Photograph by Art Streiber, ’84

A Leader in Full

As a scientist and as an executive, Marc Tessier-Lavigne has made a career out of making a difference.

Stanford Magazine
Published in
22 min readAug 30, 2016

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BY KEVIN COOL

One of the celebrated virtues of executive leadership in the 21st century is the willingness to be bold. In an age when disruption is always around the corner, calculated risk with large promise trumps cautious prudence that limits the downside. But someone has to walk out on that limb.

So when Rockefeller University was faced with reconciling its space needs with severe growth constraints, President Marc Tessier-Lavigne embraced an audacious plan. It involved prefabricating a large laboratory building as a series of steel modules — 19 in all, each weighing about 700 tons, shipping them to the Manhattan construction site via a barge up the East River, and setting them in place using an enormous crane, which was also on a barge in the river. If those logistical demands weren’t complicated enough, there was this: The building, three city blocks long, would sit astride FDR Drive, a New York City highway, forcing construction to be done in the middle of the night, when the road could be temporarily closed. It would be the most expensive project in the university’s history and require unprecedented fundraising success. Add to that a stew of stakeholder concerns and a tangle of permits needed from the city. As Rockefeller’s executive vice president, Timothy O’Connor, joked: “What could possibly go wrong?”

When the $500 million River Campus is completed, Rockefeller will have added about two acres to its campus, which is hemmed in by the East River on one side and by spectacularly expensive and seldom available real estate on the other. It will be, says O’Connor, “a transformative project,” not to mention an engineering marvel and an extraordinary example of modern leadership.

“It is very appropriately viewed as Marc’s project,” O’Connor notes.

And nobody seems surprised that Tessier-Lavigne was able to pull it off. Stanford’s 11th president, who took office on September 1, is an adventurous optimist whose indefatigable nature, intellectual prowess and management skills are a formidable combination, according to those who have worked closely with him. What’s more, says O’Connor, Stanford’s new leader is that rare individual who inspires both respect and affection. “You’re really going to like him.”

Not since Gerhard Casper was installed in 1992 has a new Stanford president required a lengthy introduction. Whereas Casper came from the University of Chicago and was virtually unknown to most people at Stanford, his successor, John Hennessy, had been a faculty member for 22 years, not to mention dean of the School of Engineering and provost, when he took over in 2000.

Now comes Tessier-Lavigne, a neuroscientist credited with pathbreaking discoveries who is also hailed for his two highly successful tenures as an executive, first at the drug company Genentech and then at Rockefeller, one of the world’s leading biomedical research institutions.

Although he is a relative newcomer, Tessier-Lavigne is no stranger to the Farm. He was a professor of biological sciences at Stanford from 2001 to 2005. (For two of those years, he was on leave.) He and his wife, Mary Hynes, have lived in the Bay Area on and off for 20 years. Hynes, also an esteemed neuroscientist whose work attempts to unravel the mysteries of Parkinson’s disease, led a small research group at Stanford for eight years before joining her husband at Rockefeller. (See sidebar below.) She will reopen her lab on the Farm this fall. Also this fall, the couple’s daughter, Ella, joins the freshman class of 2020. Ella applied and was admitted early decision last year, before her dad became a candidate for the Stanford presidency. To say she had the upper hand in setting some ground rules might be an understatement. “If I see her on campus, I’m not allowed to wave,” Tessier-Lavigne says, grinning.

He inherits an institution that is healthy and well-positioned. “The strength across all sectors of the academy and all of the schools is a sight to behold,” he says. “Thanks to the work of John Hennessy and John Etchemendy and their teams, the university has assumed a world-leading position.”

It’s too early to say with much specificity what he might do differently, or what goals he would establish in his first year as president, Tessier-Lavigne says. Ensuring that the university remains strong across the board will be important, he notes, “with particular attention to the importance and relevance of the humanities and the social sciences.”

