The molecule meets the computer chip

Harnessing the power of computers is essential as biologists work to decipher mountains of new data.

It is difficult to imagine two places more different than The Eagle Pub and Celera Genomics, each of which provided the setting for signal events in modern biology. The cozy Eagle, in Cambridge, England, was already a smoky anachronism fitted with burnished brass and dark wood in February 1953, when Francis H.C. Crick famously burst through the door to inform James D. Watson that they had jointly deciphered “the secret of life”—the structure of DNA. Nearly 50 years later, in Celera’s sterile, starkly lit “sequencing rooms,” and in similar rooms at institutions responsible for the government-sponsored Human Genome Project, the complete human genome was painstakingly unraveled by row upon row of humming computers.

The pub and the sequencing room are apt metaphors for the vast changes wrought by Watson and Crick’s discovery, which unleashed a torrent of research in molecular biology that has revolutionized our understanding of evolution, physiology and disease. Watson and Crick confronted a blank slate, but today’s scientists are awash in a fast-moving river of information so thick with possibility that the American Association for the Advancement of Science recently felt compelled to sponsor a symposium for biologists called “Inundated With Data.”

The collective efforts of the world’s scientists have allowed us to construct diagrams of intracellular signaling pathways that would make a New York subway official blanch, and the complete genomes of over 100 organisms are now in hand. However, biologists have been so busy amassing fine details that they have had little time or incentive to step back from the bench, take a breath and begin to grasp the essential patterns in the big picture.

Luckily, computing power has increased in tandem with biological knowledge at an exponential rate, setting the stage for the recent emergence of the cutting-edge, multidisciplinary field of computational biology. The field embraces genomics and proteomics (the latter aims to catalog the complete inventory of proteins encoded by genomes), but also promotes computational modeling of intracellular processes and cell-cell interactions, as well as the “high-throughput” data-mining techniques of bioinformatics, which can unveil common mechanisms underlying seemingly diverse diseases and compare genomes to discern subtle evolutionary relationships among organisms.

In 2003, Yale established an interdisciplinary Ph.D. program in computational biology and bioinformatics. That same year, the university’s Biological Sciences Advisory Committee (BSAC), under the leadership of H. Kim Bottomly, Ph.D., professor of immunobiology, began a study which concluded that computational approaches would play a central role in 21st-century biology. The committee has just produced its final report, a blueprint for Yale to stay ahead of the curve in faculty recruitment, funding and facilities.

The committee’s efforts also led to “A Look to the Future,” an October symposium at the medical school’s Anlyan Center chaired by Perry L. Miller, M.D., Ph.D., professor of anesthesiology and director of the Center for Medical Informatics; Mark B. Gerstein, Ph.D., the Albert L. Williams Associate Professor of Biomedical Informatics and associate professor of molecular biophysics and biochemistry; and William L. Jorgensen, Ph.D., the Conkey P. Whitehead Professor of Chemistry.

The symposium assembled seven top researchers from around the world who use computational approaches to attack a variety of biological problems, from untangling phylogenetic relationships between species to manipulating gene sequences to create completely new proteins and enzymes with customized biological functions.

In addition to providing a forum for these scientists to present their latest work, the symposium also included several informal brainstorming sessions where Yale scientists and administrators learned how the speakers’ home institutions have risen to the structural and organizational challenges of integrating computational biology into teaching and research.

The BSAC report argues that Yale must increase its research and teaching strengths in computational biology and bioinformatics. It recommends the creation of thematically oriented clusters of faculty at the medical school and on Science Hill. And it proposes the formation of a universitywide center for computational biology and bioinformatics that would foster campuswide interactions of faculty and trainees and provide administrative support.

No one doubts that computational biology is here to stay. “The old view was that biologists were the scientists who didn’t like to think quantitatively,” said Carolyn W. Slayman, Ph.D., Sterling Professor of Genetics and deputy dean for academic and scientific affairs. “Now, biologists must face up to the fact that there’s going to be a demand for greater computational skill and greater expertise in informatics than ever before—it’s the future of the field.”

—Peter Farley

A new hospital pavilion, set to open in 2008, will house $430 million cancer facility

Services for cancer patients are currently scattered at six sites across the Yale-New Haven Medical Center, but that will change by 2008 with the planned opening of a new hospital facility that will offer all cancer services under one roof and significantly enhance the medical school’s ability to conduct clinical research.

At a press conference on November 30, Yale-New Haven Hospital (YNHH) President and CEO Joseph A. Zaccagnino, M.P.H. ’70, announced that YNHH would add a 497,000-square-foot north pavilion to the YNHH complex that will house a comprehensive clinical cancer center. The plan will add 112 inpatient hospital beds and an estimated 400 permanent jobs.

