Darryl R. J. Macer, Institute of Biological Sciences, University of Tsukuba, Ibaraki 305, JAPAN; Eubios Ethics Institute, 31 Colwyn Street, Christchurch 5, New Zealand
Shiro Akiyama, Institute of Biological Sciences, University of Tsukuba, Ibaraki 305, JAPAN
Angeles Tan Alora, Southeast Asian Center for Bioethics, University of Santo Tomas, Espana, Manila, Philippines
Yukiko Asada, Institute of Biological Sciences, University of Tsukuba, Ibaraki 305, JAPAN
Jayapaul Azariah, Department of Zoology, University of Madras - Guindy Campus, Madras 600 025, INDIA
Hilda Azariah, Center for Advanced Study in Botany, University of Madras - Guindy Campus, Madras 600 025, INDIA
Maureen V. Boost, Department of Health Sciences, Hong Kong Polytechnic, Hung Hom, Kowloon, HONG KONG
Prasert Chatwachirawong, Faculty of Agriculture, Kasetsart University, Kamphaeng Saen, Nakhon Pathom 73140, THAILAND
Yuko Kato, Institute of Biological Sciences, University of Tsukuba, Ibaraki 305, JAPAN
Vijay Kaushik, Institute of Philosophy, Russian Academy of Sciences, Moscow, RUSSIA
FrankJ. Leavitt, Jakobovits Center for Jewish Medical Ethics, Faculty of Health Sciences, Ben Gurion University of the Negev, 84105 Beer Sheva, ISRAEL.
Nobuko Y. Macer, Eubios Ethics Institute, 31 Colwyn Street, Christchurch 5, New Zealand
Chin Choon Ong, Department of Chemical Process and Biotechnology, Singapore Polytechnic, 500 Dover Rd, SINGAPORE 0513
Peerasak Srinives, Faculty of Agriculture, Kasetsart University, Kamphaeng Saen, Nakhon Pathom 73140, THAILAND
Miho Tsuzuki, Institute of Biological Sciences, University of Tsukuba, Ibaraki 305, JAPAN
Gene therapy is in clinical trials in a number of countries, raising the question of whether different ethical standards can be justified in different countries. One key issue is how divergent are the perceptions and bioethical reasoning of peoples around the world.
An International Bioethics Survey with 150 questions including 35 open ones was developed to look at how people think about diseases, life, nature, and selected issues of science and technology, biotechnology, genetic engineering, genetic screening, and gene therapy. The mail response survey was conducted in 1993 among the public in Australia, India, Israel, Japan, New Zealand, Russia, and Thailand, and the same written survey was conducted among university students in Australia, Hong Kong, India, Japan, New Zealand, The Philippines, Russia, Singapore and Thailand. Similar questions were included in an international high school education bioethics survey among high school teachers in Australia, Japan and New Zealand. Further international comparisons to the USA and Europe are made.
About three quarters of all samples supported personal use of gene therapy, with higher support for children's use of gene therapy. The diversity of views was generally similar within each country. The major reasons given were to save life and increase the quality of life. About 5-7% rejected gene therapy considering it to be playing God, or unnatural. There was very little concern about eugenics (0.5-2%), and more respondents gave supportive reasons like "improving genes", especially in Thailand and India. Support for specific applications was significantly less for "improving physical characters", "improving intelligence" or "making people more ethical" than for curing diseases like cancer or diabetes, but there was little difference between inheritable or non-inheritable gene therapy.
The application of human genetics raises ethical issues, and some of these issues have been a major stimulus for bioethics and medical sociology. The ethics of gene therapy has been debated for many years and this debate is also closely linked to public and political opinion (Carmen, 1993). There have been several surveys published concerning public acceptance of gene therapy (OTA, 1987; Macer, 1992a, 1992b; March of Dimes, 1992). There have been many surveys in a range of countries published on attitudes to biotechnology and genetic engineering in general (Eurobarometer, 1993; Macer, 1994a, 1994b; Zechendorf, 1994). However, opinion surveys are prone to bias and numbers may be misused only to provide a scientific aura to reinforce pre-existing views. We need to develop approaches to examine the reasoning that people have, which may allow us to better predict the social impact of genetics. Therefore in this survey some open questions were used to explore the reasoning that different people used (Macer, 1994b).
The widening international use of gene therapy also makes us ask whether regulations should be national and or international, and whether different standards can be justified in different countries. The call for international approaches (including education and guidelines) is based on several arguments, including shared biological heritage and destiny of human beings in all "nations", and the transitory nature of "nations" and the precedents for international law to protect common interests of humanity (Macer, 1994c). There are currently efforts to make international guidelines for gene therapy, particularly by UNESCO (Butler, 1994). Those calling for national guidelines argue that each culture should make its own standards because of national autonomy (Bonnicksen, 1994), and because people in each country have different attitudes. Perhaps the key balancing issue is how divergent the perceptions and bioethical reasoning of peoples around the world are.
It has become standard in ethical debates about gene therapy to divide it into somatic cell gene therapy and enhancement, and germ-line gene therapy and enhancement (Anderson and Fletcher, 1980; Anderson, 1989; Walters, 1991). In the US NIH and FDA guidelines, the only class that is generally approved is somatic cell gene therapy to treat a disease or somatic cell gene transfer as a marker involved in development of medical therapy (Kessler et al., 1993). This is also true of all European (Mauron and Thevoz, 1991), Australian, Japanese (Macer, 1994c), and Canadian (Canada, 1993) guidelines and reports. We also see this reflected in the 1994 Council of Europe Draft Bioethics Convention (Nelki, 1994), which bans germ-line interventions, but notes that possible future exceptions could be permitted. There have been concerns that scenarios of germ-line gene enhancement may ignite public opposition to somatic cell gene therapy, and therefore a distinction has been maintained (Anderson, 1992). However, there are still frequent calls for its discussion (Fletcher and Anderson, 1992; Wivel and Walters, 1993).
