1THE MAGAZINE OF NEW YORk UNIVERSITY SCHOOL OF MEDICINE

NYUPhYsiciaN

Physician researchers are mobilizing for the coming tidal wave of disabling arthritis

Baby Boomer knees

1FALL 2009

volume 61 • No.

Preserving Fertility through Cryopreservation

$100 Million Gift Creates Neuroscience Institute

New Approaches to the Big Apple’sHealth Problems

PlUs

EvEry aspiring physician drEams of this day: the day someone calls him or her “Doctor” for the first time. But getting there takes a lot more than patience, perseverance, and hard work. It takes resources—for library enrichment, for state-of-the-art research and teaching technology, and for financial assistance. By contributing to the School’s Alumni Campaign, you will help our students fulfill their dream of becoming a physician. In so doing, you will also help us maintain one of our proudest traditions: no student is ever forced to withdraw for lack of financial resources. Someday you may even have the privilege of being one of their patients . . . and calling them “Doctor” yourself.

easy to doUse the postage-paid return envelope inserted into this issue of NYU Physician. Or visit www.med.nyu.edu/alumni.

For special giving and memorial opportunities, call anthony J. Grieco, Md, associate dean for alumni Relations, at 212-263-5390.

Help Us Make Dreams Come True

thank you for your generosity.

NYU PhYsiciaN fall 2009

ThE MaGaZiNE OF NEW YORk UNiVERsiTY schOOL OF MEDiciNE

New York University

Martin Lipton, Esq. Chairman,

Board of Trustees

John sexton President

Robert Berne Senior Vice President

for Health•

NYU Langone Medical Center

kenneth G. Langone Chairman,

Board of Trustees

Robert i. Grossman, MD

Dean and Chief Executive Officer

Deborah Loeb Bohren Vice President,

Communications and Public Affairs

•NYU Physician

steven B. abramson, MD

anthony J. Grieco, MD (63)

Editors, Science and Medicine

Frank W. Lopez Managing Editor

Marjorie shafferSenior Editor

Royce Flippin Contributing Editor

Rob hewitt Art Director

Mel MinterCopy Editor

• On the COver:

Illustration by Bryan Christie

NYUPhYsiciaN

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1Baby Boomer knees As the nation’s largest generation begins to feel the painful signs of aging, advances in research and surgery promise relief.

Who Will Get Worse?Scientists at nYU and Duke are

working together to create blood tests that identify those at high risk of severe osteoarthritis, a major obstacle in the quest for better treatments.

knee animationsYou want to know exactly what

the inside of a knee looks like? exquisitely detailed computer animations offer an extraordinary view of this complex joint.

The Better knee?Bioengineers at hospital for Joint

Diseases are performing partial knee-replacement surgery using new materials and computer-generated models. the promise: less pain, faster recovery, better mobility. tennis anyone?

Frozen in TimePrior to 2004, only a handful of

births from thawed, frozen ooctyes were reported. But over the last four years, the technique has flourished, providing new options for women who want to extend their fertility.

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Cover Stories

Departments02 From the Dean Inspiring Innovations

03 Support $100 Million Gift establishes neuroscience Center

04 News from Medicine22 Patient Stories24 Faculty News26 Around Campus28 Medical Education36 Obituaries

FaLL 2009nO. VOluME 61

“ at least one in 10 americans now has osteoarthritis.”

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alumni News Special TribuTe To Saul J. Farber

Four distinguished physicians recall confrontations, conversations, and lunches with a revered master physician and teacher.

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TInspiring Innovations

The use of Technology in medicine has been an enabler of amazing advancements in research and treatment, ultimately leading to a higher level of patient-centered care. Thanks to the powerful triumvirate of technology, medicine, and science, we have been inspired to imagine “what if” in a way that those who practiced medicine before us could not.

In this issue you’re going to read about a wonderful $100 million gift from the Druckenmiller foundation to establish our new neuroscience Institute—a place where interdisciplinary teams will be inspired to conduct translational research on brain physiology and function and future neuroscientists can dare to imagine. you’re also going to read about innovations that have been pioneered here at nyu langone Medical center for the diagnosis and care of osteoarthritis and for the cryopreservation of oocytes to safeguard fertility.

osteoarthritis, rapidly becoming known as the baby-boomer condition, is being looked at from many vantage points. our researchers are identifying molecular biomarkers to predict “who will get worse,” devising biochemistry-based imaging to detect cartilage erosion, and performing robot-assisted partial knee-replacement surgery.

Preserving fertility for women cancer patients or those who want to delay motherhood to a later age has led to promising advances in oocyte cryopreservation, or “egg freezing.” our Medical center has one of the most successful egg freezing programs in the world.

This issue also includes a special tribute to saul farber, former dean and provost of nyu school of Medicine. Reading these collected reminiscences is a wonderful reminder of the lasting influence he had on a generation of physicians and scientists and the wonderful things he did for our institution. •

Message from the Dean & CEO

Dean & Ceo rObErt i. grOssMan, MD

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U.S. News Ranks nYU Langone one of nation’s Top hospitals

In a resoundIng affIrmatIon of our progress toward becoming a

world-class academic medical cen-ter, U.S. News & World Report placed nYU Langone Medical Center on its elite “honor roll” in its most recent annual survey of america’s best hospitals. it was nYU Langone’s first appearance in this exclusive group

in over a decade. to be on the “honor roll,” hospitals must be ranked at or near the top in at least six medical specialties.

the Medical Center’s ranking

as one the top 21 U.s. hospitals puts it in the top two-fifths of 1 percent of the 4,861 medical centers evaluated by the magazine. in addition, three of the Medical Center’s specialties—rehabilitation, orthopaedics, and neurology and neurosurgery—were ranked among the top 10 in the country. this marked the 20th consecutive top 10 ranking for the rusk institute of rehabilitation Medicine, which was also rated the best in new York state in its category. the Medical Center’s rheumatology and heart and heart surgery areas also performed extremely well, each rising from 16th place to 11th, while the Cancer institute’s ranking jumped from 37th place nationally to 25th. •

nNYU LaNgoNe MedicaL ceNter’s research program in neuroscience is poised to undergo a major expansion following the announcement this past summer of an extraordinary $100 million gift from the Druckenmiller foundation, establishing a new state-of-the-art neuroscience institute at the Medical center. The institute, comprised of an integrated community of basic scientists and physician-researchers, will provide nyu langone with a multidisciplinary framework to carry out the study of brain physiology and function in relation to various brain disorders. In addition to extending nyu’s strong translational research efforts, in which laboratory advances are fast-tracked to produce innovative clinical treatments, the gift will also fund the recruitment of new neuroscience faculty and the education of

builds on nyu langone’s long-standing expertise in both basic and clinical neuroscience, leaves the Medical center positioned to play a leading role in a field that is expected to grow significantly in coming decades. greater knowledge of the brain’s anatomy and biological processes, together with a growing understanding of how genetic factors influence brain activity, opens the door to the possibility of customized brain therapies tailored to each patient’s personal genetic and biochemical profile.

Inaugural Symposium HeldA symposium dedicated to the Druckenmillers was held in late october at the Medical center. featuring the work of nine neuroscience researchers, the symposium underscored the wide ranging interests of nyu’s investigators. Among the speakers were: Rudolfo R. llinas, MD, PhD, the Thomas and suzanne Murphy Professor of neuroscience and chairman of the Department of Physiology and neuroscience; evgeny nudler, PhD, the Julie Wilson Anderson Professor of Biochemistry; Daniel K. sodickson, MD, PhD, vice chair for research, Department of Radiology, director, center for Biomedical Imaging, and associate professor of radiology, physiology and neuroscience; Margaret Rice, PhD, professor in the Department of neurosurgery and the Department of Physiology and neuroscience; gordon James fishell, PhD, professor in the Department of cell Biology; and edward Ziff, PhD, professor in the Department of Biochemistry.

“The Druckenmillers conceptualized this gift out of their interest in the healthy brain and understanding how the brain functions,” said Ken langone, chairman of the Medical center’s Board of Trustees. “We are especially grateful that they have chosen to support neuroscience, one of the Medical center’s strategic areas.” •

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stanley and Fiona Druckenmiller

support

future neuroscientists.The institute’s benefactors, fiona

Druckenmiller, a Medical center trustee since 2006 and a former portfolio manager at the Dreyfus corporation, and her husband, stanley Druckenmiller, founder of Duquesne capital Management and chairman of harlem children’s Zone, have previously donated $46 million for various long-term initiatives at nyu langone, including the campus transformation project, the centers of excellence, and an endowed professorship in emergency medicine.

“The brain is one of the last great frontiers in medicine,” noted Mrs. Druckenmiller. “We believe that breakthroughs in neuroscience and stem cell research will yield huge benefits in both quality and length of life.”

The Druckenmillers’ gift, which

$100 Million Gift from Druckenmiller Foundation establishes neuroscience institute

“ The brain is one of the last great frontiers of medicine. We believe that breakthroughs in neuroscience and stem cell research will yield huge benefits in both quality and length of life.”

illustrations by paul blow

News from Medicine

in the nucleus in this instance, and when they deleted STAT3 from either type of cancer cell, the cells reverted to a more normal pattern of growth.

Based on those data, the investigators concluded that STAT3 function is necessary for the growth in both types of cancer cells. The catch, though, is that in one type of cancer cell, STAT3 works its dark magic by controlling gene activity in the nucleus, while in the other type, it causes trouble by altering mitochondrial function. “This is a paradigm shift,” Dr. Levy says. “There are many examples in biology where the completely out-of-the-box result pushes the field forward, and finding STAT3 in the mitochondria is certainly one of those results.”

While the connection between STAT3 and the mitochondria was unexpected, the connection between mitochondrial function and cancer is an old one. Nearly a century ago, Otto Warburg, a German physiologist and Nobel laureate, noticed that cancer cell metabolism is substantially different from that of normal cells. Cancer cells rely more heavily on glycolysis, the fermentation pathway for converting sugar into adenosine triphosphate (ATP), than do healthy cells, which tend to rely on the more efficient oxidative phosphorylation process. However, scientists had not been able to fully understand what controls this metabolic shift; the recent discovery in Dr. Levy’s lab adds new insight into this problem. His team was able to show that when they deleted STAT3 from cancer cells that were transformed by the oncogene Ras, the cells’ metabolism shifted from a cancerous fermentation-heavy pattern to a more normal oxidative phosphorylation–dependent one.

Investigators had talked about blocking STAT3 nuclear activity to slow tumor growth, but because the protein is important for numerous physiological processes, including immune response, it had been feared that knocking out its function would cause serious side effects. The mitochondrial function, however, appears to be more cancer specific. So if the team can find a way to block only that function, leaving the nuclear one intact, they may be able to develop a targeted therapy with few side effects. •

— rabiya tuma

4 NYu phYsiciaN fall 2009

IImAGINe yOu LIve IN CHICAGO. One night you’re at a party, and someone tells you that a close friend has been leading a parallel life in Atlanta for years. you are amazed, but oddities you had noticed suddenly begin to make sense.

(signal transducers and activators of transcription) family of proteins in the 1990s. Since then, they had identified a paradigm for how the STAT proteins (as well as many other signaling proteins) operate: The protein hangs out in the cytoplasm until the cell receives a signal telling it to modify STAT3 and send it to the nucleus. Once the protein arrives there, it binds to DNA and turns on genes that promote growth and cell survival, functions critical to both immune responses and tumor formation.

But then the Levy team did a set of ex-periments that threw a wrench into this prevailing view. They knew that when a particular group of oncogenes, called ty-rosine kinase proteins, are overexpressed, STAT3 moves from the cytoplasm to the nucleus and promotes cancer formation. But when they looked in cancer cells that express a different type of oncogene called Ras, a guanine phosphatase, they found that STAT3 did not travel from the cyto-plasm to the nucleus, and yet was still required for tumor growth. It was func-tioning in the mitochondria rather than

That experience is a bit like what happened last year to David e. Levy, PhD, the Dr. Louis A. Schneider Professor of molecular Pathology, vice chair for science, and professor of microbiology. After studying the STAT3 protein for more than a decade and deciphering how it contributes to cancer by turning on genes in the nucleus, his team was surprised to learn that STAT3 also drives tumor growth from inside the mitochondria, the cell’s power plant.

Just as mutual acquaintances might doubt you if you told them about that other life in Atlanta, scientists outside Levy’s group who hear about STAT3’s role in mitochondrial function are skeptical at first. “When we describe the work to other researchers, there is a little disbelief initially,” says Daniel Gough, PhD, a postdoctoral fellow in the Levy lab and first author on the paper published in the June 26, 2009, issue of Science. “The field has been adhering to a simpler paradigm for decades. Once they get past their disbelief, they are usually pretty excited.”

Biologists first identified the STAT

a secret life in the Mitochondria of cancer cellsAn unexpected discovery about an industrious protein

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subverting the immune system’s sentinels to protect the Growing Fetus

FFOR mOST PReGNANT WOmeN, the first trimester is filled with anxiety and hope for a healthy pregnancy. Prospective mothers marvel at the notion of a human life growing inside, but few know that although fetal cells are foreign to her body, there is a biological imperative that prevents her immune system from attacking them.

For more than 50 years, physicians and scientists have pondered how immune evasion in the uterus is possible. A recent study by Adrian erlebacher, mD, PhD, assistant professor of pathology, and mary K. Collins, a graduate student in his laboratory, has revealed new insight into the adaptive role of the uterus in controlling an immune response. Their findings were published in the June 22, 2009, issue of The Journal of Clinical Investigation.

In a 2007 study in mice, Dr. erlebacher had shown that a mother’s T-cells, the immune cells that destroy foreign invaders, appear to be unaware of the fetus and placenta in the first half of the gestation period. Then in the second half, T-cells detect the presence of the fetus but are rendered powerless. In his most recent study, Dr. erlebacher set out to understand how the fetus and placenta escape detection. The answer appears to lie within the decidua—a protective lining that forms around the fetus and placenta—and its entrapment of immune cells called dendritic cells (DCs).

