Chil­dren with 3-way DNA are healthy

Daily Freeman (Kingston, NY) - - FRONT PAGE - By Marilynn Marchione and Mal­colm Rit­ter Chief med­i­cal writer Marilynn Marchione can be fol­lowed at http://twit­ MMar­chioneAP Science writer Mal­colm Rit­ter can be fol­lowed at http:// twit­­colm­rit­ter

More than 15 years ago, 17 ba­bies were born after an ex­per­i­men­tal in­fer­til­ity treat­ment that gave them DNA from three peo­ple: Mom, Dad and an egg donor.

Now re­searchers have checked up on how the ba­bies are do­ing as teenagers. The pre­lim­i­nary ver­dict: The kids are all right.

With no sign of un­usual health prob­lems and ex­cel­lent grades in school at ages 13 to 18, th­ese chil­dren are “do­ing well,” said em­bry­ol­o­gist Jac­ques Co­hen of the In­sti­tute for Re­pro­duc­tive Medicine & Science at Saint Barn­abas in Liv­ingston, New Jersey, where the treat­ment was done.

That in­cludes Emma Foster, 17, of Red Bank, New Jersey. “I turned out nor­mal,” Foster said in an in­ter­view Tues­day. A cheer­leader since age 10, she is now look­ing at col­leges and think­ing of ma­jor­ing in engi­neer­ing.

The in­fer­til­ity pro­ce­dure is no longer per­formed. But the study of the chil­dren is timely be­cause just last month, the first baby was born from a dif­fer­ent pro­ce­dure that also mixed ge­netic ma­te­rial from three peo­ple. That tech­nique is aimed not at in­fer­til­ity but at pre­vent­ing the child from in­her­it­ing harm­ful genes from the mother. Crit­ics are con­cerned about its long-term safety.

So find­ing no prob­lem so far from the in­fer­til­ity treat­ment is help­ful and “a good mes­sage” for peo­ple con­sid­er­ing the dis­ease-pre­ven­tion pro­ce­dure, Co­hen said. But he em­pha­sized that his find­ings can­not be taken as proof that the newer pro­ce­dure is safe and should be per­formed.

Cells carry DNA in two places: the nu­cleus, where the chro­mo­somes are, and to a much smaller de­gree the mi­to­chon­dria. Mi­to­chon­dria are the lit­tle pow­er­houses in the cy­to­plasm, the liq­uid part of the egg cell out­side the nu­cleus.

Both DNA-mix­ing pro­ce­dures in­volve the mi­to­chon­dria; the one that re­cently pro­duced the baby was aimed at re­plac­ing a mother’s de­fec­tive mi­to­chon­dria. Co­hen’s pro­ce­dure in­jected a bit of mi­to­chon­dria-con­tain­ing cy­to­plasm into the mother’s egg.

Genes in the mi­to­chon­drial DNA don’t af­fect traits like eye and hair color but are im­por­tant for keep­ing cells healthy through­out the body.

Co­hen’s hos­pi­tal per­formed the in­fer­til­ity treat­ment be­tween 1996 and 2001 on 33 cou­ples who failed to con­ceive after roughly five tries at in vitro fer­til­iza­tion.

“We felt that there was some­thing wrong with the cy­to­plasm” and that in­ject­ing a small amount of it from a healthy egg donor might aid em­bryo de­vel­op­ment, Co­hen said.

Four­teen of the 33 pa­tients be­came preg­nant, and 13 ul­ti­mately gave birth to 18 ba­bies, in­clud­ing two sets of twins and one of quadru­plets. (One of the 18 ba­bies was a twin from a stan­dard egg do­na­tion; doc­tors also in­cluded data on that child in the fol­low-up study.)

Co­hen and col­leagues pre­sented their find­ings Wed­nes­day in the jour­nal Re­pro­duc­tive Bio­Med­i­cine On­line.

The par­ents of the quadru­plets re­fused mul­ti­ple re­quests for fol­low-up in­for­ma­tion; doc­tors know only that all four are alive and in high school.

In de­tailed sur­veys, par­ents of the 14 other chil­dren all re­ported their kids in good health. One has chronic mi­graines, two have mild asthma, one is obese, seven have al­ler­gies, and one has at­ten­tion deficit disor­der. None of those rates are un­usual for that num­ber of chil­dren, doc­tors said. One boy was di­ag­nosed with a bor­der­line devel­op­men­tal disor­der at 18 months but not when he was older, and he has an A av­er­age in school.