For the first few months, he plans to listen a lot, and to learn. Much will be new to him, including the sheer scale of the university. (Rockefeller, small by design, has 175 students and fewer than 1,200 alumni.)

But Tessier-Lavigne brings skills, experience and a sensibility that those close to him — including several who have studied or worked at Stanford — say make him a good fit for a big job at a complex place. General Atlantic CEO Bill Ford, MBA ’87, has been a Rockefeller trustee for 10 years and vice chair of the board since 2015. He watched as Tessier-Lavigne energized the university with his ideas and enabled them with fundraising acumen and exceptional interpersonal skills. He expects he will do the same at Stanford. “To run a place like Stanford you need someone who can build genuine relationships with all constituencies, and I think that is one of Marc’s signature strengths. He is an authentic leader who builds great relationships with people who are very different.”

While leading Genentech’s drug discovery efforts, Tessier-Lavigne eventually oversaw 1,400 scientists whose work transformed oncology.

Ryan Watts, PhD ’04, collaborated with Tessier-Lavigne first as a teaching assistant at Stanford, later at Genentech and finally as a co-founder of Denali Therapeutics, a company aimed at developing drugs for neurological diseases. “I’m thrilled that a neuroscientist will be leading Stanford,” says Watts, who refers to himself as a “die-hard” alumnus. “But what’s interesting about Marc is that from the humanities to engineering and beyond, he thinks very broadly. He can lead any organization.”

Cori Bargmann, a neurobiologist at Rockefeller and a colleague of Tessier-Lavigne’s for 10 years at UCSF, sums up his credentials this way: “Brilliant. Fair. Genuinely interested in many things. Cares about people. And Canadian.”

Yes, Canadian. Tessier-Lavigne’s national origin — he was born in Trenton, Ontario — is more than a footnote in his biography, says Bargmann, only somewhat facetiously: “Anybody who is that accomplished and brilliant and also that humble, it has to be because he’s Canadian.”

Whether a product of geography or not, Tessier-Lavigne conducts himself with a gracious formality that seems almost anachronistic in this day and age. (During a photo shoot on campus in May, he went out of his way to shake hands and introduce himself to every member of the seven-person crew.)

Yet beneath that gentlemanly manner burns a relentless drive. “The guy is incredibly energetic; he’s always on the go,” says O’Connor. “Those of us closest to him initially wondered, ‘When is he going to run out of gas?’ ”

“He is extremely ambitious,” says Andrew Plump, chief medical and scientific officer of pharmaceutical company Takeda, who was a postdoctoral fellow in Tessier-Lavigne’s lab at UCSF and remains a good friend. “That can have a positive connotation or a negative one; in his case it is very positive. He wants to solve problems; he wants to contribute.”

Plump pauses for a moment trying to find the right adjective to describe his former mentor. “Earnest,” he says, nodding.

“That’s the word for Marc — earnest.”

Tessier-Lavigne grew up in a military family — his parents met while both were serving in the Canadian armed forces. As a result, his early childhood was punctuated by frequent moves, bouncing from Toronto to London to Brussels as his father took on new assignments. Between ages 6 and 9 he attended three different schools in three different countries, speaking two different languages. “That very rapid succession was hard,” he recalls. “You’re leaving your friends; you’re entering a classroom in which you don’t understand a word of what’s being said. But in each case I made friends; I found people who were welcoming.”

The crucible of serial transitions shaped him in some important ways. “It instilled a humility because you come to learn that not everyone views the world the way you do,” Tessier-Lavigne says. “And it stimulated my interest in many, many things. I’m just fascinated by the whole range of human experience.”

It also taught him not to fear change. “Change might seem scary, but it’s also a growth experience. I feel blessed to have had that experience. It fueled my optimism further. It made me love people and interacting with people. My upbringing really triggered a lot of that.”

As he and his siblings reached high school age, their father took a job with NATO so the family could remain in Brussels. Tessier-Lavigne went back to Canada to attend McGill University, becoming the first member of his immediate family to attend college. Soon after graduating in 1980, he made one of the pivotal decisions of his life. It came, of all places, on a boat ride.