DCs are sentinel cells, constantly on alert, monitoring their environment for invading forces such as viruses and bacteria, or in the case of organ transplants, foreign tissue cells that don’t belong. Once they capture an invader, they remove a sample fragment and travel through the blood stream to lymph nodes, where they warn T-cells to trigger an attack.

During pregnancy, however, the function of DCs in the decidua is subverted. “They’re somehow stuck without their usual means to travel to lymph nodes and alert T-cells,” says Dr. erlebacher. “It’s as though all the dendritic cells’ horses are paralyzed at the frontier, and the message can’t be delivered.” What’s particularly surprising is that DCs in the uterus and other organ

NYu phYsiciaN fall 2009

tissue are usually the most aggressive activators of T-cells.

To test whether DCs could leave the decidua, Dr. erlebacher and his team created an experiment to activate DCs throughout the body of a pregnant mouse. They witnessed universal DC activation, including the migration of DCs from the muscular layer of the uterus, which surrounds the decidua. “They got on their horses and reported back to the lymph nodes that something was definitely wrong,” says Dr. erlebacher. But within the decidua, though DCs were activated, they stayed put.

This remarkable protective mechanism appears to avert an attack from the mother’s immune system and allow a healthy fetus to grow to term. But what if the process or the decidua is somehow flawed and DCs escape? Dr. Erlebacher speculates that such an immune response might cause a fetus to spontaneously

abort, which may explain why some apparently healthy women who have no chromosomal abnormalities experience recurrent miscarriages. Further research may eventually enable scientists to harness the protective mechanism of the decidua and help these women to keep their pregnancies.

unfortunately, the same mechanism may prevent cancer from being recognized by the immune system. When DC behavior is better understood, Dr. erlebacher and other researchers speculate that DCs could ultimately be manipulated and unleashed to deliver their critical message and alert T-cells to invade a tumor.

Dr. Erlebacher’s findings have also piqued the curiosity of infectious disease researchers. In a commentary published with his findings, Rana Chakraborty, mD, PhD, at emory university School of medicine, and Bali Pulendran, PhD, at yerkes Primate Research Center in Atlanta, observed that the research provides new insight into the “privileged” immune conditions that support maternal-fetal coexistence. They speculate that DCs in the decidua may play a protective role by restricting the entry of viruses such as HIv into the placenta. Before birth, the rate of transmission of HIv infection from mother to fetus is only 7 percent.

Dr. erlebacher’s team is now poised to study why dendritic cells are trapped within the decidua. • — sharon kay

illustration by jeFFreY decoster

News from Medicine

building social support for teens with hiV

NYu phYsiciaN fall 2009 6

or Hispanic—died in the first few months of life from opportunistic respiratory infections. Of those who survived infancy, about half were dead by age two.

But with the advent of effective antiretroviral drug therapy in 1996, maternal testing and treatment have meant that babies are rarely infected at birth anymore, and those that are account

IIN 1995, Nyu PeDIATRICIAN Sulachni Chandwani, mD, evaluated an emaciated seven-year-old girl who had arrived at Bellevue Hospital with an unusually severe case of chickenpox. “Her immune system was so ravaged, we decided to test for HIv,” she says. The test led to a positive diagnosis for the girl, a younger sister, and their immigrant mother, who, until then, never knew that she had the virus and had passed it on to two of her three children at birth. That very ill little girl became a regular patient. Today, she works part-timeand is herself the mother of a healthy, uninfected two-year-old.

The Bellevue clinic for children with HIv/AIDS began almost at the start of the epidemic in the early 1980s. “We actually saw our first patient in 1981,” says William Borkowsky, mD, professor of pediatrics and director of infectious pediatric diseases. “By 1983, we started seeing a number of infants we thought were infected.” many of those babies— most of them poor black

for less than 1 percent of the 1 million or so Americans now living with HIv and AIDS. Older teens, who acquire the infection through sexual behavior, account for about 5 percent of the total, or 56,500, according to the Centers for Disease Control and Prevention. The most recent data from the New york City Department of Health and mental Hygiene show that of the 100,000 New yorkers now living with HIv and AIDS, 591 are children and 1,584 are teens.

As effective drugs have turned HIv/AIDS from a fatal disease to a chronic illness, Bellevue’s pediatric infectious disease patients are now reaching adolescence and young adulthood, with all the issues affecting that age group—and then some.

many have watched a parent die. Some are in group homes or foster care. even in stable homes, parents or caregivers are generally overprotective and want to hide their children’s illness, “just because of the isolating nature of HIv, and that can be fraught with mental health issues,” says researcher Susan Abramowitz, PhD, assistant professor in the Division of Pediatric Infectious Diseases and Immunology and co-director of Nyu School of medicine’s Lower New york Consortium, a provider network in lower manhattan and Staten Island that provides a continuum of care for people living with HIv and AIDS.

Dr. Abramowitz and her colleagues reported on the social isolation of HIv-infected teens in the may 2009 issue of AIDS Patient Care and STDs. As a result of this study, the two sets of HIv-infected teenagers—those infected at birth and those who acquired the disease later—have been brought together by clinic staff to help

“ When you ask them directly, 50 percent will identify other issues as more important than HIV, from losing a parent to witnessing someone shot on the street.”

7NYu phYsiciaN fall 2009

advocating early treatment of hiV in third-world Nations

IIN THe LAST FIve yeARS, SHAFFIq eSSAJee, mD, has seen only two HIv-infected babies at Bellevue Hospital, whose doctors deliver one of the largest populations of HIv-infected women in the country.

“When I visit mombasa in Kenya, my home, I see dozens of kids on the wards who are HIv infected. So the discrepancy between the developed and developing world is gaping,” says Dr. essajee, an assistant professor in the Division of Pediatric Infectious Diseases and director of clinical activities for the William J. Clinton Foundation’s HIv/AIDS initiative. The foundation, established by the former president in 2002 to widen global access to antiretroviral treatment, supports Dr. essajee’s work in Kenya.

Of the 33 million people in the world living with the disease, some 90 percent live in developing countries, which have been slower than wealthier nations to embrace early treatment. The developed nations remain “stuck on the notion that drugs are expensive and need to be used in a parsimonious way,” essajee says.

In a review of the recent literature supporting early treatment in the may 2009 issue of Current Opinion in HIV and AIDS, Dr. essajee and Charlotte v. Hobbs, mD, an attending physician with the medical Center’s Department of Pediatrics, predict that global adoption of early treatment will lower drug costs, strengthen care-delivery systems, and reduce transmission of the disease itself.

“The advent of antiretroviral therapy (ART) in the mid-1990s resulted in dramatic improvement in HIv patient care, resulting in the recommendation to ‘hit early and hit hard’ with treatment,” they write. But that early enthusiasm was dampened by drug toxicity at higher-than-currently-used doses and the realization that even transient nonadherence could lead to viral resistance.

Since then, “HIv treatment has come full circle, from sparing use to avoid long-term toxicity, to the realization that early initiation of treatment actually

offers better outcomes,” he says. “modern approaches now are actually very safe, with no toxicity.”

In the united States, physicians now routinely initiate antiretroviral therapy for their HIv-positive patients before they become sick or before a precipitous decline in specialized white blood cells of the immune system known as CD4 cells, which normally range between 500 to 1,500 cells/µl.

Since 2008, both the u.S. Department of Health and Human Services and u.S. International AIDS Society guidelines support starting treatment before cell levels fall below 350 cells/µl, the same treatment threshold that prevents maternal transmission of the virus in pregnant women.

“This is not wasted on the global health community. They get this,” essajee says. Countries like Thailand and Brazil have made it a priority to treat HIv-infected patients early and aggressively. “And those strategies have begun to pay off.” • — aubin tyler

each other deal with issues like managing feelings, understanding their illness, taking care of themselves, and developing goals for the future.

“The younger kids like listening to the older kids, who are much more fluent about sex-related issues. The older kids are more unsteady about their diagnosis, something the younger kids have been living with for a long time,” Abramowitz says. Talking with peers confronted by the same issues appears to help make them more aware of their options with the goal of improved decision making.

“One of the problems with teens who have chronic diseases is adherence to their medication,” she says. “Adolescents don’t want to be reminded that they’re sick.” For older teens, their lives may be too chaotic to start or stay on regular treatment. That becomes a problem with HIv medications, which require strict adherence to avoid drug resistance. For those who have been taking medicine since childhood, there’s a fatigue factor. There are side effects, too, including headaches, nausea, and cognitive impairment.

Teens infected later in life tend to have more friends who know their status, but this rarely translates into more emotional, psychological, or even practical support. They also tend to take a different stance toward their diagnoses. “When you ask them directly, 50 percent will identify other issues as more important than HIv, from losing a parent to witnessing someone shot on the street,” says Bret Rudy, mD, associate professor and vice chair of the Department of Pediatrics, who works extensively with HIv-infected youth and conducts national clinical trials. He joined the medical Center in early 2009. “There’s a lot of loss, a lot of trauma.”

“The challenge is how to address low adherence and risky sexual behavior, because both affect their health,” observes Abramowitz. “Taking care of adolescents is a challenge. The real goal is to try to figure out how to help them stay healthy. Improving the social support availale to infected youth may be one way to help.”• — aubin tyler

“ When I visit Mombasa in Kenya, my home, I see dozens of kids on the wards who are HIV infected. So the discrepancy between the developed and developing world is gaping.”

A team of chemists, radiologists, rheumatologists, cell biologists, and geneticists is tackling the toughest question in treating osteoarthritis: “who will get worse?”

By

bryn nelson

Illustration by Paul Blow

NYU PhYsiciaN

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or more complex than the hingelike joint of the knee. This wonder of anatomical engineering, built to support seven times our body weight, is the workhorse that carries us through a lifetime of walking and running, climbing and descending, skipping and dancing. The knee, in short, is where the action is—and therein lies the problem: as the joint most prone to injury, it is increasingly succumbing to a devastating but poorly understood disease known as osteoarthritis.

At least one in 10 Americans now has osteoarthritis, and with people living longer, more active lives than ever, the disease is threatening to dismantle the lifestyles of seniors and baby boomers approaching retirement age. Its telltale signs are now appearing on the X-rays of up to 40 to 50 percent of people over the age of 70.

One of the few studies to examine its heavy financial toll concluded that in 2003, arthritis and other rheumatic maladies, of which osteoarthritis is the undisputed kingpin, cost the United States nearly $81 billion in medical expenses and $47 billion in lost wages. “From a public health point of view, this is probably the single-largest cause of disability in the industrialized world,” says Steven Abramson, MD, senior vice president and vice dean for education, faculty, and academic affairs; director of the Division of Rheumatology; and co-director of the NYU Musculoskeletal Center of Excellence.

While osteoarthritis can affect the hips, hands, back, and other joints, knees are especially vulnerable. About 542,000 total knee-replacement surgeries, the treatment of last resort for severely arthritic joints, were performed in the United States in 2006, compared to 231,000 total hip replacements. A 2007 study in the Journal of Bone and Joint surgery projected that by 2030, the number of knee replacements will grow by an astounding 673 percent to nearly 3.5 million procedures annually, far outpacing the demand for hip replacements, which are projected to increase to about 570,000 per year.

Despite its prevalence, this cartilage-destroying disease has so far resisted nearly every effort to slow or halt its progress. The only drug treatments now available are designed primarily to alleviate the disease’s often-excruciating pain. Many of these medications come with their own baggage. Dr. Abramson says concerns about heart attack risks from nonsteroidal anti-inflammatory drugs in the wake of the 2004 Vioxx recall tilted treatments toward less effective medications

NYU PhYsiciaN fall 2009

like Tylenol or more dangerous ones like the opioids Oxycontin and Percocet. Constipation, nausea, falling, and mental impairment are among the opioids’ side effects.

What’s more, the effectiveness of pain medications diminishes as osteoarthritis advances. For some, the shock-absorbing cartilage pads that cushion the attachment points of knee or hip joints can wear away until bone rubs on bone, making even simple movements nearly unbearable. At that point, joint replacement is the only viable option.

The search for signposts • To counTer The disease, Dr. Abramson is working with an impressive array of specialists from NYU Langone Medical Center and other institutions on new ways to hold the disease in check. The collaboration, he says, comes down to one main question: “Who’s going to get worse?”

The soft-spoken and much sought-after expert in arthritis and inflammation, now in his 30th year as an NYU faculty member, believes that the main obstacle to better arthritis treatments is the lack of predictors, or warning signs, to indicate the 15 percent or so of patients whose joints will deteriorate and who are most in need of early intervention. By the time doctors can identify those fast-progressing patients, their cartilage is already decimated.

This inability to pinpoint the most susceptible patients earlier in the disease process, experts agree, has all but shut down the pipeline for effective treatments and cures. Essentially, the pharmaceutical industry has balked at conducting expensive tests for new osteoarthritis drugs—medications that might have a significant effect in only 15 percent of the patient population—in the absence of any clues as to who those patients are.

For Dr. Abramson, the solution to the stalled-out pipeline is clear: biomarkers. These genetic, imaging, and biochemical markers, he says, can be used to identify the cases most likely to worsen and, therefore, most likely to benefit from new medications.

Dr. Abramson’s research is supported in part by the William & Lynda Steere Foundation and Frank and Sarah Olson.

His ongoing collaboration with Duke University, drawing in part from a pool of 200 osteoarthritis patients at NYU Langone Medical Center’s Hospital for Joint Diseases (HJD), has identified several candidate markers linked to the gene for interleukin-1, an infection-fighting protein also known to contribute to cartilage

Of the 400 jointsin the human body,none is larger

Shown clockwise from top left: Mukundan Gopalakrishnan Attur, PhD; Steven Abramson, MD; Ravinder Regatte, PhD; and Alexej Jerschow, PhD.

