 3,4,6 3 thousands more apps remain untested. The market is satu- a set of factors that contribute to a successful app interven- for treatment. Other people may tions. The paradigm offered by rated with mental health-related apps, and few measures are tion.4 Apps that implement cognitive-behavioral therapy to live in locations where they sim- the mental health app had a con- implemented to gauge their effectiveness.4 For example, a address both the symptoms of anxiety and the low mood of ply cannot to find a therapist. “While the smartphone- siderable effect as well. Mindful- review of fourteen mental health apps recommended by the depression were demonstrated to be effective.4 Targeting and Finally, some may even avoid ness apps helped to relieve symp- National Health Service of England found that just two of the treating both anxiety and depressive disorders yields favor- treatment because they fear the based interventions in toms among participants with 3 apps used valid assessments such as the Patient Health Ques- able results because of the high rate of comorbidity between stigma attached to mental illness. the above studies helped mild depressive symptoms. Par- tionnaire-9 or the Warwick-Edinburgh Mental Well-being the two disorders.4 Many of the apps using cognitive-behav- Enter mental wellness apps. ticipants with severe depression, Scale to evaluate their clinical performance.8 The majority of ioral therapy treatments are thought to be effective because of With the introduction of smart- improve conditions for on the other hand, benefitted the apps did not even report any measure of user outcomes.8 their interactive nature.4 These apps ask users to report their phones in the past decade, many more from behavioral activation Even for the apps deemed effective, the exact aspect or thoughts and feelings in order to better accommodate them people now have access to thou- participants, many thou- apps, which help users identify function of the app that benefits the user may be unclear. The through treatment.4 They can generate personalized recom- sands of apps on the App Store and engage in healthy, proactive 3,5 active control group, as it was defined by the meta-analysis, mendations for behaviors and activities that help improve or Google Play. Among these sands more apps remain behavior. paired limited app use with other methods of treatment.3 Par- users’ mental health.4 The apps also educate users on the include apps that are geared Another study was done on an ticipants in the active control group recovered from depres- sources of their distress and methods of relief, so that users toward improving mental health, untested.” intervention developed at North- 4 6 sive symptoms to a degree that resembled the results of those can be more conscious of their conditions. Increased emo- teaching self-help methods, and western University. Researchers who were given free rein with the mental health apps.3 The tional awareness promotes the user’s ability to avoid destruc- mitigating the symptoms of depression. Treatments can be assembled a conglomerate of fourteen mental health apps data could not support the apps being more beneficial than tive and maladaptive patterns of thought.4 To motivate users, delivered through numerous methods, from mindfulness under the name “IntelliCare,” which participants with depres- therapy or medication.3 Additionally, mental health apps will apps use game-like elements such as simple point systems or training to gamification of healthy behavior to AI that can sion and/or anxiety disorders used over the course of eight 3,4 6 likely be unable to replace traditional treatment methods for progress reports to amplify intrinsic reward factors and make converse and correct negative thoughts. These treatments weeks. The apps covered an assortment of functions, includ- everyone. the intervention enjoyable.4 follow a range of psychological paradigms, such as behav- ing planning, sleep scheduling, and negative thought restruc- Clinical limitations aside, some practical concerns must The tentative conclusion is that some apps work. Of ioral, cognitive, or humanistic models, and often resemble turing.7 The intention was to provide an interactive program 3 be considered. Increasing digitization of health data puts course, a level of caution must be exercised so that users select actual psychotherapy. However, for every app that delivers from which participants could select treatments that they felt 9 6 patient privacy at risk. Like any other health data, user infor- apps that have been tested using evidence-based practices. valid content, there are many more that are neither tried nor best suited their needs. The study also employed coaches to mation gathered by mental health apps should be subjected Users should also seek apps that apply cognitive-behavioral true. Even apps that follow psychotherapeutic methods may check in on participants and help them use the apps.6 After 6 to the Health Insurance Portability and Accountability Act therapy techniques, and users with both anxiety and depres- not imitate clinical settings perfectly. A smartphone may not eight weeks, treatment outcomes were measured. A majority (HIPAA).9 Password protected accounts and data encryption sive disorders should seek apps that address the broad set adequately replace a human therapist who is present to listen of the participants used the apps on a daily basis, and of those on the client side, during transmission, and server side are of symptoms they may experience.4 Other considerations to a patient’s concerns. This raises the question: do these apps who did, many expressed some level of recovery from depres- the basic safeguards necessary to ensure user privacy.9 Users include identifying apps that use legitimate metrics to mea- work? sive symptoms. Thirty-seven percent of participants were in should be wary that some apps may circumvent regulations sure user outcomes and apps that encrypt data to protect user A meta-analysis of eighteen randomized controlled tri- remission after treatment, classified by minimal symptoms of by marketing themselves as not-for-medical purposes. So, privacy.8,9 With these precautions in mind, these apps offer a als looked into the effects of mental health apps on depres- depression as defined by the Patient Health Questionnaire-9.6 3 while it is sometimes difficult to do so, users or care providers valuable at-hand support service for people who suffer from sive symptoms. About 3,400 participants were analyzed for While the smartphone-based interventions in the above are encouraged to verify whether an app meets privacy pro- depression, whether or not they have access to traditional at least one week.3 Participants in the studies were divided studies helped improve conditions for participants, many 3 tection standards and complies with HIPAA law before using mental health care. into experimental groups or control groups. The participants the app.9 in the experimental groups received an intervention through Author contact: Kurtis Chien-Young is a sophomore at Tufts Uni- Despite these limitations, some recommendation can be References for this article can be found at the use of some mental health app. Meanwhile, participants versity. Author correspondence to [email protected] made for what kinds of apps to seek. A literature review found TuftScope.squarespace.com

16 TuftScope | Fall 2017 • Volume 17, Issue I Fall 2017 • Volume 17, Issue I | TuftScope 17 INSIGHT INSIGHT Overuse of Antipsychotics in Nursing Homes The Plugged-In Physician Allison Kannam Nikita Chaubal

OR MANY FAMLIES, THE CHOICE TO TRANS- know patients better.2 On the other hand, not everyone agrees ITH THE ADVENT OF PERSONAL COMPU- The arrival of the Digital Age resulted not only in an evo- fer aging relatives to a nursing home feels like a neces- that simply intensifying penalties will eliminate the problem; ters and the World Wide Web, and subsequent lution of the doctor-patient relationship, but also in a new sary and natural step to keep them safe and comfort- some argue that there is “chronic understaffing” in nursing development of the Digital Age, information of breed of patient altogether: an informed and possibly more able.F The high prevalence of dementia in the elderly is a large homes and that overworked nursing assistants feel they must everyW type became rapidly available with the click of a few educated patient, capable of entering the doctor’s office with contribution to this decision, as assisted living facilities are use chemical restraint to control behavior.5 buttons. The need to purchase an encyclopedia set or visit insight into their own condition already, capable of receiv- structured to care for dementia, relieving stress on both the Given continual high rates of antipsychotic use and insuf- the library has been abated by near instantaneous access to ing an immediate second opinion from the portable device individual and their family. Dementia is one of the leading ficient penalties in Texas, some believe that a CMS “partner- thousands of resources online, eventually including medical in their own pocket. In the past, the standard patient was a causes of disability among the elderly.1 What many fami- ship” is misguided. According to Toby Edelman of the Cen- journals and databases. One of the first instances of medi- layperson, ill-informed and a “passive [recipient] of informa- lies are not aware of, however, are the alarming statistics on ter for Medicare Advocacy, “the initiative has been all about cal digitization was the National Library of Medicine’s 1971 tion that was filtered and dispensed by healthcare providers.”4 the excessive prescription of antipsychotic drugs in nursing training, teaching, cajoling, encouraging, but not enforcing creation of MEDLINE, an online database created for physi- Education is highly-valued in our society, and so it would homes, and the current lack of regulation to prevent this t h e l aw.” 2 Instead, she calls for better enforcement of the Nurs- cians to stay up to date on the most cutting-edge and recently- seem that increased patient education and awareness should abuse. ing Home Reform Act, published research.1 Eventually in 1998, after the creation and also be highly valued. If a patient following the instruction Antipsychotic which prevents the use large success of the World Wide Web, and in order to give the of a physician is taken to be analogous to a consumer buy- drugs are primarily of antipsychotic drugs public access to this same research, MedlinePlus was created.1 ing a product, the importance of patient education should recommended to treat for chemical restraint.2 But by then, there were already maturing plans that would be at least as highly regarded as the importance of consumer serious mental illnesses The overuse of anti- revolutionize healthcare. The release of MedlinePlus was soon education. It is clearly deemed advantageous for a patient to such as schizophrenia psychotic drugs in nurs- followed by the merger of healthcare service providers Heal- corroborate their doctor’s assessment with symptom check- and bipolar disorder.2 ing homes is extremely theon Corporation and WebMD, leading to the creation of ing websites, and patients are clearly utilizing these resources, Recently, there has been alarming and change WebMD, Inc. and its namesake with WebMD alone receiving increased attention on is crucial to protect the website.2 While one of the more over 145 million visits in the past the inappropriate use health and well being popular online medical informa- “The physician-patient re- six months.7 Does this newfound of these drugs to treat of a large population of tion providers, currently ranked reluctance to accept a doctor’s nursing home patients, the United States. Cur- as the most visited website in the lationship has been perma- professional opinion at face- many of whom suf- rently, there are 6.3 mil- “Conditions and Diseases” cat- value, however, undermine the fer from dementia, for lion Americans over the egorization on SimilarWeb.com, nently changed by the digi- physician-patient relationship? A the agitation or hostil- age of 65 in long-term WebMD is one of many resources study of a hospital in São Paulo ity they may express care facilities. And by to reference for medical advice.3 tization of medical journals reported that while 56.9 percent related to the symptoms 2050, that number will There has been a rapid expan- of doctors viewed their patient’s Image Source: http://flickr.com/ of dementia. This prac- (Sean Hayford Oleary, “Rolfsrudhjemmet Nursing Home”) double. To combat the sion in the nature and volume and resources, but not all of use of the internet as positive and tice is called “chemical issue, raising awareness of medical information available constructive, 27.6 percent of doc- restraint,” and in 2010 an estimated 185,000 nursing home or increasing fines to noncompliant nursing homes could cre- online, from articles published by these changes have been neg- tors viewed this use as an inter- residents nationwide received anti-psychotic drugs “without ate the necessary change. Additionally, given that many nurs- the National Institute of Health, ference in their relationship, and valid reason”.3,4 Many of these drugs are known to have dan- ing homes are under-resourced and may not have the capac- to independent bloggers offering at i v e .” 15.5 percent of doctors viewed gerous side effects when used for dementia. In 2005, the FDA ity to implement programming to work with violent patients their home remedies for runny it as damaging.8 Another study issued a black box warning to the drug Seroquel regarding its without using medication, an increase in government funding noses. Diagnoses for almost any ailment are available, with involving the internet usage of Australian men with prostate possibly fatal side effects when used with dementia patients.4 for nursing homes to increase their programmatic capacity the search term “symptom checker” turning up over four cancer revealed that some physicians even viewed patient Although this overuse is now widely recognized to be a prob- could hugely aid in preventing over-prescription. Communi- million results in a fraction of a second. In fact, a 2015 study education as a challenge to the traditional power dynamic, lem, the issue largely goes unpunished. Dr. Madeleine Bion- cation is key in resolving this over-prescription, whether it is based on over sixty million Google searches and a survey of and as a result assumed the role of a disciplinarian in a con- dollilo of the Massachusetts Bureau of Health Care Safety and between and elderly individual and their care staff, nursing 1013 adults in the UK determined that 21.8 percent of people sultation to reestablish a position of authority.9 Quality, reminds us that implementing harsher punishment homes and their staff, nursing homes and the government, or elected to self-diagnose their own condition on the internet, Other studies, however, found the opposite to be true, is complicated: “Federal rules are ambiguous, and harm from the government and the public. rather than visit their primary care provider.4 A similar 2013 with no overt negative effect on the doctor-patient relation- inappropriate use of antipsychotics can be subtle, indirect… study completed by the Pew Research Center determined ship being identified.10,11,12,13 Based on a 2014 survey of 202 making it difficult to penalize a facility.”4 Contrarily, the chief that thirty-five percent of adults in the U.S. had turned to the hematology out-patients, increased use of online health infor- medical officer at Centers for Medicare and Medicaid Ser- References for this article can be found at internet for diagnoses for themselves or someone else.5 While mation was shown to improve the doctor-patient relation- vices (CMS), Dr. Patrick Conway, insists that the government TuftScope.squarespace.com before the dawn of the Information Age, the first place to seek ship, not disturb it.10 A survey of Canadian cancer patients is extremely serious about enforcing penalties.2 Nationwide, professional opinion was a doctor, now it seems out of place and oncologists determined that even with the internet being CMS has launched a campaign to reduce antipsychotic use in to book a doctor’s appointment without first consulting a few a frequently-referenced source for information, 83 percent of nursing homes and has considered nursing homes partners in of the innumerable medical diagnostic websites online. With patients maintained that their physicians were their primary this initiative.2 They have distributed training materials that this clear shift in the path to healthcare diagnosis, it begs the information source, with the same sentiment being echoed encourage an individualized approach that allows nursing Author contact: Allison Kannam is a sophomore at Tufts Univer- question: how does the digitization of medicine affect the staff to address the root causes of misbehavior by getting to sity, Author correspondence to [email protected]. doctor-patient relationship? Author contact: Nikita Chaubal is a Sophomore at Tufts University. Author Correspondence to [email protected].

