Matthew Cobb

The New York Review of Books - - Contents - Matthew Cobb

The Gene Ma­chine:

How Ge­netic Tech­nolo­gies Are Chang­ing the Way We Have Kids— and the Kids We Have by Bon­nie Rochman.

Sci­en­tific Amer­i­can/Far­rar, Straus and Giroux, 272 pp., $26.00

DNA Is Not Des­tiny:

The Re­mark­able, Com­pletely Mis­un­der­stood Re­la­tion­ship Be­tween You and Your Genes by Steven J. Heine.

Nor­ton, 344 pp., $26.95

A Crack in Cre­ation:

Gene Edit­ing and the Un­think­able Power to Con­trol Evo­lu­tion by Jen­nifer A. Doudna and Sa­muel H. Stern­berg.

Houghton Mif­flin Harcourt,

281 pp., $28.00

In re­cent years, two new ge­netic tech­nolo­gies have started a sci­en­tific and med­i­cal rev­o­lu­tion. One, rel­a­tively well known, is the abil­ity to eas­ily de­code the in­for­ma­tion in our genes. The other, which is only dimly un­der­stood by the gen­eral pub­lic, is our new­found ca­pac­ity to mod­ify genes at will. Th­ese in­no­va­tions give us the power to pre­dict cer­tain risks to our health, elim­i­nate deadly dis­eases, and ul­ti­mately trans­form our­selves and the whole of na­ture. This de­vel­op­ment raises com­plex and urgent ques­tions about the kind of so­ci­ety we want and who we re­ally are. A brave new world is just around the corner, and we had better be ready for it or things could go hor­ri­bly wrong. The rev­o­lu­tion be­gan in be­nign but spec­tac­u­lar fash­ion. In June 2000, Pres­i­dent Bill Clin­ton and Prime Min­is­ter Tony Blair an­nounced the com­ple­tion of the first draft of the hu­man genome. Ac­cord­ing to a White House press state­ment, this achieve­ment would “lead to new ways to pre­vent, di­ag­nose, treat, and cure dis­ease.” Many sci­en­tists were skep­ti­cal, but the pub­lic (who footed much of the $3 bil­lion bill) prob­a­bly found this highly prac­ti­cal jus­ti­fi­ca­tion more ac­cept­able than the mere de­sire to know, which was in fact a large part of the mo­ti­va­tion of many of the sci­en­tists in­volved.

Dur­ing the 2000s, Clin­ton’s vi­sion was slowly put into prac­tice, be­gin­ning with the de­vel­op­ment of tests for ge­netic dis­eases. As th­ese tests have be­come wide­spread, eth­i­cal con­cerns have be­gun to sur­face. Bon­nie Rochman’s The Gene Ma­chine shows how ge­netic test­ing is chang­ing the lives of prospec­tive par­ents and ex­plores the dilem­mas many peo­ple now face when de­cid­ing whether to have a child who might have a par­tic­u­lar dis­ease. Some of th­ese tech­nolo­gies are rel­a­tively straight­for­ward, such as the new blood test for Down syn­drome or the Dor Yeshorim ge­netic data­base for Jews, which en­ables peo­ple to avoid part­ners with whom they might have a child af­fected by the lethal Tay-Sachs dis­ease (par­tic­u­larly preva­lent in Ashke­nazis). But both of th­ese ap­par­ently an­o­dyne pro­cesses turn out to raise im­por­tant eth­i­cal is­sues.

Whether we like it or not, the Dor Yeshorim data­base and other sim­i­lar ini­tia­tives, such as ge­netic tests for sickle-cell ane­mia, which largely af­fects African-Amer­i­cans, are en­abling us to de­lib­er­ately change the fre­quency of cer­tain hu­man genes in the pop­u­la­tion. This is the tech­ni­cal def­i­ni­tion of eu­gen­ics and might seem shocking, since eu­gen­ics is for­ever as­so­ci­ated with the forced ster­il­iza­tion of the men­tally ill and Na­tive Amer­i­cans in the US or the mur­der of those deemed ge­net­i­cally de­fec­tive by the Nazis. But the abil­ity to use ge­netic test­ing when de­cid­ing whether or not to have chil­dren is clearly a form of soft eu­gen­ics, al­beit one car­ried out vol­un­tar­ily by those af­fected and clearly lead­ing to a re­duc­tion of hu­man suf­fer­ing. With the best of in­ten­tions and, for the mo­ment, the best of out­comes, we have drifted across a line in the sand.

