but rather a study of nuclear transplantation (the original nucleus is removed from the cell and replaced by a nucleus taken from the cell of a different mouse strain). Dr. Hoppes work is the only study of this type currently being funded by the NICHD. Question: Please comment on the potential bioethical impli cations of the research. Answer: Research applications submitted to NIH which would propose the transfer of genetic material between humans are subject to screening by review boards at the applicant institutions as well as by NIH offices, as a safeguard to prevent misuse of the gene transfer technology. These regulations would be utilized to assure consideration of the bioethical implications. At present, the mouse is the highest animal in which cloning technology has been successful. There has been much discussion about the bioethical implications of possible future applications of this technology in man, without consensus. These discussions are continuing and will be of value to review boards in the future, if and when they are asked to review proposed research involving cloning of human material. MAINTAINING NEW RESEARCH GRANTS Question: The Fiscal Year 1982 Budget continues to emphasize the stabilization of new, investigator-initiated research grants at 5,000. How much funding will you need in Fiscal Year 1982 to maintain your share of the NIH goal of 5,000 new and competing research grants? Answer: The revised budget request, proposed by President Reagan, provides for the funding of approximately 4,900 new and competing research project grants for $571,621,000. The NICHD share of that amount is $41,560,000 and 378 grants. Question: How is inflation impacting--or how will it impact--on this goal: What inflator are you using? Answer: An inflation factor of 9.5 percent was taken into account in developing the cost of funding the 4,900 new and competing research project grants. Question: Why is it so important to stabilize new Research Grants regardless of other budget priorities within NIH? Answer: Research project grants have been the dominant form of NICHD support of research. They continue to have the highest priority because these grants fund investigator-initiated projects at the grass roots. In order to sustain superior quality research, all research investigators periodically must compete for available funds. Similarly, these researchers need an indication that the government is committed to support their research. It is important that reasonable levels of support be established and protected to the extent possible by giving it the highest priority. In this way gifted researchers will continue to be motivated to accept the challenge, and the risks, of cyclical competition for research grants. Question: What happens if, in a particular year, the quality of new research proposals declines? To what extent would you then want to fund fewer new grants and put greater emphasis on research contracts or intramural research? Answer: It is indeed a remote possibility that the quality of new research proposals would decline to the extent that the NICHD would fund fewer new grants. The NICHD is already funding fewer grants than it did in prior years. The Institute is anticipating funding 31% of approved competing research project grant applications in FY 1981 and FY 1982. Clearly, we are far from being able to fund all the highly meritorious applications which have been approved. If, however, the situation of lower quality research project grant applications should occur, the NICHD would propose to increase the funding of its research center grants. These grants provide research resources for investigator-initiated projects, and their unique multi-disciplinary approaches to solving complex research problems in the areas of mothers and children and in population provide special opportunities not possible under other mechanisms of support. Question: To what "Payline" will you fund new and competing grants in fiscal 1981 and if you can estimate it in FY 1982? What percentage of grants will you fund in both years? Answer: The NICHD estimates that the payline for 1981 and 1982 will be approximately 190 and that 31% of approved competing grant applications will be funded each year. WHERE TO CUT Question: If faced with a major budget cutback, what are your priorities? Where could cuts be made without impairing essential research? Answer: In making reductions from the budget submitted to you in January, we have attempted to develop a budget which maintains a viable research program for FY 1982 and strikes a balance among research grants, intramural activities and training. While these reductions will not impair essential research, further cuts may alter this balance as well as our research capability. Question: How much can be saved through more efficient management, less official travel and fewer consultant contracts? Answer: In 1981 cuts were made in travel, consultant services, procurement contracts and personnel compensation because of the hiring freeze. Further reductions in consultant services were made in the estimate for 1982. Additional cuts in these areas in FY 1982 could not be absorbed without affecting essential research activities. Question: Please provide for the record the effects of various levels of funding reduction on your major activities. Answer: The budget justification recently submitted to the Congress has attempted to depict the effects of reductions made from the budget proposals submitted in January. These justifications clearly show the levels of funding reductions by budget mechanism and major disease category. NATIONAL EYE INSTITUTE STATEMENT OF DR. CARL KUPFER, DIRECTOR ACCOMPANIED BY: DR. DONALD S. FREDRICKSON, DIRECTOR, NATIONAL INSTITUTES OF DR. RONALD G. GELLER, ASSOCIATE DIRECTOR NORMAN D. MANSFIELD, DIRECTOR, DIVISION OF FINANCIAL MAN- ANTHONY ITTEILAG, ACTING DEPUTY ASSISTANT SECRETARY, BUDGET PREPARED STATEMENT Senator ANDREWS. Our next witness is Dr. Kupfer, Director of the National Eye Institute. Research supported by the National Eye Institute is aimed at reducing or preventing the physical, emotional, and economic hardship caused by eye diseases which impair the vision of one out of every 20 Americans. Dr. Kupfer, you are most welcome to our hearings. We ask that you very briefly highlight your opening statement, so that we may move on to questions from the subcommittee. and I first hope you will introduce your colleagues, and then you may proceed with your statement. [The statement follows:] STATEMENT OF DR. CARL KUPFER Americans fear blindness more than any other disability except cancer. It is a handicap that can have a profound effect on one's life. And