Medicine on the Midway - Fall 2008

Nonprofit Organization U.S. Postage

PAID

Chicago Medicine U N I V E R SI T Y OF

Biological Sciences Division

ON T H E M I DWAY

Balancing

inequities in

health care page 22

FA L L 2 0 0 8

Medical & Biological Sciences Alumni Association 1170 East 58th Street Chicago, IL 60637

Chicago, IL Permit No. 5179

Contents

features Balancing Inequities in Health Care Health disparities research shows radical differences in medical conditions and care for some patient groups. Chicago faculty members seek ways to even out those inequalities.

by Suzanne Wilder____________________________________________

22

The New Bio Home

Under wraps

As two men removed a glass case from around the patient, a petite 30-year-old female who was headed to a CT scan, an observer leaned forward with a question: “Does she have a mummy smell?”

This is no ordinary patient. She is Meresamun, an Egyptian mummy embalmed nearly 3,000 years ago and now housed at the University of Chicago’s Oriental Institute.

The observer, OI research associate Emily Teeter, PhD, helped coordinate the scan with Michael Vannier, MD, professor of radiology at the University of Chicago Medical Center.

The goals: To create a three-dimensional reconstruction of Meresamun’s face, analyze her pubic bones to determine whether she had children, and examine evidence on her nutrition, dentition, age and injuries.

The information garnered from the images will enhance a new exhibit featuring Meresamun and her life as a temple singer.

Her profession, like her name, is printed in hieroglyphs on her intricately painted coffin.

Meresamun was scanned here more than 15 years ago, but since then technology has drastically improved. In the first scan, researchers learned she had fractured her left jaw and left arm during her life. They also estimated her age but could not pinpoint a cause of death. The first set of scans took hours; the most recent finished in minutes.

The Ricketts Regional Biocontainment Laboratory will bring high-tech—and high-security—facilities to researchers at Argonne.

by Megan Seery______________________________________________ For the scans, Meresamun remained sealed in her coffin and wrapped in an additional box for transit across campus. The medical equipment, typically used for living patients, became “an anthropological tool,” Vannier said.

On a sunny July morning, a U-Haul van arrived at the entrance of the Mitchell ER. A team of conservators and medical staff moved a wooden crate, marked in hieroglyphs with the word “fragile,” to radiology. Meresamun came out of the crate for the 64-slice CT scan, where technologists captured thousands of images from head to toe. Kristin Runion, one of the CT technologists helping with the scan, snapped photos with her cell phone and listened to details about the mummy.

“I just got a history lesson,” she said as Meresamun slid in and out of the tunnel-like machine.

“You should come by and see her when she’s on display,” Teeter told Runion as images gradually appeared on a computer screen nearby. “You’ll be able to say, ‘I know this mummy inside and out.’”

—Suzanne Wilder

30

A ‘Dream Job’ for an Evolutionary Biology Student Nathan Smith studies dinosaurs, digs for fossils and travels the world— all part of his work at the Field Museum and as a PhD candidate at the University of Chicago.

by Katie Scarlett Brandt________________________________________

34

departments Midway News Catch up on the latest research and news in medicine and biology at Chicago, plus the latest books by faculty and alumni.________________

2

Medicine off the Midway Charis Eng couldn’t decide between medicine or chemistry, clinical work or research. Ultimately, she brought them all together.

by Katie Scarlett Brandt________________________________________

36 Class Update_________________________________________ 40 Perspective Dean of the Biological Sciences James L. Madara and Dean of Medical Education Holly J. Humphrey share their thoughts on the value of staying small at Pritzker._______________________________________

On these pages: Meresamun in her coffin at the University of Chicago Oriental Institute and in the CT scanner at the Medical Center, and a digital image from her scan; scan courtesy of Michael Vannier, MD. Photos by Dan Dry

46

Midway News

Illinois public schools fall short in sex ed “Uninformed teens often become uninformed young adults.”

—Adjoa Tetteh, research assistant and a college peer sex educator

Only two-thirds of Illinois public school teachers provide comprehensive sex education, University of Chicago researchers report in the Februar y 2008 issue of the journal Obstetrics and Gynecology.

Sixty-five percent of teachers who responded to the researchers’ survey covered the four basic topics required to be rated “comprehensive”: abstinence until older or until marriage, HIV/AIDS, other sexually transmitted diseases and contraception. When the researchers added a widely recommended fifth topic—where to get condoms, birth control and health-related services—only 42 percent of sex education teachers passed the comprehensive test.

The survey also found that 30 percent of the state’s sex-education teachers had never received training in the subject, well above the national average of 18 percent. Although most teachers with training reported that they felt “very comfortable” teaching adolescents about sex, only 56 percent of those who lacked such training said they felt comfortable.

“For this study, we set the bar for comprehensiveness fairly low relative to what most medical and public health organizations recommend,” said senior author Stacy Tessler Lindau, MD, assistant professor of obstetrics and gynecology and medicine, “and one out of three programs failed to clear it.”

“Our children learn many of the skills they need to be healthy citizens and to take responsibility for their own health in school,” she said. “That should include information about sexual aspects of health. Physicians who care for adolescents need to know what students are or are not learning in school in order to fill gaps caused by deficits in program content, quality and teacher training.”

Previous studies showed that nearly two-thirds of 12th-graders have engaged in sexual intercourse and that accurate knowledge can delay sexual debut and increase the use of condoms or other forms of contraception when adolescents do become sexually active.

“Most parents support school-based sex education, and teens regard it as an important source of information,” Lindau said, “yet we found that several important health topics and skills are omit ted, more of ten t ha n not, from most Illinois public school sexeducation criteria.”

“Uninformed teens often become uninformed young adults,” said second author Adjoa Tetteh, research assistant and a college peer sex educator. “Working with college students, I have witnessed this firsthand. Many students come to college with years of sexual experience but are learning for the first time about effective ways to prevent [sexually transmitted infections] and unintended pregnancy.”

The researchers used data collected by the National Opinion Research Center (NORC), a survey research firm at the University of Chicago. NORC mailed self-administered questionnaires to 335 sex education teachers from 201 public middle and high schools in 112 Illinois school districts during the 2003– 04 school year. Sixty-two percent of the teachers, representing 91 percent of schools, responded.

Teachers were asked which of 17 possible topics they taught and, if they omitted certain topics, to explain why.

They also were asked about their training and how they would grade the sex education curriculum.

Of the responding schools, 93 percent offered sex education; 7 percent did not.

The most frequently taught topics, covered by 96 percent of teachers, were HIV/ AIDS and other sexually transmitted diseases. Almost 90 percent of teachers covered abstinence. Among those who taught abstinence, 57 percent emphasized it was the “best alternative,” 39 percent said it was the “only alternative” and 4 percent described it as “one alternative.”

Practical skills—such as contraception, condom use, decision-making and communicating with a partner—and morally debated topics, such as abortion and sexual orientation, were among the least frequently taught. Teachers who had not received sex-education training were less likely to spend time on practical or morally debated topics.

Of the 17 topics, emergency contraception was mentioned least, taught by only 30 percent of teachers. Only 32 percent of teachers brought up homosexuality or sexual orientation, 34 percent taught how to use condoms, 37 percent taught how to use other forms of birth control,

39 percent discussed abortion and 47 percent taught students where to get contraception a nd sexua l health services.

The most common reason for omitting a topic was “not part of the curriculum.” Those who omitted condom use, however, most often cited “school or district policy.”

Teachers gave themselves the highest grades for instruction on reproductive basics and abstinence, with nearly four out of five ranking that part of the curriculum as good or excellent. About two-thirds gave themselves comparable grades for teaching their students about the emotional consequences of sex, dealing with pressures to have sex, or where to access contraception or services.

Though about half rated their instruction on how to use condoms or other forms of birth control as good or excellent, a quarter rated instruction on these topics as average and another quarter rated them as poor or very poor.

“Although a recent study has called into question the effectiveness of abstinence-only sex education, the trend over the last 10 years, supported by federal

incentives, has been to emphasize abstinence and exclude information about contraception,” Lindau said. “Given that a large number of young people are sexually active, we worry that such restrictive approaches leave students unprepared to prevent pregnancy and/or sexually transmitted diseases.”

“In most cases,” she added, “they are not even given access to information about how to talk about these issues or where to get help should they need it.

Doctors need to be aware of this and should be proactive in initiating discussion about sexuality with parents and adolescents. Doctors may also be an important resource for providing teachers with medically accurate information and training.”

“Our study provides important new data from the teachers’ perspective,” said study co-author Melissa Gilliam, associate professor and section chief of family planning and contraceptive research. “It supports other recent studies showing that large numbers of teens, especially low-income and youth of color, received no instruction about birth control methods before they first had sex.”

—John Easton

Not only was University of Chicago gastroenterologist Donald Jensen selected one of 355 of the area’s best physicians by Chicago magazine, but his photo also graces the cover of the January 2008 issue in which a total of 54 University of Chicago Medical Center physicians—about one of every seven—are listed. The list, according to the magazine, includes “physicians most highly regarded by their peers.”

It is based on mail and telephone surveys and electronic ballots sent to physician and medical leadership of “leading local hospitals to identify highly skilled exceptional doctors.”

In his profile, Jensen emphasized the need for better treatments for patients with hepatitis C, the need for physicians to combine technical expertise with empathy and the ability to put patients at ease, hear their concerns and give them “all the attention he would want if in their position.”

Fall 2008 3

IN BRIEF E-paper meets better breathing

Lack of deep sleep may increase risk of type 2 diabetes “A decrease in slow-wave sleep resembles the changes in sleep patterns caused by 40 years of aging.”

—Esra Tasali, MD, assistant professor of medicine

Suppression of slow-wave sleep in healthy young adults significantly decreases their ability to regulate bloodsugar levels and increases the risk of type 2 diabetes, University of Chicago scientists reported in the Early Edition of the Proceedings of the National Academy of Science in December.

Deep sleep, also called “slow-wave sleep,” is thought to be the most restorative sleep stage, but its significance for physical well-being has not been demonstrated. This study found that after only three nights of selective slow-wave sleep suppression, young healthy subjects became less sensitive to insulin. Though they needed more insulin to dispose of the same amount of glucose, their insulin secretion did not increase to compensate for the reduced sensitivity, resulting in an increased risk for type 2 diabetes.

The decrease in insulin sensitivity was comparable to that caused by gaining 20 to 30 pounds.

Previous studies have demonstrated that reduced sleep quantity can impair glucose metabolism and appetite regulation resulting in increased risk of obesity and diabetes. This current study provides the first evidence linking poor sleep quality to increased diabetes risk.

“These findings demonstrate a clear role for slow-wave sleep in maintaining normal glucose control,” said lead author Esra Tasali, MD, assistant professor of medicine. “A profound decrease in slowwave sleep had an immediate and significant adverse effect on insulin sensitivity and glucose tolerance.”

“Since reduced amounts of deep sleep are typical of aging and of common obesity-related sleep disorders such as obstructive sleep apnea, these results suggest that strategies to improve sleep quality, as well as quantity, may help to prevent or delay the onset of type 2 diabetes in populations at risk,” said Eve Van Cauter, PhD, professor of medicine at Chicago and senior author of the study.

“These f indings shed light on a problem faced by many elderly, that of fragmented sleep and less time spent in 4 University of Chicago Medicine on the Midway

restorative sleep,” said Andrew Monjan, PhD, chief of the neurobiology of aging branch at the National Institute on Aging, which partially funded the research. “More research is needed into the link between insufficient sleep and common metabolic disturbances of later life, such as type 2 diabetes and obesity.”

The researchers studied nine lean, healthy volunteers, five men and four women between the ages of 20 and 31.

The subjects spent two consecutive nights in the sleep laboratory, where they went to bed at 11 p.m., slept undisturbed but carefully monitored, and got out of bed 8.5 hours later, at 7:30 a.m.

The same subjects also were studied for three consecutive nights during which they followed identical nighttime routines. During this session, however, when their brain waves indicated that they were drifting into slow-wave sleep, they were subtly disturbed by sounds administered through speakers beside the bed.

These sounds were loud enough to disrupt deep sleep but not so loud as to cause a full awakening. This technique enabled the researchers to decrease slowwave sleep by about 90 percent, shifting the subjects from the onset of deep sleep (stage 3 or 4) to a lighter sleep (stage 2) without altering total sleep time.

“Our system proved quite effective,” Tasali said. When asked about the sounds the next morning, study subjects vaguely recalled hearing a noise “three or four times” during the night. Some recalled as many as 10 to 15. On average, however, subjects required about 250 to

300 interventions each night, fewer the first night but more on subsequent nights as “slow-wave pressure,” the body’s need for deep sleep, accumulated night after night.

“This decrease in slow-wave sleep resembles the changes in sleep patterns caused by 40 years of aging,” Tasali said.

Young adults spend 80 to 100 minutes per night in slow-wave sleep, while people over age 60 generally have less than 20 minutes. “In this experiment,” she said, “we gave people in their 20s the sleep of those in their 60s.”

At the end of each study, the researchers gave intravenous glucose (a sugar solution) to each subject, then took blood samples every few minutes to measure the levels of glucose and insulin, the hormone that controls glucose uptake.

They found that when slow-wave sleep was suppressed for only three nights, young healthy subjects became about 25 percent less sensitive to insulin. As insulin sensitivity decreased, subjects needed more insulin to dispose of the same amount of glucose. But for eight of the nine subjects, insulin secretion did not go up to compensate for reduced effects.

The result was a 23 percent increase in blood-glucose levels, comparable to older adults with impaired glucose tolerance.

The alarming rise in the prevalence of type 2 diabetes is generally attributed to the epidemic of obesity combined with the aging of the population. “Previous studies from our lab have demonstrated many connections between chronic and partial sleep deprivation, changes in appetite, metabolic abnormalities, obesity and diabetes risk,” Van Cauter said. “These results solidify those links and add a new wrinkle, the role of poor sleep quality, which is also associated with aging.”

“Chronic shallow non-REM sleep, decreased insulin sensitivity and elevated diabetes risk are typical of aging,” the authors conclude. “Our findings raise the question of whether age-related changes in sleep quality contribute to the development of these metabolic alterations.”

—JE

Imagine discovering a principle of physics with the potential to create electronic paper and to help people with respiratory distress syndrome.

A team of researchers, including University of Chicago MD-PhD student Luka Pocivavsek, entered such territory when they documented the dynamics of wrinkling and folding in different materials during a study on a lung surfactant called dipalmitoylphosphatidylcholine, or DPPC. Lung surfactant has the ability to wrinkle and fold under pressure and then gracefully pop back into a stiff configuration when relaxed, like a thin elastic sheet. When first compressed, an elastic material begins to form a trough or peak. Lung surfactant has the ability to reverse this stress, allowing the folding that occurs on exhalation to smoothly stretch back into its previous state with inhalation. This principle means it is possible, Pocivavsek said, “to create a polymer composite that would never wrinkle.”

Helping pain meds Thirty years after it was discovered, methylnaltrexone, a drug developed to relieve a major side effect of pain therapy for cancer patients, received marketing approval April 24 from the U.S. Food and Drug Administration.

The FDA’s European equivalent rendered a “positive opinion” for methylnaltrexone on the same day; Health Canada approved the drug March 28. The drug, to be marketed as Relistor, “will be helpful to patients who experience severe constipation associated with the continuous use of morphine or other opioids, which are an important part of care for patients with late-stage, advanced illness,” said FDA’s Joyce Korvick, deputy director for the Division of Gastroenterology Products. More than 1.5 million Americans who suffer from advanced illnesses such as cancer take powerful opioid-based pain relievers such as Percocet, OxyContin or morphine. Methylnaltrexone, invented in 1979 by the late University of Chicago pharmacologist Leon Goldberg, blocks the side effects without disrupting pain relief.

Fall 2008 5

IN BRIEF Pritchard named HHMI investigator

Impact of free drug samples, Medicare Part D “Physicians should use caution in assuming that the use of free samples ultimately reduces patients’ out-of-pocket prescription cost.”

—G. Caleb Alexander, MD, assistant professor of medicine

Prescription drug programs have significant effects on how patients use their medication and on the prices they pay, but those effects may not always be the expected ones, according to a pair of studies headed by a University of Chicago researcher.

G. Caleb Alexander, MD, assistant professor of medicine, examined both the Medicare Prescription Drug Benefit (Part D) and the practice of providing free samples of prescription drugs to certain patients.