Such distinctions are also being discussed in the formulation of international law in UNESCO. The UNESCO International Bioethics Committee is drafting general guidelines and an international declaration on the human genome and human genetics, that it is hoped will be approved by the United Nations General Assembly in 1998, the 50th anniversary of the Declaration of Human Rights (Butler, 1994). As one of the members of this committee, I would summarise the positions adopted in the 1994 report on gene therapy as:
1) encouragement of somatic cell gene therapy for any disease, not only genetic disease,
2) not making somatic cell gene enhancement or germ-line gene therapy illegal,
3) outlawing germ-line gene enhancement.
It is therefore interesting to look at how public opinion relates to the academic discussion of the ethics of gene therapy, given that public opinion will be an important factor in deciding what sort of applications of gene therapy that companies and researchers can implement.
This paper describes a survey method that may be used to provide data to explore people's reasoning about gene therapy, and data on perceptions of gene therapy in Australasia and Asia as a reference point for further international comparisons. Respondents made very interesting comments, and some are given. The diversity of comments was generally found to be the same in different countries, suggesting that reasoning about these issues goes deeper than cultures, or religions; which in itself is interesting from a sociobiological viewpoint, and also supports international approaches to regulation. This paper also reports relevant results from a high school bioethics education survey conducted in Australia, Japan and New Zealand.
International Bioethics Survey
Questionnaires including 150 questions in total, with 35 open-ended questions, were developed to look at how people think about diseases, life, nature, and selected issues of science and technology, biotechnology, genetic engineering, genetic screening, and gene therapy (Macer, 1994b). The questions about gene therapy were based on surveys conducted in the USA in 1986 (OTA, 1987) and 1992 (March of Dimes, 1992), and 1991 in Japan (Macer, 1992a, 1992b, 1994a). The two open questions (Q26, Q27) are below:
The simple open question, "why?", should not lead respondents into set responses, and was added to look at people's reasoning. The ideas in each comment were assigned to different categories, which were compared.
Another question directly concerning gene therapy was Q28 (See Table 3), which used specific cases and fixed response options and compares approval of therapy for different cases. There was also a question "Can you tell me how much you have heard or read about each of these subjects?", with a list of eight topics including "human gene therapy", and the responses, "Not heard of", "Heard of", or "Could explain it to a friend" (Table 1). Respondents who gave the third response could be generally assumed to know something about gene therapy, however, there was no question asking the respondents to explain what they thought gene therapy meant.
The survey was performed in 1993 in ten countries of the world, in English in Australia (A), Hong Kong (HK), India (IN), Israel (IS), New Zealand (NZ), The Philippines (P) and Singapore (S); in Japanese in Japan (J); in Russian in Russia (R); and in Thai in Thailand (T). Translations were checked by professional translators and questions were pretested (Macer, 1994b). Three population samples were chosen for these International Bioethics Surveys: the general public, university students and high school teachers. The questionnaires consisted of 6 A4 size pages with a 1 page introductory letter including a form for the public and teachers to request a summary of the survey results. The public and student questionnaires were identical. The teacher's survey included some of the same questions, but half of the questions were about teaching and curriculum in bioethics and genetics (Macer, 1994). The surveys to public and teachers were sent within each country with stamped return envelopes, and people were asked to respond. The responses rates and sampling dates are in Table 1.
Questionnaires were distributed randomly nationwide by hand to the public in Australia, India, Japan, New Zealand, and Thailand. The samples were chosen by a clustered random sampling method, involving selection of a representative cross-section of the community on maps combining both rural and urban areas chosen by randomly choosing names from all possibilities within the chosen provinces. Inside those localised areas every second house on both sides of every second street had a questionnaire delivered into the letterbox. Personal contact was avoided to attempt to standardise response, even if this may have adversely affected response rates. In each cluster of sampling no more than 50 questionnaires were delivered, and generally around 30 questionnaires per area. More than 80% of the questionnaires in Australia, Japan and New Zealand were delivered by D.M. and N.M., to help standardisation.
In India and Thailand some members of universities and institutes were also asked to deliver questionnaires, and although the clustered sampling method was used, this explains the higher representation of more educated persons in the samples than the general population. The survey in India and Israel was also restricted to areas where it could reasonably be expected to find English speaking persons, as the questionnaire was written in English. The sample size from Israel is not sufficient nor random, and this sample is only included as a preliminary observation. The survey in India is large but is not representative of the whole country, rather only of those who can speak English, and of the southern regions of India where most of the sampling was made.
The surveys in Israel and Russia included half public and half academics (including philosophers, molecular biologists, general humanities and science, and medical graduates), and included random delivery to institute members and to households, in the manner described above. The Russian sample included 56% from Moscow, 22% from Ufa, and 22% from Peterozavodsk, and does not therefore represent the rural section of the population of Russia.
Some sample characteristics are shown in Table 1 (Macer, 1994b). The public samples from New Zealand (N=329), Australia (N=201) and Japan (N=352) were representative of the general population, while the samples from India (N=568), Israel (N=50), Russia (N=446) and Thailand (N=680) had higher education than the general population, and this must be considered in discussion of the results. In India and Israel surveys were conducted in English, which is not spoken by the whole population, introducing a selection bias for higher education level.
