Several years ago, a Chinese scientist, He Jiankui, performed a radical experiment on embryos that had been fertilized in-vitro in a lab. The embryos’ father was HIV positive, and the scientist’s stated goal was to use a DNA intervention to provide resistance to HIV infection in the offspring.
The scientist used CRISPR gene editing technology to alter the DNA in the lab, then implanted the embryos in the mother’s womb. She gave birth to twin girls, both genetically altered. About a year later, the scientist repeated the experiment with another woman, who gave birth to another genetically-modified girl.
The international scientific community was shocked and outraged. Editing the DNA of an embryo will affect every cell in the body. The changes will be passed down through generations, unlike the widely-accepted CRISPR interventions in adult non-germ cells. CRISPR gene editing, for all its potential, is not perfect and can create unexpected genetic changes.
The Chinese government sentenced He Jianku to three years in prison for violating the country’s medical ethics laws. He was released early in 2022.
Now, it appears that the alarm of the scientific community was justified. The three girls, now toddlers, are likely to have genetic abnormalities. The problem now is how to provide care for them, should they need it, without infringing on their privacy.
How Can CRISPR Gene Editing Go Wrong?
CRISPR is a gene editing system that has already shown enormous potential for treating genetic diseases, increasing crop yields, and even generating biofuels. On paper, it sounds like it is very precise. The CRISPR system contains an enzyme called Cas9 that is often described as being like a pair of “molecular scissors.” Ideally, the enzyme cuts the DNA strand at a specific site, and then the cell’s own repair mechanism rejoins the cut ends.
The problem is that it doesn’t always work exactly like that. Cas9, rather than being like a scissor making a precise cut, can be more like someone tearing a piece of paper. The cell’s repair mechanism can also be imperfect, deleting or adding extra base pairs.
CRISPR can also make the cut in the wrong place, a problem called an “off-target edit.” The cut could happen anywhere on the DNA strand, and could cause entire pieces of chromosomes to be deleted. This could potentially cause many developmental problems. One of the worst risks would be changes to genes that are related to cancer.
Unfortunately, it looks like He Jianku’s experiments did create off-target edits. Scientists reviewing his data found two issues. First, there were off-target edits in unknown positions. Second, edits were different in different cells, a problem called “mosaicism.” This can cause tissues to act in unexpected ways and can cause heart disease or other health issues.
Scientists are now concerned about how best to monitor and treat the gene-altered girls. One group of scientists has proposed creating an institute that will provide life-long monitoring and, when needed, care for the girls’ genetic abnormalities. The institute would also study the girls to advance scientific knowledge of the heritability of human gene alterations, to improve the technology to make it safer, and to be prepared in the event of further illegal experiments.
Others object to the proposed dual purpose of caring for the girls and monitoring them for the sake of research. They say that the best interest of the patients must be the top priority, the girls’ privacy and confidentiality must be protected, and they must be given the chance for as normal a life as possible.
Ultimately, the decision will be up to the Chinese government.