Attitudes to Genetic Engineering

Japanese and International Comparisons

Darryl R. J. Macer, Ph.D. Eubios Ethics Institute 1992


Copyright 1992, Darryl R. J. Macer. All commercial rights reserved. This publication may be reproduced for limited educational or academic use, however please enquire with the author.

7. Genetic Screening and Gene Therapy


page 110-124 in Attitudes to Genetic Engineering: Japanese and International Comparisons D.R.J. Macer (Eubios Ethics Institute, 1992).
7.1. Medical Ethics and Medical Genetics

The Medical Profession

Before moving on to look at the opinions of people over some issues in medical genetics, a brief introduction to medical ethics should be made. The healing situation requires special morals as it involves a sick, vulnerable person with a healer who is required to help, and not to exploit the vulnerability of the patient. Some physicians ground their ethical obligations in a pledge and group loyalty, claiming that physicians are a privileged group given high rank and they have a special duty to promote the welfare of others. They even claim that society has bestowed this special status on their profession. One method of controlling behaviour was the following of ethical codes and the taking of Oaths. There are various ancient oaths that have been discovered from different cultures, but the most universally honoured is the Hippocratic Oath.

The Hippocratic Oath contains a pledge of professional secrecy, which is certainly also found in the medical profession today, in a wide variety of countries. Doctors often attempt to close the discussion of medical ethics to within the profession. The pledges or promises made by the medical profession are not necessarily those desired outside of the professional group. The medical tradition is commonly called the Hippocratic Tradition, it is the system of ethical behaviour involved in the doctor/patient relationship. Some of the ideas today associated with this tradition are not to be found in the Oath itself. It is used as a basis for many traditions, such as the maintenance of high quality medical education, the idea of confidentiality, the importance of the person, the idea that medicine is more than a science but an Art of comforting, the advancement of the profession rather than the individual doctor, and the idea of medical consultation for the benefit of patients.

Japanese medical ethics is a mixture of Buddhist and Confucian influences combined with Shinto influence, and later Western influences. From the fifth and sixth century the medical profession has been restricted to the privileged classes. With the centralisation of government in the seventh and eighth centuries there was a bureau of medicine established, with the Yoro penal and civil codes creating an official physician class. Because of shortages of doctors there was room for some others. After the Heian period the government-sponsored health service was replaced by professional physicians. One code of practice was similar to the Hippocratic code. It required that physicians should always be kind to people, and devoted to loving people. There is a very strong paternalistic attitude by doctors even today. There was also a directive to keep the Art secret, and to form a brotherhood. There was concern about quacks also. Modern Japanese medical thinking has been influenced by western ideas, however the revolution of the 1960's in American and Western medical ethics is taking a long time to be accepted in Japan. Certain features of the Hippocratic tradition, especially the reinforcement of the eliteness of the medical profession, have been readily accepted by the medical profession in Japan.

The behaviour most characteristic of Japanese doctors can be called paternalism. Paternal means coming from the father, and paternalism means behaving as a father would to his children. The sick patient is vulnerable, like a child, and seeks the care of a doctor. The doctor may know what is physically best for the patient, but this may not always be what is best for the patient given the patient's life values. A recent example from Japan can be used to illustrate this point. The medically easiest procedure to treat breast cancer is to cut off the entire breast. However, in many cases the breast does not need to be cut off to effect safe treatment of the cancer, in fact targetted surgery and radiotherapy may be safer. In any rate, some women, they might even go as far as to accept a 5% risk of recurrent cancer while retaining the breast. However, for many women there is not even this degree of risk. The human being is more than a physical body, it is a complex psychosomatic whole, and not to seek the patient's opinion about which option they prefer is to treat them in a way like a dog. Doctors must ask themselves why they do not ask the patient, and what is their motive for not doing so? Is it to avoid any possibility of legal action if cancer recurres, or a loss of reputation? If the risks are explained to the patient, then the patient assumes responsibility for any future recurrence. Anyone in authority in Japan is called a teacher, "sensei", and they may feel their authority is challenged if anyone debates their decision. Doctors, politicians, or others in authority, should not be concerned about being questioned, rather this should be normal.

In October 1990 the Prime Minister's Office (N=2209, PMO 1991b) interviewed members of the public throughout Japan, who were 20 years old or more. They asked people if they thought that some new medical techniques required special ethical consideration. 75% said that some fields do, 6% said they did not, and 19% said they did not know. The following issues were raised, and the percentage of the total people that were interviewed who thought that these fields require special ethical consideration were; brain death (46.5%), organ transplantation (34.7%), terminal care (26.1%), in vitro fertilisation (24.0%), gene therapy (23.6%), and prenatal screening (20.3%). The people who thought that special ethical consideration was needed (75% of the total), were then asked how this could be done in practice (by choosing between options). 23.9% said that a multidisciplinary committee should assemble, to make a social standard, 23.1% supported the use of a special committee of doctors, who should make nation-wide standards, 9.1% supported individual hospitals and universities making their own individual standards, 36.5% supported case-by-case decision-making involving the patient, with family and attending physician, and 7.2% said they "don't know", with 0.1% saying something else. There is support for nation-wide standards by 47% of the people, but also there needs to be room for individual case decisions. In any event, a code of professional ethics needs to be accessible to the general population because it applies to them.