Student samples were obtained with the kind assistance of the persons indicated below. The surveys were distributed by staff of the universities, and returned to a following class or departmental mail box. The samples include: medical schools in Australia (Peter Singer, Monash University, N=110), Japan (Michio Hirayama and Norio Fujiki, Fukui Medical School, N=127; Hideo Hayashi, University of Tsukuba, N=308), New Zealand (D. Gareth Jones, Otago University, N=96), the Philippines (Angeles T. Alora, University of San Tomas, N=164); a medical laboratory course in Hong Kong (Maureen Boost, Hong Kong Polytechnic, N=105); and biology students in India (Jayapaul Azariah and Hilda Azariah, University of Madras, N=325), Singapore (Lim Tit Meng, University of Singapore, N=23; Ong Chin Choon, Singapore Polytech, N=227) and Thailand (Peerasak Srivines and Prasert Chatwachirawong, Kasetsart University, N=232).
The high school teacher surveys were national, using randomly selected schools from published school lists. All 438 high schools in New Zealand were surveyed. Two copies of the questionnaire, with two stamped return envelopes, were sent along with a covering letter to the principal requesting that they randomly give one each to a biology and a social studies teacher. The samples of respondents included more biology teachers than social studies teachers; Japan (N=560 biology; N=383 social), New Zealand (N=206 biology; N=96 social) and Australia (N=251 biology; N=114 social); and these are treated separately.
General information gathered in the surveys included sex, age, marital status, children, education, religion, importance of religion, race, income and rural/urban locality (Table 1). Results of the other questions, further background, and more examples of open comments have been published (Macer, 1994b). In this paper the word "significant" implies a statistical significance of P<0.05.
|%'s of total respondents|
|N (returned questionnaires)||329||201||352||551||568||689||446||50||96||110||435||325||232||164||250||104||206||96||251||114||560||383|
|Response rate (%)||22||13||23||26||57||36||43||<20||60||70||66||65||50||70||80||52||61||28||47||21||37||26|
|More than2 children||31||29||14||17||7||13||5||21||0||0||0||0.4||0||0||0||0||28||38||32||35||18||18|
|2 year college/technical||18||15||19||22||6||3||18||20||48||4||6||13||18||0||77||3||1||2||0.4||1||0.2||1|
|How important is religion?|
|Not too important||27||24||40||-||15||8||28||34||18||20||34||18||7||0||22||26||33||32||19||10||45||36|
|Not at all important||20||26||17||-||18||2||24||12||34||20||45||22||0.4||0||5||13||30||22||16||17||23||17|
|Awareness of human gene therapy|
|Not heard of it||26||23||23||-||27||10||22||20||7||16||6||19||15||8||25||29||2||26||4||20||3||21|
|Heard of it||57||50||58||-||47||70||57||48||28||48||56||55||71||66||59||55||22||44||16||40||35||61|
|Could explain it to a friend||17||27||19||-||26||20||21||32||65||36||38||26||14||26||16||16||76||30||80||40||62||18|
1J91 from Japan 1991 survey (Macer, 1992a, 1992b).
Awareness of gene therapy
The awareness of gene therapy was examined only by personal opinion of the respondents, with the results shown in the bottom of Table 1. The awareness of gene therapy was the lowest among the 8 developments in science listed (others included pesticides, in vitro fertilisation, computers, biotechnology, nuclear power, AIDS, genetic engineering) (Macer, 1994b). The samples with the greatest awareness were biology teachers, next were medical students (New Zealand, Japan, Australia and the Philippines), followed by the other groups, social studies teachers, biology students and the general public (Table 1).
In the USA in 1992, when asked "How much have you heard or read about gene therapy, 60% said "almost nothing", 26% said "relatively little", 10% a "fair amount", and 3% "a lot" (March of Dimes, 1992). In the International Bioethics Survey, the term "genetic engineering", was significantly more familiar in all samples. Awareness of both terms was significantly related to educational attainment. There was no question requiring respondents to explain their understanding of technologies. An indirect measure of the depth of knowledge was gained through the responses to the open questions.
Reasoning expressed about gene therapy
About three quarters of all samples supported personal use of gene therapy (Q26), with higher support for children's use of gene therapy (Q27), as shown in Table 2. The acceptance of gene therapy was somewhat higher among students than the public, but there was greater difference seen among countries. Indians were the most supportive, and Thais the least for personal use, but when asked about use on children, Thai respondents were among the most willing. When compared to the USA results, we find a general tendency for Asians to be more accepting of gene therapy. We did not find any significant differences dependent upon sex, age, education or religiosity.
It is interesting methodologically that we find the least number of people who say that they "don't know" in the USA surveys using telephone interviews. We think it is inconsistent with the idea that the low response rate of mail surveys selects those who are more informed and have made up their mind compared to the higher response rates of telephone surveys. Separate questions in the US surveys exploring knowledge of gene therapy did not find the samples to be especially well informed (OTA, 1987, March of Dimes, 1992). We also know the educational attainment of the respondents in the mail surveys were at least as high as the US sample, so the response "don't know" refers to the decision itself, and the results suggest it is relatively independent of education (i.e. no significant general trends were found in the data). One third of Russians said that they did not know, the highest of all samples, however, as noted, their level of education was high (Table 1). The low percentage of don't know responses in the USA makes us question the reliability of telephone surveys for predicting decision-making, and it is a point for further analysis in the future. There are several ways to interpret this, and it may be that people don't like to admit they don't know on the telephone.