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breakdown in osteoarthritis. An emerging hypothesis holds that overactive interleukin-1 drives osteoarthritis, meaning that a better understanding of its activity could yield insights on how to best it with well-aimed drug interventions.

Dr. Abramson’s previous research suggested that a natural opponent of interleukin-1, called interleukin-1 receptor antagonist (IL1RN), could block the protein’s cartilage-destroying effect. In his latest study, he and his collaborators discovered that an IL1RN gene variant found in about 30 percent of the general population offered significant protection against knee osteoarthritis progression in two independent patient populations.

“It’s a very wonderful advance, and it makes sense given what we know about the role of interleukin,” says Virginia Kraus, MD, PhD, a co-author of the study and an associate professor of pathology at Duke University Medical Center in Durham, North Carolina.

Dr. Kraus, who first worked with Dr. Abramson on a consortium charged with developing a new classification scheme for osteoarthritis biomarkers, credits him with bolstering the notion that osteoarthritis is an inflammatory disease. Until the 1990s, most researchers did not believe inflammation played a role. That prevailing attitude began changing some 20 years ago, when researchers led by Dr. Abramson and Mukundan

Long before a throbbing knee

or aching hip points to trouble from deteriorating cartilage, subtle bio-chemical changes in a patient’s joints may provide the first hints of osteoarthritis. A collaboration between an NYU chemist and radiologist is now helping doctors detect these warning signs while there’s still time to intervene.

The gold standard for monitoring osteoarthritis in the knee is an X-ray radiograph measurement of the joint space between the femur and the tibia. As the disease evolves and the shock-absorbing cartilage tissue begins breaking down, that joint space narrows until the bones eventually rub against each other. But there’s a catch: “By the time you see evidence of arthritis on the

conventional radiograph, the bulk of the cartilage tissue is already gone,” says Ravinder Regatte, PhD, assistant professor in the Department of Radiology. Even if new cartilage-repairing drugs were developed, he explains, “at that point, there’s no longer enough cartilage matrix to regenerate it biochemically.”

A new generation of noninvasive, biochemistry-based imaging techniques being developed by Dr. Regatte and his colleagues could give doctors a head start. If validated in larger patient populations, these screens may replace radiographs or invasive imaging procedures as the go-to standards for evaluating and diagnosing osteoarthritis. The new methods would give doctors time to counsel at-

risk patients on preventive measures like losing excess weight and strengthening the muscles around the affected joints. They could also be used to provide early indications of the effectiveness of drugs in the development pipeline.

“One of the early osteoarthritis warning signs is the loss of glycosaminoglycan molecules, or GAG, in the cartilage,” says Alexej Jerschow, PhD, an associate professor of chemistry at NYU’s Washington Square campus and one of Dr. Regatte’s principal collaborators. “Since with our method we can measure that concentration, we should be able to track early cartilage degeneration.”

Capitalizing on the Medical Center’s state-of-the-art 7-tesla MRI machine—140,000 times stronger than the earth’s magnetic field —Drs. Regatte and Jerschow are testing noninvasive

alternatives. One, known as sodium [23Na] MRI, requires a scan of only 15 minutes, yet may be particularly diagnostic. “The connective tissues have the highest concentrations of sodium in the entire body,” Dr. Regatte explains. When GAG sugar chains are lost, sodium concentrations drop as well, providing a biochemical marker of cartilage damage.

In a pilot study with the 7-tesla MRI, Drs. Regatte and Jerschow and their collaborators found that the knee joints of osteoarthritis patients contained 30 to 60 percent less sodium than those of healthy volunteers. The more severe the osteoarthritis, the lower the sodium concentrations. While a larger study is needed to verify the correlation, Dr. Jerschow says the noninvasive technique can be tested relatively quickly since it doesn’t require the same FDA scrutiny as other methods.• — Bryn nelson.

Color-coded sodium concentration maps created by 7-tesla MRI reveal key biochemical differences between the knee joint of a healthy volunteer, above two panels, and an osteoarthritic patient, right two panels.

Less red coloring within the outlined joint space means lower sodium concentrations, and thus less cartilage, which the patient above is losing due to osteoarthritis.

A Radiologist and a Chemist See Early Warning Signs

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Attur, PhD, an assistant professor of medicine at NYU Langone, implicated the molecule nitric oxide in osteoarthritis. The presence of nitric oxide, which had already been linked to damage in other body tissues, supported the idea that inflammation was to blame, at least in part, for osteoarthritis, as well.

“Since cartilage doesn’t have a blood supply, you don’t get the classical redness and swelling in inflamed cartilage that you get with other tissues,” Dr. Kraus explains. “But you do have molecules that get released from cartilage and cause surrounding tissue to become inflamed.”

The joint Duke-NYU study, done in collaboration with the Waltham, Massachusetts–based biotech firm Interleukin Genetics, showed that arthritis patients carrying the protective IL1RN genetic variation, or polymorphism, had lower levels of two inflammatory molecules released by knee cartilage. A planned follow-up will investigate whether that genetic variation translates into significant differences in pain, fitness, and ability to function.

“It could well be that the people without the protective polymorphism are the ones we’ll want to treat more aggressively,” Dr. Kraus says. “This finding also suggests that this pathway could be a very important target for drug development.”

Broadening the attack • on The 16Th fLoor of hJd, dr. aTTur is surveying the aftermath of an advanced case of osteoarthritis: the freshly excised hip socket of a patient who has undergone hip replacement surgery. “The cartilage is completely eroded and the bone is exposed. That’s why you have a lot of pain,” he says. He continues to turn it over in his gloved hands, as if hoping to find some traces of cartilage tissue. “There’s nothing here—it’s completely gone.”

Every day, Dr. Attur’s lab receives a handful of tissue samples, mostly donated from osteoarthritis patients on the hospital’s lower floors. A collaborator on the new study with Dr. Abramson and Dr. Kraus, Dr. Attur hopes to match clinical information gleaned from such patient samples with what their genes, biochemical molecules, and other markers might say about their disease state.

Dr. Abramson, who frequently mentors younger investigators and sees patients once a week despite his heavy workload, has repeatedly championed the idea that the only way forward will be to attack osteoarthritis on multiple fronts. Dr. Attur and other NYU Langone researchers are joining him in doing exactly that. Already, genetic screens based on these and other patient samples have identified dozens of genes potentially linked to osteoarthritis. “You can identify genes that you would never even imagine would have a role in the disease process,” Dr. Attur says.

The association with interleukin-1–related genes, in fact, arose in part from genome-wide screens of patients’ gene activity levels. For an encore, Dr. Abramson, Dr. Attur, Dr. Kraus, and their collaborators have proposed a massive study that would tap into a National Institutes of Health repository of X-rays and DNA, RNA, and blood plasma samples from 5,000 osteoarthritis patients studied over five years. In conjunction with Interleukin Genetics, the team hopes to affix DNA from these patients onto a gene chip, a device seeded with specific DNA probes, and scrutinize the activity levels of 76 genes tentatively linked to osteoarthritis. The interleukin genes will be included in that panel. If the study can link unusually high or low gene levels to cases of advanced osteoarthritis, it could provide the most definitive biomarkers yet for disease progression and severity.

cartilage clues • on anoTher fronT, ThorsTen Kirsch, Phd, professor of orthopaedic surgery and cell biology, and director of the Musculoskeletal Research Center at HJD, is taking aim at osteoarthritis by focusing on the cells that build and maintain the structural components of cartilage.

During the normal development of our bones, cartilage forms

first and is then largely replaced by bone. Children’s kneecaps, for example, do not fully transition from cartilage to bone until the age of three to five. This transition depends on a process in which car-tilage cells stop dividing and eventually die out, allowing bone to fill the void. Dr. Kirsch believes that during aging or osteoarthritis, a similar process may trigger a shutdown of cartilage cells in af-fected joints, ultimately leading to their destruction.

“If we can find the mechanisms that regulate this process during development, we could then see if these same

12

The fLexing Knee on John Qualter’s

computer screen has just taken a wince-inducing turn for the worse. Fortunately, there’s no actual pain involved: Qualter, a medical animator and research assistant professor in the Division of Educational Informatics, is demonstrating a realistic animation of a medial collateral ligament tear.

It’s the same injury he sustained as a wrestler in college, and the depiction still resonates with him, even though his own experience wasn’t quite as bad. “It definitely brings back memories,” he says. Qualter’s high-quality musculoskeletal animations are likewise resonating with medical students, internists, and patients, who can use them to view everything from rotator cuff injuries to

the cartilage-depleting effects of osteoarthritis.

“Anytime anyone ever sees the animation, they get it. It’s so powerful—the picture is worth a thousand words,” says Adina Kalet, MD, associate professor of medicine and surgery, and director of educational research for the Division of Educational Informatics.

Using the same software employed by the animators behind the Hollywood blockbusters Spiderman, Up, and Monsters, Inc., Qualter and his team of artists are in the process of completing a detailed, three-dimensional biodigital representation of the entire human body. His most recent effort, focusing on the musculoskeletal aspects of the knee and rotator cuff of the shoulder, is a core element of a new fellowship supported

Animation shows the knee’s anatomy and common injuries in realistic detail. Above, arrows point out the torn ends of an anterior cruciate ligament, which runs from the back of the femur (thighbone) to the front of the tibia (shinbone).

New Tools for Educating Students, Doctors, and Patients

Knee Animations

NYU PhYsiciaN fall 2009

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by the Merrin Family Bedside Teaching Faculty Development Program, which Dr. Kalet directs along with Mitchell H. Charap, MD, the Abraham Sunshine Associate Professor of Clinical Medicine. The program is funded by Vivian and Edward H. Merrin.

Merrin MasTer cLinician feLLoWs Richard Greene, MD, and Sapana Shah, MD, both clinical instructors in the Division of General Internal Medicine, aim to improve the bedside teaching and physical exam skills among departmental faculty, staff, and students. With Qualter’s assistance, the instructors are devising online learning materials to help medical providers better understand the functional anatomy of knee and shoulder joints, thereby improving their ability to evaluate physical complaints. “John’s animations are essential to this online module and have already been

the highlight at national workshops we have given,” Dr. Shah says.

These animations can show why some falls produce certain injuries. “To make that clear in an animation is a break-through,” Dr. Kalet says.

Demonstrating his computerized creation, Qualter begins to move the biodigital body’s joints with a few simple keystrokes while turning off the virtual skin, circulatory, digestive, and respiratory systems to reveal the detailed musculoskeletal mechanics. He bends back several muscles to reveal redness and inflammation beneath the kneecap.

From his models, Qualter can create what he calls a “living textbook of information.” Using motion-capture sensors or detailed information from a physician, for example, he can demonstrate the impact of osteoarthritis on a patient’s gait. Even his still images are instructive. One

shows a knee overextension leading to an anterior cruciate ligament tear. Another depicts the results of osteoarthritis: jagged red gaps cutting into the cartilage attached to the femur part of the knee joint.

To get the details right, Qualter and his team have been working closely with anatomist Victoria Ort, PhD, assistant professor of cell biology. It also helps that the animators have ready access to the donated cadavers in the medical school two floors below. This attention to detail has already served Qualter well in previous projects, including NYU School of Medicine’s successful Web Initiative for Surgical Education, or WISE-MD. Designed for third-year medical students, Qualter’s animations of surgical procedures are accompanied by online lectures by doctors, allowing students to explore topics of interest on their

own. With his biodigital human rapidly taking shape, Qualter hopes to expand his WISE-MD work to include even more learning modules.

In the same practical vein, Dr. Kalet says that one goal of the Merrin program is to prepare general internists to care for the American population as it ages. Baby boomers, in particular, are expected to become the first generation to show up en masse with the long-term consequences of knee, shoulder, and hip use and overuse syndromes.

Incorporating powerful animations into that learning process, Dr. Kalet says, can enhance doctor-patient relationships and the bedside exams that comprise the essential clinical tools of medicine. “This kind of computer-assisted instruction,” she says, “just allows us to be better doctors.”•

— Bryn nelson

A depiction of an osteoarthritic knee features red lesions in cartilage attached to the femur (right) compared with a healthy knee’s intact cartilage pad (left).

A 3-D model of the knee joint with surrounding bones, ligaments, and muscles allows animators to realistically depict movements. For some of these animations, see http://dei.med.nyu.edu/node/323.

mechanisms reoccur in osteoarthritis and whether we can block them,” he says. Such work might also offer a new class of biomarkers warning of impending cartilage demolition. So far, his research has implicated a family of proteins known as annexins. Early studies in mice suggest that one annexin may be the chief regulator and that curtailing its activity could significantly slow osteoarthritis progression.

In yet another promising advance, NYU Langone researchers are developing imaging techniques to scan joints for their levels

of glycosaminoglycan, a molecular building block of cartilage, and sodium—both of which drop as arthritis worsens (see sidebar on page 11).

With new signposts like these to guide them, pharmaceutical firms could finally be better positioned to work toward more effective osteoarthritis therapies. That would mean, in turn, that the knees of millions of older Americans will be better positioned to support many more years of running, dancing, and enjoying life.•

NYU PhYsiciaN fall 2009

By josie glausiusz Photographs by rené perez

Advances in robotic surgery promise to end pain with a partial knee replacement.

The beTTer knee?

To the soft throb of

Michael Jackson’s “Thriller,” orthopaedic surgeon Ivan Fernandez Madrid, MD, guides a robotic arm over an incision in a woman’s left knee. Attached to the arm, a tiny round rotating drill called a burr is gently grinding over a small area at the end of her femur, the long bone that extends from the hip to the knee. Dr. Fernandez Madrid, assistant professor of orthopaedic surgery at NYU Langone Medical Center’s Hospital for Joint Diseases (HJD), isn’t looking directly at the patient’s knee; his eyes are focused on a computer screen displaying a three-dimensional CT scan of her joint.

An infrared camera tracks the position of the robotic arm, and a green-shaded area on the screen tells the surgeon exactly how much bone to cut from the femur; if he goes beyond a preset limit, the robot will stop drilling. “It’s almost idiot proof,” he says.

