But there are other places where you are simply applying these techniques in the practice of medicine, and they are not research in the ordinary sense of the word.

Senator HARRIS. I can't see the difference in what you were saying. Dr. DUNHAM. There is really quite a difference. Our training and education group has a small budget for granting equipment that is used in training and in teaching nuclear energy techniques, radiation safety, and that sort of thing.

Dr. NABRIT. As you would understand, you are talking about large accelerators, things of this sort, in order to get the other types of energy sources available for treatment of disease. These could probably only be afforded in regional setups, such as the regional medical centers, and these probably could not be purchased by the individuals in those areas. This would have to be federally funded. But you would be able to get off neutrons and other broad beam treatments, which would be effective in treatment of cancer and other diseases that now would not be available to them at all, simply because of the cost, and the fact that these are ordinarily thought of as research tools.

Dr. DUNHAM. We have been having informal discussions with Dr. Endicott, head of the Cancer Institute, on this very subject. Senator HARRIS. Very good.

Dr. Nabrit, Dr. Dunham, and Dr. English, thank you very much for your presence. We appreciate your testimony and the time and preparation that has gone into it.

The subcommittee will now stand in recess until 2 p.m., when we will hear from Dr. Nathan S. Kline, director of research, Rockland State Hospital, Rockland, N.Y.

(Whereupon, at 11:50 a.m., the subcommittee recessed until 2 p.m. the same day.)

AFTERNOON SESSION

Senator HARRIS. The subcommittee will be in order.

This afternoon we wind up this week's hearings on "Research in the Service of Man." Our last witness for the week is Dr. Nathan S. Kline, director of research, Rockland State Hospital, Rockland, N.Y. Dr. Kline is also president of the American Academy of Neuropsychopharmacology, holding an M.D. degree, which he received in 1943. Without objection additional biographical data concerning Dr. Kline will be inserted in the record at this point.

Biographical Sketch: Nathan S. Kline, M.D.

Director of Research, Rockland State Hospital, Rockland, New York and President, American Academy of Neuropsychopharmacology. M.D. 1943.

Background data: Director, Psychiatric Services, Bergen Pines County Hospital, Paramus, New Jersey. Director of Research, Worcester State Hospital, Worcester, Massachusetts. Associate, New York State Brain Research Project; Columbia Greystone.

Assistant Clinical Professor of Psychiatry, Columbia University, College of Physicians and Surgeons. Research Associate in Department of Psychiatry, Neurology at Columbia University.

Member of many national and international professional societies, and recipient of many awards.

Senator HARRIS. Dr. Kline, I am sorry you have had to wait so long. We are very grateful for your presence here. I understand you have a prepared statement.

Dr. KLINE. I do, sir.

Senator HARRIS. You may proceed as you desire.

TESTIMONY OF NATHAN S. KLINE, M.D., DIRECTOR OF RESEARCH, ROCKLAND STATE HOSPITAL, ROCKLAND, N.Y.; AND PRESIDENT, AMERICAN ACADEMY OF NEUROPSYCHOPHARMACOLOGY

Dr. KLINE. Thank you. "The proper study of mankind" wrote Alexander Pope, "is man." Although the United States has a gross national product of $740 billion, it would be gross exaggeration to say that 1 percent of the total was devoted to biomedical research. Even the 2 or 3 percent expended to care for all our physical, emotional, and mental well-being barely equals the $20 billion which goes annually for alcohol and tobacco. Lone and usually cantankerous individuals have assayed evaluations of the present state of affairs in the health sciences with incomplete, inaccurate, and usually unrecognizable descriptions. The Federal Government devotes more dollars to research in this field than any other source and therefore has not only the right but the responsibility to review its investment in the present state of biomedical development. Investigation or even attention to what is being done will immediately be decried by some as an intrusion, an usurpation, an invasion of "scientific privacy."

We should not only consent to, but welcome, open scrutiny since it reassures the honest questioner and discredits the false and malicious accuser. The fear of the scientists and clinicians is that the purpose of such investigation is to obtain complete control and then to operate within a framework of politics as opposed to science. Despite certain basic conflicts of temperament, methodolgy, and even conclusions we are not forced to make an absolute choice between one set of values and the other since they exist in different but overlapping universes. There are incontrovertible political as well as scientific realities but this does not preclude that the meeting between the two should be productive rather than destructive. The collaborative approach which has thus far been encouraged by this committee bodes well. There has been a minimum of witch-hunting for either "irresponsible, selfish scientists" or "self-seeking, irresponsible politicians."

