Medicine on the Midway - Summer 2011 by University of Chicago Medicine

SUMMER 2011

Conquering Biological Horror University of Chicago scientists investigate the worldâ&#x20AC;&#x2122;s deadliest pathogens Medicine on the Midway Summer 2011

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The Winners of Mass Extinction Graduate student Lauren Sallan examines success and failure in an ancient battle between predators and prey By Rob Mitchum ven a mass extinction can have benefits. The Hangenberg event, a mass extinction 360 million years ago, devastated the vertebrate species of the time period, bringing an end to the “Age of Fishes.” But for the animals that fed those species, the Hangenberg event was an unexpected blessing. The next 15 million years were dominated by crinoids, species similar to modern sea lilies, and starfish that thrived when their predators disappeared. Only when fish returned and resumed the feast did this age of the crinoids come to an end. This natural tug-of-war is what ecologists classically see when predators are

Hangenberg event. A newspaper article about her research alerted Thomas Kammer, PhD, Eberly College Centennial Professor of Geology at West Virginia University, to a solution he had long pursued in the crinoid fossil record. “We’ve been puzzled for many years as to why there were so many species and specimens of crinoids,” Kammer said. “There had to be some underlying evolutionary and ecological reason for that.” Like two pieces of the puzzle, Kammer’s

added to or removed from an environment. But by analyzing the fossil record data for vertebrates and crinoids side by side, researchers from the University of Chicago, Ohio State University and University of West Virginia made the first such discovery in a prehistoric world. “This is the first time that specific, longterm predator-prey interactions have been seen in the fossil record,” said Lauren Sallan, graduate student in the Department of Organismal Biology and Anatomy and lead author of the study published in May

crinoid data and Sallan’s vertebrate data completed each other’s story. When the fish disappeared, crinoid species diversified and multiplied. In fact, their fossils are so abundant that they make up entire limestone deposits from the era. But that period of unbridled success made them vulnerable. When new types of fish appeared 15 million years after the Hangenberg event, their new predation strategy of using crushing teeth rather than shearing teeth easily triumphed over the obsolete armor of the crinoids. In the absence of a predator-prey arms race, a species’ inherited defenses may become outdated, Sallan said. “When a new form of predator appears,

in Proceedings of the National Academy of Sciences. “It tells us a lot about the recovery from mass extinctions, especially mass extinctions that involved a loss of predators.” The collaboration arose after Sallan published a study in 2010 about the

they can go directly for the best solution to cracking a crinoid, which is crushing,” Sallan said. “The Devonianera armor of crinoids isn’t suited for defending against that attack, but they can’t lose it without losing all of their residual defenses.” ■

An artist’s rendering of a shallow marine ecosystem during the early Carboniferous Period (359 to 318 million years ago). Prehistoric ﬁsh that fed on the plantlike crinoids were wiped out by the Hangenberg extinction event, leaving the crinoids to thrive as the dominant form of ocean life for roughly 15 million years. Illustration by Robert Nicholls ABOVE

University of Chicago Medical Center

CONTENTS FE ATU R E S 8

COV E R S T O RY: CO N Q U E R I N G B I O L O G I C A L H O R R O R As infectious diseases take on “superbug” status, microbiologists at the University of Chicago continue to research, discover and develop new remedies to ward off these deadly bacteria before they reach pandemic proportions. By Brooke E. O’Neill 15

How to Work with Dangerous Bugs Get a behind-the-scenes look at the war on super pathogens, bacteria and more at Ricketts Lab at Argonne National Laboratory. By Brooke E. O’Neill

Mapping Bacterial Worlds, from Sea to Stomach Exploration of the ecosystem within the human gut could provide new insight for physicians treating infectious diseases. By Rob Mitchum

Free Clinics Beneﬁt Future Physicians As Well As Patients University of Chicago Pritzker School of Medicine students gain valuable experience while donating their time in the community to staffing free clinics around the South Side of Chicago. By Kelin Hall 20

Medical Residents Make the Most of Limited Resources Uninsured patients from Englewood have a place where their medical needs can be met and where Medical Center physicians strengthen ties in the community. By Kelin Hall

As Landmark Study Turns 40, Risks of DES Exposure Subside Arthur L. Herbst, MD, changed the way physicians thought about a once oft-prescribed drug for pregnant women. By John Easton

D EPARTM ENTS 2

Letter from the Editor: An Evolving Medical Center An epicenter of change, the Medical Center continues to advance and evolve with new leadership, new opportunities and renewed direction within these pages. By Cheryl L. Reed

Midway News Find out the latest news from the Medical Center.

Q&A: The View from the Top Kenneth S. Polonsky, MD, dean and executive vice president for medical affairs, gave his thoughts and insight at an alumni event in New York. By Stephen Phillips

Medicine Off the Midway: The Power of No What could have been an epidemic of birth defects in the United States was prevented by the voice of an FDA heroine unafraid to take on powerful drug companies. By Stephen Phillips

Pritzker Proﬁle: A Legacy’s Triumph over Cancer One Pritzker student’s family ties have deep roots within the medical school. By Shane Graber

Class Notes Read updates from Pritzker and BSD alumni.

Pritzker News 30 Military Match Day Two Pritzker students await their Match Day results that will enable them to serve both patients and their country. By Kelin Hall

35 For microbiologists who study “superbugs,” like anthrax, plague and MRSA, growing cultures in petri dishes is a common trick of the trade. Getty Images ON THE COVER

Pritzker’s Class of 2011 Marks Match Day Pritzker fourth-year students matched at programs in 22 states, with 22 percent starting a residency at the Medical Center. By Kalyn Belsha

Reunion 2011 Pritzker alumni gathered in June to remember and reconnect. By Gretchen Rubin

Convocation 2011 Pritzker and BSD students receiving their MDs and PhDs said goodbye to classmates and celebrated the next step in their medical careers. By Molly V. Strzelecki

Perspective: Bloggers, MD Doctors are reaching out through the blogosphere to connect with colleagues and patients. By Stephen Phillips

Medicine on the Midway Summer 2011

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An Evolving Medical Center “It is not the strongest of the species that survive, nor the most intelligent, but the one most responsive to change.” — Charles Darwin

his spring has brought many changes at the University of Chicago Medical Center and at the Marketing and Communications Department. In February, the Medical Center hired a new department vice president, Kathy DeVries, who comes to us from Barnes-Jewish Hospital in St. Louis, where she worked with Dean and Executive Vice President Kenneth S. Polonsky, MD, and the Medical Center’s new president, Sharon O’Keefe. In fact, DeVries arrived at the Medical Center just days before O’Keefe, who came aboard in late February. The new leadership team is setting a clear path for the future of the hospital, the medical school and the University, a plan you can learn more about in a Q & A with the dean on page 6. The magazine and its online version will continue to give you updates as these plans progress. DeVries, who has a 20-year-plus career in hospital marketing and communications, also has charted a specific course for a more robust marketing and communications department. As part of her plan, we have expanded the department to include a team of referring physician relations professionals who will be spreading the news about our specialties and developing and strengthening relationships with physicians who send their patients here. We have great stories to tell at the Medical Center and Division of Biological Sciences. So we’re starting two new magazines, one for referring physicians that will extend nationwide and the other targeted at more than half a million consumers in the Chicagoland area. This will allow Medicine on the Midway to

University of Chicago Medical Center

At ﬁrst baffl ed by the male peacock’s colorful showmanship, Charles Darwin later explained Pavo cristatus’s tail feathers as a trait evolved to attract mates. Science Photo Library

return to its original intent — to keep alumni and friends abreast of medical and scientific discoveries at the Medical Center and the Division of Biological Sciences as well as connected to former colleagues and classmates at the Pritzker School of Medicine. I’m very excited about these changes and, as a part of them, I’ll be leaving these pages. This is the last edition of Medicine on the Midway I’ll be editing. In my new role as director of strategic communications, I’ll be focusing on improving our image in the media, implementing a social media program, improving internal communications and expanding our reach in the medical and surrounding communities. Having said that, I’m still around and I’ll be working with my replacement, Ginny Lee-Herrmann, who takes the helm in August. Lee-Herrmann is a veteran journalist who joins us after a long career at

the Daily Herald, where she was the deputy managing editor. In addition to Lee-Herrmann, we have expanded our team of writers and media professionals, all of whom are experts in their fields. I feel in many ways we are launching our own newsroom on the South Side, and many people are eager to join us. Please feel free to email us at momedit@uchospitals.edu and as soon as Lee-Herrmann is in place, we’ll post her direct email and phone number. I hope you all have a great summer.

Cheryl L. Reed Director of Strategic Communications

M I D W AY N E W S

PSA for Elderly Often Unnecessary

any elderly men undergo unnecessary prostate cancer screenings, while men in their early 50s — who are more likely to benefit from early diagnosis and treatment — do not, according to a new study published March 28 in the Journal of Clinical Oncology. Surveys conducted in 2000 and 2005 show that nearly half of men in their 70s had a prostate-specific antigen (PSA) screening, a blood test that can detect early signs of prostate cancer, in the past year. As a result, 750,000 men with an estimated life expectancy of approximately five years received PSA screenings each year. These men are unlikely to reap a meaningful benefit. Because prostate cancer tends to grow slowly, many men in their 70s and older will die of other causes before prostate cancer requires medical attention. Overuse of PSA screening may lead to unnecessary treatment, which can cause complications such as incontinence, impotence or bowel dysfunction.

“Our findings show a high rate of elderly and sometimes ill men being inappropriately screened for prostate cancer,” said Scott Eggener, MD, assistant professor of surgery at the University of Chicago. “We were also surprised to find that nearly three-quarters of men in their 50s were not screened within the past year. These results emphasize the need for greater physician interaction and conversation about the merits and limitations of prostate cancer screening for men of all ages.” Physicians should be more selective in recommending PSA testing for older men, particularly those with a limited life expectancy, the study authors suggest, and physicians should consider screening younger, healthier men more routinely, since these patients are most likely to benefit. “Excessive screening for prostate cancer in elderly men who have limited life expectancies in the United States results in unnecessary anxiety, diagnoses, over-

Overuse of PSA screenings can lead to unnecessary treatments, determined Scott Eggener, MD, and colleagues, in a new study published in the March 28 issue of Journal of Clinical Oncology. Photo by Dan Dry

treatment, treatment-related morbidity and health care expenditures without meaningful clinical benefit,” the authors conclude. ■

New Hospital Pavilion Project Helps Beneﬁt Minority- and Women-Owned Businesses

Konrad Shegog works on the New Hospital Pavilion project. The Medical Center’s goal is to award 40 percent of construction contracts to minority- and women-owned business enterprises. Photo by Joan Archie

he New Hospital Pavilion (NHP) is the largest single health care investment in the history of the University of Chicago Medical Center. Scheduled to open in 2013, the impressive 1.2-million-square-foot building is already an economic engine fueling minority- and women-owned companies in the greater Chicagoland region. As the project has evolved since 2008, the Medical Center has awarded and paid close to $97.6 million in contracts to 94 minority- and women-owned business enterprises, such as material suppliers, construction contractors and professional services firms. “Our goal is to ensure that at least 40 percent of our construction contracts are awarded and paid to minority business enterprises and women-owned business enterprises,” said Joan Archie, executive director of construction compliance at

the Medical Center. “It’s our aim to strengthen these firms.” Since 2001, the Medical Center has paid more than $200 million to minority- and women-owned businesses and to minority and female workers in construction and renovation projects. The Medical Center monitors these numbers closely as part of its larger commitment to diversity and community investment, said Bill Huffman, vice president of facilities, design and construction. “We want our construction projects to mirror the diverse workforce we have at the Medical Center itself,” Huffman said. “Beyond this, our minority and female firms and workers have done a top-flight job. On the NHP, the work has been outstanding. We are on schedule and the expenses have been at or under budget. This is going to be a state-of-the-art facility, and we couldn’t be more pleased.” ■

Medicine on the Midway Summer 2011

M I D W AY N E W S

A New Trigger in Celiac Disease

n celiac disease, the immune defenses of the gut are triggered by what should be a harmless visitor: gluten, a dietary protein found in wheat, barley and rye. Currently, celiac disease patients have no better option than to avoid foods containing gluten. But in a recent paper, scientists located an immune factor in those patients that may be a trigger — and a potential treatment target — for celiac disease and other food allergies. A multi-center team, including several researchers from the University of Chicago Celiac Disease Center, studied the signal interleukin-15 (IL-15), which is elevated in celiac patients. Normally, immune factors known as regulatory T cells suppress the immune response to foods, but IL-15 interferes with this protection. When scientists increased IL-15 levels in mice, they exhibited symptoms of early celiac disease. Conversely, when the signal was blocked, the mice recovered. When another factor was added to the mix — retinoic acid, or vitamin A — the symptoms of celiac disease were even stronger in the mice. The result was unexpected, as vitamin A is occasionally prescribed to suppress inflammation in the gut. But

Bana Jabri, MD, PhD, is the senior author of a study that looked at an immune factor that could be a trigger and treatment target for celiac disease. Photo by Bruce Powell

it helps explain an observed link between acne medications based on retinoic acid and inflammatory bowel disease. The research suggests that a “dysregulated intestinal environment may be the underlying cause for food allergies,” said Bana Jabri, MD, PhD, associate professor of medicine and pathology, and senior

author of the paper published in Nature in March. Moving back and forth between “human data, where we develop our ideas, and mouse experiments, where we test them,” was extremely helpful, Jabri said. “In turn, the mouse model gave us insights into the human disease.” ■

Pediatric Specialist Dies on Rafting Trip

ames Nachman, MD, pediatric cancer specialist and professor of pediatrics at the University of Chicago, died June 10 of a heart attack while on a rafting trip in the Grand Canyon. Nachman was an authority in the medical management of childhood cancers, particularly in leukemia and lymphoma. He helped develop a treatment regimen known as “augmented post-induction therapy” for acute lymphoblastic leukemia (ALL) and led the clinical trial, published in 1998, which demonstrated a substantial improvement in survival for patients with the disease who had a slow response to initial therapy. These studies helped lead to the high cure rate for this disease today. Nachman also was a key player among Chicago specialists in the treatment of bone and soft tissue sarcomas, serving as the medical oncologist for the University of Chicago’s limb-salvage program, which works to save the arms and legs of adolescents with bone cancer.

“He was an incredible chemotherapist, devising novel therapies for patients who did not respond to standard therapies,” said colleague Charles Rubin, MD, associate professor of pediatrics at the University of Chicago. “Jim was totally devoted to his work. He spent all of his time taking care of patients, teaching students, residents and fellows. He always encouraged the patients to live their lives and do everything that other kids do. He helped them by obtaining tickets for ball games and insisting on them going to school. There was no one quite like him.” Nachman was active in the national Children’s Oncology Group, and he chaired three international committees on the use of augmented acute lymphoblastic leukemia therapy. He was also a founding member of the Ponte de Legno ALL Consortium. A recognized yet accessible leader in his field, he served as a consultant for physicians dealing with difficult cases from around the world. ■

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Internationally known cancer expert James Nachman, MD, served as the medical oncologist for the University of Chicago’s limb-salvage program, working to save the arms and legs of adolescents with bone cancer.