“Th­ese chil­dren have done well,” Co­hen said. “It’s what we ex­pected or at least had hoped.”

At least two other clin­ics in the U.S. and sev­eral in other coun­tries tried the tech­nique after Co­hen started it, but the U.S. work stopped after the Food and Drug Ad­min­is­tra­tion stepped in to reg­u­late it. Co­hen said his group tried to com­ply with the FDA’s re­quire­ments for a per­mit to con­tinue the work but lost fund­ing be­fore it could meet them.

It’s not clear why the treat­ment worked for the 13 cou­ples, Co­hen said. One pos­si­bil­ity is the in­fu­sion of mi­to­chon­dria, but cy­to­plasm con­tains other mol­e­cules and struc­tures too, he said.

In any case, it was a suc­cess for Emma’s par­ents, Su­san and Peter Foster, who had been try­ing for about seven years to have a baby.

When Co­hen’s ex­per­i­men­tal pro­ce­dure was de­scribed to them and they were asked if they were in­ter­ested, they had no doubts, Peter said.

Su­san gave birth at 33. Emma was healthy and has con­tin­ued that way, her par­ents say.

Emma is the only child in the sur­vey to have been told about the pro­ce­dure. She said she has long known her ori­gins were un­usual — her mom keeps a book that shows her as an em­bryo — but she didn’t know the specifics un­til re­cently.

“I think it’s re­ally cool,” she said. “It makes me dif­fer­ent.”

She may no longer carry any trace of the donor. Only two of eight ba­bies tested after birth showed any sign of donor mi­to­chon­dria, and Emma was one who showed none. Co­hen said the tests, which were not as sen­si­tive then as now, might have over­looked some traces.

The fol­low-up study has some lim­i­ta­tions. It’s based on a sur­vey of par­ents, and the ac­cu­racy of such sec­ond­hand in­for­ma­tion can be shaky. And it in­cludes just 13 teens, with no com­par­i­son group.

Still, Dr. James Grifo, di­rec­tor of in­fer­til­ity treat­ment at New York Univer­sity, said the re­sults sug­gest that crit­i­cism of re­search that mixes DNA from three peo­ple ap­pears un­founded.

“The out­comes looked uni­formly good ... sug­gest­ing that no harm was done,” said Grifo, who did not par­tic­i­pate in the new study. The donor cy­to­plasm “cer­tainly may have played a role in al­low­ing their em­bryo to de­velop to a stage that al­lowed a preg­nancy.”

In 1999, after years of ex­per­i­ments in mice, Grifo and col­leagues made em­bryos with DNA from three peo­ple and trans­ferred them to sev­eral pa­tients’ wombs, but no preg­nancy re­sulted. Then the FDA stepped in and stopped the work.

“I think it should be al­lowed,” Grifo said.

But Dr. Alan Cop­per­man, di­rec­tor of in­fer­til­ity at Mount Si­nai School of Medicine in New York, said the jury is still out on whether us­ing a third party’s ge­netic ma­te­rial is safe.

“I don’t think that we’re yet able to de­clare vic­tory and that we’ve fig­ured out how to fix an un­healthy egg or em­bryo,” Cop­per­man said. Most eggs that fail to de­velop nor­mally, es­pe­cially with older pa­tients, are be­cause of ab­nor­mal chro­mo­somes, so tin­ker­ing with the cy­to­plasm is not likely to be a so­lu­tion for many peo­ple, he said.

But it ap­par­ently worked for the Fos­ters.

Emma “is a bless­ing and a mir­a­cle,” Su­san Foster said, “and med­i­cal science made that pos­si­ble.”


From left, Peter Foster; adopted daugh­ter; Kerry, 12; his wife, Su­san, and their bi­o­log­i­cal daugh­ter, Emma, 17, walk on the grounds out­side St. Barn­abas Hos­pi­tal, in Liv­ingston, N.J., Tues­day. More than 15 years ago, 17 ba­bies, in­clud­ing Emma, were born after an ex­per­i­men­tal in­fer­til­ity treat­ment that gave them DNA from three peo­ple: Mom, Dad and an egg donor. On­line: Study: http://bit. ly/2eODF5K

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