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...

OUT THE WINDOW

Dick Pountain/ Idealog 283/ 9th February 2018 09:38:21

A few days ago my Chromebook told me it would like to reboot in order to update its operating system. I‘d just made a cup of tea at the time (Bai Mu Dan if you’re interested). I hit the power button and nervously watched the progress bar – a habit picked up from 30 years of Windows use – and it finished updating while the tea was still hot. With the reboot completed a pop-up informed me that I could now download and run Android apps on the Chromebook. That was worth another biscuit (Biscoff Lotus if you’re interested). 

Running Android apps on the Chromebook had been an ambition for most of the previous year, but up until now it had involved techie adventures in developer mode that I didn’t feel like attempting. The first driver of this ambition was a need to program in Python on the machine, satisfied instantly by downloading the Android version QPython3. It compiled and ran everything I’ve written under Windows, the only change required being to prefix any file paths with “/storage/emulated/0/” (of which more later). 

Almost as strong was a desire for certain Android apps I’d come to depend upon, like the PC-Pro-Award-winning Citymapper which enables me to navigate through London with unprecedented ease. I had tried the browser-based version for Chrome, but it was so inferior to the Android app in UI terms, particularly the interactivity of the maps, that I preferred to use it on my phone or tablet. And that brings me to the main point of this column: just like Windows native applications, Android apps nowadays exploit the hardware (especially screen real-estate) so much better than browser-based versions that there’s no contest. 

Another application I use every day is Spotify, on which I listen to music at home via Windows or Chromebook, while walking on heath or park on my phone. But until this update I had three different versions of the Spotify client, differing from one another in various ways, some subtle, some downright infuriating. The Windows version is still the most complete in that it supports playlist folders to organise my scores of lists, and also drag-and-drop to rearrange these folders and their contents. The Android version has folders that aren’t drag-and-drop, but does support a new UI with a taskbar at the bottom that’s easier to use on small phone screens. The browser version I’d been using on the Chromebook is a nightmare that doesn’t support folders at all and steamrollers them into un-navigably flat lists which aren’t even complete: the Artists tab only displays a fraction of what’s there. Spotify is nowadays ambivalent about playlists and deprecates them in favour of its newer, non-hierarchical Your Music (Save| Songs| Artists| Albums) system, hence this bodge which I thoroughly enjoyed uninstalling.

The combination of Google Contacts, Calendar and the ever-increasingly-wonderful Google Keep ensures that all my appointments, addresses, notes and other important data are always automatically synced between Windows, Chrome and Android machines – I can even do voice dictation on my phone and have it there waiting on the desktop when I get home. 

So what about writing? Well, the answer is that I’m writing this column in Google Docs. Running Android means that I could now have Microsoft Word, but in truth I’d stopped using MS Office even under Windows several years ago, in favour of LibreOffice. Google Docs does everything I need except for its lack of simple macros. Under Windows I used an external app Macro Express, plus a few Word Basic scripts. I’ve found an almost complete replacement in a Chrome extension called ProKeys that stores ‘snippets’ of text, complete with placeholders and automatic date and time stamping, which covers 90% of what I want to do. It can’t do my text editing macros – swapping pairs of letters or words under the cursor – but I can’t be bothered to learn Google Docs’ JavaScript API and will do without. 

Is there a downside? Well yes, the confusion of three different file locations, the default My Drive in the cloud, the small local Download drive and a completely separate local Android drive. Apps mostly hide this from you, but it really is time Google did that long-promised merger of Android and ChromeOS. As a grizzled pioneer of the personal computer revolution I’ll never be entirely happy having everything in someone else’s cloud and will always want local copies of current work and vital data, so here’s a suggestion. A merged OS (ChromDroid?) might have a file attribute that takes these three values:

  l = local only
  c = cloud only
  s = local first, then sync to cloud

Give me that and Windows would go right, er, out the window.