The Founding of the Stanford Department of Neurobiology
By Nicholas Weiler
Introduction
The Department of Neurobiology at Stanford University was founded in October 1975, and was among the first departments of its kind in the world. In its first 10 years it quickly became a powerhouse in the field of neuroscience, and has since gone on to train scores of renowned scientists and produce hundreds of scientific discoveries about the nature of the brain and nervous system.
Looking back, the department’s success seems inevitable, but in fact it nearly fell apart before it began. And for all its influence on the burgeoning field of neuroscience, the department’s founding members say they never thought much about the impact their small department would have on the field. In the department’s “golden years,” they say, the passion for excellence and beauty in the pursuit of knowledge was what they cared for most.
What follows is a history of department’s founding and first decade as recalled by three of the department’s founders: Denis Baylor, Jack McMahan, and John Nicholls. More
Opportunity in Crisis
In the early 1970s, medical education at Stanford was in a funk. Medical students complained of inadequate instruction and the school suffered an exodus of senior clinical professors and researchers. Many departments repeatedly failed to name chairmen. The departments of anatomy and physiology — two of the pillars of medical research and education — had operated without the guidance of a chairman for 9 years. By the middle of the decade, the situation became so bad that medical students held public protests and the American Medical Association came close to putting the School of Medicine on probation.
The medical school’s administration knew they had to do something urgently to resolve the situation. “They decided to call in somebody to revitalize the whole system for the medical students,” Nicholls said. “And of course they wanted research at the same time because this isn’t Podunk University.”
Clayton Rich, newly hired as dean of the School of Medicine in 1971, was also keen to expand the school’s focus on brain research. There was already a small graduate program in Neurosciences, founded in 1963, but no central department to house neuroscience researchers. In a coup for Rich, the Sherman Fairchild Foundation donated $7.5 million in January of 1973 for a new Center for the Neurosciences at the medical school. Now all that was needed was someone to lead it.
Rich reached out to Stephen Kuffler, the influential Harvard neuroscientist who—in the mid-1960s—had famously succeeded in bringing together scientists from across the broad spectrum of brain research into a single department dedicated to understanding the workings of the nervous system, and coined the term neurobiology for his unified, multidisciplinary approach.
Kuffler declined Rich’s offer of a move to Stanford, but recommended that the school approach Maxwell Cowan, a South African neuroanatomist who had recently led the department of anatomy at Washington University to prominence, and was known for his invention of modern neuroanatomical tract tracing techniques and application of these techniques to numerous systems within the mammalian brain.
“Cowan was a well known and a very confident organizer,” Nicholls said, and immediately recognized Stanford’s crisis as an opportunity. “He said: ‘I’ll solve anatomy and physiology for you and make you one department. We will take care of the teaching, and the main focus of the research will be neurobiology,’” Nicholls recalls. “He would solve everything.”
The administration was impressed, and offered Cowan the chairmanship of a combined department of anatomy and physiology to be housed in the new Fairchild Center. Cowan, whose attention to detail was famous, began charting out space for 20 anatomy and physiology faculty in the new building and making elaborate plans ranging from large spaces for dissections of human cadavers to details of the equipment that would be needed for the department’s darkrooms.
Hopes for the new department and center for neurosciences were high: In an October 1973 statement announcing Cowan’s appointment, Dean Rich wrote:
“We believe that a major frontier for important scientific advances in the next decade will be the field of neurosciences—the search for better understanding of the brain and nervous system, intellectual processes, and mental disorders.
“Because of this fine appointment, construction of the Fairchild Center, and an opportunity to attract additional outstanding faculty members, Stanford is in a unique position to advance the study of the brain.”
A Vision for Neurobiology
First on Cowan’s list of faculty to recruit to the new department was Eric Shooter, a highly respected neuroscientist in Stanford’s powerhouse departments of biochemistry and genetics. Shooter was widely admired for the elegance of his research, his inspiring strength of character and his warm and generous personality.
A chemist by training, Shooter had become passionately curious about how the structure of proteins determined their function and had published important work on the genetics of hemoglobin as a lecturer at University College London before moving to Stanford in 1963. By the early 1970s, Shooter was using all the biochemical tools at his disposal to purify and characterize nerve growth factor, a protein discovered by Stanley Cohen and Rita Levi-Montalcini in the 1950s that seemed to hold the key to understanding the early growth and development of the nervous system.
