Medicine on the Midway - Fall 2012

Medicine Midway UNIVERSITY OF CHICAGO

on the

FALL 20 12

The magic of zebrafish

Biological Sciences Division

How renowned scientist Victoria Prince, PhD, is studying vertebrate development, with the potential to improve medical treatment of diabetes

Dean’s Letter

B In this edition, we cover some diverse ground, from developmental biology, gene markers and ethics to the impact of social and cultural taboos on public health.

Kenneth S. Polonsky, MD The Richard T. Crane Distinguished Service Professor

Dean of the Biological Sciences Division and the Pritzker School of Medicine

Executive Vice President for Medical Affairs The University of Chicago

eing at the forefront of medicine means pursuing the most innovative and comprehensive methods for combating disease, often through painstaking research that can progress in increments over decades. In this edition of Medicine on the Midway, we cover some diverse ground, from developmental biology, gene markers and ethics to the impact of social and cultural taboos on public health.

Yet through these subjects runs a common theme: the ingenuity and dedication of those we are privileged to call our colleagues at the University of Chicago Medicine.

That dedication is clearly visible in Victoria Prince, PhD, who has devoted much of her career to studying vertebrate development through zebrafish. A University of Chicago professor of organismal biology and anatomy, Prince focuses on pancreas and hindbrain development in these tiny vertebrates, and her research holds promising implications for diabetes research. “If we can work out how an embryo builds a pancreas, we can potentially co-opt those same molecular pathways and use them in a dish on embryonic stem cells,” said Prince, who also serves as associate dean and director of the Biological Sciences Division’s Office of Graduate Affairs.

We learn about dedication in another way from J. Alfred Rider, SB’42, MD’44, PhD’51, who devoted much of his life to paving the way for research into Batten disease, a little-known hereditary neurodegenerative disorder. A successful physician-scientist, Rider founded the Children’s Brain Disease Foundation and lobbied for governmental funding to support Batten research after his eldest son was diagnosed with the disease at age 7. His younger son, Dean, MD’78, the third generation of Riders to train in medicine at the University of Chicago Pritzker School of Medicine, continues the fight with the help of Glyn Dawson, PhD, professor of biochemistry and molecular biology and of pediatrics at the University.

Also in this edition: Liese Pruitt, a third-year Pritzker School of Medicine student, cuts through the misinformation and cultural taboos about breast cancer in Nigeria; hematologist-oncologist Mark J. Ratain, MD, the Leon O. Jacobson Professor of Medicine and director of the Center for Personalized Therapeutics, leads a team including Assistant Professor Peter H. O’Donnell, MD’03, that is translating genetic findings into personalized medicine; cancer researcher Habibul Ahsan, MD, MMedSc, Louis Block Professor of Health Studies, Human Genetics and Medicine, works to reverse decades of damage done by arsenic-laced water in Bangladesh; and Lainie Friedman Ross, MD, PhD, the Carolyn and Matthew Bucksbaum Professor of Clinical Medical Ethics, ponders some of the ethical qualms faced by biobanks.

With heavy hearts we also share the obituaries of two members of the University of Chicago Medicine family, Donald Liu, MD, PhD, and Charles Metz, PhD. Liu, the Mary Campau Ryerson Professor of Surgery and Pediatrics, and Metz, professor of radiology and a member of the Committee on Medical Physics, were medical and scientific innovators who each embodied the University of Chicago spirit in his own way. Both will be sorely missed.

T a b l e o f C o n t e n ts

Cover Story 16 Victoria Prince, PhD, and her research team study zebrafish to better understand how organisms keep their blood-sugar levels steady and to clarify how neurons migrate and build the circuits to regulate functions such as respiration and heartbeat.

As associate dean and director of the Biological Sciences Division’s Office of Graduate Affairs, Prince helps create more opportunities for young researchers to explore a range of professions.

Cover photo: Bruce Powell

Features 08

Pharmacogenomics: How researchers at the University of Chicago Medicine are aiming to translate genetic findings into personalized medicine.

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Medical student helps uncover taboos about breast cancer in Nigeria in hopes of freeing women to seek treatment and start building a community of survivors.

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Cancer researcher searches for ways to reverse devastating effects of long-term exposure to contaminated drinking water in Bangladesh.

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Family heartbreak fuels father and son philanthropy to research Batten disease.

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Diabetes: Dean Kenneth S. Polonsky, MD, among an elite group of experts invited to contribute articles to the New England Journal of Medicine.

Departments Letter from the Dean

Pritzker News

Midway News

24-25 Images from Day of Service and Reflection

and White Coat Ceremony

2 The promise for education and research at the new hospital 26

Pritzker Poetry Contest

4 Research targets toxoplasmosis

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Named professorship to honor Janet D. Rowley, MD

5 Biobanks and ethical obligations

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Pritzker students recognized for excellence

3 Bucksbaum Institute names Master Clinician, 2012 Scholars

7 EMR and bedside manners

Fall 2012 Volume 65, No. 2 A publication of the University of Chicago Medicine and Biological Sciences Division. Medicine on the Midway is published for friends, alumni and faculty of the University of Chicago Medicine, Biological Sciences Division and the Pritzker School of Medicine.

University of Chicago Pritzker School of Medicine and Biological Sciences Executive Leadership Kenneth S. Polonsky, MD, Dean of the University of Chicago Biological Sciences Division and the Pritzker School of Medicine, and executive vice president for Medical Affairs for the University of Chicago T. Conrad Gilliam, PhD, dean for research and graduate education, Biological Sciences Division Sharon O’Keefe, president of the University of Chicago Medical Center Holly J. Humphrey, MD’83, dean for medical education, Pritzker School of Medicine

uchospitals.edu/midway

Editorial Committee Chair Chris Albanis, AB’96, MD’00 Lampis Anagnostopoulos, SB’57, MD’61 Arnold Calica, SM’61, MD’75 Melina Hale, PhD’98 Noah Schwartz, MS1 Jerrold Seckler, MD’68 Coleman Seskind, AB’55, SB’56, SM/MD’59 Madeleine Shapiro, MS3 Jack Stockert, AB’05, MBA’10, MD’10 Editor Ginny Lee-Herrmann

Assistant Editor Anna Madrzyk

Email us at momedit@uchospitals.edu Write us at Editor, Medicine on the Midway The University of Chicago Medicine 950 E. 61st St., WSSC 334 Chicago, IL 60637

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Class Notes: Hear from your classmates, near and far.

31-32 In Memoriam

Professor Emeritus: Ernest Page, MD, 1927-2012 Faculty: Donald Liu, MD, PhD, 1962-2012 Charles E. Metz, PhD, 1942-2012

33 Memorial held on campus to remember

Joseph B. Kirsner, MD, PhD

Editorial Contributors Kevin Barrett John Easton Caroline Kraft Linda Lepp Photo Contributors David Christopher Megan Doherty Boshiun Lai Jean Lachat Bruce Powell

Anna Madrzyk Ellen McGrew Heather Mendelson Brooke E. O’Neill

Stephen Phillips Gretchen Rubin Anita Slomski Matt Wood

Thomas Rossiter (Rafael Viñoly Architects) Medical & Biological Sciences Alumni Association Pritzker School of Medicine Archives University of Chicago Library Special Collections Research Center

Design Stacy Sweat Designs

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O u r n e w h o sp i t a l

Midway News

The promise for education and research at the Center for Care and Discovery John C. Alverdy, MD, the Sara and Harold Lincoln Thompson Professor of Surgery, director of the Center for the Surgical Treatment of Obesity and director of Minimally Invasive Surgery at the University of Chicago Medicine, talks about the Center for Care and Discovery, set to open in early 2013.

How will the new hospital impact medical education?

Our operating rooms are going to be fully integrated with a level of connectivity and technology that will enable the surgeon to be a more effective educator at the point of and throughout the entire process of operating on the patient. The promise of the new operating suites is to embed educational content throughout this enabling technology, to take advantage of the high-tech, high-visibility atmosphere.

How will the new hospital help study and improve the doctor-patient relationship?

It is not only that it’s a brand new, spacious hospital designed with great connectivity and beautiful spaces for people to talk to patients, but that it is at the University of Chicago. It’s on the campus of the University of Chicago, it’s adjacent to the Gordon Center for Integrative Science and the Knapp Center for Biomedical Discovery.

Photo by Megan Doherty

John C. Alverdy, MD, talks about the promise of the new, 10-story hospital.

Courtesy Rafael ViÑoly Architects, ©Thomas Rossiter

The Center for Care and Discovery, with its showcase Sky Lobby on the seventh floor, opens in early 2013 in the heart of the University of Chicago medical campus.

It’s the placement of this state-of-the-art facility on a campus where the humanities are so strong, where the Law School is so strong — our medical school, the basic sciences are so strong. It’s a place where really motivated scholars are interested in the fundamental questions of human behavior, how biology governs that behavior, and how doctors, on a very personal and emotional level, can affect human health beyond their knowledge and technical skills. These things all come together in one place. This is the ultimate promise of the Center for Care and Discovery.

How will the new hospital impact the multidisciplinary approach to medicine?

One of the greatest promises of the Center for Care and Discovery, beyond its steel, cement and wires, is to be able to study the sociological and health impact of the multidisciplinary approach. It is not enough to simply enable connectivity between disciplines but rather to study how those connections reliably predict the best outcome within the doctor-patient relationship. All these instruments — iPads, Skype — are nothing more than an extension of a human neural network. We need to understand how that network can be used most effectively so the patient feels that they have a more intimate relationship with their doctor, their health care team and the health care network in general.

The Center for Care and Discovery The University of Chicago Medicine’s new 1.2 million-

Courtesy Rafael ViÑoly Architects, ©Thomas Rossiter

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square-foot hospital, set to open in early 2013, has been named the Center for Care and Discovery, underscoring the commitment to innovative medical research and patient-centered care. “It’s not just a new hospital. We chose ‘Center for Care and Discovery’ because it will transform how we care for

all patients, using leading-edge technology and innovative research to deliver advanced clinical treatments in a setting that offers a superior healing environment,” said Sharon O’Keefe, president of the University of Chicago Medical Center. The Center for Care and Discovery is strategically located near the Gordon Center for Integrative Science and the Knapp

THE University of Chicago Medicine and Biological Sciences Division

Center for Biomedical Discovery, two world-class research facilities that unite scientists from the biological and physical sciences who continually strive to translate fundamental scientific discoveries into better care for patients. The $700 million, 10-story facility will serve as the new core of the University of Chicago Medicine campus.

C l i n i c a l e x c e ll e n c e

T r a n sl a t i o n a l r e s e a r ch

Master class Bucksbaum Institute Names Master Clinician, 2012 Scholars

The Bucksbaum Institute for Clinical Excellence, a new initiative aimed at improving the doctor-patient relationship and communication in medicine, has appointed Ross Milner, MD, associate professor of surgery and co-director of the Center for Aortic Diseases, its first Bucksbaum Master Clinician. During his three-year term, Milner will serve as a role model for the student and faculty scholars.

“Dr. Milner was chosen for his clinical skills and judgment, his exemplary doctor-patient relationships and his teaching skills with trainees and colleagues,” said Mark Siegler, MD, the Lindy Bergman Distinguished Service Professor of Medicine and Surgery, founding director of the University of Chicago’s MacLean Center for Clinical Medical Ethics, and executive director of the Bucksbaum Institute.

The Bucksbaum Institute also announced the selection of the 2012 Junior Faculty Scholars and Student Scholars.

Junior Faculty Scholars receive funding for advanced scholarship and are chosen for their dedication to patient care, collaborative decisionmaking and clinical experience. Appointed this year are Nita Karnik Lee, MD, MPH, and John Yoon, MD. Lee, a specialist in gynecologic oncology, will examine the personal networks of AfricanAmerican women to gain a better understanding of behavior and attitudes regarding cancer, obesity and lifestyle changes. Yoon, an academic hospitalist and medical educator, will study the role of virtue in establishing good doctor-patient relationships. Lee and Yoon join 2011 Junior Faculty Scholars Monica Peek, MD, MPH, and Alexander Langerman, MD. Student Scholars selected in 2012 are Annie Lauer, MS2, Elizabeth Rhinesmith, MS2, and Robert Sanchez, MS2. They join Jasmine Taylor, MS3, Liese Pruitt, MS3, and Alexander Ruby, MS3, named in 2011. The scholarship supports these students with tuition and fees for the second through fourth years of medical school.

The Bucksbaum Institute for Clinical Excellence was established in September 2011 with a gift of $42 million from the Matthew and Carolyn Bucksbaum Family Foundation. uchospitals.edu/midway

Master Clinician

Ross Milner, MD, associate professor of surgery and codirector of the Center for Aortic Diseases

Junior Faculty Scholars

Nita Karnik Lee, MD , MPH

John Yoon, MD

Study reveals the flip-side benefit of grapefruit juice It began with a mixed drink. In 1989, some pharmacists wanted to study the effects of alcohol consumption on a calcium-channel blocker. To mask the flavor of alcohol, they mixed it with grapefruit juice. The alcohol, they discovered, made no difference. Yet blood pressures plummeted and drug levels increased dramatically, whether test subjects got the alcohol or not. This led to the discovery that this semi-sour citrus supplement could increase blood levels of some drugs, which led to the little stickers often pasted onto pill bottles proclaiming: “Do not take with grapefruit juice.” Now researchers at the University of Chicago Medicine have found a way to exploit the flip side — deliberately using a citrus concoction to increase levels of certain, often expensive, medications. In a study published in Clinical Cancer Research, they show that 8 ounces of grapefruit juice a day can slow the body’s metabolism of a drug called sirolimus, which has been approved for transplant patients but may also help many people with cancer. Patients who drink a glass a day of grapefruit juice increased their sirolimus levels by 350 percent. A drug called ketoconazole that also slows drug metabolism increased sirolimus levels by 500 percent. The combination could help patients avoid gastrointestinal side effects associated with high doses of sirolimus and reduce the cost of taking this medication. “Grapefruit juice, and drugs with a similar mechanism, can significantly increase blood levels of many drugs,” said study director Ezra Cohen, MD, associate professor of medicine and associate director for education at the University of Chicago Medicine Comprehensive Cancer Center. “This has long been considered an overdose hazard. Instead, we wanted to see if grapefruit juice can be used in a controlled fashion to increase the availability and efficacy of sirolimus.”

