COMMITTEE ON APPROPRIATIONS

GEORGE H. MAHON, Texas, Chairman

KENNETH SPRANKLE, Clerk and Staff Director

DEPARTMENTS OF LABOR AND HEALTH, EDUCATION, AND WELFARE APPROPRIATIONS FOR 1967

WEDNESDAY, MARCH 2, 1966.

NATIONAL INSTITUTES OF HEALTH

WITNESSES

DR. JAMES A. SHANNON, DIRECTOR, NATIONAL INSTITUTES OF HEALTH

DR. STUART M. SESSOMS, DEPUTY DIRECTOR, NATIONAL INSTITUTES OF HEALTH

DR. G. BURROUGHS MIDER, DIRECTOR OF LABORATORIES AND CLINICS, NATIONAL INSTITUTES OF HEALTH

DR. JOHN F. SHERMAN, ASSOCIATE DIRECTOR FOR EXTRAMURAL PROGRAMS, NATIONAL INSTITUTES OF HEALTH

RICHARD L. SEGGEL, EXECUTIVE OFFICER, NATIONAL INSTITUTES OF HEALTH

CHARLES MILLER, FINANCIAL MANAGEMENT OFFICER, NATIONAL INSTITUTES OF HEALTH

JOSEPH S. MURTAUGH, CHIEF, OFFICE OF PROGRAM PLANNING, NATIONAL INSTITUTES OF HEALTH

DR. WILLIAM H. STEWART, SURGEON GENERAL

HARRY L. DORAN, CHIEF FINANCE OFFICER

JAMES B. CARDWELL, DEPARTMENT DEPUTY COMPTROLLER

Mr. FOGARTY. We have before us this morning the National Institutes of Health.

GENERAL STATEMENT OF THE DIRECTOR

Dr. Shannon, do you have a statement for the committee?

Dr. SHANNON. Yes, Mr. Chairman. I have a statement of some 13 pages which I can read or insert, at your pleasure.

Mr. FOGARTY. Whatever you want to do.

Dr. SHANNON. Then I shall read it. It is not too long.

Mr. Chairman and members of the committee, it is once again my pleasant duty to report to you on the progress of the NIH programs and to testify to the needs of these programs for the next fiscal year. As always, I welcome this opportunity to appear before you.

In my opening statement last year I discussed, in some detail, the directions in which biomedical research seems to be moving and the role which Federal support programs and the NIH programs in particular-might most usefully play in the years immediately ahead. I described the growing importance to the understanding of disease—

Of comprehensive studies of human development;

Of research in molecular biology, especially into the mechanics of genetics;

Of a thorough exploration of environmental and behavioral factors in the cause of disease:

And of the application of the techniques and tools of the physical sciences and mathematics to the solution of biological problems.

These are long-term trends in medical research. What I said about them last year is equally true today-perhaps just a little more so.

As my views on the goals and future directions of the NIH programs are already on the record, I shall confine myself to a brief account of the present state of the NIH programs and to a summary of the 1967 budget request. I shall, of course. be glad to discuss in more detail any points which members of the committee may wish to raise.

Each of the Institute directors will report to you on the specifie accomplishments in the various categorical areas. To illustrate the heartening progress made during the past year all along the frontier of the war against disease, I should like to mention a few examples of research achievements and of promising new projects.

RESEARCH ACHIEVEMENTS

As prevention is the only feasible "cure" for many serious congenital anomalies and diseases, it is particularly important to develop better techniques for predicting under what conditions these defects are likely to occur. One such new technique is a blood test for identifying women who may be carriers of a gene causing progressive muscular dystrophy. This form of the disease, which accounts for two-thirds of all cases of muscular dystrophy, is inherited-half of the male children born to women who carry the gene will have the disease even though the mother shows no sign of it. The new blood test will identify 75 percent of such women. If the test is widely adopted-and, more importantly, if affected women heed its results-a large number of these tragic cases could be prevented.

The new blood test for carriers of progressive muscular dystrophy is only one of a steadily growing array of tests and procedures for detecting genetic defects that may be passed on by a parent to a child. There are now a score of inheritable errors in metabolism which can be identified in apparently healthy adults who are unwitting carriers. These include galactosemia; various blood abnormalities, such as certain types of anemias; a form of rickets that resists treatment with vitamin D abnormal drug sensitivities; and, of course, the disease now widely known as PKU. Many of the abnormalities for which prenatal tests are already available are fairly rare but this is no consolation to the family that is stricken by one of them.

PREMARITAL COUNSELING BY MEDICAL PROFESSION

These developments are beginning to make it possible for the medical profession to offer a kind of premarital counseling that could ultimately result in a sharp reduction in the incidence of a number of congenital abnormalities including some which result in severe-and tragic-mental retardation.

