ETHICAL ASSESSMENT OF GENE THERAPY IN ASIA.

ETHICAL ASSESSMENT OF GENE THERAPY IN ASIA.

Journal: pp 213-236 in Interdisciplinary Approaches to Gene Therapy. Legal, Ethical and Scientific Aspects, eds. Muller, S, Simon, JW., & Vesting, J. (Springer, Berlin, 1997).
Author: Darryl R. J. Macer


1. Gene therapy in Asia

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. Gene therapy research is underway in many countries all around the world, and several clinical trials have been commenced in Asia. Asia is geographically and anthropologically varied, and ranges from the East with Japan and Korea and China, to the West, with Israel and Arabia, to the South with India. All of the major world religions were started in Asia, and it contains the widest diversity of cultures of any continent. In the broad sense we would also include the Pacific reaches of Asia in Australia and New Zealand, and this region of the world will also be included in this paper.

The regulation of gene therapy has a mixed history in the Asian-Pacific region. Australia was one of the first countries in the world to make a government report on the ethics of gene therapy in 1987. China was the first country in the region to start clinical trials, with US collaboration in a cancer trial in Shanghai in 1992. Japan has the most elaborate ethical assessment scheme, based on the work of two committees, the Ministry of Health and Welfare and the Ministry of Education, Science, Sports and Culture. Since most clinical trials will proceed in university hospitals, as the first one which commenced on a boy with ADA deficiency in the University of Hokkaido in August, 1995, the approval of both Ministries is needed. In Japan a program of 15 trials until the end of 1996 is envisaged. In March 1996 two babies flew into New Zealand from the USA, with gene therapy trials for a neurological disorder occuring within a few weeks using a vector made in the USA. This raises another issue of off-shore gene therapy trials, and international regulation.

In this paper I will look at the ethical assessment of gene therapy in the Asia-Pacific region, from two angles. First the ethical concerns and hopes that the public in different countries have, the descriptive side of bioethics; and second, the regulatory framework that has been set up and the arguments for international regulation of gene therapy.

2. International approval of gene therapy

2.1. International Bioethics Survey

In 1993 the International Bioethics Survey was conducted in Australia, Hong Kong, India, Israel, Japan, New Zealand, The Philippines, Russia, Singapore and Thailand. The results were compared to North America and Europe. The full results and list of collaborators are published (Macer, 1994a; Macer et al. 1995).

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, 1994a). 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, 1994b). 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, in Table 2.

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.

Three population samples were chosen for these International Bioethics Surveys: the general public, university students and high school teachers, which also allows comparisions within groups with different familiarity with biology. 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 1994a; Macer et al. 1996). 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 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 addtional persons listed in the acknowledgements. 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, Japan, New Zealand, the Philippines; a medical laboratory course in Hong Kong; and biology students in India, Singapore and Thailand. 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.

The high school teacher surveys were national, using randomly selected schools from published school lists. 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 and these are treated separately (Macer et al. 1996).

2.2 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, 1994a). 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.

