Arthur L. Caplan, Ph.D.
Director, Center for Bioethics
University of Pennsylvania
Ethics of Genetic Testing from keynote address, Second National Undergraduate Bioethics Conference
March 31, 2000

Arthur Caplan: Genetic testing has been around for some time. I see John Fletcher who is here, one of the giants of the field of Bioethics. John ran a group over 25 years ago now that I had a chance to sit in on as a student, that looked at some of the issues around genetic testing and genetic screening and published a pioneering work in the New England Journal of Medicine about the ethics of gene testing and gene screening. If you haven’t looked at it you might want to go back and take a look because many of the issues being talked about today were talked about and anticipated then. Obviously what’s changed is not so much the ethics of genetic testing in that New England Journal article, there’s a lot of forecast about problems that could arise, particularly things like stigma and problems of fighting groups made less well off by having lower scale programs of genetic testing, but what changed is the ability to do genetic testing is moving quickly because of technological advance. I’m not going to spend too much time here talking about what those changes are in terms of PCR technology and gel runs and so on, but basically we all know in this room that we are better in terms of teasing out genetic information base pair by base pair than we were 25 years ago.

A little aside on this…I’m not gonna ask the people in this room to pass this test, but about 8 months ago I got asked by the Governor of Pennsylvania (a fellow named Tom Ridge) to come to Harrisburg and talk to him and some state legislators and other bureaucrats about the Genetic Revolution. And they wanted to know what they should do to regulate areas like genetic testing. What should they do? So I went there and I said to them, "Well before we start, let me just ask you a question. Where are your genes?" Now you all know this, right? About a quarter of the elected officials in Pennsylvania think their genes are in their gonads. They may not be as surprised as many of you that they think this, but that’s where they think they are. And they’re not completely wrong…there are genes there. About half of them thought that their genes were in their brains, which I found an amazingly optimistic assessment. And about a quarter of them knew that their genes were in their body parts. Indeed in every cell of their body, except for …there’s the extra credit question here… (?) Right. So no red blood cells, no DNA, for reasons, by the way, evolutionary wise. No one can quite figure out why the oxygen-carrying cells don’t need DNA. But okay, they don’t. Anyway, it may not be time in Pennsylvania to start regulating anything since people don’t know where their genes are, and that might be a good starting point. But we all know in this room of course, that we’ve gotten very good at opening up that big encyclopedia of information, looking instead of volume by volume, which was the old chromosome type testing for genetic anomalies, and being able to open up the volume and look at the sentences and start to see patterns and start to see typos. No dictionary yet…that’s the next 20 years of NIH funding that all scientists will be fighting for to get the dictionary done, so we can read the words that are inside these books that we can now open up and see. But we see patterns. And as we see patterns of DNA-based pairs unfolding, we can correlate them with diseases. That’s what happened with breast cancer. That’s what’s happened with Huntington’s diseases. That’s what’s happening with cystic fibrosis and soon will happen as the genome project gets completed in the next year, with many other diseases and conditions. It’s also the case that we’re correlating diseases and disabilities with DNA, because it’s easier to see what’s wrong and observe those patterns, than it is to see the multiple contributions that different bits of DNA make to ordinary physiology and ordinary behavior. It’s harder to find what’s correlated. But if something is wrong, if you’re born with limbs missing, if you die prematurely, you can look for that adverse and terrible outcome and correlate it with patterns of DNA, sometimes, that seem to be playing a role in pre-disposing or causing these easily observed outcomes in human beings or animals, or for that matter, sometimes in plants.

So testing is moving fast, not because no one ever tested. People have been doing genetic testing since the end of the second World War, looking for PKU disease, mass screening of infants that are born for Maple Syrup disease and other anomalies. That’s been going on 30-40 years, a mandate in most states. But what is new is new technology that is just opening up many, many, many forms of testing to correlate disease and behavior.

