HUMAN EMBRYOS: STATUS AND REGULATIONS FOR USE (Discussion Paper No. 33)

Transcription

1 Summary For Inquiry about the content, please contact to: Yasushi MAKIYAMA 2 nd Policy Oriented Research Group, National Institute of Science and Technology Policy TEL , FAX Homepage HUMAN EMBRYOS: STATUS AND REGULATIONS FOR USE (Discussion Paper No. 33) 1. Introduction January 2004 National Institute of Science and Technology Policy Ministry of Education, Culture, Sports, Science and Technology This paper discusses the social system for using human embryos, which is a controversial issue today as a social and bioethical problem emerging from biotechnological progress. In the supplementary provision (Schedule) of The Law concerning Regulation Relating to Human Cloning Techniques and Other Similar Techniques (Act 146, 2000), which prohibits human reproductive cloning, has been defined as an issue to be investigated within three years following the enforcement of the law. (1) Background: In assisted reproduction, human embryos (eggs in the early ontogenetic stage of development after fertilization or cell nuclear replacement) have been produced and used in in vitro fertilization for infertility treatment and related research for the past two decades. In addition, the use of human embryos has recently resulted in the development of embryonic stem (ES) cells for application in regenerative medicine. Japan currently has no law that directly regulates the use of human fertilized embryos, and the tacit understanding or sentiment in society is that it is inappropriate to use human embryos without restriction and sufficient precaution. This is likely to impede research that uses human embryos. Moreover, the clinical use of human embryos is not yet governed by a public organization to protect the human rights of patients and the welfare of children who may be born as a result of such treatment. (2) Aim: Considering the alternatives to using human embryos under the strict control of society, this report examines the social framework under which human embryos can be used, reconciling progress in medical care/research that uses human embryos and social acceptance of this area of research and medicine. (3) Methods: The current conditions of Japan and the conditions of other countries are investigated, considering the use of human embryos and regulatory action on the issue. Policy directions that should be taken are examined by reviewing information and opinions obtained through interviews with the individuals involved, research on the relevant literature, and study into theory development vis-à-vis the areas of discussion in the Expert Panel on Bioethics of the Council for Science and Technology Policy. This report is also a part of the project for research on the construction of a social governance system in Japan for progressive life science and technology. 1

2 2. Outline of the report Part 1. Present status I. Biotechnology and Society Biotechnology wields a very significant influence on individuals and society through its application in medicine and industry. Hence, progress in this area and the bioethical problems that accompany it are issues that must be simultaneously addressed. With these considerations, the Science and Technology Basic Plan (2001) and the Biotechnology Strategy Guidelines (2002) attempt to resolve these bioethical problems. With the growing complexity and sophistication of science and technology, the Council for Science and Technology Policy was established in 2001 as an organization to lead the science and technology policy of Japan from a broader perspective than the interests of each ministry. The Expert Panel on Bioethics was established under the Council and is currently investigating dealing with human fertilized embryos as rudimentary forms of human individual life. Decisions to be made on the proper use of human embryos are expected to lay the foundations for future science and technology policymaking in assisted reproductive medicine, and regenerative medical research that includes the derivation and utilization of ES cells. Therefore, this report emphasizes directions for a future framework using human embryos with social acceptance and studies on policies that address the social issues related to clinical treatment and research in this area. II. Three perspectives in investigation into human embryo use There are three perspectives biological, ethical, and legal required for study into the status of human embryos. The fertilized human embryo continues to grow within the uterus after implantation (the process of the growth of the placenta by attachment to the endometrium). Implantation begins about 5 days after fertilization, which is completed within roughly 12 days with the start of uteroplacental circulation. The growth of a human being is impossible without undergoing implantation in the uterus. Implantation can be inhibited by contraception devices, such as intrauterine devices or the postcoital pill (emergency oral contraceptive). In Japan, the abortion of fetuses that are younger than 22 weeks old (about 140 days after fertilization) is permitted. A questionnaire survey (conducted nationwide on men and women aged 18 and older; 1,394 valid responses received; 63.4% collection rate; Nomura Research Institute, 2000) revealed that 40.5% of those surveyed were in favor of research on human embryos provided that strict regulation is imposed, whereas only 3% accept the free use of human embryos; 21.2% were opposed, leaving 30.8% undecided. In