18 TuftScope | Fall 2017 • Volume 17, Issue I Fall 2017 • Volume 17, Issue I | TuftScope 19 Patients with more access to medical information are more informed and better equipped to improve their own RESEARCH HIGHLIGHT health condition. They can get the opinions of many doctors, even if the opinion is non-specific and directed at a broad A Look into Lymphatic System Therapy range of people as opposed to a single patient. Furthermore, Kurtis Chien-Young physicians with access to research and a more immediate erebrospinal fluid is the fluid that surrounds the brain.1 connection to their peers can stay up-to-date. On the other CIt is produced throughout the day in the cerebral ven- hand, for the patient looking at research addressing other tricles and eventually drains out of the cranial cavity.1 Past physicians, research lingo and medical jargon does not always researchers hypothesized that cerebrospinal fluid could translate easily into colloquial language; Medical papers can drain through either veins or lymphatic vessels, but they be misinterpreted and cause confusion and miscommunica- were not adequately equipped to determine the exact path- tion between patient and physician, not to mention undue way of drainage.1 Recent research by Ma et al. 2017 was able stress or panic. to determine the predominant pathway by which cerebro- Furthermore, physicians can themselves develop a pres- spinal fluid leaves the brain by using radiolabeled tracers.2 ence on the internet, giving patients a way to stay connected to Researchers infused the lateral ventricles of mouse brains them in between checkups. Take Doctor Mikhail Varshavski, with tracer molecules of various sizes.2 When the brains or as he’s popularly known, Doctor Mike, a physician who were imaged, it was found that the tracer molecules were has amassed over two million followers on Instagram. Social transported to the lymph nodes.2 The researchers also deter- media stardom is atypical for the average physician, and may mined that the flow of cerebrospinal fluid exiting the cranial Image Source: https://www.pexels.com/photo/computer-desk-electronics-indoors-374074/ even seem unprofessional, but Doctor Mike insists that “it’s cavity decreased as the mice aged.2 by a study conducted with parents of patients in Ireland.11,13 A diagnostic website still cannot deliver individualized patient incredibly important for a doctor and a patient to be able to The brain has few immune cells, so one of the purposes third study analyzing what information most influenced “rec- care, as it has no information about an individual’s family his- relate to one another … [because] gone are the days when of cerebrospinal fluid is to wash out toxins.1 These toxins can ommended treatment regimen as well as patient’s compliance tory or personal medical history. Websites also lack the ability patients go to the doctor and the doctor barks orders at them”. include misfolded proteins, which could otherwise accumu- with their physician’s advice” established that physician qual- to give patients a physical examination, which is an important He believes that having a presence on social media can lead to late to cause neurodegenerative diseases such as Alzheimer’s more open and easy communication and even “push people disease.1 So, with the current mechanism of cerebrospinal ity was the most important factor, more than online health and invaluable component of a doctor’s appointment; a physi- 16 information quality.12 Based on the research currently pub- cian is trained to recognize certain physical symptoms, some to go get physicals and checkups”. This new model of the fluid drainage in mind, a proposed method of treatment for lished, physicians are still considered the most reliable source that even a patient would not recognize. The patient’s lack of provider-patient relationship is nontraditional, but appeals to these neurodegenerative diseases may be to increase the flow of medical information. awareness of their own condition, then, would hinder a web- younger generations, who use the internet and social media of the lymphatic system.1 The theory follows that a greater Even so, there is still understandable concern as to the based diagnostic tool from accurately diagnosing them. Fur- as a primary form of communication. lymphatic flow would mean more cerebrospinal fluid exit- quality and depth of medical information available online thermore, practicing physicians have the irreplaceable experi- As further research is conducted on the developing nature ing the cranial cavity, which would flush more toxic proteins that patients are consuming. Many websites are authored by ence of seeing and dealing with many different illnesses on a of the physician-patient relationship, it is important for physi- from the brain.1 non-medical personnel, and therefore the information may day-to-day basis. A 2013 Pew Research Center study deter- cians to use the internet to their advantage in fostering open The concept would require further research, and a start- be inaccurate. It is dangerous for patients to consult disrepu- mined that of sixty percent of American adults who report- relationships with patients. The apparent general consensus is ing point could be to determine if mice with Alzheimer’s dis- table websites and follow the advice they give without first edly self-diagnosed a condition online, thirty percent were that providers should encourage patient education by provid- ease do express a slower rate of lymphatic flow, which would checking with a primary care provider. In addition, medical given a different opinion during a follow-up appointment ing high-quality healthcare resources and use these resources signify insufficient cerebrospinal fluid drainage.2 Such data research can often be misinterpreted or misunderstood by with a practicing physician.5 In addition, a different study con- as a tool for furthering discussion and improving and devel- could further clarify the role of the lymphatic system and individuals who do not have a background in the sciences. ducted on emergency room patients determined that only 29 oping the rapport between patient and physician. A study support therapeutic techniques that interact with the lym- Studies are often published, attesting the carcinogenic, tera- percent of these individuals had located the correct diagnosis conducted in central Israel clinics determined that individu- phatic flow.2 togenic, or otherwise dangerous effects of certain medicines online prior to seeing their physician.14 While online medical als who used online medical resources and shared the infor- and therapies, but there are many different factors that need resources are fine supplemental materials, they are not quite mation they discovered with their doctors overwhelmingly References felt that it had a positive effect on their relationships.15 Of the to be accounted before concluding that the medicine or ther- strong enough to replace the sheer experiential knowledge of 1. ETH Zurich. (2017, November 10). Dementia treatment adults surveyed, however, only 28 percent had been directed apy is unsafe. For example, a study with an animal model that a physician. Online resources, however, can be of great help to research: Exit through the lymphatic system. ScienceDaily. to medical resources by their physician.15 By proactively rec- determines a medicine is carcinogenic does not decisively physicians. The internet makes it easier to stay up-to-date on Retrieved November 11, 2017 from www.sciencedaily.com/ ommending these resources to patients in the first place, the indicate that the same conclusion can be applied to humans, new research, techniques, and theories being published on a releases/2017/11/171110084307.htm provider can begin to establish a positive dynamic with their as human and animal models have many important differ- daily basis. With the internet as a resource, doctors can there- 2. Ma, Q., Ineichen, B. V., Detmar, M., & Proulx, S. T. (2017, patient and the internet. In this way, the digitization of medi- ences. In addition, some animal models use an animal dos- fore implement new strategies into their own practices as they November 10). Outflow of cerebrospinal fluid is predomi- cine, a new and permanent fixture to the medical field, need age-to-body weight proportion that is significantly different are found and shared online. The ease of communication over nantly through lymphatic vessels and is reduced in aged not be framed as a unilateral hindrance. than the typical human dosage-to-human body weight ratio; the internet also means that physicians can constantly be in mice. Retrieved November 10, 2017, from https://www.na- The physician-patient relationship has been permanently for example, if humans consume .5 percent of their body contact with their peers, thereby collaborating across spe- ture.com/articles/s41467-017-01484-6 weight of a specific chemical, and an animal study involves cialties in order to provide the patient with a more complete, changed by the digitization of medical journals and resources, giving an animal ten percent of its body weight of that same holistic experience. but not all of these changes have been negative. Physicians chemical, then the study is not necessarily translational. All So, consider again, is the internet damaging the traditional must continue to adapt the way they operate in order to of this research can be easily misconstrued, rendering read- physician-patient relationship? Simply put, the dynamic accommodate the changing services available to patients, ers vulnerable to drawing incorrect conclusions or arriving at between patient, web interface, and physician is clearly multi- and continue to keep the development of a collaborative and inaccurate appraisals. faceted and complex, so there is no clear-cut way of knowing. empowering physician-patient relationship at the top of their Therefore, it is important to remember the expertise of priorities, especially in this Digital Age. our physicians, as they can interpret research and determine References for this article can be found at Author contact: Kurtis Chien-Young is a Sophomore at Tufts Uni- its relevance to a patient. Additionally, the most high-quality TuftScope.squarespace.com versity. Author Correspondence to [email protected].

20 TuftScope | Fall 2017 • Volume 17, Issue I Fall 2017 • Volume 17, Issue I | TuftScope 21 INSIGHT Why Won’t People Eat Their Vegetables? Jesie Fu

OOD CAN SERVE AS EITHER THE BEST MEDI- least one fourth of a cup of vegetables at lunch.4 Consump- cine, or the worst form of poison. A plant-based tion of a meager quarter cup of vegetables at lunch makes diet, which emphasizes unrefined fruits, vegetables, obtaining the daily goal of at least two and a half cups of veg- Flegumes, and whole-grains, appears to be the solution to pre- etables challenging. Unlike the questionnaire from the previ- venting disease, mitigating the obesity epidemic, and capi- ous study, which provided subjective data when considering talizing on a multitude of health benefits. Despite these pay- the accuracy of self-reports, the mountain of vegetable waste offs, vegetable consumption remains low. A deeper analysis presented unambiguous evidence that highlights the dearth of current behavior, attitudes, and barriers to consumption of plant-based foods in the diet. sheds insight on how to effectively switch to a more plant- To further complicate this concern, the aforementioned based diet. study makes it evident that in many schools, plant foods are not of short supply, but are widely available and actively CURRENT INTAKE OF PLANT-BASED FOODS ACROSS discarded as trash. Even when vegetables are placed on stu- Image Source: www.dole.com DIFFERENT DEMOGRAPHICS dents’ trays, students often opt out in a concerted way. This at your fruits and vegetables is a ubiquitous phrase, yet conscious refusal across the large student body indicates that levels through the examination of participant food diaries vegetables would be valuable.1 These interventions are easy Emost people do not consume the recommended five people need more incentive and creative means to incorpo- during 2007, 2009, and 2013. The study concluded that for to implement, as they are simple and inexpensive. Taste- fruits and vegetables a day. At times, in the average person’s rate more plant-based foods in their diets. an increase of eight portions of fruit and vegetables a day, testing events, the incorporation of more vegetable toppings, quotidien diet, processed foods dominate, sugar, fat, and salt happiness increased by 0.24 life satisfaction points, which and more green smoothies may also yield positive results.4 prevail, while fruits and vegetables are less prominent. One PLANT-BASED FOODS AS AN IMPROVEMENT TO is equal to the psychological gain from unemployment to More simple approaches, such as strategically placing fruits study published in the International Journal of Public Health PHYSICAL AND MENTAL HEALTH employment.3 The study accounted for confounds, such as and vegetables in more accessible locations, paying close determined just how few people comply with the five-a-day pproximately 1.7 million (2.8%) of deaths can be attrib- personal income and changing circumstances, ensuring that attention to portion sizes, and making a conscious effort to model. This study examined students from 27 universities in Auted to inadequate fruit and vegetable intake.7 High plant foods were solely responsible for the improvement. incorporate vegetables all have the potential to revolutionize low, middle, and high-income countries across Asia, Africa fruit and vegetable intake is known to decrease the risk of The researchers also noticed that the mental health benefits the way people approach food. A variety of solutions exist, and the Americas. Through anonymous questionnaires to noncommunicable diseases, including obesity, cancer, car- from a plant-based diet materialized sooner than physical and a collective effort can lead to critical improvements. analyze vegetable consumption among 17,789 undergradu- diovascular disease, and diabetes. Plant-based foods confer health benefits.3 By providing immediate gratification, a ate students, researchers discovered that 82.8% consumed these benefits because they are lower in saturated fat and plant-based diet focused on the benefits of mental health can CONCLUSION less than the recommended amount of fruits and vegetables.5 contain fiber, antioxidants and phytochemicals.2 Plant-based be incentivizing as an alternative to waiting for the physical ualitative and quantitative studies indicate that plant- This alarming percentage of students failing to meet the diets also reduce the risk for hypertension, gallstones, kidney benefits to manifest. Qbased food consumption stands undesirably low across requirement mandates a need stones, constipation, and the world, regardless of income level. Few heed the five-a- for intervention. Considering “The benefits of a plant- diverticular disease.2 These BARRIERS TO CONSUMPTION AND INTERVENTION day fruit and vegetable model, contributing to the progres- the study’s large sample size, benefits indicate plant-based STRATEGIES sion of non-communicable diseases. A greater consumption varied socioeconomic span, based diet are not just diets are one compelling urrent vegetable consumption across the world is inad- of fruits and vegetables provides a plethora of physical and recent data, and global scale, answer to combating disease Cequate, and the barriers to consumption are diverse. mental health benefits, from reducing chronic diseases such inadequate vegetable con- and alleviating ailments. “Eat- Common barriers include financial concerns, lack of nutri- as heart disease, diabetes, cancer and obesity to improving sumption poses a pervasive limited to physical ing the rainbow,” or eating a tion education, limited time, taste perception, and absence life satisfaction and mental wellness. Barriers to vegetable issue. variety of plant-based foods, of motivation. In a qualitative study of 29 New Zealand Uni- consumption include absence of incentive, shortage of time While some expect under- attributes, as eating more ensures the body receives a versity students between the ages of 18 and 24, researchers and money, and lack of appetizing recipes. Depending on graduate students to make diverse range of nutrients, to detected that taste and health awareness were prime barriers the country in question, culture and family at times play a less healthy choices due to fruits and vegetables optimize health. to vegetable consumption.1 In another survey in developing greater role in deterring vegetable consumption. Interven- lack of parental supervision, a The benefits of a plant- countries, lack of family support emerged as a main barrier tion methods include creative and quick recipes, increased closer look at middle and high improves mental health.” based diet are not just limited to consumption.6 An emphasis on plant foods during family knowledge of affordable plant options, strategic placement of school students’ dietary habits to concerns for physical meals reduces the risk of plant food deficiency in children plant foods in the environment to increase accessibility, and reveals that children and ado- health, as eating more fruits later in life, as families build the foundation for healthy encouraging families to build the foundation for plant-based lescents are just as negligent in meeting dietary recommen- and vegetables also confers mental health benefits. A habits. These barriers signal that a psychological investiga- eating habits. These intervention methods are sustainable, dations. One study published in the Journal of School Health longitudinal study conducted on 12,385 randomly selected tion ought to be conducted to target the absence of produce and collaborative efforts across the globe will generate a used quantitative methods to evaluate vegetable consump- Australian adults determined the correlation between in the diet. greener world, both in our diets, and our surroundings. tion, focusing on vegetable consumption across seventeen increased fruit and vegetable consumption and happiness When students were asked how they could be per- elementary, and sixteen middle and high schools in Ohio. suaded to eat more plant foods, they responded that cooking After examining 11,250 trays containing vegetable waste, Author contact: Jesie Fu is a student at Boston University. Corre- sessions, quick and easy recipes, more varied nutritional References for this article can be found at researchers concluded that only one in four students ate at spondence can be sent to [email protected] information, and increased awareness of cheap fruit and TuftScope.squarespace.com

