Genetic Editing: Where Do We Draw the Line in Using Animals for Medical Research?
“Primates are highly intelligent and social animals. It is not ethical to deliberately harm them, and especially when the chance of tangible benefit for human patients is so small. Such research is very irresponsible.”
— Andrew Knight, Professor, Animal Welfare & Ethics, University of Winchester
The first primate clones, macaque monkeys, occurred early in 2018 in China. Chinese researchers have now successfully repeated this process, cloning five gene-edited macaque monkeys, using the same somatic cell nuclear transfer method. But these monkeys were cloned from a primate whose genome was edited using CRISPR-Cas9 to get rid of a gene that is important in determining circadian rhythm.
The scientists altered a number of fertilized monkey embryos in a way that resulted in circadian sleep disorders, a disorder with known serious mood and physical effects. The researchers then selected the animal with most severe disease characteristics to clone. A statement was made announcing the success and an expectation that populations of customized gene-edited macaque monkeys with uniform genetic background for specific diseases and conditions will soon be available for biomedical research.
The monkeys exhibited a number of symptoms included reduced sleep time, elevated night-time activity, dampened circadian cycling of blood hormones, and severe anxiety, depression, and schizophrenia-like behaviors. This gene was selected out as disorders of circadian rhythm can result in many human diseases, including sleep disorders, diabetes mellitus, cancer, and neurodegenerative diseases.
According to the investigators, this study demonstrates that this method could be used to generate cloned monkeys that are identical to a genetically edited monkey. They believe this sets the stage for developing macaque monkey disease models with uniform genetic characteristics. Yet, ethical questions have been raised in response to this research.
One such questions has to do with this entire line of research aimed strictly at proving that groups of genetically identical monkeys with a variety of diseases, conditions and symptoms can be created. Yet simply proving this can be done without any purpose for the monkeys afterwards does not seem like ample reason to cause such suffering.
According to bioethicist Carolyn Neuhaus of The Hastings Center, “It’s very clear that these monkeys are seen as tools.” She took particular issue with the fact that the researchers considered the monkeys’ suffering a success and as the intended outcome as opposed to using them in order to investigate a scientific hypothesis directly. If asked to evaluate this research as part of an ethics review board, Neuhaus said that she would likely not be able to do so. Minimally, she stated that she would require more information regarding the methods of the study and what benefits the project would yield.
Another ethical problem raised is one that is common to experiments conducted with primates. Researchers have stated that the value from these experiments lie in the fact that macaque monkeys are very similar to humans. Yet, there are ethical issues regarding using a species so similar to humans for this type of invasive research that causes the monkeys subjective suffering.
Alan Bates, an Oxford Centre for Animal Ethics fellow, was particularly concerned, saying, “If monkeys’ mental processes were sufficiently close to humans to provide a valid model, then it would certainly be unethical to experiment on them”.
Bates raised another issue. He pointed out that laboratory-reared animals have been known to exhibit symptoms of mental illness without them being caused genetically. So given the study was on mental illness, it would be difficult to determine which symptoms might be similar to what humans experience and which might have just been a manifestation of being raised in a deprived laboratory setting.
Related to the laboratory setting, something else that could have led to symptoms of mental illness was the presence or absence of maternal support and nurturing. The monkeys were most likely kept alone without their mother available to help them cope with whatever symptoms developed. Alternately, if the mother was kept with them, she had been altered to display the same severe symptoms of mental problems and would not have been able to provide the support her young needed.
As she would have displayed the same symptoms, her presence could have reinforced and worsened their problems. Studies have long determined that young monkeys that didn’t have access to comforting maternal support displayed symptoms of being maladjusted included depression and anxiety. Causing suffering in animals when it can’t be determined what directly led to the symptoms making the monkeys of limited use for research purposes would seem highly unethical.
Unlike Mr He’s recent experiment editing human genes that resulted in the birth of a baby girl, the Chinese government authorized and funded the macaque monkey trial, which was carried out by researchers at the country’s Institute of Neuroscience. However, there are a number of ethical issues that should be further considered prior to continuing this line of research including cloning, animal rights, and gene editing.
The main thing that needs to be discussed is whether the potential benefits to science are enough to justify the amount of harm done to these monkeys. Until we can determine how much we could benefit from research conducted with genetically edited and cloned animals, considering the potential suffering caused, we should consider whether this technology should be used for such purposes.