Chapter 20 : The Path of Biomedical Research

Abstract:

At the National Institutes of Health (NIH), the author focused on animal viruses and was the first to isolate a polymerase encoded by an animal virus. His research for the past twenty-eight years has focused on the molecular mechanisms underlying the replication of a cryptic human virus, adeno-associated virus (AAV). Although all of us are infected by AAV, the virus has never been associated with any human disease and thus was little known until recently. It was not discovered until 1965, when it was found as a contaminant of supposedly pure preparations of adenovirus, a common human pathogen. It was quickly shown that AAV required coinfection with an adenovirus for productive infection in cell culture. On purification the complementary strands would anneal to form duplex DNA. Virus particles containing normal-density DNA were mixed with particles containing heavy-density DNA. When the DNA was purified, the double-stranded DNA we isolated had a hybrid density. As it does not cause disease, AAV was not initially of great medical interest; this situation changed with the recognition that the virus could integrate its genome. Coupled with the virus's persistence, this characteristic made it a strong candidate to serve as a vector for human gene therapy. Now clinicians and entrepreneurs in large numbers are interested.