Table 1: Sample Characteristics for International Bioethics Survey

%'s of total respondents
Public
Medical/Biology students
High School Teachers
NZ
A
J
J91
India
Thai
R
Israel
NZ
A
J
India
Thai
P
S
HK
NZb
NZs
Ab
As
Jb
Js
N (returned questionnaires) 329 201352 551 568689 446 5096 110 435325 232 164250 104 20696 251 114560 383
Response rate (%) 22 1323 26 5736 43 <20 6070 66 6550 70 8052 61 2847 21 3726
Female 5955 48 4739 52 6462 59 5033 47 5854 77 5536 38 5237 12 8
living in Urban locality 77 7173 - 7854 90+ 8085 89 4985 58 8796 88 3173 75 7963 66
Mean age (years) 47.4 45.241.7 39.8 30.637.2 36.3 33.420.8 18.1 21.121.8 21.3 21.119.3 21.0 40.842.5 41.8 42.040.7 40.0
Married 59 6266 66 4559 54 623 0 12 0.4 10.4 0 8386 79 7077 74
Had no child 33 3940 35 5522 41 4897 100 10098 96 10099 100 2215 24 2430 28
Education
High school 43 3637 37 42 13 1629 94 547 4 023 71 10 1 10 0
2 year college/technical 18 1519 22 63 18 2048 4 613 18 077 3 12 0.4 10.2 1
graduate degree 25 2831 31 3135 37 3920 2 3827 60 500 6 6458 59 5778 82
postgraduate degree 9 1610 7 5259 28 253 0 051 13 470 8 3037 39 4121 17
other 55 3 37 1 40 0 02 2 53 0 44 3 0.40 0.8 0.3
How important is religion?
Very important 27 2310 - 4046 10 3828 19 536 54 8932 21 2017 42 477 10
Somewhat important 26 2733 - 2744 38 1620 41 1624 38 1141 40 1729 23 2625 37
Not too important 27 2440 - 158 28 3418 20 3418 7 022 26 3332 19 1045 36
Not at all important 20 2617 - 182 24 1234 20 4522 0.4 05 13 3022 16 1723 17
Awareness of human gene therapy
Not heard of it 26 2323 - 2710 22 207 16 619 15 825 29 226 4 203 21
Heard of it 57 5058 - 4770 57 4828 48 5655 71 6659 55 2244 16 4035 61
Could explain it to a friend 17 2719 - 2620 21 3265 36 3826 14 2616 16 7630 80 4062 18

1J91 from Japan 1991 survey (Macer, 1992a, 1992b).

Table 2: Acceptance and reasoning about gene therapy

%
Public
Students
US86
US92
J91
NZ
A
J
Ind
Thai
R
Isr
NZ
A
J
Ind
Thai
P
S
HK

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?
++ 35 30 25 4750 42 6135 23 5452 43 4460 34 4349 40
+ 43 49 29 2527 24 1620 24 1634 44 3014 30 3534 38
- 12 9 18 96 15 511 6 43 2 112 11 116 6
-- 9 9 12 44 6 424 13 03 2 54 16 32 3
DK 2 2 16 1513 13 1410 34 267 6 1020 9 89 13
N 318 195335 529 684414 50 96110 421 310230 151 249104
Not stated 16 1432 37 2360 58 1517 29 3815 38 3835
Don't know 2.5 0.52.7 1.1 3.17.0 0 00 3.3 1.92.2 1.3 0.40
Saves life 34 4326 41 1913 24 5238 38 4121 39 3943
Saves family 4.4 5.63.3 4.7 2.60 2 2.10 0.2 3.231 1.3 2.01.9
Improve quality of life 15 139.6 3.4 5.61.2 4 7.315 4.5 5.216 5.9 3.61.0
Depends on situation 19 259.0 4.3 124.8 12 2838 11 3.99.5 3.3 6.411
Improve genes 1.9 0.55.4 5.5 8.60.2 0 2.10.9 1.9 6.16.0 2.6 2.83.8
Other benefit 7.0 4.111 1.1 2.92.7 0 2.11.8 2.9 3.20.9 0 0.82.9
Economic comment 1.9 1.00 1.3 1.31.4 0 01.8 0 1.30.9 0.7 1.60
Eugenics/Misuse 0.9 01.8 0.4 0.90.5 0 00 1.7 00 0 00
Playing God/unnatural 5.3 7.25.1 4.5 150 2 9.35.5 5.2 1.620 2.0 5.26.7
Against ethics 0.6 00.3 0 0.30.5 0 00.9 1.0 00 0 00
Health risk 8.0 105.7 2.8 3.45.1 8 3.13.6 10 4.20 12 6.411
Other harm 3.1 2.13.6 1.5 0.23.4 2 00 2.4 0.30 1.3 1.21.9

