Precision genetic editing may be the most significant development in molecular biology in the past 50 years. It offers promising new therapies for otherwise incurable diseases, and ways of shaping the world around us for the betterment not just of humanity but of the environment too.
But CRISPR-Cas9,the technique at the heart of this breakthrough, has developed some unforeseen complications, putting it into a boat of unintended gene-related consequences shared last week by no less an unlikely fellow creek-paddler than the family entertainment mega giant, Disney.
Disney is dealing with its own genetic headache right now, thanks to its merger with Rupert Murdoch’s 21st Century Fox.
In the $71-billion deal, Disney does not get Fox News, the so-right-it’s-wrong network news channel so beloved of the US president. What it does get, among other things, are all the genetically superpowered mutants that Marvel sold to Fox in the 1990s, well before its own acquisition by Disney nearly 10 years ago.
Back into the fold come Magneto, Professor X and the rest of the X-Men — beloved comic book characters who will be a good fit for the family-friendly megacorp. We may finally see Wolverine join the Avengers, or a Wakandan wedding between T’Challa and Storm.
Unfortunately for Disney, though, the deal also includes Deadpool.
A psycho mutant mercenary with a mouth as foul as his sense of humour, Deadpool’s films are slick and very, very funny. What they are most certainly not, however, is family friendly.
Technically the superpower conferred on the foul-mouthed mutant by his X gene is the ability to regenerate rapidly when injured, but it might just as well be his ability to pack as much depravity and profanity into a 90-minute movie as possible.
And now the House of Mouse finds itself the owner of a successful film franchise built on exactly the kind of displays of depravity and profanity that led it to fire Guardians of the Galaxy director James Gunn just a few weeks ago. On the one hand: pots of money. On the other: children in therapy for the rest of their lives. What is Disney to do?
The genetic migraine brought about by unintended consequences is of a different order in the world of molecular biology and CRISPR-Cas9. Short for “clustered regularly interspaced short palindromic repeats”, CRISPR is, strictly speaking, a family of DNA sequences found in certain single-celled microbes. As it occurs in the wild, CRISPR is the system by which bacteria “remember” the attacks of viruses they encounter, filing away a tiny bit of the attacker’s DNA in its own genetic library.
The next time the virus attacks, its DNA is hauled out of storage and used to weaponise an enzyme called Cas-9. This little protein torpedo uses the retrieved sample to seek out and destroy its match in the virus’s genome, which then neutralises the virus.
But by manually loading DNA to CRISPR, researchers discovered in 2012 that they could programme the Cas-9 to edit specific genes in other organisms, with pinpoint precision.
This technique has helped scientists to accomplish incredible feats of genetic engineering. In one project, scientists completely eliminated HIV infections in mice. In another, researchers used CRISPR-Cas9 to switch off mosquitoes’ ability to reproduce, leading to a cascading colony collapse that in the field would halt the spread of diseases such as Zika or malaria.
It has been used to cause viruses to self-destruct, to slow the growth of cancer and, in the field of alternative energy, to engineer strains of algae to produce double their normal amount of biofuel. No top-secret Weapon-X super-soldier projects that we know of. So far.
CRISPR-Cas9’s responsible use has been welcomed as an important stride in medical research and molecular biology. Especially after researchers at the University of California developed an “off” switch in 2016.
But the shine is starting to wear off. A study published in the July 16 edition of Nature Biotechnology, titled “Repair of double-strand breaks induced by CRISPR-Cas9 leads to large deletions and complex rearrangements” observes that the technique’s effects lead to “complex genomic rearrangements at the targeted sites”.
The research team from the Wellcome Sanger Institute in the United Kingdom found that the technique damaged genomes in unexpected ways — not just in mice stem cells but also in human cell lines — and warned of unintended and harmful pathogenic consequences.
More research is needed to figure out whether these effects can be predicted and managed, but it is a significant speed bump in CRISPR-Cas9’s otherwise spectacular development.
As for Deadpool, what Disney will do with its gift-wrapped psychopathic merc-with-a-mouth remains to be seen. Chances are they’re searching frantically for their own off switch.