Public concern about social and ethical issues associated with scientific advancements in genetic medicine is widespread. Genetic testing, gene therapy trials, and stem cell and human embryo research are discussed by media around the world.
To allow scientists who are specialists in human genetics research to share their views with colleagues and the general public, to assure continued discussion about the ethics of technologies still in their nascent stages, and to establish a base line of attitudes, which may change as the field advances, I surveyed members of international professional societiesthe European Molecular Biology Organization (EMBO) and the European membership of the American Society of Human Genetics (ASHG).
After analyzing preliminary data and finding some consistent differences between German respondents and other European scientists, it was decided to survey, in addition, members of the German Society of Human Genetics (DSHG) and the German Human Genome Project (DHGP). Surveys were completed during 2003.
Survey Goals and Findings
This article offers the views of 196 German researchers and 198 European researchers from 30 other countries, the largest from: England (21%); France (12%); Belgium (8%); The Netherlands (8%); Italy (7%); Switzerland and Israel (5% each); Spain (4%); Denmark, Sweden, and Iceland (3.5% each); and Ireland (3%).
Most respondents to the survey had been working in the field for more than 10 years (60% of German scientists, 73% of the non-Germans), almost all of the rest for more than three years. Most are academic researchers (82% and 75% respectively).
The survey demonstrates where they stand on a variety of ethical issues important to the general public and essential to national, European Union, and international policy decision-making.1
They include: genetic testing and questions of privacy that result from screening techniques; the possibilities for gene therapy and its potential uses, as well as criticisms that have been leveled against this aspect of genetic medicine; and the concerns involved in human embryonic stem cell research and therapeutic cloning. The survey also reveals the issues on which German researchers appear to have a distinct perspective.
Genetic testing raises questions about its use under differing conditions. Forty-nine percent of German respondents approved of testing for a gene that suggests an increased risk of developing a serious disease (28% were opposed), compared with 59% of other European respondents (23% opposed).
Forty-six percent of German respondents approved of testing for a disease that denotes a serious disease for which there is no cure (35% were opposed), compared with 56% of other European respondents (26% opposed).
Though positive on the whole, attitudes were mixed and not sure answers were substantial (ranging from 1823%), because of the unknowns and potential psychological distress for patientseither not knowing whether they would ever get the disease for which they have a contributing gene or knowing they have a disease for which there is no cure.
Moreover, viewpoints varied somewhat (by 10 percentage points) between German and other European scientists, a pattern of caution on the part of German respondents that this paper will demonstrate.
When the survey asked about controversial cases in which genes indicative of tendencies toward breast or ovarian cancer, so-called time-bomb genes, were diagnosed, but where no symptoms were present, German researchers showed greater reluctance than others to take action: over 20 percentage points more (55% versus 34%) disagreed with patients and doctors who would opt for precautionary surgerymastectomies or hysterectomies.
Genetic Testing, Genetic Risk, and Pregnancy Termination
Genetic testing also raises questions about the uses that might be made of its results. One question in the survey asked respondents to weigh the ethical acceptability of parents terminating pregnancies in a number of situations in which in utero tests could determine high probabilities of a variety of problematic outcomes.
A similar pattern emerged for both German and other European scientists: their positions varied by both the perceived severity of the outcome and the age at which any negative effects would appear (Figure 1).
The acceptability of therapeutic abortion was highest for conditions defined as disease or debility, especially when the onset was early in life. Termination was considered ethically acceptable by similar majorities of both groups of scientists if the unborn child would most likely be severely mentally retarded, die of a disease by age four, or develop a chronic painful disease in childhood.
Opposition to termination occurred for less serious infirmities or where the onset was later in life. Abortion was considered acceptable by a minority of respondents if the unborn child would most likely develop a disease causing death as a young adult, develop a totally debilitating disease around age 50, or be mildly mentally retarded.
While German researchers exhibited somewhat more reluctance on all these latter items, they diverged most from the viewpoints of other European scientists (a 17-percentage-point difference) where there was the most uncertainty surrounding the diagnosismild mental retardation (12% versus 29%). That is, half as many Germans as non-Germans thought abortion was acceptable if the child were to be mildly mentally retarded.