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?
++ 51 52 37 60 5753 73 6735 62 5849 51 7079 57 6759
+ 35 36 29 22 2521 10 1624 18 2639 25 913 24 2426
- 7 5 11 3 210 3 25 2 54 7 31 7 34
-- 4 4 7 2 21 3 56 0 11 2 42 3 03
DK 3 3 16 13 1415 11 1030 18 107 15 145 9 68
N 317 196335 527 675436 50 96110 417 309230 150 173104
Not stated 16 1329 41 2362 62 1616 32 3915 39 6035
Don't know 1.0 0.52.1 1.3 3.94.8 0 00 2.6 1.32.2 1.3 0.40
Saves life 42 4436 42 2417 22 4947 40 4321 37 2743
Saves family 1.6 2.62.7 2.1 8.40 2 3.10.9 0 0.631 0 1.20
Improve quality of life 23 1913 8.3 170.9 6 1316 5.0 9.116 11 7.62.9
Depends on situation 20 3113 2.3 335.5 10 2733 16 2.90.9 4.0 2.014
Improve genes 0.3 02.7 5.7 9.90.5 0 00.9 1.2 4.97.4 0.7 0.40
Other benefit 6.0 2.06.6 1.3 2.52.5 0 1.01.8 1.2 1.90.9 1.3 0.41.0
Economic comment 0.9 1.00 1.1 0.91.4 0 00.9 0 0.70 0 00
Eugenics/Misuse 0.6 01.2 0.4 0.30 2 00 1.2 01.3 0 00
Playing God/unnatural 2.2 4.62.1 2.3 2.20 0 1.02.7 2.4 0.30.9 1.3 0.81.9
Against ethics 0.3 00.3 0.2 00 0 00.9 0.7 00.4 0 00
Health risk 4.4 7.75.7 2.1 3.64.4 6 6.32.7 8.9 4.50.9 9.9 4.88.7
Other harm 0.6 0.52.4 1.1 0.31.6 2 1.00 1.2 1.01.7 0.7 0.42.9

++ Very willing + Somewhat willing -Somewhat unwilling -- Very unwilling DK Don't know

Abbrevations: J91 - Japan 1991 (Macer, 1992a, N=532); US86 (OTA, 1987, N=1273); US92 (March of Dimes Survey, 1992, N=1032).

2.3. 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.

About 70-80% in all countries were willing to undergo therapy themselves, and 80+% willing for their children to undergo gene therapy to cure a usually fatal disease. The major reasons expressed in open questions ("Why?") 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 actually more people gave supportive reasons like "improving genes", especially in Thailand and India. The open comments suggest eugenic thinking is found in most countries, and considering that over half the people of the world live in Asian countries which appear to be more supportive of eugenic enhancement than Americans or Europeans, it makes the future of gene therapy very interesting.

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.

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.

2.4. Little distinction between somatic cell and germ-line gene therapy

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.

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.

