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Curious About Everything

Bacteriologist Stanley Falkow never met a microbe he didn't like.

September/October 2011

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Curious About Everything

Photo: Linda A. Cicero

After he retired in March 2010, Stanford professor Stanley Falkow moved to a new space in the Fairchild building, a few floors above the old one, which he had occupied for the better part of two decades. As an office-warming gift, he received an immaculately framed collection—of poop. The assortment of fake feces includes such specimens as "kitty crap" and "party pooper."

"He especially loves the bear poop," says longtime colleague Sara Fisher.

This decoration may seem more appropriate for a 7-year-old boy than a 77-year-old emeritus professor. But it is less surprising for a man whose most famous quote is "It may be shit to you, but it's my bread and butter."

Falkow dedicated his academic career to studying several bacterial species that cause diarrhea—work that included analyzing fecal samples sent to him from all over the world. "We literally looked at shit," says Denise Monack, PhD '02, a former technician and student to whom Falkow handed over part of his lab upon retirement. Manuel Amieva, PhD '97, MD '97, a former postdoctoral researcher, took over the remainder, and this year Falkow let the last of his laboratory grants lapse.

He might have continued indefinitely, were it not for a health issue (unrelated to gut bacteria) that posed a major personal challenge and drained much of the energy required to run a world-class laboratory. While he remains well, Falkow's pace has slowed in retirement, and his focus has turned to family and unusual hobbies. Meanwhile, his legions of former students and postdocs carry on his elemental work.

Falkow is considered a founder of the modern field of bacterial pathogenesis, which seeks to understand how bacteria cause disease. During a career that spanned half a century, beginning before the discovery of DNA's structure, Falkow studied a variety of bugs, from diarrhea-causing E. coli and Salmonella to the bacteria that cause whooping cough and bubonic plague. Through it all, he says, "I always tried to stay in the lab, working with my hands."

In the early '50s, Falkow started off staining and observing bacteria under a microscope. His early work also involved extracting and comparing genetic material from different bacteria, a laborious task that required spinning the DNA in a centrifuge to separate it out based on density.

Eager to apply the latest genetic and molecular biology techniques, Falkow was among the first to cut and paste DNA from different bacteria to isolate the genes that made them destructive. He was instrumental in developing the first National Institutes of Health guidelines for DNA recombination.

After coming to Stanford, Falkow became an early proponent of studying how bacteria interact with human and animal cells, rather than just growing the bugs in Petri dishes, to find out "what was in it for the organism." This combination of microbiology and cell biology—called cellular microbiology—has become commonplace. He also used the latest technology to study which genes were turned on and off in both bacteria and their hosts.

One of Falkow's groundbreaking discoveries was that little circular pieces of DNA called plasmids can carry a single gene that renders bacteria resistant to antibiotics. Ahead of his time in predicting the spread and clinical implications of antibiotic resistance, he urged the Food and Drug Administration in the late 1970s to remove antibiotics from animal feed.

Falkow demonstrated that genes from disease-causing bacteria could convert benign bacteria into harmful ones. This discovery allowed him to identify the key bacterial toxins responsible for "traveler's diarrhea," a major cause of disease and death in developing countries. "E. coli was a suspect, but we nailed it," he says.

Speaking about these favorite research subjects, Falkow's voice is gravelly, but his face sports an impish grin. His short hair is now very white, in contrast to some of the framed photos in his office taken with his wife, Lucy Tompkins, a physician and professor at the School of Medicine. Also on display are photos of students and postdoctoral researchers who populated his lab through different eras. The office floor is littered with toys belonging to Honey, the golden retriever puppy Falkow adopted soon after he retired.

The office walls are conspicuously free of framed evidence of his many awards. In 2007 he was elected to the United Kingdom's Royal Society, becoming one of fewer than 150 foreign members of the esteemed scientific body. In 2008 he received the prestigious Lasker-Koshland Award for Special Achievement in Medical Science—widely known as the "American Nobel"—for his "51-year career as one of the great microbe hunters of all time."

A set of office shelves with photos of Falkow and others, a row of binders, and what appear to be cultural effigies.LIFE's WORK: Shelves in Falkow's office hold mementos of a 51-year career. (Photo: Toni Gauthier)

These were very meaningful to him, says colleague Fisher. "But he's not someone to blow his own horn."

"He never expected to earn any amount of money, or earn any awards," says Tompkins of her husband of 27 years. "[He] has never been motivated by any of that. He just always wanted to follow his nose."

Falkow was born in 1934 in Albany, N.Y., and grew up in a family of meager means. His father, an immigrant from Kiev in Soviet Ukraine, sold shoes. After the elder Falkow was drafted to serve in World War II, the family moved to Newport, R.I.

They owned no books apart from a dictionary and one or two volumes of an encyclopedia, so Falkow—who claims he was a very poor student—sought out the local library's tiny science section. It was there, when he was 11, that he came across Paul de Kruif's Microbe Hunters. Captivated by the stories of Louis Pasteur, Robert Koch and others who first showed that microbes caused disease, he decided right then to someday become a bacteriologist.

After study at the University of Maine, he worked for several years in a pathology lab where, among other things, he assisted with autopsies. He received his PhD from Brown University and worked at the Walter Reed Army Institute, Georgetown University and the University of Washington before coming to Stanford.

But Falkow's professional ambitions were nearly derailed when, before he even started graduate school, he developed acute anxiety. "It crippled me," he says. He avoided movie theaters between 1956 and 1981; for a time he couldn't even leave his house.

