6.1. Guidelines for Genetic Testing in Japan

 pp. 77-81 in Bioethics and the Impact of Human Genome Research in the 21st Century

Author: Ichiro Matsuda (Hokkaido Health Science University Institution for Developmental Disabilities)

Editors: Norio Fujiki, Masakatu Sudo, and Darryl R. J. Macer
Eubios Ethics Institute

Copyright 2001, Eubios Ethics Institute All commercial rights reserved. This publication may be reproduced for limited educational or academic use, however please enquire with the author.
Recent progress on molecular genetics has made feasible DNA testing in clinical practice. In addition to monogenic diseases, polygenic or multifactorial diseases, such as diabetes mellitus, hypertension, cancers and others will be included in this category in the near future. However, only when gene-related information is available to health care providers, as based on general principles of bioethics, will patients and families benefit. Two guidelines established by the Ethical Committee of Japan Association of Human Genetics (ECJSHG); "Guidelines for genetic counseling and prenatal diagnosis (1995)" and "Guidelines for genetic testing, using DNA analysis (1996)"were revised in 2000, as "Guidelines of genetic testing"[1]. Medical research institutions, medical facilities, clinical testing companies, all persons related to the testing plus the media must be made aware of the importance of genetic testing, so that all related persons will follow the guidelines.

Before starting the discussion in the ECJSHG, we confirmed the general concept concerning the genetic testing; 1) what is genetic testing, 2) the form of genetic testing available, 3) the principles of genetic testing and 4) what divulge to a client at the time of genetic testing. Genetic testing was defined as a search for a particular genetic condition, by analyzing DNA, chromosomes, gene products (protein or enzyme) and certain metabolites in order to identify the genetic disease-related genotype, karyotype and phenotype [2]. Health care providers can then propose genetic testing for diagnosis of a specific disease or condition, carrier detection, pre-symptomatic diagnosis, susceptibility testing and preimplantation diagnosis. Genetic testing must be implemented only on established and practical methods, for which validity and usefulness are proven scientifically. The test should be voluntary, but not mandatory. We proposed that genetic testing be done only after written informed consent is obtained, and prior to this, genetic counseling is required to provide correct information to the client. Post-testing counseling is also necessary, but this should be done only when the tested individuals requested this.

In children, pre-symptomatic or susceptibility testing for adult-onset diseases or conditions, specially when no approved prevention or treatment is available, should be avoided until they can make their own decision. We accepted the statement developed by WHO [3] concerning genetic counseling as follows; we should tell a client 1) the purpose of the test, 2) the likelihood that it will be a correct prediction, 3) implications of the test results for individuals, 4 ) tested person's option and alternatives,5) potential benefit and risk of the test, including social and psychological factors, 6) whatever decision individuals and families make, their care will not be jeopardized, and 7) individuals' genetic information must be confidential. Most discussion was directed to issues of rejection of client's proposal and disclosure of individual's information family members. Our final conclusion is as follows; even though the client may desire genetic testing, the doctor can refuse to provide testing, if the request is against social and ethical norms, or against their private principle. When refused because of personal disagreement, the doctor should explain the situation in detail and should outline other available medical facilities [3]. All personal genetic information must be kept confidential and basically not be divulged to another person unless the subject gives permission to do so. Utmost care is needed so this information will not be used as source of discrimination. It is suggested the result be disclosed to family members and to have tested, if the test result can be used to prevent or treat the disease in family members for both single and multiple gene-related disorders. When the subject does not wish to reveal the information to his/her family after repeated persuasion, and if that information could prevent suffering of the family, it may be ethically acceptable to disclose the genetic information by requesting family, but only for diagnosis, prevention and treatment. Whether or not to share the information must be following the judgment of the ethics committee, not by the counselor.

We added two notes to the new guidelines. The first is relevant to maternal serum marker test for chromosomal abnormalities. In 1997, a survey of prenatal testing revealed that the maternal serum marker test was inadequate without correct information being available [4]. Therefore, regarding maternal serum marker test, we strongly recommended that it be conducted following the views previously stated by our committee and by the Committee of Ministry of Health and Welfare. It was stated that committee members agreed that trisomy 21 is not subject of prenatal screening, but rather the subject of non-directive counseling, a dilemma created because of the under development of genetic counseling system in Japan. They expressed an idea that medical doctors have a moral duty to inform patients about the latest medical techniques, but the maternal serum marker test need not be informed "actively" for young pregnant women, when the low risk and concern for expansion of the test as population based prenatal screening are taking into account. The second concerns pre-implantation diagnosis, no case has to date been reported in Japan. The Ethical Committee of Japan Society of Obstetrics and Gynecology (ECJSOB) held the approval in the first case of pre-implantation diagnosis of Duchenne muscular dystrophy. We expressed the idea to respect ECJSOB's decision.

