There’s No Monkeying Around With Cloning

Wanna clone a cow? A Massachusetts company guarantees a healthy calf for $19,000 -- and two for $34,000.

Wanna clone a cat? A California-based company says it’s gearing up to offer that service soon, maybe next year.

Wanna clone a cute monkey? Good luck.

Almost seven years after the birth of Dolly the sheep shocked scientists and the public, cloning has shown mixed progress. Scientists have achieved it in more than a dozen mammal species, including mice, rabbits, goats, pigs and horses. They’ve cloned a calf from a slaughtered cow. They’ve even cloned a wild sheep from a carcass found in a pasture.

But an efficient cloning process still eludes them. Clones are more prone to physical defects than regular animals are. And researchers haven’t been able to duplicate monkeys from adult or fetal tissue, a goal that could help medical research.

Hovering over these biological challenges are two other issues. The U.S. Food and Drug Administration is pondering the safety of consuming meat and milk from clones and their progeny, a matter of obvious importance to ranchers contemplating cloned pigs and cattle. The FDA recently said such food doesn’t appear to be hazardous, but the agency wants more public comment. Because of a voluntary industry moratorium, no products from clones have been allowed into the food supply.

And the big hot button -- the prospect of making human babies through cloning -- still glows. Would that present a breakthrough for treating infertility and provide parents a genetic duplicate of a dead child? Or would it be ethically repugnant and unacceptably risky?

The United States recently campaigned unsuccessfully for a United Nations ban on human cloning. But the international body voted Thursday to put off any decision for two years.

Member nations are divided over how far such an agreement should go. Some say it should only ban cloning to make babies. Others, including the United States, also want to outlaw so-called “therapeutic cloning,” which produces and then destroys week-old embryos to harvest stem cells. Scientists hope to use stem cells for treating such illnesses as diabetes and Parkinson’s disease.

Meanwhile, Clonaid, a company founded by the leader of a religious sect that believes space aliens created life on Earth, claims that it has produced five babies through cloning. Clonaid grabbed headlines in December by announcing the first such baby had been born, but that claim has been dismissed by scientists for lack of proof.

Most scientists who deal with cloning oppose using it to make human babies.

“Human reproductive cloning is unsafe, unethical and ought to be illegal everywhere in the world,” said Gerald Schatten of the University of Pittsburgh.

Schatten is close to the debate because he’s been trying to clone monkeys, which belong to the same overall classification -- primates -- as humans. The implications of any success for the prospects of human cloning are clear, and Schatten said he’s already exploring ways to make sure that if he succeeds, others won’t be able to use his work to produce human babies.

Schatten wants to make identical monkeys for medical research, providing a more human-like version of the genetic uniformity found in mouse strains. But so far, his efforts have failed even to produce a pregnancy. What’s going on?

To understand the apparent answer, you have to know a little about cloning. The basic idea is to take the DNA-bearing nucleus of an animal’s cell and plop it into an unfertilized egg. The implanted DNA drives the egg to develop into an embryo, which is placed in a surrogate mother, where it grows into a newborn -- the genetic clone of the animal whose DNA you started with.

An egg has its own nucleus, so that has to be removed before the egg receives the new one. Normally, that doesn’t pose a problem. But with monkeys, it does.

Schatten’s scientific team reported earlier this year that removing the nucleus from a monkey egg also removes two key proteins. Without them, the egg doesn’t stand a chance of growing into a new monkey.

Schatten figures that this problem will be overcome and that newborn monkeys will eventually follow. And he’s philosophical about bumping into the hurdle in the first place.

“I feel like nature has given us a scientific reprieve” to block human cloning with current techniques, giving time to develop laws, he said.

With barnyard animals, researchers can produce newborn clones, just not as consistently as they’d like. The problem becomes apparent after embryos are planted in surrogate moms.

“We can make thousands of embryos,” said Steve Stice of the University of Georgia. “The real cost and real problem for us is when we transfer that embryo and we don’t produce a [successful] pregnancy, because that costs us time and money.” And the agricultural industry won’t be interested in cloning if it’s not efficient enough at producing newborns, he said.

