Haiti under the direction of Dr. Pincus have established the value and safety of "the pill" as a practical agent in family planning, and these findings have been amply confirmed by others.

Another example has been in the discovery of the electrolyte regulating adrenocortical hormone, aldosterone. This substance was discovered by Dr. and Mrs. James Tait, now senior scientists on our staff. They made these discoveries in England before joining us and in recent years they have developed important procedures for the analysis of aldosterone in body fluids and have investigated its role in health and disease through collaborative studies with clinicians in Boston hospitals.

Dr. Oscar Hechter, some years ago, was making basic investigations of the role of the enzyme, hyaluronidase, a substance that may be extracted from a variety of tissues, particularly from umbilical cords. This substance, produced by some bacteria, aids them in invading cells by attacking the polysaccharides of hyalin membranes. It also may aid sperm in penetrating eggs in the process of fertilization. In studying the action of this enzyme on permeability of rabbit skin, Dr. Hechter became impressed with its possible ability to facilitate hypodermoclysis in young infants suffering from infectious diarrhea. In these infants the great loss of water may be fatal, and the small size of their veins usually precludes intravenous injection at a sufficiently rapid rate to make up for the dehydration. Dr. Hechter and a pediatrician he asked to collaborate with him found that a minute amount of hyaluronidase added to fluid to be injected under the skin facilitated by manifold its rate of absorption, and the use of this substance became standard practice in pediatrics.

These are a few examples from our institution of significant applications of basic science to practical applications. Scientists in research institutes such as ours are men who have chosen a research career in preference to university positions in which teaching is the main concern. It is necessary for such an institute to possess a "critical mass" of people with ideas to stimulate each other and to have ready access to communicate with those from other institutions through seminars and meetings. It is my understanding that the Kaiser Wilhelm Institute in Germany, with its various branches, functions in this way.

In August of 1965 I went to Moscow and Leningrad with a group of neurologists, neurosurgeons, and physiologists to visit research institutes in the Soviet Union. There are 87 medical schools in the Soviet Union, 82 of which are independent, and only five are parts of universities. These schools are concerned with teaching and very little research. Most biomedical research is done at special research. institutes, which I discovered are very much like the Worcester Foundation both in size and organization. I was told that there are 368 research institutes in science in the Soviet Union and those in the medical sciences are not parts of medical schools. The larger ones grant the Sc. D. degree to those with the equivalent of the Ph. D., called "Candidate in Science Degree" and those holding the M.D. degree. This Sc. D. degree is regarded as essential for promotion to top positions in Soviet science.

The Moscow Institute of Neurology is fairly typical and has been in existence since 1944. It is doing intensive research on Siberian

encephalitis and its investigators believe they have identified the virus for this disorder. They are studying other types of encephalitis. This institute handles statistics of all the neurological services throughout the Soviet Union. It is concerned with problems of vascular disease, particularly of the brain, and with problems of strokes and brain infections. It is doing research on haematomas and has developed impoved surgical procedures. It has a department of genetics in relation to inheritance of neurological disease and a department of rehabilitation. The institute has reported evidence that multiple sclerosis is due to a virus but that only persons with a particular genetic constitution are susceptible to this virus. It has 200 beds and their use, as in other research institutes, is determined entirely by the research staff. Eighty-five percent of the patients have been selected for research purposes and the 15 percent remaining beds are used for patients sent in for diagnosis. The institute contains laboratories for basic research in neurochemistry and neurophysiology.

Another interesting Moscow Institute is devoted to the study of death and resuscitation. Here extensive studies are being made of animals in the process of dying and of animals that have been resuscitated after "death." Conditioned reflexes are studied in relation to processes of death and recovery and the failure of cardiac and respiratory centers are intensively investigated. Death is brought about in animals by a variety of ways and the physiology of resuscitation is studied. The institute has its own ambulance service, which brings dying people from hospitals and from street accidents in the hope that experts in the physiology and pharmacology of resuscitation can save them. Five to eight cases of this kind are treated each week. Dogs can be revived 7 minutes after all signs of life have ceased and man after 5 minutes. Brain is the most susceptible organ and its failure due to toxins and lack of oxygen is the commonest cause of irreversible changes leading to death.