Now I made the claim that what we’re doing right now, with respect to genetic testing, is unethical. And why am I so worried and concerned about how this goes? Well when people were trying to advance the argument for spending three billion dollars of public money to map and sequence the human genome, they argued that if we could do this, we could unleash and uncork into the American public a host of diagnostic and information abilities that would just be a boon to medicine and the public health of Americans. If we could get this genome done, we could have all this information come out. We could find all this correlation between disease states and propensities to problems. And we would be able to advance medicine rapidly. But in fact if you went to UVA hospitals or you went to University of Pennsylvania hospitals or anywhere, there is relatively little genetic testing being done. Relatively little. Very few people have had a genetic test at this point for anything. Why is that? What happened? What went wrong? Where was the promise of ten years ago that if we could just get this advance or quantum leap in genetic analysis done then all of us would have a little DNA analyzer at the doctor’s office, and they would take a little swab of cheek or skin sample and grind it up and pump it out of a machine and the doctor would say, "You are going to have this, you are going to be sick that way, you will be dead by this and that will be $300."

So what went wrong? Where is it? Where is the genalizer? Where is the use of genetic testing for people who worry if the disposition for different things?…Well fair enough, some of the tests just are not here yet. Coming soon, but they are not here yet. But even in areas like breast cancer there is no massive program at the national level to test for carrier states or to find out in at risk families what’s going on. And in fact, the reverse is true. Groups that have been identified at somewhat higher risk, people of Oshkinasi Jewish descent women, are fighting the idea that maybe they don’t want to have large-scale testing within groups that are identified at high risk.

I have to tell you another little aside about groups at high risk. I got an ad sent to me two or three years ago now from Johns Hopkins by a scientist there, and he said, "I’m worried about this ad." And what the ad said was, "Recruiting Jewish men and women for a study of the genetic basis of depression." And I thought, "Yeah, that could be. Maybe they want to recruit among the Jewish people. Sort of Woody Allen disease or something. They are looking to see if they are sad or more depressed." But on the other hand, that didn’t ring exactly right and I wondered – Why look there? So I called up the scientist at Johns Hopkins who was doing this work, and she said, "Well." I said, "is it true that there is a higher incidence of depression in this group?" She said, "No. But they are very compliant." And there are a number of studies, by the way, on Mormons, on Minnesotans, and on Jews – groups that are likely, if you tell them to come back for their second appointment, they show up. Right away, in areas like breast cancer, the idea that Jewish women of European ancestry are at higher risk…They may be but that is just because we haven’t done a large scale sampling of all groups. There may be groups at higher risk than that. They may turn out to not be higher risk than the average population. But it’s sort of ‘who is looked at’ becomes one of the dilemmas. You sort of look at where the street lamp is shining and that’s where you tend to see problems. But in any event, where even people might suspect that there are ethnic or racial or group things that predispose, or family histories that predispose, large scale genetic testing is not here.

So what went wrong, aside from technological slowness? What’s holding things up? And that’s where the ethical issues come to the forth. If you are going to do genetic testing, one of the things I think you have to be sure of, is that you are going to do something for the person that empowers them, that makes them better off. That old principle of "do good or be beneficent," I think does come in to play. And why someone would want to do genetic testing in the health care setting? It may not be in place if you are going to do it in the employment setting; it may not be in place if you are going to use genetic testing to screen for eligibility for a job, or even for eligibility for insurance, you may not care about being benevolent. But if you are trying to do good for a patient as a nurse or doctor or someone involved in genetic counseling, then I think you want to do genetic testing and say I’ve done genetic tests to empower you in some fashion. You can make decisions better than you might have if we give you this genetic test. You may change your reproductive plans. You might engage in a different lifestyle. Or you may choose to have information that you share with family members about things that might happen. You might order your own life differently if you knew that you were at high risk of dying of something like Huntington’s disease. You might not decide to pursue a career in bioethics with decades of intense study that are required before you could possibly understand anything. (That’s a warning. Well, can’t be true…look at me.) So you may be able to live differently, to take proactive measures to prevent problems from happening. Maybe there are cures or innovations you could undergo if you knew, having genetic information. That’s the reason to do any health care is to do good for the patient, empower them, make them better off.

Does genetic testing as it presently exists, do that? My argument would be that it does not. And the reason we don’t see more genetic testing going on is because people who might benefit from genetic testing are not sure, or maybe have the view correctly that they won’t be any better off by being tested.

What are the limits? Well first let me just describe what happens for breast cancer testing at Penn. If you come to my school and you say "I’m in a family that has a lot of breast cancer transmitted over generations. My aunt had it and we think great grandma had it and two of my sisters have it and I want to know if I’m at risk too. I want to know am I a carrier of a mutation or a set of mutations in my DNA that might put me at higher risk of getting this?"