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Midway News

T a r g e t i n g t o x o pl a sm o s i s

T h e V F o u n d at i o n

Antisense approach promising for treatment of parasitic infections

Wu wins V grant

A targeted approach to treating toxoplasmosis, a parasitic disease, shows early promise in test-tube and animal studies, where it prevented the parasites from making selected proteins. When tested in newly infected mice, it reduced the number of viable parasites by more than 90 percent, researchers from the University of Chicago Medicine reported in the Proceedings of the National Academy of Sciences in August.

This precisely focused therapy combines short strands of “antisense” nucleic acidCourtesy of Boshiun Lai like material with a small peptide that Toxoplasma gondii tachyzoites (the rapidly can transport those strands through cell growing life cycle stage) in tissue culture. membranes and into parasites, where they The tachyzoites are green. The plant-like disrupt genetic signals. A similar approach, plastid organelle is yellow orange. The host cell nucleus is blue. Peptide morpholino published in April, showed comparable (PPMO) reduces an enzyme in this plant-like promise as a treatment for the parasites that organelle, stopping replication. cause malaria. “This was proof of concept,” said study author Rima McLeod, MD, professor of ophthalmology and visual science and pediatrics, as well as medical director of the University of Chicago Medicine Toxoplasmosis Center. “We were able to cross multiple membranes, to insert the antisense strands into parasites living within cells and prevent them from making several different proteins. We now think we can shut down any of this parasite’s genes.”

The same approach is currently being tested in drug-eluting stents, as a treatment for bacterial or viral infections, including Ebola, and in patients with Duchenne muscular dystrophy, where it can block production of the defective segment of a dysfunctional gene. The parasite McLeod and colleagues focused on, Toxoplasma gondii, is “probably the most common parasitic infection in the world,” she said. The first author of the study is undergraduate honors biology student Boshiun Lai.

The V Foundation for Cancer Research, one of the nation’s leading cancer research funding organizations, has selected Xiaoyang Wu, PhD, an assistant professor in the Ben May Department for Cancer Research, as a recipient of a two-year, $200,000 V Scholar grant for 2012. These awards, given to 17 outstanding young researchers in 14 states, fund “rising star” physicians and scientists as they begin their careers in cancer research. V Scholars are selected through a competitive process conducted by the foundation’s scientific advisory board. The awards fund specific research conducted by young investigators, providing much-needed resources Xiaoyang Wu, PhD to help them advance their cutting-edge research. Wu studies the role of the Wnt signaling pathway in colorectal cancer.

Mutations of key genes in this pathway are found in virtually all patients with colorectal cancer and are thought to be the critical initiating step in malignant transformation. The V Foundation for Cancer Research was founded in 1993 by ESPN and the late Jim Valvano, legendary North Carolina State basketball coach and ESPN commentator. Since 1993, the foundation has funded more than $100 million in cancer research grants nationwide.

M e n t a l h e a lth a n d g e n e t i cs

Foundation supports next-generation mental health research The Brain & Behavior Research Foundation has awarded Young Investigator grants for up to $60,000 to two researchers from the University of Chicago Department of Psychiatry and Behavioral Neuroscience.

These grants support projects that could lead to breakthroughs in understanding and treating mental illness. The grants, accord-

ing to the foundation, are “among the most competitive in biomedical research.” On average, grantees receive 11 to 19 times their original grant amount in subsequent funding.

Postdoctoral scholar Ney Alliey-Rodriguez, MD, will look for an association between bipolar disorder and copy-number variants in the genomes of those with the disorder.

Assistant Professor Stephanie Dulawa, PhD, will look at the impact of epigenetic alterations in a gene called CALCA on depression-related behavior in mice exposed to prenatal stress.

Items written by John Easton

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The University of Chicago Medicine and Biological Sciences Division

R e s e a r ch a n d e th i cs

Uncertain attitudes about biobank dividends

By Matt Wood

“We know this from every biobank study, in the United States and internationally, that every participant says they want information back.”

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o biobank researchers have an ethical obligation to tell donors of blood and tissue samples if they discover crucial information about a disease from one of the samples?

Through biobanks, scientists can access a collection of blood and tissue samples and health data to conduct large-scale research to try to understand the genetic underpinnings of disease. People donate samples to biobanks for the greater good, and the health records linked to these samples are scrubbed of any identifying information that could connect them to a specific person. But if that research finds crucial information about a disease, what is the researcher’s ethical obligation to communicate those results back to the biobank participants?

Lainie Friedman Ross, MD, PhD, the Carolyn and Matthew Bucksbaum Professor of Clinical Medical Ethics at the University of Chicago Medicine, led a yearlong study of 45 African-American adults who receive care at two different health care facilities on the South Side of Chicago, to assess their attitudes about these ethical questions. She said that for the most part, the study results were not surprising.

“We know this from every biobank study, in the United States and internationally, that every participant says they want information back,” she said. Despite efforts to educate the group uchospitals.edu/midway

Lainie Friedman Ross, MD, PhD

on the difficulty and ambiguity of explaining what their results mean, their general attitudes changed very little during the study.

The most interesting responses came when participants were asked what information they wanted to know about their children — basically, they wanted to know everything they wanted to know about themselves. The problem is that research might discover information that isn’t relevant to a person until adulthood. Does a parent have a right to know everything about the health issues that their children may experience as adults? At what point does a parent’s right to know stop and a child’s right to privacy begin?

“We are more protective of children, in part because there is some information you as an adult might not want your parents to

have known about you,” Ross said.

During this project, Ross and her colleagues also encountered a common misunderstanding about basic research called “therapeutic misconception.”

This is the mistaken belief by research subjects that any study they participate in will have a direct medical benefit. Ross said this happens because, for most people, their only interaction with physicians is in the context of traditional clinical care.

“People trust their doctor and believe he would only do things that are going to benefit them,” she said. “They don’t understand he’s wearing another hat as a researcher.”

As research progresses and technology improves, initial findings could be reversed or rendered invalid. Ross said the participants in this project wanted that information anyway

because they didn’t want to believe that medicine didn’t have an answer. “There is this belief that medicine can do everything and will do everything,” she said.

Ross said she was encouraged by the work overall. “The whole experience of really thinking and learning about these issues was viewed very positively by the community participants,” she said. “You could see that the average American is really interested in this stuff.”

Some of the study participants even offered to give samples to biobanks at the University of Chicago before they left. While that wasn’t what Ross had in mind when she started this project, any study that can make participants more interested in science and volunteer an ounce of blood is definitely worth the effort.

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Midway News

State-of-theart approach to keeping children calm in the ER

By Matt Wood

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trip to the emergency room can be a scary experience for a kid. Unfortunately, often the only way to keep an upset, frightened child still long enough to put in stitches or set a broken bone is to sedate them or use physical restraint. In the pediatric emergency department at the University of Chicago Medicine Comer Children’s Hospital, physicians and child life specialists are experimenting with a new way to keep kids calm and make their visit a little less scary: iPads.

Alisa McQueen, MD, assistant professor of pediatrics and director of the pediatric emergency medicine fellowship program, said children often don’t understand what’s going on in the ER. “It’s not their fault. They’re just too developmentally young and they can’t process it. So they end up kicking and screaming and thrashing, and it’s no fun for anybody,” she said.

Emergency department physicians and nurses have all kinds of tricks for distracting children from scary procedures, from stuffed animals to games, music and videos, but success often depends on having the right toy at the right time. McQueen said that when Chelsea Cress, MS, CCLS, a child life specialist from the Child Life and Family Education Program, started experimenting with using an iPad to entertain kids, they could tell that they were on to something.

“If I was going to do a procedure with a kid before the iPad, I would have had a portable DVD player, a light spinner, bubbles, all of these things that I would carry around in a bucket,” Cress said. “The procedure is happening whether I’m ready or not. If

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I didn’t have the right thing with me, by the time I went to get it, it might have been too late. Having the iPad is like having my box of tricks all in one.”

McQueen said that besides lowering the stress levels in the emergency room, the iPads also help with the workload.

Sedation requires extra nurses and physicians who could be treating other patients, and restraining an unruly child might mean two or three more people in the room. But if a child life specialist can distract a kid with a game of Angry Birds, those people can go do something else.

Anything to take the edge off the emergency room experience for families helps. “Going to the ER in general is a stressful experience no Alisa McQueen, MD matter what, especially if your kid’s been hurt,” McQueen said. “If we can alleviate that a little bit it makes the whole experience nicer.”

The potential uses for iPads in a children’s hospital are as limitless as the combinations of apps, games, music and videos you can put on them. Cress said she plans to keep pushing their limits at the University of Chicago Medicine.

“We know that kids can use their imaginations to take them to a place that most grownups can’t,” she said. “Using the iPad really helps them to cope with procedures better and forget about what’s happening at the hospital.”

THE University of Chicago Medicine and Biological Sciences Division

Teaching the bedside/desktop manner

“The people who already had good communication skills actually did well. The computer amplified their skills.”

Maria Alcocer Alkureishi, MD

By Matt Wood

Wei Wei Lee, MD

Their tips center on keeping attention directed toward the patient and not the screen. For example: • Engage with the patient directly to begin the exam, and don’t sit down immediately to type.

• Take a few notes that can be filled in later instead of trying to record every last detail during the visit.

• Position the lower body toward the patient while using the computer, and turn the screen to share visual information like charts and graphs.

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onsider this scenario. A physician enters an exam room, and instead of asking the patient, “What brings you here?” and speaking face to face, he sits down at the computer and starts peppering the patient with questions, typing away furiously.

Electronic medical records are invaluable tools, but the presence of a computer in the exam room can create awkward situations with patients. To fix this modern-day breakdown of communication, two fellows from the University of Chicago Medicine are developing a curriculum to teach medical students how to use electronic medical records effectively while keeping their focus on the patient.

Maria Alcocer Alkureishi, MD, assistant professor of pediatrics, and Wei Wei Lee, MD, assistant professor of medicine, first noticed how the presence of computers in the exam room complicated the dynamic between physicians and patients during their clinical rotations.

Some physicians adapted to the new tools and were able to fit them into exams naturally, while others struggled.

“We’ve seen it go well and not go well with colleagues,” said Alkureishi. “The people who already had good communication skills actually did well. The computer amplified their skills.

For the people who did poorly without the

computer, introducing it to the exam room just made things worse.”

Seeing these struggles made them want to address this problem in a group project for their fellowship. The curriculum they propose would incorporate a variety of teaching tools to show students how to engage a patient with their electronic medical records on a computer screen and provide opportunities to observe and critique each other as they practice their interactions.

Lee said she envisions a longitudinal curriculum, introduced in phases throughout a medical student’s education as the student’s skills develop. “The earlier we can get them to think about patient-centered electronic medical record communication, the easier it will be for them as they become practicing physicians,” she said.

Computers and mobile devices have altered all of our personal interactions, not just at the doctor’s office. Alkureishi said we should apply the same rules there that we do at home to keep our teenagers from texting during family dinner.

“You have to know when to turn it off and when to use it,” she said. “I think it’s a larger issue of how you use all these things while still being respectful, engaging and compassionate.

You have to acknowledge its presence with the patient, but don’t let it dominate what’s going on in that room.”

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Pharmacogenomics

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The University of Chicago Medicine and Biological Sciences Division

The New Rx

How University of Chicago researchers are aiming to translate genetic findings into personalized medicine

By Brooke E. O’Neill

atients know the warning: “Contact your doctor immediately if you experience any of the following symptoms.” It’s the standard prescription-drug language, typically accompanied by a discomfiting list of possible side effects qualified by terms like “in rare cases.”

Take the cholesterol-lowering simvastatin, the country’s second most-prescribed medication. Roughly 1 percent to 2 percent of those who take it develop myopathy, a painful muscle injury that can lead to kidney complications and even death. And too high a dose of the blood thinner warfarin can lead to internal bleeding, while too little may result in a blood clot. “The way we practice medicine now is a bit antiquated, in that it’s primarily trial and error,” said University of Chicago Medicine hematologist-oncologist Peter H. O’Donnell, MD’03, assistant professor of medicine.

“In a sense, you’re treating every patient with the same disease in the same way. We can do better than that.”

O’Donnell is on a team, led by hematologist-oncologist Mark J. Ratain, MD, that is trying to take medicine to the next level.

“Drugs can do more harm than good,” said Ratain, the Leon O. Jacobson Professor of Medicine and director of the University of Chicago Medicine Center for Personalized Therapeutics (CPT). Recipient of a 2011 Translational Research Professorship from the American Society for Clinical Oncology’s Conquer Cancer Foundation, Ratain has written extensively on individualizing cancer care based on genotype.

Continued on page 10

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Continued from page 9

“What we’re moving toward,” he explained, “is tailoring drug therapies to maximize the benefit and minimize the risk.”

“It’s really the next frontier of pharmacology,” said O’Donnell, who trained under Ratain in the University of Chicago’s fellowship in clinical pharmacology and pharmacogenomics, one of the few such programs in the country.

With the recent addition of Yusuke Nakamura, MD, PhD, considered one of the world’s top geneticists, as the center’s deputy director and an ambitious project to make genetic testing a routine part of the doctor’s visit, the center is leading the charge to translate pharmacogenomics from the lab into the clinic. Ratain’s CPT team also includes associate directors Nancy J. Cox, PhD, professor of human genetics, and M. Eileen Dolan, PhD, professor of medicine; and assistant director Michael Maitland, MD, PhD, assistant professor of medicine.

