pp. 27-29 in Protection of the Human Genome and Scientific Responsibility

Editors: Michio Okamoto, M.D., Norio Fujiki, M.D. & Darryl R.J. Macer, Ph.D.

Copyright 1996, Eubios Ethics Institute All commercial rights reserved. This publication may be reproduced for limited educational or academic use, however please enquire with Eubios Ethics Institute.

Tokyo Session

Issues Related to Chromosomal Mutations

Masamichi Sakanoue(
Vice-President, Japan Medical Association


In the 1950s, the study of chromosomes began with the creation of a genetic map concerning amino acid-requiring genes of microorganisms that served as a method to identify what genes were on chromosomes. This genetic map thereafter evolved to deal with living things when a study was made on Drosophila, a suitable species for chromosome research, to investigate frequency in the emergence of mutations.

Biological theory to prove that genes determine the body and structure of a human being, reached the argument taken for granted today that DNA on chromosomes transfers information to ribosomes through m-RNA, and amino acids in protoplasm are transferred by T-RNA to form polypeptides. The fact that information transfer between DNA and RNA is performed by Watson-Crick's combination of bases - adenine (A), thiamine (T), guanine (G) and cytosine (C), (Uracil (U) to replace T for RNA), was discovered in the mid 1960s and is now a matter of common knowledge.

Exemplification of Mutations

It is common knowledge in the clinical field that sex chromosomes involve Turner's syndrome and Klinefelter's syndrome. A full account of their clinical symptoms is not given here, but they occur at the respective rate of about l/800 and about l/500.

Most common to groups D, E and G of chromosomes, is trisomy that keeps a man alive after birth. There may be no need to explain in detail its clinical symptoms, but the occurrence rate is allegedly 1/3000 to 1/5000 for Group-D trisomy and 1/6000 to 1/1000 for Group-E trisomy. The incidence of Group-G trisomy, 21 trisomy or Down's syndrome is 1/677 in Japan; 1/765 in Denmark, 1/636 in the USA and 1/666 in the UK. As shown in Table 1, however, the higher the age of mother, the higher the rate of occurrence. The reason given for this phenomenon is that as the ootid continues to exist from prenatal life of the mother to adulthood, they remain under a stronger effect of environmental factors. However, in view of Terry Hassold's data shown in Table 2 that proves the contribution of paternal genes to trisomy, it would be proper to say that the cause of trisomy is still unknown.

Response to Mutations

Discussed now are ethical, legal and social issues. Antenatal diagnosis of amniotic fluid permits the diagnosis of chromosome abnormality. In the event of chromosome abnormality, abortion can be a choice of parents. Whether or not to permit abortion must be resolved by the Ethical Committee in the facility taking the wills of parents into consideration. The Ethical Committee is required to be in operation on a regular basis as per specific principles.

Artificial miscarriage due to embryonic abnormalities including mutations, requires a profound debate, in order to reach a conclusion because no stipulations are available for embryos or fetuses in the Japanese laws. Close communications with parents are of critical importance in the process of making a decision.

Down's syndrome is classified into trisomy, a mutation, and translocation that is illustrated in Figure 1. In the case of translocation, as a parent or parents have causative genes, unlike in the case of a mutation, there is a strong possibility for members of the family to suffer Down's syndrome. In this case, genetic counseling is necessary.

Mutations are abnormalities that occur at a certain probability as long as the human race remains to exist. It should, therefore, be assumed that any families can be destined to this syndrome by accident, and a certain percentage of all carriers of this syndrome are from these families. Society calls for principles and specific measures to deal with this issue as an issue involving society at large. This is the idea of "Normalization" that advocates socio-ethical consideration for the handicapped.


Table 1: Occurrence rates for Down's syndrome by Mother's Age

Mother's Age; Frequency of DS birth; Frequency of repeated delivery of DS baby
20-24 1/1500 1/500
25-29 1/1000 1/400
30-34 1/800 1/300
35-39 1/400 1/100
40-44 1/80 1/30
45-49 1/40 1/10

Table 2: Contribution of Parental Age (T. Hassold - abbreviated for on-line)

Trisomy N. of cases Paternal %
2-12 16 19
13 7 29
14 8 25
15 11 27
16 62 0
18 73 4
21 436 7
22 11 0
XXY 133 44
XXX 47 6

Figure 1: Various Types of Trisomy 21


Appendix: The Ethics Committee of Kitasato University School of Medicine and Hospital

The Ethical Committee is comprised of three subcommittees A, B and C whose functions partially overlap with each other. We could picture a set of three mutually overlapping circles. Subcommittee A is constantly engaged in ideological discussion. The Institute of Medical Humanities is an academic organization supporting this subcommittee A. Subcommittee B serves as IRB to control research from an ethical viewpoint. Subcommittee C is responsible for ethical judgments on medical service in the hospital. These subcommittees respectively call a meeting once a month. One third of their members are expected to include women and experts from outside. Additionally, our hospital has Medical Audit and Advisory Committee currently in service on a full time basis to control the quality of medical services.

Principles of Ethics Committee of Kitasato Univ. School of Medicine & Hospital

Medical care is a service to remove human suffering, rendered by the medical worker with professional expertise to meet the expectation of those suffering from mental as well as physical distresses, but its goal is achievable only through the collaboration of the service provider and receiver. Thus medical care is both scientific and ethical acts presupposing the interaction between the patient and the medical worker. In the similar way medical research which underlies the medical care involves ethical issues.

In either case, we understand that the so-called "medical ethics" is an idea inherently and originally present in medicine per se rather than something that controls medicine. It should respect life and integrity of an individual above anything else.

School of Medicine, Kitasato University and its Affiliated Hospitals have installed the Ethics Committee to ensure a high ethical standard in the fields of medical researches and clinical medicine, and to pursue an ideal in an attempt to find its application to practical measures.

Persons expected to meet the challenge are characterized by their multidisciplinary backgrounds. First of all, medical workers should learn what is the ideal way of medical care. In medical profession, be it clinical or basic, both individuals and groups need to strictly abide with ethical standards and at the same time request similar ethical compliance from their peers.

Secondly, medical care is a responsibility consigned to medical workers by the society to respond to the sufferings and pains of the patient. With the rapid advance in medicine and medical technology and changes in the pattern of diseases in recent years, medical care has come to involve the life of many people extensively and has become available to all the people. It is compelled, on the other hand, to meet the diversified needs and respect individual sense of values of those requiring medical care. This means that medical workers should not be preoccupied with their specialities alone in choosing the methodology for medical care and in making practical judgments in the daily care of patients. They should constantly be made aware of the ways of people's thinking and of the society and to make appropriate feedback.

The Ethics Committee consists of three sub-committees each of which is characterized by its distinct composition and operation. For there is a need to function in response to the medical ambivalence as mentioned above, and to utilize and convert occasional inconsistencies to active energy, thereby approaching the goal as soon as possible.


To next chapter
To contents list
To contents list in Japanese
To book list
To Eubios Ethics Institute home page