Recently in Japan, commercial clinical laboratories proposed genetic testing for the general public, including cancer-relating gene, hypertension-relating gene, Alzheimer-related gene, without adequate guidance and genetic counseling. Being concerned with this issue, several scientific societies in Japan, including JSHG, Japan Society of Familial Cancer Research, Japan Society of Clinical Genetics, Japan Society of Molecular Medicine, and Japan Society of Inherited Metabolic Diseases proposed that such inappropriate testing should not be continued. We understand that commercialization of medicine is a fact, where bioethics and profit making are divergent. Enlightenment of the public and mass media is most important to avoid "genohype"[5] and a rational development of genetic testing can better be achieved. Another conclusion is that we should have an official committee to evaluate analytical and clinical validity and the clinical usefulness of the each testing [6]..

References

1, Ethical Committee of Japan Society of Human Genetics. Guidelines for genetic testing. J Hum Genet in press

2, Holtzman NE, Watson M.ed. Promoting safe and effective genetic testing in the United States. Final report of the task force on genetic testing. Johns Hopkins University Press, Baltimore, 1998

3, WHO. Proposed international guidelines on ethical issues in medical genetics and genetic services, 1998

4, Matsuda I, Suzumori K: Prenatal genetic testing in Japan. Community Genetics, 3:12-16, 2000

5, Holtzman NA: Are genetic testings adequately regulated? Science 286: 409, 1999;

6, Secretary's Advisory Committee on Genetic Testing; Enhancing the oversight of genetic testing; Recommendations of the SACGT. In http://www4.od.nih/gov/oba/sacgt.htm

Appendix: Guidelines for genetic testing from the Japan Society of Human Genetics, Council Committee of Ethics

Here we have revised the previous two guidelines proposed by the Japan Society of Human Genetics, "Guidelines for genetic counseling and prenatal diagnosis" (1995) and "Guidelines for genetic testing against genetic disease". (1996). We intend to draw the attention of medical research institutions, medical facilities, clinical testing companies, all persons related to the testing, and the media, to the importance of genetic testing, and to explain the meaning of its importance so that people would respect and follow the guidelines.

The advances in cell genetics and molecular genetics have contributed to the development of human genetics research. On the other hand, some people point out that this new knowledge has created additional bioethical debates. molecular genetics have contributed to the development of human genetics research. On the other hand, some people point out that this new knowledge has created additional bioethical debates. As a background to this lays the fact that most private infoation relating to one's biological life is contained in the human genome. tion relating to one's biological life is contained in the human genome. Also genes are inherent to the family, and by using present analytical technology, identification of an individual is possible along with the detection of specific chromosomal kartypes. ypes. Especially the number of genetic diseases that can be tested or diagnosed is increasing year by year, and the usefulness of clinical genetic analysis is widely accepted. Following this situation, important problems such as, pre and post-test genic counseling, confirming informed consent prior to the test, how to deal with remaining samples and information that were given for the genetic tests, still remain. c counseling, confirming informed consent prior to the test, how to deal with remaining samples and information that were given for the genetic tests, still remain. These problems need to be considered whether genetic tests are by chromosome tests or getic analysis (including prenatal tests, carrier tests, pre-symptomatic tests and morbidity tests), when applied in the actual genetics clinic to elucidate and diagnose genetic information. tic analysis (including prenatal tests, carrier tests, pre-symptomatic tests and morbidity tests), when applied in the actual genetics clinic to elucidate and diagnose genetic information. Persons who are involved in the genetics clinic in genetic counling or testing, must protect the person taking the test (henceforth called the subject) and their family's human rights. ing or testing, must protect the person taking the test (henceforth called the subject) and their family's human rights. Subjects must not be discriminated because of their chromosomal karyotype or their genotype; also appropriate medical care should bgiven to persons who need care. iven to persons who need care. The subjects' decision must be respected in the genetic testing. For this purpose, we propose the following items be followe


1. Genetic counseling should be conducted by a genetic counselor that has sufficient knowledge and experience of medical genetics.

