SUMMARY REPORT

BIOETHICS AND BIOTECHNOLOGY: WHAT IS AT STAKE FOR HUMANITY NOW?

Elizabeth Rose Hall United Nations University, Tokyo 2 June 2003

Organizers: Embassy of France in Japan Embassy of Germany in Japan/Japanese-German Centre Berlin (JDZB) United Nations University Institute of Advanced Studies (UNU/IAS), Tokyo

INTRODUCTION The Roundtable was conducted under four different themes to explore the different cross-disciplinary aspects of biotechnology, i.e. scientific, social, ethical and legal. The day-long seminar was broadly divided into four sessions to delineate these issues: Where biotechnology revolution is leading us? Future applications in human health. The cultural limitations to biotechnology revolution what is desirable? Regulating biotechnology applications for humans what is feasible? Ethics - where are boundaries and tradeoffs with biotechnology? There was a sizable turnout of about 120-130 participants which included officials from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT), ambassadors and other officials, scholars from universities, heads of research institutes, faculty of the research institutes, the Press and research students.

The speakers and the topics were 1. Genomics: Potentials and Challenges Professor Ken-ichi Arai, Dean, Institute of Medical Sciences, University of Tokyo 2. Cloning: Where Are We Heading? Professor Detlev Ganten, Max Delbrck Center Berlin, Member of the National Ethics Council, Germany 3. The Japanese Cultural Perspective on Biotechnology and its Advancements Professor Rihito Kimura, Director, International / Asian Bioethics Program, Waseda University 4. Morality, Decision-making and Biotechnology in Europe Professor Didier Sicard, President of the National Ethics Committee, France 5. The Precautionary Principle: Is it a Bridle to Technological Progress? Professor Jean-Pierre Contzen, Chair of the Board, UNU/IAS, Tokyo 6. Who Owns the Human Genome? Professor Jochen Taupitz, University of Mannheim, Member of National Ethics Council, Germany 7. Ethical Choices and Legal Strategies: The Case of Human Embryos and Stem Cells Professor Catherine Labrusse-Riou, University of Paris 8. Ethics Beyond National Boundaries: How to Go Forward? Professor Ryuichi Ida, University of Kyoto, President of UNESCO Bioethics Committees 9. Prospects for a Universal Consensus on Bioethics? Dr. Nicole Questiaux, Member of UNESCO Bioethics Committee, President of the European Conference of the National Bioethics Committees The final session was followed by a panel discussion which was thrown open to the audience also. The session was chaired by Prof.Menon, member of UNU/IAS Board and Former Minister of Science and Technology, India.

OBJECTIVES OF ROUNDTABLE In order to foster an international dialogue on bioethics issues between France, Germany, Japan and the body of nations represented by the United Nations, the French and German embassies based in Tokyo in conjunction with UNU/IAS and the JDZB (Japanisch-Deutsches Zentrum Berlin) decided to conduct a roundtable conference on bioethics and biotechnology. This Roundtable aimed to facilitate an

in-depth debate to forge an international consensus by bringing together experts from France, Germany, Japan and the UNU/IAS. Human cloning research, stem cell research and ownership of the human genome are some of the crucial issues raised by the development of biotechnology. Who owns the human genome? What are the implications of altering the genes of unborn children? Is it acceptable to use human stem cells to restore organs? Does bioethics impede biotechnology? These questions raised by the biotechnology revolution have scientific, legal, ethical and cultural implications that the experts of the Roundtable tried to grapple with. Given the rapid progress in life science, it is essential that the international community keeps pace with these developments. Last year, Germany and France launched a joint initiative at the United Nations for an international convention banning the reproductive cloning of human beings. The General Assembly of the United Nations failed to arrive at a consensus but it will be taken up again in the session this September. The debates in the assembly clearly showed that the issue of banning reproductive cloning despite having nearly universal acceptance throws up other serious ethical issues. The issue of therapeutic cloning comes hand in hand with reproductive cloning. OUTCOMES Very interesting issues emerged from the presentations under the four different themes. Since developments in biotechnology are so rapid and new knowledge is added very fast, some of the speakers provided a learning experience for the audience, for some it was an eye-opener. The talk on cloning revealed some new ethical issues that warrants discussions. The legal issues were clearly elucidated and it was worthwhile to have an unpacking of the complexities in the matter of the ownership of the genome. The cross cultural and borderless nature of bioethics issues were highlighted time and again and the United Nations as a forum for discussion on such an important issue found echoes in more than one speaker. The move in the General Assembly towards developing a legally binding instrument to ban reproductive cloning was seen as a first step. 1. The Promises of Medical Biotechnology A. Personalised Medicine Professor Arai, a recognized geneticist presented the major paradigm shift in medicine. This shift is from the age-old deductive approach used i.e. to describe the patient patho-physiology to the ability to predict what may happen based on the patient genotype. The technology is now available to detect SNPs (single nucleotide polymorphisms) and thereby facilitate research on the cause of the multifactorial diseases. Genome clinical epidemiology will help in developing personalised medicines where the drug will be tailored to the patients need. Systems biology approach integrating biotechnology, information technology, nanotechnology and