The reasons people gave are among the more interesting parts of the surveys, and are the major benefit of mail surveys with open questions. Many are given in Macer (1994a). The ideas expressed in each comment were assigned to categories, with up to two categories per comment. This method was used for general questions on genetic engineering in a Japanese survey in 1991 (Macer, 1992a, 1992b). In that survey the same two questions were used (Q26, Q27), and it was found that some respondents wrote comments on the questionnaire. Therefore we decided to add the question "why?" to the specific gene therapy questions, as well as to other questions.
To illustrate the process that was used, some comments are quoted below. The questionnaires provide an interesting resource of peoples comments, and further analysis is possible on more specific themes within the comments. The following are examples of open comments, under the "reasons" which appear in Table 2 (Abbreviation codes: V=very willing; W=somewhat willing; U=somewhat unwilling; X=very unwilling; D=don't know; Q26 or Q27; comments from the same person are separated by ";")
I don't know how I would react if faced with life or death. 26D
It is doubtful whether such therapy exists or is possible. 26D
I don't know without consideration of the future with my family. 26D
I cannot answer by only this information. 26,27D
I feel like taking it to be healthy, however, I am afraid also because it may be against God's will. But when I think of my children, I might have them take the therapy because I am sorry for them and I have responsibility as their parent. 26,27D
Endeavour to save life or make the child more comfortable. 27V
To prolong my life! 26V
Mother instinct to try anything for her child. 27V
To possibly prevent future illness. 26V
Basic survival instinct. 26W; Would step over all principles to save my child. 27V
If I can become healthier. 26W
The happiness of mine and my family is more important than the future of the human race. I cannot be such a good-natured person. 27V
I cannot understand the meaning of the question. There must be no parent who doesn't want to treat a fatal disease of their child, except those who believe in a peculiar religion. Many parents may be at a loss when to answer to this question. 27V
Since I think it is an instinct to want to be helped without reasons if the death is faced immediately. Also, since it is parental love to want to help the life of their child above anything else. 26,27V
I don't want to see my kids go through life with pain and not knowing when or what's going to happen to my kid latter on in life. Or whether my kid will live through life. 27V (+save live)
So I won't be a burden on anyone. 26V
If it would help I would - I have a young family that I feel responsible for and I would feel I'd let them down if I didn't try. 26V
To live a full life, ease the burden on care giver. 26V (+ quality of life)
I would take what help is available - so that I am not a bother to other people. 26V (+ save life)
I love my daughter and could not live without her. 27W (+ save life)
People around me may have trouble and I don't want them to do so. 26,27V
Because we have the right to give birth to babies. 26V
Not to have a heavy burden to people who are around, like family. 26V
Improve quality of life
To enjoy life as best as possible.26V
Must improve quality of life in later years. 26,27V
It would depend on the quality of life it could offer and its affordability. 17D (+depends on situation)
To help your quality of life and those close to you. 26U; Hopefully to improve your quality of life. 27U
I want to have a reasonable quality of life. 26V; I would also want my child to have a reasonable quality of life. 27V
To give the child every opportunity to live a full and natural life. 27V
I want my child to be same as a normal person who doesn't have a disease. 27V (+save life)
Now in Japan, it is rather hard for weak people to live. And social security has not been prepared yet. I want to spend my life more normal if possible because the life is only one time. 26,27V
Since we have the right to the pursuit of a better life. 26,27V
It's good for the person if she/he can live a happy social life. 26V
Depends on situation
It would depend on type of disease, cost of treatment, my age, and responsibility to others. 26D
I am 85 and ready to go when my time is up. 26D; Depends on the treatment and what the result would be. 27D
I know what I feel morally but may change my mind if I needed help. 26,27D
I cannot understand the meaning of correcting genes very much (what is done and what result actually happens) , though, personally I would like to live facing my life as long as my body has a life. About my child, I may think of it if it can be treated, however. 26X,27D
Respecting my child's will. 27W
Well, about my child. It's OK to change it partly, though, I don't want to change reproductive cells. 27D
To live longer and not to pass it on to offspring. 26W (+save life)
I don't care if it is only my problem, however, I want to avoid a defect down to my child. 26,27V
Because I want to end the genetic disease in my generation if possible. 26V
I cannot bear to hand a bad gene down to my descendant and to have troubled them. 26W
By thinking about my descendants. 26V (+ save life)
Because bad genes should be removed. 26,27V
Because I feel responsibility since genetic diseases are because of parents' gene. But I don't want them to take it if it's dangerous. 27W (+health risk)
I would rely much more on the power of the Lord Jesus in prayer. 26W
Help advance scientific knowledge for future sufferers. 26W; As above, and at least there is hope. 27W
It might fail, though, we will die anyhow and the treatment method may be researched progressively one after another if there are others who have the same disease. 26V
Waste of money. 26,27U
The thin edge of the wedge. Play on personal preservation notion as a persuasive argument in favour of unleashing 'Pandoras Box'... 26,27X
Fear of unknown, potential for where this type of treatment might lead. 26,27U
Danger of unforeseen consequences to human race. 26,27U
Because a bad gene is needed from the viewpoint of the species. 26U
Playing God / Interfering with Nature
Nature put it there so nature can take it away. 26X
I am wondering whether mere human beings might fumble with the genes of living things. 26D
Whether it is a gene or a body, an important thing is that it is temporarily left in my keeping until the day my life comes to an end. However I want to take good care of it. I don't want to make it more or less than it is. 26U
Because I suppose it may be my destiny. 26U
Because it is against nature. 26U
I don't want to correct genes which were inherited from my parents. 26X
I will take it if there's little risk. But such genes should be naturally selected. 26U,27W
When I ethically think of it, I don't like to correct genes, though, we cannot take such a resolve attitude for an emotional problem. 26,27D
Though I cannot declare whether it is right or not ethically, I would like to cure the disease. 26,27V
If there were minimal risks. 27V
Short term relief (therapy) may trigger complications. 26,27U
If my child was not in pain and there was no increased risk to her health. 27W
Though I don't spare my cooperation as possible, the safety to next generation could not be guarantied. 27U
Because I am not sure of the details of the treatment and the risks. 26,27D
I don't want my child to be used as a guinea pig. 27D
I do not have absolute faith in the medical profession. 26U
One problem is risk. Another one is that it may not be only disadvantage, such as sickle cell disease has resistance to malaria in Africa. 26,27U
Because there's a possibility not to be taken ill. I am very afraid to play with genes. 26,27U
Because I don't think everything will be good by the therapy. 26U
The numerical description of the results is in Table 2. The major reasons were to save life and increase the quality of life. The same responses were given for Q26 and Q27 by many persons. Significant proportions of the New Zealand and Australian respondents gave a reason that it depends upon the situation. In Thai students one third gave a reason that it would save their family, which was significantly higher than any other sample, and the same result was found for Q26 and Q27, because most replied in Q27 "same as in Q26". This may suggest a close family structure, however in questions about the privacy of genetic disease, there was similar sense of family interdependence in most countries, with Japan, the Philippines and Thailand showing most willingness to share genetic information inside the family (Macer, 1994b).
