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important new grants in the area of genetic origins of MS, and the related issue of the cause of myelin-producing cell disorders.

Finally, let me remind you that Congress has declared the 1990's the "Decade of the Brain" in recognition of the maturation of the field of neuroscience and the unusually exciting neurologic research opportunities that now exist. In response, NINDS has developed an implementation plan that identifies multiple sclerosis as one of the neurological disease research areas within the next few years. In order to make the leap, additional funding is needed.

I am here today to request that you support increased funding for the National Institutes of Health. Specifically, we urge you to support increased funding for the two Institutes involved in research on MS-namely, the National Institute of Neurological Disorders and Stroke (NINDS), and the National Institute of Allergy and Infectious Diseases (NIAID).

NINDS currently supports the lion's share of MS research at NIH, spending about $55.5 million of its $542 million fiscal year 1991 appropriation on MS-related research. For fiscal year 1992, we request that you provide $765 million for NINDS, an increase of $182 million over the President's budget. With this amount, NINDS could spend $69.7 million for multiple sclerosis research. For NIAID, we urge you to provide $1.33 billion for fiscal year 1992. With this amount, NIAID could spend $13.8 million on multiple sclerosis research.

These levels of funding would permit the Institutes to proceed with funding of high priority MS research programs within their specific areas of expertise. Among the critical research areas are the following:

-The_immunologic processes related to MS, especially the role of myelin and myelin components in the disease.

-The role of genetic factors in MS, including efforts in the molecular genetics of MS.

-Development of autoimmune gene bank facilities.

-Expanded efforts to define the role of viruses in MS.

-Improved diagnostic capabilities.

-Conduct of clinical trials of improved therapies for treating MS.

-Basic research and support of animal models.

We recognize that you are in the unenviable position of having to divide limited resources among multiple worthy projects. I urge you to remember that the current opportunities in medical research are greater, more numerous, and more promising than they have ever been in the history of modern medicine. I would also note that the Congress can take credit for much of this opportunity as it was your foresight in establishing and supporting the NIH that has led to these breakthroughs in basic research.

Designation of the 1990's as the "Decade of the Brain" recognizes both the tremendous opportunities presented by recent and anticipated research advances in neurological sciences and the enormous costs that disorders of the brain exact in human suffering, financial sacrifice, and national resources. The compelling message of the "Decade of the Brain" is that the neurological sciences are rich with scientific means and opportunities to reduce the personal burden of neurological and neuromuscular disorders. Now is the ideal time to take maximal advantage of these opportunities.

Thoughtful review by professionals and members of the advisory committee predicted that adequate funding for the "Decade of the Brain" would lead to finding the cause and an effective treatment for multiple sclerosis.

Thank you again. I would be pleased to answer any questions.

Senator ADAMS. Thank you very much, Representative Keys. You noted that the committee provided $2 million to NINDS for genetic research. What priority should we give to continuing genetic origins research? Is there a specific funding amount that you are suggesting for this?

Ms. KEYS. We believe that it is a very, very promising area, and I would like to submit further for the record some additional testimony from a researcher. We believe it is so promising that with our own research funds we are using some directed research money in the area of genetic research.

As I said in my testimony, it is our strong hope that overall NINDS could be funded at a level of $765 million becauseSenator ADAMS. I understand. So you would

Ms. KEYS [continuing]. If that is so, I believe that then they would be able to fund about $69.5 million of MS-related research, and that is what we would like to see.

Senator ADAMS. Thank you very much, and thank you for your testimony this morning.

Ms. KEYS. Thank you, Senator.





Senator ADAMS. Our next witnesses are Dr. Bruce Alberts and Dr. Susan Gerbi, and I hope they will be accompanied by Representative Peter Kiros. If not, we know why Peter is unable to be here.

Oh, he is here. Very good. I served with Peter in the House of Representatives when we were on the Commerce Committee and used to do a great deal of work in health matters. We are very pleased to welcome you with your colleagues here this morning, and we look forward to hearing your testimony.

Mr. KIROS. Thank you, Mr. Chairman. It is a pleasure to be here with you and to bring before you two scientists, Dr. Bruce Alberts from the University of California at San Francisco, and Dr. Susan Gerbi from Brown University, who will tell you some of the things in which I am sure that you are highly interested.

Dr. ALBERTS. Chairman Adams, it is a privilege for me to be here. today. I am here with Dr. Gerbi to testify on behalf of three major scientific societies. We are going to talk not about any specific diseases but about the overall NIH budget for 1992. I have submitted testimony, and obviously I can only make a few points. I want to make four points

Senator ADAMS. Without objection, your entire testimony, if you wish to submit it, will be placed in the record in full.

Dr. ALBERTS. Thank you. Yes; my first point concerns the many opportunities in biological research today. I have been working in this field for 30 years. I am a microbiologist. I have been playing with protein machines, taking them apart and putting them back together. Each of the cells in our body is made up of a collection of these machines, much like a factory. We might have a few thousand such machines in every cell of the human body. It is obviously very complicated to understand humans because we are plicated organisms, but due to the explosion of new tools we have the ability to do that.

