Edited embryos. Why to say yes or no

embryo-mainThe exploit announced last week by Nature marks an advancement in CRISPR performance in human embryos big enough to say that yes, germ line editing will probably become a viable option sooner or later. It means that some genetic diseases (at least those caused by a single mutation) can be corrected not only in the treated individuals but also in their offspring. The idea of genetic diseases disappearing from the face of Earth is bound to remain a dream, as Eric Lander explained at the 2015 Washington Summit on Human Gene Editing. In short, with rare Mendelian diseases, the vast majority of situations can currently be addressed by in vitro fertilization and preimplantation genetic diagnosis, while complex diseases are, well, too complex to handle. Anyway, when you come to efficiency and accuracy, results achieved by Shoukhrat Mitalipov and colleagues are exciting: CRISPR science walks on robust and fast legs. As for the bioethics of the experiment, we should try not to get stuck with overused labels.

The “slippery slope argument” would make us replay earlier discussions. Furthermore, this kind of experiment is not eugenics, a word that according to science historian Francesco Cassata is too ideologically compromised to be helpful in any honest debate. Even if Hitler came directly to Jennifer Doudna in a nightmare, as she wrote in her book, playing the Nazis card is misleading.

If you believe human embryos are inviolable nothing is going to persuade you. If you think it’s unethical to compensate women for donating their eggs for research, you necessarily dislike this kind of experiment. But if you are interested in finding a careful balance between the rights of all involved subjects, patients and researchers included, by restricting instead than forbidding embryo research, the information below may help to form an opinion. Let’s stick to the hard facts as told by Science.  

Three years ago Mitalipov asked the Oregon Health and Science University (OHSU) for the go-ahead to edit the mutation of the MYBPC3 gene causing hypertrophic cardiomyopathy. The university set up an ethics committee and a scientific committee to examine the proposal, and some of their members were skeptical. First of all, previous results from research carried out in China seemed to show that the technique was still too unreliable in human embryos. However, this objection is partially overcome in retrospect by Mitalipov’s improvements. Researchers apparently have solved gene editing main problems (off target mutations and mosaics) by directly injecting the CRISPR system ready for use (instead of DNA encoding its components), and by doing it early, at the same time as they injected the sperm to fertilize eggs. This means embryos must be created ad hoc, cannot be excess embryos obtained from fertilization clinics. Many (but not everybody) think that this makes a big difference from a bioethical point of view because supernumerary frozen embryos are already existing embryos having no chance of survival anyway.

The second objection is why anybody would want to use gene editing as a fix. People usually have only one copy, not two copies, of the disease-causing variant, meaning that half of their embryos will be disease free. Identifying and selecting healthy embryos is easier than editing the affected ones. Mitalipov replies that discarding 50% of embryos, knowing that you could actually correct the mutation, is morally wrong. Personally, I find this reasoning unconvincing, because taking charge of the fate of all embryos produced by medically assisted procreation is frankly impossible. But I agree with Luigi Naldini from San Raffaele-Telethon that even if conditions for which it may be useful to edit the human germline are few, and even if it could help only a few individuals, one should not close the door.

Because the experiment required creating and destroying human embryos, it was not eligible for US government funding. The OHSU lab used institutional funds, collaborators at the Salk Institute for Biological Studies in San Diego used money from three charities, while Korean and Chinese partners received federal or regional funds for the project. If you think the US model is inconsistent, you will probably like better UK rules, where creation of human embryos for research aims is not forbidden, but only a very few selected experiments are given the green light by a central authority, evaluating pros and cons case by case. 

Photo: Human embryos edited by CRISPR, newly fertilized (left) and at the eight-cell stage (right)

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