-Darryl Macer, Ph.D.
Director, Eubios Ethics Institute
Visiting Professor, United Nations University
Eubios Journal of Asian and International Bioethics 13 (2003), 125-127.
As some readers are already aware, I am involved in the community engagement and ELSI team for the Haplotype Mapping (HapMap) Project in Japan (1). As others are also aware, in 1995 I co-chaired the UNESCO International Bioethics Committee subcommittee on population genetics and ethics (2), which especially considered the proposed Human Genome Diversity Project (HGDP). The HGDP was nick-named the "Vampire project" when it planned to collect blood samples form members of about 500 indigenous groups across the world (3, 4). There was so much controversy that the HGDP did not progress as a coordinated global project, although population genetics studies have continued, some with less ethical oversight than what was proposed for HGDP. As a response to those debates, elaborate theoretical frameworks were proposed to seek community engagement in the HapMap project. There are some questions for the international ethics community to consider about these frameworks.
The HapMap project was officially launched on 29 October, 2002 at NIH, as a joint project involving financial contributions from USA, Japan, UK, China, and Canada (5). The goal is to develop a human Haplotype Map, based firstly on analysis of about 270 DNA samples from 4 populations (90 Yoruban from Nigeria, 45 Japanese/45 Han Chinese and 90 CEPH in U.S. residents of Northern and Western European ancestry). The genetic data will be on-line in a free public database for study of human genetic variation. There will be a repository of cell lines accessible for researchers around the world, held at Corriell Repository (6), in the USA. Please refer to official publications for the purposes and procedures.
Simply speaking, bioethics is the love of life (7). As anyone who has lost their son, sister, and mother from genetic disease would say, we need to understand genetics more to cure disease. People suffer everyday from disease. The benefits to the future from this project are sure to come, and it is important that different population groups are included so that the full diversity of SNPs and haplotypes can be assessed and utilized to improve medicine.
Let me share some of my thoughts about this project as part of the community engagement, and as editor I welcome further papers on this topic in the journal. In fact in this issue are also papers from a survey of the situation of ethics committees in Japan, and genetic research, by Shirai (12), and Tsuchiya (11), which are relevant background for those looking at the situation in Japan. A full report on the community engagement process in Japan will be published later, and one preliminary report has just been published (1), but with the liberty of an individual in an editorial let me share some reflections on the ethics of HapMap. There has been little published on the ethical issues of the HapMap Project, so I want to raise some issues here. This article is not intended to be offensive to anyone involved, but in the spirit of academic openness I think some issues need to be discussed.
By targeting four major population groups the HapMap project hoped to avoid the criticism against the HGDP that it focused on minority groups. In April 2002 when I accepted to start working on the ELSI team for Hap Map in Japan (with Prof. Ichiro Matsuda, President of Japan Society of Human Genetics, and when I asked Mrs. Eiko Suda, to work with me here in Tsukuba on the project), there was high hopes internationally that the community engagement and ELSI approaches for HapMap would be the best ever used in international genetics research.
Protocols were developed with good cooperation inside the ELSI group in Japan, and with the chair of the first International HapMap ELSI group, Dr. Ellen Wright Clayton, and the NIH ELSI co-director, Dr. Jean McEwen. The ELSI team in Japan, in particular Suda and Macer gave public lectures about the project and plans, receiving suggestions, at conferences in Taiwan, Canada, South Korea, and Brazil, and at 6 public meetings/lectures in Japan. As individuals all the ELSI team members also talked to numerous persons about the project. The term public consultation was adopted over community engagement, as being more suitable in Japan.
The target is to obtain 130 donors from which 100 cell-lines will be randomly selected to send to Corriell Repository, and from which 45 will actually be used. Sample donors will have their privacy protected by standards that are internationally accepted. In fact in some meetings that are being held, not even the name will be recorded in the coding sheet (which in any case will be disposed of after it is kept in private by one person). The name or organization in the case of group donations will not be recorded. This is what will be written:
Blood tube: random code number, with gender (M/F), e.g. 13729M
Coding sheet (kept by the responsible person in handwriting, to be destroyed within 2 months): 13729M - Taken on xx July. [group donations]
In the case of individual donations [recruited through focus groups] it will be:
12023F - Name, taken on xx July.
