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Director of NIH Discusses Biological Research, Funding in Luria Lecture

By Orli G. Bahcall
Staff Reporter

Dr. Harold E. Varmus, the director of the National Institutes of Health, delivered the annual Salvador E. Luria Lecture in Life Sciences in Room 10-250 last Tuesday.

The talk, entitled "Building Animal Models of Human Cancers," was part of the lecture series dedicated to the memory of Luria, who was "an important force in the department," said Professor of Biology Richard O. Hynes. During the 1970s, Luria was one of the founding members of the Cancer Center.

Varmus was awarded the Nobel Prize in Medicine or Physiology in 1989 for research undertaken with Dr. J. Michael Bishop at the University of California San Francisco on the basic mechanisms involved in cellular transformation. The research led to the discovery of cellular proto-oncogenes - normal cellular genes that, when damaged by mutation, become converted into active oncogenes that drive the cellular proliferation that leads to human cancer.

"Until the time of this discovery, many assumed that cancer is created by infectious viruses," said Professor of Biology Robert A. Weinberg. "With the Varmus-Bishop discovery, it became apparent that the seeds of cancer lie in our normal genes, and that such genes represent the targets of damage by mutagenic agents, leading to mutated cells that exhibit the properties of runaway growth," Weinberg said.

Varmus obtained an MD from Columbia University and served on the faculty of the University of California, San Francisco until he was appointed Director of the National Institutes of Health in 1993.

Cancer research has long history

Cancer is one of the most serious of modern diseases, Varmus said. Animal models of cancer are can be made to simulate this disease, he said. They have proved "an important source of knowledge about cancer," over the course of the last 100 years, he said.

Cancer researchers began using animal models because of the great successes of Peyton Rous, who used animals to identify chemical carcinogens, Varmus said. Animal models of cancer are important in cancer research today that "seeks the causes of cancer," he said.

This research includes attempts to induce cancer in animals, to "find and validate cancer genes," and to analyze the multistep nature of tumorigenesis.

Animals models have been extremely important in "providing a model to test therapeutic and preventive strategies," he said. Despite all these benefits to using animal models in cancer research, there are still some drawbacks, Varmus said. There is extensive regulation on the use of animals in research. While the regulations are important, at times it they can make the research burdensome and costly, he said. In addition, individual research is complicated by issues of patenting and intellectual property rights. Varmus said he is working hard at the NIH to refine these regulations.

Varmus showed the applicability of animal models in cancer research, by turning to the specific case of brain tumors, one of his lab's current research interests. Gliomas are primary brain tumors, and are clinically divided into four grades, ranging from the lowest, which averages a 5 to 10 year survival time, to the highest, which averages a 6 to 12 month survival time.

"These types of cancers are not uncommon in children and also appear in older adults, in both cases frequently lethal" said Phillip A. Sharp, Chair of the Department of Biology.

"The ideal animal models for gliomas," Varmus said, would both resemble human gliomas in terms of the molecular basis, and provide a system of study to allow for further analysis of the specific causes of this cancer and possible strategies for intervention.

For one, the disease should arise from normal cells in the brain. Secondly, tumor cells should contain the genetic alterations observed in human gliomas. Finally, the animal models should allow for "experimental control over contributions of mutations," he said.

Researchers in Varmus's lab have recently begun to build such an animal model for gliomas. This was accomplished by transferring oncogenes, genes that promote cancer, to mice, he said. Indeed, many of the characteristic of human gliomas were seen to arise in these mouse models, he said.

The next step for this research, Varmus said, is to consider possible interventions. "We can use a gene-specific intervention system to transfer to specific cell types" those genes that are important in human gliomas in order to follow the development of cancer, he said.

Varmus has "developed nice system with which to work to explore the factors involved with brain tumors," Elad B. Gil G said.

"This research will provide insights into both the process generating these types of tumors as well as models for testing of new therapies for cures," Sharp said.

Students discuss science funding

Varmus also spoke at an afternoon luncheon on science policy for the biology graduate students.

Graduate students brought forward lots of concerns, including research funding and the future of science.

Students were very interested to hear how the NIH budget was broken down, Anna Lau G said. Specifically, Varmus explained how research money is divided up among different areas of biology research. Cancer research receives the highest allocation, followed by AIDS research, she said. Overall, the NIH budget will increase over the next five years, she said.

Many graduate students left feeling positive about the future of biological research. "I am very optimistic for our future," said biology graduate student Anna Lau G. The discussion "made me feel more confident about my position in the future."

It was also nice to hear that the NIH has the money to support biological research and that the government is continuing to increase its budget yearly, she said.

Varmus also pointed out several areas of research which would probably be the focus of increased attention in the future. "Varmus raised tropical diseases, as malaria, as an example of areas of research that is vastly understudied," said David B. Lombard G. "A disproportionately [small] amount of money is spent on them versus the number of people who suffer from these diseases"

Varmus also discussed the field of bioinformatics and the growing use of computers in research, Gil said. There is a great need for an improvement in systems of bioinformatics, he said. For example, clinical trials are currently mostly conducted on paper, Gil said. This system should be set up to make it easier to monitor.

Varmus also discussed "big increases for projects which improve the infrastructure of science, such as the [large-scale] genome sequencing project," Chris M. Armstrong G said. Varmus "placed a lot of emphasis on technology development and the interfacing of biology and technology," he said.

Overall, students found this an interesting experience to have an informal discussion with a knowledgeable and respected scientist, who has gained perspectives on the political "The NIH is in good hands-- Varmus is a very thoughtful, and down to earth scientist," Lombard said.

While Varmus has not attended MITin a teaching position, he does have a close relationship with many faculty members in the Department of Biology.

"It was great to learn that he is still thinking about science while leading NIH" Sharp said.

"Dr. Varmus continues to be interested in the mechanisms of cancer formation and continues to run an active and productive laboratory while administering the complex NIH organization" Weinberg said. Varmus spent a year-long sabbatical in Weinberg's laboratory at the Whitehead Institute for Genome Research.