Rewriting the code of life
The new technology of gene editing has the power to reshape the world as we know it. How does it work and what could it do?
What is meant by gene editing?
It’s a kind of microsurgery applied to the DNA of a living cell, allowing scientists to customise its genetic make-up, so as to alter traits in some way that is beneficial. The possible applications are many and, in all likelihood, massively significant: they range from curing diseases to creating new crops and even to resurrecting extinct species. Attempts to engineer genes date back to the 1950s, when Francis Crick and James Watson discovered the structure of DNA; but despite the huge advances made in the analysis of genes since then, scientists have lacked sufficiently precise editing tools to make much headway. That changed in 2012, when scientists at the University of California, Berkeley made what is already considered one of the most important discoveries in the history of biology.
What was their discovery?
Two researchers, Jennifer Doudna and Emmanuelle Charpentier, worked out how to exploit a quirk in the immune systems of bacteria to edit genes in other organisms – whether yeast, plants, mice or humans. The result was a system called CRISPR-CAS9: Crispr for short. The acronym stands for Clustered Regularly Interspaced Short Palindromic Repeats, a mechanism deployed by bacteria to identify the DNA of invading viruses; this is used by geneticists to target a particular gene. Cas9 is an enzyme; it acts like a pair of molecular scissors, cutting the DNA. Essentially, Crispr enables scientists to snip out a piece of any organism’s DNA, insert a new gene if desired, and stitch it back together – as a film editor would cut and splice an old film reel. The entire process takes just days and costs very little. “In the past, it was a student’s entire PHD thesis to change one gene,” says geneticist Bruce Conklin. “Crispr just knocked that out of the park.”
What are the implications of this?
There are many. By changing a few pieces of genetic code in plants, for instance, scientists have created new strains of rice that yield 30% more grain and wheat that is resistant to the fungal pest powdery mildew. Peanuts without allergens, soybeans that don’t produce harmful trans fats, and castor beans that do not contain the toxin ricin are also in the pipeline. The process is different to traditional genetic modification: it is simpler, more precise and does not involve introducing foreign genes to the crop – unlike GM “frankenfoods”, such as the tomato given a fish gene. For these reasons, the European Court of Justice’s recent decision to categorise gene-edited plants with genetically modified ones has been widely denounced (see box).
What else could gene editing do?
It could be used to eliminate some of the world’s most lethal diseases. Crispr has already been used to edit the genes of the Anopheles mosquito so they resist the parasite that causes malaria, and, in another experiment, so that the females are prevented from producing fertile eggs. In theory, these mosquitoes could be released into the wild, spreading either malaria resistance or infertility (in time, this could wipe out the species altogether). Another project is under way that aims to rid the island of Nantucket of Lyme disease, by editing the genes of white-footed mice to make them resistant to it: the mice are the main reservoirs of Lyme; they pass it on to the ticks, which give it to humans.
What about treating diseases?
Gene therapy – modifying a patient’s genes to treat a disease – predates Crispr, but looks set to be transformed by it. Four patients at Great Ormond Street with “incurable” leukaemia have already been treated with white blood cells edited to target the cancer and have gone into remission. Gene therapy treatments for HIV have been developed, allowing some patients to come off their anti-retroviral drugs. In the lab, scientists have treated muscular dystrophy, diabetes and blindness in mice and rats. More radically, scientists could use Crispr to cure single-gene disorders such as Huntington’s disease or cystic fibrosis, by excising the gene responsible from the DNA of an embryo in the womb. This would not just cure the individual, but eliminate it from the germ line: the DNA they pass to their children.
But how about the risks?
It’s unclear whether Crispr can be used safely on human foetuses. Geneticists admit that they have only scratched the surface in their understanding of human DNA and the effects that Crispr might have on a person’s 20,000 to 25,000 genes, which interact in ways we still don’t understand. In China, a team at Guangzhou’s Sun Yat-sen University tried to snip out a defective gene responsible for a blood disorder, in dozens of human embryos. The embryos created were not viable: inexplicable gene mutations resulted. The experiment also, of course, raised much alarm about whether scientists should be tinkering with the human gene pool at all. At some point, researchers could switch their attention from curing hereditary diseases to editing in desirable traits, such as night vision or, conceivably, high intelligence.
How worried should we be?
Crispr is, arguably, the most powerful biological tool yet invented, with vast potential for both good and bad. Human gene editing is tightly regulated in the West, but fears about “playing God” remain. Furthermore, in 2016, the then US director of national intelligence, James Clapper, listed gene editing as a potential weapon of mass destruction: if you can make a malaria-resistant mosquito, you could also make one capable of transmitting pathogens. Crispr editing kits can be bought cheaply online, and it’s possible that a “bio-hacker” could transform a common virus into a biological weapon at their kitchen table. “Great things can be done with the power of technology – and there are things you would not want done,” said Doudna. “Most of the public does not appreciate what is coming.”