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Legal Aspects

What might be encompassed within a discussion of the legal aspects of the genetic revolution? DNA fingerprinting and the O. J. Simpson trial? The federal regulation of recombinant DNA research? Over the past twenty some years, the Recombinant DNA Advisory Committee (RAC), which was recently almost put out of business by the director of the National Institutes of Health, moved from laboratory safety issues to spending most of its time looking at human gene therapy. How about intellectual property issues? The patenting of gene sequences has been a controversial matter; the National Institutes of Health (NIH) filed many patent applications, until the current director, Harold Varmus, came in and decided NIH would no longer seek patent protection for the strings of cloned DNA decoded by its gene sequences.

Breast cancer genetic testing raises another legal aspect, namely the role of the Food and Drug Administration in regulating the products coming out of the genetic revolution. A fifth area is anti-discrimination laws. The Equal Employment Opportunity Commission has recently announced that under the Americans with Disabilities Act the diagnosis of a genetic sequence associated with disease susceptibility could be regarded as a disability. Sixth is tort law, and seventh is medical practice acts and the licensing not only of physicians but also of genetic counselors. Another legal area is the need to protect the confidentiality of genetic information, such as through evidentiary privileges in judicial or regulatory processing. Finally, a ninth area concerns access to genetic services and the regulations that govern reimbursement and coverage decisions made by public and private insurers.

This is hardly an exhaustive list of legal issues raised by the genetic revolution. I intended it to be merely illustrative. In other parts of the world the law has already directly or in draft form gone far beyond this. The Council of Europe has put forward a proposal that would protect "the inviolability of the human genome," suggesting that the genome is something which is under attack and needs to be protected from the depredations of scientists and physicians. If this view is accepted, it would probably filter into our own legal system through finding some sort of basic protection in our Constitution under the due process clause for a person's genetic identity. That would certainly be a complex and controversial move.

Indeed, it's the complexity of all of these topics that would require, I suppose, not forty-five minutes, but forty-five hours to begin to delve into. But that's not the only reason why I don't believe it's helpful at this symposium to think of a "law of genetics" as the appropriate way to respond to the question, what are the legal questions raised by what we heard about this morning?

It seems to me that rather than rush onto the statute books the various methods of controlling the "genetic revolution," it would be far preferable for us to follow the precedent that was set twenty years ago when, for most people, the issue of genetics first became front page news. At that time, concerns raised within the scientific community resulted in scientists themselves imposing an international moratorium on certain aspects of the original "gene splicing" research. This effort, led by Paul Berg of Stanford and Maxine Singer of NIH, led to an international conference at the Asilomar Conference Center in Monterey, California. The conference attracted a good deal of public attention because it was an unprecedented attempt by scientists, first, to stop their work and examine it, and, then, to decide the ways in which it could go forward and to engage in a form of self-imposed regulation.

Not surprisingly, this self-regulation was doubted by some people, who called for federal legislation to limit and restrict this area of research. Hearings were held in the United States Senate, and proposals were made. I think it is fortunate that at that time the decision was made that this was an area which was not ripe for legislation. Instead, the committee I mentioned moments ago, the RAC (Recombinant DNA Advisory Committee), was established by the director of the NIH to provide advice on federally supported research, which was the bulk of all the research in gene splicing at the time. There's now a good deal of industrial work in the field, and for many years, that work was also brought voluntarily before the RAC.

Now, one might say there is only a very small difference between the establishment of a federal committee to look at the work and the establishment of laws and regulations. But if we looked at the twenty-plus-year history of that committee we would see that it was constantly able to reevaluate the standards it had set and, with experience, discover that many of the original causes of alarm were overblown. (We did not need to be protected from many, many areas of recombinant DNA research, which, indeed, are as safe, if not safer, than other kinds of virology research and the like that goes on according to accepted biomedical standards of safety.)
As burdensome as meeting with the RAC may have seemed to scientists and physicians eager to move forward faster than the committee was prepared to agree, the process they would have faced would have been far, far more complicated if we had moved quickly to legislation.

