Volume 16 Number 3, SPRING 1999

frankly optimistic

DEAN EUGENE BAUER'S CANDOR AND OPTIMISM

HAVE WON HIM THE APPRECIATION OF HIS COLLEAGUES.

TOGETHER THEY'RE READYING

STANFORD UNIVERSITY SCHOOL OF MEDICINE

FOR THE 21ST CENTURY.

By Evelyn Strauss

Instead of power red or subtle blue silk, Eugene Bauer has chosen frogs for his tie. White, green and red amphibians sit on leaves or hop about. Some, apparently anxious to get on with their lives, are wearing crowns. This nod toward whimsy (and visual reference to his early research subjects) is just one indication that his position as dean of Stanford's medical school has not propelled Bauer into a pretentious state.

Bauer has built a successful academic career. With his wife Gloria and their four children he has created a loving family. And with two business partners he has launched Connetics Corp., a biotech company specializing in therapeutics for skin and rheumatologic diseases -- taking the company public in 30 months.

Still, Bauer refuses to allow his story to read like a fairy tale. Experience, he says, has taught him the value of attending to life's darker passages. With characteristic candor, he insists that his family's encounter with alcoholism and drug addiction be included in the narrative.

"The genetics of addiction are strong in our family," says Bauer. Shortly after Bauer started his job at Stanford in 1988, first Gloria and then several other family members revealed that they were struggling with alcohol and drug addiction. With the substance abuse problems in the open, the family began to heal; today the addictions no longer have the upper hand. "Going through recovery is very tough on everyone," he says. "One thing it has taught us, though, is that shying away from our problems, while extremely tempting, only leads to bigger problems. Our family is enormously grateful to the Stanford Alcohol and Drug Treatment Center."

The experience has strengthened his family and has vitalized his working relationships as well, says Bauer. "If I can be considered successful as a dean, I owe that success in a large part to being open and honest -- which is something I learned as a result of going through the process of Gloria's recovery from alcoholism," he says.

Bauer's honesty and irrepressible optimism in the face of adversity have won him the appreciation of his colleagues. And while Bauer is circumspect when it comes to touting his accomplishments, his colleagues are much more forthcoming. According to them, his leadership and personality style have sparked fresh ideas in the medical school and boosted confidence that these dreams might actually become reality. He has already helped shepherd the medical

center through the merger with the University of California at San Francisco. Now he is busy promoting the unconventional interactions between people that he says will be key to stimulating cutting edge research projects in the 21st century.

NURTURING INSPIRATION

Like many people who excel, Bauer, 56, pays attention to what works. Even as an undergraduate at Northwestern University, pipetting away on his first research project, he recognized how the principal investigator in the lab fostered a stimulating environment. He was supportive, but hands-off, says Bauer. "He gave as much time and resources as people wanted, but left them alone to struggle with their problems." Bauer has carried that leadership model through his career. "If you put talented people in the right environment, they'll be incredibly creative," he says. During his seven-year stint as chair of the Dermatology Department at Stanford, he used those principles to "recruit and attract a talented group of young investigators and see them succeed," he says. Now as the School of Medicine's dean and the Carl and Elizabeth Naumann Professor, he's trying to make a similar contribution to the medical school, relying on the same philosophy.

So far, so good. It's easy to find people bubbling with enthusiasm for Bauer and his approach. "He's a really positive-thinking person and he's encouraging," says Suzanne Pfeffer, PhD, professor of biochemistry, who became chair of the department in September. "He's given the department chair the impression that if anyone has a good idea for a new program in the medical school, he'll help make it happen. He's providing a sense of tremendous optimism."

Bauer has apparently accomplished this in part by making himself accessible. "I never have trouble getting a hold of him," says Pfeffer. "He responds to e-mail. That's refreshing." He not only listens, but gets involved in solving problems. "I go in and talk to Gene; I'm able to flit from topic to topic, and he doesn't miss a beat," says William Mobley, MD, PhD, chair of the Department of Neurology and Neurological Sciences and John E. Cahill Family Professor. "He knows exactly what I'm talking about and he has actually thought about it. He always offers good advice even though it's specific to me and my department."

