This CRISPR Mo­ment

Edit­ing hu­man DNA the way we edit text — are we ready?

The Walrus - - MISCELLANY - Françoise Baylis & Janet Ros­sant il­lus­tra­tions by Katty Mau­rey

It reads like an all-caps typo from the tech­ni­cal man­ual that comes taped to the side of a new re­frig­er­a­tor. But CRISPR is go­ing to change your world. It may even — quite lit­er­ally — change the face of humanity.

Since its dis­cov­ery four years ago, the gene-edit­ing sys­tem known as “clus­tered reg­u­larly in­ter­spaced short palin­dromic re­peats” has been used by sci­en­tists to make pre­cise al­ter­ations in the DNA se­quences of liv­ing cells. It of­fers the prospect of treat­ing (and per­haps even erad­i­cat­ing) de­bil­i­tat­ing ge­netic con­di­tions, im­prov­ing fer­til­ity treat­ments, fight­ing can­cer, and al­low­ing the safe trans­plan­ta­tion of tis­sues and or­gans be­tween species.

He­mophilia, sickle-cell ane­mia, and mus­cu­lar dys­tro­phy are just three of the dis­eases that could even­tu­ally be­come treat­able thanks to ther­a­pies de­vel­oped through CRISPR. In late 2015, for in­stance, three groups of sci­en­tists re­ported that they could in­fect mus­cle cells in liv­ing Duchenne mus­cu­lar dys­trophic mice with a virus car­ry­ing the CRISPR/CAS9 edit­ing cas­sette. (The lat­ter al­phanu­meric term refers to a CRISPR sys­tem that em­ploys the Cas9 pro­tein.) The re­searchers then edited the de­fec­tive dys­trophin gene in enough cells to im­prove mus­cle func­tion.

On the other hand, CRISPR also raises the spec­tre of a Gat­taca- style bioeth­i­cal dystopia. The tech­nol­ogy, some warn, might open the door to large-scale bioter­ror­ism or mon­strous, ge­net­i­cally al­tered hu­man vari­ants. Us­ing CRISPR/CAS9, sci­en­tists can make pre­cise ge­netic al­ter­ations to early-stage em­bryos that are pre­cur­sors of all the cells con­tained in a hu­man body. Cru­cially, this in­cludes the eggs and sperm. Al­ter­ations to these “germ cells” are her­i­ta­ble, mean­ing they will carry over into suc­ceed­ing gen­er­a­tions. This is com­monly re­ferred to as “germ-line gene edit­ing.” So far, lines of ge­net­i­cally al­tered plants, flies, fish, mice, and even mon­keys have been pro­duced us­ing such gene-edit­ing tech­niques.

The clus­tered reg­u­larly in­ter­spaced short palin­dromic re­peats em­ployed by CRISPR are ge­netic se­quences that were first dis­cov­ered in bac­te­ria some twenty years ago. A clever se­ries of ex­per­i­ments and DNA de­tec­tive work in the early part of this cen­tury led to the dis­cov­ery that CRISPRS carry bits of vi­ral DNA — and use copies of this se­quence to rec­og­nize and tar­get any in­vad­ing virus with an en­zyme (typ­i­cally Cas9) that cuts up and de­stroys vi­ral in­vaders.

In­ter­est­ingly, many of the early ad­vances in this tech­nol­ogy took place in the yo­ghurt in­dus­try, where sci­en­tists were look­ing to get rid of vi­ral in­fec­tions in the

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