stanford medicine


The Catalysts: by Calef Brown

The Catalysts

How the farm became a giant force in biology

It was 1959, and Stanford University Medical Center was just about ready to open its doors. For two years, microbiology department chair Arthur Kornberg, MD, and five of his faculty at the University of Washington in St. Louis had been getting ready — designing their new Stanford labs and planning a teaching program.

The group packed their equipment onto vans and headed west. Their students, secretaries and technicians, even a shop manager, all made the move as well. They were on their way to Stanford, where Kornberg would lead the biochemistry department and they’d spark biomedical innovation at the new medical campus.

Innovate they did. Upon discovering some air and gas vents that blocked shelf space, they simply unscrewed the fixtures and capped the protrusions. When it came time to test the new building’s gas lines, so many leaks sprang that the fire department had to be called in. Later that year, Kornberg won the Nobel Prize.

A new era had begun.

With the Bay Area’s biomedical industry thriving from as far back as most college students can remember, brilliant biology at Stanford seems as natural as blue skies in Palo Alto all summer long. But inevitable it wasn’t, says Paul Berg, PhD, a member of Kornberg’s original Stanford department, whose work in gene splicing technology led to the Nobel Prize in 1980. “It was planned,” says Berg.

Stanford’s leaders of the day were beginning to sow the seeds of Silicon Valley, and their vision included a powerhouse in biological sciences. They saw great potential in relocating the medical school’s clinical training program, which was in San Francisco, to a state-of-the-art medical center in Palo Alto, adjacent to Stanford University’s resources.

Before the move, the students spent their first year and a quarter on the Palo Alto campus taking traditional medical school science courses: anatomy, biochemistry, histology, medical microbiology and physiology. Their professors by and large were more inclined toward teaching than research.

Leading up to the move, the university’s president, Wallace Sterling, PhD, informed department heads they were expected to resign before the 1958 fall semester began. The medical school’s dean, Robert Alway, MD, went on to hire department chairs with research in their blood. Recruiting Kornberg, with his red-hot research, was a major coup.

True to the plan, the biochemistry department’s influence spread through the medical school. Stanford quickly acquired a reputation as a great place for basic science, where conversation and collaboration were encouraged, where resources were abundant and where researchers worked together in comradeship rather than competition.

Looking back to the department’s early days, Berg recalls the intensity of the interactions among the faculty, the excitement of sharing ideas and even reagents. “Departmental decisions were generally arrived at by consensus, not by a chairman’s fiat. The faculty took their teaching obligations very seriously and each of us was encouraged to sit in on each other’s lectures. Lab space was a shared resource: Students and postdocs were given a place to work but its location was not necessarily in the lab they were assigned to. It was an exciting way to do science.”

Today, biomedical leaders recognize the biochemistry department’s way as the ideal way to do science. Now institutions throughout the world try to foster interdisciplinary research, and Stanford hones new ways to expand on its success.

A good start

“One of the attractions of coming to Stanford was that we were given free rein in designing our own department and a brand new curriculum,” says Berg. “We all moved out here at about the same time, and four of us moved into campus houses that were built before we arrived and are within a shout from each other. We still occupy the same houses, sharing social as well scientific lives.”

An infusion of young rising stars was matched by a surge of funds from the National Institutes of Health and other agencies, which allowed Stanford to compete for still more research funding and recruits, and garner a reputation as being the place for promising research. Income from federal grants increased almost sixfold within a decade. Emerging technology companies leased campus land, generating additional funds for the school to expand its programs. Virtually every department had at least one luminary in research, and Stanford positioned itself as a place where ideas — not traditions — were the driving force. Within 10 years of its move, Stanford was cited by the British Royal Commission on Medical Education as one of the most influential pacesetters in research and medical education.

“Kornberg created a nucleus of a culture where people felt free to explore. It was completely without boundaries, with shared resources and a real sense of collaboration. It’s tough to duplicate,” says Jeremy Berg, PhD, director of NIH’s National Institute of General Medical Sciences (and no relation to the biochemistry department’s Paul Berg).