Cowan next recruited John Nicholls, a leading neurophysiologist in Kuffler’s neurobiology department at Harvard who was well known as a dynamic and inspiring teacher. Nicholls—an Englishman like Shooter—had worked with the great physiologist Bernard Katz at University College London before making a pilgrimage to Harvard as a research fellow in 1960. He had become a professor of physiology at Yale then returned to Harvard as a professor of neurobiology in 1968. By the early ‘70s, Nicholls was in the midst of a series of influential experiments to explore how the relatively simple nervous system of the medicinal leech confers upon the blood-sucking invertebrate the ability to sense touch and respond to danger.
Nicholls leapt at the chance to move to California and to work with Shooter, whom he greatly admired, and immediately recommended two former colleagues as ideal recruits for the new department: Baylor and McMahan.
Baylor had been a postdoctoral researcher with Nicholls at Yale, where they collaborated on important studies on the leech nervous system. Baylor had since taken a position at the University of Colorado Medical Center, where he had begun to create new methods for recording electrical activity in the retina of the turtle, techniques which he and his team would soon use at Stanford to crack wide open our understanding of how retinal rod and cone cells transform light into electrical nerve impulses.
Baylor had begun to feel claustrophobic at the University of Colorado and was impressed by Stanford’s commitment to top-notch science. On a visit to campus, he recalls, “At some point Dean Rich said to me, ‘What you’re expected to do out here, son, is have excellence in research and teaching.” And I thought, my God, I’ve never heard this before. This is a different kind of place that somebody talks about excellence. That more or less sold me.”
For his part, McMahan had spent the previous decade developing new microscopic tools to study the fine structure of synaptic contacts between nerves and muscles in animals such as the frog, leech, and mudpuppy. After several years as a lecturer at Yale, where he had overlapped with Nicholls and Baylor, he had moved to Kuffler’s department at Harvard.
When Cowan attempted to recruit him to Stanford, in the early 1970s, McMahan was tempted, but was loath to leave Kuffler’s department. “I was very happy at Harvard — I loved the department,” he said. He greatly admired all the members of the faculty there, especially his mentor, Kuffler.
So, for the time being, McMahan declined Cowan’s invitation. But it would only be a few years before everything had changed and McMahan considered the move again.
The Vision Totters
By the fall of 1973 Cowan had sold his home in St. Louis and moved to Stanford, where he began to look for a house while preparing to build out the rest of the new joint department. Nicholls had also arrived and begun setting up his research in the Fleischman labs at the medical school.
Then, in early November, just two weeks after Dean Rich had formally announced the creation of the new joint department and Cowan’s appointment as chair, Cowan announced to his colleagues that he was leaving.
Nicholls and Baylor each recall getting phone calls from Cowan on a Friday afternoon, announcing he was through with the whole project, claiming that Stanford had acted in bad faith by refusing him the sole discretion to make faculty appointments in the new department. The next week it was announced that Cowan was returning to Washington University as chair of a freshly renamed department of Anatomy and Neurobiology.
Cowan’s sudden departure seemed likely to scuttle the whole enterprise of joining anatomy and physiology at Stanford. “The administrators looked around and thought, maybe this is all crazy,” Baylor recalls.
A committee was quickly assembled to decide what to do next and see if a new chairman could be found to pursue Cowan’s grand vision.
Nicholls was convinced from the start that Shooter was the ideal man for the job. Shooter was the director of the interdepartmental neurosciences PhD program. He was a prominent scientist, thoughtful, kind, a strategic thinker, and well-respected by Stanford’s powerhouse biochemistry and genetics departments, which would soon play such a transformative role in the genomic revolution of the 1980s and ‘90s. But other members of the committee, Nicholls recalls, were adamantly opposed to Shooter’s appointment.
In particular, key neuroscience researchers from other departments were outraged by Shooter’s insistence that the new Neurobiology department would be closed to joint appointments. Shooter felt that dozens of shared faculty members would hopelessly dilute the departmental culture and mission that he hoped to instill. But to others, it smacked of exclusivity. Shooter stood firm on this point, and so the committee was deadlocked, and remained so for nearly two years.
