Recorded: 23 Feb 2012
In the '70s what then became important after the identification of the oncogene is the rest of the viral genome. It became important to know what are the other gene functions. What are the proteins they are calling for. What is the make-up of the genetic map for these viruses. And at that time there was a very popular technique of RNA fingerprinting, and that RNA fingerprinting allowed the mapping of the individual viral genes. It was essentially done by Peter Duesberg's lab and together with his post-docs and students, with some help and input from my lab because we were providing the mutants that were necessary to achieve these mapping results. So [there] was the mapping of the viral genome, the identification of the gene products, and their-- Inder Verma here, who is now at the Salk Institute, played an important role. We were isolating mutants in every gene, and then looked at the phenotype of these mutants. So the '70s really was a period of the genetics of retroviruses. Including the oncogene, but also now focusing on the genes that are required for replication of the virus. Then of course you had at that time the discovery of reverse transcriptives, and that gave this whole field a tremendous boost.
Well in the '70s, as I mentioned, the focus was mainly on the viral genome. And then in the late '70s we started looking at other oncogenes. And the first oncogene we were able to identify is the myc oncogene which is an important determinant in human cancer. After the myc, we looked at various relatives of the sarc oncogene and then, with the discovery of the cellular origin of oncogenes, it sort of made viruses unnecessary. And oncogenes were being discovered that had no viral connection. We thought we wanted to use the viruses still as a source for novel oncogenes. So in the early '80s I went out to chicken slaughterhouses in Los Angeles and isolated spontaneous tumors in chickens to find new oncogenes. And we identified a few of those, the best known is perhaps jun, which is an import transcriptional regulator. And that was actually a very exciting time, the discovery of Jun and the identification of jun, collaboration with Bob Teaching, later with Michael Caring[?]. It was very exciting. And then when I moved down here, we were actually working also on a new oncogene which called qin, but that's an oncogene that really hasn't caught on. Although the family to which it belongs is an important transcription factor family. The qin oncogene really hasn't captured-- was not really popular. So we dropped qin and at the same time one of my post-docs wanted to look at another virus, and she found the PI3-kinase oncogene. And that was a very interesting one of course, because PI3-kinase have been found to be related and needed for oncogenic transformation of other viruses, and could interact with oncogenes. Could bind with oncogenes. This was the isolation of PI3-kinase as a retroviral oncogene was the first time when PI3-kinase was found to be oncogenic by itself. And that was interesting by itself, but it became even more interesting when PI3-kinase was found mutated in human cancer. That really changed the field completely. That was a discovery by a post-doc, then in Fogelstein's lab, Sam Yules[?]. And she really changed the field with that discovery.
It's not so new now, but it has become such a promising cancer target that a lot of people are working on getting inhibitors, and we're testing inhibitors. We're generating inhibitors. We hope that we can get very specific inhibitors and images that maybe just are effective against the mutants, but not against the wild type of the oncogene. These are the things which we are involved now. We're also still very actively working on myc, and again what we try to do there is to get inhibitors of an adaption.
Dr. Peter Vogt, M.D., Ph.D., serves as Member of Scientific Advisory Board of Onconova Therapeutics, Inc. Dr. Vogt is at the Scripps Institute in La Jolla, CA. He is a member of the National Academy of Sciences and a Lasker Award winner. His fundamental studies on oncogenic avian retroviruses led to the identification of oncogenes in human cells. Dr. Vogt is the editor-in-chief of Virology, a scientific journal.
Dr. Peter Vogt intends to continue his work at the Scripps Research Institute. He is currently working to generate small molecule inhibitors that interfere with the spread of cancer as a new therapeutic approach.