environmental technology is key to the development of personalised medicine. Translational medicine is necessary to translate technology into medicinal applications and safe experimental techniques need to be developed to realise the dream of personalised medicine. There are many bottlenecks before personalised medicine becomes a reality: i). legal questions of ownership of the material used in immune cell therapy, for example; the patient may claim that it is originally his material. But the company might say that they have processed it; ii) the cost factor of personalised medicine and who will bear it? Tax payers, the patient?; iii) the balance between public health goals and individualized medicine Finally, the promise of genomics in relation to the 10/90 health gap is a major issue. 87% of the 3 trillion dollars spent globally in the health sector are on 16% of the population. 10% percent of the global disease burden takes 90% of global research. Out of the 30 billion dollar investment on health research, only 5% deals with problems of the LDCs (least developed countries). Out of the 1223 new drugs between 1975 and 1997, only 11 are primarily those for developing countries. This is the degree of inequity. What promise does genomics hold to bridge the gap? asked Dr.Menon. B. Cloning and Its Future Reproductive cloning is unacceptable to the community of nations and there are rumours that it has been attempted by some weird people. Professor Ganten immediately set the stage by stating that cloning to produce human beings was probably not possible and therefore ethically not relevant. The big issue remains cloning for biomedical research. It will have a great impact in addressing the problem of transplant rejection during cell therapy. Stem cell research is at a very early stage and it is too soon to tell which approaches (adult vs. embryonic) will prove most useful and for which diseases. Some of positive signs in the use of stem cells have been for the treatment of Parkinsons disease with dopamine neurons derived from embryonic stem cells. Treatment of heart infraction, bone and cartilage disease, cancer and other immune system diseases and diabetes are some that might benefit from stem cell research and cloning. A startling hypothetical statement made was that somatic cells i.e. ordinary body cells like skin, bone, muscle etc, could be dedifferentiated and made totipotent! (See diagram below)the implication of which is that all our 3 billion cells in the body are potentially embryonic stem cells. The experiment has not been done, but from the fact that one can use the adult nucleus under specific conditions (at the present time it is the female oocyte) and reprogram it to a totipotent cell, there is no reason to believe that the adult stem cells, which are even earlier in the programming process, cannot be converted back to a totipotent cell. Ganten has proposed an international Stem Cell Project, where the very controversial stem cell research could be reinforced by coordinating the research and involving commercial as well as ethical issues. A forum can be established for the purpose. However Ganten is of the opinion that genomics and stem cell research as a practical applied science is largely overestimated, just healthy nutrition will help in many of the instances.

Differentiated Somatic cells Adult Stem Cells Bone Marrow Multipotent Stem cells Pluripotent Embryonic Stem cells (ES) Totipotent cells Zygote Early Embryo 2. The Importance Of Socio Cultural Aspects A wide range of social and cultural aspects have to be considered in the context of the biotechnology revolution. The goal of bioethics is to balance the interests of law, science, economics and public opinion. Reflection on the interconnectedness of these interests must constantly evolve and keep pace with the scientific progress. Advancements in the science itself are commendable. However, the technically possible should not be the justification for the development of applications. The distinction between technology and science should be clear and workable so that there is scientific progress and technological development that integrates well into society. Science should be unhindered since it is a furtherance of our knowledge, it is technology and application that needs to be brought under scrutiny and evaluated ethically. This evaluation should be integrated into a wider vision of the sense of humanity. The one question that must be pondered upon is: "What type of humanity do we want?" emphasized Professor Sicard. Bioethics tries to answer this question and these answers must then be translated into laws. The French laws on bioethics (1994 currently reviewed) introduce a constraining juridical interpretation in addition to the ethical one. The European bioethics is based on a strong conception of the human individual, beyond its physical and social existence. It relies on the respect of the individual dignity, the inviolability of the body and its non-commercialisation and the protection of the person's autonomy. This supposes that within the quest for scientific knowledge, we must detect the underlying material motivations (power, money, desire of infinite maintenance of the human body). The progress of biotechnology involves inherent risks. They should not be considered in the sole context of the precautionary principle. Instead, they should be fully recognized and implemented in the political decision making process. This is the only scenario for scientific progress to carry on while at the same time avoiding the development of undesirable applications for humanity.

