(2) An evaluation of existing Federal procedures for the establishment of research priorities and long-range plans in the field of biomedicine.

My answer is: that viewed over the whole spectrum of biomedicine, the existing procedures and planning is quite good. There are a few emerging problem sectors, however, for which new institutional forms will have to be invented to meet the need. In these sectors, it must be appreciated how relatively small is the body of knowledge we have to plan with.

(3) Are existing techniques for implementing plans and priorities adequate? If not, what suggestions do you have for improving them?

My answer is that for that immense body of biomedical knowledge that can be applied by the individual physician to the individual patient, our existing techniques are excellent. What is needed lies elsewhere and requires first that we develop institutional forms whereby we may acquire new knowledge, including its means of practical application for the emerging problems that have been identified.

(4) An evaluation of existing means of communication between the scientific community (research scientists, engineers, medical practitioners, and hospitals) and Federal agencies concerned with biomedical research.

My answer is that they are quite good now and that the Government, notably the National Library of Medicine, is constantly studying ways to make them better.

(5) Are new, or additional Federal institutions needed to further development and application of biomedical knowledge.

My answer is that a few new and at least one additional Federal institution are needed to meet certain emerging problems that have been identified above.

Finally, may I say that I consider the overall biomedical question to which the subcommittee is addressing itself to be one of the most important of those questions concerning the whole science-government interface which so very much concerns us all in these times. Our Federal biomedical institutions have been thoughtfully developed, are serving us very well, and have shown that capacity for orderly adaptation to change that characterizes institutions that continue to meet their social purpose. My remarks have been directed to a few sectors in which further adaptation has become necessary and has already begun; I am very pleased to have had the opportunity to present them to the subcommittee.

Senator HARRIS. Dr. McDermott, we thank you for your presence and for the great deal of thought and preparation that has gone into your study. I am sorry that the Senate has gone into session now and I have to be over there at 12:30. So we won't have time for much discussion.

But I do want to say that I think you have followed very well, the preceding statement by Dr. Bennett, who said we need to do more about identifying needs. I also think you have started us on that task with your inventory of problem areas infant mortality here in the United States; infant mortality abroad; manipulation of our environment, which as you say, is a new and very broad subject; and lastly, the delivery of technological developments, which, as you say, is a

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field where we have to think in terms of large sums of money if we are to do something about that.

I appreciate very much your statement and your inventory of these needs and your specific recommendations about how these needs might be met. Again I say I am sorry that I have to go over and be a Senator for awhile instead of a student.

We will resume at 2 o'clock when we will hear from Dr. Max Tishler and Dr. Joseph Cooper. But until 2 p.m., then, we will stand in recess. Thank you.

(Whereupon, at 12:30 p.m., the subcommittee recessed until 2 p.m. of the same day.)

AFTERNOON SESSION

Senator HARRIS. The subcommittee will be in order, resuming our hearings on Research in the Service of Man: Biomedical Development, Evaluation of Existing Federal Institutions.

Our next witness is Dr. Joseph Cooper. Dr. Cooper, will you come forward, please.

Dr. Cooper is Professor of Government at Howard University, here in Washington, D.C., and Adjunct Professor of Public Administration at the American University here in Washington. His Ph. D., which he received in 1951, is in the field of Political Science.

Without objection, we will place a brief biographical sketch concerning Dr. Cooper in the record at this point.

Biographical Sketch: Dr. Joseph Cooper

F.ofessor of Government, Howard University, Washington, D.C., Adjunct Professor of Public Administration, The American University, Washington, D.C., Ph.D. 1951 Field: Political Science.

Background Data: Currently engaged in studies of the interplay of science, public policy and politics. Consultant to the Commission on Research, American Medical Association and contributor to medical publications.

Entered Federal service in 1934 and advanced progressively to executive positions, the most recent having been Executive Assistant to the Deputy Postmaster General, Executive Director, U.S. Salary Stabilization Board and Chief, Procedural Coordination Branch of the U.S. Department of State.

Senator HARRIS. Dr. Cooper, we are very pleased you are here, we will be pleased to hear from you at this time.