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As you read the newspapers, I just want to stress one aspect of many I could. We are on the verge of understanding what makes cells grow and what makes them not grow. The failure of cells to obey the normal growth constraints is what causes cancer. On that

disease in particular, we are getting a molecular handle to really understand the cancer cell. As I have stated in my testimony, that promises completely new kinds of therapies for the many people who suffer from this terrible disease.

There are really an amazing number of opportunities today because of new methods, and particularly I want to stress the new interface between people like me who are microbiologists and pinnacle medicine. There are tremendous new opportunities for new kinds of research.

My second point is one that Dr. Gerbi will take up in detail. That is, because of these opportunities we need to bring new people into the field, young people, and this will require, in my opinion, a modest continued increase in the total number of new grants that are awarded for the next decade-not only for this year but for the next decade. There are just a tremendous number of opportunities that are now exciting all biologists.

My third point of concern is the President's budget for this year. I want to commend Congress and this committee in particular for the vision and generosity you displayed last year in helping out in what was really a crisis situation, in my opinion. You had a wonderful goal of the NIH funding 6,000 new and competing grants for this year while ending the dollar negotiation process that they had been forced to undergo previously.

Unfortunately, the NIH reports that they can only fund 5,785 grants this year, not the 6,000 that you expected, and predicts that the President's budget will only allow this same number to be funded next year. Even to do this has required a new process of reducing grant budgets for the first year by large amounts below the amounts recommended by the scientific review groups.

My final point is to stress the fact that the progress of this country and the future of this country I think depend on the individual initiator type of research grant. Individual investigator-initiated grants are the lifeblood of the whole enterprise. You mentioned $1 billion that has been recommended as an increase by both the Federation of American Societies for Experimental Biology and by the ad hoc group for biomedical research funding. Our groups support this recommendation.

However, we all realize that this is a very difficult year, as you stated. If this full level of funding cannot be realized, we urge you to give top priority to finding the additional money needed to fund at adequate support levels the number of grants recommended by these two societies this year, the number of new and competing awards, which is 6,143.


Mr. Chairman, I want to just stress that even a modest increase in the funding for NIH targeted for this particular purpose will attract young people in the field that we need to carry this enterprise forward. There are tremendous opportunities that have made this country No. 1 in the world in this area both in research and in biotechnology. I would like to thank you and the committee for your past support which has made all this possible.

[The statement follows:]


Chairman Adams and members of the subcommittee, it is an honor for me to have the privilege of speaking to you here today. I am here to comment on the funding for the National Institutes of Health (NIH) for 1992. I speak as a working scientist and reflect the opinions of three major scientific societies. I made the trip from California because I believe that the budgetary decisions made by your Subcommittee will have important implications for the future success of this country.

Why am I a scientist? The reason is simple. Since my college days, I have been fascinated by the very small machines in our bodies that enable cells to grow and divide. For 30 years, I have been doing research to find out exactly how these machines work. The machines that I speak about are made from protein molecules, and they are so small that billions of them could fit on the head of a pin. Picking apart these machines into their tiny parts and then putting them back together again may sound esoteric. But in the 1970's, this type of work led to the explosive development of the new methods of molecular biology, which have since revolutionized all biological research.

The results have been astounding. At least they have certainly astounded me! When I was a student 30 years ago, the possibility of understanding a living cell in a human being seemed like a very distant dream very much like establishing a colony of humans on a distant galaxy. The tools available for achieving this understanding at that time were primitive. It took tremendous vision, and faith in the scientific process, for Congress to support the research that created the new tools that biologists have today. I commend you for that support. As a result of your wisdom, we now find ourselves confronted with a great opportunity. The methods that we have today are so powerful that biologists have the ability to find and study every one of the 100,000 protein molecules in a human being that make it possible for me to sit here and talk to you today-and for you to listen and understand. The tools are now available, but our bodies are very complicated, and there is a great Ideal to do before we can understand all of those tiny protein machines that enable humans to exist.

Why should the American public care about understanding the tiny machines that make up their bodies? They should care because this understanding will have tremendous implications for their future health. An analogy may help make this clear. Imagine someone trying to repair an automobile who had only a very vague idea about how the automobile works. Suppose, for example, that this hypothetical "mechanic" knows only what is immediately visible that the car is powered by burning gasoline inside a large metal block (the engine) and that a rotary motion created by this block is somehow transmitted to the rear wheels through a long series of connectors. This mechanic could fix some of the problems with the car, but not


Our mechanic's situation is not very different from that of a doctor in many areas of medicine today. Consider cancer, for example. Cancer is a disease that I think a lot about and that large numbers of Americans know all too well from direct experience. If the disease is localized, a surgeon can remove the offending tumor cells and often will cure the patient in this way. But when the tumor has spread, the doctor is forced to resort to treating the body with radiation or chemicals that do serious damage to the patient's normal cells. This is rather like having a mechanic try to repair a misfunctioning automobile by covering all of its parts with oil, or by overtightening all of its screws and bolts. Like this mechanic's remedies, cancer treatments today are not very sophisticated, but they are the best we have.

