In sheep’s clothing: Human-ovine experiment sparks debate
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.
The 100 or so sheep fenced off in this corral have internal organs that are partly human.