By Michela Reinink
For years, gene editing was progressing at a timely rate, ethical and safety concerns addressed as they were raised. In November 2018, this changed – Chinese geneticist He Jiankui revealed two genetically modified twin baby girls, an unorthodox move that shocked the world. With CRISPR-Cas9 editing, He Jiankuitargeted the CCR5 gene, naturally-occurring mutations at this locus having previously resulted in HIV-resistance.
CRISPR-Cas9, a gene editing system that allows for targeted, specific changes, was only proposed in 2012. He Jiankui’s lab initially experimented on mice and monkeys, reporting that the animals had no resulting health issues. The lab then proceeded to make the enormous leap to modifying human genomes in an effort to make HIV-resistant children. The babies, nicknamed Lulu and Nana, are both in good health, according to the lab, but Nana is not resistant to HIV.
The numerous safety concerns associated with human gene editing have led to widespread confusion as to why this took place. To list a few of the concerns: vulnerability to other infectious diseases, risk of cancer, off-target mutations, and mosaicism – the state of being composed of two genetically different cell types. This could happen if the division of the egg starts before the edits, and if the immune system develops from a unedited cell, the individual would not have the modified immunity.
As human genome editing methods are not fully developed, it is impossible to be sure that these problems were avoided with Lulu and Nana. With the unforeseen development of the CRISPR babies, as they are called, there is now an urgent need to improve biotechnology so that off-target mutations may be detected with a higher degree of accuracy.
There are also numerous ethical concerns to address. On December 30th, 2019, He Jiankui was fined and sentenced to three years in prison, with two of his collaborators also receivinglesser sentences. It was found that numerous ethical documents had been forged, and that participants had been paid off to keep the research confidential as a means of securing personal monetary gain from the technology. The three were charged with illegal medicinal practice, as none have certification to practice medicine, and the clinical genome-editing trial was categorized as medical activity.
It is clear that He Jiankui’s results cannot yet be trusted: little evidence has been presented, and the work has not been peer reviewed. This has pushed previously unexplored questions to the forefront of the scientific community regarding the ethics ofhuman genome editing. If we can modify human genetics to give resistance to disease, what is to stop us from giving embryos full genetic makeovers, producing ‘perfect’ children with blue eyes and straight teeth?
These questions, which seemed years away from relevance, are now of utmost importance. While some countries have laws regarding gene editing, no international laws as of yet exist. There is a key difference between editing somatic and germline cells: germline cell edits are heritable, which means they will ultimately have an effect on the entire species. Therefore, we must be on the same page internationally regarding human genome editing as we move forward. He Jiankui himself stated that he is not in favour of genetic modification for the purpose of enhancement, but this may be the logical next step as human gene editing becomes more widespread.
While most science professionals would agree that it is far too early to edit the human genome, Lulu and Nana provide a unique opportunity to study the effects of a CRISPR-Cas9-induced edit. Doing so could provide valuable insights and lead to the development of improved genetic editing systems. That said, it would be wise to prevent any more genetically modified children from being produced until scientific methods improve, and international guidelines are solidified. After the international backlash that was sparked by these CRISPR babies, it seems natural to put laws into place to prevent human genome-editing on germline cells to be put into place. He Jiankui’s work should be used as a cautionary example: an unethical, as of yet unsafe scientific practice that must be condemned by the international community to ensure that dangerous procedures like this do not become commonplace.