2. Genetic counselors must try to give the most recent and correct information to the visitor (henceforth called the client). 2. Genetic counselors must try to give the most recent and correct information to the visitor (henceforth called the client). This includes; frequency of the disease, natural history, rate of recurrence (genetic progsis) and information about genetic tests such as carrier tests, prenatal tests, pre-symptomatic tests, morbidity tests. sis) and information about genetic tests such as carrier tests, prenatal tests, pre-symptomatic tests, morbidity tests. There is variety of genetic mutation, phenotype, prognosis, response to treatment, etc., within the same genetic disease, and personinvolved in genetic counseling should keep this fact in mind.


3. Genetic counselors should try to use simple and comprehensive words to explain all matters. 3. Genetic counselors should try to use simple and comprehensive words to explain all matters. When the client wishes, and/or it is judged that it is better to have a third person, it may be eful to have an accompaning person. eful to have an accompaning person. Explanations should be written on a clinical record book, and stored for a set time perio


4. In the case of counseling prior to genetic testing, the counselor must draw attention to the provision of accurate information concerning the purpose, method, accuracy, and especially the unavoidable limitations of testing to the subject, beyond ordinary genetic counseling. ion concerning the purpose, method, accuracy, and especially the unavoidable limitations of testing to the subject, beyond ordinary genetic counseling. In addition to oral explanation, written disease-specific information should be provided to ensure nomissions.


5. Client and their family have both the right to know and the right not to know, which should be equally respected. 5. Client and their family have both the right to know and the right not to know, which should be equally respected. Therefore, genetic counseling and genetic tests using personal identifying samples, should be based on the autonomous decisiomade by the person taking the test. made by the person taking the test. This decision should not be instructed or guided by the counselor. Under this situation, the client has the alternative not to take the test, and that they will not suffer any disadvantage should be explained. Espeally for pre-symptomatic diagnosis of adult onset genetic disease, there need to be multiple counseling sessions prior to any tests, and the decision of the subject must be shown to be the result of their own autonomous decision making.

6. Genetic tests can only be practiced after informed consent.

7. Even though the client may desire genetic testing, the doctor can refuse to provide testing, if the request is against social and ethical norms, or against their personal principles. 7. Even though the client may desire genetic testing, the doctor can refuse to provide testing, if the request is against social and ethical norms, or against their personal principles. When refusing because personal disagreement, the doctor should introduce other medical institutions.


8. In the case when a surrogate representative makes the decision, because the subject is judged to be unable to exercise autonomous decision-making, the decision for genetic testing must be made protecting the best interests of the subject. testing must be made protecting the best interests of the subject. Therefore testing children for adult onset genetic diseases that have no clear cure or prevention should be avoide


9. The fact that the symptoms vary between diseases and rely on penetrance should be explained for morbidity tests related to cancer or multifactorial inherited disease, even if a mutation is detected. ance should be explained for morbidity tests related to cancer or multifactorial inherited disease, even if a mutation is detected. Also, the fact that even if the target gene does not have any mutation, there is some possibility that the symptoms willrise, and the kinds of medical treatment needed after the test, should all be explained.


10. Genetic testing must be only performed using established and practiced techniques. 10. Genetic testing must be only performed using established and practiced techniques. The laboratories or organizations that are providing testing services should monitored according to a minimum standard, and they should conduct their own follow-up research and always strive to improve the accuracy of diagnosis.


11. The results of the genetic testing must be explained in easily understandable language to the subject. ect. Even if the testing was unsuccessful or the result was inconsistent, the results must be told to the subjec


12.When genetic counselors judge it is preferable to tell the results of the test to the subject when they are accompanied by a person whom the subject trusts, rather than on their own, the counselor should suggest this possibility. The subject can terminate the analysis of the sample at anytime, including in the middle of the analysis, and they can also decide not to know the results. Also the subject should never suffer any disadvantage for that decision.

13.Counseling after testing is essential, and should be continued as long as it is understood to be necessary. Also, medical/welfare support including psychological and social support should be prepared as needed.

14.All personal genetic information must be kept confidential and basically it cannot be told to another person unless the subject allows doing so. Utmost care is needed so this information is not used as a source of discrimination.