Some respondents gave a reason like "improving genes", which will be discussed below under "enhancement". About 5-7% rejected gene therapy considering it to be playing God, or unnatural. There was very little concern about eugenics (0.5-2%). The most significant reason for disapproving of gene therapy was health risk, except in Thailand where more people gave a response that it was unnatural.
Q26. 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 before symptoms appear? Why?
|Improve quality of life||15||13||9.6||3.4||5.6||1.2||4||7.3||15||4.5||5.2||16||5.9||3.6||1.0|
|Depends on situation||19||25||9.0||4.3||12||4.8||12||28||38||11||3.9||9.5||3.3||6.4||11|
Q27. 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? Why?
|Improve quality of life||23||19||13||8.3||17||0.9||6||13||16||5.0||9.1||16||11||7.6||2.9|
|Depends on situation||20||31||13||2.3||33||5.5||10||27||33||16||2.9||0.9||4.0||2.0||14|
++ Very willing + Somewhat willing
-Somewhat unwilling -- Very unwilling DK Don't know
- Japan 1991 (Macer, 1992a, N=532); US86
(OTA, 1987, N=1273); US92 (March of Dimes
Survey, 1992, N=1032).
Table 3: Acceptance of gene therapy for specific cases in International Bioethics Survey
Q28. How do you feel about scientists changing the genetic makeup of human cells to:
++ Strongly Approve + Somewhat Approve - Somewhat Disapprove - - Strongly Disapprove DK Don't know *UK sample from 1994, see text.
|a. Cure a usually fatal disease, such as cancer|
|b. Reduce the risk of developing a fatal disease later in life|
|c. Prevent children from inheriting a usually fatal disease|
|d. Prevent children from inheriting a non-fatal disease, such as diabetesdiabetes|
|e. Improve the physical characteristics that children would inherit|
|f. Improve the intelligence level that children would inherit|
|g. Make people more ethical|
|h. As an AIDS vaccine|
The responses to another question about gene therapy (Q28, Table 3) show people have significant discretion between therapeutic and cosmetic applications of gene therapy, but little distinction is made between somatic cell or germ-line interventions. There was little distinction between inheritable or non-inheritable gene therapy in any sample, as in the USA (OTA, 1987; March of Dimes, 1992). This is consistent with the 1992 US survey in which 36% thought that gene therapy was "replacing your gene to prevent your children from getting a particular disease" (March of Dimes, 1992). In the 1987 survey, 62% answered that both patient and offspring should be targets of gene therapy, when asked "Suppose someone had a genetic defect that would cause usually fatal disease in them and would likely be inherited by their children. Do you think that doctors should be allowed to correct only the gene affecting the disease in the patient, only the gene that would carry the disease to future generations, both genes, or neither gene?" (OTA, 1987). Only 8% said only affecting the patient, while 14% said only the offspring, and 11% neither.
Some of the open responses to Q26 and Q27 were also supportive of germ-line genetic change, as listed above under the reason "improving genes". Currently gene therapy is not inheritable, and many would say that we should have wider discussion about the ethics and social impact before we make inheritable changes, but we can say that currently there is little difference in public acceptance of somatic cell and germ-line gene therapy.
Significantly more respondents in Thailand and India gave reasons of "improving genes" than other samples. This was not due to a low general educational level, as noted above (Table 1). In a separate question on acceptance of prenatal genetic screening, Russians were the sample with the greatest proportion of respondents who gave reasons of improving genes (11% of the total respondents, Macer, 1994b), however, for gene therapy only 0.5% (Table 2) gave such reasons, and they gave more general reasons for saving life. There may also therefore be some differences in perception between negative and positive genetic change, a topic for further research.
Perceptions of enhancement
There is extremely high support for use of gene therapy to cure disease, both as somatic cell (a - fatal, b - late onset) or inheritable (c - fatal, d - non-fatal); and high support as an AIDS vaccine. There was lower support for enhancement uses (Q28efg - improving physical characters, intelligence, making more ethical) than for treating disease, suggesting some discretion (Table 3). A significant preference for therapeutic (Q28abcd) over cosmetic (Q28ef) applications of gene therapy was also seen in the USA (OTA, 1987; March of Dimes, 1992). This is encouraging for many ethicists, and a similar difference was shown in a question about use of genetic engineering to make a sports fish, compared to a disease-resistant crop (Macer, 1994b).
