Almost one year ago, Dr. He Jiankui at the Southern University of Science and Technology in Shenzhen, China announced to the world he had used gene editing on human embryos resulting in the birth of a set of twins: “Lulu” and “Nana”. Jiankui claimed to have used CRISPR, a gene editing tool, to remove the CCR5 gene, in hope to increase their resistance to HIV infection. CCR5 is a receptor protein that plays an important role in immune system signaling, and when present, it allows HIV to enter white blood cells to start the infection process. The twins’ father is HIV-positive, providing a potential risk for infection throughout their lives. Since this announcement, Jiankui has been fired, collaborators worldwide have been investigated, and an international outcry has been made to halt all research to create gene-edited babies. In China, such experimentation is illegal and the National Institutes of Health is prohibited from funding embryonic gene editing research. This begs the question, why were the CRISPR twins such a big deal?

The CRISPR/Cas9 system was first discovered in 1993 in bacteria. It wasn’t until 2013 the system was first utilized in eukaryotic cells. CRISPR is often compared to genetic scissors. The CRISPR system uses guide RNA to scan the DNA for a matching sequence, and the enzyme Cas9 cuts out the DNA that the guide was designed to recognize. The possibilities of using CRISPR to improve human health are seemingly endless; the system has potential for use in treating sporadic disorders to even curing inherited diseases. However, as is the case with most new technological advances, there are risks. CRISPR is not perfect and can result in unintended cuts in the DNA, known as off-target effects. There is also little research on how modifying one gene can alter others. Despite these potential complications, Jiankui used CRISPR to edit the genes of the embryos, and scientists are just beginning to understand the implications.

Jiankui defended his research at the International Human Genome Editing summit in Hong Kong in November of 2018; however, researchers in the audience responded with pointing out many short comings. He was not successful in removing both pairs of the CCR5 gene from both twins. The data showed that only “Nana” had both copies of the gene disabled, while “Lulu” only had one. There is no evidence to suggest that having lost one copy of the gene would provide her any protection against HIV. Additionally, both twins showed signs of mosaicism, meaning not all of the cells of the embryo contained the same DNA.

The gene Jiankui chose to mutate provides a further complication. Jiankui attempted to mimic the delta 32 mutation of CCR5, in which 32 base pairs of the gene are deleted to impair HIV’s ability to infiltrate immune cells. The natural mutation is prevalent in about 1% of people of European descent and promotes resistance to HIV while simultaneously increasing risk to West Nile virus and Japanese encephalitis. However, Jiankui did not delete all 32 base pairs of the gene associated with the mutation. It is possible this could cause an altered protein with unknown functions. Furthermore, new research from UC Berkeley has shown that people who carry both mutants of CCR5 are on average 21% more likely to die by the age of 76.

This experiment has increased pressure on scientists to explore the ethical and societal implications of editing inheritable genes of human embryos. It is clear the experiment performed by Dr. He Jiankui has opened a door that cannot be closed.

By Stephanie Baringer