Public
Medical or biology students High school teachers
NZ A J In T R Is U86 US92 NZ A J In T P S HK UK* NZb NZs Ab As Jb Js
a. Cure a usually fatal disease, such as cancer
++ 5860 42 5478 72 5848 57 6763 41 6286 67 7054 61 6360 65 6537 29
+30 29 4131 18 1130 35 3026 33 4727 13 2628 44 3527 35 2722 45 45
-4 5 35 1 210 7 51 1 32 0 50.4 2 12 2 44 6 7
-- 43 2 41 7 07 7 11 0.2 20 1 10 0 62 1 13 4
DK 42 12 62 8 22 1 52 9 71 1 0.40 3 21 4 89 15
b. Reduce the risk of developing a fatal disease later in life
++ 4247 35 4850 46 5039 41 4546 31 5346 49 5647 46 5342 49 4927 19
+36 34 4035 32 3334 38 3737 41 5032 40 3938 39 4531 44 3827 45 46
-9 6 56 12 614 12 117 7 75 11 72 9 35 5 815 12 11
-- 65 1 43 7 09 8 32 0.2 22 2 10 0 84 2 34 4
DK 78 19 73 8 22 3 84 12 81 3 25 6 35 3 613 20
c. Prevent children from inheriting a usually fatal disease
++ 5963 37 6375 68 5251 52 6258 33 6886 57 6157 54 6253 58 5624 22
+26 24 4324 21 1730 33 3225 31 4820 12 3434 30 4123 42 2923 44 44
-5 5 36 2 516 8 63 4 52 1 71 8 24 0 511 12 10
-- 52 1 21 5 07 7 23 0.5 21 1 11 0 73 2 15 4
DK 56 16 51 5 21 3 84 13 80.4 1 34 3 42 6 915 20
d. Prevent children from inheriting a non-fatal disease, such as diabetesdiabetes
++ 4350 25 4263 45 4041 28 3229 18 3859 39 4337 27 5642 49 4716 14
+34 29 3731 28 2630 36 3844 43 4335 34 4344 48 4029 45 3430 35 31
-11 8 1510 6 1020 12 188 14 1413 4 118 9 195 6 68 22 23
-- 75 2 82 11 49 14 74 3 53 5 22 2 74 5 87 6
DK 58 21 91 8 62 3 910 22 90.4 2 34 12 33 6 720 26
e. Improve the physical characteristics that children would inherit
++ 1015 12 3654 16 1016 16 24 3 3652 16 1411 2 64 2 73 3
+14 13 1627 29 2012 28 2711 12 831 35 2730 26 310 10 812 6 11
-17 19 3511 11 1234 22 2114 31 4713 7 2934 31 2819 17 1816 43 39
-- 4744 16 153 38 4231 33 6750 25 143 25 1714 61 5960 66 5834 29
DK 129 21 113 14 23 3 63 17 63 3 518 6 69 6 714 18
f. Improve the intelligence level that children would inherit
++ 1115 13 4148 18 618 17 21 3 4058 18 1513 2 74 3 62 4
+13 12 1329 26 1716 26 258 13 728 22 3126 23 67 13 912 6 8
-21 21 3510 16 1132 22 2014 26 4512 12 2631 33 2317 15 1618 40 40
-- 4641 19 136 38 3831 35 6953 28 115 21 2320 65 5860 65 5439 30
DK 911 20 74 16 82 3 77 17 93 4 511 4 118 7 1013 18
g. Make people more ethical
++ 1418 14 3168 19 10- - 33 3 2465 37 178 2 -- - -- -
+13 16 1025 18 1222 - -11 13 528 17 2125 63 7- - -- - -
-12 10 3212 11 724 - -10 23 3812 9 1927 34 28- - -- - -
-- 4334 21 166 44 32- - 6241 36 166 15 1614 44 -- - -- -
DK 1822 23 167 18 12- - 1420 18 203 8 1523 19 -- - -- -
h. As an AIDS vaccine
++ 4952 33 4975 74 48- - 5353 27 5475 62 6343 56 -- - -- -
+24 28 3622 17 1128 - -18 26 4017 20 2520 31 31- - -- - -
-6 8 46 3 218 - -6 11 65 2 55 9 3- - -- - -
-- 74 0.3 82 6 2- - 62 3 91 5 36 0 -- - -- -
DK 148 27 153 7 4- - 178 24 152 3 911 10 -- - -- -


2.5. 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. In 1994 the International Bioethics Survey was conducted by C. Laughlan and S. Mastana among human sciences students at Loughborough University in the UK (Macer et al. 1995). The results for Q28 are shown in Table 3, and they show significant rejection of enhancement by the student population. In Australia, Japan and New Zealand the students rejected enhancement significantly more than the public, which may also be true of the UK. The changes over time make the data useful for future studies on the impact of education upon people's attitudes, and we should note that there were 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).

3. Education of 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 (Macer et al. 1996). 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, 1994a). 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 et al. 1996).

Table 4: High school teaching of genetics and bioethics in Australia, Japan and New Zealand

%
New Zealand
Australia
Japan
Subject
biology
social
biology
social
biology
social

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 8436 9156 7631
Explain 9886 9792 9055
Heard 212 38 1045
Prenatal diagnosis Taught 7231 7625 --
Explain 8267 8965 --
Heard 1729 1029 --
Eugenics Taught 3614 3822 3817
Explain 4826 5226 5428
Heard 3335 2734 3456
Human gene therapy Taught 6615 7121 5115
Explain 7631 8040 6218
Heard 2244 1640 3561
Bioethics Taught 6722 7042 4539
Explain 7639 7763 5037
Heard 2243 2031 4757
Genetic engineering: Taught 8836 8542 6922
plantsExplain 9356 9156 7418
Heard 740 943 2567
Genetic engineering: Taught 8112 7618 669
microorganisms Explain 9030 8639 7210
Heard 1053 1350 2771
Genetic engineering: Taught 8138 8544 5920
animalsExplain 9152 9157 6717
Heard 944 943 3268