The new ge­netic test for Down syn­drome also hides eth­i­cal traps. The test de­tects tiny amounts of fe­tal DNA in the mother’s blood­stream, and in the US it has largely re­placed the wide­spread use of in­va­sive al­ter­na­tives (am­nio­cen­te­sis or chori­onic vil­lous sam­pling, in which cells are taken from the pla­centa) that in­volve a risk of mis­car­riage. The ad­vent of a safe way to de­tect Down is a pos­i­tive de­vel­op­ment (in the UK it is pre­dicted that the test will pre­vent up to thirty in­va­sive test–in­duced mis­car­riages each year), but some women feel that its sim­plic­ity means they are be­ing in­ad­ver­tently pres­sured into hav­ing a test for Down, and po­ten­tially into hav­ing an abor­tion if the test re­sult is pos­i­tive.

It is ex­tremely dif­fi­cult to ob­tain re­li­able data on how of­ten iden­ti­fi­ca­tion of Down syn­drome in a fe­tus has led to a de­ci­sion to ter­mi­nate a preg­nancy, but a re­cent study in Mas­sachusetts sug­gested that prior to the in­tro­duc­tion of the safer test in 2011, around 49 per­cent of such preg­nan­cies were aborted. Since many par­ents opted not to have an in­va­sive test for fear of mis­car­riage (in the UK the fig­ure was around 40 per­cent), it is rea­son­able to ex­pect that an in­creased rate of iden­ti­fi­ca­tion of fe­tuses with Down syn­drome will lead to more abor­tions. This has led to crit­i­cism from fam­i­lies with Down syn­drome chil­dren, who un­der­stand­ably want to em­pha­size the joy they feel liv­ing with a child who has the con­di­tion. Rochman nav­i­gates th­ese dif­fi­cult waters with skill and com­pas­sion, draw­ing on con­ver­sa­tions with fam­i­lies and physi­cians and set­ting out the eth­i­cal chal­lenges and the range of so­lu­tions adopted by dif­fer­ent peo­ple, with­out be­ing preachy or moral­is­tic.

In the last few years, ge­netic test­ing has en­tered the com­mer­cial mainstream. Di­rect-to-con­sumer test­ing is now com­mon­place, per­formed by com­pa­nies such as 23andMe (hu­mans have twenty-three pairs of chro­mo­somes). Much of the in­ter­est in such tests is based not only on the claim that they en­able us to trace our an­ces­try, but also on the in­sight into our fu­ture health that they pur­port to pro­vide. At the be­gin­ning of April, 23andMe re­ceived FDA ap­proval to sell a do-it-your­self ge­netic test for ten dis­eases, in­clud­ing Parkin­son’s and late-on­set Alzheimer’s. You spit in a tube, send it off to the com­pany, and af­ter a few days you get your re­sults. But as Steven Heine, a Cana­dian pro­fes­sor of so­cial and cul­tural psy­chol­ogy who un­der­took sev­eral such tests on him­self, ex­plains in DNA Is Not Des­tiny, that is where the prob­lems be­gin.

Some dis­eases are in­deed en­tirely ge­net­i­cally de­ter­mined—Hunt­ing­ton’s dis­ease, Duchenne mus­cu­lar dys­tro­phy, and so on. If you have the faulty gene, you will even­tu­ally have the dis­ease. Whether you want to be told by e-mail that you will de­velop a lifethreat­en­ing dis­ease is some­thing you need to think hard about be­fore do­ing the test. But for the vast ma­jor­ity of dis­eases, our fu­ture is not writ­ten in our genes, and the re­sults of ge­netic tests can be mis­lead­ing.

For ex­am­ple, Heine re­veals that ac­cord­ing to one test, he has “a 32 per­cent in­creased chance” of devel­op­ing Parkin­son’s dis­ease. Be­hind this alarm­ing fig­ure lurks the re­al­ity that his risk is only slightly higher than the small like­li­hood that is found in the gen­eral pop­u­la­tion (2.1 per­cent for Heine, 1.6 per­cent for the rest of us). That does not sound quite so bad. Or does it? What does a risk of 2.1 per­cent re­ally mean? Peo­ple have a hard time in­ter­pret­ing this kind of in­for­ma­tion and de­cid­ing how to change their life­style to re­duce their chance of get­ting the dis­ease, if such an op­tion is avail­able. (It is not for Parkin­son’s.)