From Pharmacology to Pharmacogenomics

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hen the human genome was first sequenced a decade ago, it opened up the promise of personalized medicine like nothing before it. “As genomics became more accessible, we got into looking at variability at a genetic level,” said Ratain. The ability to peer inside an individual’s DNA quickly gave birth to pharmacogenomics, the study of how someone’s genotype can influence his or her drug response. As researchers have discovered, small differences in pieces of one’s genetic code can predict whether someone is likely to benefit from a medication — or suffer dangerous side effects.

Unlike disease-risk genetics, which focuses on whether individuals’ genotypes make them more susceptible to developing, say, breast cancer or Alzheimer’s, pharmacogenomics concentrates exclusively on genetic markers that interact with and respond to medications.

The Center for Personalized Therapeutics’ flagship pharmacogenomics initiative is known as The 1200 Patients Project and is the largest-scale clinical study of its type to date. The study, said O’Donnell, is

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Photo by David Christopher

The University of Chicago Medicine Center for Personalized Therapeutics team includes R. Stephanie Huang, PhD, left, Peter H. O’Donnell, MD’03, Director Mark J. Ratain, MD, and Mark Maitland, MD, PhD. Ratain’s CPT team also includes Deputy Director Yusuke Nakamura, MD, PhD, and Associate Directors Nancy J. Cox, PhD, professor of human genetics, and M. Eileen Dolan, PhD, professor of medicine.

designed to pinpoint the most effective ways to incorporate published pharmacogenomic data into medical decisionmaking. Investigators are collecting DNA samples Photo by Bruce Powell f ro m 1 , 2 0 0 p at i e nt Yusuke Nakamura, participants. These are MD, PhD being tested for hundreds of DNA markers potentially impacting drug responses or side effects and then a personalized pharmacogenomics profile is created for each participant. That information is then immediately accessible to the patients’ physicians through a secured informatics database.

“This is really the first broad approach at implementation,” explained Ratain. The project is aimed at laying the groundwork for more tailored care, lowering medical costs and improving outcomes. It meets a particularly pressing need in oncology, where, as Ratain and O’Donnell wrote in Molecular Oncology this past January, the window between therapeutic and toxic for drugs “is often narrow, the need for favorable drug response is often acute and the consequences of drug toxicity can be life-threatening.”

Ratain, for example, got his start in the field studying irinotecan, a drug used to fight colorectal cancer. Irinotecan causes

The University of Chicago Medicine and Biological Sciences Division

severe diarrhea and neutropenia, a decrease of white blood cells, in 20 percent to 35 percent of patients. In the early 2000s, Ratain and colleagues discovered that patients with a common genetic variation in their UGT1A1 enzyme were most likely to suffer the deleterious effects. Their findings led directly to the Food and Drug Administration’s 2004 decision mandating that the label for irinotecan be amended with pharmacogenomic data alerting physicians to the increased risk. Ratain’s team also developed and patented a test that determines which patients are likely to have a serious adverse reaction to the drug.

As part of their ongoing research, Ratain and O’Donnell are actively seeking out genetic biomarkers that shed light on how cancer patients will respond to different treatments. A recent University of Chicago study identified single nucleotide polymorphisms (SNPs), sections of variation in DNA’s building blocks, that play a role in predicting head and neck cancer patients’ response to platinum-based chemotherapy. The study, by O’Donnell; head and neck cancer specialists Everett E. Vokes, MD, physician-in-chief and chair of the Department of Medicine, and Ezra Cohen, MD; and several investigators from the CPT team and Department of Human Genetics, was published in the May 2011 Translational Research.

Cancer-fighting drugs are just one group among hundreds of medications that have been linked to genetic biomarkers during the past decade. Warfarin, one of the most researched drugs in the field, is another.

Patients with a particular genetic variation will eliminate the anticoagulant more slowly from their system and, thus, require a lower dosage. There’s even a commercially available test to find out whether a patient falls into that group, noted O’Donnell.

So why aren’t more physicians using genetic screening before prescribing such drugs?

Overcoming Obstacles

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ven though genetic testing has existed for more than a decade (and become increasingly inexpensive), roadblocks have largely kept it out of the clinic. Among the most significant barriers: lack of knowledge and lack of accessibility.

“There is tremendous potential for this information to improve patient care. My colleagues at UChicago have recognized that one of the bigger hurdles is just to get clinicians familiar with information that already is available,” Maitland said.

“Because this field is still relatively new,” O’Donnell said, “a lot of physicians aren’t familiar with how to use pharmacogenomic information.” A 2009 Medco Health Solutions survey of more than 10,000 U.S. physicians found that 98 percent agreed with the central premise that patients’ genetic makeup influences drug therapy, but a mere 10 percent felt sufficiently informed about pharmacogenomic testing. Only 13 percent reported ordering a genetic test in the prior six months.

“Even if a physician orders the test and wants to consider it, they might not know what to do with the result,” O’Donnell said. “So a major part of The 1200 Patients Project is really trying to translate this information into something clinically meaningful.”

There’s also the practical issue of expediency. Right now, said O’Donnell, “even if you do the test, it could be days — even weeks — before you get results. But your patient needs a prescription now. Waiting on a genetic test isn’t practical.”

That’s why The 1200 Patients Project emphasizes pre-emptive testing. When a uchospitals.edu/midway

Bringing together a patient’s genetic test results and relating those to clinical, published knowledge about pharmacogenomic relevance, the portal gives physicians instant access to drug risks or benefits specific to an individual’s genotype.

patient enrolls in the study, he or she gives a one-time DNA sample via a simple blood test. The sample is analyzed for hundreds of gene sections known to influence either positive drug responses or negative side effects, and then the patient’s information is stored in the secured database.

A physician considering prescribing simvastatin for high cholesterol, for example, might consult the system and find out the patient has a genotype with an increased risk for developing simvastatininduced myopathy. Knowing that, the physician could choose from other cholesterol-lowering drugs to treat that particular individual.

In addition to highlighting drug risks, pharmacogenomics can help identify drug benefits. For example, a physician might use genetic testing and discover that someone with heart disease carries a marker predicted to respond well to a specific type of beta-blocker.

To create the informatics database, O’Donnell and his team conducted an

extensive review of a decade’s worth of pharmacogenomics findings, filtering out all but those backed up by the most rigorously designed studies. While a handful of medical centers around the country are doing similar projects, the University of Chicago’s is the widest ranging, assessing patients for literally hundreds of possible drug interactions.

“Our scope and our size are unique,” O’Donnell told Nature Medicine in November. The project encompasses many drugs commonly prescribed in the primary care setting, including various medications for hypertension and cholesterol. On the roster: hydrochlorothiazide, atorvastatin, amlodipine, simvastatin and others.

Open to any adult receiving ongoing care at the University of Chicago Medicine, the multiyear study has already enrolled more than half of its projected 1,200 participants since launching in January 2011. With a pilot group of 12 physicians whose diverse specialties include cardiology, primary care and oncology, the project, O’Donnell said, “really spreads across all disciplines, all drug classes, all diseases.”

The idea, added Ratain, “is to do this across the medical center. That’s our mission.”

The initiative already has made significant strides toward personalized treatments through its custom-designed informatics. Bringing together a patient’s genetic test results and relating those to clinical, published knowledge about pharmacogenomic relevance, explained O’Donnell, the portal gives physicians instant access to drug risks or benefits specific to an individual’s genotype.

“If everyone could be tested up front for these genetic markers,” said O’Donnell, “then physicians could reference them immediately and use them to inform prescriptions.

What we’ve done, essentially, is encapsulate patient-specific pharmacogenomic information in a 30-second summary that translates the genetic findings into what they mean clinically. We’ve included all that information in the system.”

The hope is that by providing busy clinicians with this information quickly and concisely, their patients will begin to see direct benefits from this genetic research.

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Poison in Cancer researcher works to reverse decades of damage in Bangladesh

By Brooke E. O’Neill

There are tragedies we might have seen coming: the reckless driver who crashes into a median, the drug addict who overdoses.

Then there are those that blindside us, like a well-meaning government accidentally poisoning its citizens while trying to provide fresh drinking water.

That’s precisely what happened in Bangladesh, where some 5 million hand-pumped wells installed by the government and the United Nations in the 1960s and 1970s were later found to contain groundwater contaminated with arsenic, a human carcinogen.

A naturally occurring chemical, arsenic is generally odorless and tasteless, making it all the more insidious. By the 1990s, Bangladesh’s previously high mortality rates from waterborne pathogens had been replaced by an epidemic of arsenic-related skin lesions.

The crisis has struck as much as a third of 12

Staff working with Habibul Ahsan, MD, MMedSc, conduct a community health education session, above, to increase awareness of the arsenic problem and its health effects and potential avenues of prevention.

the country’s population, with devastating long-term effects. “Once you get critically exposed for 20 or 30 years, even if you get clean water, your risk of arsenic-induced diseases will remain high for the rest of your life,” said University of Chicago Medicine epidemiologist Habibul Ahsan, MD, MMedSc, Louis Block Professor of Health Studies, Human Genetics and Medicine.

Among the associated diseases: skin, lung, bladder, liver, kidney and prostate cancers.

A Bangladeshi himself, Ahsan has spent

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the past 15 years researching the public health fallout — and searching for solutions.

In 2000, he launched the Health Effects of Arsenic Longitudinal Study (HEALS) to test arsenic levels in wells and track the health of 12,000 men and women in the country’s Araihazar region, a rural area heavily afflicted by contamination.

The findings, published in the June 2010 Lancet, were sobering. Individuals with high levels of arsenic ingestion, measured through urine samples, were 70 percent

water the

Photos courtesy of Habibul Ahsan, MD, MMedSc

The clinic building that Dr. Ahsan’s group established to provide free primary health care to our research participants and their immediate family members

more likely to die from chronic disease than those not exposed. Even moderate arsenic intake increased one’s risk by 20 percent to 30 percent.

The average concentration among study participants? Roughly 27 times the recommended safe levels.

In search of antidotes “As many as one-fifth of all deaths in this population could be attributed to arsenic,” said Ahsan, director of the University of uchospitals.edu/midway

A group of field staff with Dr. Ahsan, middle front, in front of the clinic building.

Chicago Medicine’s Center for Cancer Epidemiology and Prevention and associate director for population research at the Comprehensive Cancer Center. Black lesions on the hands and feet are one of the telltale exposure signs, later morphing into festering sores and gangrene. Reproductive issues, heart disease and cancer often follow.

Not everyone suffers equally, however.

“Just like people who smoke don’t all have the same effects, people exposed to arsenic don’t all exhibit the same outcome,” said

Ahsan, who studies how environmental and genetic factors influence disease progression and prevention. The idea is to pinpoint specific DNA markers, nutritional elements or other lifestyle variables that make a person more or less susceptible to arsenic’s effects, and then design preventative measures accordingly.

To better understand the hows and whys of arsenic poisoning, Ahsan and his team expanded their longitudinal study to 35,000 Continued on page 14 MEDICINE ON THE MIDWAY

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Continued from page 13

men and women. They set up a medical clinic at Araizahar’s center to collect blood, urine and other biomedical samples, as well as provide local residents the preventive and critical medical care they otherwise lacked.

At any given time, the clinic and the field operation employ anywhere from 250 to 300 physicians and research staff.

“The clinic serves a dual purpose,” said Ahsan, who established the center in 2001.

“It not only gives the local people access to quality health care, it allows us to detect diseases we need to track in order to understand the consequences of arsenic and know which ones we can prevent by intervention.”

Among their most promising discoveries is the finding that arsenic-related skin cancers often involve biological pathways that can be altered by selenium and antioxidant supplements like vitamin E. Associated with lower risk of skin lesions, such nutritional supplements may reverse the dangerous molecular anomalies that arsenic can create.

To test the hypothesis, Ahsan is overseeing one of the largest clinical trials ever organized among a rural population of a developing country. Participants take a daily dose of 200 micrograms selenium and 100 milligrams vitamin E, a nontoxic amount greater than what an individual can get from a regular diet. Researchers are tracking subjects for a decade to see if their cancer risk decreases.

With 7,000 Bangladeshis recruited and promising results so far, the ongoing study is the most comprehensive preventative attempt ever to address a high-risk population for environmentally induced cancer. “If we find that these supplements minimize risk,” Ahsan said, “they could be potentially adopted for widespread public health implementation.”

Inexpensive and easy to access, therapies like selenium and vitamin E are well-suited to a developing country like Bangladesh, where securing biomedical resources can be particularly challenging.

Inside the double helix Even if treatments like vitamin E or selenium prove effective, however, distributing them among tens of millions of people chronically exposed to arsenic is no small 14

Research staff in the field laboratory process blood samples collected from study participants. Habibul Ahsan, MD’s group is conducting one of the largest clinical trials ever organized in a rural population of a developing country, to determine if some subgroups of Bangladeshis are more prone to arsenic’s damaging effects than others.

feat. That’s why Ahsan’s team is using gene studies to determine if some subgroups of individuals are more prone to arsenic’s ill effects than others. “What that means,” he said, “is we look into the variation across the human genome and see whether any of those variants make a difference in cancer risk.”

In a study published in February’s PLoS Genetics, Ahsan and several Department of Health Studies colleagues found that a genetic variant known as rs9527 is associated with higher risk of skin lesions from ingested arsenic. Called a genome-wide association study, the project was the first large-scale genomic analysis of arsenic metabolism and toxicity. The findings pave the way for designing new treatments and therapies. At the most basic level, simply knowing an individual has a genetic susceptibility alerts physicians to monitor him or her more closely for arsenic-related disease and prescribe preventatives, such as vitamin supplements.

With several research projects ongoing, Ahsan, who also studies breast cancer epidemiology and risk factors, favors a multifaceted approach. “We are trying to identify by different methods — clinical trial, genome scan — all possible avenues of modifying disease risk, so they can be

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adopted to a large-scale country policy for biomedical intervention.”