Also in Moscow we visited the Brain Research Institute founded in 1927. This contains many laboratories-chemical, biochemical, neurophysiological, anatomical, electronmicroscopy, neurohistological, and neurochemical. The work is in the field of comparative physiology and biochemistry and studies of the metabolism of the central nervous system under normal and pathological conditions. It has close working relations with various clinics.

An especially interesting visit was to the Neurosurgical Institute. There are three of these-in Moscow, Leningrad, and Kiev. Basic research goes on in these institutes as well as all forms of neurosurgery. Thus the Moscow Institute has laboratories of biochemistry, neurophysiology, ophthalmology, and some 17 postdoctoral students enter each year to study to be neurosurgeons. The institute has 42 neurosurgeons on its staff and the postdoctoral training period lasts from 3 to 5 years. There are 130 research workers and 40 postdoctoral students at this institute where 1,000 brain-tumor operations are performed annually. It accepts some 2,500 brain-tumor cases a year, of which 60 to 65 percent are operated upon. Some patients refuse operation and receive radiation therapy and, of course, many tumors are inoperable. There are 60 beds in the Moscow Institute for head injuries. Other institutes we visited were the Institute of Pharmacology and Chemotherapy, the Pavlov Institute of Physiology, and the

Psychiatric Institute. The research program of this last is biologically oriented where work is going on on biochemical factors that may be involved in schizophrenia.

I was impressed with these samples of institutes we visited. Unbeknownst to me until then, I found that they function in a way similar to that of our own Worcester Foundation for Experimental Biology, in which a group of investigators are concerned with both basic and applied aspects of biomedical science. On a much larger scale this is also true of the Clinical Center of NIH at Bethesda.

CONSIDERATIONS OF SOME SPECIFIC QUESTIONS

Senator Harris asks, "Is there need for additional attention by Federal agencies in the field of biomedical development?" As I have indicated, I think the Federal Government has done a good job in the support of biomedical science. For reasons I have outlined, I believe that more Federal suport for research institutes holds promise. I have been alarmed over the last year or two at increasing difficulties investigators encounter in testing new drugs because of redtape and excessive caution on the part of the FDA. Basic animal research can take us only so far and clinical tests are essential. Of course, investigators must be frank with their experimental subjects and the Code of Helsinki seems to cover the situation very well. The Panel on Privacy and Behavioral Research, appointed by the President's Office of Science and Technology, has ably discussed this matter (Science, Feb. 3, 1967). Well-qualified investigators have had what seems to me unnecessary difficulty in obtaining permission from the FDA to use drugs for experimental purposes. For example, LSD, the effects of which are well known when administered under proper conditions by competent investigators, has proved to be remarkably harmless despite the evils of its promiscuous uncontrolled use. But LSD has been treated as if it were a new drug. I feel that FDA permission should be obtainable without great delay to responsible investigators. Perhaps by increasing the budget of FDA and establishing committees of scientists rapidly to evaluate proposals for research, drug research can be facilitated.

In reply to the question as to improving existing techniques for implementing plans and priorities in the biomedical field, I believe that plans and priorities must originate with the working scientists themselves who are best informed as to the "State of the art" and whose imagination and drive must be fully enlisted. Directors of research programs, themselves scientists, are, of course, important here since, within limits, they can guide programs into desirable channels. I have expressed my interest in the independent research institute which, because of its size and fluidity of operation, if properly supported by grants, can implement plans and priorities perhaps more effectively than can larger, more administratively cumbersome organizations. I believe that institutional grants are desirable of the program supporting kind made to the Sloan Kettering Institute to replace the large number of special project grants to institutions of proven excellence. As to the question of evaluating existing means of communications between the scientific community and Federal agencies concerned with biomedical research, I believe that there are ample channels available

through the National Science Foundation-National Research Council, the study sections of NIH and NSF and the VA special committees convened by Government agencies to deal with specific problems and, of course, the important advisory committees of scientists to the President and to the Congress.