Young Altruistic Kidney Donor Starts Chain Reaction across the Country

Brieﬂy New Institute Created at the University The University of Chicago has created a new institute that will intersect quantitative biology, neuroscience and the study of social and individual behaviors. The Grossman Institute for Quantitative Biology and Human Behavior is a collaborative effort between the Division of Biological Sciences and Division of the Social Sciences. According to Kenneth S. Polonsky, MD, dean and executive vice president for Medical Affairs, the Institute will build on existing strengths within the University to address fundamental questions about the biological, social and environmental factors that shape social behaviors and interindividual variation in model organisms and humans. The Institute is named for University Trustee Sanford Grossman, AB ’73, AM ’74, PhD ’75, chairman of QFS Asset Management, LP, in recognition of his long service and ﬁ nancial support to the University.

Noteworthy Rich Cummings (right), procurement coordinator, and Piotr Witkowski, MD, prepare the kidney to be shipped to New York City. Photo by Dianna Douglas

achel Garneau could have done what most college students do after exams — take a trip, relax or start a summer job. Instead, the 20-year-old from Elmhurst, Illinois, took advantage of her spring break to give one of her kidneys to a complete stranger, starting a national chain of kidney swaps and giving kidney patients at the University of Chicago Medical Center new hope for a match. As an altruistic donor, Garneau got nothing out of the arrangement except for the satisfaction of saving the life of someone she’s never met, thousands of miles away. Yolanda Becker, MD, professor of surgery and director of the kidney and pancreas program, was amazed at Garneau’s persistence in trying to donate a kidney. “There is a lot of good that will come downstream from Rachel’s donation,” Becker said. Garneau’s kidney went to a patient in New York City who desperately needed it. That patient had a loved one who was willing to donate, but whose kidney didn’t match. Instead, the New York donor sent a kidney to a patient in Madison, Wisconsin. Kidney chains like this are arranged by the National Kidney Registry, which takes detailed information about kidney transplant patients and tries to give will-

ing donors the possibility of exchanging kidneys with strangers on behalf of their loved ones. Because of Garneau’s donation, the University of Chicago can now register 30 patients without donors on the National Kidney Registry to look for a match. The University of Chicago Medical Center participated in its fi rst kidney chain in March, when a donor from Loyola gave to a patient here, his wife gave to someone in New York, which allowed a donation to New Jersey, and then to California — all in one day. A few weeks later, Becker and the transplant team arranged an exchange with four people in Illinois, where a Chicago man donated to someone in Peoria in exchange for a kidney from Peoria for his wife. The surgeons, nurses and staff of the kidney transplant program hope to continue matching up willing donors with patients who need kidneys. Kathy Davis, RN, transplant coordinator who organized the Medical Center’s effort in this swap, said the logistics of joining kidney chains and exchanges are huge. “The amount of time and effort that go into making sure everything is OK is worth it,” she said. “It’s intense and exciting.” ■

Vinay Kumar, MBBS, FRCPath, professor and chair of the Department of Pathology and formerly the Alice Hogge and Arthur A. Baer Professor, has been named a Donald N. Pritzker Professor. Michelle Le Beau, PhD, professor of medicine and human genetics, has been named the inaugural Arthur and Marian Edelstein Professor. Cathryn R. Nagler, PhD, professor of pathology, medicine, and the College, has been named the inaugural Bunning Food Allergy Professor. This professorship was established to build a basic science and translational program in food allergy research at the University. Kenneth S. Polonsky, MD, professor of medicine and dean of the Division of Biological Sciences and the Pritzker School of Medicine and executive vice president for Medical Affairs, has been named the Richard T. Crane Distinguished Service Professor. Manyuan Long, PhD, professor of ecology & evolution and the College, has been named the inaugural Edna K. Papazian Distinguished Service Professor.

Medicine on the Midway Summer 2011

Q&A

The View from the Top A wide-ranging conversation with Kenneth S. Polonsky, MD, touches upon the importance of “good scientiﬁc taste,” the role of social media in marketing and the signiﬁcance of the “two-crane project” well on its way in the heart of the campus

Andrew Alper, AB ’80, MBA ’81, (left) interviewed Kenneth S. Polonsky, MD, at a University event in March. Photo by Deborah Suchman Zeolla

By Stephen Phillips

ow several months into his tenure as dean of the Division of Biological Sciences and the Pritzker School of Medicine and executive vice president for Medical Affairs, Kenneth S. Polonsky, MD, traveled to New York City in March for an intimate conversation with alumni and friends of the University at a reception hosted by former dean Donald King, MD. Chair of the University’s board of trustees Andrew Alper, AB ’80, MBA ’81, turned interviewer for the occasion, and Polonsky opened up about what is top of mind for him. Here are edited excerpts:

Andrew Alper: What are the biggest opportunities and challenges that you see ahead for the University of Chicago Medical Center? Kenneth S. Polonsky: We have an exciting opportunity in translational research, that is, translating basic discoveries made at the bench into benefits for human health. The revolution in technology, with high-throughput genome sequencing, advanced imaging and sophisticated methods for

measuring proteins and metabolites, is allowing scientists to perform rigorous research in humans. This is providing unique insights into the normal function of the human body and the biologic basis of disease. We are ideally positioned to be among the leaders in this work, thanks to our compact campus, interdisciplinary culture and expertise in computation, bioinformatics and clinical science, as well as our ability to form new cross-cutting research programs. What keeps me up at night is not so much internal issues — our people are very able, hardworking and productive — but the external factors over which we have less control: state and federal budgets, particularly reimbursement for Medicare and Medicaid. On the other hand, I came to this country from South Africa 35 years ago, believing it to be the best place in the world to live, and nothing I have seen since has dissuaded me from that, so I have faith that as a nation we can address these issues. Alper: What will the new Institute for Molecular Engineering mean for the biological sciences at the University? Polonsky: I met with Matthew Tirrell, the Institute’s

“We are ideally positioned to be among the leaders in this work, thanks to our compact campus, interdisciplinary culture and expertise in computation, bioinformatics and clinical science, as well as our ability to form new cross-cutting research programs.” — Kenneth S. Polonsky, MD

University of Chicago Medical Center

director, upon his appointment in March, and he clearly understands the value of working closely with biological scientists. We expect to establish many opportunities for our scientists to interact and collaborate with the Institute. Matt brings a stellar track record of building relationships with industry. This focus has the potential for substantial positive impact on the University. The new technologies the Institute will help generate will stimulate economic development for the Chicago area.

Alper: Tell us about your leadership team. Polonsky: Sharon O’Keefe, the president of the Medical Center,

is an extraordinary new leader for our hospitals. We conducted a nationwide search for a seasoned, accomplished hospital administrator, and we found the best person in Sharon. I had worked closely with her at Barnes-Jewish Hospital in St. Louis, where she was chief operating officer. She is a nurse by training and has devoted her career to improving hospital operations. For our staff, the appointment of a nurse as president of the Medical Center was an important symbolic event, and the reception she’s received has been tremendous; there were long lines of people who wanted to shake her hand when we introduced her in February. She spent her fi rst weeks on the job immersing herself in our operations, shadowing staff in every unit and meeting all the nurses, which also meant a lot. One of our priorities is developing an effective faculty practice plan. This is the mechanism whereby different specialists coordinate and implement joint programs. We have great individual programs, but now we’re connecting the dots. This is especially important because our patients rarely have simple needs and often must see multiple doctors. Richard Baron is spearheading this effort. As radiology chair, he showed himself to be highly patient-centric and service-oriented, and in his new role as dean for clinical practice, he has already made substantial efforts to reach out to our faculty and to understand their concerns.

(Left to right) Kenneth S. Polonsky, MD, Andrew Alper, and Donald King, MD. Photo by Deborah Suchman Zeolla

will empower our faculty to deliver world-class, leading-edge care to patients facing the most challenging, complex conditions and to drive new breakthrough treatments for patients. An integrated communications system will create a feedback loop between our clinicians caring for patients and our research scientists in their labs, capturing data we can harness to push the frontiers of medical knowledge and refine medical practice. It will also support advanced surgery. Stateof-the-art now requires very advanced technology for day-to-day care of patients with complex diseases. The new hospital will give us dedicated space and the infrastructure to provide this. “The new hospital will be a launchpad for At the same time, we have very deliberately not comthe next wave of University of Chicago mitted ourselves just to current technology. The building’s design features a modular layout that can readily be contributions to medicine.” repurposed to accommodate new innovations as they — Kenneth S. Polonsky, MD emerge. We are also incorporating amenities that ensure patients The other person I’d mention is Conrad Gilliam, dean for and their families feel comfortable. The rooms will be priresearch and graduate education. He is an eminent scientist vate and spacious enough to allow family members to spend and chaired our human genetics department before assum- time with patients — including staying overnight — with ing this new role. He is leading a process to identify scientific facilities for them to prepare food. These are important conareas where we can excel and make the biggest contribution. siderations for the people we serve, many of whom face He has extremely good scientific taste and brings an acute complicated procedures and extended stays. understanding of the fields that are important to us. Visually, the new hospital will be stunning. It is a magnifI would also single out our dedicated and energetic mar- icent structure, very imposing. I live downtown facing south, keting team under the direction of our new vice president for and you can see that it is the biggest structure on the South marketing and communications, Kathleen DeVries. We are Side. When I came, I was told it was the only two-crane projgoing to be aggressive in advertising the name of the University ect in Chicago, and I think it still is. of Chicago. And I have learned that Facebook and Twitter What will set the facility apart, though, will be the presare not just for your kids; they are an essential part of hospi- ence of our brilliant, dedicated faculty. The new hospital will tal advertising. Social media are not something I am equipped really light a fi re under their work. to comment on, but the world is changing in dramatic ways, and I will try to facilitate the use of these new technologies Alper: How can alumni help the Medical Center? to benefit our programs. Polonsky: Participate! There are a wealth of opportunities via committees and events. Your input is invaluable; you know Alper: Tell us about the new hospital and what it will mean the place but have also been elsewhere, so your perspective for the Medical Center. and keen insights can help us in myriad ways. Staying engaged and letting us know what is on your mind are key. You have Polonsky: The new hospital will be a launchpad for the next wave of University of Chicago contributions to medicine. It a vital role to play in the future of this institution. ■

Medicine on the Midway Summer 2011

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Conquering Conquering the Biological Horror Biological Horror Cabinet University of Chicago scientists investigate the world’s deadliest pathogens

Investigating some of weeks the most deadly bacteria, University It was barely two after the September 11, 2001, terrorist attacks when Robert Stevens, of Chicago microbiologists are developing new remedies 63, came down with a fever. A photo editor at Florida’s Sun tabloid, he ﬁgured he’d sleep it designed to tackle an ever-changing arsenal of bugs — and later was struggling to breathe. His wife rushed him to the local hospital. wardoff offbut thetwo nextdays outbreak.

By October 5, Stevens was dead. The culprit: Bacillus anthracis, or anthrax. By Brooke E. O’Neill By Brooke E. O’Neill

For more information, call 1-888-UCH-0200 or visit uchospitals.edu

y now, we know the horrific story. Envelopes were laced with lethal anthrax spores and mailed to government offices and news outlets, like the one where Stevens worked. Ultimately, the attacks killed five people and sickened 17 others, prompting the FBI to call it one of the “worst biological attacks in U.S. history.” Bioterrorism fears quickly spread. Soon University of Chicago infectious disease researcher Olaf Schneewind, MD, PhD, Louis Block Professor and chair of microbiology, was getting panicked calls from business school colleagues worried their mail might be contaminated. “I was the most popular guy on campus,” recalled Schneewind, who studies pathogens such as anthrax, plague and Staphylococcus aureus, the so-called superbug. Characterized by high mortality rates and capable of spawning epidemics, these dangerous microbes are part of what Schneewind calls the “biological horror cabinet.” And while the 2001 incidents catapulted B. anthracis into the national spotlight, such bacteria are hardly a novel threat. From the estimated 25 million who succumbed to a rodshaped bug called Yersinia pestis — Black Death — in the 14th century to the roughly 40,000 Americans who die of staph infections every year, infectious organisms have long exacted a devastating toll. That’s why Schneewind and his microbiology team are working against time to conquer these pathogens before a pandemic erupts. Analyzing molecular structures and dissecting some of the most deadly bacteria, they’re developing new vaccines and therapies designed to tackle an ever-changing arsenal of bugs — and ward off the next outbreak. “These diseases inflict a lot of casualties,” Schneewind warned. “Our job is to stop them in their tracks.”

Know the Bug To defeat a pathogen, you have to first understand how it operates. While many infectious diseases have been floating around for decades, even centuries, University of Chicago researchers are shedding new light on their inner workings. At the heart of their efforts is the Howard T. Ricketts Regional Biocontainment Laboratory at Argonne National Laboratory, a high-security facility where federal background checks and protective Tyvek suits are the norm. The lab is located at Argonne, 25 miles southwest of Chicago (see page 15). The Howard T. Ricketts Laboratory provides researchers a controlled environment for studying pathogens. Opened in December 2009, it houses “select agent” microbes that the Centers for Disease Control and Prevention (CDC) considers a “severe threat to public health and safety.” “These organisms are also known as bioweapons,” said Schneewind. “They disseminate with-

Olaf Schneewind, MD, PhD, Louis Block Professor and chair of microbiology, studies deadly pathogens at the Howard T. Ricketts Regional Biocontainment Laboratory at Argonne National Laboratory.

“These diseases inﬂict a lot of casualties. Our job is to stop them in their tracks.” — Olaf Schneewind, MD, PhD out an explosion — and it happens for free. Someone gets infected, transmits the disease, then it spreads.” Bioterrorism concerns aside, many of these organisms are clever enough — and common enough in nature — to wreak havoc all on their own. Anthrax spores, for example, can lie dormant in soil for years before they infect a living host, typically sheep, cattle or other livestock. Rickettsia, the group of bacteria responsible for typhus and Rocky Mountain spotted fever, lurk inside ticks until the pest bites an animal or human, allowing the pathogen to sneak inside and seize the host’s own cell machinery to replicate itself. “Many pathogens use variants of the same tricks because they need to accomplish the same goals: Get into the human tissue, survive there, avoid the immune response,” said Juliane Bubeck-Wardenburg, MD, PhD, assistant professor of pediatrics and microbiology. “These are all things every pathogen must do successfully.” One of the trickiest — and deadliest — is S. aureus, the leading cause of infectious disease death in the

Medicine on the Midway Summer 2011

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United States. The reason is twofold: the microbe commonly lives on humans — and can be extremely virulent when it sneaks into the bloodstream. “When people say, ‘He got an infection and died from it,’ what they mean is this bug,” Schneewind said. A round bacterium that forms grapelike clusters, S. aureus can hang out harmlessly on the body for years. In fact, there’s about a 50 percent chance you’re carrying it on your skin or in your nose right now, asserted Dominique Missiakas, PhD, associate professor of microbiology. In most cases, it manifests as minor skin infections, like pimples.

