biomedical research, where we have been cut by 5 percent this year, and will be cut by more than 10 percent next year. Therefore, this makes the disproportion between minus 5 percent and plus 24 percent.

Of course, I am not competent to advocate support or not support basic research for military purposes, but what I can definitely advocate, for the sake of the future of this Nation, is basic research on a more balanced basis for civil needs, and especially for biomedical science.

Let me point out that we should not concentrate exclusively on individual research grants, although these individual research grants have been the motor of our progress over the last three decades. We should realize that the infrastructure is suffering at present, and this infrastructure is not only equipment, it is in addition to the other facilities. For example, animal facilities which are now the object of considerable public interest, and which, at present, are underfunded and undersupported. But the technologies developing at present are such that many other instruments of support will be needed, for facilities, for protein chemistry, nuclear chemistry, regional and national resources for centers for producing and disposing of transgenic animals, or for creating libraries for genes, and DNA molecules, and quite a number of others.

We have to maintain our focus on individual grant support because this is what past experience tells us we should do, but we should also take care of the infrastructure considering all of the facilities that are needed for research.

PREPARED STATEMENT

I am not going to cover other issues because I believe I have already spoken too long, but I would be happy to answer questions.

[The statement follows:]

STATEMENT OF DR. GEORGE PALADE

By most measurements, the United States ranks first among nations of the world in its commitment to combat disease. This first rank was achieved in part because U.S. scientists, supported by their government, have exercised free initiative to tackle the most interesting and exciting scientific challenges before them, an effort that has led young people to choose science as a career goal because of the intellectual rewards. This is especially true in basic biomedical research, an area in which American scientists have advanced ahead of their colleagues in all other countries.

The results of this commitment to basic research can be measured in the improvements to the length and quality of our citizens' lives. It has also given rise to a valuable national resource: great and growing biotechnology and pharmaceutical industries.

American leadership in the health sciences is not merely scientific and economic, but moral as well. Other nations look to the United States for solutions to their own health problems.

But biomedical science in the United States is in crisis:

It is choked at the top and there is no opportunity for expansion.
The contributions that could be made by many fine scientists are
ignored and young people, sensing a weakening of national
commitment to excellence, are looking elsewhere for careers.

Health costs are out of control and without strong resolve and the
charting of a clear course toward solution, the health of many of
our citizens is in jeopardy.

Without solid support for our biomedical community, we have
already begun to yield to competing nations the leadership role we
have taken for granted, one that has provided not only improved
health for most of us, but economic rewards as well.

The climate that supported the U.S. rise to its leadership position began at the end of World War II, when the nation acquired its first experience with managing major scientific efforts. Prior to World War II, Europeans made most of the critical advances in health science. But the climate that nourished the health sciences is changing. The cost of doing basic research and developing improved health methods is rising, so competition for funds from federal granting agencies is increasing also. This increased competition ties the hands of some workers, forcing them to channel their research into those areas for which funds have been appropriated, setting aside research that may have been more promising. Many in government would slow the advance of basic research in exchange for short term improvements in the federal budget deficit.

It is time for those who guide our nation's science policy to take stock and determine the nature of the science establishment in the year 2000. At minimum, by 2000 the U.S. biomedical system should have:

Enunciated a strong, clear intent to be second to none in combatting
disease, particularly those that kill and maim or shorten and
diminish life for our citizens.

Made a clear policy statement that we will have organized our
biomedical science establishment so that it will have reached
"steady state" that is, we will have stabilized so that the number
of good young scientists entering the field matches those retiring;
our support structure will be in good repair with new equipment
coming in on a regular basis to replace the faulty and obsolete.

Let the world know in certain terms that a significant portion of
our research capability will work on major diseases that afflict
Third World nations.

Created a business climate that will insure that our pharmaceutical
and biotechnology industries can thrive.

The biomedical community today is one that is awkwardly skewed, with the bulk of researchers in their 30s and 40s. Few retire so that with the current limit on the absolute number of NIH grants, our researchers will gradually get older and there will be few young people coming along to replace them. This is a situation that would bode ill for any field of endeavor. For science it is national suicide, because we need our young people not only for the many long hours of low-paid dedication they give to their jobs, but we need thern for their ideas, for in biology and medicine many of the good new ideas come from graduate students and postdoctoral fellows.

