In 2002, Thomas J. Kelly joined Memorial Sloan-Kettering Cancer Center as Director of the Sloan-Kettering Institute after a 30-year career at The Johns Hopkins University School of Medicine, where he served as Director of the Department of Molecular Biology and Genetics and Director of the Institute for Basic Biomedical Sciences. He was recently a cowinner of the 2004 Alfred P. Sloan Jr. Prize for his seminal contributions to the understanding of the molecular mechanisms of DNA replication.
I'm one of those lucky people who knew he wanted to be a scientist from day one. Starting in fifth grade, I did science fair projects every year. Early on, they had to do with electronics — making transistor radios, Geiger counters. One year, I made a cloud chamber. Then they began to be more “biological.” In my junior year of high school, I looked at the biochemistry of amethopterin [an antimetabolite that blocks an enzyme needed for cells to reproduce, often used to treat certain cancers]. That project was selected to go to the National Science Fair. So even as a teenager, I was interested in the subject of DNA, the duplication of the genome, and the relationship of that process to cancer.
I skipped my last year of high school and, at 16, entered Johns Hopkins. They offered a “2-5” medical program — you'd be an undergraduate for two years, then go over to the medical school. After my first three years of medical school, I decided to get a PhD in biophysics. During that time, my thesis advisor left to go to Harvard, and I moved with him. I finished my PhD work at Harvard but received my PhD and MD degrees from Hopkins.
As a graduate student, I worked on bacteriophage DNA replication. Bacteriophages are viruses that infect bacteria. In 1970, I went as a fellow to the National Institutes of Health, where I moved from studying bacterial systems to what was then an emerging field: molecular virology — the study of viruses at the molecular level. I studied the replication of a tumor virus called SV40 in monkey cells, and adenovirus, a virus that infects humans. Then, in the mid-1970s, I came to the conclusion that these animal viruses represented potentially powerful model systems to explore the mechanisms of DNA replication in mammalian cells. Up to that time, almost all of the biochemistry of DNA replication and genome replication had been done in bacterial systems.
“ I’m one of those lucky people who knew he wanted to be a scientist from day one. “
Thomas Kelly , Sloan-Kettering Institute Director
My colleagues at Hopkins and I developed what's called a cell-free DNA replication system. This means we were able to achieve complete duplication of the genome of the virus outside the cell in a test tube, using proteins extracted from the mammalian cells. The first system we developed was for adenovirus DNA replication. Shortly thereafter, we were able to get a system that duplicated the genome of SV40. This proved to be an extremely powerful model for analyzing mammalian DNA replication, because SV40 relies almost entirely on the replication machinery of the host cell for the duplication of its genome.
In the early 1990s, I took a sabbatical year to work in the laboratory of Paul Nurse [now President of The Rockefeller University] at Oxford University. As a result of that year, I moved my lab away from studying viral DNA replication and toward studying DNA replication in fission yeast [S. pombe]. The focus moved from studying the machinery of DNA replication to studying the mechanisms that control it. These mechanisms are very important for ensuring the accuracy of DNA replication during the cell cycle and are highly significant for understanding cancer.
I thought I'd finish my career at Hopkins. So when Harold Varmus first approached me, I didn't believe I'd move. But I found the whole Sloan-Kettering environment extremely stimulating and the plans for expansion extraordinarily ambitious. It was fascinating and, I'll admit, even a bit daunting, but I knew that becoming Director of Sloan-Kettering Institute would be a tremendous challenge. I was also attracted to the excitement of New York, and the idea of living here started to grow on me.
I'd say that I've been busier in the last two years than I've ever been in my life. Most everything we've done at Sloan-Kettering Institute has been directed toward the opening of the new research building. The vision is essentially twofold: First, to keep our basic science program — one of the best in the nation — strong and allow it to grow; and second, to build stronger bridges between the basic and clinical sciences by creating new programs that bring together basic research and disease-oriented research.
We'll eventually be able to add 70 new laboratories. We've done a reorganization of all the Sloan-Kettering Institute programs and added several new ones: Computational Biology, Cancer Biology and Genetics, Developmental Biology, and Structural Biology. We've also put a heavy emphasis on chemistry and chemical biology and have built a new high-throughput screening facility that will enable investigators to screen for small molecules or drugs that affect processes that are important for cancer. We've been recruiting as well. Since my arrival, we've recruited 11 new faculty members. And we've applied for degree-granting status so that we can grant PhDs in cancer biology through the new Sloan-Kettering Graduate School of Biomedical Sciences.
One of the attractions of this job was that it was mostly about science — thinking about where science is going, where Sloan-Kettering Institute should be going, and planning for the future. I have great optimism that, given the tools that basic science has produced over the past quarter-century, we're poised to make enormous progress. And I want to be part of that.