In sheep’s cloth­ing: Hu­man-ovine ex­per­i­ment sparks de­bate

The Washington Times Weekly - - National - By Maxim Kni­azkov

RENO, Nev. — If there was a hu­man side to them, it was tucked deep inside and re­sisted all in­vi­ta­tion to bond­ing.

The black olives of their eyes be­trayed vis­ceral dis­trust as the sheep hud­dled in the op­po­site cor­ner of the cor­ral, un­set­tled and ap­pre­hen­sive. “Care for a leaf of let­tuce, sis­ters?” “Ba-a-a-a-ah,” came a plain­tive re­ply.

They looked like sheep, bleated like sheep and dis­played be­hav­ior that was, in one word, sheep­ish. Yet there was no hid­ing from the fact that the fid­gety an­i­mals in a cor­ral on the east­ern out­skirts of town were, at least from a med­i­cal stand­point, partly hu­man.

“They have hu­man cells in their liv­ers, pan­creases, guts, hearts and mus­cles,” said Dr. Es­mail D. Zan­jani, the white-haired chief biotech­nol­o­gist at the Univer­sity of Ne­vadaReno and cre­ator of the flock.

“About 10 per­cent of each of th­ese or­gans are made of hu­man cells. Their brains, by con­trast, have very few.”

It was the stuff of science fiction, a glance into a bot­tom­less in­tel­lec­tual precipice that hid moral, eth­i­cal and po­lit­i­cal dilem­mas be­yond the im­me­di­ate hu­man grasp.

Baby boomers, who grew up mes­mer­ized by a 19th-cen­tury novel by H.G. Wells about the bril­liant and icon­o­clas­tic Dr. Moreau, who de­fi­antly crossed an­i­mals with hu­mans, now had a chance to greet real-life chimeras — myth­i­cal crea­tures from Greek folk­lore that dis­played a lion’s head, a goat’s body and a ser­pent’s tail.

Dr. Zan­jani, who came to the U.S. from Iran in 1958, is no stranger to irony or con­tro­versy. About two decades ago, he used private money to ex­e­cute the na­tion’s first fe­tus-tofe­tus stem-cell trans­plant that has pro­duced strik­ing re­sults.

In 1989, Guy and Terri Walden were ex­pect­ing a baby who, while in the womb, was di­ag­nosed with Hurler’s syn­drome, a de­gen­er­a­tive dis­ease that dis­fig­ures a child, makes him men­tally im­paired and, in most cases, kills be­fore age 10.

Most cases of that na­ture end up in abor­tion clin­ics. But for Mr. Walden, a Bap­tist min­is­ter from south­ern Texas, and his de­voutly re­li­gious wife, that was out of the ques­tion.

Dr. Zan­jani of­fered a so­lu­tion that seemed to con­form, at least par­tially, with their re­li­gious con­vic­tions: a stem-cell trans­plant from a fe­tus al­ready aborted. Af­ter days of tor­ment, the Waldens agreed.

Dur­ing the pro­ce­dure, healthy cells from the fe­tus were in­jected into the un­born child. The cells started grow­ing, sup­plant­ing the dam­aged ones. When the child was born, the clas­sic symp­toms of Hurler’s syn­drome were ab­sent.

The child was saved, but there was no hid­ing the fact that be­hind his res­cue lurked the specter of a lost life: the aborted fe­tus.

This moral dilemma lies at the heart of the dis­pute over em­bry­onic stem-cell re­search. Sev­eral con­gres­sional at­tempts to lift a ban of fed­eral fi­nanc­ing of such stud­ies have fallen flat in the face of Pres­i­dent Bush’s veto pen.

But what if there were no need to har­vest healthy stem cells from dead hu­man em­bryos be­cause of the ex­is­tence of some other re­li­able and less con­tro­ver­sial source?

Dr. Zan­jani thinks his sheep of­fer a way around this. Healthy stem cells har­vested from an­other re­li­able and less con­tro­ver­sial source could un­tie the eth­i­cal and po­lit­i­cal Gor­dian knot around stem-cell re­search.

“What we do is trans­plant stem cells from an adult per­son into an un­born lamb in the first half of its ges­ta­tion pe­riod,” Dr. Zan­jani said. “Th­ese cells get dis­trib­uted through­out the body of the fe­tus and re­pro­duce them­selves ev­ery­where ex­cept the an­i­mal’s re­pro­duc­tive or­gans.”

