The legendary microbe hunter has helped launch the careers of more than 100 scientists, including those of several Stanford faculty members.
August 23, 2017 - By Kathy Zonana
When Stanley Falkow was awarded a National Medal of Science last year at the White House, he was lauded not only for “his monumental contributions toward understanding how microbes cause disease and resist the effects of antibiotics,” but also for a lesser-known, albeit perhaps equally significant, legacy: “his inspiring mentorship that created the field of molecular microbial pathogenesis.”
Over the course of his career, Falkow, PhD, a professor emeritus of microbiology and immunology at the School of Medicine, became known for his generosity and inspiration as an adviser to young researchers trying to forge careers in science.
He has mentored more than 100 graduate students and postdoctoral scholars in his lab. Three of them — Manuel Amieva, MD, PhD, associate professor of pediatrics and of microbiology and immunology; Denise Monack, PhD, professor of microbiology and immunology; and David Relman, MD, professor of medicine and of microbiology and immunology — have made their faculty careers at Stanford.
Although Falkow is quick to deflect any credit, these faculty members are deepening his legacy at Stanford in several ways: in the teaching of microbiology, in research that underscores the impact of microbes on human health, and in big, connect-the-dots ideas that bridge basic science and medicine.
The Robert W. and Vivian K. Cahill Professor in Cancer Research, Emeritus, Falkow “is one of the most generous people with his ideas and with his time and with his energy and of course with all of his other resources as well,” Relman said. “He never has done any of that giving with anything other than obvious evidence of joy. And it’s not just the joy of being a generous person, but the joy of sharing interesting ideas and having such a wonderful job, so that you can’t help but leave his room feeling like we are so lucky to get to think about these interesting questions and work with such great people and try to do useful things.”
But first, how not to mentor
Falkow’s journey to becoming a master mentor began with a mistake. He was in his first faculty job, at Georgetown University, and a former co-worker from Walter Reed Army Institute of Research had, at the urging of Falkow and others, just earned a PhD in a colleague’s lab.
“The day he got his degree, he walked into my office and said, ‘Falkow, I hope you’re satisfied, because this is for you and not for me,’” Falkow remembered. “I was stunned. And he said, ‘All I wanted to do was go into the lab every day, do experiments and go home, and now my life is ruined because I can’t go home and enjoy it.’”
Falkow would never again be so directive, or push someone toward an aspiration that might not be theirs. “I decided the best thing to do was to just listen,” he said. “And in the years when I listened, I listened very carefully to what my students said, and then I told them to do what they said they wanted to do. And they usually thought I was very wise.”
Amieva recalled visiting Falkow’s office as a postdoctoral scholar to talk about his research. “He would just listen and then he would make some insight that could have several meanings,” Amieva said. “It was almost like some parable. I would leave trying to figure out what he meant and spend the whole day doing it. It’s a technique he uses to make you think through things.”
On the side of microbes
Amieva was first inspired by Falkow during medical school. “I was a little bit disappointed with the classes in medical school; they were very dry and about all these facts, and I remember being a little bit angry about the lack of inspiration,” he said. “And then I took a class from Stanley Falkow.
“He would come in and tell all these amazing stories about microbes,” Amieva continued. “And he would say, ‘You know, I am on the side of the microbes.’”
Amieva joined Falkow’s lab as a postdoc after earning an MD and a PhD in cancer biology and completing a pediatrics residency and a fellowship in infectious diseases. “I realized that a lot of the best science comes from making connections between fields or looking at the same thing from a different focal point,” he said. During his postdoctoral training, he studied the relationship of Helicobacter pylori to its human hosts. “It had just been discovered that it had these little microneedles, and it injected a protein into the host cells, and it seemed like a form of communication between the bacteria and the host,” Amieva said. “That injection system and the protein were associated with cancer, so that kind of sold the project for me. But I was a little hesitant because I’m a pediatrician; this is a disease of adults.”
