Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University have developed a robotic device made from DNA that could potentially seek out specific cell targets within a complex mixture of cell types and deliver important molecular instructions, such as telling cancer cells to self-destruct. Inspired by the mechanics of the body’s own immune system, the technology might one day be used to program immune responses to treat various diseases. The research findings appear in today’s issue of Science.

The programmable DNA nanorobot was modeled on the body's own immune system in which white blood cells patrol the bloodstream for any signs of trouble. Image courtesy of Wyss Institute

Using the DNA origami method, in which complex three-dimensional shapes and objects are constructed by folding strands of DNA, Shawn Douglas, a Wyss Technology Development Fellow, and Ido Bachelet, a former Wyss Postdoctoral Fellow who is now an Assistant Professor in the Faculty of Life Sciences and the Nano-Center at Bar-Ilan University in Israel, created a nanosized robot in the form of an open barrel whose two halves are connected by a hinge. The DNA barrel, which acts as a container, is held shut by special DNA latches that can recognize and seek out combinations of cell-surface proteins, including disease markers. When the latches find their targets, they reconfigure, causing the two halves of the barrel to swing open and expose its contents, or payload. The container can hold various types of payloads, including specific molecules with encoded instructions that can interact with specific cell surface signaling receptors.

“We can finally integrate sensing and logical computing functions via complex, yet predictable, nanostructures—some of the first hybrids of structural DNA, antibodies, aptamers and metal atomic clusters—aimed at useful, very specific targeting of human cancers and T-cells,” said George Church, a Wyss core faculty member and Professor of Genetics at Harvard Medical School, who is principal investigator on the project.

For the complete news story, and a video describing the project, please visit the Wyss Institute website.

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Third-year experiences in the clinic spur a remarkable transformation

Everything changes during the third year of medical school. Leaving classrooms for the clinic, students begin to apply lessons learned from textbooks, lectures and labs to real patients. And for the first time, future MDs begin to feel like doctors.

In a new podcast, Focus explores this intense—and rewarding—year, known at Harvard Medical School as the Principal Clinical Experience, or PCE. Listen as students and faculty members share, based on personal experiences, how the approach fosters mentoring, communication and empathy.

HMS student Kat Wakeham (far right) and her mentor David Hirsh discuss their perspectives on the third year of medical school in a new podcast. Hirsh, an HMS assistant professor of medicine at Cambridge Health Alliance, champions an integrated, longitudinal experience for students. Credit: Leonard Rubenstein

For decades, researchers have sought a genetic explanation for idiopathic dilated cardiomyopathy (DCM), a weakening and enlargement of the heart that puts an estimated 1.6 million Americans at risk of heart failure each year. Because idiopathic DCM occurs as a familial disorder, researchers have long searched for genetic causes, but for most patients the etiology for their heart disease remained unknown.

Now, new work from the lab of Christine Seidman, a Howard Hughes Investigator and the Thomas W. Smith Professor of Medicine and Genetics at Harvard Medical School and Brigham and Women’s Hospital, and Jonathan Seidman, the Henrietta B. and Frederick H. Bugher Foundation Professor of Genetics at Harvard Medical School, has found that mutations in the gene TTN account for 18 percent of sporadic and 25 percent of familial DCM.

iStockphoto/JCL Photography

“Until the development of modern DNA sequencing platforms, the enourmous size of the TTN gene prevented a comprehensive analyses – but now we know TTN is a major cause of DCM,” said Christine Seidman, who reported the findings February 16 in the New England Journal of Medicine.

Idiopathic DCM is one of three different types of cardiomyopathy (the term “idiopathic” indicates that acquired causes for DCM such as atherosclerosis, excess drinking or viral infections have been excluded). It affects only about 4 in 10,000 Americans, but may be under-diagnosed because symptoms often appear late in the course of disease. DCM may cause shortness of breath, chest pain, and limited exercise capacity. DCM increases the risk of developing heart failure, for which no cure is available, and the risk of stroke and sudden cardiac death.

These findings will not only help patients understand the cause of their DCM symptoms, but also help to screen family members who might be at risk of developing the condition. Early identification of those at risk allows early intervention with medications that reduce workload on the heart and help prevent the changes in heart muscle, called remodeling, that lead to heart failure.