By creating new departments, the medical school set itself up as fertile ground for science pioneers, says J. Rogers Hollingsworth, PhD, a University of Wisconsin history professor who studies how institutional organization influences scientific breakthroughs. “Stanford is an example of how strong leadership can transform a place,” he says. “Back in the late 1950s, these key leaders saw the relocation as a move with the potential of transformation. They were riding a wave, the timing was right, and they were very convincing about promoting Stanford as the best place to try something new.”

While Stanford was not alone in cultivating a rich environment for basic science, all the pieces were in place for the new medical school to excel, Hollingsworth says. In the biochemistry department, Kornberg discovered the enzymes responsible for DNA replication, while Paul Berg pioneered recombinant DNA technology. Dale Kaiser, PhD, took off exploring developmental biology and David Hogness, PhD, started working on Drosophila genetics — fields they helped found.

And with the genetics department just on the other side of a swinging door, collaborations were easy to start and maintain. The founder and chair of the fledgling genetics department — one of the first established in a medical school — was Joshua Lederberg, PhD. Another pivotal recruit, Lederberg had won the 1958 Nobel Prize for his discovery of how bacteria transfer genes, laying the groundwork for genetic engineering and modern biotechnology. He and Kornberg worked together to establish Stanford as a leader in biomedical research.

Staying loose

With so many faculty living on campus, and a relatively small medical center, members of the research community cross paths often, making it easy to strike up conversations and discuss projects. Stanford became known for promoting conversation and collaboration, the most powerful tools behind successful basic science. Communication among scientists is easy when there’s a strong sense of community.

“Many of us see each other all the time because our kids go to the same local school. We’ll be attending some parent event and people just start talking — very casual, very easy,” says John Boothroyd, PhD, a professor of immunology and microbiology and the medical school’s former senior associate dean for research and training. “A lot of science is being discussed during those concert intermissions and, as a result, you soon learn who’s the local expert in whatever. The culture is just more friendly, and it humanizes the process of making contacts.”

Boothroyd, who studies intracellular parasitism and protein trafficking, recalls a postdoctoral fellow in his lab who was interested in hypoxia — low-oxygen conditions. Because he had met the university’s top hypoxia researcher at their kids’ kindergarten activities, Boothroyd not only knew the right person to contact but was perfectly at ease making the call to connect the fellow.

But again, there’s been more than happenstance at work: The school’s leaders are working the collaborative angle.

One example is the school’s Beckman Center for Molecular and Genetic Medicine, established in 1989 and directed by Berg for more than 10 years. The building brings together basic scientists from many departments, and — following the template established by the department of biochemistry — scientists share resources like equipment for DNA sequencing and protein measurements, reducing competition for funds.

The university’s Bio-X program, launched 10 years ago, furthers this communal sensibility by merging bioengineering, biomedicine and biosciences programs from schools across the university. The initiative has led to more than 200 scientific partnerships in proteomics, genomics, protein engineering, regenerative medicine, molecular biology, signal processing and other multidisciplinary projects, and it awarded more than $70 million in its first two rounds of research grants and fellowships.

This program is one of several at the medical center emphasizing that independent research does not have to fall within a specific program or department. In the School of Medicine, 23 of the 105 faculty in basic science departments have a joint appointment in another department. Of these, 15 are in another basic science department and eight are in clinical departments.

“The faculty are not islands,” says Mark Schnitzer, PhD, an assistant professor of biological sciences and of applied physics, an HHMI investigator and a member of Bio-X. “There’s an exposure to other perspectives that lends itself to complementary projects. It’s part of the culture here — students move around and get to know each other in different environments. And a diverse lab benefits the faculty as well.”

Schnitzer’s lab, for example, uses imaging, electrophysiological, behavioral and computational strategies to understand the brain activity underlying learning and memory. His students and postdocs have backgrounds in physics, engineering, computer science, molecular biology, neurology, mathematics, biophysics and biomechanics.

