Believe it or not, as an undergraduate, I initially majored in a field known as "pulp and paper technology," with the aim of becoming an engineer for the paper industry. It didn't take me long to realize that what I really liked were the chemistry and biology aspects of the program, so I switched my major and received my BS in chemistry.
I had decided at this point that I wanted to get both an MD and a PhD. Even back then, I liked the interface between basic science and medicine, and I knew that I wanted to apply serious science to questions of clinical interest. At the time, I knew few role models for this dual approach and had to blaze my own trails, which is an approach I've applied throughout my career.
I received my PhD in biochemistry at the University of Chicago. The lab I worked in studied the way in which cell-membrane proteins are produced and folded. This was back in the days when cloning was in its infancy. It was during this work that I was fortunate enough to clone the gene of one of the very first protein receptors and produce it synthetically in a test tube.
Directly after finishing my doctorate, I entered medical school at Stanford University. At the same time, I pursued a postdoctoral fellowship at Stanford in the lab of Paul Berg, a co-recipient of the 1980 Nobel Prize in Chemistry. Our research focused on the way in which HIV regulates its gene expression. This was in 1987, right at the time when the subject was becoming increasingly critical. We ended up making an important observation that described how a particular protein coded by the virus activates the production of the remainder of the viral proteins.
After trying various fields in my medical school rotations, I eventually chose to specialize in neurosurgery. Many people at the time who were aware of my research interests couldn't understand my choice, but I decided that neurosurgery would provide one of the biggest clinical challenges, a prospect I found attractive. It wasn't just "the road less traveled" — for the most part there was no road at all.
The next step for me was a very rigorous residency at UCLA, where there was little time to think about science — or anything else for that matter. I compressed the seven-year program into five years, making things harder on myself in the short run, but allowing me to do a second postdoctoral fellowship at the National Institutes of Health with Harold Varmus. When I decided to do a postdoctoral fellowship investigating brain tumors, little clinical progress had been made in the field in decades. Knowing that new ideas were desperately needed, I went to the smartest person I knew, Harold, and asked him if he would sponsor me.
It was Harold's idea to try using a viral gene transfer strategy to model brain tumors in mice. As a postdoc in his lab, I helped develop the somatic cell gene transfer technique known as RCAS/tv-a, which uses a bird virus to deliver tumor genes into specific cells in mice. Using this method, we have created realistic mouse models of several gliomas, including glioblastoma, the most lethal brain tumor in humans. These animal models allow us to identify the probable genetic causes of particular tumors and provide tumor-bearing animals, which can then be used to develop and test potential treatments.
After finishing my second postdoctoral fellowship, I accepted a joint clinical and research position at M.D. Anderson Cancer Center in Houston. Then, after some time there, I decided I wanted to work in an environment that was more fertile for new scientific ideas and applications, which is certainly one of the strengths here at Memorial. As a result, in 2001, I moved my lab and clinical practice to Memorial Sloan-Kettering Cancer Center.
In my lab, we're beginning to use our mouse models of gliomas to test the effects of individual drugs and combinations of drugs against brain tumors. I am hopeful that we will come up with drug combinations that will have a significant effect on these cancers, many of which are essentially impervious to any current treatments. Besides helping us devise new treatments, our new understanding will also allow us to know why previous treatment attempts weren't working, which we can then revise.
The role of the MD/PhD is a special one because we understand the languages and cultures that are native to both the clinic and the laboratory. In addition, we can act as catalysts, bringing people on both sides together to create new opportunities that wouldn't exist otherwise. This is a very exciting time to be standing on the center span of the bridge that connects the two worlds, especially in the field of brain cancer. The coalescence of knowledge and technology might very well take us from a dark, shadowy world to a much brighter place.