However, in India and Thailand more than 50% of the 900+ total respondents in each country supported enhancement of physical characters, intelligence, or making people more ethical. It could suggest several things: that poor living standards and infectious disease make people more pragmatic about "improvement", or that people in those countries have not thought about the implications (even though they were relatively highly educated samples). It is interesting if this is a general trend in developing countries, as it could have significant implications for international policy.
We should also note the results of Q26 and Q27 on Chinese medical staff and students in 1993 found 73% "willing" for personal use and 80% "willing" for children's use (Lo et al., 1994). The policy for avoiding births of handicapped persons in China, which many consider to be close to a social eugenics program to lower the proportion of handicapped babies born in the population, also suggests Chinese may follow this trend (Editorial, 1994). There is the additional pressure in China of the one child per family policy. In this survey, the largely Chinese populations of Singapore and Hong Kong biology students were intermediate between the industrialised countries of Australia, Israel, Japan, New Zealand, Russia, and the USA, and Thailand and India, in their acceptance of enhancement. It is future question to more closely examine factors behind people's acceptance or rejection of enhancement, for example, how much culture, education, religion, familiarity with medicine, or living standards, influence this.
A 1994 Gallup poll in the UK also reports up to 20% of people accepting enhancement gene therapy, which is much higher than 1993 (Verrall, 1994). The Gallup poll asked whether they would use genetic methods to affect "aggression", and in 1993 5% approved whereas 18% approved in 1994. The same result was found for "alcoholism", with "homosexuality" increasing from 4% to 10% and "good looks" from 2% to 5% approval. We find more approval to all of the enhancement questions in Q28 than to these in the UK, and it suggests some interesting research could be performed to follow up these comparisons. The changes over time also make the data useful for future studies on the impact of education upon people's attitudes, and we should note that there have been significant changes in acceptance of gene therapy in Japan between 1991 and 1993 (Table 2). At least we can say that some people agree with enhancement, and the proportion is of concern to those who consider enhancement to be unethical.
In the open question (Q26,27, Table 1) up to about 5% in all countries gave a reason like "improving genes", including Japan which was generally negative towards eugenic or economic reasons for genetic screening (Macer, 1994b). About 10% of Thai respondents gave "improving gene" reasons for gene therapy. There was very little fear of "eugenics" anywhere (0.5-2%). We use the term eugenics in a broad sense, meaning the idea that we should improve the frequency of "good genes", or decrease the frequency of disease-causing genes (alleles). The fears of eugenics included both fears of social programs to enforce eugenics, and the idea that we should not alter gene frequency because it may affect the future of the human gene pool. The comments in this survey suggests the main reasons for rejection of enhancement gene therapy are that it is seen as "unnatural", "Playing God", "unpredictable" or "unnecessary", rather than "eugenics".
About 10% of the respondents in this survey in Russia, and many in India also, gave eugenic reasons for support of genetic screening (Macer, 1994b), significantly more than in the other countries. If we combine this with the economic reasons, we find Australia, New Zealand and Thailand also show eugenic or economic reasons for supporting prenatal genetic screening, and we should note that one of the arguments of past eugenic movements has been the economic type (Macer, 1990). Japanese showed the least support for this way of thinking.
In general open questions on the benefits and risks of "genetic engineering", some eugenic concerns were expressed. The same conclusion was made from different open questions on the benefits and risks of "human genetic manipulation" in the 1991 Japanese survey, and a 1990 New Zealand survey (Macer, 1992a, 1992b, 1994a). The more specific the question is the less eugenic concerns are expressed. To most people the critical point is that genetics may offer hope to save life and improve the quality of life, and we even find positive support for eugenics in genetic screening or therapy is stronger than fears. Those who argue against genetic medicine for eugenic reasons may not actually represent the public, when we consider the degree of support given for eugenics. At the same time, the past history of eugenic abuses means that we need to educate about the dangers of misuse of compulsory eugenic programs.
We also need to look at the balance between pragmatic reasons, e.g. distributive justice and economy, or quality of life, versus theological beliefs that we should accept what nature or God should bring us for a child. Even within religious belief there are dual considerations of leaving things "as God created them" or the common religious command of Jews, Christians and Muslims to govern the earth (Genesis 1:28) which could include active genetic intervention, a partnership with God in creation just as we have practiced selective animal and crop breeding. The issue of playing God is a real issue seen in the comments of some persons about gene therapy and genetic engineering (Macer, 1992b), and has also been discussed academically (Gustafson, 1994). It is associated with our concept of humanness (Anderson, 1994), and needs further exploration, as in Europe and the USA it already has emotional and political connotations. This survey suggests however, that for "gene therapy", people think primarily of quality of life and safety of medical intervention. The opinions are divided, as typified by Thai respondents, which were the samples with the highest proportion of both "improving genes" and "playing God" comments to Q26 (Table 2).
Education of Gene Therapy
There has been a significant increase in approval of gene therapy in Japan between 1991 to 1993 (Table 2). This is most likely the result of media publicity, however, the 1991 survey did not include a question on the awareness of gene therapy so we cannot directly measure it. The frequency of newspaper articles about gene therapy did increase significantly in this period, as the media reported the development of guidelines by the Ministry of Health and Welfare and the Ministry of Education, and the proposals for gene therapy trials, over the same period. Interestingly, no change in the USA between 1986 and 1992 could be detected in surveys (OTA, 1987; March of Dimes, 1992), despite the increased media coverage of gene therapy as a result of the first clinical trials. When we consider the change reported in the UK between 1993 and 1994 discussed above (Verrall, 1994), it makes us wonder what opinion in the USA is like now. The change in Japan suggests that public opinion is still being formed about gene therapy.