He was 20 years old and headed to Oxford on a Rhodes scholarship. He had signed up to do a PhD in physics and had already selected a faculty mentor. His path was set.

In those days Rhodes recipients from North America met in New York and traveled together across the Atlantic on the Queen Elizabeth 2. The journey lasted the better part of a week. During it, says Tessier-Lavigne, “I met fascinating people, some of whom became long-term friends.” He was inspired by the breadth and variety of their interests, and by the time he disembarked from the QE2, his plan had changed. “Being exposed to those other people and having time to think made me realize I wasn’t in a rush.”

So the would-be physicist turned his gaze elsewhere. “They had this book that described all of the degrees,” he recalls, including an unusual one called PPP — a blended program that combined study in philosophy, physiology and psychology. Students were to take all three subjects and specialize in two. Typically, Tessier-Lavigne says, students chose philosophy and psychology. “That made sense — psychology and philosophy fit together. But I looked at this and saw my bookends — philosophy and biophysics.” So, although he had already earned a bachelor’s degree at McGill, Tessier-Lavigne switched from a PhD program in physics to an undergraduate program in philosophy and physiology. “I was the first person in living memory to take that combination,” he notes, “because it made no sense.”

BELGIAN STUDIES: Tessier-Lavigne, far right, attended high school in Brussels. (Photo: Courtesy Marc Tessier-Lavigne)

“I’m so glad I followed my instinct, because philosophy turned out to be one of the most important influences in my life.” Indeed, he says his exposure to philosophy — and the critical thinking skills that his humanities courses equipped him with — is a testament to the importance of providing all students with such experiences.

And when he took his first neuroscience course, he was smitten. “I was fascinated by the complexity of the brain.”

He went on to earn his doctorate in physiology at University College London and followed that with postdoctoral training in neurobiology, first at UCL and then at Columbia. It was at the latter that he met another postdoctoral fellow named Mary Hynes. Thus ensued a “romance over test tubes,” Tessier-Lavigne says.

“I thought he was cute when he wore his sneakers and brought me doughnuts,” Hynes says. “We were engaged eight months later.”

His first professional appointment was at UCSF in 1991 as an assistant professor of anatomy. He spent 10 years there, distinguished both by important breakthroughs and a growing reputation as a skilled and caring mentor. “The way he managed his lab was very different from any other brilliant scientist that I had encountered,” Andy Plump says. “They’re often a sort of absentminded professor type. Marc isn’t that at all — he is very attentive to people. He has high EQ, high IQ and high LQ — leadership quotient.”

Plump remembers one situation in particular that illustrated Tessier-Lavigne’s human-centered approach. In 1998, a couple of months after she earned her PhD at UCSF, 28-year-old Christine Mirzayan was murdered while walking home in Washington, D.C. Her fellow lab members were devastated. Tessier-Lavigne, who had been Mirzayan’s thesis adviser, shouldered the job of telling the others, Plump says. “He brought us all into a room and was able to balance his emotions — I’m sure he was deeply burdened and sad — to walk us through what had happened. He allowed us to be together and to go through that in a way that was necessary to begin healing. It showed just how deeply he understands people.”

As a scientist, he had few peers, says Cori Bargmann. He was the first to identify molecules responsible for guiding axons, the cables that neurons send out to make connections in the brain’s circuitry — a finding that cracked open an entire field of exploration. (See sidebar below.) In 1994, “after three years of backbreaking biochemistry,” says Bargmann, Tessier-Lavigne’s team was able to isolate the proteins involved in axon guidance.

His work provided a gateway for determining how neural circuits are assembled, helping efforts to regenerate circuits after injury and to stop neurological degeneration. “It is hard to overstate how little we knew when he started and how much he contributed,” says Bargmann.

He joined Stanford’s faculty in 2001. He remembers it as a rich and productive time. “Such a fabulous community and colleagues, and our lab was hitting on all cylinders,” he says.

