It’s in her DNA

CRISPR coin­ven­tor Jennifer Doudna talks about de­vel­op­ing the ge­need­it­ing tool that’s poised to change the world.

Fast Company - - Contents - Pho­to­graphs by Car­los Chavar­ría

Jennifer Doudna, coin­ven­tor of the gene-edit­ing tool CRISPR, on the ter­ri­fy­ing power of be­ing able to ma­nip­u­late na­ture.

Sci­en­tists now have a rel­a­tively easy and in­ex­pen­sive way to read, write, and edit the build­ing blocks of life—the genome-edit­ing tech­nique known as CRISPR-CAS9. And while the tech­nol­ogy was de­vel­oped only five years ago, CRISPR’S abil­ity to tar­get—and mod­ify—spe­cific sec­tions of DNA is al­ready su­per­charg­ing the pace of sci­en­tific break­throughs in medicine and agri­cul­ture. It’s even be­ing used to try to bring the woolly mam­moth back to life. In­vestors (in­clud­ing Bill Gates and Sean Parker) and phar­ma­ceu­ti­cal com­pa­nies have plowed mil­lions of dol­lars into

Crispr-driven re­search; phi­lan­thropies have granted mil­lions more to sup­port sci­en­tists work­ing on cures for ge­netic dis­eases; and in China, at least seven hu­man clin­i­cal tri­als are mov­ing for­ward. But it all started when a small group of sci­en­tists, work­ing in col­lab­o­ra­tion, stum­bled on an or­ganic bi­o­log­i­cal process that had ex­isted for mil­len­nia. Among the lead­ers was molec­u­lar bi­ol­o­gist Jennifer Doudna, who heads the Doudna Lab at the Univer­sity of Cal­i­for­nia, Berke­ley. She’s the coau­thor of a new book trac­ing CRISPR’S evo­lu­tion, A Crack in Cre­ation: Gene Edit­ing and the Un­think­able Power to Con­trol Evo­lu­tion. “[CRISPR] is a great il­lus­tra­tion of how tech­nolo­gies are born,” says Doudna. “They of­ten come about in unexpected ways.” And the out­comes can be just as un­pre­dictable, and dan­ger­ous—a fact that has prompted her to be­come a global ad­vo­cate for the re­spon­si­ble use of CRISPR. In this ex­cerpt, Doudna talks about its trans­for­ma­tive power. —Noah Ro­bischon To­ma­toes that can sit in the pantry slowly ripen­ing for months with­out rot­ting. Plants that can bet­ter weather cli­mate change. Mosquitoes that are un­able to trans­mit malaria. Ul­tra-mus­cu­lar dogs that make fear­some part­ners for po­lice and sol­diers. Cows that no longer grow horns.

These or­gan­isms might sound far-fetched, but in fact, they al­ready ex­ist, thanks to gene edit­ing. And they’re only the be­gin­ning. As I write this, the world around us is be­ing rev­o­lu­tion­ized by CRISPR, whether we’re ready for it or not. Within the next few years, this new biotech­nol­ogy will give us higher-yield­ing crops, health­ier live­stock, and more nu­tri­tious foods. Within a few decades, we might well have ge­net­i­cally en­gi­neered pigs that can serve as hu­man or­gan donors—but we could also have woolly mam­moths, winged lizards, and uni­corns. No, I am not kid­ding.

It amazes me to re­al­ize that we are on the cusp of a new era in the his­tory of life on earth—an age in which hu­mans ex­er­cise an un­prece­dented level of con­trol over the ge­netic com­po­si­tion of the species that coin­habit our planet. It won’t be long be­fore CRISPR al­lows us to bend na­ture to our will in the way that hu­mans have dreamed of since pre­his­tory. When that will is di­rected to­ward some­thing con­struc­tive, the re­sults could be fan­tas­tic—but they might also have un­in­ten­tional or even calami­tous consequences.

The im­pact of gene-edited plants and an­i­mals is al­ready be­ing felt in the sci­en­tific com­mu­nity. For ex­am­ple, re­searchers have har­nessed CRISPR to gen­er­ate an­i­mal mod­els of hu­man dis­ease with far greater pre­ci­sion and flex­i­bil­ity than be­fore—not just in mice, but in what­ever an­i­mals best ex­hibit the dis­ease of in­ter­est, whether it be mon­keys for autism, pigs for Parkin­son’s, or fer­rets for in­fluenza. One of the most in­ter­est­ing as­pects of the CRISPR tech­nol­ogy is the way it en­ables the study of fea­tures unique to cer­tain or­gan­isms, such as limb re­gen­er­a­tion in Mex­i­can sala­man­ders, ag­ing in kil­li­fish, and skele­tal de­vel­op­ment in crus­taceans. I love the notes and pic­tures col­leagues send me de­scrib­ing their CRISPR ex­per­i­ments—the beau­ti­ful but­ter­fly-wing pat­terns whose ge­netic un­der­pin­nings they’ve un­cov­ered, or the in­fec­tious yeast whose abil­ity to in­vade hu­man tis­sues they’ve dis­sected at the level of in­di­vid­ual genes. These kinds of ex­per­i­ments re­veal new truths about the nat­u­ral world and about the ge­netic sim­i­lar­i­ties that bind all or­gan­isms to­gether. They’re enor­mously ex­cit­ing to me.