As DCM progresses, remodeling of the heart tissue makes the heart more prone to disturbances in the normal heart rhythm that can lead to stroke, heart attack and sudden death. “One of the added values to knowing that you are at risk for developing DCM is that we can do prophylactic screening so that silent arrhythmias are picked up before they become harmful,” said Christine Seidman. “The discovery is immediately translatable into clinical practice to provide patients with gene-based diagnosis.” The Partner’s Laboratory for Molecular Medicine, an HMS affiliate, has incorporated TTN analyses.

The Seidmans and others had previously linked other gene mutations to about 20 to 30 percent of idiopathic DCM cases — and, with more success, to a related disease, hypertrophic cardiomyopathy. They had examined almost all of the genes linked to muscle units known as sarcomeres, but saved the biggest for last: TTN, which encodes the protein titin. At approximately 33,000 amino acids, titin is the largest human protein.

“Titin was a missing link,” said Christine Seidman. “A very large missing link.”

The Seidmans’ collaborated with researchers from the Imperial College (London) and the University of Washington. Traditional sequencing methods had previously found only a few TTN variants in patients with DCM because complete, accurate sequencing was too expensive.

Using next generation sequencing tools that substantially reduce the cost per base (the TTN sequence contains 100,000 bases) by orders of magnitude over earlier standards, the Seidmans were able to perform comprehensive screening for TTN mutations for the first time. They analyzed TTN in 312 DCM patients, 231 HCM patients, and 249 individuals with no disease.

Of the many mutations identified, 72 make the titin protein shorter.

Called TTN truncating variants, these specific mutations appeared almost exclusively in patients with DCM. “Our hypothesis is that any variant that shortens titin is going to cause DCM, which will lead to heart failure by the same mechanism,” said Jonathan Seidman.

To identify the pathological mechanism, the Seidmans plan to model a handful of TTN truncating mutations in mice.

One concern in the search for disease causing genes is that, while there will be many gene variants discovered, only a few will cause disease. This is particularly true for missense mutations that cause single nucleotide changes — changes that substitute a single amino acid within the protein.

“We often don’t know if a missense mutation significantly impacts a protein’s function, until we model it and study its effects,” said Jonathan Seidman.

However, in the case of truncating mutations, “it’s the converse,” he continued. “We don’t have to model all of those different mutations that truncate titin, becuase they all foreshorten the protein. We can pick a few representative ones and expect that they will reveal a common mechanism.”

A better understanding of the mechanism may lead to better and more direct therapies for treatment and prevention of DCM.

This research was funded by Howard Hughes Medical Institute; National Institutes of Health; Leducq Foundation; American Heart Association and Muscular Dystrophy Association; and the UK National Institute for Health Research Cardiovascular Biomedical Research Unit.

— Elizabeth Dougherty

The study’s findings describe elements of social network structures that may have been present early in human history, suggesting how our ancestors may have formed ties with both kin and non-kin based on shared attributes, including the tendency to cooperate. According to the paper, social networks likely contributed to the evolution of cooperation.

“The astonishing thing is that ancient human social networks so very much resemble what we see today,” said Nicholas Christakis, professor of health care policy (medical sociology) at Harvard Medical School and professor of sociology in the Harvard Faculty of Arts and Sciences, and senior author on the study. “From the time we were around campfires and had words floating through the air, to today when we have digital packets floating through the ether, we’ve made networks of basically the same kind.”

“We found that what modern people are doing with online social networks is what we’ve always done—not just before Facebook, but before agriculture,” said study co-author James Fowler, professor of medical genetics and political science at the University of California, San Diego, who, with Christakis, has authored a number of seminal studies of human social networks.

The findings will be published January 26 in Nature.

Roots of altruism

The natural world, red in tooth and claw, has a gentle side. While individuals compete fiercely to ensure the proliferation of their progeny, a few animals, including humans, also cooperate and act altruistically. Researchers have wondered if human social networks are a product of modern lifestyles, or if they could have emerged under the kind of conditions that our distant ancestors faced. This question has been challenging for classic evolutionary theory to explain neatly.

For cooperation to arise, an altruistic act, like sharing food with a non-relative, must have a net benefit for the sharers. Otherwise, purely self-serving individuals would outcompete and eventually replace the selfless. All theoretical explanations for the evolution of cooperation—kin selection, reciprocal altruism, group selection—rely on the existence of some system that allows cooperators to group together with other individuals who tend to share.

