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NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
STATEMENT OF DR. RUTH L. KIRSCHSTEIN, DIRECTOR
DR. DONALD S. FREDERICKSON, DIRECTOR, NATIONAL INSTITUTES OF HEALTH
DR. LEO H. VON EULER, DEPUTY DIRECTOR
WILLIAM T. FITZSIMMONS, EXECUTIVE OFFICER
NORMAN D. MANSFIELD, DIRECTOR, DIVISION OF FINANCIAL MANAGEMENT, NATIONAL INSTITUTES OF HEALTH
ANTHONY ITTEILAG, ACTING DEPUTY ASSISTANT SECRETARY, BUDGET, DEPARTMENT OF HEALTH AND HUMAN SERVICES
Senator ANDREWS. Our next witness is Dr. Ruth Kirschstein, Director of the National Institute of General Medical Sciences. NIGMS is the basic research institute of the National Institutes of Health, and the mission of the Institute is not to study a specific disease or groups of diseases, but rather to develop new knowledge of the human body and how it works. NIGMS focuses on the cell and chromosomes and genes. I am intrigued with this. Back in my previous reincarnation on the House Appropriations Committee, we were proud that we directed a good deal of research through the Department of Agriculture in human nutrition labs. We found that we knew far more about pig nutrition than we did about people nutrition in this country. Tragically, I think that is still true, but in discovering more in basic human nutrition, we're finding out how to address a whole host of problems, and I'm sure in the work that you're doing, you are finding out how to address a host of problems, and we certainly welcome you here.
And again, in the interest of time, we would appreciate it if you would briefly highlight your opening statement which will appear in full in the record and in the meantime introduce your associates and proceed with your statement.
[The statement follows:]
STATEMENT OF DR. RUTH L. KIRSCHSTEIN
Many years ago, Louis Pasteur observed that "the secrets of the infinite will be found in the infinitely small."
In the past few years, the virtual explosion of knowledge about the hereditary material contained within the cell has made it plain that Pasteur was right in more ways than he knew. If anything is certain in our time, it is that many of the most exciting advances in our knowledge about human life will flow from basic studies about the "infinitely small": the human cell, its internal structures, and the molecular and genetic materials that direct and control fundamental life processes.
The research and research training programs of the National Institute of General Medical Sciences (NIGMS) support studies in the sciences basic to medicine, which are fundamental to the activities of the other Institutes.
The major share of research supported by NIGMS comprises studies of cell structure and function and of basic genetics that seek clearer insights into the molecular mechanisms of human inheritance in health and disease. Other areas of research inquiry are closely related--for example, studies of the effects of drugs within the body, focusing on events at the cellular and molecular levels; studies of intricate responses of many body systems to severe burns and trauma; and development of new, increasingly sophisticated technology to advance this work.
Though the research supported by NIGMS is not targeted toward a specific disease or category of diseases, it provides the fundamental understanding of body processes that is the sine qua non for a truly effective attack on the broad range of illnesses which afflict mankind.
Often, these basic studies find their way quickly and dramatically to clinical application. For example, just a few years ago, experiments involving the insertion of foreign genetic material into loops of bacterial DNA, or plasmids, fascinated molecular biologists--and few others. Who would have guessed that, by 1981, the development of recombinant DNA technology would make possible the manufacture, in bacteria, of large quantities of important biological substances needed for biomedical research, such as human insulin, growth hormone, and interferon--or that this technology could be used, as is now being done, for prenatal diagnosis of certain genetic disorders.
This year, again, as in all previous six years that I have appeared before you, I am pleased to report that NIGMS grantees have been the recipients of national and international recognition for their research achievements. Drs. Paul Berg, of Stanford University, and Walter Gilbert, of Harvard, were co-winners of the 1980 Nobel Prize in Chemistry; and Dr. Berg and three other grantees-Drs. Stanley Cohen, A. Dale Kaiser, and Herbert Boyer--won the prestigious Lasker Award for Basic Research, all for studies involving recombinant DNA technology.
