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what the very lower limit of the gray zone is. We have to exercise, of course, great care as medical researchers in determining exactly how we design experiments to help you in making that decision.

Senator BAYH. Well, it certainly is an area that goes far beyond just the scientific data and the scientific expertise. I am very well aware of that. But inasmuch as you did expouse an opinion, your statement that I quoted there

Dr. EDELMAN. I realize that. As a physician licensed to practice medicine in New York and California, and as a person who has worked on the structure of spermatozoa, as a scientist

Senator Bays. With some degree of success.

Dr. EDELMAN [continuing]. Somewhat familiar with developmental biology and particularly the development of the immune system, I would say that in my opinion the third trimester of pregnancy would be the time in which the responsibility would sharply rise.

Senator Bayh. Significantly that you could forbid an abortion during that period ?

Dr. EDELMAN. In the sense that if there were a threat to the life of the mother, for example

Senator BAYH. No, take that out.

Dr. EDELMAN. Even if I took that out, if the law in fact agreed, I would say yes. Under ordinary circumstances, if viability is defined as such and there is no evidence of genetic abnormality of the type that was discussed before that would surely lead to suffering, I would say yes. But if there were, I would certainly take sharp issue. To take your example of Tay-Sachs disease, it seems to me if you knew that this were the case, at very early stages of pregnancy, I should think that intervention would prevent an enormous amount of human suffering.

Senator BayH. Dr. Zinder, I do not think I have asked you that same question that I have asked your two colleagues.

Would you care to comment on that before we recess here, relative to the possibility of there being a point where that developing human being beocmes more than just a mass of cells?

Dr. ZINDER. This again, I can only answer as a matter of opinion. I would agree with my colleagues that this would be—when the fetus is viable, can live independently of the mother, and this is a grey area. There is very little scientific competence that I have in this particular area. I can only answer this question as an individual.

Senator Bay. Well, I realize that. But we asked all three of you here, and I appreciate your accepting our invitation, as well as the preceding witnesses, to bring us scientific and medical expertise. But forgive me for stretching your testimony a bit to ask you to talk as a citizen and a human being as well, which of course you are. You have been very kind, gentlemen.

I appreciate the fact that you are all very busy, and that you can give us your time and help us in our search for the truth in this matter.

Thank you.

[Whereupon, at 5:35 p.m., the subcommittee recessed, subject to the call of the Chair.]




Washington, D.C. The subcommittee met, pursuant to recess, at 10:10 a.m., in room 318, Russell Senate Office Building, Senator Birch Bayh (chairman of the subcommittee) presiding.

Present: Senators Bayh (presiding) Fong, and Cook.

Also present: J. William Hechman, Jr., chief counsel and Abby Brezina, chief clerk.

Senator BAYH. We will reconvene our hearings this morning. I appreciate the fact that my distinguished colleague from Hawaii is again taking his time to share the studies that we are undertaking.

I might note for the record this morning that Dr. Gordon, who is chairman of the department of genetics at the Mayo Clinic, is high on our list of prospective witnesses. Unfortunately, Dr. Gordon had a heart attack. We hope that he has a rapid recovery, and that we will be able to have the benefit of his expertise when he has recovered.

Our first witness this morning is Dr. Margaret Horrobin, assistant professor, department of pediatrics, of the University of Minnesota. Dr. Horrobin is also the director of the Minnesota Human Genetics Council.

Doctor, we appreciate your being here with us this morning. STATEMENT OF DR. JEAN MARGARET HORROBIN, ASSISTANT


Dr. HORROBIN. Mr. Chairman, I am Dr. Margaret Horrobin. I have been a physician for 14 years and have practiced pediatrics exclusively for the past 13 years. I am licensed to practice in the United Kingdom and in the State of Minnesota, and I am a Board certified pediatrician. I have been on the faculty in the department of pediatrics at the University of Minnesota since 1965.