Soon enough, Amieva found himself on the side of the microbe. “As I started to study it, I realized that this is a pediatric infection,” he said. “We acquire it in childhood, and we really don’t know much about this interaction until some people get sick later on. And then I started realizing, ‘Oh, it’s been in humans since humans began.’ So it’s one of those few microbes that have really co-evolved with humans. The more I think about it, it’s the perfect microbe to study. It’s part of our normal microbiota, and it has some beneficial aspects, but it can turn nasty and lead to cancer, so it is in this balance between being a pathogen and being a commensal,” or symbiotic, organism, Amieva said. “And Stanley’s always asking these kinds of philosophical questions, like ‘What’s a pathogen?’ I’ve been trying to figure that out for H. pylorisince I was in his lab, and I think that’s led to a lot of adventures for my students.”
Falkow said, “Manuel and I share a great love of teaching. He mentors one-on-one and is very hands-on. And he is an exquisite teacher. To see him in a classroom is to understand seeing somebody at the center of their being.”
Amieva and his colleagues have revamped the microbiology course in which he and Falkow’s paths first crossed. “We made it a very modern flipped classroom, where students watch videos at home and then they come and do activities,” Amieva said. “Stanley is now one of our best facilitators. He’ll come and tell some story, like when he put poop in pills for patients before they went into the hospital [at Walter Reed], to prevent diarrhea — essentially, he started doing fecal transplants and got fired for it. Students love it.”
A ‘gentle shove’
Monack also makes sure Falkow stays in touch with students. His office is right outside hers. “Which I finagled,” she said. “He was sitting in some office in someone else’s lab and was kind of isolated. I knew if he was here and students had to walk through his office, he would like that. He loves it. And they love it. It’s perfect.”
It also gives Falkow an up-close view of how Monack mentors her students. “She does what I think is the most important thing: She has an open door,” he said. “The student comes and says they want to talk; she drops what she’s doing and invites them in if at all possible, closes the door and talks to them as long as they want. I saw her do it today.”
Monack and Falkow have been working together in close quarters since 1984, when Falkow hired her, fresh out of college at UC-Davis, as a lab technician. For the next 14 years, Monack managed Falkow’s lab and conducted her own research experiments, developing an animal model for pertussis and investigating host cells’ proclivity to commit suicide rather than be infected with salmonella.
“We had to learn more and more about the biology of animal cells and human cells, and it was a difficult transition, but we made it,” said Falkow. “And in no small measure thanks to her, because she was the common denominator through all these generations of students, and she was the giver of lore to the lab. It got to the point where if you wanted to know something, you asked Denise.”
That said, Falkow was concerned about his lab manager’s future. “She was able to publish, but she was stuck here, and there was no way for her to advance in the system,” he said. “She was basically giving away a lot of her knowledge and her skill to other people.”
It was time for what Falkow called a “gentle shove.” As Monack remembered it, “He said, ‘You know, Denise, I really think you, in the future, would be happiest if you got your PhD. When I go to the big petri dish in the sky, it’s going to be hard for you to find another position where you have the freedom that you’re used to, and you might be miserable.’ And I thought about this, and I realized, ‘He’s 100 percent right.’”
During graduate school at Stanford, Monack rotated through several faculty members’ labs, ultimately completing her PhD in Falkow’s. “I guess I had been brainwashed by then,” she said. She accepted a faculty position shortly after Falkow closed his lab in 2005.
Although he is reluctant to use the term “legacy,” Falkow will allow that Monack “shares something with me, and I’m very grateful for that.” And yet, he emphasizes, she has carried on her work investigating host-pathogen relationships with her own style. “She has her own personality of science,” he said. “It’s everything that you look for in a student that you train. You don’t want them to be clones of yourself — I don’t — it doesn’t behoove you. And she’s turning out students who are in their own right successful, and she takes great joy in their success.”
That, Monack said, is something she learned from her mentor. “I do think I’ve modeled my managing style after Stanley’s, and it clearly has worked for him. I give graduate students and postdocs a lot of freedom, but I monitor what they’re doing, and if they’re struggling, I help them. I think it’s best to allow people to be creative on their own. You get the best out of people when you make it clear that you trust them and you respect them.”