Recognition of Autonomy

There is one event that every human being will share. We all must die, though the process of dying may be different. Because of its importance to our lives we should recognise that decisions about death should especially involve elements of free choice. Medicine involves caring for the sick. This includes treating disease, but many diseases are untreatable, and ultimately all people will die. We need to recognise this and accept that dying should be an important part of life. We will not discuss euthanasia here, but there is a more general consequence of recognising people's differences and the importance of death and disease. That is that we allow people to make choice in many parts of their life, such as activities, marriage, occupation, and religious belief, so we should also allow them choice in their medical treatment.

This is a challenge to all health care workers, doctors, nurses, counselors and dentists. If we live in a democratic society our medicine should also be democratic. It is a challenge, especially for Japan, because patient's autonomy is generally ignored in Japan. Such a change is possible, and has occurred in America and Europe since the 1960's. In the 1990's human autonomy must be respected in medicine, politics, law, and all aspects of life. More than the challenge of new technology and increasing knowledge, is the challenge for us to respect all human beings as people with the same status but expressing different values.

Informed Consent

A vetenarian surgeon could treat a dog with a tumour on its leg without the dog's agreement. However, people are different, patients are not just animals. They have life values that are important to them that doctors should not ignore. In Japan there is a high proportion of University graduates. The educational standard of the schools is very high. As seen in this survey, the awareness of developments of science and technology is very high (chapter 3). There is no reason to treat patients as uneducated, and who are unable to understand. A good doctor can explain the situation to the patient, so the fault is clearly with the doctors. For every procedure the patient should be offered an explanation of the problem and possible solutions, and then their consent asked. This is called informed consent. This is the most important lesson of medical ethics and the most challenging problem of medical practice in Japan. The exceptions to informed consent are what we mean by the word exceptions, the general guiding principle is respect for patient's autonomy.

The doctrine of informed consent, simply stated, is that before a patient is asked to consent to any treatment or procedure that has risks, alternatives, or low success rates, the patient must be provided with certain information. This information includes at least the following, which must of course, be presented in language the patient can understand:

1. A description of the recommended treatment or procedure
2. A description of the risks and benefits of the recommended procedure, with special emphasis on risks of death or serious bodily disability
3. A description of the alternatives, including other treatments or procedures, together with the risks and benefits of these alternatives
4. The likely results of no treatment
5. The probability of success, and what the physician means by success
6. The major problems anticipated in recuperation, and the time period during which the patient will not be able to resume his or her normal activities
7. Any other information generally provided to patients in this situation by other qualified physicians

Many people would like to accept this responsibility. There are a few who may not, but this should be an exception rather than the rule, and is no reason not to apply the rule of informed consent. In the 1990 Prime Minister's Office survey mentioned before (PMO 1991b), there were also questions concerning informed consent. 63.2% said that informed consent is necessary and needs to be emphasized more, and 23% said it is necessary but is already used. Only 5.2% said that it was not especially necessary, and 8.3% said they did not know. There was more support among the young, though even among people older than 60 years more than 80% said informed consent was necessary, and only 6.4% said that it was not especially necessary. Even if one of these 5% of the people who do not think informed consent is necessary say to a doctor you should do what you think is best, it still does not mean the doctor should not talk to the patient about something major. In modern medicine there are often many alternative therapies, which present the doctor with such dilemmas. The patient may not realise there is such a variety of choices, but the doctor is still obliged to attempt to explain something of these techniques to form in their own mind which therapy is most suitable respecting this individuals life values. Remember, this is an exceptional case, not the rule. 86% of the Japanese population say that informed consent is necessary. There are also scientific studies to show that effective doctor-patient communication has a positive influence on health outcomes (Simpson et al. 1991).

Responsibility may be a burden, but we need to take it otherwise autonomy and democracy will break down. We should make decisions even if they are a bit complicated. Health care workers need to make patients make decisions, we must find the best way to do this. It will involve some time. Health care workers should have good counselling skills. Health care workers should be decision facilitators, the patients should make the decisions. This is especially true in the questions about genetic screening and gene therapy, that were the topics questioned in this survey.

Genetics and Justice

Genetics is an entire subject. The lack of national health funding for genetic screening in Japan is a major problem, and it is further complicated by the lack of any central record keeping. However, when central records are kept privacy must be absolutely maintained, which is another change required. There are many problems that are found in reproductive technology and the use of new genetic techniques. One of the areas lacking in medical ethics is distributive justice, which is a basis of the ethics behind a national health service. Medicine until very recently, has lacked any full theory of justice or the duty of physicians to treat those in need, this is in contrast to many religious views which compel physicians to actively seek out the sick. The Hippocratic ethic is individualistic, very different from the approach of classical utilitarian ethics. Physicians still seem to maintain that the physician has a special ethical obligation to benefit the patient, ignoring the net consequences for others who are nonpatients. In 1957 the American Medical Association instructed physicians that "the principle objective of the medical profession is to render service to humanity, not the individual patient", an idea also found in the Soviet physician's Oath. We cannot be individualistic, the sick must not mean the individual only, but the plural. Public health questions are important in the use of genetic screening.

Charitable medical care is an ethical duty without Hippocratic roots, but is a worthy ideal. However,with the runaway costs of modern medicine there will be times when individual patients can not be treated unless broader health policy is improved. The principle of justice will be even more essential in the next century because people can be genetically screened, and this information can reveal much sensitive information that can influence the choices that a person makes in their life. We are all different, and have different physical and mental weaknesses, but we must seek a just health care system, so that all people can be fairly treated.