Even more un­help­fully, dif­fer­ent com­pa­nies test­ing for the same dis­ease can pro­duce dif­fer­ent re­sults. Heine was told by one com­pany that he had a higher-than-av­er­age risk of prostate cancer, Parkin­son’s, melanoma, and var­i­ous other dis­eases, whereas another said his risk for all th­ese con­di­tions was nor­mal. Th­ese dis­crep­an­cies can be ex­plained by the dif­fer­ent cri­te­ria and data­bases used by each test­ing com­pany. Faced with vary­ing es­ti­mates, the av­er­age cus­tomer might con­clude that con­tra­dic­tory in­for­ma­tion is worse than no in­for­ma­tion at all. As Heine puts it, “The or­a­cle’s crys­tal ball is made of mud.”

More trou­blingly still, how­ever im­per­fect its pre­dic­tive value, the tsunami of hu­man ge­netic in­for­ma­tion now pour­ing from DNA se­quencers all over the planet raises the pos­si­bil­ity that our DNA could be used against us. The Ge­netic In­for­ma­tion Nondis­crim­i­na­tion Act of 2008 made it il­le­gal for US med­i­cal in­sur­ance com­pa­nies to dis­crim­i­nate on the ba­sis of ge­netic in­for­ma­tion (al­though strik­ingly not for life in­sur­ance or long-term care). How­ever, the health care re­form leg­is­la­tion recently passed by the House (the Amer­i­can Health Care Act, known as Trump­care) al­lows in­sur­ers to charge higher pre­mi­ums for peo­ple with a pre­ex­ist­ing con­di­tion. It is hard to imag­ine any­thing more pre­ex­ist­ing than a gene that could or, even worse, will lead to your get­ting a par­tic­u­lar dis­ease; and un­der such a health sys­tem, in­sur­ance com­pa­nies would have ev­ery in­cen­tive to find out the risks present in your DNA. If this com­po­nent of the Repub­li­can health care re­form be­comes law, the courts may con­clude that a ge­netic test qual­i­fies as proof of a pre­ex­ist­ing con­di­tion. If genes end up af­fect­ing health in­sur­ance pay­ments, some peo­ple might choose not to take th­ese tests.

But of even greater prac­ti­cal and moral sig­nif­i­cance is the sec­ond part of the rev­o­lu­tion in ge­net­ics: our abil­ity to mod­ify or “edit” the DNA se­quences of hu­mans and other crea­tures. This tech­nique, known as CRISPR (pro­nounced “crisper”), was first ap­plied to hu­man cells in 2013, and has al­ready rad­i­cally changed re­search in the life sciences. It works in pretty much ev­ery species in which it has been tried and is cur­rently un­der­go­ing its first clin­i­cal tri­als. HIV, leukemia, and sickle-cell ane­mia will prob­a­bly soon be treated us­ing CRISPR.

In A Crack in Cre­ation, one of the pi­o­neers of this tech­nique, the bio­chemist Jen­nifer Doudna of the Univer­sity of Cal­i­for­nia at Berke­ley, to­gether with her one­time stu­dent Sa­muel Stern­berg, de­scribes the science be­hind CRISPR and the his­tory of its

dis­cov­ery. This guide­book to the CRISPR rev­o­lu­tion gives equal weight to the science of CRISPR and the pro­found eth­i­cal ques­tions it raises. The book is re­quired read­ing for ev­ery con­cerned ci­ti­zen—the ma­te­rial it cov­ers should be dis­cussed in schools, col­leges, and uni­ver­si­ties through­out the coun­try. Com­mu­nity and pa­tient groups need to un­der­stand the im­pli­ca­tions of this tech­nol­ogy and help de­cide how it should and should not be ap­plied, while politi­cians must con­front the dra­matic chal­lenges posed by gene edit­ing.

