From the Economist:
ABOLISHING thalassaemia is a noble goal. This inherited blood disease, which can cause severe anaemia and consequent organ damage, sometimes fatal, is a scourge to those who suffer it. And abolished it could be, if the broken gene that causes it (which is called HBB and encodes part of the haemoglobin molecule) were itself to be abolished.
That is not an abstract thought. A newish DNA-editing technique called CRISPR/Cas9 is able, at least in principle, to make precise changes in particular genes. Several groups of researchers are trying to work out a way to use it to clear up beta thalassaemia in individual sufferers, by genetically modifying the stem cells which generate red blood corpuscles. But it is theoretically possible to go further. By modifying HBB in a fertilised egg (known technically as a zygote), and letting that zygote develop into a human being, you would abolish the disease not only in the resulting individual but also in his or her "germ line"—the line of descent. By doing this, though, you would create one of the bugaboos of bioethics: a genetically modified human.
That controversial prospect has just been the subject of a real experiment. Huang Junjiu of Sun Yat-sen University in Guangzhou, China, and his colleagues have just published, in Protein & Cell, a description of an attempt to do this, as a proof of principle, in non-viable zygotes. The attempt failed. But it yielded lessons that might make a subsequent try more successful.
CRISPR/Cas9 is a large bit of molecular machinery (see picture) derived from a bacterial defence system that chops up the DNA of invading viruses. In nature, it recognises DNA sequences that are foreign to the bacterium, but the recognition mechanism can be modified to search for any given sequence and cut the DNA there. If this is done to a gene in an animal or plant cell, the cell will try to repair itself using the other copy of the gene present (for there is one from each parent) as a template. That can be subverted by injecting an artificial template of the desired DNA sequence, thus effecting a repair to a previously broken gene.
Dr Huang and his colleagues tried this on HBB with 86 zygotes they had obtained from local fertility clinics. These zygotes were unviable because each had been fertilised by two sperm. They were, nevertheless, suitable for experiment.
Of the 86, 71 survived the procedure and 54 of these were tested to see if it had worked. In 28 the DNA had indeed been cut by CRISPR/Cas9 and then repaired by the cell. In only four of these cases, though, had the artificial template been used for the repair. On top of this, Dr Huang found that there were many “off-target” mutations in other parts of HBB, or in other, similar genes, which would have caused serious damage if expressed in an actual human being.
On the face of things, then, the experiment did not work. But even failure can provide lessons. Knowing which bits of DNA are susceptible to off-target modification, for example, might allow the approach to be refined. Moreover, Dr Huang’s team are probably not alone in their endeavours. A report in Nature says at least four groups in China may be working on human germ-line gene modification.
The controversial nature of the work also led to the paper’s actual publication being a cloak-and-dagger matter. Though neither journal has commented, rumours in the field suggest Dr Huang offered it to Nature and Science (generally regarded as the world’s premier research journals), but both turned it down. Meanwhile Protein & Cell, the work's eventual home, labels it as having been received on March 30th and accepted on April 1st. That is a speed of acceptance most researchers can only dream of.