“If you can get cooperators to cluster together in social space, cooperation can evolve,” said Coren Apicella, a post-doctoral research fellow in Health Care Policy at Harvard Medical School and first author on the paper. “Social networks allow this to happen.”

While it is not possible to quiz our distant ancestors about their friendships or habits of sharing and collaborating, a team of researchers from Harvard Medical School, the University of California, San Diego, and the University of Cambridge have characterized the structure of social networks among the Hadza, an ethnic group in the Lake Eyasi region of Tanzania, one of the last surviving groups of hunter gathers. (There are less than 1,000 Hadza left who live in the traditional way).

Getting connected

The Hadza lifestyle predates the invention of agriculture. The Hadza eat a wide range of wild foods, foraging for tubers, nuts, and fruit and hunting a great variety of animals, including flamingos, shrews, and giraffes. Honey is one of their favorite foods, known by half a dozen different names in Hadzane, their primary language.

Apicella took the lead in collecting the data for the study, interviewing 205 adult Hadza over the course two months, measuring their tendency to cooperate and mapping their friendships.

Apicella, Fowler and Christakis designed the study and experiments, working with Frank Marlowe, lecturer in the Department of Archaeology and Anthropology of the University of Cambridge, and author of the only book-length ethnography on the Hadza in English.

Collecting the data was not easy. The nomadic Hadza roam over 4,000 rugged square kilometers. Apicella and her research assistants travelled the region by Land Cruiser battling mud-drenched trails—at one point forcing her and her colleagues to pave the ground with felled trees—and, on an earlier trip, even fleeing a horde of marauding elephants.

In order to construct a social network, Apicella and her colleagues took a dual approach.  First, they asked Hadza adults to identify individuals they would prefer to live with in their next encampment. Second, they gave each adult three straws of honey and were told they could give these straws as gifts to anyone in their camp. This generated 1,263 campmate ties and 426 gift ties.

In a separate activity, the researchers measured levels of cooperation by giving the Hadza additional honey straws that they could either keep for themselves or donate to the group.

When the networks were mapped and analyzed, the researchers found that co-operators and non-cooperators formed distinct clusters.

The researchers also measured the connectedness of people with similar height, age, handgrip strength, etc., and other characteristics, such as food preference. They also analyzed the transitivity of friendship—the likelihood that one’s friends are friends with one another, and other network properties.

The structure and dynamics of the Hadza hunter-gatherer social networks were essentially indistinguishable from existing social network data drawn from modern communities.

“We turned the data over lots of different ways,” said Fowler. “We looked at over a dozen measures that social network analysts use to compare networks and pretty much, the Hadza are just like us.”

“Human beings are unusual among species in the extent to which we form long-term, non-reproductive unions with other members of our species,” said Christakis. “In other words, not only do we have sex, but we also have friends.”

Previous work by Christakis and Fowler, who are coauthors of the book “Connected,” has shown that our experience of the world depends on where we find ourselves within social networks. Particular studies have found that networks influence a surprising variety of lifestyle and health factors, such as how prone you are to obesity, smoking cessation, and even happiness.

For the researchers, the Hadza offer strong new evidence that social networks are a truly ancient, perhaps integral part of the human story.

This research was funded by the National Institute on Aging and by the Science of Generosity Initiative of the University of Notre Dame.

—Written by Jake Miller

Photo by Mim Adkins.

Twenty years ago, the Family Van hit the road. Last month, the wellness services center on wheels celebrated two decades of providing free curbside health education, screenings and referrals to more than 40,000 people in Boston neighborhoods.

“It’s fascinating to think about what’s the same and what’s changed over 20 years,” said Jennifer Bennet, executive director of The Family Van and Mobile Health Map. “The program was designed by community members and in partnership with them, and to this day, that’s very much the way that we run the program.”

The Family Van was envisioned by Nancy Oriol, now HMS dean for students, who launched the project with co-founder Cheryl Dorsey, then an MD student and now the president of Echoing Green, a venture philanthropy. The Van hit the streets on Martin Luther King, Jr. Day in 1992, with a mission to increase access to health services in medically underserved neighborhoods. The Van originally served six sites; a seventh site, in East Boston, was added in October 2011.

