Microbe hunter Stanley Falkow receives 2008 Lasker Award

Stanley Falkow has spent his life studying how bacteria cause human disease. But ask him whose side he's on, and he's likely to pause. Or maybe not. Actually, it's been pretty clear all along - as evidenced by an experiment in graduate school that required him to feed hapless bacteria to a hungry slime mold.

Credit: Krista Conger Stanley Falkow

Stanley Falkow played a critical role in advancing the understanding of how microbes develop resistance to antibiotics.

'I felt like a traitor,' recalled Falkow, PhD, the Robert W. and Vivian K. Cahill Professor in Cancer Research at the School of Medicine. He was supposed to be learning more about the mold. Instead, he trained his microscope on the lucky bacterial survivors, exhibiting an affinity for microbes that has lasted more than 50 years and spawned the careers of nearly 100 students, postdocs and fellows.

The breadth and depth of Falkow's career is being recognized with the 2008 Lasker-Koshland Award for Special Achievement in Medical Science. Sometimes referred to as 'America's Nobels,' the Lasker Awards are this country's most distinguished honor for researchers in basic and clinical medical sciences. The Special Achievement award, which has been renamed in honor of the late biochemist Daniel Koshland Jr., is given only once every two years to commemorate a life of scientific contribution and service. The awards were announced Sept. 13 by the Lasker Foundation and are to be presented at a ceremony Sept. 26 in New York City. Falkow's award carries a cash prize of $300,000.

Interview with Stanley Falkow

Stanley Falkow discusses his life's work as a microbe hunter with the school's executive director of communications, Paul Costello. Length: 20 mins.

'Dr. Stanley Falkow is one of the most remarkable and respected scientists of our time,' said Philip Pizzo, MD, dean of the medical school. 'His elegant research contributions to the field of bacterial pathogenesis, which he fathered, have been enhanced by his incredible leadership as teacher and mentor for a generation of physicians and scientists worldwide.'

Falkow, PhD, now 74, is most well-known for his work on extrachromosomal elements called plasmids and their role in antibiotic resistance and pathogenicity in humans and animals. Yet throughout his career, he has been committed to exploring the microbe's-eye view that can only be afforded by peering into a microscope - and getting down to their level.

In particular, Falkow is fond of promoting the idea that many of the adverse effects of microbial infection are the fault of the host as much as the bacteria. 'Disease is a distraction that keeps us from understanding the biology of the relationship between the two organisms,' said Falkow, who is also a professor of microbiology and immunology. 'I never met a microbe I didn't like.'

Falkow's enthusiasm is hard to resist. 'He's given more to science than stellar ideas and new insights,' said David Relman, MD, professor of infectious disease and of microbiology and immunology, who was a postdoctoral scholar in Falkow's lab in the late '80s. 'His legacy includes a community of over 100 trainees who view each other as family and who have learned a unique way of looking at the world and of doing science.'

Marshall Bloom, MD, who has known Falkow for more than 20 years, said that a mutual love of trout fishing drew them together, and Falkow and his wife, Lucy Tompkins, PhD, a professor of infectious diseases and of microbiology and immunology at Stanford, became part of his family. 'My two sons call him zeyde, the Yiddish word for grandfather,' said Bloom. 'Stanley's wonderful personality was a major influence on their love of science and their decisions to pursue biomedical careers of their own.'

Bloom is the associate director of Rocky Mountain Laboratories in Hamilton, Mont., a division of the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. Word is that Falkow was lured to become a part-time resident of the Bitterroot Valley after first visiting the lab in 1984 because of the area's excellent fly fishing. He'll tell you it was the opportunity to pursue his first love - the microscopic examination of the human pathogens studied at the labs.

Even with his successes, Falkow has an unassuming nature, undoubtedly shaped by his mother, now 98 years old. When informed of her son's Lasker Award she responded, as she has in the past, 'Well, Stanley, better you than some stranger I don't know.'

She's had a lot of opportunities to hone her delivery: Falkow's previous 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; an election to the Institute 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.

Young Falkow inspired by microbes, not by grades

By his own admission, Stanley Falkow was a terrible high school student. So bad, his advisor told him to 'save his parent's money and set his sights on a career in the military.'

Falkow eventually landed a spot at the University of Maine, though he later discovered that the university was accepting all out-of-state applicants at the time, regardless of grades, because of their tuition money.

Falkow's fascination with his chosen field began when, at about 11 years old, he happened upon Paul de Kruif's Microbe Hunters - a classic story dramatizing the earliest discoveries of micro-organisms by Antony van Leeuwenhoek, Robert Koch, Louis Pasteur and others - in his local library in Rhode Island. After reading the book, he was hooked. He arranged a deal with a nearby toy store to work in exchange for a small microscope, and promptly became a member of what was then a relatively small group of bacterial paparazzi.

'I loved to read, but I didn't want to read what was assigned to me in school,' he recalled in a recent memoir.

Falkow's passion for bacteriology diverted most of his attention until his high school English teacher, Lottie Brindle, gave him a serious talking to. 'In those days, there were a lot of things women couldn't do,' said Falkow, whose earliest mentors were female. 'The best and the brightest tended to become teachers. They were trying to help me succeed in doing something that they had wanted for themselves.' Brindle's counsel, coupled with the looming threat of the Korean War, helped Falkow achieve straight A's during his final year in high school.

