The CRISPR Twins
A Story Of The World’s First Genetically Modified Humans
Introduction
Clustered Regularly Interspaced Short Palindromic Repeats or CRISPR is a technology that enables gene editing and is very likely to change the fate of the world.
To sum it up rather crudely, it’s a way of specifically targeting a sequence of DNA that can then be altered for various applications. CRISPR is already widely used for scientific research and has the potential to radically transform medicine, allowing us to not only treat but also prevent innumerable diseases.
The Contentious Incident
A Chinese biophysicist, He Jiankuin, attempted to use this technique to make the world’s very first CRISPR modified babies.
On 25th November 2018, He stunned the world by announcing that his team successfully created the world’s first genome-edited babies, Lulu and Nana (pseudonyms).
The twins were made from genetically modified embryos that were made HIV (Human Immunodeficiency Virus) resistant. The team recruited eight couples, each consisting of an HIV-positive father and HIV negative mother. During the in-vitro fertilization (fertilization of sperm and egg in laboratory settings, i.e. in a test tube rather than in the organism itself), the sperm was eradicated of HIV before insemination. Hence, the father-to-child transmission was no longer a concern.
The genomes of the embryos were edited using CRISPR/Cas9 by specifically targetting a gene, CCR5. CCR5 gene codes for a receptor that functions as an entry gate for HIV in cells. He was trying to create a specific mutation in the gene (CCR5 Δ32) that few people naturally have, which possibly confers innate resistance to HIV-1, as seen in the case of the Berlin Patient.
(Timothy Ray Brown was an American considered to be the first person cured of HIV/AIDS. Brown was called “The Berlin Patient” at the 2008 Conference on Retroviruses and Opportunistic Infections, where his cure was first announced, in order to preserve his anonymity. )
He said that the girls still carried functional copies of CCR5 along with disabled CCR5, given mosaicism inherent in the present state of the art of germ-line editing.
(Mosaicism is a condition in which cells within the same person have a different genetic makeup. This condition can affect any type of cell, including blood cells, egg, and sperm cells)
The work that He did could not protect the resulting children from the forms of HIV that use a different receptor instead of CCR5. A preimplantation genetic diagnosis process was used on the edited embryos, where three to five single cells were removed, and the editing was checked. He said that parents were offered the choice of using edited or unedited embryos. The couples’ children could also pass the protective mutation to future generations. The prospect of this irreversible genetic change is why the editing of human embryos, eggs, and sperms has been highly controversial. The core concern is whether such germline editing would cross an ethical red line because it could ultimately alter our species.
He sought couples that had endured the HIV-associated stigma and discrimination and wanted to spare their children that same faith by making them less susceptible to contracting the virus. Although the intent behind this experiment appears to be noble at first glance, this experimentation with the human genome instigated immense controversy in the scientific community.
Scientists and ethicists excoriated He’s medical rationale for the experiment and expressed concerns about the well-being of the girls in the long run. He was accused of flouting government laws and conducting research in pursuance of personal fame and gain.
Even if He’s work did make the twin girls less likely to get HIV, it is possible that he inadvertently increased their susceptibility to other infectious diseases. There is also a possibility that his experimentation made unintended modifications in their genomes, as often happens in gene editing experiments in the laboratory, leaving the twins vulnerable to genetic diseases. Hence, under these regulations, such gene editing experiments on humans were deemed illegal.
Conclusion
The technique has been earlier used on mice, monkeys, and 300 human embryos by He. The primary risk associated with CRISPR is that it can introduce accidental or off-target mutations. But He claimed that he found few to no unwanted changes in the embryo.
The attempt to create children protected from HIV falls into an ethical grey zone between treatment and enhancement. This procedure does not appear to cure any disease or disorder in the embryo but instead just claims to create a health advantage.
The birth of the first genetically modified humans could have been an incredible achievement for He, but where some see a new form of medicine, others see a slick slope to enhancements, designer babies, and a new form of eugenics.
References
https://www.newscientist.com/definition/what-is-crispr/
https://www.nature.com/articles/d41586-019-01580-1