22 TuftScope | Fall 2017 • Volume 17, Issue I Fall 2017 • Volume 17, Issue I | TuftScope 23 bodies. Brain and metabolic activity was INSIGHT observed in the dogs, which survived any- where from 6 hours to 2 days.12 In 1970, Getting A Head White was at it again, performing the first ever monkey head transplant. He trans- The World’s First Human Head Transplant Said to Occur by Early 2018 planted the heads of four Rhesus monkeys Helen Mizrach onto bodies, but did not make any attempt to fuse their spinal cords. The monkeys OW FAR IS MODERN MEDICINE WILLING The two physicians are now searching for a volunteer in the were able to see, hear, and chew food. Due to go to extend the human lifespan? Italian neu- country, and if one is found, the procedure could potentially to the lack of spinal cord connectivity, the rosurgeon Sergio Canavero has made headlines take place as early as 2018.10 Ren and Canavero have faced sig- monkeys survived for a maximum of 8 recently,H announcing his intention to carry out the first ever nificant skepticism and criticism from scientists and medical days in the laboratory.12 human head transplant sometime in 2017.7 Canavero is a suc- professionals, due to the controversy and risks surrounding Dr. Xiaoping Ren, Canavero’s new- cessful neurosurgeon and researcher with a primary interest the procedure.7 If the doctors do decide to go forward with found partner in the anticipated head in pain regulation, specifically central pain syndromes in their quest and perform the first ever human head transplant, transplantation surgery, claimed in 2015 which damage to the central nervous system leads to chronic, it would be a groundbreaking feat for the fields of science and that he had conducted over 1000 head difficult-to-treat pain.8 Until recently, the concept of a human medicine. transplants on mice.7 Over half of his mice head transplant was unfathomable, and sounded more like survived for periods longer than 24 hours, something out of Frankenstein than a legitimate medical WHAT IS THE HISTORY OF HEAD TRANSPLANTATION? with the longest surviving for 6 months.12 procedure.1 Due to recent devel- ver since the beginning of In January of 2016, Canavero told New opments in immunosuppres- Ethe 20th century, scientists Scientist that a successful head transplan- sive drugs and neurogenerative “Is it ethical for a doctor have discussed the possibility tation had been completed on a monkey repair technology, this procedure of head transplantation.12 One in China, although the monkey had only may not be as unrealistic as once to subject a patient to pos- of the main challenges faced by been kept alive for 20 hours for “ethical 1 7 thought. The term “human head these scientists was determin- re a s on s .” In September of 2016, Canavero Image Source: Patrick J. Lynch, medical illustrator; C. Carl Jaffe, MD, cardiologist. transplant” is ambiguous; head sibly the most complex and ing how to restore circulation revealed that he had performed a success- http://creativecommons.org/licenses/by/2.5 transplantation is essentially giv- through severed blood vessels. ful dog-head transplantation, providing and the donor’s body must be cooled to a temperature of ing a living human head a new high-risk surgical procedure Dr. Alexis Carrel, a French sur- video footage of the dog walking three weeks after the sur- 12-15o C (53.6-59o F) to induce hypothermia and decrease body to control. It is distinct geon, overcame this challenge by gery.7 In May of 2017, Canavero and his team of Chinese sur- metabolic rates. The two surgical teams will make deep from a brain transplant, as the known to mankind?” developing a technique that uses geons claimed to have transplanted the head of one rat onto incisions around each patient’s neck, carefully separating entire head including the brain is fine needles and extremely thin the back of a larger living rat, creating a two-headed animal all anatomical structures. Under an operating microscope, to be transported from one body threads as a suture for blood ves- that survived for 36 hours.13 The most promising research in the spinal cords in both subjects are to be clean-cut with an to another.7 The body to be used sel reconstruction. In 1908, Dr. the field of head transplantation today stems from Dr. Ren’s extremely sharp blade. Once all cuts have been made, the in the surgery would come from a transplant donor classified Carrel and American physiologist Dr. Charles Guthrie per- lab, who claimed in June of 2017 to have successfully repaired recipient’s head will be transferred onto the body and tubes as brain-dead but whose body is otherwise healthy and can be formed the first-ever dog head transplantation, essentially severed spinal cords in rats using the same principles that Dr. will be connected to ensure that the head connects to the kept on life support.6 A human head transplant, if performed creating a two-headed dog; The scientists did this by attach- Canavero intends to use on his human subject. 8 out of the 9 new body’s circulation. The two spinal cord stumps are to be successfully, could provide an individual with an entirely new ing one dog’s head onto another dog’s neck and connect- rats tested were still alive one month after the operation. The fused within 1-2 minutes using GEMINI technology, namely body free of pain, paralysis, or deformities. But who would ing their arteries in a way that allowed blood flow from the rats in his study that were treated with polyethylene glyol (the the aforementioned chemical polyethylene glycol.2 Polyeth- choose to undergo such a risky procedure? recipient head to the decapitated head. The dog demonstrated GEMINI agent that Dr. Canavero wants to use for neuronal ylene glycol has fusogenic potential and has been shown to Valery Spiridonov, a 30-year-old Russian computer sci- some aural, visual, and cutaneous reflex movements after the repair on his human subject) were described as nearly nor- promote the growth of spinal cord nerves in animals.1 After entist with Werdnig-Hoffman disease, elected to be the first procedure, but it was euthanized after a few hours due to its mal.2,9 Many of these and other head transplantation attempts all muscles, nerves, skin, and the blood supply have been patient to undergo this high-risk surgery. Werdnig Hoffman deteriorating condition.12 lack procedural and post-procedural details and have not reconnected, the patient will be put into a coma for around a disease is a genetic disease that breaks down muscles and kills Dog head transplantation was attempted once again in been widely circulated in the scientific literature. Recent month to recover.11 Inducing a coma will help to limit move- nerve cells in the brain and spinal cord.6 Most people with the 1950s; Dr. Vladamir Demikhov of Russia attempted mul- developments appear mostly in the research conducted by ment of the newly fused neck. During this time, electrodes Spiridonov’s condition don’t live past age 20, so he reasons tiple, slightly more successful canine head transplantations. Dr. Ren and Dr. Canavero. This lack of research has left the will be used to stimulate and strengthen the newly con- that this procedure might be his only chance to change his Demikhov’s dogs were able to move, see, and lap up water. scientific community questioning the feasibility and ethics of nected spinal cord. A large regimen of immunosuppressive fate.6 Earlier this year, however, Mr. Spirdinov elected to opt However, most of Demikhov’s dogs died within a few days this procedure on animals, let alone humans. drugs will be required to prevent the body from rejecting out of the procedure and to instead raise money for a con- due to immune rejection reactions between the donor and the newly attached head and vice versa.1 Canavero believes ventional spinal surgery in an effort to improve his quality recipient, due primarily to the lack of immunosuppressive HOW WILL THE PROCEDURE WORK? that the patient will be able to move, feel, and speak imme- of life.10 The procedure has since been delayed, and is not agents available at the time.12 In 1965, American neurosur- ergio Canavero has outlined a full procedure for a human diately after coming out of the coma. The patient will have to expected to take place in 2017. Dr. Canavero has since part- geon Robert White attempted to conduct a brain transplant Shead transplant called HEAVEN or Head Anastomo- undergo intensive physiotherapy in order to re-learn how to nered with Dr. Xiaoping Ren, a Chinese neurosurgeon of using dogs as his subjects. He came up with an “auto-perfu- sis Venture in the scientific literature. HEAVEN involves walk and perform normal daily functions, but is predicted to Harbin Medical University to help him carry out the first ever sion” system that allowed for maintained blood flow to the using GEMINI technology which takes advantage of special eventutually be able to live a normal life.1 human head transplant. Dr. Ren has performed over 1000 brain even after being severed from the body. Using this substances known as “fusogens” to repair severed spinal WHAT ARE THE LEGAL AND ETHICAL IMPLICATIONS head transplants on mice, only some of which have been suc- method, White transferred six canine brains into six canine cords, axons, or neurons.1,2 The procedure itself comes with OF HEAD TRANSPLANTATION? cessful.7,9 Regulations in China regarding medical research innumerable risks, and will require two large surgical teams. f it wasn’t already clear, a human head transplant is quite a are more relaxed than in other nations, making the country One team will be responsible for the head donor and the risky surgical procedure and has generated a multitude of 6 Author contact: Helen Mizrach is a Junior at Tufts University. 1 I an ideal place to perform such an experimental procedure. Address correspondence to [email protected] other team for the body donor. First, the recipient’s head legal, ethical, and logistical questions. To begin, is it ethical