One of the greatest challenges, he added, is getting developing countries like Bangladesh to recognize the need for such interventions. Overwhelmed with such “completely preventable infectious diseases” as dengue fever and malaria, many are focused on rooting out those killers and give scant attention to more chronic diseases. For Ahsan, who guest lectures on public health within the University of Chicago Division of Biological Sciences and supervises several doctoral students, it’s an issue shaping the future of global health policy.

“Cancer is not on the radar screen for developing countries,” Ahsan said. “But if you look at the number of lives lost because of cancer, heart disease, diabetes, more than three-fourths of those happen in poor countries.

“They may be able to overcome infectious disease mortality,” he warned, “but as their life expectancies increase, they will face an epidemic of cancer and heart disease for which they are completely unprepared.”

By tackling arsenic’s effects in Bangladesh now and raising the red flag around cancer, he hopes to prevent another homeland tragedy no one saw coming.

Diabetes: Two centuries of scientific advances tempered by two decades of societal setbacks

By John Easton

T

he year 1812 was full of historic events: French Emperor Napoleon Bonaparte invaded Russia, the United States declared war on the United Kingdom, and English author Charles Dickens was born. It was also the year when a humble Boston-based publication got its start, only to become the most widely read and respected medical journal in the world, with more than 600,000 readers in 177 countries.

As part of a celebration to mark its bicentennial, the New England Journal of Medicine has invited top experts in various fields to contribute to a series of 26 articles and essays to illustrate how far medicine has come along in those two centuries. Among articles in the October 4 issue is one chronicling “The Past 200 Years in Diabetes,” written by Kenneth S. Polonsky, MD, who is identified simply as being “from the Department of Medicine, University of Chicago.”

Although diabetes had been recognized for more than 3,000

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Although diabetes had been recognized for more than 3,000 years by 1812, “essentially nothing was known about the mechanisms responsible for the disease.” years by 1812, “essentially nothing was known about the mechanisms responsible for the disease,” writes Polonsky, executive vice president for Medical Affairs at the University of Chicago and Dean of the Biological Sciences Division and the Pritzker School of Medicine. “No effective treatment was available and diabetes was uniformly fatal within weeks to months.”

Since then, researchers have made enormous progress. Ten scientists received the Nobel Prize for work related to the disease. Insulin was hypothesized in 1910, discovered in 1921 and successfully tested in humans in 1922 — a series of events that “may be the most dramatic example of the rapid translation of discovery in basic science into a benefit for patients,” he writes.

Insulin serves as a flagship for the entire biological revolution. It was one of the first proteins for which the amino acid sequence was determined, the first hormone to have its three-dimensional crystal structure determined, the first hormone cloned and the first to be produced by recombinant DNA technology, the foundation for the biotech industry.

Unfortunately, while “there is much good news to report regarding diabetes” from the scientific viewpoint, Polonsky writes, “from a public health standpoint little progress has been made … and we are arguably worse off now than we were in 1812.”

Diabetes now affects 21 million people in the United States, nearly 27 percent of those over 65 years of age, at an estimated annual cost of $174

billion in 2007.

As physicians learned how to treat severe insulin deficiency, the common form of the disease in 1812, changes in diet and lifestyle, and the massive surge in obesity, have led to a worldwide epidemic of type 2 diabetes, which involves insulin resistance and impaired insulin secretion. As a result, diabetes has become “one of the most common and most serious medical conditions humankind has had to face,” he says.

Despite this epidemic, thanks to advances in immunology, the discovery of diabetes susceptibility genes and the identification of relevant molecular pathways and new gene targets, Polonsky remains optimistic that another breakthrough as dramatic as the discovery of insulin will occur.

“Timely prevention of this disease at the population level is essential,” Polonsky concludes.

“Lifestyle modification will undoubtedly play a key role,” he adds, but “more definitive solutions will depend on the ability of basic science to point prevention and treatment in new directions.”

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How a renowned scientist fell in love with the combination of ‘optical clarity, genetics and accessibility’ to study vertebrate development

Photo by Bruce Powell

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Zebrafish are easy to take care of and, because their embryos are transparent for the first few days of development, scientists can look directly inside to observe the process.

The magic of zebrafish

By Brooke E. O’Neill

t first glance, a zebrafish embryo doesn’t look like much. Barely 0.5 millimeters in diameter, it drifts lazily to the tank’s bottom, a tiny bubble seemingly suspended in serene inactivity.

Yet inside its clear covering is a well-oiled cellular machine hard at work. From just 45 minutes after fertilization occurs, cells start dividing every 15 minutes, quick enough to create a complete body blueprint within 24 hours. By day two, the embryo has transformed into a free-swimming larva.

“The female fish lays 100 to 200 eggs at a time, two or three times a week,” said Victoria Prince, PhD, University of Chicago organismal biology and anatomy professor, as she surveys several rows of carefully maintained tanks teeming with the silvery fish. In one corner sits an aquarium for hatching brine shrimp, a staple of the zebrafish diet. At any given time, she houses roughly 2,000 zebrafish in her Culver Hall laboratory. “They’re one of the easiest fish to take care of,” said Prince, a developmental biologist who also serves as associate dean and director of the Biological Sciences Division’s Office of Graduate Affairs.

They’re also one of the best models for

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shedding light on the murky process of how vertebrates — humans included — metamorphose from one-cell fertilized eggs into fully functioning adults. For nearly two decades, Prince has studied zebrafish to better understand how the primary body axis, or head-to-tail layout, develops with all the proper cell types and tissues in place.

Because the fish embryos are transparent their first few days, researchers can peer directly inside and observe the process.

“The way you get into the Prince lab is she gives you a dish of embryos and watches what you do,” recalled David Stafford, PhD’05, a former Prince graduate student who now is a postdoctoral fellow at the University of California,

Berkeley. “If you’re fascinated and they have to pull you away from the microscope, it’s probably going to work out pretty well. It was exactly the right choice of lab for me and a very fun place to learn how to do biology.”

“When we show students the embryos and they say, ‘That’s so cool,’ we know they’re developmental biologists,” said Prince with a laugh.

Prince’s own zebrafish observations focus mainly on two regions: the pancreas and the hindbrain. The first line of research illuminates how organisms keep their blood-sugar levels steady, while the second clarifies how neurons migrate and Continued on page 18

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Continued from page 17

build the circuits to regulate functions such as respiration and heartbeat. Slightly less close to humans than mice, but significantly closer than, say, fruit flies, zebrafish are a good model for understanding our own development. “While you can’t assume every step will be the same,” Prince said, “there’s a strong possibility.”

Producing the pancreas The pancreas is a perfect example. Located in the middle of the gut tube, this highly specialized tissue orchestrates blood-sugar levels and plays a key role in digestion. Because the zebrafish pancreas is well conserved in the mammalian system, its development has important implications for diabetes research — and potential cures. “If we can work out how an embryo builds a pancreas,” Prince explained, “we can potentially co-opt those same molecular pathways and use them in a dish on embryonic stem cells.”

Over the past decade, her team has made significant progress toward that vision. Back in 2002, she and Stafford discovered that the zebrafish pancreas can only develop with the help of a signaling molecule called retinoic acid (RA). “It was a very exciting time to be in the zebrafish field, as far as technique,” Stafford said, explaining how they used a recently developed tool to study the function of the gene responsible for RA synthesis by blocking its expression. Through a series of experiments, published in Current Biology, they determined that an absence of RA produced significant developmental defects, i.e., no pancreas.

The findings immediately caught the attention of stem-cell investigators around the globe. These days, said Prince, “pretty much any protocol that’s being used to try to generate pancreatic cells in a dish is using RA.” Those efforts, in turn, could ultimately be used to create transplantation therapies for diabetes, allowing diseased pancreatic cells to be replaced with functioning ones.

With those aims in mind, Prince’s lab continues to investigate how the RA molecule helps turn undifferentiated cells into pancreatic ones. “It’s not enough for us to say, ‘Oh, you need retinoic acid,’” she said. “We want to know what exactly 18

Photo by Bruce Powell

Victoria Prince, PhD, and her lab team study zebrafish to increase understanding of how the primary body axis develops with all the proper cell types and tissues in place. Here, Prince works with lab technician Anita Ng.

it does.” That means identifying the genes regulated by RA and pinpointing how they assemble a working pancreatic islet, the structure that responds to changing blood-sugar levels.

One such gene is mnx1. For the pancreas to operate properly, the pancreatic islets must maintain a specific balance of different cell types, including beta cells, which produce the hormone insulin, and alpha cells, which produce the hormone glucagon. These two hormones work in tandem to keep blood sugar steady.

In a study recently published in Development, Gokhan Dalgin, PhD, a postdoctoral fellow in Prince’s lab, found that when mnx1 function is blocked, the number of beta cells decreases and the number of alpha cells increases. The findings, Prince explained, suggest the gene “plays an important role in establishing the balance of different cell types.”

Eventually, Prince said, the pancreatic team hopes to assemble a comprehensive “gene regulatory network” that catalogs how genes like mnx1, signaling molecules such as RA and other cell factors take undifferentiated embryonic cells and “generate the right numbers in the right places of all cell types to make a functioning pancreas.”

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Building the brain stem The same precise cell placement required by the pancreas also must occur to create a working brain stem. “You really need to put the neurons in the right place to establish neural circuits,” Prince explained. Researchers have long known that neurons travel in a line when migrating to their final destination, but the precise mechanism of how this occurs is still somewhat mysterious.

Prince’s lab has started to unravel some of the complexity. “There’s been a model in this field for a long time, but with no actual proof behind it, that when neurons migrate maybe the first one in line is special,” she explained. This so-called “pioneer neuron” forges the course and others follow.

Recently, Sarah Wanner, PhD, a postdoctoral fellow in Prince’s lab, has been testing — and proving — the theory. Using a 2-photon microscope, Wanner targeted proposed pioneer neurons and ablated, or killed, them using a pulse of energy. Sure enough, when the suspected pioneer is no longer in commission, the other neurons don’t know where to go.

Part of the reason may be that there’s no longer a path to follow. Like Hansel dropping breadcrumbs, pioneer neurons normally leave axon trails that, researchers suspect, follower cells then move along.

Stoking intellectual passions

V

ictoria Prince also helps UChicago students embrace their own intellectual passions — in academia and beyond. As Associate Dean and Director of the Biological Sciences Division’s Office of Graduate Affairs, she has been instrumental in creating more opportunities for young researchers to explore a range of professions.

“It’s important that we recognize not all our trainees go on to academic careers,” said Prince, who has served as associate dean since June 2010. Acknowledging a tight academic job market and ongoing reductions in federal research funding, she noted, “We want to give our students the resources they need to learn about other career opportunities.”

Those efforts include bringing back BSD alumni working in different fields to share their experiences and to network with prospective and current students.

This past fall, for example, the division hosted a consulting panel featuring Michael Silverman, MD’73, head of Mas-

When Wanner cut those trailing axons from the pioneer, she saw that the follower neurons lost their way.

“There’s no real precedent we can find in the vertebrate system for a pioneer neuron leading other neurons, so we’re excited to have found this,” Prince said. “Now we’d like to know, ‘What’s special about that neuron?’” To find out, they need to look inside the pioneer cell to determine its gene expression and compare that mix to the follower cells.

Doing that, said Prince, “is really pushing the limits of technology.” Their approach will be a technique called RNA-seq, generally used to identify genes within an entire tissue. In this case, however, they’ll be targeting only a single cell, thus ramping up the task’s complexity. To aid these efforts, Prince and her team will collaborate with the University’s Functional Genomics Facility, an advanced sequencing center led in part by its faculty director, Associate uchospitals.edu/midway

“Your opinion is valued here.”

Victoria Prince, PhD

sachusetts-based BioStrategics Consulting Ltd.; Carol Ann Olson, PhD’82, MD’86; and cancer biologist Robert Schickel, PhD’09, an independent consultant based in San Diego.

And in March, Cell scientific editor Fabiola Rivas, PhD’03, and National Institutes of Health program officer Yolanda Vallejo, PhD’02, returned to campus to speak with minority graduate student applicants as well as current students.

“These alumni have a major influence on science in the broad sense,” Prince said.

“It’s great for students to hear their career trajectories.”

It’s an especially important dialogue to have as the number of prospective graduate students continues to rise. This year, the BSD saw a 15 percent leap in graduate applications — 1,076 total — a trend on par with peer institutions, and will welcome 77 new doctoral candidates this fall.

Professor of Human Genetics Yoav Gilad, PhD, with Kevin White, PhD, director of the University’s Institute for Genomics and Systems Biology.

Following your curiosity Originally trained as a biochemist at North London’s National Institute for Medical Research, Prince found her way into developmental biology studying Hox genes, cells that help establish the identity of specific regions along the body axis.

Her subjects were developing chicks until 1994, when she took a two-week embryology course at Germany’s Max Planck Institute with soon-to-be Nobelists Eric F. Wieschaus and Christiane NüssleinVolhard. At the time, Nüsslein-Volhard had just started working with zebrafish.

Prince was hooked. “We did this technique called cell transplantation where you basically take cells out of one embryo and put them into another embryo with

“The quality is as good as ever,” added Prince, who sees students coming to UChicago for the same reasons she did. “We still have a small campus where the clinical and basic science departments are genuinely interactive.” In her own research, she has worked closely with endocrinologists including Louis Philipson, MD, PhD, director of the University of Chicago Medicine’s Kovler Diabetes Center. “As soon as I came here,” Prince recalled, “Lou sought me out and said, ‘Oh! We should be looking at the pancreas of the zebrafish.’”

Such collaborations go hand in hand with the (infamous) UChicago ethos.

“We genuinely have a scholarly attitude here — and people joke a little about that,” Prince said. “But people like sitting around and exploring big problems in a way I haven’t seen elsewhere. There’s the desire to take an intellectual approach, to make the problem the first and foremost issue. It doesn’t matter if you’re a starting graduate student or an emeritus faculty,” she said. “Your opinion is valued here.”

another genotype,” she recalled. The process allows researchers to observe whether the newly transplanted cells react to their new environment or behave autonomously.