personal opinions over ethics, there are two opposing opinions the belief that human dignity can be preserved through protecting human embryos from use versus support of human embryo use that argues that the protection of individual human lives and the conquest of disability and disease through human embryos use is more consistent with maintaining human dignity. Others have rejected using life as a tool or a resource, and have expressed concerns that the manipulation of human life may have unknown dangers. Ethical views on the use of human embryos vary widely. Currently, Japan has no laws that directly govern the use of human embryos other than those cited below. (i) The civil code provides that possession of personal rights begins with birth. (Article 1-3) (ii) A clause in the Accessions Tax Law prescribes that the fetus is regarded born in terms inheritance for expected babies (under suspensive condition of birth). (Clause 1 of Article 886) (iii) Application of murder defined in the criminal code: Based on precedents, charge of murder stands when a part of the fetus s body is exposed. (Grand jury sentence, December 23, 1918) (iv) Illegal abortion as provided by criminal law (Articles ) is applied after implantation has taken place. 2

3 Meanwhile, the Law Concerning Regulation Relating to Human Cloning Techniques and Other Similar Techniques (2000) was legislated, followed by the enactment of the Guidelines for the Handling of Specified Embryos (2001). With the law and the guidelines, the production of cloned embryos and transplantation to the uterus, as well as the production and use of human/animal chimeric embryos and hybrid embryos, has been prohibited. However, the law has not defined the use of fertilized human embryos. The Guidelines for the Derivation and Utilization of Human Embryonic Stem Cells (ES Cell Guidelines) provide administrative guidance for permitting and using ES cells derived from human embryos (surplus embryos); however, there has been no regulating law. III. The state of using human embryos in medicine and research: Present state of assisted reproductive medicine and regenerative medicine (1) Assisted reproductive medicine: Assisted reproductive medicine that accompanies in vitro fertilization, which originated in England in 1978 and is widely practiced today in many countries worldwide, has raised a variety of social ethical questions; and the response of each country in terms of regulation on the issue varies widely. Every year, 12,000 (approximately 1% of the annual number of births) or more than 50,000 in cumulative total are born by in vitro fertilization in Japan. While there are no applicable laws or public regulations in Japan, an official announcement by the Japan Society of Obstetrics and Gynecology serves as the only self-regulatory guideline. However, the current situation has raised a number of complex problems, such as an increase in the number of clinicians who violate guidelines and cause complications in parent-child relationships due to the practice of assisted reproductive medical treatment for couples that involves non-spouses, such as surrogate mothers. To cope with this situation, a Special Committee on Medical Technology for Reproductive Treatment Assessment Subcommittee for Advanced Medical Care of the Health Science Council, Ministry of Health, Labor and Welfare, has deliberated upon possible legislation governing the issue. A Report on Ideal Reproductive Treatment Using Donor Sperm, Eggs and Embryos was presented in April 2003 to issue recommendations on control in certain areas of assisted reproductive medicine under law. Human embryos, which are no longer used for childbearing, are utilized in research as surplus embryos with the consent of the donor couples or are discarded. In addition, human embryos are being newly produced for research in technological advancement in assisted reproductive medical treatment. Moreover, human embryos are now being used in emerging regenerative medical research into ES cells. (2) Regenerative medicine: The approach is to revitalize dysfunctional or malfunctioning biological tissues/organs by utilizing efficient cells, mainly derived or differentiated from potential cells such as stem cells. Of the stem cells capable of growth (self-reproduction) and differentiation, ES cells derived from early-stage embryos have drawn special attention for their stable proliferation and effective potential for multi-potent differentiation. (3) ES cells: Stem cells that are characterized by: (i) possibility to supply normal human cells that have a number of properties, (ii) ease of genetic recombination and (iii) promise of application in regenerative medicine with multi-potency of differentiation. Especially in the area of regenerative medicine, ES cells are expected to pave the way to the possible treatment of disorders that cause irreversible damage and degenerative disease such as spinal damage, diabetes caused by insulin secretion malfunction, and Parkinson s disease characterized by loss of nerve cells. The distinctive characteristics of human embryo use in assisted reproductive medicine and regenerative medicine which both utilize human embryos produced by in vitro fertilization and that exist outside the mother s body are compared in the following chart. 3