24 TuftScope | Fall 2017 • Volume 17, Issue I Fall 2017 • Volume 17, Issue I | TuftScope 25 for a doctor to subject a patient to possibly the most complex and high-risk surgical procedure known to mankind? Head RESEARCH HIGHLIGHT SCIENCE REPORT transplantation in animal models has only seen mild success, so how can one justify performing it on a human?12 Will the The Bottom-Up Approach with Diazepam Planarian Went to Space, Got Two Heads surgical team face legal repercussions if the subject does not Kurtis Chien-Young survve the procedure? Will the procedure leave the subject Annie Phan physically hurt? In the event that the subject ends up in iazepam, originally sold under the brand-name Vali- 1 worse condition as a result of the operation, can they elect to um, is a sedative drug used to treat anxiety symptoms. D NE OF THE HALLMARKS OF OF BEING A They also exhibit learning, curiosity, and problem-solving end their own life or pursue a physician assisted death?5 Despite the sedative properties, current and past research 1 good researcher is to venture into unknown ter- abilities. Planarians are attractive candidates for regenera- There are a number of ethical concerns surrounding the indicate that diazepam can amplify aggressive behavior. ritories. For Dr. Junji Morokuma of the Allen Dis- tion studies because they are more genetically similar to donation of a body to be used in the procedure. First and I spoke with Dr. Klaus Miczek, a professor of psychology, coveryO Center at Tufts & Tufts Center for Regenerative and vertebrates than other model organisms like Drosophila foremost, is it worth it to transplant an entire body to save a pharmacology, and neuroscience. Dr. Miczek’s laboratory Developmental Biology (TCRDB) and Department of Biol- melanogaster or Caenorhabditis elegans. In most cases so far, single life?3 Cadavers often contain many functional organs researches the relationship between stress and drug abuse, ogy, part of his completed research involves literally ventur- microgravity has been shown to inhibit tissue growth and which can be used to save multiple human lives. Is one human as well as the brain mechanisms involved with aggression. ing into territories unknown to most of mankind. His team regeneration in mammalian tissues. As humans consider life worth more than another?7 How is the body of the donor Dr. Miczek has researched diazepam and similar benzodiaz- sent a mix of whole and fragmented Dugesia japonica worms becoming a space-faring species, it is imperative to begin to to be chosen? Would it be ethical for a younger recipient to epines in animal models. In his experiments, mice, rats, or to the International Space Station to investigate the effect understand the change in cellular, behavior and physiology receive the body of someone further along in age and vice monkeys could receive a drug treatment before encounter- 2 of microgravity and micro-geomagnetic fields on regenera- that space elements can induce. In this way, research of this versa? If an older recipient were to receive a young er body, ing another animal. The drug’s effects on the experimental tion, and whether these effects persist upon returning to nature can serve as a precursor to more complex inquiries would it extend their lifespan?3 How would sex and gender animal’s behavior toward the intruding animal could then Earth. As many biologists are aware, planarian flatworms that will become increasingly relevant. be navigated between the availability of donor bodies and be observed and manipulated with adjustments to the drug are nature’s most adept regenerators. They are able to com- the identity of the subjects? What if the subject simply wants dosage.2 “These drugs follow in a very lawful manner, an pletely recapitulate all body parts, including complex organs HOW THEY DID IT a new body to enhance their appearance or athletic perfor- inverted U-shape dose-effect curve,” Dr. Miczek tells me.2 such as centralized brains and central nervous systems from ifteen flatworms in total were amputated by hand into mance? Or perhaps simply to extend their life?3 Under what That is, along the initial segment of the curve, increasing small pieces of the body, with high morphological fidelity. three different fragments on Earth, approximately 31 circumstances should the procedure be considered an option? dosage results in a subsequent increase in aggressive behav- F 2 If the procedure is successfully completed, how will the ior. As for the latter segment, the higher doses have a seda- 2 subject adjust to their new body? Will their personality, voice, tive effect, sometimes enough to put the animal to sleep. cognition level, memories, thoughts, and feelings remain the With the drug action in mind, Dr. Miczek and other re- same? Will they adopt any of the body donor’s traits or ail- searchers set out to determine the mechanism of action. By ments? What are the psychological implications of adjusting using benzodiazepine receptor antagonists, it was discov- to a new body?3 Philosophically, the procedure even raises ered that benzodiazepines change the conformation of the 2 questions regarding how human identity should be defined.3,5 GABAA receptor molecule. These receptors are targeted by Are humans defined by their bodies, their heads, their brains, the inhibitory neurotransmitter GABA, also known as gam- and/or their thoughts? If one switches their body, have they ma-aminobutyric acid, which allows chloride ions to flow 2 become someone else? into the cell. “Turns out, that benzodiazepines share this action with alcohol,” Dr. Miczek remarks.2 Unsurprisingly, CONCLUDING THOUGHTS the graph of aggression vs. alcohol resembles the dose-effect he human head transplant, a surgical procedure once curve for aggression vs. diazepam. 2 Tthought to be impossible and outlandish, may be plau- GABAA is a receptor molecule with five subunits. The sible in the near future. If Dr. Sergio Canavero and Dr. Xiaop- α2 subunit is relevant to the regulation of aggression, and 2 ing Ren are able to successfully carry out this procedure, they it is the subunit that benzodiazepines interact with. Now, will transform the fields of science and medicine. Canavero what is left to be done is to experimentally determine the 2 has published an exact method for this procedure, utilizing genes that express these subunits. Perhaps, once the genes GEMINI technology and the latest innovations in immuno- responsible have been discovered, they can be manipulated suppressive drugs.1,2 As evidenced from the mixed success so that inactivation of aggression-related receptors can pre- rates of previous head transplantation experiments, further vent the aggression-heightening effects of alcohol and diaz- 2 research and experimentation on animal models is warranted epam. before the surgeons attempt the procedure on a human sub- However, to approach aggression in a bottom-up man- 2 ject.12 A plethora of ethical and philosophical questions sur- ner would be getting just half of the picture. Seeking and round this surgery, most of which cannot be answered.3,5 The manipulating the gene that codes for the α2 subunit on the major question that remains is: will Dr. Canavero and Dr. Ren GABAA receptor cannot account for the complexity of the 2 ever go through with it? polygenic phenomenon that mediates aggression. A top- down approach would then be to take the domain of aggression and to study the myriad of factors that control it.2 The picture would be complete when the two approaches com- plement each other.2 “But we’re far from it,” says Dr. Miczek.2 A. Fifteen planaria were trisected before being sent to space. Until then, he notes, “it’s important to remember that ag- B. Whole or segment worms were sent to space or left on Earth for thirty-two days. Worms were collected 68 hours after splashdown. 2 References for these articles can be found at gression is not explained by a single gene." C. Worms were put in Poland Spring water for analysis and data collection. TuftScope.squarespace.com Source: Regeneration published by John Wiley & Sons Ltd. www.ncbi.nlm.nih.gov/pmc/articles/PMC5469732/figure/reg279-fig-0002/

26 TuftScope | Fall 2017 • Volume 17, Issue I Fall 2017 • Volume 17, Issue I | TuftScope 27 hours before their launch into space. As illus- trated in the first figure, launched into space SCIENCE REPORT were eight sealed, 50 mL tubes with a 1:1 air-to- water ratio. In these tubes were variable num- Planarian Went to Space, Got Two Heads bers of whole worms, worm heads, pharynx, or tail fragments. Meanwhile, eight tubes of exactly An Interview with Dr. Junji Morokuma the same number of whole worms and worm Annie Phan body fragments remained on Earth, under sili- mar conditions as their space-exposed counterparts; The Earth tubes were kept in full darkness at 20 ˚C for the same period of time. The worms AP: Did you have any expectations or predictions going sent to space spent approximately 29 days in to the experiment? microgravity, and in a micro-geomagnetic field JM: We did not have any predictions, as no one has ever sent Junji Morokuma, Ph.D. in the International Space Station. Upon return- flat worms or planaria into space before. Yet, in space, we Research Associate ing to Earth, the worm samples were retrieved expected micro-gravity, micro-geomagnetic field/force, and 68 hours after splashdown. Water from the con- higher radiation. The environment was quite different and Dr. Michael Levin’s Lab not typical to Earth, so anything could happen. Thus, we did Allen Discovery Center at Tufts & current, Earth-only control and space-exposed Tufts Center for Regenerative and Develop- worm groups were frozen immediately after not expect anything specific. One can only know what will mental Biology (TCRDB) & return to Earth and stored at −20°C for chemical happen by trying it. Department of Biology analysis. Tufts University WHAT THEY FOUND The control group spent 95.5% of their time in the dark. In contrast, the worms that had experienced space travel hole worms sent into space were found spent only 70.5% of their time in the dark. Why is there read and compiled. Wto have spontaneously fissioned into such a difference while both groups were kept in the dark multiple worms, while space-exposed worm during the experiment? Do you have any hypotheses as to why, upon returning to fragments and Earth-only whole worms and Earth, the space-exposed worm replicated more slowly fragments did not. There were fewer worms in We do not know what specifically has changed within the A,B,C. Space-exposed double-headed worms were trisected. worms that went to space, yet somehow the had diminshed than the control? the container that had gone to space compared D,E,F. The pharynx segment regenerated into a double-headed worm, which each head seg- to the number of worms that had remained on ment regenerated into a single-headed worm. preference for the dark. Only one can speculate; For example, Just as in the light preference change, we do not know Earth. Similarly, there was less growth in the SOURCE: The Authors. Regeneration published by John Wiley & Sons Ltd. https://www. something could have changed within their body that detects what specifically has changed within the worms that went ncbi.nlm.nih.gov/pmc/articles/PMC5469732/figure/reg279-fig-0006/ worm fragments exposed to space compared to light, or their actions to avoid the light. to space, yet somehow the changed environment (micro- the Earth-only worm fragments. However, con- gravity, micro-geomagnetic field/force, and higher radia- trol worms on Earth were kept at a constant 20 ˚C while the Since their metabolic states had been altered, reintroduc- Whole worms sent into space were found to have fissioned tion) has affected their somatic stem cells, called neoblasts. worms in space experienced higher temperatures as part of tion into their previous standard living conditions resulted spontaneously, but control whole worms on Earth did Neoblasts are the only multiplying cells in the planaria, and their space travel. This difference in temperature could have in severe shock. Using liquid chromatography–mass spec- not. The paper pointed out that it might be because the are the very source of their outstanding regenerative ability. accounted for the whole worms fissioning in space. trometry (LC-MS) analysis on the water samples, research- temperature in the space station is different, is a change These somatic stem cells can become any part of the worm Probably the most unexpected finding from this experiment ers found out that the space-traveled planarians underwent in temperature usually account for spontaneous fission? body. Replication and regeneration all rely on neoblast’s was the occurence of the unusual ‘double-headed’ phenotype, ability to multiply, and if this is affected, so will the growth interesting molecular changes. Eleven proteins were identi- Yes, higher temperature will result in more fissioning. Con- which resulted from the pharynx fragment. This phenotype is of the worm itself. fied in the water that housed the space-exposed worms that trolling constant temperature in space was not possible for extremely rare in control populations; In this laboratory’s eigh- were absent in the water that housed the Earth-only worms. our experiment, yet in future plans, we want to try to main- teen years of maintaining D. japonica, the spontaneous double- Of the 11 proteins, genetic sequencing reviewed orthologs in tain the same temperature between Earth and space worms. One of the objectives of the experiment is to figure out what head worm had not been observed a single time. Remarkably, S. mediterranea, a different species of planarian, for 9 of them. might the impact of the lack of electric fields, magnetic upon removing the two heads of the double-headed worm, There was also a significant difference in the microbiome fields, electromagnetic fields to human regenerative health. the headless middle fragment again regenerated into a double- profiles between Earth-only and space-exposed worms. The Eleven proteins were identified using mass spectrom- How can we apply the knowledge we obtained from studying headed phenotype, demonstrating that the major body-plan number of Chryseobacterium colonies significantly increased etry in the water that housed the space-exposed worms, these worms to human? modification that occurred in this specimen persists for at least but not the Earth worms. Of all of them, you identified in space-exposed worms, and Variovorax, Herminiimonas, Experimenting on humans directly is ‘difficult’ in many way, two rounds of cutting and subsequent regeneration after expo- orthologs of S. mediterranea for nine of them, which is a and the unknown Comamonadaceae sp. It was therefore con- especially in space. So, studying basic life forms and having sure to space travel. different worm species than the one you are examining? cluded that space exposure led to metabolic changes detect- a more targeted focus in future studies will be the more There were, in addition, some behavioral alterations Why is this the case? able in the animal’s chemical composition. efficient and effective way to establish knowledge on what observed in the space worm. While the controls spent 95.5% While the S. mediterranea worm genome is fully read, unfortu- happens to life in space. The collective knowledge of life in of their time in the dark, as is normal for this species, the nately the Dugesia japonica worm genome is not, for a few rea- space will eventually be applied to humans, hopefully to worms that had experienced space travel spent only 70.5% of sons. At this moment, the only comparable genetic information advance our health and our future. their time in the dark. Upon returning to Earth, the sample are from the S. meditteranea worms. Hopefully, this will change containing 10 whole worms curled up ventrally and were soon, when the Dugesia japonica worm genome is successfully paralyzed when introduced into fresh Poland Spring water. This state of “water shock” diminished after 2 hours which led References for this article can be found at References for this article can be found at researchers to hypothesize that the worms had modified their TuftScope.squarespace.com Author contact: Annie Phan is a sophomore at Tufts University. TuftScope.squarespace.com metabolisms to accommodate the environmental change. Address correspondence to [email protected].