In the latter study, published in the March 24, 2008, issue of Medical Care, Alexander discovered that patients who receive these samples have significantly higher out-of-pocket prescription costs than those who don’t.

6 University of Chicago Medicine on the Midway

“Our findings suggest that physicians should use caution in assuming that the use of free samples ultimately reduces patients’ out-of-pocket prescription costs,” Alexander said.

Patients in the study who never received samples had estimated out-ofpocket prescription costs of $178 over six months. Patients who received samples spent an estimated $166 for a six-month period prior to getting free samples, $244 for the six months in which they received samples and $212 for the six-month period following sample receipt.

“Samples may be particularly valuable in providing patients economic relief when they are used short-term and not followed up with a long-term prescription for the same medicine,” Alexander

said. “However, all too often, physicians and patients end up continuing the medicines initially begun as samples, even though older, less expensive alternatives may exist.”

Previous surveys have found that free samples can lead to overuse of newer drugs over their older counterparts, but the prior studies usually examined just one clinical setting and not the costs associated with samples.

Alexander’s team used the Medical Expenditure Panel Survey, conducted by the Agency for Healthcare Research and Quality, to examine the characteristics of those receiving samples, as well the relationship between sample receipt and out-of-pocket prescription costs. They followed 5,709 patients from the national survey for up to two years.

The authors found there were important differences in the characteristics of patients who received samples and those who did not. The odds of sample receipt were lower among those who were older and also among those who had Medicaid as their source of insurance coverage.

Alexander said further research is needed to examine patient-physician communication about samples “as well as how physicians decide who needs samples and how samples are distributed across different types of physician practices.”

The study was supported by the Robert Wood Johnson Foundation. Additional authors of the paper include James Zhang, PhD, of Virginia Commonwealth University, and Anirban Basu, PhD, of Chicago.

In a separate study published in the Feb. 5, 2008, edition of the Annals of Internal Medicine, Alexander reported that Medicare Part D benefit led to a 13.1 percent decrease in out-of-pocket expenses for patients and a 5.9 percent increase in prescription use.

The most thorough study to date of the impact of Medicare Part D, the research involved 117,000 patients. Researchers from Chicago, Harvard University and Virginia Commonwealth University compared out-of-pocket costs and the number of pills purchased by those

who were eligible for Part D with patients who were not. They also compared Part D enrollees to patients who were eligible for, but did not enroll in, Part D. “Despite extensive debate, it was not clear to what extent Part D would save people money or allow them to obtain drugs they might not otherwise be able to afford,” Alexander said. “We found that it had a modest but significant effect on both savings and drug use.”

Using data from customers who filled prescriptions in 2005 and 2006 through the Chicago-based Walgreens pharmacy chain, the researchers found that the program saved people who enrolled before the May 15, 2006, deadline about $6 a month and gave them, on average, an extra three to four days worth of one medicine per month. After the enrollment deadline, average savings among all eligible seniors in the study increased to about $9 a month and 14 extra days of medicine per month.

Although the sample group may not be nationally representative of all beneficiaries, “our report represents one of the first analyses of the impact of Part D,” said co-author Wesley Yin, PhD, an assistant professor in the Harris School of Public Policy at Chicago and a Robert Wood Johnson Foundation Scholar at Harvard. “It reflects the experiences of millions of Americans accounting for approximately 15 percent of the market share in the United States.”

The authors also found that patients who enrolled early in the Part D program had higher rates of utilization and out-of-pocket costs prior to the Part D period and stood to benefit most from enrollment.

They conclude that Medicare Part D has, indeed, led to savings and increases in prescription drug use by older people.

However, “more research is needed to see whether these effects have any influence on people’s health,” Alexander said.

—Maja Fiket

Human geneticist Jonathan Pritchard was named a Howard Hughes Medical Institute investigator. Pritchard has studied “a wider range of topics than most biologists cover in a lifetime,” according to HHMI, which commits more than $600 million to 56 of the nation’s top scientists over their first terms of appointment. Pritchard has analyzed the patterns in human DNA created by historical migrations, the consequences of natural selection, and even the question of whether modern humans and Neanderthals interbred. Since joining the University in 2001, Pritchard has worked to understand the links between genetic variation and human traits. He plans to determine how common variations in human DNA are and link them to disease and other traits.

Hope for peripheral neuropathy Mutations in a protein called dynein, required for proper sensory nerve cell function, can cause defects in mice that may provide crucial clues leading to better treatments for peripheral neuropathy. A prevalent disease with no known cause or effective treatment, peripheral neuropathy results from damage to nerves and nerve processes that are located outside the brain and spinal cord. Symptoms include pain in the hands, arms, legs and feet—sometimes constant and quite severe—as well as progressive numbness and weakness in the arms and legs. Neurologist Brian Popko showed that mice with mutations in only one copy of a gene coding for one part of dynein protein had severe defects and a significant reduction in sensory nerve cells.

The 1.2 million-square-foot new hospital pavilion, approved this spring by both the University of Chicago Medical Center and University of Chicago Boards of Trustees, will span two city blocks and rise 10 floors. Construction on the $700 million project is slated to begin in 2009, with a 2012 open date. As the largest single health care investment in South Side Chicago’s history, the new building will house 240 private inpatient and intensive care beds; 24 state-of-the-art operating rooms; 12 rooms for gastrointestinal and pulmonary procedures; seven interventional radiology suites; and advanced diagnostic tools including high-resolution, high-speed MRI and CT scanners. “The new hospital pavilion is more than a building,” said James Madara, MD, dean of the biological sciences and Pritzker School of Medicine, and chief executive officer of the University of Chicago Medical Center. “It embodies our commitment to provide the finest possible care to those with the most challenging illnesses. It also is a model of flexibility, which will enable physicians to leverage advances in medical science for the benefit of our patients for decades to come.”

Photo by Dan Dry

Fall 2008 7

IN BRIEF Malaria drug attacks toxoplasmosis

Location matters, even for genes “This could be tremendously important . . . for understanding the underlying cause of some diseases that result from mutations in genes encoding inner nuclear membrane proteins.”

—Karen Reddy, PhD, post-doctoral fellow

Moving an active gene from the interior of the nucleus to its periphery can inactivate that gene, University of Chicago scientists reported in an article published in the journal Nature in February.

Attachment to the inner nuclear membrane, they showed, can silence genes, preventing their transcription—a novel form of gene regulation.

“Several years ago, we and others described the correlation between nuclear positioning and gene activation,” said study author Harinder Singh, PhD, professor of molecular genetics and cell biology and an investigator in the Howard Hughes Medical Institute at Chicago.

“With that in mind, we wanted to take the next step, to design an experiment that could test causality. Could we move a gene from the center of the nucleus to the periphery and then measure the consequences of such repositioning?”

In mammalian nuclei, chromatin— a complex of DNA and associated proteins—is organized into structural domains through interactions with distinct nuclear compartments. In this study, the authors developed the molecular tools to take specific genes from these interior compartments, move them to the periphery and attach them to the nuclear membrane—which turned those genes off.

Not only were selected “test” genes that served as markers turned off after being attached to the inner nuclear membrane, but so were nearby “real” genes.

Singh’s team became interested in studying the role of nuclear positioning in the control of gene activity based on work analyzing immunoglobulin heavy-chain genes. These genes are assembled by DNA recombination and code for proteins that are a crucial part of antibodies, produced in antibody-secreting lymphocytes or B-cells.

“In cells that don’t produce antibodies, like fibroblasts or T-cells, these antibody genes are attached to the inner nuclear membrane and are not recombined or expressed,” Singh said.

8 University of Chicago Medicine on the Midway

On the other hand, antibody genes are actively transcribed and recombined in developing B-cells, and therefore positioned in the nuclear interior, far away from the periphery.

Five years ago, Singh and colleagues reported in Science that even in developing B-cells, antibody genes start off at the nuclear periphery. As young cells mature and prepare to produce antibodies, however, these genes move to the interior of the nuclei.

The exact ways in which positioning at the outer edge of the nucleus prevents gene expression are still unclear. The likely suspects, Singh said, are some of the proteins that reside in the inner nuclear membrane and that may be involved in blocking transcription. “We think that these proteins are part of the molecular machinery that is used for positioning genes at the inner nuclear membrane, as well as potentially for repressing them,” he said.

In the Nature paper, Singh’s team also showed for the first time that this transcriptional repression is dependent on breakdown and reformation of the nuclear membrane during cell division.

The reorganizing of chromosomes occurs when cells divide. “This suggests that cell division is used not only to transmit the genetic information into daughter cells and create two equivalent cells,” Singh said, “but it is also an opportunity for cells to reorganize their genomes in 3-D space, sequestering parts of the genome at the nuclear periphery and rendering it inaccessible to transcription.”

Singh and colleagues are now looking for examples of striking reorganization of the genome separated by one cell division—in which active genes, that will not be active after the cell divides, get pushed away from the interior to the periphery.

The lead author, Karen Reddy, PhD, a post-doctoral fellow in the Singh laboratory, proposes that such compartmentalization “implies the existence of DNA segments that encode for ‘nuclear addresses’ acting like a nuclear zip code to direct or predispose genes to associate with specific regions within the nucleus.

This could be tremendously important,” she said, “for understanding the underlying cause of some diseases that result from mutations in genes encoding inner nuclear membrane proteins.”

—MF

Ancestral differences affect response to drugs and infections “We want to understand why different populations experience different degrees of toxicity when taking certain drugs.”

—Eileen Dolan, PhD, professor of medicine

Differences in gene expression levels between people of European versus African ancestry can affect how each group responds to certain drugs or fights off specific infections, according to researchers from the University of Chicago and the Expression Research Laboratory at Affymetrix Inc. of Santa Clara, Calif.

Using Affymetrix exon arrays, the scientists found expression levels for nearly 5 percent of the 9,156 human genes studied varied significantly between individuals of European and African ancestries.

The results were published in the March 7, 2008, issue of American Journal of Human Genetics.

The research team took an unbiased, whole-genome approach and found significant differences in several unrelated processes, especially among genes involved in producing antibodies to potential microbial invaders.

The researchers used lymphoblastoid cell lines derived from blood from 180 healthy individuals. They studied 60 nuclear families, including mother, father and child. Thirty of the families were Caucasians from Utah, and 30 were Yorubans from Ibadan, Nigeria.

“Our primary interest is the genes that regulate how people respond to medicines, such as cancer chemotherapy,” said cancer specialist Eileen Dolan, PhD, professor of medicine at Chicago and senior author of the study. “We want to understand why different populations experience different degrees of toxicity when taking certain drugs and learn how to predict who might be most at risk for drug side effects.”

In the process the research team saw several other differences. Some, including variation in the immune system’s response to microbial invaders, were expected. Previous studies have found that

African-Americans may be more susceptible than Caucasians to infection by certain bacteria, such as Porphyromonas gingivalis that causes periodontitis.

Other differences were unanticipated, including significant differences in expression levels among genes involved in fundamental cellular processes, such as ribosomal biogenesis, transfer RNA processing, and Notch-signaling—part of a complex system of communication that governs basic cellular activities and coordinates cell actions.

“Population differences in gene expression have only recently begun to be investigated,” Dolan said. “We believe they play a significant role in susceptibility to disease and in regulating drug response. Our current research focuses on how these genetic and expression differences play a role in sensitivity to adverse effects associated with chemotherapy.”

Understanding at the genetic level how individuals within and among populations vary in their response to drugs could improve treatment. The research team worked closely with Affymetrix on new technology that enabled them to perform a very comprehensive study including evaluation of expression levels of every known gene.

—MF

A new drug that will soon enter clinical trials for malaria treatment also appears to be 10 times more effective than current treatments for toxoplasmosis, a disease caused by a related parasite that infects more than 2 billion people worldwide. Research based at the University of Chicago shows that the drug, known as JPC-2056, is extremely effective against Toxoplasma gondii, the parasite that causes toxoplasmosis. “JPC-2056 has the potential to replace the standard treatment of pyrimethamine and sulfadiazine,” said infectious disease specialist Rima McLeod, senior author of the study. “The drug, taken by mouth, is easily absorbed, bioavailable and relatively nontoxic. In tissue culture and in mice, it was rapidly effective, markedly reducing numbers of parasites within just a few days.”

Even moderate drinking elevates women’s cancer risk The more a woman drinks, the higher her cancer risk. Even moderate alcohol consumption—defined as one or two drinks per day—increased risk of developing tumors classified as positive for both estrogen and progesterone receptors, according to research

by Jasmine Q. Lew, a fourth-year student at the Pritzker School of Medicine. Lew received a Howard Hughes Medical Institute-National Institutes of Health Research Scholarship to spend a year doing research at the National Cancer Institute’s Division of Cancer Epidemiology and Genetics. She presented her results on “Alcohol consumption and risk of breast cancer in postmenopausal women: the NIH-AARP Diet and Health Study,” at the American Association for Cancer Research annual meeting in San Diego.

Computation helps locate drug targets Using a novel computational approach, researchers have produced helpful new guidelines for efficient target screening for new drugs, said professor of medicine Andrey Rzhetsky at the University of Chicago. With colleagues at Chicago and Columbia University, Rzhetsky analyzed properties of human genes and proteins that serve as targets for nearly a thousand FDA-approved drugs. They identified a number of characteristics that were common among successful drug targets— especially among high-revenue drugs. “When a drug company must decide which target to pursue among pathologic pathways, this could provide useful estimates of each target’s expected success rate,” Rzhetsky said. Because the cost of developing a new drug can reach more than a billion dollars, “information that helps only a little bit,” he said, “can still be quite valuable.”

Fall 2008 9

IN BRIEF Only Caucasian women helped by stopping hormone therapy

Metabolic syndrome linked to cold tolerance “All these genes are likely to be involved in metabolic adaptations to cold climates.”

—Anna Di Rienzo, PhD, professor of human genetics

Researchers from the University of Chicago have discovered that many of the genetic variations that enable human populations to tolerate colder climates also may affect their susceptibility to metabolic syndrome, a cluster of related abnormalities including obesity, elevated cholesterol levels, heart disease and diabetes.

More than 100 years ago, scientists noted that humans inhabiting colder regions were bulkier and had relatively shorter arms and legs. In the 1950s, researchers found correlations between colder climates and increased body mass index (BMI), a measure of body fat, based on height and weight.

In a study published in the February issue of the open-access journal PLoS Genetics, scientists show a strong correlation between climate and several of the genetic variations that appear to influence the risk of metabolic syndrome.

This correlation is consistent with the idea that these variants played a crucial role in adaptations to the cold. The researchers report that some genes associated with cold tolerance have a protective effect against the disease, while others increase disease risk.

“Our earliest human ancestors lived in a hot, humid climate that placed a premium on dispersing heat,” said Anna Di Rienzo, PhD, professor of human genetics at Chicago. “As some populations migrated out of Africa to much cooler climates, there would have been pressure to adapt to their new settings by boosting the processes that produce and retain heat.”

“Thousands of years later,” she said, “in an era that combines widespread central heating with an overabundant food supply, those genetic alterations have taken on a different sort of significance.

They alter our susceptibility to a whole new set of diseases, such as obesity, coronary artery disease and type 2 diabetes.”

The researchers set out to look for correlations between the frequency of genetic variations linked to metabolic syndrome and climate variables in worldwide population samples.

10 University of Chicago Medicine on the Midway

Opiates, nicotine addiction show similarities “Research . . . reinforces the fact that these addictions are very physiological in nature and that breaking away from the habit is certainly more than just mind over matter.”

—Daniel McGehee, PhD, associate professor of anesthesia and critical care

Several gene variations that appear to play a role in energy storage or expenditure show a strong correlation with environmental variables such as winter temperatures. For example, six variants of the RAPTOR gene (shown throughout above map) —which is involved in nutrient signaling, mitochondrial oxygen consumption and oxidative capacity—were far more common in colder climates. Image provided by researchers

They selected 82 genes associated with energy metabolism—many of them previously implicated in disease risk—and looked for climate-related variations.

They studied genetic variation in 1,034 people from 54 populations, finding widespread correlations between the frequencies of certain genetic variations and colder climates, as measured by latitude, as well as summer and winter temperatures.

