To Your Health

hese are heady days for Harold Varmus and the National Institutes of Health. The 58-year-old Nobel laureate directs the world's largest and most prestigious biomedical research institute at a time when scientists are unraveling the genetic basis of cancer and other diseases, using computer imaging methods to watch how the brain works and developing new ways to understand both normal and disease processes in cells.

The importance of those efforts won Varmus a coveted seat next to First Lady Hilary Rodham Clinton at the State of the Union address earlier this year. During the address, President Clinton proposed that NIH get the largest single-year budget increase since the agency was created in 1887. Under Clinton's proposal, NIH's budget would go up by 8.4 percent, from $13.6 billion in fiscal 1998 to nearly $14.8 billion next year. Over the next five years, NIH would see an increase of nearly 50 percent, to $20.2 billion.

Meanwhile, some Republican and Democratic members of Congress, including powerful appropriations subcommittee chairmen in both the Senate and the House, want to go a step further by doubling NIH's budget by 2003.

NIH is not the only federal science agency to get a big funding boost in the President's fiscal 1999 budget. As part of the Clinton administration's "21st Century Research Fund," the National Science Foundation and the Energy Department would get 11 percent increases, and the National Institute of Standards and Technology would receive a 6 percent boost.

"There is no reason to be coy," Varmus told the American Association for the Advancement of Science's annual meeting in February. "These may be the most auspicious days-in fact, one of the most auspicious years-in the history of American science."

Biomedical research has entered a "golden age," Varmus told the scientists. Additional funds "can help us achieve the promise of biomedical sciences more swiftly and address public health needs more forcefully. This conviction is inspired by the continued productivity of the scientists we support."

Nevertheless, the prospect of a big budget boost raises questions about how NIH will spend the money. Should the agency focus on simply funding research, or put a significant portion of the money to infrastructure needs? Which diseases will it target, and who will decide how much money should go to fighting each of them?

Tied to Tobacco

Before NIH can address those questions, it has to get the money from Congress.

To get around the caps on discretionary spending agreed to by Clinton and congressional Republicans in 1997, the President said most of the extra money for NIH and the other science agencies would come from revenues generated by the settlement negotiated last year between the state attorneys general and the tobacco industry.

But while the Senate Commerce Committee approved a bill in March to implement the settlement, neither the full Senate nor the House had passed it by early June. The bill is controversial, with some arguing it requires too much of the tobacco industry, others too little. The industry has vowed to fight the bill, both in Congress and in court. Without the tobacco money, NIH's budget increase could go up in smoke.

"The five-year doubling may have to wait until next year to begin," warns Rep. John Porter, R-Ill., chairman of the House appropriations subcommittee that oversees the NIH budget. "I'm fairly confident a tobacco settlement won't go through [this year]. Revenues [to support additional funds for NIH] may have to come from economic growth."

That growth is already having its effect. An economic analysis by the Federal Reserve Board earlier this year projected a $50 billion federal budget surplus in fiscal 1999 rather than the $20 billion predicted by the President's budget in February.

The uncertainties about the tobacco settlement funds do not seem to faze Varmus. "The administration has assured me that the President and Congress will find the funds" if the tobacco settlement falls through, he says. "I am proceeding as if the money will be there."

"The President's budget does not specifically say the money will flow from a settlement," adds Anthony Itteilag, NIH's deputy director for management. "The budget increase has been very well thought out. This is a budget that will come to pass."

Health and Human Services Secretary Donna Shalala, who oversees NIH, is also optimistic. "We will work with Congress to identify a revenue source if tobacco money is not available," Shalala says. But, she quickly adds: "Congress doesn't dare go home without passing a tobacco bill. How would they explain it to their constituents? It is unimaginable."

Either way, NIH supporters are convinced the public backs biomedical science. "Americans want more research," says Mary Woolley, president of Research America, an advocacy group. The group's surveys, she says, show Americans are willing to pay more in taxes and insurance premiums or for drugs if the money goes for biomedical research.

Research America, along with other health groups and public relations firms, launched a lobbying campaign dubbed "NIH-2" earlier this year to encourage Congress to double NIH's budget. "We're committed to seeing the first installment this year," says Wendy Ruhlin, senior vice president at Fleishman-Hillard, a Washington public relations firm.

Even in recent times of tight budgets, Congress has strongly supported NIH. When President Clinton proposed a 2.6 percent increase for the agency last year, for example, Congress voted a 7.1 percent boost. NIH's increases have averaged 3 percent per year over the last half century.

Still, NIH budget increases are by no means automatic. After the Republican takeover of Congress in 1994, the deficit-conscious House Budget Committee proposed cutting the agency's budget by 5 percent.