“We were continually stymied,” Nicholls recalls. “We had to go through this list of people — we interviewed Dick Bunge, Geoff Burnstock, Bob Martin, Chuck Stevens. Those are the ones I remember. Fortunately none of them wanted the job. They said it’s unmanageable.”
Surprisingly, recalls Baylor, who arrived at Stanford in 1974 and set up alongside Nicholls in the Fleischman labs, this time of uncertainty was actually an idyllic period: “We both said, ‘Look, what could be better? These are lovely labs. We have the space that we need. We can get on with our research. Stanford’s a beautiful place. Something good will happen.’”
After many months of wrangling, Nicholls said, it became clear to most of the committee that a new strategy was needed. Nicholls, Shooter, Joshua Lederberg of the department of genetics, and Arthur Kornberg of the department of biochemistry sat down to come up with a new concept.
They would discard the grand vision of a combining anatomy and physiology department, and instead create two new departments to occupy the Fairchild building. Shooter would lead a new department of neurobiology, and Lubert Stryer, a biochemist who had been recruited away to Yale in 1969 and whom the university was eager to lure back, would be chair of a reorganized department of structural anatomy. Physiology would be folded into the department of medicine, and the new departments would share the responsibility for improving medical education.
It was with this compromise that the Neurobiology department was officially created in October of 1975.
Building the Department: A Research Family
The founders very consciously wanted build a small, collegial, family-like culture in the department. For this reason, the department has maintained a maximum of only eight researchers for most of its history. “Our great advantage was that we didn’t have more space here.” Nicholls said. “If you have more space, you lose intimacy. Calling somebody into your lab when you’re doing something nice and being called into other labs can only happen in a smallish place.”
The founders also agreed that they wanted to recruit colleagues who valued a particular style of focused, problem-oriented research in small labs where the faculty were able to actively engage themselves in the day-to-day labor of research. But they also agreed that the department would hire new faculty not just for their scientific brilliance, but also for their shared humanity and devotion to common values.
“They had to be people with whom you’d get on and you wouldn’t fight, and they wouldn’t bear grudges,” Nicholls said. “And nobody would despise anybody else and think they were better than them.”
McMahan was the first new recruit to the department. He had visited after Shooter took charge of the department and been impressed with both the people and the place. Torsten Wiesel, his chairman at Harvard, told him he might as well go West, as Harvard was not likely to make any tenured appointments for another ten years. So McMahan took the leap.
McMahan arrived in 1977, just as the department was moving into the newly completed Fairchild building. He had just published groundbreaking studies of how molecular scaffolding allowed damaged nerve fibers to regrow to their active sites at the nerve-muscle junction and restore muscle function. He continued to explore the structure and function of the nerve-muscle junction using electron and light microscopy, eventually borrowing tools from biochemistry to demonstrate conclusively that motor neurons secrete a molecule called agrin, which instructs muscle cells to build the junction needed to receive nerve inputs.
The same year, the department hired Bruce Wallace, a post-doc of Nicholls’ who initially continued his work on the leech, but became increasingly interested in McMahan’s work on the early development of the neuromuscular junction. In 1985, midway through his assistant professorship, Wallace stepped aside from the academic ladder to become a senior researcher in McMahan’s group, beginning a long and fruitful collaboration.
As the department began searching for its next new recruits, Nicholls in particular lobbied for researchers who would extend the department’s research into the brain itself. The department’s first foray into the central nervous system came with the appointment of Carla Shatz in 1978, who had worked with David Hubel and Torsten Wiesel at Harvard, exploring how a genetic mutation (in Siamese cats), known to derail connections from the eye to the brain, affects the functional and anatomical organization of the visual cortex.
“Carla was a dream recruit…who could be better?” Nicholls recalls. Building a great neurobiology department at that time required strength in the visual system, he observed: “Nobody except visual people could tell you how the brain was really working.”
The department’s next hire, in 1979, came from an unexpected direction. On a seminar visit to Caltech, Baylor encountered Eric Knudsen, who was doing postdoctoral research on how barn owls identify the source of a sound in space based on timing differences between their two ears.
