In a first, sci­en­tists edit DNA of hu­man em­bryos

The Denver Post - - FRONT PAGE - By Melissa Healy

Us­ing a pow­er­ful gene-edit­ing tech­nique, sci­en­tists have rid hu­man em­bryos of a mu­ta­tion that causes an in­her­ited form of heart dis­ease of­ten deadly to healthy young ath­letes and adults in their prime.

The ex­per­i­ment marks the first time that sci­en­tists have al­tered the hu­man genome to en­sure a dis­ease-caus­ing mu­ta­tion would dis­ap­pear not only from the DNA of the sub­ject on which it is per­formed but from the genes of his or her prog­eny as well.

The con­tro­ver­sial pro­ce­dure, known as “germ-line edit­ing,” was con­ducted at Ore­gon Health and Sci­ence Univer­sity us­ing hu­man em­bryos ex­pressly cre­ated for the pur­pose. It was re­ported Wed­nes­day in the jour­nal Na­ture.

The new re­search comes less than six months af­ter the Na­tional Acad­e­mies of Sci­ence, En­gi­neer­ing and Medicine rec­om­mended that sci­en­tists limit their tri­als of hu­man germ-line edit­ing to dis­eases that could not be treated with “rea­son­able al­ter­na­tives” — at least for now.

In a bid to make the ex­per­i­ment rel­e­vant to real-life prob­lems faced by par­ents who carry genes for in­her­ited dis­eases, the re­searchers fo­cused their edit­ing ef­forts on a mu­ta­tion that causes in­her­ited hy­per­trophic car­diomy­opa­thy.

“No mat­ter what any­body says, this is not the dawn of the era of the de­signer baby.”

Alta Charo, bioethi­cist at the Univer­sity of Wis­con­sin and chair­woman of the Na­tional Acad­e­mies com­mit­tee look­ing at gene edit­ing

In this ge­netic con­di­tion, a par­ent who car­ries one nor­mal and one faulty copy of a the MYBPC3 gene has a 50-50 chance of pass­ing that mu­ta­tion on to his or her off­spring. If the child in­her­its the mu­ta­tion, his or her heart mus­cle is likely to grow pre­ma­turely weak and stiff, caus­ing heart fail­ure and of­ten early death.

In dis­eases where one par­ent car­ries such an “au­to­so­mal dom­i­nant” mu­ta­tion, a cou­ple of­ten will seek the as­sis­tance of fer­til­ity doc­tors to min­i­mize the risk of pass­ing such a mu­ta­tion on to a child. A woman’s egg pro­duc­tion is med­i­cally stim­u­lated, and eggs and sperm meet in a lab — a process called in vitro fer­til­iza­tion. Then em­bry­ol­o­gists in­spect the re­sult­ing em­bryos, cull the ones that have in­her­ited an unwanted mu­ta­tion, and trans­fer only un­af­fected em­bryos into a woman’s uterus to be car­ried to term.

In the new re­search, re­searchers set out to test whether germ-line gene edit­ing could make the process of choos­ing healthy em­bryos more ef­fec­tive and ef­fi­cient by cre­at­ing more of them.

In the end, their ex­per­i­ment showed it could. The tar­geted cor­rec­tion of a dis­ease-caus­ing gene car­ried by a sin­gle par­ent “can po­ten­tially res­cue a sub­stan­tial por­tion of mu­tant hu­man em­bryos, thus in­creas­ing the num­ber of em­bryos avail­able for trans­fer,” the au­thors wrote in Na­ture. Co-au­thor Dr. Paula Amato, an Ore­gon Health and Sci­ence Univer­sity pro­fes­sor of ob­stet­rics and gy­ne­col­ogy, said the tech­nique “could po­ten­tially de­crease the num­ber of cy­cles needed for peo­ple try­ing to have chil­dren free of ge­netic dis­ease” if it’s found safe for use in fer­til­ity clin­ics.

Along the way, though, many of the re­searchers’ find­ings were sci­en­tif­i­cally sur­pris­ing. Long-feared ef­fects of germ-line edit­ing, in­clud­ing col­lat­eral dam­age to “off-tar­get” ge­netic se­quences, scarcely ma­te­ri­al­ized. And “mo­saicism,” a phe­nom­e­non in which edited DNA ap­pears in some but not all cells, was found to be min­i­mal.

The study’s lead au­thor, bi­ol­o­gist Shoukhrat Mi­tal­ipov, called th­ese “ex­cit­ing and sur­pris­ing mo­ments.” But he cau­tioned that “there is room to im­prove” the tech­niques demon­strated to pro­duce mu­ta­tion-free em­bryos. As for con­duct­ing hu­man clin­i­cal tri­als of the germ-line cor­rec­tion, he said those would have to wait un­til re­sults showed a near-per­fect level of ef­fi­ciency and ac­cu­racy and could be lim­ited by state and fed­eral reg­u­la­tions.

