Yale sets its sights on biomedical engineering

Program gets a boost from NIH’s newest institute with $7.1 million for imaging work in epilepsy.

In 1996, when President Richard C. Levin laid out his vision for the University’s future in an essay titled “Preparing for Yale’s Fourth Century,” he said that the principle of “selective excellence” would guide Yale as it branched out into certain new fields. “Rather than seek broad coverage of an entire discipline,” he wrote, “it may be wise to build a few distinguished groups of faculty who can compete with the best in the world in their areas of specialization.”

One of the areas Levin pointed to was biomedical engineering, a field that got its start when engineering strategies contributed to medical inventions such as X-rays and prosthetics. After World War II the field gained more formal acceptance as universities and hospitals discovered that radar and computers had medical applications. In 1998 Yale established an undergraduate biomedical engineering program, which has since become the most popular engineering major. Access to medical research facilities encouraged doctoral candidates in the applied physics and mechanical, chemical and electrical engineering departments to explore biological problems. A Ph.D. concentration focusing on medical imaging, molecular engineering and biomechanics was formally approved late last year, and five students will be admitted this year.

Biomedical engineering at Yale got another boost in April, when the National Institute of Biomedical Imaging and Bioengineering (NIBIB) awarded its first research grant to Yale and two other institutions. As a member of a team that includes the University of Minnesota and Albert Einstein College of Medicine, Yale will receive $1.4 million this year and up to $7.1 million over the next five years for the development of advanced imaging techniques for the treatment of neocortical epilepsy. Another sign that biomedical engineering’s day has come was the establishment of the NIBIB itself in 2000 as the newest member of the National Institutes of Health.

“Bioengineering, through imaging, offers a way for surgeons to examine the incredible and complex functions of the brain,” said neurosurgeon Dennis D. Spencer, M.D., HS ’76, co-principal investigator of the epilepsy project. Advances in imaging technology could eventually reduce surgery time, eliminating the need for electrodes and open-brain surgery, and instead permit targeted surgery or delivery of drugs through small openings in the skull, said Spencer, the Harvey and Kate Cushing Professor of Neurosurgery and the department’s chair.

According to principal investigator James S. Duncan, Ph.D., professor of diagnostic radiology and electrical engineering, mathematical models will be used to analyze an individual human brain before and during surgery to provide the surgeon with precise information in order to guide an intricate procedure that will eliminate the seizures. The technique combines data from both high-field magnetic resonance spectroscopy and functional magnetic resonance imaging to create a three-dimensional view of the brain, Duncan said in an interview in his office on Cedar Street, pointing to a rotating, computerized image of a human brain, with grids and boundaries in brilliant color.

The close collaboration of physicians and scientists from both sides of campus is not yet typical of American medicine, according to Paul A. Fleury, Ph.D., who came to Yale in 2000 as dean of engineering, succeeding Allan Bromley, Ph.D. Engineering strategies can be applied to countless biological systems and medical problems, Fleury said, yet “too often medical researchers regard engineers as ‘providers of gadgets,’ with little real collaboration. Overall, medical and engineering researchers have more to offer each other than what has been exploited so far.”

The challenge of the new educational programs is balancing breadth and depth in a number of subject areas, including mathematics and biochemistry, according to Duncan, an electrical engineer who began his career working on night vision systems at the Hughes Aircraft Company. He is the overall director of the program and also directs the undergraduate program, now in its fourth year. “We need math tools to even approach these problems, but we also need to talk with biologists and clinicians to understand the problems.”

Such collaborations cannot be dictated, but only emerge from genuine mutual curiosity, Fleury said. Engineering’s newest recruit is Cornell University’s W. Mark Saltzman, Ph.D., whose research focuses on drug delivery and tissue engineering, with an emphasis on the use of polymeric materials for these purposes rather than more costly animal proteins. His lab has designed polymer implants that permit controlled release, which could be applied to treating serious brain disease, including Alzheimer’s and brain tumors.

“The potential for collaboration between engineering and medicine is exactly what attracted me to Yale,” says Saltzman, who will be a professor of chemical and biomedical engineering. “Yale has a rich tradition of excellence in both of these areas and it has already established an interdisciplinary environment that supports the exchange of ideas across the interface. I believe that biomedical engineering is about to enter a period of tremendous growth, and Yale is well positioned to be at the leading edge of these developments.”

Citing accomplishments, Levin reappoints Kessler to a second term as dean

Five years ago, when David A. Kessler, M.D., was appointed the School of Medicine’s 15th dean, the focus was on the future. In making the announcement in a packed Harkness Auditorium on February 13, 1997, Yale President Richard C. Levin spoke of the things Kessler was likely to accomplish as dean and the support he had from the central administration. “I think this is the right man at the right time for taking the school forward.”