Part of the reason for this is that the law is a blunt instrument. It tends to speak in broad categories and to have a limited range of responses to many complex situations, particularly those situations which are not themselves simply a creature of the law. One can look at certain areas of contract law and the like and say, "Of course, we need and can have elaborations from legislators and then interpretations by judges which respond to most of the problems in a fairly sensible fashion." And yet all of you from the business world know that there are many times when the business community, in the way that it is forming its commercial relationships, gets ahead of the law. And there are times when that becomes problematic, which is why you then have expensive lawyers to deal with those problems.

Besides the question of the law's bluntness, there is also a risk of using it prematurely to deal with fields not primarily of legal creation in the first place, like sales law, but rather are themselves growing out of a sister enterprise-the scientific enterprise. Indeed, in the genetics arena, most of the important issues that ought to be resolved before we legislate have not been resolved. Let me illustrate by listing eight areas which are quite unresolved.

The first one is the anxiety that attaches to this field. No one can have been a reader of popular magazines, as Tom Beauchamp just demonstrated for us, without being made aware of the risks-the genetic risks that we all seem to face and the difficulty of knowing how our society is going to respond to them.

Part of this is the uncertainty that attaches to these figures. As Mary-Claire King made clear this morning, even when we are talking about a susceptibility to breast cancer we are still dealing with probabilities. And it is, I think, a fact that any of you who professionally deal with this can attest to, that the average member of the public and, indeed, the average member of the medical community deals very poorly with probabilities. The additional factor of uncertainty about the extent of the risk results in a good deal of anxiety. Will I have disease? What does it mean to say that one in ten American women will develop breast cancer? Is that a constant risk or does it increase over life? We know that there's a high level of anxiety when people think about this subject. Ironically, the ability to diagnose a disease or predisposition pre-symptomatically in some ways increases the anxiety. If the information is there, should I go and get it?

A second unresolved issue is one which Mary-Claire King also mentioned, the guilt that arises in passing on the genes. It isn't only the women who are found to carry the BRCA1 gene for breast cancer who feel a sense of guilt. Counselors tell me that almost the first thing out of the mouth of all women in that situation is the concern, "Have I now passed this gene on to my daughters?" And this is magnified across the board by a whole range of genetic conditions that counselors can describe.

The flip side of that, of course, is the anger that follows from being burdened by something hereditary. Henry James notwithstanding, most people think of inheritance as a blessing, not a curse. But the notion that a gene, which could cause serious illness or premature death, has been passed on in a family can be a source of anger or recrimination within the family.

A third point-confusion. With the flood of information that seems to be inundating a general public that does not understand genetics well, the potential exists for a great deal of misunderstanding and premature action.

Fourthæalong the lines of what we heard this morning about twinsæwe are often told that our identity is tied up with our genes. If that is the case, and if, through genetic testing, we find that some of those genes are defective, what does that do to our sense of self-identity? This in turn raises obvious questions then about when testing is appropriate. If testing were to be done, for example, with adolescents who were going through a period when their own sense of identity is so much in flux, would we be putting them at greater risk of thinking that science had now certified and attached to something objective and measurable to them as flawed human beings?

A fifth problem-social discrimination. Not discrimination by insurance carriers or employers, but the ostracization that can follow from genetic identification. As long ago as the early 1970s, when sickle cell carrier testing was introduced on a large level in the United States and thallasemia testing was going on in the Greek Cypriot community in London, it was discovered that people who were found to be a carrier of the mutant gene (and hence, not at any physical risk themselves for the illness that would come from having the double dose of the genes) were ostracized. And today there are, in certain Hassidic communities in New York, rabbis using genetic profiles to decide who should be marriageable, or at least decide about matings of people.

These issues are not hypothetical. Ostracization and social discrimination are issues. Likewise, the question, do we have adequate personnel to test, and especially to counsel, about testing? This is not an issue for the law. This is a basic issue of our organization of medical education as well as education of genetic counselors and the devotion of resources to this field.

A seventh, broader problem is what Professor Susan Wolf of the University of Minnesota has labeled geneticism, the framing of medical and even social problems in terms of genetic rather than environmental factors. This can have its manifestation in many ways. A simple example is that physicians in the future, armed with the ability to predict individual genetic risk for particular diseases, will be able to tailor their advice to patients, so that out of the welter of health preservation and health promotion advice that we all now get, they can target that advice in a way that should be much more powerful for patients. And that sounds wonderful.