The proposed $430 million center is a 14-story facility with space for operating rooms; infusion suites; radiation treatment rooms; adult inpatient facilities for surgical, medical and gynecologic oncology; and an outpatient women’s cancer center. It will be connected to the Yale-New Haven Children’s Hospital by way of a five-story bridge across the upper floors, so that pediatric patients will be able to receive treatment at the new center while remaining hospitalized in the children’s facility.

“I cannot overstate our level of enthusiasm and excitement about this project,” Dean Robert J. Alpern, M.D., said at the press conference, attended by city officials, patients, employees and community, hospital and medical school leaders. “Now that we’ve seen the drawings, we’re impatiently ready to move into the building. We’re going to have to control ourselves.” Yale Cancer Center Director Richard Edelson, M.D. ’70, called the move “a huge step forward.”

Alpern and Yale President Richard C. Levin both stressed the opportunities the new center opens up for conducting additional clinical trials, which are a source of promising new treatments for patients and an important revenue stream for academic medical centers. Levin noted that Yale is already one of the top biomedical research institutions in the world and does excellent cancer research in the laboratory.

“With expanded capabilities to treat cancer patients and to do research on the efficacy of new therapies, we can do much more,” Levin said. “We can establish ourselves as one of the world’s great centers for the treatment of cancer.”

The new center will be built on existing hospital property at the site of the Grace Building on Park Street, a former nursing hall now given over to offices, which is slated for demolition this spring. The hospital’s board of trustees approved plans for the center in November, following state approval of the preliminary site plan last July. Pending approval of the plans by the city and state, groundbreaking is expected in the fall.

—Michael Fitzsousa

New MBA program to help health professions with the business of medicine

At some point in the 1980s, according to Howard P. Forman, M.D., M.B.A., vice chair and associate professor of diagnostic radiology, the practice of medicine became more pain than gain for many physicians.

“Health care costs were skyrocketing and cost containment measures gained importance,” said Forman. “Physicians were targeted as the cause of the problems and were counted on to bring down costs.”

Forman and others at Yale’s schools of medicine, management and public health may have a prescription for this malaise—the Yale MBA for Executives: Leadership in Healthcare. This new program, which Forman co-directs with Stanley J. Garstka, Ph.D., deputy dean of the School of Management, and Dick R. Wittink, Ph.D., the George Rogers Clark Professor of Management and Marketing, will enroll a charter class of up to 30 students in August.

The 22-month program’s goals—besides providing a second set of skills without career disruption—are to turn the classroom into a cross section of the contemporary health care field and to train what Forman calls “change agents capable of making a positive difference in the practice of health care.” By enrolling students with a broad range of background and experience—professionals from hospitals, clinics, insurance and managed-care organizations and pharmaceutical, biotechnology and financial service firms—the program aims to change perceptions that these fields are adversaries. Then, through two intense residences, weekend classes and seminars with visiting scholars, the curriculum provides the management skills needed to navigate the complexities of health care, which is itself constantly changing due to medical and technological breakthroughs, new laws and government policies.

The seed for the executive program was planted in 1996 when medical students expressed interest in an M.D./ M.B.A. program. That joint-degree program, though geared toward medical students, has also attracted faculty and working physicians. Among the latter, Michael Apkon, M.D., Ph.D., FW ’94, M.B.A. ’02, was one of the four M.D./ M.B.A.s produced by the first graduating class in 2002. A former assistant professor in the medical school, he is now medical director of the pediatric ICU and a vice president at the Yale-New Haven Children’s Hospital.

Although that program worked for medical students, who could add a year to their studies, it was not ideal for practicing professionals. “Surgeons came to me and said, ‘I’d have to give up my career if I’m going to do this joint-degree program because I can’t do four days a week and not be in the OR.’ So we started work on an executive program targeted to health care professionals,” said Forman.

Not so long ago, even the idea of an M.D./M.B.A. was a tough sell. “There was the fear that you were either selling out to the enemy or selling your soul,” said Forman. That negative perception was changed, in part, by the University of Pennsylvania’s Wharton School, where William L. Kissick, M.D. ’57, M.P.H. ’59, Dr.Ph. ’61, led an M.D./M.B.A. program that produced some of today’s health care leaders (See Alumni Faces).

“By the 1990s, it was apparent that for those who want to be leaders this is an appropriate path—that you’re not selling out,” said Forman. “You’re fulfilling your mission to improve health care for larger numbers than you could as a pure clinician.”

—Alan Bisbort

Yale and New Haven join in pilot program for treating HIV/AIDS in Russia

Russia today is where the United States was 20 years ago in dealing with HIV/ AIDS: denial and prejudice are almost as widespread as the disease itself.