The informed consent forms will be kept by Tokyo University IRB chair, Ichiro Matsuda. All that is required is someone to be 20 years or more in age, and to have attended explanation meeting(s) where they had a chance to think about their donation. Privacy concerns are the strongest concern emerging in discussions with people, which is not surprising given the low level of trust that people have in Japan about persons to speak about biotechnology (8).
There are several phases in the HapMap project in Japan, and while the Japan ELSI HapMap Group thinks that the community engagement/public consultation phase has been completed successfully, the sample collection phase is suffering from a shortage of recruits to public meetings. Also the persons who have attended the meetings to date have mainly been persons who do not wish to donate but rather are interested in the project academically, including critically. Even though survey data suggests that a considerable number of ordinary persons in Japan are willing to donate their DNA to this type of project (9), a mixture of apathy, distrust and other factors means that we changed to target more persons who have greater understanding of the scientific benefits of the project.
While there are several persons who have said that they will donate from the process of multiple focus group meetings to date, it is clear that given the short time scale recruits from the public community would require a much greater investment in money and persons. Public recruitment through newspaper adverts led to almost no response. Therefore the plan was broadened to hold "Information Seminars" in places with groups of people that have interest in medicine and science including a presentation and discussion on the scientific aspects, as well as explaining the ELSI issues and calling for comments. In fact in those meetings by protecting the donor privacy more by making it completely anonymous, and having individual donation rooms, it would be a place I would prefer to donate at.
This process seems to be the best way to gather samples for this project in Japan, given that it cannot specifically target sick persons by the nature of the science. At the end of a circle of attempting to get the public donating samples it came back to asking those who know about science and the benefits of this project to donate, because only with much greater resources could the general public be broad into the process as donors in Japan. This may be a lesson for other countries in a similar culture, where there is a lack of a tradition of donation.
Japan, ELSI and budget
Perhaps surprising to some is that the government funding system in Japan had not included community engagement or even ELSI in the HapMap project. After several months of discussion it was agreed that the budget for our activities would be paid through the grant to Prof. Yoshimitsu Fukushima, at Shinshu University, who is making the cell lines, to be independent of the principal investigator. While the situation in Japan for ELSI of human genome studies was bleak in 1992 (10), it has not improved. Another even larger project, called Japan Biobank to collect blood samples from 300,000 persons, does not have an ELSI budget. It is 2003! After some public criticism the project might deal with ELSI, but it is unclear.
While the Japanese government does support some research in bioethics it is usually totally independent of scientific projects, and many such studies are not related to the scientific studies. There is a need for the bioethics community to work more closely with scientists. There is a gap that has yet to be bridged between bioethicists and medical genetics. Some bioethicists did not want to be associated with the HapMap project, perhaps because they like to stay outside of projects and just criticize what scientists do.
In HapMap publicity it was said that if the community engagement found that people from one area do not want to donate their blood the project would not take their sample. The ideal community engagement process is where a community could reject donation. Since the Japanese government already gave over millions of dollars to the project, it was never an issue for Japan. In that sense the hubris about community engagement leading to possible rejection was false, at least in the Japanese case. I suspect it is also really false in other countries also, despite the good sentiments of many. What government will devote millions to a project not to have any samples! It should be a reality check for ethicists.
The question about whether this was enough consultation or not was determined not by the opinion of the ELSI group or some objective measure of community knowledge (in fact there is none!), but by something more practical - the budget constraints of the project in Japan. The financial constraints mean that the samples must be collected by the end of August, 2003. By publishing this editorial I hope that anyone else who has not already made comments might do so, so the process is in the open (On the Eubios website there is a homepage in Japanese for donation). Since the necessary IRB approvals for collection at University of Tokyo, and Shinshu University, have been granted, everyone including myself intends to collect the sample donors, and it will follow international ethical standards.
