reprinted from Issue 5, Fall 2007 of Frontiers of Medicine (PDF)
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As a child, Jane Koehler, MD, first wanted to become a veterinarian. She loved animals, particularly the family cat, a Siamese named Winkie. But she developed such terrible allergies to anything with fur – cats, dogs, guinea pigs, rabbits – that she changed her aspirations to becoming a doctor.
"I got a microscope when I was 10, and I would sit there for hours, looking at amoebae and paramecia from the pond near our house," says Koehler, now a professor of medicine in the Division of Infectious Diseases. "I always liked microbiology, and I really liked animals. And now I work on zoonoses, which are diseases you get from animals."
Familiar Symptoms, New Bug
One of her most recent discoveries is a new bacterium. An American returned from Peru, covered with insect bites and suffering from fever, anemia and an enlarged spleen – symptoms associated with Bartonella bacilliformis, which is common in the Peruvian Andes. However, the patient's doctors at Massachusetts General Hospital were unable to culture the bacteria.
Hence the call to Koehler, a world expert on Bartonella and head of the only lab in the country to regularly grow it. Bartonella is a very fastidious bacterium, meaning that it grows slowly and is a picky eater. "E. coli could grow on just about anything," says Koehler. "But with Bartonella, you have to give it something that has blood in it." Bartonella also requires that its nutrients be fresh and poured thick, something impossible to achieve with standard lab materials. So like a celebrity chef, Koehler custom makes Bartonella's special meals, perfected through trial and error.
With its elegant flagella, the bacterium looked like bacilliformis under the microscope. But when Koehler analyzed its DNA, she was shocked to find that it was not bacilliformis at all. The DNA resembled another species of Bartonella, but was genetically distinct. Koehler and her colleagues reported on the newly discovered Bartonella rochalimae (background image) in the June 7, 2007 issue of the New England Journal of Medicine. The discovery also made headlines in the San Francisco Chronicle.
With the help of antibiotics, the patient made a full recovery. And the discovery, while exciting, leads to further questions about how Bartonella rochalimae is transmitted and best cured. For example, it's possible that some patients previously diagnosed with bacilliformis based on symptoms alone actually had rochalimae, which might account for different treatment outcomes.
"It's really important not to just assume that because the patient went to Peru, that it's bacilliformis," says Koehler. "We are discovering new infectious diseases all the time. With SARS and avian flu, I think people are beginning to see that we actually only know the tip of the iceberg."
Joanne Engel, MD, PhD, chief of the Division of Infectious Diseases, agrees. "Dr. Koehler's discovery tells us that there's still lots to learn about infectious disease, particularly with some of the new technologies," Engel says. "Microbes are actually a lot smarter than we are. Whatever we do to treat them, they will figure out ways to develop resistance, or avoidance. And there are at least 10 to 100 times more bacteria in a human than there are cells. We're surrounded, outnumbered and outsmarted."
Body Lice and Cat Scratches
Koehler has a long history with Bartonella. In 1987, on day seven of her infectious diseases fellowship at UCSF, she visited an AIDS patient at San Francisco General with terrible lesions. Doctors thought they might be Kaposi's sarcoma, but biopsies showed they were not cancerous. Koehler prescribed erythromycin, and the patient improved quickly. Still, no one knew what caused the lesions, which were later named bacillary angiomatosis.
That question intrigued Koehler for the next four years of her postdoctoral fellowship, even though her primary focus was chlamydia research. "Chlamydia was my day job, and Bartonella was my night and weekend job," she says with a laugh. "It was just so exciting to be a part of the discovery process. It was an extraordinary challenge to try to grow this organism for the first time, especially when all others had failed." In collaboration with dermatology fellow Jordan Tappero, MD and others, Koehler discovered that the lesions were caused by two species of Bartonella – one transmitted by body lice to homeless AIDS patients, and the other from cat scratches – the cause of cat scratch fever. It was a remarkable arc: from 1987, when doctors weren't even sure that bacillary angiomatosis was caused by bacteria, to 1997, when Koehler helped draft national guidelines on preventing cat scratch fever.
As whimsical tributes to her research, she has a framed copy of 1970s rocker Ted Nugent's album, "Cat Scratch Fever" above her computer, as well as a collection of miniature wooden cats from Thailand, Mexico and Turkey, souvenir gifts from traveling colleagues.
"The reason all this happened is because UCSF has such a great environment where people come together from all sorts of different disciplines," says Koehler. "I travel a fair amount to other institutions and do visiting professorships, and I don't believe I've seen anything as vibrant and interactive as UCSF. It's just tremendously exciting."