The story of CRISPR is a case study in how sci­en­tific in­quiry that is purely driven by cu­rios­ity can lead to ma­jor ad­vances. Be­gin­ning in the 1980s, sci­en­tists no­ticed that parts of the genomes of mi­crobes con­tained reg­u­lar DNA se­quences that were re­peated and con­sisted of ap­prox­i­mate palin­dromes. (In fact, in gen­eral only a few mo­tifs are roughly re­peated within each “palin­drome.”) Even­tu­ally, th­ese se­quences were given the snappy acro­nym CRISPR—clus­tered reg­u­larly in­ter­spersed short palin­dromic re­peats. A hint about their func­tion emerged when it be­came clear that the bits of DNA found in the spa­ces be­tween the re­peats—called spacer DNA—were not some ran­dom bac­te­rial junk, but in­stead had come from viruses and had been in­te­grated into the mi­crobe’s genome. Th­ese bits of DNA turned out to be very im­por­tant in the life of the mi­crobe. In 2002, sci­en­tists dis­cov­ered that the CRISPR se­quences ac­ti­vate a series of pro­teins—known as CRISP Ras­so­ci­ated (or Cas) pro­teins—that can un­ravel and at­tack DNA. Then in 2007, it was shown that the CRISPR se­quence and one par­tic­u­lar pro­tein (of­ten re­ferred to as CRISPR-Cas9) act to­gether as a kind of im­mune sys­tem for mi­crobes: if a par­tic­u­lar virus’s DNA is in­cor­po­rated into a mi­crobe’s CRISPR se­quences, the mi­crobe can rec­og­nize an in­va­sion by that virus and ac­ti­vate Cas pro­teins to snip it up.

This was a pretty big deal for mi­cro­bi­ol­o­gists, but the ex­cite­ment stems from the re­al­iza­tion that the CRISP Ras­so­ci­ated pro­teins could be used to al­ter any DNA to achieve a de­sired se­quence. At the be­gin­ning in 2013, three groups of re­searchers, from the Univer­sity of Cal­i­for­nia at Berke­ley (led by Jen­nifer Doudna), Har­vard Med­i­cal School (led by Ge­orge Church), and the Broad In­sti­tute of MIT and Har­vard (led by Feng Zhang), in­de­pen­dently showed that the CRISPR tech­nique could be used to mod­ify hu­man cells. Gene edit­ing was born.

The pos­si­bil­i­ties of CRISPR are im­mense. If you know a DNA se­quence from a given or­gan­ism, you can chop it up, delete it, and change it at will, much like what a word-pro­cess­ing pro­gram can do with texts. You can even use CRISPR to in­tro­duce ad­di­tional con­trol el­e­ments—for ex­am­ple to en­gi­neer a gene so that it is ac­ti­vated by light stim­u­la­tion. In ex­per­i­men­tal or­gan­isms this can pro­vide an ex­tra­or­di­nary de­gree of con­trol in stud­ies of gene func­tion, en­abling sci­en­tists to ex­plore the con­se­quences of gene ex­pres­sion at a par­tic­u­lar mo­ment in the or­gan­ism’s life or in a par­tic­u­lar en­vi­ron­ment.

There ap­pear to be few lim­its to how CRISPR might be used. One is tech­ni­cal: it can be dif­fi­cult to de­liver the spe­cially con­structed CRISPR DNA se­quences to spe­cific cells in order to change their genes. But a larger and more in­tractable con­cern is eth­i­cal: Where and when should this tech­nol­ogy be used? In 2016, the power of gene edit­ing and the rel­a­tive ease of its ap­pli­ca­tion led James Clap­per, Pres­i­dent Obama’s di­rec­tor of na­tional in­tel­li­gence, to de­scribe CRISPR as a weapon of mass de­struc­tion. Well-mean­ing bio­hack­ers are al­ready sell­ing kits over the In­ter­net that en­able any­one with high school bi­ol­ogy to edit the genes of bac­te­ria. The plot­line of a techno-thriller may be writ­ing it­self in real time.