Education of decision-making is essential for the future bioethical maturation of society (Macer, 1994a), for a world where persons have increasingly more decisions to make. The need for education is suggested by the lower familiarity with the word "gene therapy", but this is not surprising given the early stage of trials. In all samples of the International Bioethics Survey there is 90+% support for including discussion of social issues associated with science and technology in school, so that students can participate in contemporary debates.
High school education was surveyed in Australia, Japan and New Zealand. A comparison of the high school teaching of some of topics in genetics were included with gene therapy (Table 4). Two thirds of biology teachers in Australia and New Zealand had taught about gene therapy, and half of the Japanese teachers. This is rather soon after its introduction into clinical trials and reflects a general high degree of interest in it. Few social studies teachers had discussed it.
These surveys also found that the teaching of the ethical, social and environmental issues associated with genetic engineering has increased since 1990 in New Zealand and 1991 in Japan (Macer, 1992a, 1992b, 1994b). The percentages of teachers that had discussed the ethical or social issues associated with genetic engineering in 1993 are in Table 4. There was no question specifically about the teaching of ethical or social issues of gene therapy. For comparison, the percentages of teachers that had discussed the ethical or social issues associated with prenatal diagnosis are also given. About 40% of school biology teachers in Australia, Japan and New Zealand had discussed eugenics in class, but many fewer social studies teachers had done so (Table 4). About 90% of all teachers sampled thought bioethics was needed in education, in an open question, with major reasons cited being that science raises issues that students need to think about, and that students should be taught to respect life (Macer, 1994b).
Teaching of subjects
Can you tell me how much you have heard or read about each of these subjects?
Not heard of it Heard of it (Know) Could explain it to a friend (Explain)
Have you discussed it in class?
No Yes (Taught)
|In vitro fertilisation||Taught||84||36||91||56||76||31|
|Human gene therapy||Taught||66||15||71||21||51||15|
Teaching of social and ethical issues...
Have you ever discussed in class the social, ethical and/or environmental issues associated with applications of these scientific developments?
No Yes (Have)
Do you think that more room should be made in the curriculum for discussion of these issues associated with applications of these scientific developments?
No Yes (More)
Can we have international guidelines?
The UNESCO conclusions are more liberal than some national guidelines as discussed earlier. The Council of Europe Draft Bioethics Convention is the broadest attempt, in terms of the number of countries, to specifically regulate bioethical issues, involving the 35 countries of Europe. Article 16 prohibits modifications that affect the human germ cell line and can be transmitted to subsequent generations, although the Convention accepts possible future exceptions. As discussed above, the more liberal UNESCO draft report suggests we should not outlaw germ-line therapy or somatic cell enhancement (Butler, 1994). This position reflects the logic of obtaining international support and being independent of time. If we assume that the safety of gene therapy will improve, then logically inheritable, or germ-line, therapy could be acceptable. We can think of cases where it may be simpler than repeated somatic cell therapy on each generation, in the time-frame of implementation of international declarations and conventions (e.g. up to ten years from now).
A few writers have questioned the prohibition on germ-line gene therapy in the NIH guidelines, and called for formal discussion of germ-line therapy (Walters, 1986, 1991; Cook-Deegan, 1990; Zimmerman, 1991; Fletcher and Anderson, 1992; Munson and Davis, 1992; Carmen, 1993; Wivel and Walters, 1993). The public opinion data, especially from the International Bioethics survey, and the USA, suggest that the public is ready for a discussion of germ-line gene therapy. There is almost no distinction made in the responses to Q28. A discussion about germ-line gene therapy would also inform the public of differences between somatic cell and germ-line gene therapy that many academics have pointed out (Lappe, 1991; Mauron and Thevoz, 1991; CRG, 1992; Davis, 1992; Danks, 1994), and would allow us to reexamine whether these differences do make a significant difference to the bioethical decision-making at both the levels of public policy and that of families and patients themselves. Some writers have suggested that although it may be logical, we should not discuss germ-line gene therapy at the moment (Neel, 1993). The argument that because germ-line gene therapy is not currently safe we should not discuss it is inconsistent with the lengthy discussions of somatic cell gene therapy before the first clinical trials. It is also possible that germ-line change may inadvertently arise from some of the somatic cell gene therapy trials underway, and therefore a discussion would probably be more timely then many think. In practice, UNESCO is already discussing germ-line gene therapy with the above conclusion that it should not be illegal.
Enhancement, for example of the immune system or for avoiding memory loss, could also be accepted in the spirit of current medicine, but because of ethical concerns about germ-line enhancement, the UNESCO committee recommends to draw the line at somatic cell therapy. It recognises that already some enhancement is accepted, whether it be vaccination, vitamins, cosmetics, or cosmetic surgery. Nevertheless there are more concerns over enhancement seen in the opinion of the public, and also fears of a slippery slope. This would argue for waiting until we reach a wide consensus before germ-line enhancement, e.g. Fukui Statement on International Bioethics, Fukui, Japan, 1993 (Fujiki and Macer, 1994). A few writers have supported the concept of enhancement in the academic journals (Miller, 1994), but most have not gone further than saying that such distinctions between therapy and enhancement are difficult to define (Macer, 1992b, 1994c; Bayertz et al., 1994). Most think that germ-line enhancement should not be contemplated for a long time. Our children or grand-children should decide whether to use it, not us.
