Ethical Guidelines for Analytical Research on the Human Genome/Genes (Japan)

Eubios Ethics Institute World Wide Web site: http://eubios.info/index.html

March 29, 2001

Ethical Guidelines for Analytical Research on the Human Genome/Genes
The Ministry of Education, Culture, Sports, Science and Technology, the Ministry of Health, Labour and Welfare, and the Ministry of Economy, Trade and Industry have now established general ethical guidelines for analytical research on the human genome/genes, which are entitled "Ethical Guidelines for Analytical Research on the Human Genome/Genes". We inform you of the presentation of the text of the guidelines and the notification of the guidelines addressed in today's official gazette jointly by the Director-General of the Department of Research Promotion of the Research Promotion Bureau, Ministry of Education, Culture, Sports, Science and Technology, the Director of the Health Sciences Division of the Minister's Secretariat, Ministry of Health, Labour and Welfare, and the Director-General of the Manufacturing Industries Bureau, Ministry of Economy, Trade and Industry.

The guidelines shall be enforced on the first of April. Efforts shall be made for the proper application of the guidelines, and attention shall be paid to make the guidelines adequate with consideration to research promotion and social trends.

_ Regarding the public opinion survey

The results of the public opinion survey on the guidelines are summarized in a table and made public with the text of the guidelines at the Public Information Office and in the internet homepage of the Ministry of Health, Labour and Welfare for a certain period of time.

(See http://www.mhlw.go.jp/houdou/0103/h0329-2.html)

Inquiries are to be addressed to:

Health Sciences Division,

Minister's Secretariat,

Ministry of Health, Labour and Welfare

Tel. 03 (5253) 1111 (pilot no.)

03 (3595) 2171 (direct dial)

Nakagaki (ext. 3803) or Noguchi (ext. 3804)

Notification No. 266

of the Department of Research Promotion, Research Promotion Bureau,

Ministry of Education, Culture, Sports, Science and Technology, March 29, 2001

Notification No. 146

of the Health Sciences Division, Minister's Secretariat,

Ministry of Health, Labour and Welfare

Notification No. 3

of the Manufacturing Industries Bureau,

Ministry of Economy, Trade and Industry, March 27, 2001

To:

Heads of Testing and Research Facilities Concerned

Heads of Colleges, Etc.

Heads of Academic Societies Concerned

Prefectural Governors

Heads of Special Wards

Heads of Public Health Center Ordinance-Designated Cities

Heads of Organizations Concerned

From:

Akio Endo

Director-General

Department of Research Promotion

Research Promotion Bureau

Ministry of Education, Culture, Sports, Science and Technology

Susumu Sanagi

Director

Health Sciences Division

Minister's Secretariat

Ministry of Health, Labour and Welfare

Iwao Okamoto

Director-General

Manufacturing Industries Bureau

Ministry of Economy, Trade and Industry

Enforcement, Etc. of the Ethical Guidelines for Analytical Research on the Human Genome/Genes
It has been an urgent issue to establish precepts for the proper conduct of analytical research on the human genome/genes with respect for human dignity and rights and with social understanding and public support.

The Ministry of Education, Culture, Sports, Science and Technology, the Ministry of Health, Labour and Welfare, and the Ministry of Economy, Trade and Industry have now jointly issued a tri-ministerial notice of the "Ethical Guidelines for Analytical Research on the Human Genome/Genes" (Notice No. 1 of the Ministry of Education, Culture, Sports, Science and Technology/Ministry of Health, Labour and Welfare/Ministry of Economy, Trade and Industry, March 2001; hereinafter referred to as the Notice of the Guidelines), which shall apply to analytical researches on the human genome/genes in general.

In accordance with "15. Bylaws" of the Notice of the Guidelines, bylaws and notes have been established and set forth as presented in the attachment.

(Note 1)

For better understanding, the attachment presents the bylaws and the notes as insertions made in the corresponding parts of the Notice of the Guidelines (hereinafter referred to as the Guidelines, with the inserted bylaws and notes).

(Note 2)

See (Reference 4) of the attachment for the purpose of the Guidelines, course of its establishment, etc.

(Note 3)

With the enforcement of the Guidelines on April 1, the "Handling of Ethical Problems Involved in Analytical Research on Genes at Colleges, etc." (Notification No. 253 of the Research Aiding Division of the Academic/International Affairs Bureau, Ministry of Education, issued by the Director-General of the Bureau on Aug. 31, 2000) and the "Guidelines for Dealing with Ethical Problems, etc. Involved in Analytical Research on Genes" (Notification No. 305 of the Health Sciences Division of the Minister's Secretariat, Ministry of Health, Labour and Welfare, issued by the Director of the Division on May 30, 2000) shall be cancelled.

(Note 4)

The contents of the present notification and the attachment are also presented in the internet homepages of the three ministries concerned, whose addresses are shown below in the section 1, (1), (2) and (3).

Compliance with the Guidelines will be demanded widely and generally. The Guidelines will be enforced strictly and compliance thereof will be a requisite particularly in cases where grants-in-aid, etc. are sought from any of the three ministries for analytical research on the human genome/genes. All of those to whom this notification is addressed are eagerly requested to thoroughly inform those who are engaged in analytical research on the human genome/genes at their institutions or organizations or under their jurisdiction of the purpose of the Guidelines and direct them to comply with the Guidelines.

The following are the provisions regarding handling of inquiries concerning the enforcement of the Guidelines and reporting of the installation and operation of the Ethics Review Committee, which is required to be installed and operated in accordance with the Guidelines. All of those to whom this notification is addressed are also requested to thoroughly inform their personnel concerned of these provisions for smooth enforcement of the Guidelines.

Notice

1. The Guidelines Enforcement Offices
Inquiries concerning the enforcement of the Guidelines may be addressed to any of the offices of the three ministries listed below. If needed, replies to such inquiries will be made after joint consultation of the three ministries. Inquiries involving medical or technical expertise will be accepted by the Ministry of Health, Labour and Welfare, and replies to such inquiries will be made after consultation with experts. For public sharing of related information, important replies to inquires will be presented in the internet homepages of the three ministries concerned.

(1) Life Ethics/Safety Measures Section,

Life Science Division, Research Promotion Bureau,

Ministry of Education, Culture, Sports, Science and Technology

Address: 2-2-1 Kasumigaseki, Chiyoda-ku, Tokyo 100-8966

TEL: 03-3581-5271 (pilot no.) Ext. 5451

03-3509-1268 (direct dial)

FAX: 03-3509-1269

Homepage: http://www.mext.go.jp/a_menu/shinkou/seimei/index.htm.

(2) Health Sciences Division,

Minister's Secretariat,

Ministry of Health, Labour and Welfare

Address: 1-2-2 Kasumigaseki, Chiyoda-ku, Tokyo 100-8916

TEL: 03-5253-1111 (pilot no.) Ext. 3815

03-3595-2171 (direct dial)

FAX: 03-3503-0183

Homepage: http://www.mhlw.go.jp

(3) Biochemical Industry Division,

Manufacturing Industries Bureau,

Ministry of Economy, Trade and Industry

Address: 1-3-1 Kasumigaseki, Chiyoda-ku, Tokyo 100-8901

TEL: 03-3501-1511 (pilot no.) Ext. 3741

03-3501-8625 (direct dial)

FAX: 03-3501-0197

Homepage: http://www.meti.go.jp/policy/bio/main_01.html

2. Reporting of Installation and Operation of Ethics Review Committee
For the proper promotion of analytical research on the human genome/genes, the Ethics Review Committee plays a very important role. After the enforcement of the Guidelines, we therefore want to observe the installation and the operational status of the Ethics Review Committees of individual research institutions so as to obtain reference information for the proper enforcement of the Guidelines in the future. Research institutions at which analytical research on the human genome/genes is conducted according to the Guidelines are requested to report the installation and the operational status of their Ethics Review Committees to one of the Guidelines Enforcement Offices mentioned above in the section 1 in the prescribed [Report Form]. The heads of the institutions or organizations concerned are requested to report promptly the installation of an Ethics Review Committee when it has been installed in compliance with the Guidelines and then also report its operational status as of the end of every March immediately. It has to be understood beforehand that the information thus obtained will be subjected to deliberation to review our policy and may be made public to promote the public's freedom of access to information.

(Note) It is requested that the reporting of the installation and the operational status of the Ethics Review Committee be made in the electronic medium format presented in the internet homepages whose addresses are shown above in the section 1 (1), (2) and (3) or by facsimile transmission.

[Report Form]

*1: It is requested to report the installation promptly and the operational status as of the end of every March immediately.

*2: The information (8) to (14) may be omitted in the first report after the installation of the committee.

*3: It is requested to attach, if available, a list of the committee members, the operational rules, the organization bylaws, etc.

ETHICAL GUIDELINES FOR ANALYTICAL RESEARCH ON THE HUMAN GENOME/GENES

March 29, 2001

The Ministry of Education, Culture, Sports, Science and Technology

The Ministry of Health, Labour and Welfare

The Ministry of Economy, Trade and Industry

Table of Contents
Preamble
Chapter 1. Basic Ideas
1. Basic principles

2. Scope of application

Chapter 2. Responsibilities of Researchers, Etc.
3. Basic responsibilities of all researchers, etc.

4. Responsibilities of the head of a research institution

5. Responsibilities of the research leader

6. Responsibilities of the personal information manager

7. Responsibilities of the Ethics Review Committee and its organization

Chapter 3. Basic Attitude to Participants
8. Informed consent

9. Disclosure of genetic information

10. Genetic counseling

Chapter 4. Handling of samples
11. Use of existing samples, etc.

12. Preservation and disposal of samples, etc.

Chapter 5. Revision
13. Revision

Chapter 6. Definitions
14. Definitions

(1) Samples, etc.

(2) Clinical information

(3) Analytical research on the human genome/genes

(4) Genetic information

(5) Personal information

(6) Anonymization

(7) Personal information manager

(8) Informed consent

(9) Participant's representative

(10) Infant

(11) Research institution

(12) Institution where samples, etc. are collected

(13) Joint research institution

(14) Outside institution

(15) Ethics Review Committee

(16) Researchers, etc.

(17) Chief researcher

(18) Research conductor

(19) Participant

(20) Genetic counseling

(21) Existing samples, etc.