My particular areas of pediatric interest are in growth and development, ambulatory care, and birth defects. I have been the codirector of the Birth Defects Clinic for the past several years where my prime interest is in Down's Syndrome. I am also co-investigator in a research project aimed at enhancing the development of children with Down's Syndrome. From this springs an interest in the area of genetics and gentic counseling, and I have been on the board of directors of the Minnesota Human Genetics League since 1970.

My subjects today are genetic counseling and the rapidly expanding field of prenatal diagnosis of genetic defects. I speak with particular concern in light of the constitutional amendment now being considered which would proscribe abortion and thus have a direct effect on the field of genetic counseling and prenatal detection of disorders and a very direct effect on those families in which genetic disorders, which can be diagnosed prenatally, are present.

In the past, genetic counseling has consisted largely of assessing the risk for a particular couple of having a child with a known condition. The overwhelming majority of people requesting genetic counseling have been those who have already experienced the birth of a child with a particular disease or defect, and who are understandably very concerned about future pregnancies wishing to know what is the likelihood of their having another child similarly affected.

There are almost 2,000 conditions which are inherited according to the well understood and accepted Mendelian laws of inheritance. Essentially, if a condition is dominant, it requires only one gene from either parent in order that the child be affected. An example of this is the familiar condition achondoplastic dwarfish, in which the person has a normal-sized body but very short limbs, and there is a 50 percent chance that an affected parent will pass on that particular gene to his offspring. As long as the diagnosis has been made accurately in dominant disorders, there is no difficulty in giving the family a risk figure for future pregnancies. In recessive disorders, on the other hand, a gene from each parent is required in order for the child to be affected. The parents themselves are not affected, and may be totally unaware that they are carrying the gene for a particular condition until they have a child with it. An example of a recessive condition is Tay-Sachs disease, à degenerative disease of the central nervous system in which the parents are carriers of the defective gene, but also have a normal one to counterbalance it. However, in passing on genes to their children, there is a 25 percent chance with each pregnancy that the child will receive the defective gene from each parent and thus, develop Tay-Sachs disease. These two conditions are examples of classical Mendelian inheritance in which the risk is definitely known and can be clearly stated by the counselor. For dominant disorders, the risk for each pregnancy is 50 percent; for recessive disorders, the risk for each pregnancy is 25 percent.

In very many other conditions, however, the inheritance pattern is not so easily predicted, and many other factors besides genes enter into play. This is so-called multifactorial inheritance, in which the recurrence may be as high as 5 or 10 percent, or may be very much less.

What are the options when parents are given a high risk figure for future pregnancies? They may either have more children, worrying with each pregnancy that the child is going to be seriously affected, or they may decide not to have further children, using contraception or sterilization to ensure this. Adoption or artificial insemination where appropriate were the only ways to increase their family size. However, the past several years have seen the development of ways to increase the accuracy of risk assessment. If one were

able to diagnose the condition of concern in a fetus during pregnancy, the none could tell the parents that the risk is not 50 percent or 25 percent, but is 100 percent, that is, the fetus has the condition; or is zero percent that is, the fetus is unaffected. This is what prenatal diagnosis is all about. It provides the assurance of having unaffected children even though the risk of having affected children is very high. It provides a couple with a wider range of choices. Many couples who would formerly have elected not to have further children now will elect to do so, provided that the option remains open to them of having a pregnancy terminated where the fetus is shown to be affected by the condition in question. The effect of this condition, be it Tay-Sachs disease, Down's Syndrome, Lesch-Nyhan's Syndrome or whatever, with its problems and heartbreaks, is already known only too well by the parents.

Let me say a word about the present scope of prenatal diagnosis, Jest you go away with the impression that all genetic diseases and most birth defects can be detected prenatally and could be prevented by termination of pregnancy. Not so. The vast majority of birth defects are not detectable prenatally at the present time. The disorders that we are talking about in this context are relatively few, though are increasing in number and are generally very severely handicapping, if not fatal. Most are quite uncommon, which is no comfort to those parents who have a child with such a disease. At the present time, we have the competence to diagnose prenatally all the known chromosomal abnormalities, about 50 inherited metabolic diseases in which severe mental retardation is generally one feature, and comparatively recently, the congenital neural tube defects such as spina bifida. There is no cure for any of these tragic disorders, and for many of them there is no effective treatment.

