ported in "Medical Tribune," which covered the trial, Dr. Bessman, the longstanding challenger of current PKU programs, said: "This verdict by a lay jury gave recognition, loud and very clear, to the uncertainty which surrounds PKU diagnosis and testing *** and the need for objective review." 46

Let us address ourselves to legislation of medical practice. Until not very long ago, health legislation was mainly of a protective nature to protect the public from infection and from adulteration or misrepresentation of food and drugs. Laws have protected employees against harmful or dangerous work conditions. The mentally incompetent have been the subject of laws which provided for their commitment, which specified their civil rights, and which in some States provided for their sterilization. The public health has been under protection of police powers of States in diverse ways.

Recent health legislation embodies both technological and sociological elements, the latter including the financing and distribution of medical care. The public has had boundless confidence in the potential of science and technology to surmount all or most forms of disease, pestilence, and other mortal perturbations. A generous Congress has appropriated many billions of dollars to support basic and applied research programs which offer new hopes of medical breakthrough.

The area of mental retardation has been opened to medical and social advances. Instead of keeping the retarded out of view in State institutions and in our attics, thereby pretending we have disposed of a problem, we have through legislation inaugurated programs to improve the condition of these unfortunates, physically through better facilities and mentally and socially through training and rehabili

tation.

On the minus side we must take care that we not overestimate the possibilities for improvement, that we not engender unwarranted hopes for kinfolk, and that we not outpace the ability of society to absorb more enlightened approaches toward treatment of the retarded in their own communities.

The campaign to have PKU laws enacted in all of the States has been astonishingly successful. Many of the 37 enactments were passed with scarcely any legislative debate, if at all. This is understandable. Who dares testify against motherhood, babies, and good health?

The argument is sometimes made that we have ample precedent. for the mass PKU screening laws. After all, we have laws which require premarital blood tests. We have laws which call for compulsory immunization of schoolchildren and of others. Why not laws to detect and prevent or cure mental retardation?

There are differences.

The other laws are intended to protect us from the spread of disease, from contamination, from contact with invisible enemies. The other laws take cognizance of the fact that a disease carrier might propagate epidemics and that people must be protected from external, unseen hazards.

It is not so with PKU.

The problems raised here are minor compared to others looming just beyond the horizon or already beginning to nudge themselves

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

into view. Will these beginnings of legislative prescription of the practice of medicine be extended into other areas? How shall we know where to stop? Is it wise to legislate the practice of medicine when there are so many biological unknowns which can scarcely be identified let alone committed to paper. Can a legal code replace the exquisitely difficult judgments a physician must make in prescribing for a biologically unique patient? Medical practices sanctioned by law are much more difficult to change than those applied through individual judgment. Laws remain on the books, rigidly fixed, while the state of the art in medicine continues to advance and to change. Yesterday's beliefs become tomorrow's corections.

Before moving, finally, into some concrete recommendations, it should be noted that the PKU laws have provided for the substitution of clinical judgment by a single chemical determination which may or may not have a direct bearing on the disease.

What do I propose?

1. As to mechanisms of advice:

Any one solution, such as some independent ombudsman or office of review in the executive or legislative branches, would be insufficient. Rather, we need a return to old-fashioned scientific pluralism. We need open, constructive conflict of ideas from which truth may emerge. We should not discourage advocacy, dissidence, and special pleading. One approach is to dilute the concentration of advisory sources. The same people or program sources should not at once guide legislative and executive branches, from within and without, while also dominating voluntary and professional society channels. Let us round out our pluralisms and at least occasionally have some spirited debates over both ends and means, right out in the open.

2. As to program choice and priorities:

The making of choice becomes more difficult as more is learned about situations and problems. On the whole, reliance must be placed on the professional judgments of the experts and the administrators. Legislators must also play a part in choice, for they thereby bring in the popular view-provided it is really that-as opposed to the dominance of professionalism. Yet choice must be subject to criteriabased review, taking into account total needs and total resources. Thus, if PKU programs are still investigational, should we not limit their scope while resources are deployed to improvements in more prevalent areas of mental retardation?

