Editing Embryos: CRISPR and the Ethics of Human Genetic Engineering

Last updated on June 26, 2020

In November of 2018, Jiankui He, a Chinese biophysicist, announced to the world that he had created the first ever CRISPR-edited human babies. The experiment resulted in twin girls, Lulu and Nana, who developed from embryos with a modified version of the CCR5 gene meant to increase resistance to HIV. The experiment was riddled with breaches and blunders, and it quickly became an international scandal. At the end of 2019, He was sentenced to three years in prison for “illegal medical practices.” All of the flaws in He’s experiment highlight just how far we still have to go before embryonic CRISPR editing can become common practices. It also serves as an important reminder of the ethical ramifications of human genetic engineering. Changing human genes isn’t as trivial as the movies may make it seem. A change in the embryonic genome could have unintended consequences for not just the baby, but also any children that baby eventually has. Once made, the genetic change can persist through generations. At the same time, embryonic CRISPR editing could finally put an end to some of the most debilitating genetic disorders and may even be able to provide resistance to certain diseases (like Covid-19 as I mentioned last week). At what point do the benefits outweigh the risks? Who gets to decide what sorts of genes get edited? And what could be the secondary consequences of overwriting our own genetic code?

The deletion mutation Jiankui He edited into two embryos was meant to be similar to the natural Δ32 variant of the CCR5 gene. This CCR5 variant is believed to convey resistance to HIV, but the data on that has been inconclusive. Additionally, the edited CCR5 gene He generated in the embryos wasn’t completely the same as the Δ32 variant. Therefore, there is no indication as to whether He’s edited version would result in the same HIV immunity.

Along with being imprecise, He’s genetic editing was inefficient—not all of the cells in the embryos were edited. A few unedited cells may not seem like a big deal, but in an embryo, those few cells divide and develop to make up a significant portion of the baby’s body. Lulu and Nana ended up with a mix of edited and unedited CCR5 genes, a mosaic of possible HIV resistance. Unlike other forms of genetic mosaicism (like the sex-linked fur color mosaicism that results in calico cats), a mosaic of CCR5 variants is unlikely to result in any interesting physical presentation. But it does make it significantly more likely that the babies won’t have any HIV resistance.

This case of shoddy genetic engineering serves to highlight two of the most important ethical considerations surrounding human CRISPR editing: risk and benefit. The possibility of off-target effects, the unknown genetic impact of a CCR5 mosaic, and the potential for any negative effects to be passed on to future generations—all of these risks needed to be considered before the embryos were edited and implanted. While CRISPR genetic engineering is already precise and powerful enough to be utilized in plant and animal models, much more care needs to be taken with humans. Not only could bad CRISPR editing result in death or significantly deteriorated quality of life for the edited individual, but these negative effects can persist in the genome for generations.

There are a number of risks involved with human genetic engineering that cannot be taken lightly. Scientists around the world have called for a complete moratorium on embryonic CRISPR engineering. But scientists disagree over whether the government should be involved in any sort of complete ban. In 2016, the U.S. established a ban preventing the FDA from approving studies that involve genetic editing of viable embryos. This law, like the law introduced in 2001 that banned federal funding of embryonic stem cell research, is strongly rooted in religious controversy rather than scientific ethical concerns. Many scientists agree that cautious and nuanced regulation of embryonic genetic engineering is paramount, but a permanent ban may hold science back from eventually establishing therapies that could provide enormous public benefit.

The egregious risk associated with Jiankui He’s genetic engineering experiment could only possibly be justified by an enormous potential benefit. But there was practically no immediate or even indirect benefit of He’s genetic modifications. While the babies’ father was HIV positive, there are established methods for preventing transmission from father to child, and He’s team used these methods in addition to the genetic editing. Because both methods were used, there is no scientific way to determine if the children’s HIV negative status is due to the modified CCR5 or not. And, as I mentioned before, the poorly executed CRISPR makes it extremely unlikely that they are HIV resistant.

In cases where the human risk is so high and potentially permanent, the benefit of genetic engineering has to be carefully weighed against that risk. For now, scientists should focus their efforts on improving the precision and reliability of CRISPR, in order to minimize the risks involved with genetic engineering. As the future of human genetic engineering gets closer, scientists should look for ways to ensure global regulation that is separated from the volatile whims of governments and centered around creating the most public good. In addition to the risks, there is enormous potential for CRISPR misuse. CRISPR embryonic engineering could be the ultimate eugenic tool without the right regulations and ethical monitoring.

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