The CRISPR Baby Scandal: A Window into the Risks of Embryo Editing

On November 25th, 2018, Chinese biophysicist He Jiankui shocked the world by revealing he had used Clustered Regularly Interspaced Palindromic Repeats (CRISPR) technology to modify an embryo’s genes. He claimed that his intention was to reduce the would-be child’s risk of Human Immunodeficiency Virus (HIV) infection. The scientist unveiled his work with the birth of two twin girls, named Lulu and Nana, born from genetically engineered embryos in October 2018.

The technology used by He for the germline editing is known as the CRISPR-Cas9 system. This breakthrough invention builds on decades of work in the fields of molecular biology, microbiology, biochemistry, and microscopy and was pioneered by UC Berkeley scientist Jennifer Doudna and Umeå University’s Emmanuelle Charpentier in 2012. CRISPR is already revolutionizing the gene editing landscape with more promising and accessible results than any technology before, but much research into its mechanisms and impacts remains to be done.

Simply put, the technology removes a specific portion of the genome, based on the naturally-occurring bacterial immune system. When a bacteriophage invades a cell, the organism cuts out a piece of the attacker’s DNA and inserts it into its own. This foreign genetic material is called a “spacer”. As a result, when the same virus appears again, the bacteria can use the Cas9 enzyme to neutralize the threat. The CRISPR system employs the same “molecular scissors”, and couples them with gRNA (guide RNA) to steer Cas9 to the correct gene and make a cut. Once a double-stranded break (DSB) has been induced, the cell fixes the damage via its natural DNA repair pathways: non-homologous end joining (NHEJ) and homology-directed repair (HDR). The former sticks the broken ends of DNA back together, and while it is a quick and efficient method, it is prone to introducing more, potentially harmful, mutations, while the latter provides a template of the correct sequence for the gene to be replaced with.

Specifically, He targeted the removal of part of the CCR5 gene that HIV needs to enter the cell. And while his idea was scientifically sound, several key issues with his engineering of the embryo emerged. He was fined and sentenced to three years in prison, after being found to have falsified ethics documents in order to circumvent regulatory measures. In addition, several legal and ethical implications of his illegitimate work arose in the following months: Lulu has one copy of the gene that is completely normal and another with fifteen fewer base pairs while Nana has a single extra base pair added to one and four removed from the other; both carry cells containing edited DNA as well as cells inherited directly from their parents, and it is unknown to what percentage they are granted immunity from HIV. While these differences may seem trivial, a single point mutation can cause off-target effects — such as life-long, debilitating diseases. In the case of the CRISPR babies, the risk of deleterious mutation is especially significant as He edited embryos, not somatic cells, so any mutations could be passed on to all future generations. Should we make irreversible changes to the biology of our progeny without their consent? Is it ethical to decide the fate of a child’s genetic makeup before they are old enough to consent? Even if the parent’s intentions are benign, what if the child would have chosen to opt out of the experimental technology?

This exact issue is one of the primary concerns cited in the present day with the development of gene editing technology. How can we permanently and significantly change something so fundamental to our existence with no knowledge of the lasting consequences it might have? Several years after the scandal, research revealed that the CCR5 has functions extending far beyond HIV: it plays a role in Alzheimer’s, brain development, infections, cancer, and stroke recovery. What if we alter the human gene pool for the worse? The CRISPR baby scandal serves as just one example of the conflict between ethics and innovation and the responsibility to safeguard the evolution of humanity.

Finally, where do we draw the line? Where does a parent’s desire to grant their child a healthy body end, and a wish to enhance their aesthetic appeal begin? If we can prohibit selectively picking eye or skin colors, can we do the same for height, hair, or birth marks? Some marginalized communities that are often considered disadvantaged, such as those with deafness or intellectual disabilities, have developed unique and vibrant cultures, so is it ableist to perceive their differences as a negative characteristic that needs fixing? Germline editing could open the floodgates for eugenics, racism fueled by science, and dystopian beauty standards that change with the times but permanently alter the appearance of their individual and bloodline. Beauty is in the eye of the beholder, but what happens when a specific ethnicity’s traits become preferable? History will inevitably repeat itself, and in order to continue innovating in the field of geneering, we must urgently establish boundaries.

The story of Lulu and Nana will forever be remembered as a first controversial and risky use of CRISPR in the germline, a cautionary tale not of science but of oversight, ringed with fraud and failure that fortunately fell short of a more catastrophic culmination. Embryo editing could save the lives of millions, but only if we weigh our moral considerations against our technical capabilities. Every action we take in the present has a tremendous impact on the future, so we must tread carefully and protect, for generations to come, the very building blocks of life that make us human.