How far would you go to have a healthy baby?
Writer: Eleanor Gallegos
Editor: Maddie Wigmore-Sykes
In November 2018, Chinese Scientist Professor He Jiankui shocked the world of science when he announced that he had created the first ever genome-edited human babies. His goal? To create “HIV-resistant infants”. Professor He’s proclamation was met largely with criticism and condemnation, with scientists stating that the move was irresponsible and premature. But what do his actions mean for the future of science, and has he opened the door to a world where genome editing becomes the norm for couples seeking the birth of a healthy child?
What is genome editing?
Genome editing encompasses any technique used to alter DNA at a specific location in its sequence. One of the most widely used tools to perform this alteration is CRISPR-Cas9, which offers a very fast and precise method for genetic manipulation in humans based on a naturally occurring bacterial defence mechanism against viruses. In a laboratory setting, researchers create a piece of guide RNA (gRNA) which is designed to target a specific sequence of DNA in a genome. The gRNA also binds to Cas9, a molecular scissor, and guides it to the correct region of the genome where Cas9 can cut the DNA at the targeted location. The cell’s own DNA repair machinery can then be utilised to insert or delete genetic material, creating a sequence of DNA that is desired.
HIV is a deadly virus that attacks the body’s immune cells, invading and destroying CD4 white blood cells which play a vital role in our defence against illness. Despite huge improvements in the global prevention and treatment of HIV, it still remains a major health problem and a threat to human life. Antiretroviral therapy (ART) is a treatment for HIV that suppresses viral replication and thus stops the progression of the disease. If taken properly, ART can result in an undetectable viral load for infected individuals, completely eradicating the risk of transmission of the virus. However, barriers including fear of stigmatisation and discrimination as well as religious obstacles may prevent certain affected individuals from gaining access to treatment. These barriers, coupled with the fact that not all infected persons will take their medication correctly, mean that HIV transmission still occurs through mediums such as intravenous injection, sexual intercourse, and vertical transmission.
When Professor He used CRISPR-Cas9 to edit the genome of two embryos, he edited a gene called CCR5 which encodes a cell-surface receptor on white blood cells and is the mechanism by which HIV invades cells. He aimed to give the embryos a version of the CCR5 gene with a 32 base pair deletion (CCR5∆32) in a specific genetic region, which is known to protect certain individuals from HIV infection by preventing HIV entry into cells.
The actual mutations Professor He yielded in CCR5 were not the 32 base pair deletions he intended to, but instead novel mutations never studied before in humans – thus their effects on the babies are unknown. Many believe Professor He’s experiments were grossly unplanned and ill thought through, with the hypothesis that any edit within the genetic region of the CCR5 gene would create HIV resistance. The mutations created were not tested in any animal models, but transferred back to the mother with the assumption that these mutations would have the same effects as CCR5∆32. It is therefore unknown what effects the mutations will have and if unintended consequences could be suffered. There have even been reports that the gene mutations he has created will shorten the lifespan of girls, and a recent study found that people possessing the mutation Professor He was trying to engineer have a 21% higher mortality rate than people with the wild-type gene.
Professor He’s reasoning for editing the embryos was to ensure resistance so the two individuals would not be infected with HIV in the future, but this argument is severely flawed by the knowledge that CCR5∆32 cannot guarantee immunity. Although this mutation does confer resistance to the most common strain of HIV, certain strains of HIV can use another receptor CXCR4 instead of CCR5 to infect CD4 cells. Thus, although the mutation could have protected the twins from certain strains if successfully implemented, they would have still been vulnerable to HIV infection.
Finally, is genome-editing even necessary to prevent HIV infection by vertical transmission? According to the World Health Organisation, the risk of transmission between an infected mother on antiretroviral therapy and her child is just over 1%. For men, the risk is also minimal and sperm washing coupled with artificial insemination can ensure a negligible risk of transmission. Many HIV-infected couples successfully reproduce and create healthy offspring without the need for gene-editing technology, so doesn’t this make CRISPR-Cas9 editing a redundant technique with unnecessary risks when used in this setting?
Looking to the future
Unjustified, dangerous, and shockingly unethical – these are the common views of scientists on the experiments performed by Professor He. His decisions have cost him his job at his university, censure by the health ministry in Guangdong and the potential of facing criminal charges. But what is next for CRISPR babies? Some scientists have called for a global suspension of all embryo editing in order to prevent any more premature attempts, but in reality the wide range of laws governing germline gene editing leaves room for future attempts. Russian scientist Denis Rebrikov has stated that he is already planning to produce the next gene-edited babies to prevent mother-to-baby HIV transmission, stating that “I think I’m crazy enough to do it.”