ALL TOGETHER: Tessier-Lavigne, Hynes and their children, Christian, Kyle and Ella, vacationing in Prague. (Photo: Courtesy Mary Hynes)

Ryan Watts was a PhD student at the time and served as a teaching assistant for a neurobiology course taught by Tessier-Lavigne. “He had an instant impact on me,” says Watts. Tessier-Lavigne’s influence was such that Watts changed his career trajectory. He eschewed a postdoctoral fellowship and followed his mentor to Genentech, which eventually was purchased by pharmaceutical giant Roche. “I didn’t even think about going to industry until Marc was recruited to Genentech. I was like, what is Genentech? But I knew it must be something amazing if Marc went there. It was the best decision I ever made, mainly because I could continue to be influenced by Marc’s leadership.”

Leaving Stanford was difficult, Tessier-Lavigne acknowledges, but Genentech was especially appealing because it offered an opportunity “to apply science directly in ways that would help people; to develop therapies and cures for poorly treated diseases.”

During an eight-year period leading part then all of Genentech’s drug discovery efforts,Tessier-Lavigne eventually oversaw 1,400 scientists whose work transformed oncology with several new cancer drugs. Watts, who was one of those scientists, saw firsthand Tessier-Lavigne’s virtuoso leadership. “Marc can see scientific problems or organizational problems and synthesize with an incredible amount of depth in a short period of time what the problem is, and propose clear and tangible solutions.” His strategic guidance was critical to Genentech’s success, Watts says.

“There were great discoveries being made, but they weren’t necessarily being turned into drugs. Within a few years, Genentech became the number-one oncology company not only from the drugs that had been approved, but also from the robustness of the portfolio.”

‘What does better look like? What is better when you seem to be at the top? And how do we get there?’

Susan Desmond-Hellmann, now CEO of the Bill and Melinda Gates Foundation, was president of product development at Genentech when Tessier-Lavigne was there. Indeed, she helped recruit him to the company — not once, but twice, finally luring him from Stanford in 2003. Culturally, she says, Genentech’s research enterprise wasn’t all that different from academia — the company wanted its scientists to feel they were free to explore new terrain. But, she notes, the company also has “a finish line, which is the FDA saying that a drug is safe and effective for human use.” Tessier-Lavigne displayed the discipline, direction and leadership needed to ensure discoveries translated into drugs that helped patients, says Desmond-Hellmann. “What made him outstanding was his work ethic, his commitment to getting the right answer, his sense of purpose. His patience for detail and his stamina are really quite extraordinary.”

For his part, says Tessier-Lavigne, the Genentech experience was both fulfilling and an opportunity to stretch. “Private-sector experience helped me understand the importance of creating an environment of innovation and fostering collaboration,” he says. “In the private sector you see the power of teamwork. There are different centers of gravity in different places; professionals with very diverse backgrounds coming together to solve a problem. Figuring out how to do that — how to bring people together in a productive way rather than working at cross purposes because they speak different languages — that’s a very valuable experience for work in the academic sector, where of necessity we’re organized into schools and there can be less immediate interaction.”

He might never have left Genentech, he says, were it not for the fact that there is so much still to figure out, so much basic knowledge that’s needed to solve big problems. “I always saw academia and industry as a continuum of discovering new knowledge and then applying it to help people. But you can’t apply what you don’t know,” he says. Finding a cure or effective therapies for Alzheimer’s disease, for example, requires a much better understanding of how the brain works and what goes wrong in the disease. “It grew on me that where the need was greatest was in fundamental knowledge, and I could personally have a bigger impact in academia by helping stimulate the new generation of knowledge.” That insight, combined with his deep respect for Rockefeller University, led him to New York in 2011.