One of the strongest signals of selection came from the leptin receptor, a gene involved in the regulation of appetite and energy balance. One version of this gene is increasingly common in locales with colder winters. This version of the leptin receptor is associated with increased respiratory quotient—the ability to take up oxygen and release carbon dioxide— which plays an important role in heat production. The allele also has been linked to lower BMI, less abdominal fat and lower blood pressure, and is thus protective against metabolic syndrome.

Other genes that varied according to climate included several involved in heat production, cholesterol metabolism, energy use and blood glucose regulation.

Not all cold-tolerance-related gene variants protect against metabolic syndrome. Increased blood glucose levels, for example, could protect someone from the cold by making fuel more readily available for heat production, yet it raises the risk of type 2 diabetes. The version of a gene known as FABP2 that became more common as temperatures fell causes increased BMI, promotes fat storage and elevates cholesterol levels. This genetic variant would protect against the cold but increase susceptibility to heart disease and diabetes.

“All these genes are likely to be involved in metabolic adaptations to cold climates,” Di Rienzo said, “but they have opposing effects on metabolic syndrome risk. We suspect they spread rapidly as populations settled into colder and colder climates at higher latitudes, but in the modern era they have taken on a whole new significance, as the supply of calories from food has mushroomed, and the survival advantage of generating more heat has been minimized by technology.”

The authors suggest the search for genes that vary according to climate could provide additional clues about the onset of metabolism-related diseases.

“That was good! Do it again!”

This is what the brain said when people use tobacco, as well as “hard drugs” such as heroin. New research published in the Feb. 13, 2008, issue of the Journal of Neuroscience indicates that the effects of nicotine and opiates on the brain’s reward system are equally strong in a key pleasure-sensing area of the brain—the nucleus accumbens.

“Testing rat brain tissue, we found remarkable overlap between the effects of nicotine and opiates on dopamine signaling within the brain’s reward centers,” said Daniel McGehee, PhD, associate professor of anesthesia and critical care at the University of Chicago.

McGehee and colleagues are exploring the control of dopamine, a key neurotransmitter in reward and addiction.

Dopamine is released in areas such as the nucleus accumbens by naturally rewarding experiences such as food, sex, some drugs and the neutral stimuli or “cues” that become associated with them.

Nicotine and opiates are very different drugs, but the endpoint, with respect to the control of dopamine signaling, is almost identical. “There is a specific part of the nucleus accumbens where opiates have been shown to affect behavior, and when we tested nicotine in that area, the effects on dopamine are almost

identical,” McGehee said.

This research is important to scientists because it demonstrates overlap in the way the two drugs work, complementing previous studies that showed overlapping effects on physiology of the ventral tegmental area, another key part of the brain’s reward circuitry. The hope is that this study will help identify new methods for treating addiction—and not just for one drug type.

“It also demonstrates the seriousness of tobacco addiction, equating its grip on the individual to that of heroin,” McGehee said. “It reinforces the fact that these addictions are very physiological in nature and that breaking away from the habit is certainly more than just mind over matter.”

—Scot Roskelley

A recent decrease in invasive breast cancer in the United States did not extend to women of African ancestry, University of Chicago researchers report. U.S. breast cancer rates in women over 50 fell sharply during 2002 and 2003, but the decline was confined to Caucasians. For Caucasian women aged 50 to 69, the rate of invasive breast cancer decreased by more than 2 percent during that period, then stabilized in 2004. For African-Americans, there was virtually no change. Much of the disparity may result from differences in biology.

In mid-2002, many women who had been taking replacement hormones stopped taking them in response to a Women’s Health Initiative trial that warned of coronary heart disease and breast cancer risk related to hormone replacement therapy. “African-Americans are less likely to use hormone replacement therapy and less likely to develop breast cancers that are receptive to estrogen,” said health studies researcher Dezheng Huo, “so they were harmed less by taking hormones and benefited less by discontinuing them.”

Protein expression predicts breast cancer risk A novel systems-based approach—combining comprehensive gene expression profiling with genome-wide transcription factor analysis and protein-protein interaction—has led researchers to a genetic marker that can help physicians know which breast cancer patients are at highest risk and require more aggressive treatment, a research team based at the University of Chicago Medical Center reports.

They found that high expression of a protein known as H2A.Z, associated with the expression of genes within the nucleus, can help physicians predict which patients are most at risk for disease spread and death. It also could serve as a new target for therapy. “Elevated H2A.Z expression is significantly associated with metastasis and shorter survival, and it could quickly help doctors make better predictions and treatment choices for patients.

It could also provide clues to new therapies,” said geneticist Kevin White. “But perhaps more important, we think we have developed an integrated approach to genomic analysis that can be applied to a wide range of cancers.”

Fall 2008 11

‘Making a model, in reverse’ “When you actually find something, it’s rewarding.”

—Barrett Boody, first-year medical student

Clad in scrubs and hunched over stainless steel tables, a group of first-year medical students began to explore the intricacies of anatomy as more than two dozen cadavers lay waiting.

This school year, students plunged into a class called “The Human Body” on the first day of orientation—weeks before most other courses began.

“They can focus just on anatomy,” said instructor Betty Katsaros, who has taught the subject for 25 years, 15 of them at the University of Chicago.

Lectures and labs began with the development of the body, radiology and

embryology, and progressed to specific body parts and organ systems with each passing week.

With diagrams sketched on white boards a nd a natomy book s strew n across nearby stools, first-year students wrapped the bodies in cloth soaked in an antifungal solution. Each day, as they studied a new part of the body, they peeled away damp fabric to unveil the skin, arteries and organs underneath. They were discovering the patient’s health ailments along the way: Pacemakers, gallstones and cancer had all been revealed during the first month of work.

Second-year medical student Mechelle Miller (center) helps examine a liver with first-year students Jihye Ha (left) and Rebecca Levine.

12 University of Chicago Medicine on the Midway

In late August, students examined the abdomen, the intestines and the blood supply to abdominal organs. The pungent odor of formaldehyde pervaded the room as students looked at livers, pale or bright green gallbladders, arteries, veins and intestines. Teams of first-years carefully separated fat and muscle tissue looking for arteries. They traded terms such as “superior mesenteric artery” and “hepatic artery” while exploring the abdominal networks of blood vessels.

“It’s really hard to disentangle everything,” said medical student Dana Sun, while she looked for vasculature surrounding the intestines and abdominal organs.

Students paged through anatomy books with nitrile gloves, seeking roadmaps for the body. Student David Voce scribbled a diagram of the arteries of the liver on his pants for easy reference while he worked.

Manuel Diaz and his lab partners called the cadaver a gift: an invaluable way to examine the body as a whole. “It’s like making a model in reverse,” Diaz said. “All the detail is there. You have to reveal it.”

But they also recognized the relationships they were building with each other.

“This is a cool experience. We get to bond.

We really do absorb a lot,” Diaz said.

From left: First-year medical students Stephanie McCann and Mei Zhou work with fourth-year Hanna Schittek to examine the abdomen of a cadaver.

Barrett Boody, who was working with Diaz, said the learning experience was unlike anything he had before.

Though some students had taken other anatomy classes, the work with the cadavers brought more depth and emotion. “Ethically, morally, there’s a lot more involved,” he said.

Ellen Rebman was studying a cadaver with a herniated stomach, gallstone and pacemaker. Students knew the elderly patient died of cardiac arrest, Rebman said, but other details of her health were not revealed until they began studying the body. “It makes you wonder if she was in pain,” she said.

Such study led to discovery. Students excitedly spread the news when they found an artery or vein.

“When you actually find something,” Boody said, “it’s so rewarding.”

—Suzanne Wilder

Jeffrey Matthews, MD, chairman of the department of surgery, showed students some of the intricacies of the abdominal organs in the lab, after an earlier lecture on “Surgical Perspective on the Abdomen.” Photos by Dan Dry

Fall 2008 13

IN BRIEF Among the best, again

NorthShore University HealthSystem and Pritzker create new academic affiliation Gene-shuffling patterns uncovered “Genetic recombination is a fundamental process at the core of reproduction and evolution.”

—Graham Coop, PhD, post-doctoral fellow in human genetics

A Hutterite girl from an isolated, genetically similar population in the Dakotas gets tested for asthma. Photo by Jason Smith

The first large-scale, high-resolution study of human genetic recombination has found remarkably high levels of individual variation in genetic exchange, the process by which parents pass on a mosaic-like mixture of their genes.

University of Chicago researchers located nearly 25,000 recombination events that occurred in the transmission of the parental genomes to 364 offspring, described in the March 7, 2008, issue of Science. The high-resolution maps allowed the researchers to precisely locate where these genetic exchanges occur and to assess the differences in recombination rates between individuals.

“Genetic recombination is a fundamental process at the core of reproduction and evolution,” said study author Graham Coop, PhD, post-doctoral fellow in human genetics at Chicago, “yet we know very little about where 14 University of Chicago Medicine on the Midway

it occurs or why there is so much variation among individuals in this important process.”

“Now,” Coop said, “we know where it occurs. Understanding where it happens provides us with important clues as to how it happens, how it is regulated and what mechanisms control this essential biological phenomenon.”

Recombination occurs during meiosis, a special kind of cell division that takes place only in the testicles and ovaries. In the process of making sperm or egg cells, the parent-to-be takes the chromosomes inherited from each of his or her parents and reshuffles them, swapping parts of one chromosome for the matching segments of the other version of that same chromosome.

The result is a reproductive cell with a patchwork of genes, about half from each parent, but shuffled together into entirely new combinations.

This process leads to offspring having different combinations of genes than their parents and is thought to have many advantages.

The research team focused on the Hutterites, a genetically similar population of European immigrants who settled in the Dakotas in the 19th century and have maintained a communal agricultural lifestyle. One member of the research team, Carole Ober, PhD, professor of human genetics and of obstetrics and gynecology, has been working closely with this group for many years on health and inheritance issues. (See cover story, Spring 2008 Medicine on the Midway.)

The researchers collected DNA from 725 volunteers representing 82 overlapping nuclear families, most of whom had four or more children. They are part of a 1,650-person, 13-generation pedigree of the Hutterites in the United States.

The scientists used 500,000 markers of genetic variation (SNPs) to determine, along each chromosome, whether the genetic material came from the child’s maternal or paternal grandmother or grandfather. The large number of markers allowed the researchers to map out at high resolution the locations in the genome where ancestry shifts from one grandparent to another, known as recombination events.

Chromosomes from the mother (not including the X chromosome) averaged around 40 recombination events per gamete. Those from the father had only 26. The authors confirmed a previous finding that older mothers have more recombination events in the transmission of their genome to their offspring, while the father’s age has no such effect.

For both sexes, the majority of crossovers occur at genetic “hotspots,” small regions where genetic exchanges are unusually common. Although the overall rate of hotspot use was similar between the two sexes, a subset of hotspots, “seems to be used mainly by one sex or the other.”

—JE

“Medical schools achieve a diversity of settings by linking up with affiliates to give students a richer variety of patient care experiences.”

—Holly J. Humphrey, MD, dean for medical education

NorthShore University HealthSystem and the University of Chicago Pritzker School of Medicine have created an academic affiliation that will place medical students, residents and fellows from the University of Chicago Medical Center at the three NorthShore hospital locations for a portion of their educational experience.

Located in Chicago’s northern suburbs, NorthShore is an integrated health care system that includes Evanston, Glenbrook and Highland Park hospitals, NorthShore Medical Group (comprising 65 medical offices and facilities), NorthShore Home Services, NorthShore Research Institute and NorthShore Foundation.

Although students and residents participate in several small programs for clinical training off campus, the majority of medical student training has always been centered at the University of Chicago Medical Center. That will not change.

This new affiliation, however, will make the NorthShore hospital locations the primary off-site learning environment for Pritzker students and UCMC residents.

Leaders at both organizations believe the fit is natural, bringing together Pritzker, one of the premier medical

schools in the country, and NorthShore, one of the nation’s leading teaching hospitals. Both share a commitment to the highest levels of patient care and medical research, yet they expose students and residents to different patient populations, operational systems and an urban-academic-medical-center vs. a suburban-community-teaching-hospital patient care setting.

The affiliation became effective July 1, 2008, and includes a one-year transition period. In July 2009, UCMC residents and medical students from Pritzker-sponsored training programs will begin to gain clinical experience at NorthShore, working closely with physicians who are part of the NorthShorebased faculty.

“Health care takes place in a variety of different settings,” said Holly J. Humphrey, MD, professor of medicine and dean for medical education at Pritzker. “Medical schools achieve a diversity of settings by linking up with affiliates, in addition to their own teaching hospitals, to give students a richer variety of patient care experiences. That kind of broad educational exposure is incredibly robust.”

Organismal biology and anatomy professor Michael LaBarbera, teaching students in a lab session. Photo by Dan Dry

In the 2008 “Best Hospitals” issue of U.S. News & World Report, the University of Chicago Medical Center is ranked among the best in the country in 10 specialty areas. Seven programs ranked in the top 25 nationally: digestive disorders (#6), endocrinology (#11), cancer (#18), neurology and neurosurgery (#19), heart and heart surgery (#20), kidney disease (#22), and ear, nose and throat (#22).

Geriatrics (#29), respiratory disorders (#32) and gynecology (#34) also scored in the —JE top 35. Only 170 of the country’s 5,000-plus hospitals (about 3 percent) made at least one of the specialty lists. The only Illinois hospital ever to be included in the honor roll, the Medical Center has appeared on this soughtafter list 11 times since 1995. Adding to that, the magazine’s annual survey of children’s hospitals selected the University of Chicago Comer Children’s Hospital as one of the top 20 in the United States for neonatal care (the care of critically ill or very premature newborns). The 2008 America’s Best Children’s Hospitals listing ranked the 30 top hospitals in general pediatrics and six specialties based on a combination of reputation, outcomes and care-related measures such as nursing care, advanced technology, credentialing and other factors. “Neonatal care is a difficult field,” said Michael Schreiber, Comer Children’s Hospital’s chief physician, “in terms of its technical demands, the constant medical and ethical decision-making it requires, and the need for caregivers to manage their tiny, complex, fragile patients as well as the emotional roller coaster faced by the infants’ parents.” This is the first time Comer hospital, which opened in 2005, has appeared in the U.S. News survey.

The earlier, the better The early stages of ovarian cancer—when the tumor is limited to the ovary—is the best time to administer marimastat or prinomastat, a new study shows. These drugs inhibit an enzyme, MMP-2, that is necessary for ovarian cancer to attach itself to other sites, such as the peritoneal cavity, where it can spread.

Though MMP-2 inhibitors can dramatically reduce a tumor’s ability to establish itself beyond the ovary, they were abandoned after they failed to extend survival in earlier clinical trials. It was not known then that the drug had to be given before the cancer had spread, according to obstetrician and gynecologist Ernst Lengyel. By inhibiting MMP-2 activity early in the disease, the University of Chicago team was able to prevent injected ovarian cancer cells in mice from attaching to tissues in the peritoneum and omentum. This reduced growth of new tumors in mice by 68 percent, when measured four weeks after treatment.

Fall 2008 15

IN BRIEF Taking the life out of tumors

Pritzker transforms its curriculum “During an era of fragmented health care delivery systems, it is increasingly urgent that future physicians develop mastery in these fundamental areas. These are the kinds of doctors our patients deserve.”

—Holly J. Humphrey, MD, dean for medical education

In an effort to inspire the next generation of physicians, the University of Chicago Pritzker School of Medicine is launching the Pritzker Initiative, a new curriculum designed to transform medical education at the school. (See Perspective on page 46.) The initiative will increase student-faculty interaction, reduce the number of large lecture classes and replace them with small-group, hands-on learning under the direct mentorship of faculty physicians, researchers and clinical educators.

“Students will learn medicine at the cutting edge of biomedical science, translate that science into direct patient care and acquire the moral foundation of the profession as they prepare to become future doctors and leaders,” said Holly J. Humphrey, MD, professor of medicine and dean for medical education at Pritzker. “During an era of fragmented health care delivery systems, it is increasingly urgent that future physicians develop mastery in these fundamental areas. These are the kinds of doctors our patients deserve.”

The goal of the Pritzker Initiative is to improve education for the next generation of leaders in all aspects of medicine, preparing aspiring physicians for careers that combine scholarly inquiry with clinical care. It also aims to increase the number of graduates who focus their scholarship and clinical practice on improving health care delivery in underserved areas.

“The University of Chicago has always been known as a teacher of teachers, and this description has been particularly apt for our medical school,” said James Madara, MD, dean of the biological sciences and Pritzker School of Medicine, and chief executive officer of the University of Chicago Medical Center.