The patient on the operating table, a 74-year-old housecleaner with osteoarthritis in the inner part of her knee, is undergoing a new form of partial knee replacement that combines computer visualization with robot-assisted surgery. Introduced to HJD 18 months ago, the robotic technique “has the potential to improve the way we do knee surgery,” says Joseph Bosco, MD, vice chair for

14 NYU PhYsiciaN fall 2009

Orthopaedic surgeon Ivan Fernandez MadrId demonstrates on an artificial training model of the knee the use of robot-assisted device to remove diseased portion of bone.

between the bones acts as a cushion, enabling them to glide together without friction. When cartilage wears away, the femur and the tibia rub right up against each other, triggering a sharp or burning pain and making movement difficult. Replacement surgery offers the potential for a return to near-normal life.

erri Wasserman, a 64-year-old high school English teacher from Hoboken, New Jersey, was

one of the first to reap the benefits of this new robot-assisted surgery. An enthusias-tic hiker and cyclist, she once walked three to five miles a day, but a diagnosis five years ago of osteoarthritis in her left knee forced her to cut down on her beloved out-door exercise. After April 2008, “it was downhill all the way,” she says. “My knee became so bad that I had trouble walk-ing between my house and school, which is one block. I could walk up stairs, but I could hardly walk down stairs. The pain was horrific.” That’s when she called HJD and met Dr. Fernandez Madrid, whom she describes as “absolutely extraordinary, incredibly patient, incredibly kind.” He

recommended cortisone shots, and the first injection alleviated her pain—but only briefly. A holiday in Ireland turned into agony, and after further consultation, she scheduled surgery for August 28, 2008. “I wanted my life back,” she recalls.

Because her arthritis affected only the inner part of her knee—the most commonly impacted site—Wasserman was a perfect candidate for partial knee replacement using the new technology, developed by MAKO Surgical Corp., rather than the more invasive total knee replacement, in which metal prostheses completely cover the top of the tibia and the bottom of the femur. “There are three parts of the knee: the inner part, or medial part; the outer, or lateral, part; and the patella, or kneecap,” explains Dr. Bosco. “Not everyone has arthritis in all three parts of the knee, and when you do a complete knee replacement, you have to sacrifice one or more of the ligaments. It’s unnecessary to replace the entire knee

if only one part of the knee is injured or damaged.”

Ligaments aid in balance, and they remain in place after partial knee replacement, giving the joint a more natural feel, says Dr. Bosco. Partial knee replacement is not, in fact, new: it dates back about 30 years, and about 10,000 such procedures are carried out each year in the United States. But old-style partial knee replacement has its drawbacks. The surgeon has to “eyeball” the patient’s knee during surgery in order to cut the bone and then decide on the right size implants, which are cemented into the femur and tibia. Conventional instrumentation is less accurate, and errors in limb alignment or positioning of implants can lead to inconsistent results.

By contrast, postsurgical X-rays show that implants are better aligned after the new procedure, says Dr. Bosco, although he acknowledges that the long-term benefits of the procedure are unproven since it is so new.

Albert Reff, MD, a spokesperson for the American Academy of Orthopaedic Surgeons and a joint replacement surgeon at Torrance Memorial Hospital in California, points out that setting up the robot is time-consuming and that it involves a “gigantic capital outlay.”

“In my opinion, it’s overkill,” says Dr. Reff, who has performed partial knee

16

clinical affairs in the Department of Orthopaedic Surgery and one of a team of surgeons performing the new procedures. As he explains, the technique enables surgeons to cut bone without the use of conventional power saws and to place implants much more precisely. The new procedure, the surgeons hope, will lead to a better outcome for patients: improved range of motion and less pain and stiffness.

“It’s our responsibility as a leading academic medical center to provide state-of-the-art care,” adds Joseph Zuckerman, MD, the Walter A. L. Thompson Professor and chairman of the Department of Orthopaedic Surgery. “This procedure is an indication of our ability to do so.”

The robot-assisted system, the only one of its kind available in the United States for partial knee replacement, is one of two new state-of-the-art technologies that HJD now offers to patients with osteoarthritis of the knee. The other is customized total knee replacement using 3-D imagery. It allows surgeons to preplan and accurately size artificial knee implants before surgery begins, based on a computerized, 3-D image of the patient’s knee crafted from a magnetic resonance image (MRI) of the diseased joint. So far, HJD surgeons have performed 35 partial and 60 total knee replacements using the new technologies.

Osteoarthritis of the knee is among the top-five causes of disability in adults. Some 540,000 knee replacements are performed every year in the United States, according to the National Center for Health Statistics, and the number is expected to skyrocket as people live longer and indulge in strenuous sports or become obese. In 2006, the latest year for which data is available, hospital charges for knee replacements amounted to $19 billion. According to the Centers for Disease Control and Prevention, nearly one in two people, or 46 percent of Americans, will develop symptoms of osteoarthritis in at least one knee by age 85. The risk is much greater in those who are obese: two-thirds of them will experience knee osteoarthritis over their lifetime due to excessive loading on weight-bearing joints.

The knee itself is made up of three bones: the femur; the tibia, the shinbone that extends from knee to ankle; and the patella, or kneecap, which rides on the knee joint as the knee bends. Ligaments join the femur and tibia, and cartilage

NYU PhYsiciaN fall 2009

dr. Fernandez MadrId displays a model of a partial knee replacement in which ligaments remain intact.

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replacements for the past 25 years. “The bone cuts for a partial are very simple and very straightforward, and the sophistication that the robot brings to the table is more than is necessary to make it perfect.”

Dr. Bosco agrees that the robotic surgery is more expensive and can take longer, but he believes that the technology “holds a lot of promise,” and he is pleased with the progress made by his patients. They typically leave the hospital within three days and are walking normally within four to six weeks. By contrast, people who undergo total knee replacement stay in the hospital for about five days and take about three months to recover. Patients “can expect a near-normal range of motion and a drastic decrease in pain,” Bosco says. “They have a reasonable expectation for active lifestyle, in terms of biking, playing tennis, swimming, skiing. Running, probably not.”

all and jocular, Dr. Fernandez Madrid exudes a calm self- confidence, even after a full

day in the operating room culminating with a customized total knee replacement for a 55-year-old man. In this case, he used custom guides that incorporate slots showing the surgeon exactly where to insert a saw to cut the femur and tibia in order to implant prostheses prematched to the patient’s normal knee anatomy. The plastic cutting guides—molds based on a computerized 3-D image of the patient’s diseased knee, derived from a preopera-tive MRI—are placed on the joint during surgery and afterward discarded. Instead of testing a variety of implant sizes during surgery, surgeons know in advance which to pick, leading to increased precision and shorter operating times.

Although the new technique is accurate, total knee replacement always involves the removal of one or more ligaments—usually the anterior cruciate ligament (ACL), which provides stability to the knee and limits rotation of the joint. In some cases, the posterior cruciate ligament is removed, as well. The two ligaments, which connect the bones, cross at the joint, and help balance the knee and provide a sense of position, especially when walking on uneven ground. Removal of one or more of these ligaments helps the surgeon cut the bones and position prostheses correctly, but the

results can leave patients with a slightly unnatural sense that their knee is not moving correctly.

That is why Peter Walker, PhD, professor in the Department of Orthopaedic Surgery, is working on newer designs to supplant older artificial

must have total knee replacements, Dr. Walker has designed a “guided-motion knee” that would substitute the lost ligaments with mechanical components and cams, rotating disks that guide the motion of the parts. “It will make the patients feel more stable and more

confident to perform everyday activities, and should give them some extra range of flexion,” says Dr. Walker. He has a contract with a major company to develop a guided-motion knee, but does not expect that it will be available for at least a year or two.

Fortunately, Gerri Wasserman didn’t have to wait that long to feel transformed. Three days after her robot-assisted partial knee-replacement surgery, she was home and climbing up and down stairs without support. Six days later, she was teaching her English class, walking with a cane. During physical therapy, she did exercises to regain her range of motion, and although she experienced some painful swelling in the months following surgery, she is now completely recovered. “I feel like I can do absolutely anything that I could do, not

only before the surgery, but before I had osteoarthritis,” she says. One year after surgery, she spent her August holiday in Alaska with her family, white-water rafting, biking, hiking, and kayaking in Denali National Park. She no longer fears physical exercise or getting into—or even falling out of—a boat. “I have no pain in my knee at all, and every day, it gets stronger, and every day, I can bend it more,” she says. “I’m the happiest person on earth.” •

17NYU PhYsiciaN fall 2009

“ My knee became so bad I had trouble walking between my house and school, which is one block.”

english teacher GerrI WasserMan received a robot-assisted knee replacement and is now enjoying her usual activities, including walking, hiking, and cycling.

knees. The biomechanical engineer, who has been designing knees since 1970, is working today on metal-and-plastic implants that can be inserted through small incisions to replace local areas of worn cartilage without grinding down larger portions of bone. For those who

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N by gay dalyphotographs by fiona aboudWomen can now preserve their fertility by freezing their eggs

19NYU PhYsiciaN fall 2009

patient, Ekin Yasin, who learned she had cervical cancer in July 2008. Yasin was just 26, a first-year student in the NYU doctoral program in Culture, Communications, and Media, with two master’s degrees already under her belt.

Two weeks after her diagnosis, she had a radical trachelectomy in Istanbul, where her family lives. The goal of this procedure is to cut out the cancer while saving the patient’s fertility. After the surgeon removes the cervix, he stitches the uterus to the vagina.

After Yasin returned to the United States, her oncologist sent her to Dr. Noyes in January 2009 because she had not experienced a menstrual cycle since her surgery in Turkey. Yasin was also being treated for a postoperative surgical infection. The first time she examined Yasin, Dr. Noyes knew something was very wrong. Tests showed that the infection that had started in the uterus had now spread to her ovaries, an unusual complication after trachelectomy surgery. An aggressive course of antibiotics cleared the infection, and Yasin says, “Dr. Noyes saved my life.” But months later, she still didn’t feel right. A PET scan turned up a spot on her thyroid that proved to be

cancer. Fortunately, surgery successfully excised the thyroid and the cancer.

By this time, Yasin knew she could count on Dr. Noyes’ expertise and sensitivity. Once she learned that she would have to have a hysterectomy to correct the damage done by the trachelectomy, she and Dr. Noyes began to consider the possibility of egg freezing for her. The decision was not an easy one for Yasin. She was hesitant to take on another complex, expensive medical procedure. Insurance rarely covers egg freezing, and one cycle costs $9,300. What’s more, she adds, “I had not even considered having kids. I still feel like I am someone’s child.” She resented some of her doctors who had reproached her. “I have been irked,” she says, “by doctors who acted like I should preserve my maternity before my own life. I want to get healthy. I want to live.”

What helped her to keep her balance throughout this ordeal was talking with Dr. Noyes: “She is perceptive about where a patient is in the life cycle. She encouraged me to have a hysterectomy and to do the egg freezing. She has a very subtle, nuanced way of helping you save all your options while caring for yourself.”

Yasin decided that one day she might regret not having preserved her fertility when she had the chance. Knowing Dr. Noyes was at her back, she was ready—she wanted to freeze her eggs. If she could not use her eggs, she told Dr. Noyes she would donate them for medical research.

yasIN FouNd thE procEss surprisingly easy. One cycle takes about two weeks.

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A pack of daredevils, they love the high peaks at Zürs. Over the years, Dr. Noyes has come to trust Sylvester, the ski guide who challenges her to try new, more treacherous trails. “When Sylvester tells me to ski off the edge,” she says, “even if I’m terrified, I can take that leap because I trust him.” This kind of relationship is, she knows, what patients need. “It’s like that in medicine,” she says. “If you trust somebody, you can do it.”

NYU PhYsiciaN fall 2009

Her patients agree. For them, she is their trusted guide as they take a leap into the unknown—freezing their eggs in the hope of preserving their fertility.

oocytE cryoprEsErvatIoN, more commonly referred to as egg freezing, is a new option for women who aren’t ready to have babies yet—especially for women whose fertility is threatened by cancer treatment. “NYU has one of the most successful egg-freezing programs in the world,” says Dr. Noyes, associate professor of obstetrics and gynecology. Since 2004, she has been co-director of the Fertility Center’s Egg Freezing Program with Jamie Grifo, MD, PhD, director of the Division of Reproductive Endocrinology. The team has helped more than 300 women to freeze eggs, 50 of whom were cancer patients.

Nineteen babies have been born to patients who returned to thaw their eggs at NYU, which translates to a 63 percent pregnancy rate, as good as what the center achieves with conventional in vitro fertilization (IVF). Research published last June by Dr. Noyes and two colleagues identified 936 babies born from frozen eggs around the world. The study also determined that the rate of birth defects for children born from frozen eggs was no higher than the rate for all children, a finding that confirms the safety of the procedure.

WomEN choosE to FrEEZE their eggs for many reasons—often they are in their late thirties, afraid the alarm on their biological clock is about to ring loudly and finally. They come to the Egg Freezing Program hoping to keep alive the dream of having a child. As they sit on the other side of the desk in her office, Dr. Noyes sees their unhappiness. “The look on the face of a 38- or 39-year-old woman when she realizes she may never have a baby,” she says, “is a terrible thing to see.”

Even more painful for her is facing a young woman who has cancer and is scheduled for surgery or chemotherapy that will put an end to her fertility. Dr. Noyes thinks a lot about one very young

The wells seen here contain solutions of increasing concentrations of cryoprotectant, which are used to gradually dehydrate oocytes. Once passed through these solutions, the eggs are loaded into a straw, at right, for freezing.

WINtErs, NIcolE NoyEs, md, aNd hEr FamIly skI IN austrIa.

At the beginning of her menstrual cycle, she gave herself subcutaneous injections of follicle-stimulating hormone (FSH) daily. The biggest challenge, she jokes, was struggling to get up at 7:00 a.m. to arrive at the clinic on time so that the staff could monitor the progress of her eggs. Frequent blood work and ultrasounds measured the growth and number of the follicles that contained the eggs. By late afternoon, a nurse would phone to tell her if she needed to adjust the dose of FSH that evening.