A Crack in Cre­ation in­evitably fo­cuses on Doudna’s work, pro­vid­ing in­sight into her own feel­ings as the im­pli­ca­tions of CRISPR slowly dawned on her and her prin­ci­pal col­lab­o­ra­tor, the French sci­en­tist Em­manuelle Char­p­en­tier. How­ever, the book also de­scribes the work of the many lab­o­ra­to­ries around the world that contributed to the break­through. This even­handed ap­proach con­trasts with an ar­ti­cle on the his­tory of CRISPR writ­ten for Cell by the molec­u­lar bi­ol­o­gist Eric Lan­der of the Broad In­sti­tute. Lan­der’s ar­ti­cle was widely seen as un­fairly em­pha­siz­ing the work of the Har­vard re­searchers Zhang and Church and down­play­ing the con­tri­bu­tion of Doudna and Char­p­en­tier.* Th­ese con­test­ing his­to­ries seek to in­flu­ence not only who will get what seems like an in­evitable No­bel Prize for the dis­cov­ery, but above all the for­tune that can be made, for in­di­vid­u­als and in­sti­tu­tions, from the pa­tents to CRISPR ap­pli­ca­tions.

Frus­trat­ingly, Doudna and Stern­berg say lit­tle about the patent is­sue, which is cur­rently the fo­cus of a com­plex le­gal case be­tween the Univer­sity of Cal­i­for­nia and the Broad In­sti­tute over which group of re­searchers can right­fully li­cense CRISPR-Cas9. In Fe­bru­ary, the US Patent Trial and Ap­peal Board ruled in fa­vor of the Broad In­sti­tute, sup­port­ing its patent for the use of CRISPR-Cas9 in eu­kary­otic cells (in­clud­ing hu­mans). The Berke­ley team, on the other hand, had pre­vi­ously filed pa­tents on the use of CRISPR-Cas9 in any cell, which, if sup­ported by the courts, would mean that any re­searcher wish­ing to use the tech­nol­ogy would have to get li­censes from both Berke­ley and the Broad In­sti­tute. The prob­lem—apart from the ob­vi­ous fact that the main ben­e­fi­cia­ries of the US Patent Board’s de­ci­sion will be lawyers, not sci­en­tists, and cer­tainly not pa­tients— is that the out­come may limit sci­en­tific in­quiry by im­pos­ing fees for us­ing CRISPR tech­nol­ogy. More fun­da­men­tally, it can be ar­gued that it is in­her­ently wrong to patent dis­cov­er­ies made through pub­licly-funded re­search.

The story is far from over. The Berke­ley team is ap­peal­ing the ini­tial de­ci­sion; pa­tents in other ar­eas of the world, in­clud­ing Europe, have yet to be de­cided; other in­sti­tu­tions have also filed pa­tents that have yet to be ex­am­ined in court; and the use of al­ter­na­tive enzymes that are more ef­fi­cient than Cas9 may ren­der the whole process moot. Ini­tially, the Berke­ley and Broad teams were work­ing to­gether on the com­mer­cial­iza­tion of the tech­nol­ogy, but some­thing broke down in their re­la­tion­ship, and the cur­rent patent dis­pute is the con­se­quence. What caused that rup­ture has not been made pub­lic, and Doudna and Stern­berg give no hints.

The sec­ond half of A Crack in Cre­ation deals with the pro­found eth­i­cal is­sues that are raised by gene edit­ing. Th­ese pages are not dry or ab­stract— Doudna uses her own shift­ing po­si­tions on th­ese ques­tions as a way for the reader to ex­plore dif­fer­ent pos­si­bil­i­ties. How­ever, she of­ten of­fers no clear way for­ward, be­yond the fairly ob­vi­ous warn­ing that we need to be care­ful. For ex­am­ple, Doudna was ini­tially deeply op­posed to any ma­nip­u­la­tion of the hu­man genome that could be in­her­ited by fu­ture gen­er­a­tions—this is called germline ma­nip­u­la­tion, and is car­ried out on eggs or sperm, or on a sin­gle-cell em­bryo. (Ge­netic changes pro­duced by all cur­rently en­vis­aged hu­man uses of CRISPR, for ex­am­ple on blood cells, would not be passed to the pa­tient’s chil­dren be­cause th­ese cells are not passed on.)

Al­though laws and guide­lines dif­fer among coun­tries, for the mo­ment im­plan­ta­tion of ge­net­i­cally edited em­bryos is gen­er­ally con­sid­ered to be wrong, and in 2015 a non­bind­ing in­ter­na­tional mora­to­rium on the ma­nip­u­la­tion of the hu­man germline was reached at a meet­ing held in Wash­ing­ton by the Na­tional Academy of Sciences, the In­sti­tute of Medicine, the Royal So­ci­ety of Lon­don, and the Chi­nese Academy of Sciences. Yet it seems in­evitable that the world’s first CRISPR baby will be born some­time in the next decade, most likely as a re­sult of a pro­ce­dure that is in­tended to per­ma­nently re­move genes that cause a par­tic­u­lar dis­ease.