15. It is suggested that the result be told to family members and to have them tested if the test result can be used to prevent or cure the subjects' family members disease, not only for single gene disorders but also for multiple gene disorders (i.e. familial tumor). When the subject does not confirm to reveal the information to his family after repetitious persuasion, and that information could certainly stop the suffering of the family, it may be ethically acceptable to reveal the genetic information only for diagnosis, prevention and treatment. Whether to share the information or not should be following the judgment of the appropriate ethics committee, not by the counselor.

16. The remainder of the samples obtained for genetic testing can be stored for the future benefit of subject and/or family. The samples should not be used for purposes other than the original one. In the case that the sample may provide useful information in the future on this or related disease, written agreement from the subject must be obtained after clearly explaining that identifying personal information will be deleted for such potential use.

17. As for prenatal testing, considering present diagnostic technology and medical genetics knowledge, it is possible to state the same views as in the following additional remarks. Treatment after the test should respect the subjects' wishes, and the counselor may not participate in this decision-making. No matter what decision the subject makes, the subject and family should be supported psychologically and socially. Construction of such systems is strongly needed.

Additional Remark 1: Opinions regarding prenatal testing/diagnosis

  1. Prenatal testing/diagnosis for the first period of pregnancy includes cytogenetic analysis such as amniotic fluid tests, chorionic villus tests and fetal samples. Molecular genetics, genetic biochemistry, pathological analysis and automated diagnosis [3] are other methods.

  2. Invasive prenatal test/diagnosis, such as chorionic villus sampling and amniocentesis, should be considered when the mother wishes for the test/diagnosis in the following situations:

    1. Either one of the parents are carriers of a chromosome disorder

    2. The mother has carried or given birth to a child with a chromosome disorder.

    3. Late childbearing.

    4. The pregnant woman is a heterozygote for a severe X-linked hereditary disease.

    5. Both the parents are heterozygotes for a severe autosomal recessive gene disease.

    6. Either one of the parents are heterozygotes for a severe autosomal dominant gene disease.

    7. Other situations where the fetus is predicted to contract a severe disease.

  3. Except when testing an X-linked hereditary disease, the sex of the fetus may not be told.

  4. Clinics should strive to improve the accuracy of prenatal testing technology.

  5. As for the treatment of maternal serum marker tests, we strongly wish that it be conducted following the views previously stated by our committee, and by the Ministry of Health and Welfare Health and Science Commission on Prenatal Diagnosis.

Additional Remark 2: Preimplantation testing/diagnosis [4]

 Preimplantation testing/diagnosis is one of the genetic tests. When either one of the parents are carriers of severe autosomal dominant genetic disease, carriers of chromosomal disorders, the mother is a carrier of severe X-linked hereditary disease and does not wish for an abortion, or in an infertile couple's case where they wish strongly to have the test under informed consent following the instructions written above, they may become subjects. Still this test needs highly developed techniques and it is recognized to be at the stage of clinical research. Therefore institutions directly considering preimplantation testing/diagnosis should judge ethically and carefully.

Notes

  1. The Japan Society of Human Genetics, Council Committee of Ethics has announced the guidelines for gene tests. These guidelines are valid for members of the Japan Society of Human Genetics, and even if there are actions that might be unethical, unsocial and inappropriate under these guidelines, when a person out of this society takes the action, this guideline does not have the power to prohibit such action. In the future we consider discussing this matter with related scientific societies, and still we wish strongly for the government to set up a policy on genetic testing (see Note 5).

  2. At present, in Japan there are medical doctors certified as a clinical geneticist and medical counselors certified as a genetic counselee, and these two certifications will be unified after discussion with related scientific societies. Also, there should be a chance for training future medical genetics personnel, not only doctors, but widely for co-medical staff such as nurses and public health nurses, to better fulfill the needs of the users.

  3. Recently, using ultrasonic tests, it is possible to diagnose several fetal disorders. Therefore, explanation before conducting ultrasonic tests should be given to follow the same standard view given above.

  4. The Japan Society of Human Genetics, Board of Directors respects the view stated by the Japan Society of Obstetrics and Gynecology with respect to pre-implantation test/diagnosis and wishes that this would be conducted appropriate ethically and socially.

  5. Neil A. Holtzman, Michael S. Watson. Promoting Safe and Effective Genetic Testing in the United States-Final Report of Task Force on Genetic Testing. The Johns Hopkins University Press, 1988.

Please send comments to Email < asianbioethics@yahoo.co.nz >.

To contents page
To Eubios book list
To Eubios Ethics Institute home page