4 Chart: Comparison of assisted reproductive medicine and regenerative medicine Assisted reproductive medicine Regenerative medicine Purpose of human embryo use Childbirth with in vitro fertilization Derivation of ES cells from the embryo Necessity of medical treatment Overcoming diseases and disorders; Fulfilling the hope of having a child defending the right to live More than 50,000 born; based on approximately 20 years of experience Embryos are screened for transplantation. Since the chance of childbirth from transplanted embryos stands at 20%, the remainder is lost. Surplus embryos are either discarded or used for research. There are also cases of culturing fertilized embryos for research in assisted reproductive medicine. Performance as medical treatment Relationship with the loss of human embryos Whether or not effective clinical application is developed depends on future research Human embryos used are necessarily destroyed. Once ES cells are cultured, they can be used in research for a number of applications, as well as in clinical application. However, the number of embryos required for culturing ES cells is unknown. The number of ES cell strains necessary is also unknown. IV. The state of regulation in foreign countries Although the state of regulation, including the presence/absence of regulatory control by law, varies by country, the state of regulation for some leading countries in the world is reported below. State Government of Victoria, Australia: The argument concerning assisted reproductive medicine began amongst physicians in 1976, which led to the publication of a report by an advisory committee and to an enactment in 1984 of the Infertility Medical Procedure Act, which put research on human embryos under democratic control and became the first ban on human cloning. Germany: Founded on experience from the 1947 Nuremberg war crime trials in which the Nazi regime s experiments on human beings without their consent were conducted, the conservative administration passed the Embryo Protection Law in 1991, founded on the ethical principle laid down in Article 1 of the Basic Law for the Federal Republic of Germany The dignity of man is inviolable ( and to respect and protect it shall be the duty of all public authority. ) Under this law, the use of human embryos for purposes other than assisted reproductive medicine is strictly restricted and cloning is banned, as well as the production of chimeras and hybrids, imposing criminal penalty on violators. In July 2002, the use of imported ES cells that met the described restrictions was officially approved. France: In 1986, the then-prime Minister, Jacques Chirac, ordered the State Council (Conseil d Etat) to prepare drafts for a law that covered aspects of bioethics ranging from human sperm to organ transplants; this was in the face of social problems that arose from developments in in vitro fertilization. After two reports and huge debate involving public opinion, the existing three bioethics laws (for respect of the human body, control of transplantation and reproduction and registered data) were passed in 1994 to protect human embryos. To protect human dignity, the concept of respect was the restriction of personal liberty when pertaining to public order. This distinctive aspect of French law was an approach taken to declare the basic principles under law, and which, at the same 4

5 time, defined exceptions to the public health code. In addition, the pursuit of a consensus by devoting time to the construction of social rules is of the French character. United Kingdom: The United Kingdom leads the world in reproductive medicine, embryo research and cloning research, and passed the Human Fertilization and Embryology Act in 1990 to impose restrictions on the use of embryos and to authorize such use in a licensing framework. Embryonic research, including assisted reproductive medicine, is regulated under this organization. To implement the plan in the framework, the Human Fertilization and Embryology Authority was established as a review organ. Furthermore, the authorization of research into ES cell development and into human therapeutic cloning was clearly defined in Year 2001 by adding (i) increasing knowledge concerning the development of embryos; (ii) increasing knowledge about serious diseases; and (iii) enabling any such knowledge to be applied in the development of such treatment for serious diseases. In the same year, implantation of cloned embryos into uteruses (human reproductive cloning) was banned under the Human Reproductive Cloning Act. United States: In response to strong opposition against in vitro fertilization that began in the 1970s, the federal government suspended financial support into research using human embryos. However, laws and regulations regarding this issue were never enacted due to serious conflict over abortion and other issues. Assisted reproduction achieved dramatic advances in private medical clinics with research funds from medical services that they offered and were completely free from federal government assistance. In addition, a large number of human ES cells were cultured and used for research in private sections. With a decision issued by President George W. Bush in 2001, NIH has adopted a policy of approving financial assistance for the use of certified existing ES cells listed in the Stem Cell Registry. Part 2 Discussion and Proposals V. The issues in contention on human embryos The discussion in this report has been organized with reference to a draft report presented by the Expert Panel on Bioethics, prepared at the meeting held on August 27, The following chapter discusses each issue based on the analysis of information corrected and observed at points in the investigations of