Knudsen’s work was really out there at a time when most neuroscientists other than Hubel and Wiesel were still focused on the peripheral nervous system of invertebrates, Baylor recalls. “Nobody important was working on the ear at the time. Almost nobody was working on the central nervous system at the time,” he said. “But the science was just terrific. And he just seemed so brilliant and interesting.”
So Baylor invited Knudsen to visit Stanford and the rest of the department was equally impressed. “We said, okay, let’s hire the guy,” Baylor recalls, “and the rest is history.”
Shatz and Knudsen, the department’s first two hires, became part of a new wave of systems neurobiologists in the 1980s, and produced ground-breaking discoveries about the organization, and plasticity of the visual and auditory systems. Both continue to be leaders of Stanford’s neurobiology community to this day.
Foundational Values: Teaching the Next Generation
Shooter remained chair of the fledgling department for its first ten years and quickly established himself as a strong and devoted leader. He protected his faculty members from most onerous academic obligations such as committee memberships and struggles for funding, enabling them to focus purely on their research and teaching.
“He did it all. He did everything,” McMahan recalls. “And the amount of money he brought into the department through grants and from outside the university was an amazing accomplishment. So, we were all protected from that.”
At the time the department was founded, Shooter was also the head of Stanford’s interdepartmental neuroscience PhD program, and made the decision that the new neurobiology department would not issue its own degrees, but would be a key resource in training PhD students in neuroscience working in labs across the university. This interdepartmental form of graduate training established a model that most elite neuroscience programs follow today.
Video: Baylor / McMahan on Shooter
At the heart of it all, Nicholls says, was the teaching. Founded as it was in the midst of a crisis involving the training of medical students, the founders all agreed that teaching would not be an obligation to be phoned in, but a key driver of the department’s activities.
“The medical school is there for the students,” Nicholls said. “And so I thought I would try and teach well. And I saw that by teaching seriously and doing it well, it made a difference to the whole department.”
At Stanford, Nicholls spearheaded the development of a new course called Neurobiology 200 for medical students, which combined lectures, weekly discussion sections with the professors, and demonstrations of cutting-edge experimental techniques. With the addition of expanded anatomy content some years later by McMahan and Shatz, this course became the foundational Neurobiology 206 course taught to Stanford graduate students and medical students to this day.
The faculty also put on public demonstrations of experimental techniques in neuroscience, ranging from electrical recordings to stained samples of brain tissue that could be viewed by microscope. “That was definitely generating good will and convincing people to buy into neurobiology,” Baylor said. “I think it established credibility that these guys giving the lectures might actually know what they’re talking about.”
“The idea was, look, you teach well. You don’t blow it off and try to get on with your research and ignore the teaching,” Baylor recalls. As a result, he said, “the students loved it. They knew that this was the good stuff that they were getting.”
But there was more to it than just impressing medical students. “Teaching is the glue that holds the department together,” Nicholls said. “If you take it seriously and go to each other’s lectures, you see colleagues in a completely different light.”
In addition to their common values and the shared responsibility of teaching, a final important way in which the department’s faculty members were bound together into a scientific family was the departmental lab dinners, a tradition borrowed from Kuffler’s department at Harvard, which continues at Stanford to this day. Once a month, one lab would host a dinner at which students and post-docs would present the group’s most recent work to the rest of the department. These evenings were an important opportunity to catch up on other department members’ work, but also served as a spur to researchers eager to impress their colleagues.
Generally, the mood was “serious, searching and unaggressive,” Nicholls recalls, “and also partly festive with the food and stuff.” Nicholls recalls fondly his favorite lab evening tradition: “When it was my turn, I’d always have Kentucky Fried Chicken. Other people would have brought pizza and stuff, and they would say, ‘KFC, what kind of stuff are you feeding us?’ But it always went before anything else.”
Video: Baylor/McMahan on Nicholls, Nicholls on Lab Evenings
Video (Supplement): Nicholls on Teaching
Foundational Values: Getting it Right
Beyond building a collegial department and staying grounded and connected to one another’s work through teaching and lab evenings, there was another fundamental value that epitomized the early days of the department and what the founders were trying to build.