16 University of Chicago Medicine on the Midway

“Our goal is to train physicians who will change medicine by bringing new knowledge to the field and passing it on.”

In response to the renewed emphasis on mentorship, the school will reduce the average class size from 104 new students each year to 88 by fall 2009. This will enable faculty to increase interaction

have urged medical schools to train 30 percent more physicians by 2015.

Several experts, however, have questioned the benefit of training more physicians overall. Physician supply in the United States is already at an all-time high, having risen from 200 doctors per 100,000 people in 1980 to a predicted 293

The University of Chicago Medical Center in the mid-20th century. Archival photo

schools to increase enrollment. Chicago gradually raised its class size to 104. By fall 2009, that will be scaled back to 88 new students each year.

As part of a new emphasis on scholarship and discovery, Pritzker also will require every medical student to complete a significant project under the close supervision of a faculty mentor. About 70 percent of current students already undertake such a project. That will increase to 100 percent with the 2009 incoming class. Students will begin work on their projects during the summer between the first and second years.

Some curriculum changes are already in place. Instead of starting classes in late September as in the past, first-year medical students entering in 2008 arrived on Aug. 1 and immediately were immersed in a redesigned anatomy class, “The Human Body,” which combines

traditional instruction and dissection with added clinical insights from surgeons as well as experts on medical imaging. (See story on page 12.) All incoming students also participate in a course devoted to understanding health care disparities in the United States. (See story on page 22.)

Ranked 17th among medical schools in 2008 by U.S. News & World Report, Pritzker has risen faster than any other top-50 medical school in the country during the past five years. It is ranked fourth in the country—behind only Harvard, Johns Hopkins and Yale—for the percentage of graduates who go on to careers in academic medicine. Nearly 24 percent of Pritzker students who graduated from medical school between 1989 and 1998 are now on the faculty at academic medical centers, about twice the national average.

University of Chicago researchers are finding novel ways to stop the growth of cancerous tumors. In pathologist Hans Schreiber’s lab, researchers discovered ways to target and kill the non-malignant cells that surround and support a cancer. The death of those surrounding cells stops tumor growth in mice.

The stroma, the layers of cells that surround a tumor, can accumulate tumor antigens and present them on their surface, which make them cancer-specific targets for killer T lymphocytes and therefore cannot escape destruction.

These genetically stable surrounding cells retain the molecules that present tumor antigens.

“We already knew that targeting the stroma is essential for eradicating established large tumors, because the stroma is like the root of the tumor,” said Schreiber, MD, PhD. “However, effects of current treatments that target stroma are usually transient and not cancer-specific.”

Cancer scientist Marcus Peter, PhD, also has found an innovative way to treat advanced tumors. One group of small, non-coding RNA molecules could serve as a marker to improve cancer staging and may be able to convert some advanced tumors to more treatable stages.

When normal cells are transformed into cancer cells, epithelial tissue lining internal and external body surfaces can adapt the characteristics of embryonic tissue. This process can produce invasive and mobile cells that can pass through membranes and travel to distant sites, where they seed new tumors. Peter and his colleagues found that a certain family of RNA helped regulate this transition. His team also showed that these microRNA molecules could convert tumors into a less invasive form.

As a new home away from home, Ronald McDonald House Charities of Chicagoland and Northwest Indiana celebrated the recent grand opening of a new Ronald McDonald House facility near the University of Chicago Comer Children’s Hospital in Hyde Park. For families of children who require prolonged hospitalization, the new 22-bedroom, The average class size for Pritzker students will be reduced, countering national trends. Photo by Eileen Ryan

with students, devote more educational resources and financial support to each student, and restore some of the personal bonds that are often lost because of pressures on faculty time.

The decision to reduce class size runs counter to national trends. Predicting a physician shortage, the Association of American Medical Colleges and others

per 100,000 in 2010. Many argue that the problem is not one of physician supply but rather one of maldistribution.

For Pritzker, the move is a return to the school’s historical roots. Fifty years ago, the University of Chicago enrolled about 55 to 60 new medical students each year. In the 1960s and ’70s, a series of federal incentives pressured medical

30,000-square-foot Victorian-style home holds nearly twice as many families as the original home in Hyde Park that opened in 1986. Within a year, that facility—the second to open in Chicago—was filled to capacity with long waiting lists. Eventually six more bedrooms were added. In 2004, in partnership with the University of Chicago Medical Center, the facility moved to a temporary location pending completion of the new building. The new house is one of four in the Chicago area now operated by the charity.

Photo by Dan Dry

Fall 2008 17

More than 22,000 sparks of discovery Key programs, including cancer, genomics, personalized medicine and neuroscience, gained a strong foundation from the campaign.

In June, the University of Chicago Medical Center closed the books on the Spark Discovery, Illuminate Life campaign, after raising $811 million and exceeding the original goal by more than $250 million. Gifts to the Medical Center through Spark Discovery accounted for more than a third of the University-wide Chicago Initiative, which raised $2.3 billion.

A sharp increase in giving delivered record-breaking results for the Medical Center. In each of the past three years, donors contributed more than $100 million, up from an annual average of $75 million earlier in the nine-year campaign, during which more than 22,000 donors made contributions.

More than $500 million in campaign philanthropy has been invested in research. The Medical Center landscape has been transformed by new facilities including the Comer Children’s Hospital, Emergency Department and Center for Children and Specialty Care; the Gordon Center for Integrative Science; and the Knapp Center for Biomedical Discovery, set to open in 2009.

The campaign provided funding for 14 new professorships, held by distinguished faculty. There are now 73 endowed professorships in the biological sciences, with a goal of reaching 100 such positions.

More than $45 million was contributed for student aid. Almost $200 million was added to the endowment.

Key programs, including cancer, genomics, personalized medicine and neuroscience, gained a strong foundation from the campaign. In early 2009, construction will begin on the new hospital pavilion (see story on page 7), designed to accommodate emerging technologies and provide state-of-the-art care far into the future for patients with complex disease.

Spark Discovery, Illuminate Life $550 million goal

The Knapp Center for Biomedical Discovery, a 10-story, translational research building, is slated to open in 2009.

$811 million raised 22,000+ donors $45 million for student aid $200 million added to endowment 14 new professorships

www.sparkdiscovery.uchicago.edu

Chicago Initiative $2 billion goal $2.38 billion raised 117,000+ donors

The Gordon Center for Integrative Science, a 400,000-square-foot research and learning facility, opened in 2006.

Comer Children’s Hospital opened in 2004. Photos by Dan Dry

18 University of Chicago Medicine on the Midway

Fall 2008 19

Bookmark Ethics by Committee: A Textbook on Consultation, Organization, and Education for Hospital Ethics Committees D. Micah Hester, PhD, ed.

Rowman & Littlefield, 2008

Attracting docs to South Side “The high cost of college and medical education often prevents even the most altruistic young doctors from practicing in underserved areas such as Chicago’s South Side.”

—James L. Madara, MD, dean of the biological sciences

To enable young, community-oriented physicians to build a better network of care in the underserved areas where they learned their profession, the University of Chicago Medical Center is initiating the REACH (Repayment for Education to Alumni in Community Health) program, which will encourage graduates of the Pritzker School of Medicine to return to the South Side of Chicago to practice medicine in underserved communities.

The program will provide up to four years of financial support for Pritzker graduates who complete a residency in primary care or much-needed specialties and then return to practice medicine at a Federally Qualified Health Center (FQHC) or a community hospital in the Medical Center’s primary service area.

“The high cost of college and medical education often prevents even the most altruistic young doctors from practicing in underserved areas such as Chicago’s South Side,” said James Madara, MD, dean of the biological sciences and Pritzker School of Medicine and chief executive officer of the Medical Center.

“This program will enable such physicians to take on leadership roles in underserved communities. These doctors will help to set the agenda for clinical research and health care delivery in this setting.”

“This provides a support system for those who choose a career in public service,” said Holly Humphrey, MD, professor of medicine and dean for medical education at Pritzker. “Incentives in the form of loan forgiveness, scholarship support and now this program give young doctors who are just starting their careers the opportunity to contribute their expertise and enthusiasm to a vibrant and diverse community, without the pressures imposed by the burden of college and medical school loans.”

20 University of Chicago Medicine on the Midway

If you serve on a hospital ethics committee, this might be one of the few comprehensive resources available to you. Hester has compiled information from tens of thousands of people across the United States who serve on hospital ethics committees. Written specifically for educational purposes, the book draws on experts in such fields as bioethics, health law, social psychology and clinical consultation, and topics that include education, ethics consultation and policy development. It addresses such concerns as developing cultural and spiritual awareness, promoting just and ethical organizations, and preparing for the forces of group dynamics in committee discussions and consensus building. One of the chapters in the book, “Ethics in Pediatrics,” is written by Tracy Koogler, MD, assistant professor of anesthesia and critical care and pediatrics at the University of Chicago.

Dismantling Discontent: Buddha’s Way Through Darwin’s World Charles Fisher, SB ’59, SM ’60, PhD Elite Books, 2007

John Hickner, MD, (left) professor of family medicine with Kwame Foucher, MD, a physician with the Access Community Health Network. Photo by Dan Dry

“A secondary goal,” Madara added, “is to increase the number of medical graduates who will focus their research as well as their clinical efforts on improving health care delivery in underserved areas—a research field that has historically been neglected.”

REACH will provide $40,000 a year, added to the physician’s salary, for up to four years. Initially it will support five physicians who practice at one of the South Side’s FQHCs identified by the Medical Center as those most in need, or at community hospitals that are partners in the Urban Health Initiative, a collaborative effort that brings together multiple health care providers to improve the long-term health of those on the South Side.

REACH is thought to be unique. This is the first time a private academic medical center has implemented a program

that helps its young graduates manage their debt while simultaneously helping patients with limited resources and access to care. The incentive program is open to primary care physicians as well as selected specialists.

The REACH Program meets a need that many students have expressed, Humphrey said. The average debt of U.S. medical school graduates in 2007 was almost $140,000. Any Pritzker graduate can apply who has completed a residency and is practicing in primary care or one of several specialties in which there are too few physicians in the community.

Preference will be given to applicants who are “meeting the greatest need in the community.”

Fisher draws upon data from animal and human societies and from neurological findings to explore the existential dilemma defined by the Buddha: illness, old age, death and the transcendence of all of these. A meditator, teacher and Chicago alumnus, Fisher said that early hominids lived in harmony with nature and free from the existential suffering so familiar to Homo sapiens. As our ancestors’ brains and bodies evolved, our species became more capable of creative productivity and the discontent of being disconnected from our environment. Our most profound spiritual and intellectual yearnings emerged from this evolution, he suggests. Fisher shatters previous assumptions about the incompatibility of both scientific and spiritual knowing and draws us toward a “middle way” of finding greater peace for ourselves, others and the world we live in.

Amniote Paleobiology: Perspectives on the Evolution of Mammals, Birds and Reptiles Timothy J. Gaudin, PhD ’93, Richard W. Blob, SM ’95, PhD ’98, Matthew T. Carrano, SM ’95, PhD ’98, and John R. Wible, PhD University of Chicago Press, 2006 Twenty-four researchers collaborated on this exploration of 13 new and important scientific perspectives on the evolution and biology of amniotes.

The text covers new discoveries of dinosaurs and primitive relatives of mammals, the evolutionary process in plesiosaurs and mammalian locomotion and chewing.

Amniote Paleobiology emphasizes the rich variety of analytical techniques available to vertebrate paleontologists, among them multivariate morphometrics and complex three-dimensional kinematics. It addresses amniote inter-species relationships and what those relationships reveal about changes in anatomy and function over time.

Chicago alumni: Blob is an evolutionary biologist at Clemson University; Carrano is curator of dinosaurs at the Smithsonian Institution; and Gaudin is a biological and environmental scientist at the University of Tennessee-Chattanooga.

Protein-Nucleic Acid Interactions: Structural Biology Phoebe A. Rice, PhD, and Carl C. Correll, PhD, eds.

RSC Biomolecular Sciences, 2008 A horizon-broadening reference for advanced students and established scientists, this book provides up-to-date information and in-depth background on protein-nucleic interactions. Organized by general themes and principles, its chapters are written by experts who illustrate topics with current findings. Some of those topics include: the role of ions and hydration in protein-nucleic acid interactions, transcription factor and combinatorial specificity; indirect readout of DNA sequence, and single-stranded nucleic acid binding proteins. Co-author Rice is an associate professor of biochemistry and molecular biology at the University of Chicago.

Macachiavellian Intelligence: How Rhesus Macaques and Humans Have Conquered the World Dario Maestripieri, PhD University of Chicago Press, 2007 Biopsychologist Maestripieri offers us the fruits of more than 20 years of studying the macaque with their “Macachiavellian” intelligence that sometimes seems to caricature human social interaction. Maestripieri’s work helps us understand how Rhesus monkeys—and humans—have survived in a complex and sometimes hostile world. His portrayals of Rhesus monkey savvy and intelligence tell us a lot about ourselves. The book delves into the mysteries of macaque social organization and evolution, exploring the psychology of both rhesus and humans and thereby offering insights about our own relationship to sex, dominance, aggression, status, cooperation, conflict and kinship.

Maestripieri is a professor of comparative human development and a member of the Committee on Evolutionary Biology at the University of Chicago.

Sustaining Life: How Human Health Depends on Biodiversity Eric Chivian, MD, and Ari Bernstein, MD ’05, eds.

Oxford University Press, 2008 All of nature is interdependent, these authors say. Drawing on the latest research, Chivian and Bernstein present a sobering and comprehensive view of how the production of food on land and in oceans, the emergence and spread of infectious disease, human medicines and biomedical research are dependent on biodiversity. More than 100 scientists contributed to 10 chapters that cover everything from how human activity threatens biodiversity to how we can help conserve the rich diversity of the biosphere.

Sustaining Life reminds us that we can no longer see ourselves as separate from—and unaffected by—the natural world. Chicago alumnus Bernstein is a research associate at the Center for Health and the Global Environment, as well as a clinical fellow in pediatrics at Harvard Medical School and Boston University School of Medicine.

Fall 2008 21

A A South Side resident joins a clinical trial for a new

drug at the University of Chicago Medical Center.

AA A breast cancer patient learns she has an

aggressive, genetically tied form of the disease.

AAA A child at high risk for diabetes learns to eat better and exercise, along with his parents.

Balancing inequities in

health care

by Suzanne Wilder

AAAADifferent as they may seem,

all three are connected through health disparities research.

22 University of Chicago Medicine on the Midway

Health disparities: the variations in medical conditions for patients with different racial, ethnic, socioeconomic, cultural, geographic or other factors. The phrase applies to numerous conditions and involves people all over the country and the world. And, health care disparities—inequalities in medical services, health education and clinical access available to patients—are pervasive, too.

Fall 2008 23

U

niversity of Chicago physicians and social scientists are investigating these topics and creating new ways to work with the South Side community to improve the health of its residents. Researchers here delve into social factors, cultural inequities, statistical differences in disease rates, and disparities in medical treatment and quality of care. A major portion of the work aims to create interventions that eliminate disparities in care. But Chicago teams also investigate the illnesses under the skin and the way different bodies are affected by diseases, stress or medication. Collaboration among social scientists, psychologists, economists and many medical departments has led to major discoveries about health and health care disparities.

The city of Chicago provides an ideal setting for such research: The city suffers from worse disparities than many other places.

More black women here die of breast cancer, research has shown, than in many other major U.S. cities. The South Side of Chicago is home to a chronically underserved population, with high rates of hypertension, diabetes, asthma and other complex diseases.

The area also has unusually high percentages of physically disabled adults (10 to 15 percent of the population), premature births (15 to 20 percent) and three times the national rate for adult diabetes-related hospitalizations, according to many studies on disparities.

“Impossible not to see disparities”

Marshall Chin, MD, associate professor of medicine and director of Finding Answers: Disparities Research for Change. Photo by Dan Dry

dollars in grants that are distributed from RWJF. The funds support a variety of health care disparities interventions that address cardiovascular disease, depression and diabetes.

Finding Answers has become a barometer of trends and interventions in health care system disparities, Chin said, because of the number of grant applications it has reviewed

According to Chin,

disparities research falls into three categories: ADescribing the phenomena that make up the disparities, such as health and health care differences based on racial or ethnic background or socioeconomic status.