28 TuftScope | Fall 2017 • Volume 17, Issue I Fall 2017 • Volume 17, Issue I | TuftScope 29 One method of DNA analysis INSIGHT involves the assessment of Single Nucle- otide Polymorphisms (SNPs), regularly 23AndMe: At-Home Testing Controversy occurring variations in the genome which serve as biological markers for Jamie Tebeau comparing DNA samples.6 People with ancestors from the same geographical SINGLE MOLECULE EXPLAINS OUR PAST, has received a master’s degree in genetic counseling and area usually show similar SNPs.7 The present, and future; our physical characteristics and passed a national board examination, individuals are able to accuracy of determining the presence our inner workings; our ancestry and our hered- consider the gravitas of this information before they pursue and location of an SNP depends on its ity.A Deoxyribonucleic acid, known by the layman as DNA, testing, as well as process the information together with an individual sequence – which means 2 contains four simple nitrogenous bases which determine expert. It is uncertain whether 23AndMe understands the that each gene that 23AndMe analyzes our entire genetic makeup. Variation in the human genome potential psychological implications of the information that may potentially have a different rate of reveals the basis of disease as well as physical traits and they supply. The company lists a short blurb on their web- accuracy.6,7 23AndMe does note in its genetic predispositions. All of this information, contained in site with a link to search for genetic counselors based on fine print that accuracy and relevance 1 every cell in the human body, serves as an incredible tool for geographic location. But do a few sentences provide enough of results may vary with ethnicity of scientists, physicians, and now the average person, too. For information for the average consumer? the consumer.1 In addition, the estab- about one hundred dollars, any individual can purchase a 23AndMe was first approved in April of 2017 to provide lishment of predisposition towards a Image Source: https://www.flickr.com/photos/acme/7941786268 genetic analysis from 23AndMe. customers with information regarding genetic risk based on disease does not guarantee its onset, 5 Founded in 2006, 23AndMe strives “to help people access, the presence of mutations in the genome. The test looks for the time that the disease will manifest, or the severity of its not be used for research purposes without consumer consent, understand, and benefit from the human genome” by market- variations in DNA which are correlated with an increased manisfestation.8 In most cases, DNA testing cannot deter- but may be sent anonymously to third parties.1 The consumer 1 ing the first-ever FDA approved at-home genetic test. By the risk for ten different diseases, including late-onset Alzheim- mine the probability that the individual will acquire the trait should understand that information regarding their genetic 5 means of a simple saliva sample, 23AndMe claims to be able er’s and Parkinson’s Disease. Despite these results, 23AndMe or disease.8 code, including information about ancestry and health, will to provide its consumers with information regarding ancestry, writes in its fine print that the tests are not designed diag- be stored on a database without an alternative option. 1 1 disease predisposition, carrier status, and traits. Before 2015, nose disease or to be used to make health decisions. In short, PRIVACY FDA-approved genetic testing was only available through 23AndMe will provide the details of the genome, but will not major concern connected to genetic testing is the pos- CONCLUSION an individual’s physician. The federal agency’s approval has become involved if the consumer decides to make a health Asibility of discrimination based upon the results. In ver 2 million people have taken advantage of the new transformed the accessibility decision based on that genetic 2008, President George W. Bush signed into law the Genetic Oand innovative technologies of at-home DNA tests proof genetic information – but information. The company Information Nondiscrimination Act (GINA), which makes vided by companies such as 23AndMe.1 In the future, the at what cost? “Despite these results, does not provide information it illegal for United States employers to discriminate against FDA plans to accelerate the speed at which DNA testing will regarding these diseases and employees or potential employees based on genetic informa- reach the market: “[the FDA] intends to exempt additional GENETIC COUNSELING 23andMe writes in its fine does not guarantee the accu- tion or family medical history.9 The law also prevents health 23AndMe GHR (genetic health risk) tests from the FDA’s pre- ost physicians require racy of the results. insurance companies from requiring genetic testing in order market review,” which some accept as an indicator of accu- that their patients to receive coverage.9 GINA does not cover disability or life racy and safety.6 However, there are risks associated with any M print that the tests are not ACCURACY obtain genetic counseling insurance policies.9 Still, many worry about the possibility genetic testing, especially testing which is done without the from a licensed individual wenty-Three And Me of their genetic information being sold, for instance, to pri- guidance of a physician and genetic counselor or other health before undergoing a genetic designed to diagnose dis- Tdescribes its process as vate research companies without their permission. 23AndMe professional. test, due to the potentially “qualitative genotyping to assures its customers that it will not share any genetic infor- While the act of spitting in a tube and mailing it to the highly consequential and ease or to be used to make detect clinically relevant vari- mation with any third-party without consent, except by the laboratory presents few, if any, risks, knowledge of the pres- emotional information which ants in the genomic DNA of request of a subpoena or other court-ordered request.1 The ence of mutations in the genome indicating risk for untreat- may be revealed. According 1 adults from saliva collect- company claims to fully support the Genetic Information able disease has the potential to create psychological distress. to the National Society of health decisions.” ing using an FDA-cleared Nondiscrimination Act.1 While the individual has the opportunity to seek out their Genetic Counselors, genetic collection device (Oragene 23AndMe does participate in research based on genetic own genetic counselor and explore the possibilities of the counseling is “a process to DX model OGD-500.001) information when consent is given by the customer. Online testing, 23AndMe does not require a genetic consultation to evaluate and understand a family’s risk of an inherited medi- for the purpose of reporting and interpreting genetic health surveys of health information are matched up with genetic prepare the consumer for potential results. 2 1 cal condition.” Genetic counselors are trained to provide risks and reporting carrier status.” The company uses an markers in order to determine the correlation between genetic 23AndMe started as a means of analyzing DNA in a way 2 emotional support and aid their clients in decision-making. FDA-approved process which involves extracting DNA from markers and subsequent disease.1 The company promises that presented the consumer with knowledge of their ances- Results from genetic testing may reveal that an individual the cells of the saliva sample, and then “reading” the DNA to protect privacy by anonymizing the genetic information try. Perhaps the innate attraction to discover how we came to 1 is at a high risk for a particular life-threatening disease, such using a genotyping “chip.” In six to eight weeks, the results involved in this research.1 The company’s website also states be in this very moment is what makes the testing so incredibly as in the case of the presence of the BRCA 2 gene, which indi- of the analysis are made available to the consumer via their that in the case of rescinded consent, genetic information will popular. But it is still debatable whether genetic data should 3 1 cates a predisposition for breast and ovarian cancers. Amnio- online account. Naturally, the risk of false positive or false be removed from research in possible studies within 30 days.1 be stored in a database and shared with third parties, as well as centesis, a process by which cells are taken from the amniotic negative readings comes to mind. According to their website, 23andMe is clear in its fine print, which states: “By agree- whether the analysis of sensitive health information should be sack in order to test the developing fetus for genetic disorders, 23AndMe is able to guarantee that its “powerful, well-tested ing to our Privacy Statement and Terms of Service, you con- encouraged outside the realm of the doctor’s office. 4 1 may reveal the presence of Down Syndrome. Other tests may system” can estimate ancestry “down to the 0.1%.” The com- sent to the storing and processing of your personal informa- reveal whether two prospective parents are carriers of a dis- pany does not provide studies to support these claims. tion, including sensitive information, in the USA and coun- ease and could potentially pass on traits of a debilitating ill- tries outside of the country you live in” as well as a note about ness to their children.5 the possibility of transfer of sensitive information in the case References for this article can be found at Under the auspices of a certified genetic counselor who Author contact: Jamie Tebeau is a sophomore at Tufts University. 1 Address correspondence to [email protected]. of a business merge or change in authority. Genetic code will TuftScope.squarespace.com

30 TuftScope | Fall 2017 • Volume 17, Issue I Fall 2017 • Volume 17, Issue I | TuftScope 31 INSIGHT of stimulating the conversion of WAT to BAT by a hormone called irisin. Found in 2012 by The Potential of Bexarotene and Irisin Harvard Medical School biolo- gist Bruce Spiegelman, irisin is Daniel Kaltman an “exercise hormone,” meaning it is produced and excreted N EXISTING CANCER DRUG AND NATURAL cascade which ultimately increases the gene expression of only during “cardiorespiratory body hormone may turn out to be a miracle treat- Uncoupling Protein 1 (UCP1). UCP1 is a main component system engagement and muscle ment to help alleviate obesity and diabetes. The drug, of mitochondrial membranes and promotes the utilization exertion.”9 To reiterate, during namedA Bexarotene (Bex), was tested by the Gladstone Inti- of energy and thermogenesis.5 Therefore, as the amount of exercise, when skeletal muscles tute while researching fat tissues. Bex is already approved UCP1 increases, it is followed by increased numbers of mito- undergo movement, they stimu- by the FDA as treatment for a specific skin cancer. The natu- chondria and, thus, the formation of BAT. late the transcription and transla- ral hormone is called irisin. Both Bex and irisin may benefit In its medicinal use in cancer as well as in the research tion of PGC-1α in muscle tissues. obese and diabetic patients by converting white to brown fat, conducted in this study, Bex binds to various nuclear recep- PGC-1α promotes expression thus improving insulin sensitivity. Although the findings are tors called Retinoid X Receptors (RXR) that come in the forms of a protein that is ultimately nascent and these compounds may not see clinical trials until of alpha, beta, or gamma receptor types. These RXR recep- cleaved into the natural endo- a few years, they may represent a breakthrough in solving the tors have different actions and are preferentially expressed in crine hormone irisin, which global pandemic of obesity and diabetes. So, how does a can- different cell types. On the nuclear envelopes of BAT, there travels through the bloodstream cer drug, which kills malignant cells, actually have benefits are much higher amounts of Alpha and Gamma receptors, and binds to receptors on white 6 for noncancerous cells in human beings? while WAT contains higher amounts of Beta receptors. The adipose cells. When irisin binds researchers at Gladstone confirmed that Bex injections in to white adipose cells, it initiates A MIRACULOUS DISCOVERY precursor fat cells promoted overexpression of Alpha and a chain of events similar to that of or years scientists around the globe have tried to find a Gamma receptors, which “induced nearly all cells into brown Bex, the ultimate product being 4 Fdrug that can convert White Adipose Tissue (WAT) to adipocyte-like cells…and suppressed WAT-specific genes.” increased levels of UCP1 which Brown Adipose Tissue (BAT). The metabolic distinctions These findings illustrate that as Bex acts as an RXR agonist, it induce the browning of the fat between WAT and BAT are important for understanding why increases the expression of UCP1 and additionally decreases cell.10 By regulating the conver- these fats are relevant to body weight and insulin resistance. the expression of WAT-relevant genes. sion of WAT to BAT, irisin plays WAT stores body heat and energy in the form of ATP, and Increased BAT content has direct effects on calorie burn- an important role in determining The increased energy expenditure from BAT can help with weight loss and improve insulin sensitivity. Image Source: Castillo-uan, Jorge Iván, NCBI also contains low numbers of mitochondria. In contrast, ing, which may help individuals seeking care for obesity. body weight. Would it be pos- due to its large cellular concentrations of mitochondria, However, the benefits of more BAT do not stop at just weight sible to burn more fat by inject- naturally increasing levels of BAT, more fat, calories, and heat BAT produces heat, thus burning energy.1 While attempting loss. According to a 2012 study conducted by the Joslin Cen- ing synthetically created irisin into patients diagnosed with can be released from the body, which assist obese and diabetic to chemically convert WAT to BAT, the Gladstone Institute ter for Diabetes at Harvard Medical School, BAT has benefi- obesity and diabetes? individuals in maintaining a healthy weight. While irisin is a scientists tested more than twenty-thousand chemicals until cial effects on glucose tolerance and insulin sensitivity. In According to research led by Li-Jun Yang from the Uni- safe and natural hormone, Bex is a synthetic drug that con- they tested a specific cancer drug called Bex. 2012, the researchers transplanted either BAT or WAT from versity of Florida, injecting irisin into fat cells of humans led tains many side effects including low thyroid hormones, skin Drugs used in cancer treatment are well-known for some mice into the clavicles of others. In the BAT-trans- to a five-fold increase in UCP1. The researchers collected fat rashes, and headaches. In fact, Gladstone Senior Investiga- their ability to target and destroy cells that undergo massive planted mice fed a normal diet, there was improved glucose cells from twenty-eight patients who had recently undergone tor Sheng Ding stated that the “next task is to develop a safer, amounts of replication and cell division. Many oncologists tolerance compared to their WAT-transplanted counterparts. breast reduction surgery, and injected synthetically-made more targeted drug that only affects genes involved in creating prescribing chemotherapy treatments use a “cocktail” of dif- However, the most astonishing result was that of the trans- irisin into the cultures. Yang found that irisin “suppresses brown fat.”11 In its current form, Bex is used to treat cancer. ferent medications to target specific regions and metastases.2 planted BAT mice fed a high fat diet. In this group, not only [white adipose] fat cell formation” by reducing the “num- However, ongoing research shows that its structure may be By targeting healthy cells instead of cancerous ones, Bex may did glucose tolerance improve, but the mice also had “a com- ber of mature [white adipose] fat cells by a staggering 20 to slightly altered to eliminate these negative side effects while be able to help treat obesity and diabetes. Bexarotene, or its plete reversal of insulin resistance resulting from excess fat 9 60 percent.” While most of the research on irisin has been preserving its function in fat cells.11 generic form, targretin, is an FDA-approved drug used for a consumption (burning).”7 Attempting to identify the mecha- around its ability to act as a potential weight loss supplement, According to a CDC report released in June of 2016, specific non-Hodgkin lymphoma calledcutaneous T-cell lym- nism behind BAT ‘s effect on glucose levels, the researchers irisin has also been linked with many other health benefits. “only 49% of adults 18 years or over met the Physical Activity phoma (CTCL). CTCL is a form of skin cancer caused by found that the mice with transplanted BAT had higher levels In 2015, Yang’s lab concluded that irisin has the potential to Guidelines for aerobic physical activity” on a weekly basis.12 mutations in T-cells that affect the immune system and skin.3 of Interluekin-6 (IL-6). IL-6 activates glucose transporters on improve cardiovascular health by increasing the availability of The decreased amount of exercise lowers the natural levels of When the researchers tested Bex on mice, they found that pancreatic cells, thus increasing uptake from the blood and calcium required for ventricle and atrial contractions. Yang irisin, contributing to the formation of white adipose tissue mice burned more calories, had lower body fat percentages, allowing blood sugar levels to decline.8 The positive correla- continued his research on irisin and found that increased iri- which dissipates far less energy and heat than brown adipose and gained less weight than when treated with a control.4 Bex tion between Bex, increased BAT, and decreased blood glu- sin levels can help clear arterial plaque deposits in rodents by tissue does. The age of prescribing pills to obese patients to produces these changes by converting WAT to BAT. cose levels has introduced the possibility that drugs like Bex 9 “thwarting the accumulation of inflammatory cells.” Existing make them “feel full” or using liposuction surgery to decrease may help patients with type 1 diabetes. knowledge on irisin’s effect in the body, in addition to this BEX: CONVERTING WAT TO BAT body weight and fat percentages may be over. These recent nascent finding, evidence its potential in developing pharma- discoveries may mark the beginning of the new age, that of uring exercise, our skeletal muscles and fat cells undergo IRISIN: A NATURAL CONVERTING HORMONE ceutical treatment. using the natural hormone irisin or the chemical medication movement for long durations. This movement stimu- n addition to the converting behavior from WAT to BAT D of Bex to combat obesity and diabetes. lates the transcription and translation of a compound called Iby the synthetic drug Bex, our bodies have a natural way CONCLUSION PGC-1α in muscle tissues. PGC-1α expression has a direct oth Bex and irisin show promise for increasing the References for this article can be found at link to the formation of BAT. As the fat cells increase their Author contact: Daniel Kaltman is a junior at Tufts University. amount of brown adipose tissue in humans, and this B TuftScope.squarespace.com PGC-1α content, the compound leads to the activation of a Author correspondence to [email protected]. research is likely just the beginning. By chemically or

