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each geared to the point in career progress of the recipient.
Are you undertaking any new initiatives?
Answer. crease the number of minorities in biomedical research.
NIGMS is undertaking several new initiatives to in
In response to Congressional interest, in FY 1991 the MARC
MARC predoctoral fellowships have historically been awarded only
SUPPORT OF NEW SCIENTISTS
Question. Getting new scientists started in their careers is particularly important to maintaining the vitality of the country's research enterprise. What programs does NIGMS support to encourage new scientists early in their biomedical research careers?
Answer. Recruiting talented young men and women into biomedical research careers, and providing support for them during the requisite years of specialized training has always been a vital part of the Institute's mission. In all of its research training programs, the Institute stresses the importance of laying the basic foundation both for disease-oriented research and for further fundamental studies. The Institute has a number of training programs to meet the variety of training needs that exist.
Through the traditional institutional and individual National Research Service Award (NRSA) the Institute provides for the broad, multidisciplinary training that the Institute believes is necessary in preparing trainees to pursue research careers in a wide variety of areas, many of which reflect the scientific goals of other NIH components.
The Medical-Scientist Training Program (MSTP) addresses the spe. cialized need for scientists who can bridge the gap between basic and clinical research. This program, which supports research training leading to the combined M.D.-Ph.D., has been remarkably successful in training creative and productive
The 1992 budget will support an estima
The Biotechnology Training Program is another specialized training area developed by the NIGMS in response to Congressional concern that the United States must produce greater number of scientists with expertise in biotechnology if it is to maintain its position as a world leader in this field. An estimated 307 trainees and fellows will be supported in FY 1992.
Recognizing the need for an increase in the number of minority researchers, the Institute initiated the Minority Access to Research Careers (MARC) Program, which has been described above, in detail.
Agreeing that the early support of young scientists is critical to their continued involvement in and commitment to research as a career, the NIGMS offers First Independent Research Support and Transition (FIRST) Awards to provide a sufficient period of research support for newly independent biomedical investigators to initiate their own research. The grants are intended to underwrite the first independent investigative efforts of an individual; to provide a reasonable opportunity for an investigator to demonstrate creativity, productivity, and further promise; and to help in the transition to traditional types of NIH research project grants.
NIGMS also gives special consideration for funding to firsttime applicants whenever the appropriate combination of circumstances permits.
BASIC RESEARCH PAYOFFS
Question. What are the payoffs, such as in research on cancer or heart disease, of the basic research which the National Institute of General Medical Sciences supports? How long does it usually take to achieve that "payoff" in more disease-targeted research or practice?
Answer. There are well-known examples of the payoffs of the basic research funded by NIGMS, such as the Nobel Prize winning work of Drs. Michael Brown and Joseph Goldstein which began as basic studies of cellular steroid receptors, moved to more focused work on a specific steroid cholesterol, and culminated in research into the mechanisms that control cholesterol metabolism. The findings from that work have obviously been important in understanding atherosclerosis and in developing improved treatment regimens. However, there are innumerable, perhaps less spectacular examples from many areas supported by the Institute that illustrate the importance of basic research to the progress of research on many diseases. Some of these are summarized below:
Dr. James Boyd of the University of California, Davis, has been investigating how DNA is repaired in Drosophila flies. In the process, he has identified a Drosophila model for the human disorder known as Fanconi Anemia, a genetic defect that affects all types of blood cells and is associated with malformations of the heart, kidney, and limbs and a predisposition to leukemia and other cancers. He discovered that a particular mitochondrial enzyme, nuclease, which is altered in a mutant strain of Droso
phila, is also defective in all patients of one subtype of Fanconi Anemia. Dr. Boyd's discovery provides a potentially valuable tool for identifying and isolating the defective gene in humans and for developing appropriate mammalian model systems to investigate possible treatment for Fanconi Anemia patients.
Several years ago, Dr. Charles Laird of the University of Washington in Seattle developed a hypothesis about the genetic basis of the most common inherited form of mental retardation, known as the fragile-X chromosome syndrome. Dr. Laird's work in Drosophila led him to conclude that the syndrome was caused by the abnormal activation of a gene or genes.
Now scientists here and abroad have found evidence in humans substantiating Dr. Laird's theory. This should permit the development of diag. nostic tools and, perhaps, even treatments for this disorder.
Recently, Dr. Stuart Schreiber of Harvard University, a grantee whose research focused on synthesizing molecules of immunologi. cal importance, found during the course of his work a series of small molecules that bind to the AIDS virus at the site where the virus would normally bind to and infect the T cells of the immune system.
Now Dr. Schreiber and others are building on this work in order to determine whether these or similar molecules could be used to disrupt the infective stages of the AIDS virus.
