Chinese researchers have cloned five genetically modified monkeys with a variety of genetic disease symptoms, according to two scientific papers published today. The researchers say they wanted to use the genetically-modified macaques for biomedical research; Basically, they hope that the development of sick primates will reduce the total number of macaques used in research. However, your experiment is a minefield of ethical dilemma – and lets you wonder if the potential benefits to science are enough to justify all the damage to these monkeys.
The researchers used CRISPR / Cas9 to manipulate a donor's DNA Macaque CRISPR / Cas9 is the oft-discussed gene editing tool that comes from bacteria and combines repeating DNA sequences with a DNA-cutting enzyme to match DNA sequences. Experts and the press have announced this as an important step forward, as it is quick and inexpensive to change DNA, but recent research has shown that it can cause more adverse effects than previously thought.
In this experiment, the researchers switched off a gene called BMAL-1, which is partially responsible for the circadian rhythm. Monkeys with this gene turned off show increased anxiety and depression, reduced sleep times, and even "schizophrenia-like behaviors," according to a Science China Press press release. Circadian arrhythmias have even been linked to diabetes and cancer.
The team then transferred the cores of donor monkey tissue cells to an egg cell to make the clones. The result was five cloned monkeys, each of which showed symptoms of the genetic disorder introduced into the donor monkeys. The researchers described their findings in a pair of articles published in the National Science Review.
But why? The researchers hoped to develop individual model organisms closer to humans to understand and find potential cures for genetic diseases, including brain diseases, cancer and other diseases, such as Hung-Chun Chang, senior author and investigator of the Chinese Institute for Neuroscience said in a statement. By creating identical animals, they may be able to locate causes and healings more quickly.
This research combines a lot of ethical issues in one package, from animal rights rights to cloning and gene manipulation. As bioethicist Carolyn Neuhaus of the Hastings Center, she summarized her reaction to the announcement: "Whoa, this is an idiot."
"It is very clear that these monkeys are seen as tools," she explained. The team of scientists behind the new announcement warned the monkeys' suffering – anxiety, depression and "schizophrenia-like behaviors" – as a success. She found that the researchers did not have any scientific hypotheses or treatments that they tried to prove or disprove, and instead they basically just tried to see what would happen if they were working on a crucial gene. It's like deleting a cryptically named file from your system's system folder to see what happens.
In addition, these monkeys appear to have behaviors that are analogous to human disease, but the comparison between monkeys and humans eventually ends. It is possible that turning off the BMAL-1 gene in humans has different effects. And finally, the monkey's identical DNA could be a weakness instead. Man has many genetic differences, so a remedy that works for identical macaques may not work when presented to the much more chaotic human genome.
That does not mean that we should not genetically treat monkeys, said Neuhaus. However, she said, "If I was on an ethics review committee, I would be very hesitant to agree [this research] because the animals were so incredibly injured. I would expect the scientists who propose this research to have very good answers to very hard questions about their methods and the expected benefits of their research.
Gizmodo turned to Chang for these ethical concerns, but he did not respond at the time of publication. We will update the post when we hear again.
Cloning and gene editing are progressing rapidly. Chinese scientists (including some of the same researchers behind this new work) announced the birth of the first cloned monkey nearly a year ago, and we have suggested that this might be the potential use of the cloned monkey. The CRISPR technique is already being used in humans, and Chinese scientist He Jiankui recently claimed to have produced the first genetically engineered infants that caused outrage by many other scientists. The Chinese government has said that he violated the law.
Scientists are already discussing the ethics of genetically modified humans, and some have cautiously agreed that it is "morally permissible" to genetically alter babies in some cases. New technologies are always raising new ethical issues, but the principle that potential benefits should outweigh the harms is not new. In this most recent case, it is by no means clear that research meets this fundamental standard.