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3.4. Germ-line Gene Therapy from the Lens of Confucian Ethics

-ZHANG Xinqing 
Center for Science and Society, Peking University
Center for Bioethics, Peking Union Medical College,
Beijing, CHINA
Email: zxqclx@vip.sina.com

1. Introduction

On September 14, 1991, a four-year-old girl, Desilva, became the first patient under an approved protocol to be treated by gene therapy. [1] She lacked the gene for producing adenosine deaminase (ADA). Without ADA she would almost certainly develop cancers and opportunistic infections that can't be effectively controlled by conventional treatments. Gene therapy showed her immune systems was functioning effectively. At the moment, the therapy can't be said to have produced a cure for ADA, but W. French Anderson believes that eventually it will. Although somatic cell therapy holds wide promise for ADA, the therapy, however, will do nothing to alter the probability that another child of Ashanthi's parents will inherit the same defective gene. If they hope to eliminate ADA disease from their family, the most direct and effective way to achieve this is to replace the defective gene with a normal gene in an ovum or sperm cell. Suppose the gene-line cell therapy is mature in clinic, how will Ashanthi's parents make a decision? While germ-line cell gene therapy remains a distant prospect, a series of moral questions have raised. In what follows I will examine the arguments against and for germ-line cell gene therapy respectively.

2 Arguments against germ-line gene therapy

There seems to be good ethical, social, religious, or legal reasons to forbid particularly to germ-line cell gene therapy, besides the concerns about the technical difficulties involved. These concerns have resulted in a fairly robust consensus that human germ-line cell gene therapy should be unacceptable. For example, German Embryo Protection Act(1994) recommended strong restraints of any human germ-line cell experiments. Now, let's examine three main objections: (1) Do not play God; (2) Violating the autonomy of future generations; (3) Why open another Pandora Box. I agree with the conclusion drawn by Munson and Davis that none of the objections justifies prohibiting germ-line cell gene therapy. [2] What's the difference is that I try to provide counter-arguments from a perspective of Confucian ethics.

(1) Do not play God

One argument against germ-line gene therapy may be that changing the genetic makeup of germ cells is tampering with the very order of nature created by God. Such an argument is popular in Judeo-Christian culture. One possible counter-argument may come from Lao Zi (403-221B.C.), an alleged founder of Taoism, who claims:: "I don't know where Tao (the way)was born of, (I only know) it appeared before the Lord."[3] In the world of Confucius, however, the way is to be achieved, rather than discovered and instantiated according to Taoism (there is an inconsistency: Confucius v. Taoism). There is no personal God in the moral discourse of Confucianism and Taoism in general, and the very discussion of playing God does not exist at all.

The second argument may be that only the wisdom of God can be relied when the present risk-benefit analysis doesn't work. This argument is plausible, but not so convincing.. One possible counter-argument may be that although we ought not to irrationally harm future offspring for every reason, it doesn't mean that intervening with future individual's genome is unavoidable to result in biological tragic. My answer is if we do not do scientific research about germ-line cell gene therapy, most serious genetic diseases remain unsolved. Let alone we have some examples to show it is useful in animal experiments. However, the argument does warn us of not expecting too much.

In my opinion, the other counter-argument may be that the talk about "playing God" is ambiguous, the reason is that Bible does not discuss the method of creation, but merely says that God created the world by his Word. In modern societies, human beings intervene with nature everyday. To which extent we are playing God or not playing God, nobody provides an explicit answer. In this case any new technological advance can be labeled as Playing God and rejected including in vitro fertilization and somatic cell gene therapy.

In sum, Confucians supports full the realization of one's Mandate and all sorts of talents to be well informed, appropriate. There is no predetermined pattern, no cosmic blueprint, against which to check one's progress [4]. For Confucians, they welcome any study that could extend our knowledge and experience to find medical treatment of many currently incurable genetic diseases. For Confucians, gene therapy, as a way of making up for the defects of Nature, it is by all means moral.