32 TuftScope | Fall 2017 • Volume 17, Issue I Fall 2017 • Volume 17, Issue I | TuftScope 33 INSIGHT The Artificial Pancreas: A Personal Narrative Machlan Sawden

AIT SAWDEN WAS DIAGNOSED WITH TYPE indicating improved glucose control. His blood sugar now 1 diabetes in the fall of 2011 when he was just eight spends a significantly higher percentage of time in the target years-old. His pancreas was losing its ability to pro- range of 70-180 mg/dL. duceT insulin, the hormone that allows the body to remove Tait also enjoys a greater amount of freedom. He has glucose from the bloodstream so that it can be processed by always had an active lifestyle playing highly competitive lev- his cells. His life immediately began revolving around peri- els of hockey and baseball. Because he once had to take off odic finger pricks to test blood glucose, counting carbohy- his pump to play in the past, he risked undetected swings drates for every modicum of food and drink he consumed, in blood sugar during his games. Tait has the ability to feel painful insulin injections, and the constant risk of uncon- extreme highs and lows in blood sugar, so if he felt something trolled blood sugar highs and lows that could threaten his wrong and tested for either, he would have to immediately life. He was told that he would eventually be given an insulin stop playing and make an adjustment to his pump, pull him- pump to alleviate the constant need for injections, but the self out of the game for fifteen minutes or more to treat the technology that could fully replace his malfunctioning pan- condition. He had been put in the difficult situation of having creas was twenty-plus years away. As of today, type 1 diabetes to tell his teammates that he has to leave a game because of is an irreversible and permanent disease. his disease. Six years later, Tait is among the first wave of adolescents No longer; the 670G is water-proof and can remain on Image Source: Discover Magazine, Jay Smith and adults to have the Hybrid Closed-Loop 670G Insulin Tait while he plays sports. Now, he can even activate a new Delivery System from Medtronic, branded the first and only function of the 670G that increases the target blood glucose blindness, kidney failure, cardiovascular disease, stroke, and Rico, delivered significant damage a major Medtronic man- artificial pancreas approved by reading from 120 mg/dL to damage to lower extremities necessitating amputation.6,7 A ufacturing facility.2 As a result, there has been a shortage of the FDA.1,2 This truly remark- 150 mg/dL when he is exer- 1% increase in HbA1c is associated with a 30% increase in subcutaneous interstitial glucose sensor components of the able combination device mon- “[the artificial pancreas] cising, as the body requires risk for all-cause mortality for people with diabetes.8 Con- 670G, elongating the wait time.2 Not only does Medtronic itors interstitial blood glucose more sugar during exercise. versely, a reduction in HbA1c by 0.2% could lower mortality expect to lose $250 million in revenue due to the storm, but with a subcutaneous sensor is an upstream approach The device also adjusts insulin risk by 10%.8 This is why the artificial pancreas is crucial; it they were forced to evacuate four facilities in the Santa Rosa inserted into the abdomen deployment based on the time is an upstream approach to reducing the possibility of com- and Sonoma counties in California because of the October or upper arm and continu- of day, for insulin needs dif- plications that often plague people with diabetes.9 However, forest fires that have claimed the lives of over 40 people.12,13 ously relays the data wirelessly to reducing the possibility fer at day and night. Updating multiple events in the last several months have made this The diabetes management industry has experienced a via an insulin pump.1,3 Every insulin dosage every five min- revolutionary technology difficult to acquire. shake-up in the last few months. Boston Scientific, Merck, five minutes, the pump uses of complications that utes based on real-time blood For the original rollout of the 670G, Medtronic estab- and Abbott Laboratories all have product facilities that were an algorithm that takes into sugar ensures stability.1,3 lished a Priority Access program that only offered the oppor- impacted by Hurricane Maria.12 Animas Corporation, a pro- account current blood glu- often plaque people with Tait isn’t alone in his posi- tunity to purchase the 670G for a discounted price of $299 ducer of insulin pumps owned by Johnson & Johnson, has cose levels as well as a history tive experience with the 670G, (which can be reimbursed by Medtronic after completion of a pulled out of the U.S. and Canadian diabetes technology mar- of personal trends in order to diabetes.” either. A 2016 study of 124 survey) to those who owned its predecessor, the 630G.10 This kets, directing its 90,000 customers to Medtronic.2 This is of calculate the exact amount of adolescents and adults with was convenient for people like Tait, but not those who used particular concern to the Juvenile Diabetes Research Founda- insulin needed to nudge the type 1 diabetes by Bergenstal another model or brand. People who wanted to be eligible tion, which released a statement on the move, noting with dis- blood sugar towards the set ideal reading: 120 milligrams per et al. saw the average HbA1c of the patients drop from 7.4% for the 670G had difficulties negotiating with their insurance appointment that “Innovation and competition are essential deciliter (mg/dL).1,2 during a two-week study period with their old insulin pump company for a new pump that would just serve as a place- to the development of next-generation therapies.”2 Now, Tait just needs to enter the amount of carbohydrates system to 6.9% over the course of three months with the 670G holder until the new technology arrived, so many paid as Despite the monumental arrival of the 670G, a shrinking he eats each meal into the pump component of the device pump and sensor device.4 The percentage of glucose readings much as $4000 for the 630G to save their spot in line.10 This market for technology producers could hold back the surg- and use a glucose meter twice daily to calibrate the sensor. that fell in the target range of 71 to 180 mg/dL also increased investment was considered worth the lifestyle improvements ing process towards more sophisticated artificial pancreas Long gone are his days of having to measure exact amounts of from 66.7% to 72.2% with the artificial pancreas.4 that the 670G promised, but for those insured by Anthem products, meaning fewer options for diabetes patients seek- insulin for injections multiple times a day. He no longer has Not having to constantly worry about exact glucose lev- Blue Cross & Blue Shield, it stranded with a big bill and no ing critical devices that have the potential to significantly to worry about entering blood sugar readings into his insulin els and insulin makes day-to-day life much easier for people artificial pancreas. improve lifestyle and health outcomes. This is all happening pump or adjusting his dose in case there is some unforeseen with diabetes, but the real impact of the artificial pancreas Anthem, which insures over 40 million Americans, during a period of great uncertainty in the healthcare system. spike or low. is the long-term benefit of blood sugar stability. Hypogly- declared the 670G “investigational and not medically neces- There is cause for concern regarding whether insurance com- The artificial pancreas even has some capabilities beyond cemia, the condition of chronic low blood sugar, presents sary under all circumstances” and has refused to cover the panies like Anthem will cover these products, and how the that of its biological counterpart. It records every reading it risk for seizures, neurological damage, and death.5 Elevated product.10,11 Medtronic has urged its customers to contact federal government will cover pre-existing and chronic condi- processes, allowing Tait to look at long-term indicators of HbA1c concentration and hyperglycemia (sustained high Anthem and voice their opinions concerning the importance tions. When the dust falls, hopefully concerns of accessibility diabetes management.1,3 In a little over a month with the blood sugar) are linked to significant risk for nerve damage, of 670G, but Anthem remains the only major insurer in the to healthcare will be less prevalent, and those who need less 670G, he has seen his HbA1c levels (a measure of how well U.S. that does not cover the pump.10 cumbersome treatment options will have access. the body has removed sugar from the bloodstream over time) Access to the 670G has also been restricted by natural fac- References for this article can be found at drop considerably from 7.8% with his old pump to 7.1%, Author contact: Machlan Sawden is a sophomore at Tufts Univer- tors. Hurricane Maria, which devastated the island of Puerto sity. Article correspondence to [email protected] TuftScope.squarespace.com

34 TuftScope | Fall 2017 • Volume 17, Issue I Fall 2017 • Volume 17, Issue I | TuftScope 35 INSIGHT A Controversial Step Towards Life Rebecca Moragne