Finally, there was the least support when it came to conditions where there is no general acceptance that something is a disease rather than a situation susceptible to choice: the possibility of extreme overweight (3% and 6% respectively), of depression (2%, 6%), of homosexuality (1%, 2%). And when the fetus was not the sex parents had hoped for, respondents were totally against termination.
Researchers were also asked if they agreed with accusations against parents and/or doctors, made by individuals with serious illnesses or deficiencies (discovered in utero), that they should not have been born. A clear majority disagreed with this concept of a wrongful life or wrongful birth (66% of German respondents; 58% of other Europeans).
Screening and Confidentiality
Genetic information gathered on individuals, from voluntary screening or participation in genetic studies, raises concerns about privacy and potential discrimination. Regardless of how legitimate respondents thought testing to be, almost all feared its potential effects on privacy and were uniformly concerned with protecting individuals genetic rights.
German and other European researchers alike believed that disclosure of genetic information to certain social institutions presented a threatdisclosure to employers, 90% and 88% respectively; disclosure to health insurers, 88% and 89%.
Understandably then, both groups of respondents overwhelmingly advocated passing legislation to prevent genetic discrimination: 89% championed legislation prohibiting employers from collecting genetic information on prospective/current employees; and 84% backed prohibiting health insurers from requiring genetic information on applicants.
Three organizational processes were also rated as potential threats to privacy: inadequate consent procedures (82% among German respondents, compared with 76% among non-Germans) and the creation of computerized data (75% and 70% respectively), and DNA databanks (40%, 43%).
Finally, the idea of mandatory premarital testing for genetic disorders was universally opposed: 84% among German and 88% among non-German scientists.
From the beginnings of the Human Genome Project (HGP), leaders envisaged generating technologies that would profoundly improve human health in the 21st century.2 Health system watchers referred to a future biomedical revolution, with gene therapy the expected outcome: all diseaseshave a genetic component, and the best possible treatment in many cases would be to repair the genetic defect that permits the disease.3
But while the conceptual part of the revolution can be seen, with new genes continually being discovered, the technological mastery required to correct disease through gene therapy is slow coming.4 As a result, critics have made a number of accusations.
One frequently heard criticism of the field of human geneticsan exaggerated emphasis on the significance of genes and genetic explanations of disease/behaviorshas led to a conclusion that has shaped a second criticism: that this overemphasis on searching for marker genes and genetic solutions to disease diverts resources from studying important social and environmental roots of ill health.
Asked to measure their views on these criticisms, more German respondents concurred (11 percentage points higher in both cases): 57% versus 46% for the first; 41% versus 30% for the second.
On the other hand, large majorities of both groups were in accord (75% and 73% respectively) regarding a third criticismthe creation of unrealistic expectations of questions that can be answered from genetic data.
However, many scientists, in their written comments, maintained that geneticization is not actively promoted by the genetic society/community, but is being exclaimed by journalists and critics. Some admitted, though, that geneticists had not always been quick to restrain public and media over-interpretation of genetics research.
Somatic Cell Gene Therapy
The prospect of somatic cell gene therapy appears to be a logical extension of current techniques for treating disease. Some analysts think gene therapy may become as routine and pervasive as immunizations or antibiotics. But others have argued that the associated high costs, along with improvements in alternative (typically drug) treatments, will make such therapy untenable.
On this forecast respondents were split. While significant numbers of both groups (around 40%) expressed uncertainty about its ultimate success, a somewhat higher proportion (47% of German and 42% of other European scientists) were optimistic.
The possibility of gene therapy raises ethical issues regarding unprecedented decisions that would have to be made, thereby challenging societys ability to make informed and reasoned choices about whether and how to proceed withdevelopment and use.5
When asked whether the objective of in utero gene therapy would be ethically appropriate if only serious diseases were targeted and the risk-benefit ratios for both mother and fetus were acceptable, a large and like-minded majority of respondents (79% of Germans, 82% of non-Germans) said yes.
Only 6% and 5% respectively viewed this goal as unacceptable. However, somatic cell gene therapy, whether for existing children and adults or for embryos and fetuses, was considered more or less appropriate depending upon the potential applications to which it would be put (Figure 2).
