In her review, Andrea Bonnicksen (1994) focuses on preimplantation diagnosis and future preimplantation therapy as a vehicle for germ-line gene therapy. Germ-line gene therapy means genetic change that is inheritable, and there are other methods to effect it (Macer, 1990). One is to change the germ-line of adults by altering reproductive cells by a safe targeted vector, either in vitro or in vivo - which is the most "low tech" approach. Such a vector could be a liposome or virus, and could be reproduced at low cost for international use. A method already possible is to add human embryonic stem cell lines to an early embryo to correct a genetic defect, resulting in a genetic chimera, with the possibility that germ-line cells would be derived from the embryonic stem cell line. The cell lines can be selected in vitro, to ensure exact genetic treatment, and then mixed with an embryo, as is used for numerous transgenic mice lines. However, while this may offer the best immediate hope for genetic therapy of genes that need to be corrected in utero, and chimeras (which do occur in nature) could be adequate for therapy of the individual, the prospect of the embryonic stem cell line becoming the germ-line - second generation cloning - would defeat the purpose of germ-line gene therapy which is to preserve reproductive autonomy for those with some serious disease-causing gene. Many question the need for any germ-line therapy, given the alternatives of somatic medical therapy, adopting children, donation of sperm or eggs, and over population.
One of the arguments behind international approaches to regulate germ-line gene therapy is that the genome is shared by all people, who have diversified from a common African ancestor (mitochondrial Eve) - over the last 100,000+ years. The germ-line is common property under the international conventions on human rights, and should not be patented (Macer, 1991); an argument that can also be used to call for international regulation of genome modification. The other argument based on common future interest, is that people migrate and those with altered germ-lines will move across national borders thus the whole world is at potential risk (unless contraceptives are compulsory ).
These basic arguments have been behind international recommendations to date. In addition to those reviewed by Bonnicksen, we could add the Declaration of Inuyama (24th CIOMS Roundtable, 1990), and the Fukui Statement on International Bioethics from the Third International Bioethics Seminar in Fukui, held in November 1993 (Fujiki & Macer, 1994). I should also clarify that the Second International Bioethics Seminar in Fukui, in 1992 (mentioned in footnote 4, p. 6 of Bonnicksen) did have multiple international sponsors, but the major sponsor was omitted from the list she mentioned, being the Ministry of Education of Japan (Fujiki & Macer, 1992). These two seminars, and the English and Japanese proceedings of them, are the major products of the ELSI project of the Japanese Human Genome Project (Macer, 1992a). The Human Genome Project is an international project, and it is appropriate that the collaboration on ethical matters is also international.
In her review, Bonnicksen (p. 8) makes use of an argument that transnational agreements in advance of technology have some inherent problem, so we should use the successes and failures of national attempts at regulation before adopting international guidelines or declarations. However, international guidelines provide some minimum standard, as she says. Many nations will not develop their own regulations, and the peoples (present and future) of those countries need to be protected by an international umbrella guideline. The second is more fundamental, who has ethical interest in protecting the germ-line? National governments may pay health costs, but regional blocks such as the European Union may also take on this role, and international aid already covers vaccination at somatic cell level. Human rights laws are already based in international law. All people have a common interest in the germ-line, and unless we want the appearance of racial hygiene laws to protect the citizens of one country that outlaws germ-line therapy from the reproductive cells of people from the free-market genetic engineering state, transnational guidelines are desirable.
Thirdly, there are already some transnational agreements to protect common interest (and innocent parties) from future technological advances - including the law of the sea, the law against ocean dumping, the conventions against biological and chemical weapons, the laws against militarisation of space and the international atomic energy authority, the declarations of human rights (including guidance on reproductive freedom and discrimination) and conventions aimed at combating ozone depletion, and biodiversity. Are these all failures? While some people ignore both international and national law, in general these international agreements protect common interests. If we protect the commons of the sea, why should we not protect the commons of the human genome?
Within a single community one finds divisions on issues of bioethics, such as preimplantation diagnosis and gene therapy and risk perceptions - so it is obvious not all people reach the same decisions. However, data shows they do use the same ideals, which is universalism (Macer, 1994), sometimes balancing them differently to arrive at different decisions. Universal bioethics does not mean identical decisions, but it does mean that the range of decisions in any one society are similar to those found across the whole world. It is also not the same as absolute ethics, saying that there is one correct ethical decision for a given set of circumstances, rather it would say because of human rights people in any society should be given some choice over decisions of life. The study of decision-making should be scientifically made, and is a question that we can answer from data and observations. Bioethics is not just an academic endeavour or an applied part of philosophical ethics, it is rooted in the daily life and attitudes of all people, hence the title of my recent book, Bioethics for the People by the People (Macer, 1994).
At present many countries have their own standards, some of which are based on false assumptions of cultural uniqueness (Macer, 1992a). While it is important to adopt standards that are suitable to each society, such standards should be based on the views of individuals in the society. If people are the same then the same standards of bioethics may be applied - universal bioethics, while respecting the freedom of informed choice and responsibilities to society.