this report. VI. Discussion concerning contention on human embryos (1) The status of fertilized human embryos from various perspectives It is necessary to study the following ethical and legal issues concerning the application of ethical decisions to regulatory action. (i) Clarification and understanding of majority opinion on ethics (ii) Whether the invasion of human rights of persons involved caused by legal restriction is socially acceptable (iii) Consistency or alignment of such laws and regulations in the existing legal and social order Moreover, rational alignment is necessary for the legal and social status of the human embryo and that of the fetus. There is a general but vague social agreement that human embryos need to be protected to some extent. In fact, existing laws tolerate abortion, but the protection of fetuses is required as represented by penalty imposed on feticide. Considering these conditions, it is logically and socially sound to protect human embryos to a certain extent and to restrict their use. On the other hand, compared with an individual, it is evident that human embryos and fetuses rank lower in the hierarchy than a human individual as holders of human rights. In particular, extracorporeal embryos not transplanted into the uterus and [that have] not a chance of implantation, and [are not] expected to become an individual (human embryos created by in vitro fertilization not expected to be transplanted for childbearing and continuing to be in a culture dish can only grow into an aggregate of cells) should be allowed to be deleted or used for the purpose of an individual, within the rationale clearly established within society. 5

6 In Japan, medical care and research fall within the scope of the socially acceptable use of fertilized embryos. Assisted reproductive medicine has already established itself as an area in medicine that has generated more than 50,000 children. In addition, maximum respect is placed on the will of persons whose lives and quality of life are threatened by disease or disability, and who require the use of the human embryo for survival and happiness; this is as long as there is no clear violation of public interest and social order. Therefore, the use of human embryos in assisted reproductive medicine and regenerative medicine should be tolerated, and restriction by social regulation should be limited. Considering the need to unravel the mysteries of bodily functions, and to address unknown threats to the survival of future generations, research into the physiological mechanisms of the emergence of human life, reproduction etc., is very important and is valuable to humankind. Although the significance of using human embryos for other purpose than research and medical treatment has not been ruled out, there are no particular issues that require attention today. (2) Surplus embryos and time limit on the use of human embryos Surplus embryos that are set for destruction with explicit consent for own their own volition by their donors are defined as human embryos generated in the process of assisted reproduction and that are no longer used for childbearing. In certian countries where infertility treatment is practiced, the number of surplus embryos reaches tens and hundreds of thousands. Considering this availability, the use of such embryos is authorized in Japan and other countries, based on the concept of utilization rather than disposal. Human embryos are sometimes allowed to use be used only within a limit of 14 days after fertilization (or until the appearance of the primitive streak) as prescribed in the ES cell guidelines of the Japanese Ministry, or that of the Japanese Society of Obstetrics and Gynecology, British law, etc. The 14-day time limit is partly based on developmental traits, such as the differentiation of cells (organ formation) and the beginning of the formation of the central nervous system associated with the appearance of the primitive streak. Although arbitrarily and temporarily defined, this regulation is maintained as a time limit for the in vitro manipulation of embryos unless a viable counterargument emerges. This restriction prohibits in practice the trial for extra-uterine that grows the human embryo into a fetus. (3) Use of human embryos The use of human embryos is a social issue that should be decided by society because of its impact on personal moral standards, social order and the biological preservation of mankind In addition, it is important in childbearing to pay attention to the welfare of the child to be born. Therefore, appropriate social control should be implemented before any debate over the proper use of human embryos. Consequently, using human embryos by persons other than licensed personnel is not appropriate, and should not be permitted considering the need for responsible social control. Based on this understanding, rules should be established as follows. Principle 1 on human embryo use: Regulation by law Human embryos should not be handled without authorization. Principle 2 on human embryo use: Regulation by law Decision-making on the use of the human embryo should be made by the couple (parents) or the maternal donor who agrees to have the embryo implanted in her uterus (the couple, etc., make decisions on production, use, deletion, etc., of the human embryo). However, actual use should be implemented in compliance with social consensus. Principle 3 on human embryo use: Regulation by law Welfare of the child who may be born should be considered in the use of the human embryo for childbearing purposes. The use of human embryos for bearing a child is closely linked to the human rights of the child 6