Yet there is a downsideæfor the physician-patient relationship and also for patients' healthæin adding further tests of whatever type. Already, Dr. Eric Casell has written, technology is the sorcerer's broom of medicine. What he means is that physicians, in grasping for some certainty in the face of the great uncertainty that attaches to all attempts to talk with patients about their future health state, want to grab hold of what they regard as "definitive" and "objective" information that they can get from tests, rather than what they get through the methods that have served good physicians for so long.

Now, I would not follow Dr. Casell's view if it led to the conclusion that we don't want to have any of these tests. Nonetheless, particularly as tests are first identified and the glamour of the high-tech medicine comes upon the medical profession, the risk is that they will substituteæor even obliterateæthe existing evaluation of the individual in all of her or his manifest complexity before the doctor, to be replaced instead by a number read off a machine or a lab report identifying a genetic sequence on a chromosome.

Beyond this effect in the medical sphere, geneticism also carries the risk of altering the way in which we view human beings, both because the power of genes and their malleability is now overwhelming our thinking. However hard we try to keep in mind the interaction of genes within the environment, every time we turn to something like the twin studies, with those remarkable coincidences that seem to exist in the life of the identical twins separated at birth, we run the risk again of reifying genes and of doing what Professor Dorothy Nelkin calls, "Turning them into a kind of cultural icon."

The risk lies in thinking that we could explain individuals by knowing their genes. This goes far beyond the quote we had from Walter Gilbert this morning-because Professor Gilbert went beyond saying that in the future you would be able to go to the drug store and get a CD-ROM with your genotype. He also said he would hold the CD-ROM up and say, "Here I have the person." Ecce homo, this is the man on this disk. The risk then is that we will come to believe that this statement is true, and forget that what is really on the CD-ROM is a genetic message which will manifest itself in the light of particular environments as a human being. That risk cannot be underestimated.
Let me underline this point by using a very extreme example, derived from the discussion this morning of Down Syndrome. I am sure that a Down Syndrome child who did not have lethal physical abnormalities that required surgery would have had a much easier time in nineteenth-century America than at the brink of the twenty-first century. A simpler world is easier for people who don't comprehend complexity and deal with it very well. They can survive more easily in that setting.

Now, it is true that most Down Syndrome children used to die at a younger age because of the complications that came with infections and the like. But, without downplaying the advantages of contemporary medicine, I believe there are negative consequences from our current tendency to explain Down Syndrome in terms of an extra chromosome, to pretend that with this explanation we need not think about the environmental contribution, not just to the physical manifestation of that disease, but to what we think of its burdens and problems as they are experienced by people with Down Syndrome.

Even in the case of the twins who were separated at birth, we need to remember that they shared an intrauterine environment, as recent findings emphasize these parental effects on the manifestation of given genes as seen in the baby after birth and then in the adult. Indeed, recent data have confirmed some earlier findings that the weight of a female at birth has a correlation with breast cancer. And that weight, in turn, seems to have to do with something in the intrauterine environment. So when we start talking about "genetic diseases" we should be aware that from the moment of conception we must also talk about the environment in social as well as physical terms. These factors may be more subtle and less measurable than our DNA but they are no less important.
Eighth and, finally, we come to the whole question of human nature and what it means to be a human being, which is being raised by the Human Genome Project and all the other attempts to understand genetics.

Now, when I raise these as issues and questions it is precisely because I do not think the law is going to provide any very good response to any of these. The law operates in most situations as kind of an on-off switch. We either allow something (or encourage it, through collective support) or we prohibit it. Sometimes the prohibition is modulated through regulation, allowing it in some cases and disallowing it in others. But the law does not bring to these issues much that will help us to decide about the answers we should give to the fundamental questions of genetic determinism or geneticism, or of the effect of our understanding of genes on the levels of anxiety and guilt that people have, or of the ways in which we ought to respond to the risks to our sense of self-identity.

These are problems fundamentally within a human philosophical, ethical, social sphere. And until we can address these in a satisfactory way we will not be able to write laws that will serve our society well. I would go so far as to say that the genetic information will raise questions beyond any that we have faced, but I'm not sure that we can look to the law to give us answers.