Questions

The question of genetic screening and genetic therapy were addressed by a series of questions, Q9-14, which were modified from those used in the USA (OTA 1987). These questions are written in the tables, together with the results. There have been some questions on selected groups of Japanese in the past concerning these techniques, which provides some comparison (see the following sections).


7.2. Genetic Screening

Every person has a different genetic sequence, except for identical twins. The genes are made of DNA. DNA is a long chain of units, called bases, and there are only four kinds of base. Each position of the DNA can be one of the four base, and the sequence is the order of these bases. In the same way the sequence of this sentence determines what we understand in reading it, the sequence of DNA determines what happens in living organisms. There are only four possible characters for each position, but even a short sequence of 20 positions could have many possible combinations of sequence. DNA is a long chain of these units. In the cell it is normally found in pairs, two chains bound together by specific pairs between the four units. We could call one chain the parent chain and the other the complementary chain. The four bases are given the symbols, A,T, G, and C. The base A binds with T, and the base G binds with C, between these long chains, as is shown below:

------ATTCCGAAGCTGACTGA---- parent chain

------TAAGGCTTCGACTGACT---- complementary chain

DNA in the cell is normally found as a pair, it is more stable. To understand genetic screening we do not need to know any more then the fact that these four bases bind together, A to T, and C to G.

Genetic screening involves the use of this binding. A sample of DNA is taken from a cell, and then the DNA is split into single chains. The bases in this single-stranded DNA will bind to the pairing bases. To make it easier to test, this single-stranded DNA may be fixed to a plastic filter. We can test for the presence of a certain sequence in this fixed DNA by adding a solution of single-stranded probe DNA, a short sequence of synthetically made DNA with a label on it, like a fluorescent dye. After mixing the probe with the sample the probe that is not bound to the complementary sequence is washed away. If there are copies of the sequence in the sample, we will be able to see the probe when we hold the filter under ultraviolet light, because the probe is fluorescent. If there is no complementary sequence in the sample to the probe, then we will not see any fluorescence. In this way, many samples can be tested, with many probes, and this is genetic screening. We screen for the presence or absence of particular DNA sequences that represent different genes.

There are many types of genetic disease, some minor and others untreatable and fatal. One of the most common genetic diseases is inherited forms of cancer. Some genes that increase susceptibility to cancer have been shown to be very common in the population, for example, one inherited breast cancer will result in breast cancer in about one in 170 women (Beardsley 1991). The information about whether an individual has a particular DNA sequence and gene, can be very powerful, especially in the diagnosis of genetic disease. There has been further discussion of the ethical and legal issues arising from this in recent books (Holtzman 1989, CIBA 1990, Macer 1990). It is very important that privacy is respected, because the information in a person's genes identifies some of our risk to disease that medical insurance companies and employers could use to discriminate people. There are already cases of discrimination of individuals after genetic testing in North America (Billings et al. 1992).

DNA sequences can be used to identify individuals, and have been used for forensic cases. When the DNA is specifically cut up by restriction enzymes and the pieces are separated unique patterns are made, called DNA fingerprints. They have been used for over 500 court cases in the USA, and also in many other countries including Japan. In the USA a genetic register of criminals is being established by the FBI, and there is also a database in Britain. DNA fingerprints are also used for immigration cases to prove genetic parenthood. There have been disputes about the probability of two individual's DNA fingerprints matching, and calculations have recently been revised, but there is still a low probability of such fingerprints matching (when the size of the fragments of DNA made after digestion with the restriction enzymes, are the same in two individuals) (Anderson 1992a, Risch & Devlin 1992). Privacy is the key ethical issue to protect individuals, and until we can guarantee privacy and no abuse of the information, we should not establish genetic registers.

The number of human genes that have been sequenced is exponentially growing, about 5-10% may have been identified at the time of writing. An international project to map and sequence all the human DNA is called the Human Genome Project (OTA 1988a). The countries that are involved at the time of writing are the USA, Europe (especially France and the UK), Japan (Matsubara & Kakunaga 1992) and South Korea. In Europe, the European Parliament delayed scientific funding of the genome project until it had established a system to examine the ethical issues. In the USA about 3% of the human genome project research grants are being spent on research on the educational, ethical, legal and social impacts of genetic technology and genetic information. In Japan only 1% of the specific Ministry of Education research grants are to look at the educational, ethical, legal and social impacts. Even more contrast in approaches can be illustrated by comparison of two international conferences discussing bioethics and the genome project held in March 1992. At a conference held in Houston, USA (Houston 1992), scientists, theologians and ethicists gathered to join in debate on the ethical issues, with all the scientists discussing ethical and social aspects of their work reasonably well and participating in all the bioethical discussions. At a conference held in Fukui, Japan, the Second International Bioethics Seminar in Fukui (Fukui 1992), scientists joined ethicists only on paper, there was little cross discussion of the ethical issues, and many scientists actually left the meeting when the time came to talk about the ethical issues arising from their research! The discussion of bioethics and genetic technology in Japan is almost non-existent. More effort is obviously needed to educate scientists, as well as the public, and even genetic counseling is not taught at many medical schools in Japan yet.

