Advances in cloning pose problem for ethicists
Breeding techniques move from animals to humans
By Diedtra Henderson
Denver Post Science Writer

Thursday, January 16, 2003 - Despite the firestorm that has dogged cloning, experiments in human reproduction continue to flow from animals to humans while ethicists struggle to keep pace.
Take, for example, the Pennsylvania lab where a colony of pink, hairless mice sprout bumps on their backs.

Each mound is a tiny testicle that grew from another animal's sperm stem cells. With the mice acting as incubators, the pig and goat cells grew into sex organs whose sperm produced piglets and baby goats.

That can't be done with human sperm yet, but researchers hope someday it might.

It's just one cutting-edge experiment among many across the nation to speed, simplify and stretch animals' breeding ability.

Ranchers and horse owners applaud and - in many cases - finance the work. But troubling ethical questions arise when techniques tested in animals, such as cloning, move into the world of humans.

"One of the things that have hurt science the most has been the failure to think about ethical implications ... and the failure to articulate them for society," said Bernard Rollin, a Colorado State University Distinguished Professor and nationally renowned ethicist. "That gap will be filled by doomsayers, opportunists, religious people and ill-considered ethics."

Most recently, ethics - or the lack of it - has been in the spotlight because of a religious cult's claims that it has cloned the first human, a baby named Eve.

But other techniques currently used to boost animal reproduction raise the specter of future fights when - not if - largely unregulated human infertility clinics seize upon them, too.

"Certainly there will be controversy," said Stuart Meyers, an assistant professor in the school of veterinary medicine at the University of California at Davis, where scientists are trying to produce horse sperm using mice as surrogates.

"They're going to think this is Frankensteinian. Think about a room full of mice creating a man's sperm."

Scientists growing sperm inside other animals say they are motivated by the desire to preserve the reproductive prowess of champion stallions.

If all the kinks get worked out, mice could one day produce sperm on behalf of young men made infertile by cancer therapy, enabling them to father children.

Before a prepubescent male goes into cancer treatment, his sex-organ cells could be collected. Those cells would be coaxed to grow in mice treated with chemicals so they don't produce mouse sperm.

"When this individual gets finished with irradiation, you could transplant the stem cells back into the cancer patent," Meyers said. "You could repopulate the guy's testicles with his original stem cells."

Using the technique with humans and tinkering with the sperm to correct genetic defects before it is used are "pie-in-the-sky" goals that Meyers acknowledges are a good five to 10 years away.


There are a number of technological hurdles that need to be worked out by studying farm animals and nonhuman primates.

"The majority of this technology is just not ready yet. It has to be proved in the lab before it can become clinical," he said. "In medicine, we've made a lot of things go to clinical application before it was ready."

To be sure, some technologies will never make the leap from the animal to human world. Researchers, for instance, now genetically modify cows. That genetic tinkering has created cows that, among other things, self-medicate to protect against viral diseases and produce humanlike milk that fussy infants are less likely to reject.

Much of the veterinary work in assisting
reproduction is basic research to answer fundamental questions: What temperature works best to preserve the health of eggs still encased in ovaries? Is snap-freezing an option for preserving tissues? How long will sperm or eggs remain lively after the death of the donor animals?

"My whole goal is what we call preservation of equine genetics," said Ed Squires, CSU's horse research expert. "We're trying to develop techniques to preserve genetic material, which means freezing sperm, freezing eggs, freezing embryos. And also trying to get pregnancies out of older stallions."

To do that, scientists use a variety of methods. Researchers rely on "phantom mares" - really just padded telephone poles the confused stallions mistake for raring-to-go mares - to collect semen.

Thawed sperm gets jazzed with a jolt of caffeine so they're fit to compete in the race to fertilization. And scientists mature eggs in rooms warmed to 101.5 degrees, the temperature of a cow's womb.

They've had scores of successes. Already, in-vitro fertilization, sperm injection and superovulation - getting aging females to produce five or six eggs per cycle, instead of just one - have become increasingly common technology used by cattle and horse breeders. And those same technologies are now used to help human couples have babies.

The Englewood-based Colorado Center for Reproductive Medicine now implants embryos after they've grown in culture for five days, to the blastocyst stage. But the revolution came after eight years of animal studies that showed waiting that long reduced birth defects.

