Don Ganem is a modern-day microbe hunter. Inspired in his youth by Paul de Kruif's captivating account of the 19th-century scientists who traced epidemics to their microbial origins in Microbe Hunters, Ganem has devoted his career to unlocking the secrets of some of life's most infectious organisms: viruses. His studies have uncovered how the viruses responsible for hepatitis B and Kaposi's sarcoma infect humans and wreak havoc on the body. Now, following in the footsteps of his microbe-hunting heroes, Ganem is on the front lines of discovering new viruses that cause human disease.
Ganem's first exposure to research came as a Harvard undergraduate, when he landed a job in the laboratory of Nobel laureate James Watson, the codiscoverer of DNA's molecular structure. There, Ganem studied bacterial genetics. While he found the work immensely challenging and intellectually stimulating, Ganem longed for a closer connection to patients and human disease. He opted to go to medical school, where he also pursued research in virology and eventually decided to apply his training in molecular biology to the study of infectious diseases.
When Ganem started his own laboratory at the University of California, San Francisco, his research focused on hepatitis B, a virus already known to cause chronic liver disease. His studies probed how hepatitis B reproduces itself inside its host cell and how the virus particles orchestrate their assembly and release. Over a 15-year span, Ganem's discoveries pieced together many of the molecular details of the virus. Then, in 1991, he set his sights on solving a medical mystery: tracking the microbial source of Kaposi's sarcoma. Found almost exclusively among gay men with AIDS, this disease is noted by purplish, disfiguring lesions on the skin and mucous membranes. After another team isolated snippets of viral DNA from a tumor sample of Kaposi's sarcoma, Ganem and his colleagues developed a cell culture system that allowed them to grow the virus in the lab. They later developed a blood test for the infection that helped Ganem establish that the suspect virus, herpesvirus 8, is indeed responsible for Kaposi's sarcoma.
Today, Ganem continues to unravel the molecular basis of Kaposi's sarcoma. And with HHMI investigator Joseph DeRisi, he is searching for new viruses responsible for pneumonia, upper respiratory infections, hepatitis, meningitis, and encephalitis. All are diseases already known to be caused by viruses, but many cases remain undiagnosed and are likely to be traced to new viral sources.
Using a genomics-based approach, Ganem and DeRisi have employed a DNA microarray that bears the telltale gene fragments of all known viruses of humans, animals, plants, and microbes on a microscopic slide. If a sample from a suspected viral genome has a chunk of genetic material that matches one on the slide, it will adhere to that spot and light up when the slide is put into a scanner. While the method is more likely to identify viral genomes related to known viruses, Ganem thinks it also will be useful for detecting novel viruses.
The team has already used this approach to identify the genome of the newly discovered SARS (severe acute respiratory syndrome) virus. They are now using the same technology to search for viruses that are more likely to cause severe upper respiratory infection in patients with asthma. Ultimately, Ganem hopes to determine whether viruses may be responsible for certain cancers and autoimmune diseases, including rheumatoid arthritis and multiple sclerosis, for which a viral infection has never before been established. This type of research, Ganem acknowledges, is risky: "There are only two results—you either get a home run or you strike out. There's no such thing as a base hit in this kind of work. But this is what I've always wanted to do. This is what I feel like I was born to do."