“It’s one of those really tricky techniques that’s really fun when it works,” explained Prince. “That was the thing that made me think, ‘I have to work on this.’”

As a Princeton postdoctoral fellow in the lab of Robert Ho, now chair of the University of Chicago’s Department of Organismal Biology and Anatomy, she became part of a small, but growing cadre of scientists working with the zebrafish system. Today, thousands of researchers use the fish to study vertebrate development, thanks to its unique combination of optical clarity, genetics and accessibility.

When she started out, use of the zebrafish system for research “was still new enough that it wasn’t clear whether it would become respectable,” Prince said with a laugh. “Luckily, it did.”

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Helping Nigerian women get treatment for breast cancer

Photo courtesy of Liese Pruitt

Liese Pruitt, MS3, fourth from left, traveled to Nigeria to learn about cultural barriers to early treatment for breast cancer.

By uncovering taboos about breast cancer in Nigeria, medical student Liese Pruitt hopes to free women to seek treatment and build a community of survivors.

By Anita Slomski

Keeping money in your bra causes breast cancer. So do cell phones if you hold them against your chest.

Those are some of the things that Liese Pruitt, a third-year student at the University of Chicago Pritzker School of Medicine, heard from a group of women at the University College Hospital (UCH) in Ibadan, Nigeria, in May as she studied the social and cultural obstacles that cause women there to delay treatment for breast cancer until it is too late. Pruitt knew she was hearing rarely discussed beliefs and attitudes. “Nigerian women see breast cancer as an invariably fatal disease. And like HIV/AIDS, it has a real stigma attached to it, so they don’t talk about it,” said Pruitt, who was on her second trip to Ibadan.

Despite the taboo, women opened up to Pruitt, 24, as did physicians and NI GERI A

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“We think it is remarkable that Liese has been able to discover important cultural reasons why Nigerian women delay treatment for breast cancer. We wanted to establish this Global Health Scholarship because it’s important for future doctors to understand Liese Pruitt, MS3, visited communities in Nigeria in the backgrounds and beliefs of the different hopes of finding ways to get women treatment for breast patients they may encounter in a multi-ethnic cancer sooner. country like the United States or if they choose to practice abroad. Only then can a doctor provide education and treatment in a sensitive and effective manner.”

Anita Cheng Lee, MD’91, and Dennis Lee, MD’91 Alumni whose donation created the Global Health Scholarship

religious leaders whom she interviewed. “That I would come so far to talk to them bought me a lot of good will,” Pruitt said.

Her recent research was funded by the Dennis Lee, MD’91, and Anita Cheng Lee, MD’91, Global Health Scholarship, made possible by a generous gift from two of the Pritzker School of Medicine’s alumni. Olufunmilayo I. Olopade, MD, FACP, professor of medicine and human genetics and director of the Cancer Risk Clinic at the University of Chicago Medicine, also paved the way for Pruitt.

Olopade, who went to medical school in Nigeria, introduced Pruitt to radiation oncologists at UCH, a government-funded tertiary medical center.

Pruitt understands how fissures in the physician-patient relationship can lead to less than optimal care. Last spring, she was named one of three inaugural Bucksbaum Medical Student Scholars through the Bucksbaum Institute for Clinical Excellence, which was created to help improve physician-patient communication.

In Nigeria, that relationship often is nonexistent — with dire consequences. A woman who finds a lump in her breast, for example, typically attributes it to a boil and goes to the chemist, who dispenses medication for common medical problems, Pruitt said. When selftreatment fails, the patient may go to a private physician or clinic and get more pills that she’ll take for months or even a couple of years. Finally, when the cancer can no longer be ignored because it breaks through the skin, the woman may travel for days to stand in line at UCH, one of only five hospitals in Nigeria that offer radiation treatment for cancer. Provided the physicians and nurses aren’t on strike, the radiation equipment is in working order and the woman can pay the full cost, she gets treatment, which often is palliative at this stage. Sometimes women wait in line, only to return home in shock upon hearing they need a mastectomy.

“There are so few opportunities for these women to interact with a physician and form a relationship” that would lead to understanding of their disease and its treatment, said Pruitt. “If you’ve been taking medication for two years and it hasn’t helped, uchospitals.edu/midway

why would you believe the oncologist who says you need very expensive surgery?”

Pruitt, who is interested in a career in global health and oncology, thinks there are ways to cut through misinformation about breast cancer and get women care sooner. After her third year of medical school, she hopes to pilot a breast cancer education program by collaborating with clerics. “Many women, including those with a university education, actively avoid learning about breast cancer because they believe it will increase their risk, or they say that God doesn’t want them to know about the disease,” Pruitt said. Her hope is to gain the support of respected religious leaders who will urge women to seek medical care in addition to pursuing spiritual healing when they find a breast lump.

“Liese’s work has opened new opportunities for interventions to improve breast cancer outcomes in low-resource settings,” Olopade said. “We have been studying the genetic basis of breast cancer in Nigeria for more than a decade, but it took a medical student who studied anthropology to ask the right questions and learn that ignorance about breast cancer at multiple levels is the No. 1 reason why women are diagnosed at late stages and die needlessly. When physicians and patients can communicate openly and knowledgeably about breast cancer, we’ll see more women survive breast cancer, which is the only way to eliminate the stigma attached to a diagnosis of cancer.”

Although the magnitude of Nigeria’s systemic health care problems is daunting, Pruitt is heartened by the quick progress the United States has made through various programs in raising awareness of breast cancer and erasing its stigma. “That energizes me to try to change attitudes about breast cancer in Nigeria” to improve the current dismal survival rates, she said. Nigeria also has taught Pruitt how to be a better physician at home, honing her sensitivity to patients’ different cultural, social and religious attitudes about medicine “so we can find a middle ground that everyone can live with.”

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Family heartbreak fuels father and son philanthropy

By Stephen Phillips

J

. Alfred Rider, SB’42, MD’44, PhD’51, carved out a successful career after graduating from the University of Chicago.

During the 1950s, he directed a landmark University study corroborating the link between colon and rectum polyps and cancer. In 1960, then at the University of California, San Francisco, he pioneered, with Hugo C. Moeller, MD’48, PhD’53, simethicone therapy for stomach gas, paving the way for antacids like Mylanta.

He and Moeller subsequently developed the Rider-Moeller dilator, a device that eases swallowing for people with achalasia, a condition that causes constriction of the esophagus. Later, he was named to, and ultimately led, the Medical Board of California and counseled three governors of that state, including Ronald Reagan, a personal friend, who as president appointed Rider to his Committee on Mental Retardation.

But as a young physician-scientist in the mid-1950s, Rider found himself just another worried parent of a sick child. A previously stellar student, his eldest son, Charles, then 7, began having difficulty at school, his eyesight was failing, and he was getting clumsy. Every specialist the family consulted was mystified. The quest for answers took Rider, who died in 2004 at age 83, on a harrowing two-year odyssey that wound up finally at the door of Indiana University neuropathologist Wolfgang Zeman, MD, an expert in a little-known hereditary neurodegenerative disorder called neuronal ceroid lipofuscinosis or Batten disease. “He made a diagnosis,” said Rider’s younger son, Dean L. Rider, MD’78, a gastroenterologist in San Francisco.

“This was absolutely Batten disease.”

Batten disease is a particularly cruel blow. In its various forms it strikes children, from infants to adolescents. One variant affects adults. The National Institutes of Health estimates that two to four babies in every 100,000 will develop it. The progression of symptoms is remorseless, and the condition is uniformly fatal. The burden on families is massive; sufferers rapidly become non-functioning, unable to care for themselves.

“You can have a 21/2-year-old who’s talking and running around,”

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The University of Chicago Medicine and Biological Sciences Division

Photos courtesy the Rider family

Charles Rider, left, and his younger brother Dean, just before Charles began showing signs of Batten disease. Dean L. Rider, MD’78, later joined in his father’s quest to raise awareness of and research the disease.

A previously stellar student, his eldest son, Charles, then 7, began having difficulty at school, his eyesight was failing and he was getting clumsy.

Every specialist the family consulted was mystified.

University of Chicago Professor Glyn Dawson, PhD, top, a leading Batten disease researcher, and the late J. Alfred Rider, SB’42, MD’44, PhD’51, above, who began searching for answers to Batten disease after his eldest son, Charles, showed signs of the then-little-known disorder at age 7.

said Glyn Dawson, PhD, University of Chicago professor of biochemistry and molecular biology and of pediatrics, and a leading Batten disease researcher. “Then suddenly they start bumping into walls and behaving erratically.”

“You go from a normal, healthy child to one who’s deteriorating before your eyes, and if there are younger siblings, the parents begin to wonder if they have it also.”

Mercifully, Dean was unaffected. The family cared for Charles at home (where he lived to 43 — thought to be the most advanced age reached by someone with Batuchospitals.edu/midway

ten disease). But Alfred Rider’s mind went to other parents in the same position with an afflicted child, trying to get a diagnosis, but without his medical training. “He said, ‘If it was that hard for me to find help, what would it be like for [a non-physician],’” recalled Dean.

In 1968, Rider used his savings to launch the Children’s Brain Disease Foundation, a philanthropic fund dedicated to elevating awareness of Batten disease and advancing research into it.

He plowed his earnings into the foundation and organized golf tournaments, casino nights, walkathons and car raffles, using the proceeds to fund research. To bring researchers together, he convened an annual conference. “It was the connection with Al Rider, the annual meetings and the plight of the children that kept us interested in Batten disease,” said Dawson.

Dawson’s introduction to Batten disease came when he was a young researcher in the early 1970s. A colleague showed him the brain of a 3-year-old who had died of it, and he glimpsed firsthand the devastation it can wreak. Remarkably, the child’s brain contained no neurons — the result of accumulated fats and proteins, dubbed lipofuscins, clogging the brain, depriving its cells of nutrients.

“What . . . could be happening to cause such massive disruption?” he remembered thinking.

To answer such questions, Rider recognized the need for federal funding, then nonexistent for Batten disease.

He tapped his political contacts. Dean Rider joined the effort also. For his senior elective project at the University of Chicago Pritzker School of Medicine, he worked in California Sen. S.I. Hayakawa’s office. “The real purpose was to learn how Congress worked in order to bring Batten disease to national attention,” said Dawson.

In 1978, Alfred Rider made the first of several annual pilgrimages to Capitol Hill to lobby lawmakers for National Institutes of Health support. In 1991, Congress directed NIH’s National Institute of Neurological Disorders and Strokes to earmark specific funds for Batten disease research.

The resulting funding was a catalyst for strides made during the 1990s, when researchers identified several genetic subtypes

of Batten disease and developed a blood test.

At the University, Dawson’s team, with his son, Philip Dawson, PhD, associate professor of chemistry at San Diego’s Scripps Research Institute, has developed a “molecular chaperone” targeting the specific cellular mechanism that goes awry in some forms of Batten disease. Thanks to a collaboration with the Naval Research Laboratory, they have devised a means by which the drug may be delivered directly to the brain, traversing the blood-brain barrier that has been an impediment to other attempted therapies. The approach offers a means by which therapies could be administered to combat other related brain disorders, Dawson added.

The work is supported in part by the foundation. Since its inception, the foundation and Rider family members have donated $423,266 directly to the University.

At least $371,000 of this has gone toward research into Batten disease, including Dawson’s work.

Earlier this year, Dean Rider pledged $175,000 over five years to establish an endowment to support the work of Dawson and others at the University in Batten disease.

The Riders’ ties to the University run deep. Dean is the third generation of University of Chicago-trained physicians in the family: As well as his father, both paternal grandparents earned their MDs from the University. Dean’s mother attended the Laboratory Schools. His parents were married in Bond Chapel.

He describes his own time at the Pritzker School of Medicine as “the best thing that ever happened to me.”

“It’s a unique place. I just had so much personal growth and when I came out felt ready to take on the challenges of life.”

This sense of connection coupled to the momentum of Dawson’s research made the University a natural fit for the endowment, said Dean.

“With the endowment the foundation has under the banner of the University of Chicago, there will always be money for Batten disease research and things will progress. . . . That’s important because . . . I’ve seen for myself the importance of [philanthropic funding] as a catalyst [for research and discovery].”

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D ay o f S e r v i c e

F a c u lt y t e x t b o o k

Pritzker News

Neurobiology textbook receives accolades

Pritzker students pitch in

A medical textbook written by University of Chicago professor of neurobiology Peggy Mason, PhD, has received a 2012 “Highly Commended” stamp of approval for books on basic and clinical sciences from the British Medical Association. Although written specifically for medical students, Mason’s “Medical Neurobiology” reads like a novel as it teaches readers how the nervous system works normally as well as how it can contribute to illness. Mason has taught aspiring physicians at the Pritzker School of Medicine for nearly two decades.

Students from the Pritzker School of Medicine spent the day on May 19 at the EPIC Academy and Bethel Terrace Senior Apartments in Chicago, as part of the Spring Day of Service, organized by Joanna Perdomo, MS2, and Clair Naus, MS2.

F o u r th - y e a r st u d e n ts h o n o r e d

C a lv i n F e n t r e ss F e ll o w sh i ps

Fentress Research Fellows named

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ine Pritzker School of Medicine students were selected to receive Calvin Fentress Fellowships. The awards, named in honor of a grateful patient, were created to encourage research by students during their final year in medical school. Fentress Fellows receive a $1,000 stipend for completing a research project. Students will present their research findings during the annual Senior Scientific Session, to be held on May 16, 2013. The following fourth-year students were selected: Rajiv Agarwal, Tharian Cherian, Michael Combs, Kiran Kumar, Samuel Lee, Tarak Trivedi, Joshua Williams, Joyce Woo and Jordan Yoder.

