In late November, He Jiankui announced that twins had been born with a gene that he had edited to make them resistant to infection with HIV (see China: birth of two genetically edited babies). The changes were made to the CCR5 gene, which has been the subject of research since the mid-1990s. It plays a much broader role that scientists are just now beginning to understand. The gene editing performed by the Chinese researcher could therefore have much wider and more dramatic implications.
Although the CCR5-Δ32 gene edit protects against HIV infection, it also increases the risk of serious or fatal reactions to other infectious diseases such as West Nile virus, dengue fever, yellow fever and even the flu. It has also been shown that the CCR5 gene plays a role in learning in mice, and in certain chronic diseases in humans. “CCR5 deficiency is not benign,” says Philip Murphy, an immunologist in Maryland. “The absence of CCR5 can have severe disadvantages,” explains Marcus Kaul, an immunologist in California, including a severe reaction to the yellow fever vaccine.
The CCR5 gene encodes a protein expressed on the surface of certain immune cells that HIV uses to gain entry into the cells. A mutation of this gene identified in 1996 counters this effect and makes the carrier resistant to HIV. He Jiankui intended to endow the twins with this mutation, but his data presented at the International Summit on Human Genome Editing in Hong Kong shows another result: he seems to have produced three different mutations, and although one of the girls has both copies of the inactivated gene, the other has just one. In addition, the consent forms signed by the parents of the twins did not include any of the consequences mentioned above.
On the other hand, studies show that the CCR5 mutation in mice could have a positive effect on their cognition. While some scientists believe that the girls will learn faster, others caution that thousands of genes contribute to human intelligence, and that the mutation could even have the opposite effect.
In short, genome editing has unpredictable effects, but probably much broader consequences than those demonstrated so far. “What we know may be the tip of the iceberg,” says Philip Murphy.
For further reading:
Nature, David Cyranoski (12/12/2018)