When the follicles reach 17 millimeters, an intramuscular shot of human chorionic gonadotropin (HCG) is given that night to trigger ovulation. This shot involves a much bigger needle. When Yasin couldn’t bring herself to do it, her boyfriend did it for her.

The next morning, Dr. Noyes retrieved Yasin’s eggs while she was under a light anesthesia. Using a long hollow needle, Dr. Noyes deftly poked each follicle to make it release its egg; then, through tubing attached to the needle, she suctioned the egg into a test tube kept in a rack heated to body temperature—eggs are exquisitely sensitive to temperature. The procedure went smoothly, and 33 eggs were harvested. (Sixty-five is the maximum number of eggs ever retrieved in one cycle at the Fertility Center.) Later, Dr. Noyes told Yasin that she was “a superstar of egg production.”

Once she awoke, Yasin’s first thought was for the juice and graham crackers she had been promised—she was keenly hungry.

Over the next two hours, her eggs were evaluated in the lab, and then, those mature enough to make embryos someday were frozen. Under a special polarized microscope, a technician checked the size and symmetry of each egg and examined its meiotic spindle, the chain of proteins that must align so chromosomes can divide properly during fertilization. The best eggs were then frozen by two methods: slow freezing and vitrification.

How to freeze eggs had eluded scientists for decades. The problem was that a human egg is 80 percent water. When that water froze, it expanded and broke through the cell wall, destroying the integrity of the egg.

Finally, a solution to the problem was found in cryoprotectants: chemical compounds capable of gently dehydrating the egg. In addition, these agents lower the freezing temperature of the egg, allowing more time for water to escape, preventing ice crystal formation. Once cryoprotectants have been added, slow freezing is done by a machine that

precisely lowers the temperature in slow stages. The frozen straws containing the eggs are then plunged into a tank of liquid nitrogen for storage.

Vitrification is a newer method. Dr. Grifo established the protocol at NYU. Eggs are dehydrated in just seven minutes, using a bath of highly concentrated cryoprotectants, and then stored in liquid nitrogen. Vitrification is in vogue at the moment, but Dr. Noyes and Dr. Grifo have found they get the same results with slow freezing and vitrification, so for now, they are freezing half of each patient’s eggs by one method and half by the other.

After the procedure, Yasin experienced a bloating she describes as “a discomfort from which there was no escape.” The clinic had warned her about this, but she had not taken them seriously. She was known to be a stoic, so she scared the staff at the center when she phoned for help. One of the fellows phoned her seven times that day to make sure she was OK. Yasin was touched by their solicitousness. But the next couple of days before the pain began to subside were rough.

When the clinic phoned Yasin on Monday to tell her 28 of her 33 eggs had been frozen, she says, “there was nothing sentimental about this news for me.”

Someday, if she uses those eggs to have a baby, there will be cause for elation, but that day, for her, is far down the road. For the moment, she says, “it’s like buying a crib for a baby you might never have.”

Dr. Noyes believes in Yasin: “She has met her situation with maturity and dignity. She faces life’s challenges head on. She will fulfill her dreams.” For Yasin, the trust she has with Dr. Noyes will help her meet those challenges: “If I need to make a medical decision, I will call her and talk it over. It’s like having a doctor friend.”

For the last Five years, egg freezing has been the principal focus of Dr. Noyes’ research as well as her clinical practice. One of her most important results is a finding that the eggs of cancer patients appear to be just as hearty as those of well patients. She has also found that cancer patients make, on average, almost the same number of viable eggs as other patients—17 as opposed to 18. “This is amazing,” she says, “given their added pressures—the time constraint, the cancer itself, preparations for cancer treatment, and the emotional and physical stress of it all.”

Currently, with Dr. Grifo, Dr. Noyes is conducting a study of slow freezing and vitrification to see if one method is superior to the other. With Andrea Reh, MD, a fellow at the Fertility Center, she has started a cancer registry to track quality-of-life issues and pregnancy outcomes for cancer survivors who freeze their eggs.

Since she became a fellow in infertility in 1990, the field has offered Dr. Noyes one challenge after another. “Then, IVF was just taking off. IVF was followed by ICSI [intracytoplasmic sperm injection].” Egg freezing may be the most exciting and rewarding work of her life. In medical school, she dreamed of becoming a gynecological oncologist, but as a resident, she realized the work made her too sad. Now, at 50, she has found another way to help these vulnerable patients, which gives her profound satisfaction: “I love being a doctor,” she says. “I love being a doctor.” •

21NYU PhYsiciaN fall 2009

“ I have been Irked by doctors who acted lIke I should preserve my maternIty before my own lIfe.”

Frozen oocytes are stored in liquid nitrogen–filled tanks (top). The small, floating white receptacles (bottom) can hold up to six straws of frozen eggs. Tanks are connected to an elaborate computer-controlled alarm system that immediately notifies personnel in advance of any change in storage conditions.

Patient Stories

OOn April 23, 2009, Dariusz Reszuta awoke in the 17th-floor iCU of nYU langone Medical Center’s Tisch Hospital to the news that his liver transplant had gone perfectly. normally, such a report would elicit a sigh of relief, if not a celebratory cheer. instead, reszuta, a 33-year-old commercial plumber from Queens, was dumbfounded. “i didn’t know what was going on,” he says. “i didn’t even remember being sick. The last thing i could recall was that i was out shopping with my son.”

22

As the fog of a week-long coma slowly lifted, reszuta learned that in mid-April, his liver had started to fail for no apparent reason. A few days later, he was brought to nYU langone’s Emergency Department, unconscious. Toxins that the liver normally clears from the blood had begun accumulating in his body, turning his eyes and skin a sickly yellow and causing his brain to swell. He didn’t have long—at most a day or two, more likely just hours—until irreversible brain damage set in and his other vital organs failed.

reszuta, who emigrated to the United States from poland in the 1990s, was immediately moved to the top of the regional transplant waiting list. “But there wasn’t a single donor organ available in the whole country,” says his surgeon, lewis Teperman, MD, vice chair of surgery and director of transplantation at nYU langone. To buy time, the

transplant team pumped the patient with the first of 24 units of blood plasma, in an effort to dilute the life-threatening toxins.

This was only a temporary stopgap, however. The patient’s one remaining hope for survival was an experimental bio-artificial liver, a blood-pumping machine packed with human liver cells

that had just been approved by the FDA for a nationwide clinical trial. The device—the Extracorporeal liver-Assist Device, or ElAD, manufactured by Vital Therapies, inc., of San Diego—would take over for his liver, much like a dialysis machine does for failing kidneys, until a suitable donor organ could be found.

There were significant obstacles to using the ElAD, however. “This device had been used in several preliminary clinical trials but never with a patient who was so sick and about to die,” Dr. Teperman explains. What’s more, the liver cells were in storage in California, the machinery was still in Massachusetts, and the only technicians trained in its use were in Michigan. Finally, the device’s trial hadn’t yet been approved by nYU’s institutional review Board (irB), an independent committee that reviews all clinical trials to ensure that the rights and welfare of patients are protected.

Undaunted, Dr. Teperman and the reszuta family pressed forward, setting in motion a frenzied scramble to win emergency IRB approval and fly in the necessary parts and personnel. Amazingly, in less than 24 hours, everything was in place.

At 5:15 p.m. on April 22, reszuta was brought to the operating room, where

NYU PhYsiciaN fall 2009

photograph by wesleY maNN

Dr. Lewis Teperman

One Foot in Heaven

“ This device has been used in several preliminary clinical trials, but never with a patient who was so sick and about to die.”

a tube was inserted into his jugular, diverting his blood into the ElAD. inside the device, his blood plasma was separated out and passed through four filter cartridges containing about 15 ounces of human liver cells (one-quarter the weight of an intact liver), cleansing his blood of toxins and synthesizing life-sustaining proteins. After passing through these filters, the blood was reinfused, streaming continuously from patient to machine and back again.

The secret to the ElAD is the liver cells. Far from ordinary, the cells are derived from a liver tumor taken from an adolescent boy 20 years ago. While normal liver cells die outside of the body in a matter of hours, these cells are essentially immortal. They can be continuously replicated in bioreactors at Vital Therapies’ lab and packed in dry ice for up to 48 hours for shipment to hospitals.

An important safety feature of the ElAD is that the patient’s blood never comes into direct contact with the immortalized cells. instead, the blood flows through semipermeable hollow fibers in the cartridges that allow toxins and proteins to be exchanged with the

NYU PhYsiciaN fall 2009 23

After being close to death, Dariusz Reszuta survived thanks to an experimental device and a liver transplant.

Canisters packed with human liver cells act much like a human dialysis machine, enabling patients to survive until a human donor can be found.

A Bio-Artificial Liver

liver cells. Within hours, reszuta’s blood levels of ammonia and lactic acid began to drop. “We knew the machine was working,” says Dr. Teperman. “But because he had deteriorated so much, we didn’t know if he had already suffered permanent brain damage.”

in the meantime, a donor organ became available in Tennessee and arrangements were made to fly it to JFK airport. Bad weather delayed the flight, adding more tension to an already tense situation, but finally the liver arrived in New York. Eight hours later, Dr. Teperman and his team performed the transplant and turned off the ElAD.

“Would he have survived without it?” Dr. Teperman wonders aloud. “i can’t tell. But i do know that he had one foot in heaven. A month and a half ago, we transplanted someone who was just as ill. He survived the operation, but his brain didn’t. There’s such a critical organ shortage in this country. About 2,000 patients die each year waiting for a liver. So having a bridge is a wonderful idea—if we can prove that ElAD works.”

Dr. Teperman never did figure out what caused reszuta’s liver to fail, which happens in about a quarter of all acute liver failure cases, though he was able to rule out all known viruses and Tylenol poisoning, the most common culprits. nonetheless, reszuta made a full recovery. He will have to take immunosuppressant medications for life to prevent his body from rejecting the new liver, but he isn’t complaining. Sitting in Dr. Teperman’s office one month after his brush with death, reszuta is all smiles—thankful for the opportunity to spend precious time with his son and family and perhaps pursue a new career in information technology. “i’m lucky i chose the right hospital,” he says. •—gary goldenberg il

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Faculty News

charles marmar, mD, has been appointed the new chairman of the

Department of Psychiatry. a leading expert on post-traumatic stress disorder (PTsD), Dr. marmar joins NYU langone medical center from the University of california, san Francisco (UcsF), where he was professor and vice chair of psychiatry, and the san Francisco Veterans affairs medical center, where he was associate chief of staff for mental health and director of the center’s Posttraumatic stress Disorder research Program.

Dr. marmar’s wide-ranging research on PTsD has included investigations into the link between the disorder and changes in brain function and anatomy, identification of risk factors, and studies of prevalence in different populations, including combat veterans, law enforcement officers, rape survivors, political refugees, and earthquake victims. He was one of the principal investigators for the National Vietnam Veterans’ Readjustment Study, the first systematic exploration of PTSD among Vietnam veterans. He is currently principal investigator on over a half-dozen PTsD-related research projects, including a recent $3.5 million grant from the U.s. Department of Defense to develop biomarkers of PTSD for use in diagnosing and treating troops returning from Iraq and Afghanistan.

In addition to his many academic publications, Dr. marmar has contributed to numerous textbooks on the psychiatric effects of traumatic stress and also maintains a clinical practice focused on trauma and grief counseling.

after receiving his bachelor’s and medical degrees from the University of manitoba in Winnipeg, canada, Dr. marmar completed his residency training in psychiatry and neuropharmacology at the University of Toronto, and in traumatic stress and grief at UcsF, where he joined the faculty in 1978. he is past president of both the society for Psychotherapy research and the International society for Traumatic stress studies. •

Dr. Marmar Appointed New Chairman of Psychiatry

NYU PhYsiciaN fall 2009

$10 Million Grant to Dr. Javitt Establishes Silvio O. Conte Center for Schizophrenia Research

a receNt $10 millioN graNt from the National institutes of mental Health

established a new center devoted to schizophrenia research and treatment at NYU langone medical center and its affiliate, the Nathan S. Kline institute for Psychiatric research. the Silvio o. conte center for Schizophrenia research, named after the late U.S. congressman, a champion of mental health research, will be headed by Daniel c. Javitt, mD, PhD, professor of psychiatry. it will investigate a promising approach to treating this surprisingly common and misunderstood mental illness, which affects one in every 100 people over the course of their lives.

Dr. Javitt has spent much of his career investigating the link between a brain transmitter called glutamate and schizophrenia. “For many years, overproduction of the neurotransmitter dopamine was thought to be the main cause of schizophrenia,” explains Dr. Javitt. “But excess dopamine doesn’t account for schizophrenia’s cognitive symptoms, such as the inability to decipher vocal tones.” instead, his research suggests that schizophrenia is caused primarily by dysfunction in one of the receptors, or binding sites, on neurons to which the neurotransmitter glutamate binds.

this type of receptor is called N-methyl-D-aspartate (NmDa), and it plays a critical role in memory, learning, and the ability of the brain to adapt to changes in the environment. Several drugs of abuse,

such as PcP (angel dust) and ketamine (special K), cause symptoms that resemble schizophrenia by blocking NmDa receptors, suggesting that these important receptors may be functioning abnormally in individuals with schizophrenia.

Dr. Javitt and his colleagues in the new center will be investigating how NmDa receptors influence brain function as well as evaluating medications that boost the receptors’ activity. “Several naturally occurring amino acids—glycine, D-serine, and sarcosine—improve symptoms significantly in large doses,” he notes, adding that these compounds raise NmDa receptor production. also promising are glycine-transport inhibitors, which block removal of glycine from the brain, allowing glycine levels to build up without need for supplements. (Dr. Javitt holds several patents related to the use of D-serine, along with other compounds used to treat schizophrenia.)