Q9-12 were questions asking people about applications of genetic screening. The results are summarised in Table 7-1. A schematic representation of the comparative results between Japan and USA (OTA 1987) is in Figure 7-1.


Table 7-1 Attitudes to genetic screening

Sample:
Public
Students
HighSchool Biology Teachers
Total

Academics
University of Tsukuba Staff
Total Scientists
Number532 198225 706238 540

Q9. Some genetic diseases can be detected in the fetus during the early stages of pregnancy. Do you think such tests should be available under national health insurance?National health insurance
Yes76.3 74.773.3 71.471.9 71.1
No7.0 6.18.0 8.59.2 8.3
Don't know16.7 19.218.7 20.118.9 20.6

Q9b. Would you personally want such a test during (your/your spouse's) pregnancy?
Yes56.9 58.060.5 59.256.6 59.8
No16.7 12.315.3 17.220.4 17.3
Don't know26.4 29.724.2 23.623.0 22.9

Q10. If there were genetic tests that would tell a person whether they or their children would be likely to have serious or fatal genetic disease, would you approve or disapprove of making those tests available under the national health insurance through a physician?
Approve72.8 71.973.7 72.071.9 72.7
Disapprove8.1 5.08.0 7.07.2 7.1
Don't know19.1 23.118.3 21.020.9 20.2

Q11. If genetic tests become available that would indicate whether or not a person is likely to develop a fatal disease later in life, although it hasn't started yet, would you personally take such a test or not?Presymptomatic screening
Would take53.3 50.050.4 56.550.9 57.0
Would not21.3 20.223.7 20.421.6 20.6
Don't know25.4 29.825.9 23.127.5 22.4

Q12. If genetic tests become available that would indicate whether or not it was likely that your children would inherit a fatal genetic disease, would you personally take such a test before having children or not?
Would take63.2 71.466.1 68.363.6 68.8
Would not12.7 9.512.0 12.014.0 12.4
Don't know24.1 19.121.9 19.722.4 18.8

Table 7-2 Attitudes to gene therapy

Sample:
Public
Students
HighSchool Biology Teachers
Total

Academics
University ofTsukuba Staff
Total Scientists
Number532 198225 706238 540
Q13. If tests showed that you were likely to get a serious or fatal genetic disease later in life, how willing would you be to undergo therapy to have those genes corrected?
Very willing25.2 19.734.8 23.720.8 25.4
Somewhat willing29.1 31.830.4 28.926.8 28.1
Somewhat unwilling 18.026.8 11.115.1 19.215.6
Very unwilling11.7 9.610.7 13.414.9 13.6
Don't know16.0 12.113.0 18.921.3 17.3

Q14. If you had a child with a usually fatal genetic disease, how willing would you be to have the child undergo therapy to have those genes corrected?
Very willing36.9 28.439.5 30.325.1 32.1
Somewhat willing29.3 37.633.2 31.731.9 30.1
Somewhat unwilling 11.211.3 5.89.5 10.29.7
Very unwilling7.0 5.28.1 7.59.8 7.6
Don't know15.6 17.513.4 21.023.0 20.5


Figure 7-1 Comparative attitudes to genetic screening in Japan and the USA (Q12, Q11, Q9b)
Prenatal Genetic Screening

Prenatal genetic screening involves screening of the fetus, inside the mother's womb. The term prenatal screening is included in the broader term prenatal diagnosis, which also includes other tests such as those measuring protein levels. The ethical issues involved are essentially the same, except that "diagnosis" generally implies only disease is screened for, whereas genetic "screening" can be abused for screening for non-disease genes. There are several safe and commonly used methods to allow samples to be taken from the fetus (Macer 1990). In Japan there is very limited information available about prenatal diagnosis, even the existence of prenatal diagnosis services is unknown to many people. In addition to ultrasound imaging, and the sampling methods of amniocentesis and chorion villi sampling, new methods are being developed. One of the most promising is the sampling of fetal cells from the maternal bloodstream, which has already been practically performed. There are always some fetal cells that enter the mother's blood, and these cells can be separated. When the method is developed to a simpler procedure, this will allow convenient and safe genetic examination of the fetus by a simple blood sample from the mother (Lo et al. 1990, Roberts 1991). We can also screen for genetic disease in embryos before they are transferred after IVF (Handyside et al. 1990), and at the time of writing almost 20 babies have been born after preimplantation diagnosis. However, this technique will only be applicable to a few people because it is expensive and has a low pregnancy rate.

Q9 asked about prenatal genetic screening, including a question whether people thought it should be available under national health insurance, and also Q9b asked whether people would personally use prenatal genetic screening. 77% of the public answered that prenatal genetic screening should be available under national health insurance, and only 7% said that it should not be. 16% said that they were not sure. The students gave a similar result. The results from the scientists and high school biology teachers were similar, with slightly less support (71-73%), partly because of more uncertainty (19-21%).

There was greater doubt over the personal use of such testing, with 57% of the public saying that they would personally use such tests, and 17% said that they would not, with 27% undecided. Teachers and scientists were somewhat keener to personally use such tests, with 60% saying yes and 15-17% saying that they would not. The personal acceptance of prenatal genetic screening (Q9b) appears to be lower in Japan than it is in the USA, though there are less people who state that they would not use such tests, if we compare these results with those of question 32 of the OTA (1987) survey in the USA, in which 69% said that they would use the test but 27% said that they wouldn't. In the USA only 4% said that they are not sure, but in Japan 26% said they were not sure. A recent US public telephone survey (Singer 1991) found that still two thirds of respondents want to personally use prenatal genetic screening.