“The first ingredient of good work is that it’s right,” Nicholls said. “The minimum requirement is that if you do these experiments and get these results, somebody doing the same experiments in the same way will get similar results.”
As fundamental as it sounds, Nicholls said, the commitment to being absolutely certain one is right about the science seems to have fallen out of fashion in modern science, though he declined to name names: “I can think of people today who are in fantastically high positions who have gotten their results completely wrong,” he said. “They go ahead and move on to the next project and leave others to mop up behind them. Nowadays that’s a good way to get fame, it’s a good way to get success; make mistakes, and let other people correct them. But we didn’t want that.”
Getting the work right, Nicholls and the other founders said, meant doing it yourself, thinking of all kinds of reasons why you might be wrong, and developing your own tools and techniques to test your ideas with incontrovertible rigor.
McMahan gives the following example:
“In the 1980s my lab was trying to uncover how nerves tell muscles to form the post-synaptic apparatus crucial for neuromuscular transmission. There were several labs working it on the time, but we didn’t think that they were looking at it in the right way.
“We did our experiments in a very painstaking and slow way to make sure that we were really following the right leads all the time. All through the 1980s we’d come in every day, excited that we’d see little bits of progress because we knew every little bit of progress that we made was right. We were ready the whole time to drop the project in an instant if we came up with evidence that we were beginning to drift off in the wrong direction.
“It took a decade to get there, but one day we finally knew. We had established that the nerve releases a particular protein, which we named Agrin, and this triggers the formation of the post-synaptic apparatus. We realized that this was going to open up the whole field of the development of the neuromuscular synapse. Now many labs around the world have studied Agrin and used it to help explain the cause of diseases like myasthenia gravis. I must say that I still have dreams about that day—that moment that we realized that we really had it.”
Video: (Supplement) McMahan on Early Days of Agrin
It was a style of doing science, the founders said, that recognized that only after laboring carefully to build a perfectly sturdy edifice for many years do you have the opportunity to hope for a truly transcendent discovery, which was of course the implicit goal all the department’s founders had for their work. “You can’t deliberately set out to do something beautiful, of course,” Nicholls said. But after long years of careful labor, pursuing one’s curiosity with firmness and rigor, “you can hope that perhaps it may be beautiful one day.”
Video: Nicholls on Beauty and Getting it Right
The “Golden Age”
Looking back, the founders all speak of a “golden age” of the department, from just before its founding in 1975 and lasting into the early 1980s. Though aware that some of this period’s recalled glory is undoubtedly the gilding of memory, all recall a sense of excitement, infinite possibility, and the joy of doing good and important work with a family of colleagues who were all on the trail of something true and potentially beautiful.
By the early 1980s it was clear that the department’s good work and its well-trained graduates were having an impact on the field: “The people that this department sent out into the world were terrific, and it got out into the grapevine.” Baylor said. “People that trained at Stanford, they end up doing well.”
And despite the department’s growing success, its founders say they never thought much about their impact on the field, or something as lasting as a scientific legacy: “We just thought—or at least I did—about having fun doing science,” McMahan recalls. “It wasn’t hard to get money. It wasn’t hard to get papers published. We were just having fun. And I think we all said it at one time or another, ‘If we didn’t get paid to do this, we would pay to do it.’”
The founders shared the belief that their slow and steady chipping away at the basic principles of nervous system function would one day lead to a transformative understanding of the brain’s higher workings, Baylor said, when the most seemingly intractable neurological and psychiatric diseases would suddenly become tractable. “Of course, it hasn’t happened yet,” he added, “but I have no doubt that it’s coming. It’s going to change our understanding of the human condition in a profound and revolutionary way. And it’s going to be as a result of these bricks that were put in the foundation by the kind of fundamental research that has been going on in this department for 40 years.”
This shared sense of joyful dedication to the slow pursuit of truth is what the founders felt was best about their era, and what made the Stanford Neurobiology Department such a success.