(22) Human cell/gene/tissue bank

Chapter 7. Bylaws
15. Bylaws

Chapter 8. Date of enforcement
16. Date of enforcement

Preamble
Promotion of scientific research is one of the important keys to realize health and well-being for all humanity. Analytical research on the human genome/genes, which was started in the late twentieth century, is expected to contribute greatly to the promotion of life, health and medical sciences and play an important role in the promotion of human health, development of welfare and new industries, etc.

Analytical research on the human genome/genes largely depends on analysis of individual persons' genomes/genes, and the genetic information obtained in the course of the research reveals the genetic predisposition of participants (individual subjects who provide samples, etc. for analytical research on the human genome/genes) and their blood relatives and abuse of such information may cause various ethical, legal or social problems. It is therefore essential that analytical research on the human genomes/genes be properly conducted with respect for human dignity and human rights and with social understanding and public support. In compliance with the ethical principles set forth by the Declaration of Helsinki by the World Medical Association and other instruments, each participant's human rights must be ensured and given priority over scientific or social benefits. This aspect should be explained sufficiently to society, and it is desired that research on the human genome/genes be conduced with the understanding of society thus obtained. In Japan, however, rules that facilitate such social understanding have not adequately been established and it is therefore an urgent issue to set forth concrete guidelines for the proper conduct of research activities on the human genome/genes in general with full respect for human dignity and the human rights of the participants and their blood relatives or families.

The present Guidelines have now been established jointly by the Ministry of Education, Culture, Sports, Science and Technology, the Ministry of Health, Labour and Welfare and the Ministry of Economy, Trade and Industry based on the principles set forth by the "Fundamental Principles of Research on the Human Genome" (drafted on June 14, 2000 by the Bioethics Committee of the Council for Science and Technology), which have their basis in the "Universal Declaration on the Human Genome and Human Rights" adopted by the United Nations Educational, Scientific and Cultural Organization (UNESCO) and other related instruments, and with reference to the "Guidelines for Dealing with Ethical Problems, etc. Involved in Analytical Research on Genes" (drafted on April 28, 2000 by the Advanced Medical Technology Evaluation Committee of the Health Sciences Council) to present to society as the ethical rules that shall apply to analytical researches on the human genome/genes in general.

It is demanded that all concerned with analytical research on the human genome/genes observe the present Guidelines.

<Note>

The "Guidelines for Dealing with Ethical Problems, etc. Involved in Analytical Research on Genes" shall be cancelled after the enforcement of the present Guidelines, whose purpose comprehends the purpose of the guidelines to be cancelled.

Chapter 1. Basic Ideas
1. Basic principles
The present Guidelines have been established, with consideration to the nature of analysis of the human genome/genes, as ethical guidelines that shall apply to all analytical research activities on the human genome/genes and be observed in the research practice. The purpose of the present Guidelines is to promote analytical research on the human genome/genes with respect for human dignity and human rights and with social understanding and public support. The following are the basic principles of the present Guidelines.

<Note>

The definition and scope of the research to which the present Guidelines shall apply is formulated in 14 (3) with consideration to the nature of analytical research on the human genome/genes, which is that the genetic information obtained in the course of research may reveal the genetic disposition of participants and their blood relatives and thus elicit various issues.

(1) Respect for human dignity.

(2) The consent of the participant on his/her own free will obtained after sufficient explanation given beforehand (informed consent).

(3) Strict confidentiality of personal information

(4) The conduct of socially beneficial research that promotes the intellectual foundation, health and welfare of humanity.

(5) The priority of individuals' human rights over that of scientific or social benefits.

(6) A research plan prepared in accordance with the present Guidelines and compliance therewith, and the appropriateness of research ensured by the prior deliberation and approval of an independent Ethics Review Committee.

(7) On-the-spot inspection by a third party to observe the operational status of research, and the transparency of research ensured by disclosure of the research outcomes.

2. Scope of application
The present Guidelines shall apply to analytical research on the human genome/genes and be observed by researchers, etc. who are engaged in such research.

The present Guidelines shall not apply to on-going analytical research on the human genome/genes that has already been started before the enforcement of the present Guidelines. It is however desired that such research be conducted properly in accordance with the present Guidelines.

1. In the case where a joint research is to be conducted with an overseas research institution or institutions, the ideas of the present Guidelines on collection and handling of samples, etc., the significance of analytical research on the human genome/genes, etc. should also be observed in their countries with respect for human dignity and human rights.

2. The overseas activities involved in such research should be conducted in compliance with the relevant laws, regulations, guidelines, etc. of their countries and in principle in accordance with the present Guidelines.

3. If the standards of their countries are stricter than the present Guidelines, such research should be conducted in accordance with the stricter standards.

The present Guidelines are not intended for clinical laboratory tests medically established to obtain genetic information for direct therapeutic benefits to the subject or his/her blood relatives and analyses of the human genome/genes conducted as such in the clinical practice, which are of concern to health care and an issue to be deliberated carefully in the future. It is however desired that such tests and analyses of the human genome/genes be properly conducted on the responsibility of the physician attending the subject with due respect for the aims of the present Guidelines and with reference to other guidelines, etc. established by related academic societies, etc.

Chapter 2. Responsibilities of Researchers, Etc.
3. Basic responsibilities of all researchers, etc.
(1) All researchers, etc. should aim at the elucidation of life phenomena, the improvement of methods for prevention, diagnosis and treatment of diseases, the promotion of health, etc.

(2) All researchers, etc. should confirm social benefits of analytical research on the human genome/genes and at the same time give priority to every individual's human rights over scientific or social interests.

(3) All researchers, etc. should conduct analytical research on the human genome/genes, as a basic rule, only after sufficient explanation having been given to the participant or his/her representative beforehand and his/her consent on his/her own free will (informed consent) having been obtained.

(4) All researchers, etc. should not leak, unless justified, the personal information that they have come to know in the performance of duty. This responsibility shall continue after the termination of duty as researchers, etc.

(5) All researchers, etc. should protect the confidentiality of personal information and respond sincerely to complaints, etc. about handling of it.

(6) All researchers, etc. should report promptly to the head of the research institution or the chief researcher in case of any event of serious concern to the assurance of the human rights of the participant, etc., such as the leakage of personal information.

(7) All researchers, etc. should conduct analytical research on the human genome/genes with respect for human dignity and human rights in compliance with the present Guidelines and the research protocol prescribed in accordance with the present Guidelines, approved by the Ethics Review Committee, and authorized by the head of the research institution.

(8) All researchers, etc. should ensure the transparency of research by ensuring the proper procedures of research conduct, accepting on-the-spot inspection by outside experts, responding appropriately to queries of the participant, etc. about the research progress, disclosing the research outcomes, and taking other necessary measures.

(9) All researchers, etc. should preserve properly and make the best use of existing samples, etc. so as to minimize samples, etc. to be collected from humans, with awareness of the fact that they are provided with good intentions.

4. Responsibilities of the head of a research institution
(1) The head of a research institution has the final responsibilities for the conduct of analytical research on the human genome/genes at the institution and should supervise the chief researcher and research conductors to conduct the research properly in accordance with the research protocol. The head of the research institution should thoroughly inform all of the institution's personnel concerned with the research that the research should be conducted with full respect for the human rights of the participants, etc. and that there may be penalty, such as disciplinary action, in the event of violation of the present Guidelines, the research protocol and other relevant rules.

The head of the research institution is instantiated as follows:

_ The head of a hospital.

_ The head of a public health center.

_ The dean of a medical school.

_ The head of a research institute of a private corporation, etc.

(2) The head of a research institution should take adequate measures to prevent the leakage of personal information.

The procedure, facilities and system for strict control of personal information should be established. If personal information is processed by the use of a computer, measures should be taken such as keeping the computer unnetworked with any other computers.

(3) The head of a research institution where personal information is handled, such as an institution at which samples, etc. are collected, should install a personal information manager in order to protect the confidentiality of the personal information obtained in the course of analytical research on the human genome/genes. The head of the research institution may install, as needed, a submanager(s) or assistant(s) to the personal information manager, who actually conduct personal information processing activities under the supervision of the personal information manager and a clearly defined chain of command for control of personal information.

1. The personal information manager and submanager should be individuals who are prohibited from leaking secret that they have come to know in the performance of duty by Article 134 of the Criminal Law (Law No. 45, enforced in 1907), Article 100 of the National Civil Service Law (Law No. 120, enforced in 1947), and other relevant laws (medical doctors, pharmacists, etc.).

2. The personal information manager and submanager should not take the duty of the chief researcher or a research conductor of the analytical research on the human genome/genes conducted with the use of the samples, etc. collected from the participant(s) whose personal information they are to handle (besides collection of samples, etc.).

(4) The head of a research institution should install an Ethics Review Committee as an advisory body for examination of the validity of execution, etc. of analytical research on the human genome/genes. If it is difficult for an institution at which samples, etc. are collected to install an Ethics Review Committee because of its limited size as an institution or other such reasons, the Ethics Review Committee installed by its joint research institution, a public corporation or an academic society may serve as its Ethics Review Committee.

If a research institution's similar committee already existing is reorganized to serve as the Ethics Review Committee in accordance with the present Guidelines, the committee's name may not be Ethics Review Committee.

The plan of a joint research should in principle be approved by the Ethics Review Committee installed at each of the research institutions participating in the joint research. The head of each of the research institutions should obtain important information such as on the status of approval to the research plan, the status of acquisition of informed consent and the status of anonymization at the other research institutions and provide the information to the Ethics Review Committee with a request for advice on the validity of execution of the joint research at the institution concerned.

(5) The head of a research institution should decide whether to authorize or not each research plan or alteration to a research plan with respect for the Ethics Review Committee's opinion on it. The head of a research institution should not authorize the execution of any research the plan of which has been disapproved by the Ethics Review Committee.

(6) The head of a research institution should receive reports on the operational status of analytical research on the human genome/genes from the chief researcher regularly more than once a year, have an outside expert(s) conduct on-the-spot inspection regularly more than once a year and take other necessary measures to perceive the operational status of the research regularly, and, as needed or based on the Ethics Review Committee's opinion that the research plan should be altered or the research should be discontinued, direct the chief researcher to alter the research plan or discontinue the research.

1. The head of a research institution should have an outside expert(s) conduct on-the-spot inspection to confirm whether the research protocol is complied with in respect of the procedure for obtaining informed consent and the maintenance of the confidentiality of personal information.

2. The head of a research institution should have the chief researcher and research conductors cooperate in the on-the-spot inspection.