The two Prime Minister's Office surveys asked a general question about prenatal diagnosis in Japan (Dec 1985, N=7439, PMO (1986a), Oct 1990, N=2209, PMO (1991b)). People were asked whether it was good for humans in general to use prenatal diagnosis, in 1985 63.6% said yes, 24.7% said no, and 11.7% didn't know, and in 1990 70.3% said yes, 16.6% said no, and 13.1% said they "don't know". The results in Q9, performed in Oct 1991 on the public, suggest that the trend of increasing approval may be continuing, with 77% saying yes, and 7% saying no, though different questions were used and the question used in this survey had the extra qualification that the tests should be performed under national health insurance. The Prime Minister's Office surveys also asked people whether they thought it was good for couples to know the sex of the fetus before birth (not for sex selection, but just for knowledge), the responses in 1985 and 1990 were similar, with 35-36% saying yes, and 52-54% saying no. There was much clearer acceptance of prenatal diagnosis for the purpose of disease, the first question, than for merely knowledge of fetal sex. Similarly, the US public also reject the use of prenatal testing for fetal sex determination (Wertz et al. 1991), except in the case that a couple already has three offspring of the same sex (Singer 1991).

Prenatal genetic screening of the fetus can be used to detect characteristics of the fetus, and should only be performed for serious diseases. These include diseases that would result in serious mental or physical health damage to the fetus. In most cases the fetus is found not to be afflicted, thus removing much anxiety from the parent's mind. Without the use of such tests to confirm the absence of disease, some mothers would have an abortion. In the case that the fetus is found to be afflicted from a disease there are two different possible courses of action. If there is a therapy available and treatment before birth is necessary to avoid health damage, the fetus can be treated for the detected disease. There have been increasing numbers of operations performed on fetuses in the womb (in utero), which have avoided permanent health damage to the fetus. Sometimes the fetus is removed from the womb, operated on, and then replaced to complete normal gestation. If the detected disease is untreatable, and is serious, then the option of selective abortion is available. In Japan there is no specific law permitting selective abortion of fetuses suffering from a genetic disease, but such abortions are performed for other "reasons".

This survey did not examine the question of abortion, and it is a further issue. Genetic screening to detect fetuses suffering from disease is worthwhile if only for the above reason, of being able to treat fetuses so detected. Abortion is a personal decision, and is a much more complicated ethical issue. Some couples may decide to abort a fetus suffering from a serious disease, and other couples will not. It is still useful for a couple who do not want to abort a fetus to know if their fetus will suffer from a disease, so that they can prepare for the birth emotionally, educationally, and financially. In one study of women's attitudes to selective abortion in Japan, 407 women in Aichi prefecture returned questionnaires, including pregnant women, and mother's of children that were and were not suffering from a serious disease. 89% approved of prenatal diagnosis, and 88% agreed with abortion in the case of a diseased fetus compared to 47% who agreed with abortion in the case of an unaffected fetus (Shirai 1989). There was a trend for higher educated women to be more approving of abortion in both cases. However, there were conflicting attitudes found, such as 28% of the total approving with the right of life of a diseased fetus. In the USA, willingness to use prenatal diagnosis and attitudes toward abortion if a fetus is found to be suffering from a serious disease appear to be distinct (Singer 1991). The fetal age and severity of disease are very important determinants (Wertz et al. 1991). In the USA, even people belonging to conservative religious groups support the use of genetic testing (Miller & Schwartz 1992), but there may be a higher proportion of people who "don't know" than suggested by the OTA survey (Figure 7-1).

In the USA, families whose members suffer from cystic fibrosis appear unwilling to personally use selective abortion (Wertz et al. 1991, Miller & Schwartz 1992), though they support the right of others to use prenatal diagnosis and selctive abortion. Nowadays the life expectancy of persons with cystic fibrosis is about 40 years of relatively normal life, questioning the "need" for selective abortion of fetuses with this disease. There is a fear in Japan, especially by handicapped people groups, that the use of prenatal diagnosis and selective abortion will worsen the discrimination against handicapped adults, therefore they oppose prenatal diagnosis being used at all. There continues to be discrimination against handicapped people in Japan, and it may still be difficult for their families to get married. Another problem is that traditional people will check the family register book of their child's prospective fiance. Although the permission of the family is required to see the register (koseki), there is often pressure to show it at premarriage meetings. Part of this discrimination based on investigation of family history could be solved by dismantling the family register book, recognising people's privacy. Some people make searches of the prospective fiances' family history for signs of genetic or mental disease. Could we envisage a future request for a genetic profile? There is also discrimination of a poorly recognised minority group of people in Japan, the burakumin. They include about 2% of the population, and are generally not mentioned. It is extremely difficult for them to get married outside of their group, yet the association with the group is based only on occupation, originally including vagrants and those people dealing with the slaughter of animals. Many major companies possess an unofficial book called the Buraku chimei sokan (Buraku Locations Register), which makes it easier to detect people from this group, based on their birth towns, and not only is employment of people avoided, but there have been cases where employees have been dismissed after discovery of their roots. It is in this background that genetic screening must be viewed.

