Oh no! Not again! Such must be the sentiments of stem cell scientists after a paper to be published in Nature cast cold water on landmark research about editing the genome of a human embryo.

On August 2, a team led by Shoukhrat Mitalipov, of Oregon Health and Science University, announced in Nature that they had successfully deleted a disease-causing faulty gene and replaced it with a healthy copy using the CRISPR-Cas9 technique. Their innovative experiment introduced the CRISPR machinery earlier. When they examined the embryos, they found that they did not contain the faulty sequence.

This discovery was greeted around the world as a first step towards freeing mankind from genetic disorders or towards a eugenicist society, depending on your attitude towards modifying the human genome. Technically, it was a tour de force, as it was relatively easy and accurate and did not result in mosaic embryos.

With 10,000 harmful single-gene mutations known, there is a lot at stake.

However, a closer examination of the exciting paper has sparked a lot of debate amongst stem cell scientists. In a preprint release of a paper in Nature on bioRxiv, Dieter Egli, of Columbia University, and Maria Jasin, of Memorial Sloan Kettering Cancer Center, along with Harvard geneticist George Church, have questioned whether Mitalipovs team has actually succeeded, as the new technique contradicts the conventional wisdom about how fertilisation occurs. They point out that although the disease-causing gene had disappeared, there was no proof that the correct sequence had been inserted.

Furthermore, the DNA from the sperm and the egg are probably not close enough in the brief interval after fertilisation to interact or share genes. Mitalipov and his team had speculated that the embryos used the DNA of the egg as a guide to repair the mutation carried by the sperm.

In my view Egli et al. convincingly provided a series of compelling arguments explaining that the correction of the deleterious mutation by self repair is unlikely to have occurred, Gatan Burgio, a geneticist at the Australian National University told Nature News.

Mitalipov has responded, promising to answer the critiques point by point in the form of a formal peer-reviewed response in a matter of weeks.

Inevitably, this latest breakthrough recalls a string of too-good-to-be true-and too-amazing-to-reject articles about stem cell research. They were published in leading journals, hyped in the media and then crashed and burned. Time will tell whether Mitalipovs paper will be vindicated.

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Landmark stem cell paper questioned - BioEdge

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