Japanese culture has its own unique characteristics. Initially, the Japanese culture was not for too much of intervention with nature and it advocated the principle of harmony with nature. Even now, the growth of science and technology must be in harmony with nature. Lessons must be learnt from the ghastly deeds of armies around the world which committed unspeakable atrocities in the name of experimentation. 3. Legal Issues A. The Precautionary Principle The Precautionary Principlea fairly recent political and legal tool (initial formalisation in 1987)constitutes an attempt for meeting the preoccupation of society towards risk. Principle 15 of the 1992 Rio Conference first used the precautionary principle at the international level. It was first incorporated into national law by the French code rural. The European Commission in 2000 took the following approach: Preventive measures should be taken in the specific circumstances where scientific evidence is insufficient, inconclusive or uncertain and that there are indications through preliminary objective scientific evaluation that there are reasonable grounds for concern that the potentially dangerous effects on the environment, human, animal or plant health may be inconsistent with the chosen level of protection. However all these texts leave ample room for interpretation about the triggering factor for the application of the principle. It is not easy to decide on whether the application of the precautionary principle is justified or not. The answer lies in good governance. The four essential elements of good governance are: Serenity: decision-makers should avoid any bias or pressure in their treatment of the question Responsibility: the scientific community should follow verantwortungsethik or ethics of responsibility Proportionality: extensive, unconventional, cost/benefit analysis should be performed before applying the principle Reversibility: once made, decisions should be reviewed periodically in the function of the evolution of scientific knowledge Currently there is a lot of ambiguity in the application of the precautionary principle. The rationale for the introduction of the principle has been quite a laudable one: preserving our common good, containing the excesses of globalisation etc. It was not intended to be an agent against further scientific and technological progress. The alteration of this rationale has occurred mostly when national or ideological interests have been in question. It is time to restore the original value of the principle. According to Dr. Contzen this can be achieved through good and strong governance.

B. The Ownership of The Human Genome The human genome is in jeopardy between ownership and personal rights. Nature is a common asset and a common property. This principle cannot be applied all the time since nature can be compartmentalised for its utility. For example, exclusive rights are given over certain parts of nature. Genome is only a part of nature. So can exclusive rights be applied to the genome? Is the sequence of the genome a patentable asset? were the questions raised by Professor Taupitz. As opposed to this Is there any social duty for the individual to accept request for sharing his/her genome? Every culture and country confers personal rights to a human: right to live, right to be protected against damage or harm, rights over part of the body which is separated from the person It is possible to transfer the rights of a body sample to a researcher but not to sell it. The interpretation is that isolated body parts actually take the title to the rights with it. However, the information contained in it is still of some relevance to the person and public disclosure of this information cannot be done without the permission of the person. There is a distinction between ownership and personal rights, though both are rights. The major difference is that with ownership, transfer of rights is possible by way of sale. However, personal rights will always stay and can never be sold. It is an inseparable part of an individual. Within the framework of personal rights, there is a right to utility that can be transferred. In some other instances the trade-off between personal rights and the public good is considered. If the public good is greater than ensuring personal rights then the former will be given more importance. In conclusion, the genetic material can be subject to property/ownership rights at the same time there are some personal rights inherent in it. What is the public interest in the genome? Can exclusive patent rights be exercised over the human genome? This is an international problem. There are many objections to patentability of the genome. It is not an invention, but a discovery. Patenting is against human rights. Patenting will affect research carried out on the genome. These are the various arguments against patenting. If criteria of patent law are seriously and ethically studied. What is the real problem with respect to filing for a patent for human genome? If patented, then it will exclude others from using it for a particular number of years. One solution would be to stipulate within the patent itself the licensing process for the patent and social obligation goes along with patent. Genome is not the common asset according to western constitutions. Genome is under the exclusive disposal right of the individual and then the patent holder can transfer it to others. Tradeoff between individual interest and public interest is very important. This proportionality approach is a justifiable approach. Individual rights have to be upheld, but public interest aspect and dignity of the human being have to be safeguarded.