However, we should remember that many people become handicapped by accidents or diseases after birth, and these will continue even if some people use selective abortion. The outlook for a handicapped person born in Japan, is like many countries, not always good. Some families are unable to emotionally or financially support a child suffering from serious disease, and these may be the major reasons given for selective abortion. In some opinion surveys some respondents have suggested that they would not support selective abortion if the social services in the country for care and education of afflicted children and families were better. Other families may find the opposite situation, that if they keep the fetus, the child that is born may become a blessing to the family in other ways.

In many European countries routine prenatal diagnosis is offered under national health schemes to all women at high risk of having a fetus with genetic disease or chromosome abnormality. This includes all women older than about 35 years of age, and there is strong support from those women for the provision of these services to screen for serious diseases to all pregnant women (Sjogren 1992, Tymstra et al. 1991).

There is clear support for prenatal genetic screening, and that it also should be available under national health insurance in Japan. We need to avoid abuses of such screening, for non-disease conditions, such as sex selection, and for eugenic purposes, by some regulations. An extra insurance against abuse is to improve social support services for handicapped people in Japan, and to continue to educate people away from discrimination that is based on any apparent difference. Such education measures can change social attitudes towards "handicapped" as shown by studies in Canada between 1975 and 1988 (Rees et al. 1991). Most Japanese receive medical insurance from the government, and extending the coverage of national health insurance to include genetic testing would ensure all people have free and open access to such services. There is a lack of information about the availability of prenatal diagnosis outside of large cities, and there must also be concerns about the practice of genetic counselling after the results of surveys of genetic counselors in Japan (Ohkura & Kimura, in Wertz & Fletcher 1989, Shirai 1992). It may also allow the establishment of some national statistics on genetic services to ensure that the quality of services could be monitored.

Genetic Testing

Q10 asked about genetic screening for serious or fatal diseases in children and adults. 73% of the public approved of these tests being available under national health insurance, and 8% disapproved, with 19% undecided. Teachers and scientists gave similar responses. In the USA there was greater general acceptance of these genetic tests, with 89% approving and a similar 9% disapproving (OTA 1987), but the US question (Q28a) did not include the phrase "available under national health insurance". This question looks at the general idea of genetic testing, it is not linked to any particular case. A recent survey of the US public has confirmed that the majority supports genetic testing, while also finding that people are still not very aware of genetic testing technology.

Q11 asked about presymptomatic genetic testing, and 54% said that they would personally take such tests, and 21% said not, with 25% undecided. Teachers were somewhat less willing, with 50% answering that they would take and 24% saying that they would not. Scientists were slightly more willing to undergo such tests, with 57% answering that they would and 21% that they would not. In all samples there was a significant proportion of respondents who did not know (21-29%), being highest among University staff and students.

Presymtomatic testing is important for some diseases such as Huntington's disease and Polycystic kidney disease, but it must be only performed with extensive counseling. Huntington's disease generally afflicts people in their 40's, and is very disturbing. The disease-causing allele of the gene is dominant, and the children have a 50% chance of inheriting it. The children, may be close to marrying age when the parent first shows symptoms, and they may desire testing before marriage, or testing of their fetus. It is interesting to see that the level of acceptance is lower than for genetic testing in general, suggesting that people do recognise the complexity of knowing whether they will get sick in the future, or die at a premature age. Such services should be available, but only where adequate psychological counseling can be ensured. These diseases are particularly difficult because the people may experience 40 years of unaffected life (though often they experience the disease in one of their parents). Should they alter life plans if they have the gene? On the benefit side, there is considerable personal relief for people who were at risk if they learn they do not have the disease-causing allele.

Q12 asked whether people would take genetic tests to indicate whether their children would inherit a fatal genetic disease, before having children, and 64% of the public said that they would, 13% said that they would not, and 24% were undecided. High school biology teachers gave similar replies. Scientists were a little more decided, with 68% saying that they would take the tests but still with about 12% saying that they would not, and only 19% were undecided. Students were the most in favour of such tests.

The comparative results to Q11 and Q12 in the OTA (1987) survey were also marked by the low proportion of people that were not sure in the USA (3-4% only). The proportion of respondents that said that they would take the tests versus those who would not take such tests was similar in both countries (Figure 7-1). Maybe there had been greater public exposure to the possibility of such tests in the USA in 1986, compared to Japan in 1991, or it may be related to a greater tendency of Japanese to be undecided about such applications in general, as seen throughout these comparisons.

There have been genetic tests performed in Japan since the 1970's. The major motive for many people to seek genetic counseling until 1990 was premarital testing, especially by women in their 20's (Fujiki et al. 1991). The other reasons include prenatal testing, and screening as part of diagnostic therapy. There was also significant use of tests to look at the frequency of consanguinity and for signs of mental retardation (Fujiki 1988). This testing has been associated with psychological counseling, and guidelines have been developed during the course of the counseling.

The most striking result is the similarity in the responses of all groups, the public, high school teachers, and scientists have very similar mixtures of opinions. This suggests that the results obtained may be close to the real opinion of the population. Despite the support, we should only screen for treatable diseases, or to get a useful result for the individual (President's Commission 1983, Fletcher & Wertz 1990).