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The University of Chicago Medicine and Biological Sciences Division

Alpha Omega Alpha awards

T

he 2013 University of Chicago Alpha Omega Alpha Honor Medical Society inductees and award winners were named. Fourth-year students who are in the top academic quartile of their class and who demonstrate leadership, compassion and fairness in dealing with their colleagues are considered.

They are: Nikita Alexiades, Leonardo Aliaga, Brittany Betham, Abby Cutler, Allison Hickey, Gregory Kauffmann, Aaron Miller, MS, Margaret Naunheim, Katie Raffel, Samantha Smith, Robert Stern, Tarak Trivedi, Joshua Williams and William Zeiger, PhD.

Wh i t e c o a t c e r e m o n y

Steven Bhutra, MS1, takes a moment to capture a photo of his fellow medical students during the White Coat Ceremony at Rockefeller Memorial Chapel.

Taking the Hippocratic Oath

T

he Pr itzker S cho ol of Medicine welcomed 88 new students to its ranks on August 5 at the annual White Coat Ceremony, held at Rockefeller Memorial Chapel.

It is during this ceremony that first-year medical students recite the Hippocratic Oath, as family, friends and new colleagues watch.

Farr Curlin, MD, associate professor of medicine at the University of Chicago, served as the keynote speaker. Curlin is a hospice and

palliative care physician, researcher and medical ethicist, and founding co-director of the Program on Medicine and Religion.

The White Coat Ceremony began at Pritzker in 1990 to mark students’ formal induction into the medical profession. Since then, the idea spread and the White Coat Ceremony now is widely practiced at medical schools across the country.

To view more photos of the ceremony, see flickr.com/photos/ psom.

Caroline Kuhn, MS1, second from right, and fellow medical students take part in the White Coat Ceremony, during which they read the Hippocratic Oath.

S c i e n t i f i c R e s e a r ch P r i z e

Awards inspired by research mentor Three fourth-year students were named as recipients of the inaugural John D. Arnold, MD’46 Scientific Research Prize.

The research funding was made possible through a gift from Charles Pak, SB’58, MD’61, in honor and recognition of the inspiring relationship he developed with his research mentor, John D. Arnold, MD. The students who received the awards will present their research at the 2012 Senior Scientific Session. The recipients are: • Nikita Alexiades. Mentor: Maciej Lesniak, MD. Project: An uchospitals.edu/midway

evaluation of the role of the VEGFR2 receptor in neural stem cell tumor tropism.

• Clifton Brock. Mentor: Suzanne Conzen, MD. Project: An exploration of the glucocorticoid’s role in molecular pathways involved in diabetes and insulin resistance.

• Jasmine Swaniker. Mentor: David Glick, MD’90. Project: An exploration of the handling and use frequency of anesthetic syringes to determine if there is a relationship between syringe exposure and likelihood of contamination.

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Physician of Tomorrow

Pritzker News

Fourth-Year Student Abby Cutler Named One of the AMA’s 2012 Physicians of Tomorrow

Pritzker fourth-year student Abby Cutler has been named a recipient of the American Medical Association Foundation’s 2012 Physicians of Tomorrow Scholarship. The scholarship, which was established in 2004 to help offset the cost of medical school debt, acknowledges a very select group of students who have displayed academic excellence.

Abby’s scholarship includes the support of the Johnson F. Hammond, MD, fund, which recognizes students who have demonstrated a commitment to a career in medical journalism.

Abby Cutler, MS4

A n n u a l p o e t r y c o n t e st

Poetic License

Y

ou may not see the phrase “sinus tachycardia” appear in too many poems published in Granta, but the winner of Pritzker School of Medicine’s first annual poetry contest weaved that term and other physician lingo into an artful description of a two-year-old critically ill hospital patient.

Joshua Williams, MS4, won the open poem category with his poem entitled “H.I.E.” More than 80 poems were submitted and the winners were announced in May. The idea to tease out the poetic side of physicians originated with Rama D. Jager, MD, clinical assistant professor of ophthalmology and visual science. Jager saw a newspaper story about similar contests at the Yale and University College London medical schools and thought that the concept would help students and faculty here express their feelings about their work and their relationships with patients. With the help of Rebecca Levine and Margaret Nolan, both members of the Class of 2012, and faculty advisor Shalini Reddy, MD, associate professor of medicine, the first Pritzker contest was created.

The 2012-13 contest is open for new entries through January 15, 2013. For more information about this year’s contest and to see last year’s entries, see duchess.bsd. uchicago.edu/poetry.

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First place winners: O pen P oem E ntry H.I.E.

by Joshua Williams, MS4 You are G-tube, trach-dependent, deaf, blind, devastated, orphaned, forgotten, and two years old today.

Of peppermint breezes and thrumming valleys, burning bushes and albino woods, bottomless sun and twisting caverns, marshmallow clouds and rose petal rains.

You are an incredible teacher.

Of swiftwater farms with slow-flowing trickles over cotton rocks past hand-dripped castles under deafening moonrises through endless time without shadow.

You are cerebral palsy, septic shock, multi-drug resistant organisms, broad-spectrum antibiotics, pulmonary edema, acute renal failure, fluid resuscitation, epinephrine, chest compressions, epinephrine, epinephrine,

Without a shadow.

Of a doubt.

You are neither a carrot nor a cucumber.

What gift can I give you?

I will still say “Good Morning” when I enter your room.

sinus tachycardia.

Good.

Mourning.

I wonder . . . do you dream?

Happy Birthday.

S i x-Word P oem C ategory A patient

by Kunmi Sobowale, MS3 “They listened this time. Sans stethoscope”

The University of Chicago Medicine and Biological Sciences Division

R o w l e y P r o f e ss o r sh i p

Named professorship created in honor of cancer researcher Janet D. Rowley

By John Easton

D

onations from Jim and Karen Frank and others will endow the Janet Davison Rowley, MD, Professorship in Cancer Research at the University of Chicago Medicine. This new named professorship will honor one of the University’s most distinguished scientists and alumni, Janet D. Rowley, LAB’42, PhB’45, SB’46, MD’48, the Blum-Riese Distinguished Service Professor of Medicine, Molecular Genetics and Cell Biology, and Human Genetics.

Rowley, 87, a pioneer in understanding the connections between genetics and cancer, remains an active member of the faculty. She rides her bicycle to work every day.

In the early 1970s, Rowley made the first of a series of fundamental discoveries demonstrating that specific chromosomal changes caused certain types of leukemia.

She then struggled for years to convince fellow researchers that cancer was essentially a genetic disease.

Her discoveries eventually gained acceptance. They brought her widespread recognition, including the Lasker Award, the National Medal of Science, the Presidential Medal of Freedom, and recently the Ernest Beutler Prize and the Japan Prize for Healthcare and Medical Technology.

“Dr. Rowley, a graduate of the University’s Laboratory Schools, the College and the Medical School, has long been a shining example of the power of a University of Chicago education,” said medical center trustee Jim Frank, of Winnetka, Illinois.

“She is also a model of what that kind of training, combined with enormous talent and dedication, can do. Karen and I are proud to help celebrate her accomplishments and support the outstanding researchers who will be honored to hold this endowed chair.”

“All of us in the Cancer Center are

uchospitals.edu/midway

Photo by Jean Lachat

Janet D. Rowley, LAB’42, PhB’45, SB’46, MD’48, the Blum-Riese Distinguished Service Professor of Medicine, Molecular Genetics and Cell Biology, and Human Genetics

excited to see Janet’s remarkable career recognized in this enduring way,” said colleague Michelle M. Le Beau, PhD, director of the University of Chicago Medicine Comprehensive Cancer Center, who trained under Rowley. “She has received just about every imaginable honor. Now someone with extraordinary promise will benefit from this support, from the history of Janet’s discoveries and the immediate recognition that comes with selection as the Rowley Professor.”

Rowley made her first big discovery in 1972. She found that the chromosomes of a patient with acute myeloid leukemia (AML) appeared to have made a trade: part of chromosome 21 had broken off and moved to chromosome 8, and part of 8 had moved to chromosome 21 — an exchange now known as a “translocation.” When she looked at more patients with this same kind of leukemia, she saw the same process.

She later found that patients with a different disease, chronic myelogenous

leukemia (CML), had a different translocation. One end of chromosome 22 was exchanged for a piece of chromosome 9.

Because of this transfer, important genes that regulated cell growth and division were no longer located in their normal position. The result was the uncontrolled cell growth of cancer.

The two consistent translocations — one in AML and one in CML — argued that such translocations were tied to specific types of leukemia. In 1977, Rowley and colleagues identified a third example, the 15;17 translocation that causes acute promyelocytic leukemia, a rare disease but one where every patient had the same genetic flaw. “That made me a believer,” she would later recall. “That was the frosting on the cake.”

Understanding the 9;22 translocation eventually led to the development of the drug imatinib (Gleevec), one of the most successful targeted cancer therapies to date. Gleevec blocks an abnormal growthregulating protein produced by the 9;22 translocation.

Picking up on her lead that specific translocations defined specific forms of cancer, scientists around the world joined the search for chromosomes that either exchanged genetic material or lost it altogether. Others used the translocations as road maps to find specific genes disrupted by chromosome damage, thus opening up the current era of cancer genetics.

“Establishing the Rowley Professorship is one more way to celebrate Janet’s remarkable series of discoveries, a process that is still under way,” said Kenneth S.Polonsky, MD, Dean of the Biological Sciences Division and the Pritzker School of Medicine, and executive vice president for Medical Affairs at the University of Chicago. “Any future professor to hold this chair will find that the honor comes with high expectations.”

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Pritzker News

g o ld h u m a n i sm h o n o r s o c i e t y

R e s e a r ch w i th m e n t o r s

Fourth-year medical students named to the Gold Humanism Honor Society

Summer Research Awards

Seventeen fourth-year medical students were named as members of the 2013 Gold Humanism Honor Society.

C h a p t e r Ad v i s o r M i n d y S c hw ar t z , M D, a s s o c i at e professor of medicine, and the Gold Humanism Honor Society Selection Committee made the announcement of membership, which honors fourth-year medical students who consistently demonstrate excellence in clinical care, leadership, compassion and dedication to service. Election to the honor society is based upon recommendations

from the rising fourth-year class, with final deliberations made by the GHHS Selection C ommittee. The students selected are: Brittany Betham, Laura Blinkhorn, Valerie Chen, Abby Cutler, Jason Espinoza, Uchenna Ewulonu, Kevin Heaton, Daniel Kozman, Toussaint Mears-Clarke, Aaron Miller, MS, Margaret Naunheim, Katie Raffel, Gabrielle Schaefer, Samantha Smith, Robert Stern, William Uffmann and Joshua Williams. The Gold Humanism Honor Society induction ceremony will take place on March 5, 2013.

The 18th Annual Pritzker Summer Research Program proved to be another successful year of scholarship for second-year students, allowing them to work closely with faculty mentors across the clinical, translational and basic sciences. The program provides students a platform for ongoing research and a chance to present their work on a national level, thanks to the continued guidance of Vineet Arora, MD, MAPP, associate professor of medicine and associate program director of the Internal Medicine Residency Program; David Boone, PhD, assistant professor of medicine; Eugene Chang, MD, the Martin Boyer Professor of Medicine and associate section chief for research; and V. Leo Towle, PhD, professor of neurology, surgery, pediatrics and psychiatry and behavioral neuroscience.

Students who received awards of excellence for their work are: Richard Schroeder, Philip Carullo, Claire Shappell, Lara Delamater, Rishi Pandya, Brian Thurber, Kyle Ericson, Alexandra Garnett and Ramin Morshed.

The following students received honorable mentions for excellence: Noura Choudhury, Camil Correia, Michael Hayes, Amy Kaufman, Ellis Kim, Paras Patel, Jack Peace, Robert Sanchez and Emily Stockert.

2 0 1 2 g r a d u at i o n

Chicago Mayor Rahm Emanuel addresses Class of 2012

T

he Pritzker School of Medicine’s Class of 2012’s keynote speaker on graduation day in June was Chicago Mayor Rahm Emanuel.

He spoke to Pritzker’s 99 fourth-year students, their fellow doctoral graduates in the Biological Sciences Division, friends and family during the event, held in Rockefeller Memorial Chapel at the University of Chicago. “Your patients will never forget you,” Mayor Emanuel told graduates after recounting a story of the team that helped save his life after an accident when he was in high school. He also highlighted the spirit of the University of Chicago — “one that embraces curiosity and questioning in the pursuit of discovery.”

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The University of Chicago Medicine and Biological Sciences Division

“When I got the call that I was accepted at the University of Chicago, I was so ecstatic that I forgot for a while that I would be going to medical school without any financial support from my family. Without the kindness of those who helped establish the Thomas Park Class of 1989 Memorial Scholarship, it would be impossible for me to attend the Pritzker School of Medicine.”

— Tyler Friedrich, second-year student, Pritzker School of Medicine

every contribution makes a difference Like Tyler, many of the brightest students aspire to a Pritzker education, and it is tough to finance. The estimated cost of educating a future physician at the University of Chicago is $500,000. We provide financial aid to 80 percent of our students—and there is more we need to do. Your gift to the Medical & Biological Sciences Alumni Annual Funds and scholarship funds will help us make sure the best minds of the future are free to choose Pritzker.

To learn more about the Alumni Annual Funds and other ways you can make an impact, contact: The Annual Funds Office 5801 South Ellis Avenue Chicago, IL 60637 uchospitals.edu/midway

773-834-9166 annualfunds@bsd.uchicago.edu medbsd.uchicago.edu/alumni/gift MEDICINE ON THE MIDWAY

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NEW S

Class Notes

Alumni, get the latest news and stay connected with your classmates through the Medical & Biological Sciences Alumni Association (MBSAA) website at medbsd.uchicago.edu/alumni.