At the other end of the spec­trum are gene-edit­ing ap­pli­ca­tions that read more like science fic­tion than the con­tents of a sci­en­tific jour­nal.

For ex­am­ple, I was amazed to learn that sev­eral re­search teams are us­ing CRISPR to “hu­man­ize” var­i­ous genes in pigs in the hope that life-threat­en­ing or­gan-donor short­ages might one day be solved by xeno­trans­plan­ta­tion—the trans­fer of or­gans grown in pigs (or other an­i­mals) into hu­man re­cip­i­ents. In a sign of the kinds of aes­thetic changes to an­i­mals that are now pos­si­ble, com­pa­nies have used ge­need­it­ing tech­nolo­gies to cre­ate new de­signer pets, such as gene-edited mi­cropigs that never grow larger than small dogs. And in a page taken straight out of a fa­mous book-to-film sci-fi fran­chise, some lab­o­ra­to­ries are pur­su­ing a ven­ture known as de-ex­tinc­tion, which is noth­ing less than the res­ur­rec­tion of ex­tinct species through cloning or ge­netic engi­neer­ing. My friend Beth Shapiro, a pro­fes­sor at the Univer­sity of Cal­i­for­nia, Santa Cruz, is ex­cited to use this strat­egy to re-cre­ate ex­tinct species of birds for the pur­pose of study­ing their re­la­tion­ships to mod­ern species. Along the same lines, ef­forts are al­ready un­der way to con­vert the ele­phant genome into the woolly mam­moth genome, bit by bit, us­ing CRISPR.

Iron­i­cally, CRISPR might also en­able the op­po­site: forcible ex­tinc­tion of un­wanted an­i­mals or pathogens. Yes, some­day soon, CRISPR might be em­ployed to de­stroy en­tire species—an ap­pli­ca­tion I never could have imag­ined when my lab first en­tered the fledgling field of bac­te­rial adap­tive im­mune sys­tems just 10 years ago.

Some of the ef­forts in these and other ar­eas of the nat­u­ral world have tremen­dous po­ten­tial for im­prov­ing hu­man health and well-be­ing. Oth­ers are friv­o­lous, whim­si­cal, or even down­right dan­ger­ous. And I have be­come in­creas­ingly aware of the need to un­der­stand the risks of gene edit­ing, es­pe­cially in light of its ac­cel­er­at­ing use.

CRISPR gives us the power to rad­i­cally and ir­re­versibly al­ter the bio­sphere that we in­habit by pro­vid­ing a way to re­write the very mol­e­cules of life any way we wish. At the mo­ment, I don’t think there is nearly enough dis­cus­sion of the pos­si­bil­i­ties it presents— for good, but also for ill. It’s a thrilling mo­ment in the life sciences, but we can’t let our­selves get car­ried away. It’s im­por­tant to re­mem­ber that, while CRISPR has enor­mous and un­de­ni­able po­ten­tial to im­prove our world, tin­ker­ing with the ge­netic un­der­pin­nings of our ecosys­tem could also have un­in­tended consequences. We have a re­spon­si­bil­ity to con­sider the ram­i­fi­ca­tions in ad­vance and to en­gage in a global, pub­lic, and in­clu­sive con­ver­sa­tion about how to best har­ness gene edit­ing in the nat­u­ral world, be­fore it’s too late.

It won’t be long be­fore CRISPR al­lows us to bend na­ture to our will in the way that hu­mans have dreamed of since pre­his­tory.

From A Crack in Cre­ation: Gene Edit­ing and the Un­think­able Power to Con­trol Evo­lu­tion, by Jennifer Doudna and Sa­muel H. Stern­berg. Reprinted with per­mis­sion of Houghton Mif­flin Har­court.

Re­spon­si­ble science

Af­ter help­ing to dis­cover CRISPR, Doudna has been lead­ing the dis­cus­sion around us­ing it eth­i­cally.

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