“Many pathogens use variants of the same tricks because they need to accomplish the same goals: Get into the human tissue, survive there, avoid the immune response.” — Juliane Bubeck-Wardenburg, MD, PhD

L E F T B. anthracis, anthrax, is capable of surviving outside a host for decades. Getty Images

“But every now and then,” Missiakas explained, “it gets inside the bloodstream and starts replicating like crazy.” Capable of infecting every part of the body — soft tissue, skin, lungs, brain, kidneys, heart — the organism gains a foothold by foiling immune cells that normally fight off such invaders. Scottish surgeon Sir Alexander Ogston first identified the spherical microbe lurking in surgical wound infections in the 1880s. Today, the pathogen remains the most frequent cause of skin and soft tissue abscesses (pus-filled lesions) in humans. Historically, staph infections were largely confi ned to hospitals, where weakened immune systems and invasive procedures make individuals more vulnerable. Open surgical wounds and medical devices like catheters can breach the body’s natural barriers, creating pathways for infection. Additionally, hospital personnel may carry the microbe on their skin and without proper hygiene may transmit it to patients. Currently, the average rate of infection for any person entering an American hospital is 4 percent. “And that’s admission for any reason at all,” Schneewind stressed. “Someone might come in to get a tooth removed, and they die of an S. aureus infection.” Over the past 50 years, increasingly virulent strains known as methicillin-resistant S. aureus (MRSA) have developed, rendering once-effective antibiotic treatments obsolete. The risk continues to escalate as strains resistant to vancomycin, the antibiotic of last resort, crop up. Meanwhile, the bug has sneaked out of hospitals into communities, an alarming phenomenon fi rst reported by a team from the University of Chicago Medical Center. Popping up in schools, locker rooms and prisons, it spreads via skin-toskin contact, as well as transmission through clothing, towels, sheets, athletic equipment and other objects handled by infected individuals. Roughly half of all community-associated S. aureus strains are the insidious MRSA version. With no preventive vaccine available on the market, “the magnitude of the problem is staggering,” said Bubeck-Wardenburg, who began investigating the pathogen after seeing several previously healthy children succumb to MRSA lung infection during her pediatric clinical training at the University of Chicago.

Dissect the Machinery That’s why she and other University of Chicago researchers are investigating the bug’s pathogenesis, or disease progression, at a basic molecular level. By studying the infection in mice, the team has pinpointed how the pathogen uses its devastating abscesses to survive in the body.

University of Chicago Medical Center

Normally, the body relies on immune cells to track down bugs, eliminate them and produce natural antibodies that safeguard against future infection. But S. aureus is a pro at hijacking the body’s immune response. Missiakas describes its attack as a “play in four acts”: Act I: The microbe infiltrates the bloodstream, typically through skin cuts and wounds. Act II: The bug sets up camp in the tissue. The body detects an invader and sends immune cells to kill it. These natural defenses are no match for S. aureus, which binds to immune cells and disables them. Act III: Within four to five days of entering the body, S. aureus has transformed the infected area into a growing lesion. The bacteria surround themselves with a protective outer coating and multiply inside. More immune cells flock to the infected area, but are killed off and end up as pus in the abscess. Act IV: The abscess ruptures, releasing a massive army of S. aureus microbes to attack other parts of the body and repeat the cycle. The fallout can be any number of life-threatening conditions, including pneumonia, a bloodstream infection known as septicemia and inflammation of heart chambers and valves. Ultimately, roughly half of all individuals with a severe MRSA infection will die. Those who survive do not develop immunity and infections recur in roughly 20 percent of cases. Schneewind calls S. aureus the “world champion of immune suppression.” Bubeck-Wardenburg agrees: “I think of it as a bug that we constantly chase.”

Find the Weakest Link Over the past few years, the microbiology team at the University of Chicago has homed in on a target, developing a broad experimental vaccine to prevent MRSA outbreaks. Supported by a major multinational pharmaceutical company and moving toward human clinical trials, the breakthrough treatment pinpoints some of the weakest links in S. aureus’s molecular structure. “What we’re looking for is the core activity that is required for virulence,” Missiakas said. “What are the factors that are absolutely essential in this pathway to cause disease — the one step the pathogen cannot go around, regardless of strain?” As an entry point, the researchers focused on the bacteria’s cell wall. Like most human pathogens, S. aureus is surrounded by a thick, meshlike envelope made of amino acids and sugars. To

RIGHT S. aureus, or staph, often lives harmlessly on the skin, but once in the bloodstream it can affect every part of the body. Getty Images

“What we’re looking for is the core activity that is required for virulence. What are the factors that are absolutely essential in this pathway to cause disease — the one step the pathogen cannot go around, regardless of strain?” — Dominique Missiakas, PhD infect its host, the bug must attack through this barrier by secreting proteins. Through a series of animal and in vitro (test tube) experiments, Schneewind’s team identified a handful of proteins that enable S. aureus to undermine our immune system. One culprit is Protein A, which disables antibodies that fight infection and also kills off master cells that produce antibodies. Another is a group of proteins that cause blood to clot and form abscesses. Once researchers identified these staph proteins as indispensable to infection, they tested whether either could be used to create a vaccine against the bug. They used polymerase chain reaction, a standard technique for analyzing and replicating DNA sequences, to produce mutant versions of S. aureus that lacked the genes responsible for creating Protein A and the clotting proteins.

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Sure enough, mice inoculated with the mutants produced antibodies that protected against staph infection. When exposed to one of the most common MRSA strains, these animals experienced less severe tissue damage and lower death rates than those that did not receive the vaccine. The findings, published last August in both the Journal of Experimental Medicine and PLoS

“We choose particular molecular mechanisms important to causing disease and design vaccines around them.” — Dominique Missiakas, PhD R I G H T Rickettsia are the bacteria behind typhus and Rocky Mountain spotted fever. Science Photo Library

Pathogens, followed an earlier discovery by BubeckWardenburg that a staph protein called alpha toxin is indispensable to MRSA pneumonia. As with Protein A and the clotting proteins, the discovery led the team to create a modified version of the toxin that successfully protected mice against S. aureus lung infection.

Change the Approach Such breakthroughs are not only an innovation for combating S. aureus, but also for vaccine development in general. Ever since Edward Jenner discovered in 1796 that cowpox protected against smallpox, scientists have used weakened strains of disease to inoculate people. Schneewind and his colleagues take vaccine therapy to the next level with their targeted approach. “We choose particular molecular mechanisms important to causing disease and design vaccines around them,” said Missiakas, who also studies anthrax. Historically, vaccine creation has been mostly by trial and error, explained Howard Shuman, PhD, professor of microbiology and director of the Ricketts Laboratory, where all of the University of Chicagosponsored select agent research takes place. “You take a version of the bug that’s unable to cause illness or only causes a very minor illness. You inoculate people with it and, hopefully, they become immune.” As a result, many common vaccines remain somewhat mysterious on a molecular level, despite their effectiveness. This includes Bacillus anthracis strains widely used to inoculate livestock against anthrax. Capable of surviving in hostile environments outside a host for decades, anthrax infiltrates the bloodstream when a victim inhales its spores. Coated in a protective capsule, the microbe evades immune cells, replicates and secretes powerful toxins. “It’s a very fast disease,” explained Missiakas. “After a certain point, even if you know you’re infected and you kill the microbe, there’s enough toxin floating around in the body to kill you.” It’s an insidious bug with a notable history: B. anthracis was the pathogen Nobel Prize winner Robert Koch was studying when he proved in 1876 that living bacteria are the cause of disease. At the time, the panic around anthrax was linked to basic livelihood, not bioterror. Animals that people needed to live on were dying off in large numbers, hence Koch’s focus on the disease. Together with Louis Pasteur, the physician developed one of the earliest vaccines against anthrax.

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R I G H T Y. pestis, the source of plague, killed approximately 25 million people in the 14th century. Shutterstock

A weakened strain of the live bacteria, it is not well understood how it operates in the body. It’s a reality Missiakas finds unacceptable. “We don’t have a well-defined understanding as to why these attenuated strains afford immunity, but we use them because they are convenient,” she said. “That was fi ne in the 20th century. But in the 21st century, we have to understand why these vaccines work.” After all, anthrax remains extremely common in nature, typically affl icting livestock that consume or inhale spores while grazing. “The reason why there isn’t anthrax worldwide is because we vaccinate nearly every single four-legged animal that we use for nourishment,” Missiakas said. Should there be an economic collapse that led to less frequent vaccination, however, she warned, “there would be anthrax disease again.” There is no effective vaccine for humans. That’s why Missiakas and others are using groundbreaking technology to peer inside the microbe and demystify its weapons. Teaming up with Andrzej Joachimiak, PhD, director of Argonne National Laboratory’s Structural Biology Center, they used powerful X-rays to map out the three-dimensional structure of a critical B. anthracis protein. Known as CapD, this enzyme helps the pathogen form its protective outer capsule. Immune cells cannot recognize the coating because of its unusual amino acid structure. “That’s how it fools the system,” Joachimiak said. Identifying CapD’s crystal structure is an important step toward creating a viable anthrax treatment for humans. If researchers can pinpoint a molecule that binds to CapD, they may be able to disrupt its activity, making the microbe more susceptible to the body’s natural immune defenses. Such breakthroughs pave the way for protection against one of our most formidable — and least understood — pathogens.

Prepare for the Worst Schneewind and his team are applying similar strategies to less common but equally deadly organisms, such as Yersinia pestis, the source of plague. “Most people view plague through a historical lens,” he explained. “They say, ‘Thank God it’s no longer medieval times.’ ” But the disease still lurks, affecting roughly 4,000 people annually, mostly in developing countries where poor hygiene and sanitation increase the chance that rodents will spread the bug. Manifestations include bubonic plague, characterized by swollen infected lymph nodes, and pneumonic plague, a lung infection that can be transmitted from person to person though the air.

“Most people view plague through a historical lens. They say, ‘Thank God it’s no longer medieval times.’ ” — Olaf Schneewind, MD, PhD Capable of being turned into an aerosol and spread rapidly, Y. pestis also raises bioterrorism concerns. Like anthrax, it is on the CDC’s select agent list. In nature, the bug infects rats, squirrels, mice, prairie dogs, gerbils and other small mammals. It jumps to humans via fleas that feed on infected rodents. The flea transports the pathogen in its gut and regurgitates the toxin when it bites a human. Early signs of bubonic plague, the disease’s most common form, include fever, headache, chills and tender lymph glands, particularly in the groin and armpits. Unless treated with antibiotics within 24 hours of onset, 50 percent to 90 percent of victims die. Because its symptoms mirror other illnesses, the disease often evades detection until it’s too late. Once a critical mass of bubonic plague cases

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Methicillin-resistant S. aureus (MRSA) has rendered once-eff ective antibiotic treatments obsolete. Getty Images

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occurs in a population, explained Schneewind, roughly 5 percent to 10 percent of infected individuals develop a secondary pneumonia as the bacteria spreads to the lungs and replicates in the tissues. The hardy microbe evades the immune system’s attempt to devour it and creates destructive lesions that ravage the airways. Individuals with pneumonia then transmit the disease to others through air droplets emitted when coughing or sneezing. The result: explosive plague outbreak. Three major plague pandemics, during the 6th, 14th and early 20th centuries, have caused more human fatalities combined than any other infectious disease to date. And what if another were to hit? “It would catch the United States by surprise,” Schneewind said. In May 2000, the government ran a $3 million simulated bioterrorist attack with Y. pestis to gauge national readiness. In the hypothetical scenario, an aerosol of the bacteria was released at the Denver Performing Arts Center. Four days later, the disease had infected, by some counts, nearly 2,000 people on three continents. That’s why Schneewind and his team have developed a vaccine that targets proteins critical for infection. While various plague vaccines have existed since the late 19th century, con-

cerns about their safety make an alternative highly desirable. As with S. aureus, researchers focused on a key activity the bug must carry out to cause disease: the smuggling of toxins into cells. At the molecular level, Y. pestis strikes victims by injecting its poison into cells using a syringelike mechanism. Embedded along the bacterial wall, this complex system of needles allows the pathogen to secrete proteins directly into the host cell. Once inside, the proteins cripple the immune response by preventing phagocytosis, the body’s normal process of engulfi ng and eliminating foreign microbes. To counter the bug’s sneaky ways, the microbiologists homed in on a protein factor called LcrV that sits at the tip of the secretion needle and helps transport toxins across the membranes. Essential for infection, it also prompts the host to produce antibodies, making it a key source of protection against plague. Inoculating mice with different variations of this antibody, the researchers isolated one version that conferred 100 percent immunity against plague. When they later inserted the same variation into samples of plague-infected human blood, it killed off much of the bacteria. By disabling a fundamental infection mechanism, the vaccine enables immune cells to work their magic. The promising treatment is currently undergoing human clinical trials.

Stay Vigilant Whether mobilizing against natural threats like MRSA, bioweapons like anthrax or future plague outbreaks, University of Chicago microbiologists remain on guard against the unforeseeable. “One has to be ready for the next thing there is to fight,” Missiakas said. “We never know where it’ll come from.” Yet unlike ordinary folks who fret about apocalyptic scenarios, she and her colleagues forge ahead, unraveling the proteins and molecular behaviors that make these pathogens so dangerous. As they inch closer to stamping out disease, they stay focused on the task at hand. “One could work endlessly and have nightmares about the next move of a bug,” Missiakas said. “That’s why, ultimately, I prefer to be rational.” ■

University of Chicago Medical Center

How to Work with Dangerous Bugs A behind-the-scenes look at how University of Chicago microbiologists handle lethal organisms By Brooke E. O’Neill “You going in?” lab director Howard Shuman asked a tall man in green scrubs. Researcher Sean Crosson, PhD, assistant professor of biochemistry and molecular biology, nodded. “We’re doing an array experiment in a few minutes,” he said, heading toward his lab at Howard T. Ricketts Regional Biocontainment Laboratory. Located at Argonne National Laboratory, 25 miles southwest of Chicago, the Ricketts Laboratory offers University of Chicago scientists one of the nation’s most secure, state-ofthe-art facilities to study dangerous pathogens. From the outside, it looks like any suburban office park. Yet housed inside the Howard T. Ricketts Laboratory are bacteria that cause some of nature’s most insidious diseases: anthrax, plague and other microbes the Centers for Disease Control and Prevention (CDC) deems significant threats to public health and safety. Once these bugs infiltrate the body, all have high mortality rates. Named after University of Chicago microbiologist Howard Taylor Ricketts — he discovered Rickettsia, the bacteria that cause typhus, and died during a 1910 outbreak in Mexico City — the lab builds on Chicago’s history of infectious disease investigation. Federally funded by the National Institute of Allergy and Infectious Diseases, the Ricketts Laboratory went “hot” with live pathogens in December 2009. Before Crosson can enter his workspace, he’ll pass through a biometric fingerprint scanner, suit up in a protective Tyvek suit and put on a respirator, an astronaut-type helmet to shield his head and face. As he works, multiple security cameras monitor his every move. Come end of day, nothing can leave the lab, and his protective clothing is decontaminated while he takes a mandatory shower. Inside the lab space awaits Crosson’s bug, Brucella abortus. Primarily an agricultural organism, the bacterium jumps from animals to humans through contaminated food or dairy. Extremely difficult to kill, it causes flulike symptoms and often leaves victims with chronic joint pain, a risk Crosson and his colleagues face on a daily basis. Not surprisingly, the notion of a lab filled with lethal bacteria can conjure nightmarish doomsday visions, said Joseph Kanabrocki, PhD, CBSP, assistant dean for biosafety and associate professor of microbiology. “Some people imagine that the minute you walk into the building, you’re walking into a cloud of anthrax.”