“current schizophrenia medications have troublesome mental and physical side effects, so compliance is often very poor,” says Dr. Javitt. “the hope is that these newer treatments can control or prevent cases, so that current medications won’t be needed.” •

25

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NYU PhYsiciaN fall 2009

Dr. Lowenstein Receives NYU’s Distinguished Teaching awardJerome loWeNsTeIN, mD, professor of medicine (nephrology), has been named a recipient of NYU’s 2008–2009 Dis-tinguished Teaching award. a graduate of both NYU (’53) and NYU school of medicine (’57), Dr. lowenstein is famous for converting his research and clinical insights into innovative approaches to teaching medical students and young phy-sicians—a process he called “rewarding, exciting, and intellectually stimulating.” a founding editor of the Bellevue literary Press, he is credited with transforming the teaching of cell biology through his book Acid and Basics: A Guide to Understand-

ing Acid-Base Disorders, pub-lished in 1993. Dr. lowenstein “personifies the humanistic physician,” wrote Dean and ceo robert I. Grossman, mD, in recommend-ing him for the award, “and has

inspired an entire generation of medical students, house staff, and colleagues to follow in his footsteps to become caring healthcare professionals.” •

DaVID l. keeFe, mD, has been appointed chairman of the Department of obstetrics

and Gynecology. Dr. Keefe brings a unique blend of skills to his new position, including extensive experience in both clinical care and basic science, as well as a record of innovative medical leader-ship. he joins NYU langone medical center after serving as the James m. Ingram Professor and chair of obstetrics and Gynecology at the University of south Florida, where he helped im-plement well-received procedural improvements in the department’s clinical ob-gyn program at Tampa General hospital.

a physician researcher, Dr. keefe has devoted his laboratory research to stem cell and embryo biology, establishing an impressive publishing record of more than 150 papers and abstracts. Before joining the University of south Florida, Dr. keefe headed the Division of reproductive medicine and Infertility at Brown University, where his research team investigated how oocytes reprogram the genome during early de-velopment and during an experimental process called therapeutic cloning, or somatic cell nuclear transfer, which is used to obtain stem cells from oocytes. The team’s work received many honors, including the General Program Prize of the american society for repro-ductive medicine. Dr. keefe also holds several patents relating to his team’s research on in vitro fertilization techniques. During his time at Brown, Dr. Keefe was also invited by Jack Welch, then CEO of General Electric, to become one of the first U.S. physicians to study “lean management” business techniques, which use in-depth analyses of work processes and customer needs to achieve quality and productivity gains.

Dr. keefe received his undergraduate degree from harvard college and his medical degree from Georgetown University school of medicine. he did postgraduate training in medicine, obstetrics, and psychiatry at Yale–New haven hospital, cambridge hospital/harvard Psychiatric service, and the University of chicago, followed by fellowships at Northwestern University and Yale University school of medicine. he has been a reviewer for the American Journal of Obstetrics & Gynecology and the New England Journal of Medicine, among other publications, and belongs to numerous professional associations. •

Dr. Keefe appointed chairman of Obstetrics and Gynecology

Faculty News

Peter M. Kilbridge, MD, Named Chief Information Officer

Peter m. KilBriDge, mD, has been named chief medical information

officer at NYU langone medical center. Previously, Dr. Kilbridge was based at St. louis children’s Hospital and Washington University School of medicine, where he led the institution’s

inpatient electronic medical records initiative and was executive director

of its Pediatric computing Facility. During his career, he also held a National laboratory of medicine–sponsored fellowship in the medical informatics library at massachusetts general

Hospital, and he served Duke University as chair of its Health System medication committee and as associate chief information officer for patient safety and clinical effectiveness. a graduate of case Western reserve School of medicine, Dr. Kilbridge completed a residency in general pediatrics and a fellowship in pediatric cardiology at Boston’s children’s Hospital.•

Around Campus

N26

New York UNiversitY and NYU school of Medicine have created a new partnership with New York City’s Health and Hospitals Corporation aimed at improving the health of the city’s poor and underserved.

the scope of the new Ctsi at NYU is vast, involving 9 schools and colleges, 15 major medical and dental facilities serving 2 million patients, 75 departments, and 200 laboratories. At NYU Langone Medical Center and HHC, potentially hundreds of researchers, physicians, and clinicians will participate.

the Ctsi will be directed by Bruce Cronstein, MD, the Dr. Paul r. esserman Professor of Medicine and professor of pathology and pharmacology, and co-directed by Judith Hochman, MD, the Harold snyder Family Professor of Cardiology. in addition to NYU school of Medicine, the collaboration includes researchers at the school of Dentistry; College of Nursing; wagner school of Public service; steinhardt school of Culture, education, and Human Development; stern school of Business; silver school of social work; Courant institute for Applied Mathematics; and Graduate school of Arts and sciences.

eight HHC facilities will also participate in the institute, including Bellevue,

Metropolitan, Gouverneur, Coler- Goldwater, woodhull, Coney island, kings County, and Lincoln Hospitals.

“our Ctsi is truly innovative and will play a critical role in our shared goal of transforming medical research and reducing healthcare disparities in New York City and beyond,” says robert i. Grossman, MD, dean and Ceo of NYU Langone Medical Center. •

NYU PhYsiciaN fall 2009

NiH Funds Major effort by NYU to improve Health of Big Apple

ReseaRcheRs fRom NYU LaNgoNe medicaL ceNteR were awarded

more than $30 million in federal stimulus funds to pursue innovative basic science and clinical research projects over the next year.

The news was welcome proof that the Medical Center’s massive push to submit hundreds of stimulus-grant proposals last spring to the National Institutes of Health (NIH) has succeeded beyond expectations.

“Given the intense competition by scientists for funding at many respected institutions, the grants we’ve been awarded are a true testament to the quality of the investigators and their research here at the Medical Center,” says Vivian S. Lee, MD, PhD, MBA, senior vice president and vice dean for science.

The funding for these grants is part of the $5 billion in federal money provided for critical research projects through the American Recovery and Reinvestment Fund, known as the economic stimulus package.

Altogether, as elsewhere NIH has given the green light to 86 projects at the Medical Center in a wide range of fields, from neurology, immunology, and oncology to environmental medicine and rheumatology. Among these projects are studies that will explore the relationship between intestinal microbes and rheumatoid arthritis, analyze how HIV infection suppresses the immune response, and evaluate the carcinogenic effects of toxic metals in smokestack emissions.

In addition, the NIH stimulus funds will allow the hiring of additional faculty, laboratory technicians, and other support staff. Other monies will go to purchasing advanced technology. •

Stimulating GrantsFederal stimulus funds to Medical Center exceed $30 million

A mosaic of storefronts in New York City shows the city’s diversity.

Funded with a five-year, $29.4 million grant from the National institutes of Health (NiH), the newly formed Clinical and translational science institute (Ctsi) will focus on reducing existing healthcare disparities across New York City.

the new institute joins a national consortium of NiH-funded medical institutions dedicated to transforming the way clinical and translational research is conducted in the United states. the NYU-HHC objective is to significantly improve the way community-wide health issues are identified, analyzed, and addressed—particularly among populations that historically have been underserved in terms of medical care. the Ctsi encourages scientists and physicians to work together in a multidisciplinary fashion to accelerate the transition of lab discoveries into clinical treatments, engage local communities in cutting-edge clinical research projects, and train new clinical and translational researchers in these community-based investigative approaches.

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EEvEry succEssful startup has its origins in a good idea backed up by long hours of intense work, and Nyu’s award-winning medical blog, clinical correlations (www.clinicalcorrelations.org), is certainly no exception to that rule. But in this case, the long hours weren’t limited to those invested by Neil shapiro, MD, and the other dedicated physician-editors who launched the site in late 2006. the long, grueling hours being clocked by weary internal medicine residents are what helped convince them to create the blog in the first place.

28

“Good doctors become better doctors when they have a sense of inquisitiveness,” says Dr. shapiro, associate program director of the Internal Medicine residency program and assistant chief of medicine at Manhattan’s va Medical center. “But our residents were so bogged down with long hours and innumerable administrative tasks that they seemed to have lost that. I thought starting a blog might inspire them and

encourage them to read about medicine on a daily basis.” the blog might serve as a reminder, as the clinical correlations mission statement puts it, to “physicians young and old that internal medicine is much more than a job.”

With input from a cadre of like-minded internists—including residents raj Khandwalla, MD, and cara litvin, MD, as well as Judith Brenner, MD, another associate program director of the Internal

Medicine residency program—Dr. shapiro’s idea quickly took shape: clinical correlations would be written by and for Nyu’s internal medicine community; medical students, residents, and faculty members at the university’s three teaching hospitals would all be encouraged to contribute original articles of broad interest to internists. It was also decided that access would be password protected, in part to safeguard the privacy of patients whose cases might be discussed on the blog.

Inspiring weary residents turned out to be only one of the benefits envisioned for the blog. As they began fleshing out their concept for the site, Dr. shapiro’s team realized that it would also help hone young doctors’ diagnostic skills, improve the care of “complicated” patients, and keep house staff up to date on need-to-know information. Most important, it would foster close mentoring relationships between physicians who might otherwise go unacquainted.

In the fall of 2006, Dr. shapiro pitched his idea to Martin J. Blaser, MD, frederick H. King professor of Internal Medicine and chairman of the Department of Medicine. “I recognized right away that this was going to be a great thing,” Dr. Blaser recalls, adding that he quickly gave the venture his blessing. there was no funding or office space for the project, and the only income its all-volunteer staff could expect would be of the psychic variety. But Dr. shapiro and his team were undeterred. clinical correlations went live a few weeks later, on November 27.

fast-forward three years, and clinical correlations has hit its stride. Instead of a skeleton staff, it has a large editorial board and more than 100 regular contributors.

NYU PhYsiciaN fall 2009

photograph by wesleY maNN

fostering a sense of Inquisitiveness

Medical Education

Neil Shapiro, MD, and Judith Brenner, MD, are among the physician-editors of an award-winning medical blog that encourages residents to read about medicine on a daily basis. Dr. Shapiro serves as the editor-in-chief.

Medical Education

NYU PhYsiciaN fall 2009 29

A recent view of the home page of Clinical Correlations.

“ The site features evidence-based answers to clinical questions, reviews of recent journal articles, synopses of medical conferences, and discussions of thorny ethical dilemmas. There’s even a section that aims to separate medical myth from reality. ” ( Recent entry: “Does weather really affect arthritis?”

Find out at http://www.clinicalcorrelations.org/?p=1096. )

clinicalcorrelations.org/?p=1096.)In the beginning, Dr. shapiro, who has

served as editor-in-chief since the blog’s inception, thought it would be hard to get enough contributions for the site. But nowadays, he says, content is never a problem. More than 560 articles have been posted so far, with more going up on an almost daily basis. “We’re good schmoozers,” explains Dr. Brenner. “We’re in touch with the whole Nyu community, and there’s no one who is not impressed with the site.”

Traffic to the site was a trickle at first, but the number of daily visits started to rise in mid-2007 when, at Dr. Blaser’s suggestion, password protection was abandoned, and the site opened its doors to the world outside Nyu. things took off in earnest last January, when Medgadget.com, a respected voice on medical innovation, called clinical correlations “one of the most professional and meticulously edited medical blogs” and named it Best clinical sciences Weblog of 2008. today, clinical correlations has about 2,500 regular readers and averages between 700 and 800 hits a day, with visitors from 145 countries.

While Dr. Shapiro is deeply gratified by the site’s success to date, he and his team are focused on the future—and on a clinical correlations that’s bigger, more popular, and more professional. He’s now looking into having the blog indexed by the National library of Medicine’s Medline® service, and exploring possible sources of funding in order to secure office space and hire an administrative staff.

Dr. shapiro’s ultimate goal—one shared by Dr. Blaser—is to grow clinical Correlations into a full-fledged online academic journal. the process may take a while; in the meantime, though, the blog will continue to offer “a daily dose of medicine.” says Dr. shapiro, “If we can remind our physicians on a daily basis about the reasons they were interested in medicine in the first place—what they found fascinating or inspiring—then we will have done our job.” • —DaviD Freeman

the home page, recently updated for the fourth time, is attractive and easy to navigate. content, including much that is peer reviewed, is more robust than ever. In addition to medical news, the site features evidence-based answers to clinical questions, reviews of recent journal articles, synopses of medical conferences, and discussions of thorny ethical dilemmas. there’s even a section that aims to separate medical myth from reality. (recent entry: “Does weather really affect arthritis?” find out at http://

S

his “having a terrible time,” and “never wanting to see her again,” according to Mrs. Farber, things improved, and they became engaged. They were married on March 13, 1949, and in the same year, Dr. Farber joined the faculty of the School as an assistant in the Department of Medicine.

He rose steadily in the academic ranks.He became chair of the Department of Medicine in 1966 at the age of 48. He was acting dean several times and, in essence, served as dean of NYU School of Medicine from 1979 to 1998. After stepping down as dean, he served as professor of medicine for the rest of his career. Most notably, he was a master clinician and outstanding teacher.

His love of medicine was exceeded only by his love of family. He and Doris had two children, Josh, who also became a physician, and Beth, who became an attorney. Each married: Beth to Stephen Lowentheil, and Josh to Nancy Hardy. Saul Farber had four grandchildren: Kara, Nathaniel, and Jacob Lowentheil, and Daniel Farber. He spent many happy hours with his family. In his later years, he studied the Talmud and visited with his many friends. Until the very end of his life, he remained an active teacher of medicine.

Saul Farber died on October 11, 2006, at the age of 88. He left behind a deep legacy in the hearts of his students and colleagues. I was fortunate to have been a student of Saul Farber when I attended NYU School of Medicine in the early seventies, and a colleague from 2000 until his death. He had so much to teach and gave of it so willingly.