For this reason alone, we must expand the number of research grants awarded by the NIH and assure that each grant contains adequate funds to complete the proposed research. But we must also recognize that our resources are not limitless so our expansion must be measured. We believe that the United States should issue an increased number of grants each year until, in the year 2000, the total is 10,000. This is a number warranted by the number of scientists of exceptional quality who will be available and by the scope of the research effort that can be managed. It is a number that need be increased no further in the foreseeable future. Funding at a reduced level is not an appropriate policy, but rather an inappropriate accountancy measure.

SO THE UNITED STATES IS AT A HEALTH CROSSROADS:

If we are to be in the position of leadership described here by the Year 2000, we must begin to make decisions now to repair and improve the machinery of our health sciences establishment, to provide the trained people and resources that will place our health sciences system in a "steady state" operation, in which young scientists replace those who retire and new laboratories come "on stream" to replace those that are obsolete, where ideas move quickly from university or NIH laboratory to hospital or to pharmaceutical or biotechnology company.

While we continue to lead, we are ailing. Our institutions are in large part old and in need of renovation. We have limited the number of scientists participating in health research so severely that in the next generation many who would have been talented U.S. biologists or medical researchers may choose to be computer scientists or lawyers. We have not looked ahead, but have planned from year to year and as a result the means to continue at the cutting edge of science may soon not be at our disposal.

How easily we forget that until three decades ago, polio stole away the summers of much of our society and left thousands horribly crippled. It was basic research that provided the tools for a scientific onslaught that wiped out polio in this country. Despite our major scientific advances, in the United States today 60 million suffer from cardiovascular disease; 400,000 die each year from cancer; 2,000,000 elderly Americans have Alzheimer's disease, 300,000,000 worldwide are afflicted with malaria; and 2,000,000 children--and many more adults--have severe mental disorders. The list is endless. But what is happening to our basic research capability today? Are we in fact dismantling through neglect the system that provides our best hope for combating disease as well as providing major contributions to such other societal problems as hunger and pollution?

Today there are major research efforts underway that promise to provide relief soon against hepatitis and herpes, and in the longer term against cancer, AIDS and heart disease. But, our scientific apparatus is stumbling and we may have to prolong the time necessary to control these diseases that are currently so widespread in American society.

The U.S. Commerce Department forecasts a worldwide market for biotechnology products of $100 billion by 1990, up by a factor of ten. Japan and West Germany devote higher portions of their gross national products to civilian R&D than we do. From 1973 to 1982 the U.S. proportion of science and technology in biomedicine remained constant.

It costs $2,000 per person each year for health care for Americans. Annual federal investment in medical research is only $25 per person.

Our national goals today and in the Year 2000 should be to:

Prevent and cure disease;

Foster industrial innovation;
Enhance our international prestige;

Educate a new generation of scientists.

If we are to be in that position in the Year 2000, then we need a cogent plan now that will, by the Year 2000, do the following:

1.

2.

3.

4.

5.

Gradually increase the number of new NIH grants funded each year to
10,000 and provide the funds to support them productively. The present
maximum of 6000 excludes large numbers of talented scientists.

We must recognize that modern equipment and instrumentation is
extremely costly and work out new grant mechanisms that will purchase
equipment for individual laboratories and provide for joint use.

Older laboratories need to be renovated now and a plan must be placed in
force to provide for al! laboratories to be renovated every 20 years.

To accommodate the additional scientists who will be supported by an
expanded grant system, our laboratories will need to be enlarged, and
perhaps some new ones built, over the next 15 years. Since it takes five
years to design and build a laboratory building, funding for the first of
these buildings must come soon.

The strength of our scientific establishment depends upon a firm national
political commitment that will imbue students with the feeling that their
country wants them to put heart and soul into a struggle to improve the
health of all citizens, and will honor and respect them for their efforts.

WHY INCREASE THE NUMBER OF GRANTS TO 10,000?