7 who may be born, the safety and public welfare of future generations, and the continuity of the human species. Thus, human embryos used for this reproductive purpose are subject to special (rigorous) regulations based on attention to the welfare of the child. However, there is an important point of note, which is that a child may be born. This does not include those children who have not yet been born (in vitro fertilized embryos and not transplanted into the uterus). (4) Human cloning: Ban on human reproductive cloning (production of human cloned individual) should remain in effect. From the standpoint of this report, human reproductive cloning cannot be tolerated because there is no guarantee of safety, and, therefore there is no assurance of the welfare of the child to be born. Notwithstanding, therapeutic cloning (production of human clone embryos for medical and research use) should be approved, but under regulatory and licensing control as in IVF. (5) Other designated specified embryos An animal-human chimeric embryo (human somatic cells with animal embryo): These are used for testing the ability of cultured human ES cells to differentiate. However, transplantation into the uterus is prohibited due to the fact that the possibility of development of a human/animal chimeric individual cannot be precluded. Human split embryos and pre-implantation diagnosis: The purpose of creating and using human split embryos (separated cleavage-stage human embryos) would be (i) to secure a sufficient amount of samples for preimplantation diagnosis (genetic selection of human embryos), and (ii) storage for possible future use by the child to be born, etc. In the future, top priority should be placed on review into safety, for both human split embryos and for pre-implantation diagnosis. The production and use of human split embryos for research should be authorized under licensing and regulatory control. However, transplantation to the uterus and production of an individual from this organ should be prohibited until an adequate prognosis is available, for the sake of safety. Future of preimplantation diagnosis: There are two concepts involved in a preimplantation diagnosis: (i) the selection of embryos and (ii) the manipulation of embryos. These procedures will require social acceptance as well as study into possible applications of the human genome information in the future. A comprehensive social system for following up the children concerned, who may be born with the technique would be required for appropriate practice and the assessment of the application of the technology. VII. Policy proposal Social governance organization As a rule, it is necessary to respect the diversity that exists through a personal sense of conscience and ethical values. When imposing regulations, sufficiently justifiable rationale and social debate are required for restricting personal freedom. Furthermore, society should develop a mechanism for dealing with uncertainties (conditions in which the results are unforeseeable) with an effective risk management system equipped with eyes for surveillance and "hands" for implementing the necessary measures. Uncertainty is a major problem in creating consensus and security in society so that a reliable procedure and framework of social regulatory organization is needed. The regulatory framework must also allow latitude for individual decision-making partner, which pays attention to personal conditions and values. The development of such a social organization necessarily incurs costs (in manpower, in society and economy-wise) compared to single rigid regimented regulations such as complete prohibition by law. However, an adaptable social system would enable cuttingedge research even with uncertainty, because such a system could lead the public acceptance on 7

8 safety, and which realizes an appropriate relationship between the partner between society and practitioners of such research. The partnership should be fulfilled by participation of the public in the decision-making process, and in partner and transparent trustworthy risk management. In other words, consequently, it is possible to avert huge costs brought about by failure in risk management. As a regulatory framework to realize advances in biotechnology development and social acceptance, while utilizing the characteristics of laws and guidelines, the following requirements should be considered. (i) Legal enforceable framework (ii) Respect for freedom in research and academic disciplines (iii) Adaptability toward change (iv) Social trust Japanese society proposes the establishment of an effective and comprehensive system of governance that fulfills these requirements the Social Review Program with Comprehensive Governance Organization (hereinafter referred to as Social Review Program). The Program is outlined in the following chart. Based on establishment of a licensing and management authority by law that mediates between science and technology, a society with the participation of its citizens and with transparency and with publicity that realize the sharing of information between decision making process and society, this program also fulfills the following role. Organization for management and licensing on human embryos The licensing and management organization plays the role of intermediary between advances in biotechnology and medicine. This utilizes