The use of recombinant DNA technology has permitted rapid and farreaching progress in our basic understanding of the genetic makeup of a wide variety of organisms from bacteria to man. It has recently been shown that the pneumococcus bacterium that causes lobar pneumonia has become resistant to penicillin, formerly the antibiotic of choice in treating this disease. However, Dr. Walter Guild, an NIGMS grantee at Duke University, has shown that the type of resistance of these bacteria is clearly different from that of others. Antibiotic resistance in this particular organism can be transferred when the chromosome of one resistant bacterial cell passes into an adjacent bacterium. As far as is now known, the transfer of such antibiotic resistance by this process--known as "conjugation"--is unique for the pneumococcus, since, in other bacteria, antibiotic resistance is transferred by bacterial plasmids, which are free within the cell and which, up to now, have always been found separate from the bacterial chromosome. Dr. Guild has shown that the antibiotic-resistant genes of the pneumococcus are present as large chromosomal insertions of extra DNA, as though the plasmids had become part of the bacterial chromosome. Thus, this new discovery uses the most advanced techniques of molecular biology to explore the important and growing clinical problem of resistance to antibiotics.
Cellular and Molecular Basis of Disease
Studies supported by the Cellular and Molecular Basis of Disease Program are designed to elucidate the normal and abnormal structure and function of the fundamental unit of the body, the cell--a "small universe" that has turned out to be immeasurably more complicated than had been anticipated. Researchers are just beginning, in fact, to nibble at the edges of this complexity. They have found, for example, that the membrane which covers a cell is a dynamic structure through which essential chemicals enter and leave the cell. As seen by high-powered electron microscopy, this membrane has depressions lined internally by a specific protein. These so-called "coated pits" are the locations of the membrane receptors which permit the uptake into cells of such important substances as low-density lipoproteins (which play a role in coronary artery disease) and epidermal growth factor (which is essential for growth of many of the body's cells to form tissues and organs). Detailed chemical studies regarding these membrane receptors may seem far removed from clinical interests but hold the key to an understanding of many serious health problems, such as heart disease, diabetes, and arthritis.
Burn and Trauma Research
Studies at the cellular level are still needed to enable us to understand the body's response to trauma and burn injury. In order to consolidate the knowledge that is available and to assure that physicians are using the most up-to-date methods of caring for burn patients, in November, 1980, NIGMS held a two-day follow-up conference to the Consensus Development meeting held two years ago, and about which we reported to this Committee in the past. Several recommendations from the previous meeting were modified, based on new research developments. Most important, however, was the report of the results of a survey among physicians caring for burn patients which indicated that the widely disseminated recommendations of the first meeting are now well known and have had a real impact on the care of such patients throughout the nation.
As part of the care of severely burned patients, skin grafting is essential. If the grafted skin is from another donor, the patient's immune system must be suppressed to allow the graft to "take." A grantee of the Institute's Pharmacological Sciences Program is studying the correlation between the action of certain immunosuppressive drugs and their rate of metabolic breakdown. Dr. Leslie Benet, of the University of California, has shown that the immunosuppressive activity of these drugs can be better correlated with the amount of drug circulating free in the blood than with the level of drug bound to blood proteins. These findings will enable burn surgeons, as well as those doing kidney transplants, to more accurately calculate the dosage needed to provide immunosuppression and yet avoid the severe secondary infections that sometimes result.
Behind these remarkable new insights lie not only brilliant and creative minds, but also the availability of new, highly sophisticated instrumentation that now makes possible a wide variety of technical procedures, ranging from visualization of large molecules to physical and chemical analyses of minute particles. Modern instruments of these kinds are, not surprisingly, extremely expensive and often beyond the provisions of the normal budgets of research project grants. In order to provide as wide an availability as possible of this new instrumentation, NIGMS is offering a shared instrumentation program. Under this program three or more NIH grantees (at least two of whom must be grantees of NIGMS) may apply for funds to purchase a major piece of equipment on the basis of a plan for sharing it not only among themselves, but also, on a limited basis, with younger investigators who may not be fully acquainted with the potential uses of the instrument.
To maintain the momentum of such research advances, a continuing supply of well-trained basic biomedical scientists is vital. Το ensure that these highly qualified investigators will continue to be available, NIGMS provides research training through institutional awards and individual fellowships.
Minority Access to Research Careers
The Minority Access to Research Careers (MARC) Program is a unique research training program designed to increase the number of minority scientists in biomedical research. Encouraged by this Committee's interest in the MARC Program, NIGMS has just established a new predoctoral individual fellowship for graduates of the MARC Honors Undergraduate Program. Its purpose is to assure support for the very best students to attend the finest biomedical graduate programs in the country. It is anticipated that several such awards will be made this year.
Mr. Chairman, I shall be pleased to try to answer any questions and supply any additional information desired.