On May 7, Kessler was reappointed to a second five-year term, and the focus was on the dean’s track record since 1997.

In a message to the medical school community, Levin praised Kessler for making “a succession of outstanding appointments to positions of departmental leadership” and for planning and initiating the construction of the new Congress Avenue Building. He also cited Kessler for establishing the new Clinical Program Development Fund in partnership with Yale-New Haven Hospital and for overseeing significant improvements in medical education.

Kessler, a graduate of Amherst College, Harvard Medical School and the University of Chicago School of Law, was commissioner of the Food and Drug Administration from 1990 to 1997 under former Presidents Bush and Clinton. He served as medical director of the Hospital of the Albert Einstein College of Medicine from 1984 to 1990 after training in pediatrics at The Johns Hopkins Hospital and working on Capitol Hill.

Kessler said he “couldn’t be more thrilled to remain at Yale and continue to work hard on advancing the school’s three missions” of patient care, research and education.

“What I knew before coming here was that Yale is a world leader in medicine and science,” he said. “What I’ve come to appreciate even more since then is just how special the medical school is, and how packed it is with academic talent and clinical expertise. We have a very bright future ahead of us.”

Under Kessler’s deanship, new chairs have been appointed in the departments of Cell Biology, Cellular and Molecular Physiology, the Child Study Center, Genetics, Obstetrics and Gynecology, Pharmacology and Surgery. He also recruited Herbert Chase, M.D., as the school’s deputy dean for education and negotiated an affiliation agreement with Yale New Haven Health System that established a fund to develop cutting-edge clinical programs with Yale-New Haven Hospital.

Construction of the Congress Avenue Building, a 457,000-square-foot teaching and research facility, began in early 2000 and is nearing completion; more than 700 faculty and staff will begin moving in this coming winter to conduct disease-oriented research in eight key areas; to teach anatomy, histology and other medical school courses; and to support teaching and research activities.

Genomics innovator, bold as ever, makes a few waves during visit to Yale

When the name J. Craig Venter, Ph.D., appears in print the words “genome” and “maverick” are seldom far behind. Venter, one of the prime movers behind the sequencing of the human genome, has made a career out of doing things his way. “I have learned,” he told an audience in the Fitkin Amphitheater “to ignore people’s advice on many occasions.”

Indeed, Venter has not only rejected conventional wisdom, but often run counter to the scientific establishment. His independence has worked for him: even before he set out to sequence the human genome he discovered hundreds of new genes, decoded the first full genome of a living organism (the bacterium H. influenzae) and deciphered the genome of the fruit fly.

It was his impatience with what he considered the plodding methods of the National Human Genome Research Institute (under the leadership of Francis S. Collins, M.D., Ph.D. ’74, FW ’84) that led him into a race to sequence the genome. Venter had developed methods that he believed would be faster and cheaper. Yet the National Institutes of Health (NIH) denied his early requests for funding because it was thought they wouldn’t work. “The NIH is not very good at funding new ideas,” Venter said, “but when an idea is established, they are extremely good at funding it.”

Venter came to Yale in April to deliver the 54th annual keynote lecture to the Associates of the Cushing/ Whitney Medical Library. He also spoke at grand rounds for the Department of Internal Medicine and attended a lunch with about 20 medical students.

What, he was asked, were his future plans?

The scientific community has been waiting for this shoe to drop. In January Venter left Celera Genomics, the company he founded in 1998, because of a disagreement over business strategy. The company chose to pursue drug development, considering that a more profitable pursuit than subscriptions for its genome data.

While at Yale, Venter had little to say about his future plans. Not one to steal his own thunder, he saved his announcement for an interview he gave The New York Times during his stay in New Haven. But he offered a hint to medical students. “One of the many things I’ll be spending a little time on is trying to deal with the social and ethical issues of sequencing the human genome,” he said.

During the next few days Venter would twice grace the pages of the Times, first with the revelation that Celera’s decoding of the genome was based on a sample of his own DNA. A few days later came the news that Venter plans to write his autobiography and start two not-for-profit institutes to explore issues such as genetic discrimination and the genetics of race and to develop clean energy alternatives possibly by developing or discovering new microbes that can convert carbon dioxide into hydrogen.

In his keynote address at the Historical Library, Venter traced the history of genomic sequencing and his role in it. Applying the power of new computers and algorithms, Venter and colleagues at The Institute for Genomic Research sequenced the H. influenzae genome in 1995. The project was a challenge to the NIH, which was also working to sequence the genes of the bacterium. “We thought we could sequence the genome in a year at about a tenth of the cost of current projects,” Venter said, adding that his group did apply for federal funding only to be turned down. “What we were doing,” he recalled NIH officials telling him, “was absolutely impossible and could never work.”