There are many ways to assess the performance of a university president. Fundraising success often tops the list, and in that regard Tessier-Lavigne was a star at Rockefeller, mobilizing support for a range of ambitious initiatives, including the River Campus. But according to Bill Ford, that is only the most visible aspect of the president’s imprint. Tessier-Lavigne led a strategic planning process that sought and got widespread input and buy-in, Ford says. One outcome of that process was a comprehensive plan to reform hiring practices with the aim of increasing faculty diversity.

Growing the number of female and minority faculty in STEM fields is a common aspiration among universities, but Tessier-Lavigne wanted more than lip service. “It wasn’t enough to have good intentions,” he says. “We needed a systematic process.” An aggressive outreach campaign bolstered the pool of candidates. Training sessions for interviewers addressed problems of unconscious bias. Initial interviews were conducted via Skype to augment traditional practices. The university’s day care facility was expanded, among other efforts, to make Rockefeller’s workplace even more family-friendly. The result: When Rockefeller extended offers for four faculty positions in the 2015–16 academic year, two went to women and one to an African-American man. All of them accepted.

Ursula von Rydingsvard has her own set of metrics, including how the community feels about a president. If the reactions to his departure are any indication, Tessier-Lavigne, with whom von Rydingsvard developed a strong friendship, was beloved. “We all are in mourning; there is no other word for it,” says von Rydingsvard, an acclaimed sculptor and the wife of Nobel laureate and Rockefeller professor Paul Greengard. (Coincidentally, Stanford recently commissioned her to do a sculpture that will be situated near the Quad.)

During a 30-minute interview in which she declares “there is a lot to say about this man,” von Rydingsvard unspools one story after another about acts of generosity and a personal style that, by her account, endeared Tessier-Lavigne to virtually everyone he encountered. Within weeks of arriving as president, he visited von Rydingsvard at her studio and attentively listened as she described her work, she recalls. “I was so moved by that.”

He and Mary regularly played host to gatherings at their home, inviting faculty, postdocs, heads of laboratories, curators from the city’s museums. They held Sunday brunches for PhD students. “It came from a deep desire to want to know these people better,” says von Rydingsvard.

Tim O’Connor marveled at Tessier-Lavigne’s ability to connect with people from every segment of the community, whether it was at an annual barbecue for security personnel or a Super Bowl party with university leaders. “One of the first things he did was go out and meet people where they were, at their workplaces,” O’Connor recalls.

And he was a pleasure to work with, O’Connor reports. Every Monday morning for the past three years, O’Connor sat down with Tessier-Lavigne to walk through what the president needed to deal with that week. Often, they were not happy topics. “I initially went into those meetings bracing myself because I was essentially taking bad news to the boss,” O’Connor says. “But every time, it was met with ‘OK, how do we fix it?’ Marc rolls up his sleeves and helps you solve the problem. Those meetings were the highlight of my week.”

ON THE JOB: Tessier-Lavigne will spend his first few months “listening and learning.” (Photo: Art Streiber, ’84)

Even on his way out, says von Rydingsvard, Tessier-Lavigne showed why the folks at Rockefeller were so sad to see him go. At his final Board of Trustees meeting, ostensibly to honor him for his service to Rockefeller, Tessier-Lavigne instead redirected the emphasis away from himself. He presented a sculpture — entitled Plate with Dots — that he and Mary had purchased from von Rydingsvard, and said he wished to donate it to the university.

Ford, who was there, said it was a powerful, emotional moment. “There were some tears shed,” he recalls.

“It was such a noble and considered way to say goodbye,” says von Rydingsvard.

As Tessier-Lavigne moves to the other side of the country, it’s not only a professional opportunity but also a chance for him and Mary to have their family closer together. Ella will be in the freshman class, and the couple’s son Kyle, 23, is a software engineer at Sighten, a San Francisco start-up. Their oldest son, Christian, 25, is completing an internship in cancer biology at Rockefeller. “I’m prouder of my family than anything else,” Tessier-Lavigne says. The entire family vacationed together in Yellowstone in August.

