Dr. SCHIMMEL. You would say the scientists who want this program are very much concerned that there be no foundation in Washington that regiments them as far as specific techniques of scientific research are concerned?

Dr. RICHARDS. Absolutely.

Dr. SCHIMMEL. Regardless of what is the top organization, that is the one thing they want to be absolutely certain of?

Dr. RICHARDS. Right.

Dr. SCHIMMEL. One last question. Is it the general thought of scientists in the medical field that there should be as rapid and free a publication of the results of research in the field of medicine?

Dr. RICHARDS. By all means. That has been a tradition for hundreds of years. That was to some extent interrupted during the war, in some cases unfortunately so, but certainly that is a complete desideratum.

Dr. SCHIMMEL. Isn't penicillin an outstanding example of a drug on which there were no proprietary patents, which came into rapid use with a great many manufacturers participating in its development?

Dr. RICHARDS. Yes; it certainly is a conspicuous example, but in CMR's capacity as adviser to the Commissioner of Patents under the wartime secrecy laws, we know that manufacturers protected their processes in the manufacture of penicillin by filing many applications for patents on their individual processes. As I recall there were over 100 cases referred to CMR for review and recommendation.

Senator CORDON. Thank you very much, Doctor. Our next witness is Dr. Francis Blake, of the Yale University School of Medicine. Dr. Blake.

I assume, Doctor, you would prefer, as far as possible, to complete your major statement without questions?

Dr. BLAKE. Yes.

Senator CORDON. Will you just go ahead, please?

TESTIMONY OF FRANCIS G. BLAKE, DEAN AND STERLING PROFESSOR OF MEDICINE, YALE UNIVERSITY SCHOOL OF MEDICINE

Dr. BLAKE. I shall confine my remarks to comments on the importance of fundamental research in the progress of medicine, on the one hand, and on the other, to the place of the medical schools and universities in medical research. In addition I propose to state briefly what I conceive to be the necessary procedures and safeguards, if medical research is to be fostered, developed, and expanded in the most productive and useful fashion through the aid of Federal funds.

Much of what I have to say is based on 30 years' experience as a teacher and research worker in clinical medicine and more recently, through an intimate acquaintance with the operations of the Army Epidemiological Board, on experience with methods by which Federal funds may be used through contracts with universities with adequate safeguards for the freedom of inquiry, the display of imagination, and the exercise of initiative so essential to productive scientific research worthy of the name.

Dr. Richards has already recited the many remarkable, even spectacular achievements of medical research, and the useful applications

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of the new knowledge deriving from this research, in preventive and curative medicine during the war. He has pointed out the highly important contributions of the Committee on Medical Research under the Office of Scientific Research and Development in this accomplishment.

If I may, I would like to modify the next sentence slightly, after hearing Dr. Richards' testimony.

He has clearly stated the need for an expanded program of medical research and has expressed agreement with others who have advanced arguments in favor of the establishment of a governmental organization to foster the program of science in this country.

I accept without hesitation the force of his arguments for the need of Federal support, provided appropriate safeguards are set up in the procedure adopted for implementing this support-a procedure which should not contain within itself the seeds of self-defeat.

Indeed I would go further than call it need and venture to express the opinion that Federal support of scientific research in our medical schools and universities, particularly of so-called basic or fundamental research, which envisages no immediate practical result, presents a challenging and compelling opportunity for Government to foster the public welfare in an area of action in which we can no longer afford to lag behind.

Conspicuous examples have been given of the spectacular accomplishments which can issue from planned, organized, and coordinated medical research directed toward the solution of specific practical problems. Such accomplishments, however, do not constitute a valid argument that other unsolved problems of medicine, such as the prevention or cure of cancer, cardiovascular disease, and other degenerative diseases can be as expeditiously solved by a similar approach. A great deal of basic knowledge of living tissues will perhaps have to be won before these bastions of disease can even be attacked intelligently.

Moreover, I am constrained to express a considerable, and I hope a healthy, degree of skepticism that scientific research workers can profitably be deflected from their intrinsic interests into other fields of organized research. We must not forget that the undeniably successful record of medical research during the war, though impossible without the generous expenditure of Federal funds, would have been impossible without our great reserves of basic science. No amount of money, in the absence of these reserves, could have accomplished the desired result.