The question must have arisen in your minds as you listen to the details of various biomedical research programs as to whether it would be not only more economical but more effective to combine all these resources into one vast biomedical program capable of conserving not only equipment, space and supplies, but also the personnel of which there is such a desperate shortage. In principle at least such a system exists in the Soviet Union and is even advantageous for programed research with specific objectives based on "known" theory and with a predetermined methodological approach. On the other hand, it is multiplicity that nourishes originality especially of the unconventional type which is productive of most of our real "breakthroughs." The competition for funds whether between individual investigators seeking grants or between government or nongovernment agencies competing for support through their representatives, constitutes a healthy influence in determining which activities should be supported. The system is not automatically perfect and there are needless duplications not only in individual research projects but in whole areas. The major

fault lies not in the research itself but in the failure of biomedical communication. Research is repeated because investigators do not know it has already been done or that relevant work is available which would radically alter the whole approach to the problem. Even when an investigation is completed it is usually a year before the results are printed and no certainty exists that all, or even a majority of those for whom the results would be important, will ever get to see them. A particularly difficult situation arises because most journals do not like to publish negative findings and there is no place at all where investigators can describe projects they have abandoned when it became evident that they were wasting their time. The lack of knowledge about such failures perpetuates itself since other investigators in ignorance proceed to repeat the same work and again have no means of communicating their lack of success.

Over 50,000 scientific journals exist and each year somewhere between 5 and 10 million individual articles are published. How can an investigator possibly avoid duplicating work already done, learn of discoveries relevant to his field and report his own findings so that someone in addition to himself will read them? Sulfanilamide, the first of the modern wonder drugs, was synthesized as a dye in 1908 by Gelmo but not until 30 years later was any clinical use made of it. Penicillin was first described in the 1870's and for decades had been a nuisance because it contaminated Petri dishes and interfered with the growth of bacteria being cultivated. In 1928 Fleming had the brilliant idea that this nuisance might have clinical application and published his findings a year later. Ten more years were to elapse before there was demonstration in humans and in 1942 Fleming was poetically able to save the life of a personal friend who would otherwise have died of meningitis. How many hundreds of thousands of individual lives were sacrificed because these findings were not communicated even though, once known, the path was obvious? And how many more hundreds of thousands died prematurely before the utility of the drug became widely known?

Rauwolfia, a plant root, was used in India for thousands of years to treat both high blood pressure and insanity. Yet it was not until 1954 that one of its derivatives, reserpine, and a synthetic preparation, chlorpromazine, were tested for the treatment of mental illness. Initial skepticism was rapidly converted to enthusiasm in no small measure because of an appropriation of $2 million by the Congress of the United States on recommendation of a subcommittee such as this under the leadership of Senator Lister Hill and that other great friend of medicine, the late Representative John Fogarty. As a result, instead of the increase of 10 to 12,000 patients per year in public mental hospitals which had occurred for the 11 years up to 1956, the rate of accumulation not only slowed up but was dramatically reversed. In the past 11 years instead of the anticipated increase of 110,000 to 132,000 more inmates in such institutions there has been an almost incredible reduction of 85,000 patients despite a near doubling of the admission rate. This difference of 200,000 patients should be measured not only in terms of the $5 billion saved but of the 200,000 individuals most of whom were restored to their families and to the function and enjoyment of life. Here was a real triumph of communication and application once the potential was recognized. There are so many aspects

of the biomedical problem that need explication and discussion. How can one protect the rights of the individual from unnecessary or unjustifiable use as a research subject without at the same time creating a restrictive atmosphere which encourage the safest rather than the most effective treatment? How can we retain integrity but avoid regulations which give such precedence to privacy over progress that we die needlessly—but inviolate? Adequate understanding of the purpose and methods of biomedical research would go a long way toward encouraging the development of satisfactory but not unworkable safeguards.