"We had a ton of data that suggested it would almost be harmful not to switch to this new system," said Dr. William Schoolcraft, senior physician.

Critics have targeted other advancements, such as sorting sperm by sex, that leaped into the hands of infertility clinics more quickly.

"Sexed semen tends to attract dreamers and charlatans," said George Seidel, a physiology professor in CSU's veterinary school. "So, there have been claims of sexed semen for decades."

The technique appeals to ranchers. Sorting sperm increases the odds that pregnant cattle and horses give birth to females. Cows and mares are worth more.

Just one slim year separated the publication of the first scientific paper explaining its success in rabbits to the first human births. And, for now, just one group in Fairfax, Va., offers the technology for parents who simply want to select the gender of offspring.

"Ethically, it's more of a problem," Squires said. "The Chinese government certainly would like to have it so they can produce the desired sex."

The fact that just one group in the world now sorts sperm for family balance is fine by E. Scott Sills, co-founder of a Georgia infertility lab where the technology is used at a later stage, embryos, solely to reduce genetic defects.

"We would not want to offer such a service just because a couple wanted to have a female or male child. The risk of carrying out (pre-implantation genetic diagnosis) on an embryo is not zero" and the technology is relatively new, Sills said.

"Few people who are concerned about the welfare of their children want their children to be experimented on," said Sills, also division director for reproductive endocrinology at Atlanta Medical Center. "There are people who want to be in the vanguard. ... Somebody had to be the first kidney transplant recipient. Someone had to be the first heart transplant recipient."

One day, another couple will likely become breeding pioneers. They'll be the first to bear a child using an egg extracted and fertilized after the death of the biological mother.

In Colorado, researchers this year snatched life from death, coaxing eggs from a long-dead mare to produce a colt the elated owner called Heaven Only Knows.

CSU researchers harvested immature eggs from the prized mare after her unexpected death. They ripened the eggs, transforming them from dense clumps into starburst shapes with channels for sperm to swim through.

Some doctors are trying to produce such miracles with humans.

Sills is among the small group of fertility doctors who have tried to cheat death, using semen from a man killed in a "freak accident" to attempt to impregnate his widow. The couple had just visited his lab, wanting to have a child, hours before the man's death.

Post-mortem sperm remains viable for about 72 hours. The weaker link is the egg. A human egg loses fertility in as little as 12 hours after the woman's death.

"It's going to be a much narrower target to hit," he said.

Only one researcher has even published a paper about the technique in humans.

"It's probably something that is so delicate and so controversial that it really has to be something the clinician has to help out on a case-by-case basis," Sills said.

Critics say this is precisely the problem. Maverick fertility clinics and rogue scientists can co-opt research advances in assisted reproduction that legitimate scientists publish in respected journals.

Veterinary scientists have been among the first and most vocal critics of the religious cult that claims to have cloned a human. The cloning technology remains problematic in animals, creating abnormal placentas, producing obese mice, and throwing off the timing of turning on and off crucial genes in the clones.

In addition, scientists still worry that problems during an infant's formative weeks can lie in wait for years to wreak havoc, making those children more prone to cancer, diabetes and heart disease later in life.

"That, to me, is the irresponsibility of the entire thing. There are not enough animal studies out there to predict what might go wrong," said Mark Westhusin, an associate professor at Texas A&M who led the project that cloned the first kitten, "cc."

In many ways, some say, Congress has only itself to blame.

The National Institutes of Health in 1975 created an ethical advisory board to oversee human reproduction research. Because of partisan politics, a chair could not be agreed upon. The board disbanded in 1980. But until the mid-90s, any in-vitro fertilization research needed to be reviewed by that board.

"You had to go through this committee that didn't exist," said Dr. Michael Soules, immediate past president of the American Society for Reproductive Medicine. "The U.S. can't get beyond the politics of abortion. Are embryos humans or not?"


Meanwhile, to every NIH appropriations bill a rider is attached saying the funding can't be used for in-vitro fertilization work. Because the research is financed by private dollars, there's little federal oversight.

"It's real murky out there," Soules said. "The IVF industry would welcome funding and oversight. If you're not funding it, you're not a player."

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