no one knows that better than the ten million people in the United States who suffer from visual impairment and blindness. That is one in every twenty Americans. The toll in human terms is, of course, incalculable; the costs to society of treating these eye disorders and caring for affected individuals is nearly so. According to figures from a 1976 study updated for inflation, the annual bill totals at least seven billion dollars a year. We at the National Eye Institute are committed to reducing these costs to society--as well as human suffering--by supporting research aimed at improving our ability to prevent, diagnose, and treat blinding and disabling eye disease. This research can take two primary forms: studies conducted in the laboratory, or clinical research conducted on human subjects. I would like to discuss today the synergistic relationship between laboratory and clinical research and give you some examples of the interplay between these two. One of the most exciting examples is the story of diabetesassociated cataracts. Usually, human cataracts develop slowly, as a function of the aging process. But in people with diabetes, this process seems to be accelerated; and, as a result, cataracts are more common in diabetics than in nondiabetics. In laboratory animals treated to make them diabetic, cataracts appear so quickly their development can be easily followed by investigators interested in the developmental process of these so-called sugar cataracts. It is now known that "the process begins with a rise in the level of sugar in the blood and in the lens cells. An enzyme called aldose reductase, which is present within the lens cells, then becomes active and converts these large amounts of sugar into a product which draws water into the lens cells and eventually causes them to burst, thus destroying the clarity of the lens and producing a cataract. After having identified aldose reductase as the key to the formation of sugar cataracts, investigators at the National Eye Institute tested chemicals until they found inhibitors potent enough to block the activitiy of aldose reductase and halt the progression of sugar cataract in the diabetic animals. Now aldose reductase inhibitors are emerging from the laboratory and are ready to be tested in human diabetics to discover if they can block one of the minor ocular complications of diabetes--the swelling of the lens that occurs in many juvenile diabetics and often causes blurring of vision. A clinical trial of aldose reductase inhibitors in diabetics with incipient cataract is also in the planning stages. In addition, these agents will be tested to determine if they can improve wound healing in diabetic patients who have to undergo eye surgery. Surgeons have observed that the ability to replace the outer layer of the cornea is impaired in diabetics. Recent studies in diabetic laboratory animals indicate that eye drops containing aldose reductase inhibitors may speed corneal healing and reduce the likelihood of post-surgical complications. But this is not the limit of our hopes for aldose reductase inhibitors. We are beginning to suspect that cataract researchers may have uncovered one of the basic mechanisms responsible for other, even more serious, complications of diabetes. It has been suggested, for example, that aldose reductase inhibitors may also be effective in treating the peripheral nerve disease and small blood vessel disease that is associated with diabetes. The story of how laboratory scientists and clinicians cooperated on the investigation of aldose reductase inhibitors would not be complete without mention of another type of collaboration on this project--between the scientific community, the Federal Government, and private industry. Development and testing of aldose reductase inhibitors have been supported over the years by both the Federal Government and by companies interested in the commercial potential of these agents. In fact, at least 12 companies are now testing a variety of aldose reductase inhibitors in the United States, England, and Japan. The series of studies I have just described is one example of how tightly interwoven are laboratory and clinical research, but let me give you another. It concerns research on diseases of the retina, the eye's light-sensitive, innermost layer. Retinal diseases account for nearly one half of all cases of severe visual impairment and blindness in the United States. Of all these diseases, the most frustrating to the clinician are the ones which are inherited. Many of these strike in childhood, adolescence or young adulthood, and unfortunately, there is no known way to prevent most of them. Because of the difficulty in obtaining living human retinal tissue to examine, scientists interested in studying hereditary retinal disease have turned increasingly to animal models. For example, studies of certain mice and Irish setter dogs with inherited retinal degenerations resembling retinitis pigmentosa have shown that a specific biochemical defect may be responsible for the breakdown of retinal tissue. Now that the defect responsible for the breakdown is known, it is possible to devise an approach to treatment. In fact, studies are now underway to test a treatment aimed at correcting the defect chemically, thereby slowing down or preventing retinal damage. This approach to treatment in animals offers hope that it may be possible to intervene biochemically in the course of hereditary retinal degenerations in people. In fact, that is exactly what some investigators have been doing with the human retinal degenerative disorder called gyrate atrophy, which is similar in many ways to retinitis pigmentosa. Working closely together, laboratory scientists and clinicians have discovered that people with gyrate atrophy have an enzyme defect which causes the amino acid ornithine to accumulate in their blood. This is the first demonstration of a specific inborn error of metabolism associated with a human retinal degeneration. In the last year, two people with gyrate atrophy who were put on special diets to correct this metabolic imbalance have shown objective evidence of improvement. Furthermore, scientists in the laboratory have discovered that ornithine is toxic to retinal tissue. Thus, there is a clear and direct connection between the metabolic problem and the retinal damage that leads to blindness. This is a very interesting laboratory finding which complements and confirms the preliminary clinical results. Cooperation between laboratory and clinic has been the key to success in developing a treatment for another eye problem called uveitis, which is the name given to a group of inflammatory diseases |