As Bauer navigates what must often amount to conflicting needs and desires among different people and departments, he has managed to win people's trust. "Gene honors his agreements," says Mobley. This confidence in Bauer's integrity seems widespread. "You never get fooled by him," says Judith Swain, MD, Arthur Bloomfield Professor of Medicine and chair of the Department of Medicine. "You always have a feeling that he's trying hard to make things work."

Indeed, Bauer is working hard. He meets with faculty members, department chairs, other university administrators, and UCSF people from 7 a.m. to 7 p.m. most days, and then attends official functions once or twice a week. He sleeps for only about four or five hours a night. "He just keeps chugging away," Mobley says. "He's able somehow to stay very fresh, probably because of his energy and outlook on life." Bauer says his greatest difficulty is when his colleagues don't see or respond to the big picture. "The hard part is when people behave selfishly and don't look at how their position might adversely affect the situation as a whole," he says.

Yet Bauer doesn't seem to think his job is as taxing as other people do. He says he stays on top of things in large part by keeping in touch. When he's out of town -- for business or pleasure -- his secretary sends him a fax every day. "That way I know there are no bombshells waiting for me," he says. Tension comes when he's disappointed in himself. "I feel stress when I don't feel as if I've done as good a job as can be expected."

The situation smacks of one of those happy arrangements in which everyone thinks that someone else is doing the hard part. "I feel incredibly privileged to be able to work with the talented people at Stanford," says Bauer. "Part of being the dean is trying to make sure of the best possible outcome for faculty and students. That's not something you can do from the top down. I don't have the answers. I have to listen to the people who do have the answers." His colleagues seem to have gotten that message. "He has been extremely open and receptive to input from the faculty," says James Spudich, PhD, professor of biochemistry. "At the same time, he's been a strong leader who has his own convictions as to where we should be going."

Although people glow with respect and affection for Bauer, they don't idolize or attribute magical powers to him. His colleagues simply seem to appreciate that he's got a difficult job and he's performing well. "You don't mind if your parents make mistakes once in a while if you know they're on your side and they mean well," says Spudich. "You don't even remember the screw-ups."

FROM TADPOLES TO TREATMENTS

Bauer wants Stanford to be a place where discoveries in basic science find practical application as clinical tools. He is especially equipped to understand how to make laboratory findings benefit patients, say his colleagues, because he has acquired such a strong background in both research and clinical medicine.

It almost didn't happen. Research so captivated Bauer that at one point, the bench nearly lured him away from medicine. About six months before he graduated from Northwestern University Medical School, he came close to quitting so he could train as a researcher. A faculty member talked him out of that idea, pointing out that he could master investigative skills later and it might not be wise to throw away the years he had invested in medical training. Still, that incident illustrates something about both Bauer's attraction to research and his innate flexibility. "Life's not linear," he says. "Every step along the way, life inserts vagaries, impediments, opportunities. As a result, you change directions."

In fact, this willingness to bend swung him onto a new and fruitful route early during his research career. He was studying the metamorphosis of tadpoles into frogs while he was a postdoctoral fellow at Washington University School of Medicine in St. Louis. At the center of tadpole morphogenesis lies a protein called collagenase, which helps reshape the growing animal by breaking down collagen, a predominant component of connective tissue. As tadpoles turn into frogs, they must dramatically resorb and remodel their tissue. Shortly before Bauer started his project, investigators isolated collagenase from humans and found that children with an inherited blistering skin disorder called epidermolysis bullosa (EB) had unusually high amounts of the enzyme. This observation caught Bauer's attention. "From tadpole metamorphosis I backed into human disease," he says.

Since that serendipitous start, he has "completely revolutionized our understanding of the disease," says Paul Khavari, MD, PhD, associate professor of dermatology and molecular pharmacology and chief of the dermatology service at the Veterans Affairs Palo Alto Health Care System. A number of proteins, including collagen, normally form a chain to connect the outer layer of skin with the underlying tissue layer. Bauer played a prominent role in figuring out that some of these proteins fall apart too easily in some patients with EB. As a result, the links break and the skin blisters.