After sequencing a few more small organisms, such as other bacteria and the fruit fly, Venter tackled the human genome. The NIH had already begun its sequencing project, but Venter believed his methods and tools—supercomputers, expressed sequence tags, mathematical algorithms and shotgun splicing—could do it faster. The race was on.

Ultimately the two teams realized the value of working together and in February 2001, in a tentative and at times testy collaboration, they published their results simultaneously in the pages of Science and Nature.

For his last appearance at the medical school at grand rounds, Venter discussed the genome’s impact on medicine. “Within 10 years,” he told a resident, “the medicine you practice will be based on knowing the genetic code of your patients. This information can give individuals power and more control over their own lives. If you know what is likely to affect you, you can do something about it early enough to make a difference.”

For the next generation of students, Hope 110 will be known as “Rosenberg”

When former Dean Leon E. Rosenberg, M.D., HS ’63, returned to Yale in May for the dedication of a lecture hall in his honor, it was very much a family affair. He was joined by his wife, brother, children and grandchildren, along with dozens of former colleagues, mentors and students. The family members traveled a distance, one of his sons suggested, because the family itself had come a long way.

Robert L. Rosenberg, Ph.D., pointed to the new sign above the door to Hope 110 bearing his father’s name. “Back in Waunakee, Wis., there was another sign that said ‘Rosenberg.’ It hung over the door of the general store my grandfather owned,” said the younger Rosenberg, who earned his doctorate at Yale in 1985 and is an associate professor of pharmacology at the University of North Carolina. “Coming here today, I thought about what makes this one here as important and significant as that big one in Wisconsin. The answer, I think, comes down to the three most important words in real estate: location, location, location.”

It was an observation that provoked laughter as well as the realization that for others in the room, too, location was indeed key. Hope 110—where generations of medical students have attended countless lectures—is now The Leon E. Rosenberg, M.D., Lecture Room. “Within these walls, students will have their first classes, drink their coffee, read their newspapers and even fall asleep,” Dean David A. Kessler, M.D., said during the dedication. “Most importantly, they will establish friendships that will last a lifetime.”

Rosenberg joined the Yale faculty in 1965 and served as dean of the medical school from 1984 to 1991, when he left academia to head Bristol-Myers Squibb’s Pharmaceutical Research Institute. In 1998, he joined the faculty at Princeton.

The former dean said he was “grateful beyond words” for the tribute and particularly touched by the location chosen for the honor. “I’ve been on both sides of the podium in 110, many times, and I know what it means to the school and the thousands of students who have passed through it.”

He closed by recounting a comment that his son David made upon hearing that the room would be renamed in his father’s honor: “David said, ‘Just think, in 10 years, two Yale medical students will be passing in the hall and one will say, “I’ve got to get to class at 11 o’clock in Rosenberg.” ’ ” The former dean paused and smiled. “I wouldn’t have thought of it myself,” he said. “But it has a nice ring to it.”

Et Cetera

Surgical residency revamped

The days of surgery “boot camp” may be over. To avoid reaccreditation problems, Yale-New Haven Hospital is shifting to a maximum work week of 80 hours for its 48 general surgery residents. The Chicago-based Accreditation Council for Graduate Medical Education warned the hospital in March that it must reduce work weeks; end every-other-night, in-house call; and improve documentation of procedures done by residents. (The general surgery residency, one of 28 at Yale-New Haven, has had provisional accreditation since obtaining new-program status when combining with Bridgeport Hospital’s general surgery program in 1995.) The hospital plans to hire physician assistants and part-time doctors to reduce overnights for residents. Chair of Surgery Robert Udelsman, M.D., predicted that the “standard practice” of 100-hour workweeks would end nationwide. “We must develop techniques to teach an ever-increasing wealth of both information and skills, and we must do this in an efficient and humane environment.” The accreditation group will check in again on August 7.

Biotech boomlet

The end of 2001 was less than spectacular when it came to investment in startup companies nationally, including those in the biotech sector. Despite this, according to a survey by PriceWaterhouseCoopers, Yale-founded firms managed to raise $92.8 million in venture capital in the fourth quarter, or 38 percent of the $246 million raised in New England’s biotech industry. The Yale total is actually higher when other deals not included in the survey are counted. Achillion Pharmaceuticals led the list with $45 million, followed by Agilix Corp. with $20.8 million, Rib-X Pharmaceuticals with $20.5 million and Archemix Corp. with $6.5 million. All but Cambridge, Mass.-based Archemix are located in New Haven. According to Alfred “Buz” Brown, Ph.D., director of cooperative research, three additional transactions—initial funding for Asilas, Aureon and Protomoetrix—added $24 million to the fourth-quarter total. Half a dozen more Yale-founded companies are in the pipeline.


			Originally published in Yale Medicine, Summer 2002. Copyright © 2002 Yale University School of Medicine. All rights reserved.