Tessier-Lavigne visited campus several times over the past few months to meet people and begin to assimilate. (He will bring his lab with him from Rockefeller to enable his current trainees to complete their studies, but he plans to wind down his research activities to concentrate on presidential duties.)

He knows he has a lot to learn. He hasn’t recently worked among undergraduates, although as the father of a current one, perhaps he has a leg up. He will be relating to a large, diverse and highly engaged alumni body. And he looks forward to immersing himself in intercollegiate athletics, a key part of Stanford’s identity and a powerful agent for alumni bonding. “This is a whole area that will be new to me, but I’m really excited about it,” he says. He has ample experience as a fan, having watched his kids compete in soccer, football, basketball, lacrosse and tennis. “I love sports; I love watching sports.”

Tessier-Lavigne professes a “deep reverence” for the work Stanford does and the mission it pursues. He lists a few of the areas that will occupy his attention in the coming years. Sustaining strength in research and teaching across all academic disciplines. Reaffirming the value of a liberal education. Preserving access for students of all means. Continuing efforts to diversify the faculty, staff and student body, and assuring a culture of inclusion. Managing twin pressures of constrained federal funding and uncertain financial markets. Charting future land-use needs.

He has his eye on the long view, to position the university “for maximum impact.”

“I’m excited about working with the community to build a vision for the next decade. What does better look like? What is better when you seem to be at the top? And how do we get there?

“I can’t wait to get started.” •

ARM IN ARM: Hynes and Tessier-Lavigne earlier this year in Austria. (Photo: Courtesy Mary Hynes)

IN A LEAGUE OF HER OWN

Mary Hynes, who returns to Stanford this fall along with her husband, Marc Tessier-Lavigne, has had a distinguished career as a neuroscientist. She is a leading expert on the development of dopaminergic neurons, critical nerve cells whose degeneration causes the symptoms of Parkinson’s disease.

She received her undergraduate degree from the University of Vermont and a PhD in neuroscience from the University of North Carolina. She held a postdoctoral fellowship in the Howard Hughes Medical Institute at Columbia University and performed additional postdoctoral work at Genentech. She then held positions at Genentech and at Renovis, before joining Stanford in 2003 as a senior research scientist.

In an email interview with Stanford, she discussed her future plans and her roles as a scientist, a presidential spouse and a mother of a Stanford undergraduate. This is an edited transcript.

What drew you to neuroscience?
I started as a psychology major interested in behavior and thought initially that I wanted to be a clinical psychologist. However, as an undergrad I had an amazing professor who taught a yearlong course on experimental neurobiology that inspired me. It was because of her that I decided to become an experimental neuroscientist.

What do you find most satisfying about it?
Like many scientists, what is most satisfying to me is the discovery of something new: You ask a question, and when the answer is clear, interesting and novel — well, there is nothing better than that.

You will be bringing your lab back to Stanford. How are you feeling about returning to the Farm?
Great; it will be fabulous. Stanford is an incredible place to do science, and I am anxious to get started.

Obviously it will be different because of Marc’s role and the presence of your daughter, Ella, as a Stanford freshman. What challenges do you anticipate? Will you have a different set of goals this time?
Well, funnily enough, our daughter was present on campus last time, too, in the Bing Nursery School and then at various camps. It will be fantastic to have her on campus, but of course we plan to let her have her own college life, as our sons did when they were far away at college. We have many friends who are either faculty at Stanford or who live nearby and have had children at Stanford, and it is a well-worn and happy path.

As for how it will be to be back with Marc’s new role: Yes, that will be different, but also very similar to his and my role at Rockefeller for the past five years. I think it works out really well. At Rockefeller, I was totally immersed in the day-to-day workings of the university, its science and culture, but I also got to experience the university from a 10,000-foot level. Both are interesting, and each benefits the other.