To head off the proposed reductions, Porter and Varmus arranged for members of a House appropriations subcommittee to meet with NIH scientists in their Bethesda, Md., labs. Porter also invited Varmus and a group of Nobel prize winners to testify on Capitol Hill about the importance of biomedical research. Porter used the attention the hearings garnered to convince Gingrich and House Appropriations Committee Chairman Bob Livingston, R-La., to back a budget boost for NIH. The result was a $630 million increase in fiscal 1996, a $780 million increase in 1997 and a $900 million increase in 1998.

"This is not a political issue between the parties," Porter says. "This is a democratic area of the budget. Disease affects everybody. Investing in biomedical research is investing in families, in the future of our economy and our ability to ensure high-tech jobs."

Not all economists, however, believe increasing NIH's budget provides a significant economic stimulus. "The economic benefits [of biomedical research] pale in comparison to the health benefits," says David Cutler, a Harvard University economist.

Keeping Pace

To get those health benefits, however, the NIH budget must keep pace with the demands of biomedical research. Recent NIH budget increases have been insufficient to fund most of the grant proposals judged worthy of support or to provide the sums scientists say they need to buy the latest equipment, maintain their facilities, train young researchers and ensure the stable, long-term support science needs to thrive. "An influx of new funds is critical to keeping biomedical discoveries flowing," says Kenneth Shine, president of the Institute of Medicine at the National Academy of Sciences.

This year's budget provides such an influx, but NIH is not free to spend the money entirely as it pleases. First of all, the agency depends on scientists who propose studies-and then on outside reviewers who judge their merit-for most of the research it funds. "There is no sense in putting money into areas where no one has any good ideas," Itteilag says.

Second, nearly 75 percent of the $7.5 billion NIH allotted to individual researchers this year is committed to multi-year projects approved earlier. So the agency can't easily make radical changes in how research money is spent.

Third, not all the money budgeted for individual NIH institutes dedicated to particular diseases goes specifically to fighting those diseases. "It is very difficult to draw boundaries and say this money is for disease X and that for disease Y," Varmus says. "We fund scientists with good research ideas based on our understanding of where the best research opportunities lie. Pursuit of cancer research can lead to a better understanding of diabetes or stroke."

Varmus also says NIH recognizes the dangers in over-promising research results based on the number of dollars spent. "What we do is risky business," he says. "We are different from other government agencies. We can't just spend money and pull something off the shelf that will benefit people."

Still, while all 24 NIH institutes and centers will get at least a 7.5 percent increase under the President's proposed budget, some will gain more than others. "We do not want to just do what we've done before," Varmus says. NIH will continue its primary mission of supporting basic research, he adds, but "we want to expand in some promising other directions."

One of those directions is in new infrastructure. In the President's budget, NIH's National Center for Research Resources, which gives universities and other research centers funds to build new labs and maintain facilities, is slated to get the largest percentage increase-13.5 percent-of any NIH unit. Varmus has also promised to increase the number of new grants funded in fiscal 1999 to 8,300, up 1,300 from this year, and to raise the rate of approved grant proposals funded from 29 percent to 33 percent.

Similarly, Varmus says, NIH plans to increase funding levels for each new grant by 10 percent. That will let scientists buy advanced computers and other costly equipment and hire more young researchers. NIH will also provide $80 million for stipends to help attract more medical school graduates and new Ph.D.s to biomedical research.

Research Priorities

In terms of research priorities, NIH has proposed the biggest budget increases for cancer, neurological disorders and the human genome project, which seeks to identify and locate all human genes. The National Cancer Institute is slated to get a 9 percent increase, the National Institute of Neurological Disorders and Stroke an 8 percent jump and the National Human Genome Research Institute a 10 percent raise.

The budget increase will let the National Cancer Institute "accelerate our ability to take advantage of scientific opportunities," says Richard Klausner, NCI director. "I can think of no area where we are better poised to take advantage of the new science of genetics than cancer. [A budget increase] will let us look broadly across the human genome in ways that were not doable a few years ago. That will lead to new therapies and means of diagnosis."

Already, NCI-funded scientists have identified the genetic pathways that lead to some forms of breast, colon and kidney cancers, among others. "We want to be able to read an individual's genes to distinguish between different types of cancer and to know who is at risk of getting them," Klausner says.

Klausner also hopes to use the extra money to speed up the clinical trials NIH uses to test new therapies. Clinical trials are the gold standard of scientific studies. Culminating years of research, they are used to test a new therapy, drug or medical procedure-sometimes on thousands of subjects-to determine which ones work under what circumstances and what side effects may result.

But clinical trials take time, much of it spent recruiting potential subjects. More money, Klausner says, will let NCI-funded researchers complete the studies in a more timely fashion. "We want to get the answers faster so we can move on quickly to test the next question," he adds.

