A Chinese biophysicist He Jiankui made waves in the science community and news when he announced having tweaked the DNA of twin embryos and helped bring three genetically-modified human babies into the world as of 2018. His intentions were reportedly to make them immune to HIV infection.
The genes of twin babies, he had said, were edited while they were still embryos, before they were implanted into the womb. Now, the twins are at least a year old, possibly older. As more details questioning the rationale of his study emerge, it seems increasingly like Jiankui went further with the study despite knowing it wasn't working.
Researchers familiar with the nuances of gene editing and CRISPR have different theories for as to exactly what to expect from Jiankui's 'targetted' changes. Yet, they are in agreement that the risk of unplanned mutations from the gene-editing procedure is high – and made worse by the fact that it just isn't predictable in the one-cell or few-cell stage of life.
The MIT Technology Review published snippets from the manuscript that Jiankui was apparently working on, with edits made to it as late as November 2018. Jiankui’s big announcement – which came in the form of an exclusive interview with The Associated Press and a YouTube video – came before the manuscript saw a peer-review or a review for publication in a scientific journal.
From the bits of Jiankui’s manuscript shared by Tech Review, it looks as if the experiment may have failed, and that Jiankui will have known that it did. The manuscript, titled "Birth of Twins After Genome Editing for HIV Resistance," is a 4,699-word record of research that, till date, remains unpublished, and rejected by a pair of esteemed journals Nature and JAMA. A second manuscript we also received discusses laboratory research on human and animal embryos.
More than a decade ago, a breakthrough trial on an American HIV-positive patient Timothy Brown, known as the "Berlin Patient," made him the first person medically cured of HIV. This, after he underwent a bone marrow transplant from a donor that has a mutation in the CCR5 gene. The gene supposedly lends a natural resistance to HIV infection in some people.
Evident in the manuscript excerpts is the likely possibility that Jiankui was not successful in editing the only gene his entire hypothesis revolved around – CCR5. His study also had implications for CRISPR technology, a gene-editing tool invented only seven years ago. It was known in the scientific community that CRISPR wasn’t 100 percent effective long before Jiankui’s announcement. CRISPR technology has undoubtedly transformed the accessibility of gene-editing technology, made it child's play, and the strategy is still prone to errors.
As powerful a technology as CRISPR is, it also has the potential to introduce mistakes or unpredictable errors in important, sacred sites of a living subject's DNA. Mutated, or incorrect DNA, can cause any number of problems in an otherwise healthy person's body – from developmental problems and serious neurological conditions to diabetes and cancer. And this would technically be the "side effect" of a supposedly hefty benefit – "HIV resistance".
It appears from the bits of the study Tech Review has published, that Jiankui and his team weren’t able to reproduce the mutation of a gene called CCR5, which lends a resistance to HIV-1 – the viral strain that causes half of all AIDS infections globally. This was the highlight – the main claim that Jiankui clung on to in November 2018, to justify the use of gene-editing on an unborn foetus. It was his belief that his experiment would help “control the HIV epidemic”.
If it worked, Jiankui will have found a new way to prevent one form of HIV transmission. Jiankui had also resorted to a myriad of unethical practices, drawing criticism from scientists around the world, but also from within China.
Jiankui's real contribution may have been entirely elsewhere – in drawing a bold line in the sand, for all genetics researchers as to where the community collectively stands where gene editing in humans is concerned: we're just not there yet.
Also read: After CCR5 gene, scientists find second, rare gene mutation that protects against HIV
Scientists that edited babies' genes probably gave them a brain boost too: Study