The Howard T. Ricketts Regional Biocontainment Laboratory is located at Argonne National Laboratory, 25 miles southwest of Chicago. Photo by Jennifer Crotty

Employees at the Ricketts Laboratory must go through a personal protective equipment training. The equipment is required for entry. Photo by John C. Bivona, RBP

The reality isn’t quite so alarming. For starters, the quantity of live biological agent at the facility is extremely small. “Even in our worst case scenario, we don’t have a lot of material stored here,” said Kanabrocki, who oversees biosafety protocols. “We grow it as we need it.” All pathogens studied at the Ricketts Laboratory must have at least one available antibiotic therapy. As a Biosafety Level 3 facility — the second-highest of four risk levels designated by the CDC — the lab is cleared to house organisms that cause severe to fatal disease, but not agents that have no treatment. To handle their microbes safely, researchers undergo extensive training led by Kanabrocki, a member of the National Science Advisory Board for Biosecurity. “To understand what the risks are for a particular experiment, you have to understand the bug,” he explained. “Are there going to be infections that involve the use of needles? Is the pathogen transmitted via the aerosol route?” Not just anyone can work with such pathogens. “Everyone who works here has been vetted by the government and given a security clearance,” Kanabrocki said. Being located at Argonne adds yet another layer of security. Owned by the U.S. Department of Energy, the national laboratory was founded by the University of Chicago in the 1940s to house nuclear chain reaction research. A perimeter fence surrounds the grounds, and no one can enter without a gate permit. Inside the Ricketts Laboratory itself, any photos or description of how corridors and rooms connect are strictly forbidden. In addition to the extra security, Argonne also puts some of the world’s most powerful genetic sequencing and X-ray technologies right at University of Chicago researchers’ ﬁngertips. “They do things at Argonne that cannot be done anywhere else,” director Shuman said. One example is analyzing bacterial structure using Argonne’s Advanced Photon Source, which produces the Western Hemisphere’s most brilliant X-rays. Such collaborations put scientists one step closer to ﬁnding cures for some of our worst diseases. With bacteria forever evolving into more powerful enemies that outwit our best treatments, those efforts couldn’t come at a more critical time. After all, Kanabrocki said, “infectious diseases aren’t going away.” ■

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Mapping Bacterial Worlds, from Sea to Stomach The study of an ecosystem within our bodies may redeﬁne how physicians approach infectious diseases By Rob Mitchum

umans are a minority in their own bodies. For every human cell, there are at least 10 times as many bacterial cells living inside and outside of the body. Millions of individual cells from thousands of species inhabit the digestive system, body cavities and the surface of the skin. Yet, until recently, we have only understood a mere fraction of these ecosystems within our bodies, how they sustain us in health and how they harm us in disease. The collective genomes of these microbial worlds are known as the human microbiome. Scientists are just beginning to discover the role that a faulty microbiome plays in acute and chronic disease, creating a new kind of science that applies the methods of ecology to the biomedical domain. “Everything we eat, the things we are exposed to, our lifestyles — all of that changes our microbiome,” said Eugene B. Chang, MD, the Martin Boyer Professor of Medicine. “Its potential in terms of drug and reagent discovery is the equivalent of an Amazon rain forest. There exists enormous untapped ABOVE An artist’s rendering of a human stomach. DEA Picture Library

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biological opportunity for discovery.” While microbiologists were classically limited to studying only bacterial species they could get to grow in a laboratory dish, the new method of metagenomics has allowed ecologists to discover thousands of new species in a single scoop of soil or teaspoon of seawater. Now that technology is being applied by University of Chicago Medical Center researchers, in collaboration with Argonne National Laboratory, to the ecosystem of the human gut.

New Insights into Microbial Diseases Before a baby is born, its gut is sterile, entirely free of bacteria. During delivery, the baby’s fi rst bacterial colonies are seeded by bacteria from the mother, and early exposure to the environment and diet fill in the rest of the ecosystem. But in some babies born prematurely and underweight, the construction of the microbial community is defective, leading to a potentially fatal bowel disease called neonatal necrotizing enterocolitis.

New genetic techniques have given a group led by Erika Claud, MD, associate professor of pediatrics, deeper insight into how a premature microbiome can cause the disease. A 2009 study used sequencing techniques on fecal samples from premature infants with and without the disease, and it identified that afflicted infants tended to have fewer bacterial species in their gut. “It wasn’t one bacterium causing this disease,” Claud said. “It seemed to be the overall community structure that was favorable or unfavorable in these patients.” Claud’s study also reinforced the remarkable individuality of the microbiome. Even in premature infants only weeks old, the bacterial population in the gut of each infant was already dis-

merely adding or killing off one species is too simplistic. “We’d love to think we’ll be able to pull all the levers to make a microbial community do what we want it to do,” said Dionysios Antonopoulos, PhD, assistant professor of medicine at the Medical Center and assistant biologist at Argonne. “But at this stage, it’s pretty much like we’re riding a tricycle, and the controls of that system are like flying a 747.”

A Change in Strategy

The tranquility of the microbiome may also be destroyed when its human home becomes less hospitable. After intense surgery, a minority of patients contract serious infections. Traditionally, these infections were thought to be the result of contamination during the surgical procedure. But over a century of improved “Its potential in terms of drug and reagent discovery sterile techniques has yet to completely is the equivalent of an Amazon rain forest. There eradicate postsurgical infections, causing some researchers to look at the bacteria exists enormous untapped biological opportunity within the patient. for discovery.” — Eugene B. Chang, MD John Alverdy, MD, professor of surgery, has been studying one such microbial restinct and unique — even in genetically identical twins. The fact ident, called Pseudomonas aeruginosa. Normally docile, that microbiomes are as different as fingerprints may present a P. aeruginosa can be transformed after surgery by the patient’s short-term challenge to researchers studying the systems, but it overstressed immune system into what Alverdy calls a “triggercould have long-term benefits for personalized medicine. happy killer.” He and his collaborators have identified the immune “If we knew exactly what bacteria each individual has, we and metabolic signals that trigger the alarm system of P. aeruginosa, could be more selective in terms of the treatments that we give research that may define a new type of protection against infecthat person,” Claud said. “I think it would be very beneficial.” tion. Rather than indiscriminately slaughtering gut bacteria through prolonged use of antibiotics, maintaining a healthy system that interrupts these alarm signals might convince bacteria Steps toward Disease Prevention In adults, the microbiome has accumulated complexity thanks that their home remains stable. “It’s sustaining the ecosystem therapy,” Alverdy said. “It’s to diet, lifestyle, antibiotic use and other lifetime influences. Most of the time the microbial colonials live in happy equi- a new way of thinking about infection, because we’re already librium, but when the structure breaks down in a process doing everything we can — washing our hands, sterilizing called dysbiosis, inflammatory bowel diseases are a poten- the site, giving our patients antibiotics — and some of the infections seem to be getting worse. There’s got to be a strattial result. Chang’s research group is looking for warning signs of egy change, and I think we’re at the forefront of impending dysbiosis in a group of ulcerative colitis patients understanding that.” The work merges with new ecological data about the bacat risk for recurrent disease. These patients have had their colons surgically removed and a section of the small intes- terial ecosystems in the world around us. The Earth Microbiome tine reconstructed to serve as a pseudorectum called the ileal Project, an international collaboration co-directed by Jack pouch. Many of these patients, within one year of surgery, Gilbert, PhD, assistant professor of ecology and evolution at develop a new inflammatory condition of the ileal pouch the University of Chicago and environmental microbiologist at Argonne, has the ambitious goal of systematically characcalled “pouchitis.” Interestingly, patients with other diseases who undergo the terizing all microbial life on Earth. Researchers with the same procedure rarely develop this complication, indicating project are repeatedly sampling soil, seawater, animals and that the condition is inherent to ulcerative colitis. Moreover, many other sources to fi nd out what bacteria live there and most patients can be treated with antibiotics, indicating this how populations change over time. By measuring water from the English Channel over six condition is likely caused by inhabitants of the gut. In collaboration with Argonne and other institutions, Chang is years, Gilbert discovered that the roster of players in a bacfollowing these patients before recurrence to gain rare insight terial ecosystem does not change, but the environment selects which species will be abundant at different times of the into the microbiome before the disease manifests itself. “We have one of the very, very few studies that actually year. This “everything is everywhere” principle might also prospectively follows the patients,” Chang said. “If we iden- have implications for medicine, Gilbert said, where the fight tify a dysbiotic profile, that becomes a diagnostic tool for us against infectious diseases has traditionally focused on exterto predict who’s going to get ulcerative colitis, and we can nal invaders. “We don’t have to try and fi nd out where that pathogen hopefully do something to prevent that dysbiosis, so we can came from,” Gilbert said. “That pathogen might have already prevent the onset of disease.” The latter goal, however, may be further down the road. Though been there, and the environment would have selected for it to some “probiotic” bacteria have been tested for treatment of bowel suddenly bloom and therefore attack its host. If that’s true, diseases, the complex nature of the microbiome suggests that then we can change the way we do medicine.” ■

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Free Clinics BeneďŹ t Future Physicians As Well As Patients Pritzker students gain hands-on experience by volunteering at community health care sites

ABOVE Pritzker student Neha Sathe examines Almer Fields, a patient at the Maria Shelter on Chicagoâ&#x20AC;&#x2122;s South Side. Photo by Jason Smith

University of Chicago Medical Center

By Kelin Hall

n the bright back room of CommunityHealth West Town, first-year medical student Tyler Friedrich scanned a patient’s medical history. “She’s 25, Spanish-speaking and has one child,” he told three classmates, a fourth-year student and an attending physician who were all volunteering that night. “She requested an IUD, and she also came in for rapid HIV testing.” Friedrich looked sheepishly at his classmate Kimberly Clinite, who’d been reading the patient history over Friedrich’s broad shoulder. “Maybe you should see her,” he said. “The patient might be embarrassed to talk about gynecology with me or....” Friedrich trailed off, clumsily shuffling the papers. The patient had traveled more than an hour to the clinic at 2611 W. Chicago Ave., risking her restaurant job to keep the appointment. Clinite nodded and headed to the patient’s exam room. About half an hour later, Clinite emerged from the exam room, a bit flushed, and sighed. “As a future physician I need to work on three things,” she told her colleagues. “One, taking blood pressure. Two, knowing where to write my notes. Three, thinking about what I am going to say before I say it.”

Giving Care, Learning Lessons Volunteering at CommunityHealth offers first-year students at the University of Chicago Pritzker School of Medicine one of their first opportunities to work directly with patients. There and at three other free clinics around Chicago, students take medical histories and vital signs, present them to fourth-year students or physicians and then watch the physician complete the physical exam. The first-year students say they give more than 4,000 volunteer hours each year, providing care for more than 1,000 uninsured patients. For more than a decade, these free community clinics have exposed Pritzker School of Medicine students to populations they see infrequently within the University of Chicago Medical Center’s main campus in Hyde Park. CommunityHealth serves mostly Spanish- and Polish-speaking immigrants, and New Life Volunteering Society’s clinic, farther north at 2645 W. Peterson

The free community clinics like CommunityHealth West Town give Pritzker students like Kimberly Clinite their ﬁrst chance to work with patients, and give community members access to health care they wouldn’t otherwise receive. Photo by Shahzad Ahsan

and Washington Park Children’s Free Health Clinic are entirely run by Pritzker students, with guidance from faculty advisers. They keep medical records in order, stock and dole out prescriptions, order vaccinations and follow up with each week’s referrals. As walk-in clinics, both make a concerted effort to refer all patients to primary care homes they can afford and access.

A New Comfort Zone

Jasmine Taylor put the key in the ignition of a borrowed van and drove four of her first-year peers away from gleaming science buildings on 57th Street, continuing west along 55th Street. Taylor’s passion for health care for the homeless began in college, when she volunteered in South Africa with street children. The opportunity to volunteer at the Maria Shelter was critical in her decision to attend Pritzker. Taylor flipped on the turn signal as the van approached B & B Pizza King and KFC, then hung a left onto State Street. Driving south, “As a future physician I need to work on three things. the number of churches to vacant lots One, taking blood pressure. Two, knowing where seemed implausible: Were there enough to write my notes. Three, thinking about what I am people in the abandoned landscape to fill those pews? going to say before I say it.” — Kimberly Clinite From the back seat, Wenjing Zong admitted that she was nervous about Ave., sees mostly South Asians. The Maria Shelter, in Englewood, her first time volunteering at the shelter. Though Zong went serves homeless women and their children, and the Washington from college at the University of Chicago to Pritzker, she is no Park Children’s Free Health Clinic, at 5350 S. Prairie Ave., treats stranger to new experiences — she emigrated from China at age 13 speaking limited English. children without a relationship with a primary care provider. Her peer, Neha Sathe, reassured her: “The women are really “Talking to patients at the clinics gives students a better understanding of the feasibility of what they ask their patients to do,” patient and appreciative. I’ve never encountered someone diffisaid Kristine Bordenave, MD, who advises Pritzker volunteers cult to work with.” Sathe organizes wellness activities at the at CommunityHealth. “They ask themselves questions like ‘Does shelter, where she is happy to serve women after working last my patient have access to the medicine I prescribed?’ or ‘What year at a Veterans Affairs hospital with mostly male patients. Vikrant Jagadeesan, another student in the van, was eager to is the likelihood that my patient can actually exercise three times arrive. He’d met homeless patients briefly while volunteering in a week?’ It prepares them to be better doctors.” The students also learn what it takes to collaboratively run a the emergency room at John H. Stroger Jr. Hospital of Cook clinic. At CommunityHealth, students work with staff to ensure County, and he hoped that in the security of the Maria Shelter that patients see the same volunteers each time; at the other clin- he could actually learn about patients’ lives. When they reached 73rd Street, Taylor drove west toward a ics, students are the staff. Students from all over Chicago run New Life Volunteering Society, whereas the Maria Shelter Clinic vibrant sunset that backlit a Citgo station and a row of three-story

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Jasmine Taylor is one of several Pritzker students providing care at the Maria Shelter in Englewood. For over a decade, Pritzker students have been the sole providers of medical care to homeless women and children at the shelter. Here Taylor is taking the blood pressure of patient Darlene Glover. Photo by Jason Smith

apartments. She turned left three times down one-way streets, the last one completely unmarked. She slowed the car across the street from a vacant lot, where a lone tire sat frozen in a puddle. “We’re here,” she said, parking in front of a brick building with Greek columns and barred windows.

The Maria Shelter was founded in 1974 by Sister Margaret Ellen Traxler, a Catholic nun who often spoke out on behalf of women’s rights. Through counseling and training, the shelter helps women chart a path to independence. Since the mid-1990s, Pritzker students have administered the Maria Shelter Clinic, providing the only medical care at the shelter. Zong led her first patient, Sarah Garrison, to an examining room to take her medical history. Garrison was several months pregnant and troubled by back pain. She had moved recently from another shelter, where the staff had thrown away her prenatal vitamins and medical records. When Garrison arrived at the Maria Shelter, the medical students helped her get back on track with her obstetrician. While Garrison waited for the attending physician to complete her examination, Zong presented the patient’s medical history to fourth-year student Melissa Weston. “I didn’t know what to ask her!” Zong confessed. “I’d never seen a pregnant patient before.” Weston walked Zong through the questions appropriate to each phase of pregnancy. After seeing the volunteer attending physician, Garrison received pain medication and referrals to a dentist and optometrist, along with all-day bus passes to take her to the appointments. “The students always help me to get what I need,” Garrison said. “If I can help them to learn in any way, that’s great.”