This remembrance is intended to show Dr. Saul Farber through the eyes of some of the students who knew him best—his residents and chief residents. •

30 NYU PhYsiciaN fall 2009

Saul Farber waS born on February 11, 1918, at home on Monroe Street on the Lower East Side. His father, Isador Farber, was an immigrant from Lithuania and a descendent of the Vilna Gaon, an important 18th-century Jewish scholar and leader. His mother, Mary Bunim, also was an immigrant. He was followed by siblings Samuel, Emmanuel, and Rochelle.

In 1935, he began his relationship with NYU, which continued for more than 70 years. He studied chemistry at the Washington Square campus, commuting every day from Borough Park. He graduated in 1938 at the age of 20. He then enrolled at NYU School of Medicine, fulfilling his ambition to become a doctor. Despite the outbreak of World War II, he completed a full four-year course of study at the School, graduating in 1942. He served as a medical intern at Sinai Hospital in Baltimore for nine months. In 1943, he accepted a commission as a lieutenant in the U.S. Navy. He was very proud of his navy service in the South Pacific theater, where he participated in several of the amphibious assaults against entrenched Japanese positions on fortified islands. When he returned, he completed a residency at Goldwater Memorial Hospital and at Bellevue. In 1948, he was a fellow in nephrology at NYU.

Nineteen forty-nine was a momentous year for Saul Farber. In 1939, his cousin had introduced him to Doris Balamuth, but they did not date until 1947. Despite

When he was a child, his family moved to the Borough Park section of Brooklyn to be nearer to his maternal grandmother, Minnie Bunim. Saul’s mother was ill during his childhood and died when he was 16. He was very much raised by his grandmother, aunts, and uncles. Family life was central. Two of his uncles, Louis and Joe Bunim, were doctors who provided his models in life. His uncle Joe, a graduate of NYU School of Medicine, served as the first clinical director of the National Institute of Arthritis and Rheumatic Diseases.

Saul’s education began at the Rabbi Jacob Joseph School on the Lower East Side and continued at the Etz Chayim Yeshiva in Brooklyn. He then attended public school, graduating from New Utrecht High School.

a Brief Biographyby martin j. blaser, md (’73), Chairman, Department of Medicine, NYU School of Medicine

alumni newsSpecial

look back at Saul farber

Dr. farber and his wife, Doris.

editor’S note: this special section on dr. Farber was edited by jerome lowenstein, md, (’57, ’63Hs), Professor of medicine, who refers to himself as dr. Farber’s “most senior chief resident.”

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Dr. Farber as a Role Model

i came to bellevue in 1974 primarily because of the lure of the big- city hospital. This was the fabled hospital described by Lewis Thomas in The Youngest Science. It was the place that cared for the sick regardless of their ability to pay and provided the best medicine that any academic center in the world could provide. After six months of my internship year, I wanted to be a chair of a Department of Medicine. This was due entirely to the role model that Dr. Farber presented to me as a house-staff officer. Later on, he continued to influence my career in surprising ways.

In 1975, the Committee of Interns and Residents (CIR) organized a four-day strike in which 3,000 interns and residents struck 15 private voluntary hospitals and 6 municipal hospitals, demanding reductions in their 120-hour work weeks. I was the CIR delegate who represented the house staff at NYU and Bellevue. The event was probably more symbolic than it was effective in altering house-staff duty hours. That occurred decades later, in 2002, when the Accreditation Council for Graduate Medical Education (ACGME), following the recommendations of the Bell Commission in New York, mandated a limitation of work hours.

Today, as the chair of the Department of Medicine at the University of Massachusetts Medical School, I would not be open to the suggestion that the house staff walk out, regardless of what the residents’ duty hours were. I don’t think Dr. Farber was open to that suggestion, either. I don’t believe he thought I was going to join the strike, but as the CIR delegate, I did, in fact, do just that. After the strike was settled, several people suggested to me that having acted against Dr. Farber’s wishes, I might want to go see Dr. Farber. I took the elevator up to the 16th floor of the new Bellevue, where he had his office. As in the old Bellevue, his office was still on a patient floor. I walked into his office, a windowless room, originally designed as an X-ray suite.

He was sitting there in his trademark rocking chair in the spare, lead-lined room. I was not sure what to expect. I gave

Dr. Farber my account of the story, and he told me that the stories he had heard from those negotiating on behalf of the hospital were different from the ones I had heard from those negotiating on behalf of the house staff. He suggested that it would be best if, before I did anything like walking out of the hospital again, I let him know in advance.

He said, “It has been my experience that not everyone agrees with my point of view, and sometimes they act on a totally different set of facts than the ones I am working with. It has always been my practice to try to understand what they were thinking rather than trying to get even with them.” This is just one of the lessons that I learned from Dr. Farber.

It was he who taught me the most about

NYU PhYsiciaN fall 2009

how to interact with patients, colleagues, and students, and I am constantly aware that it is my job to pass down the lessons I learned from Dr. Farber to my students and colleagues. The way we practice medicine has changed dramatically in the last 30 years, but our interactions as human beings have not. In the end, those are the hardest and most important lessons to teach. •

by robert W. Finberg, md (HS ’77), Chairman, Department of Medicine, University of Massachusetts Medical School

dr. Farber said, “it has been my experience that not everyone agrees with my point of view, and sometimes they act on a totally different set of facts than the ones i am working with. it has always been my practice to try to understand what they were thinking rather than trying to get even with them.”

Dr. finberg, circa 1977

illustrations by + jilliaN taMaki

Tsaturday lunches with saul Farber: a Former chief Resident’s Perspective

NYU PhYsiciaN fall 2009 32

LeSSon 2: never rush your patient experience. A patient was more than an illness. Dr. Farber insisted on seeing each patient presented to him, taking complete medical and family history, never rushing his time with them. He expected the same of us.

LeSSon 3: learn from patients. Every patient teaches you something. This concept has been central throughout my career, relating patient experiences to clinical research.

LeSSon 4: build your team with the right people. Dr. Farber was very proud of his faculty. He genuinely appreciated their expertise as teachers, caregivers, and investigators. Our colleagues challenge us by constantly asking “Why?” and “What if?”

LeSSon 5: Set your priorities. Family

the tradition oF Saul Farber’S Saturday lunches with the chief residents began in 1974. We chief residents—Paul Tunick, George Martin, Michael Rudikoff, and I—reported each Saturday for a meeting with Dr. Farber in his office on the sixth floor of the Bellevue C&D Building.

One memorable Saturday around noon, George Martin said, “Dr. Farber, we really enjoy having these meetings with you, but it is late, and we get hungry! Do you think we could meet at East Bay Diner instead of your office?” Paul, Michael, and I were aghast at George’s nerve. But Dr. Farber was hungry, too, so we all went for lunch. That was the beginning of a tradition that continued throughout our tenure as chief residents and for the next two decades.

I still carry the legacy of those Saturday lunches, breaking bread with the remarkable Dr. Farber. That legacy can be captured in 10 of Dr. Farber’s lessons.

LeSSon 1: each patient is important. Treat all patients with respect. Bellevue patients weren’t able to choose their doctors, so house staff were expected to dress—and act—in a manner that demonstrated respect.

was Dr. Farber’s first priority, and he frequently talked with pride about his family. His patients, students, house staff, and faculty also were top priorities. If anything was a second or third priority for him, we never knew it.

LeSSon 6: never forget why you went to medical school. Although I aspired to a career in clinical research, Dr. Farber instilled in me a commitment to always set aside time for patients and patient care.

LeSSon 7: remember that hospitals are complex organisms. Dr. Farber counseled, “If you ever lead a hospital, never forget that what may seem like a simple change in one activity can have unexpected and profound consequences.” This has been profoundly relevant to me in my present position as director of the National Institutes of Health’s Clinical Center.

LeSSon 8: be proud of your heritage. Dr. Farber drew strength from his family background, his many years living in Brooklyn—even taking the subway to Manhattan.

LeSSon 9: Give back to your profession. Dr. Farber was never too busy to help, a commitment we all noticed, experienced, and worked hard to emulate. He and his wife, Doris, donated furniture for the Bellevue house-staff lounge. In addition to what he did for NYU and Bellevue, he was incredibly generous in his service to the American College of Physicians and the American Board of Internal Medicine.

LeSSon 10: enjoy what you do. His great jokes punctuated our Saturday chief resident lunches. Even more enjoyable was his good-natured probing, his robust give-and-take discussions that led us to find new and better ways to improve the environment of care at Bellevue.

My chief residency year was the last year in the old Bellevue. We chief residents planned a major campaign to help ease the transition into a new building. Dr. Farber was attentive to every detail. He even helped design and paid for the commemorative buttons we commissioned for the campaign.

Saul Farber was an important mentor. He encouraged me to pursue my dreams. I relied on him for sage advice, but most of all he was a friend to me and lasting inspiration. •

the transition to the new bellevue was commemorated with this button, which Dr. farber helped design and paid for.

last liver rounds at the old bellevue Hospital, May 30, 1975. left to right: Saul farber (holding cup), paul tunick, and John Gallin.

by joHn i. gallin, md (HS ’75), Director, NIH Clinical Center,National Institutes of Health

T33NYU PhYsiciaN

fall 2009

a Man Who Wears One Watch

the medical claSS oF 1974 arrived at NYU in late August to begin our education. Most of us knew little about Bellevue and its importance: the great brick facades, the huge Emergency Room run by house staff, the excitement in the halls, which seemed to epitomize the city itself.

It was a time of change. We baby boomers—the television generation who grew up with an unprecedented self-awareness from the communion of a global, TV culture; who awoke to the assassination of President John F. Kennedy; whose adolescence was fueled by Vietnam, sex, drugs, and rock and roll; whose sense of self and other was forged in the protests of 1968 and by the assassinations of Bobby Kennedy and Martin Luther King, Jr.—came to medical school swaggering. We would soon stop our parents’ leaders’ war.

Early in our first year, we rose up and refused to take a “superfluous” exam. We were invited to meet the chairman of the Department of Medicine, Dr. Saul J. Farber.

The title of this encounter? “The television generation meets the greatest generation.” We took an ancient elevator to the sixth floor of the old Bellevue. The door opened to his office. A small, white-haired man appeared and said to come in. We sat or stood across the desk from Dr. Farber. He asked, softly, “What do you think you’re doing?”

After a very long pause, one of us began to speak, explaining who we were, what we were doing at medical school, talking about the lack of educational value in all these examinations. Dr. Farber raised his eyebrows—this was a very bad sign—and

he said, not so softly: “I know what you did. I asked you exactly what you think you were doing.”

There was no further conversation. There was, I recollect, a gentle soliloquy about being a physician, the special nature of that unique privilege and all its responsibilities—to a single patient and to humanity. It was his touchstone, and we would hear it in countless circumstances over the decades, unchanging in its truth and eloquence.

I have thought a great deal about why the experience of working in the oldest and most distinguished public hospital in America was so powerful and launched so many wonderful careers. I still am not certain. Perhaps the noted scientist and late essayist Lewis Thomas knew what it was. He said in his book The Youngest Science: “Today, Bellevue is a spectacular new building, a huge white square dominating the East River south of Thirtieth Street. . . . I regard it still, as I did when I first walked through the unhinged doors of the old building, as the most distinguished hospital in the country, with the most devoted professional staff.” He called Saul Farber and Jerry Lawrence “the best clinician-scientists I have ever encountered” and concluded that “these men, and their colleagues, were in love

with Bellevue—the whole hospital.”If you became a chief resident, as I did,

you got to the inner sanctum. You got to sit often in Dr. Farber’s office. You told stories, you listened to stories, you got advice during a year or two of executive leadership training—many of us thought this was our best year. You learned Farber’s aphorisms. One of my favorites was “A man who wears one watch always knows the time; a man who wears two can never be certain.” This was about loyalty, about the fact that in a complex and nuanced moment with a patient, you would have to make a decision that eliminated all but a single pathway. It was about courage and the strength to act, and the necessity for action.

But the principles were quite simple and binary: you either accepted that the responsibility of being someone’s physician was absolute, or you didn’t; you were either for NYU Shool of Medicine, or you weren’t. He used that fearsome and simple power to build the School and its relationship with the three great hospitals, federal, municipal, and private, that form a biomedical corridor along First Avenue. He had as much to do with the last century’s history of this place and American medicine as anyone.

During my first year of residency, I had a private session on career counseling with Dr. Farber. Timidly, on a post–call day, I tried out the possibility of a career in practice and teaching. He said, “Levin, there are a lot of unhappy doctors out there. They chose the wrong way. I don’t want you to be one of them. You’ve been doing research, you’ve done pretty well. You ought to think about this. I think you could have a great career in academic medicine.”

I listened. That was 1976—more than 30 years have passed. The message of Farber’s simple rules have carried me and many others very far. We are practitioners, scholars, scientists, chiefs, chairs, directors, deans. He managed to make the message personal to each and to wrap the message in the very simple rules by which he seemed to live his life. Longfellow captured some of this in these famous lines:

The heights by great men reached and keptWere not attained by sudden flight,But they, while their companions slept,Were toiling upward in the night.He never tired—that was also one of the

remarkable lessons: passion for the work could tap infinite energy.

Dr. Farber wore one watch. It was a great privilege to train with him. •

by ricHard i. levin, md (’74), Vice Principal (Health Affairs) of McGill University, Dean of the Faculty of Medicine

alumni newsSpecial

look back at Saul farber

D

preserving their dignity—made it clear that saving someone’s life had to be coupled with treating the person with sensitivity and compassion.

Third , a celebration of diversity. By choosing to make his career in New York City, choosing Bellevue Hospital as the centerpiece of the NYU education programs, and choosing to locate his academic office on a patient floor at Bellevue, where he regularly helped confused patients wandering the halls find their way back to their beds, Dr. Farber demonstrated by deed his commitment to all patients regardless of their religion, race, or socioeconomic status.

Fourth, an appreciation of the complexity of the human condition and how circumstances make it particularly difficult for people to meet society’s expectations for their personal and interpersonal behaviors. This subtle message was conveyed in the respectful way in which Dr. Farber sympathetically listened to patients as they told their life stories, recounting the hardships they endured and the impact their experiences had on their lives, including their flight into the use of illicit drugs and alcohol to escape the harsh realities of their lives.