Today, Van clinicians stay busy, sometimes seeing up to 30 people during a three-hour neighborhood stop. Much of the work involves undiagnosed chronic illnesses such as hypertension and diabetes.
Although Massachusetts has made health insurance more widely available, Van staffers stress that insurance does not translate directly to access to care. Last year, only eight percent of Family Van clients were uninsured. “We primarily are working with people who have coverage, but their lives are too complex, usually because of poverty, to access healthcare,” said Benet.

“Dean Oriol came up with a very elegant, user-friendly design,” said Caterina Hill, research and evaluation program manager for The Family Van and research associate in the HMS Department of Global Health and Social Medicine, citing drop-in appointments and free services. “Even in Boston with all the amazing hospitals, there’s still a need for mobile clinics as a means for providing outreach and between-visit care for health symptoms. The Van’s success is built on trust and on meeting people where they are, both geographically and in terms of their health.”

In addition to preventative screening and testing, health education and student training, the Van team has expanded efforts in research and analysis. Mobile clinicians now upload data using an online tool called Mobile Health Map. A return-on-investment algorithm developed at HMS analyzes cost savings. “Now we’re able to really play a national role,” Benet said, “in terms of helping other mobile clinics understand that they really are having an impact.”

To date, more than 450 mobile health vans across the United States are using the online service. “Any van across the country can use it,” Benet said. “And it has shed light on a community that was previously really unstudied.”

One in three Van clients, Hill said, learn for the first time that they have borderline or high blood pressure, total cholesterol or blood glucose. The Van offers referrals and lifestyle coaching. “We’re saving the city of Boston more than  $1 million annually in avoided emergency room visits because we’ve been able to identify folks who are at high risk early on, and help them avoid becoming acutely ill,” said Hill.
Half of regular clients who presented with a health problem on their first visit to the Van controlled the condition by later visits. And savings aren’t just in dollars.

“This is a way to support the goals of primary care doctors, but we do so outside of a primary care setting,” Benet said. The Van team is moving in the direction of increased collaboration with care providers. “Doctors have an incredibly important role, and we need to make the best possible use of their time. Is it cost effective for doctors to be doing the education and counseling component of this part of treating people? Does that have to happen in a doctor’s office?” asked Benet.

“It was no accident that we were founded on Martin Luther King, Jr. Day,” said Hill. “Despite all the changes and growth, we’ve maintained the social justice aspect of our mission.”

—Angela Alberti

For roughly two thousand years, Chinese herbalists have treated Malaria using a root extract, commonly known as Chang Shan, from a type of hydrangea that grows in Tibet and Nepal. More recent studies suggest that halofuginone, a compound derived from this extract’s bioactive ingredient, could be used to treat many autoimmune disorders as well. Now, researchers from the Harvard School of Dental Medicine have discovered the molecular secrets behind this herbal extract’s power.

It turns out that halofuginone (HF) triggers a stress-response pathway that blocks the development of a harmful class of immune cells, called Th17 cells, which have been implicated in many autoimmune disorders.

From left to right, Malcolm Whitman, Tracy Keller, and Ralph Mazitschek. Photo by Angela Alberti

“HF prevents the autoimmune response without dampening immunity altogether,” said Malcolm Whitman, a professor of developmental biology at Harvard School of Dental Medicine and senior author on the new study. “This compound could inspire novel therapeutic approaches to a variety of autoimmune disorders.”

“This study is an exciting example of how solving the molecular mechanism of traditional herbal medicine can lead both to new insights into physiological regulation and to novel approaches to the treatment of disease,” said Tracy Keller, an instructor in Whitman’s lab and the first author on the paper.

This study, which involved an interdisciplinary team of researchers at Massachusetts General Hospital and elsewhere, will be published online February 12 in Nature Chemical Biology.

Prior research had shown that HF reduced scarring in tissue, scleroderma (a tightening of the skin), multiple sclerosis, scar formation and even cancer progression. “We thought HF must work on a signaling pathway that had many downstream effects,” said Keller.

In 2009, Keller and colleagues reported that HF protects against harmful Th17 immune cells without affecting other beneficial immune cells. Recognized only since 2006, Th17 cells are “bad actors,” implicated in many autoimmune diseases such as inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis and psoriasis. The researchers found that minute doses of HF reduced multiple sclerosis in a mouse model. As such, it was one of a new arsenal of drugs that selectively inhibits autoimmune pathology without suppressing the immune system globally. Further analysis showed that HF was somehow turning on genes involved in a newly discovered pathway called the amino acid response pathway, or AAR.