the human embryo and social acceptance. To this end, it is necessary to secure independence and transparency in the organization, as well as appointment of qualified personnel to win the trust of the public. Furthermore, the organization must be equipped with research functions and be capable of utilizing these functions in assessing conditions through inspection, etc. With this function, the organization is able to accumulate information, data, knowhow, theories and arguments concerning issuing accurate decisions. In addition, effective public relations must be constructed publicly, and the information service function for sharing knowledge between the decision-making body and society at large. In other words, the focus of this organization is to secure transparency, have social trust and at the same time, remove barriers between will of society and administrative action. To sum up, the functions of this organization, among others, are: Licensing, development of guidelines, research, inspection, risk management, information feedback, public relations and information service. It is important that it guarantees transparency, independence, and effectiveness and that it is founded on social trust. All the more because of this importance, personnel appointment must be based on transparent screening to get social trust. In order to achieve appropriate management and prevent the organization from deteriorating into a void or lacking in continuous incentives, establishment as NPO, independent agency or organization entrusted to the private sector should be taken into consideration so that the organization can have adaptability in establishment and restructuring (including commission to another qualified organization if the organization is not managed appropriately) for proper reformation. 8

9 Chart: Mechanism of the Social Review Program Regulation by law Licensing authority Limited General public, operating body Licensing & control organization Licensing, inspection, research & public relations Non-binding guidelines Independency, Transparency Versatility, caseby-case decisionmaking A law defines the licensing authority of the organization. In turn the organization establishes and manages guidelines with versatility and at the same time exercise legal right of licensing against violators. Overseas counterparts of Social Review Program are, for example, National Commission for Information Technology and Liberty (NIL), the personal information protection agency in France, and Human Fertilization and Embryology Authority (HFEA) of the United Kingdom. There are issues regarding the proposed Social Review Program whether necessary manpower can be satisfied for management and administration of the system; whether autonomy and responsibility of researchers or clinicians can be developed; whether there is possibility of the system being ineffective because of its not being assimilate into practical conditions in this area of research and medicine; whether freedom in research will be restricted through excess reinforcement of regulation and control in licensing; whether it is difficult to position the organization amid administrative government structure; and whether it is possible to bear the burden in human resources and cost incurred by establishment of a new organization. It is necessary that these problems are resolved under implementation of appropriate measures to achieve the goal in the future one by one. In the future, through the verification of adaptability, the Social Review Program is expected to become the basic structure in the social organization, which governs various problems in bioethics, such as (i) use of the human embryo; (ii) issues concerning organ transplants; (iii) issues pertaining to genetic information in the human genome; (iv) issues in personal information management and protection, including medical history; (v) issues in euthanasia and death with dignity; and (vi) issues in the protection of testes in clinical research. 3. Conclusion There is diversity in ethical values, moral values and emotional sentiment regarding the human embryo, and not one of them is right. With attention to the consensus that exists vaguely in a society in which a human embryo should not be treated lightly or negligently, this report concludes that the use of the human embryo should be authorized within a limited scope, such as for medical treatment and research, considering current social conditions that regard the status of fetuses and the freedom and the rights of individuals. At the same time, such research and medical treatment that uses human embryos should be implemented in a social framework of comprehensive social governance with 9

10 licensing, regulations and risk management system. With the conviction that a social system that enables the activity of a regulatory organization equipped with research functions based on law is beneficial as a future system of social governance for biotechnology, the introduction of a social review program for handling the human embryo has been proposed as such a system. 10