The official HapMap website in several languages coordinated through NIH is only now being established. It is coming as most of the samples are already being collected or even have been collected. There will be an ongoing Community Advisory Group (CAG) established in each country where the samples are taken, and Corriell Repository has said it will fund them for 10 years at least. The precise functions of the CAG are still being worked out. Until now (16 July 2003) google searches on HapMap still bring up old documents, or the 29 October 2002 press release.
In May 2003 a new International HapMap ELSI committee was formed, to be independent of sample collection and ELSI teams in each country. The Japanese members of this, Prof. Norio Niikawa and Dr. Kazuto Kato, have been helpful in the practical dilemmas of sample collection and ELSI, and in bridging the cultural gap between ELSI and genetics research in Japan. The co-chairs of the committee, Prof. Ellen Clayton and Prof. Bartha Knoppers, are well respected and helpful practical bioethicists. However, the debate should be open and wider. There are so many aspects to discuss from an anthropological and ethical perspective in this project, which has taxed everyone involved in many ways. The proper independence of the ELSI groups from the principal investigators has been difficult to achieve. Bringing people with different expectations to work together and accept each other is very difficult, and future projects should have much better planning at all levels in these aspects.
On the ethical risks of this project, we should not reasonably expect to see any individual discrimination from the results. For group discrimination of one of these groups, there is no need to use genes. As a foreigner in Japan, or seeing Japanese or other minorities living overseas, genes are not needed for someone to discriminate another. We must all try to make the world free of discrimination. If anyone has a fear of discrimination from this, it is when members of those identified populations are living as a minority in a country. Probably they already face discrimination that will not be worsened by this. In my personal study on the background in Japan I learnt more of the discrimination faced by Ainu people in the "colonization " of Hokkaido in the Meiji era, or of the Korean and Chinese populations in Japan. Those are another story, and not one that could be researched in the time frame that this project was operating under. It would take years, and science must proceed. Go to a hospital if in doubt about the moral imperative of beneficence. However, I sincerely hope that ELSI research on these aspects will continue, as the uses of the data will only come in the future.
I hope in a future issue we can report the success of the project. I welcome your comments on my personal opinion, and appreciate the support of Eiko Suda and Ichiro Matsuda in the past year. I appreciate the comments of Bartha Knoppers on a draft of this paper. The details and reports from this project will be extensive, but for now I wrote some individual reflections. While there is usually no shortage of bioethicists to criticize science, I hope that this project will be successful so that people can never call it a vampire project like the HGDP (3-4), and scientists in countries that have different traditions of considering ethics of research, will work with those in the ethics field to produce and use scientific knowledge in ways appropriate for their communities.
1. Suda, E. and Macer, D.R.J. "Ethics of Conducting the Hap Map Genetics Project in Japan", pp. 32-48 in Bioethics in Asia in the 21st Century, ed. Song SY, Koo YM. & Macer, DRJ. (Eubios Ethics Institute, 2003).
2. Chee, H.L., El-Hamamsi, L., Fleming, J., Fujiki, N., Keyeux, G., Knoppers, B.M. and Macer, D., "Bioethics and human population genetics research", Report of the UNESCO International Bioethics Committee Third Session, 1995, from the subcommittee on bioethics and population genetics
3. Lock, M., "Interrogating the human diversity genome project", Social Science & Medicine 39: 603-6 (1994).
4. Macer, DRJ. "Bioethics and genetic diversity from the perspective of UNESCO and non-governmental organizations" pp. 265-274 in Knoppers, BM. et al., eds, Human DNA: Law and Policy. International and Comparative Perspectives (The Hague: Kluwer Law International 1997).
7. Macer, DRJ. Bioethics is Love of Life (Eubios Ethics Institute, 1998).
8. Inaba, M. & Macer, DRJ. (2003) "Attitudes to biotechnology in Japan in 2003", Eubios Journal of Asian and International Bioethics 13 (2003), 78-89.
9. Suda, Inaba and Macer. Manuscript in preparation.
10. Macer, Darryl (1992) "The far east of biological ethics", Nature 359, 770.
11. Tsuchiya, Takashi "Provisions For Review of Genetic Research in Japan", EJAIB 13 (2003), 127-30.
12. Shirai, Yasuko, "The Status of Ethics Committees in Japan", EJAIB 13 (2003), 130-4.
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