That sense of having the freedom to explore is what attracted neuropathologist Marius Wernig, MD, to Stanford last September after five years at the Whitehead Institute for Biomedical Research in Boston. “I had always heard that Stanford was the MIT of the West Coast, but it’s clearly got a different atmosphere,” says Wernig, a member of the Stanford Stem Cell Biology and Regenerative Medicine Institute. “There’s an attitude that’s more collegial and an overall feeling that people seem to want to work together and get things done. People are going after the important scientific questions rather than focusing on outcomes.”

Investigators at Stanford have pioneered research in the neurophysiology of addiction, co-invented nuclear magnetic resonance technology for anatomical imaging, isolated nerve growth factor involved in the development of neurons, tracked the pathophysiology of sleep, and discovered the role of human leukocyte antigens in the immune system, a discovery that advanced tissue typing for organ transplant. Later researchers refined gene splicing, applied monoclonal antibodies as cancer treatments and isolated stem cells.

“Stanford is indeed one of the best research institutions in the world, remarkable for both its breadth and depth,” says structural biology professor Roger Kornberg, PhD, winner of the 2006 Nobel Prize in chemistry and one of Arthur Kornberg’s sons. “But competition is constantly increasing, as the numbers of scientists grow around the world. The challenge is to maintain the level of performance and productivity that has been achieved.”

The answer to that challenge, says Jeremy Berg of NIGMS, lies in the next generation of scientists and how they are trained to study the increasingly complex and interrelated questions of systems biology.

Of the more than 1,000 aspiring scientists who apply to Stanford’s bioscience PhD programs each year, only about 180 are accepted. More than half choose to attend — an impressive statistic since the top schools are all competing for the best students.

“The most important thing is the people, especially the graduate students and postdoctoral fellows,” says Kornberg. “They have been a major force behind the rise and continued success of the institution. Working closely together on problems of passionate interest to us, we have forged personal as well as scientific bonds, which will last for life.”

Graduate students in the biosciences take part in a rotation that places them in three different labs, which are not necessarily in the same department or even field of research.

“It’s truly amazing to see,” says Ben Barres, MD, PhD, a professor of developmental biology and of neurobiology. “They start going, ‘Hey, in so-and-so’s lab, we did this. Have you thought about trying it this way?’ It’s unavoidable for them to share new knowledge.”

“There’s no sense of turf here. For students especially, there are no closed doors,” says microbiologist Boothroyd, who also serves as associate vice provost for graduate education. “And with spectacular departments of chemistry, physics, computer science and all sorts of engineering right next door, each full of equally free-thinking students and postdocs, you’ve got a recipe for some really phenomenal collaborations.”

Stanford’s tried-and-true approach remains biology’s best hope, says Jeremy Berg. “Courtesy of the incredibly powerful tools available now, it’s clear that biology is more complicated than we ever imagined. Progress will depend on expanding on that basic pattern of community and trust,” he says.

The solution? “It’s actually pretty simple,” says Barres. “Put great people together and then get out of the way.”


By the Numbers

Stanford breeds astonishingly successful biomedical research. Factor in Stanford’s relatively small size — about 800 full-time medical faculty, compared with more than 2,500 at Johns Hopkins, and more than 8,000 at Harvard — and the record appears even more awesome.

• Three living medical school faculty hold Nobel Prizes.

• Over the past five years, Stanford faculty received 11 of the 62 National Institute of Health Director’s Pioneer Awards, highly competitive grants intended to support highly innovative investigators.

• Three Stanford investigators were among the 31 who received a 2008 NIH New Innovator Award.

• Stanford is home to 14 recipients of coveted awards from the Howard Hughes Medical Institute — one of the highest concentrations of HHMI investigators in the country.

• The National Research Council’s most recent (1995) assessment of academic research and doctorate programs ranked Stanford first in the top 15 U.S. universities for its number of programs and overall score. It ranked first in biological sciences, second in biochemistry, third in chemistry, fifth in neuroscience and in genetics, and sixth in cell biology. It ranked first in computer science and biostatistics. A new assessment is expected this fall.





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