ALL ORGANISMS suffer from viral infections, and all have developed immune systems of one sort or another to combat them. Bacteria are no exception. Some snip small sequences of DNA from viral interlopers and copy them into their own genomes, thus creating a genetic scrapbook by which to recognise such aggressors, should they come again.
Helping to work out the details of this process has won Emmanuelle Charpentier of the Max Planck unit for the science of pathogens, in Berlin, and Jennifer Doudna of the University of California, Berkeley, this year’s Nobel prize for chemistry. Their prize is not, though, for the mere discovery of a bacterial mechanism of immunity. It is also for the adaptation of that discovery into the most important gene-editing tool yet invented—CRISPR-Cas9—which is already helping to design disease-resistant crops and new therapies for cancer, and which may, perhaps, end hereditary disease in human beings.
If an organism’s collective DNA can be seen as the book of its life, CRISPR-Cas9 allows for any specific sequence of words within it to be identified, selected, removed and replaced. This is done by creating a molecule called a guide RNA, which matches the target DNA sequence, and pairing it with an enzyme, Cas9, that is capable of snipping the DNA helix at this point. Then, if so desired, a new piece of DNA can be inserted.
The laureates’ path to Stockholm began at a café in Puerto Rico in 2011. That was when Dr Charpentier, who had discovered intriguing and unexplained RNA fragments in a bacterium, engineered a meeting with Dr Doudna, an expert in the DNA-snipping capability of Cas proteins. Since the collaboration bore fruit in 2012, progress has been rapid. By February 2013 Feng Zhang, of the Broad Institute, and George Church, of Harvard Medical School, had independently demonstrated the technique’s effectiveness in mouse and human genomes, paving the way for the treatment of human diseases. Clinical trials are now under way to test CRISPR/Cas9 against sickle-cell anaemia and certain cancers, with animal experiments showing promising results in the treatment of muscular dystrophy.
There has also been controversy. In 2018 He Jiankui of the Southern University of Science and Technology, in Shenzhen, China, announced the birth of twin girls whose embryos he had edited with the help of CRISPR-Cas9. Dr He’s stated goal was to induce immunity to HIV, by disabling the gene for a protein which that virus uses to gain admission to cells. This was too much for the authorities. Even ignoring the issues of consent involved when a procedure is carried out on an embryo, making genetic edits so early in life means that they will be incorporated into germ cells, and thus passed down the generations. That raises serious ethical questions, and what Dr He did was declared illegal by the Chinese government. Dr He is now in prison.
Nor is germ-line editing the only controversy surrounding CRISPR-Cas9. A further complication concerns who gets the patents that will monetise it. The University of California and the Broad have been engaged for some years in a legal battle over the matter. In awarding the prize to Dr Doudna and Dr Charpentier, Sweden’s Royal Academy of Science may have put their thumb on the scales. By picking them it has also, for the first time, awarded a Nobel science prize to an all-female group. Dr Charpentier, via a phone link to the room where the announcement was made, said “I hope this provides a positive message to young girls. Women in science can also be awarded prizes. But more importantly, women in science can also have an impact.”