3. As to applications of knowledge:

Before particular disease targets are selected for widespread preventive or therapeutic application, there must first be a base of adequate knowledge derived through fundamental and controlled clinical research. Consistent with advances in clinical experience protracted pilot tests should be conducted in one or more States under controlled, scientifically modeled conditions, in order to derive adequate experience. Progressively, as wider field trials are conducted under varying conditions, independent medical judges without personal cause should evaluate progress. Then, assuming that the program demonstrates its worthiness, it should be expanded at a rate consistent with the development of adequate clinical and laboratory facilities and professional

manpower.

The public should be fully informed as to whether a program is investigational or service-ready. Evaluations against criteria of benefit should be continuous.

The need for developing informational bases as prerequisites for action is just as important in all other areas of public medicine, whether in the regulation of drugs or in the extension of medical services to the public.

4. As to legislative prescription of medical practice:

Legislative enactments of medical practice should be limited to assuring good practice, to protecting the public against hidden or unseen external hazards, and to protecting the rights of patients, especially the incompetent. Laws cannot specify action, when individuals are biochemically and biosocially unique and when the knowledge of medicine undergoes constant change. Laws cannot substitute for the professional judgments of physicians.

Senator HARRIS. The bibliography attached to your statement will be included in the record at this point.

1

(The bibliography referred to follows:)

EXHIBIT 1

BIBLIOGRAPHY FOR STATEMENT "CREATIVE PLURALISM: MEDICAL OMBUDSMAN" By Dr. Joseph D. Cooper

1G. A. Jervis, "The genetics of phenylpyruvic oligophrenia (a contribution to the study of the influence of heredity on mental defect)." J. Ment. Sci., 85:719, 1939.

'Children's Bureau, U.S. Department of Health, Education, and Welfare: An inventory of children with phenylketonuria. November 1962.

3

A brief description of the history of diagnosis and treatment of PKU and of current methods is to be found in W. R. and S. A. Centerwall, Phenylketonuria. Children's Bureau Publication No. 388, U.S. Department of Health, Education, and Welfare, 1965.

4

R. Guthrie, "Blood screening for phenylketonuria," J.A.M.A., 178:863, 1961. 5 U.S. Department of Health, Education, and Welfare, Welfare Administration, Children's Bureau, State Laws Pertaining to Phenylketonuria as of November 1966 (1967).

R. Guthrie and S. Whitney, PKU screening program progress report #2. March 20, 1963. (Distributed to U.S. Children's Bureau, state agencies and others). Also, addendum May 1, 1963.

7

"Treatment of phenylketonuria; report to the Medical Research Council of the Conference on Phenylketonuria." Brit. Med. J., 1:1691-1697, 1963. "Comparative Study of PKU tests," news report, J.A.M.A., 198 :2, Oct. 10, 1966,

p. 42.

9

Information acquired through personal sources.

10 T. J. Vecchio, "Predictive Value of a Single Diagnostic Test in Unselected Populations," New Eng. J. of Med., 274:21, May 26, 1966, p. 1171; Ann Sproul. "Influence of Conditional Probability on the Effectiveness of Mass-Screening Programs," J.A.M.A., 196:315. April 25, 1966; "Mass-Screening Programs," editorial, J.A.M.A., 196:360, April 25, 1966.

"R. J. Allen, et al, "The Influence of Metabolic Variations in the Diagnosis of Phenylketonuria in Infancy." Soc. Pediat. Res., abstracts, 67:922, November

1965.

12

Efron, Mary L.. "Aminoaciduria." New Eng. J. Med., 272:1058-1067, 11071113, 1965; M. L. Efron, Phenylketonuria and phenylalaninemia: Conclusions to be drawn from the mass PKU screening program, paper presented November 21, 1965, at the Rosewood State Hospital, Owings Mills, Md.