Pediatrics in the University’s Backyard On another icy evening in February, six students arrived at the Chicago Youth Programs Community Center, a block northwest of the Garfield Green Line train stop. Like every Tuesday, the students unlocked a small office and

Medical Residents Make the Most of Limited Resources New Englewood clinic serves a growing population of uninsured patients By Kelin Hall Gwendolyn Gilmore was one of the first patients to visit CommunityHealth Englewood when the clinic opened on September 27 at 641 W. 63rd St., just two blocks from her home. The 60-year-old, uninsured, elderly care worker has benefited from the free primary care ever since. “The staff here really listen to you,” Gilmore said during a visit last winter. “There are a lot of uninsured people around here, and I tell them to come on over.” At many free clinics, physicians are hard to come by; medical students and nurses provide most of the care. But at the Englewood clinic, University of Chicago Medical Center physicians provide the bulk of medical care. The rotating staff has welcomed 250 patients during the clinic’s first three months of operation. The clinic, which is currently open two afternoons per week, is a satellite site to CommunityHealth West Town, the largest volunteer-based free clinic in Illinois. Englewood patients can be referred to the West Town clinic for specialized services ranging from gynecology to chiropractic care.

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“We’re improving health literacy,” said Amber Pincavage, chief resident in internal medicine. “Primary care is a new concept for many uninsured patients who have always relied on walk-in clinics and emergency rooms. The idea that you would come regularly to manage things like hypertension and diabetes — which are both very common in the community — is new.” Other patients, like Gilmore, know they need primary care. “Some patients have sought us out and are ready to make major life changes,” Pincavage said. Gilmore was diagnosed with diabetes 15 years ago and has maintained a consistent regimen of medications. But when Gilmore came to CommunityHealth, resident Shantanu Nundy, MD, took some tests and found that some of the medications Gilmore had been taking for years were unnecessary and even harmful. “Nundy is young and learning all the new discoveries,” Gilmore said. “I want to learn with him. He’s taught me things my old doctor never knew.” The residents face their own learning curves at the clinic, building different skills and understanding than they would build within

“The students always help me to get what I need. If I can help them to learn in any way, that’s great.” — Sarah Garrison rolled three examination tables into what normally serves as a playroom, classroom and kitchen. They pulled blue curtains between the tables, set up a laptop at each station and voilà! The Washington Park Children’s Free Health Clinic was ready to see patients. Three children under the age of 6 burst into the clinic with their mother. “I think they have pink eye, which would keep them out of school,” the mother told the medical student conducting intake. Many parents take their children to the clinic to receive vaccinations, physicals or other treatments children need to meet state medical regulations for public school attendance. A medical student lifted the youngest daughter onto an examining table. The child bounced around, her braids, barrettes and arms flying as the student tried to look inside the child’s ear with a pointy otoscope. At the next table, another medical student asked a 5-year-old boy, “Do you ever have trouble eating?” “I’ll never eat a pickle!” the boy replied with gusto. When the students completed the children’s medical histories and vital signs, the volunteer attending physician, Barrett Fromme, MD, completed the physical examination. As Fromme examined one child’s eyes, another child clung to the physician’s leg.

Internal medicine resident James Kim, MD, records prescriptions at the CommunityHealth Englewood Clinic. Photo by Shahzad Ahsan

the Medical Center’s main campus in Hyde Park. Appreciating this, the Medical Center counts time at the clinic as part of residents’ ambulatory care training and as part of physicians’ paid attending duties. At the clinic, residents often see patients who have undiagnosed conditions or who lack consistent documentation of their past medical histories. “It really pushes their clinical skills,” Pincavage said. The clinic’s lean resource base also challenges medical residents: “You learn to work with less and to trust the physical exam and your clinical instincts more,” said resident Ethan Molitch-Hou.

Pritzker student Vikrant Jagadeesan gives patient Darnen Brown a checkup at the Washington Park clinic. Photo by Shahzad Ahsan

Fromme casually asked the children important questions that the medical students hadn’t thought or dared to: “How often do you brush your teeth? And take a bath? With soap and water?” After a quick dance-off between Fromme and the children, the patients headed out with the prescriptions that would let them go back to school, and the medical students turned the clinic back into a playroom. ■

Though most tests, such as CT scans or high-tech echocardiograms, can be ordered through Medical Center partners, Molitch-Hou said it can take several months to get them. “You have to ﬁgure out how to provide the best care possible with what you have in the moment.” The clinic also keeps costs down by running with little paid staff. Without a nurse, pharmacist or lab technician, the residents ﬁll in the gaps: giving injections, counting out medications and teaching patients how to give themselves insulin injections for diabetes. “We do it all,” Pincavage said. It’s good training, she explained, for future work in any resource-restricted settings, whether in Chicago or globally. Playing many roles also gives the trainees more face time with patients, allowing them to build trust that can lead to better outcomes. “I just spent 15 minutes with a patient reviewing how to take each of his medications and then had him teach it back to me,” Molitch-Hou said. “No one had ever done that for him.” As the number of uninsured patients in Englewood increases, more and more current and potential medical trainees seek to integrate work with the underserved and uninsured into their medical careers, said James Woodruff, director of internal medicine residency. “Everybody wins,” said Woodruff, who was integral to making the Englewood clinic a reality. Recognizing the opportunity, in January the Medical Center’s Urban Health Initiative contributed $50,000 to help sustain and expand the clinic. ■

Medicine on the Midway Summer 2011

S P E C I A L F E AT U R E

As Landmark Study Turns 40, Risks of DES Exposure Subside Arthur L. Herbst, MD, recalls the detective work that led to a change in medical thinking By John Easton

orty years ago, in its April 22, 1971, issue, the New England Journal of Medicine published a three-page paper linking a few unusual vaginal cancer cases in young women whose mothers had taken an estrogen pill (diethylstilbestrol or DES) early during their pregnancy. Even by academic standards, the language of the paper was remarkably restrained as it indicated an association with DES. It predicted that more patients with this tumor “will likely appear” as those who were exposed in utero came to maturity. The problem was that in the previous 25 years approximately 4.8 million women in the U.S. received this drug during pregnancy. The cases described in the research paper were the first warning of a rare, delayed, but devastating side effect. “Making the connection between DES and this rare cancer required some clever detective work and some luck,” recalled study author Arthur L. Herbst, MD, the Joseph Bolivar DeLee Distinguished Service Professor Emeritus and former chair of the Department of Obstetrics and Gynecology at the University of Chicago. DES, created in 1938, was the first orally active and inexpensive synthetic estrogen. The FDA approved it in 1941 for a wide range of estrogen-deficient states. In 1947, the FDA approved DES for miscarriage prevention. That same year, urologist Charles Huggins, MD, of the University of Chicago demonstrated its effectiveness in treating metastatic prostatic cancer, part of a project that brought him the 1966 Nobel Prize. It was two of Herbst’s professors, George and Olive Smith, both MD, at Harvard, who first suggested DES could prevent miscarriages. “There were data indicating these problem pregnancies had a faulty endocrine environment,” recalled Herbst, “specifically the excretion of progesterone in the urine. Some tests suggested this deficiency could be corrected by administering DES, but those results turned out to be erroneous.” Four years after DES was approved for pregnant women, William

University of Chicago Medical Center

Dieckmann, MD, chair of obstetrics and gynecology at the University of Chicago, launched the first randomized, case-control clinical trial of the use of DES for that purpose. His results, published in 1953, showed DES had “no beneficial effects.” Nevertheless, the drug remained in use with pregnant women.

Developing Suspicions “In the late 1960s, Dr. Robert E. Scully, gynecologic pathologist at Massachusetts General Hospital, and I began to study a few odd cases of vaginal adenocarcinoma in young women and published their characteristics,” said Herbst. He also presented these seven cases at a meeting in Montreal and was asked what had caused the cancers. “I had to say I did not know.” Then one mother brought her daughter, who had been treated for cancer, for follow-up to Howard Ulfelder, MD, chief of gynecology at Massachusetts General. The mother reported taking DES during pregnancy and wondered if this might have caused her daughter’s cancer. “I also was in contact with a mother whose daughter . . . had unfortunately died because her cancer had never been properly diagnosed and treated,” Herbst said. “The mother reported taking DES.” So Herbst, Ulfelder and epidemiologist David Poskanzer designed a casecontrol study. By the time their study began, the physicians had come across an eighth case. Herbst and his colleagues elected to have four comparable controls for each cancer case. They went to the hospitals where the eight cancer cases were born to find four females born at the closABOVE Created

in 1938 and approved by the FDA in 1941, DES was the ﬁrst synthetic estrogen. It was used to treat estrogen-deﬁcient states in humans and livestock. In 1947 the FDA added miscarriage prevention. This advertisement, which ran in professional journals, claimed that DES could prevent abortion, miscarriage and premature labor and was “recommended for routine prophylaxis in ALL pregnancies.”

est time to each of them. Herbst then called the mothers and asked them to participate in the questionnaire study and remarkably, he said, 32 of 34 agreed. Seven of the eight mothers of the cancer cases had taken DES during pregnancy, but none of the 32 controls had. The odds of that happening by chance were less than one in 100,000. “The women were given the drug in good faith by physicians who believed it would help their pregnancies,” Herbst said. “They took the drug because they wanted to have a baby, and then they discovered this terrible result years later. The guilt feelings were powerful.” As soon as the paper was published, To observe the 40th anniversary of the classic paper by Hersbt et al demonstrating the association “it was all over the news,” said Herbst. of DES exposure in utero with a rare form of cancer in young women, Herbst met with (left to right) Fran Howell and Kari Christianson of DES Action and Susan Helmrich, a DES daughter and prominent advocate An accompanying editorial in the New for affected women, to share stories and record an extended video account of the circumstances behind England Journal of Medicine described the discovery and its consequences available at http://bit.ly/k6KAXo. Photo by Shahzad Ahsan it as a work of “great scientific importance and serious social implications.” The press called it a “time bomb.” Herbst the next few years, I had several more surgeries and many hospitestified at congressional hearings, and the FDA withdrew its approval talizations.” for DES in pregnancy seven months after the publication. Other problems have been detected. Mothers who ingested DES appear to have an increased risk of breast cancer, estimated at about 30 percent. The exposed daughters also appear to have an Outrage from Victims “While the medical community was being cautious,” recalled increased risk of breast cancer after the age of 40. The genital tract Susan Helmrich, 55, a DES daughter, “mothers who took changes in the daughters have made it more difficult to conceive a the drug were hysterical. They worried that their daughters child or to carry a pregnancy to term. DES sons have some genital tract abnormalities but no increased would all get cancer.” The daughters risk of cancer. There is nothing demonwere also terrified. strated in the grandchildren so far. One of the most remarkable responses came from Olive Smith, whose studies led to the use of DES. She brought Herbst Changing Attitudes her research records and the note cards The DES story convinced scientists of of those who had been treated with the vulnerability of the developing DES, urging him to “locate and follow fetus. A perspective article in the New these women to see what is wrong with England Journal of Medicine 40 years them.” These studies led to a number after the original article emphasized of original articles describing changes how the discovery “changed medical in DES daughters who did not have thinking” about embryologic develcancer but did have numerous genital opment and carcinogenesis. tract changes. “I think it is fair to say,” Herbst mused, Herbst also established the Registry “that if I, or someone, had not been in for Research on Hormonal Transplacental Boston when that cluster of cases occurred, Carcinogenesis while he was in Boston this might have never been discovered.” to study the cancer cases. When he Many people are glad he was, stressed came to the University of Chicago in Helmrich. “As a representative of the Arthur L. Herbst, MD, the Joseph Bolivar DeLee 1976, he continued the Registry studcancer daughters, I cannot thank you Distinguished Service Professor Emeritus and former chair of the Department of Obstetrics and ies and began to follow the patients enough for what you did,” she told him Gynecology at the University of Chicago from the original Dieckmann study, when they met in April. “I never forincluding about 800 mothers, 400 get my cancer experiences, but I am sons and 400 daughters. These studies are still funded by eternally grateful to Dr. Herbst for having made the DES/clear the National Cancer Institute. cell cancer association. Had he not, I’m not so sure I’d still be As predicted, the cancers were very rare, developing in about 1 here today,” she later said. in 1,000 DES-exposed daughters. Although four of five cancer “The DES paper changed my life, too,” recalled Herbst. The patients were alive five years after diagnosis, most survived thanks weekend before the paper was published, “my wife and I took to extensive surgery. “I had a 10 1⁄2-hour operation when I was 21 a holiday in the country. ‘We had better enjoy this long weekyears old,” recalled Helmrich. “They removed my reproductive end,’ I told her. ‘It’s not going to be this relaxing for a while.’ organs and reconstructed my vagina with part of my colon. Over And it wasn’t.” ■

Medicine on the Midway Summer 2011

M E D I C I N E O F F T H E M I D WAY

The Power of No FDA heroine Frances Kelsey, PhD ’38, MD ’50, is lauded by President Barack Obama half a century after one of the most fateful decisions in U.S. pharmaceutical history By Stephen Phillips

he auditorium at the Food and Drug Administration’s headquarters was buzzing. For the massed ranks of FDA officials, it was an opportunity to mark a defining moment in the agency’s history. Half a century almost to the day, the central figure in a case that changed the face of drug regulation was returning to the FDA. As the car carrying her pulled up, Frances Oldham Kelsey, PhD ’38, MD ’50, now 96, marveled at the FDA’s manicured new campus set in the rolling Maryland countryside. It was a far cry from the World War II-era prefab in downtown Washington, D.C., she had occupied as a new recruit. Frail and hard of hearing now, “Lobbying at the FDA could be Kelsey was chaperoned by her done, but this took it up a notch.” two daughters for the occasion. She beamed as FDA leaders hon— John Swann ored her in speeches before presenting her with the Dr. Frances O. Kelsey Award for Excellence and Courage in Protecting the Public Health. “It was pretty moving,” recalled FDA historian John Swann. As much as any other single person perhaps, Kelsey, during a storied 42-year career in drug regulation, is credited with making the agency what it is today. The personal tribute read aloud from President Barack Obama testified to Kelsey’s impact in the wider world: From September 1960 through November 1961, Kelsey and a handful of FDA colleagues were all that stood between the nation and the ABOVE In

1962, President John F. Kennedy presented Frances Kelsey, PhD ’38, MD ’50, with one of the pens he used to sign the Drug Amendments of 1962, which gave important new regulatory powers to the FDA in the aftermath of the thalidomide case. Photo courtesy of the FDA History Office

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Frances Kelsey’s fame following the thalidomide case prompted the Federal Civil Service to make her its poster child in this 1963 commemoration of its 80th anniversary.

drug thalidomide, which caused massive birth defects and fetal deaths throughout the world. At the time, the drug was available in more than 20 nations, including Britain and Germany, where it was given to pregnant women to ease morning sickness. Swann dubs the thalidomide case the agency’s “most impactful near-miss.” It was a drama in which the University of Chicago loomed large. Kelsey had trained at the University and later became a faculty member alongside her future husband, F. Ellis Kelsey, PhD, another key player in the thalidomide case. The University also was home to the revered scientist Eugene Geiling, MD, PhD, who mentored Kelsey and brought her to the agency. Geiling was part of a clutch of University of Chicago alumni and faculty who shaped the course of drug regulation. It was at the University of Chicago that Kelsey got her first exposure to the perils of lax drug oversight. As a graduate student in 1937, she played a part in the other landmark drug regulation case of the 20th century — one that triggered an earlier round of regulatory reform and bequeathed to the FDA the very powers that Kelsey would wield to such effect more than two decades later.