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)

Genetic engineering Have 8541 9057 5227
More 7261 5764 7172
Prenatal diagnosis Have 6729 7429 4019
More 5650 5053 5561

Table 5: Approval of fetal diagnosis and gene therapy in groups in Japan

*Yes = Yes, or Very willing and somewhat willing

No = No, or Very unwilling and somewhat unwilling DK=Don't Know

%
Public
Students
Academics
Nurse
BT91
Sci
Date 1991 1993 1995 1991 1993 1991 1995 1993 1991 1991
N 532 352 76(T) 198 435 706 171 293 225 540
Some genetic diseases can be predicted in the fetus during the early stages of pregnancy. Do you think such tests should be available under government-funded Medicare? Why?
Yes 76 76 72 76 74 71 54 82 73 71
No 7 8 7 7 9 9 28 3 8 8
DK 17 16 21 17 17 20 18 15 19 21
Would you want such a test during (your/your spouse's) pregnancy? Why?
Yes 57 61 56 58 66 59 42 57 61 60
No 17 16 24 12 10 17 39 10 15 17
DK 26 23 20 30 24 24 19 33 24 23
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?
Yes 54 66 51 51 74 53 56 54 65 54
No 30 21 16 36 16 28 32 25 22 29
DK 16 13 33 12 10 19 12 21 13 17
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?
Yes 66 74 55 66 76 62 64 64 73 62
No 18 11 8 16 9 17 20 16 14 17
DK 16 15 37 18 15 21 16 20 13 21

Table 6: Acceptance and reasoning about gene therapy

%
Yourself*
Children*
S93
P93
A95
S93
P93
A95
Very willing 4442 2851 5336
Somewhat willing 3024 2825 2129
Somewhat unwilling 1115 117 109
Very unwilling 56 212 110
Don't know 1013 1215 1516
N 421335 175 417335 175

Reasons
Not stated 2932 2032 2919
Don't know 33 13 21
Saves life 3826 2540 3626
Saves family 0.23 30 38
Improve quality of lifequality of life 510 45 138
Depends on situation 119 1716 1313
Improve genes 25 31 31
Other benefit 311 31 75
Economic commentEconomic comment 00 0.50 01
EugenicsEugenics/Misuse 22 01 10
Playing GodGod/unnatural 55 102 27
Against ethicsAgainst ethics 10.3 10.7 0.31
Health risk 106 109 68
Other harm 34 31 23

*Yourself: 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?

Children: 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?

4. Attiudes of Academics in Japan

One of the fundamental questions in opinion studies is whether attitudes to gene therapy differ between dfferent groups in the population. Academics are disproportionately represented in the committees which oversee most uses of science and technology, including its ethical evalution. Between 1991 and 1995 I have conducted a number of surveys of attitudes to gene therapy within Japan. The fundamental question asked is whether the attitudes of academics (Macer et al. 1996b) differ from those of the public and other groups that have been surveyed in 1991 (Macer, 1992a; 1992b), 1993 (Macer 1994a; Macer et al. 1995), and 1995 (Macer et al. 1996). Some of those questions from those surveys were used in 1995, and the results show some differences with the acceptance of fetal diagnosis and gene therapy despite a positive view towards science.

The sample descriptions are given in the references. Comparisons are made in Tables 5 and 6 between the following samples (abbreviations): Public 1991 (P91), Biology students (S91), Academics 1991 (A91), Scientists (Sci), High school biology teachers (BT91), from Macer (1992); Fukui Nurses 1993 (Nu) from Macer (1994, 1994b - surveys collected by Dr. M. Hirayama and Prof. N. Fujiki; using 1991 questionnaire); Public 1993 (P93) and Medical students 1993 (S93) from Kato and Macer in Macer (1994a); High school biology (BT93) and social studies (ST93) teachers from Macer et al. (1994, 1996a); a pilot public random digit telephone survey of Macer conducted in 1995 (with Shiro Akiyama, Ayumi Okada & Nobuko Macer, which had a response rate of 50% (P95(T)); and of members of the Japan Association of Bioethics (A95) with a 45% response rate.

