DISCUSSION PAPER: PROSPECTS Irving Schulman Department o f Pediatrics Stanford University School of Medicine Pa10 Alto, California 94305
I have decided to comment on an issue that may determine, to a large degree, whether the advances we have heard about today and will hear about in the next two days can indeed continue at the thrilling pace we have been privileged to witness. This meeting is devoted to a disorder that is probably one of the oldest of recorded illnesses of man. It is a disease that has changed the course of history. and it is one that has enormous biologic and very broad clinical significance. I need not tell this audience of the extraordinary advances that have been made in the past 25 years in the diagnosis, treatment, and basic understanding of the disorder. And I also need not tell you that the problems are far from resolved. It is also clear, I believe, that a very high proportion of the advances have come from studies with humans and that evaluation of the fruits of research must ultimately be tested in humans. Most of you are aware that there is developing in this country a rapidly increasing volume of legislation and potential legislation-federal, state, and local-with the very laudable stated goals of assuring the safety of human subjects involved in clinical investigation and of guarding the rights of such subjects. Now anyone who knows the history of the past four decades also knows that those in the medical and scientific communities have not always adhered to the humanitarian principles to which all have sworn at some point in their careers. We also know that those humans who inhabit this planet are not beyond actions that no subhuman species has yet demonstrated. And so. we must certainly applaud all efforts to protect the individual and to guarantee his or her rights. Since many of the proposed regulations are aimed at the protection of children, I can state that as a pediatrician I applaud all efforts to protect children and guarantee their rights. However. one such right, I believe, is the right to optimal health, and there exists in the proposed legislation elements that may impede the advances of medical knowledge and prevent application of new knowledge for the benefit of affected patients. I can cite three brief examples apropos of this afternoon’s session. The first applies to products of conception. In recent proposed legislation a very considerable step forward was made in finally determining that the product of conception, delivered very early in gestation, is not viable. And yet these same regulations may prohibit any investigation that may prolong biological life as such fetuses or fetal tissues or may in some way shorten it. If rigidly applied, such regulations may prohibit culture of tissues, analysis of blood, investigation of the developmental biology of genetic aberrations, all of which we must certainly know if understanding is to progress. The second applies to the pregnant woman. The proposed regulations suggest that nothing in the way of clinical investigation of a pregnant woman may be done if such investigation imposes any risk to the fetus. Dr. Hirshhorn
147
148
Annals New York Academy of Sciences
has discussed the amniocentesis. He has pointed out that this is now an accepted medical procedure having the capability of diagnosing, before birth, some 50 genetically determined disease states. He has pointed out that in experienced hands amniocentesis carries a minimal risk but has also indicated that there is certainly some risk. In the prenatal diagnosis of hemophilia we can determine only sex of the infant, but no more as yet. Certainly, more must be known in order for parents to be given meaningful alternatives upon which to make a reasoned decision concerning the future of the unborn infant and the future of their own particular family. Thus, it seems, that research on women who are pregnant is an area that we must continue to address. The third area relates to investigation with the child himself or herself. The proposed regulations state that the child must give consent as soon as he or she reaches “the age of discretion,” and this age is given as seven years. As a pediatrician I believe firmly that children should be involved to the fullest extent in all decisions affecting their health and welfare. Appropriate involvement of the child supports the goal of optimal care in health and disease. For this to be achieved, however, requires that the degree of involvement be based upon a careful assessment of each individual child’s level of understanding and comprehension. Indeed, studies have shown that when consent is sought from children who do not have the degree of understanding and comprehension to permit “informed consent” serious anxieties may be induced. Those who work with children would agree that understanding and comprehension of a child are not directly correlated with chronologic age. And thus, the establishment of any arbitrary age for the consent of a child certainly seems unwise. I raise these points in my comment not to criticize the framers of regulations who, like the rest of us, are human and who, like the rest of us, have a variety of motives and beliefs. I raise them to indicate that we can no longer afford the luxury of speaking only to each other. We must be aware of proposed regulations and comment appropriately. Each of us, like Caesar’s wife, must be above reproach. We must let the public know how clinical investigation is conducted, why it is conducted, and what the fruits of such endeavors are or may be. And we must let it be known and demonstrate that we are as concerned as any citizen with the protection of our fellow man and in the guaranteeing of his rights.
