Donald E. Ganem, M.D.
While other kids' parents were reading them tales of Peter Rabbit and Robinson Crusoe, Don Ganem's father read bedside stories to him from the Encyclopaedia Britannica. "I discovered the joy of knowing things at a fairly early age," says Ganem. "Especially things other people didn't know. So I developed an addiction to facts. And if you're brought up with a fact addiction, science is a natural choice for a career."
Still, it wasn't always clear that Ganem was headed for a career in biomedical research. In eighth grade, for example, he got an F in algebra because "I was holding hands with a girl in class," he says. "I wasn't paying very much attention to y=mx+b." In high school biology, however, he learned that researchers were figuring out how specific molecules perform critical jobs inside cells, and slowly his interests began to veer in that direction. "To think you could understand life at that level was quite mesmerizing," he adds.
Diseases first captured Ganem's attention when he read The Microbe Hunters, Paul de Kruif's book about 18th and 19th-century medical scientists who tracked epidemics to their microbial origins. Impressed by the acumen and ingenuity these men demonstrated as they met immense challenges without the benefit of modern tools, Ganem quickly adopted these medical scientists as his heroes. During his senior year of high school, his parents gave him an 800-page medical microbiology text for Christmas. Undaunted by its length, Ganem looked on this tome as a fantastic treat. "The idea that there was that much to know I found really cool," he says. "This seemed like a field you could really sink your teeth into."
A second book, The Double Helix, Nobel laureate James Watson's account of how he and his colleagues worked out the structure of DNA, also made a big impression. "Watson described very vividly the lifestyle of research scientists: not only the hard work and the long hours but also the glamorous partsinternational travel, intense competition with photo finishes, and, especially, the thrill of discovery." Ganem says, "The people in the book displayed an extreme level of commitment, almost fanaticism. It was the same level of devotion that professional athletes have for their sport, but you could be a part of it even if you were a klutzwhich I was."
Starting in his second year at Harvard College, Ganem pursued research in bacterial genetics in Watson's lab and found that "what I had read in his book was really true. The lab really was full of these phenomenally talented people who stayed up all night and discovered things no one knew before." His undergraduate lab experience inspired him, but it also unnerved him. "The Watson group's postdocs were so brilliant," he says. "I felt like I would never measure up to their level. It seemed like you had to be a transgalactic superstar to be a scientist."
Nevertheless, he persevered. But although Ganem's work at the bench taught him that he loved the intellectual rigor and challenges of studying basic biology, he felt something was missinga more direct connection to human disease. So he decided to go to medical school, where he also did research, this time in virology. But there he discovered that he also enjoyed clinical medicine. "I liked taking care of people," says Ganem. "Diagnosis was especially interesting. It was a deductive, scientific process with great immediacy. If you diagnosed people right, you could make them better. That was fantastic." Infectious disease seemed particularly attractive in this regard, since it combined his early interest in microbes with his new interest in medicine.
By the time Ganem began his internship, he had made his life plan. He wanted to apply his training in molecular biology to the study of an infectious disease of humans. So he made a list of the viral diseases that he thought could be fruitfully studied. Scientists had just isolated the genetic material of the hepatitis B virus (HBV). "It was a small piece of DNA with interesting biology, and very few people were studying it," he says. "This seemed like the perfect place for me to work."
To train in infectious disease, Ganem knew that he would have to do an internship. Ultimately, he decided that if he were going to invest in an internship, he had "better find the hardest medical residency program I could find, so I could be sure when it was over that this was something I could do really well." In addition to his "fact addiction," Ganem explains, he had a quality addiction. "I got this from my mother," he says. "She's a big believer in the top of the line." He stayed at Harvard for his internship and residency.
Not many researchers were studying HBV when Ganem was ready to resume his research, but he figured that a stimulating environment mattered more than expertise with that particular microbe. Ganem asked Harold Varmus, then a professor of microbiology at UCSF (now director of the National Institutes of Health and winner of a Nobel Prize for cancer research) whether he was interested in HBV. "It turned out that Harold was interested even though he wasn't working on HBV at the time," he recalls. With Varmus, Ganem studied how HBV reproduces itself inside its host cell and how the virus particles orchestrate their assembly and release. After he finished his fellowship with Varmus, Ganem stayed on as a faculty member at UCSF and continued to study HBV.
The HBV work satisfied Ganem's desire to uncover the molecular details of a known infectious disease. But Ganem's heroes still were the microbe hunters who worked at an even more remote frontier: the discovery of previously unknown infectious agents. So in the early 1990s, Ganem decided to broaden the scope of his work. He made another list, this time of "diseases likely to be infectious but for which the causes weren't known." At the top was Kaposi's sarcoma (KS), a type of tumor that occurs on the skin or mucous membrane.
The pattern of KS in the population strongly suggested that an infectious agent was involved. First, KS was very rare before the HIV epidemic but common afterward. Only a select group of people with AIDSgay mengot KS, which suggested that it was associated with sexual contact. And although people with KS also harbored HIV in their bodies, HIV didn't appear in the KS tumor itself. Ganem thought that it was likely that some other infectious agent was transmitted with HIV. "The epidemiology was crystal clear to me," he says. "There's a second infection here."
After another group recovered fragments of the DNA of a suspect virus from KS tumors, Ganem's group developed a cell culture system that allowed researchers to grow the virus in the lab. Using this new technique, Ganem developed a blood test for the infection. With this tool, he provided a critical piece of proof that the suspect virus, called herpesvirus 8, was the culprit. It was present in people at high risk for infection and absent in people at low risk for infection. His group then found not only that people with KS carry herpesvirus 8 in their blood but also that tumors contained the genetic material of the virus.
Satisfied that he and others have pinpointed the guilty virus, Ganem is now working out the molecular basis of the disease. He is especially interested in how the KS virus interacts with HIV and which of the KS virus genes play critical roles in the development of the cancer.
Despite these accomplishments in the lab, Ganem says his real talents lie in teaching. "It's one thing I know I'm really good at. And I love to teach." With regard to research, he says, "I don't compare myself to the people with whom I trained. Those people (Watson and Varmus) are men of genuine genius on a global scale. My talents are much more modest." But Ganem does find comfort in contemplating one of his heroes, Louis Pasteur. "Pasteur was a thoroughly conventional stick-in-the-mud bourgeois Frenchman. And yet he made magnificent contributions to science and medicine. For someone thoroughly conventional like me, that's comfortingmaybe even inspiring."
Dr. Ganem's research group has made major advances in understanding three important human pathogens: human herpesvirus 8, a newly identified virus that appears to cause Kaposi's sarcoma (a cancer that often affects AIDS patients); hepatitis delta virus; and hepatitis B virus. The latter two viruses cause chronic liver disease. In addition to being an HHMI investigator, Dr. Ganem is a professor of microbiology and immunology and of medicine at the University of California, San Francisco (UCSF). He received his B.A. and M.D. degrees from Harvard University. He then undertook postdoctoral work in virology at UCSF with Nobel laureate Harold Varmus.
© 2013 Howard Hughes Medical Institute. A philanthropy serving society through biomedical research and science education.