These reserves were:

(1) The accumulated scientific knowledge derived from years of fundamental research in the basic sciences of physics, chemistry, biology, physiology, pharmacology, bacteriology, immunology, and so forth, upon which innumerable advances in scientific medicine depend and without which the even reasonably prompt solution of practical problems in the prevention or treatment of disease would rarely be possible.

(2) The ready availability of numerous scientific research workers experienced in medical research, who had been trained in our colleges, universities, medical schools, and teaching hospitals during the last three decades prior to the war and who under the necessities of the war were willing to be diverted from their own work to the solution of problems essential to its efficient and successful conduct.

(3) The existence of university, medical school, hospital, and research institute laboratories and other facilities immediately available for utilization, even though often inadequately equipped and staffed for the purposes required. Here emphasis must be placed not only upon the basic scientific equipment, but also upon the clinical facilities: Hospital beds filled with hospital patients, and cared for by specially trained and interested physicians, for the hospital is the final testing ground for all medical theory.

Of these three aspects of medical research, the first, namely the background of fundamental knowledge in the scientific fields basic to clinical medicine, is so important that I would like to elaborate upon it.

IMPORTANCE OF FUNDAMENTAL RESEARCH TO THE PROGRESS OF

MEDICINE

Medical research, in the broadest sense, includes all scientific research which has a bearing on medicine. It may be pursued in a variety of ways and by the utilization of a great variety of scientific techniques. It is often classified as being fundamental research or practical applied research, although the methods used in both types of research are in essence quite similar. In both the investigator has an idea, he is curious about something, and desires to satisfy his curiosity by seeking a solution to his problem through experiment. He wishes to see whether his idea is correct or not. In so-called fundamental research he is curious about something the solution of which has no immediately obvious practical value, what the late Walter B. Cannon called "curiosity research." He wants to understand the fundamental mechanisms of human physiology; the mechanism of an enzyme; the shape of a protein molecule; the effect of electric force on diffusion; the pattern of electric currents given off by the brain; or how fish live in salt water, or seals, or whales.

In the intermediate zone are problems which at one moment appear to be fundamental, at the next, practical, such as the cause of a certain strange pathological lesion; the characteristics of bacteria or viruses or other agents of disease; the nature of the conditions which determine epidemics, the why's and wherefore's of parasites.

In so-called applied medical research the investigator seeks to answer questions, the solution of which may be practically applied to the prevention, the amelioration or the cure of disease. Basic or fundamental research, though aimed at answering specific questions, is very likely to lead to new ideas, entirely new conceptions, which will completely reorient the direct attack on practical problems of medicine. Applied or developmental research may provide answers to practical problems of great importance, but there it is apt to stop. It rarely leads to new ideas of fundamental importance. Both methods are important and should go hand in hand, but fundamental research is essential and must come first, for it is the source of new facts and new ideas and more new facts, which can then be profitably utilized in the elucidation of the practical problems of medicine.

Without the curiosity of a Fleming when he noticed that a contaminating mold inhibited the growth of bacteria on a culture plate, the subsequent developmental and practical research on the therapeutic applications of penicillin would presumably not have occurred. Nor would we have had penicillin had Fleming not had the freedom

to putter away with this curiosity to his heart's content. And without years of previous fundamental research in bacteriology by numerous investigators, often unconcerned with practical problems of medicine, Fleming would not have had the opportunity to notice the contaminating mold and its inhibiting effect on bacteria in the first place.

Let us consider the practical use of gamma globulin for the prevention of measles and of infectious hepatitis, both applications being the result of Government-fir anced research sponsored through the Committee on Medical Research and the Army Epidemiological Board. Had not many years of fundamental laboratory research on animal and human antibodies preceded, it probably would not have occurred to Chapin and Richardson in 1919 to see whether convalescent measles serum would prevent measles. No further significant practical advance resulted from this observation until Cohn, as the result of years of research on the physical properties of proteins, separated a pure globulin from plasma. This pure globulin has now found practical application in the prevention of measles through the applied research of Stokes, Janeway, and their collaborators, and more recently in the prevention of epidemic infectious hepatitis or jaundice through the studies of Stokes, Paul, and their colleagues.