Still, his independent streak remained. 'I couldn't stand having someone tell me to do something,' he said. 'I wanted to do experiments my way. That's probably why I could never bring myself to tell my students what to do. In the end, I always let people do it themselves.'

In some ways, Falkow's career can be described as a series of fortunate coincidences. He learned medical bacteriology during summers off as an undergraduate at the University of Maine by working in a laboratory at Newport Hospital in Rhode Island. He met sick patients by rounding with the doctors, identified patients' bacterial infections by culturing them on plates and even helped with autopsies when treatment was unsuccessful. The experience filled him with a lasting desire to understand why some bacteria made people sick, when others coexist with us peacefully.

Falkow pursued his study of microbes as a graduate student in the early 1960s, first at the University of Michigan, next at Brown University, and then as a researcher at Georgetown University. During this work, he learned the biochemical and microbiological techniques necessary to deduce how bacteria transmit antibiotic resistance to one another by sharing circular extrachromosomal elements called plasmids.

At that time, scientists found that some bacteria were resistant to antibiotics to which they had never been exposed - a phenomenon that at first confounded the researchers. 'Bacteria are smart, but they're not that smart,' said Falkow, who subsequently discovered that bacteria gained their resistance by sharing their genes much more promiscuously then had been thought possible.

Although few scientists of that era were skilled in both bacteriology and microbiology, his colleagues did not support Falkow's drive to determine why some bacteria are more dangerous to humans than others. 'There was a kind of euphoric feeling that infectious disease had been mostly conquered,' said Falkow, 'so I was encouraged to abandon my focus on pathogenicity.'

As a result, Falkow switched gears to focus on understanding plasmids that confer antibiotic resistance, called R factors. His research came full circle, however, when he learned that some bacteria carry plasmids encoding toxins that can wreak havoc on their hapless hosts.

When Falkow arrived at Stanford in 1981, he set aside his study of plasmids to concentrate fulltime on how organisms as diverse as cholera and whooping cough cause disease in humans. In addition to experiencing a fortuitous intersection of bacteriology and molecular biology, of plasmids and pathogenicity, he participated in the first discussion of recombinant DNA, or the splicing together of genes from different organisms. 'As soon as we proposed the idea, it was immediately clear that it would work,' said Falkow, who provided one of the plasmids used in the first recombination experiments. 'All great experiments in science are simple. When we hear of one, we all say, 'Why didn't I think of that?''

Such creativity and free thinking in science resulted primarily from an influx of funding for research in response to the Soviet Union's Sputnik program, according to Falkow. 'In the '50s and '60s, the philosophy was to fund the best and the brightest, no matter what,' he said. 'The idea was that creativity was very important and should be encouraged, and that paid off in the explosion of genomic research findings in the '90s.'

In contrast, the current structure of government funding allows little leeway for trial and error, Falkow believes. 'Students today talk about proving a hypothesis, rather than testing it,' Falkow said. 'It's a subtle, but very real difference. Very creative people often don't really follow the same drum. There may be an argument for going from A to B to C to D, but some people go directly from A to F. There has to be room for both of them.'

Mentoring students and fostering their creativity is something Falkow takes seriously. He insists that the relationship is a learned skill. 'You listen carefully to a student and let them finish talking it out. And then you tell them to do what they said they wanted to do. And then they think you are very wise. I might ask them, 'How long are you going to do this?' if I'm not convinced, but I would let them do it.'

One of Falkow's recent postdoctoral students, Manuel Amieva, MD, PhD, assistant professor of pediatrics and of infectious diseases, said: 'He is incredibly generous. He never keeps anything for his own research when his students leave to start their own careers. He's never afraid of running out of new ideas.'

Falkow is also willing to speak out. 'I got to get to know Stanley in 1977 when I was the commissioner of the Food and Drug Administration,' said Donald Kennedy, PhD, who went on to serve as the president of Stanford University and is now the Bing Professor of Environmental Science, emeritus. 'Stanley, who was on an advisory committee for the agency, was very concerned about the overuse of antibiotics in animal feed. I needed a world-class science expert to help with this issue, and I was very fortunate to find Stanley.' Not only did Falkow testify before Congress in an effort to ban the practice, he also argued against a proposal in 2003 to censor the publication of scientific information, such as the sequence of the polio virus, that could possibly be used for bioterrorism.

Since closing his lab in 2006, Falkow's life has assumed an only slightly more relaxed pace. In addition to fishing, he's learned to pilot small aircraft. Asked recently what he looks forward to, he responds promptly, 'Flying,' thinking of a missed opportunity that morning.

The joy of both pastimes stems as much from the process as from the outcome. Bloom, who takes extended fishing trips with Falkow, describes a typical excursion. 'Well, I'm right-handed, and Stanley is left-handed. So he catches all the fish looking one way, and I catch the ones looking the other way. But neither one of us catch all that many.'

This willingness to accept what comes is another Falkow hallmark. 'One of the difficulties we deal with is the attitude is that, if you pour enough money into a project, you can come up with a vaccine or a treatment,' said Falkow. 'I think that's not true. You have to understand the fundamental biology behind the question. Finding a biological law that doesn't have an exception or a variation is very, very difficult. And the idea that humans can come up with something that is better than what happens naturally is extremely daunting. Very often, people can't.'

Still, they can have fun trying.

When Falkow told his mother he wanted to be a bacteriologist, she wondered, 'A man can make a living doing this?'

Indeed he can.

 


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