It took 29 implanted embryos to produce Dolly and, since then, “we haven’t been able to increase efficiency as we thought,” said Jose Cibelli of Michigan State University.

In cattle these days, only 1-in-7 to 1-in-15 transferred embryos produces offspring, Stice said.

At Cyagra Inc. of Worcester, Mass., which has produced more than 100 calf clones for dairy and beef farmers, marketing manager Steve Mower says the track record is about 15%.

“We have to do better,” he said, and the company is aiming at efficiencies of 60% to 70%.

It’s not just cows. It took 113 implanted embryos to produce three cloned mules this year, an efficiency just below 3%, said one of the cloners, Ken White of Utah State University.

To deal with the efficiency problem, some scientists are scrutinizing the raw materials, looking for ways to identify the most promising eggs and the best cell nuclei from animals to be cloned. Cibelli, for example, is looking for chemical markers that can identify a nucleus that’s ready to be introduced into the egg.

“We’re getting good results,” Cibelli said.

In fact, many scientists believe that the nucleus of the donor cell holds the key for why cloning works so sporadically, as well as why clones show unusual rates of birth defects.

For scientists, Dolly the sheep was stunning because she showed that the DNA in the nucleus of an adult animal cell could undergo an amazing career change. After all, its job had been to drive the everyday activities of an adult cell, with certain genes active and others switched off to achieve that goal. But once it was placed in an egg, it had to reprogram its gene activity to start the process of creating all the tissues of a whole new individual.

“If you have a nucleus that has been committed to be skin for a number of years, then in a matter of minutes you have to turn it into an embryonic nucleus that can make anything,” Cibelli said. “Not all the genes will be ready to be reprogrammed.”

If the changeover isn’t complete enough, the egg and resulting fetus just won’t be equipped for developing normally, scientists say. That can doom a pregnancy.

Even in animals that make it to birth, faulty reprogramming could lead to observed abnormalities in clones like breathing problems and defects of the liver, heart and brain. Some abnormalities may also be due to manipulations of the embryo before implantation.

Despite the appearance of defects in some clones, scientists point out that many animal clones turn out just fine.

“We have seen cloned cows that are thriving at the moment and indistinguishable from non-cloned animals,” Cibelli said.

Stice said that’s been the experience of his clones. “The vast majority of them are just fine,” he said. “They look like any other pig or cow out there.”

Visitors to a home in Texas say roughly the same thing about a calico cat that frolics there. It’s cc, the domestic shorthair who gained fame in February 2002 when she was announced as the first clone of a cat. This year, she moved in with Duane Kraemer, one of the Texas A & M researchers who made her birth possible.

She’s an “absolutely normal cat in every aspect we can determine,” Kraemer said. She does have a heart murmur, like the cat she was cloned from. Neither animal has had any trouble with it, he said.

Scientists say they hope to achieve cloning in more species. Mark Westhusin of Texas A & M, who directed the research that produced cc, said he’s trying to clone white-tailed deer to help ranchers who supply game for hunters. White of Utah State hopes to clone an endangered wild sheep called the argali, known for its massive curved horns.

AviGenics Inc. of Athens, Ga., is trying to clone chickens. Genetic Savings and Clone Inc., based in Sausalito, Calif., is not only gearing up to clone more cats but is also trying to duplicate a dog for the first time. For technical reasons, dogs are harder to do than cats.

But “we think there’s some likelihood we’ll produce a dog clone within the next year,” said Ben Carlson, the company’s vice president for communications.

Maybe that’ll happen and maybe not. But the cloning field is moving so fast, it’s hard to rule anything out, said Gary Anderson of UC Davis.

So when he’s asked if the DNA reprogramming problem that hinders cloning can be overcome, he turns unpredictability into optimism.

“One wouldn’t want to say we’re stuck; we can’t do anything about it,” Anderson said. “You’re proven wrong almost every day.”