In November of 2018 reports began circulating that a pair of genetically modified twins had been born in China. The two girls, named only as Lulu and Nana, were the result of In Vitro Fertilisation (IVF) after CRISPR mediated modification of their genome. The lead researcher, He Jiankui, claimed it as a a “success” in the battle against HIV. But a year later He is under house arrest and his work unpublished. What happened?
The Ethical Oversights
He’s goal in this experiment was to create a human that is resistant to HIV by changing part of a gene called CCR5. The modification occurs naturally in some individuals and grants them immunity to HIV infection. So He took sperm and egg cells from a volunteer couple, combined them to produce embryos and tried to introduce the change using CRISPR. The embryos were then implanted in the volunteer mother.
Experiments involving gene editing and CRISPR had been performed in the past but never had the embryos been allowed to grow into a child. He did this without informing the doctors involved in the procedure, without the approval of the Chinese regulatory authority and without informing his university.
It is also possible that the only reason the parents consented to this was due to the father being HIV positive. In the late 1980’s China introduced a ban on HIV positive individuals entering the country. This was paired with severe limitations placed on HIV positive residents including a restriction on receiving IVF. It is speculated that the only way the parents could receive IVF was by partaking in this experiment. It is also important to note that there are commonly used procedures for eliminating the chance of HIV transfer between parents and embryo.
The Scientific Failings
Once ferilised eggs were obtained He’s team injected into them Cas9 and an RNA sequence to direct the modification. They then allowed the eggs to grow and replicate for just under a week before taking a cell sample. They tested the cells to see if the correct modification had occurred. It had not.
Indeed the CCR5 gene had been modified but it was not the same change as the one that occurs naturally. He’s team stated that they expected this change to be enough for HIV resistance. Further, the researchers claimed that there was only one other unintended change found in the cells checked. But it is impossible to ensure that no other modifications have taken place without checking every cell and destroying the embryo in the process. By only checking a sample of cells the researchers only showed that those specific cells had no other changes.
After the birth the researchers checked the DNA sequence of the umbilical cord and placenta to check if the modification had occurred in every cell. This was due to an mosaic like effect being observed in animal embryonic studies where only some of the embryo’s cells are modified. The data He’s team produced was insufficient to confirm that all the cells had been modified. As a result it is likely that only some of the twins cells were genetically resistant to HIV. He would have been aware of the issue of incomplete cell modification when designing this experiment but did nothing to reduce the risk.
The Aftermath
In the immediate aftermath of twins birth He gave a talk at a genome editing conference in Hong Kong. His 20 minute talk was livestreamed to over 1 million people and was followed by a 40 minute question and answer session. He then left Hong Kong driving directly to Schenzhen where He was placed under house arrest. He has not spoken publicly since.
In the meantime restrictions have been placed on embryonic research in China but no government investigation has occurred so far. This is compounded by the lack information forthcoming by both He and the other individuals involved in the project. Many have, understandably, distanced themselves from He’s work claiming not to know or understand what was going on. But without the full co-operation from all parties involved it is unlikely the full story will ever be known.
This story could be seen is an example of the risks that come with genome editing as it develops to the point of therapeutic use. But I think that would be unfair to the many researchers working to make genome therapies a reality whilst following correct procedures. By misinforming doctors, by ignoring the red flags raised by their own experiments and by manipulating the desperation of an infertile couple He’s team drove forward with an ethically misguided experiment. Their failure to recognise is the real story and both regulatory bodies and the wider scientific community should take steps to ensure it cannot occur again. Finally, since Lulu and Nana were not the twins real names and their date of birth misreported the true consequences of this sorry saga may never be known.
Further reading: https://www.sciencemag.org/news/2019/08/untold-story-circle-trust-behind-world-s-first-gene-edited-babies