ADetermining why the disparities exist, and the social or other factors that influence them.

A Creating solutions and interventions to improve the quality of care for underserved populations or for the patients affected by disparities.

The diversity of the city’s population makes it a “rich place to study and make a difference,” said Marshall Chin, MD, associate professor of medicine and director of one of the primary disparities research programs at the university—Finding Answers: Disparities Research for Change.

“Frankly, I think disparities are common everywhere,” Chin said. Differences in health conditions and medical care, he added, are “equally unacceptable no matter where we are.”

The issue reaches far beyond the campus, the South Side or the city of Chicago. Three years ago, the Robert Wood Johnson Foundation (RWJF), a national, private foundation devoted to improving health and care for Americans, launched a set of initiatives to reduce racial and ethnic disparities in American health care. Chin’s Finding Answers project found a home at the University of Chicago.

As its director, Chin is a mentor to many faculty members— Monica Peek, MD, a physician researcher at Chicago, calls him her “guru”—and oversees the administration of millions of 24 University of Chicago Medicine on the Midway

for support. A quarter of its 177 applications had community health worker components, with community educators, links to community resources or assistance navigating the medical system. The 11 proposals that won grants focused on diabetes, patient empowerment, systematic changes to chronic care treatments, depression care management and other topics in American Indian, Latino, Asian and Pacific Islander, and African-American communities.

Finding Answers is just one component of the University of Chicago health inequities research. Another is the Health Disparities Collaboratives, a national effort that works to improve treatments for chronic conditions such as diabetes.

The collaboratives bring together community health centers across the country to determine what systematic improvements work best.

“Health centers love it,” Chin said. “They see an improvement for their patients, and it makes a lot of sense.

A common bond unites researchers in disparities work: “We all have a social justice mission,” Chin said.

Christopher Masi, MD, PhD, also speaks of that mission, of wanting to improve health and medical care for all patients. “I guess I have this optimistic streak,” said Masi, assistant professor of medicine. “It said, ‘We could probably do something about this.’”

Perhaps that concern for the greater good contributes to some of the collaboration that researchers in the field embrace.

“People in this field tend to be pretty collegial and team-oriented,” Chin said. Because “the challenges are enormous,” he said, the strengths and expertise of many academic and community players are required to make a difference.

Sarah Gehlert, PhD, director of the university’s Center for Interdisciplinary Health Disparities Research, comes to the field with the perspective of an anthropologist and social worker but has seen progressively more research in the field emerge during her 17 years at Chicago. The topic, she noted, has become a priority for U.S. policymakers.

“If you’re in health care and you’re working with vulnerable populations,” Gehlert said, “it’s impossible not to see disparities.”

During her early research, Gehlert wondered “how disease got under the skin, how poverty made people sick.” At the same time, University of Chicago pathologist Thomas Krausz, MD, was studying breast cancer cells.

“For years, he looked at breast cancer cells through a microscope,” she said, “and also wondered what the patients’ lives were like.”

By working together at the center and looking at the social and cultural elements that may affect health, Gehlert said, “It is, for each of us, an ‘Aha!’” As principal investigator of the National Institutes of Healthfunded center, Gehlert has been a leader for many of the disparities initiatives here. Researchers at the center have focused on the gap between breast cancer mortality rates for black and white women and brought together many disciplines to investigate the difference.

Now Gehlert and a team of researchers—including Martha McClintock, Funmi Olopade, and Suzanne Conzen—are looking at the lives of local women newly diagnosed with breast cancer. The researchers meet with the women repeatedly, go into their homes, observe their social situations, screen for depression and ask about their work, sleep and life habits. They observe what happens inside the home and in the women’s neighborhoods and analyze nearby crime statistics.

Groups of medical students involved in the work also study the neighborhoods. They analyze how the body changes after years of living in environments with high crime rates, poor housing conditions or tense social situations.

Reaching out Stress and the body’s response to it are an important part of health disparities research. Masi, is working with John Cacioppo, PhD, a psychologist who has been studying a diverse cohort of 200 people over several years.

Masi, who analyzes the effects of psychological stress on hormone metabolism and blood pressure, called the data from the study “invaluable.” The research team he works with identified racial and ethnic differences in stress hormone levels, which may be important to solving disparities in high blood pressure and heart disease.

In his PhD work at the School of Social Service Administration, Masi investigated birth outcomes disparities in Chicago neighborhoods and showed that infants born in areas with higher violent crime rates had lower birth weights, even after adjusting the results for race, income, maternal smoking, mother’s age and other factors. Chronic stress, the results showed, had serious health effects.

“When I think about the long-term, eliminating health disparities in this country will require some philosophical shifts and a new approach,” he said. “One that emphasizes social justice as much as health care justice.”

Fall 2008 25

Through such collaborative research, Gehlert said, “likeminded people across the campus have connected.” The university’s reputation on the subject of disparities has also brought in top-notch scholars such as geneticist Rick Kittles, she added.

Kittles, PhD, associate professor of genetic medicine, found that a genetic variation on a particular region of chromosome 8 increased the risk of prostate cancer among black and white men. But African-American men also carried an additional genetic variation, with an even greater cancer risk.

Prostate cancer, the second leading cause of cancer death in men, strikes African-Americans at a disproportionately high rate. By further studying this genetic variation, Kittles has said, researchers “may be able to develop molecular targets for improved screening, early detection and possibly treatment.”

The study shows that ancestry plays a role in disease genes, Kittles said. “Since African-Americans vary significantly in genetic ancestral proportions and the prevalence of prostate cancer is almost two-fold higher among African-Americans compared to European Americans,” he said, “the use of ancestry-informative markers for association with prostate cancer is quite powerful.”

Genetic research at Chicago has shown other staggering differences between races, revealing how diseases can differ under the skin. Professor Funmi Olopade, MD, who studies breast

cancer and genetics, discovered that women of African ancestry are more likely to be diagnosed with a virulent form of the disease than women of European ancestry. By studying cancer patients in Nigeria, Senegal and North America, her research team found that cancerous tumors from African women were more likely to originate from a different group of cells and don’t respond to some standard therapies.

“We have known for a long time that breast cancer is not one disease and that it may be somehow different in Africa,” said Olopade, director of the Center for Clinical Cancer Genetics at the University of Chicago and a 2005 MacArthur Fellow. “But there was no real sense of how much of that was biology and how much was environment. Now we have clear evidence that nature plays an important role. These tumors are biologically quite different in ways that make this a worse disease.”

Angel Jacobs, a 29-year-old Chicago resident, is one of Olopade’s patients. After Jacobs found a lump, she was diagnosed with breast cancer at the University of Chicago Medical Center, where she came for regular care. Chemotherapy and radiation treatment have left her cancer-free, but the knowledge lingers that her genes carried this high-risk disease.

“I feel like I manage it pretty well,” said Jacobs, who visits Olopade and a radiologist every three to six months for checkups. “It’s just something that you deal with forever. It’s not something that’s curable at this point.”

Disparities researchers at the University of Chicago

From left: Tonya Payton-Campbell, McKenzie Campbell and Jamon Thomas learn about healthy eating and exercise at a Reach In! Reach Out! weekly meeting. Photo by Dan Dry

Part of the struggle with treating breast cancer and its related inequities in the city of Chicago is educating patients about the disease and the availability of mammograms.

Monica Peek, MD, an assistant professor of general internal medicine, knew Chicago had serious health disparities with breast cancer mortality when she moved to the city in 2001 and was concerned that the women most affected were not getting the health education they needed.

While working at Cook County Hospital and Rush Medical Center, she started a program to train women who lived in the Chicago neighborhood called Rockwell Gardens, an aging

American College of Physicians and the American Medical Association, attempt to address health disparities.

Intervention and education programs, like the one Peek created, put disparities research into practice in affected communities. Internist and pediatrician Deborah Burnet, MD ’89, founded a community-based research project called Reach In! Reach Out!, in which community leaders teach families about healthy eating and exercise. The goal is to lower the risk for diabetes and obesity for African-American youth on the South Side.

That program, in its pilot phase and current version, has helped more than 100 families learn about nutrition and activity.

Genetic research at Chicago has shown

other staggering differences between races,

revealing how diseases can differ under the skin.

Monica Peek, MD

Christopher Masi, MD, PhD

John Hickner, MD

John Cacioppo, PhD

Rick Kittles, PhD

Assistant Professor, Medicine

Assistant Professor, Medicine

Professor and Vice Chair, Family Medicine

Professor, Psychology

Assistant Professor, Medicine

Scott Cook, PhD

Funmi Olopade, MD

Deborah Burnet, MD

Sarah Gehlert, PhD

Deputy Director, Finding Answers

Professor, Medicine and Human Genetics Director, Cancer Risk Clinic

Section Chief, General Internal Medicine Associate Professor, Medicine and Pediatrics

Director, Center for Interdisciplinary Health Disparities Research Professor, Social Service

26 University of Chicago Medicine on the Midway

housing project, to become community health advocates. Peek crafted a program, supported by grants from several different nonprofits and government agencies, that informs women of major health issues, teaches them how to be advocates in their communities and sends them into their neighborhoods to encourage mammograms and spread awareness to families, friends and neighbors. “It’s going to take all of us to care about changing disparities,” she said. “I can’t be everywhere. The reason I train people is so I can extend my reach.”

Peek has moved to the University of Chicago, where she continues her health advocacy work and health disparities research.

Her energy now is focused on a new intervention to help diabetes patients and the medical professionals who treat them to better manage medical care and health. She’s also researching workforce diversity and disparities in health care, and looking at ways that physician professional organizations, such as the

“It helped me learn so much about nutrition and exercise,” said Althera Steenes, who started as a community educator for the program and has become a full-time community outreach specialist. “Diabetes is very prominent in my family.”

Since she got involved with the project more than two years ago, Steenes has lost about 50 pounds through diet and exercise, she said. She takes what she has learned to schools and churches, where she talks to parents and kids about their lifestyle choices and the risk of diabetes and obesity.

“I see obesity being a problem when I go out and talk to kids,” she said. But she also sees changes in the families she teaches. One mom lost 40 pounds through healthier eating habits. The program is not created for weight loss specifically, but the participants become more mindful of making changes that can lead to healthy weight and lower diabetes risk.

Fall 2008 27

Diverse disparities research As these outreach programs demonstrate, much work focuses on racial, ethnic or socioeconomic disparities. But research on the topic goes far beyond skin color, income or the community in which patients reside.

Before Scott Cook, PhD, became deputy director of Chicago’s Finding Answers program, he was on the ground level of disparities interventions, working as a clinical psychologist at the Howard Brown Health Center, a Chicago organization that serves the lesbian, gay, bisexual and transgender (LGBT) population. That background gives Cook a unique perspective on health and care disparities based on LGBT medical needs.

Health disparities such as high rates of HIV infections, particularly in gay men of color, higher smoking rates than the mainstream population, and high rates of syphilis necessitate research on care and interventions that cater to the LGBT community. Disparities in medical care can arise when doctors are not comfortable with or educated about cultural and medical issues specific to LGBT patients. Cook’s work and expertise show disparities that impact people who may not first come to mind when discussing the subject.

Cook worked with four community organizations to develop a smoking cessation intervention program based on an existing American Lung Association curriculum but tailored to the LGBT community in Chicago. He is now working on a similar project targeted to help HIV-positive men stop smoking.

Through Finding Answers, Cook helps iron out problems that grant recipients may have: finding resources, staying on budget, following their plans or struggling with technology. He is part of the team that analyzes program results to determine how the successful interventions can be applied to other health centers and promoted around the country.

Other major projects at the university are tied closely to health disparities research, though that label is not always used. One such initiative is the Clinical and Translational Science Award, a $23 million grant from the National Institutes of Health to rapidly transfer innovative scientific research into treatments for patients. The project will connect disease research, which may yield discoveries about how diseases differ among diverse patient populations, to efforts to bring better treatments to patients, particularly those on the South Side of Chicago who often lack access to clinical trials and the cutting-edge medicine they offer.

The definition of disparities research can be a bit nebulous, said John Hickner, MD, professor and vice chair of family medicine. Hickner, who has worked with Access Community Health Network and other community health centers on quality improvements, doesn’t consider himself a health disparities researcher. He’s focused on system improvements to get patients faster, more efficient care or to connect them with primary care physicians for regular medical checkups and needed medical care. He also evaluates how medical tests are administered and how patients manage their medications. His work is focused on primary care and delivery of care, but because he is working on the South Side now, the research is frequently based in clinics with underserved patient populations.

28 University of Chicago Medicine on the Midway

‘ You r ea lize you’r e ta lkin g a bou t p eop le’ First-year Pritzker students toured area clinics and hospitals, including Jackson Park Hospital, pictured here. Above, Jackson Park’s director of surgery Gerrie Pate, RN, (pictured in white lab coat) talks to students about surgical beds and common procedures at the hospital. Photos by Dan Dry

Opening students’ eyes to inequality

“All of us who are working on care for the underserved get labeled as disparities researchers,” Hickner said, adding, “If people put that label on me, that’s fine.”

Alyna Chien, MD ’01, has always been interested in vulnerable populations. A University of Chicago “trainee” from undergraduate through her MD, and as an instructor of pediatrics she worked with refugee and immigrant populations as a social worker prior to medical school, as well as with uninsured and underinsured African-American patients on the South Side during her medical training.

Her research, now based at Children’s Hospital Boston, investigates health care performance incentives—such as payfor-performance and public reporting attempts to tie physician rewards or penalties to the quality of care they deliver and patient outcomes. This strategy is being adopted by many commercial health insurance companies and Medicare. While Chien’s main focus is on whether these incentives work, she is also studying how performance incentives impact the care of vulnerable populations.

“What the mainstream does can impact underserved populations,” she said. The incentives could help vulnerable groups, she noted, because health care overall may improve by aligning payment with quality. But vulnerable populations—with resource-constrained settings—may not be able to compete with clinics practicing in more affluent areas, particularly if rewards tend to be earned by wealthier providers in the first place. “In general,” Chen said, “care is getting better—but faster for mainstream improvements than for underserved populations.”

Dean Shumway grew up in Idaho where he was relatively unaware of the concept of health care disparities, he said. So when he arrived at the University of Chicago Pritzker School of Medicine, he had a blank slate on the topic—but not for long.

His orientation in 2006 included a class called “Health Care Disparities in America.”

“I didn’t know what to expect,” he said, adding, “I thought it would be interesting.”

Shumway and his peers heard lectures, statistics, and historical and hypothetical cases about disparities. But what hit many students hardest were visits to local clinics and Cook County Hospital.

“I was struck by the reality of the situation,” said Shumway, a third-year student this fall. “When you go into the clinics, you realize you’re talking about people.”

More than two years ago, assistant professor Monica Vela, MD ’93, assembled a faculty team to teach first-year students about health care disparities. The one-week elective course during orientation expanded the next year to include all firstyear students. This fall, the class will span the first eight weeks of the quarter.

The course is an anomaly in modern medical education, and other medical schools have contacted Vela about how to start similar ones. But Vela said that part of the success here is that Chicago has so many experts in disparities who can provide leadership and insight on the topic.

Celine Goetz, who finished her first year at Pritzker this spring, said the class opened her eyes to the complexity of health disparities and how health inequities affect her medical education and future career.

“Once you recognize these realities in medicine, you’re acutely aware of them,” Goetz said. “It’s clear to me that this isn’t going away.”

The curriculum has a wide scope, with lessons on cultural differences, health literacy, language barriers, history, Medicare and Medicaid, and uninsured patients. The lectures also include health conditions that have socioeconomic or racial disparities, such as diabetes, hypertension, obesity and diet.

The class particularly focuses on “making things relevant to Chicago,” said Eric Chen, a Pritzker student who will start his second year this fall. Since taking the class, Chen has volunteered in the community and with the Health Professions Recruitment and Exposure Program, a medical-studentrun project that teaches local high school students about health care careers.

Students in the class take excursions to community health care centers such as the Washington Park Children’s Free Clinic, Cook County Hospital, the Friend Family Health Center, Access Community Clinics and the University of Chicago Medical Center emergency room.

The class includes several sections of discussion time, as well, for students to tackle lingering questions and analyze their experiences and lessons. The subject can be highly controversial and emotional.

“I think that has to be handled in just the right way,” said Vela, who closely monitors students’ reactions to topics and the reviews the class garners each year.