Reunion in June Attention alumni emeriti and those from the Classes of 1963, 1968, 1973, 1978, 1983, 1988, 1993, 1998, 2003 and 2008. Reunion is coming up in June 2013. So that you stay up to date, be sure to submit your current contact information at medbsd.uchicago. edu/alumni/get-involved/updateyour-info.

1970s Nathan M. Szajnberg, AB’74, MD’74, gave the Ticho Memorial Lecture for the American Psychoanalytic Association Meeting in Chicago on June 15 at the Palmer House. The award honors Ernst and Gertrude Ticho.

Szajnberg’s lecture was titled “Mimesis of Inner Lives in Western Literature: How Psychoanalysts Got Our Ideas About Inner Life.”

1980s Steve Gerber, MD’88, was named Specialist Teacher of the Year for the third time at one of the two Family Practice Residencies in South Bend, Indiana. In addition, he is director of Ophthalmic Education for the Indiana University School of Medicine, Notre Dame branch campus.

2012-13 Alumni Council Robert Doroghazi, MD’77, President Anthony Cutilletta, MD’68, Immediate Past President Rene Mora, PhD’88, MD’89, Vice President Paul R. Rockey, MD’70, Reunion Chair Arnold B. Calica, SM’61, MD’75, Regional Chair Michael H. Silverman, MD’73, Chicago Partners Chair Chris Albanis, AB’96, MD’00, Editorial Committee Chair Dianne Altkorn, MD’82 Diana Chung, MD’92 Lawrence Cutler, MD’80 Mark Ferguson, MD’77 Melina Hale, PhD’98 David Holtzman, PhD’67, MD’68 Maga Jackson-Triche, AB’71, MD’75, MSH Julian Katz, MD’62 Si-hoi Lam, AB’76, MD’80 Dennis Lee, MD’91 Jacqueline Moline, AB’84, MD’88 Dean Rider, MD’78 Patricia Simmons, MD’77 Donald Steiner, MD’56, SM’56 Jack Stockert, AB’05, MBA’10, MD’10 Leo van der Reis, MD’54 David Whitney, MBA’78, MD’80 Lifetime Members: Lampis D. Anagnostopoulos, SB’57, MD’61 Coleman Seskind, AB’55, SB’56, MD’59, SM’59 Russ Zajtchuk, SB’60, MD’63

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If you would like your next editions emailed, please send us a note at momedit@uchospitals.edu. In addition to sending the note from your preferred email address, please include your full name and street address, so that we can confirm the switch to your email account.

Edward Andrew Michals, MD’88, was inducted as a fellow in the American College of Radiology (ACR) at a formal convocation ceremony during the 89th ACR Annual Meeting and Chapter Leadership Conference April 21-25, 2012, in Washington, D.C. Michals is a radiologist at the University of Illinois Chicago, where he is the director of diagnostic neuroradiology and the radiology residency program director.

He is a member of the ACR; the Radiological Society of North America; the American Roentgen Ray Society; the American Society of Neuroradiology, where he currently serves as chair of the audio/visual committee; the Association of University Radiologists; the American Society of Spine Radiology; and the American Medical Association. Michals also is immediate past president of the Chicago Radiological Society and the Illinois Radiological Society. The ACR is a national nonprofit association serving more than 34,000 radiologists, radiation oncologists, interventional radiologists, nuclear medicine physicians and medical physicists with programs focusing on the practice of radiology and the delivery of comprehensive health care services.

1990s Charles M. Rudin, MD’93, PhD’91, of the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medicine, will be honored by Uniting Against Lung Cancer at its “Strolling Supper with Blues and News” gala in New York City on November 14.

The event raises awareness and critical funds for lung cancer research. NBC’s Brian Williams will present the award.

Rudin is one of the nation’s leading thoracic oncologists and has authored more than 100 publications of original research. He is co-director of the Upper Aerodigestive Cancer Program and associate director for clinical research at Sidney Kimmel. A member of Uniting Against Lung Cancer’s Medical Committee since 2009, Rudin will be honored for his contributions to advancement in the field of lung cancer and for guiding the foundation’s Scientific Program.

2000s Anthony Shum, MD’00, assistant professor in the Division of Pulmonary and Critical Care at the University of California, San Francisco, was awarded an American Thoracic Society Foundation/Pulmonary Fibrosis Foundation Research Grant. The award will provide funding for the project “Defining the Molecular Basis of Interstitial Lung Disease in Rheumatoid Arthritis.” The grant provides $80,000 in funding over two years. The grant is supported through a partnership between the ATS Foundation and Pulmonary Fibrosis Foundation. Approximately 10 percent to 30 percent of patients with rheumatoid arthritis develop interstitial lung disease (ILD), which is characterized by inflammation or scarring in the lung. ILD worsens the prognosis of rheumatoid arthritis. There is currently no way to predict which patients will develop this potentially crippling complication, and there are very few therapies available to specifically treat lung damage in rheumatoid arthritis.

Shum will take advantage of a new technology called exome sequencing to identify the genes that trigger ILD in rheumatoid arthritis patients.

Ultimately, he hopes that his work will improve understanding of how these genes cause disease, which will in turn lead to development of new diagnostic and treatment strategies for pulmonary fibrosis in rheumatoid arthritis.

Gordon Wood, AB’98, MD’02, has been named lead physician for the Midwest Palliative & Hospice CareCenter’s Palliative Care Services program at Northwestern Lake Forest Hospital in Glenview, Illinois. Wood has focused his career on promoting and providing palliative care for patients with serious, complex illness. Wood was previously at the University of Pittsburgh Medical Center, where he served as assistant professor of medicine in the Section of Palliative Care and Medical Ethics and fellowship director for the university’s fellowship in palliative medicine. After receiving his medical degree from

THE University of Chicago Medicine and Biological Sciences Division

the University of Chicago Pritzker School of Medicine, he completed his residency in internal medicine at the University of California, San Francisco.

He subsequently completed a palliative medicine fellowship at Northwestern University, where he also received a master’s degree in the science of clinical investigation.

2010s Elizabeth (Liz) Brown, MD’10, recently was selected to be a Robert Wood Johnson Clinical Scholar at the University of Pennsylvania starting in July 2013.

Through the program, scholars spend two years examining the delivery, impact and organization of health care, and train in leadership, health policy and health services research methods.

Liz currently is in her third year as a family medicine resident at Brown University in Providence, RI. In other news: Book chronicles road to inner strength Psychologists call it personality hardiness. Buddhists refer to it as strong life force. Alex Lickerman, MD’92, clinical associate of medicine, has titled it “The Undefeated Mind.” His new book, which was released in early November, describes his struggle to overcome adversity when he was in medical school and offers nine principles, inspired by his patients, to develop resilience and overcome suffering. Anyone, he writes, can incorporate these into their thinking.

Kahn named president of American Roentgen Ray Society Charles E. Kahn Jr., MD, MS, who completed his residency at the University of Chicago Medicine and currently is a professor of radiology at the Medical College of Wisconsin (MCW) and radiologist at Froedtert Hospital, was installed as president of the American Roentgen Ray Society (ARRS), the first and oldest radiology society in the United States. Kahn, who also is the chief of imaging informatics at MCW, has joint appointments at the University of Wisconsin-Milwaukee (UWM) as an adjunct professor of computer science and as the co-director of UWM’s Biomedical and Health Informatics Doctoral Program. He received his medical degree from the University of Illinois College of Medicine at Chicago in 1985. From there, he went to the University of Chicago Medicine to complete a residency in diagnostic radiology in 1989 and earned his master of science in computer sciences from the University of Wisconsin-Madison in 2003. He joined the MCW faculty in 1991 and specializes in body imaging, particularly computed tomography (CT) and ultrasound. Kahn has authored more than 85 peer-reviewed articles and has given more than 140 presentations at national and international radiology meetings.

In Memoriam William E. Hummel, MD’49, died July 16, 2012, in Everett, Washington, at the age of 89. Hummel served in World War II before medical school and in the Korean War after his internship at the University of Oregon. After completing a residency in orthopaedic surgery at the University of Oregon and Shriners Hospital for Children of Portland, Oregon, he had a long and successful private practice in Everett, Washington, until his retirement. He specialized in trauma and reconstruction. Hummel also served on the staff at Shriners Hospital in Seattle, Washington.

He is survived by his wife of 67 years, Doris, sons Todd and John, and daughters Robin Johnson and Lisa Wilson.

Jeffrey A. Kant, PhD’74, MD’75, age 65, of Franklin Park, Pennsylvania, died on September 29, 2012. Born in Boston, Kant was a lifelong Red Sox fan. He grew up in Watertown, New York, received his AB degree (biology-chemistry) from Princeton University, and completed his MD and PhD (biochemistry) at the University of Chicago. After internship and residency in pathology and laboratory medicine at the University of Washington in Seattle, he received a fellowship appointment in the hematopathology section of the Laboratory of Pathology at the National Cancer Institute in Maryland. After 12 years on the faculty

of the University of Pennsylvania, he moved to Pittsburgh as professor of pathology and human genetics at the University of Pittsburgh and director of the Division of Molecular Diagnostics in the Department of Pathology. During his five years directing the pathology residency training program, his residents honored him as “the Residency Director with the open door, open appointment book, and open mind.” Kant also founded and directed the Molecular Diagnostic Fellowship program where he inspired a generation of pathologists, passing on his considerable knowledge, guiding individual aspirations and careers, and instilling in his fellows a deep commitment to patient care. He helped found and was first president of the Association for Molecular Pathology (AMP). Kant served on many committees for AMP, the College of American Pathologists, and other professional organizations. He was an elected fellow of the American Association for the Advancement of Science. Just weeks before his passing, Kant was awarded the College of American Pathologists’ Lifetime Achievement Award. He enjoyed traveling, particularly to Hawaii, and he loved playing with his grandchildren. Beloved husband of Julie Kant; father of Benjamin (Sarah) Kant and Peter (Laura Zajac) Kant; brother of William (Myriam) Kant, Christopher (Debra) Kant, Alan (Helen Misczuk) Kant and grandfather of Rebecca, Talia, Max and Nathaniel.

Kant was preceded in death by his parents, Alfred and Martha Kant.

David Adam Raskin, AB’84, MD’92, died at age 49 on June 13, 2012, after a 10-month courageous battle with acute myeloid leukemia. Born on August 26, 1962, in Chicago, Raskin spent the majority of his childhood in Owings Mills, Maryland. He attended the McDonogh School, graduating high school in 1980. He attended the University of Chicago, graduating with a bachelor’s degree in 1984, and later graduated from the Pritzker School of Medicine in 1992. Raskin completed his residency in anesthesia at the University of California, San Francisco. Since 1997, he had worked as a physician for the John Muir Health Care System in Walnut Creek, California, where he served in many leadership positions. Raskin was an accomplished distance runner and top-ranked amateur triathlete. He competed in track and field and cross country in high school and in the College, and was a varsity letterman in both sports at the University. After college, he became a triathlete and became a top nationally ranked amateur. As a fourth-year medical student, he took time off from school in order to train for and compete in the Ironman Triathlon in Kona, Hawaii, finishing in 10 hours, 51 minutes, 44 seconds. His pure heart made him a bright light to all who knew him in this world.

He was a devoted and loving husband to his wife, Deanne, and adored his two daughters, Ava (age 7) and Hanna (age 5).

p r o f e ss o r e m e r i t u s Ernest Page, MD, 1927-2012 Ernest Page, MD, professor emeritus in medicine and neurobiology, pharmacology and physiology, died from complications of long-term neuromuscular disease on July 21, 2012, at his home in Jerusalem. He was 85. Page, a member of the Committee on Cell Physiology at the University of Chicago Medicine, was a pioneer in using the electron microscope to study biological processes and in developing rigorous mathematical techniques to analyze highly magnified images to understand the biology of heart muscle cells and the diseases that impair heart function. Page was born May 30, 1927, in Cologne, Germany. His family fled Germany soon after the Nazis came to power. They went to Paris in 1935 and then moved to San Francisco about a year later. In 1945, when he turned 18, he was drafted into the U.S. Army. After World War II, he earned his bachelor’s degree from the University of California, Berkeley, in 1949, followed by his medical degree from the University of California, San Francisco, in 1952. He did his residency training at the Harvard-affiliated Peter Bent Brigham Hospital in Boston, with additional fellowships in heart research at the University of Alabama, enzyme chemistry at the University of Wisconsin and biophysics at Harvard Medical School. After completing his clinical training in 1958, Page was awarded a biophysics research fellowship at Harvard. A year later he was appointed an American Heart Association Established Investigator at that university, a position he held until 1964. At Harvard, he became an instructor of biophysics in 1961 and an associate in biophysics in 1963.

Page came to the University of Chicago in 1965 as an associate professor. He quickly built a large cardiac muscle biology research program. He was

uchospitals.edu/midway

promoted to professor in 1969. He met his wife Eva in his UChicago laboratory. They were married in 1967 and published one paper together, “Distribution of Ions and Water Between Tissue Compartments in the Perfused Left Ventricle of the Rat Heart” in 1968. She completed her residency at what was then called the University of Chicago Hospitals and became a practicing dermatologist. A prolific researcher, Page published more than 100 peer-reviewed articles and another 100 research abstracts. He played a leadership role in many of the local and national cardiology associations, serving as a member of the American Heart Association research committee and as chairman of the Chicago Heart Association research committee. From 1981 to 1986, he was editor of the American Journal of Physiology, and from 1987 to 1991 he was associate editor for Circulation Research. He and two colleagues edited the “Handbook of Physiology: The Heart” for Oxford University Press, published in 2001. Page was also a Renaissance man, a popular teacher as well as a respected researcher. He loved classical music. He read extensively, wrote poetry and completed three novels, none of them published. When he retired after 34 years at the University, he told everyone he had had a good time because he spent those years doing all the things he loved. After teaching physiology to medical students for 25 years, Page retired in 1998. He and his wife moved to Israel to be closer to their son. In addition to his wife, Page is survived by their son, David, and his wife, Menucha, and four grandchildren: Daniela, Ben-Tzion, Betzalel and Elazar. A funeral service was held in Jerusalem.