N 2015, A UNITED STATES-BASED MEDICAL THE PATIENT team in Mexico delivered the first child born from in- he success of three-parent IVF in Mexico required vitro fertilization (IVF) with three parents.1 News of Tthorough investigation of safety concerns and spurred theI success spread around the world, and eight months considerable ethical debate. A Jordanian mother learned later, clinics in the United Kingdom could apply to perform that she was a carrier of Leigh syndrome when her first the controversial procedure.2 In this first case, the method child developed the disease. After this child’s death, the was used to prevent Leigh syndrome, a lethal mitochon- woman and her husband sought an intervention that would drial disease.2 Using genes from three individuals allowed allow them to conceive a healthy child. Dr. John Zhang and fertilization that excluded disease-carrying mitochondrial the New Hope Fertility Center in New York City provided DNA. Mutations in mitochondrial DNA can lead to the this solution. Dr. Zhang had been working on developing a development of many other genetic diseases in addition three-parent IVF technique to prevent mitochondrial dis- to Leigh syndrome, that affect 4,300 children born each eases but the method had not been approved in the United year.3 Leigh syndrome, for which there is currently no States. In order to carry out the procedure, Dr. Zhang and cure, damages tissue in the brain leading to serious con- his team traveled to Mexico with the Jordanian couple. For sequences.5 Most patients of the disease die within two to many people, this move seemed radical, but the Jordanian three years of birth.4 couple pursued their opportunity to bear a healthy child. Today, this child, a boy, is thriving and carries no chance of Image Source: CNN Health, “FDA warns ‘3-parent’ baby fertility doctor over marketing” THREE- PARENT IVF developing Leigh syndrome.1 mice are also present in primates. This work must be com- about possible harmful effects on future generations, germ- esearchers developed IVF with three genetic sources to pleted before human clinical studies may begin.8 line intervention has been strongly discouraged or legally provide affected families with an opportunity to bear a SAFETY CONCERNS R banned.”7 To distinguish the three-parent IVF procedure child without a lethal mitochondrial disease. Mitochondrial oday, the U.S. has yet to approve three-parent IVF ETHICAL CONCERNS from direct nuclear DNA modifications, the UK government DNA is passed maternally in a mitochondrial inheritance pat- for preventing mitochondrial diseases. Dr. Zhang has T ny proposal to alter the human genome sparks ethical labeled the procedure as a genetic modification instead of a tern. Therefore, the three-parent IVF procedure centers on argued that “to save lives is the ethical thing to do.”1 How- concerns. Many people fear that adjusting the human germline modification. Because mitochondria contribute so altering the female egg.6 If the mother is a carrier of the disease, ever, there do exist safety concerns regarding the procedure. A genome for the aforementioned reasoning could be a first little DNA compared to the forty six nuclear chromosomes, she will pass on the mitochondrial mutation to all of her off- According to the U.S. Food and Drug Administration, step towards other genetic alterations, potentially leading to many argue that alteration of mitochondrial DNA does spring. How the mutation affects human studies investigating its alterations to the genome that are purely aesthetic or medi- not affect an individual’s genetic composition enough to be the offspring is difficult to predict safety have not been conclu- cally unnecessary. However, removing fatal disease-causing considered germline modification. However, many people because the type and amount “Researchers developed IVF sive.8 In order for a medical mutations is a far step from preferentially modifying non-life oppose this categorization because the donor contributes more of each mutation dictates the procedure to be approved, its threatening characteristics such as eye color and intelligence than just mitochondrial DNA; the enucleated egg contains extent of the symptoms and dis- with three parents to provide successes, as well as instances of level. Nevertheless, some frame it as a scientific step in that other cellular components including endoplasmic reticulum, ease in the offspring.6 In three- failure or complication, must be direction; It can be argued that with the ability to remove Golgi apparatus, and egg’s membrane.7 However, the majority parent IVF, a female carrier’s affected families with an well-documented. This docu- disease-causing mutations comes greater ability to modify the favored approval and the British parliament passed the law. mitochondrial DNA is replaced mentation must also include genome ,and therefore potential to do so under many different Robert Meadowcroft, chief executive of the Muscular Dystro- by a female non-carrier’s mito- opportunity to bear a child multi-generational information, circumstances. When the British Parliament voted to approve phy Campaign, stated, “We have finally reached a milestone chondrial DNA. In addition to as this type of genetic engineer- the three-parent IVF mitochondrial technique in February of in giving women an invaluable choice, the choice to become a fertilizing the mother’s egg, the without a lethal mitochondrial ing may result in complica- 2015, conservative lawmaker Fiona Bruce stated that passing mother without fear of passing on a lifetime under the shadow father’s sperm also fertilizes a tions that arise only in future the law would be equivalent to “letting ‘the genie out of the of mitochondrial disease to their child.”10 donated egg. Each of the two disease.” generations. For a procedure to b ott l e .” 9,10 She asked, “Where will it lead? The answer has to sperm and egg sets develops into be approved, there cannot be be that we stop here. The answer has to be that we say this is a CONCLUSION a zygote. The nucleus is removed any lingering uncertainties or red line in our country, as in every other country in the world, ost would agree that more information is essential from each, and the one from the cell produced by the mother questions regarding its safety.8 Studies in mice have shown that we will not cross.”10 In 1994, the International Bioeth- for verification of three-parent IVF as a viable proce- and father is then placed into the enucleated zygote produced harmful effects in adulthood, including decreased fertility, M ics Committee on the United National Education, Scientific dure. This information requires investigation into the safety by the father and donor. The nucleus from the mother and especially in males. In 2009 and 2010, two research groups and Cultural Organization (UNESCO-IBC) released a report of altering a zygote and the ethical concerns of how this father stores all autosomal and sex chromosomes, the major- reported successful three-parent IVF procedures in rhesus that read, “All major statements about germline interventions procedure could develop in the future. Couples in the United ity of the child’s DNA. The mitochondrial DNA is not housed monkeys. The offspring were followed until age three, and condemn its present use. That position is clearly correct… States who are interested in three-parent IVF, but unwilling in the nucleus as mitochondria are cytoplasmic organelles their health persisted during this time. Research is neces- The use of germline interventions for enhancement purposes to travel to a location where the procedure is legal, will have with their own transcriptional machinery.7 The end product is sary to track the health of the monkeys further, at least until should be categorically prohibited.”7 In 2003, a follow-up to wait until the FDA is presented with enough research to a zygote with the mother and father’s nuclear DNA and the sexual maturity, to see if the negative effects exhibited in report stressed similar positions and stated, “On ethical make an informed legalization decision. donor’s healthy mitochondrial DNA. The zygote develops into grounds most national and international institutions have an embryo, which is then placed into the uterus of the mother. strongly discouraged or prohibited germline intervention… References for this article can be found at This process is known as three-parent IVF.5 Author contact: Rebecca Moragne is a junior at Tufts University. Address correspondence to [email protected]. Because of the many technical problems and uncertainties TuftScope.squarespace.com

36 TuftScope | Fall 2017 • Volume 17, Issue I Fall 2017 • Volume 17, Issue I | TuftScope 37 INSIGHT A Hoarse Cough: The Case of the Icelandic Horse Epidemic Ted Midthun

HETHER IT’S CAUSED BY BACTERIA, carrying heroes like Gunnar Gunnarsson in Njal’s Saga.4 For viruses, parasites, or fungi, the impacts infectious centuries, the horse was the only means of transportation and diseases have on our health continue to be pro- was the most important working animal before machinery.4 found.W Infectious diseases come in all shapes and sizes, but Today, around 77,000 Icelandic horses populate the island’s have one common goal – to transmit the infection from one terrain, and while they no longer provide the same services individual to another. Some diseases are mild and can often they did for centuries, they nonetheless remain an integral be self-treated, such as the common cold. Others are often part of Iceland’s culture and economy. Riding shows, com- fatal when left untreated, such as meningitis. Not only are petitions, tourism, breeding, and export continue to provide they deadly, but infectious diseases are also costly; the World major business, boosting agriculture and industry in many Bank estimates the cost of the recent Ebola epidemic to reach areas.4 Because the Icelandic horse has been geographically $32.6 billion, placing more strain on already burdened West isolated for more than a thousand years, it has remained African countries.1 Furthermore, human-to-human contact nearly disease-free.4 In order to ensure this iconic horse is not the only way infectious diseases are spread. Zoonotic remains healthy, the country takes stringent steps: regulating diseases are infectious diseases spread between humans and imports of riding materials, and sanitation of objects com- animals. Scientists estimate that nearly 6 out of 10 existing ing into contact with the horses.4 The measures taken are infectious diseases, and 3 out of 4 emerging infectious dis- so extreme that the World Icelandic Horse Championships eases, come from human-animal contact.2 are not held in the home country of Iceland, because any While infectious diseases are ubiquitous, epidemic infec- exported Icelandic horse can no longer return.4 tious diseases get most of the attention. The term epidemic Because the Icelandic horse has been isolated both geo- refers to a disease in which there is a usually rapid increase in graphically and culturally for so long, little immunity towards disease prevalence, while the term endemic refers to the con- mainland diseases remain. On any island, only a matter of stant presence of a disease.3 Epidemic diseases occur when time is needed for colonization, and in this instance, the colo- there is a change in the susceptibility of obtaining the dis- nizing agent was an infectious disease. On April 7th, 2010, the ease, or an increase in virulence of the pathogen.3 In order Veterinary Authority of Iceland received a phone call from an to mitigate the effects of a disease, identifying an epidemic equine center in northern Iceland. A quarter of the resident Icelandic horses grazing in Kálfafellsdalur, Iceland 5 disease from an endemic one is extremely important, par- horses were found to have clinical respiratory tract infections. Image Source: Nathaniel Stott, natestott.com ticularly when the disease has the potential to be costly and Numerous notifications from horse owners and veterinarians deadly. Furthermore, identifying an epidemic disease from throughout Iceland prompted the Veterinary Authority of an endemic one in animals can help to prevent transmis- Iceland to send out a questionnaire to the top 200 equestrian researchers collected nasal swabs of both affected and healthy whole genome sequencing on 305 S. zooepidemicus samples, sion to humans and maximize not just our health, but the centers. Shockingly, 90% of these locations had confirmed horses and used PCR amplification, paired blood samples, called isolates. 257 isolates were recovered from 100 horses health of other animals as well. While identification of infec- the disease within just one week of the first reported case.5 and cell lines to compare the virus with other viruses com- residing in 31 different locations across Iceland, while the monly associated with respiratory disease in horses, humans, remaining isolates were taken from cats, a dog, several peo- tious disease in animals is difficult, for the first time a team Throughout the spring and summer, nearly all of Iceland’s 5 of scientists at the University of Reykjavik have used whole 77,000 horses contracted the disease, with the most common and other animals. Despite the initial assumption of a viral ple, archived isolates of various animals from Iceland, and disease, all tests came back negative isolates of S. zooepidemicus outside genome analysis to identify the cause of a zoonotic epidemic symptoms including a persistent dry cough, coexisting with 5 that affected nearly the entire Icelandic horse population. mucopurulent nasal discharge and mild conjunctivitis.5 As a with the exception of equine gam- “Throughout the spring of Iceland. Phylogenic analysis of the By understanding how infectious diseases like this occur, result, nearly all equine activities and exports ceased, caus- maherpesviruses, isolated from small whole genome sequencing helped the 5 numbers of both healthy and clini- and summer, nearly all researchers gain insight into Icelan- researchers facilitate our ability to determine the best meth- ing major strain on Iceland’s agricultural economy. As these 5 ods to maximize human, animal, and environmental health events unfolded, determining the pathogen’s identity became cally affected horses. Because this dic S. zooepidemicus. 77% of the iso- virus was found in small numbers of Iceland's 77,000 horses lates fell into four distinct clades by around the world. a matter of substantial importance if Iceland was to curtail 5 the grip the disease had on the horse population. Thankfully, regardless of disease presence, the sequence type, called clones. In each THE ICELANDIC HORSE AND THE EPIDEMIC a team of researchers at the University of Reykjavik utilized researchers determined a virus was contracted the disease...” of the four clones, the isolates con- he history of the Icelandic horse stems from Iceland’s a novel method of disease identification, allowing not only not to blame. However, in absence of tained both horses with the disease colonization by the Vikings in the 9th century. Vikings the identification of the pathogen, but as well as the mode of a viral pathogen, the researchers noted that the Gram-pos- and those without. However, out of the 45 horses in clone 1 T itive bacterium Streptococcus zooepidemicus was present in (ST209), 43 of them had clinical signs of respiratory disease who settled in Iceland brought with them horses of various disease transmission. 5 4 almost all nasal swabs taken from coughing horses and dis- or had died. Also included in the isolates of ST209 was one origins, thought to be mostly of Germanic decent. However, 5 5 after more than a thousand years of isolation, the Icelandic IDENTIFYING THE CULPRIT eased tissues of fatal cases. While associated with several dis- cat and an Icelandic woman who had suffered a miscarriage. horse has become a unique pure-bred, as iconic to Iceland as ince the rate of disease transmission was so rapid, the eases affecting both horses and humans,S. zooepidemicus was With the first clone already standing out from the other three, its geological volcanoes. In heathen times, the Icelandic horse researchers first thought that a virus was responsible. not initially considered relevant because it is routinely found the researchers looked at the genetic variation within each S 5 was renowned in Norse mythology, the most famous horse In order to begin determining the pathogen’s identity, the in healthy horses and considered to be commensal. clone by comparing single nucleotide polymorphism (SNPs), being Sleipnir, Oðin’s eight-legged steed.4 The horses were In order to determine if the epidemic was associated with changes in nucleotide sequences, of the respective isolates. also the major mode of transportation in the Icelandic Sagas, Author contact: Ted Midthun is a junior at Tufts University. Author a particular strain of S. zooepidemicus, the researchers used correspondence to [email protected].