One particular discussion from the class sticks in Shumway’s memory. How, he asked, could physicians with radically different backgrounds from their patients relate to the people they serve? The words he heard in response from Monica Peek, MD, a physician and assistant professor, made an impression: The fact that you want to understand your patients’ lives will make all the difference.

—SW Fall 2008 29

The new bio home at Argonne

By Megan Seery

The Latin names conceal the peril within: Yersinia pestis and Bacillus anthracis. To non-scientists, they are known as plague and anthrax— words that have struck fear into the hearts of many.

Now, University of Chicago researchers will study such virulent killers at an elite, government-sponsored facility, the Howard T. Ricketts Regional Biocontainment Laboratory, a place where fingerprint-scanning security, Tyvek uniforms and latex gloves will be part of daily routines.

State-of-the-art security is in place at the new building, which will be run by the University of Chicago and function as one of the few U.S. labs capable of safely working with viruses and diseases such as West Nile virus, anthrax and plague.

“These measures look like overkill to everyone else, but when you work with this kind of stuff, they make sense,” said Lauriane Quenee, PhD, a microbiologist and one of a handful of University of Chicago researchers chosen to open the facility on the campus of Argonne National Laboratory.

30 University of Chicago Medicine on the Midway

Fall 2008 31

“The most important thing from the scientists’ point of view is that they are able to do their science. You need to think about safety from a scientific approach.

You can’t just come in and start measuring things.”

Joseph Kanabrocki, PhD, assistant dean for biosafety and associate professor of microbiology “We’ll have enough space to coordinate this and allow people to test their vaccines in a contained environment,” he said, even if it’s not for a University of Chicago-led project.

Working at Washington University in St. Louis during the 2001 anthrax scare, Kanabrocki said he received about six calls a day asking him to clean up Coffee-Mate, which resembles the white powder identified during the scare. Since those anthrax cases, in which five people died and more than a dozen became ill from contact with the substance, the government has channeled millions of dollars into research

Located 25 miles from the university’s main campus, on Department of Energy land, the $32.4 million, 54,100-square-foot Ricketts Lab is part of a larger

biodefense initiative

launched by the National Institutes of Health in 2003 to develop drugs, vaccines and diagnostics that counter bioterrorism and emerging infectious diseases.

“We’re talking about food, water and air,” Quenee said. “If you are a bioterrorist, you don’t want to waste time stabbing people with needles. To do maximum damage, you want to create something that spreads quickly and affects a large number of people at once.”

Ricketts Lab researchers will study microbial organisms classified as either Risk Group 2 (agents that cause mild to moderate symptoms in humans but are not life threatening) or Risk Group 3 (agents that have the potential to cause lethal human infections but have at least one effective treatment). The building, named after renowned University of Chicago pathologist and “microbe hunter” Howard Taylor Ricketts (1871–1910), is among the 13 labs funded for the biodefense initiative. It is a step down from the two Risk Group 4 facilities, one in Massachusetts and one in Texas, approved by the NIH for the purpose of studying the most

severe pathogens.

All organisms that will be studied at Ricketts are treatable with antibiotics, said Olaf Schneewind, MD, PhD, chairman of microbiology and director of the Great Lakes Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research (GLRCE), a consortium of 27 research institutions in the Midwest.

Work at the Ricketts Lab will support GLRCE, which also is funded by the NIH through the National Institute of Allergy and Infectious Diseases.

Animal technicians are among 24 staff members who will open the site initially, Schneewind said. Over time, the building may house up to 75 employees, ranging from security guards to scientists. As a safety precaution and to limit access to the building researchers stationed there will clean the facility themselves.

Air flow will be controlled by High Efficiency Particulate Air, or HEPA, filters that suck up and screen out airborne particles before the air is released outside.

Protecting the public from destructive diseases also means shielding the scientists who study them.

In addition to their suits, Ricketts researchers will be required to take showers every time they leave the level 3 laboratory.

32 University of Chicago Medicine on the Midway

In addition to the researchers’ individual efforts and the building’s extensive security protocol, the lab’s operations will be inspected frequently by federal, state and local agencies, and trained personnel will monitor the site’s 60-plus security cameras 24/7.

With the lab safe from a physical and operational perspective, Joseph Kanabrocki, PhD, assistant dean for biosafety and associate professor of microbiology, said the key to its design was to let research drive how procedures would be conducted inside its concrete walls.

“The most important thing from the scientists’ point of view is that they are able to do their science. You need to think about safety from a scientific approach,” he said. “You can’t just come in and start measuring things.”

Before they can set up their dream lab, however, the Ricketts team must secure final approval from a host of regulatory bodies, including the U.S. Centers for Disease Control. It also will go before the university’s Institutional Biosafety Committee and the Institutional Animal Care and Use Committee.

Small facilities already exist at Chicago and Argonne, but the space available at Ricketts will enable other institutions in the Great Lakes region to use the site as a testing ground. While the day-to-day operations won’t change much from what already occurs on campus, the scale and speed of research will increase, Kanabrocki said.

at universities and other institutions to study the bacteria and other potential biological weapons.

“Had this kind of center existed then, it would have been used as a place where diagnostics were set up and investigated,” Kanabrocki said.

The Ricketts building includes 3,904 square feet of space for research involving subjects in Risk Group 2 and 3,617 square feet for those in Risk Group 3. That size makes it much more convenient for testing vaccines, Quenee said.

“Right now we’re limited by space, and we can’t have all the studies we want to perform going on at once,” she said. “With the Ricketts lab, I won’t have that worry.”

Clockwise from above: An elevator-sized autoclave at the Ricketts lab is big enough to disinfect large equipment or entire racks of contaminated cages; fingerprint scanners add extra security at lab entrances; and a sophisticated air-handling system controls and filters all airflow into, within and out of the labs. Photos by John Zich

Fall 2008 33

DREAM JOB

A‘ ’ for an evolutionary biology student

By Katie Scarlett Brandt

One floor below Nathan Smith’s office in Chicago’s Field years ago during the Triassic period. The precursors generally were Museum, a little boy runs back and forth among the dinosaur smaller than dinosaurs and their bones more fragile. Dromomerbones on display. on’s length, for example, only reached about three feet, and it was “Look at all these fossils they dug up, Mom!” he shouts in bipedal, walking on its two hind legs. unconcealed awe.

Until recently, general scientific thought was that the precurDistracted by the boy’s younger siblings, his mom doesn’t sors went through a rapid extinction at the end of the Middle respond immediately, but that doesn’t dampen his enthusiasm.

Triassic period, never co-existing with dinosaurs, whose arrival Upstairs, Smith is just as enscientists marked with the thusiastic about fossils. Since Late Triassic period 227 mil2005, he has been working lion years ago. The theory was toward a PhD in evolutionary shaky, but there wasn’t strong biology through the program enough evidence to refute it. that the University of Chicago That is, until Smith’s group, offers in conjunction with the Dromomeron and studies of a Field Museum. As the introfew similar fossil assemblages ductory sign reads in the in North America began to exhibit below, “Everything prove otherwise. on Earth that has ever lived The Hayden Quarry in New is connected through, and the Mexico where Smith and his result of, evolution. This is colleagues discovered Dromwhere our story begins.” omeron had preserved ideal The statement fuels Smith’s evidence. The area’s smooth zeal. “Paleontology gives us mudstone maintained the access to life’s history. We small, fragile bones better than need that historic perspective,” most sites. And in the same he said. layer of sediment, the earth Earth’s history began 4.5 held Dromomeron and other billion years ago, but Smith precursor fossils side-by-side focuses on the Triassic and with true dinosaur fossils. This Jurassic periods, beginning indicated to Smith that the diabout 248 million years ago. nosaur precursors co-existed As a third-year student, he with dinosaurs through the spends most of his time either Late Triassic period, perhaps at the Field Museum creating even for millions of years. phylogenetic trees or out in Part of Ghost Ranch, an the field digging. educational center 50 miles Nathan Smith (above) works at the Field Museum while pursuing a PhD at His work has taken him to northwest of Santa Fe, Hayden the University of Chicago. Right: Smith and his colleagues at work on digs.

Photo of Nathan Smith by Dan Dry; on-site photos provided by Nathan Smith Antarctica, China, Argentina Quarry didn’t exist until 2002. and remote parts of the southAn amateur archaeologist western United States. He’s published seven papers from those trips, innamed John Hayden was hiking there when he discovered fossils in cluding an article in the July 20, 2007 issue of Science—all braggable the soil. Since then, Smith’s team has developed a relationship with feats for a 20-something graduate student, though Smith considers the ranch and makes regular excavation trips. the work of his peers at the university much more interesting.

Back in 2006, only a few inches of brownish-gray bone jutted out from the large chunk of rock that he and his colleagues pulled from the ground. Smith couldn’t say for sure what they’d found, but they labeled it “reptile A” and trusted their instincts.

The Science paper focused on a new species, Dromomeron “You develop an eye,” he said, “but you don’t always know what romeri, which Smith and a team of graduate students from instituyou have until you have it prepped.” tions across the country discovered in 2006. Dromomeron wasn’t In the field, they placed the chunk of rock in a plaster jacket, a dinosaur, but part of a group of reptiles that scientists refer to and “reptile A” joined Smith on the return trek to the Field as “dinosaur precursors.” It roamed the Earth roughly 212 million Museum labs.

‘Reptile A’

34 University of Chicago Medicine on the Midway

Summer in Antarctica

Digging at the Field To reach his office in the Field Museum, Smith takes an elevator near the north entrance that slides past the two-story Roman columns on its way to the third floor. Then he follows a hallway beneath fluorescent lights to a tiled room. Tall cabinets, stocked with shoebox-like containers of fossils from all over the world, divide the long room. His desk sits in the corner next to the door; across from it, more shoeboxes filled with bird skulls cover a table.

The skulls and other delicate bones comprise another of Smith’s projects: his dissertation, which he defended this past fall and plans to complete during the next two years. He’s mapping the size, shape and structure of pelicaniformes, modern birds that include the brown pelican and the blue-footed booby. Their webbed feet make shore life easier, and many species have a pouch in the lower bill that enables them to scoop up the fish they dive or swim to catch.

Smith chose the topic because he said he loves systematics and tree-building. “It’s open-ended,” he said of choosing what to study.

“We’re given a lot of leeway.”

His advisor, Peter Makovicky, offers guidance, and Smith shares an obvious passion with him. “People make fun of Pete and me because we just like to work,” he said. On digs, this includes staying in the field and passing up opportunities to absorb an area’s culture.

As Smith analyzes each species’ bones and plots their characteristics into a spreadsheet on his computer, he also traces their lineages, creating trees that lead from these modern birds back to dinosaur ancestors millions of years old. He essentially works from scratch, since birds don’t possess a strong fossil record because of their light, delicate bones.

“These things are 200 million years old, and they have so much that they share with birds,” he said as he pulled a box containing a small fossilized dinosaur femur from a cabinet.

In order to map their lineages, Smith looks at the relationships of each bird’s bones and finds dinosaurs that possess the same structure. Because so many researchers in the Field Museum travel the world on their own excavations, Smith can tailor their findings to his own research.

One group, for example, makes regular trips out to the Green River in Southwestern Wyoming. Smith has never joined, but he uses some of the “exquisitely preserved” fossils they bring back to trace his own birds’ phylogeny.

“It’s great because there are so many people here doing so many different things. There’s always an expert right down the hall you can talk to,” he said.

Smith may rely on other people’s excavations to aid his research on pelicaniformes, but he makes his own trips, too. This past December, Smith and co-author Diego Pol, a paleontologist at the Museo Paleontológico Egidio Feruglio in Chubut, Argentina, announced they had discovered a new species of dinosaur on Antarctica’s Mt. Kirkpatrick. Their work appeared in the journal, Acta Palaeontologica Polonica.

It took two excavation seasons to dig the fossils completely. The researchers traveled in summer, camped on the glacier and, Smith said, “even with no wind and the sun beating down,” the weather didn’t bother him.

The team helicoptered inland, trailed only by skuas, birds that had followed the helicopter in hopes of finding food, much like their North American gull relatives who chase cars to fast-food parking lots. The helicopter touched down near the Beardmore Glacier, where the team uncovered the partial foot, leg and ankle bones of a massive plant-eating sauropodomorph, the largest animals to ever roam the earth. Significantly larger and younger than the Dromomeron fossils Smith had found in New Mexico, it lived roughly 190 million years ago and weighed between 4 and 6 tons.

Previously, researchers had found fossils of only one other Jurassic period dinosaur in Antarctica, so this latest one helps show how widely distributed sauropodomorphs were during the Early Jurassic period. Smith and his colleagues dubbed their discovery Glacialisaurus hammeri, after the Augustana College professor who led the trips that eventually uncovered it.

Professor Bill Hammer was not only the man who coordinated the Antarctica digs, but he was the one who ignited Smith’s interest in paleontology during Smith’s undergraduate days at Augustana College in Rock Island, Ill. As a student, Smith joined Hammer on an excavation trip to the White River Badlands in Nebraska.

The Badlands earned their name from the Sioux Indians who struggled across the rugged terrain, exceedingly short on water, which stretches from Wyoming and Colorado through South Dakota. Despite the name, the land and Smith’s journey there inspired him, and he decided to make paleontology his career.

Originally a chemistry major, Smith was tired of “spending eight hours on nice days inside waiting for a chemical reaction.” The wide stretches of land and possibilities Smith saw on that first trip made him realize that science didn’t have to keep him indoors.

“This would be a dream job,” Smith said of what his work has since evolved into at the Field Museum. “I want to do research, and I want to teach classes with everyone on the edges of their seats.”

Similar dreams take place just a flight of steps below Smith’s office, where one little boy’s excitement propels him through the “Evolving Planet” exhibit.

“I wonder how they got this out,” he whispers. His mouth hangs agape as he cranes his neck up at Cryolophosaurus ellioti, the first dinosaur found in Antarctica.

Smith could explain.

Medicine off the Midway

From make-believe doctor to physician-scientist

Charis Eng, PhD ’86, MD ’88, (left) pictured with colleagues at the Cleveland Clinic, where she heads the Genomic Medicine Institute. Photos provided by the Cleveland Clinic

BY KATIE SCARLETT BRANDT

E

When Charis Eng was only 4, her father presented her with two gifts: a doctor’s play set and a chemistry set.

ither might confound the average 4-year-old, but both ignited Eng’s interest immediately. In fact, she found it impossible to choose one over the other—so she combined the sets and played with them simultaneously.

That desire followed Eng, PhD ’86, MD ’88, through the decades. Now in her 40s, she has combined scientific research and patient care to the benefit of both—and to a degree few physician-scientists can match.

Eng’s new institute at the Cleveland Clinic in Ohio, which she grew from a staff of six to 90 in less than three years, is the only one of its kind in the country, proving Eng is a visionary who not only knows how to get what she wants, but also how to create it herself.

Eng joined the Cleveland Clinic in September 2005. Before that, she had created and run a cancer-genetics training program as the founding director of the division of human genetics at Ohio State University in Columbus. But the Cleveland Clinic made her an offer too tantalizing to pass up: to create a new 36 University of Chicago Medicine on the Midway

kind of clinical science center that would bring scientists, clinicians and patients closer together. She dubbed it the Genomic Medicine Institute.

“The Cleveland Clinic is a wonderful place and a very funny place,” Eng said. “There was no human genetics research to speak of before I came. They seemed to look down on medical and human genetics.”

But with a change of leadership about a year before she arrived, things changed. “And now that they’ve seen us in action,” she said, “I believe they love the idea of genetics and genomics pervading all of medicine.”

The institute, which fills the entire fifth floor of her building, focuses on all aspects of translational human genetics and genomics. In it, Eng has placed patient rooms side-by-side with laboratories.

The waiting room, for example, overlooks a lab. When patients sign forms indicating that their blood samples may be used for research, their minds don’t wander to an image of some cold,

distant lab where stern scientists in sterile white coats hunch over test tubes and barely utter a word to anyone. Patients and researchers exchange hellos in the hallway, and patients know where their samples end up—right in the next room.

For some new patients, Eng said, the set-up can be intimidating initially. They admit that they’re not sure why their doctors have sent them to this specific clinic and assume that something serious must be wrong. But after Eng describes her research and what it can do for the patient, “they say, ‘My goodness, I wish I had known this beforehand. I was so nervous,’” she explained.