Al­ready in the early days of her re­search, Doudna seems to have been haunted by the im­pli­ca­tions of her work—she de­scribes a dis­turb­ing dream in which Hitler keenly asked her to ex­plain the tech­nique to him. Over the last cou­ple of years, fol­low­ing meet­ings with pa­tients suf­fer­ing from ge­netic dis­eases, Doudna has shifted her po­si­tion, and now feels that it would be un­eth­i­cal to le­gally for­bid a fam­ily to, say, re­move a de­fec­tive por­tion of the gene that causes Hunt­ing­ton’s dis­ease from an em­bryo, which other­wise would grow into an adult doomed to a hor­ri­ble death.

Like many sci­en­tists and the vast ma­jor­ity of the gen­eral pub­lic, Doudna re­mains hos­tile to chang­ing the germline in an at­tempt to make hu­mans smarter, more beau­ti­ful, or stronger, but she rec­og­nizes that it is ex­tremely dif­fi­cult to draw a line be­tween re­me­dial ac­tion and en­hance­ment. Re­as­sur­ingly, both A Crack in Cre­ation and DNA Is Not Des­tiny show that th­ese eu­genic fan­tasies will not suc­ceed—such char­ac­ter­is­tics are highly com­plex, and to the ex­tent that they have a ge­netic com­po­nent, it is en­coded by a large num­ber of genes each of which has a very small ef­fect, and which in­ter­act in un­known ways. We are not on the verge of the cre­ation of a CRISPR master race. Nev­er­the­less, Doudna does ac­cept that there is a dan­ger that the new tech­nol­ogy will “tran­scribe our so­ci­eties’ fi­nan­cial in­equal­ity into our ge­netic code,” as the rich will be able to use it to en­hance their off­spring while the poor will not. Un­for­tu­nately, her only so­lu­tion is to sug­gest that we should start plan­ning for in­ter­na­tional guide­lines gov­ern­ing germline gene edit­ing, with re­searchers and law­mak­ers (the pub­lic are not men­tioned) en­cour­aged to find “the right bal­ance be­tween reg­u­la­tion and freedom.” The fail­ure to re­solve the is­sue of how to reg­u­late ge­need­it­ing tech­nol­ogy is even more strik­ing when Doudna and Stern­berg de­scribe what they ac­knowl­edge is the most dan­ger­ous po­ten­tial ap­pli­ca­tion of their tech­nique: the de­ploy­ment of what are known as gene drives, es­pe­cially in species with short gen­er­a­tion times, such as in­sect pests. Gene drives are ar­ti­fi­cial bits of DNA that rapidly spread through the pop­u­la­tion, un­like ex­ist­ing GMO tech­niques in which mod­i­fied genes spread at a very slow rate and eas­ily dis­ap­pear from the gene pool. When a gene drive is used, the fre­quency of the al­tered gene in­creases ex­po­nen­tially with each gen­er­a­tion, rapidly flood­ing the whole pop­u­la­tion. This is the tech­nol­ogy that sci­en­tists have been propos­ing as a way of ren­der­ing all mosquitoes ster­ile or pre­vent­ing them from car­ry­ing malaria, and it could clearly have an enor­mous ef­fect on the epi­demi­ol­ogy of some of the most deadly dis­eases. Over 300,000 chil­dren die each year of malaria; CRISPR gene drives could po­ten­tially save them by al­ter­ing the mos­quito’s genome.

The prob­lem with a gene drive is that it is es­sen­tially a bi­o­log­i­cal bomb that could have all sorts of un­in­tended con­se­quences. If we make the mos­quito in­hos­pitable to the malaria par­a­site, we might find that, just as with the overuse of an­tibi­otics, the par­a­site mu­tates in such a way that it can evade the ef­fects of the gene drive; this change could also mean that it is im­mune to our cur­rent an­ti­malar­ial drugs. Mean­while, the al­ter­na­tive ap­proach of erad­i­cat­ing the mos­quito from a par­tic­u­lar en­vi­ron­ment, as Doudna and Stern­berg point out, may lead to un­ex­pected changes in the ecol­ogy of the re­gion—we sim­ply do not know enough about ecol­ogy to be able to pre­dict what will hap­pen. Claims that a gene drive that goes wrong could be reengi­neered (this is facilely called “undo” by its ad­vo­cates) ig­nore the fact that other species might have been ir­re­versibly dam­aged by the ini­tial ge­netic change. Ecosys­tems are frag­ile. A vac­cine against malaria might even­tu­ally be­come an eco­log­i­cally