The most legitimate candidates for modification, and also the most agreement among researchers about these speculative uses (there was little or no difference between German and other European respondents), involved treating serious diseases or disordersto cure a life-threatening disease or remedy mental retardation.
On the other end of the spectrum, few respondents were open to nonhealth-related enhancement, such as to eliminate a propensity for baldness (8% of Germans and 11% of non-Germans), improve intelligence (6% and 13% respectively), or decrease sleep dependence (4% and 8%). One respondent made it perfectly clear: Tampering with nonmedical traits is wrong.
The middle ground involved less serious physical and mental disabilities as well as a moral disorderall of which could benefit from improvement, and for which there was, with one exception, only minority approval. The middle ground also produced, again, the most disparity: correcting a learning disorder, for which a remarkable 29 percentage points fewer Germans than other European respondents, half as many, checked ethically acceptable; eliminating a propensity for obesity (a 14 percentage point difference in the same direction); and reducing a propensity for aggression (12 percentage point difference).
It appears that cures/treatments versus improvements/enhancements is a particularly significant distinction for German researchers.
One question in the survey posed the choice outright: how morally acceptable is the use of genetic techniques to improve human capabilities rather than solely to cure disease in prospective children?
Clear majorities (82% and 73% respectively) said such enhancement was unacceptable. In fact, most (56% and 47% respectively) checked not at all acceptable rather than not generally acceptable. Only 14% and 17% viewed enhancement as acceptable to at least some degree.
Historically, definitions of eugenics typically have assumed an agent that attempted to interfere with reproductive processes to produce a coerced, desired goal. Newer viewpoints have tried to tone down the negative connotations and separate out acceptable forms of eugenics that focus on producing better human offspring.
But present concerns point to the dangers arising from what have been called in the literature back-door or homemade and soft or laissez-faire eugenics in which families, not the state, voluntarily set about choosing the type of children they wantfamily eugenics rather than population eugenics, as one respondent to the survey put it.
Respondents brought up other important questions that will require examination and discussion as well: of cost and of equality of access to this potential technology. Who will benefit from it?
They also referred to enhancing capabilities by improving educational and social environments instead of altering nature: We should cherish human diversity and underscore differences in talents and aim at improving nurture for enhancement.
The human genetics debate in Germany and other German-speaking countries is especially complicated. Philosophically, German ethical thinking is said to derive from general principles of reason and a Kantian emphasis on duty rather than pleasure and happiness.6
And the German constitution of 1949 is unusual in that it rules explicitly that the dignity of man is untouchable. Historically, Germany is haunted by barbarous acts of human instrumentalization, including eugenics, euthanasia, and nonvoluntary medical experiments on peoplecommitted during the Nazi regime.7
In contrast to somatic cell gene therapy, inheritable genetic modifications (IGM), traditionally called germ-line treatment, would entail correcting genetic flaws in the DNA of human embryos, thus eliminating the defect from succeeding generations as well as the child-to-be, and would thereby reduce the incidence of certain inherited diseases in the human gene pool.
Compared with the 96% of all respondents who supported somatic cell gene therapy to cure life-threatening diseases, only a minority of scientists in Germany (34%) and other European nations (41%) viewed germ-line genetic intervention to prevent serious disease as ethically acceptable (if and when gene repair/replacement were to become a safe and validated technique).
The survey measured next the extent to which different reasons provided justification for interceding in this manner (Figure 3). Only a minority of all respondents thought that these items were justifiable grounds for involving the germ line.
Any such acceptability seems to rest largely on a concept that has been described traditionally in medical science as the duty of the present generation to protectthe genetic quality of the next or to promote the good of a distant futurity, by selectively reducing the genetic load passed on to future generations.8
Compared to other European researchers, Germans were even somewhat less persuaded by seven out of eight arguments posed. The exception was the use of germ-line therapy as a replacement for abortion and selective discard.
In fact, German researchers were found to be more concerned about avoiding termination as a medical answer to genetic disease on all questions related to this topicanother possible example of the nations sensitivity to its tarnished history.
For example, one question presented researchers with two alternative practices to compare: (1) current reproductive procedures for avoiding disease or disorder in prospective childrenboth prenatal testing followed by abortion and in vitro pre-implantation testing followed by selection/discard; as opposed to (2) gene therapy to treat effected embryos or fetuses.