Fortunately, an entirely different type of treatment for cancer is possible, one that should be much more effective. For this type of medicine, we will need to know exactly what prevents the billions of normal cells in our body from growing out of control. This knowledge would enable doctors to find out what has become abnormal in a particular cancer cell by analyzing each patient's tumor in molecular detail. Cancer cells are mutants, and treatments that are aimed at the particular weaknesses in these mutant cells will enable them to be killed much more selectively than is possible now.

Is this a pipedream? I honestly don't think so. Instead, I believe that we may be less than 10 years away from such therapies. What is required to make this a reality is the marriage of two scientific cultures. We need to bring young molecular and cell biologists-whose skills may have been honed by five to ten years of research on fruit flies, yeast, or bacteria-together with more clinically-oriented scientists to work on the cancer problem. At my medical school, UCSF, we have begun a new research and training program, called Molecular Medicine, with exactly this aim. But to make this type of opportunity successful, we will also need a steady, measured growth in biomedical funding. And that is why I am here today.

As you all know, 1989-90 was an extremely difficult time for biomedical researchers. Young scientists especially felt that they had been squeezed out of the competition for grant funds and this after 10 years of research training during which most of them had worked 60 hour weeks, with an average salary (5 years graduate and 5 years postdoctoral) of only about $15,000 per year. Congress realized the seriousness of the problem, and last year's increase in funding has had beneficial effects on the morale and career plans of young people. But the fine goals you set for the NIH in the 1991 fiscal year of funding 6,000 new and competing grants, while ending downward negotiation of on-going grants, have not been met. The NIH has only been able to fund 5,785 new and competing grants this year, and it sadly reports that it will only be able to fund the same number with the President's budget in 1992. Moreover, to make even this number of grants possible has required the institution of a severe "cost containment" process that decreases grant budgets substantially below the levels recommended by the scientific review groups. While these reductions are much preferable to the across-the-board downward negotiations made after grants are started, it would be best if the NIH could fund new and competing grants more adequately.

The United States is frequently criticized for looking only at short-term benefits and for not investing enough in our future. Biomedical research is a major exception. With your support, this country has developed outstanding training programs for young people. Even more importantly, we have evolved an effective system for selecting only the most promising scientists, regardless of their age, and providing them with resources to direct their own independent research groups. At the heart of this mechanism is the competition for individual investigator-initiated (R-01 and similar type) grants, as judged by peer review. The result is obvious to everyone. The United States is presently the uncontested world leader in both biomedical research and in biotechnology. Knowledgeable Japanese scientists have been urging their government to emulate our system of supporting young scientists, thus far without success.

A system like ours is difficult to establish, because it requires that older scientists like me compete with young people for grants every four years, with no special rights or privileges. But it is relatively easy to maintain. What is required, most of all, is a continued measured growth in the funding available for investigator-initiated research. Only in this way can we encourage outstanding young people to make the personal sacrifices necessary to enter into this field. And these people are urgently needed if we are to exploit the enormous opportunities available for improving the health and economic success of the American people.

The research I am talking about is cost-effective. The U.S. pharmaceutical industry spends 7 percent of its resources on research; in contrast, the annual budget for the NIH is only about 1.5 percent of the $600 billion spent annually in the United States for health care. I believe that it would be in the best interests of this country to find the resources required to provide approximately one billion dollars over the President's request, as recommended by both the Federation of American Societies for Experimental Biology and by the ad hoc group for Medical Research Funding. However, I realize that this is a very unusual year. If this full level of funding can not be realized, I urge you to give top priority to providing additional funds specifically for individual investigator-initiated grants, so as to make it possible for the NIH to fund adequately the 6,143 new and competing awards recommended by the above two groups-without downward negotiations.

Individual investigator-initiated grants deserve top priority because, as NIH Director Healy told you, they represent the health and diversity of the research effort in this country. They also are the grants most accessible to young people. Even a modest increase in the funding of NIH for this purpose would keep the momentum building, and thereby enable us to attract the brilliant young people we so urgently need into biomedical research.

Thank you for your support and for giving me this opportunity to testify.


Senator ADAMS. Thank you, Dr. Alberts. I do not mean at all to cut you off, but Dr. Gerbi, do you have some additional remarks you would like to make?

Dr. GERBI. Yes; thank you. Thank you, Senator Adams, for allowing me to come and testify before you and your committee today. I am Susan Gerbi, professor of biology at Brown University, and I speak to you as a working bench scientist and also as a trainer of

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