THE worldwide shock over the announcement of the birth of gene-edited twins isn’t just because it may be a scientific first. The scientist who led the work, He Jiankui, has also been widely criticised for acting unethically towards the couples and the babies involved in the trial.
The biggest concern is that He used a technique that hasn’t had enough safety testing. One of the main known problems with the CRISPR technique is that it can cause unintended “off-target” mutations elsewhere in the DNA that may be harmful.
This fear is particularly pertinent when it comes to editing whole embryos. Unlike gene-editing treatments for cancer, for example, which alter only some cells, using CRISPR on embryos has the potential to change the DNA in every cell in the body.
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This includes those that will go on to produce eggs or sperm. Such “germline” editing is ethically difficult, because these artificially induced mutations – and their unknown effects on health – may be passed on to the next generation, and ultimately become part of the human gene pool. The idea that harmful mutations could start accumulating in future generations is the biggest fear for most people about gene-editing embryos.
He says the two babies don’t have off-target genetic changes. But many CRISPR experts think it is too soon to say. Even if the twins seem healthy, it is possible that an undetected, random genetic change could, for instance, make them prone to cancer in later life.
The rare, naturally occurring mutation He was attempting to mimic stops some strains of HIV from entering cells by disabling a protein called CCR5.
People have two copies of the CCR5 gene that make this protein. But in one of the embryos, only one copy was disabled. This means this twin will still be vulnerable to HIV, prompting many to question why the embryo was implanted. This baby has been exposed to all of the risks of gene editing, but for seemingly little benefit.
The second embryo had both copies of the gene disabled, so may have protection from at least some HIV strains. But none of the CCR5 mutations induced in the twins are identical to the natural variant. “It’s possible that any one of these mutations could have an unintended effect,” says Sean Ryder at the University of Massachusetts. “It was irresponsible to implant these embryos.”
Responding to such criticisms, He has said that the prospective parents were informed of the risks and chose to go ahead. But questions have been raised over whether the couples fully understood what they were agreeing to.
He has shared online a form that he says was used to obtain consent from the couples. The form’s wording includes several red flags for medical ethicists, including a stipulation that couples would have to repay their treatment costs if they left the trial. According to global research standards, trial participants should be free to pull out of studies without reprisal.
It is these issues that have led to widespread condemnation from many of He’s peers worldwide. According to the organising committee of last week’s gene editing summit in Hong Kong, where He spoke about his trial, “the procedure was irresponsible and failed to comply with international norms”.
This article appeared in print under the headline “A brave new world?”