Let me end this list of things to which the law can not provide the answer by taking up a suggestion that Hans Mark made this morning. He was talking about understanding the genetics of neurons and the notion that one could take neurological cells and put them in a petri dish and in his words, wire them up so they became a computer. I want to know the point at which, when we put those neurons in the petri dish and wire them up, they become a human being. That is the issue that we will ultimately face.

Right now biologists could breed half human-half chimpanzees. In the opinion of the biologists I've spoken with, it is technically possible and it would have great payoff for developmental biology. But, of course, part of what holds people back is concern about what the resulting creature would be. Would it be a chimpanzee or a human? Would it be entitled to vote and go to school? What would we do? How would we regard that entity?

When the Constitution tells us that there are certain protections for persons it presupposes we know what persons are. And probably the single issue that has most roiled us socially as a country for the last twenty-three years comes out of the debate over what that Constitutional provision means. Is a fetus a person? The Supreme Court answered in Roe v. Wade by saying, "No, it is not." It didn't say it wasn't a human being though. It's just an unborn human being, and an unborn human being is not, in the view of the Supreme Court, a person in Constitutional terms. And so the special protections that would apply to persons don't apply there. That, of course, is an enormously controversial notion in our society.

What would happen if we found ourselves able to create not the architecture of a human being, but that thing which we, most of us, regard as what makes us distinctively human, which is the human brain, that marvel of which Drs. Goldstein and Brown spoke this morning. If we could create that, at what point would we say that creation, even in a petri dish, has to be regarded differently than some other collection of cells if it can operate in a self-conscious fashion? What would that mean?

Such issues are not going to be well-dealt with by the blunt instrument of the law. So I come before you as a lawyer urging you not to press our institutions of society to move ahead too rapidly to deal with these issues as legal issues.

The law brings to all this, after all, only certain principles which rest upon a presupposition that we know the direction that we're going in. Three distinctively legal principles in our system are the principles of fairness, embodied in such things as our Equal Protection clause; procedural regularity, in other words, due process; and the balancing of personal liberty with community well-being, which we do in all sorts of sometimes contradictory ways in the law of property, torts, nuisance, and contract, and which is manifested in Constitutional law through the notion of a protected sphere of privacy, on which the community should not intrude.

Now, all of these can supply some rules of relevance to the genetic area. Certainly, genetic testing and the use of genetic procedures ought to proceed, as all medical care does, under a regime of informed consent, which has been a contribution of the law, along with philosophy, embodying a long-standing tenant of Anglo-American law, namely protection of bodily integrity. From that has grown an important set of understandings between society and the medical profession about the ways in which information must be provided and consent sought before medical interventions go forward. And there's no reason to think that genetic interventions should be any different than this.

But that only begins to scratch the surface, because if all the complexities that I described before about the likely consequences of undergoing genetic testing exist, what would a conscientious physician tell his or her patient about the consequences of the test? Is it, for example, necessary to talk about all those feelings of guilt and recrimination, of anger, of profound misunderstanding that can come from having a test that yields a nice, clean result that isn't so clean in its application? Is it appropriate for testing to be done only after people are warned about their risk of being discriminated against by their friends, relations, employers, or insurers? Is that part of appropriate genetic testing in this area? So that even a simple rule like the rule of informed consent becomes quite problematic?

A couple of weeks ago, at an international conference I organized in San Francisco, a group from Stanford University reported on the results of their study over a fifteen-month period of the proper grounds for going ahead with breast cancer genetic screening. I'd like to read you a couple of their conclusions, which seem, on their face, unproblematic.

They concluded, "For most people BRCA 1 and 2 mutation testing is not appropriate. For people at high risk of carrying a mutation, either as a result of family history or their own early onset of disease, testing is an option that should be discussed and that could reasonably be accepted or declined. Even for those not at high risk, testing, though not encouraged, should not be prohibited." And then they went on to say in a separate recommendation, "Marketing of genetic tests for BRCA 1 and 2 mutations should be carefully limited."
If I were sitting as the chief counsel of the FDA and saying, I want to do exactly what this thoughtful group from Stanford has urged me to do, I don't know what I would do because I'm told that it's not appropriate for the general population to undergo screening. Yet there are companies out there that are now promoting that. In fact, the FDA, at the end of October, granted approval and Myriad Genetics of Utah has now begun marketing an approved test. Previous to this, you may know that a number of companies were doing breast cancer screening. But they were doing it as a clinical laboratory test, and they were regulated, therefore, under CLIA, the Clinical Laboratory Improvement Act. They were not marketing this test, so they didn't need FDA approval. Well, FDA approval has now been given to a test and it is being marketed.

