COLUMN ONE : Funding Science--for a Price : As public money dries up, medical researchers must turn to industry for help. Private backing creates some controversial partnerships, raises fears of commercialism, conflict of interest.

In a perfect scientific world, Joan Sabate never would have limited his work to walnuts.

The 38-year-old Loma Linda University researcher had a hypothesis: that a diet high in nuts but low in other fats could cut cholesterol.

But to prove it, he would need money. He contemplated applying for a grant with the National Institutes of Health, but figured he would be turned down. And he did not want to wait for the lumbering federal bureaucracy to make a decision.

So he shopped his idea around. He met with a trade group of nut packers and handlers, but they couldn’t afford the $150,000 price tag. He wrote to the government of Turkey, where hazelnuts are an important industry, but never heard back. Finally, the California Walnut Commission, which promotes and markets the nuts, agreed to finance his work.

And that is how walnuts made headlines in March, with the publication of Sabate’s results in the New England Journal of Medicine. That the doctor suspected all nuts--not just walnuts--could lower cholesterol was a nuance lost in the hoopla.

The walnut study is a simple example of a larger and more complicated trend: the privatization of academic medical research. As government funding becomes scarce, university scientists are seeking private sources--industry associations, biotechnology firms and drug companies--to finance their work.

The benefit is that studies that might not be conducted receive funding, adding to the nation’s body of medical knowledge. But the drawback, critics say, is that special interests are subtly--and perhaps not so subtly--shaping the course of medical research, and possibly coloring findings as well.

The trend also means that basic research--investigation into the genes that cause disease or the way the brain works--is giving way to applied research, studies directed toward developing drugs and medical devices that will make a profit.

What is lost, critics say, is research born of sheer scientific curiosity.

Moreover, they warn that scientists whose work is tied to corporate money may be less likely to share information with colleagues, creating an atmosphere of secrecy that contradicts the spirit of open investigation. And they worry that what the public presumes to be pure research will be tainted by imperceptible commercialism--or outright conflict of interest.

“In the past, when most research was funded by the federal government, scientists felt more free to follow their own notions of what was scientifically interesting,” said Patricia Woolf, a Princeton University lecturer who has written extensively about conflicts of interest in science. “With private funding, there are a number of problems that arise. One is that the research may become skewed to the interests of the sponsor.”

“There are a slew of issues here,” said Arthur Caplan, director of the University of Minnesota’s Center for Biomedical Ethics. “Are we going to wind up bringing the bottom-line mentality into the laboratory? Are we going to raise a generation of scientists whose first impulse is to patent, or keep a trade secret rather than to share news with their colleagues? . . . This is tearing at the very moral fiber of academic (research) centers.”

The National Institutes of Health estimates that 59% of all biomedical research in the United States is financed by private sources, up from 40% in 1979, the year that government funding peaked. That year, the NIH funded 41% of medical research while other federal agencies, including the military, paid for 19%. Today, those figures are down to 30% and 11% respectively, and experts say the decline will probably continue.

As the government’s share of funding shrinks, it has become tougher for researchers to get federal grants. NIH officials say they approve one out of four worthwhile grant proposals they receive, compared to one in three a decade ago.

Next year, if budget estimates hold, the odds of getting NIH funding could drop to as low as one in five, said David Moore, an official of the Ad Hoc Group for Medical Research Funding, a coalition of research institutions, professional societies and volunteer agencies.

The numbers are drastically changing the way universities and their scientists do business. As medical schools hunt for alternative sources of funding, Moore said, researchers are growing concerned about “the implications of industry calling the shots, and what that means about how much freedom you have to pursue research ideas.”

One such scientist is John Wasmuth, a molecular geneticist at UC Irvine. He is thinking about asking biotech companies to help pay for his research into the identification of disease-causing genes.

Wasmuth, who played a role in the highly publicized discovery of a gene for Huntington’s disease, runs a laboratory with a staff of 11 on an annual budget of $350,000. Most of the money comes from NIH, the rest from philanthropic groups devoted to researching Huntington’s disease and muscular dystrophy.

But the professor of biological chemistry worries that his government funding might not be renewed. He also knows that if he taps into industry for support he could be forced to spend at least some of his time developing products--diagnostic tests or treatments, for example--that could earn his backers a profit.

“These companies are not dumb,” he said. “They are not out there to throw away money and hope for a return. . . . The question is how much money are you willing to take from them, at what price? How much of your basic academic freedom are you willing to sell off?”

Marriages between business and academia blossomed during the administrations of former Presidents Ronald Reagan and George Bush, who believed that that would help keep the nation competitive in global technology markets. Federal legislation enacted in 1980 to give universities the right to enter into exclusive licensing agreements with corporations helped create partnerships--some of them controversial--between industry and the ivory tower.

At Irvine, Wasmuth works in a 40,000-square-foot laboratory built by Hitachi in 1988. University researchers occupy the first floor while the company’s scientists work on the second and third floors. In return, Hitachi has access to other campus facilities, such as the biomedical library--and presumably an inside chance in the stiff bidding wars that companies engage in to market the university’s inventions.

In Boston, cosmetics manufacturer Shiseido has signed a 10-year, $8.5-million annual contract with Massachusetts General Hospital. The money pays for Harvard University researchers who are affiliated with the hospital to study the biology of the skin. In exchange, Shiseido gets the first option to market inventions that arise from the research.

Although Harvard officials say the arrangement does not affect their researchers’ decisions about what to study, the deal has drawn criticism from the National Coalition for Universities in the Public Interest, a nonprofit group that is affiliated with consumer activist Ralph Nader.

“Basically, what Shiseido is buying is research suited to their needs,” said Leonard Minsky, the group’s executive director.