3. The outside inspectors should not leak, unless justified, the information that they have come to know in the on-the-spot inspection, even after the termination of their duty.

(7) The head of a research institution should send to the personal information manager copies of the research protocol that he/she has authorized, the regular reports on the operational status of research and the reports of on-the-spot inspection by outside experts.

(8) The head of a research institution should send to the Ethics Review Committee copies of the regular reports on the operational status of research and the reports of on-the-spot inspection by outside experts.

(9) The head of a research institution should take appropriate measures, such as installing an office of participant relations services, to deal with complaints, queries, etc. from participants, etc.

(10) The head of an institution at which samples, etc. are collected should in principle anonymize samples, etc. when providing them to an outside institution (if analytical research on the human genome/genes is also conducted at an institution at which samples, etc. are collected, the department conducting the research is regarded as an outside institution).

Samples, etc. may be provided to an outside institution without anonymization if the participant or his/her representative, etc. has consented to provision of samples, etc. to an outside institution without anonymization and the research protocol, which has been approved by the Ethics Review Committee and authorized by the head of the research institution, stipulates provision of samples, etc. to an outside institution without anonymization.

(11) The head of an institution at which samples, etc. are collected should make arrangements for genetic counseling available to the participants and their blood relatives by taking measures as needed such as establishing an appropriate genetic counseling system or explaining about genetic counseling and referring to an appropriate institution for genetic counseling.

If an institution at which samples, etc. are collected does not have a genetic counseling system and the participants or their blood relatives wish to have genetic counseling, the head of the institution should refer them to an appropriate institution for genetic counseling.

5. Responsibilities of the chief researcher
(1) The chief researcher should prepare the research protocol beforehand and obtain the authorization of the head of the research institution for it, for the conduct of analytical research on the human genome/genes. The chief researcher should follow the same procedure for amendment of the research protocol.

(2) The chief researcher should, in the preparation of the research protocol, fully deliberate the necessity of the research, research methods to prevent disadvantage to the participants, etc. with consideration to the expected effects, etc. of the planned analytical research on the human genome/genes on the participants, etc.

If a research is to involve participants having a disease, such as a monogenic disease, for which there is no established treatment or preventive measures and which is complicated by mental disorder, mental retardation or serious physical disability, the chief researcher should deliberate particularly carefully the necessity of the research, the medical and mental effects of the research on the participants, the validity of the methods of the research with consideration to the foregoing aspects of the research, etc. and the Ethics Review Committee should also examine these aspects of the research particularly carefully.

(3) The chief researcher should prepare the research protocol with due consideration to the peculiarity of analytical research on the human genome/genes. In particular, the chief researcher should clearly describe in the research protocol the procedure and manner of obtaining informed consent, measures to protect the confidentiality of personal information, expected outcome of the research, idea about disclosure of the outcome, methods of preservation and use of samples, etc., and idea about genetic counseling.

The contents of the research protocol should generally include the following topics, which may vary depending on the nature of research.

_ Manner of selection of participants (A concrete method for rational selection. If the participants are to be those having a disease, abnormal drug responses or other health problem, the manner of declaration of the disease name or an equivalent description of the abnormality should also be described.)

_ The significance, objective and methods of the research (The target disease, analytical method, etc. Expected additions or amendments if any. If a disease such as a monogenic disease is targeted, the necessity of the research, measures to prevent disadvantage to the participants, etc. and other issues peculiar to the disease.), the research period, the expected outcome and risks, and the manner of protection of confidentiality of personal information (if samples, etc. are not to be anonymized, handling of personal information).

_ The kind and quantity of samples, etc.

_ The names of the chief researcher, etc.

_ The procedure and manner of obtaining informed consent.

_ The informed consent form and written information to be provided to the participants.

_ If it is difficult to obtain informed consent from participants in person, the importance of the research, the reason why provision of samples, etc. by the participants is essential for the conduct of the research, and an idea for selection of the participants' representatives, etc.

_ An idea about disclosure of genetic information.

_ If existing samples, etc. are to be used, whether informed consent was obtained, whether they are to be used within the scope of the said consent, the time of provision of them, the compliance with the present Guidelines regarding this matter.

_ If another research institution provides samples, etc. or genetic information to the research institution, whether they are to be used within the scope of informed consent.

_ If samples, etc. or genetic information is to be provided to an outside institution or part of the research is contracted out to an outside institution, the method of anonymization and other related matters (including the contents of the contract).

_ The method of preservation of samples, etc. and the necessity of their preservation (including the possibility of their use in other researches and the expected contents of these researches).

_ If samples, etc. are to be provided to a human cell/gene/tissue bank, the name of the bank, the method of anonymization, and other related matters.

_ The disposal procedure for samples, etc. and their anonymization in disposal.

_ The necessity of genetic counseling, and the genetic counseling system.

_ Fund raising for the research.

(4) The chief researcher should supervise all research conductors so that they comply the provisions of the authorized research protocol and other applicable rules to conduct analytical research on the human genome/genes properly.

(5) The chief researcher should report the operational status of analytical research on the human genome/genes to the head of the research institution in writing at least once a year regularly.

The regular report on the operational status of research made by the chief researcher to the head of the research institution should generally include the following topics, which may vary depending on the nature of research.

_ The quantity of samples, etc. provided for the research.

_ The quantity of samples, etc. or genetic information provided to an outside institution, and the reason for the provision.

_ The quantity of samples, etc. subjected to analytical research on the human genome/genes.

_ The results and progress of the research.

_ Whether any problems have arisen.

_ At an institution at which samples, etc. are collected, the quantity of samples, etc. anonymized should also be mentioned in the regular report.

(6) The chief researcher should in principle conduct analytical research on the human genome/genes with the use of anonymized samples, etc. or anonymized genetic information.

Samples, etc. or genetic information may be used without anonymization if the participant or his/her representative, etc. has consented to provision of samples, etc. or genetic information for the use of research without anonymization and the research protocol, which has been approved by the Ethics Review Committee and authorized by the head of the research institution, stipulates the use of samples, etc. or genetic information without anonymization.

(7) The chief researcher should in principle not provide non-anonymized samples, etc. or non-anonymized genetic information to an outside institution.

Samples, etc. or genetic information may be provided to an outside institution without anonymization if the participant or his/her representative has consented to provision of samples, etc. or genetic information to an outside institution without anonymization and the research protocol, which has been approved by the Ethics Review Committee and authorized by the head of the research institution, stipulates the provision of samples, etc. or genetic information to an outside institution without anonymization.

(8) In the case where part of analytical research on the human genome/genes is to be contracted out, the chief researcher should in principle anonymize the samples, etc. or genetic information to be provided to the contractor.

In the case where part of analytical research on the human genome/genes is to be contracted out, samples, etc. or genetic information may be provided to the contractor without anonymization if the participant or his/her representative has consented to provision of samples, etc. or genetic information without anonymization and the research protocol, which has been approved by the Ethics Review Committee and authorized by the head of the research institution, stipulates the provision of samples, etc. or genetic information without anonymization.

(9) The chief researcher should explain understandably to the participants, etc. or make public the progress status and the results of analytical research on the human genome/genes, excepting information that needs to be unrevealed to ensure the human rights of the participants, etc. and protect intellectual properties, regularly and as wanted by the participants, etc.

6. Responsibilities of the personal information manager
(1) The personal information manager (or submanager) should in principle anonymize samples, etc. or genetic information prior to the commencement of analytical research on the human genome/genes at the request of the chief researcher. If research conductors, etc. are engaged in the operation of anonymization as assistants, the personal information manager (or submanager) should supervise so that the operation of anonymization should be conducted properly.

Samples, etc. may not be anonymized if the participant or his/her representative has consented to provision of samples, etc. without anonymization and the research protocol, which has been approved by the Ethics Review Committee and authorized by the head of the research institution, stipulates the use of samples, etc. without anonymization.

(2) The personal information manager (or submanager) should in principle not provide personal information, which is separated from samples, etc. or genetic information by anonymization, to an outside institution.

Personal information may be provided to an outside institution if the participant or his/her representative has consented to provision of samples, etc. or genetic information to an outside institution without anonymization and the research protocol, which has been approved by the Ethics Review Committee and authorized by the head of the research institution, stipulates the provision of samples, etc. or genetic information to an outside institution without anonymization.

(3) The personal information manager (or submanager) should keep information containing personal information under strict management with appropriate supervision over the research conductors who conduct anonymization or handle samples, etc. yet to be anonymized so that such information should not leak.

7. Responsibilities of the Ethics Review Committee and its organization
(1) The Ethics Review Committee should review the validity of execution of the research plan and other related matters from ethical and scientific points of view in compliance with the present Guidelines and advance its opinion to the head of the research institution in writing.

(2) The Ethics Review Committee should be able to advise alteration of the research plan of an on-going research, discontinuation of the research, or other necessary measures to be taken in relation to the research to the head of the research institution when it considers necessary.

(3) The members of the Ethics Review Committee should not leak, unless justified, the information that they have come to know in the performance of duty. This responsibility shall continue after the termination of duty.

(4) The Ethics Review Committee should be appropriately comprised of members from various standpoints and administered properly to conduct its function in an independent position so that the scientific and ethical aspects of research should be reviewed neutrally from academic and pluralistic viewpoints.

_ The members should include persons well informed on cultural or social science or specializing ethics or law, persons well informed on natural science, and persons at the common standpoint of the public.

_ It is desirable that more than a half of the members are independent of the research institution. If it is difficult, at least more than one member should be independent of the research institution.

_ More than a half of the members independent of the research institution should be persons well informed on cultural or social science or persons at the common standpoint of the public.

_ The members should include persons of different sexes.

_ More than one person well informed on cultural or social science or at the common standpoint of the public should be present when the Ethics Review Committee reviews a research or makes a decision on a matter related to a research.

_ The head of the research institution, the chief researcher and research conductors of a research subjected to the Ethics Review Committee's review should not be present when the Ethics Review Committee reviews the research or makes a decision on a matter related to the research. They may, however, be present at meetings of the Ethics Review Committee to give explanations at the request of the Ethics Review Committee.

The Ethics Review Committee should have its administration rules on the following matters:

_ The procedure for election of the chairman.

_ The requirements for a valid meeting.

_ The procedure for decision making.

_ The duration of retention of the minutes of meetings.

_ Matters related to publication.