We say some things to those people. One thing we might ask them right away is, "How are you paying for this?" That’s an initial question, because almost no one’s insurance would pay for breast cancer testing. In the health care system that we have, outpatient testing is usually not covered. To do the breast cancer testing of an individual will probably cost about $800. It will come with a test and a lot of biochemical work to get it done and it is something that most people are not going to have $800 around to find out about their risk factor. So an immediate problem for someone who wants information is the barrier of cost. It’s not linked to genetic testing, it’s linked to a health care system that has never been able to figure out how to get preventive testing and outpatient services covered. Until the system does those things, there will be a fiscal barrier in front of those who might want this information.

Alright, let’s assume that the person says, "Well I’m lucky. I’m in one of the insurance plans or managed care plans that say we’ll pay for this or part of it." Then we turn the tables on them and say "Ah, but there’s something else that you need to worry about. Do you know that if you take this test it may turn out that you lost your health insurance?" Why? Well the way we do health insurance eligibility in this country now is to risk-rate it. We underwrite it so that we try to determine who has certain risks of getting diseases. And insurers try to avoid high-risk candidates. They don’t want adverse selection. They don’t want people buying a lot of insurance who know that they are going to get sick of something that’s going to be costly. Whether it’s life insurance or disability or just plain health. And they want to avoid people who are going to cost a lot of money to other people who are in the plan. If you take the breast cancer test and you show positive, your insurance company may say, "Well gosh, that was a preexisting condition, that was something we needed to know about." Or if you change jobs and lose your health insurance and have to reapply, they may say, "We don’t want you."

So the good news is, you’re at high risk of breast cancer and the better news is, you won’t have any insurance. This qualifies as not empowering. So what we say then is, "You know, you’d be better off if you just paid for this out of your own pocket. If you just paid for it out of your own money, if you could do it. Because that way your insurance company won’t know." (We engage in mild fraud.) In other words, what we’re telling people is, "Keep it a secret. Keep it a secret." Why is that a problem? Well we have not done anything in this country still to deal with the problem of increased information about risk and how that works in an underwriting health care system that does risk-rating for life, disability, and health insurance. Now you may not think of life insurance as something that people have to have a right to or have to be able to get. That’s debatable. I would argue that health insurance is something that people do need and ought to have available. Whether you do it by government means or private means or mixed market means, we can debate that some other time. My only point is, it’s hard to say in the United States, in the year 2000, that an adult or child isn’t better off by having a shot at equal opportunity by making sure that they get basic health insurance. If you have a breast cancer risk and you can’t get health insurance, we haven’t done anything for you. It’s worse. If it’s hereditary then maybe your child won’t get health insurance. This is not a good thing either.

So until we figure out how to absorb increasing information about risk into our insurance schemes. Whether we continue to pool, or whether we insist that there be a basic plan available, regardless of risk profile, and, by the way, until we figure out what to do to prevent adverse selection (loading up on more insurance when you know you have a risk), we are not going to see much genetic testing. I don’t care how many tests come down the road. The technology is not going to drive it. The ability to be penalized will.

Ah, but it’s worse still. Because if you take that genetic test and we store that information in your records, say for US Health Care EDNA, or Pacific Care, or whatever third party, Blue Cross might be carrying your insurance. Or if you’re at a company that self-insures, say a large outfit like IBM, or Hewlett-Packard, one of those companies, then they’re gonna have that information. And as you know you have absolute privacy in this company for your medical records, right?

Who has been in the emergency room lately? What’s the first thing you get asked? Your social security number, then how are you paying. And after you get asked, ooh the big question in American health care, "how are you paying? How are you paying." Then the next thing that happens is, you are asked, after you figure out how you are paying, would you sign this form for your insurance company that gives them the complete right to look at all your medical records and information. Now you have a right to privacy. Actually most states protect individual medical records and what the insurance company and managed care plans demands is that you sign it away as a condition of reimbursement. So it is immediately floated off into the vapors.

Now once that information about your genetic tests enters your medical record, it is free-fire zone for all kinds of people to see it. There is no privacy. None. I have had managed care plans call up and say, "We see that Mr. X has taken his child for the sixth time to the emergency room with broken bones. And we want to know if we should blow the whistle on this clear case of child abuse because he’s not getting picked up. That’s a great thing. But it tells you that individual by individual, the third party payer can track everything that is going on and they do. They also exchange information. When companies merge, information moves together in medical records.