For many years, Dr. Glenn Dryhurst of the University of Oklahoma has been examining the chemistry of a basic chemical grouping, called the indole moiety, found in certain proteins, including the neurotransmitter serotonin, Recently, he observed unusual oxidized forms of the indole moiety of serotonin in the spinal fluid of people with Alzheimer's disease, but not in that of matched controls. This finding has led Dr. Dryhurst to postulate that this unusual indole chemistry could be toxic and might help account for the degeneration of brain tissue seen in Alzheimer's disease. Dr. Dryhurst and others are currently investigating this possi-bility, hoping to further our understanding of this devastating disease.
Just as there is no way of predicting which fundamental studies will uncover findings critical to progress on particular diseases, it is equally difficult to estimate how long the process of turning a basic finding into a clinical application will take. However, there is no doubt that the availability of the tools of molecular biology has, in many instances, accelerated this process.
There are instances of this taking only a few years, while in other cases, where the problem is less tractable, it might take far longer.
NATIONAL EYE INSTITUTE
STATEMENT OF DR. CARL KUPFER, DIRECTOR
BUDGET REQUEST Senator HARKIN. Dr. Kupfer, your fiscal year 1992 budget request is $272.2 million, 7.5 percent more than 1991.
The Eye Institute's new vision plan, which encompasses your research agenda for the next 5 years, is a subject we hope to hear more about today. Dr. Kupfer, please proceed.
Dr. KUPFER. Thank you, Mr. Chairman.
I would like to briefly summarize my opening statement. There is increasing blinding eye disease especially in older Americans. In 1995, it is estimated that there will be about 34 million Americans over the age of 65. Almost 2 million of them will have visual disability from a condition called age-related maculopathy, which is the leading cause of new adult blindness in the United States. That means about 1 out of 17 older Americans will have a visual problem from this condition. As an ophthalmologist, it is very distressing to me that at the present time we really do not have any way of treating the vast majority of them successfully. There is a small subgroup that we can help, but for all practical purposes, this is a very serious problem indeed.
Toward this end, we have begun a study on age-related eye disease in which we want to collect basic information on who is at risk to develop this condition, and at a later date, perhaps in a year or so, to begin to look at some treatments that might be of benefit. This is one of the overwhelming concerns that we have at this present time.
PROGRESS AND OPPORTUNITIES
On a more optimistic note, we have made progress against nearsightedness, myopia. This is a condition which affects some 60 million Americans. Basically, it results when the eye is too large to allow the images to be focused sharply on the retina. We now have very important evidence from animal models that there are neurotransmitters in the retina which apparently play a very important role in the growth of the eye. In the next few years, we are going to be able to see this basic laboratory information turned into a treatment to slow down the progression of nearsightedness, or myopia.
Two clinical trials have reached a very satisfactory conclusion in the past year. We now know that there is a way to determine the amount of surgery that should be done in a child whose eyes turn in. A very simple test can be done before the surgery to determine exactly how much surgery should be done. In doing this test, we
have improved the success rate of surgery to straighten eyes 80 that the need for a second operation is markedly reduced.
The second clinical trial has been the question: How safe and effective is laser treatment of glaucoma. This treatment has often been reserved later on in the therapy of glaucoma because one was not sure whether it was both safe and effective. We have just concluded 2 years of a 5-year study, and early indications are that laser treatment is both safe and effective in lowering the pressure in the eyes. This study will, of course, continue.
We are carrying out a clinical trial on the treatment of involvement of the retina, the seeing part of the eye, in patients with AIDS. Some 25 percent of all AIDS patients will eventually develop a viral infection of the retina which can lead to blindness. We are now comparing two different drug therapies for slowing down the loss of vision in such patients, if not preventing it.
VISUAL BRAIN SYSTEM
Finally, I would like to end with some considerations about something you heard several people talk about, and that is the Decade of the Brain. We are particularly focusing our attention on the visual system, which provides almost 40 percent of all the input to the brain, in three areas.
The first is that we want to develop techniques to prevent degenerative changes in the brain. We now have some basic information on how to prevent degeneration in the retina which is part of the brain. This is accomplished with the use of what is called a basic fibroblast growth factor. This is a major stride forward in which the possibility of preventing degeneration can be approached.
The second interest we have is whether brain tissue can be transplanted. Our scientists have shown for the first time that retinal tissue can be transplanted and take and set up connections.
Finally, we want to find ways to maintain the regenerative capacity of tissue in the brain in the visual system. We know that in the very young, this regenerative capacity is present, but as the individual matures, it is lost. We are trying to find ways to maintain this regenerative capacity. We have now found that there is a group of proteins called growth associated proteins which, if we can keep them active, will allow brain tissue to regenerate.
So, we are very much involved in brain research, utilizing the visual system to make a major impact on preventing degeneration, maintaining the possibility of transplantation, and keeping regenerative capacity at a maximum.
As you mentioned, the budget request for fiscal year 1992 is $272,260,000.
I would be happy to answer any questions. [The statement follows:]