PATCHES ON YOUR GENES

Dick Pountain/ Idealog 284/ 7th March 2018 11:29:07

When I was 8 or 9 one of my Christmas presents was a lavishly illustrated book called “How And Why It Works”, which explained everything from airliners to oil-wells to reflecting telescopes. It immediately became my favourite, along with a nature book about curious animals like the echidna. My course in life was set right there and then. I just wanted to know how everything works – including you and me – so I became a biochemist, and then through a series of flukes a computer nerd.

Books can still have that sort of effect on me, but fairly rarely nowadays, and when one does I occasionally write about it here. The last time that happened was back in August 2016 when "Endless Forms Most Beautiful" by Sean B. Carroll overcame my reluctance to get to grips with Evolutionary Developmental Biology (Evo Devo). That book helped me understand that all living things are indeed computational systems, but not in naive way that the AI brigade would have us believe. Every living thing contains a genetic apparatus which combines a database of inherited features with a collection of distributed, self-modifying, real-time processors and 3D printers whose outputs are flesh, blood and bones, leaves, bacterial cell walls, and also those nerves and brains that AI concerns itself with.

Well, it’s just happened again. I’d been vaguely aware for several years of a revolution in the technology of gene editing, one that will enable us to actually reprogram this system for ourselves (for better or for worse). But as with Evo Devo, I’d pushed it to the back of my mind, unwilling to tackle the mental effort needed to understand. What’s fortified me this time around is a short article (https://www.lrb.co.uk/v40/n04/rupert-beale/diary) in the London Review of Books by Dr Rupert Beale, a scientist at the MRC Laboratory of Molecular Biology in Cambridge, which explains in admirably lucid and non-technical fashion the new techniques of CRISPR.

Beale’s knows his stuff because he researches bacteriophages, viruses that infect bacteria. It was work on phages around 20 years ago (by a Danish industrial yoghurt company among others) that triggered this revolution. Bacteria, though just single cells, have evolved a very simple immune system – whenever they survive a phage attack they snapshot a chunk of its genetic sequence into their own DNA as a memory of the crime. In any future infection a bacterium can recognise that sequence and use an enzyme called Cas9 to snip it out, thus killing the invading phage. These snapshots consist of “clustered regularly interspaced short palindromic repeats”, or CRISPR for short.

Those of you involved in computer security (hi Davey) might recognise this as much the same mechanism used by AV software to detect computer viruses from their “signature” code sequence. Molecular geneticists can now deploy the combination of CRISPR and Cas9 as tools to cut-and-paste gene sequences into the DNA of other creatures besides bacteria, up-to-and-including homo sapiens. In practice they don’t actually snip out target genes but rather disable

them: Cas9 cuts the DNA strand but the host cell repairs it, over and again until it makes a mistake so that gene stops working. Knock out all 20,000 genes in the human genome one at a time, and you can build a vast library of gene-removed cells, for example to test cancer chemotherapy drugs by finding which genes are involved in a response. As Beale explains: “With CRISPR-Cas9 techniques we can kill genes, switch them on and, if we are lucky, replace bits of one gene with another. It doesn’t stop there: the guidance system can be employed to perform almost any function that can be bolted onto a protein.” In other words CRISPR will make it possible to directly code the human genome, and we’ll soon be seeing patches that cure specific genetic diseases, add resistance to infections and more. Patch Tuesday could eventually become something you do at your local clinic as well as on your PC.

Of course the risks as well as the benefits of such patching will pretty quickly become apparent (hopefully they’ll not be as bad as Windows 10). CRISPR has become big business and there are ongoing squabbles over the patent rights between various corporations and universities. Jennifer Doudna, a leading CRISPR researcher at Berkeley, in her excellent popular book “A Crack in Creation”, tackles some of the ethical problems that will arise as we supplant “the deaf dumb and blind system that has shaped genetic material on our planet for eons and replace it with a conscious intentional system of human directed evolution”. If GM lettuces created a ferocious worldwide protest, expect way more at the prospect of GM babies...