In its short history, the institute has served more than 2,600 outpatients. Eng, whose job carries mostly leadership responsibilities now, still sees patients one day each week and makes time for her busy research agenda. And she couldn’t be happier.

“It’s not possible for me to just be a physician alone or a scientist alone,” she said. “I would feel that part of me is missing.”

A necessary hybrid

Clinical medicine and research had formed a hybrid in Eng before she could even explain what either was. By the time she turned 12, her play with the chemistry and medical sets had developed into something more serious. Her family moved from Singapore to Chicago in 1975 when Eng was 13, and her father entered the University of Chicago’s doctoral program in economics of education. His low salary combined with the poor exchange rate brought pity from people closest to the Engs, and one neighbor—a graduate student at the university—donated his TV and radio to them.

Eng had left the strict, all-girls school she’d known in Singapore and won a scholarship to a co-ed private school in Hyde Park—University of Chicago’s Lab School. There, she could learn at her own pace, and reveled in taking 12th-grade honors courses as a freshman. She was also exposed to the world of genetics for the first time—and was captivated by genes.

After three years of self-described bliss, Eng’s parents told her to pack her bags. Her father had his degree, and the family was going home. But Eng didn’t want to leave. She thrived in the educational environment she’d found in Chicago, which offered opportunities she feared she wouldn’t have in Singapore.

Eng’s choice to stay in Chicago after her parents returned home was larger than any decision she’d made before. “I was a homely Singapore girl who liked living with parents,” she once wrote in an essay. Now she was on her own—kind of.

As a high school student, she couldn’t stay in the United States. So she applied early to the University of Chicago’s undergraduate biological sciences division. She was 16, and the university accepted.

Though somewhat anxious and overwhelmed, Eng knew she was in the right place. She had long ago decided what she wanted to be when she grew up. In Singapore, there were doctors and there were scientists. But there were no doctor-scientists. At Chicago, she could make that combination a reality.

Only Eng and her parents knew what she potentially was giving up by remaining in the United States. Two of her uncles were very prominent scientists in Singapore—one was the prime minister’s personal physician and a professor of medicine; the other was a professor and chairman of geography at Fall 2008 37

In its short history, the institute has served more than 2,600 outpatients. Eng, whose job carries mostly leadership responsibilities now, still sees patients one day each week and makes time for her busy research agenda. And she couldn’t be happier. a university. Eng could have ended up in a very different place had she returned to their support and guidance half a world away.

At Chicago, Eng started early on genetics research, prep work for a doctoral degree. In 1982, after completing her bachelor’s degree, she continued at Chicago where she entered the combined MD-PhD program.

In the people around her, she found mentors. There was her genetics professor, Ed Garber, PhD (“He didn’t travel like we do now—lucky him. He was in the lab everyday, and he’d sit right next to you and teach you,” she notes); Janet Rowley, MD, now internationally famous for discovering translocations; and Funmi Olopade, MD, a fellow when Eng was a student and someone who, “has looked after me ever since.”

Research and patient care

In the early ’80s, the concept of a physician-scientist still wasn’t all that common when Eng enrolled in the MD-PhD program at Chicago which, at the time, was one of only a few universities that offered the dual degree. Popularity, however, didn’t matter because Eng found herself shoulder-to-shoulder with others who wanted to see their research help the patients they treated.

In 1986, Eng completed her PhD; her MD came two years later. She then moved to Boston for a three-year residency at Beth Israel Hospital [at that time], where she learned about the Dana-Farber Cancer Institute affiliated with Harvard University.

The institute provided clinical care for cancer patients and conducted research to help fight the disease. Eng set her sights on Dana-Farber and started there in 1991 on a medical oncology fellowship.

She realized then, as she said she still believes now, that “This is the future of all of medicine.”

38 University of Chicago Medicine on the Midway

A year later, Eng accepted another fellowship to the University of Cambridge in England, where she was formally trained in clinical cancer genetics at the bedside and human cancer genetics at the bench. In 1995, she returned to Dana-Farber as an assistant professor of medicine and set out to put into practice everything she’d learned over the past 17 years.

“She wouldn’t pose many research questions where she couldn’t see the direct link between research and her patients,” said Debbie Marsh, PhD, who joined Eng’s lab at Dana-Farber as her first post-doc.

Eng focused on genetic links to cancer and in 1996, published a paper on Cowden syndrome, a rare disorder affecting one in 200,000 that increases the risk of breast and thyroid cancers. This study narrowed the search for the gene involved in Cowden to a location on a particular chromosome. That work, published in Nature Genetics, laid the groundwork for the discovery of a gene called PTEN, which was announced a year later by researchers at Columbia University. In a collaboration between researchers at Columbia, the Eng lab identified PTEN as the Cowden syndrome gene.

PTEN is a tumor suppressor gene whose normal function is to stop cell growth, enabling cells to repair damaged DNA, which is found in cancer cells. If the DNA is beyond repair, PTEN triggers apoptosis—a type of programmed cell death.

In either case, the damaged DNA is eliminated and the cancer can’t spread. The gene produces a protein that modifies other proteins and fats and may be involved in cell movement, cell adhesion and the development of new blood vessels—functions cancer cells often hijack.

But, as Eng discovered, PTEN doesn’t always function normally. A few months after PTEN was identified, Eng found germline mutations in PTEN that predisposed patients to Cowden syndrome. Individuals with PTEN germline mutations are particularly susceptible to cancers of the breast, thyroid and uterus, Eng learned.

After Eng’s discovery, she excitedly called all the patients who had participated in the research to share the good news.

“Something we thought we wouldn’t realize in 20 years, we came to within a few years and we could help the patients and others,” Eng said. “My patients felt pretty good about that.”

A sense of pride

Eng’s next move was to Columbus, Ohio. Within a few years, she had made the short list for several university jobs, but one was more appealing than the others.

Ohio State University wanted Eng to create a top clinical cancer genetics program and recruit more people like her. Since there was a paucity of clinical cancer geneticists, Eng proposed creating the nation’s first clinical cancer genetics training program there, to offer the type of educational experience Eng had to go to England to get. Beginning in 1999, she would teach others how to translate science into patient care in cancer.

On the clinical side, Eng saw patients from OSU’s James Cancer Hospital, providing genetic counseling to people with a high risk of heritable cancers. In the lab, she pursued her studies of PTEN, work that led to the better tests to identify germline PTEN mutations in patients before they developed cancer.

Knowing of their increased risk, patients can work more closely with doctors to prevent the disease—or at least catch it early.

Eng was at the top of her game. She had wanted to do something good for the country who had adopted her for her unique education. So, the moment her five years on the green card arrived, she immediately applied for U.S. citizenship. Calling on her knowledge of American history and politics, lessons she learned at the Lab School and the College, she was prepared for her citizenship exam. By the time test day arrived, Eng’s old knowledge of American history had returned, especially her favorite topic of the key battles that led to Cornwallis’ surrender to Washington at the Battle of Yorktown.

When the proctor laid the exam in front of her, deep disappointment washed over Eng. “They asked the simplest questions,” she said. Instead of political and cultural history, the test required Eng to “write down the number of colors in the American flag.”

Yet, when Eng received her passing grade and took the oath of citizenry, she couldn’t deny her sense of pride—not so much for her newly acquired knowledge of American history, but the knowledge that she’d contributed to her country as a physician and a scientist. She was sworn in during an emotional

ceremony held in downtown Columbus just two months after Sept. 11, 2001.

Becoming a U.S. citizen meant Eng could remain in this country, but it also meant she could bring her parents to live in Ohio. Her father, Soo-Peck Eng, PhD ’79 had long since retired and he and Eng’s mother, Siok-Mui, were living in Vancouver. Having them nearby was a great relief to Eng. Her strong sense of family enables her to work well with families in her clinical practice. It also endears her to those who work alongside her.

Kristin Waite, PhD, who joined Eng’s lab at OSU in 2001 as a research scientist, called Eng innovative, loyal and “scary smart.” Eng’s commitment to her patients and her staff led Waite to follow her when she left OSU in 2005 for the post at the Cleveland Clinic.

“For someone who is not married and who does not have kids, Eng is very cognizant of family values and the impact that work has on family,” Waite said.

Micheala Aldred, PhD, can attest to Eng’s values. She was the first scientist Eng recruited for the new institute in Cleveland. “In building her department, Charis looks more at people’s motivations rather than their research topics,” she said. Aldred studies chromosomal deletions implicated both in Wilms tumors, a rare childhood cancer, and also in a rare but devastating childhood condition. Her work has little in common with Eng’s research, but the underlying theme is the same. “She wants people to be interested in translational medicine.”

Eng is definitely doing something right. While other scientists fear for the state of science in America and struggle to find funding, Eng has been extremely successful, and is “just grateful.”

She still relishes every moment of work, and just as she did after she discovered the link between PTEN and Cowden syndrome, Eng continues to share news from the bench with patients in her clinic, which she said gives them an important sense of contribution.

So, though she’s all grown up, Eng in many ways is still the little girl who found a way to play doctor and scientist at the same time.

Fall 2008 39

Class Update 1940s Walter Lawrence Jr., PhB ’44, SB ’46, MD ’48, serves as professor emeritus of surgery at Virginia Commonwealth University and also teaches at an affiliated hospital.

Richard Kekuni Blaisdell, MD ’48, is professor emeritus at the University of Hawaii’s John A. Burns School of Medicine, where he also works as a consultant in the Department of Native Hawaiian Health.

1950s Bob Levine writes, “I’m careful not to neglect tennis and fly fishing.”

Ernest Beutler, PhB ’46, SB ’48, MD ’50, was the subject of the article, “Ernest Beutler: Independent Thinker and Astute Observer,” in the May/June edition of The Hematologist. The piece notes he was 15 years old when he enrolled at the University of Chicago, where he later developed an interest in hematology and studied under famed Chicago researcher Leon Jacobson.

Richard J. Neudorfer, MD ’51, retired from his White Plains, NY, orthopaedic surgery practice several years ago. He and his wife, Elinor, reside in Palm Beach, Fla., and would love to hear from classmates and friends. Neudorfer can be reached at neudorfer@ bellsouth.net.

Bob Levine, MD ’53, is “having a ball” working with Advocates for Senior Issues in Kent County, Mich., where he spends time advocating for universal health care. But, he writes, “I’m careful not to neglect tennis and fly fishing.”

1960s Burr S. Eichelman, SB ’64, MD ’68, PhD ’70, shares that, “Yes, there is life after being a chairman.” He left his position as chair of the psychiatry department at Temple University and headed back to the Midwest, where he now leads psychiatric consultation and emergency services at the University of Wisconsin. “Less politics and more teaching and clinical care are just fine,” he writes. “Ten grandchildren, an attorney wife/partner, and Dapne the Doberman take up the rest of my life at present.”

David Holtzman, PhD ’67, MD ’68, headed the child neurology divisions at Stanford and Tulane before moving to Cambridge, Mass., where he spent two years at the Massachusetts Institute of Technology learning in vivo nuclear magnetic resonance spectroscopy. Holtzman then began clinical programs and teaching on brain energetics at Harvard University’s Children’s Hospital Boston and Massachusetts General Hospital. His research focuses on the mitochondrial physiology in lymphoblasts from autistic patients.

Leonard Korn, MD ’68, works as a psychiatrist in Portsmouth, N.H., private practice and is president of the New Hampshire Psychiatric Society.

1970s James J. Madden, MD ’73, works as a hospitalist at the Reading Hospital and Medical Center in Reading, Pa., following a 26-year stint as a general internist at the Lansdale Medical Group. He and

Maryellen, his wife of 32 years, have three children: Brian, Tim and Kate. “Going back for reunions is always great fun,” Madden wrote, “It goes without saying that it can’t really be 35 years!”

Swati Singh, AB ’88, MD ’93, specializes in refractive and aesthetic surgery in the Bay area, where she has been in practice for almost 10 years.

Robert John Dempsey, MD ’77, and his wife, Diane, teach at the University of Wisconsin, where he serves as the chair and Manucher J. Javid professor in the department of neurosurgery. Dempsey also maintains a cerebrovascular research lab and teaches domestically and internationally.

Gina Kim Song, SB ’94, MD ’98, started a pediatric practice five years ago. It has grown into a small medical group with three physicians and more to come. She’s been married for almost nine years and has three children.

Patricia Simmons, MD ’77, lives in Minnesota with her husband, Les Wold, MD ’77. Simmons serves as director of pediatric and adolescent gynecology at the Mayo Clinic and professor of pediatrics at the Mayo Medical School. She also chairs the Board of Regents for the University of Minnesota.

Victor Elner, MD ’79, began his installment as the Ravitz Foundation Professor of Ophthalmology and Visual Sciences at the University of Michigan this past June. A physician-scientist who has shown that inflammation is often the cause of eye disease, Elner helped develop an instrument that detects eye disease long before the first symptoms occur. He is now concluding studies on its use in screening for diabetes and diabetic retinopathy.

1980s Carl L. Kalbhen was inducted as a fellow in the American College of Radiology at its annual meeting this past May. James J. Foody, MD ’80, began serving as Governor of the Illinois Northern Chapter of the American College of Physicians this past May. He serves as professor of medicine and vice chairman of clinical affairs at Northwestern University’s Feinberg School of Medicine and chairs the pharmacy and therapeutics committee at Northwestern Memorial Hospital.

Carl L. Kalbhen, MD ’89, was inducted as a fellow in the American College of Radiology at its annual meeting this past May. A clinical assistant professor of radiology at Loyola University Medical Center in Maywood, Ill., he also serves as a staff radiologist at Northwest Community Hospital in Arlington Heights, Ill. Manju Nath, MD ’89, PhD, specializes in physical medicine for rehabilitation and is the associate medical director at Health South Rehabilitation Hospital in Midland-Odessa, Texas. His son, Vikas, is a freshman at Texas Tech University Health Sciences Medical School, where Nath is also a clinical associate professor of internal medicine.

1990s Shahab A. Akhter, MD ’93, completed his general surgery residency at Duke University Medical Center in 2000 and his cardiothoracic fellowship at the University of Michigan Medical Center in 2002.

He was a member of the cardiac surgery faculty at the University of Cincinnati until 2007, when he was recruited back to the University of Chicago. His clinical interests include surgery for advanced heart failure, mitral valve reconstruction and arrhythmia surgery. Akhter married his wife, Pamela Jane Wells, in 2001 and their daughter, Sophia, was born in December 2006.

Nancy Keating, MD ’93, and her husband had their first child, Thomas, in 2006 and welcomed their second baby this July.

Michael McMann, MD ’97, served as a U.S. Army physician and ophthalmologist before beginning his own practice. “It’s been a very challenging and rewarding experience,” he writes. “Please look me up at www.oahulasik.com.”

Taehyun Philip Chung, MD ’98, is finishing a fellowship in colon and rectal surgery at Barnes-Jewish Hospital and the Washington University School of Medicine.

2000s Pat Basu was elected chief resident at Stanford University in the Department of Diagnostic and Interventional Radiology.

Suparna Mullick, MD ’02, and Matthew Lyons, MD ’02, live in St. Louis, Mo., where Mullick works as a pediatrician at a community health center and Lyons is a cardiology fellow at Washington University. Their son, Sachin Lyons, was born in June 2007.

Pat Basu, MD ’04, MBA ’05, was elected chief resident at Stanford University in the Department of Diagnostic and Interventional Radiology.

In Memoriam 1950s John Douglas Arterberry was a pioneer in the development of paramedic and hazardous material services in Los Angeles County.

Ethel M. Bonn, MD ’51, had a busy career in psychiatric administration before retiring in 1989. She died this past March.

An editorial board member for the Journal of Hospital and Community Psychiatry from 1982–1990, Bonn continued to serve as a reviewer for the journal for several years following her time on the board. In recent years, she enjoyed devoting more time to her lifelong hobbies—gardening, rock hounding, photography, fishing and travel.

John Douglas “Doug” Arterberry, MD ’56, of Rancho Mirage, Calif., died in December 2007. Born in Los Angeles, he was a longtime resident of South Pasadena and San Marino. Following his 33-year career at Los Angeles County hospitals and Northridge Hospital, he continued to practice medicine in Palm Springs and Yucca Valley until his retirement in 2005. A pioneer in the development of paramedic and hazardous material services in Los Angeles County, he is survived by his wife, Linda, his brother, William, three children, two stepchildren and five grandchildren.

