The Galton Institute was represented at the conference on the ethical, legal and social issues of human genome research, in Fukui, Japan 20-21 March 1992, held under the auspices of the Japanese Ministry of Education, Fukui Medical School, UNESCO, WHO and the IAHB. Smoothly organised at the prestigious Phoenix Plaza Conference Centre by Professor Norio Fujiki it provided a most unusual opportunity to discuss in person issues of common interest with colleagues from a variety of cultures aided by the efficient simultaneous translations. Professor Fujiki is to be congratulated on the success of the meeting.
There were six working sessions in addition to the formalities of opening and closure and a public lecture. The first session was opened by Santiago Grisolia, the chairman of the coordinating committee for the human genome project of UNESCO, a body which has organised and supported a number of meetings and workshops, and provided fellowships for scientists in third world countries. He sees the role of UNESCO as not to develop a scientific programme but to protect the interests of the third world in this topic, since the human genome is the inheritance of humanity as a whole. UNESCO, like HUGO (the human genome organisation) and the French National Committee of Ethics, strongly oppose the proposal by investigators of the NIH in the USA and of the MRC in Great Britain to obtain patents for partial cDNA sequences, the so-called expressed sequence tags. Their opposition rests on ethical as well as scientific considerations. He poses the question ``To whom do scientific discoveries belong?''. In earlier times when scientists received subsidies from private patrons or foundations, their proprietary interest could be defended, but the massive support which science receives from society today overrides the specific issues of intellectual property. The free flow of information derived from the human genome project is crucial, and should come into the public domain by the normal routes of publication and entry into data banks. He regards the identification and description of all human genes as a worthwhile pursuit, particularly when the findings can be translated into services for human benefit, which he sees as accruing to all countries, including those technologically less developed, who for example may benefit from applying molecular genetic techniques in new, simple, rapid and inexpensive tests for identifying pathogenic organisms. Professor Kenichi Matsubara's review of studies carried out in the human genome project in different countries attempted to clarify the similarities and dissimilarities due to their differences in history, tradition, and structure.
The second topic was the present status of human genome research in Japan, where the ``top down'' approach, starting from macro-scale mapping and working down to gene identification, is being applied to chromosomes 3, 6, 8, 11, 21 and 22. Dr Yoshiyuki Sakaki, taking chromosome 21 as an example, demonstrated the utility of rare-cutter linking clones (restriction endonucleases whose cleavage sites are rare in the genome) as principal landmarks for genome analysis. The entire region of chromosome 21 covering the location of the b-amyloid precursor protein gene related to familial Alzheimer's disease has been mapped and a novel gene responsible for leukaemia identified. Dr Tasuku Honjo and colleagues are characterising the human immunoglobin heavy chain (IgH) locus, which is mapped to the distal region of chromosome 14, and are well on the way to constructing a physical map of the entire human IgH locus by isolation of cosmids.
The third topic was the historical background of bioethics in human genome research. Mr Michael Yesley reviewed from the legal viewpoint the situation in the United States, particularly with reference to government controls through legislation, administration, and the judiciary, and discussed the attitudes of state legislatures and courts to problems such as the right to fertilised ova, abortion, surrogate parenthood, newborn screening, informed consent, the right to die. He painted a somewhat frightening picture of the activities and effects of minority pressure groups. Dr Kiyoshi Aokei examined the historical background of bioethics in medical genetics in Japan, starting from the first conference in 1984. He saw the true bioethical problem to be not the conflict between scientific-technical value and spiritual values in modern society but as emanating from the disintegration of values within each of these two systems. The cause of this disintegration is the post-Renaissance philosophical spirit of analysis, which is essential to the promotion of science but is incompatible with some religious attitudes, such as those of Zen Buddhism.
In the next topic, clinical applications, Professor Norio Niikawa discussed genomic imprinting, the mechanism by which each allele in a child differs in expression depending on the parent from which it derives. Evidence was presented for imprinting by the observation of abnormal phenotypes in persons with uniparental disomy, which are seen as due to the lack of an active allele from the second parent. Genetic diseases which may be due to imprinting include the Beckwith-Wiedemann syndrome, Wilm's tumour, Prader-Willi syndrome, Angelman syndrome, Huntington's chorea, myotonic dystrophy, neurofibromatosis type I, and the fragile X syndrome.