The IndIvIsIbIlITy of MedIcal ResponsIbIlITy • Although I never heard him articulate it, over the years I came to realize that Dr. Farber built the medical service around the principle of the indivisibility of medical responsibility, meaning that a physician must feel uniquely and solely responsible for his or her patient’s care. Dr. Farber’s brilliance as a medical leader lay in his ability to make each member of the medical care team—medical student, intern, resident, chief resident, attending, and I am certain, himself—feel uniquely and solely responsible for each patient’s care. This principle is both a logical impossibility and a pedagogical necessity. I can vouch from firsthand experience that in many of those roles, I felt as if I truly had absolute and sole responsibility. I believe that the hallmarks of the NYU medical service under Dr. Farber’s leadership reflected this conviction, including the emphasis on the general internist as the medical team leader and the relatively limited role of subspecialists as consultants. Throughout my subsequent career I tried to stay true to Dr. Farber’s principle, always being on guard to identify potential forces that

34 NYU PhYsiciaN fall 2009

dr. Saul J. Farber had a proFound influence on me at a formative stage of my medical career, including my four years as an NYU School of Medicine student, from 1966 to 1970, and my two years as a “straight medical” intern and junior assistant resident (JAR) at Bellevue Hospital, from 1970 to 1972, before I left to enter the National Institutes of Health.

achieve social justice. Medical science is precisely defined, but medical humanism has multiple dimensions and is rarely defined with precision. I believe that there are four core elements of medical humanism, and Dr. Farber’s example had a major impact on my thinking about each of them.

First, an appreciation of the preciousness of each human life. This was the defining feature of the medical service under Dr. Farber’s leadership, with each person displaying an absolute commitment to use all of his or her intellectual and physical capacity to achieve that goal.

Second, a commitment to uphold the dignity of each individual. The way he treated each patient—showing them respect, protecting their modesty, and

I continued to be in contact with Dr. Farber for career advice, and when I returned to New York City as chair of the Department of Medicine at Mount Sinai in 1993, we periodically had dinner together with the other chairs of medicine in the New York area. Dr. Farber’s legacy lives on most brightly in the example he set by his own commitment to the highest ideals of the medical profession, and in his unique method of proffering advice, requiring the recipients to carefully interpret his pithy comments for themselves. I offer my homage in the form of my guess as to what he wanted me to learn.

MedIcal huManIsM • The most wonderful aspect of medicine is that it allows one to integrate humanism and science to improve human health and

Medicine as a learned Profession: the legacy of Dr. saul j. Farberby barry s. coller, md (’74) David Rockefeller Professor of Medicine, Physician-in-Chief, Rockefeller University

alumni newsSpecial

look back at Saul farber

35

would diffuse responsibility, and actively educating students, house-staff officers, and attendings on the importance of designing systems and defining roles that would reinforce the indivisibility of medical responsibility.

MedIcIne as a leaRned pRofessIon • In my discussions with Dr. Farber after I became chair of the Department of Medicine, I was struck with his repeated concern about preserving medicine as a “learned profession.” Typically, he didn’t provide much detail, but it made me think more clearly and precisely about what distinguishes medicine from other occupations. So I incorporated an explicit discussion of medical professionalism into the medical student curriculum. I realized that contrasting the professional ethic with the business ethic helped to highlight some of the key differences; for example, instead of the business principle of Caveat emptor (“Let the buyer beware”), the medical professional is expected to explain all of the benefits and risks of a given therapy as an integral component of obtaining informed consent. Instead of hiding new discoveries from others as trade secrets, physicians are expected to fully and rapidly disseminate that knowledge so that it can help patients throughout the world. Most important, other physicians are not one’s competitors; they are one’s colleagues. And instead of being responsible to shareholders, physicians are responsible to all humanity.

In my last meeting with Dr. Farber before I left NYU to go to the National Institutes of Health, he reminded me of one of the core elements implicit in the physician’s oath, namely a commitment to lifelong learning. He said that as I focused on medical research over the next few years, I had to remember that my MD degree was my “life insurance policy,” and therefore, each year I had to pay the premium. That admonition has guided my career, as I have repeatedly made strategic decisions designed to maintain my medical knowledge and skills.

huMoR wITh a poInT • As seen through my eyes as a medical student, Dr. Farber was an awesome figure whose countenance emphasized that medicine is a serious enterprise. It was only much later that I came to realize how much he loved clever wit and delighted in

telling a good story. Thus, I was totally unprepared when I experienced his humor for the first time as a student. My medical school years at NYU were ones of great civil unrest and confrontation for the nation. One common response to the intergenerational polarization was to invite students to participate in institutional governance. Thus, by a most unlikely series of events, I was selected to be a student representative on the dean’s search committee of 1970. The behind-the-scenes frank discussions of notable candidates provided an eye-opening introduction to academic politics.

A discussion at one of the meetings re-mains vivid to this day. The members of the committee were asked to describe what they thought was the dean’s most impor-tant responsibility. I was amazed by the

NYU PhYsiciaN fall 2009

range of views expressed by the other mem-bers of the committee, but having done my homework by polling the other students, I came ready to defend my choice—the ad-mission of new medical students.

After I finished my impassioned plea for greater involvement of the dean in the admissions process, Dr. Farber looked at me and recounted how, when he had been acting dean several years before, he used to take home the applicants’ folders and spread them on the floor of his apartment so that he could study them in detail. I immediately began to feel uneasy that perhaps Dr. Farber thought my comments were unfairly critical. Dr. Farber didn’t stop there, however; he went on to say that his daughter would look at the pictures of the applicants and tell him to accept the “cute” ones. As I sank deeper and deeper into my chair, he concluded by looking directly at me and saying, “And some people think that’s how you got into NYU!” So much for student governance.

It is a difficult challenge to explain how and why Dr. Saul J. Farber had such a profound and lasting impact on so many people. While I do not have a single answer, I believe that his unique persona reflected the authenticity of his deep convictions: the sanctity of all human life, medicine as a quasireligious calling charged with the obligation to protect the precious gift of life, mentoring patterned on paternal concern and loyalty, and the importance of personal humility as a crucial counterweight to the arrogance that commonly accompanies advanced knowledge and the power to effect cures. That combination remains unbeatable, but not easy to achieve.•

dr. Farber’s brilliance as a medical leader lay in his ability to make each member of the medical care team—medical student, intern, resident, chief resident, attending, and i am certain, himself—feel uniquely and solely responsible for each patient’s care.

Dr. coller in 1972 and today.

36 NYU PhYsiciaN fall 2009

Obituaries

Joseph Goodgold, MDJoseph GoodGold, Md, professor eMeritus at NYu school of MediciNe, former chairman of the department of rehabilitation Medicine, and director of

NYu langone Medical center’s rusk institute of rehabilitation Medicine, passed away on august 29, 2009. he was 89 years old. during his 40 years at NYu, dr. Goodgold helped shape the field of electrodiagnosis (the evaluation of nerve and muscle func-tion by measuring their electrical activity). One of the first U.S. practitioners to make extensive use of computers in his investigations, his research led to numerous advances in the diagnosis and treatment of nerve and muscle disorders. In addition to his many academic publications, dr. Goodgold wrote the seminal textbooks on electromyography.

as a professor, he trained generations of physicians and researchers and also helped establish the first credentialing exam for electrodiagnostic medicine.

after attending Brooklyn college, dr. Goodgold received his medical degree from Middlesex University, followed by an internship at Brookdale hospital. he entered the army during the Korean War and was assigned to train at the Mayo clinic’s department of physical Medicine and rehabilitation under electrodiagnosis pioneer dr. edward lambert—an experi-ence he described as “a year of training in [three] months.”

in 1953, dr. Goodgold came to NYu school of Medicine as a fellow in the department of physical Medicine and Rehabilitation (now the Department of Rehabilitation Medicine). He was appointed to the howard a. rusk chair of rehabilitation research in 1975 and was named chair of the department of rehabilitation in 1982. dr. Goodgold also

served as president of the American Academy of Physical Medicine and Rehabilitation (AAPMR), the American Association of Electromyography and Electrodiagnosis (now the American Association of Neuromuscular and Electrodiagnostic Medicine, or AANEM), and the Association of Academic Physiatrists. His many honors include the Gold Medal from the american college of physical Medicine, aapMr’s frank Krusen Lifetime Achievement Award and Distinguished Clinical Award, and AANEM’s distinguished physician award.

“the major challenges for us in electrodiagnostic work are to decide how best to educate and evaluate the competency of our trainees and how to standardize outcomes,” wrote dr. Goodgold in 1996. “My life has taught me that the best work can’t be accomplished in part-time efforts. . . . Strive for full-time dedication.”

Dr. Goodgold is survived by his wife, Mildred; his daughters, Ellen and Shelley; and six grandchildren. •

Simon Karpatkin, MD, professor of medicine and director of

the Division of Hematology, passed away at his home in Manhattan on August 21, 2009. He was 75 years old. Dr. Karpatkin was internationally renowned for his research on blood platelets and coagulation, including his pioneering work on autoimmune thrombocytopenia (low blood platelet count) in patients with HIV and other conditions. Among other achievements, Dr. Karpatkin was the first investigator to show that an antibody can cause platelets to self-destruct. His recent discovery of the ability of an amino acid fragment to dissolve platelet aggregates, published in Blood this year, is credited with opening new approaches to stroke, myocardial infarction, and other blood-clot–related disorders.

A magna cum laude and Phi Beta Kappa graduate of Brooklyn College, Dr. Karpatkin attended NYU School of Medicine in the class of 1958. After residencies at Bellevue and Bronx Municipal Hospitals, he accepted a fellowship at Washington University, where his work with Dr. William Harrington, a world expert on platelet disorders, and Dr. Carl Cori, a Nobel Prize–winning biochemist, launched his career in platelet study.

Dr. Karpatkin returned to NYU in 1964 to join the faculty of the Department of Medicine and was named to head the Division of Hematology in 1993. During his 45 years at NYU, he received numerous professional honors, including election to the American Society of Clinical Investigation, the Association of American Physicians, and the Interurban Club. In 1991, he was presented with the Solomon A. Berson Alumni Achievement Award in Basic Science, awarded to an NYU School of Medicine alumnus for major accomplishments in fundamental scientific research.

“His great energy, passion, curiosity, and drive all converged on his work. He was an artist, and science was his canvas,” said Dr. Karpatkin’s col-league and former student Martin Bla-ser, MD, the Frederick H. King Professor of Internal Medicine, professor of

simon Karpatkin, MD

microbiology, and chair of the Depart-ment of Medicine. In addition to his legacy as a pioneering researcher, Dr. Karpatkin is remembered as a fiercely dedicated teacher and mentor, a generous friend and colleague, and an avid sailor who loved good food and good conversation. He is survived by his wife, Margaret, professor emeri-ta of pediatrics and medicine; his son, David; and his daughter, Judith. • p

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plant a seed

Mary C. AgnelloJoan AntonucciFrances Bailen-Rose, MD ’38Marvin BakerPearl BarlowMitchell M. Benedict, MD ’26Betty BeranbaumCharles G. BlumenauerSidonia E. BlumenauerCharlotte BowmanLucille BrusselSylvia Brustor Josephine CasconeJoan CherryAntonina P. ChiaramonteAlan ClahrJanet CohnGeorge D. CornellLeroy G. Dalheim, MD ’53Dorothy Irene De BearElizabeth K. DollardEhrman Family TrustFlorence T. EisnerHelen K. Ferguson, MD ’32

Charlotte FleckKenneth M. Gang, MD ’43Ena GilbertHelena GloverEugene David Glynn, MD ’51Anita Goulet, MD ’52Kermit H. Gruberg, MD ’42Vivian GruderHelen G. GrunebaumWalter A. Guensch, MD ’43William H. Gutstein, MD ’46Marshall J. Hanley, MD ’45Abraham HasesCurtis HausmanRose HellerWilliam HellerWayne A. Hening, MD ’78Benjamin HomanMary IrishStanley A. Isenberg, MD ’43Gertrude JeffersonBlanche JonesJames JonesJulius Joseph, MD ’34

Grace T. KahnPeter KalatAnthony Kasich, MD ’26Henry KayMagda KrooMilton LanzWilliam LaughlinEvan LillyFreda Hall LipmannMartha J. LoewensteinRuth LuboweFrederick LuedersIrwin D. MandelClaudia McClintock, MD ’76Lillian MesseloffEdouard Jerrold MillerWilliam J. MillerDoris H. Milman, MD ’42Joseph F. Moriarty, MD ’46Marie MuscarneraLeonard NaiderAbraham M. Oshlag, MD ’41 Ann D. Stuckey, MDEmile G. Pensa

During their lifetimes, they generously planted seeds of growth and change by naming NYU Langone as a beneficiary of their estates. Their support helps our talented physicians, scientists and educators continue to provide model patient care, groundbreaking research and transformative medical education, ensuring a brighter future in health care at our Medical Center and beyond.

Today, we remember these dedicated leaders with special admiration.

Gordon PivarEleanor Daughaday PopperCharles R. Ream, MD ’50Reed M. RobertsDavid RobinsonLouis SandersJames L. SaphierGertrude SchardingMona SchwartzPeggy SholtzTona SoglowMartin Spatz, MD ’40Florence SpencerToby StarrBernard SternAbraham Sunshine, MDWalter G. Terwedow, MD, ’43Priscilla ThomasZary Armand ToulaPeggy VaradyJo-Anne WeissbartCharles F. Wolf, MD ’32

in the past two years, these men and women advanced a tradition of selflessness at NYU Langone Medical Center by leaving legacies to benefit many:

FOR MORE INFORMATION:Marilyn Van Houten, Senior Director of Planned Giving, at 212.404.3653 or

marilyn.vanhouten@nyumc.org

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