Scientists have only recently appreciated the role of the nutrient sensing-AAR pathway in immune regulation and metabolic signaling. There is also evidence that it extends lifespan and delays age-related inflammatory diseases in animal studies on caloric restriction. A conservationist of sorts, AAR lets cells know when they need to preserve resources. For example, when a cell senses a limited supply of amino acids for building proteins, AAR will block signals that promote inflammation because inflamed tissues require lots of protein.

Flowering hydrangea. Photo by iStock/Andyd

“Think about how during a power outage we conserve what little juice we have left on our devices, foregoing chats in favor of emergency calls,” said Whitman. “Cells use similar logic.”

For the current study, the researchers investigated how HF activates the AAR pathway, looking at the most basic process that cells use to translate a gene’s DNA code into the amino acid chain that makes up a protein.

The researchers were able to home in on a single amino acid, called proline, and discovered that HF targeted and inhibited a particular enzyme (tRNA synthetase EPRS) responsible for incorporating proline into proteins that normally contain it. When this occurred, the AAR response kicked in and produced the therapeutic effects of HF-treatment.

Providing supplemental proline reversed the effects of HF on Th17 cell differentiation, while adding back other amino acids did not, establishing the specificity of HF for proline incorporation. Added proline also reversed other therapeutic effects of HF, inhibiting its effectiveness against the malaria parasite as well as certain cellular processes linked to tissue scarring. Again, supplementation with other amino acids had no such effect. Such mounting evidence clearly demonstrated that HF acts specifically to restrict proline.

The researchers think that HF treatment mimics cellular proline deprivation, which activates the AAR response and subsequently impacts immune regulation. Researchers do not yet fully understand the role that amino acid limitation plays in disease response or why restricting proline inhibits Th17 cell production.

Nevertheless, “AAR pathway is clearly an interesting drug target, and halofuginone, in addition to its potential therapeutic uses, is a powerful tool for studying the AAR pathway,” said Whitman.

This research was funded by the National Institutes of Health and a Harvard Technology Accelerator Award.

—Cathryn Delude

The TEDMED style conference featured talks by 17 of the Hospital’s clinicians. Children’s Chief Innovation Officer Naomi Fried welcomed a packed house, which included attendees from across the country.

Medical innovation can take surprising forms. A simple idea like a Mylar-lined hat can help infants retain body heat and improve the post-surgical rewarming process.

Cutting edge technologies can be used to bring a surprisingly personal touch to distance medicine, like a mobile medical robot that lets pediatric patients check in with caregivers without traveling to the hospital.

Read more about these and other featured techniques and technologies on Children’s Vector blog.

Since babies spend so much time sleeping on their backs it's important to make sure their heads don't become flat. A new technique to triage plagiocephaly using simple telemedicine techniques will enhance clinical efficiency and save parents time.

Flier then introduced guests who were invited to the meeting to join in the discussion: David Dawson, HMS professor of neurology (who appears in the film), and three current medical students, Adam Was, Vamsidhar Chavakula, and Dayron Rodriguez.

Flier introduced Martin Samuels, HMS professor of neurology and head of the Department of Neurology at Brigham and Women’s Hospital, who gave a brief history of the film. Samuels said the film was professionally made for fundraising during Dean George Packer Berry’s tenure and that it was never released.

Following the film, Samuels opened the meeting to discussion and encouraged the students, Dawson and others to contribute to the discussion of the principles demonstrated in the film. Dawson spoke briefly about his experiences. The issue of hierarchy in medical education past and present was discussed.  The hierarchy was very much present in the film and there was a belief in the method that anxiety activated learning.  The students commented that today there is a respect for the hierarchy and that students will get as much responsibility as they are willing to take and that today’s students may have more opportunity to speak out and to make mistakes. They also said that the film gave the impression that there was more time for senior faculty interaction with students in the clinical setting.

Several people agreed that the philosophy of science using one’s mind and knowledge to make advances, as seen in the film, is timeless.  The topic of the value of team effort versus individual exploration was also discussed.

Flier adjourned the meeting.