1960s

Jennifer Zumsteg, MD ’05, was selected as co-chief resident in physical medicine and rehabilitation at the University of Washington Medical Center.

Julian J. Rimpila, SM/MD ’66, retired from Lincoln Park Hospital and served as a member of the Chicago Medical Society Council for 14 years. He died this past March. A former lieutenant colonel in the U.S. Army, Rimpila leaves behind his wife, Beverly, five children and many grandchildren, nieces and nephews.

Former Faculty

Former Faculty/Housestaff

Charles Brendler, MD, was endowed as the Ronald L. Chez Family and Richard Melman Family Chair of Prostate Cancer at Evanston Northwestern Healthcare this past June. An internationally recognized urologist, Brendler served as professor and chief of urology at the University of Chicago before joining ENH in October 2006.

Frances Stutzman, a longtime secretary and coordinator of special events for the Biological Sciences Division, died this past June. A university employee for almost 35 years, she moved to Wilmette, Ill., after her retirement and stayed active with the University of Chicago Service League. She is survived by King, her husband of 72 years, as well as two sons and three grandchildren.

Medicine on the Midway Bulletin of the Medical and Biological Sciences Alumni Association Fall 2008, Volume 61, No. 1 Editor Suzanne Wilder Contributing editors John Easton, Catherine Gianaro, Tom Hallman Editorial contributors Katie Scarlett Brandt, John Easton, Maja Fiket, Scot Roskelley, Megan Seery, Susan Soric and Suzanne Wilder Design firm Words&Pictures, Inc. Editorial committee Chairman Coleman Seskind, AB ’55, SB ’56, SM/MD ’59; Chris Albanis, AB ’96, MD ’00; Lampis Anagnostopoulos, SB ’57, MD ’61; John Benfield, MD ’55; Arnold Calica, SM ’61, MD ’75; James Hopson, PhD ’65; Patricia Martin, AB ’74, MD ’78; and Jerrold Seckler, MD ’68

Medicine on the Midway is published for alumni, faculty and friends of the University of Chicago Biological Sciences Division and Pritzker School of Medicine. Articles may be reprinted in full or part with permission of the editor. We welcome your comments and letters to the editor.

Address correspondence to Editor, Medicine on the Midway University of Chicago Medical Center 5633 S. Maryland Ave. Chicago, IL 60637-1470 Telephone (773) 702-6241 Facsimile (773) 702-3171 E-mail editor momedit@uchospitals.edu E-mail class news alumni@mcdmail.uchicago.edu Find us on the Web www.uchospitals.edu/midway

© October 2008. University of Chicago Medical Center Divisions of Communications and

40 University of Chicago Medicine on the Midway

Marketing

Fall 2008 41

A Look Back:

Class of 1968 Shares Memories

By Megan Seery Before members of the class of 1968 secured their medical degrees, they had already worked as a hospital labor force.

“It was the only time they let us out of class,” said Stephen Cohen, MD ’68, remembering the week he cranked the mangle, or wringer, in the laundry room of Billings Hospital.

Cohen and his wife, Gretchen, reminisced with friend Stanley Siefer, MD ’68, about the Chicago blizzard of 1967 when a single snowfall covered the city in 23 inches of snow, stranding thousands. Conversations like these helped to jump start Reunion 2008 this past June.

“The draft board wanted the university to hand over students’ names and their grade point averages, and a number of students took over in protest,” said Constan, who attended medical school on a scholarship and didn’t want to jeopardize it by protesting.

“Nothing came down from the university about that, but at a lesser school, the students could have gotten in serious trouble for civil disobedience.”

Counterclockwise from above: Paul Russel, MD ’47; Robert Weiler, MD ’58, and wife Patricia Weiler; Leong Tan, MD ’58, and Richard Kekuni Blaisdell, MD ’47.

Photos by Tricia Konnig

“I learned that the patients weren’t just saying nonsense,” he said.

“You have to pay attention to the cause of their ailment and not just the ailment itself. If you worked hard, you could understand them.”

They also recalled spending plenty of time at Jimmy’s, a bar now known as The Woodlawn Tap, on 55th Street.

Back on campus, Leonard Kern, MD ’68, passed the John Crerar Library for biological, medical and physical sciences and commented that research at the university is more accessible and student-centered now, a far cry from the tiny bookshelves he once scoured for journal articles.

“We had a small library in the hospital, and now they have a place with a million books,” he said. “We would look up what we wanted in the index and then go to the shelves to pull the journal, which might not even be there.”

42 University of Chicago Medicine on the Midway

He worked as a nurse’s aide on the psychiatric unit between the summer of his third and fourth years of medical school to see if he wanted to be a psychiatrist. His first week on the job, he met with a young woman who had jumped off a building.

In their conversation, Parzen learned that the woman wasn’t intentionally suicidal, but instead following what she believed to be a divine order sent down to her.

“The weather paralyzed the university, and the medical students did all the jobs. They ran the hospital,” recalled Gretchen Cohen, who met her husband in the Billings pediatric unit where she worked as a lab technician and he served his pediatric rotation.

“Sawdust on the floor, plank tables and bare light bulbs,” Siefer said.

“It was a dive, but there was classical music playing and it had some interesting graffiti that said more than ‘P.J. was here.’ You could tell it must’ve been written by a student at the university.”

A decade earlier, the most memorable moments occurred within the hospital walls, said Zane Parzen, MD ’58.

Getting doctors to open up took significantly more work, Parzen found.

David Kaufman, MD ’68, agreed with Kern’s assessment. And he was surprised to learn that first-year medical students arrive at school in August, instead of late September as in years past.

“Teachers are better now because teaching has gained more credibility as a profession. It’s not only about research anymore,” he said. “But I can’t say if we had it harder or if kids today have it harder because they have so much more to learn now.”

For one graduate marking his 40th reunion, the weekend brought powerful memories of politics. Lou Constan, SB ’68, MD ’72, remembered students taking over the administration building in protest against the Vietnam War draft.

Initially, he said, nobody wanted to discuss the things he wondered about the most: How does a physician feel when a patient dies? Does the staff mourn? Is it better to maintain distance with patients or be close enough that the physician knows who prefers Jell-O? “If the doctors felt like they were talking to someone on the outside, they wouldn’t say much,” said Parzen, who eventually asked a few U of C surgeons if he could scrub in and watch their operations. “They wouldn’t tell me anything at first. But if I was there experiencing a situation with a doctor, he’d open up a lot more.”

Clockwise from left: Pritzker Reunion Class of 1993: Swati Singh, Lisa Seung Turner, Jonathan Katz, Sung-Lana Kim, Peter Kjeld Slotwiner-Nie and Magdalena G. Krzystolik; Coleman Seskind, AB ’55, SB ’56, SM/ MD ’59, and University of Chicago Medical Center development officer Phyllis Dunigan; Gerald Herman, MD ’58, and wife Constance Herman; Darlene Ann Kuhn and husband Paul Richard Kuhn, AB ’52, SB ’54, MD ’56,; and alumni development director Holly Hadden and Robert Costarella, MD ’64. Photos by Tricia Konnig

Fall 2008 43

Graduates say a fond farewell

By Megan Seery

From left: Members of the 2008 Pritzker Class: Jun Matsui; Alan Thong, Sara Tanaka, Nithya Swamy, current student Elizabeth Sullivan and Adam Suchar; Alleda Flagg, PhD ’07; and Joseph Novak. Photos by Tricia Konnig

A

s the new crop of biological sciences and medical school graduates venture into the world, they’ll be amazed at how little most of the country knows about basic science, said Ira Flatow, host of National Public Radio’s Science Friday, during the University of Chicago’s annual Divisional Academic Ceremony this past June.

Mentors, family and friends then took black sashes and “hooded” the graduates, who were teeming with emotions of their own.

It is imperative for the 155 newly hooded MDs and PhDs to convey their work in a manner accessible to the lay public, Flatow urged, so they can “bridge the great divide between two cultures: scientists and other people.”

Jennifer Ballinger, MD ’08 ran to hug her uncle, David Ballinger Jackson, who put a work project in Angola on hold to attend the ceremony, while Jocelyn Slaughter, MD ’08, greeted family friend Barbara Wade.

“America needs scientists,” he said. “We need you to learn to speak English. We need to be able to translate your heavy thoughts into jargon we understand.”

“She’s leaving us, but she’ll still be in a progressive city,” Wade said of Slaughter’s fall residency at the Morehouse School of Medicine in Atlanta. “The heat down there will be the biggest change.”

Both Flatow and Catherine DeAngelis, MD, editor of the Journal of the American Medical Association, used their convocation platform to persuade graduates to view their work not only through a scientific lens, but also with a humanistic approach.

While many graduates said they’d miss friends and faculty, Michael Jurczak, PhD ’08, said it was food he would miss the most as he begins his post doctoral program at Yale University.

“It’s ‘MD,’ not ‘M Deity,’” DeAngelis said, emphasizing the importance of integrity in a profession where conflicts of interest are a constant challenge. “You might be the last face that some poor soul sees before he or she leaves this earth.”

After completing his bachelor’s degree at Northwestern University and earning his medical degree at Chicago, Horace Rhee, MD ’08, PhD, feels ready to leave the city and experience a change of pace this fall at Stanford University, where he’ll complete his residency in internal medicine.

The guests spoke to the idea that, in a world fraught with diverse and powerful business interests, new doctors can’t leave behind their hearts nor their consciences when they walk into work.

In closing, DeAngelis reminded graduates of a popular saying: “People may not remember what you did or what you said, but they will always remember how you made them feel.”

“I’m going to miss working beside my best friend in the lab,” said Parisha Shah, PhD ’08, hugging Eliza Small, PhD ’08.

“Not so much the pizza,” he said. “I like Mexican food.”

Megan Dunning, PhD ’08, also expressed excitement about moving for her next project, though she won’t travel quite as far.

“I’m going to manage the natural history education program at the Morton Arboretum,” she said, referring to the internationally famous tree conservation organization in Lisle, Ill. “Wish me luck.”

From top: Sujit Janardhan, PhD; Catherine DeAngelis, MD; and Ira Flatow Photos by Tricia Konnig

“People may not remember what you did or what you said, but they will always remember how you made them feel.”

—Catherine DeAngelis, MD

From left: Members of the 2008 Pritzker Class: Robert Guzy, PhD ’05, and Richard Gil; Lizette Durand, PhD ’07; Gmerice Hammond and Jonathan Hemmert; and Monica Burts, PhD ’07. Photos by Tricia Konnig

44 University of Chicago Medicine on the Midway

Fall 2008 45

Perspective

‘FOR US, PROGRESS MEANS GETTING SMALLER.’

By James L. Madara, MD, and Holly J. Humphrey, MD

Just like pat ient s, doctors and medical students, institutions— even big ones, such as medical schools—have personalities.

They grow and mature over time, in response to internal inspiration or external pressure. But a core of beliefs and practices should determine how any institution functions. Moving too far away from that core means losing sight of your mission.

46 University of Chicago Medicine on the Midway

Predicting a physician shortage, the Association of American Medical Colleges and others have been urging medical schools to train 30 percent more physicians by 2015. In response, more than eight out of 10 schools have vowed to increase class size. Many have already done so, but not us.

The University of Chicago Pritzker School of Medicine has always been comparatively small. It is who we are.

Fifty years ago, the University of Chicago enrolled 55 to 60 new medical students each year. Most of them went on to combine the practice of medicine with distinguished research and teaching careers.

In the 1960s and ’70s, however, a series of federal incentives put pressure on all medical schools to increase enrollment, so the University of Chicago gradually raised its class size to 104 new students per year. But in fall 2009, despite being exhorted to grow, we will scale back to 88.

This decision is based entirely on our mission to train outstanding physicianscientists and to develop leaders in academic medicine. Our focus is not on training more doctors but better doctors.

For us, progress means getting smaller.

Instead of increasing the number of students, we are choosing to increase student-faculty interaction. Instead of big lecture classes, we are choosing small-group, hands-on learning under the direct mentorship of our full-time faculty. Our students not only will learn about the cutting edge of biomedical science, they will help make discoveries, learn how to translate that knowledge into patient care and acquire—through example, experience and osmosis—the moral foundation of the profession.

These are the kinds of doctors our patients deserve.

While it’s easy enough to make a big lecture class bigger, it is more challenging to go the other way, to take a lecture class with 50 or 100 students and break it up into smaller groups—one professor and, say, five to eight students. This new emphasis on personal instruction,

THE UNIVERSITY OF CHICAGO PRITZKER SCHOOL OF MEDICINE HAS ALWAYS BEEN COMPARATIVELY SMALL. IT IS WHO WE ARE. intense faculty mentorship and a handson approach to teaching places extraordinary demands on our faculty—a bit more, perhaps, than we are equipped to handle with 104 new students a year.

Others share our concerns about class size. A recent survey published in Academic Medicine found most medical schools were thinking about the consequences of increasing class size, which “clearly has the potential to adversely affect student education, faculty recruitment, and faculty morale.”

So we will now devote the same educational resources and financial support to fewer students. We will increase student-faculty contact and, in the process, restore to medical education some of the personal bonds that may have been lost because of pressures on faculty time.

What about our obligation to increase the physician workforce? As scientists, we have yet to be convinced of the reality of this looming shortage. The institutions that train new doctors—and collect tuition for it—have been predicting such a shortfall for decades. Yet the U.S. physician supply is at an all-time high, up from 200 doctors per 100,000 people in 1980 to a predicted 293 in 2010.

Having more than 40 percent more doctors per capita has not led to better care, easier access or improved patient satisfaction, noted Dartmouth’s David C. Goodman, MD, MS, and Elliott S. Fisher, MD, MPH, in the April 17, 2008, issue of the New England Journal of Medicine.

They argue that by simply adding physicians, we are treating the symptoms while ignoring the disease: “a largely disorganized and fragmented delivery system, characterized by lack of coordination, incomplete patient information, poor communication, uneven quality and rising costs.” Training more physicians, they write, may only worsen existing problems and potentially create new ones.

We think it is less important how many doctors we produce and more important what those doctors do—and where they do it. Neither the Hamptons, nor South Beach, nor Beverly Hills needs another cosmetic surgeon. But the 1.1 million residents of the South Side of Chicago could benefit from a few more

doctors with an interest in chronic disease. This radically underserved community—despite being just a few miles from the largest public medical school in the country—has extremely high rates of hypertension, diabetes and asthma, all largely untreated.

When a person is 32 years old, $150,000 in debt and about to start a first real job, it’s hard for even the most compassionate doctor to commit to a career caring for the poor. But having fewer students, and the same financial aid resources, will enable us to graduate new doctors with about 40 percent less debt.

We also have taken an innovative next step. Beginning this fall, we will encourage our graduates to return to the underserved communities of the South Side of Chicago to practice medicine by providing four years of financial support— enough to pay off the average graduate’s debt. That program, Repayment for Education to Alumni in Community Health (REACH), brings Pritzker alumni back to the neighborhood where they learned their craft, after they complete their residencies.

Although they could make other choices and earn higher salaries, we want our graduates to follow their passions, not their pocketbooks. This program will give carefully selected doctors who are just starting their careers the opportunity to do just that, without the burden of college and medical school loans.

When she first heard about this project, fourth-year medical student Mia Lozada wrote: “When thinking about my future career I went with my heart”—despite a substantial loan debt looming over her. Primary care “may not reap huge financial rewards,” she added, “but it is where I feel I can make the most impact with this education that I’ve been so lucky to receive.”

We want all our graduates to emerge feeling lucky, like Dr. Lozada, and confident that they have the power to make an impact and the freedom to follow their hearts. That’s ultimately why, despite constant pressure to move in the opposite direction, we’re getting smaller rather than bigger. It is who we are and who we are meant to be.

James Madara is chief executive officer for the Medical Center, dean of the Biological Sciences Division and Pritzker School of Medicine, and vice president for medical affairs at the University of Chicago. Holly Humphrey is professor of medicine and dean for medical education at Pritzker.

Fall 2008 47

Nonprofit Organization U.S. Postage

PAID

Chicago Medicine U N I V E R SI T Y OF

Biological Sciences Division

ON T H E M I DWAY

Balancing

inequities in

health care page 22

FA L L 2 0 0 8

Medical & Biological Sciences Alumni Association 1170 East 58th Street Chicago, IL 60637

Chicago, IL Permit No. 5179