I would now like to discuss the techniques of prenatal diagnosis for a few minutes, and I will abbreviate in the interest of saving time.

Senator BayH. This is important enough that you do not need to feel obliged to shortchange us.

Dr. HORROBIN. I would be glad to read it.
Senator BAYH. I think it would be well worth that.

Dr. HORROBIN. I hope it has been made clear that in talking about prenatal diagnosis, I am talking about diagnosis at a time in pregnancy at which abortion, if desired, can be performed. Before discussing amniocentesis, which currently has the widest application, I will briefly mention two other methods. Ultrasonic means of determinating the size of the fetal head, the presence of twins, and the exact location of the placenta are being used more and more with increasing accuracy and with great safety. The size of the head can be determined readily by the 16th week of pregnancy, so that a severe abnormality of the head, such as anencephaly, where the cranium and brain of the fetus fail to develop, should be detectable by this means.

Direct viewing of the fetus is also becoming more feasible with the development of increasingly sophisticated equipment. In fact, a fiberoptic endoscope no more than 2 millimeters in size has been used to inspect the fetus directly by inserting it into the amniotic

cavity where the fetus lies. This is a technique which is in its early days yet, and further developments are awaited, but it is likely that certain physical abnormalities that are not as yet amendable to prenatal diagnosis could be detected this way. I have in mind abnormalities like those caused by unwitting administration of certain drugs during early pregnancy. The thalidomide disaster in Europe some years ago is an example of a drug causing severe physical defects. Mrs. Finkbein, who is known by some people as having suffered the effects of the drug thalidomide, has submitted a statement to the committeee about her fetus in this regard. Under direct viewing, sampling of fetal tissue or blood very likely will be possible for use in diagnosis tests.

Now I will talk about amniocentesis, currently the most important technique for prenatal diagnosis. At the back of my statement, I have appended a schematic representation of the process of amniocentesis. As you will see, amniocentesis consists of withdrawing a sample of the amniotic fluid which surrounds the fetus in the uterus, and subjecting the fluid, or the cells in the fluid, to certain tests. It is best performed at about 16 weeks from the 1st day of the last menstrual period. Ideally ultrasound studies for localization of the placenta and diagnosis of multiple pregnancy should be done before amniocentesis, in order to avoid the risk of puncturing the placenta with the needle. In cases of multiple pregnancy, it would be possible to obtain amniotic fluid that pertained only to one of the fetuses so that the diagnosis reached would apply only to that one fetus, a somewhat estoeric thought. The procedure of amniocentesis is performed through the abdominal wall: under local anesthesia a needle is inserted into the womb and a sample, 15-20 ml.-12 to 2/3 of an ounce of fluid is withdrawn. The total amount of amniotic fluid at this time is generally between 150–250 ml.—5–9 ounces—so that the removal of the sample is of no consequence.

The sterile amniotic fluid is then sent to the laboratory, where it is centrifuged and the portion containing cells is cultured. Cells in the amniotic fluid at this time in pregnancy are derived from the fetus, having been shed from the skin or from the lining of the respiratory tract. The cells are grown in a suitable medium, and when adequate amounts of cultured cells are available, diagnostic tests can be performed. This usually requires 3 weeks or so of growth. In expert hands, approximately 95 percent of specimens from amniocentesis provide useful uncontaminated amniotic fluid and cells for diagnostic purposes. In the remaining 5 percent, the procedure may need to be repeated. The cell culture is satisfactory in the best tissue cuture laboratories in 90–95 percent of cases. Sometimes, the cells fail to grow, or become contaminated and die. I say this to emphasize that this is a skilled technique and it is certainly not one that should be undertaken by every small hospital laboratory Though it is possible to do some tests on the fetal cells shed directly into the amniotic fluid without culturing them first, this is not the generally preferred technique and on some occasions, error has arisen through the use of uncultured amniotic cells. In competent

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