The Eurobarometer (1993) is a regular public survey in Europe, including different questions each time, and is conducted in all 12 countries of the European Union. In 1991 Eurobarometer 35.1 looked at biotechnology and genetic engineering, and in 1993 Eurobarometer 39.1 repeated the same questions, which included the question, "Science is also trying to apply some of the new methods of biotechnology/genetic engineering [half the survey used each word] to human beings, or their cells or tissues, for various purposes such as detecting, or curing diseases, and characteristics we night have inherited from our parents. Please indicate to what extent you agree or disagree with each of the following statements concerning such research on human beings, medicines and vaccines." The options for agreement or disagreement were, "such research is worthwhile and should be encouraged", "such research may involve risks to human health or to the environment", or "in any case, this research needs to be controlled by the government". 72.5% of Europeans approved of it, compared to 74% in 1991; with 16% and 19% disapproving, respectively. For the risk question, people saw more risks from farm animal and food genetic engineering than for human application, but still 64% saw possible risks. 91% of the respondents said there should be government control. In general about 6-7% said they didn't know. The Eurobarometer poll is limited because of the fixed response choices, however it is the most comprehensive and random international survey. Inside this survey, the UK was a fraction higher then the EU average for approval and risk perception in the above question, which allows some comparison to the UK survey on enhancement discussed above. However, there is diversity within Europe, although gene therapy trials are underway in various countries, including Germany, which has generally the highest general opposition to genetic engineering (Zechendorf, 1994).
In Japan there are two separate committees regulating gene therapy, from the Ministry of Education and the Ministry of Health and Welfare. The seven overlapping members have formed a working committee to assess the safety and efficacy of gene therapy proposals, and they are generally consulting with the FDA in the USA to obtain background documents (Swinbanks, 1994). Both Japanese guidelines basically follow those of the NIH in the USA. In this way the regulation of gene therapy is already international. The duplication of the review process in the USA was amended for some proposals in 1994, with the possible removal of NIH-RAC review leaving only FDA review (Marshall, 1994). This trend reflects not only increased cost effectiveness but the increasing familiarity and acceptance of gene therapy.
One criticism of the International Bioethics Survey is that it contains a mixed group of samples; 3 national random public samples in Australia, Japan and New Zealand; 4 mixed public and academic samples in India, Israel, Russia, and Thailand; and selected medical schools and other university departments in 10 chosen countries, as described above. We also include the results from national random high school surveys, which examine teaching. Nevertheless, we still believe the samples obtained are useful, given the limited resources that were available for this project. It is also common in social science to use various sample groups. However, we acknowledge that ideally international attitudes need further investigation among random national public samples, and we would hope that this paper encourages such further studies.
One of the interesting results of a 1991 survey conducted in Japan among public, biology students, academics, scientists, and high school teachers (Macer, 1992a, 1992b) was that for questions of gene therapy there was no significant difference between these groups in acceptance of gene therapy (Q26 and Q27 in the 1993 survey), nor acceptance of genetic screening, despite differences in responses to general questions about genetic engineering. These groups had significantly different knowledge of the techniques, yet their opinions on clinical use were the same - suggesting some of these questions may be independent of technical knowledge. To explore this question would be useful for study of decision-making associated with the use of medical genetics.
These results show people do have the ability to balance the benefits and risks of genetic technology. People in all countries surveyed can perceive both benefits and risks (Macer, 1994b). This is necessary for bioethics, the balancing of good and harm, and is some indicator of the "bioethical maturity" of a society (Macer, 1994a). The results provide some data that allow us to look at bioethical decision-making, and to examine the question of universality. These data generally show the diversity within each sample is greater than the differences among samples. In every society there are people who want to use new genetic techniques, and there are some who reject the concept. The issue goes deeper than religion or culture, and suggests that opinion on these issues will always be divided even if it may change to some degree. We should build a society that respects this division of opinion, and offers improved services to those who want to use them - while also providing counseling to help people reach decisions. Although some would question whether the best way to protect the rights of people holding a diversity of views is to build a world in which every society is pluralistic, this survey suggests every society surveyed is already pluralistic in their views - even if the policies are not.
We also recognise the usefulness of some plurality at the national policy level, but find the data consistent with the concept of international guidelines for protection of the human genome, which is shared among the human race. In the end, international declarations cannot be enforced within countries who oppose them, and we could also question whether we are sufficiently certain on a moral line for such an intervention even if it was possible. Such guidelines could provide minimum standards for ethical protection of users and to enable availability of service, like the Declarations and Coventions on Human Rights. If countries do not implement national laws, international guidelines could provide important guidance for providers and users of gene therapy.
In all societies we see high support for gene therapy for therapeutic purposes. When specific details of an application were given there was generally greater acceptance (Macer, 1992a, 1992b). This suggests that if details are given the public will show greater acceptance of an application, especially for human gene therapy. In the future, there will be an option of enhancement, whether it be for improving the immune system as a vaccine, which may have broad support, or for improving other characters of persons, and their children, with a range of possibilities. One of the basic social questions we need to examine is how much "genetic freedom" (Macer, 1990) people have to change or select the genetic traits of their children. It may be helpful to consider this in light of the freedom given to parents to change environmental and social factors, and the perceptions of parental responsibility. While gene therapy represents advanced medicine, it makes us think about some more basic issues of life.
We would like to thank T. Jacob, D. G. Jones, T. M. Lim, G. Masilamoni, Y. Oguma, R. Rich, Y. Shirai, P. Singer, and A.K. Tharien for invaluable assistance in sampling and distribution of surveys, and the comments of reviewers of this paper. The funding for these surveys comes from principally from the Eubios Ethics Institute, with assistance from the ELSI group of the Japanese Ministry of Education, Science and Culture Human Genome Project, and The University of Tsukuba. The high school survey in Japan was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Culture (Nos. 05680147, and 60240686).
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