safe al­ter­na­tive, but the ad­vo­cates of gene drives un­der­stand­ably ar­gue that if we carry on with our cur­rent ap­proach, us­ing in­sec­ti­cides and bed nets, malaria will con­tinue to kill those hun­dreds of thou­sands of chil­dren each year, to­gether with thou­sands more who are in­fected with other mosquito­borne dis­eases, such as Zika, dengue, West Nile virus, and chikun­gunya. At the mo­ment, there are no reg­u­la­tions gov­ern­ing if and how gene drive tech­nol­ogy should be de­ployed. Part of the prob­lem is that this is ef­fec­tively a global ques­tion—in­sects travel eas­ily, and they and the dis­eases they trans­mit can mu­tate as they go. An ap­par­ent so­lu­tion in one part of the world might turn into a catas­tro­phe in another, as ma­nip­u­lated in­sects and pathogens move un­hin­dered across fron­tiers and en­ter new ecosys­tems. Global reg­u­la­tion of gene drives—much as we have global reg­u­la­tion of other po­ten­tially dan­ger­ous tech­nolo­gies such as civil­ian air travel or nu­clear power—is cru­cial, but many gov­ern­ments, and es­pe­cially the cur­rent US ad­min­is­tra­tion, have lit­tle ap­petite for in­ter­na­tional reg­u­la­tion. Whether th­ese de­vel­op­ments ex­cite us or ap­pall us, we can­not un­learn what we have dis­cov­ered. CRISPR is al­ready speed­ing up sci­en­tific dis­cov­ery, mak­ing it pos­si­ble to ma­nip­u­late genes in or­gan­isms and pro­vid­ing stun­ning in­sights into evo­lu­tion, such as last year’s study by Neil Shu­bin at the Univer­sity of Chicago that ex­plored how fish fins were re­placed by feet in land ver­te­brates nearly 400 mil­lion years ago. CRISPR will soon be ap­plied to health care, mak­ing some pre­vi­ously lethal or de­bil­i­tat­ing dis­eases a thing of the past. Not all dis­eases will be eas­ily cured— for ex­am­ple, the de­vel­op­ment of a cure for Duchenne mus­cu­lar dys­tro­phy is likely to be hin­dered for many years by tech­ni­cal dif­fi­cul­ties as­so­ci­ated with the de­liv­ery of CRISPR se­quences to all the af­fected mus­cle cells—but we truly are emerg­ing into a new world. To pre­vent gene edit­ing from tak­ing a dystopian turn, strict reg­u­la­tion through in­ter­na­tion­ally rec­og­nized guide­lines must be found to pro­tect our ge­netic in­for­ma­tion from un­scrupu­lous states or com­mer­cial ex­ploita­tion, pre­vent the ir­re­spon­si­ble re­lease of gene drives, and pro­hibit any form of dis­crim­i­na­tion against peo­ple be­cause of their genes. Hos­til­ity to such dis­crim­i­na­tion should be­come a ba­sic moral prin­ci­ple shared by so­ci­eties around the world. The first step to­ward such an out­come is to en­sure that the pub­lic and law­mak­ers un­der­stand the new tech­nol­ogy and its dra­matic im­pli­ca­tions. A Crack in Cre­ation—the first book on CRISPR to present a pow­er­ful mix of science and ethics—can help in this process. As Fran­cis Ba­con said, knowl­edge is power.

Adult fe­male Anophe­les stephensi mosquitoes, im­por­tant malaria car­ri­ers in ur­ban In­dia, trans­formed in ge­netic ex­per­i­ments to study whether they can be made in­hos­pitable to malaria par­a­sites

The bio­chemist Jen­nifer Doudna, a pioneer of the tech­nique of DNA mod­i­fi­ca­tion known as CRISPR, at her lab at the Univer­sity of Cal­i­for­nia, Berke­ley, 2015

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