To return to the problem of communication within the scientific field itself, it is evident that the one-quarter billion dollars now spent by the Federal Government for this purpose could be used more im aginatively and more constructively. In contrast to the research itself, where a multiplicity of approaches is valuable, biomedical communication definitely calls for a unified coordinated attack on the problem. The present method of multiple small-scale attempts at communication has resulted in such a sea of information that most of us would be drowned if we really had to swim through any substantial part of it. We have no choice but to ignore most of what is produced if we want to get any of our own work done. How we would welcome a system which provided the information we want and allowed us to disseminate our own contributions rapidly to those who would be interested! A great economy of effort and a great increase of productivity could result from the functioning of an Agency for Biomedical Communication charged to investigate the most effective means of such communication and also adequately financed to provide such a service. Not only could this be done for less than the quarter of a billion dollars a year presently being expended but many times that amount would be saved by preventing duplication of work already done and by making available other information on which more adequate and advanced hypotheses could be based and tested.

Let me give one small illustration of how such a communication network might work since at the moment we are engaged in developing a system for use in psychiatry which has the support not only of Dr. Alan Miller, Commissioner of Mental Hygiene for the State of New York, but also of Dr. Stanley Yolles, Director of the National Institute of Mental Health, who is hopeful that it may have countrywide application. Utilizing precoded forms the psychiatrist in the hospitals, community mental health centers, clinics, and even private practice will be able to rapidly check appropriate answers for items which appear on any psychiatric history, mental examination, progress, and discharge note. This can be done in an eighth to a quarter of the time normally occupied in dictating such a history into recording apparatus or to a secretary. An optical scanner is able to read the sheets at a rate of 6,000 to 7,000 an hour and a computer program has been developed which converts these data into an ordinary narrative case history which is printed out at a rate of 300 to 1,200 lines a minute. This circumvents the great shortage of typists as well as record storage for the information is then available for almost instantaneous retrieval. The system will not only provide such valuable clinical information as the characteristics of patients responding to one or another type of medication, the costs of different and sometimes

alternate methods of care and treatment, but also make possible sufficient epidemiological information to enable us to plan patient care on a nationwide basis and also to give insight into some of the factors related to continuance of improvement, causes of relapse, and perhaps ultimately to the prevention of certain types of phychiatric disorders. At another level the use of more individualized and much less expensive on-line typewriters would make possible a system by which individual investigators or physicians could indicate areas of relevance for their own work and by communicating with a central computer via the typewriter have specific data provided immediately. By indicating in advance such areas an investigator could leave his machine hooked up at night so that in the morning references which he had requested could be typed out, new articles appearing in journals or delivered at meetings which related to his work could be brought to his attention, and general information about his field provided to him. A half hour or so spent reviewing such material every day would keep him reasonably abreast of the latest developments and encourage communication with others working in the same area. There might also be provisions for him to feed back certain types of information which in turn would lead to enhanced efficiency of other investigators and clinicians. For instance, he might easily be put in touch with four or five other investigators working on essentially the same problem at a stage when their cooperative efforts might save years or enable them to achieve some objective which might not otherwise ever be accomplished. Also knowledge about the side effects or safety or efficacy of various drugs could be widely checked upon at almost any time and those with sufficiently dangerous side effects could then be immediately withdrawn whereas the safety of those otherwise threatened with withdrawal could be preserved if concern was unwarranted. This latter possibility constitutes another peculiar problem since reports of toxic or undesirable side effects presently receive widespread attention and almost everyone "plays safe" and accepts them. It is indeed rare for researchers to deliberately go out and demonstrate that the claimed toxic side effects are not present in actuality or at least not to the degree stated; as a result, such claims, even when inaccurate are rarely challenged. This misinformation is then rapidly included as part of the "literature" on the drug and at times results in erroneous withdrawal or needless restrictions as to usage of a drug that can deprive patients of valuable treatment. I can easily name examples of this type which exist at the present time. With an adequate communication network this type of perpetuation of misinformation would be much less likely to occur.

Certain biomedical information is almost impossible to transmit without it being seen. There already exists a substantial library of medical films but the problem is to find the time and place for the physician to do the viewing. With the availability of ultra-highfrequency channels plus the scramblers of the type used in pay television it is possible to transmit programs on highly technical subjects which would be available only to the person (in this case the physician or investigator) whose set possessed an "unscrambler." Thus films that might be frightening or unpleasant or subject to misinterpretation by the general public could be limited in their distribution to the physician or investigator. Further, devices exist to store such broadcasts so that