Some people wrote comments on the questionnaires relating to these questions, and a few examples are presented below. Most were spontaneous comments, with a few comments written in Q15 of the public questionnaires which also referred to genetic screening (unmarked are public comments, T=teacher and A=academic). Some examples:


Q9-13: "If Q7b was limited like Q9-13, my answer would be different" (Q7b was on the acceptability of human cell genetic manipulation)
Q9b: "Depends on my partner's wish" A
Q9b: "Only if there is a risk" A
Q9-14: "I don't know if Q9-14 is under present technology or in the future when you can screen for genetic disease with 100% accuracy, or if the method for changing the critical genes is established" (Q9a-1, Q9b-2, Q10-1, Q11-2, Q12-2) A
Q15: "Whenever I see the teachers and parents inside public transport trying very hard to teach the handicapped students to behave nicely, or trying to educate them that they can be loved by people in society, I feel the existence of some phenomena. A phenomena which appears as a certain % as a result of a complicated mechanism to keep the species and could apply to myself, and one which cannot be avoided for the maintenance of all human humanity. At present in Japan there is no shortage of food and it is natural to aim to make a society which includes all these people. Because I'm pregnant at the moment I always think about this." (answered "no" to Q9-12)
Q10: "We must be aware that there is some probability that a child who has a defect or hereditary disease can be born. I consider it more distressing to use therapy and tests" (answered "no" to Q10) T
Q9,12: "This question should be considered on the condition that there is sufficient social security to handicapped people. The nation or administration could make discrimination among people and challenge their right to live" T
Q10: "If it's a bad result I may get shocked"
Q10: "I don't know how the test is done" (therefore "don't know")
Q12-13: "My answer depends on whether there is an established treatment or not"
Q11-12: "If I can get well I would take the test, and if I cannot I would not take it" A
Q10: "On the condition that privacy should be respected" A
"If you can tell me 100% correctly its OK, but if I get sick after being told that I was OK I would get angry"

7.3. Gene Therapy

Many genetic diseases may be able to be treated by correcting the defective genes, by gene therapy. Gene therapy is "a therapeutic technique in which a functioning gene is inserted into the somatic cells of a patient to correct an inborn genetic error or to provide a new function to the cell" (Anderson 1992d). There are a number of human gene therapy trials currently underway, for several different diseases including several cancers (Culliton 1991, Gutierrez et al. 1992). At the time of writing there have been 16 human gene transfer or therapy trials approved by the Recombinant DNA Advisory Committee (RAC) in the USA, and trials approved in Lyon, France and Shanghai, China. It is still an experimental therapy, but if it is safe and effective, it may prove to be a better approach to therapy than many current therapies, because gene therapy cures the cause of the disease rather than merely treating the symptoms of a disease. Also, many diseases are still incurable by other means.

Currently such gene therapy is not inheritable, we need to have much wider discussion about the ethics and social impact before we start inheritable gene therapy (President's Commission 1982, OTA 1984, EMC 1988, Macer 1990). However, non inheritable gene therapy to treat patients involves similar issues to any other therapy, and if it is safer and more effective, it should be available to patient's who consent to it. There are many approaches being developed (Macer 1990, Bluestone 1992) and we can expect rapid introduction of these techniques, because of more than 20 years of preparatory experiments on animals, and the success of some of the current clinical trials.

The results of questions on public acceptance of gene therapy are presented in Table 7-2. Q13 asked whether people would personally undergo gene therapy to correct a serious or fatal genetic disease later in life, and it used a four point acceptance scale, and a "don't know" answer. 54% of the public sample were either very or somewhat willing, and 29% were somewhat or very unwilling, with 16% undecided. Q14 asked people whether they would be willing for their child to undergo genetic therapy, and there was higher acceptance, with 66% willing and 18% unwilling, with 16% undecided. Teachers were more accepting, with 65% willing and 22% unwilling, and 13% undecided, about gene therapy on themselves, and 73% willing and 14% unwilling to allow gene therapy on their children. Scientists were slightly more willing to use gene therapy on themselves than the public in general, but gave similar responses for gene therapy on their children. Students were somewhat less willing to use gene therapy, but similar in total agreement to the use of gene therapy to the public.

There is less willingness to use gene therapy in Japan than in the USA, though as in the cases involving genetic screening, there is a high proportion of undecided respondents in Japan (in the USA only 2-3% of the people were undecided (OTA 1987)). Like the US survey, there was greater acceptance of using gene therapy in children than personal use, see Figure 7-2.

In the two Prime Minister's Office surveys of public opinion in Japan, described above (PMO 1986a, 1991b) people were asked whether they thought it was good for humans to use gene therapy to cure genetic disease. In Dec. 1985 45.7% said yes, 29.5% said no, and 24.9% didn't know. In Oct. 1990 52.3% said yes, 23.9% said no, and 23.8% didn't know. In the mid-1980's some people in Fukui were asked the question whether they agreed with the use of gene therapy to correct thalassemia (Fujiki 1988). The sample was people who came for genetic counseling (78 men and 93 women), plus some samples of housewives, nurses and medical students. The general level of agreement was about 60%, with about 10% disagreing, and about 30% undecided. Junior medical students expressed 75% support for gene therapy before seeing patients suffering from genetic disease, but only 61% support after, in both cases 4-5% disagreed (Fujiki et al. 1991). They were also more undecided about selective abortion of a Down's syndrome fetus (from 68% agreement to 52% agreement, with 5-9% disagreement), after such an experience.