Curiosity and intuition
Relman was a postdoc in Falkow’s lab for 5½ years, until a faculty position opened up in the Division of Infectious Diseases. “Stanley always used to say he would have to take out adoption papers, because this was getting to be a bit long,” Relman said. It was a joke, but the familial regard was authentic. “He was warm and direct and funny and genuinely interested in me and in his people and in his role as a mentor,” Relman said. “But I realized that he didn’t view that relationship as a hierarchical one at all. It was his creation of an extended community with a familylike feel.”
Relman found the gateway to much of his life’s work one day when he and Falkow attended the weekly clinical conference of the infectious diseases division. The presenter was Lucy Tompkins, MD, PhD, the Lucy Becker Professor in Medicine and professor of microbiology and immunology. (She’s a Falkow lab alumna herself, and now his wife.)
“She was presenting an interesting case of a disease that clearly seemed to be caused by a bacterium, but no one had been able to grow this organism, and because of that, no one knew what it was, and the usual kinds of testings were all negative,” Relman remembered. “So Stanley said, listening and looking at these clumps of bacteria sitting in the spleen or liver, ‘There’s got to be a way to identify these things that doesn’t involve trying to cultivate them.’ So I said, ‘Well, I’m interested.’”
I think all of us can only dream to have the kind of influence the way Stanley has had.
With a couple of well-placed hunches from Falkow, Relman soon found himself collaborating with microbiologists in Indiana who had found a way to reveal the nature of bacteria in soil without cultivating them, and with scientists in the East Bay, one of whom had just invented the polymerase chain reaction technique to amplify DNA. Using a new experimental approach, Relman and his colleagues identified the bacterium, now classified as a Bartonella, that causes the disease, bacillary angiomatosis. It turned out also to cause cat-scratch disease.
“It was just because of Stanley’s curiosity, his willingness to put himself in someone else’s world and think hard about their problem, and then as is often the case with Stanley, he has an idea of where the right direction might be,” Relman said. “He might not know the details of how to get it done, but he knows, ‘Head in that direction; you’ll see something that way.’ I have since then found myself and maybe deliberately put myself in the position of being one of relatively few clinicians working in an area of science that is mostly populated by nonclinicians, but who have an interest in understanding the clinical ramifications of the story.”
Relman used the same method on other diseases, and he ended up using it to look at commensals in the human body. Today, that microbiome research is his main focus.
“That event led to my beginning to do this work on the human microbiome, and that was clearly influenced by Stanley’s worldview,” said Relman, who is now the Thomas C. and Joan M. Merigan Professor. “He’d always been interested in commensals, although nobody was studying them, but also promoted the general value of curiosity and exploration and risk-taking. I think I pursued all of that work on the microbiome because of him, and about 15 years ago that became the only thing I did.”
Falkow is impressed by Relman’s ability to collaborate broadly. “David is in full command of at least a cruiser, if not a battleship,” he said. “He walks two lines of infectious diseases and basic science, and a lot of people who don’t know him wonder at that. I don’t know how he handles that many students. That’s the amazing thing to me.”
The admiration, of course, is mutual. Falkow’s mentoring legacy “is exactly the kind of contribution that has a much longer-lasting impact than any particular finding,” Relman said. “With the pace of science, there is no paper, no matter how important, that will have continuing impact in the way that a subsequent generation of people will, who if trained especially well or potently, or with sufficient power of influence, will in turn bestow that upon their trainees. There are second- and third-generation Stanley people now who recognize Stanley’s contribution to the way in which they do science as not via direct means but by vertical inheritance. I think all of us can only dream to have the kind of influence the way Stanley has had.”
‘A microcosm of my life’
When Falkow looks at the careers of Amieva, Monack and Relman, he sees, “more or less, a microcosm of my life.” Each, he said, has a segment of his personality. “If David is Darwin walking around the Galapagos measuring beaks, Manuel is Darwin walking around the Galapagos enjoying the beauty of the situation,” he said. “Denise is more of a generalist and she’s moving into immunology — places I didn’t go. She’s a very practical, pragmatic person.
“When it all comes down to it, when the four of us — or any group of us — are together, we’re talking about science,” he said. “And the science is the most fascinating part of it.”
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