Discussion for Session 5pp. 72-76 in Bioethics and the Impact of Human Genome Research in the 21st Century

Editors: Norio Fujiki, Masakatu Sudo, and Darryl R. J. Macer
Eubios Ethics Institute

Copyright 2001, Eubios Ethics Institute All commercial rights reserved. This publication may be reproduced for limited educational or academic use, however please enquire with the author.
Miki: We are moving to the last session for today, on the clinical use of DNA Polymorphism. The first paper is by myself on DNA polymorphism in age-related genes. The next paper is from Robert Kneller on genetic privacy. Are there any questions or comments.

Wertz: I have a comment. I was involved in conducting a survey of refusals of employment or insurance, for people who have a genetic predisposition, or are carriers of a gene but have no symptoms. This is part of an overall survey of ethical views in 36 nations, of 2900 genetic service providers. One thing I found was universal distrust of insurance companies, they just hated insurance companies. Another thing I found was very few cases of refusals of employment or insurance. Mostly in the U.S. there were 550 cases reported. But when you figure that these geneticists had 14 years of experience of average, and saw 6 patients a week, and that the cases also included family members not just the patients, that really is not a lot of refusals. We also asked patients in U.S., they were working class women, and about 5 % of them reported refusals of employment or insurance. But none of them could be really called genetic discrimination. It is interesting to see what people think is genetic. Somebody said, "I was refused a job as a fire fighter because I have chronic bronchitis". Somebody else said, "I was refused an operation for my child with Down syndrome, a cosmetic operation on the face, because the insurance company doesn't pay for cosmetic surgery". That is insurance practice, not genetic discrimination. Most of the cases were either justifying employer refusal on the basis of inability to do the job, or they were insurance practice. I am not defending insurance practices, I think there is a lot of unfairness, but you can't chalk it up to genetics. I think what happens in the area of genetics is that the public is so afraid that they will be denied something on the basis of something they cannot change, that they attribute a lot of what is wrong with the insurance generally to genetics. That is my general response to the situation.

Miki: Thank you, and the next paper is by Dr. Sharma. Are there any questions?

Leavitt: I have a simple question out of shear ignorance. You mentioned the in utero effects. I've been curious to know if there is any research in progress, I haven't seen anything published although maybe I just missed it, on whether or not if there are long-term studies of potential effects of in vitro fertilization, on the baby or the child or the adult after the baby is born. This seems to me to be a possibly traumatic event; it is a very different event from the normal conception. I wonder if you, or anyone else knows whether there are any longitudinal studies being carried out to see if in vitro fertilization has any effect on the human being afterwards.

Sharma: There may be a postnatal psychological affect, but I do not think there is any in utero affect.

Leavitt: No, I am talking of postnatal affects of in vitro fertilization. Is there any difference between IVF babies and other babies. We will also want to know about for adults later too.

Sharma: I don't know of any formal studies so far. But we can imagine that there would be psychological effects on the developing child if they came to know.

Leavitt: What we can imagine and what really happens are two different things.

Miki: Thank you, we will move to the next paper by Dr. Leavitt. Are there any questions?

Macer: Since you mentioned I may have a comment about the UNESCO Declaration on the Human Genome and Human Rights. Professor Fujiki and myself were members of the UNESCO bioethics committee. Let me read Article 5e of the UNESCO Declaration: "If according to the law a person does not have the capacity to consent, research affecting his or her genome may only be carried out for his or her direct health benefit, subject to the authorization and the protective conditions prescribed by law. Research which does not have an expected direct health benefit may only be undertaken by way of exception, with the utmost restraint, exposing the person only to a minimal risk and minimal burden and if the research is intended to contribute to the health benefit of other persons in the same age category or with the same genetic condition, subject to the conditions prescribed by law, and provided such research is compatible with the protection of that individual's human rights." The point in your paper was for babies and neonates their individual human rights were violated by exposing them to risk, I agree. The intention here, the minimal risk and minimal burden is what you suggested but for the baby to have a blood sample taken, if that will lead to a significant research result, it's only a minimal risk and minimal burden. Where as for example, liver biopsy will not be considered a minimal risk or minimal burden.