(5) The Ethics Review Committee may, by its own decision, have a quick reviewing procedure conducted by a member designated beforehand by the chairman for this purpose or its subordinate organization. The member or subordinate organization having conducted quick review should report the results of quick review to the other members or to the Ethics Review Committee.

1. In general, the following matters may be subjected to a quick reviewing procedure:

_ A minor alteration of a research plan.

_ A research plan made by using a research plan already approved by the Ethics Review Committee as its template.

_ A joint research plan having been approved by the Ethics Review Committee of the leading joint research institution.

2. After receiving the report of the results of quick review, a member may request the chairman to subject the matter concerned to the Ethics Review Committee's usual reviewing procedure, with the reason for the request. If the reason for the request is considered valid, the chairman should hold a meeting of the Ethics Review Committee promptly to review the matter concerned.

(6) The Ethics Review Committee should make public information about its organization, its administration rules, and, in principle, the minutes of its meetings.

The information about the organization of the Ethics Review Committee that should be made public should include the following:

_ The organization of the Ethics Review Committee (including its subordinate organizations if any).

_ The names of the members, the organizations they are engaged in and their positions.

1. The minutes of meetings should be made public so that the proceedings of meetings can be known concretely.

2. The Ethics Review Committee may, by its own decision, conceal information which, if made public, may affect the human rights of the participants, etc., the originality of the research, and intellectual property rights. If concealing any information, the Ethics Review Committee should make public the reason for concealing the information.

Chapter 3. Basic Attitude to Participants
8. Informed consent

The chief researcher (not of a research conducted with the use of samples, etc. provided from an outside research institution; this definition applies hereafter in the section 8 excepting (4) and (7)) should not select candidates for participants in an irrational, unjust or unfair manner.

If it is difficult to obtain a participant's own informed consent as described above in (2), the chief researcher can obtain informed consent from the participant's representative upon condition that such act should have been approved by the Ethics Review Committee, with its acknowledgment that the proposed research is of high importance and samples, etc. provided by the participant is essential to the research, and authorized by the head of the research institution.

Cases where informed consent can be obtained from the participant's representative because it is difficult to obtain the participant's own informed consent and the procedure to be followed in such a case are defined below. In any of the cases, the chief researcher should describe the importance of the research, the reason why the samples, etc. provided by the participant is essential to the research and the idea about the selection of the participant's representative in the research protocol, which should be approved by the Ethics Review Committee and authorized by the head of the research institution.

* When it is objectively judged that the participant is incapable of giving a valid informed consent because of a condition of unsoundness such as dementia.

* When the participant is a minor. In such a case, however, the chief researcher should give sufficient explanation to the participant in comprehensible terms aiming for his/her full understanding of the explanation. When the participant is 16 years or older, informed consent should be obtained from the participant in person and the participant's representative.

* When the participant is a dead person and the provision of samples, etc. is not contradictory to his/her will expressed explicitly while alive.

The participant's representative should in general be selected from the persons listed below, with consideration to the familial structure of the participant, the circumstances under which he/she is placed, etc. The participant's representative should basically be a person who is considered to be able to represent the will that the participant is supposed to have and his/her interests. Taking these basics into account, the chief researcher should describe in the research protocol his/her idea about the selection of the participant's representative.

1. A voluntary guardian, a person with parental authority, and a lawful guardian or assistant.

2. The participant's spouse, adult offspring, parent, adult sibling or grandchild, grandparent, relative living together, or a person considered equivalently close to the participant.

In case where the participant is a dead person, the dead participant's representative should in general be selected from the persons listed below, with consideration to the familial structure of the dead participant, the circumstances under which he/she was placed while alive, his/her customary conducts, etc. The dead participant's representative should basically be a person who is considered to be able to represent the will that the dead participant was supposed to have while alive. Taking these basics into account, the chief researcher should describe in the research protocol his/her idea about the selection of the dead participant's representative.

* The dead participant's spouse, adult offspring, parent, adult sibling or grandchild, grandparent, relative living together, or a person considered to have been equivalently close to the dead participant.

(4) The participant or his/her representative should be able to withdraw his/her informed consent at any time without penalty by expressing the intention of doing so in writing.

(5) In case where the participant or his/her representative withdraws his/her informed consent, the chief researcher should in principle anonymize and destroy the samples, etc. provided by the participant and the research results concerning the participant.

1. In the cases defined below, the samples, etc. and research results need not be destroyed with the withdrawal of informed consent.

* In the case where the samples, etc. are unlinkably anonymized.

* In the case where there is very little possibility that personal information will be elicited even if they remain undestroyed, and it is unavoidable to leave them undestroyed because of reasons such as an unaffordably extensive destruction process.

* The research results need not be destroyed in the case where they have already been made public.

In the process of obtaining the participant's or his/her representative's informed consent, the chief researcher should give a document explaining necessary information and provide sufficient explanation to the participant or his/her representative so as to obtain a full understanding from him/her. In the case where the participant has a disease such as monogenic disease, the explanation given to the participant or his/her representative should include information about the use of genetic counseling and he/she should be given access to genetic counseling as needed.

The written information given to the participant or his/her representative should in general include the following topics, which may vary depending on the nature of research.

* That the donation of samples, etc. is voluntary.

* That the person requested to donate samples, etc. may refuse the request without any penalty.

* That the participant or his/her representative may withdraw his/her informed consent at any time without penalty by expressing the intention of doing so in writing.

* That with the participant's or his/her representative's withdrawal of informed consent, the samples, etc. donated by the participant and the research results concerning the participant will be destroyed unless they are unlinkably anonymized.

* The reason for being selected as a participant.

* The significance, purpose and procedures of the research (The target disease, analytical methods, etc. should be mentioned. If any, expected additions or alterations of the research plan should also be mentioned. If a disease such as a monogenic disease is targeted, the importance of the research, measures to be taken to prevent disadvantage to the participant, etc. and other issues peculiar to the disease should be mentioned.), and the research period.

* In the case where it is difficult to obtain the participant's own informed consent, the importance of the research and the reason why the donation of samples, etc. by the participant is essential to the research.

* The name and post of the chief researcher.

* The expected outcomes of the research and the foreseeable risks or inconveniences to the participant, etc. (including inconveniences in social life such as social discrimination).

* That the participant or his/her representative can, if so wishes, have access to, or have copies of, documents concerning the research plan and the research procedures to the extent that the confidentiality of personal information concerning the participant, etc. and the originality of the research may not be jeopardized.

* Whether the samples, etc. donated and the genetic information derived from them will be anonymized linkably or unlinkably, and the concrete procedure of anonymization. If anonymization is not to be conducted, the fact with the reason for it.

* Whether or not the samples, etc. donated or the genetic information derived from them will possibly be provided to an outside institution. If the samples, etc. or the genetic information will possibly be provided to an outside institution, that the Ethics Review Committee has approved the procedure of handling personal information, the outside institution to which the samples, etc. or the genetic information is to be provided, and the purpose of use of the samples, etc. or the genetic information at the outside institution.

* In the case where part of the research is contracted out to a third party, the method of anonymization, etc.

* Matters related to disclosure of genetic information.

* That the outcomes of the research may possibly produce intellectual property rights such patent rights in the future, and the party to whom such intellectual property rights will belong.

* That the genetic information derived from samples, etc. may be presented in an anonymized form in academic meetings, etc.

* The methods of preservation and use of samples, etc.

* The method of preservation, use or destruction of samples, etc. after the research (including the possibility of being used for another research and the expected purpose, etc. of the research).

* In the case where samples, etc. will possibly be provided to a human cell/gene/tissue bank for general research use, the academic significance of the bank, the name of the organization managing the bank, the method of anonymization of the samples, etc. to be provided to the bank, and the name of the head of the bank.

* Information about the use of genetic counseling (In the case where the participant has a disease such as monogenic disease, that genetic counseling is available to the participant, etc.).

* The source of the research funds.

* That provision of samples, etc. is gratuitous.

* Information about participant relations such as the person or office to contact when the participant, etc. have questions, complaints, etc.

(7) In the case where samples, etc. or genetic information is provided by an outside research institution, the chief researcher should confirm, by related documents, etc. provided by the outside research institution, that there is valid informed consent pertaining to the samples, etc. or genetic information provided by the outside research institution.

(8) In the case where informed consent is obtained from the participant or his/her representative before the commencement of analytical research on the human genome/genes on the presumption that the samples, etc. donated by the participant will be used for analytical research on the human genome/genes or related medical research, the chief researcher should explain to the participant or his/her representative the concrete purpose for which the research is expected to be conducted, how personal information will be managed and protected, and the possibility of anonymization to obtain the participant's or his/her representative's understanding.

9. Disclosure of genetic information

Concerning analytical research on the human genome/genes which reveals genetic information of individual participants, if a participant wishes his/her genetic information to be disclosed to him/her, the chief researcher should in principle disclose his/her genetic information to him/her. This shall however not apply to the case where the disclosure of genetic information is not of sufficient significance and the participant has given his/her informed consent which stipulates that the participant's genetic information will not be disclosed.

The chief researcher should in principle not disclose a participant's genetic information to any person other than the participant himself/herself unless the participant has given his/her consent.

1. In case where the representative of a participant (who is not a minor) wishes the participant's genetic information to be disclosed to him/her, he/she should explain the reason for wishing so or the necessity to know it to the Ethics Review Committee and, based on the Ethics Review Committee's opinion, the head of the research institution should decide the handling of the matter.

2. In case where the representative of a participant who is a minor wishes the participant's genetic information to be disclosed to him/her, the chief researcher may disclose it to him/her. If the participant is a minor at the age of 16 years or over, the chief researcher should respect the participant's wish for disclosure or nondisclosure of his/her genetic information to his/her representative. If there is a fear that the disclosure of a minor's genetic information to his/her representative may lead to any undesirable effect on him/her such as being discriminated and being disowned or on his/her medical treatment, the chief researcher should report it to the head of the research institution beforehand and the head of the institution should as needed canvass the Ethics Review Committee's opinion with regard to whether his/her genetic information is to be disclosed to his/her representative, the extent of his/her genetic information to be disclosed, and the method of disclosure and have a discussion with him/her and his/her representative before the disclosure of his/her genetic information to his/her representative.

3. In case where information pertaining to a genetic predisposition to a disease or drug responses has been derived from a participant's genetic information and all of the following conditions are satisfied, the chief researcher may disclose the information to the participant's blood relatives even if the participant does not wish his/her genetic information to his/her blood relatives.