Bauer characterized the proteins involved and correlated their absence with specific disease subtypes, says Khavari. In addition, he discovered a number of details about how the body degrades the proteins, a process that contributes to disease in some patients. "He's made fundamental scientific observations and has brought them directly to the realm of relevance for people," says Khavari.

Now that the EB group at Stanford is about to embark on the first clinical trials for treating the disorder, Bauer remains involved. The group plans to test the success of a gene therapy for the most severe subtype, in which children die in infancy or early childhood. "When they're alive, their skin pulls off like wet tissue paper at the slightest trauma," says Khavari. As soon as the patient is diagnosed, the researchers will harvest cells from the patient and insert into them a normal version of the gene that encodes the defective protein. Then they'll graft the cells back onto the patient. Bauer has provided strategic advice on how to achieve this goal on all levels: administrative, clinical, financial, regulatory and scientific, says Khavari. Echoing the comments of others, Khavari says Bauer has delivered on everything he has promised. "When he was appointed dean, it would have been easy for him to give up the effort to launch a gene therapy project for EB, but he didn't," says Khavari. "We wouldn't be in the position we're in now -- getting close to initiating human trials -- if it weren't for his unfailing effort. He doesn't micromanage, but when there's a key issue that needs to be addressed, he's there to help."

Although the practice of science feeds Bauer's intellectual curiosity, he says he had always been "casting about to do something more, an inclination to build something bigger for the future." That interest in exercising a wider range of his talents and interests led him into the "organizational and human resources part of science."

FORGING ALLIANCES

Bauer is trying to write some strong new themes into the tale of Stanford University School of Medicine. Among them is his interest in bringing people together in new ways. "The future of biomedical science is at the point where there's more room for collaborative, collegial relationships between basic and clinical science," he says. "If there are good will, common interests, and mutual benefits, collaborations will flourish."

He has been inspiring collaborations on a number of levels. He stresses that research requires a strong infrastructure, and says he is concerned that the federal government has lost sight of that in the last few years. In particular, he thinks it's important to build buildings and equipment that will foster interaction, but that aren't necessarily constructed with a particular research goal in mind. "We need to support core facilities that serve the needs of the community," he says. "Not every investment can be targeted to uncover the cause of cancer or any other specific disease." Because there's less federal money available for these purposes, he says, funding special equipment or even the "bricks and mortar" for new buildings is requiring an increasing amount of his attention. "At the local level, we have to figure out how to use available funds from discretionary sources to make sure the scientific infrastructure is what it needs to be, whether it's an NMR [nuclear magnetic resonance] facility or a zebrafish facility. Once it's in place, it's available to everyone and contributes to not just the needs of an individual investigator, but to the intellectual and scientific pursuits of the broader community."

Bauer is trying to weave his interdisciplinary philosophy into the fabric of the medical school by recruiting leaders who share his vision and by soliciting research fund gifts that specifically demand interactions between basic researchers and clinicians. Along these lines, Bauer has set up a new program -- the Interdisciplinary Research Initiative -- to which investigators can apply for funds for interdisciplinary projects, says Swain. The four-year grants of more than $500,000 a year are available through the School of Medicine's senior associate dean for research.

REACHING ACROSS CAMPUS

In addition to encouraging unconventional alliances within the School of Medicine, Bauer says the school has a unique opportunity because of its proximity to so many basic science departments on the main campus. "We're not blocks apart; we're yards apart. There's tremendous potential to create novel research programs. Stanford is one of the few places in the world that can provide an integrative approach with its scope of engineers, educators, computational scientists, physicians, and basic biologic and physical scientists. Ours is not an insular medical center. The university and medical school can contribute to -- and enrich -- one another."

Bauer is excited about a project on learning disorders, for example, that involves people from the School of Humanities and Sciences, the School of Engineering, the School of Education, as well as the School of Medicine. Another project, involving microbiologists, structural biologists, and clinicians has a goal of attacking the major world problem of hepatitis C. "These scientists would -- in the ordinary course of events -- not otherwise be working on this health issue," Bauer says.