38 TuftScope | Fall 2017 • Volume 17, Issue I Fall 2017 • Volume 17, Issue I | TuftScope 39 Interestingly, clone ST209 had significantly less nucleo- origins of this particular S. zooepidemicus strain is difficult. tide diversity compared to the other clones, despite contain- The researchers proposed that perhaps this strain came from SCIENCE REPORT ing isolates from 45 horses located across 21 farms through- a similar strain identified in 2008 from a coughing horse in out Iceland.5 These results indicated that clone ST209 of S. Sweden, or contaminated riding equipment as a possible A Potential Type 1 Diabetes Vaccine zooepidemicus was likely responsible for Iceland’s unmatched related route of transmission.5 However, recall that ST209 horse epidemic. was recovered from an Icelandic woman, and isolates from Julia Greco Once the researchers determined the probable cause for three other closely related strains also came from humans.5 the disease, their next step was to use results taken from a The ability ofS. zooepidemicus strains, ST209 in particular, HE PREVALENCE OF DIABETES IN THE UNI- 43% inpatient care, 18% medication to treat diabetes-related prior experiment during the epidemic. Three healthy horses to cross host boundaries provides an alternative mechanism ted States has significantly increased over the past complications, 12% supplies and anti-diabetic agents, 9% from the University of Iceland were transferred to a barn whereby the infection of a human may have facilitated onward fifty years. In 2015, it was was 9.4% of the popula- office visits, and 8% residential facility stays.9 Diabetics with- where the 17 resident horses had contracted respiratory anthroponotic transmission to the Icelandic horse. While the tion.T1 This percentage starkly contrasts that of nearly fifty out health insurance have 79% fewer doctor’s office visits and disease two weeks prior.5 Of the resident horses, 10 of them mechanism of transmission remains unknown, the intersec- 5 years ago; In 1958, the proportion of the population with are prescribed 68% fewer medications than others with health tested positive for clone ST209. Following their introduction, tion between human, animal, and environmental health is diabetes was as low as 0.93%.1 Diabetes mellitus, com- insurance.9 But diabetes is not just a financial burden. A typi- the three horses were monitored for signs of disease. Nasal essential to consider when infectious diseases are to blame. monly referred to as diabetes, is a metabolic disorder that cal day for a diabetic consists of repeatedly testing blood sugar discharge was apparent at day 10, became mucopurulent at While we like to think infectious diseases are only caused causes defects in insulin secretion and function. Diabe- levels, administering insulin via insulin pump or injections, day 19, and was followed by the first observation of cough- by other animals or the environment, pathogens do not fol- tes is recognized as an autoimmune disease, consisting of and monitoring the way the sugar level makes their bodies feel. ing.5 Two of the horses were euthanized on day 30, while the low one-way street signs. As much as we wish diseases would 5 numerous etiologies, including continuous hyperglycemia other was euthanized on day 23 post-introduction. Postmor- stay in their lanes, humans too possess the ability to pass dis- and trouble metabolizing carbohydrates, protein, and fat.2 RISKS tem examination of the horses confirmed respiratory disease eases from themselves to other animals. A pertinent example 5 iabetics must be especially careful in the heat, as the and infection. Seven of eight isolates of S. zooepidemicus of this this phenomenon that can have severe consequences is ETIOLOGY OF DISEASE disease renders their bodies more sensitive to ris- that were recovered from two of the horses post-day 28 were the human-related paramyxovirus and its effect on Tanzania’s D 5 ype 1 diabetes develops when the body falsely recognizes ing temperatures than non-diabetics. This occurs because strain ST209. However, no isolates contained ST209 prior Mahale Mountains National Park chimpanzee population. beta cells as “foreign invad- nerve damage, a common symp- 5 T to 28 days in all three horses. The researchers believed that A popular research and tourist destination, the park con- ers” and attacks them using auto- tom of diabetes, affects the sweat ST209 needed time to accumulate to detectable levels, which tains the largest remaining endangered eastern chimpanzee 2 10 6 antibodies. Beta cells produce “The BCG vaccine was glands. Diabetes is also known explains why none of the horses had ST209 initially, and why population, which has been steadily declining since 1965. and secrete insulin in the islets of to increase the risk of mental ill- the horse that did not have strain ST209 was euthanized less In 2003, 2005, and 2006, acute and fatal respiratory illnesses Langerhans within the pancreas.3 ness, which could be related to the than 28 days post-introduction.5 In order to confirm the were recorded in the chimpanzees, each during peak tourist found to destroy T cells 6 Insulin assists in regulating hyper- stress associated with the drastic ST209 isolates in the three introduced horses were the result season. The outbreaks had a high morbidity (98.3, 52.4, and glycemia and preventing the state change in lifestyle that the treat- of transmission of the pathogen from horses at this particular 33.8% respectively), with deaths observed in young chim- in diabetic mice, leaving 6 of diabetic ketoacidosis (DKA) by ment demands; Depression is barn, the researchers looked at the spacer sequences within panzees. Collected fecal samples confirmed the presence of allowing the body to utilize sugar healthy levels of beta cells in twice as common for diabetics.1 the ST209 isolates from the resident horses. They noted that human-related paramyxovirus, which was believed to be the from carbohydrates to produce In teenagers, type 1 diabetes also there was a unique spacer sequence found only in horses that result of increased research and tourist exposure within the 4 6 energy. DKA is a chemical imbal- the pancreas.” increases the risk of developing had contracted the disease at this particular barn, and the iso- national park. Examples of infectious diseases carried from ance in the blood that occurs due eating disorders, which can lead lates from two of the introduced horses with ST209 had the humans to animals highlight the importance of how infec- to cellular insulin deficiency.5 If to unstable or unmanageable glu- same unique spacer sequence, indicating that these horses did tious diseases have the potential to spread. While not fully the cells are not receiving enough insulin and consequentially cose levels. Some teenagers will administer less insulin than is indeed contract the disease from the horses residing at this understood by the Icelandic researchers, the arrival of strain 12 5 are not receiving sugar, ketones build up in the bloodstream. required to avoid gaining weight, resulting in DKA. It is also specific barn. ST209 into Iceland could have potentially been the result of DKA can be life threatening if left untreated.5 Once the body dangerous for diabetics to drink alcohol because it induces Using collected isolates, whole genome analysis, genetic human transmission. destroys 80% of the beta cells, it is unable to efficiently regu- hypoglycemia, releasing stored glucose from the liver into the diversity comparisons, and experimental results, the research- Our ability to prevent disease transmission is becoming late blood sugar levels.6 blood.13 This poses a compounded conundrum for younger ers identified the particular strain ofS. zooepidemicus that more difficult as our world continues to become increasingly Type 2 diabetes is the most common form of the disease.7 diabetics whose peers may encourage such alcohol consump- caused the Icelandic horse epidemic. The last step was to find mobile. The economic burden infectious disease brings can In patients with type 2 diabetes, the body produces insulin tion, rendering the stakes of their underage alcohol consump- the initial disease location. Using the surveyed data collected severely impact countries, imposing trade and travel bans, but the muscle, liver and fat cells display insulin resistance, tion uniquely high. from the University of Iceland, network analysis was used to and result in heavy agricultural damage. Ourselves aside, the and cannot use insulin efficiently.7 This is known as insulin identify a single common training yard as the primary center importance of protecting threatened and endangered species resistance, and is typically a result of lifestyle factors, includ- THE VACCINE for transmission. The culprit, a water treadmill that contained relies on the acknowledgement that not only do animals pose ing weight, diet, and lack of exercise, though it is sometimes r. Denise Faustman, the director of Massachusetts Gen- no disinfectant and changed rather infrequently, created threats to human health, but humans too possess the abil- attributed to genes. Researchers are now closer than ever to eral Hospital’s Immunobiology lab, set out to find a cure an ideal condition for the transmission of S. zooepidemicus ity to greatly affect some of the world’s most fragile popula- D 5 finding a cure for type 1 diabetes. A drug to prevent the dis- for type 1 diabetes. Her lab discovered a vaccine that was between visiting horses. The first transmissions likely began tions. Thankfully, strain ST209 had low mortality. However, ease may finally be tested on humans in 2018.8 successful in curing diabetes in humans for a short period in the first couple weeks of February, and as two horses left despite near isolation for more than a thousand years, the Ice- of time.14 The vaccine is called Bacilllus Calmette-Guérin, or the training yard on February 19th, they carried the disease landic horse epidemic embodies the increasing coexistence DISEASE BURDEN BCG. The vaccine has been successfully used in the past to and commenced the transmission of ST209 that would even- between animal and human health. In order to successfully 5 Both type 1 and 2 diabetes require extensive medical care, treat tuberculosis in infants and children, and has also been tually affect nearly all of Iceland’s horses. protect ourselves, our pets, endangered species, and the envi- the cost of which can be burdensome. Within the last five used in the treatment of bladder cancer.16 The BCG vaccine ronment, we must understand the implications we can each years, there has been a 41% increase in the cost of diagnosed was found to destroy T cells in diabetic mice, leaving healthy CONCLUSION: INTERSECTION OF INFECTIOUS have towards one another and work to identify and effectively diabetes. In 2012, the economic burden of diabetes in the U.S. levels of beta cells in the pancreas.15 After this treatment DISEASES respond to potential infectious threats, because after all, none reached 245 billion dollars; 176 billion of which came from was completed, the mice remained non-diabetic, therefore While S. zooepidemicus may have propagated in stag- of us exist in isolation. direct medical costs, and 69 billion in “reduced productiv- nant water, how did this strain reach Iceland? Because strains References for this article can be found at i t y ”. 9 The breakdown of medical expenditures are as follows: Author contact: Julia Greco is a freshman at Tufts University. have the ability to create successful variants, determining the TuftScope.squarespace.com Address correspondence to [email protected].

40 TuftScope | Fall 2017 • Volume 17, Issue I Fall 2017 • Volume 17, Issue I | TuftScope 41 Image Source: healthimpactnews.com reversing type 1 diabetes.15 This treatment could potentially be effective for humans, because the T-cells in humans are THE FUTURE OF TYPE 1 DIABETES similar to those in mice.17 The vaccine rarely has side effects, f further research is successful, BCG may be the long- but should not be administered to patients with compromised Iawaited cure for type 1 diabetes. At $15 per dose, it is immune systems.18 For diabetics, the vaccine rids the body of inexpensive to administer, which will make it accessible to the white blood cells responsible for this disease. Dr. Faust- much of the general diabetic population.24 According to exist- man says the vaccine has the potential to reset the genes that ing research, the vaccine has few apparent side effects. As cause this autoimmune disease.19 However, other diabetes more research is carried out on the BCG vaccine, the larger researchers have said that because islet cells are not com- sample size will shed light on the impact of age demograph- pletely destroyed, this leaves the possibility of regeneration.20 ics and interference with other medication; Phase I trial only An FDA-approved phase one trial has already been com- included 15-year-old patients, potentially skewing the data.25 pleted for this vaccine, and results have been successful. It Furthermore, although the vaccine was only effective for a was discovered that BCG increases the production of tumor short period of time. With different dosages, it is possible that necrosis factor, or TNF, which was thought to be the only way the treatment becomes longer-lasting. to regenerate islet cells.20 For patients with diabetes, the TNF is The BCG vaccine may also have the potential to cure insufficient for regulation of the abnormal number of immune other autoimmune diseases, such as food allergies and Celiac cells.21 Normally, TNF kills all autoreactive T-cells, but Faust- disease.24 According to Faustman, Australian researchers are man’s lab wanted to find out if TNF could spare healthy T-cells currently conducting trials to determine if the vaccine can and only kill the harmful ones.15 In the study, three diabetic reverse allergies.24 Furthermore, billions of BCG vaccinations patients were treated with the BCG and three patients were have been employed in areas with higher prevalence of tuber- treated with a saline placebo. Two of the diabetic patients culosis. In those areas, the prevalence of diabetes is only 3%.24 that received two injections over four weeks were found to In the United States, where not nearly as many tuberculosis have lower attacking T-cell count, and contained dead auto- vaccines are administered, 44.3 million people have diabe- immune cells in their bloodstream.22 Insulin production also tes, which is about 13%. of the population.25 This correlation increased, proving the islet cells were not completely gone. speaks volumes to the potential of the BCG vaccines as it per- However, the insulin production only lasted one week.22 tains to the treatment of diabetes. However, before a phase Faustman had hoped to administer more frequent BCG shots two trial is carried out, there is no way to fully ascertain the to additional patients, but faced opposition from the Juvenile full extent of the risks of BCG as a type 1 diabetes treatment. Diabetes Research Foundation.20 There is ongoing fundrais- If BCG shows promising results in the phase two trial, type 1 ing for a phase two trial, and researchers are only $5 million diabetes may become preventable in the near future. short of the $25.2 million they need.23 The goals of the second trial are to recreate results from phase I with a larger sample size, and to determine the optimal dosage of the BCG drug References for this article can be found at to render the vaccine effective for longer periods of time.23 TuftScope.squarespace.com

42 TuftScope | Fall 2017 • Volume 17, Issue I Fall 2017 • Volume 17, Issue I | TuftScope 43 TUFTSCOPE Mayer Campus Center Mailbox #146 Tufts University Medford, Massachusetts 02155 ISSN: 1534-7397 Website: TuftScope.squarespace.com Email: [email protected]