Now, is that a mistake? Suppose Myriad Genetics started taking ads out in newspapers all over the country saying to women, "Here is a way of finding out about your risk. If you are a young woman who has not yet had children, you may want to know whether you will be passing this dreaded gene on to your children." Would that be appropriate or inappropriate? Can that be limited? It should not be prohibited, it says here in one recommendation, but it should be limited. I don't know exactly what the Stanford group would be telling the FDA to do in this area. And they spent a whole year thinking about it.

Another issue: those studies that we saw displayed by Dr. King involving families requiring the gathering of information from many family members. Indeed in some cases it was not possible to identify the gene in question until one had data from a number of affected and unaffected members of the family.

Now suppose that someone comes in for testing for a genetic condition and finds that he or she carries that gene, and then at the conclusion the physician says, "Well, we'd understand a lot more about this if we could talk to your relatives." And the individual says, "I don't want you to talk to my relatives. I don't want that information to go out of this room, and you are bound by a duty of confidentiality not to let it leave this room."

Is that an obligation if the physician knows who those relatives are because of information that has been provided previously or perhaps even the physician has other members of that family in his or her care? Does the injunction of confidentiality apply in this situation?
We generally regard people as being free to insist that medical information not be disclosed, though we make certain exceptions. One of the exceptions that has emerged in the law is where the person who has the information is regarded as having a special relationship with a potential victim. If the information is not being disclosed and its absence seriously endangers the individual's health, should the exception be invoked? Depending upon what the genetic information is, it seems to me that it is possible to construct a case in which one could say that the absence of that information to the relative seriously threatens that relative. Now, in a way, the relative is no worse off than he or she was the moment before that genetic result was uncovered. And it is also possible that whatever led the first person to come in to be tested is information available to those relatives, and if they were so moved they would go in and be tested.

Perhaps the non-disclosing relative is doing the right thing, saying, "They could be tested if they wanted. I don't want this information thrust upon them." And part of the notion that the law protects privacy suggests that we don't have to have unwanted information. What information we have about ourselves does affect us in our evaluation of our life and our prospects. And part of the notion of privacy is the ability to shape one's own life and one's own self-identify. If you don't want that information because it would be disruptive, I think a coherent case can be made that that's correct. But perhaps that's not the reason, or perhaps that's a paternalistic reason in any case.
One famous case that you may be aware of, the Tarrasoff case in California, said that in certain situations psychiatrists have an obligation to warn the potential victims of patients who have in psychiatric sessions made statements indicating that they intended to harm the victim. Among psychiatrists that was a controversial decision when it was handed down, although it turns out that psychotherapy has proceeded and has not been destroyed in California or elsewhere by the insistence that psychiatrists exercise that degree of protection of third parties. Is that the model we want to apply to this genetic information?

A good deal of reference has been made to the advantages, therapeutically, in having genetic information. One area where for the past twenty-five years genetic information has been widely used has been in prenatal diagnosis. I gather that it has been widely thought that this has been a pretty straightforward and useful medical development. And I would agree with that evaluation.

A couple of years ago the American Medical Association's Council on Ethical and Judicial Affairs addressed the issues of prenatal diagnosis because it recognized that there were ethical complexities here. In particular, the Council addressed an issue which has been controversial in medicine, the use of genetic technology to avoid the birth of a child of a particular sex, predominantly avoiding the birth of female children. The medically related issue, of course, is the use of prenatal diagnosis to discover the existence of a male fetus where the family is at risk for an X-link disease, which will manifest itself in male children, like hemophilia, but not female children. But this is the reverse. This is a situation in which the diagnosis would be undertaken because the parents want to avoid the birth of a child of the female sex unconnected to any "medical" situation.