11 Chart: Approach in Regulation; Comparison of Views of this Report and Various Countries Country and Its Basic Law United States (Federal level) No federal law Diversity of state laws United Kingdom Human Fertilization and Embryology Act 1990 Germany Embryo Protection Act in 1991 France Bioethics Acts in 1994 Summary of form of regulation Present status in Japan Recommendations in the report (law) Supplementary notes to the recommendations in this paper Principles of Human Embryo Use No regulations Production and Use of Human Embryos No regulations for production and use Purpose of Using Human Embryos Licensing system Licensing system Licensing system (for assisted reproductive medicine and research) Protection as an individual after fertilization (after pronuclear fusion) Protection based on the general basic principle of dignity of the human body Varies by country, but regulation under law if regulation exists in the country. Restricted to self-regulation based on recommendations by Japan Society of Obstetrics and Gynecology No other regulation Human embryos should not be treated without authorization (licensing) Society demands restricted use, such as for medicine and research, and implementation under rigorous standards. For assisted reproductive medicine only Assisted reproductive medicine Observation of embryo Licensing system Varies by country, but regulation under law if regulation exists in the country. Only Society recommendations (accepted with registration) No regulation Licensing system The human embryo requires some measure of protection. Artificial manipulation of the human embryo is linked closely with human dignity and biological characteristics. Jurisdiction over Human Embryos Gene Manipulation of Embryos Time limit on Use of Fertilized Embryos for Research No regulation No regulation Banned No regulation NIH funding is limited to the utilization of existing registered ES cells. Assisted reproductive medicine Assisted reproductive medicine Restricted to use in assisted reproductive medicine or research, if regulation exists Only Society recommendations No regulation Purpose of medical treatment and research Respect for human embryos protection Assurance of safety in embryo manipulation Preservation of human dignity Assurance of social acceptance Guideline establishes basic principle of self-determination by couple, including non-spouse Banned by guideline Before appearance of primitive streak or within 14 days after fertilization. Regulation by law Banned Banned as general rule Regulation by law Banned Banned as general rule Varies respect for self-determination by the couple or regulation by law Only Society recommendations Administrative guideline for the self-determination of the couple No regulations Decisionmaking by parents (the couple) or by maternal donor Because of the human embryo's self-reliant, dependent existence and its importance by nature in reproduction, respect for self-determination by the couple regarding creation and use is an appropriate form of decisionmaking Widespread ban on genetic manipulation of embryos. Banned by administrative guideline Banned under present conditions Embryo gene alternation is possible by nuclei replacement. For this reason, further deliberations are necessary in the future. Not regulated, 14-day limit after fertilization, etc. Within 14 days of fertilization under Society recommendations and administrative guidelines Within 14 days of fertilization, for the time being Time limit after fertilization is not an absolute benchmark but an artificially created standard for tolerance of in vitro procreation Culture of ES Cells Human Cloning Respect for the Welfare of the Unborn Child Licensing system Not permitted Use of imported ES cells permitted. Not permitted. The use of ES cells is now under review. Some countries permit deriving and using ES cells but others don t; use permitted with imported ES cells The use of surplus embryos is accepted under administrative guidelines Licensing system Use of newly produced fertilized human embryos and human therapeutic cloning (human cloned embryos for research and therapy) is permitted, provided with justifiable reason and objective The draft for total ban on cloned human embryos and individuals passed in the House of Representatives. Ban on individuals. (by special act) Licensing of cloned embryos Banned Banned in law interpretation. Ban on creation of individuals. The split between permission and ban on cloned embryos. Banned (by special act) The generation of cloned embryos is banned in the guideline. Ban on creation of individuals. Licensing on cloned embryos In human reproductive cloning, the current safety issue is the vital element in prohibition. Apprehensions over human dignity, etc., rely heavily on the state of social tolerance. None in particular Explicit expression of respect in guideline Right to know one's parentage Not specified. Right to know parentage denied. Not necessarily specified. Diverse standpoints regarding human embryo protection Not regulated. Respect stated explicitly in administrative committee report Respect for the welfare of the unborn child Although the fetus and the embryo ranks inferior to the individual as holder of human rights, they are entities in a continuing process. Administrative Organization None in particular Licensing and regulating organization Medical association based on compulsory subscription develops and manages guideline No organization with comprehensive control *1. Act 2003 is expected to include establishment of such a body. Existence or review into establishment of organization for comprehensive control in some of the countries Self-regulation and administrative committee without legal binding Organization for licensing and governance Effective governing system based on guidelines and a regulatory organization executing licensing, inspection, etc., under law *1 In France, CECOS has provided sperms as organization active in limited area only.