Without some form of better privacy protection, genetic testing is not going to flourish. Genetic testing is not going to go anywhere because it’s going to founder on the rock of privacy.

Who knows where the biggest DNA bank in the world is? Not far from here. It’s the Defense Department’s DNA bank in Gaithersburg. They’ve been collecting samples of DNA from all military personnel for about 15 years. They have about 40 million Americans in the bank. The purpose has been a good one – to prevent the problem of unknown soldiers. Do you remember that pilot in Colorado who flew his plane into the side of a mountain, maybe a suicide, a couple years ago. He was identified by the DNA bank. They didn’t know who had taken the plane. They didn’t know who he was, but they matched him. So it has a good purpose. But there is absolutely no guarantee that the Defense Department DNA bank would not be given over to other government agencies. In fact, it’s just a promise of the guy who runs it that he won’t do it. That’s what stands between that databank and the FBI, that databank and medicare or medicaid insurance files, that databank and the Department of Justice, whatever. For those of you who don’t think that things are moving that way, the original FBI fingerprint file started as the Armed Forces Identification file in the 1910’s as a way to identify people in World War I. And Congress ordered it transferred to the FBI in the 30’s. Now you may say, "It’s great. I’d like to see DNA information used to prosecute criminals and chase down bad people and tax evaders and immigrants and illegal aliens and dead beat dads and people who default on their student loans." So there are all kinds of purposes for which you may not want to see your name popping into government files that way. No privacy protection.

There is no way to pay. There is no protection against discrimination. There is no privacy. There are two other problems.

If you were to start a massive genetic counseling program now, well let’s just say in Philadelphia, we have some pretty good genetic counselors, excellent people, and we have some doctors who are very knowledgeable about clinical genetics. And if we brought every woman in an alleged at-risk group to talk with people and get tested and counsel, there are not enough person-hours in the universe of the personnel available to counsel people. Now I know all of you are far more expert than I am at probability and statistics. (I am just being nice. We are all pretty bad.) And if you are going to get genetic information, you are entering into the realm of probability, probability assessment, probability interpretation. There is no infrastructure in the United States to counsel people about genetic information. There are about 2500 genetic counselors out there, there are some physicians and nurses who are knowledgeable about genetics. They could not possibly handle the massive amount of genetic testing that could go with cystic fibrosis screening, breast cancer screening, even Huntington’s disease screening at present levels of incidence in the population, much less what’s to come. It is true that certain genes can put you at risk. It is also true that if you come into genetic counseling I have seen, smoking 3 packs a day and eating twinkies, you might want to stop doing those things before you worry about your genes.

So how do we counsel? And can advertisers play on this fear? Here’s another ad that you see at a clinic not far from here. Joe Schulman’s idea of clinic over outside of D.C. They run ads in the New York Times magazines as do other IVF clinics around the world. "Get your embryos tested for disposition of BRCA-1. Get your in-vitro fertilization treatment for infertility in our clinic as we will pull a cell off your embryos and make sure that it’s not carrying a disposition of breast cancer." Well maybe that’s reasonable, but is it? Do you need counseling about that. For one thing breast cancer, even in it’s most aggressive form is not going to kill anybody before they get into their twenties. And most people predisposed are not going to see it until their 30’s, 40’s, 50’s, or later. You could actually cure breast cancer in the time frames we’re talking about. If you’re predisposed to breast cancer and you throw those embryos out, were they also predisposed to other diseases? Well who knows. We don’t have any tests for those yet. So does it make any sense to say, "well we’re not going to use those breast cancer embryos and then just produce the demented neurotic babies that are left over after we throw out all the rest of those embryos." Who knows? There’s no counseling here and there are advertisers playing upon people’s misunderstanding, misapprehension, lack of information about genetic information and not having counseling. The market forces for advertising and recruitment will overwhelm in a very unethical way, the ability of people to make choices. Choices, true informed choices, about genetic testing. So that is a major problem. A lack of counseling, a lack of adequate infrastructure to process out information that comes from the world of genetic testing. That is simply not fair.

