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Renowned microbe hunter Stanley Falkow dies at 84 | News Center

Renowned microbe hunter Stanley Falkow dies at 84 | News Center

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“Somehow I discovered the public library and happened on a book called Microbe Hunters by Paul de Kruif,” he recalled in a 2008 autobiographical career retrospective published in the Annual Review of Microbiology. “De Kruif describes in colorful detail the microbe hunters Louis Pasteur, Robert Koch, Paul Ehrlich, Elie Metchnikoff, and others, who showed that microbes could cause disease. … These microbe hunters became, and remain, my heroes. Their search to understand microbes was to me the most extraordinary adventure that I could imagine. It still is.”

As an enterprising 11-year-old, Falkow bartered his time working at the local toy store for a Gilbert Co. Hall of Science microscope with which he caught his first glimpse of the world that would fascinate him for the rest of his life — bacteria swimming in spoiled milk. “At the age of 11, I decided to become a bacteriologist,” he recalled.

An indifferent high school student, Falkow managed in 1951 to land an acceptance to the University of Maine (he later learned that all out-of-state students were accepted in order to boost the university’s tuition fees) where he faced a bump in the road: “I suddenly realized I had fallen in love with a fantasy I had conjured up from a description in a book,” he wrote. He threw himself into his studies and cemented his love for microbes when he secured an unpaid summer position at the Newport hospital’s clinical laboratory, helping a bacteriologist identify patients’ infections.

There he first began to understand the delicate dance between pathogenic bacteria and their human hosts. He’d spend the rest of his life trying to map out this intricate choreography and sharing his enthusiasm with students.

“I never thought bacteria were that interesting until I heard all the things Stanley told me they could do,” Amieva said. “He was so charismatic and told all these stories about being on the side of the microbes. Some people say that Stanley himself was infectious — his personality and humor could hook you and draw you in. I found myself wanting to know more, which is why I’ve focused my research on infectious diseases.”

Dealing with anxiety

In 1955, Falkow started graduate school at the University of Michigan, but recurrent panic attacks soon caused him to drop out and return to his hospital job. Although he successfully completed graduate school and then postdoctoral studies — first at Brown University and subsequently at the Walter Reed Army Institute of Research — his ongoing anxiety and developing agoraphobia, about which he spoke freely, colored his early professional life. He described “living [his] life both scientifically and personally in a kind of cocoon, always half-afraid and ready at a moment’s notice to run.” A colleague at the hospital taught him how to fly fish in an attempt to alleviate his anxiety, sparking a lifelong love.

“When I first met Stan as a graduate student at Georgetown in 1967, he would come straight to the lab from his home or therapy and stay all day,” Tompkins said. “He would send us out for sandwiches so he wouldn’t have to leave.”

In graduate school, Falkow discovered a new way that bacteria could transmit certain traits to one another through the transfer of plasmids, which are separate from bacterial chromosomes. One of these plasmid-transferrable traits was, crucially, the ability to break down compounds that would normally kill the bacterial cell.

Now at Georgetown, he and his students investigated the molecular basis of how plasmids encoding these antibiotic resistance factors, or R-factors, were transmitted between individual bacterium.

My feeling when that first molecule came into view remains one of the most exciting moments in my scientific life.

It was there that Falkow also discovered his love of teaching and mentoring, a skill he cultivated throughout his life. “The mentor’s role is that of an advisor or counselor,” he wrote in his retrospective. “It cannot be a friendship in the usual sense of the word nor can it be paternalistic. … It requires absolute honesty and trust.” Many generations of students would benefit from Falkow’s careful attention to this role.

“Stanley was incredibly gifted in his ability to bring out the best in people,” Amieva recalled. “I try to think about his generosity to me and emulate that with my students.”

Denise Monack, PhD, is one such example. For 14 years, she worked as Falkow’s lab manager at Stanford, working and publishing alongside his many graduate students and postdoctoral scholars. But Falkow was concerned about her 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 in a 2017 article about his mentorship skills. “She was basically giving away a lot of her knowledge and her skill to other people.”

Monack recounted, ““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.’” Monack is now a professor of microbiology and immunology at Stanford, with an office next to Falkow’s.

As Falkow’s scientific renown began to increase, it became apparent that he would have to overcome his anxiety and fear of flying in order to travel and speak at scientific conferences. In the fall of 1968, he forced himself to attend the Ciba symposium on extrachromosomal elements in London.

“I remember it was a very snowy, icy day,” Tompkins said. “But somehow he got himself to the airport and then went all the way to London. And after that he never stopped traveling.”

Public speaking never became easy for Falkow, however. “Stanley was more comfortable in many ways around microbes than he was around people,” Relman said. “He certainly didn’t feel he was gifted in his human interactions, although of course he was. We all saw him give talks many times. He would sweat bullets. It was really hard for him, and in some ways this anxiety brought out this kind of self-deprecating humor that made him immensely likable and effective.”

“One of my greatest joys at Stanford has been teaching a course with Stan,” said Justin Sonnenburg, PhD, associate professor of microbiology and immunology. “Although he was teaching with three junior faculty (and all of us idolized him), he always just acted like one of the crowd, and was always joking around. He loved calling ‘B.S.’ on lofty theories that he didn’t buy. The only really bad part was having to lecture after him — his lectures were always a lively journey filled with wit and storytelling, and always saturated with brilliant insight that he made really accessible. There was no way to follow that act.”