For students planning careers, medicine, law, computers or business are appealing. They are reasonably assured of making a comfortable living, both near term and in the more distant future, while working in a stable field that does not confront them repeatedly with career ending threats. Not so in biomedical research. Since only 15-17,000 NIH grants are in force at any one time and there are three or four times that many researchers, there is little room at the entry level. We estimate that our system can support perhaps twice as many able researchers as are now supported. Presently only 30 per cent of grant applications are awarded. Those responsible for the other 70 per cent keep reapplying until they are discouraged and abandon their careers. In short, there is much good science not being funded. An increase in the award rate in synchrony with an increased number of new grants should result in perhaps twice as many able investigators working in the field by 2000. This would salvage a large pool of native talent and trained skills, encourage the more adventurous scientists to take risks on innovative ideas, and encourage the nation's youth to plan careers in science.

HOW MUCH GOVERNMENT CONTROL CAN WE HAVE?

While effective long-range planning is mandatory, we must not lose sight of the fact that our leadership position came about because our scientists have been unfettered. Answerable only to their peers, our scientists were able to pursue their best ideas, rather than try to mold their research to conform to a government-mandated program. The Soviets tried it the other way, following Lysenko's lead, and today have no significant biomedical research underway, and certainly no biotechnological industries. Long-term planning means keeping the best of the United States'

present highly successful biomedical science enterprise intact while implementing reasonable measures to insure its stability and flexibility. Too much planning, could be more destructive than the present lack of long-term thinking.

LONG-TERM COMMITMENTS THE GOVERNMENT SHOULD MAKE

The National Institutes of Health is the flagship of our nation's biomedical research effort. It is unique in the world. It provides leadership and quality control for scientists in universities and independent laboratories throughout the nation and its own laboratorics produce some of the finest research in our nation. It is non-political, professional and dedicated. Yet it must exist in a political climate that requires compromise and a willingness to "play the game," both anaethma to the sponsorship of good science. The NIH must be insulated from some of this pressure so that the quality of the science it supports is not diluted. The same is also true of many other agencies in government that make up the complex fabric of American health sciences: the Alcohol, Drug Abuse and Mental Health Administration; the centers for Disease Control; the Food and Drug Administration, and there are others. Som institutional arrangements that can be made are:

1. Protect NIH's prime focus on basic research. There is a tendency in our
country to create specialized institutes to focus on single diseases or
problems. This dilutes the NIH mission, which is to foster basic research to
provide a floor of understanding that will lead, with time, to cures. The
long-term trend should be to take those specialized institutes that outrun their
missions and fold their research back into the mainstream, while resolving
not to create new ones.

2. Provide the NIH director with increased discretionary authority to encourage
flexibility and faster response. At present, the various institites in the NIH
are nearly autonomous and the director does not have the funds or the
authority to shift funds to apply to problems of the moment. While some
restrictions upon the director are necessary to avoid violent swings in research
directions, the director needs to have more power to influence the course of
research than is the case at present.

3. Review the roles of all biomedical agencies, restructuring where they are in
conflict, redundant or unnecessary and providing strong multi-year budgets to
sharpen and enhance their productivity.

4. Institute a plan that will progressively strengthen the basic peer-review
system for grants, while reducing paperwork and other red tape. This can be
done in part by encouraging a lengthening of the average term of grants,
particularly initial grants, which are currently for three years. With these
grants, researchers find themselves able to work for only two years before
beginning the grant application program over again, a lengthy, tedious,
frustrating and non-productive process. A more realistic plan would be to
make the norm of all NIH project grants five years of support, while keeping
in place current mechanisms for review.

5. Establish a series of goals over the next 15 years for construction of new
facilities and for purchase of major equipment, as well as for renovating
existing facilities.

THE MATTER Of PRIORITIES

Care must be taken in setting long-term goals. Because of the nature of the scientific search process, it is often impossible to define priorities and directions with precision. Science determines its own goals as it proceeds from one discovery to another. To focus on priorities and directions--as opposed to talent and creativity-can be retrogressive, returning government to an unenlightened