Molecular Biology

December 8, 1999

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Number1CMRFan: What is the most interesting thing you have studied in your career as a biologist?

Dr. Joan Brugge: If I had to say what my most significant accomplishment was in my career it would be a finding that I made 22 years ago as a post-doctoral fellow with Ray Erikson. At that time, the most attractive model system for understanding the mechanisms of tumor genesis was a virus called Rouf Sarcoma virus. This virus carries a single gene which single-handedly is capable of transforming a normal to a tumor cell. We identified the protein that was encoded by this gene. It is an enzyme which catalyzes the transfer of a phosphate group from ATP on to other proteins. It is now known that this process of adding phosphates to protein regulates most processes within the cell and, importantly, controls cell proliferation, cell invasion, and cell rvival. At this point, many different genes that are altered in human cancer have been identified. In fact, there has been an explosive burst of new information on what cellular processes are involved in the development of human cancer. And now, a great deal of effort is being devoted to determining how we can use this information to block tumor development. On the front page of many newspapers across the country this week was an article demonstrating the effectiveness of the first drug that was developed against one of these genes that was first identified in association with a tumor virus and later found to be responsible for chronic Myelogenous Leukemia. The initial trials of this drug from Novartis Pharmaceutical Company, in collaboration with Brian Drucker from the University of Oregon, look very promising. This is very exciting for all investigators in the cancer field.

Dr. Gary Firestone: I would say one of the most satisfying contributions we've made is some of our current work on trying to utilize compounds found in broccoli and cabbage as a novel class of potential therapeutics for breast cancer. What is exciting to us is the fact that we can simultaneously characterize at a molecular level how the compounds work and also be collaborating at the same time with some local biotech companies to develop compounds with structural changes to the compounds that you find in the plants. So, it relates to doing basic research that at the same time has some potential clinical value and I think that is what I find very exciting, for myself -- the fact that we may be working on a basic mechanism that is directly applicable to targeting a disease state.

Laura: While the Human Genome Project will go on record as one of the great achievements in biology, I fail to see how having a "list of components," as one of your experts called it, will tell you anything about how biological systems work. Anyone care to comment?

Dr. Allan Spradling: No one is proposing that the lists or the sequence all alone is going to answer very many questions, but it is going to make getting those answers possible in many ways that were never possible in the past. So it's a tool. It is beginning, not a final stage in biology as many people may imagine. Without a lot of additional types of knowledge it doesn't answer the kinds of questions that most of us want to know and doesn't provide directly the therapies that we want to find for human disease, but now we will be able to find those more effectively.

Dr. Gary Firestone: It gives us the full platter of potential genes and knowing the sequence means we can take some logical guesses as to how they work. Many of the guesses will be right and many will be wrong, but it gives us a new set of genes to directly establish function which, as Allan said, is extremely important to do.

Dr. Allan Spradling: In terms of understanding how humans relate to other living things and the diversity of all of the human race, there are many kinds of knowledge that can come out of having sequence information at the gene level besides simply its medical applications.

Dr. Peter Devreotes: To go along with what Allan just said, when we have the sequences of many organisms and are able to compare them, we will have a much more comprehensive view of evolution.the relationship of organisms to one another, which currently relies a lot on the way they look and not on the composition of their genes.

Dr. Gary Firestone: One brief viewpoint is what are the functional connections between all of these genes that we are uncovering in an organism specific cell specific and context specific matter and I think that is something that will be driving molecular biologists for a long time--much beyond five years.

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