1) The participant's genetic information has been found to indicate that there is a genetic effect which is very likely to endanger the lives of the participant's blood relatives, and there is an effective measure to deal with the genetic effect.

2) After receiving the chief researcher's report on the fact described above in 1), the head of the research institution should canvass the Ethics Review Committee's opinion with regard to whether or not the participant's genetic information pertaining to the genetic effect is to be disclosed to the participant's blood relatives, the extent of the genetic information to be disclosed and the method of disclosure. The Ethics Review Committee's opinion should be based on due deliberation particularly on the below listed matters. Based on the Ethics Review Committee's opinion, the head of the research institution should consult with the chief researcher and decide to disclose the information necessary for the participant's blood relatives.

a. The possibility that the participant's blood relatives have the same disease or medical problem.

b. The effect on the lives of the participant's blood relatives.

c. The availability of effective therapeutic measures and the health condition of the participant's blood relatives.

d. The stipulation of informed consent pertaining to disclosure of the research results.

3) In accordance with the result of the consultation mentioned above in 2), the chief researcher should confirm the participant's consent to the disclosure of the necessary information to his/her blood relatives after giving sufficient explanation.

4) After giving sufficient explanation to the participant's blood relatives, the chief researcher should confirm that they wish the information to be disclosed to them.

In case where genetic information pertaining to a disease such as monogenic disease is to be disclosed to a participant or his/her blood relative, the chief researcher should disclose the information in close cooperation with the physician in charge of the participant's or his/her blood relative's medical care giving due consideration to the medical significance, mental effects, etc. and providing the opportunity for genetic consulting to the participant or his/her blood relative.

<Note>

Since the significance of genetic information disclosed is largely dependent on medical care, it is desirable that genetic information be disclosed in close cooperation with the physician in charge of medical care especially as a specialist in genetic medicine. The disclosure of genetic information may be done as part of medical care by the physician in charge of medical care by the request of the chief researcher, or by the chief researcher under the direction of the physician in charge of medical care, or in such a manner which is considered appropriate.

10. Genetic counseling
(1) Purpose

The purpose of genetic counseling in analytical research on the human genome/genes is to extend support or assistance to participants and their families or blood relatives to allow them to choose their courses of life in the future of their own free will and act accordingly by providing accurate information to them through dialogue to have them gain a deeper understanding of genetic diseases and other relevant matters and responding appropriately to the questions and anxieties or concerns they have about research on the human genome/genes, genetic diseases and other matters.

(2) Implementation

Genetic counseling should be provided by medical doctors and other healthcare professionals who have an adequate knowledge about genetic medicine and well versed in genetic counseling.

<Note>

The arrangements for genetic counseling by the head of a research institution where samples etc. are collected are stipulated in (11) of 4 in the Guidelines; the description of the conception about genetic counseling in the research protocol, in (3) of 5; explanation about genetic disease and availability of genetic counseling at the time of obtaining informed consent, in (6) of 8; and accessibility to genetic counseling at the time of disclosing genetic information, in (4) of 9.

Chapter 4. Handling of Samples etc.
11. Use of existing samples etc.
(1) Whether or not to use the existing samples that have been provided and preserved before the undertaking of analytical research on the human genome/genes should be decided by the head of a research institution with the approval of the Ethics Review Committee, in accordance with the provisions of the following Paragraphs (2) through (4), by considering the presence or absence or the consent of informed consent by participants or their representatives etc. and the time samples etc. were provided.

(2) In regard to existing samples etc. that were provided after the enforcement of the present Guidelines, the head of a research institution and the chief investigator should carefully judge whether or not to use them in the research, and the Ethics Review Committee should carefully review whether it is appropriate to use them in the research.

(3) As to Group A of existing samples etc. (for which consent was given for use in research including the human genome and gene analysis when they were provided), they may be used in research on the human genome/genes within the scope of the consent.

(4) As to Group B of existing samples etc. (for which consent was given only for use in research not explicitly including human genome and gene analysis when they were provided), and Group C of existing samples (for which consent was not given for use in any research at the time of their provision), they should not in principle be used in research on the human genome/genes unless informed consent is newly obtained from the participants or their representatives etc. concerned in accordance with the procedure and method as stipulated in the present Guidelines.

The head of a research institution and the chief researcher should judge how to handle samples etc. of this group by considering such factors as how much explanation was given, at the time of informed consent, about possible use in other research on the human genome/genes, including its significance, objectives, method of handling samples etc. anonymously and other pertinent details, and at what point in time informed consent was obtained. The Ethics Review Committee also should consider such factors in reviewing the use of samples etc. of this group in a proposed research on the human genome/genes.

Where either of the conditions as set forth below is satisfied, Group B of existing samples etc. provided before the enforcement of the Guidelines may be used in research on the human genome/genes, provided that their use in the research is approved by the Ethics Review Committee and acknowledged by the head of a research institution.

1) Samples etc. are made unidentifiable and cannot be linked to participants etc., and there is no possibility that the research will cause any risk or disadvantage to participants etc.

2) Samples etc. are made unidentifiable but may be linked to participants etc., but the possibility is extremely small that the research will cause any risk or disadvantage to participants etc. Besides, the research is highly useful and would in effect be impossible or very difficult to undertake by any another means.

To qualify for the use in human genome research and gene analysis of Group B of existing samples etc. provided after the enforcement of the Guidelines, either of the conditions as set forth in <Bylaw 2> above should be satisfied. Additionally, the participants�f right to refuse their use in research on the human genome/genes should be guaranteed. Therefore, especially for the research where samples etc. are made unidentifiable but may be linked to participants, it is necessary to consider such factors as how much explanation was given, at the time of informed consent to provide samples etc., about possible use in other research on the human genome/genes, including its significance, objectives, method of handling samples etc. anonymously and other details, and when informed consent was obtained. Samples etc. of this group may be used in research on the human genome/genes only when their use in the research is approved by the Ethics Review Committee and acknowledged by the head of a research institution after considering these factors.

Group B of existing samples etc. provided before the enforcement of the Guidelines may used in research on the human genome/genes only where either of the conditions as set forth below is satisfied and where their use in the research is approved by the Ethics Review Committee and acknowledged by the head of a research institution.

1) Samples etc. are made unidentifiable and cannot be linked to participants etc., and there is no possibility that the research will cause any risk or disadvantage to participants etc.

2) Samples etc. are made unidentifiable but may be linked to participants etc., while all of the following conditions are satisfied:

a The possibility is extremely small that the research on the human genome/genes will cause any risk or disadvantage to participants etc.

b The research using the samples etc. in question will contribute a great deal to the interests of the public.

c The research would in effect be impossible to undertake by any another means.

d Information will be disclosed about the status and progress of the research. At the same time, measures will be taken to contact the participants involved or their representatives etc. for inquiry and provide them with an opportunity to refuse the use of their samples etc. in the research.

Either of the conditions as set forth in <Bylaw 4> above should be satisfied before Group C of existing samples etc. provided after the enforcement of the Guidelines may used in research on the human genome/genes. In addition, especially in the research using samples etc. that are made unidentifiable but may be linked to participants etc., the number of potential participants will be limited, or the research may need to be conducted with urgency. Samples etc. of this group may be used in research on the human genome/genes only when their use in the research is judged to be indispensable and is approved by the Ethics Review Committee and acknowledged by the head of a research institution.

12. Methods of preservation and destruction of samples etc.
(1) General principle of preservation

When preserving samples etc. within the research institution, the chief researcher should comply with the conditions agreed on with the participants or their representatives etc. and follow the method as prescribed in the research protocol.

(2) Provision to a human cell/gene/tissue bank

When providing samples etc. to a human cell, gene or tissue bank, the chief researcher should confirm that the bank has made provided samples etc. not identifiable in any way with the participants concerned. The chief researcher also should comply with the conditions, including the provision of samples etc. to such a bank, agreed on with the participants or their representatives etc.

(3) Destruction of samples etc.

When the period of preservation of samples etc. as prescribed in the research protocol has elapsed, the chief researcher should destroy them by making them unidentifiable in accordance with the conditions agreed on with the participants or their representatives etc. This provision, however, does not apply to the cases where samples etc. are preserved by the chief researcher himself or provided to a human cell, gene or tissue bank.

Chapter 5. Review
13. Review
The present Guidelines should be reviewed in their entirety, as needed or at a time of about five (5) years after their enforcement.

Chapter 6. Definitions of Terms
14. Definitions of terms
(1) Samples etc.

Samples etc. mean samples from parts of the human body, such as blood, tissues, cells, body fluids and excreta or DNA extracts obtained from them, and medical information pertaining to participants (including those obtained from dead persons), which are to be used for analytical research on the human genome/genes. However, they do not include the tissues, cells, body fluids and excreta, DNA extracts obtained from them and other samples whose value in scientific research is well documented by research and which are in widespread use for research purposes and generally available.

When samples etc. are to be obtained from a person who is judged to be brain-dead under the Law Concerning Transplantation of Organs (Law No. 104 of 1997), it is assumed that they should be obtained only after the �gtriple signs of death,�h i.e., cardiac arrest, respiratory arrest and absence of pupillary response, following removal of organs have been confirmed.

The research using donated fertilized ovaries, embryos, fetuses, ES cells, etc. needs to take account of the purport of the Guidelines but also requires careful review from ethical and other points of view separately. In conducting such research, it is not sufficient to comply with the present Guidelines only.

(2) Medical information

The information about diagnoses, medications used, laboratory and medical examinations, etc. that is obtained in the course of diagnosis and treatment.

(3) Analytical research on the human genome/genes

The research that aims at elucidating the structures and functions of human genomes and genes that are commonly present in the cells that make up individuals and that may be conveyed to offspring by individuals, with the use of samples etc. obtained from them. Obtaining samples etc. alone from individuals for this purpose is regarded as part of the research.

1) The analytical research on the human genome/genes that the present Guidelines govern is the research that is conducted to analyze structures or functions of complementary DNA sequences etc. obtained from DNA or mRNA by using tissues such as leukocytes provided by participants. A major type of this research is to analyze germline mutations or genetic polymorphisms. The present Guidelines do not apply in principle to the research on the mutations of genomes or genes which manifest non-congenitally in lesional sites in such diseases as cancer and are not passed on to offspring (i.e. analytical research on somatic mutations including analysis of normal tissue to confirm mutations); the research on gene expression; and the research on structures or functions of proteins. However, when these latter researches are to be undertaken for the purpose of obtaining information on genomes or genes that may go down to offspring, they will be subject to the present Guidelines. As for the researches on somatic mutations, gene expression and protein structures and functions, it is recommended to take appropriate measures by taking the purport of the Guidelines into consideration.