The medical profession has a moral obligation to warn prospective parents of the disabilities they may pass on to their children when this is known or readily determinable. The time has come when this responsibility must be taken seriously. Advances in medical research are making it possible for medical practitioners to save the lives of many children with a transmissible birth defect who, a decade or so ago, would have died before reaching child-bearing age. The effect-if I may put it bluntly, Mr. Chairman-is that we are gradually weakening our genetic inheritance. By our humanitarian interference with the operation of natural selection we are saving many lives but we are also to some extent degrading the health of the Nation. Genetic counseling is thus becoming not merely a moral obligation of the medical profession but a serious social responsibility as well.

The prevention of the congenital abnormalities for which premarital or preconception tests are available is, of course, only possible if the affected couples do not have children. This is certainly not always a very happy solution.

It would be a much better solution if we could remedy such genetic defects. This is, as yet, but a distant hope. However, fundamental research in genetics is making progress on the problem of identifying which part of a gene is responsible for passing on certain characteristics to an offspring and a beginning is being made on techniques for altering genetic traits. This very new field sometimes called "genetic engineering," presents a possible avenue toward the prevention of inherited diseases and disease-proneness about which only the most imaginative scientists dared to dream a few years ago.

I have a listing of a series of these inborn errors of metabolism that are identifiable in healthy carriers which might be interesting to put in the record.

Mr. FOGARTY. Very well.

Dr. SHANNON. They are now reaching a very substantial number. Mr. FOGARTY. Give us the list with an explanation of each one; also how to pronounce them.

(The list referred to follows:)

PRONUNCIATION OF TERMS IN THE ACCOMPANYING SUBMITTAL, ENTITLED "INBORN ERRORS OF METABOLISM IDENTIFIABLE IN HEALTHY CARRIERS IN TRAITS"

albinism (al'bin⚫izm)

cholinesterase (ko"lin es'tur.ace)

chromosome (kro'mo sohm)

dehydrogenase (dee high drah'gen ase) or (de high'dro.gen⚫ase)

diabetes (dye"uh bee'teez)

dystrophy (dis'tro fee)

galactose (ga⚫lack'toce)

galactosemia (ga·lack" to see'me⚫uh)

gene (jeen)

gluecose (glōō'koce)

glycogen (glye' ko⚫jen)

heme (heem)

hemoglobin (hee”mo glo’bin)

hemophilia (hee"mo-fill'ee⚫uh)

histidine (hiss' ti⚫deen)

histidinemia (hiss ti di nee' me uh)

hypophosphatasia (high"po foss"fuh taze'ee⚫uh)

insipidus (in sip'i dus)

isoleucine (eye'so lew"seen)

leucine (lew'seen)

mellitus (mel'it us)

methemoglobin (met hee"mo glo'bin)

methemoglobinemia (met hee" mo glo"bin⚫ee'mee.uh)

phenylalanine (fen"il al'uh neen)

phenyketonuria (fen"il·kee"ton your'ee⚫uh)

phosphatase (fos'fuh tace).

pseudocholinesterase (sue"do ko"lin es'tur·ace)

thalassemia (thal'uh see"me.uh)

pyruvate kinase (pie'roo⚫vate

valine (vay'leen)

vasopressin (vay"zo·press'in)

kye'nace)

INBORN ERRORS OF METABOLISM IDENTIFIABLE IN HEALTHY CARRIERS OF TRAITS

INTRODUCTION

Healthy carriers of hereditary diseases exist because, in general, the information, which controls the development and the adult function of an individual, exists in duplicate within a fertilized egg and without all the cells which develop from it. In one of his two sets of hereditary units (called genes) the carrier has a gene which directs the production of an abnormal state in the body. The detrimental effect of this errant gene does not become manifest because of its normal partner, the products of which are sufficient to carry out relatively normal functions during development and in adult life. A gene whose effects can be hidden in this way is called recessive as opposed to a dominant gene whose effects are not masked.

The carrier of such an abnormality has a roughly 50-50 chance of contributing the normal or the defective gene to each offspring, since each parent normally only transmits one gene of his or her gene pair to the fertilized egg. The two parental genes are then the pair for the child. (The other genes are discarded in the process of making spermatazoa or eggs; otherwise there would be a constant piling up of surplus genetic material in succeeding generations.)

If the transmitted gene is an abnormal one and that from the other parent is similarly abnormal, the offspring will get defective products from both and will show the full-blown effects of the disorder. If the gene from the other parent is normal, the child too will be a carrier.

One special exception to these rules needs mention. The genes of human beings, like other animals, are carried on those parts of the human cells called chromosomes. There are normally 46 chromosomes in each human cell. Of those, 44 exist as 22 different pairs, each pair containing partners which are indistin