(2) Violating the autonomy of future generation

The common argument may be that germ-line gene therapy will unavoidably violate the autonomy of our offspring. There are some problems in this argument. The principle of autonomy only be applied to rational individuals, who are uniquely qualified to decide what is in their own best interest, and they should have the right to self-determination. To use Kant words, persons are ends in themselves, not mere means to some other's end. However, this powerful argument is unfit for germ-line cell gene therapy. No future baby could make an informed consent and choice at the stage of pre-life. From a Confucian perspective, however, we should not deny its inherent worth. It is our duty to respect that worth and to avoid manipulating it improperly, but their autonomy is problematic. Any future child cannot have autonomy.

The response to my counter-argument may be that the act in which we change germ-line cell genome without informed consent of future generation would be labeled as paternalism. Some claim that how could we know whether or not our future children like the changed genetic makeup ? This is true , provided parents or clinic researchers try to design the capacity and traits of a child by non-therapeutic gene enhancement. But it does not mean that parents have not an obligation to treat defect in germ-line cell when the benefits of doing so greatly outweighs the risks(an utilitarian argument). Moreover, autonomy is not an absolute or unconditional value; it is, at best, only a prima facie duty as Ross says.

In a weak version of paternalism, we are justified in restricting the freedom of future generation to act if the restriction is necessary to prevent harm to them. Take Baby Jane Doe Case for example. On October 11, 1983, Jane Doe was born in Port Jefferson, New York. Her parents were told that without surgery she might live from two weeks to two years, because she suffered from meningomyelocele, anencephaly, and hydrocephaly .With surgery she might survive twenty years, but would be severely retarded, epileptic, paralyzed, and likely to have constant urinary and bladder infections. The parents decided surgery was not in the best interest of the child and opted, instead, for the use of antibiotics to prevent infection of the exposed spinal nerves. In such a case, the autonomy of Jane Doe (suppose she would have preferred surgery) is compromised, violated , and even deprived of. Most people, however, consider that her parents' decision was in the best interest of the infant. Supposed Confucius would survive to nowadays, he might say that Jane Doe's father and mother are Ren(humanity).Therefore, our future generations could give up just a little autonomy to bring about a great deal of benefit. The same is true in germ-line cell gene therapy.

(3) Why open another Pandora Box

The next popular argument against germ-line cell gene therapy may be that because the technique of intervening germ-line cell genome is uncertain, and even dangerous, opening a new Pandora Box is wrong. Some may say we are changing not merely a single individual but a host of future individuals as well, with potential for harm to those individuals and (perhaps) to humanity as a whole. However, at least we cannot say germ-line cell gene therapy would be an unpleasant monster at its origin. And whether this technique opens a new Pandora Box is still an open question.

The more plausible argument is that some worry about that germ-line cell gene therapy technologies would as easily be applied to the enhancement of human traits as to the prevention of disease [5].The response to this argument may be that such an argument will be led to the issue of whether germ-line cell gene therapy should be applied to improve human's intelligence, color of eyes, length of life span, and so on. Thus, it is only a slippery slope argument. This is a reason for us to stringently regulate it, but not reject it: we can open the Pandora Box slowly and carefully with all necessary precautions taken. In some cases, however, gene intervention with germ-line cell may be the only possible way to relieve pains and sufferings of our descendents and future generations. Of course, this intervention may cause some or even grave negative consequences.

2. Arguments for germ-line gene therapy

The powerful arguments for pursuing germ-line cell gene therapy include: (1)germ-line cell manipulation would be more efficient and less costly than somatic cell gene therapy;(2) it offers the only true cure for many diseases. [6] But the ethical critic of germ-line cell gene therapy is well underway. The crucial question they ask is: will the germ-line cell gene therapy bring great substantial benefits to future individuals? They argue that the mechanism of interaction between genes has not been detected by foreseeable technology. So, the therapy fails to be directed at alleviating actual suffering. The proponents respond that it is a plausible warning but does not constitute a strong reason to reject. They admit that it would be unconscionably foolish to risk massive future harms for the sake of trivial gains now; and we have no calculus that would permit one to calculate with precision when future risks are acceptable for the contemporary gains. But what they insist is: our current ignorance only justifies postponing human trials of germ line cell therapy until their promise can be improved. It seems clear to Watson that viral transmission of DNA to other cells than their target cells are, given the techniques being pursued in these cases, relatively rare events [7]. So it seems that geneticists may overcome the technological puzzle in the near future.