Mail response opinion surveys about bioethical reasoning of public, high school teachers, and medical students in Australia, Hong Kong, India, Israel, Japan, New Zealand, the Philippines, Russia, Singapore, and Thailand, were conducted with numerous collaborators in 1993. Full details of the results, including collaborators, interpretations, and open responses are elsewhere (Macer, 1994). The questionnaires included about 150 questions in total, with 35 open ended questions topics from images of life through agricultural, environmental and medical biotechnology issues. The open questions were designed to look at how people make decisions - and the ideas in each comment were assigned to different categories which were compared among all the samples. Comparisons to surveys from the USA were made for gene therapy questions. Open response questions are preferable to fixed response surveys which "lead" the respondent to a particular answer, and the results can differ significantly (Macer, 1992b, 1992c, 1994). The data from the International Bioethics Survey is, like all observations, a challenge to all of us to incorporate or explain into any description of the real world.
There was strong support for gene therapy, with about 70-80% in all samples willing to undergo it themselves, with 10-20% unwilling, and about 75-85% willing for their children to undergo gene therapy to cure a usually fatal disease and 5-15% unwilling. Similar results were seen in all countries, except Thai people were less willing (59%) for themselves, and Russians were the most undecided with one third saying they don't know. In all samples about a third to a half of the respondents wrote a comment saying that they wanted to save their life or their child's life as a reason for gene therapy, the most common reason. Very few said they wanted to improve their genes, but 10-15% said they wanted to improve their quality of life, and 10-20% said that they wanted to improve the quality of their child's life. Less than 1% were afraid of eugenics, confirming the results of a different open question in 1991(Macer, 1992b, 1992c), and 5-10% said they thought it was unnatural or playing God, for themselves, but only 2-5% did so for children. 5-10% were afraid of bad health for themselves, and 3-8% for their children. The comments were generally similar in each samples.
People do have significant discretion over therapeutic and cosmetic applications of gene therapy. About 85-90% support use of somatic cell or germ-line gene therapy to cure fatal disease, with high support also as an AIDS vaccine. There is over 80% support for reducing the risk of a late onset disease, or for preventing children from inheriting a non-fatal disease. There is rejection of enhancement genetic engineering, but only weak rejection in India and Thailand. The need for discussion of the consequences of germ-line gene therapy and especially for genetic enhancement, is international and many developing countries do not possess resources to have national education programs. The success of cosmetic surgery suggests that once it is possible, the 20-30% who accept genetic engineering to improve intelligence, physique, or personality, may do so in practice; as will the majority of people in developing countries. Whether this is acceptable is a much bigger question and may require stricter control than today's cosmetics as heritable changes affect future generations.
The purpose of regulation is to avoid doing harm. At the same time, love also demands us to do good, so medical treatment should not be banned unless it exploits some people, for example, there is some ground to restrict commercial sale of organs if this exploits the poor. However, genetic therapy curing disease is a good, and those who want to ban it should prove otherwise. In the easy cases of severe disease, safe and inexpensive germ-line gene therapy can make sense, the same genetic sense that tells us not for sisters and brothers to marry each other.
Eugenic ideas were debated long before genetic engineering, in both philosophy (e.g. Plato) and religion (e.g. Jewish marriage laws). We should encourage discussion of these complex issues, extending our discussions from the debates of old (Macer, 1990). As shown in the data from the International Bioethics Survey, the people of the world agree with gene therapy (Macer, 1994). Above all, we need to educate people how to exercise informed choices in medical therapy, restricting choice only if this will harm others or society in general. Regulations should postpone the general use of germ-line genetic therapy or enhancement until people can make such difficult decisions more wisely, but the decision is above artificial boundaries of culture or nation.
Bonnicksen, A.L. (1994) "National and international approaches to human germ-line gene therapy." Politics and the Life Sciences 13(1): 1-11.
Fujiki, N. & Macer, D.R.J. (1992), eds., Human Genome Research and Society. Christchurch, N.Z.: Eubios Ethics Institute.
Fujiki, N. & Macer, D.R.J. (1994), eds., Intractable Neurological Disorders, Human Genome Research and Society. Christchurch: Eubios Ethics Institute.
Macer, D.R.J. (1990) Shaping Genes: Ethics, Law and Science of Using Genetic Technology in Medicine and Agriculture. Christchurch: Eubios Ethics Institute.
Macer, D. (1991) "Whose Genome Project?" Bioethics 5: 183-211.
Macer, D. (1992a) "The 'far east' of biological ethics." Nature 359: 770.
Macer, D.R.J. (1992b). Attitudes to Genetic Engineering: Japanese and International Comparisons. Christchurch: Eubios Ethics Institute.
Macer, D. (1992c). "Public acceptance of human gene therapy and perceptions of human genetic manipulation." Human Gene Therapy 3(5): 511-8.
Macer, D. (1994). Bioethics for the People by the People. Christchurch: Eubios Ethics Institute.
Darryl Macer is Foreign Professor in the Institute of Biological Sciences, University of Tsukuba, Ibaraki 305, Japan. He has a Ph.D. in molecular biology, and teaches and researches bioethics. He is director of the Eubios Ethics Institute, based in New Zealand and Japan, which includes an international network on bioethics and genetics. He is a member of the UNESCO Committee on Bioethics.
Please send comments to Email < Macer@sakura.cc.tsukuba.ac.jp >.