The first is less risky and less costly but allows only the diseased-free to continue development; the second, while mostly hypothetical and potentially expensive, has the advantage of avoiding termination.
Weighing the two options: Only 30% of Germans agreed more with the firstcontinuing present methods, compared with a higher 42% of other European respondents.
Some 38% of German respondents opted for the secondmoving toward gene therapy in order to move away from termination, in contrast to fewer (30%) of the other Europeans.
Returning to ethical arguments regarding germ-line gene therapy, respondents were also presented with a set of reasons that might warrant prohibiting such therapy.
The most important one for researchers was unanticipated negative effects that, if not correctable, would be passed on to descendants (62% of German and 71% of other European scientists).
This finding is consistent with the traditional ethic of long-range responsibility to protect future generations described above. But high on the list also, at 52% for both groups, was their aversion to enhancement (pressures to use the technique for genetic enhancement), as well as concerns about questionable, possible malevolent uses to which the technique might be put (52% and 48% respectively).
There was a sharp drop-off in support for a number of other arguments against germ-line gene therapy, where support ranged from 1930%: a childs right to have a genome that has not been tampered with; that such treatment would go beyond limits humans ought not to exceed or is contrary to religious beliefs; that it would reduce the diversity of the human genome; that it would interfere with human evolution/natural selection, and, therefore, the genome should never be altered; and that it would be too costly to be made available to most couples.
Human Embryonic Stem Cell Research and Therapeutic Cloning
The isolation of human pluripotent stem cells in 1998, a major breakthrough in biomedicine involving a self-renewing cell line that gives rise to all cells and tissues of the body, caught the world by surprise and prompted ethical questions for science and medicine. The discovery has presented further challenges for shaping adequate regulatory and public policy.
A high 81% of German and 88% of other European researchers advocated therapeutic cloning of human cells for replacement tissue, whereas there was virtually no support (1% and 4% respectively) for reproductive cloning of whole human beings.
In political discussions around the world, opposition to stem cell research and therapeutic cloning is based most often on the reliance on human embryos for the development of potentially therapeutic stem cells. When asked about the acceptability of using embryos to produce medically valuable cells for treatment purposes, only 33% of German, but 55% of other European scientists agreed.
Germanys Embryo Protection Law proscribes any manipulation or use of the in vitro human embryo other than to implant it into the woman whose egg produced it. Together with Germanys emphasis on human dignity, it excludes categorically any instrumentalization of a human being for means other than its own existence, thus prohibiting procreation of a human embryo solely for scientific or medical purposes9
The intense debate over the ethics of stem cell research in Germany at first hinged on the fundamental question of the moral status of the early human embryowhether dignity pertains at a point when it consists of only a few hundred cells. But central also to the question of appropriateness of stem cell research, in Germany and elsewhere, is the source of human embryos obtained for medical research.
Respondents were in accord that the most desirable way for human stem cell research to proceed was taking cells from patients bodies to produce stem cells for their own treatment (95% of Germans and 90% of non-German) and producing stem cells without the intermediary stage of existing as an embryo (77% and 78% respectively). But these methods have had questionable success to date.
Considering the alternatives, the most acceptable source for acquiring human embryos was from those retrieved from aborted fetal tissue (59% among all respondents), while obtaining excess embryos originally created for fertility treatment was a close second for non-German scientists (52%), but not so much so for the Germans (41%).
Both involve embryos that would ultimately be destroyed anyway. Creating human embryos for research purposes garnered little support (7% and 15% respectively). Finally, significantly fewer German researchers (28%) than other Europeans (46%) were comfortable with both the destruction of human embryos in the research process and the mixing of cells from different species (19% versus 34%).
In 2000, Bonn University neuroscientist Oliver Brstle submitted a proposal to Germanys main research funding agency, the Deutsch Forschungsgemeinschaft (DFG), to use imported embryonic stem (ES) cells in his research, and in 2001 the DFG announced that it was prepared to fund research on such stem cells.
These events instigated stepped-up discussions that included a new possibilityusing ES cells produced outside Germany for research, since they were no longer potential human beings.