They worry, however, that such a happy “family operation” would be difficult to pull off in the hypercompetitive scientific world of today. In decades past, writing grant applications was an occasional and refreshing opportunity to step back and see the big picture, the founders recall, but they never worried about getting the money. Today, in contrast, the stress of competing for increasingly scarce funds has forced brilliant scientists to spend the bulk of their time writing grants and traveling around to “sell” their research, rather than working with their own hands in the lab. (see Alberts et al. PNAS 2014)
Universities and funding agencies, the founders feel, have lost the will to support slow, steady progress towards long-term scientific goals, and now reward those who employ armies of junior researchers to quickly churn out exciting but frequently shaky results, and hype their work in a way that seems undignified at best to the older generation of scientists. As a result, the founders worry that many promising young researchers are dropping out of science altogether and those who remain are more likely to compete with their colleagues than build a community of trust and mutual respect.
But ultimately, they agreed, the best scientists still do their work because they value truth and beauty, and these are the things that will win out in the end: “Ultimately I think the field will be fine,” McMahan said. “Young people are going to work out how to succeed. They’re all in this together, and they’ll sort through the mess. It’s always kind of been a mess, but there are some eternal truths. And that is that truth always wins out, that quality always wins out. That it’s extremely important to get the story right.”
Video: All on “golden age”, then vs. now
The Department of Neurobiology Today
By Bill Newsome
The Department of Neurobiology at Stanford turned 40 years old during the writing of this article. In these four decades, many of the foundational values put in place by Shooter, Nicholls, Baylor and McMahan have endured and proven to be a source of great strength .The department has remained small (9.5 faculty as of December 2015), allowing faculty to make most decisions by consensus and contributing to a genuine sense of community. The lab evening tradition continues to promote regular, open discussion of the research being performed within the department, and to provide trainees with an opportunity to practice clear, concise talks for a general neurobiology audience. The Neurobiology 206 course, Principles of Neurobiology, is still taught to medical and graduate students and continues to build on the structure laid down in the formative years of the department. Sadly most faculty no longer have time to attend one anothers’ lectures.
Most importantly, the department still adheres to the founding value of “getting the story right.” This core value is reflected in numerous aspects of departmental life: careful hiring and promotion of outstanding faculty, teaching talented trainees to pursue important scientific questions and value rigorous, replicable results, and critical but supportive discussion of lab evening presentations.
Of course, much has changed as well. Neuroscience is a dynamic field that promises answers to age-old question about the human mind as well as new treatments and even cures for devastating neurological and psychiatric diseases. Many of the brightest young minds from many disciplines—engineering, physics, chemistry, and psychology as well as the traditional biological sciences—are attracted to this growing field of research. Future progress in understanding the workings of the brain will depend on blending concepts and technical approaches from fields far more diverse than in the past. To take advantage of these new intellectual opportunities, the Department of Neurobiology is considering expanding to include more diverse faculty members and is incorporating interdisciplinary perspectives through courtesy appointments of faculty from Electrical Engineering and Applied Physics—a substantive departure from past practice.
Since the 1970s, public financial support for science has not kept up with the rapid growth of the scientific enterprise. In just the past 10 years, the real purchasing power of the National Institutes of Health has declined by 20 percent, creating anxiety at all levels about professional futures in biomedical research. Department of Neurobiology faculty are not immune to the financial pressures that are affecting the scientific research culture across the nation. Current faculty spend far more time pursuing funding than did the founders, which detracts from their opportunity to be involved in “hands-on” science. This financial pressure also feeds the general hypercompetitive atmosphere that risks rewarding slipshod methods and salesmanship over rigorous scientific work that generates true progress.
Now more than ever, the Department of Neurobiology aims to remain true to its core values of scientific integrity, taking the time to get the story right, delighting in the success of every department member regardless of rank, and maintaining perspective to have fun along the way. Even in rapidly changing times, the founders and their values infuse our departmental culture. We are deeply grateful for that legacy.
Founders Interview for Neurobiology Department
Selected Sources
SUMC Press Release 10-22-75
Stanford Daily 01-18-1973, 05-10-74, 06-25-1976,
Schulman Graduate Program History ~1996
Rich letter to Executive Committee 11-08-1973
Neurochemical Research, Vol 12, No 10, 1987 – dedication essay to Shooter and Varon
Cowan obituary by Van Essen & Price, 2002