More money will also let the National Human Genome Research Institute expand what is known about genes and how they affect our growth, behavior and diseases. "What we're doing is fundamentally different than the other institutes," says Francis Collins, NHGRI director. "What we're doing will benefit the entire NIH, not just a single disease."

One area of scientific opportunity opened up by NHGRI's budget increase is represented by the lowly mouse. "If we can sequence the mouse genome we could compare it to humans," Collins says. Such knowledge would help researchers know where to find genes in humans equivalent to those in mice that cause a particular disease.

Tuberculosis, malaria and other infectious diseases that continue to spread worldwide provide another NIH research opportunity, Varmus says. Every year, 10 million Americans are exposed to malaria. "We have an interest in making the world as healthy as possible," he says.

Beyond scientific opportunities related to specific diseases, NIH plans to focus more on areas that cross disease and institute boundaries. One is behavioral research. "We need to better understand why people smoke if we are going to reduce the incidence of lung cancer," Varmus says. "We need to understand why some people become addicted [to nicotine] if we are going to get them to stop smoking. Despite all our efforts, we have not been able to get many to stop."

To that end, NCI has added a new behavioral research program to its cancer control efforts. "This is a paradigm shift for us," says Barbara Rimer, newly appointed director of NCI's division of cancer control and population sciences. "We've done behavioral research before, but it tended to get lost within the bureaucracy. That won't happen now."

NIH has already launched a $22-million, 17-state study designed to test new ways to get more Americans to stop smoking. Other studies, Rimer says, will focus on ways to encourage women to get mammograms.

"Behavior is a risk factor for more than just cancer," notes Norman Anderson, director of NIH's Office of Behavior and Social Sciences Research. "It affects heart disease, stroke, diabetes and a host of other diseases." Anderson's office will coordinate a new $13-billion, four-year, multi-center study to test innovative ways of preventing disease through behavior changes. The study is expected to begin later this year.

Yet another area of opportunity, Varmus says, lies in those scientific disciplines beyond the immediate biomedical sciences NIH usually funds. Research in bioengineering and physics has contributed to the development of computers, laser surgery, brain imaging equipment and fetal sonograms now widely used in day-to-day medicine. "Most of the revolutionary changes that have occurred in biology and medicine are rooted in fundamental discoveries in many different fields," Varmus says.

The Rising Tide

To the extent that anticipated budget increases present problems for Varmus and NIH, they are "ones that any government agency director in this town would love to have," says William Raub, deputy assistant HHS secretary for science policy.

Still, some observers have raised questions about Varmus' spending priorities. One issue involves NIH programs to help research centers build and maintain their facilities. "I'm not sympathetic to investing big dollars in infrastructure," says Michael McGinnis, former director of HHS' Office of Health Promotion and Disease Prevention. "Invest first in quality science and scientists. NIH's first goal should be to produce new knowledge."

McGinnis says that even with NIH's proposed increase, some areas of research will be underfunded. Human nutrition research, currently pegged at $500 million a year, is slated for a 2.7 percent raise next year. That is not enough, says McGinnis, now a scholar in residence at the Institute of Medicine and a visiting lecturer at Princeton University.

"We're learning every day how diet and nutrition affect health, but we are still dancing around the margins of doing something about it," McGinnis says. Diet and nutrition "should be one of NIH's major investments, not just a research curiosity."

Other observers suggest that more money is needed to test such alternative practices as herbal medicine, acupuncture and mind-therapy. "We need to know whether they are beneficial, harmful or useless," says George Lundberg, editor of the prestigious Journal of the American Medical Association.

Varmus says NIH's Office of Alternative Medicine is doing just about what it should be doing. OAM will get a 7.5 percent budget increase in fiscal 1999, to $21.5 million. More money is not needed, he says, because alternative medicine got an $8 million increase last year.

Of greater concern is how much discretion NIH will have in deciding where and how to spend its budget. Beyond allocating funds to individual NIH institutes and programs, Congress earmarks only about 2 percent of the funds the agency gets for specific diseases and medical conditions. But congressional appropriations committees often write report language suggesting areas or specific diseases.

Some worry that individual Senators and Representatives, supported by patient and disease advocacy groups, will seek to earmark more money for their personal causes. Rep. Porter vows to resist such an approach. "We should not fund NIH by disease," he argues. "NIH should remain a scientific animal and not become a political animal."

Varmus isn't worried that will happen. "All disease interests will be met in the President's proposed budget," he says. "A rising tide raises all ships."

A rising tide is also likely to drown out most other spending questions and controversies for NIH, says HHS' Raub. These are heady days indeed.

Jeffrey P. Cohn is a Washington-area journalist who writes frequently for Government Executive.