Unfortunately, people who argued against it did not take the argument seriously. This reminds me of an early Confucian, Xun Zi. He said, Man couldn't run fast as horse. Yet horse and ox are used by man. Why? Because man has the ability and intelligence for organization. Man in the Confucian tradition is a free individual who emphasis on learning and innovation, as the Book of Great Learning says: reviewing the old in order to know the new. If we do research on germ-line cell gene therapy under a rational way, and learn from errors, we will do good to people with this technology.

Now let me turn to examine the other arguments for germ-line gene therapy. One argument for many may be that although the misuse of it is possible, such as eugenics, it can be prevented by stringently regulatory precautions. One Chinese adage says: "We cannot refrain from eating for fear of choking". Fletcher and Anderson, however, argued that there were several criteria that needed to be satisfied before the practice. First, considerable experiences with somatic gene therapy can establish the effectiveness and safety of treatment of somatic cells. Second, adequate animals studies of germ-line cell therapy using the same vectors and procedures that would be used in humans can establish its reproducibility, reliability, and safety in humans.,. Third, public awareness and approval of the procedure since unborn generation will be affected [8].

According to those two pioneers in gene therapy, it is necessary to delay any kind of germ-line cell study until somatic cell gene therapy has proven clinically successful in adults. A strong counter-argument may be that germ line cell gene therapy should not wait for all the relevant questions being answered by adult somatic cell gene therapy. The reasons are as follows: 1) germ-line cell gene therapy is somehow independent to somatic cell gene therapy; 2) from the pre-clinical animal experiments of germ-line cell gene therapy, productive results have been made; 3) it is possible of manipulating mitochondrial DNA in germ-line cell to treat a relatively rare form of infertility via ooplasmic transfer. In short, many scientists disagree with the following claim "Inheritable Genetic Modifications should not proceed at this time before any somatic genetic therapy applications is a reasonably foreseeable possibility "

3. Conclusion

After examining the arguments for and against germ-line cell gene therapy in the debate, it seems to me that there is a conceptual issue that we have to make clear---- substantial and procedural ethical issues.. Some are unable to discern those two concepts The former is concerned with "whether it ought to be done", while the latter answers "how it ought to be done "We may reach a conclusion of the presentation above that it is better to interpret that at the substantial level there is no convincing reason to ethically reject the germ-line cell gene therapy. Nonetheless, according procedural ethics, there should be stringent criteria that need to be satisfied before the practice.

Notes

[1]W.F. Anderson et al. The ADA Human Gene Therapy Clinical Protocol. Human Gene Therapy,1. 331-362, 1990.
[2] Munson, R. and Davis, L.H. 1992: "Germ-Line Gene Therapy and the Medical Imperative" Kennedy Institute of Ethics Journal 2(2):137-158
[3]Ren Jiyu. The Book of Lao Zi, Foreign Language Press. Beijing. 1993. p18.
[4]R.P. Peerenboom. Law and Morality in Ancient China: The Silk Manuscripts of Huang-Lao. State University of New York Press.1993. p105.
[5]Frankel, M.S. and Chapman, A.R. 2000 Human Inheritable Genetic Modifications: Assessing Scientific, Ethical, Religious, and Policy Issues, American Association for the Advancement of Science. Pp. 40-44 Available at: http://www.aaas.org/ssp/dspp/sfrl/germline/main.htm
[6]Resnik, D 1994 "Debunking the Slippery Slope Argument Against Human Germ-Line Gene Therapy" The Journal of Medicine and Philosophy 19(1):23-40
[7]Watson, J.D. et al 1997Molecular Biology of the Gene, 4th edition, Benjamin/Cummings Publication. Co, Inc. Menlo Park, CA. p 1032-1033
[8] Fletcher, J.C., W.F. Anderson, 1992 "Germ-line therapy: a new stage of debate." Law, Medicine & Health Care 20(1-2): 26-39

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