2) The research that does not aim primarily for human genome/gene analysis but that partly includes it is subject to the present Guidelines.

3) The research that secondarily uses samples etc. or genetic information obtained in the course of medical care is subject to the present Guidelines.

4) The present Guidelines do not apply to the registration-oriented clinical studies and post-marketing surveillance of drugs to be conducted under the Pharmaceutical Affairs Law (Law No. 145 of 1960): The former are regulated by the �gMinisterial Ordinance on Standards for Conduct of Clinical Studies of Drugs (GCP)�h (MHW Ordinance No. 28 of 1997) and the latter by the �gMinisterial Ordinance on Standards for Conduct of Post-marketing Surveillance of Drugs�h (MHW Ordinance No. 10 of 1997). They do not apply either to the registration-oriented clinical studies and post-marketing surveillance of medical devices to be conducted under the Pharmaceutical Affairs Law.

5) The present Guidelines do not apply to practical training in gene structure analysis using genes with known structures and functions that may be provided for educational purposes in biology courses etc., provided that the samples etc. and outcomes of analysis are not utilized for other purposes than training.

(4) Genetic information

The information about genetic characteristics and diathesis of individuals that has been obtained in the course of analytical research on the human genome/genes conducted by using samples etc. or that already accompanies the samples etc. provided.

(5) Personal information

The information about individuals that contain their names, dates of births and other descriptions and that identifies each of them (including information that may easily be collated with other available information and identifies specific individuals).

There are arguments about legal grounds on which to protect personal information of dead persons. For the purposes of the present Guidelines, it is required that personal information of a dead person be protected from the viewpoint that human dignity as a dead person and feelings of the surviving family should be respected and that genetic information of a dead person is shared by his/her blood relatives.

Besides the name, birth date, address and telephone number, typical personal information may include the number or code assigned to each individual in medical records or other information contained in it. Whether particular information constitutes personal information under the present Guidelines is to be judged individually by considering specific circumstances involved.

(6) Anonymity

Each individual is made anonymous by removing, from his/her personal information, all or part of the information that identifies him/her, but instead, assigning a code or number unrelated to the individual, so as to prevent the leakage of personal information to the outside in violation of legal regulations, the present Guidelines or the research protocol. In the case of information that accompanies samples etc. provided, identification may be made impossible by removing part of the information but it may be made possible by collating with other information accessible elsewhere such as various lists of names. In this case, anonymity involves removing all or part of the information that allows such collation for identification. There are two types of anonymity as follows:

a Anonymity that may be linked to subjects

Samples etc. are made unidentifiable, but a table that links them with codes or numbers assigned to research subjects is retained to allow identification if necessary.

b Anonymity that cannot be linked to subjects

Samples etc. are made unidentifiable without retaining a table that links them to codes or numbers assigned to research subjects.

(7) Personal information manager

The person responsible for managing personal information of research subjects and making it unidentifiable under the instructions of the head of a research institution that deals with subjects�f personal information including an institution where samples etc. are collected.

(8) Informed consent

The consent voluntarily given for provision and handling of samples etc. by research subjects who are requested to provide them after having been explained in detail beforehand by the chief researcher about the significance, objectives and methods of a planned research, anticipated outcomes and inconveniences and other relevant information and having fully understood such details. The present Guidelines require that informed consent be obtained in writing.

(9) Representative etc.

The person who gives informed consent on behalf of a research subject requested to provide samples etc. who is incapable of giving informed consent himself/herself. If a research subject is a dead person, his/her family is to give consent for the dead person. When the surviving family is excluded, a person who gives consent on behalf of a research subject is called the �grepresentative.�h

<Note>

The representative etc. is essentially a person who decides whether or not to give consent for provision of samples etc. and other related matters on behalf of a research subject from the standpoint of protecting the latter�fs human rights. As for genetic problems on the part of the representative etc., it is necessary to consider how to deal with them separately.

(10) Minors

Persons who are less than 20 years of age and unmarried.

(11) Research institutions

The research institutions that undertake analytical research on the human genome/genes (including institutions where samples etc. are collected).

(12) Institutions where samples etc. are collected

The institutions, such as hospitals or public health centers, where samples etc. are collected from individuals.

(13) Joint research institutions

The research institutions, such as national, public, or private research institutions including university research institutes, that jointly undertake an analytical research on the human genome/gene research in compliance with the same research protocol. When a joint research institution receives samples etc. from another institution where they are collected, the latter institution is to be included as a joint research institution.

(14) Outside institutions

The research institutions other than those with which researchers are affiliated. When a research institution where samples etc. are collected has a research on the human genome/genes undertaken by a research department within it with the use of the samples etc. collected, the research department is regarded as an outside institution.

(15) Ethics Review Committee

A committee organized as an advisory body to the head of a research organization to collectively deliberate and review the appropriateness of conduct of a proposed research on the human genome/genes and other related matters from an ethical point of view to assure human rights and other ethical considerations of participants etc., as well as from a scientific point of view.

(16) Researchers etc.

The chief researcher, research conductors (including those who are responsible for supply of samples etc.), persons providing genetic counseling, persons responsible for protection of personal information, and other personnel involved in research on the human genome/genes at a research institution, including the head of the institution.

(17) Chief researchers

The researchers at research institutions who are responsible for conduct of analytical research on the human genome/genes and supervision of all the operations involved with the research and who have an adequate knowledge about the usefulness and limitation of human genome/gene research and about bioethics.

(18) Research conductors

The researchers, medical doctors, pharmacists, nurses, laboratory technologists or other persons who conduct research on the human genome/genes with the instructions and authorization of the chief researcher and who have a professional knowledge and skills necessary to perform the work assigned.

(19) Participants

The individuals who provide samples etc. for research on the human genome/genes. When other persons who may have to do with the genetic information of a participant, such as his/her family, blood relatives, or representative are included, they are referred to as �gparticipant etc.�h

(20) Genetic counseling

Extending support or assistance with a view to dissolving or alleviating medical or psychological concerns that may be associated with genetic diseases by providing consultation and information repeatedly with the use of knowledge of genetic medicine and counseling techniques.

(21) Existing samples etc.

The samples etc. that have been provided to and preserved at research institutions before the undertaking of research on the human genome/genes. They are divided into the following groups depending on the status of informed consent given at the time they were provided:

a Group A of samples etc.

Samples etc. for which consent was given for use in research including the human genome and gene analysis when they were provided.

b Group B of samples etc.

Samples etc. for which consent was given only for use in research not explicitly including the human genome and gene analysis (e.g. consent given for �guse in medical research�h) when they were provided.

c Group C of samples etc.

Samples etc. for which consent was not given for use in research when they were provided.

(22) Human cell/gene/tissue bank

A non-profit organization that maintains quality control of human cells, genes, tissues, etc. provided, as research resources, and dispenses them for use by researchers in general.

Chapter 7. Supplementary Rules
15. Supplementary rules
In addition to the bylaws as set forth herein, other matters necessary for the enforcement of the present Guidelines should be stipulated separately.

Chapter 8. Date of Enforcement
16. Date of enforcement
The present guidelines shall be enforced on April 1, 2001.

Ethical Guidelines for Analytical Research
on the Human Genome/Genes

(Reference Documents)

[Table of Contents]

(Reference Document 1) Outline of Ethical Guidelines for Analytical Research on the Human Genome/Genes

(Reference Document 2) Basic Points along the Course of Analytical Research on the Human Genome/Genes

(Reference Document 3) Outline Figure of Use of Existing Samples, Etc.

(Reference Document 4) Backgrounds and Courses of Establishment of �gEthical Guidelines for Analytical Research on the Human Genome/Genes�h

[Separate Sheet 1] List of Members of the Drafting Committee for Common Guidelines for Analytical Research on the Human Genome/Genes (draft)

[Separate Sheet 2] List of Members of the Drafting Working Committee for Common Guidelines for Analytical Research on the Human Genome/Genes (draft)

[Separate Sheet 3] Tri-Ministrial Meeting for �gEthical Guidelines for Analytical Research on the Human Genome/Genes (draft)�h

[Separate Sheet 4] Course of Deliberations in the Concerned Councils, etc. on �gEthical Guidelines for Analytical Research on the Human Genome/Genes (draft)�h

[Separate Sheet 5] Summary of Opinions Collected for �gEthical Guidelines for Analytical Research on the Human Genome/Genes (draft)�h

(Reference Document 5) List of Members of Tri-Ministrial Secretariat in Charge of Establishment of �gEthical Guidelines for Analytical Research on the Human Genome/Genes�h

(Reference Document 1)

Outline of Ethical Guidelines for Analytical Research on the Human Genome/Genes
1. Spirit and Purpose
¡ The present guidelines have been established as the ethical guidelines to be applied to all analytical researches on the human genome/genes and to be complied with at all research sites, based on the Helsinki Declaration (approved at the 18^th meeting of the World Medical Association in June 1964), �gFundamental Principles of Research on the Human Genome�h (drafted on June 14, 2000 by the Bioethics Committee of the Council for Science and Technology) and others.

¡ The purpose of the present guidelines is to properly promote analytical research on the human genome/genes with respect for human dignity and human rights with social understanding and public support.

2. Definition of �gAnalytical research on the human genome/genes�h
The research to attempt elucidation of structure and functions of genome/genes, that exist commonly in the cells constituting the body of the participant and are inherited by descendants by using samples, etc. Only supply of such samples, etc. for the research shall be included.