Dr Isamu Nishisho presented his results on germ line mutations of the gene for familial adenomatous polyposis coli, important for understanding their contribution to colorectal neoplasia and for designing effective methods for genetic counselling and presymptomatic diagnosis: in kindred in which the mutation is identified, presymptomatic diagnosis can be made with virtually 100% accuracy. Dr Kaoru Suzumori illustrated preimplantation diagnosis of genetic disease by analysis of DNA of a blastomere removed from the pre-embryo, and described cases in which it had been successfully applied. Dr Hiraku Takebe, noting that genetic counselling has not been generally practised in most university hospitals in Japan, recommended more attention to genetics and genetic counselling in medical training. Dr Yasuo Nakagome had isolated ten new probes from a Y chromosome-specific phage library, using DNA samples from 69 patients with structurally abnormal Y chromosomes. Using these 10 probes as well as 6 previously reported, the nonfluorescent region of the Y chromosome could be divided into 23 segments. One of these segments was deleted in 7 patients with azoospermia, and another segment seemed to contain genes related to gonadoblastoma and short stature.
The next topic, social issues in medical genetics, opened with a discussion by Professor Kenji Mahino of the social effects of genetic testing and genetic counselling; he called for governmental guidelines to limit the applications of new technologies, and stressed the need to keep the public informed. Dr Assao Fujiyama gave a concise review of the human genome programme, and showed how little had as yet been completed, with only 2,000 genes out of an estimated number of 50-100,000 already mapped, and with 6.4x106 base pair sequences out of an estimated total of 30x109. Professor Daniel Wikler pointed out that the most immediate ethical and social problems in medical genetics are not posed by the doctors' clinical work, but lie in the use by others of information which may have been obtained for therapeutic purposes. He sees the new advances raising not only the possibility of social and economic discrimination now; there is also the question of responsibility for future generations, a question which the old eugenic movement endeavoured to meet and which is still with us. Professor Wikler asked whether it is our duty only to ensure the well being of people who happen to be born, or whether we should attempt to decide what kinds of people should be born. For the Galton Institute Professor Roberts saw few new social issues arising from the application of genome research that had not been encountered by the clinical geneticist in the management of families over the last few decades, and recommended adherence to the accepted ethics of medicine, as is the case with clinical genetics which is practised in the context of family and preventative medicine. Professor Paul Billings thought that in the United States the human genome project and interest in genetic information is increasing the prevalence of genetic discrimination. Though Americans have an enviable system of laws and government which may protect entitlements and rights, there is no evidence that such protection will be adequate to avoid genetic discrimination in the future. He urged that a goal of applying human genome information internationally should be to maximise the benefits while avoiding further social stratification in all countries, and to achieve this may require a slowing of the project and limits on scientific exchanges.
In the next session on opinion surveys Dr Darryll Macer presented his results from a survey on Japanese attitudes to genetic technology, in what was perhaps the most interesting formal presentation. Among the public there was a broad consensus that genetic manipulation of plants and micro-organisms is acceptable and so is the use of genetically manipulated bacteria to be released in order to clean oil spills. There is substantially more concern about the genetic manipulation of animals and most concern about manipulation of human cells, higher in Japan than in New Zealand. There is strong support for the availability of general genetic screening tests for serious diseases in national health services; the majority of respondents would personally use prenatal genetic screening tests for fatal diseases of adulthood (72%). There was little approval of the patenting of genetic material extracted from humans (only 29%).
Makiko Osawa presented results of an opinion survey among practitioners on the aims of genetic counselling. Dr H Kawashima recounted her experience of the responses of clients attending a genetic clinic, and found great differences between Japan and the United States. Professor Yung Sun Yang was concerned to find that in Korea the most acute bioethical problem is decline in appreciation of the dignity of life, particularly in the new generation, which he attributed to widespread use of abortion for population control and to inadequate education. Professor Nianhu Sun spoke of her experience in her prenatal diagnosis service in Beijing. Out of 420 malformed fetuses, 98% of the couples asked for abortion. Ethical confusion arose when the malformation was diagnosed at birth. The parents took great care of the mildly malformed child, but for the severe cases only a few parents asked for surgical intervention. The majority did not. They could not afford the expense of surgery, and chose to save their energy and money, and hope for a more favourable outcome in the next pregnancy. Professor Matsunaga advocated a code of practice to cover the situations of carrier detection and prenatal diagnosis for genetic diseases for which at present there is no treatment, the confidentiality of information regarding carriers of genes for hereditary disease, and the prevention of discrimination and abuse of genetic information. Subsequent speakers discussed these issues from the point of view of an educationist, a mother, and an obstetrician. Finally Professor Natuhiko Yasida reminded the meeting that logically speaking the human genome project is independent of ethics, it is the use and possible misuse of its findings that pose the problems.
The meeting thus provided an interesting combination of scientific and philosophical presentations and discussions. One was left after it with a broad appreciation of the considerable differences that exist between individuals of different cultures, and the unlikelihood of attaining a universal concordat on what is or is not acceptable in applications of the new technology.