But Cynthia Glott, Harvard’s assistant director for corporate relations, said strict boundaries are made clear at the outset: “It’s not about our investigator sitting down with the company to figure out the best way to put their product on the market.”

In La Jolla, officials at Scripps Research Institute recently signed a 10-year, $300-million agreement that gives Sandoz, the giant Swiss pharmaceutical concern, first rights to market any technology developed at the facility.

That arrangement generated protest when NIH Director Bernadine Healy described it as contrary to the spirit of science and said it raised questions about whether U.S. taxpayers--whose money goes to support Scripps and other research institutions through NIH grants--are being used to help generate a profit for private companies.

Although such agreements may indeed give America a competitive advantage in marketing products, some fear that the heavy emphasis on applied research could cost the nation its status as a worldwide leader in basic research.

“We’re at a time now in the development of biological science in which the opportunities that are before us are really just enormous,” said Purnell Choppin, president of the Howard Hughes Medical Institute in Bethesda, Md., the nation’s largest private sponsor of biomedical research. “If we don’t put enough into basic research, a decade or two from now we will feel the difference.”

Moreover, the web of financial entanglements between companies and university researchers has raised concern about conflict of interest, particularly in the wake of several scandals.

In one highly publicized case, a University of Pittsburgh doctor who was studying antibiotics for childhood ear infections was criticized by a colleague who complained that money from drug companies had influenced the doctor’s research. Although the government was paying for the studies, the doctor had accepted $225,000 in fees, mostly for speaking engagements, from companies whose products he was studying. His research largely supported their use.

To guard against conflicts, many universities have adopted strict guidelines requiring scientists to disclose not only who pays for their work, but whether they have any outside income from industrial or corporate sources, or any stock in companies whose products they test.

The government will soon follow suit. President Clinton is about to sign a bill permitting the use of fetal tissue for research. Tucked inside is a conflict-of-interest provision that requires scientists who receive government funding to disclose their ties with industry.

The editors of medical journals--whose publications play an important role in determining what makes medical news--are also paying attention to the issue. It has long been common for journals to include, in fine print at the bottom of a study, who is paying for it. The New England Journal of Medicine attached this note to the walnut study: “Supported by a grant from the California Walnut Commission.”

Such disclaimers, intended to alert the reader to possible bias, are growing more detailed, according to Dr. Robert Fletcher, co-editor of the Annals of Internal Medicine. Fletcher’s publication has begun listing not only who paid for a study, but whether the private sponsor of the research was involved in collecting data, analyzing it or approving the final article.

“We feel like the readers ought to know more than just funded or not funded,” Fletcher said. “They need to know a little bit more about the extent of the involvement of the funding agency . . . to interpret whether they were going to believe in the article.”

Fletcher said he does not object to financial ties between business and medical research so long as they are disclosed. But others, such as ethicist Caplan, contend that something intangible--trust--is lost when studies are accompanied by fine print that may cast doubt on their findings.

“The public has its trust undermined when it thinks that the fair, disinterested arbiter of information is suddenly suspect,” Caplan said.

Among the harshest critics of corporate sponsorship of research is Minsky, who advocates an extreme solution: banning the practice.

“The easy answer is to let government pay,” he said. “Medical knowledge in particular can be biased. And you don’t want it to be. The best way for it to be unbiased is for it to be sponsored by the government, not by special interests.”

But advocates of corporate funding say industry provides invaluable money that government could never match. Moreover, they say, society benefits immeasurably from the medical devices and drugs that grow out of industry-sponsored research.

“It’s a win-win situation as far as I’m concerned,” said Charles A. Sanders, chairman of Glaxo, a North Carolina-based pharmaceutical company that sponsors research at the University of North Carolina, Duke University and other institutions.

“The good researchers, the researchers that really are there to do quality research, are not going to have their heads turned just by the money,” he said.

Others contend that the choices scientists make are no more influenced by corporate money than they are by funding priorities set by the federal government. They argue that the age-old maxim of science--that research goes where the money is--still holds, no matter who is paying the bill.

“Look at research in the AIDS area,” said Harvard’s Glott, who recruits corporations to finance research at the university. “When the AIDS crisis was surfacing and federal agencies were prepared to support research in that area in a big way, suddenly a lot of academic investigators became very interested.”

As for Sabate, the walnut researcher, he said there is only one bottom line: whether industry sponsors give academic investigators free rein to conduct studies as they see fit, and to publish the results no matter what they reveal. Of his own study, he said: “I had full freedom. They gave me the money, no strings attached.”

Still, the doctor said he would have preferred that his study examine the effects of all nuts. But he knows that compromise is often a fact of life in the imperfect world of money and medical research.

“Nowadays research money is scarce,” Sabate said. “I don’t think we (scientists) can make all the decisions as far as our preferences. We have to take what we can and do the best that we can.”

Who pays for medical research?

As government money grows scarcer and competition stiffens for federal grants, scientists are increasingly turning to industry to finance their work, as illustrated below (In billions)

Other National Institutes Other Industry private In of Health federal* funding funding** billions 1979 41% 19% 29% 11% $7.2 1980 40% 19% 31% 10% $8 1981 38% 17% 34% 11% $8.7 1982 36% 16% 37% 16% $9.6 1983 35% 15% 39% 15% $10.8 1984 35% 15% 39% 15% $12.1 1985 36% 14% 39% 14% $13.6 1986 34% 13% 42% 13% $14.9 1987 35% 12% 42% 12% $17 1988 33% 11% 44% 11% $19 1989 32% 11% 45% 11% $21 1990 31% 12% 46% 12% $23 1991 30% 12% 47% 12% $26 1992 30% 11% 48% 11% $28

* Includes the Department of Defense and Centers for Disease Control.

** Includes non-profit groups and voluntary health agencies.

SOURCE: National Institutes of Health