Uh oh, there’s a dis­or­derly Dead­pool in the gene pool

Mail & Guardian - - News - Matthew du Plessis

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?

Pro­tein tor­pedo

The ge­netic mi­graine brought about by un­in­tended con­se­quences is of a dif­fer­ent or­der in the world of molec­u­lar bi­ol­ogy and CRISPRCas9. 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 self­de­struct, 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.

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