One of the more ambitious projects, called BioX, aims to break down the barriers that have existed for years between different disciplines in science. "As the disciplines of physics, chemistry, biology, engineering and medicine have matured, there have been more and more reasons to have interdisciplinary interactions," says biochemistry professor Spudich, who co-heads the BioX Planning Committee. People in engineering, for example, interact with the clinical world to produce mechanical devices and biosensors for use in medicine. "This is not a new business," he says. "Obviously pacemakers and other such equipment have always required involvement outside the sphere of medicine. But the need is increasing a great deal." To address that need, BioX will literally bring together people from these disciplines into a new building that will act as a hub. "It will be a place to get people together and let new ideas surface as a result of the interaction."

OPENING MINDS

Bauer's penchant for combining different disciplines extends to teaching. "My research experience incredibly biased my way of looking at medical education," he says. Instead of sticking to the conventional approach of memorizing "volumes and volumes," he emphasizes the value of asking questions. "The goal of medical education is that our students leave knowing how to think, not what to think," he says. "The goal is not the diagnosis. It's the process you go through to move from a list of a patient's problems to solving them."

Bauer says he wants Stanford to create an environment that supports inquiry and education and that attracts the very best students and gives them the opportunity and flexibility to explore and follow their own interests and pursuits. "Overall, we hope to create the leaders in biomedicine of tomorrow," he says. Projects such as BioX, for example, generate novel educational opportunities for students, says Bauer. "We can expose young people to new ways of thinking about problems -- not just medical students and graduate students but undergraduate students as well."

Bauer has also provided more concrete support for students. For the first time, says Pfeffer, the dean's office is financially supporting graduate students. This has helped departments tremendously, she says, because NIH training grant stipends do not cover student costs. "He has raised specific funds to supplement the stipends so students can live in the Bay Area."

Khavari, whom Bauer recruited to Stanford as a PhD student after his residency, says Bauer is deeply committed to his role as a mentor. "He has a real generosity of spirit," says Khavari. Early during Khavari's training at Stanford, he sent Bauer an abstract he had submitted to a meeting, on which Khavari had listed Bauer as a co-author. "He said, 'My name shouldn't be on it. I didn't contribute enough scientifically to this,' " says Khavari. "He really tries to nurture young investigators, not just take credit."

Bauer's grounding as a basic researcher will prove invaluable in the next era of medical instruction, adds Khavari. "Every year medicine is more of a science and less of an art. Unless you understand the scientific basis of medicine, you'll miss educating the new generation properly. His vision is a very scientific one."

AND THEY ALL LIVED HAPPILY EVER AFTER?

What does someone do after figuring out the molecular mechanism of a disease, helping to find a possible way to cure it, and ushering a world class medical school into a new era? For one, he wants to create a center focused on alcohol and drug abuse that will integrate research, patient care and community outreach. "We must begin to remove the stigma from these diseases and bring them into the open," he says. "With new pharmacologic agents, the time is ripe."

Bauer says if he ever leaves Stanford, he'll go to biotech rather than to another academic institution because of his high regard for Stanford: He can't think of an academic institution with which he'd rather be affiliated. Maybe he'll use his time to write his version of "The Great American Novel." He hasn't yet mapped out the plot, but has filled a notebook with character sketches.

And there's always a good movie to watch. Bauer has collected 400 films from a wide variety of genres. He enjoys both escaping into the stories they depict, and analyzing how the cinematography creates a certain mood or atmosphere. "I think it's probably that I'm a visual person," he says. "Often I'll sit on airplanes and just watch a film without the headset. It forces me somehow inside the characters to pull out what's going on without the verbiage." One can't help wondering if that kind of attention to human interaction has something to do with his ability to inspire people and win their warmth and admiration as well as to help his family members heal.

Perhaps most important for Stanford, Bauer's diligence, enthusiasm and original thinking seem to catalyze positive plot developments even in the real world with all its imperfections -- making Stanford School of Medicine's story-in-progress seem rosy. "You just have a sense of possibility," says Pfeffer. "What could be better than that?" SM