Wednesday 30 January 2019

Crispr: the craic is mighty

Someone who loves me and thinks I spend too much time bloggin' and not enough reading gave me a copy of A Crack in Creation by Jennifer Doudna and Sam Sternberg. Doudna is in line for getting a Nobel Prize for her invention of a gene-editing technology called CRISPR-Cas9. Sternberg was her graduate student, is now a professor at Columbia U, and can tell a story better than most scientists. He's not exactly a ghost writer because he gets full author credit. But you get the feeling that when publishers hunted down Doudna to write a popular science book about her journey, she turned to her most literate friend and brought him on board. After a few style-and-substance quirks that had me fling the book to the other end of the sofa in a pet, I settled down and read it through to the end without skipping much. I'm a scientist; I've known about CRISPR for half a decade; I know it is important; I know it is ethically controversial; I know that there are fortunes to be made; but I couldn't have explained how it works. To be honest, I'm not now better able to explain it after reading this book.

That is partly because the methodological explanation is at the start when I was aggravated by the stylistic yo-yo of alternating between over-simplifying the easy stuff and making unwarranted Curse of Knowledge assumptions about the trickier concepts. The Curse of Knowledge is when you've learned something (hard) it is impossible to unthink that knowledge to understand how an absolute beginner approaches the problem. I'll give you an unscientific example: on p232 "linkages between class and genetics would ineluctably grow from one generation to the next". In a popular book relentlessly or unavoidably would do just fine; ineluctably is a college-boy word. Next page exacerbate is used rather than worsen. I'm a college-boy - I've had to edit my fancy vocabulary [herbivore - salient - indelible] so my students know wtf I'm on about.

If you want to know how CRISPR works you could do worse than listen to Paul Anderson a high-school teacher from Bozeman Montana as he explains the system. I use his channel in my Human Physiology classes - his animations are better than I can do with words and static pictures. MIT, an institution with $ignificant $kin in the CRI$PR-CA$ game (and load$a money for propaganda), has produced their own video with fancier graphics than Bozeman's but gaping holes in their story. MIT don't trouble to explain that CRISPR is an acronym [clustered regularly interspaced short palindromic repeats] but tell us <yawn> that A pairs with T and C pairs with G. Every word in [clustered regularly interspaced short palindromic repeats] is a key clue to how the system works and what is its potential. No surprise that Jennifer Doudna was invited to address TED-Global in London in 2015, her technical explanation isn't as good as the high-school teachers perhaps because she's too close to it. WIRED's Biologist Explains One Concept in 5 Levels of Difficulty isn't what it says on the tin (he's hopeless with the easy stuff and seems to know less than the experts) but advances the discussion in useful directions. One could wish that youtube presenters would consider not-Anglophone watchers and Enunciate Clearly: problem not pro'm; ability not abil'y. tsk!

If a 7 minute video is tl;dw for you, you can skip to the fact that this technique has the potential to precisely remedy the genetic damage that causes cystic fibrosis or retinitis pigmentosum or thalassaemia <etc.> and leave all the other genes unchanged. Parents who bonk bonk love each other very much but are carriers for one of these diseases can have children "of their own blood" but no chance of developing the disease that dogged their ancestors. You'd have to be a hard-hearted god-botherer to be against such tilting of Fortune's table IF the precision and reliability of the edit could be guaranteed.

But what about cosmetic changes [getting rid of all those Irish freckles] or smoothing out natural variability so that everyone has faster reflexes, nobody is on the autistic spectrum. If you can change such factors reliably and cheaply (which is a probability) then people who don't or can't or won't avail of the opportunity to change themselves and their children may get excluded. Me, I'd rather cherish and support The Different because diversity is intrinsically interesting: when conditions change [think End of World issues like carbon footprint] then maybe slower more deliberative folks will be an asset while the rest of us run around like headless chickens. We need to think about these ethical issues because genetic editing is at the gate and a lot of rich people have invested a chunk of their money in the technology and want a return of their investment.

Did someone mention money? In her book, Jennifer Doudna [L above] absolutely avoids talking about the Patent Law dispute her Institution, UC Berkeley, [and her pal and co-inventor Emmanuelle Charpentier [R above] of the Helmholtz Centre for Infection Research in Braunschweig, Germany] is fighting with Feng Zhang [sandwiched above], the Broad Institute and its parents Harvard and MIT. Berkeley & Co. want exclusive use and licencing of the whole field. Broad & Co. hold that their boy was the first to make a usable product out of CRISPR . . . perhaps while Doudna was agonising about the ethical issues and holding workshops to discuss them. The US Law is currently supporting the case from The East Coast while the Europeans are favouring The Californians - perhaps because Emmanuelle Charpentier is Euro-french. That split decision will play havoc with the development of CRISPR-tech because drug-companies work best in a Global Village - bigger population and a uniform playing field = more profits. I hope Doudna, and indeed the other two, makes a fortune out of these ideas and that they share it with all the people who inched the idea along the way. And watch the Nobel space!

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