The Council on Ethical and Judicial Affairs concluded as follows: "Selective practices, such as sex selection, may result in lasting social harms such as the exacerbation of discrimination, a tendency to view children as products, and eugenics." Likewise, recognizing the potential for social harms, the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research, in a report in 1982, strongly discouraged the use of prenatal testing for sex selection, stressing the need to confine such testing to "seeking genetic information in order to correct or avoid unambiguous disabilities or to improve the well-being of the fetus."
Now, you'll understand that since I directed that commission, the critical remarks I'm going to make about the utility of that statement are not casting bricks at somebody else's glass house, but recognizing that I live in one. It seems to me that our growing understanding of genetics over the past fifteen years has shown how problematic this is. Nor is it an issue only in those cases in which we have something like the use of prenatal diagnosis for sex selection.

Let me give you an example, of which I was reminded last night by Dr. Goldstein. There is a form of dwarfism called achondroplastic dwarfism, which is a dominant disorder. Most all of the achondroplastic dwarfs are so-called spontaneous mutations. There's also the tendency in this particular condition, as in any number of others, for what's called assortative mating, where people with the same genetic condition come together and end up as spouses. Indeed, in this area there's a whole organization-the Society of Little People. They live a life unto themselves. Now that the particular genetic cause of achondroplastic dwarfism is known, it is possible to do prenatal screening. It is, of course, useful to know, although not determinative, to find out that the fetus would have gotten a double dose of the gene from both parents, a lethal condition which doesn't lead to a survivable child. Now, however, that obstetricians at some centers are able to manage the pregnancy--and I guess through Caesarian birth carry the pregnancy to term-- the parents are saying, "We want to give birth to a child who has this genetic condition, not to a child who didn't inherit it from either of the parents and would be a so-called normal statured person."

This is shocking to a lot of people because it would be like sex selection-the use of a genetic technique to lead to the abortion of a child who doesn't have any genetic condition that threatens its own life or existence. And the reason given by the families is that their lives are centered around a lower height. Their houses are built that way. Their furniture is built that way. In effect they say, "This child will be an aberration in our community, and we don't want to tolerate that."

I don't think that this decision on their part is the same threat to the normal statured individuals that the sex-selection decision of people would be if it were widely carried out-as we know through studies, it would be widely carried out-to have a roughly 60-40 or 65-35 percentage of male births to female births if everyone can predetermine the sex of their children. That is a threat to our understanding of human equality because it would affect half of the population, whereas we, the normal statured, are so much the dominant in the population that we're not really threatened by a few achondroplastic dwarfs saying they want to have dwarf children.

But what their case illustrates to me is a reminder of how utterly socially determined our sense of normality is. And, in this area, until we have a better understanding of what the normal means, or, indeed, whether it makes any sense when we talk of genetic variations across all the capabilities, not just the few that have manifestations in lethal conditions, but across all the capabilities, it doesn't seem to me it is possible to talk about legislating to avoid discrimination when we would thereby be embodying a model of discrimination which exists in our usual anti-discrimination law which says, We know what the normal is. The normal is white and male.

What we have to do is protect those who are not white males by getting them treated equally to white males. That is our reigning paradigm for anti-discrimination. We say, you can't treat women differently than men, and, indeed, the Constitution says you have to afford people of color equal rights to white residents. That is the whole idea. That is our anti-discrimination paradigm.

How in the world do we apply it now that we understand the variations in genetics? In that paradigm we have to have a norm. We need to recognize that the norm does not make sense anymore, just as we have to recognize that races don't really exist. When you look at the genetic data it turns out that there is more variation on all the other genes except skin color within the so-called race than between races, so that all the other factors that we would look at deny the notion of race, and we ought to obliterate that. But, of course, race is a social construct in our society.

Likewise, the whole notion of genetic normality, I think, is going to turn out to be a social construct. And that is a fundamental challenge. If we are going to respond as a society in a sensible way, whether it is in the issuance of insurance policies, protection of people in the work place, or our basic understanding of what it means to participate in our society, these are the issues we must resolve. And, again, I would suggest to you that the law ought to have a great deal of modesty in approaching these issues and realize that most of the heavy work that has to be done must precede any attempt to legislate.