The Tale of Two CRISPR Babies
Life sciences has been evolving ever since the elucidation of the structure of the DNA in the 1960s. Soon after discovering the “secret of life”, we have witnessed a paradigm shift in life sciences research which led to the human genome project made possible through cutting-edge technology for gene sequencing. Subsequently, many other inventions such as high resolution microscopy and recently of course, gene editing technology, have impacted our approach to biological processes and diseases like never before. We are on the brink of a technological revolution. But will controversial research on human embryos lead to devastating results only pictured in science fiction stories until now?
Two months ago, a Chinese scientist had shared the results of his work that shook, not just the scientific community, but the entire world. Dr. He Jiankui, the scientist who had revealed at the Second International Summit on Human Genome Editing held in Hong Kong in November last year, claimed to have used gene editing technology on human embryos to make them resistant to HIV – the virus that causes AIDS. He claimed that the first twins that have been gene edited have been born, with sketchy details of their identity, only to be named as Lulu and Nana to the world. He now faces serious consequences for his work which has been suspended by the Chinese government with He himself being under house arrest until a final verdict follows.
The Southern University of Science and Technology has now fired him on the grounds of conducting unethical research. Dr. He has not been shy about sharing his thoughts regarding his work saying that he is only passionate to see the stigma against HIV-infected people being erased from the society. He used a technique called CRISPR-Cas9 which is being employed by many labs around the world albeit only on ethical grounds. However, his work has sparked a huge controversy than accolade mainly calling his work as impulsively unethical.
What is CRISPR-Cas9?
When the Human Genome Project was underway, there were many other labs that were simultaneously elucidating the genomes of much smaller organisms which had smaller genomes than humans like bacteria, Archae (a specialized group of bacteria) and certain viruses called phages, known to be the arch-nemesis of bacteria.
It was observed that most of the bacteria and Archae genomes contained short DNA sequences that were repeats which scientists termed as CRISPR sequences and they were separated by spacer sequences. Interestingly, these non-repeating spacer sequences were also found in phages that attacked bacteria. The CRISPR sequences were associated with yet another set of genes called the CRISPR-associated (Cas) genes.
The discovery soon led to speculations that the CRISPR and Cas genes were involved in some sort of bacterial immunity. Various types of CRISPR-Cas systems belonging to different strains of bacteria were examined and it was found that the Cas9 gene belonging to the strain, Streptococcus pyogenes was found to be relatively simpler and is now the most widely used gene editing tool for research.
The biggest breakthrough was the ability to modify the CRISPR-Cas9 system to aid gene targeting in other organisms. This meant that we could use CRISPR for modifying specific genes i.e., a disease-causing gene to revert it back to its normal state.
In comparison to its predecessors, CRISPR is far efficient and takes less time to modify the targeted gene. However, the CRISPR technology is not without its problems. Non-specificity of the target, mosaicism and unwanted alterations in the target gene may render the technology inefficient and must be dealt with precariously.
Even though CRISPR is a suitable gene editing tool, there are many aspects that require the technology to be carefully examined as altering the germline could not only affect the embryos but also their future generations – as is in the case of the CRISPR babies.
Dr. He altered the gene encoding a key protein used by the HIV virus to enter the human immune cells known as the CCR5 receptor. Previous studies have shown certain individuals with CCR5 gene deletion to be resistant to HIV.
However, the CCR5 protein is also known to have other roles.
One study showed its involvement in proliferation and differentiation of certain blood cells (granulocyte lineage) in the body. And recently, the findings of a study which was featured in MIT Technology Review (click here to read) has shown CCR5 gene deletion to have profound alterations in cognition (thought processes).
Moreover, to what extent has He explained the study to the participating families is still under question, as the coordinator or the principal investigator of the study explain in lucid terms what the study is about along with advantages and disadvantages.
There are two sides to the story here: on the one side, we are able to empathize with the sufferings of families with the risk of genetically aberrant offspring and that this technology could bring about hope for a better future for them. On the other hand, however, this could spurn into a Frankenstein’s haven for experimenting with desirable traits known as designer babies.
Zhou et al. 2016 showed that the altered CCR5 proteins in the brain cells would lead to better neuronal plasticity and better recovery from stroke. This points to the fact that the deletion itself could lead to various other effects in the individual.
One can’t help but think if this work was done for undisclosed motives? The much debated and controversial designer babies that could result from these experiments draws out ethical concerns of choosing specific traits in babies which has been unanimously condemned by the global scientific committee.
In his paper, Dr. He emphasized the need for clarity and transparency in the intention of such procedures that lead to gene manipulation. He also mentioned that a large population of the general masses may be receptive to gene alteration that may be useful for treating diseases and hereditary disorders.
However, there is no actual evidence that Dr. He had conducted these experiments – proof in the sense that he had not published his results in any peer-reviewed journals for scientists and ethicists to examine his findings. His claim had been through a series of YouTube videos taken initially before he had presented the results in his talk at the conference in Hong Kong. Being all the more familiar with fraudulent claims in the past (click to read Washington Post article: Cloning a Previous Hoax?), we could surmise this as a possible hoax.
He’s actions were well-planned to avoid anyone from impeding his claims beforehand. He ensured that the clinical trial was registered later after the work was conducted so as to avoid investigation and premature shut down of his work. It is noteworthy that He was interested in the fame he was to receive while revealing his controversial work.
The lack of transparency in his work, itself speaks volumes of his liability to ethical conduct because he has not adhered to the protocol of publishing his results or heeding expert advice on such a matter.
All of this points to only one thing – are we plunging head first into the sort of lifestyle portrayed in the dystopian novel, A Brave New World or we making a mountain out of a molehill?
Let’s say if this experiment has been actually conducted on the twins and is not a hoax as many would say: what would happen to the babies?
As quoted elsewhere, “if this experiment has allowed the modification of the CCR5 gene, then these twins will be under perpetual scientific scrutiny for the rest of their lives”. This means that we have not only altered their physiological state but have also caused a psycho-social alteration in their lives without their consent. If that is the case, only time can tell the effects of gene editing on human embryos.
Adli M. The CRISPR tool kit for genome editing and beyond. Nature communications. 2018 May 15;9(1):1911.
 Zhou M, Greenhill S, Huang S, Silva TK, Sano Y, Wu S, Cai Y, Nagaoka Y, Sehgal M, Cai DJ, Lee YS. CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory. Elife. 2016 Dec 20;5:e20985.
Jiankui H, Ferrell R, Yuanlin C, Jinzhou Q, Yangran C. Draft ethical principles for therapeutic assisted reproductive technologies. The CRISPR Journal. 2018 Nov 1.
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