Even­tu­ally, Mi­tal­ipov said, such germ-line gene edit­ing might also make it eas­ier for par­ents who carry other gene mu­ta­tions that fol­low a sim­i­lar pat­tern of in­her­i­tance — in­clud­ing some that cause breast and ovar­ian can­cers, cys­tic fi­bro­sis and mus­cu­lar dys­tro­phy — to have healthy chil­dren who would not pass those genes to their own off­spring.

“There is still a long road ahead,” pre­dicted Mi­tal­ipov, who heads the Cen­ter for Em­bry­onic Cell and Gene Ther­apy at the Port­land univer­sity.

The re­search drew a mix of praise and con­cern from ex­perts in ge­netic medicine.

Dr. Richard O. Hynes, who cochaired the Na­tional Acad­e­mies’ re­port is­sued in Fe­bru­ary, called the new study “very good sci­ence” that ad­vances un­der­stand­ing of ge­netic re­pair on many fronts.

Univer­sity of Cal­i­for­nia molec­u­lar and cell bi­ol­o­gist Jen­nifer Doudna, one of the pi­o­neers of the CRISPRCas9 tech­nique, ac­knowl­edged the new re­search high­lights a prospec­tive use of gene edit­ing for one in­her­ited dis­ease and of­fers some in­sights into the process.

But Doudna ques­tioned how broadly the ex­per­i­ment’s promis­ing re­sults would ap­ply to other in­her­ited dis­eases. She said she does not be­lieve the use of germ-line edit­ing as a means to im­prove ef­fi­ciency at in­fer­til­ity clin­ics meets the cri­te­ria laid out by the Na­tional Acad­e­mies of Sci­ence, which urged that the tech­niques be ex­plored as treat­ment only for dis­eases with “no rea­son­able al­ter­na­tive.”

Doudna said she wor­ried that the new find­ings “will en­cour­age peo­ple to pro­ceed down this road” be­fore the sci­en­tific and eth­i­cal im­pli­ca­tions of germ-line edit­ing have been fully con­sid­ered.

“A large group of ex­perts con­cluded that clin­i­cal use should not pro­ceed un­til and un­less there’s broad so­ci­etal con­sen­sus, and that just hasn’t hap­pened,” Doudna said. “This study un­der­scores the ur­gency of hav­ing those de­bates. Be­cause it’s com­ing.”

Alta Charo, a bioethi­cist at the Univer­sity of Wis­con­sin who is co-chair­woman of the Na­tional Acad­e­mies com­mit­tee look­ing at gene edit­ing, said that con­cerns about the work are overblown.

“What this rep­re­sents is a fas­ci­nat­ing, im­por­tant and rather im­pres­sive in­cre­men­tal step to­ward learn­ing how to edit em­bryos safely and pre­cisely,” she said. How­ever, “no mat­ter what any­body says, this is not the dawn of the era of the de­signer baby.”

Re­searchers who worked on the heart-con­di­tion ex­per­i­ment ap­pear to have dif­fer­ing views on where their work is headed.

Paula Amato, a re­pro­duc­tive en­docri­nol­o­gist with Ore­gon Health, was ex­cited about the idea of be­ing able to edit out dis­eases be­fore birth. She said that while pre-im­plan­ta­tion ge­netic screen­ing of em­bryos is now avail­able, it isn’t per­fect. She talked about how one of her pa­tients went through three cy­cles of in vitro fer­til­iza­tion but all of the eggs that were har­vested had the gene mu­ta­tion that causes a dis­eases.

With gene cor­rec­tion tech­nol­ogy, Amato said, “we could have res­cued some of those em­bryos.”

But Izpisua Bel­monte said he is fo­cus­ing on us­ing the find­ings to fur­ther re­search into gene mod­i­fi­ca­tions dur­ing a preg­nancy or af­ter birth into adult­hood. “I feel that the prac­ti­cal thing to do is deal with the dis­eases peo­ple have, not with the dis­ease they may have,” he said.

Mi­tal­ipov said he hopes reg­u­la­tors will pro­vide more guid­ance on what should or should not be al­lowed.

Other­wise, he said, “this tech­nol­ogy will be shifted to un­reg­u­lated ar­eas, which shouldn’t be hap­pen­ing.”

Em­bryo Cell Nu­cleus

Newspapers in English

Newspapers from USA

© PressReader. All rights reserved.