Leavitt: However, with respect to a child we have a duty to decide for the child and some times to treat coercively, if it's for the clear medical benefit of the child. With respect to taking a blood sample, if you took the blood sample for a health reason, and then the next day you say "wow I want to use this in my research!" I don't see any problem with that. That's already retrospective. But to go ahead and take the sample for the purpose of your study, which is subjecting the child to perhaps even a minimal burden, I see this is an infringement of the child's rights. Even taking up his time without his consent. And the fact that it's for others in his same age group or others in the same genetic category doesn't seem to help, because it is not for the benefit of this particular person. I know that if you pull out one hair for the sequencing of the hair, the burden is so minimal so what do we care? But there is a slippery slope and BMJ did publish a study where newborn babies were subjected to a low atmosphere environment, and there was some ethical debate about it but it was published in a very major journal and I'm afraid of this slippery slope.

Wertz: How would you then do first phase on clinical trials of drugs for childhood diseases on children if you can have more than minimal risk, by which you seem to mean no risk at all. Just how would you do something that involves a risk that has to be tested on children, because the test on adults may not give you the right data?

Leavitt: If the child were in clear medical need, then I would even allow more than minimal risk. We have to use clinical judgment in this case. I'm talking about cases where there is no clear medical need for this child. Clinical trials of drugs can certainly be carried out. I do however have problems with what's considered to be a medical need and what isn't. I was on a team, which published a paper highly critical of clinical trials of genetically engineered human growth hormones for short stature healthy children, because I didn't see such a clear medical need. However if there is a clear medical need and the child is sick, and you want to try a drug on a sick child I cannot object to that, if other things are in order.

Wertz: But the first phase of clinical trials is usually for safety rather than efficacy and there is no benefit promised to anybody. These are usually done on healthy volunteers. But some times you might have a situation where the effect of the drug and the safety of the drug will be different for the children than for adults. How would you approach this?

Leavitt: We must have extremely good evidence from laboratory and animal studies that it is safe. I would not be able to agree with carrying it out on healthy volunteers when it is children, or psychiatric patients or mentally compromised geriatrics patients.

Wertz: So even for children and children's diseases?

Leavitt: I would not do the tests on children for safety and I would be willing to forego that research. The compensation that I am offering is that we open up retrospective studies.

Wertz: So you would open up a set of samples, samples which are linked to individuals or are they anonymous?

Leavitt: All effort should be made to anonymize, however if some identification of individual slips through, I don't consider that to be a terrible loss if there is no risk to the person's health. I would even disagree with the medical editors association with their restrictions on case studies, if there were clear health benefit to publishing the case study. You're taking a risk of infringing somebody's privacy, but it's not as bad as a risk to someone's health.

Wertz: In the case studies you could conceal identity by changing some of the social demographic data.

Leavitt: Yes, maybe that is possible by fictionalizing some parts. On the otherhand maybe the author would have to forego getting a publication in his cv, because he is a Professor at a medical school so how can he hide where he works.

Wertz: Maybe he can say it was not at his school.

Leavitt: That might be done.

Vogel: I have a similar question, which maybe more clinical. We all know that many people can be helped by organ transplantation, for example, heart or kidney transplantation. However, there are always not enough organs available for transplantation and many people who could be helped in this way will die from heart disease before they get an organ. Now the organs have to come from persons who have died in accidents for example, for example younger persons who have died in an accident who were in a similar age. Now the legal situation, at least in my country, is that you cannot use their organs despite the fact that they are completely healthy, unless the person themself has written beforehand a kind of declaration, "in case of an accident my organs will be available", and all the closest relatives agree. It would be much more reasonable to say that agreement of the person and family is presumed unless the person has declared beforehand "incase of my death or an accident my organs shall not be available". This is my opinion and I would like to hear what you think on this point.