A comparison of Q26 and Q27 from the International Bioethics Survey among the other groups shows that A95 and P95 were less willing to support gene therapy than the other groups in 1993 (Table 5). The results from the telephone survey also found more people say that they do not know. The P95 survey was conducted at the end of 1994, early 1995, when their was discussion in the media of the eminent approval of the Hokkaido University gene therapy trial, however, that trial did not commence until August 1995. Therefore the differences could be due to the different methodology, and may suggest that there are more people uncertain of gene therapy than mail response surveys suggest (Macer et al. 1995). If we were asked suddenly on the telephone we may be more uncertain of a response than if we had several days or weeks to think about a reply with a written questionnaire. However, it is noted that few people in the USA studies said don't know (Table 2). Whether the trend for increased willingness to accept gene therapy seen between P91 and P93 has reached a peak is uncertain, and it will be interesting to investigate opinion in another year or two when there have been more gene therapy trials in Japan.

There was generally no statistically significant difference with demographic characteristics, however, in A95 there was a significant difference in the acceptance of gene therapy with religiousity. There were more serious religious believers among members of Japan Association of Bioethics (A95) than other samples in Japan. By using the scale: 1 = very willing, 2 = somewhat willing, 3 = somewhat unwilling, 4 = very unwilling: the average values for the respondents who answered that religion was very important, somewhat important, not too important or not at all important, for personal use was 2.72, 2.12, 2.11, 2.00, and for child's use, 2.29, 1.90, 1.89, 1.24, respectively. The difference between those who said religion was not at all important and very important was significantly different (P<0.01).

The A95 survey is the only survey of these that has been conducted after the actual gene therapy trial in Hokkaido University. Therefore a set of questions about that particular trial were asked. We found 92% said they had heard of the trial, 53% said that they knew the name of the disease but only 31% could correctly name the disease (ADA deficiency or immunodeficiency) that is the subject of the trial. We also asked them the question: "Considering the gene therapy that is done now, how do you think about gene therapy in the future in Japan?", and the responses were: 13% Not stated, 3% Don't know; Benefits: 0.4% For family benefit, 12% save life, 1% health care is right, 1% Improve quality of life, 4% Right to choose such medicine, 8% another benefit; Concerns: 4% need ethics committees, 6% need to be open to public, 11% said it depends on situation, 4% ethics, 2% play God/unnatural, 2% economy, 2% misuse, 0.4% eugenics, 15% had health concerns, 10% another harm. The results of 1995 surveys suggest that there are some significant differences in the approval of fetal diagnosis by members of the Japan Association of Bioethics in Japan from the general public, scientists, high school teachers and students. This is despite similar or more positive views on the general benefits of science to society. This result makes us ask whether the JAB does represent the general community views in some questions of bioethics.

There are two major demographic distinctions of the A95 group compared to all other samples, the older age, and increased religiousity. They generally had high educational qualifications, income, and had more male than the public, however, these characters were shared by the 1991 academic and scientist samples. However, generally we did not see many age associated differences, and if there was a tendency actually older respondents of A95 were more accepting of gene therapy and fetal diagnosis than younger. While we could link greater religiousity of A95 with more negative opinions to selective abortion and fetal diagnosis, this result was not seen within the public samples, and also was not reflected by the international comparisons (Macer, 1994b; Macer et al. 1995).

The greatest difference between the A95 and the doctor samples are that they are selected groups of the population, doctors could be expected to value life more because they attempt to save life in their vocation (though this should be confirmed by data), and members of JAB share the similar interest to study bioethics. "Bioethics" has a somewhat suspicious attitude to biotechnology because it includes technology assessment as one of the ideas, but in the survey only negative feelings towards human genetic applications were found, not to other applications of science.

5. Regulation of gene therapy

There are a variety of ethical challenges that practitioners and regulators face, including the experimental nature of novel procedures, restrictions to fatal diseases with no alternatives, commercial interests, patient privacy versus public review, and somatic versus germ-line cell targets. There are various models for regulation as presented in previous papers in this book.