And just as a last point, have we done what we need to do to make sure that people understand genetic information as they see it in terms of their own identity and sense of who they are? No. There is a bill that’s up now in a state legislature in a western state that says, "If you want to share in Indian gambling casino profits, then you should take a genetic test to establish your membership in a Native American tribe." Well, maybe we are our genes, and maybe our sense of whether we are Native American is determined by our genetic pattern. It is however possible for someone to be a tribal elder, speak a particular Native American language, live somewhere in a Native American community, and not have that gene pattern. So are they not Native American at that point? Or what are they? Are we actually going to see genetic testing not just for medical application but people saying, "well I thought I was black, or I was under the impression that I was of German ancestry or something. But I see these genotypes and I understand now that I’m not the real thing. I’m some Mongol. I’m something else."?

Well do we test backwards in time and allow people to rifle around in the genetic histories of the dead? There is no protection that stops us from digging up anybody. Some of you may have noticed, there was a big interest some years ago and it’s come back again that Abraham Lincoln was thought to have Marfan’s Disease. He’s tall, he’s gangly. That’s a classic Marfan presentation for that particular genetic disease and we’ve got a good marker now for that disease. And one of the things that Marfans does is give you joint pain because the connective tissue that hold your bones together, the tendons and ligaments, does not form correctly. It can be fatal because that same connective tissue binds your aorta, and if it bursts, you die. Flo Hyman, the volleyball player some years ago, died of that problem. But Abraham Lincoln as many of you know was not happy. Through much of his presidency he was sad and some physicians and biologists have speculated this was due to his Marfan’s, that he was in constant pain, like he would be if he had arthritis. Now somebody might want to point out that maybe he was unhappy because he was also president during the Civil War. That’s a nature nurture thing that you all can… I understand that he and his wife weren’t getting along so well, so maybe that made him less than happy. I don’t know. But maybe he was just achy and painy. That’s possible. Should Abraham Lincoln be tested to establish his markerness? I wrote a little column recently that said we should not test anybody without their consent. And one of my biology colleagues came and told me, "You know, I know you are a philosopher and ethicist and oh so wise, but he’s dead, so it will be difficult to obtain his consent. So we can’t do that, right?" And I said, "Well maybe then we should appoint a board or a panel to review requests."

Should testing always be done with consent? A fundamental question about voluntariness. Would anybody be forced to undergo it? And just because you are dead, are you a free-fire zone? Can we dig you up and find out what your genetic makeup is, what diseases you were predisposed to, whether or not you had the APOE marker (Ronald Reagan, Alzheimer’s disease)? There turn out to be biological samples from a couple of presidents at the Smithsonian. We have Abraham Lincoln’s samples, by the way, because medicine, in its effort to be scientific, did perform an autopsy to determine the cause of death on Abraham Lincoln. I mean, he was shot, like that, with a big hole in his head. But they did establish everything. He was shot in the head with a big hole in his head. But they kept samples and that’s there. There are also samples there from Chester A. Arthur. Although they notice no on seems to care what his predispositions and biological propensities were. But my point is, without protection, without some discussion of who may access your DNA with or without your explicit knowledge and permission, genetic testing is dangerous.

So going backwards: can’t pay, no privacy, discrimination possible, no counseling, no guarantee that it’s up to you whether you get tested. This is the ethical void into which genetic testing moves. It is not a technological problem that has hindered it. It is these factors that have hindered it. If they are not attended to or repaired, then genetic testing, I will predict, will go nowhere. It won’t move. That would be a loss because I am not against giving people information that they can use. There may be treatments that will follow in the wake of establishing risk profiles and that would be a great thing. There are many wonderful things that genetic testing could give. Even the knowledge itself in how you live your life, some would want it, and I think that’s empowering for those people and that’s a good thing. They may just want to know if they are going to die prematurely or if they have risks or, as some people have said to me, "it’s my body and I’d just like to know about it." And I think those are good things. But they are not going to happen and one might even argue that they should not happen, until those ethical issues are fixed. That is what is hindering that genetic testing revolution. It is an ethics problem. It has been a problem in some dimensions for 25 or 30 years, flagged early by bioethicists, remains a problem. And some of the problems are driving directly out of a health care system that hasn’t figured out how to deal with prevention and hasn’t figured out how to deal with increasing knowledge about risk into a system that presumed ignorance about risk as a way to underwrite an insurer. Until those things are fixed, the goods of the genetic testing revolution won’t happen.