Leavitt: It's a little bit off the subject of my paper, but you asked the right question for the place and for the person. I think the two places with the biggest cultural barriers to heart donation are Japan and Israel. In both countries, brain death is recognized by law, heart transplants are recognized by law since 1997 in Japan and for longer, 20 years, in Israel. However, people are not rushing to donate their organs, because there is a strong spiritual association between the heart and the flow of blood and life. This is seen by some people as a problem, personally I don't see it as a problem, because I'm not sure if I either want to give or take a heart transplantation. I tend to sympathize with these ancient views. However the solution which you proposed, as I understand it is exactly the same as the Israeli law. That is to say that according to law, you can take the organs, you do not need a consent, unless the individual has specifically declared in a legal way that he doesn't want his organs taken. I have a fifth year student in Israel who has an anti-organ donation transplant card in his pocket. It is also an-anti-living will card. However the fact is, even in Israel the family's refusal is legally binding. In another words, we could have a brain dead person and we need the heart, the family says no, but the doctors can take the heart anyway. However, it is universally respected. This is a problem that if the family does not want, even if the doctors disagree and say we want to save this person's life. But the feelings of families have to be respected, and they are in practice.

Miki: The next paper is by Dr. Tadujin. The paper is now open for discussion.

Macer: I agree when you talk about what should be patented, regarding my genome sequence which is basically the same as yours. However, how do we deal with the innovation reward for companies who do research, and invest lots of their time and money? How can we protect and encourage their innovation? Ethically how do you consider the principle of beneficence, if we achieve a greater knowledge and greater discovery by this commercial system that we have, than we do by not rewarding inventions. Of course there is the question whether it is an invention or a discovery. The development of a genetic sequence into a product, would you consider that an invention?

Tadujin: That is a very difficult question to answer. Indeed as we have heard this morning, incentives to do research and to develop products should be there, if a product is to be developed, at least in a reasonable span of time. Other matters of incentives to developing products maybe something like a profit sharing method for the discoverers or the inventors of the product. In Indonesia, we have a method for oil exploration. Oil is one of the products we export and we are one of the OPEC countries. The incentive to explore for oil in Indonesia is production sharing. We do not give them license to explore and then get all the products. Of the oil produced, about 60-80% goes to the state, the public, and the rest goes to the company. Something like that could be developed for other areas also. On the question of what do I consider as an invention and as a discovery. I think a discovery is something that is already in nature. But only it may need advanced technology or some other methodology to be able to use it or to see it. In this case maybe the discovery could not be patented but the methodology how to discover it or how to amplify it could be given a reward or patent so that people who do the work can also get some benefit from it. On the question of beneficence and maleficence, beneficence is when it does good to a lot of people of course, but then again some other people would contest this view. There is no a zero sum game. Somebody will also lose something. Mike would say animals would become a victim of what is beneficent to man and it is not so beneficent to animals. So I believe this question should be discussed in each cultural setting to determine for them, which criteria is beneficent or maleficent for them.

Leavitt: I'm not sure whether the patenting of genes is an ethical question at all. It might just be a matter of etiquette or a matter of practicality. By etiquette I mean the rules of the game for behavior within a certain group. In Japan you're not supposed to mix your rice with your soup, or in India you can eat with your fingers, where as you don't do it in certain other countries. Here we have a group of profit motivated corporations and researchers, etc. So they decided to patent. Maybe they could get along without patenting with some other method. I don't see why it really has to concern most of the people in the world all that much. The second thing is, which Darryl said, is while there is beneficence if you have the profit motive, which can be guaranteed through patenting, then more people would do more research. That also seems to be a technical, practical question. It can be debated whether profit motive or other motives are more efficient. Since the Soviet Union fell a few years ago, it's been considered to be axiomatic that profit motive is the best thing in the world, and that non-profit oriented societies are out-moded. But I don't think we have sufficient evidence for that. Maybe other motives would work. Furthermore, for so far as most of the people in the world are concerned, huge millions of people can't get basic, most simple medical care at all, and these things are irrelevant to them. So I don't see why this is considered an ethical debate?

Tadujin: The ethical debate of patenting genes would be besides the profit motive. There will be also questions of patient autonomy, and individual autonomy of the persons whose genes have been patented. Why doesn't he get any benefits or profits from what has been discovered from his body. So that aspect should also be considered. Indeed, people are motivated by profits. That is something we all know. We should not make profit in something which is exploitation. Profit is OK but do not exploit what you have for your own purposes.