The final question asked is whether new or additional Federal institutions are needed for further development and application of biomedical knowledge. I do not feel competent to answer this with assurance. Over postwar years, it seems to me, that the Federal institutions, especially the National Institutes of Health, have done well to further the developments and applications of biomedical knowledge. Presumably more institutions like the NIH Clinical Center of Bethesda could be built to integrate basic and applied science more effectively, but this is being very well done in a number of private institutions with the aid of Government grants and contracts. I have mentioned independent research institutes collaborating with hospitals. I am much impressed with the brilliant research that is conducted at some hospitals associated with medical schools such as the Massachusetts General Hospital in Boston where, for example, basic biomedical work by Fritz Lippmann brought him a Nobel Prize and in which clinical research and patient care is carried to a high degree of excellence. Another of a number of teaching hospitals affiliated with Harvard is the Peter Bent Brigham Hospital which is effectively bringing to bear fundamental medical science on clinical problems. Medical centers of this kind are to be found in increasing numbers in major cities throughout the United States and Federal research grants are the backbone of their research programs.

Senator HARRIS. Thank you very much. There is that rollcall we were talking about earlier.

I do have several comments and questions. If you would not mind, I think it should not take me over 5 or 10 minutes at the most, to go over and make this rollcall, and then I shall be back.

The committee will be in recess for about 5 or 10 minutes, until I can answer the rollcall and return.

(Whereupon, there was a short recess.)

Senator HARRIS. The subcommittee will resume.

Dr. Hoagland, thank you for waiting. I do not think we will have another rollcall this afternoon.

You touched on a subject which is not directly involved in these hearings, but is a concern of this subcommittee. That is what has been called a geographical distribution of the Federal research grants. You say:

I think that this should be done by increased appropriations of special funds and not by curtailing Federal support to those centers, since this will deteriorate the quality of our science and slow its advance, including advances in technology and bedside medicine.

I would agree. There is no question but that it not only is elementary, but also true, to say, that any changes in regard to distribution to research contracts should: (1) do nothing which will dismantle existing centers of excellence; (2) recognize that it is in the interest of our citizens that mission-oriented agencies, particularly, go where the quality is so they can get quality results; and (3) that excellence is primarily and basically a local responsibility.

Having said that, let me ask you this: In your own Institute of Experimental Biology, the Worcester Foundation for Experimental Biology, is there teaching connected with the Foundation?

Dr. HOAGLAND. Yes. We have an active teaching program for postdoctoral students. There are three training programs, one in the field of steroid chemistry, with applications to medical problems. This we have had for many years now, financed by NIH.

Another is just started, which is in the field of neuroendocrine studies, neuroendocrinology. Then we have one which has been going on for about 7 years, financed by the Ford Foundation, in the field of reproduction. The first two are for American citizens. The students are postdoctoral students. The last one is almost entirely foreign students who come from countries where population problems are acute. They come for training to go back and set up research centers concerned with population control.

We have asked the Commonwealth of Massachusetts to allow us to give an advanced degree, an earned doctor of science degree, to a selected group of our postdoctoral students.

The Commonwealth has granted us this request, but we were embarrassed to find that if we implemented it we would lose our general research support from NIH, because we would then be classified as a college. If we were giving and M.D. or an accepted degree in medical science, this would still be all right, because medical schools get this particular formula that we have as a research institute.

As a research institute, we get about $325,000 a year as a general research support grant, but where we to take just one student on toward this degree that the State has permitted us to do, we would lose that grant. We would come under a different formula that would apply to colleges, and this would cost us about $200,000 per year net loss.

So we decided we had better postpone this luxury.

We also arranged through the Department of Education for a loan for housing for our postdoctoral students, who have been living around in various places. But, also, we found that if we accepted that loan, we would also lose our status as a research institute. Everybody, the people at NIH were very unhappy about it, but this was the ruling and we could do nothing about it.

On the other hand, we hope this may change at some time.

Senator HARRIS. That is an internal ruling of the NIH, I suppose? Dr. HOAGLAND. I think so; yes. On the other hand, somehow or other, I got the impression it was by act of Congress. Is that true? Senator HARRIS. We do not know.

Dr. HOAGLAND. I think that would be worth looking into, because this was a very embarrassing thing to NIH and to us. Everybody over there said they would like to see us able to grant degrees and that we were qualified to do so, but we could not afford it.

Senator HARRIS. That is a very important point, and we will look into that.

Dr. HOAGLAND. I wish you would. I think it is worth looking into. Senator HARRIS. What I started to say earlier is, Do you agree with me that the presence of research activities complements the teaching process?