13 J. Allen and M. Gibson. "Phenylketonuria with normal intelligence." Am. J. Dis. Child., 102: 115–122, July 1961.

14

1 V. Caudle. "Phenylketonuria without mental retardation." Pediat., 26:502, September 1960.

15 S. Coates, A. P. Norman, and L. I. Woolf, "Phenylketonuria with normal intelligence and Growers' muscular dystrophy." Arch. of Dis. in Child., 32:313– 317, August 1957.

16 V. A. Cowie, "An atypical case of phenylketonuria." Lancet, 1:272-273, February 3, 1951.

17 V. Cowie and M. W. Brandon, "Follow-up note on an atypical case of phenylketonuria." J. Ment. Def. Res., 2:55–58, December 1958.

18 Y. Hsia, W. Knox and S. Paine, “A case of phenylketonuria with borderline intelligence." J. Dis. Child., 94 :33-39, July 1957.

19 A. Leonard and L. McGuire, "Phenylketonuria: an unusual case." J. Ped., 54:210-214, February 1959.

20 J. Low, D. Armstrong, and J. W. Carlisle, "Phenylketonuria. Two unusual cases." Lancet, 2:917-918, November 3, 1956.

"M. W. Partington, "Variations in intelligence in phenylketonuria." Can. Med. Assn. J., 86:736–743, April 1962.

22

2B. S. Sutherland, H. K. Berry and H. C. Shirkey, "A Syndrome of phenylketonuria with normal intelligence and behavior disturbances." J. Ped., 57:521–525, October 1960.

*W. E. Knox, An Evaluation of the treatment of phenylketonuria with diets low in phenylalanine." Pediat., 26:1-11, July 1960.

24 R. A. MacCready, "PKU testing: A reply to Professor Cooper," editorial, Med. Trib., April 6, 1966, p. 15. See also E. S. Kang, et al., “Clinical observation in PKU," Pediat., 35:932, June 1965; R. A. MacCready and M. G. Hussey, “Newborn Phenylketonuria detection program in Massachusetts," A.J.P.H., 54:2075, December 1964.

25 R. Fuller, "Psychological results in treated phenylketonuria. I. Gesell Findings," in J. Zubin, ed., Psychopathology of Mental Development (in press); R. Fuller, "Phenylketonuria: Psychological and developmental evaluation,” paper presented at the Washington Conference on Phenylketonuria, April 6-8, 1966. J. Kennedy et al., "Early treatment of phenylketonuria," Am. J. Dis. of Child., 113:67, January 1967.

27 D. S. Kleinman, "Phenylketonuria. A review of some deficits in our information," Pediat., 33:123, January, 1964.

28 G. Solomons, L. Keleske, and E. Optiz, "Evaluation of the effects of terminating the diet in phenylketonuria,” J. of Ped., 69:596–602, October, 1966.

29 Fuller, loc. cit.

30 "Treatment of Phenylketonuria," report to Medical Research Council of Conference on Phenylketonuria, Brit. Med. J., 1 :1691, 1963.

1 A. I. Terr, R. J. Allen, and N. A. Vanselow, "Immunologic responses in phenylketonuria," J.A.M.A., 198:1185, December 12, 1966.

33 D. W. Woolley. The Biochemical Bases of Psychoses, Wiley, 1952.

33 6

"Statement on Treatment of Phenylketonuria," Committee on the Handicapped Child, Pediat., March 1965, pp. 501-503.

M. K. Wilson, B. E. Clayton, "Special diets in the treatment of biochemical disorders of mental handicap," in J. D. Allan and K. S. Holt (eds.), Biochemical approaches to mental handicap in childhood. Edinburgh and London. E. & S. Livingstone Ltd., 1965.

* K. S. Holt, "Difficulties and dangers in the management of phenylketonuria,” Acta Paediat. (Stockholm) 52: 417-23, July 1963.