Traveling to scientific conferences and giving seminars "took a huge emotional and physical toll." He vividly remembers his first lecture to medical students: "I got up in front of the audience, and I was dripping with sweat, visibly shaking. I thought I would faint, and I needed something to sit down on. I saw a stool on stage. I walked over and got the stool. As I did this, I said 'If you want to talk about enteric bacteria, as a physician you have to start with the stool.' It was totally unintentional, but the students laughed hysterically. They thought it was something I had planned!"

The laughter helped him relax, and thereafter Falkow incorporated humor into his self-therapy. "It's helped enormously. I have a tendency to reduce things to their funniest essence." Nearly everyone who knows him remarks upon his irreverence and humor. "He gets great joy from making people laugh," says former student Monack. She has heard stories of Falkow at scientific conferences, saying funny things at urinals in public restrooms. "All these scientists are standing there," she says, "and he'll say something just to see if he can make one of them laugh and piss on himself."

Fisher, who has edited Falkow's manuscripts and taken care of his administrative work for 18 years, says he only asked her one question during her job interview: "Can you work with a 10-year-old boy who is curious about everything?" She thought about it, and agreed. In retrospect, she says, the job also required an appreciation for toilet humor.

Despite his anxiety, Falkow made a concerted effort to become an active member of the scientific community, and says the turning point came when he traveled to a major conference in London in 1968. The panic attacks gradually abated by the early 1980s, not long after he arrived on the Farm in 1981 to become the chair of the department of microbiology.

After he and Tompkins wed, Falkow began to spend more time pursuing a life outside the lab. Prior to that (and to some extent even after), lab work had consumed all Falkow's time, Tompkins says. "One of my jobs when we got married was to develop his outside interests."

Falkow had learned fly-fishing early in his career, but hadn't pursued it for decades. He rediscovered the pastime when he was invited to spend summers at Rocky Mountain Laboratories in Hamilton, Mont. There he not only used the lab's electron microscopes to photograph bacteria infecting animal cells, but also pursued his hobby in the Bitterroot River. "It's one of the best fly-fishing spots in the West," Tompkins says. The couple returns there every summer.

To the more than 100 students, postdoctoral researchers and clinical researchers Falkow has trained, he is a wise, Obi-Wan Kenobi-like figure. Falkow maintains that his own scientific contributions ended when he first became a professor. Since then, "it's been all about my students," and he still spends much of his time in retirement writing letters of recommendation. "Everybody says there's got to be a letter from Stanley Falkow," says Tompkins. "They haven't really let him retire."

Falkow points to a framed photograph of his first lab members and smiles. "They were a wild bunch," he says. Wild perhaps, but wildly successful for certain. Most of Falkow's former students and postdoctoral researchers are now bacteriologists famous in their own right. Almost all of them continue to work on the same species of bacteria they first studied under Falkow, who says he ceased his work on a given species as soon as at least five of his former students started working on it in their own labs. "I never wanted to compete with students."

Former students say his style of mentorship was very hands-off. He admits he never tried to tell them what to do because "I could never stand to have someone tell me what to do." And he quickly learned that he couldn't be their friend or father. "There's a bridge, a tiny ledge that distinguished the relationship."

Nevertheless, Igor Brodsky, PhD '04, one of Falkow's last graduate students at Stanford, says Falkow is both mentor and friend. Whenever he wanted advice, Brodsky would listen for the sound of a jingling leash. It was a sign that Falkow was walking his dog. (Falkow's first dog, Brandy, was his constant companion until she died in 2009.)

"That was actually the best time to talk to him," Brodsky says. "We'd have a half-hour walk and we'd talk science. It helped a lot. And we got to be closer friends." Now an assistant professor at the University of Pennsylvania, Brodsky says Falkow told him recently that "being a mentor is about trying to help students be happy."

Evelyn Strauss, a former postdoctoral researcher with Falkow, says he allowed her and other students to pursue high-risk projects that often yielded cutting-edge results—except when they failed miserably. But Falkow played an even more important role for Strauss in supporting her decision to leave science and become a journalist.

"He sensed that maybe I wasn't headed into academia," she says. Falkow told her that he would support her no matter what she decided, and was generous in letting her explore non-academic careers. Monack, too, felt that Falkow mentored each individual with insight. "He finds people's strengths," she says, "and helps them work through their weaknesses."

Monack joined Falkow's lab as a technician in 1984, right after her undergraduate studies. He allowed her to pursue independent research and publish papers as a technician, which was extremely unusual then and remains so. She completed her doctorate in his lab and is now an assistant professor at Stanford. Monack credits Falkow for instilling the confidence in her to successfully land a faculty job. "I wasn't sure I could do this," she recalls, but never "for one second" did Falkow reflect a lack of confidence in her.

In 2004, Falkow, who had always joked about "going up to the big Petri dish in the sky," was found to have genetic abnormalities that could lead to acute myeloid leukemia. Doctors told him he would develop the disease within a year. At first, "I expected every blood count to be a death sentence," he says.

Seven years later, Falkow remains healthy. "The diagnosis was correct," he says, "but the prognosis was wrong." The reminder of his mortality has led him to pursue many long-delayed passions. "What I first thought was a death sentence actually turned out to be a better-quality-of-life sentence in many ways."

One of these passions was flying. Falkow earned his pilot's license at 72—a source of considerable pride—and now owns a Cessna 172. Tompkins has been taking flying lessons since 2009 and started joining Falkow's flights only after she qualified to fly solo. On several occasions, they've flown together to Montana.

Honey is another source of enjoyment. "Stan couldn't live without a dog," says Tompkins. As our interview is wrapping up, the puppy pads into the office. Falkow tells her to sit, but she's restless, so he starts taking her leash out. Framed poop on the wall is one thing, but even Stanley Falkow avoids poop on his office floor.


Sandeep Ravindran, PhD '09, is a science writer in Washington, D.C.

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