Jane Koehler, M.D.
Passion and Persistence
Perhaps success in research comes down to two things: passion and persistence.
Jane Koehler, M.D., recipient of a 2003 Burroughs Wellcome Fund Clinical Scientist Award in Translational Research and a professor of medicine at the University of California at San Francisco (UCSF), seemed to have both as a little girl.
“I was always doing experiments,” she recalls. In sixth grade, she bred mice to study the inheritance of coat color—until she had accumulated 49 of them and even her scientist mother told her to stop. Still, her path into research wasn’t without detours. She left graduate school, after three and a half years of studying species of soil-dwelling bacteria, because “I really wanted to do something relevant to patient care,” she said.
She worked in a laboratory at UCSF for a year and a half and volunteered at night in the hospital’s intensive care unit. “I absolutely loved it,” she said of the volunteer experience.
Inspired, she enrolled at the George Washington University School of Medicine and Health Sciences. The newly minted M.D. then returned to UCSF for her residency, then a clinical fellowship in infectious diseases, and eventually to lab work.
Initially, she wasn’t sure if lab work was quite right for her. But during the first week of her fellowship, she saw something that would jump-start her career: a strange kind of lesion in AIDS patients that looked like Kaposi sarcoma, a type of cancer. On further examination, however, the lesions were really a bacterial infection, now known as bacillary angiomatosis. This meant the potentially fatal infection could be treated with antibiotics.
Identifying the bacteria that caused the infection was no small job, as no one had been able to culture them. Her microbiology experience from grad school helped her to succeed—which happened on July 4, 1991, she said, perhaps the most crucial moment of her career.The trick: she added human blood vessel cells to the cultures, because the bacteria grew next to such cells in the lesions.
When she came to the lab that day and found her cultures to be cloudy, she initially thought they were contaminated. But under the microscope, the cloudy stuff looked like bacteria different from those usually found as contaminants.“This was an exciting clue,” she said.“So I stayed the rest of the day and night to prepare, preserve, and freeze the cultures.”
She identified two species of bacteria, Bartonella henselae and Bartonella quintana.“So here we had evidence that both B. henselae and B. quintana were causing the same disease,” she said. She published the work in 1992 in the New England Journal of Medicine.
In a later collaboration with an epidemiologist, she found that cats are the source of B. henselae bacteria that infect some AIDS patients. This finding also suggested that in people without AIDS, the same bacteria may be the cause of “cat scratch disease,” which affects some 24,000 Americans each year, causing such minor symptoms as lymph node swelling.
Initially, this suggestion was met with some skepticism, as other researchers thought they had isolated a different agent as a cause for cat scratch disease. But the skepticism disappeared when Dr. Koehler published a study in 1994 which concluded that 41 percent of the cats in the San Francisco Bay area had B. henselae in their blood.“This was a major moment in my career,” she said, adding that the study caused a media frenzy.“I was on CNN and had my own PR person here at the university.”
But she didn’t stop there. Where did the other 47 percent of AIDS patients who didn’t own cats get their bacillary angiomatosis infection? she asked. Again collaborating with an epidemiologist, she found that these patients were infected with B. quintana. The patients also were often homeless and exposed to body lice. This made sense, Dr. Koehler said, because B. quintana was known to cause trench fever, which is transmitted by body lice, in soldiers during World War I.
With that finding, she had come full circle to understand the disease. She sat on a panel of the federal Centers for Disease Control and Prevention and the U.S. Public Health Service to draft national guidelines advising AIDS patients about potential health risks posed by their pets.
And in 1999, researchers who described a new Bartonella species isolated from cats named it after her: Bartonella koehlerae.
As her next challenge, Dr. Koehler set out to understand how the bacteria work at the molecular level to infect people. She focused on proteins the bacteria produce on their surfaces up to 70 days after they have infected a host, at which time the proteins disappear. This behavior suggests that the proteins, known as VOMPs, must somehow be important, she said, because in some other diseases, such as malaria, the parasite removes certain proteins from its surface to escape detection by the immune system.
But again,Dr.Koehler faced resistance. She said the National Institutes of Health expressed skepticism about whether these proteins represented virulence factors, and that they were reluctant to fund the more clinical aspects of her study. So she approached the Burroughs Wellcome Fund. “Reviewers there apparently like to think about the big picture,” she said, adding that BWF’s support has helped her do much of her recent translational work. This work, she said, has demonstrated that the bacteria do, in fact, need the VOMP proteins to adhere to and infect host cells. Now, Dr.Koehler wants to figure out how the bacteria regulate the expression of VOMPs so they disappear.
And every few months, she takes off her lab coat to serve as the attending physician in UCSF’s infectious disease service.“It keeps me in touch with patients,” she said, adding that being able to combine research and clinical work makes hers “the perfect job.”
Outside of work, her passion expresses itself in orchids, which she grows in abundance in both her office and her home.Orchids, like bacteria,“take consistency and a lot of patience,” she said.
By Andreas von Bubnoff, a freelance science journalist based in Washington, D.C.