The science behind the first CRISPR babies


by Sarah Agapito Tenfen and Anne Ingeborg Myhr

The headlines exploded this week with the news that two twin babies had been born in China after gene-edition using CRISPR-Cas9. The experiment indeed, which is not a simple metaphor; incites many discussions. The researcher claims he has altered the sequence of a gene called CCR5 which is known to confer resistance to HIV infections.

The reaction of both the media and the scientific community relates to CRISPR applications not having a history of safe use. In other words, it is a recent technology which has great potential but still lacks important understanding about its function and impacts.

Ethics aside, we would like to discuss three major issues of this experiment that might open our eyes to future CRISPR applications, either as gene-therapies or even as CRISPR-food.

Point 1 – Confining the genetic modification to one gene

It is not yet possible to confine CRISPR mutation to a single gene or sequence. Depending on certain circumstances, and this ruling is not yet completely understood, CRISPR might also alter the sequence of other genes in the cell. One and each cell might react differently. When CRISPR is delivered to an organism, each cell of the body has the potential to generate a different mutation, what is known as mosaicism. Unintended genetic changes can lead to severe health problems.

Therefore, after CRISPR application, it is necessary to verify the mutation. Because of the chance of mosaicism among the babies cells, the researcher would have to investigate many body tissues to look for off-target mutations. According to the data presented in a conference, the researcher only looked at a few cells and, thus, the confirmation of only one intended mutation is yet pending.

Point 2 – A change in the gene might not result in a change in trait

The researcher has shown data that confirms that the intended gene sequence has been changed. However, mutated sequences are sometimes still functional. The investigation of the effect of that DNA change, in other words the effectiveness of the CRISPR intervention, must be verified and this has not yet been done in those babies. In vitro testing can be performed using the babies blood cells. But a complete verification would have to be done in vivo, and because those babies have never been exposed to HIV virus, it is ethically and morally unacceptable to promote that. In that case, the ultimate proof of gene-editing efficiency is just not possible.

Point 3 – One gene, many functions

Even if no other but the intended gene has been altered by CRISPR, and if the intended mutation was effective and preventing HIV infections; still that is no guarantee that there will be no adverse effects. Gene regulation in living organisms is not linear. It means that one gene by rule interacts with many other genes and gene products in a fine tuned and elegant network. It is relevant to remember that the CCR5 gene has an important role in the immune system and it is present in the genome of human beings irrespective of their exposure or not the HIV virus. Therefore, it is expected that a change in this gene might have implications throughout the body.

The way forward

The study has not been peer-reviewed yet. It is therefore of crucial importance that the experimental approach, methods and raw data are shared and peer-reviewed by other scientist with expertise in cell biology, immunology and genetic engineering. This can be done by submission through bioRxiv which is a preprint repository for Life sciences or to a well-known scientific journal. The findings must be verified preferably by another research group or by the researcher itself. There is also a need for the scientific community to take the potential for off-targets effects by gene-editing seriously, and to discuss methods and approaches for such investigations. Studies of off-targets effects need to be performed in parallel with applications of gene-editing in a transparent way.

Photo: Dollarphotoclub_49597598