First on the schedule in genetics clinic one afternoon were two sisters, ages 8 and 10, who had an appointment for evaluation of a “possible connective tissue disorder.” I remember thinking that they were much younger than the teenagers I had previously seen in clinic for similar reasons, referred by their pediatricians for newly elongated limbs or mild scoliosis. In the elevator up to clinic, my mind conjured vivid images from a seminal textbook on heritable connective tissue disorders. Stark black and white photographs depicted slender children with disproportionately long, spindly limbs and fingers, serpentine spines, sunken chests, and narrow faces with noses wedged between the frames of coke-bottle glasses.

By Sameer Chopra

Stepping into the clinic room, I sighed with relief. Seated before me were two well-appearing young girls, gleefully passing the time with their idle chatter. The overweight older sister playfully swung her normally-proportioned legs to and fro beneath her chair. Her younger sibling, both shy and slight in habitus, rested her hands on the front of her knees. I looked at her unremarkable fingers, the petite nails harboring flecks of paint. Even before reaching for the bright red measuring tape dangling from my shirt pocket, my suspicion was low that anything insidious could be afflicting these lovely children.

Their mother described the events that had brought them to Children’s Hospital. Several months earlier, the girls’ seemingly healthy father had suddenly developed severe chest pain. He was taken by ambulance to his local emergency room where a CT scan revealed a menacing tear in the wall of his aorta. Both fulminant and morbid, an aortic dissection is not uncommonly the presenting feature of an undiagnosed disorder of connective tissue, the biological fabric that binds together the skin, vital organs and blood vessels. Although his dissection was life-threatening and required immediate operative repair, he survived the event.

Later testing identified a deleterious mutation in the gene Fibrillin-1. The result meant that he had Marfan syndrome. Marfan is a disorder of connective tissue which predisposes individuals to a variety of serious ocular, skeletal, and cardiovascular problems, such as aortic dissection. The condition results from a single mutation in a single gene and is inherited in an autosomal dominant fashion. When diagnosed early, patients are often closely followed by a geneticist and a cardiologist, and they can live a long and full life.

After learning everything she could about Marfan syndrome, the girls’ mother wondered desperately whether either of her children could have the disorder. After closely examining the girls, I reassured their mother that neither child met the clinical criteria. I explained that because some features of the syndrome may appear as children grow, the plan would be to obtain an echocardiogram to assess for aortic root dilation and then follow the children in genetics clinic on an annual basis. Before I could finish discussing my tentative plan, the mother asked the obvious question: Couldn’t we just test the girls to determine whether either had inherited her father’s Fibrillin-1 mutation?

Although I appreciated mom’s desire for a definitive answer, I had mixed feelings. Is it appropriate for physicians to test well-appearing, asymptomatic children for genetic disorders? What were the implications? On one hand, knowing that a child carries a Fibrillin-1 mutation means that she could receive comprehensive anticipatory guidance for various features of the disorder, as well as take certain precautions to avert a future aortic catastrophe. Perhaps more compelling, medications are being developed to counter the specific cellular perturbations that cause the aorta to weaken in the first place. Certainly, the availability of an effective preventive intervention might warrant assessment of a child’s Fibrillin-1 genotype well in advance of any clinical signs.

On the other hand, I worried about the consequences of identifying a genetic mutation in an asymptomatic young child. Regular doctors’ visits and annual echocardiograms would make her a patient. Her mutation status may complicate relationships with family, friends, and the opposite sex. She might be discouraged from pursuing certain interests, talents, or vocations. Her physical activity would be restricted to limit the stress on her aorta. I also wondered about the psychological impact of knowing that one might die suddenly in the future. Any of these possibilities seemed compelling enough to consider a delay in genetic testing.

Ultimately, the difficult decision to test the girls was not mine to make. Based on the mother’s strong wishes, each girl had her blood drawn that day. The results returned several weeks later: Both sisters had inherited their father’s Fibrillin-1 mutation. I imagined mom’s anguish upon hearing the news. I was also heavy-hearted for a reason that had little to do with the future health of the sisters. I realized that the lives of these young children would henceforth never be the same, forever changed by the results of a single genetic test. Whether they had been altered for better or worse was impossible to know. Only time will tell.

Sameer Chopra, MD PhD, is a third-year resident in internal medicine and genetics at Brigham and Women’s Hospital. The opinions expressed are not necessarily those of Harvard Medical School, its affiliated institutions, or Harvard University.

The deadline for nominations is March 9, 2012. Winners will be announced April 12th in Sanders Theatre in Cambridge.

Learn more at ­green.harvard.edu.