3. Major contents
¡ To be based on informed consent

l Consent of the participant on his/her own free will obtained after sufficient explanations made beforehand using written information

l To decide whether or not to disclose the genetic information with respect for the participant�fs will

l Careful handling of the existing samples, etc

¡ Thorough protection of personal information

l Conduct of research under anonymization of samples, etc. as a basic rule

l Thorough protection by the personal information manager

l Strict confidentiality of personal information

l Preservation of samples, etc. with respect for the participant�fs own will and disposal under anonymization

¡ That the Ethics Review Committee is properly organized and operated

l That the Ethics Review Committee is installed as a consultative organ for the head of a research institution and its opinion should be respected

l That the Ethics Review Committee is properly constituted with experts and ordinary people (including outside members) for fair and neutral deliberation

l To ensure transparency by disclosing the members, proceedings, etc

¡ To secure appropriateness of the research

l Prior review of the research protocol by the Ethics Review Committee

l Approval of the research protocol by the head of a research institution

l Proper conduct of the research in accordance with the protocol

¡ To secure transparency of the research

l On-the-spot inspection by the outside experts

l Publication of the research results

l Installation of a complaint-receiving liaison

¡ Considerations for genetic diseases

l Conduct of genetic counseling in the event of genetic diseases

Considerations for protection of benefits of the participant in the event of genetic diseases

(Reference Document 2)

Basic Points along the Course of Analytical Research
on the Human Genome/Genes

Judgment of benefits of the research

¡ To judge whether the research to be conducted is socially beneficial and each participant's human rights are given priority.

¡ To judge whether the research to be conducted is applicable to the analytical research on the human genome/genes specified in the present guidelines.

Preparation of research protocol

¡ The following items should be described : methods of obtaining informed consent, foreseeable results of the research and policy to disclose the results, methods of protecting personal information including a method of anonymization, methods of preserving and using the samples, etc.

¡ In case of single genetic diseases, etc., necessity of the research and measures to protect the benefits of the participant should carefully be judged, and in a case where the analysis results are disclosed to the participant, a system to conduct genetic counseling should be established and the concept and methods for genetic counseling should be described in the research protocol.

¡ In a case where the existing samples, etc. are used for the research, the necessity of the use and the status of informed consent should be described in the research protocol.

Review by the Ethics Review Committee

¡ Review of the research protocol by the Ethics Review Committee

Decision of the head of the research institution

¡ Based on the opinions of the Ethics Review Committee concerning the research protocol, the head of the research institution shall decide whether or not to permit conduct of the research

Conduct of the research

¡ The research should be conducted in accordance with the research protocol, using anonymized samples, etc., as a rule.

¡ The status of the research should be periodically reported to the head of the research institution. On-the-spot inspection by outside experts should be performed.

Publication of research results

¡ The progress status and results of the research should be published periodically or per request.

(Reference Document 3)

Outline Figure of Use of Existing Samples, Etc.

¡ Whether or not to permit use of the existing samples, etc. shall be decided by the head of the research institution based on the following items after approval of the Ethics Review Committee.

· Presence/absence or content, if any, of consent of the participant.

· Timing of supply of the concerned samples, etc.

(Reference Document 4)

Backgrounds and Courses of Establishment of �gEthical Guidelines for Analytical Research on the Human Genome/Genes�h
¡ Analytical research on the human genome/genes, which was started in the late twentieth century, is expected to contribute greatly to the promotion of life, health and medical sciences and play an important role in the promotion of human health, development of welfare and new industries, etc.

¡ On the other hand, analytical research on the human genome/genes largely depends on analysis of individual persons' genomes/genes, and the genetic information obtained in the course of the research may reveal the genetic predisposition of individual subjects who provide samples and their blood relatives and abuse of such information may cause various ethical, legal or social problems.

¡ It is therefore essential that analytical research on the human genomes/genes be properly conducted with respect for human dignity and human rights and with social understanding and public support, and it has been desired to establish rules for such research.

¡ In this regard, already established are :

(1) The "Fundamental Principles of Research on the Human Genome" (drafted on June 14, 2000 by the Bioethics Committee of the Council for Science and Technology), and

(2) "Guidelines for Dealing with Ethical Problems, etc. Involved in Analytical Research on Genes" (drafted on April 28, 2000 by the Advanced Medical Technology Evaluation Committee of the Health Sciences Council).

The (1) above has presented only the basic ideas as the premises for concrete guidelines, and the (2) above, the so-called �gMillenium Guidelines�h, has involved only particular analytical researches on human genome/genes called �gMillenium Projects�h. It has therefore been desired to urgently establish concrete guidelines concerning general analytical researches on human genome/genes.

¡ Under these circumstances, the Ministry of Education, Culture, Sports, Science and Technology, the Ministry of Health, Labour and Welfare, and the Ministry of Economy, Trade and Industry have now established �gEthical Guidelines for Analytical Research on the Human Genome/Genes�h as ethical guidelines to be applied to general analytical researches on the human genome/genes.

¡ On establishing the present guidelines, through examinations with questionnaires performed in the course of preparation of the draft in the Drafting Committee [Separate Sheet 1], opinion exchange in the Drafting Working Committee installed [Separate Sheet 2], collection of public comments (December 20, 2000 - January 31, 2001), Tri-Ministrial Meeting [Separate Sheet 3], and deliberations in the Concerned Councils [Separate Sheet 4], the best effort has been made to reflect various opinions as far as possible.

In particular, as to public comments, a total of 577 opinions were contributed from a total of 92 individuals or organizations [Separate Sheet 5] , and based on 108 opinions accounting for approx. 20% of those, the guidelines have been modified.

¡ As to the positioning of the present guidelines, compliance with the present guidelines will be obligatory for those analytical researches on the human genome/genes which are performed at concerned national research institutions or which are performed under the national grants-in-aid, but all of those to whom this notification is addressed are eagerly requested to thoroughly instruct those who are engaged in analytical researches on the human genome/genes at private institutions or organizations to comply with the present guidelines.

(Reference Document 4) - [Separate Sheet 1]

List of Members of the Drafting Committee for Common Guidelines for Analytical Research on the Human Genome/Genes (draft)

	Hiroshi Amemiya	Director, National Children�fs Medical Research Center
	Ryuichi Ida	Professor, Graduate School of Law, Kyoto University
	Kunihiro Ueda	Professor, Institute for Chemical Research, Kyoto University
	Shin Utsugi	Professor, Department of Law, School of Law, Tokai University
	Junko Obata	Professor, School of Law, Sophia University
��	Tadao Kakizoe	Director, National Cancer Center Hospital
	Ichiro Kanazawa	Professor, Department of Neurology, Faculty of Medicine, Graduate School of Medical Sciences, The University of Tokyo
	Hiroshi Tomojima	Trustee, R&D Management, Yamanouchi Pharmaceutical Co., Ltd.
	Toshio Kuroki	Director, Institute for Molecular Biological Research of Cancer, Showa University
	Hideya Sakurai	Regular Trustee, The Japan Medical Association
	Takehiko Sasazuki	Director, Medical Institute of Bioregulation, Kyusyu University
	Susumu Kiyono	Professor, Graduate School of Medicine, Chiba University
	Toshihito Takashiba	Lawyer
	Yoshifumi Jigami	Vice-president, National Institute of Bioscience and Human Technology
	Yoshimitsu Fukushima	Professor, Department of Hygiene, Shinshu University School of Medicine
	Saku Machino	Professor, School of Law, Sophia University
	Eiji Maruyam	Professor, Faculty of Law, Kobe University
	Suna Minami	Vice-Director, Department of Comment, Editorial Office, Yomiuri Newspaper Company
	Ken Yamaguchi	Vice-president, National Cancer Center Research Institute

(Reference Document 4) - [Separate Sheet 2]

List of Members of the Drafting Working Committee for Common Guidelines for Analytical Research on the Human Genome/Genes (draft)

	Yoshitoshi Aono	Editorial Staff, Department of Science and Environment, Mainichi Newspaper Company
	Wakiko Ajiki	Group Leader, Epidemiology & Investigation, Osaka Medical Center for Cancer and Cardiovascular Diseases
	Hiroyuki Yuya	Associate Professor, Research Center for Advanced Science and Technology, The University of Tokyo
	Kyoji Ikeda	Director, Department of Geriatric Research, Chubu National Hospital, National Institute for Longevity Sciences
	Toshiya Inada	Chief, Laboratory of Aging, National Institute of Mental Health, National Center of Neurology and Psychiatry
	Shin-ya Uchino	Surgeon, Noguchi Hospital
	Michitaro Urakawa	Professor, Waseda University School of Law
	Mami Oh-yama	Senior Researcher, National Institute of Science and Technology Policy
	Shin-ichi Oka	Director, Clinical R&D Department, AIDS Therapy Research & Development Center, International Medical Center of Japan
	Naoko Kakee	Advanced Research Center for Human Sciences, Waseda University
	Yutaka Kikuchi	Senior Researcher, Division of Microbiology, National Institute of Health Sciences
	Nobuo Kurata	Associate Professor, Faculty of Humanities and Social Sciences, Mie University
	Masayuki Kurosaki	Assistant, Tokyo Mediacl and Dental Univeristy
	Hirohisa Saitoh	Director, Department of Immunology and Allergy Research, National Children�fs Hospital
	Yukiko Saito	Principles of Medicine, School of Medicine, Kitasato University
	Keiko Sato	Clinical Study Control Unit, National Cancer Center Hospital
	Sumio Sugano	Associate Professor, The Institute of Medical Science, The University of Tokyo

	Koukichi Sugano	Oncogene Laboratory / Cancer Prevention Laboratory, Tochigi Cancer Center
	Mariko Tamai	School of Allied Medical Sciences, Shinshu University
	Toshihiko Tsukada	Chief, Growth Factor Department, National Cancer Center Research Institute
	Shoichiro Tsugane	Director, Department of Clinical Epidemiological Research, National Cancer Center Research Institute
	Shoji Tsuji	Professor, Brain Research Institute, Niigata University
	Takashi Sotoguchi	Director, R&D Promotion Department, The Organization for Pharmaceutical Safety and Research
	Tatsushi Toda	Professor, Biomedical Education Research Center, Graduate School of Medicine
	Tohru Nakagawa	Hitachi Health Management Center, Hitachi Corporation
	Jiro Katsushima	Senior Researcher, Social Life Science Laboratory, Mitsubishi Kasei Institute of life Science
	Katsuyuki Hashimoto	Chief, Division of Genetic Resources (Gene Bank), National Institute of Infectious Diseases
	Tomoko Hasegawa	Chief Physician, Division of Clinical Genetics, Shizuoka Children�fs Hospital
	Hitoyasu Futami	Chief, Growth Factor Department, National Cancer Center Research Institute
	Yukio Matsuura	Director, Department of Information Promotion, Bio-industry Information Consortium
	Tsuneo Matsumoto	Professor, Hitotsubashi University School of Law
	Hiroshi Mizusawa	Manager, Section 3 (Cell Bank Lab.), Division of Genetics and Mutagenesis, National Institute of Health Science
	Shinji Miyamoto	Manager, Fund Control Section, Department of Fund Management, The Pension Welfare Service Public Corporation
	Isao Morikawa	Visiting Researcher, Advanced Research Center for Human Sciences, Waseda University
	Takayuki Morisaki	Director, Bioscience Department, National Cardiovascular Center

	Masatake Yamauchi	Senior Researcher, Genome, National Institute of Radiological Sciences
	Zentaro Yamagata	Professor, Department of Health Science, Yamanashi Medical University
¡	Ken Yamaguchi	Vice-president, National Cancer Center Research Institute
	Teruhiko Yoshida	Director, Genetics, National Cancer Center Research Institute
	Yoshinobu Yoshimura	Director, Drug Function Research Laboratory I, New Drug Research Division, Takeda Pharmaceutical Co., Ltd.