“A quaint little course called pharmacology” Growing up on Vancouver Island, Kelsey’s chance meeting with a vacationing teacher ignited an interest in biology. As a high school senior, she took biology classes at nearby Victoria College. There, Kelsey discovered a passion for zoology, and in 1932 she traversed Canada on the transcontinental railroad to Montreal to pursue a degree at McGill. But she found zoology “dull” as an undergraduate, branching into biochemistry and “a quaint little course called pharmacology.” She stayed on to pursue a master’s degree in it, and when Eugene Geiling, fresh from Johns Hopkins, established a pharmacology department at the University of Chicago, she was accepted as his first PhD student in 1937.

Frances Kelsey, now 96, at home in Chevy Chase, Maryland. Photo by Robb Hill

Chicago Connections

After earning her PhD, Kelsey remained at the University during World War II to conduct research into antimalarials — work that sensitized her to the distinct effect of drugs on fetuses. Having married colleague F. Ellis Kelsey in 1943, the couple faced restrictions on spouses serving on the same faculty, so Frances Kelsey — who was more interested in medicine and had already completed most of the basic sci“What Geiling, his students and his colleagues ence courses required — enrolled in the School of Medicine in 1946. While attending medioffered was a combination of basic medicine, cal school, Kelsey bore her two daughters. After up-to-date pharmacological training, specialty earning her MD in 1950, she worked for a knowledge in toxicology, and professional time as an editor for the Journal of the American Medical Association, then located in Chicago. esteem.” — Daniel Carpenter, PhD It was Geiling who recruited Kelsey at the FDA in 1960. Geiling had been hired the previous Kelsey got to Chicago in the midst of a national emergency. year to head its new Pharmacodynamics Branch. The agency had The FDA was scrambling to impound supplies of the S. E. long made a habit of poaching Chicago’s brightest talents. In his Massengill Co.’s Elixir Sulfanilamide, a medicine widely pre- authoritative study of the FDA, “Reputation and Power,” alumnus and Harvard political scientist Daniel Carpenter, PhD ’96, scribed for colds and other infections that was linked to a mounting nationwide death toll. Kelsey was assigned to a writes of a “fluid recruitment” between Geiling’s pharmacology center and the FDA. team assembled by Geiling to identify the toxic agent. The “What Geiling, his students and his colleagues offered,” group identified the culprit as diethylene glycol, used as a solvent in the preparation. It is better known today as the Carpenter wrote, “was a combination of basic medicine, up-todate pharmacological training, specialty knowledge in active ingredient in antifreeze. The scandal exposed the inadequacy of existing regulation. toxicology, and professional esteem.” Just one month in, Kelsey was assigned to review an applicaMassengill had failed to conduct any toxicology testing on a drug that claimed 107 lives, yet the only negligence it had com- tion to sell a sleeping aid already widely prescribed in other mitted under the law was an infraction in billing the product nations for morning sickness, among other conditions. as an “elixir,” a description reserved for alcohol-based solutions. The case spurred legislation in 1938 requiring companies “This couldn’t be the perfect drug” to file an application with the FDA to market a new drug. If Kelsey’s memory of her first reaction to the application from the the agency was not satisfied the drug was safe, it had a 60-day William S. Merrell Co. to market thalidomide, under license window in which to reject the application. from German manufacturer Chemie-Grünenthal, in the United

Medicine on the Midway Summer 2011

M E D I C I N E O F F T H E M I D WAY

Frances Kelsey in the lab at the University of Chicago with Eugene Geiling, PhD, MD, founding chair of the department of pharmacology and Kelsey’s PhD supervisor. Geiling would be pivotal in bringing Kelsey to the FDA. Photo courtesy of University of Chicago archives

States is sharp. “It was just too positive; this couldn’t be the perfect drug with no risk,” she recalled. The transcript of the subsequent communications between Kelsey and Merrell offers a glimpse into a distant era of regulation in which there were no formal requirements governing data submitted in support of new drug applications, and pharmaceutical companies regarded “open-door access” to FDA officials as a prerogative. But even by the standards of the day, Merrell waged an aggressive campaign for approval. West Germans were consuming 1 million doses a day of thalidomide in 1960. If such success could be replicated in America, the world’s largest and most lucrative drug market, the firm could expect blockbuster profits. “Lobbying at the FDA could be done,” Swann said, “but this took it up a notch.” Merrell executive F. Joseph Murray, PhD, peppered Kelsey with phone calls, letters and visits. Based on thalidomide’s distribution elsewhere, Merrell regarded approval to sell it in America — under the brand name Kevadon — as a formality. But Kelsey insisted on hard evidence to back Merrell’s claims for the drug’s safety and refused to be browbeaten. In Merrell’s initial application, Kelsey noted the reliance on anecdotal testimony in place of clinical data. She ran it by her husband, who then worked as a pharmacologist at the National Institutes of Health. One section of the submission he branded “an interesting collection of meaningless pseudoscientific jargon apparently intended to impress chemically unsophisticated readers.” Elsewhere he noted “the very unusual claim that thalidomide has no [lethal dose].” “No other substance can make that claim,” he wrote. Kelsey’s concerns escalated when in February 1961 she saw

University of Chicago Medical Center

President Barack Obama sent a personal tribute to mark the FDA’s honoring of Frances Kelsey. Her actions “prevented countless birth defects in American children,” he wrote. “Our nation relies on dedicated public servants like Dr. Kelsey to create a better, healthier future for our children and grandchildren.”

“She’s the embodiment of someone who took her responsibilities seriously and [impacted] not just Americans, but people worldwide through the regulatory structure that emerged from her.” — Leslie Ball a letter from a physician in the British Medical Journal reporting cases of peripheral neuritis — nerve damage in the hands and feet — among patients he’d treated with thalidomide. “The burden of proof that the drug is safe . . . lies with the applicant,” Kelsey wrote Murray on May 5, 1961. “In this connection, we are much concerned that apparently evidence [of] peripheral neuritis in England was known to you but not forthrightly disclosed.” An indignant Murray telephoned Kelsey’s boss, Ralph Smith, MD. “He said . . . he considered [the letter] somewhat libelous,” Smith reported. “He inquired whether the firm was dealing personally with Dr. Kelsey in this connection and if so whether the letter was subject to reconsideration.” Smith affirmed that Kelsey had the agency’s backing. The peripheral neuritis report was significant in another respect. It prompted Kelsey to request, with grim prescience, proof the drug was not harmful to the fetus. Merrell insisted that this and the other concerns could be dealt with through a warning label and in September initiated a fresh push for FDA approval. Around the same time, reports had begun to trickle in of a spike in birth defects in Europe and Australia. Authorities scrambled to connect the dots and identified thalidomide as the common denominator. Four times Kelsey had invoked the regulatory lever available to her under the 1938 legislation to reject Merrell’s application on the grounds of insufficient data. Now on the company’s fifth attempt to secure approval, Merrell notified Kelsey it was rescinding its application.

Civilian Service at a ceremony in the White House. The case’s visceral impact prompted regulatory reform. Legislation signed by Kennedy in October 1962 required the agency’s assent before a drug could be sold. Kelsey was appointed to head the Investigational Drug Branch, the new FDA division charged with implementing the regulations on the ground, presiding over a new oversight regime that transformed drug regulation and, by extension, drug development. The regulations stipulated that evidence of drugs’ safety and efficacy be “based on adequate and well-controlled studies.” The agency used the edict to introduce sweeping new protocols governing clinical trials, specifying distinct phases and control studies. It also adopted a provision of the 1962 drug amendments that required human subjects give informed consent. The latter requirement addressed a glaring omission. Many patients given Kevadon under Merrell’s trial were unwitting guinea pigs. Later, Kelsey helped spearhead the new Division of Scientific Investigations, tasked with inspecting clinical sites to vet the integrity of data. The group earned the moniker “Kelsey’s cops.” She finally retired at 90 in 2005. The agency’s preoccupations today are different from those of Kelsey in her prime. But her personal example still resonates. “I felt an instant connection,” said Leslie Ball, Kelsey’s successor as director of the Division of Scientific Investigations. “She’s the embodiment of someone who took her responsibilities seriously and [impacted] not just Americans, but people worldwide through the regulatory structure that emerged from her.” ■

A Global Tragedy Worldwide, the births of roughly 8,000 infants with missing or malformed limbs (a further 5,000 to 7,000 may have perished in utero) were linked to thalidomide’s widespread usage among pregnant women. Americans did not escape the tragedy. The FDA subsequently identified 17 cases — 10 linked to Kevadon that Merrell had distributed to 1,267 doctors under the auspices of its “investigational” trial. But the country was spared the broad-based catastrophe visited upon Europe. Still, the U.S. public might have remained oblivious to their close call but for contemporary political machinations. Democratic Senator Estes Kefauver of Tennessee had been investigating pharmaceutical companies — chiefly their pricing practices — since 1959, but he had failed to rally support behind reform. In the aftermath of the revelations from Europe about thalidomide, the senator’s staff dug into the FDA’s deliberations on the drug and unearthed Kelsey’s dealings with Merrell. Spotting the story’s political capital, they leaked it to the Washington Post, which reported it to an unsuspecting nation on July 15, 1962. Kelsey, the self-effacing scientist, found herself thrust into the public eye. On August 7, 1962, President John F. Kennedy presented her with the President’s Award for Distinguished Federal

A world away from the limelight of the early 60s, Frances Kelsey enjoys reading in her retirement. Photo by Robb Hill

Medicine on the Midway Summer 2011

PRITZKER PROFILE

A Legacy’s Triumph over Cancer Adam Mikolajczyk’s family ties to Pritzker went further than expected in a summer research program studying colonic pH in ulcerative colitis patients with his Pritzker mentor, David Rubin, MD. Rubin, co-director of the Inflammatory Bowel Disease Center at the Medical Center, also knew Mikolajczyk’s father. Rubin said it would have been understandable if Mikolajczyk had taken the summer off to focus on his health. But for Mikolajczyk, keeping his mind occupied on research helped him cope. One of his proudest accomplishments, he said, was winning an award for being part of one of the top Adam Mikolajczyk, MD ’11, (center) and (left to right) his wife, Marina Mikolajczyk, sister Beth Mikolajczyk, clinical projects that year. brother-in-law Myles Aburto, and mother, Connie Mikolajczyk. Photo by Bruce Powell “In a true sign of his character, diagnosed with Stage II Hodgkin’s he didn’t shy away from the project,” By Shane Graber dam Mikolajczyk, MD ’11, chose lymphoma — by a doctor who had studied Rubin said. medical training at the University of under Mikolajczyk’s father, Sonali M. Chicago partly because of his father’s legacy Smith, MD, associate director of the A Bright New Chapter here and the kindness shown by the Lymphoma Program. As it happened, Mikolajczyk had his last chemotherapy institution after his death. The school repaid Mikolajczyk’s father had taught Smith treatment on September 3, 2008. He how to perform bone marrow biopsies. Mikolajczyk’s loyalty by saving his life. married his girlfriend, Marina, in Mikolajczyk began six months of November 2009. He continues to get a Mikolajczyk’s father, James, was a well-liked, respected physician assistant in chemotherapy in May of that year. He chest and abdomen CT scan every six the University of Chicago Medical Center’s was hospitalized with a severe fever after months, and the results have been negative. Section of Hematology/Oncology. In 2000, his first treatment. Mouth ulcers made Mikolajczyk graduated from Pritzker at 46, he was killed by a drunken driver. eating and drinking painful, and he this June and was awarded the Richard When his father’s colleagues reached out suffered from constant nausea. As a W. Reilly Award, which goes to the to the Mikolajczyk family after his death, patient, Mikolajczyk was learning lessons graduating student with outstanding Adam was touched. He decided then that about medicine beyond the typical aptitude in gastroenterology. He plans to he wanted to attend medical school at the curriculum. He could identify as a recipient specialize in GI research as an internal University of Chicago. That way, he figured, of care. And he knew cancer patients’ medicine resident at the University of he could both honor his father and show fears and confusion firsthand. Chicago Medical Center. He had considered the University the gratitude he felt. “Physically and mentally it’s the most following his father’s specialty in oncology. Amid the tragedy of losing his father, challenging thing you could go through,” “But I was too emotionally invested Mikolajczyk focused on his studies. A he said of his cancer treatment. “Everything in that field,” he said. “Every patient I Dyer, Indiana, native, he managed to do felt chaotic, out of control. My heart pours would see would remind me of myself. well in high school and later excelled at out now to these other people in treatment.” In order to be sane, you need at least the University of Notre Dame. Seven years some separation.” after his father’s death, Mikolajczyk was Resolutely Forging Ahead Rubin doesn’t think that will be a problem still determined to attend the University As Mikolajczyk’s treatments continued, he for Mikolajczyk. of Chicago. To his delight, the Pritzker lost his hair and gained weight from one of “Some people are born with a strong School of Medicine accepted him. his medications. He worried about infertility. role in life, and I think he’s born to be a Worse, he struggled with his suddenly physician,” Rubin said. “That’s a part of uncertain mortality — and the possibility who he is.” A Harrowing Coincidence Cancer specialist Smith said Mikolajczyk, In February 2008, during Mikolajczyk’s of leaving his fiancée and family behind. “They were so important to me through as well as his family, has handled the ordeal first year of medical school, he began getting persistent fevers, and a lymph node in his all of this,” he said. “They’re the most with “amazing grace.” “I am so proud of Adam,” she said. neck grew. He went for tests at the same important thing to me in the world. I department where his father had worked. didn’t want to put them through an even “He has never let major life obstacles, including his father’s death and cancer, “Irony of all ironies,” said Mikolajczyk, harder ordeal.” So Mikolajczyk devised a plan for coping stand in the way of becoming the kind now 25. Results revealed a softball-size tumor with the difficult treatments. He set goals of physician who wants to make a in his chest. At the end of April, he was to propose to his girlfriend and participate difference.” ■

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CLASS NOTES

C L ASS N OT E S With Medicine on the Midway now online, we are capable of linking straight to classmates’ websites, as well as YouTube videos, with a simple click of the mouse. When sending in your updates, please include links to your websites and JPEGs of your most recent headshots that we can run in the magazine. You can send them to alumni@mcdmail.uchicago.edu.

1950s Walter B. Eidbo, MD ’56, is retired after 50 years of surgical practice and enjoys returning to campus for reunions.

Memorial Hospital, Shriners Hospital for Children, the Jesse Brown VA Medical Center and the Rehabilitation Institute of Chicago.

2000s

Theodore J. Jacobs, MD ’57, is practicing psychoanalysis and psychotherapy in New York City, teaching at the New York Psychoanalytic Society and Institute and the New York University Psychoanalytic Institute, and doing a fair amount of writing and speaking on psychoanalytic topics.

Lieutenant Commander Andrew Stan Flotten, MD ’07, just returned from a seven-month deployment as senior flight surgeon for all U.S. Marines in Iraq and is currently stationed on the Outer Banks of North Carolina. He was recently selected for a radiology residency. Feel free to contact him at andrew.flotten@med.navy.mil.