Some examples of the comments people wrote on the questionnaires regarding gene therapy are below. In the questionnaires received by mail response from the public, Q15 asked people what source was important in making their choices. It was intended in a general way, but some comments specifically referred to Q13 or Q14, and are interesting. Some examples:

Answered "don't know" to Q14:
Q13: "Because I don't know the conditions now. According to the circumstances I would select 'somewhat willing' for Q13"
"Rather than changing the genes I won't give birth"
"Can't judge because I don't know how dangerous the treatment is, how serious the disease, and what it costs, etc."
"Because I don't have a problem with such children"
"At present I don't know, but we have to think carefully about curing genetic disease by science, because to have genetic disease is also that child's destiny"

Answering 1 or 2 to Q14 (willing to use gene therapy):
"Only if I recognise myself as ill, and could recover from my disease"
"Because I hope that people are in good health"
"It's good if we can prevent disease beforehand"
"Our own child had a heart disease, the operation failed, and he died aged 4 years, 7 months and 25 days old."
"I will want to do everything to cure"
"Rather than giving up 100%, even if there is little chance of success it's good to try"
"In the past we couldn't do, but if present techniques can make these things possible, I want to treat"
"When the treatment has a high % success rate its OK"
"No special information, but it's a parent's responsibility to children"
"I haven't got any special information source, but as a parent"
"If it will contribute tohuman life, like lengthening life or curing disease, science should be developed"
"Because as a parent I want to save my children"
"From a religious viewpoint I'm against artificial things, but if my children will be killed otherwise I want to use it"
"Because I want normal children"
"If that person can lead a healthy life by doing this"
"Because I have a light hereditary disease"
"I'm not confident that I can bring my children up if they are handicapped"
"Love of child"
"Depend's on the children's wish" A

Answering 3 or 4 to Q14 (not willing to use gene therapy)
"It is natural for recessive genes to exist and we shouldn't artificially remove them"
"It's too selfish to think of lengthening human life, we should keep research within the context of protection and harmony of the natural environment"
"Children become adults, and they should decide for themselves"
"Against nature"
"It's unclear whether it is 100% successful or not"
"Shouldn't make a child. If it's my own thing I leave to destiny" T

The responses expressed in this survey obviously also depend on the circumstances that people have experienced. The conclusion is that there is support for gene therapy to treat disease in Japan, and only about one fifth of the population are against it, and this proportion may be decreasing since 1985. The results of the Prime Minister's Office surveys are consistent with the values obtained in the current survey, though the questions were somewhat different. There is, however, stronger support for the use of gene therapy on children than in the general case, or for personal use, which was the situation examined in the public opinion surveys by the Prime Minister's Office.


Table 7-2 Attitudes to gene therapy

Samples arranged in columns across the page:
Public; Students; HighSchool Biology Teachers; Total Academics; University of Tsukuba staff; Total Scientists

Number 532 198 225 706 238 540

Q13. If tests showed that you were likely to get a serious or fatal genetic disease later in life, how willing would you be to undergo therapy to have those genes corrected?
Very willing 25.2 19.7 34.8 23.7 20.8 25.4
Somewhat willing 29.1 31.8 30.4 28.9 26.8 28.1
Somewhat unwilling 18.0 26.8 11.1 15.1 19.2 15.6
Very unwilling 11.7 9.6 10.7 13.4 14.9 13.6
Don't know 16.0 12.1 13.0 18.9 21.3 17.3

Q14. If you had a child with a usually fatal genetic disease, how willing would you be to have the child undergo therapy to have those genes corrected?
Very willing 36.9 28.4 39.5 30.3 25.1 32.1
Somewhat willing 29.3 37.6 33.2 31.7 31.9 30.1
Somewhat unwilling 11.2 11.3 5.8 9.5 10.2 9.7
Very unwilling 7.0 5.2 8.1 7.5 9.8 7.6
Don't know 15.6 17.5 13.4 21.0 23.0 20.5


Figure 7-2 Comparative attitudes to gene therapy in Japan and the USA (Q13, Q14)
Table 7-3 (EXTRA) Attitudes to gene therapy in Japan and the USA
Sample:
Public
Students
School Biology Teachers
Total

Academic
Total Scientists
USA

Public

(OTA,1987)
Number532198 225706540 1273
Q13. If tests showed that you were likely to get a serious or fatal genetic disease later in life, how willing would you be to undergo therapy to have those genes corrected?
1. Very willing25.2 19.734.823.7 25.435
2. Somewhat willing 29.131.830.4 28.928.143
3. Somewhat unwilling 18.026.811.1 15.115.612
4.Very unwilling11.7 9.610.713.4 13.69
5. Don't know16.0 12.113.018.9 17.32
Mean of 1-42.192.30 1.972.222.21 1.97
Q14. If you had a child with a usually fatal genetic disease, how willing would you be to have the child undergo therapy to have those genes corrected?
1. Very willing36.9 28.439.530.3 32.151
2. Somewhat willing 29.337.633.2 31.730.135
3. Somewhat unwilling 11.211.35.8 9.59.77
4.Very unwilling7.0 5.28.17.5 7.64
5. Don't know15.6 17.513.421.0 20.53
Mean of 1-41.861.92 1.801.931.91 1.63

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