Verma: This is not a question to the speaker but it addressed a problem which came up in the discussion to session 2 from what Dr. Skolnick mentioned. If you patent something in USA, does that patent apply in India or in Indonesia? At the moment, what is patented in USA or in Japan, may not apply in India. But there is WTO and GATT, under these agreements, within a few years whatever is patented in one country would be accepted to be a patent in other countries. That is the issue. Now it may not apply in developing countries, but the developed countries are putting lots of pressure on the developing countries to accept the GATT agreement. Which means that they will have to accept the patents that are filed in their countries. What the developed countries, at least the US are doing, they are filing patents for certain things, which, say had been known in India for centuries. There are some plants we have been using for wounds, for example, neem. The juice of this plant has been used for centuries in India to heal wounds. Our government had to spend a lot of money to fight that patent which had been granted, which in the end we won.

Kneller: Even with TRIPS there is no international patent. You still have to apply for a patent in each individual country. What TRIPS requires is that all members of WTO to have an intellectual property protection regime, somewhat similar to the U.S. or Japan. So if the company wanted to, it could go to the Indian Patent Office and file a patent on an invention. The idea of being an international patent where you apply for it in the U.S. and it automatically applies to India etc., is a very long way off. What we'll see first maybe is an international patent that will develop between US and Japan and Europe, but for it to involve the rest of the world is a long way off. I think I understand the Indian position concerning neem. The US patent law says that something that is in public use in the U.S. for one year before that patent is not patentable, but it's in the US. It's interesting that if it is published or patented anywhere in the world, then it cannot be patented in the US. However the public use bar to novelty applies only to public use in the U.S. I think what the Indian government did, show rightly, is that there has been some publication of this, and that could destroy the U.S. patent.

Miki: The last paper is Dr. Wang. We have some time for discussion.

Leavitt: It is commendable you could do such an extensive survey comparing European and Chinese people, and both doctors and nurses. I was under the impression that genotyping for drug metabolism is not very well developed yet. So I thought that the responses to this question may not be very indicative because that is the role of the doctor. It may not be a real option. Is it sufficiently developed enough to be a real option, so that answers to questions would be significant?

Wang: We still wanted to know what people think, even if is preliminary. Even if the genotyping is not so well developed in China, the physician and nurses know these things from the media and publications. So we can ask their attitude through a survey.

Wertz: The professional genetics societies in both Japan and U.S. have made statements on the issue of disclosure to relatives against the patient's wishes. Both societies said, if there would be severe harm to the relatives without disclosures and if this disclosure would prevent harm, the physician is morally allowed to disclose, but not legally required to do so. In other words, the physician has a right to disclose but not a legal obligation. The Japanese Society of Human Genetics has added the provision that the case go before an ethical review board before the physician is allowed to disclose. I think it's a very good provision because it prevents an over eager physician from telling too much in cases where disclosure might be more harm than good. My question is whether the Chinese professional society is working on any policy about disclosure.

Wang: I don't know the current policy of disclosure. They are dealing with it case by case at an individual level, so there is no policy.

Wertz: What do you think the policy should be and what should be done?

Wang: It's a difficult issue. We need to balance confidentiality and disclosure. Now in China, under such conditions, it is dangerous to issue such a policy now. Also if we think the physician has a legal duty, I don't think it is good.

Mao: I worked in China as a geneticist for many years, and then I moved to the UK. When did you do this survey?

Wang: This survey was done in 1999. We had two conferences; one in Hong Kong with geneticists, and another amongst philosophers in Shanghai. Two months later we gave out the surveys in Beijing among nurses, and then also in Europe.

Mao: Are the Chinese genetic physicians from Mainland China or Hong Kong. What is the ratio?

Wang: There are responses from mainland, Hong Kong and Taiwan, but most of them from Mainland China.

Macer: I wanted to follow up on Frank's comment. What do we do when discussing a technique before it's common, as in the case of individual genotyping? What then if the response from the country is negative to that technique. What do people here think, should the country limit the provision of those services to the population because the majority of professionals or philosophers or ordinary people reject that technique. Do they have a right to stop the provision of a new technology to the public?

Leavitt: What was really troubling me, was I think we have wasted so much time, a few years ago, discussing in so many articles whether it is OK to have germ-line enhancement gene therapy for character traits. This stuff is so far from being a reality that the only thing that was gained was that people published lots of articles and fattened their CVs. So consequently I'm always very suspicious of ethical debates about things that are still far from being reality.

Miki: Thank you to all speakers and for the discussion.

Please send comments to Email < asianbioethics@yahoo.co.nz >.

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