Dawn of the designerbaby? Brave New World is nowhere near

When the first push messages came in last week, my scientific enthusiasm reached almost unprecedented heights. Scientists had managed to correct a potentially fatal gene mutation in human embryos. #designerbaby was trending topic.

The promise is great. Potentially fatal genetic defects can apparently be removed from the DNA without deleterious effects. On the other hand, there is the fear of a future as Aldous Huxley described in Brave New World — a future in which propagation becomes a product and delivering designer babies will be the default. Is Huxley’s dystopia closer than ever?

If one puts the study under a magnifying glass, one has to answer this question with a clear ‘no’. The devil is in the details. The researchers used the so-called CRISPR technique to successfully cut the piece of unhealthy DNA from the genome and offered a synthetic piece of DNA, a template, for repair. To their surprise this synthetic piece was not used. Instead, the embryos used the mother’s healthy gene as a template for repair. This was unforeseen but has important implications for the clinical relevance of the technique.

To fully understand this, it is important to distinguish dominant and recessive diseases. In dominant diseases, the unhealthy gene is the boss and claims victory over the healthy gene. When you inherit the unhealthy gene from either parent you become ill, even though the other parent’s gene is healthy. In recessive diseases, on the other hand, the healthy gene is the boss, and these therefore only occur when you inherit the unhealthy gene of both your father and mother. It now seems that the CRISPR technique can only correct dominant defects: the bad gene is excised, and the good gene is used as a template for repair. Of course, this only works if the other parent’s gene is healthy. Since in recessive diseases the genes of both parents are unhealthy, the genetic defect cannot be repaired.

One could therefore argue that it would be better to achieve the ultimate goal, the prevention of hereditary disorders, by pre-implantation screening of embryos during the in vitro fertilization process. In this way, the healthy embryos are simply separated from the unhealthy by genetic screening, and therefore no risky CRISPR treatment is required. If performed at the whole-genome level, this has the additional advantage of uncovering unanticipated recessive diseases.

Second, and for the ethical discussion potentially more relevant, is that this unexpected finding makes it much less likely that designer babies will be born in the near future. Designer babies require the creation of synthetic pieces of DNA with the desired properties. The idea is to replace the piece of DNA encoding certain properties with this synthetically designed model piece. But this won’t work if, instead of the added synthetic piece, the other parent’s gene is used as a template for repair. Compare it with a visit to the garage: you drop by with your Volkswagen to have a broken rim replaced with an expensive Ferrari-rim, but the fitter opts for a Volkswagen rim anyway.

In addition, when you’ll ask future parents about their idea of ​​the perfect child, you will hear things like ‘intelligent’, ‘cheerful’, ‘athletic’, etc. These are all so-called complex traits, properties that are not only encoded by DNA, but also determined by the environment. And the pieces of DNA that do control these traits are scattered over a mishmash of genes. Even if we find out which genes are exactly responsible for intelligence, rewriting all these genes to increase intelligence is implausible. For many diseases, we encounter the same problem: they are spread over too many genes and at the same time not genetic enough (other factors also play a role) to be able to correct with CRISPR.

Finally, there are safety issues. The CRISPR scissors can snip out of control, and possibly cause destructive and irreparable damage. This risk increases exponentially when multiple genes are rewritten, for example in the case of complex traits. It should also be noted that evolution sometimes has its reasons to make mistakes. In the case of sickle cell anemia, two defective copies lead to a serious illness, but one wrong copy protects against malaria.

A technical tour-the-force? No doubt. A good time to start the public debate? Hell yes. But despite the hype, it seems that Brave New World is further away than ever.

A Dutch version of this article was previously published in NRC Handelsblad https://www.nrc.nl/nieuws/2017/08/08/designerbaby-brave-new-world-is-nog-ver-weg-12434988-a1569306).

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