In the 1997 Sci-Fi movie Gattaca, genetic engineering has reached such advanced levels of understanding and acceptance that babies are no longer conceived, but are designed. Nothing is left to chance. Eye colour is selected, myopia is removed. Athleticism is enhanced, aggressive behaviour curtailed. This leads to a two-tier society of ‘faith-births’, also called ‘invalids’ – those that are born through standard conception – and ‘valids’ – those that have their genomes tweaked to perfection.
Whilst we are technologically and ethically very far from the world in Gattaca, in September 2015 five leading UK biomedical research funders signed an open letter calling for a national debate on human genetic engineering. The letter, signed by the Wellcome Trust, the Medical Research Council, the Academy of Medical Sciences, the Association of Medical Research Charities and the Biotechnology and Biological Sciences Research Council, was prompted in part by a new tool called CRISPR-Cas9, which has been taking genetics research by storm since it was discovered in 2012.
What is CRISPR-Cas9 and how does it work?
CRISPR-Cas9 is part of a natural defence system bacteria use to fight viruses. When viruses attack, they inject their DNA into the bacteria with the aim of hijacking it, and using the bacteria to make lots of copies of the virus. If this happens, the viruses produced eventually overwhelm and kill the bacteria, exploding out to infect more. As the first line of defence, the bacteria produces enzymes to cut up the foreign viral DNA, like paratroopers sent out to destroy the intruders. Most of the time these fail and the bacteria dies, but every once in a while, the paratroopers will win.
When this happens, scout enzymes are deployed to clear the debris. They find pieces of the virus’ DNA, cut them into appropriate lengths, and store them within the Bacteria's own DNA for later use. The next time the bacteria is under attack, it produces copies of this stored viral DNA, and gives them to an enzyme called Cas9 as a kind of seek-and-destroy. If the virus is the same one as last time, Cas9 recognises it from the guide, and cuts it, destroying it before it has a chance to hijack the bacteria.
When scientists at the University of California, Berkeley heard about this there was an 'ah ha!’ moment. They found that by changing the guide RNA that Cas9 was using, they could potentially cut any piece of DNA they wanted. And, if they threw in a new piece of DNA near the cut site, it would be used by the cells’ natural repair mechanism as a patch. By doing this you could potentially target a bad gene, say, one that causes haemophilia, snip, erase and then replace it with the normal version.
Editing DNA has been possible since the early 90s, and many ethical discussions were held when the technology was first developed. You might ask why these ethical conversations are suddenly resurfacing now in 2015.
It’s all to do with the cheapness and usability of CRISPR-Cas9, which has accelerated research using genome editing. CRISPR-Cas9 costs less than older techniques, it’s both easier to use and more precise, and it works in every species tried so far. Researchers all over the world have been using it to modify bacteria, plants, mammals, and even human cells, and then in April 2015, scientists in China reported that they had used CRISPR-Cas9 to edit non-viable human embryos.
There is a fear that things are moving too fast without proper engagement with the public, which may end up preventing further fundamental and applied research using genome editing tools. You only have to look at the GM crop debate to see how public backlash against new technology can slow research and prevent its adoption. In contrast, a recent change to legislation in the UK allowing mitochondrial donation was successful in part due to large efforts of public engagement.
The recent letter outlines support for genome editing research but also calls for a thorough public debate around editing human eggs, sperm and embryos. Changes to these will be passed down to the next generation with any unintended consequences, and without consent (this is currently illegal in the UK). This type of application could also raise the possibility of so-called ‘designer babies’ in the future, where genes are changed for cosmetics or enhancement.
For more information see the links below.
This article was in part inspired by the podcast Antibodies Part 1: CRISPR from radiolab.