1960s

Paul A. VanderLaan, PhD ’06, MD ’08, has been named chief resident for anatomic pathology (2011–12) at Brigham and Women’s Hospital in Boston.

David Wilbur Larson, MD ’67, retired at the end of February, four days after his 70th birthday. In addition to a fi ne party that ended minutes before another snowstorm began, there were numerous fetes culminating in a reception at the Spruce Pine Community Hospital in Spruce Pine, North Carolina. He began work there 37 years ago and, with the exception of seven years in Winston-Salem on the faculty at the Wake Forest School of Medicine and six months in Desert Storm, practiced there until retirement.

1980s Timothy G. Buchman, SB ’74, SM ’74, PhD ’78, MD ’80, has recently been honored with the Distinguished Investigator Award, the most prestigious honor given by the American College of Critical Care Medicine. He is currently a professor of surgery and anesthesiology at Emory University and is also the founding director of the Emory Center for Critical Care. Gregory A. Dumanian, MD ’87, has been named chief of the Division of Plastic and Reconstructive Surgery at Northwestern University Feinberg School of Medicine and Northwestern Memorial Hospital. He is currently professor of plastic and reconstructive surgery, neurological and orthopaedic surgery, and has been on the faculty since 1996. He holds appointments at Northwestern Memorial Hospital, Children’s

IN MEMORIAM

1950s Clayton B. Edisen, PhB ’49, MD ’53, died of surgery complications on January 8, 2011. Born in Chicago, he had practiced medicine in New Orleans since 1954. After returning from military service in Europe in 1946 with the U.S. Army, he received his medical degree from the University of Chicago and Tulane University School of Medicine. Edisen was board certified in neurology and psychiatry and formerly was a full professor in Tulane University’s department of teacher education. He was an honorary state senator. He received the gold medal for outstanding community service from the International Who’s Who in Community Service and was a life member of Sigma Xi (National Honor Fraternity). Edisen served on several committees of the Louisiana State Medical Society and published numerous articles in national and international journals. He was a member of the American Psychiatric Association, American Medical Association, Southern Medical Association, Louisiana State Medical Society and Orleans Parish Medical Society. In addition to his medical practice, Edisen was president of the Schreier-Edisen Development Corp. and the White House

Corp., both privately held companies. He also was chairman of the board for the Schreier-Edisen Foundation. Edisen loved opera and was on the board of directors of the New Orleans Opera Association for more than 25 years. He also loved to play golf and bridge and watch football. He is survived by his children, Laura, Glenn and Lynn; stepchildren, Brenda Schneider and Niki Bradley; grandchildren, Eric, Anthony, Jennifer and Joshua; and great-grandchildren, Zachary and Miles. To view and sign the family guestbook, please visit lakelawnmetairie.com. W. McFate “Mack” Smith, MD ’51, a leading expert in high blood pressure and other cardiovascular risk factors, died February 25, 2011, at his California home of complications from Lewy body disease, which causes dementia. He was 84. Smith’s career included more than 20 years of work for the U.S. Public Health Service, from which he retired in 1973 after attaining the ranks of rear admiral and assistant surgeon general. Smith also spent 20 years as a professor of medicine and director of the preventive medicine residency program at the University of California, Berkeley School of Public Health. He is survived by three children, one stepchild and eight grandchildren.

1960s Richard L. Hall, MD ’61, died of complications from a stroke on February 15, 2011, at age 75. Richard “Dick” Hall had a reputation as a natural leader and a devoted caregiver. A respected physician in the La Jolla area of California, the urologist practiced medicine in the San Diego area for more than 35 years and served as an assistant professor at the University of California, San Diego School of Medicine. Hall was past president of the San Diego Urological Society and the San Diego chapter of the American College of Surgeons. He was appointed to the Scripps Health board of trustees in 2006 as a physician member after he retired from medical practice. Hall helped set up the Scripps robotics program and also served on the board of directors of the Scripps Memorial Hospital Foundation. Hall is survived by his wife of more than 45 years, Judy; two

daughters, Nicole Hall Brown and Diana Ferguson; a sister, Lynne Goldsmith; and three grandchildren.

F O R M E R F A C U LT Y Melvin Griem, MD, professor emeritus of radiation and cellular oncology, died of pneumonia February 7, 2011, at the Grove at Lincoln Park, in Chicago. He was 85. A pioneer in the field of radiation oncology, Griem is remembered by his colleagues for his unique background in engineering, physics and medicine, which gave him the ability to build equipment needed to test new clinical approaches. He helped launch the neutron therapy unit for cancer treatment at the University of Chicago in 1975, one of the fi rst four such facilities in the nation. Griem served as a radio repairman in the U.S. Army during World War II and earned his medical degree from the University of Wisconsin in 1953. He joined the University of Chicago faculty in 1957 as an instructor of radiology and became chief of the Section of Radiation Therapy in 1966. During the 1960s, he performed radiation therapy clinical studies, developing a technique similar to one now widely used to treat prostate cancer. Griem taught at the University for 38 years and in 2010 was given the Paul C. Hodges Alumni Excellence Award from the Department of Radiology. Griem is survived by his three children, three grandchildren and sister. Charles Schuster, PhD, a founder of behavioral pharmacology, died February 21, 2011. He was 81. A professor of psychiatry, pharmacology and behavioral science from 1968 to 1986 at the University of Chicago, Schuster founded and directed the Drug Abuse Research Center. He directed the National Institute on Drug Abuse, part of the U.S. National Institutes of Health, from 1986 to 1992. In October, the Department of Psychiatry and Behavioral Neuroscience named a lecture series after him. Schuster is survived by his wife, four children, a sister and six grandchildren.

Medicine on the Midway Summer 2011

PRITZKER NEWS

Military Match Day Pritzker students serve their patients and their nation allowed to do at the Naval Academy — because some of our professors and politicians were part of the chain of command.” The Pritzker School of Medicine admissions office reports that it’s typical to have only one or two students blend military service with a University of Chicago education; Grimaldo and classmate Mechelle Miller, MD ’11, are the only students to do so in the class of 2011. Both are in the military’s Health Professionals Services Program, which offers medical students a full-tuition scholarship, health insurance, school fees and a $2,000 monthly stipend. In turn, students serve one year as active duty physicians for each year of sponsored medical education. The program’s scholars also spend residency in a military hospital, which makes their matching process distinct from that of their civilian peers. Their match day also occurs earlier. In December, Miller matched with her first choice, a family medicine residency in Fort Benning, Georgia, where she started Mechelle Miller, MD, and Felipe Grimaldo, MD, on Match Day. Photo by Bruce Powell July 1. Grimaldo also received good news in December: He’d been awarded a competitive “civilian deferral” to complete his By Kelin Hall emergency medicine residency in a civilian hospital. On March 17, hough some joke that medical school is like boot camp, those who know both worlds say the University of Chicago Pritzker standing with his civilian colleagues, Grimaldo learned his match: School of Medicine and the military have very different cultures. John H. Stroger Jr. Hospital of Cook County. “When I came to Pritzker after the Naval Academy, it was surprising how quick everyone was to criticize things — the- Choosing to Serve ories, politicians, professors,” graduating Pritzker student Felipe Though Grimaldo and Miller share the drive to serve both Grimaldo, MD ’11, said. “That was something we weren’t patients and their nation, their motivations grew out of differ-

Pritzker’s Class of 2011 Marks Match Day Excited students unveil their residency destinations By Kalyn Belsha Ifeoma Nwadei, MD ’11, likes to be in control. It’s the reason she loves surgery. But as Match Day inched closer, the lack of control she felt was maddening. The day before, she used her nervous energy to bake seven cakes, then delivered them as gifts to her professors and mentors at the University of Chicago Pritzker School of Medicine. On March 17, the graduating fourth-year woke up early, put on her Class of 2011 T-shirt — green with a leprechaun perched atop a pot of envelopes, a wink at Match Day falling on St. Patrick’s Day — and made her way to the Billings Auditorium. Soon the room was bustling with Pritzker School of Medicine fourth-years, their families and friends. Holly J. Humphrey, MD, dean for medical education at Pritzker and

University of Chicago Medical Center

the University of Chicago Medical Center, announced to cheers that all 110 students had matched. One by one, students descended the stairs to retrieve envelopes containing their residency placements. The students were among more than 16,000 fourth-years nationwide competing for ﬁrst-year residency programs, open to U.S. graduating seniors, previous medical school graduates, graduates of osteopathic schools and international students.

Hoping for Home Nwadei wanted to be matched at her ﬁrst choice, Emory University in Georgia, the state where she grew up and where her brother will begin his residency. Humphrey announced it was time and counted down

Ifeoma Nwadei, MD, holds the envelope of her colleague, Djuro Petkovic, MD, because she is too nervous to open her own. Nwadei was matched with her ﬁrst place request, Emory. Petkovic matched with orthopaedic surgery in Loma Linda, California. Photo by Bruce Powell

PERSPECTIVE

vice as a way to give back. As Grimaldo applied to colleges, cousins and friends left for Iraq, further motivating him to serve. Grimaldo was accepted to top premedical programs and to the U.S. Naval Academy, where admissions counselors bluntly told him not to attend if he was committed to medicine. Naval Academy students serve five years of active duty after college and need the military’s permission to defer service for medical school. Only 10 to 15 of the strongest students out of each class of about 1,000 are granted “I grew up in the Army; I know the culture and the deferment. demands. I want to serve families like mine.” Grimaldo went to the Naval Academy any— Mechelle Miller, MD way. “My priority was the military. Medicine had to come second.” In the end, he was allowed to apply to medical school. languages, but also to new antigens in every environment. The milk chocolate in an M&M, the preservatives in lunch meat and myriad other foods could send Miller into anaphylactic shock or A Pritzker Education trigger an asthma attack that left her blue in the face. Grimaldo’s and Miller’s paths converged when both were At each new home, she managed her allergies with the sup- accepted to Pritzker and received Health Professional Services port of a different Army physician. “If it weren’t for them,” Program scholarships. For Miller, the program became appealshe said, “I wouldn’t have made it through kindergarten.” ing as she considered financing medical school. “I grew up in She was so grateful for her military doctors that she chose the Army; I know the culture and demands,” she said. “I want to emulate them. to serve families like mine.” For Grimaldo, the scholarship was the obvious next step. After residency, he will serve a total of nine years as an active From the ER to the Naval Academy Grimaldo started considering a medical career during high school, duty physician — five years for his Naval Academy education while interpreting for Spanish-speaking patients at MacNeal and four for the health professionals program. Though he is Hospital in Berwyn, Illinois. Then, the aftermath of September excited that his residency will give him the emergency train11, 2001, pushed him to embrace his family values. His father, ing critical to war zones, Grimaldo struggles with living a civilian life while his closest friends are deployed. “I’m just who came from Mexico as a teenager, always told Grimaldo how grateful he was to the United States: He saw military ser- glad that soon I’ll get to give back,” he said. ■ ent experiences. Grimaldo wanted to serve the country that welcomed his parents as immigrants; Miller, a self-described “military brat,” was inspired by the physicians who cared for her growing up. Miller split her childhood among five states and two countries as her family moved with her father’s military posts. At each move, she adjusted to different schools, houses and sometimes

from ﬁve to one. Nwadei was so nervous she couldn’t open her own envelope and, instead, asked a classmate next to her to swap envelopes. When he read “Emory” out loud to her, she screamed and jumped. “It really dawned on me: We’re not just matching in residencies, we’re becoming doctors,” said Nwadei, who was among the 81 percent of matched U.S. fourth-years placed in one of their top three choices. “It’s like coming home, but moving forward at the same time.”

Fresh Start in a Familiar City Rows away, Sogyong Auh, AB ’03, PhD ’09, MD ’11, handed her youngest son, to whom she had given birth while applying to residency programs, to her husband. The MD-PhD student had applied to programs across the country in dermatology, one of the most competitive specialties, but she wanted to stay in Chicago. Her

stomach churning, she opened her letter. She’d been matched at MacNeal Hospital in Berwyn for her transitional year, then at the Medical Center for dermatology. “We could have ended up in so many different cities,” Auh said. “We had talked at length before the whole process: Wherever I matched, we had to go. I was relieved we were going to be in Chicago.”

nal medicine, at 25 percent. General surgery and pediatrics were the next most popular, at 11 percent each. “The placements speak for themselves,” Humphrey said. “This was a spectacular class.” ■

A Spectacular Class The highest percentage of this year’s fourth-years, 22 percent, will begin their ﬁ rst year of residency at the Medical Center. The rest will join programs in 22 states and Washington, D.C. Ten percent of the graduating class matched at programs affiliated with Harvard University; 5 percent matched at Stanford University programs. The most popular specialty among graduating Pritzker students was inter-

Sogyong Auh, MD-PhD graduate, (left) with her son Theo Han, her husband, Tom Han, and her baby, Samuel Han. Photo by Bruce Powell

Medicine on the Midway Summer 2011

PRITZKER NEWS

Reunion 2011 Pritzker alumni return, remember and reconnect By Gretchen Rubin

n the past 50 years, graduates from the University of Chicago Pritzker School of Medicine have made significant contributions to the improved health of Americans through their work in clinical medicine, scientific research and education. In early June, alumni from 11 medical school classes — spanning 1956 to 2006 — returned to campus for Reunion 2011 and were recognized for the legacy they created. An impressive 42 percent of the Class of 1961 gathered for their 50th reunion, earning the group an award for highest class attendance at the event. When class members looked back to their time in medical school, they expressed fondness, gratitude and pride in being part of the University of Chicago. George Wright, MD ’61, remembered the warmth of the faculty and how they cared about each student as an indi(Left to right) Greg Primus, MD ’01, Jessica Franklin, AB ’96, MD ’01, and Suleman Ahmad Khawaja, MD ’01, were among Pritzker school alumni who returned for Reunion Weekend to celebrate with vidual. In accepting a Distinguished classmates. Photos by Tricia Koning Service Award, David Beal, MD ’61, Speaking at the awards reception, Kenneth S. Polonsky, MD, credited the education and training he received at the University with “carrying me forward in my learning and teaching through- dean of the Division of Biological Sciences and the Pritzker School out my career.” of Medicine and executive vice president for Medical Affairs, told all returning alumni “we want your pride in the school to continue” and added that Pritzker “Degrees from the University of Chicago, recently placed 12th in national medical school whether undergraduate, medical, graduate or rankings and remains highly selective, giving its PhD, are all highly regarded and highly sought students a rich experience. In all, 180 Pritzker alumni, many accompanied by after. We owe a lot to our alumni for ensuring spouses, attended the three-day reunion. Alumni and

that reputation.” — Kenneth S. Polonsky, MD

Darlene Kuhn (left) and husband and 55th Reunion Committee Chair Paul Kuhn, AB ’52, SB ’54, MD ’56, attended the Alumni Emeriti Champagne Breakfast during Reunion Weekend.

Lauren Pachman, MD ’61, (left) and Ivan Diamond, AB ’56, SB ’57, MD ’61, PhD ’67, attended the celebration honoring leadership donors.

For more information, call 1-888-UCH-0200 or visit uchospitals.edu

William Leong Jr., MD ’61, (left) and wife Joan Leong were among the Pritzker alumni, family and friends who attended the Alumni Emeriti Champagne Breakfast.