(Reference Document 4) - [Separate Sheet 3]

Tri-Ministrial Meeting for �gEthical Guidelines for Analytical Research on the Human Genome/Genes (draft)�h
March 2001,

The Ministry of Education, Culture, Sports, Science and Technology

The Ministry of Health, Labour and Welfare

The Ministry of Economy, Trade and Industry

1. Purpose of the Tri-Ministrial Meeting
�gEthical Guidelines for Analytical Research on the Human Genome/Genes (draft)�h (hereinafter referred to as the Draft Guidelines), which has been under collaborative establishment by the Ministry of Education, the Ministry of Health and Welfare, the Ministry of International Trade and Industry and the Science and Technology Agency (the Ministry of Education, Culture, Sports, Science and Technology, the Ministry of Health, Labour and Welfare and the Ministry of Economy, Trade and Industry which have succeeded the above ministries and agency after January 6, 2001), has been separately deliberated in the Science Council of the Ministry of Education, the Health Sciences Council of the Ministry of Health and Welfare, the Council for Chemical Products and the Bioethics Committee of the Council for Science and Technology of the Ministry of International Trade and Industry. The final draft has been prepared making reference to the public comments/opinions this time. Thus, the experts including the members of the above councils of the concerned three ministries are requested to attend the Tri-Ministrial Meeting for presenting their opinions.

2. Roles played by the Tri-Ministrial Meeting
The members of the Council for Science and Technology of the Ministry of Education, Culture, Sports, Science and Technology, the Health Sciences Council of the Ministry of Health, Labour and Welfare and the Council for Industrial Structure of the Ministry of Economy, Trade and Industry as well as those experts entrusted by the Ministry of Education, Culture, Sports, Science and Technology, the Ministry of Health, Labour and Welfare and the Ministry of Economy, Trade and Industry are requested to attend the above meeting to present their opinions about the Draft Guidelines to the Ministry of Education, Culture, Sports, Science and Technology, the Ministry of Health, Labour and Welfare and the Ministry of Economy, Trade and Industry.

The Ministry of Education, Culture, Sports, Science and Technology, the Ministry of Health, Labour and Welfare and the Ministry of Economy, Trade and Industry shall finalize the Draft Guidelines making reference to the opinions to be presented in the meeting, announce �gEthical Guidelines for Analytical Research on the Human Genome/Genes�h within this fiscal year and enforce from the next fiscal year.

3. Attendants
(Experts) (In order of the Japanese syllabary)

Ryuichi Ida (Professor, Graduate School of Law, Kyoto University)

Kiyoko Okabe (Professor, School of Law, Toyo University)

Ichiro Kanazawa (Professor, Faculty of Medicine, Graduate School of Medical Sciences, The University of Tokyo)

Toshito Kimura (Professor, School of Human Sciences, Waseda University)

Fimimaro Takaku (President, Jichi Medical School)

Toshihito Takashiba (Lawyer)

Masaaki Terada (President, National Cancer Center)

Toshiharu Matsumura (Chairperson, Ethics Committee, The Japanese Tissue Culture Association)

(Drafting Committee)

Chairperson Tadao Kakizoe (Director, National Cancer Center Hospital)

(Drafting Working Committee)

Chairperson Ken Yamaguchi (Vice-president, National Cancer Center Research Institute)

(Secretariat)

Satoshi Tanaka (Director, Life Science Division, Research Promotion Bureau, Ministry of Education, Culture, Sports, Science and Technology)

Susumu Sanagi (Director, Health Sciences Division, Minister's Secretariat, Ministry of Health, Labour and Welfare)

Yosiaki Tsikamoto (Directoral, Biochemical Industry Division, Manufacturing Industries Bureau, Ministry of Economy, Trade and Industry)

4. Date of Meeting
March 15, 2001 (at Meeting Room No. 827 (8^th F) of the Ministry of Economy, Trade and Industry)

(Reference Document 4) - [Separate Sheet 4]

Course of Deliberations in the Concerned Councils, etc. on �gEthical Guidelines for Analytical Research on the Human Genome/Genes (draft)�h
March 19, 2001

Concerned Council, etc.	Aug., 2000	Sep.	Oct.	Nov.	Dec.	Jan., 2001	Feb.	Mar.
Tri-minstrial Meeting								15^th
Drafting Committee	14^th	5^th18^th	12^th	26^th	16^th			7^th
Council for Science and Technology (abolished on January 6, 2001)
Bioethics Committee						21^st
Sub-committee for Human Genome Research					20^th	11^th
The Ministry of Education Culture, Sports, Science and Technology (the former Ministry of Education)
The Life Ethics and Safety Committee of the Council for Science and Technology (the former Bioscience Committee of the Science Council)
(The former Cancer Research Committee of the Science Council)					24^th(Joint meeting)
The Ministry of Health Labour and Welfare (the former Ministry of Health and Welfare)
The Science and Technology Committee of the Health Sciences Council							26^th	19^th
(The former Advanced Medical Technology Evaluation Committee of the Health Sciences Council)		22^nd		13^th24^th	22^nd
The Ministry of Economy Trade and Industry (the former Ministry of International Trade and Industry)
The Chemistry and Biology Committee of the Council for Industrial Structure (the former Personal Genetic Information Committee of the Council for Chemical Products)	2^nd		16^th	13^th	4^th

(Reference Document 4) - [Separate Sheet 5]

Summary of Opinions Collected for �gEthical Guidelines for Analytical Research on the Human Genome/Genes (draft)�h
1. Outline of opinion collection
(1) Period December 20, 2000 - January 31, 2001

* The actual period of reception was from January 9, 2001 to January 31, 2001 due to the reorganization of ministries and agencies.

(2) Methods of announcement : Home page of each concerned ministry and announcement to press, etc.

(3) Opinion-forwarding methods : Electronic mail or regular mail

2. Number of opinions received
(1) Number of opinion presenters

92 presenters (61 individuals and 31 organizations)

(2) Total number of opinions

577 opinions (many of the presenters referred to multiple items)

3. Outline of the opinions received
(1) The opinions to the Draft Guidelines are broken down as follows.

General remarks	Major items	146 opinions
	Comprehensive opinions	27 opinions
	Method of expression	28 opinions
	Viewpoints related to human rights	14 opinions
	Relation with other standards	13 opinions
	Economic aspects	11 opinions

Preamble		18 opinions
	1. Basic principle	17 opinions
	2. Scope of application	35 opinions
	3. Basic responsibilities of all researchers, etc.	17 opinions
	4. Responsibilities of the head of a research institution	55 opinions
	5. Responsibilities of the research leader	39 opinions
	6. Responsibilities of the personal information manager	6 opinions
	7. Responsibilities of the Ethics Review Committee and its organization	61 opinions
	8. Informed consent of participants, etc.	79 opinions
	9. Disclosure of genetic information to participants	19 opinions
	10. Genetic counseling	16 opinions
	11. Use of existing samples, etc.	17 opinions
	12. Preservation and disposal of samples, etc.	5 opinions
	13. Revision	5 opinions
	14. Definitions of terms	42 opinions

(2) Outlines of opinions received and deliberations therefor

Outlines of opinions received and deliberations therefor are summarized in the form of tabulation and published in the home pages of the three concerned ministries (the Ministry of Education, Culture, Sports, Science and Technology, the Ministry of Health, Labour and Welfare and the Ministry of Economy, Trade and Industry).

(3) Publication of the texts of the opinions, etc.

The entire texts of the opinions received are disclosed, after anonymized when requested by the presenters, with the tabulations in (2) above at the Life Ethics/Safety Measures Section, Life Science Division, Research Promotion Bureau, Ministry of Education, Culture, Sports, Science and Technology, the Information Disclosure Section, General Coordination Division, Minister's Secretariat, Ministry of Health, Labour and Welfare and the Biochemical Industry Division, Manufacturing Industries Bureau, Ministry of Economy, Trade and Industry.

(Reference Document 5)

List of Members of Tri-Ministrial Secretariat in Charge of Establishment of �gEthical Guidelines for Analytical Research on the Human Genome/Genes�h
¡ Ministry of Education, Culture, Sports, Science and Technology (Life Science Division, Research Promotion Bureau)

Address: 2-2-1 Kasumigaseki, Chiyoda-ku, Tokyo 100-8966

TEL: 03-3581-5271 (pilot No.) Ext. 5451

03-3509-1268 (direct dial)

FAX: 03-3509-1269

Director Yutaka Hishiyama

Vice-Director Kenji Kohri

Staff in charge Katsuyuki Ogo

¡ Ministry of Health, Labour and Welfare (Health Sciences Division, Minister's Secretariat)

Address: 1-2-2 Kasumigaseki, Chiyoda-ku, Tokyo 100-8916

TEL: 03-5253-1111 (pilot No.) Ext. 3804, 3807

03-3595-2171 (direct dial)

FAX: 03-3503-0183

Research Planner Toshiro Nakagaki

Assistant to Director Hisahi Noguchi

Assistant to Director Daisuke Sakamoto

Group Leader Koichi Ando

Chief Chizu Okada

¡ Ministry of Economy, Trade and Industry (Biochemical Industry Division, Manufacturing Industries Bureau)

Address: 1-3-1 Kasumigaseki, Chiyoda-ku, Tokyo 100-8901

TEL: 03-3501-1511 (pilot No.) Ext. 3741

03-3501-8625 (direct dial)

FAX: 03-3501-0197

e-mail : qfsc@meti.go.jp

Manager, Section of Business Environment Arrangement Hiosanori Goto

Officer for Manufacturing Industries Nobutaka Fukushima

Group Leader Koichi Yamamoto

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