The debate pitted Germanys chancellor Gerhard Schrder against its president, Johannes Rau. Rau attacked stem cell research and genetic testing of test tube-fertilized embryos as running contrary to fundamental values of human life and warned not to forget that in Germany during World War II an uncontrolled scientific community did research for the sake of its scientific aims, without any moral scruples.10
Schroder defended researchers who sought new treatments against diseases and maintained that the ethics of healing and of helping deserve just as much respect as the ethics of creation.11
In January 2002, after the establishment of a new bioethics council and much heated debate, the German parliament voted to allow the use of human embryonic stem-cell lines, if imported from outside Germany and if created before that date, under strict conditions and strict oversight and only if the research cannot be done with alternative cells.12
These are some of the most stringent regulations in the world covering research with human ES cells, and it took another year before the first project won final approval.13 This survey spanned that period.
Regulation of Practices
Despite the fact that researchers in Germany were consistently more restrictive on most human genetic issues, they exhibited slightly less preference, however, for government regulation of new technologies: for human reproductive cloning (78% versus 83% of other European researchers), human embryo research (71% versus 75%), germ-line gene therapy to cure/prevent disease (71%, 74%), in vitro testing for genetic traits before implantation (47%, 48%), in utero testing for genetic traits in unborn children (46%, 48%), and somatic cell therapy to cure/prevent disease (43%, 52%).
The one exception was stem cell research, where German support for oversight was slightly higher: 47% versus 43%.
While seemingly inconsistent with German respondents more cautious viewpoints demonstrated throughout the survey, this pattern is in line with expert assessments of national differences in regulatory climates, in which Germanys oversight has been ranked by far the most strict.14
Given the severity of regulation already in place in Germany, researchers were not likely desirous of, nor would they see the need for, more oversight. In the past, German genetic engineering scientists have also argued against what they perceived as over-regulation, because it put German researchers, research centers, and biotechnology companies at a competitive disadvantage.15
Respondents from Germany and other European nations were in agreement that trying to cure serious diseases in an individual, even in utero, would justify the use of gene therapy or even therapeutic cloning for replacement tissue.
Presently, most believed that such diagnosis would justify pre-natal termination if a cure were not possible. Both groups were also similarly opposed in large numbers to using any of these techniques to improve human capabilities, i.e., enhancement, as opposed to curing serious disease.
German researchers and other European scientists, however, frequently differed when the issues were not posed at the more clear-cut extremes. And these differences almost always found the Germans taking a more restrictive position.
For example, both groups claimed ethical acceptability for therapeutic abortions for those predicted to be severely mentally retarded or likely to die by age four. But when such predictions involved mild mental retardation, approval among Germans dipped to 12%, as opposed to 29% among other European researchers.
Similarly, when somatic cell therapy was posited to correct a learning disorder rather than to cure a life-threatening situation, German respondents determination of ethical acceptability went from 96% to 25%, while the decrease among other European respondents was from 96% to 54%, still a majority.
German scientists were also more reluctant to opt for precautionary surgery where time bomb genes were present without symptoms, as they were when it came to using human embryos in stem cell research.
Their guarded attitudes about the origins, the use, and the destruction of human embryos in the research process were consistent with comments made about the debates within Germany dealing with governmental oversight of stem cell research, namely that the Third Reichs history of genetic experimentation had left its mark on present-day German discussions.
The higher reluctance on the part of German researchers may also be a result of the fact that they are less optimistic about the therapeutic promise of human genetics.
Some 48% thought its promise would be realized, versus 61% of other European researchers. Or it may be that German researchers reluctance has made them less able to be confident that such promises will be realized. Without further study, one can only speculate about the more conservative opinions of German respondents on some of these ethical issues.
Given the public and political debates about ethics in the field of human genetics, it is important to note that although German and other European human genetics researchers may differ on a number of issues, it is clear that they are highly concerned with impending ethical problems resulting from advancements in their field.
They urge responsible caution, especially with regard to technology that might genetically alter future generations and affect the human gene pool. Moreover, they emphatically reject the use of their science for enhancement purposes. These findings should assuage those who worry that scientists interests in fostering scientific knowledge may work to the detriment of ethical considerations.