I have decided to comment on an issue that may determine, to a large degree, whether the advances we have heard about today and will hear about in the next two days can indeed continue at the thrilling pace we have been privileged to witness. This meeting is devoted to a disorder that is probably one of the oldest of recorded illnesses of man. It is a disease that has changed the course of history. and it is one that has enormous biologic and very broad clinical significance. I need not tell this audience of the extraordinary advances that have been made in the past 25 years in the diagnosis, treatment, and basic understanding of the disorder. And I also need not tell you that the problems are far from resolved. It is also clear, I believe, that a very high proportion of the advances have come from studies with humans and that evaluation of the fruits of research must ultimately be tested in humans. Most of you are aware that there is developing in this country a rapidly increasing volume of legislation and potential legislation-federal, state, and local-with the very laudable stated goals of assuring the safety of human subjects involved in clinical investigation and of guarding the rights of such subjects. Now anyone who knows the history of the past four decades also knows that those in the medical and scientific communities have not always adhered to the humanitarian principles to which all have sworn at some point in their careers. We also know that those humans who inhabit this planet are not beyond actions that no subhuman species has yet demonstrated. And so. we must certainly applaud all efforts to protect the individual and to guarantee his or her rights. Since many of the proposed regulations are aimed at the protection of children, I can state that as a pediatrician I applaud all efforts to protect children and guarantee their rights. However. one such right, I believe, is the right to optimal health, and there exists in the proposed legislation elements that may impede the advances of medical knowledge and prevent application of new knowledge for the benefit of affected patients. I can cite three brief examples apropos of this afternoon’s session. The first applies to products of conception. In recent proposed legislation a very considerable step forward was made in finally determining that the product of conception, delivered very early in gestation, is not viable. And yet these same regulations may prohibit any investigation that may prolong biological life as such fetuses or fetal tissues or may in some way shorten it. If rigidly applied, such regulations may prohibit culture of tissues, analysis of blood, investigation of the developmental biology of genetic aberrations, all of which we must certainly know if understanding is to progress. The second applies to the pregnant woman. The proposed regulations suggest that nothing in the way of clinical investigation of a pregnant woman may be done if such investigation imposes any risk to the fetus. Dr. Hirshhorn
147
148
Annals New York Academy of Sciences
has discussed the amniocentesis. He has pointed out that this is now an accepted medical procedure having the capability of diagnosing, before birth, some 50 genetically determined disease states. He has pointed out that in experienced hands amniocentesis carries a minimal risk but has also indicated that there is certainly some risk. In the prenatal diagnosis of hemophilia we can determine only sex of the infant, but no more as yet. Certainly, more must be known in order for parents to be given meaningful alternatives upon which to make a reasoned decision concerning the future of the unborn infant and the future of their own particular family. Thus, it seems, that research on women who are pregnant is an area that we must continue to address. The third area relates to investigation with the child himself or herself. The proposed regulations state that the child must give consent as soon as he or she reaches “the age of discretion,” and this age is given as seven years. As a pediatrician I believe firmly that children should be involved to the fullest extent in all decisions affecting their health and welfare. Appropriate involvement of the child supports the goal of optimal care in health and disease. For this to be achieved, however, requires that the degree of involvement be based upon a careful assessment of each individual child’s level of understanding and comprehension. Indeed, studies have shown that when consent is sought from children who do not have the degree of understanding and comprehension to permit “informed consent” serious anxieties may be induced. Those who work with children would agree that understanding and comprehension of a child are not directly correlated with chronologic age. And thus, the establishment of any arbitrary age for the consent of a child certainly seems unwise. I raise these points in my comment not to criticize the framers of regulations who, like the rest of us, are human and who, like the rest of us, have a variety of motives and beliefs. I raise them to indicate that we can no longer afford the luxury of speaking only to each other. We must be aware of proposed regulations and comment appropriately. Each of us, like Caesar’s wife, must be above reproach. We must let the public know how clinical investigation is conducted, why it is conducted, and what the fruits of such endeavors are or may be. And we must let it be known and demonstrate that we are as concerned as any citizen with the protection of our fellow man and in the guaranteeing of his rights.