In an effort to help, last July in St. Petersburg Health and Human Services Secretary Tommy G. Thompson announced a major grant to fight the AIDS epidemic. A Yale doctor and epidemiologist were by his side, and at an October news conference in New Haven’s City Hall, they announced their own role in the initiative. The School of Medicine was one of four U.S. organizations chosen to receive $320,000 each from the U.S. Agency for International Development to provide training in care, treatment and support services to people living with HIV/AIDS in Russia.

The School of Public Health, through its Center for Interdisciplinary Research on AIDS, has worked on training and prevention programs with colleagues in St. Petersburg since 1998. But this marks the first collaboration between the two cities to address HIV/AIDS care and treatment.

The 30-month program calls for Yale, along with state and city agencies, to share information and strategies with colleagues in St. Petersburg. The grant will fund four exchanges each year; the first group of Russian trainees arrived in New Haven in early October. Yale faculty and representatives from community-based HIV/AIDS organizations will also travel to St. Petersburg to train Russian health professionals and to observe how they are managing the epidemic.

In Russia, a major obstacle is the prejudice against HIV/AIDS patients, typically young, male intravenous drug users. As part of the program, Russian visitors will observe services provided by the Yale AIDS Program and organizations in New Haven, and they will visit a methadone clinic and needle exchange program. Krystn R. Wagner, Ph.D. ’89, M.D. ’96, assistant professor of medicine and project coordinator of the New Haven–St. Petersburg partnership, said she hopes that “observing drug treatment here will help catalyze new thinking about substance abuse management and the care of drug users.”

The problem in Russia, said Robert Heimer, Ph.D. ’88, associate professor of epidemiology and public health and co-coordinator of the project, is the lack of a multidisciplinary, integrated system for managing HIV/AIDS. “Someone walks into a hospital and is treated for HIV,” said Heimer, “but what about his drug addiction, or the fact that he has tuberculosis or that he’s homeless? There’s no coordination, no system that allows them to deal with the complexities of this illness in a way that crosses traditional medical boundaries.”

The impetus for this initiative is the soaring number of HIV infections in Russia. HIV/AIDS didn’t surface in the countries of the former Soviet Union until the early 1990s, but they now report some of the world’s fastest- growing rates of new infections. Although there are 300,000 reported cases in Russia, the United Nations and Russian AIDS officials put the number at 1 million or more. Wagner, medical director of the Nathan Smith Clinic, the HIV clinic affiliated with Yale-New Haven Hospital, said this is due to many factors, including relaxed border controls after the dissolution of the Soviet Union, rising unemployment and drug trafficking. Most new HIV cases were initially among IV drug users, but now cases caused by sexual transmission are on the rise.

Heimer called the collaboration “remarkably exciting. … If we can create and implement an integrated system on a pilot basis in one small region of St. Petersburg, and if it’s successful, it can be replicated elsewhere in Russia.”

—Jennifer Kaylin

Et Cetera

Kaplan named to IOM

Edward H. Kaplan, Ph.D., the William N. and Marie A. Beach Professor of Management Sciences at the School of Management and professor of public health, has been elected to the Institute of Medicine. Kaplan, the only Yale faculty member named to the institute this year (see Alumni for more on this topic), is an operations research and statistics expert who studies problems in public policy and management. His recent research has focused on counterterror topics such as the tactical prevention of suicide bombings, bioterror preparedness and response logistics in the event of a smallpox or anthrax attack. In the early 1990s, he was the principal investigator of a landmark project that evaluated the efficacy of New Haven’s needle exchange program.

Membership, one of the highest honors in medicine, is awarded for contributions to medical science, health care and public health. The institute was established in 1970 by the National Academy of Sciences and provides independent, scientifically informed analysis and recommendations on human health issues.

—John Curtis

Yale joins national epilepsy study

Yale has been named a key member of a national group of medical centers that has received the largest grant ever for a study of epilepsy in children. The $17 million award from the National Institute of Neurological Disorders and Stroke will fund a study of the three most-used drugs for treating childhood absence (petit mal) epilepsy. The five-year study at 20 sites across the country will attempt to determine the best initial medicine for childhood absence epilepsy, which involves seizures marked by nonconvulsive staring spells.

At Yale researchers will try to identify why some treatments work, why some have side effects and what effects they have on cognition, behavior and learning. “This is the first step toward our goal of making it possible for physicians to predict patient response and tailor therapies for individual needs,” said Edward J. Novotny Jr., M.D., FW ’89, who is leading the study with colleague Susan R. Levy, M.D.

—J.C.


			Originally published in Yale Medicine, Spring 2005. Copyright © 2005 Yale University School of Medicine. All rights reserved.