Af­ter the lamb is born, he pre­dicts, its pan­creas will be able to pro­duce hu­man in­sulin and even­tu­ally of­fer a cure for di­a­betes.

The most promis­ing field, he said, is treat­ment of liver dis­eases. In­ject hu­man stem cells into a fe­tus’s liver, the pro­fes­sor said, and two months later one can have a new­born lamb with a liver that is 10 per­cent hu­man. In­ject more, and the liver will be­come more hu­man. Some adult an­i­mals in the lab now have liv­ers nearly half of which are made up of hu­man cells.

“Th­ese healthy cells can be har­vested and trans­planted,” Dr. Zan­jani said. “And since the liver has the abil­ity to re­gen­er­ate it­self, whole lobes could be trans­planted back to the hu­man.”

Be­cause the seeded stem cells can come from the same per­son or a close rel­a­tive, the prob­lem of re­jec­tion could be put to rest.

“We are now in the fi­nal stage of so-called proof-of-prin­ci­ple stud­ies,” the sci­en­tist said. “We are cer­tain that there is no fu­sion of an­i­mal and hu­man cells. That tells us th­ese cell trans­plants can be done.”

About 100 of the sheep are now skit­ter­ing inside the cor­rals ad­join­ing Dr. Zan­jani’s lab­o­ra­tory — so-called chimeric sheep, part an­i­mal, part hu­man, and all-around con­tro­ver­sial.

Some won­der whether sci­en­tists can fully con­trol their cel­lu­lar ma­nip­u­la­tions. The most dra­matic sce­nario is if hu­man cells im­planted into anan­i­mal­some­how­takeover­its­brain and re­pro­duc­tive or­gans. Imag­ine the es­teemed pro­fes­sor walk­ing into his lab one day and hear­ing from one of his woolly test sub­jects: “How do you do, doc.” Or two mat­ing chimeric an­i­mals pro­duc­ing an off­spring with hu­man fea­tures.

Henry T. Greely, a Cal­i­for­nia bioethi­cist from Stan­ford Univer­sity who has been fol­low­ing the is­sue for years, said some of th­ese con­cerns are overblown, but some are real.

“I don’t know how well we can con­trol that process,” he said. “This science is still at a very early stage.”

The sheep in Reno are not the only chimeric an­i­mals. In Min­nesota, re­searchers have pro­duced a pig with hu­man blood run­ning through his veins. A mouse whose brain is 1 per­cent hu­man has been en­gi­neered in Cal­i­for­nia.

Con­cerns that such ex­per­i­ments may one day pro­duce what some re­searchers call “a hu­man be­ing trapped in an an­i­mal body” has prompted the U.S. Na­tional Acad­e­mies of Sci­ences to is­sue in April 2005 a set of guide­lines that bar trans­plan­ta­tion of an­i­mal stem cells into hu­mans and re­quire ap­proval from an over­sight com­mit­tee be­fore hu­man cells can be trans­ferred into an­i­mals.

The non­bind­ing rules, which have been ac­cepted as guide­lines by the bulk of U.S. sci­en­tific or­ga­ni­za­tions, also pro­hibit trans­fers of hu­man stem cells into pri­mates such as chim­panzees, an­i­mals that are clos­est to hu­mans, and dis­cour­age breed­ing among an­i­mal chimeras.

Canada has re­jected the trans­fer of hu­man stem cells into a non­hu­man em­bryo or fe­tus al­to­gether and does not al­low cre­ation of chimeras.

Cyn­thia B. Co­hen, a se­nior re­search fel­low at Ge­orge­town’s Kennedy In­sti­tute of Ethics, said skep­tics might be fore­clos­ing a promis­ing area of med­i­cal re­search. “Per­son­ally, I think this re­search is very in­ter­est­ing,” she said.

Dr. Zan­jani’s sheep have been on television but have not caught the Hol­ly­wood celebrity bug. All at­ten­tion lav­ished on them has not altered their pri­mor­dial in­stinct that a feed­lot with fresh hay de­serves in­fin­itely more at­ten­tion than a photo cam­era.

“They are sheep and they be­have like sheep,” said Dr. Zan­jani.

Maxim Kni­azkov / Spe­cial to The Wash­ing­ton Times

The 100 or so sheep fenced off in this cor­ral have in­ter­nal or­gans that are partly hu­man.

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