Dr. COOPER. Thank you, sir.

and

TESTIMONY OF DR. JOSEPH D. COOPER, PROFESSOR OF GOVERNMENT, HOWARD UNIVERSITY, ADJUNCT PROFESSOR OF GOVERNMENT AND PUBLIC ADMINISTRATION, THE AMERICAN UNIVERSITY, WASHINGTON, D.C.

Dr. COOPER. The clamor for practical application of discoveries of biomedical knowledge grows louder. Medical researchers are being told they must release the secrets of their laboratories to physicians for the public benefit. This poses quite a problem for the research community which must ask itself: What are we holding back?

The situation is not an unexpected one. Sooner or later, an impatient public was bound to ask for delivery on promises made recurringly that the conquest of innumerable diseases would be achieved quickly if only enough were spent in a hurry.

Surely, the country can afford to support as much worthwhile medical research as its qualified manpower can absorb. Cost is not really an issue in that context, especially when improvement of the Nation's health is the eventual aim.

Practical application is another matter. In our haste to win the medical wars society's haste and to enjoy promised fruits of conquest, we are adventuring beyond prudent limits of risk. The hope becomes the theory which leads to selective discovery of evidence to support the wish, while contrary evidence which might slow the pace is ignored or rationalized away. This naturally stems from single-minded advocacy which sometimes has led to great gains, but more often has blocked or retarded action along other avenues of progress.

What is wrong is the absence of mechanisms for obliging proponents of action to offer evidence, in reasonable depth, to independent judges who do not have causes to espouse. Consequently, it has been too easy for bold new programs in the medical sector to come into being without scientific bases for promises or hope that benefits could or would materialize. Once activated these new programs become irreversibly committed because of public promises, dependence of program personnel on continuity of support, and force of legislation."

As an example of prematurity and the lack of constructive challenge which once was more dominant in scientific discourse, I will discuss the national program to prevent a rare disease called phenylketonuria, a disease which often results in mental retardation.

Although this program has been held out to the public as an example of a signal gain-a model for other programs-I suggest that what should have remained a combination of research and pilot demonstration activities has been advanced prematurely into a national program status. While great good might eventually result, as of now there is evidence of serious harm to children without convincing proof, in the best scientific traditions, that claimed benefits are actually being realized.

I do not impugn sincerity of purpose. In particular, I do not suggest that any groups, public or private, should be criticized. Rather, it is the prevailing system-the vogue, in a sense which I criticize. It accentuates the positive and, if it does not entirely eliminate the negative, it does not provide adequately for taking it into account. Sometimes, in fact, it looks away from it in the mistaken notion that contrary views will fade away. Of course, they don't, for truth eventually prevails, although sometimes at great pain and great cost.

The public insists on progress. This it should have, but not the illusion of progress. We have a way of hustling and bustling about, thereby conveying a sense of movement forward through sheer activity. Unfortunately, activity in and of itself is not the same as accomplishment which, in the medical sector, calls for a balance mix of scientific research and practical application.

Finally, at the conclusion of my discussion of the phenylketonuria program, I wish to make constructive suggestions for the strengthening of our pluralistic mechanisms. We owe much to those who have pioneered in bringing biomedical research to the stage it occupies today. It is in the nature of progress, however, that new problems are engendered by each new thrust forward. If we are not to have an

"incomplete pluralism," we need to bring in new viewpoints, including divergent ones.

Phenylketonuria, more commonly called PKU, is a genetically acquired disease commonly associated with mental retardation, although some phenylketonuric babies grow up to be normal or bright without treatment. Apart from, or in addition to, retardation, the child may have postural peculiarities, convulsive or jerking movements, and a characteristic musty body odor, among other symptoms. PKU belongs to a disease category called "inborn errors of metabolism." Others of these genetic errors, also rare, which find their way into the news are galactosemia, histidinemia, maple syrup urine disease, and homocystinuria.

