1. Most Chinese medical researchers were aware of the ethical issues related to using transgenic monkeys with human genes for medical research.
According to the survey, more than seventy percent of the respondents thought there were ethical issues in using transgenic monkeys with human genes for medical research. At least three kinds of arguments have been advanced against the creation of human-nonhuman chimaeras, such as creating transgenic monkeys with human genes: a dignity-related argument, a moral status argument, and the playing god argument. First, the dignity-related argument claims that the chimaera could possess human-like mental capacities, which would undermine human dignity. In our study, 23.6% of the respondents thought it was an affront to human dignity. Second, farming human-pig chimaeras for their organs risks perpetrating a serious moral wrong because the moral status of human-pig chimaeras is uncertain and potentially significant, as Koplin and Wilkinson pointed out [7]. Finally, the playing god argument holds that human beings are not gods and have no right to create genetically modified monkeys that show a disregard for animals. Of course, not all agree with the above arguments. For instance, Palacios-González criticized that these arguments confuse the ethical assessment of the creation of chimaeras with the ethical assessment of how such creatures should be treated in specific contexts (e.g., in the laboratory)[8].
2. The unacceptable risk-benefit ratio is the biggest ethical issue.
The survey shows that the “unacceptable risk-benefit ratio” was transgenic monkeys. Professor Wieland Huttner, who led the study that transferred the ARHGAP11B gene into marmosets, said their experiment was stopped because of the gene's unforeseen potential effect on brain function after the monkeys were born. Monkeys, once equipped with human genes, might be as advanced as humans or even smarter, so their research was stopped at the embryo stage. If such studies found that the gene improves memory and promotes intelligence, increasing skills of observation, memory, imagination, understanding, analysis, judgement, thinking, strain capacity, etc., it cannot be ruled out that introducing such genes opens the risk that scientists make experimental animals more powerful, even becoming superhuman. Such experiments have even been called human death experiments. James Sikela, a geneticist at the University of Colorado, argues that such experiments constitute a classic slippery slope issue in that the experiment shows disregard for the animals and will soon lead to more extreme modifications [9].
Overall, 33.7% of Chinese medical researchers believe that using genetically engineered monkeys for medical research harms the monkeys; this was the second-most reported ethical concern. There is irrefutable evidence that monkeys have rich social and mental capacities. Using transgenic monkeys with human genes for medical research destroys their original way of life, potentially causing them greater social and mental suffering than that experienced by other experimental animals. Recognition of the moral status and intrinsic value of nonhuman primates must be reflected in research programs involving the use of nonhuman primates. The use of genetically modified monkeys for medical research does them no good, only harm. By transferring genes unique to humans to monkeys, such research blurs the line between humans and animals. Transgenic monkeys with human genes might have human-like characteristics, but they do not have human rights. They will not receive a level of protection and care befitting their moral status[10].
Given that nonhuman primates have the ability to feel pain, are conscious and self-aware and have the ability to communicate socially but cannot easily communicate with humans, we recommend considering them to be similar to human “vulnerable groups”, which would require primate zoologists or experienced animal management to be hired as their guardians and participate in the animal ethical review committee or for them to participate in the research decision making. Representatives of animal protection organizations may also be invited to participate as independent consultants in the review meetings of the Ethical Committee for Animal Experiments. Scientists need to clearly articulate the scientific and translational benefits of human-monkey chimaeras to society so that any ethical or moral risks can be properly weighed.
3. Overall, 70% opposed allowing medical research using human genes to be carried out, even with the approval of their own organizations.
According to the survey, approximately 70% disagreed that medical research on genetically modified monkeys could be carried out if approved by the ethics committee of the organization in which it was conducted. For such a world-first medical study with ethically controversial implications and the biological safety risks associated with major cutting-edge research, approval by only the sponsoring scientific research institution and head of the ethics committee is not enough; approval should also be granted by the regional ethics committee, the national science and technology ethics committee, the competent department of health at or above the provincial level, or a comparable temporary committee of experts following sufficient argumentation and evaluation.
4. The use of transgenic monkeys in medical research needs to more rigorously implement 3 R content
As nonhuman primates possess cognitive and emotional abilities similar to those of humans, they have computational, memory and problem-solving skills. Their abilities make them highly sensitive to pain, and confining them in a laboratory for research results in extreme harm[11]. Therefore, animal research committees play a primary role in evaluating experimental research protocols, from their feasibility to the rational use of animals, primarily to ensure animal welfare by following the principle of the three Rs (replacement, reduction, and refinement)[12].
4.1 Replacement: Current ethical guidelines dictate that a substantial benefit must be demonstrated for the creation of transgenic monkeys using human genes or those of related nonhuman primates (and their cloned counterparts) [13]. The use of nonhuman primates for biomedical research is mostly unnecessary to achieve scientific goals [14], and approximately 9% of the studies are of little significance but cause great pain to the primates[15]. In 2008, a rhesus macaque that expressed hallmark features of Huntington’s disease became the first transgenic monkey model of human disease[16]. The 3Rs state that animals should be used only if there is no alternative[17]. For using transgenic monkeys with human genes for medical research, it is recommended that nonhuman primate research be evaluated on the basis of its scientific value, the likelihood of medical or other benefits, the availability of other alternatives, and the probability and extent of animal suffering[15].
Currently, with the progress of science and technology, the 21st century has already seen the development of promising, high-tech nonanimal models, such as organs-on-a-chip and computational approaches that, in our view, will replace animals as the default option in biomedical experimentation[18]. There are other alternatives to primate models, such as using brain imaging, noninvasive electrophysiological techniques, in vitro and computer simulations, and even human subjects.
4.2 Reduction: The 3Rs state that animals should be used only if there is no alternative, and when animals are necessary, only the most humane methods should be used on the smallest number of animals required for scientific validity[17]. Studies should also reduce the number of primates needed for research by sharing data, publishing all research results (including negative results), and regularly checking the outcome benefits and effects of studies to avoid unnecessary duplication. The ideal future will allow appropriate alternative animal models to be developed using an array of techniques, from humanizing other model organisms through genome editing to computational approaches, thus reducing the use of nonhuman primates as much as possible.
4.3 Refinement: Unlike rodents, nonhuman primates suffer not only great physical harm but also serious mental harm in experiments or studies. Providing welfare for nonhuman primates is challenging and requires a good environment to ensure their mental health. There are many issues that need to be addressed, including group placement, improving the environment, and caring for infants and young children, as well as individuals who show signs of mental problems. China has been discussing animal rights issues since 2002. In 2012, The Chinese Center for Disease Control and Prevention issued the Regulations on Ethical Review of Experimental Animal Welfare in Nonhuman Primate Experiments and Animal Experiments in International Cooperation Projects (Trial). In 2016, the national standard "Experimental Animals: Guidelines for Welfare Ethics Review (Draft for Comments)" was released. This process shows that China also paid attention to animal welfare and ethical issues related to animal experiments.