M E D I C I N E O N T H E M I D WAY A University of Chicago Medical Center Publication Summer 2011, Volume 64, No. 3 Executive and Managing Editor Cheryl L. Reed, Director of Strategic Communications Vice President for Marketing and Communications

guests had the opportunity to take an architecture boat tour on the Chicago River, visit the Smart Museum of Art, attend a picnic with medical students and residents, and listen to presentations from young, innovative faculty members. “I encourage everyone to come to Alumni Weekend,” said Robert Doroghazi, MD ’77, incoming president of the Medical and Biological Sciences Alumni Council. “It’s a great opportunity to bring back memories, see the progress that has been made on the medical campus and reconnect with your classmates and professors.”

“We forged lifelong bonds in medical school. The hospitals were under one roof in those days, so we really got to know each other. It was wonderful to be together again.” — Dennis Wentz, MD Dennis Wentz, MD ’61, co-class chair with Lampis Anagnostopoulos, SB ’57, MD ’61, heard several classmates say they wouldn’t have missed this reunion. “We forged lifelong bonds in medical school,” Wentz said. “The hospitals were under one roof in those days, so we really got to know each other. It was wonderful to be together again.” While remembering and reconnecting were on the agenda for all those attending Reunion 2011, many came with questions about the direction and priorities of the University of Chicago Medical Center and the medical school. During the annual Alumni Senate meeting, Polonsky told volunteer leaders that in building eminence, the missions of research, patient care and education must be of equal importance. He said improving educational programs broadly, in order to attract the best students and postgraduate trainees, is among the top strategic priorities for Pritzker and the Division of Biological Sciences. For example, he explained, strengthening the programs that enable students to engage in and connect to the South Side and global communities will set the medical school apart from competitors. “Across the board, our education program is doing very well,” Polonsky added. “Degrees from the University of Chicago, whether undergraduate, medical, graduate or PhD, are all highly regarded and highly sought after. We owe a lot to our alumni for ensuring that reputation.” ■

Kathleen A. DeVries Editorial Contributors Shahzad Ahsan Kalyn Belsha Jill Boba John Easton Shane Graber Kelin Hall Meredith Klein Rob Mitchum Brooke E. O’Neill Stephen Phillips Gretchen Rubin Molly V. Strzelecki Photo Contributors

(Left to right) Donald Rowley, SB ’45, SM ’50, MD ’50, Russ Zajtchuk, SB ’60, MD ’63, and Janet Davison Rowley, LAB ’42, PhB ’45, SB ’46, MD ’48. Janet Rowley received the prestigious Alumni Medal at the University’s Alumni Awards Ceremony.

Shahzad Ahsan Joan Archie John C. Bivona, RBP David Christopher Jennifer Crotty Dan Dry Dianna Douglas Robb Hill Tricia Koning Alex Lickerman, MD George Perry Bruce Powell Jason Smith Deborah Suchman Zeolla Design Firm 3C: Chicago Creative Communications, the University of Chicago

Reunion 2011 Awards U N I V E R S I T Y O F C H I C AG O A L U M N I AWA R D S Alumni Medal Janet Davison Rowley, LAB ’42, PhB ’45, SB ’46, MD ’48 Professional Achievement Award Alfred Lewy, SB ’67, PhD ’73, MD ’73 MEDICAL AND BIOLOGICAL SCIENCES ALUMNI A S S O C I AT I O N AWA R D S Highest Class Attendance The Class of 1961 (42 percent of the class) Highest Class Gift Participation The Class of 1956 (50 percent of the class) Gold Key Award Herbert T. Abelson, MD Alan R. Leff, MD

Editorial Committee Chairwoman Chris Albanis, AB ’96, MD ’00 Lampis Anagnostopoulos, SB ’57, MD ’61 Arnold Calica, SM ’61, MD ’75 Jerrold Seckler, MD ’68 Coleman Seskind, AB ’55, SB ’56, SM/MD ’59 Medicine on the Midway is published for friends, alumni and faculty of the University of Chicago Medical Center, the University of Chicago Division of Biological Sciences and the Pritzker School of Medicine. Articles may be reprinted in full or part with permission of the editor. We welcome your comments and letters to the editor. Address Correspondence to: Editor, Medicine on the Midway University of Chicago Medical Center 950 East 61st Street Third Floor, Suite 329 Chicago, IL 60637-1470 Telephone 773-834-4383 Facsimile 773-834-5926

Distinguished Service Award Robert L. Alpern, MD ’76 David Beal, MD ’61 Elliott D. Kieff, MD, PhD ’71 Thomas Quertermous, SM ’76, MD ’80 Dennis K. Wentz, MD ’61

E-mail Editor momedit@uchospitals.edu E-mail Class News alumni@mcdmail.uchicago.edu Find Us on the Web uchospitals.edu/midway © July 2011. University of Chicago Medical Center, Department of Communications and Marketing

Medicine on the Midway Summer 2011

PRITZKER NEWS

Convocation 2011 Pritzker and BSD graduates reach a goal and look to the future By Molly V. Strzelecki

elodic notes of pomp and circumstance floated across the Midway as the University of Chicago Pritzker School of Medicine and the Division of Biological Sciences graduating class of 2011 lined up to make the transition from students to alumni on June 10. The culmination of years of hard work, the 2011 Divisional Academic Hooding Ceremony was a time of celebration, a sigh of relief from the challenges students faced and long hours they’d put in, and an anxious yet excited look toward the future in front of them. California native Farbod Rastegar, MD, said the ceremony “allows graduates to look back and appreciate that they spent four years working toward a goal, and that (Left to right) Pritzker graduates Grant Barton, Adam Back, Sogyong Auh, AB ’03, PhD ’09, and Elliot Arsoniadis, all MD ’11, enjoy the address during the Divisional Academic Ceremony. Photo by Tricia Koning hard work is paying off little by little, though the journey hasn’t been “Our students are famous for their capacity for superior origcompleted.” For Marion Stanley, MD, the day was surreal and bittersweet. inal thought and scholarship,” Polonsky said. “Students who can assemble the data to challenge conventional wisdom and go “The past four years have gone by so fast, and you know these people so well now. It’s kind of sad to be leaving, and you won- in new directions, and who are not afraid to do so,” he continued, charging them to maintain and strengthen that tradition. der when you’ll get to see them next.” The 111 Pritzker School of Medicine graduates and 21 stuKenneth S. Polonsky, MD, dean of the Division of Biological Sciences and the Pritzker School of Medicine and executive vice dents receiving PhDs and 8 receiving master’s degrees from the president for Medical Affairs, opened the ceremony, his first since Division of Biological Sciences had two speakers on hand to give them guiding words for the future. becoming dean last October. He welcomed the graduates and R. Douglas Fields, PhD, chief of the Section on Nervous their friends and family, noting to the students that they were about to graduate from an institution that is among the most System Development and Plasticity at the National Institute of Child Health and Human Development, part of the National intellectually rigorous and most demanding in the country. Institutes of Health, challenged the graduates to look back on the path that got them to this day to better plot out their future path. “True pioneers plot their course into the unknown future not by peering into the empty uncharted terrain ahead, but by tracking the course of the progress they followed,” Fields said. Herbert T. Abelson, MD, the George Eisenberg Professor Emeritus and Chairman Emeritus, Department of Pediatrics at the University of Chicago, served as the faculty marshal for the hooding ceremony, and encouraged the Pritzker Class of 2011 to strike a balance between their work and personal lives. “I urge you,” Abelson said, “to invest as much energy into your personal lives as you do into medicine. The rewards associated with family The Pritzker School of Medicine Class of 2011 celebrated their Divisional Academic Hooding and friends will ultimately inscribe the final Ceremony in June. Kenneth S. Polonsky, MD, dean and executive vice president for Medical chapter in your own book of life.” ■ Affairs, noted that they were graduating from one of the most intellectually rigorous and demanding schools in the country. Photo by Tricia Koning

University of Chicago Medical Center

PERSPECTIVE

Vineet Arora, MD, assistant dean for scholarship and discovery, blogs on futuredocsblog.com about medical education thoughts, news and policy, with tips for medical students and residents. Photo by Jason Smith

Bloggers, MD Doctors share their insights from diving into the blogosphere By Stephen Phillips

edicine on the Midway talked to four faculty and resident bloggers from the Medical Center and Division of Biological Sciences to find out why they blog, how they maintain the sanctity of the doctor-patient relationship, and — perhaps most fascinating — how they find the time. The following are excerpts from their interview correspondences.

“I love movies and medicine, and love to ﬁnd ways to relate the two. I wrote a post about how residency education is like ‘Avatar.’ That was fun.” — Vineet Arora, MD

love writing; and three, I love writing so much I’m hoping to publish books and wanted to develop a platform for my writing. Shantanu Nundy: To survive my internship. Residency and, in particular, internship was in many ways a dehumanizing experience. I didn’t feel like an individual anymore or that my perspective on things mattered. Blogging about health became a way of having my voice heard and feeling like I was making a difference. John Henning Schumann: I’ve come to realize that my pas-

sion lies in communicating medical information to lay audiences. The blog is a chance for me to hone my voice, practice my writing and reflect on issues in the delivery of care.

How do you ﬁt it into your schedule? Arora: I set low expectations. When I started, I announced I’d

Why did you start blogging? Vineet Arora: To shed light on medical education and policy

issues. A friend introduced me to Twitter, but I found it was hard at times to explain things in 140 characters or less. Alex Lickerman: Three reasons: One, I thought I had a unique

perspective on the topic about which I wanted to blog; two, I

try to do two posts per month. I also try to link my blog to something I’m doing for work — maybe something I’m teaching or a conference I’m attending — so it’s not extra work but an extension of what I’m doing already. Lickerman: I keep a pretty disciplined schedule. I typically write a rough draft on Thursday, refine it on Friday, type it on

Medicine on the Midway Summer 2011

PERSPECTIVE

“I’ve come to realize that my passion lies in communicating medical information to lay audiences. The blog is a chance for me to hone my voice, practice my writing and reﬂect on issues in the delivery of care.” — John Henning Schumann, MD Have you built up a community of readers? Lickerman: I get about 10,000 hits a week. That doesn’t mean 10,000 people religiously reading my blog — they may click on a page and leave a second later — but I have almost 2,000 people signed up regularly, so my guess is I’m getting 5,000 people weekly.

What professional connections have you made through blogging?

John Henning Schumann, MD, assistant professor of medicine, blogs on glasshospital.com to demystify medicine one week at a time. Photo by Jason Smith

Saturday, and have it ready to go by Sunday. It takes a lot of work in thinking, so I’m resting from Monday to Thursday, germinating a new idea. Nundy: Sometimes I don’t. It is largely something I do for myself and others. It isn’t work per se and in a way is part of how I relax, or at least get through the week. Each article takes about five hours to write.

Lickerman: A hematologist/oncologist at the University of Warsaw found my blog and wrote to say he was coming to Chicago for a conference and wanted to meet. I was hesitant to meet any person I didn’t know personally, but he was a verifiable colleague, so I said yes. We met and had a really nice conversation. Then a friend here told me about a Polish relative she had with breast cancer, who was having trouble finding care. I was able to connect her with this guy, who took her as a patient. Schumann: Through blogging I’ve “met” people from around

the world. In April 2011, I was on two panels as a direct result of blogging: “The Examined Life,” the annual medical conference of the Iowa Writers’ Workshop where I was on a panel of physician-bloggers; and an American Academy of Arts and Sciences–hosted panel on “Privacy, Autonomy and Personal Genetic Information in the Digital Age,” where I was among scholars from multiple fields.

Schumann: I plan carefully. I make the time because I make

it a priority. From brainstorm to research to writing to revision, I average four hours per post.

Alex Lickerman, MD, interim assistant vice president for student health and counseling, blogs on happinessinthisworld.com to share his reﬂections as a Buddhist physician. Photo courtesy of Alex Lickerman, MD

What’s the most surprising experience you’ve had as a blogger? Lickerman: The biggest surprise was having an editor at one of the major publishing houses discover my blog and solicit a nonfiction book proposal based on the subject matter of the blog. I worked something up and, though it wasn’t picked up, I found an agent through the process and now have a nonfiction proposal under consideration at other publishers. Also, the editor in chief of Psychology Today found my blog and asked me to cross-post on the magazine’s blog website.

What’s the most offbeat topic you’ve found yourself blogging about? Arora: I love movies and medicine, and love to find ways to

relate the two. I wrote a post about how residency education is like “Avatar.” That was fun. Nundy: An experience I had talking about health with a taxicab driver.

For more information, call 1-888-UCH-0200 or visit uchospitals.edu

“It teaches me to listen, provides an outlet for sharing frustrations and emotional patient stories, and challenges me to think more carefully about my ideas.” — Shantanu Nundy, MD

Schumann: A reminiscence about Cleveland comic book author Harvey Pekar.

What value does blogging have for you as a physician? Arora: It provides a creative outlet and a way to think at a

broader level than regular academic physician work allows. Nundy: It teaches me to listen, provides an outlet for sharing frustrations and emotional patient stories, and challenges me to think more carefully about my ideas. Schumann: It’s a creative outlet. It helps me to be reflective in

a workaday world that paves over emotion and reflection.

What lessons have you learned about blogging? Arora: Writing a good post requires inspiration. If you have

this, they’re easy to write and will often write themselves; if not, it’s not worth trying. Shorter posts are better than longer ones. Lists or bullets can also make things easier to digest and remember.

Shantanu Nundy, MD, third-year internal medicine resident, blogs on beyondapples.org about better ways to keep the doctor away. Photo by Jason Smith

discussing breast cancer). I also wait at least a month before sharing a patient encounter. Schumann: HIPAA is paramount. No identifying information

Lickerman: Every time you put up a post, you’re tweaking

your brand. You have an online brand and persona that you can think very consciously about shaping. Schumann: Read a lot. Make time to think and write. All dead-

line pressure in solo blogging is internal; avoid the tendency to write and publish without revising. Revise. Revise again. When possible, have others read a post before publishing it. Comment and link to other blogs; it’s the coin of the realm.

What rules of engagement do you have for ethical blogging as a physician?

should ever be given, with the exception of public figures. Though tempting, Medical Center politics as blog fodder seems highly imprudent.

What would you say to Pritzker/BSD alumni contemplating blogging? Arora: It is a commitment and you should do your homework.

Consider writing some draft posts and have other bloggers or writers look at them. You can also do pre-work by setting up your blog before you go public, so you can decide if this is something you really want to do. It’s important to know who you are writing for, what you will write and how often.

Arora: I avoid discussing anything that would jeopardize my

personal relationships or professional career. HIPAA [Health Insurance Portability and Accountability Act] and FERPA [Family Educational Rights and Privacy Act] are very important rules to follow. For these reasons, I avoid detailed stories of patient care. I also avoid discussing specific interactions with people unless I have obtained their permission. That means there are things I choose not to blog about. One litmus test is whether or not something’s in the public domain. Nundy: I change patient identifier information as much as possible, including gender unless impossible (for example,

Nundy: Try it out and, most importantly, don’t do it to get a huge following or become famous. Do it for yourself. If you get recognition, great, but you can’t always control that. If you do it for yourself, you will always win. Lickerman: Figure out your unique perspective and passion. Define what your blog is about broadly enough that you don’t run out of things to talk about, but not so broadly that there’s no focus. Schumann: Take the plunge!

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