For the symptomatic child and its parents, PKU is a calamity. For society generally, PKU is a rare disease. The incidence of the disease is estimated, on the high side, about 1 out of every 10,000 births. On the low side, the incidence has been estimated at 1 in 25,000 or lower. A true figure cannot really be given due to errors of diagnosis which may yield either false positives or false negatives and to difficulties of projecting statistically from small samples. In any event, a physician may work out his life career without encountering any cases at all. The institutional population of phenylketonurics is also relatively rare, having been estimated at considerably less than 1 percent (0.793 percent), from which it has been estimated that PKU occurs once in every 20,000 to 40,000 live births.1 A survey of clinical programs for mentally retarded children throughout the country, conducted in 1961 by the Children's Bureau, yielded an inventory of only 484 with phenylketonuria known to have been admitted to the reporting programs during the preceding 5 years.2

Why, one may ask, is this disease so much in the public view, despite its relative rarity? The reasons mainly are these:

1. Universally, mothers are fearful of having a child with a birth defect. A mother's first question after delivery usually will be "Is my baby normal?" Hence, the population generally has become interested in preventing and correcting birth defects. This interest was heightened by the well-known thalidomide disaster which came to public attention in 1962.

2. Close to 6 million Americans are mentally retarded in varying degree. Mental retardation is the single largest category of childhood disease. It accounts for twice as many disabilities as the combined totals of patients with cerebral palsy, rheumatic heart disease, and blindness. A broad base of missionary interest is to be found, therefore, among parents and lay voluntary groups.

3. A medical breakthrough in PKU and other metabolic disorders associated with retardation was hailed both symbolically and practically as an opening wedge-as a gain which would be followed by other breakthroughs which eventually would reduce the incidence of mental retardation. A national PKU crusade was therefore organized by voluntary health agencies, working through Government agencies and State legislatures, partly to control this disease and partly to bolster the spirits of those who seek anxiously for additional gains. 4. There existed a small but active group of physicians and medical researchers who had begun to build investigational interests and

Ed. note. References 1-46 are set forth in Exhibit 1, pp. 61-63.

careers around the phenomena of the "inborn errors of metabolism." Some not all of the more actively disposed of these medical personalities involved themselves in the promotion of the PKU program. They became the advisers to legislators, Government administrators, and voluntary health organizations. Out of the fusion of their own professional convictions and career interests emerged a professional evangelism.

5. The public was eager for delivery of new medical breakthroughs which it had been promised and for which it had been primed through the successive miracles of the sulfonamides, antibiotics, and poliomyelitis vaccines. These advances in combating and preventing infectious disease had filled the popular mind with the notion that simplistic models of specific cause and effect-the magic-bullet theory-would be found through massive action to cure just about any disease.

I shall review now some of the things known about PKU. Phenylketonuria is a metabolic defect transmitted genetically as a Mendelian recessive factor. This disease was first recognized and described in 1934. Detection at birth was difficult because the development of the child with phenylketonuric symptoms progresses quite normally during the first few months of life. Thereafter, intellectual growth is retarded. This is believed to be caused by the failure of a liver enzyme to metabolize the amino acid phenylalanine whose excessiveness in the bloodstream causes brain damage.

For some years after this disease had been defined and was made recognizable, medical science could offer little more than identification and explanation. A first major advance which permitted widespread screening economically was the development of a simple urine test. This test was not wholly satisfactory because the presence of phenylpyruvic acid, a spillage byproduct of the excessive phenylalanine, was not readily detectable until the baby reached 6 to 8 weeks of age. At that time it was no longer under hospital control and less amenable to screening and the commencement of dietary control. Prompt therapeutic management during the first weeks of life. is believed by many to be essential to prevent development of a brain lesion, the cause of retardation. Robert Guthrie, of Children's Hospital, Buffalo, developed a blood test which utilized only a few drops of blood taken by simple puncture from the baby's heel when it is only 4 or 5 days old. This afforded hospital control of the procedure. It is at the heart of today's mass screening programs which have been instituted in many States.*

The development which really fired the imagination, which offered the hope of cure not only for PKU retardees but for other victims of inborn errors of metabolism, was the reported impression that a special diet, low in phenylalanine, apparently prevented or limited the retardation of intellectual growth and other phenylketonuric symptoms. From a public health standpoint, therefore, the formula. for action seemed clearcut: put every newborn child through a PKU screening test and then take all who are found to be PKU positive and put them on the special diet. This is the simplistic model now widely adopted for the detection and treatment of PKU. It is the model which it is hoped will be useful in the treatment of many other metabolic disorders.

Ed. note. References 1-46 are set forth in Exhibit 1, pp. 61-63.