Ernest Page, MD

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In Memoriam F a c u lt y

Class Notes

Donald Liu, MD, PhD, 1962-2012

“He had also created wonderful relationships with physicians and hospitals throughout the greater Chicago area, providing expertise and guidance in treating young patients.”

— Kenneth S. Polonsky, MD Dean of the Biological Sciences Division and the Pritzker School of Medicine and executive vice president for Medical Affairs for the University of Chicago

Donald Liu, MD, PhD, the Mary Campau Ryerson Professor in the Departments of Surgery and Pediatrics, drowned on Sunday, August 5, 2012, while attempting to rescue two children who were caught in a strong current in Lake Michigan near the town of Lakeside, Michigan. The children made it to shore but Liu was swept away by the rip current. He was 50.

Liu joined the University of Chicago Medicine as a pediatric surgeon in 2001 and was named section chief of pediatric surgery and surgeon-in-chief at the University of Chicago Medicine Comer Children’s Hospital in 2007. He also was the Endowed Overseas Chair at Jiao Tong University School of Medicine in Shanghai, China. Liu received a Biological Sciences Division Distinguished Senior Clinician Award in 2012.

“Don Liu was full of life and energy and excitement for his specialty, a devoted doctor and a family man,” said Jeffrey B. Matthews, MD, the Dallas B. Phemister Professor of Surgery and Chair of the Department of Surgery at the University of Chicago Medicine.

“He was all about the children, and his enthusiasm inspired colleagues and the whole staff at Comer Children’s Hospital.”

Liu was internationally recognized for his expertise

in applying and adapting the techniques of minimally invasive surgery to children. He developed innovative approaches to the treatment of chronic abdominal pain syndromes in children. As a researcher, he was an expert in Hirschsprung’s disease, the pathogenesis of necrotizing enterocolitis and the importance of gut bacteria in health and disease.

Liu “was passionate about his work as a pediatric trauma surgeon, both in treating and preventing childhood injury,” said Kenneth S. Polonsky, MD, Dean of the Biological Sciences Division and the Pritzker School of Medicine and executive vice president for Medical Affairs for the University of Chicago. “He had also created wonderful relationships with physicians and hospitals throughout the greater Chicago area, providing expertise and guidance in treating young patients.”

Liu is survived by his wife, Dana Suskind, MD, professor of surgery and pediatrics and director of the Pediatric Cochlear Implantation Program at Comer Children’s Hospital; and their three children, Genevieve, Asher and Amelie. Other survivors include his parents, Donald Ho Yu Liu, MD, and Emilie A. Chua, MD, and his sister, Diana.

Donald Liu, MD, PhD Memorial contributions can be made to: Dr. Donald C. Liu Research Memorial Fund University of Chicago Medicine and Biological Sciences Attention: Abbe Temkin University of Chicago Medicine and Biological Sciences Development Office 130 East Randolph Street, Suite 1400 Chicago, Illinois 60601

F a c u lt y Charles E. Metz, PhD, 1942-2012 Charles E. Metz, PhD, professor of radiology and a member of the Committee on Medical Physics at the University of Chicago Medicine, died on July 4, 2012, of pancreatic cancer at age 69. A leader in using mathematics to assess and improve the accuracy of diagnostic tests, he made contributions to radiological imaging, nuclear medicine, computer-aided diagnosis and ROC analysis. He developed the “Metz filter,” widely used to enhance resolution and remove distractions from nuclear medicine images.

Metz was perhaps best known for extending the mathematical foundations of receiver operating characteristic (ROC) analysis to the medical imaging field and for providing, free of charge, an extensive package of computer software to more than 15,000 registered users worldwide. His advancements in ROC analysis were also included in various Food and Drug Administration studies on medical imaging devices.

Metz was born in the Bay Shore area of Long Island, New York. He graduated with honors from Bowdoin College in 1964 and earned his master’s and doctoral degrees in radiological physics from the University of Pennsylvania. He came to the University of Chicago soon after graduation as an instructor in radiology and the Argonne Cancer Research Hospital, a campus facility sponsored by the Atomic Energy Commission and dedicated to the study of atomic energy in the detection and treatment of cancer. He stayed at the University for the rest of his career, rising to assistant professor in 1971, associate professor in 1975 and professor in 1980. He served as director of the Graduate Program in Medical Physics from 1979 to 1986 and

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on multiple institutional as well as national and international committees and advisory boards, including study sections for the National Institutes of Health.

Metz published more than 250 scientific papers.

His paper “Basic principles of ROC analysis” has been cited nearly 3,000 times since it was published in 1978. He presented more than 80 invited lectures throughout the United Charles Metz, PhD States, Europe and Japan.

He was named a fellow by the American Association of Physicists in Medicine in 2004, received the Paul C. Hodges Alumni Society’s Excellence Award in 2004 and was honored with the L.H. Gray Medal from the International Commission on Radiation Units and Measurements at its Conference of Medical Physics in Nuremberg, Germany, in 2005 for his “fundamental contributions to basic and applied radiation science.”

“Charles was a true scientist, educator and mentor of the highest caliber,” said Maryellen L. Giger, PhD, professor of radiology, vice chair for basic science research in the Department of Radiology, chair of the Committee on Medical Physics and director of the Imaging Research Institute at the University of Chicago Medicine. “He was one of the giants in elucidating the mathematical foundations of imaging science.”

Metz also was an extraordinary teacher for colleagues as well as the students who came to him

The University of Chicago Medicine and Biological Sciences Division

for advice. “Whether you were a tenured professor or an undergraduate, he could explain any concepts in the field in the most thorough and appropriate way,” recalled Giger, Metz’s former graduate student. “He would go through it with you until he was convinced you understood it.” He served as an advisor for 38 doctoral students, many of whom now are leading figures in the field. Students in the Graduate Program in Medical Physics demonstrated their great respect for his teaching when they bestowed upon him, the Kurt Rossmann Award of Excellence in Teaching in its inaugural year.

Ronald Thisted, PhD, chairman of the Department of Health Studies at the University of Chicago, called him “an ideal colleague. He was generous with his time, especially with younger colleagues,” Thisted said. “He would consider your ideas or read your manuscript carefully and make valuable suggestions.

His advice was always positive, encouraging and constructive.”

He also was an inspiring, generous, supportive and genuinely funny father and friend, his daughters pointed out. “Dad truly was as good as they come,” said his older daughter, Molly. “There are just not enough positive words to convey how special a man he was and the contributions he made.”

Metz was a fan of high-performance automobiles and an authority on World War II German aircraft, the machines that were the initial focus of ROC analysis.

After his death, the forum for the Large Scale Aircraft Modeling website was dominated by the loss of “his incredible knowledge,” according to one commentator, “of all things aviation-related.”

Metz is survived by his daughters, Becky Metz Mavon of Western Springs, Illinois, and Molly Metz of Seattle, Washington; grandchildren Charlie, Avery, and Oni; and former wife, Maryanne Metz of Chicago.

Remembering Joseph B. Kirsner

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enowned gastroenterologist Joseph B. Kirsner, MD, PhD, the Louis Block Distinguished Service Professor of Medicine at the University of Chicago, died on July 7, 2012 at the age of 102. Dr. Kirsner began his career at the University of Chicago in 1935 and is considered a pioneer in the understanding and treatment of inflammatory bowel disease. In September, he was honored at a special memorial service held in Rockefeller Chapel, where family, friends, former patients, and colleagues spoke about his life and legacy. Here are some excerpts from their statements: “To me, Dr. Joe was more than just a doctor. He was a truly humble hero who refused to recognize the value and breadth of his contributions made not only in medicine, but in establishing the level of care for patients that became a standard throughout the GI Section and the same standard carried on by the hundreds of doctors he’s trained.”

Seymour Taxman Long-time friend and patient Gastro-Intestinal Research Foundation board member

“In his life we see the history and origins of our values, what we believe in, who we are today and what we can be when we are at our professional best. His legacy is innovation, patient-centered research and an emphasis on the patient experience, long before these became widely used concepts in modern academic medicine. The test for all of us is to continue the work of this giant in medicine. His legacy is our challenge and obligation.”

Everett E. Vokes, MD Chair, University of Chicago Medicine Department of Medicine Physician-in-Chief The John E. Ultmann Professor of Medicine and Radiation Oncology “At the time (Joe came to the University) his specialty gastroenterology was, in his own words, ‘speculative, impressionistic, anecdotal, almost mystical at times.’ The transformation of gastroenterology into a scientific discipline based on rigorous enquiry paralleled the evolution of Joe’s career, and along the way he made many seminal contributions. He was a pioneer in understanding the nature and treatment of inflammatory bowel disease, and its immunology and genetics and was one of the first to show the increased risk of colon cancer in patients with ulcerative colitis. . . . From my perspective Joe’s most enduring and important contribution was to demonstrate that the central element in the success of his academic program was outstanding patient care. Joe believed that if we really paid attention to the patient this would enable all other elements — education, and research, which requires a robust clinical practice for controlled clinical trials, as well as philanthropy, which supports research and education. Joe put all these elements in place, and everything depended on the fact that he was a really superb doctor. He was a master at ensuring that all his patients received only the very best care.”

Kenneth S. Polonsky, MD Dean, Biological Sciences Division and the Pritzker School of Medicine Executive Vice President for Medical Affairs, The University of Chicago

“His legacy is innovation, patient-centered research and an emphasis on the patient experience, long before these became widely used concepts in modern academic medicine.”

Everett E. Vokes, MD

Joseph B. Kirsner, MD, PhD, 1909-2012 “There are many wonderful people at the University of Chicago and many people important to the history of the University over its 120 years. But there are some people who come to define the University — whose commitment to quality, to people, and to ideas are so powerful that they become for so many of us a definition of what we should all be aspiring to. Joe Kirsner was one of the few who come to define the University in this way. Joe came to the University in 1935, so his connection spanned 77 years, just short of two-thirds of the University’s entire history. Over that time, he became a leader in every aspect of what we strive to be about — scientific research, compassionate clinical care, teaching and mentoring, building a community that is greater than any individual within it. While doing any one of these things well is hard enough, Joe excelled at all of them, and was able to be so powerful in achievement and commitment, that he could continuously see through situations and behavior to advocate not just for balancing all these activities, but for excelling at all of them. He never let us forget who we were and what we were striving to be.”

Robert J. Zimmer, PhD President of the University of Chicago “What did I learn from being Dr. Kirsner’s son? First of all, I learned from Dad to make every effort to write well, with precision. I often saw him at his desk writing, at night and on weekends, producing all those journal articles. He was not satisfied with first drafts . . . he revised and revised and revised… Second, I learned to pay attention to detail. . . . Third, I learned to be careful with language, because it can communicate far more than the words themselves say. . . .

Fourth, I inherited Dad’s ‘moral stance,’ a strong sense of what is right and what is wrong in one’s profession and in dealing with others. . . . Finally, there was Dad’s strong interest in the history of his field and his cautionary words about resisting dogma, which is an affliction not only in medical research but in the humanities as well.”

Robert Kirsner, PhD Professor, Department of Germanic Languages , UCLA, and a linguist specializing in usage-based approaches to the grammar and semantics of Dutch and Afrikaans.

“In addition to Dr. Kirsner’s devotion to his patients and the University of Chicago, those of us who knew him well recognized quite a competitive streak. Let me give an example of this spirit from his clinical practice: When I started working with Dr. Kirsner in

the mid-late 70s, he had two busy clinics a week . . . on Wednesday and Saturday mornings. The schedule was not serendipitous. When we, as trainees, saw consultative patients with him he would ask us to telephone the referring doctor in the presence of the patient so that he could communicate his recommendations. Well, most private practitioners in those years were unavailable at the time of the call . . . usually out playing golf . . . a subtle message that ‘academicians’ had a tougher and more austere life.”

Stephen B. Hanauer, MD Chief, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago Medicine The Joseph B. Kirsner Professor of Medicine and Clinical Pharmacology “One of the lessons I learned from Dr. Kirsner was what is required to be a great teacher and a great leader — that is to learn from those who preceded you. Although Dr. Kirsner was a transformative role model to so many, he also looked to other role models to guide and inspire his own behaviors and aspirations. His walls were covered with quotations that he found inspirational. His bookshelves were filled with the writings of scholars and philosophers about the ‘care of the soul’ and many aspects of humanism in medicine.”

David T. Rubin, MD Professor of Medicine Co-Director of the Inflammatory Bowel Disease Center, University of Chicago Medicine Associate Section Chief for Educational Programs “His reputation was no secret. I had the job of coordinating mail applications for inpatient care received at Illinois Research Hospital. One arrived in a wrinkled but stamped envelope, postmarked ‘Chicago’ and addressed: ‘To The Greatest Doctor in the World’ — one simple line, no street address, city or state, like a hopeful child’s letter to Santa Claus at Christmastime.

The envelope’s unsigned addendum: penciled by a different hand, surely [that of] a post office employee: ‘Try Joe Kirsner, The University of Chicago, Illinois.’”

David A. Morowitz, MD Clinical Professor of Medicine, Georgetown University School of Medicine Former trainee of Dr. Kirsner “Dr. Kirsner had a great love for the University of Chicago. He served it with a loyalty that is seldom seen today. He had unbounded faith in the greatness of this institution and [he] delighted in its venerable history. Dr. Kirsner took genuine pleasure in the accomplishments of the fellows who had trained in gastroenterology. He never hesitated to write a letter congratulating an author on a recent publication.”

James L. Franklin, MD Author of “GI Joe: The Life and Career of Dr. Joseph B. Kirsner”

Read the complete transcripts of these statements and other tributes to “GI Joe” Kirsner online under “Life and Legacy” at kirsner.uchicago.edu. uchospitals.edu/midway

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