In Japan, all experimental drugs and therapies in Japanese University Hospitals must be approved by the Ministry of Health and Welfare (MHW) and the Ministry of Education, Science, Sports and Culture (MESSC) (Swinbanks, 1994). Gene therapy has additional committees and specific regulation (MHW 1994). These guidelines are based on the USA NIH guidelines (1993). First a trial must come before the Institutional Gene Therapy Committee, the Institutional Recombinant DNA committee and the Institutional Ethics Committee. Then it goes to the MHW and MESSC Ethics Committees, wuith the details being considered by a working group of the 7 common members of these two central committees, before their further consideration and the final approval of the MHW and MESSC.

The first trial in New Zealand arose when two babies from the USA, suffering from a fatal neurological condition Canavan's disease, came to New Zealand together with the New Zealand professor at Yale University to start gene therapy trials. Trials that were designed in the USA but the researcher considered faster progress could be made by conducting the trial in New Zealand. The trials were approved by the appropriate New Zealand regional ethics committee. The procedure for clinical trials is simpler, with the approval by the Institutional Ethics Committee and the Regional Ethics Committee. The law in New Zealand requires a majority of lay persons, and a lay chair person, for regional ethics committees. These trials started in early March 1996 raise the question of what happens when a trial is moved between countries for regulatory reasons.

There are currently efforts to make international guidelines for gene therapy by UNESCO Bioethics Committee, which the author is a member of (see the previous paper by Kutukdjian in this book). The committee is drafting general guidelines and an international declaration on the human genome and human genetics, that it is hoped will be also approved by the United Nations General Assembly. Standard ethical debates about gene therapy to divide it into somatic cell gene therapy and somatic cell enhancement, and germ-line gene therapy and germ-line enhancement; and only the last class is considered suitable for a legal ban by UNESCO. 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. This is also true of all European, Australian, Japanese, and Canadian guidelines and reports. The Council of Europe Draft Bioethics Convention bans germ-line interventions, but notes that possible future exceptions could be permitted.

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). 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. However, the results of the International Bioethics Survey and comparisions to other surveys suggest the perceptions and bioethical reasoning of peoples around the world are not dependent upon national boundaries.

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, and the 1994 UK student sample of the International Bioethics Survey 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).

There does not seem to be a need for further regulation of gene therapy in countries which already have ethical comittee review. In most countries existing legislation provides ample protection for subjects of experimental somatic cell gene therapy and the public (Vesting, 1996). The duplication of the review process by a series of committees in Japan or the USA is likely to continual for the foreseeable future, as for other medicines. In 1994 the possible removal of NIH-RAC review, leaving only FDA review, was discussed (Marshall, 1994). This trend reflects not only increased cost effectiveness but the increasing familiarity and acceptance of gene therapy. There are also calls by the FDA (see the paper by Grant in this book) for the NIH-RAC to look deeply at the ethical and social issues of germ-line gene therapy or enhancement. This call is being made internationally.

6. Conclusions

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. This is necessary for bioethics, the balancing of good and harm, and is some indicator of the "bioethical maturity" of a society (Macer, 1994b). The survey 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. This is shown to be the same for Asia, Australasia, Europe or North America from surveys, and probably for everywhere.

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, 1994a). 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. Within Asia the results from Thailand and India for Q28 on enhancement, suggest there could be increased willingness for enhancement by persons there. 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.

7. Acknowledgements

For essential assistance with the opinion surveys mentioned in this paper I acknowledge the aid of the following persons, Shiro Akiyama, Angeles T. Alora, Yukiko Asada, Jayapaul Azariah, Hilda Azariah, Maureen Boost, Prasert Chatwachirawong, Norio Fujiki, Hideo Hayashi, Michio Hirayama, D. Gareth Jones, Yuko Kato, Vijay Kaushik, Frank J. Leavitt, Nobuko Y. Macer, Lim Tit Meng, Yuki Niimura, Ong Chin Choon, R. Rich, Peerasak Srivines, Peter Singer, Miho Tsuzuki, Takayoshi Umeno, and Kunio Wakai.

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