By Lisa Seachrist

Washington Editor

WASHINGTON - After six years of heading the nation's leading medical institution, National Institutes of Health (NIH) Director Harold Varmus tendered his letter of resignation to President Bill Clinton Thursday.

At the end of the year, the 1989 Nobel Prize Laureate will move to New York to head the Memorial Sloan-Kettering Cancer Center. The move will likely leave Bethesda, Md.-based NIH without a confirmed leader for the last year of the Clinton administration's term.

"I take this step with mixed emotions - with regrets about leaving a job I have greatly enjoyed, with gratitude to you and Secretary Shalala for the opportunity to serve the nation in this capacity for over six year, and with excitement about assuming new and different responsibilities," Varmus wrote in his resignation letter to the president.

Clinton's appointment of Varmus in 1993 was controversial because he was a "bench scientist" rather than a medical doctor and he had no significant administrative experience. Nevertheless, Varmus proceeded to steer NIH through a period of unprecedented budgetary growth and raised the stature of the institution to the point where both Democrats and Republicans have come to support a doubling of the agency's budget. Health and Human Services Secretary Donna Shalala championed Varmus's appointment in 1993 and called that decision "one of the most important accomplishments of this administration."

"Obviously, the dramatic increase in appropriations to fund basic research through NIH has occurred in a large part because of the confidence people have in Harold Varmus," said Chuck Ludlam, vice president for government relations for the Biotechnology Industry Organization.

One of Varmus' first actions as NIH director was to receive the recommendations of the Human Embryo Research Panel. Despite the panel's recommendation that the NIH fund embryo research, President Clinton backed away from the recommendation to fund research where embryos were created solely for scientific purposes. Congress took care of research on embryos left over from in vitro fertilization by attaching an appropriations rider to NIH's budgets each year forbidding research involving the destruction of embryos.

In the wake of the development of human embryonic stem cells - cells with the potential to become any cell in the body - Varmus took the lead in establishing the legal means by which the federal government would oversee and fund research using these cells. (See BioWorld Today, Jan. 20, 1999, p. 1.)

"He has made some tough decisions," Ludlam said. "His courage involving research in embryonic stem cells was difficult, but very important for the good of public health."

In addition, Ludlam cited Varmus' courage in repealing the reasonable-pricing clause from government Cooperative Research and Development Agreements. In 1995, Varmus successfully convinced the Public Health Service to drop the requirement that drugs developed with federally funded research be subject to price controls, claiming the provision prevented private companies from building on the basic research conducted with NIH funds.

In his resignation letter, Varmus called on the president to fill his position despite the rapidly waning days of his administration. However, given the length of the confirmation process, Ludlam thinks that may be difficult, if not impossible.

"The difficulty is that the term left is not long," Ludlam said. "Selecting a nominee and securing confirmation of that nominee always take some time. Certainly, an agency as important as NIH needs a confirmed head."

Varmus was a co-winner of the 1989 Nobel Prize in physiology and medicine with J. Michael Bishop, a colleague at the University of California, San Francisco for discovering a family of genes that helped scientists understand how cancer develops.