C. The Embryos and Stem Cells For embryo and stem cells, it is difficult to balance the public interest and the interest of the individual said Professor Labrusse- Riou. The status of unborn human beings is one of the major issues of bioethics. The reconciliation of ethic values and potential uses of the embryos for research is particularly difficult. On the one hand, scientists, MDs and the biotechnology industry are actively lobbying to obtain the authorization for research on embryos. On the other hand, such research runs the risk of treating the embryo as a mere object of research, the anthropological implications of which have not yet been fully evaluated. The human embryo is the centre of growing and recurring tensions. The tussle is between two freedoms: whether the destiny of a human being can be decided by another and whether unused embryos could be used for research to serve interests of living persons, since the production of embryos in vitro is authorized. As a consequence of this tussle, Europe is divided on the issue of allowing research on human embryos. National policies in different European countries differ. The human embryo is caught between ethical requirements and necessity for a practical approach. Ethical principles are weakened by the definition of the human being through rights rather than with regards to dignity. Opposite facets of human rights arise when the embryo is viewed as object of an abortion or of research purposes. This context leaves no room for conciliation, and requires a clear choice of the legislator. The evolution of the legal framework in France remains cautious, distinguishing the embryo in utero and the embryo in vitro; the rights of the mother precede the rights of the embryo. Concerning the latter, research is prohibited as a whole, but exceptions are developed. 4. The Need for An International Consensus on Bioethics National perspectives and the international dimension of bioethics were considered. The clear message that emerged was that an international consensus must be developed and it should incorporate the concerns and features of different cultures. Bioethics is a code of conduct; simply academic discussion will not be enough. Ethical rules must be pragmatic. This code of conduct must be a common code for all humanity. It is not interstate code of conduct i.e. not international, but rather it calls upon each individual to follow it. Thats why the word universal is better suited. On the other hand cultural diversity, religions, traditions and customs must be respected. The Universal declaration of human genome and human rights, 1997 drafted by the International Bioethics Committee (IBC) and adopted by the General Assembly in 1999 is a landmark document which recognised the need for a universal outlook. The word universal has a lot of meaning. The IBC is presently engaged in a universal declaration on human genetics data. The process towards universal bioethics will need to be addressed four-fold: Necessity to have universal bioethics Methodology to reach this goal Scope and scale for the universality In universality how to ensure diversity

Nuremberg code onwards there has been a necessity for such an instrument for ensuring human rights as advancements occur in different fields. It is a core concept for peace. Bioethics is not given by God. It is created by people. As far as the methodology is concerned, there is yet no decision but the UNESCO has produced universal documents that have no legal binding value but constitute universal guidelines. Professor Ida emphasized that at the level of a nation four pillars are necessary: law or guidelines, a national bioethics committee (established in 1983 in France, 1998 in Japan and 2001 in Germany), public involvement. and education on bioethics at the junior and senior high schools. 5. Universal Bioethics and Developing Countries Dr. Menon highlighted the need for a universal bioethics which also took into consideration the health needs of the peoples of the developing countries. From the viewpoint of developing countries as one sees the miracles of biotechnology, the question one would ask is: is it a mirage- is it for real? Is it going to have an impact? Dr. Questiaux suggested four elements to promote the universality of bioethics. Promoting procedures that can be universalised. The questions raised by progress of science are difficult and are not limited to the Christian world Looking for universal principles and steps to reach them. Despite the different cultures, the different religions, and the place of these religions within the socio-cultural background, this symposium was able to bring to light the recurring principles of the freedom of research, the freedom of thought and the free access to knowledge. Translating the empirical and pragmatic reflection into law. A national framework is essential to actually transform the consensus in discussion into reality. France has succeeded in establishing Bioethics laws in 1994 but has shown the limitations of this process with regard to international recommendations: i.e. the difficulty of adopting European Guidelines on the genome in the French national law system. Fostering a dialogue with a focus on the economic component. Two recommendations were made: i) to include ethical considerations within the intellectual property rights, ii) to avoid too stringent guidelines that will hinder research.

Panellists Comments We have a huge responsibility to successfully realise a universal consensus on bioethics (Questiaux) There is not going to be a bioethics for developed countries and a bioethics for developing countries (Menon) Genetic Determinism cannot exist (Ganten) Science itself is not the culprit (Ida) Harmony with nature is the essence of Japanese culture (Kimura) Public opinion is replacing public elected opinion (Sicard) Research not for the sake of research (Sicard) Should everything that can be done also be done? (van Ginkel) What is the value of keeping alive in relation to creating new life? (van Ginkel) We are responsible for what we do not do. That is the deeper sense of the freedom of research (Taupitz) Bioethics must be considered in the context of broader ethical thinking (Menon) Ultimately one has to educate the society at large (Menon)

Compiled by K. Chamundeeswari, UNU/IAS Stphane Roy, Rafik Leneguer, Grgoire Fages, Embassy of France in Japan
Enquiries to unu@ias.unu.edu