How do you and Marc balance your working lives with the demands
of family?
To be honest, my career has taken a backseat to the family for the past 15 years, and I made a conscious decision to do this. In 2001, when our daughter was 3 and our boys 8 and 10, I was offered a tenure-track position in neurology at Stanford, which I seriously considered but ultimately declined. I decided instead to run a small lab and work part time to make room for the kids and family. I was still working, but with a completely flexible schedule. I had time to be with the kids when they weren’t in school. I was also very active in their schools, particularly at the Nueva School in Hillsborough.

As our kids have gotten older, the fact that Marc and I are both scientists has made it really fun to discuss science with them — they have all spent time in biology labs.

I think the fact that I am a scientist allows
me to totally understand how busy Marc is at times. To succeed in science at the highest levels takes an incredible amount of determination and perseverance.

What are you grateful for, and what still feels unfulfilled?
Frankly, I am grateful for everything; nothing feels unfulfilled. All future endeavors and achievements are just icing on the cake.

UNCOVERING CLUES TO REWIRE THE BRAIN

In the developing brain, hundreds of billions of nerve cells, or neurons, must wire together into the precise circuits that allow us to move, think, feel and be. But how do all these neurons manage to make just the right connections? Marc Tessier-Lavigne has been trying to work out the molecular playbook his entire career. Contained in these blueprints may be the secrets to how to rewire an injured brain or spinal cord, or prevent brain degeneration during aging.

During development, newborn neurons send out long cables — called axons — to link with distant targets. For example, neurons that control movement extend their axons down to the spinal cord. That’s like sitting on the Stanford campus and reaching your hand all the way to Yosemite, explains biology professor Susan K. McConnell, who co-taught neural development with Tessier-Lavigne during his stint at Stanford in the early 2000s. “The axons behave as if they’re following some sort of highway or a set of road signs. But the molecular nature of those highways and road signs has been one of the big questions in neuroscience,” McConnell says.

Tessier-Lavigne broke open the field in 1994 when he became the first to identify one of the molecules that directs growing axons. Scientists had long suspected that axons follow a trail of diffusible chemical “smells” wafting from the target cells. “It’s similar to how you would find the garlic festival in Gilroy or the Cinnabon store in the mall,” McConnell explains. Tessier-Lavigne’s team set out to fish the chemical attractant out of ground-up cells from the nervous system. After three years of arduous work, they succeeded in isolating the proteins, which they named netrins, after the Sanskrit word netr, meaning “one who guides.”

The discovery of the netrins touched off a wave of exciting studies: In quick succession, Tessier-Lavigne and others identified several proteins that attract or repel axons, and figured out many of the rules for wiring the nervous system. For example, an axon’s journey is broken into many short segments, and axons can change how they respond to different cues from one segment to the next.

Tessier-Lavigne soon realized that his work might have practical applications: If you understand how nerve fibers grow, then you might be able to regrow them after injury. In humans, neurons in the central nervous system (the brain and spinal cord) don’t spontaneously rewire, but neurons in the periphery of the body do — for example, when someone loses a finger, doctors can sew the digit back on and it works fine. Some animals (such as fish and salamanders) can also regenerate spinal cords. Thus, coaxing a severed spinal cord to reconnect might just be a matter of providing the right molecular cues and conditions.

Several proteins appear to act as roadblocks to axon growth in the adult nervous system. By disabling these proteins, Tessier-Lavigne and others have spurred mammalian brain and spinal cord neurons to sprout axons in a petri dish.

The details of brain wiring are also relevant to neurodegenerative diseases, such as Alzheimer’s. The developing brain initially wires up an excess of axons, some of which are then pruned to refine the circuits. Tessier-Lavigne believes that the same biological pathways that mediate axon death in the embryo may be mistakenly reactivated in Alzheimer’s and Parkinson’s diseases. He has tried to identify the players responsible for neuronal death, as some of these may be targets for drugs.

During his tenure at Genentech, Tessier-Lavigne witnessed breakthroughs in cancer treatment that came from understanding the molecular nature of cancer. He hopes that a similar story is about to unfold for neurological diseases. — Kristin Sainani, MS ’99, PhD ’02

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