What we know, and still don't know, about the CRISPR-modified twins
What we know:
- Dr. Jiankiu He, a scientist in China claims to have edited the genome of two human embryos, which were then implanted and given birth to by their mother as twins, dubbed Lulu and Nana.
- Dr. He says he edited the CCR5 gene, in order to provide the embryos with resistance to HIV infection. Jiankiu He says he did this because the father of the twins carried HIV. A version of CCR5 (CCR5-Δ32), mainly found in Northern European genomes, is known to confer immunity to certain variants of HIV.
- Based on Dr. He’s presentation at the 2nd International Summit on Human Gene Editing this week, one of the two embryos did not have all its cells edited, as a result it is not clear that this baby will have resistance to HIV. The other embryo has only a single-copy of CCR5 edited (humans have two copies of all genes), and the resulting edited gene is not yet known to confer resistance to HIV. It is possible that neither of the two babies will have resistance to HIV. It would certainly be unethical to test this!
- There are other ways, such as sperm washing during IVF, to prevent HIV transmission from father to off-spring.
- Dr. He also detected an “off-target” edit, i.e. another region of the genome that was edited by the CRISPR technology used. He suggested that this was unlikely to result in any adverse medical outcomes.
- He’s experiment was performed in secrecy. His former employer has denied involvement in the trial.
- The informed consent form used by Dr. He appears to be misleading in terms of the risks involved.
- Dr. He claims to have followed the recommendations of the US National Academies report on human gene-editing. However, his trial doesn’t seem to have followed several of these recommendations (highlighted below) and may yet ignore others.
- Dr. He says he’s in the process of submitting a scientific manuscript for publication.
- His experiment drew immediate criticism in China, with over a hundred scientists signing a letter decrying his work as unethical.
What we don’t yet know:
- The role of He’s collaborator, Michael Deem, a professor of bioengineering at Rice University in the US.
- There are media reports of a PR firm hired by He, but there’s no clarity about the role of this firm.
- As of now it is still unclear which research institutions, which medical doctors, and which hospitals were involved in this project.
- The funding for the trial is still unclear. It appears to have been funded through He’s personal funds as well as funding from the Shenzhen Science and Technology Innovation Commission according to the clinical trial registration in China. The commission however has claimed to have never funded this project.
- Documents showing ethics approval from the Shenzhen HOME Women’s and Children’s Hospital appeared on social media. However the hospital seems to have lodged a complaint suggesting this form was forged. We need to learn more about the ethics and approvals pipeline followed by He.
- Dr. He has pledged to follow up with the health of the babies for the first 18 years of their life, however there is no information about who would be involved in this effort, nor what kind of tests this will involve, or how the results would be reported.
- We do not yet know if the edits on the genome of the two babies will have any adverse effects. Some scientists have suggested that the method He used to screen the embryos for off-targets were insufficient. We will just have to wait and hope the babies do not suffer due to the editing.