In November of 2018, Chinese scientist He Jiankui made an announcement that astonished the scientific community. He claims to have helped to make the first ever gene-edited babies with the use of a revolutionary technology called CRISPR. The babies, twins by the names of Lulu and Nana, were born to a father infected with HIV, the virus which causes AIDS. If Dr He’s experiment is successful, the twins will have an immunity to the virus. While this may seem at face value to be a noble goal, many believe that the risks involved outweigh the benefits. His experiments used a type of editing called ‘germline’ editing, meaning that any children that Lulu and Nana may have in the future will also carry this immunity. Germline editing involves making changes to reproductive cells. This means that any changes made to the individual’s genome will be passed on from generation to generation. This can be distinguished from somatic editing, in which the only person affected by the edit is the person who undergoes the procedure.
One reason why somatic editing is seen as more acceptable than germline is that people who undergo somatic editing have given informed consent prior to the procedure. While the parents of Lulu and Nana have given consent, the children themselves and any future children the twins may conceive have not consented to the potentially high risks. While HIV immunity could potentially be inherited by the descendants of these CRISPR babies, so could a myriad of unwanted and possibly even deadly side-effects.
Furthermore, it is not clear that Dr He’s treatment fulfilled an ‘unmet medical need’. With modern HIV treatments, someone who is carrying the virus can have the same expected lifespan as someone who is not and their chance of transmitting the virus to their children can be brought down to just 5%. Hence, geneticists worldwide have called for a moratorium on human germline trials. Critics say that gene editing technology has not yet been developed or tested sufficiently for use on human embryos. We simply do not yet know the long-term effects of genetic modification using CRISPR.
Despite a myriad of imaginable ethical hazards, CRISPR has the potential to revolutionize the biomedical sciences. CRISPR allows biologists to edit genetic information by using an enzyme called Cas9, which has the ability to cut strands of DNA. The process was pioneered in bacteria as a defence mechanism against viruses. Geneticists use CRISPR to target specific areas of genetic code and cut it in a specified region. Cutting a strand of DNA in the right place can cause a certain gene to be disabled, activated or replaced by one introduced by scientists. The possible applications of CRISPR range from curing cancer to eliminating malaria from mosquitos. One team at Harvard led by Prof. George Church even famously claimed that they will be able to ostensibly resurrect the woolly mammoth in the next year or two using the technology.
Some scientists, including mammoth-man George Church, have come out in defence of He. While Church had reservations regarding He’s level of transparency, he suggested that enough studies had been carried out that maybe it was the right time to end the moratorium anyway. While he accepted the risk of off-target mutations, he said that the risk ‘may never be zero’ and that Dr He had done enough to minimise it. This contradicts the views of most scientists and institutions, including a statement released by Francis Collins, the director of the National Institutes of Health. Collins denounced He’s work, saying, among other things, that ‘the possibility of damaging off-target effects has not been satisfactorily explored’. Genes are extremely complex things. Locating a single gene and modifying it requires an extraordinary level of precision and even when it is successfully targeted it is impossible to fully predict the consequences. Though we have been studying certain genes for a very long time, we still do not know what the indirect effects of certain edits may be as no long-term studies of how edits affect the human body have been carried out as of yet. Such unintended effects are known as ‘off-target mutations’.
The final concern is perhaps the most serious. While CRISPR may in the future be used to treat some forms of cancer, it is possible that premature germline editing like the kind He carried out may actually increase the risk of cancer in people like Lulu, Nana and their descendants. Two recent studies have raised concerns about an off-target effect that CRISPR may have on a gene for a protein known as the ‘guardian of the genome’: p53. This protein is responsible for repairing or destroying damaged DNA. A mutated or ineffective p53 gene has been shown to be responsible for nearly half of all ovarian cancers and a significant portion of many other types of cancer too. CRISPR interventions activate p53, since DNA has been cut and must be either repaired or destroyed and p53 undoes the work CRISPR has done. The worry is that this could result in a kind of artificial selection on the cellular level, as CRISPR is more successful in cells with ineffective copies of the p53 gene, which are the more at risk of becoming cancer cells. So far, only certain forms of cells have shown evidence of raising the risk of cancer when modified using CRISPR and no company is attempting clinical trials using CRISPR on these cells. Some scientists have called the recent studies concerning p53 a ‘cautionary tale’ since they may affect future CRISPR trials that are yet to begin.
CRISPR is an incredible technology that will surely be responsible for many breakthroughs in biological and medical science. It may someday give us powers that we cannot even conceive of today. However, that time has not yet come. It is imperative that we do not jump the gun. Dangerous, premature experiments like Dr He’s harm the public perception of gene editing and, in turn, harm the funding available for important research. While we should not give up on gene editing, we should also not use it to play with human lives until we know more about the benefits and the risks.
By Adam Boland – Science Writer