Innumerable examples of this sequence of events, from fundamental research to applied and developmental research, and thence to the prevention or treatment of disease, could be cited.

As so clearly and eloquently stated in the report of the Palmer Medical Advisory Committee to Dr. Bush:

Discoveries in medicine have often come from the most remote and unexpected fields of science in the past; and it is probable that this will be equally true in the future. It is not unlikely that significant progress in the treatment of cardiovascular disease, kidney disease, cancer, and other refractory conditions will be made, perhaps unexpectedly, as the result of fundamental discoveries in fields unrelated to these diseases. * * * Further progress requires that the entire field of medicine and the underlying sciences be developed impartially.

* * *

Now, research in medicine, both fundamental and applied, basic or clinical, may be carried out effectively in several ways: first and most importantly, in my opinion, by the individual investigator possessed of curiosity, imagination, and technical competence, who at the same time has the opportunity to attack the problems which arouse his own interest, the freedom to redirect his research as the course of his experiments may dictate; who is under no immediate compulsion to arrive at a practical answer to a practical problem. Depending on the nature of the problem he may work alone or gather about him a team of research and technical assistants or even may endeavor to coordinate his attack on the problem with that of other investigators working on the same or other aspects of the same general problem. It makes little difference. He is the spark, the guiding hand, the source of ideas. Freedom and flexibility are the essence of the method. By it most of our important fundamental discoveries have been made.

The second method is by a planned and coordinated attack on a particular problem or a particular disease, usually with a practical end in view, sometimes initiated by the sponsors with promise of financial support, sometimes initiated by the investigators as a means of acquiring financial support, depending upon whether money is to be dispensed or obtained. The method has merit and a fine record of

accomplishment under particular circumstances, such as war, when the emergency require, the deflection of men from their intrinsic interests. The development and testing of penicillin may again be cited as an illustrative example, but let us not overlook the fact that one of the most important uses of penicillin was not envisaged in the original committee planning but came out of the curiosity, imagination and initiative of one investigator who had the courage to step out of bounds to see what penicillin might do in the treatment of syphilis. Nor should we forget that the skepticism and persistance of another investigator, who refused to accept the committee's dictum that penicillin was of little value in the treatment of subacute bacterial endocarditis, an almost invariably fatal infection of the heart, has forced acceptance of the fact that many cases can be cured, if large enough doses are given over a long enough time. Planned and coordinated group research supported by term grants through contract or otherwise can have great value, despite the inherent hazards that it may stifle initiative or divert investigators from their primary fields of interest and competence. Yet these dangers can be avoided, if the purposes of the grant are not too narrowly defined, are sufficiently broad and flexible. This, I think, may be illustrated by referring to the operations of the Army Epidemiological Board. This Board of seven civilian scientists experienced in the broad field of infectious diseases was set up under Preventive Medicine Service in the Office of the Surgeon General in January 1941, under the rather imposing and cumbersome title of the Board for the Investigation and Control of Influenza and Other Epidemic Diseases in the Army. The use of the words "investigation" and "other epidemic diseases" at once indicates the flexibility and breadth of the conception that lay behind its establishment.

Under the Board 10 commissions were organized, such as the Commission on Influenza, the Commission on Acute Respiratory Diseases, the Commission on Tropical Diseases, the Commission on Measles, the Commission on Neurotropic Virus Diseases, and so forth. Membership on each commission was made up of men known to have already exhibited interest and competence in the investigation of the diseases represented by the title of the commission to which they were attached. To the members of each commission was delegated the responsibility of drawing up their own plans for research, the central Board serving only in an advisory and not a directive capacity. Through contracts with the universities to which the directors of the various commissions were attached, funds were made available for research either in the university laboratories or in the field, both in this country or overseas as the situation demanded. Furthermore, I wish to point out that while the fields of activity of the various commissions might appear to be somewhat restricted as indicated by their titles, this has not been in fact the case. The administration of the Board and the terms of the contracts were purposely so flexible that it has been possible to use the talents of the members to investigate any problems of epidemic disease that were of interest and importance to the Army. By way of illustration let us take the Commission on Neurotropic Virus Diseases under the directorship of Dr. John R. Paul, of Yale. It might be supposed that it would be engaged in research on infantile paralysis and the various forms of encephalitis, and so it has been, but it has also gone far afield and made important