The mechanism of antibiotic resistance

At the Ciba symposium in 1968, Falkow was introduced to the idea that plasmids could transmit not just antibiotic resistance, but also the ability to make toxins that could harm the host cell and cause deadly diarrheal disease in animals and humans. He subsequently showed during his days as a faculty member at the University of Washington in Seattle that the genes that conferred these abilities could be swapped like trading cards between bacterial species to allow the rapid handoff of resistance or virulence in ways that vastly affect human health.

“One Saturday morning in 1975, it fell to me to sit down at the microscope to search for the telltale molecule — two identical plasmids except for a single region that would appear as a kinky insertion loop. My feeling when that first molecule came into view remains one of the most exciting moments in my scientific life,” he wrote.

After the advent of DNA cloning, Falkow participated in the Asilomar conference of 1975, which was convened to provide guidelines for recombinant DNA experiments in bacteria and plasmids. He was also a member of a Food and Drug Administration committee investigating the routine use of antibiotics in animal feed — a practice which Falkow, knowing the ease with which antibiotic resistance can be transmitted between species, advocated against strongly.  

“In retrospect, I learned a good deal about the interconnection of our political system with science. I will never forget the times I testified before Congress and I even testified before the city council of Cambridge, Massachusetts. I also learned that I didn’t want to do this if I could avoid it. Yet, it is also a scientist’s responsibility to serve the public’s interest,” he recalled.

“Stanley was often a mediator bringing together people with disparate opinions,” said Stanley Cohen, MD, the Kwoh-Ting Li Professor in the School of Medicine at Stanford, who met Falkow in 1966 at Georgetown. “We worked closely together as members on many of these committees, and his scientific insight and creativity were always apparent. He had the unique ability to get to the heart of an issue with a humorous statement.”

Arriving at Stanford

Partly at Cohen’s urging, Falkow came to Stanford in 1981 to serve as the chair of microbiology and immunology, where he recruited several young faculty members. In 1983, he and Tompkins were married at Stanford’s Memorial Church, and he began a new chapter of his life filled with travel and visits to the symphony and opera. He also began spending time at the Rocky Mountain Laboratory in Hamilton, Montana — one of the biosafety level-4 facilities in the United States. There he learned to take electron micrographs of deadly bacteria, such as the plague-causing Yersinia pestis invading animal cells, while also fly-fishing in the evenings and becoming fast friends with Bloom, a fellow fisherman.

“I’m a virologist, so when I was appointed to be the associate director of the laboratory, I relied a lot on Stanley for advice about microbial and bacterial pathogens. He was both my mentor and my friend,” Bloom said. “In many ways, he and Lucy became an extra set of grandparents for my two children.”

“Stan’s kindness and generosity amazed me,” said Fisher, his assistant for 28 years. “He treated everyone the same, from the glassware washers to the president of the United States. When he won the National Medal of Science, he wrote a lovely letter to President Obama’s science adviser John Holdren expressing how thankful he was to the United States for taking in his father’s family and allowing his father, who served in the military, to become a citizen. Stan went to a land grant college, and his work and that of his students has been supported by government funds throughout his career. It was a beautiful, heartfelt sentiment.”

Love for his students

In 2004, Falkow was diagnosed with myelodysplastic syndrome and given about two years to live. He devoted what he felt was his remaining time to turning over his research program to his former students Amieva and Monack. But every trainee held a special place in his heart.

“When he talked about one of his students, he would nearly cry,” Tompkins said. “Always. He was so emotionally attached. He got better at suppressing it, but I could always tell that he was tearing up. He was so proud of them all.”

Falkow outlived his original prognosis by many years. And he never stopped asking questions and wondering what was around the next bend, whether in the river in which he loved to fish, in the experiments unfolding on the benches of his students or behind the next cloud on the horizon. At 72, he snuck out of his Montana home for flying lessons against Tompkins’ wishes (she later relented and learned to fly herself as a precaution for when they flew together), and they loved soaring into the big Montana sky. At Stanford, he brought his golden retriever, Honey, to the lab every day and joked that he’d learned it was never possible to have enough dogs.

But until the end of his life, maintained his trademark humility, and a vestige of his anxious temperament. “He knew that he’d been nominated in the past for the Nobel Prize,” Tompkins said, “and he’d get very anxious whenever the university’s communications office would call each October to learn how best to reach him if he were to win. He’d tell me, ‘I absolutely don’t want it. It’s not who I am; it would change who I am. I’d be trotted out all over the place. I do not want it.’”

He may not have wanted it, but many feel he deserved it. “Stan’s use of molecular genetics to prove the relationships between specific bacterial genes and infectious diseases processes was a massive contribution to biomedicine,” Sonnenburg said. “The importance to human health of understanding the processes underlying the interactions between pathogens and host cells can’t be underestimated.

Four days before he died, Falkow remarked to Tompkins, “At least now I won’t get the Nobel Prize.”

Falkow’s honors include the 2000 Robert Koch Prize from the Robert Koch Foundation in Germany, considered one of the most prestigious awards in the field of microbiology; election to the National Academy of Medicine, an honorary society whose members are selected by their peers for making major contributions to health, medicine or related fields; membership in the National Academy of Sciences and the Royal Society, and a former presidency of the American Society of Microbiology.

Falkow is survived by his wife; two daughters, Jill Brooks and Lynn Short; a stepson, Christopher Tompkins; his sister Jeanette Andriesse; and four grandchildren. A celebration of life is being planned for later this month.

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