* P. R. Dodge, E. L. Mancall, J. D. Crawford, J. Knapp and R. S. Paine, "Hypoglycemia complicating treatment of phenylketonuria with phenylalanine-deficient diet: report of two cases," New Eng. J. Med., 260: 1104–1111, 1959.

37

R. J. Allen, Letter to the editor, New Eng. J. Med., 270: 1367–1368, 1964. 6.8 MacCready and Hussey, loc. cit.

39 Rebuttals on PKU testing, Med. Trib., May 30, 1966.

40

N. J. W. Royston and T. E. Parry, "Megaloblastic Anemia complicating dietary treatment of phenylketonuria in infancy," Arch. of Dis. in Child., 37:430, 1962. "S. P. Bessman, "Phenylketonuria," Med. Sci. 16:6, June 1965.

43 B. Umbarger, "Phenylketonuria-treating the disease and feeding the child," Am. J. Dis. Child., 100:908-914, December 1960.

43

Committee on Fetus and Newborn, American Academy of Pediatrics, "Screening of newborn infants for metabolic disease," Pediat. March 1965, p. 499. "Communication from Charles Upton Lowe, M.D., Chairman, Committee on Nutrition, American Academy of Pediatrics, to Ellen Kang, M.D., Children's Bureau, Washington, D.C., July 30, 1965.

C. C. Mabry, J. C. Denniston, and J. G. Caldwell, "Mental retardation in children of phenylketonuric mothers," N. Eng. J. Med., 275:1331-1336; also, "Maternal phenylketonuria," N. Eng. J. Med., 275:1379–1380.

46 Med. Trib., February 22 and 29, March 1, 1967. See also S. P. Bessman, "Some biochemical lessons to be learned from phenylketonuria," J. Ped., 64: 828-838, June, 1964; S. P. Bessman, "Legislation and advances in medical knowledgeacceleration or inhibition," J. Ped., 69:334-338, August, 1966.

Senator HARRIS. Dr. Cooper, I want to say how grateful we are for your presence here and for this very interesting presentation. We had in our conference "Research in the Service of Man," in Oklahoma City, a case study presentation by Dr. Shannon. It had to do with the Salk and Sabin vaccines in the polio situation, and he informed us about how we might go about developing a vaccine, perhaps, in a better way, or at least to indicate the exigencies involved in such development and to learn from our past mistakes and successes. The PKU case you have presented will be very helpful to us, and it is personally very impressive to me although I have no doubt that others may want to appear and dispute your case.

I am not sure how the subcommittee may make recommendations in the implementation of the proposals which you make, but I think a part of our job is to shed light on the general problems, and also to stimulate dialogue between those involved in the social sciences, and in politics and public policy on the one hand, and those involved in biomedicine on the other.

I think sometimes we are mutually suspicious of each other. But we are going to have to become less suspicious if we are going to do a better job than the one we are presently doing. So I think what you have had to say will be very helpful to us, and will be a very important part of the record of these hearings.

I haven't any questions because I think you have made your points very, very well. Do you have anything further you would like to add? Dr. COOPER. Well, your staff talked to me and asked if I might be prepared to elaborate a bit more specifically on some of the thoughts I have had.

I deliberately titled the presentation, "Creative Pluralism, Medical Ombudsman," "because I think it is only through the pluralistic approach that we are more likely to slow down precipitant advances, and bring out the truth.

The problem is, how do the institutionalized mechanisms-the Congress, the executive, the NIH within the executive, because there are different levels of the executive-get independent advice?

If we look at the Congress, it has advice available to it through various committee mechanisms, but the kinds of advice which are generated thereby depend largely on the ability of the committees to bring in people from the outside. I don't think that Congress has any independent mechanism of case building, of looking into situations and using them as case studies for the edification of the Congress, or to develop the issues in depth fundamentally, and this is one area which I would recommend to your committee for exploration.

Within the complex of the NIH, we have advisory councils, and we have study sections which pass upon grants. The advisory councils are supposed to operate at a much higher level and advise the individual institutes, and now the separate National Institute of Mental Health.