Human Clones May Be Genetically Viable

For the first time since Hwang Woo-Suk's cloned stem cells were revealed as fakes, human cloning — for medical purposes, or even for reproduction — appears to be a realistic possibility.

"We show for the first time that the same genes turned on in normal human embryos are the same genes turned on in human clones," said Robert Lanza, scientific director of Advanced Cell Technologies and co-author of a study published Monday in Cloning and Stem Cells.

Lanza's team inserted human cell nuclei into hollowed-out egg cells from both humans and animals, then stimulated them into development, a process called somatic cell nuclear transfer (SCNT), or more informally, cloning. When compared to a normal human embryo produced through in vitro fertilization, the animal-human hybrids didn't develop normally, but the human-human cloned embryos displayed many of the genetic characteristics of healthy development.

The research is the first step toward therapeutic cloning — making embryonic stem cells from a patient's own DNA capable of replacing diseased tissue, failing organs and even lost limbs. And, theoretically, the same technique could be used to produce a cloned person.

In 2001, Lanza's team claimed to have made cloned human embryos, stoking public hopes that cloning would soon produce thousands of embryonic stem cell lines — one for every common genetic group, capable of replacing diseased tissue, failing organs and lost limbs. It wasn't clear, however, whether those embryos were actually healthy, and their DNA was never analyzed.

Four years later, researchers led by the now-infamous Woo Suk Hwang claimed to have actually harvested embryonic stem cells from cloned embryos. The findings again raised public hopes, only to be revealed as fraudulent. Hwang now works for a controversial dog cloning company, and embryonic stem cells taken from a human clone remains hypothetical.

However, even if the scientific challenges of so-called therapeutic cloning are overcome, ethical problems remain. Harvesting human eggs requires women to take ovulation-inducing hormones, a process that is arguably dangerous and inarguably arduous. As a result, egg supplies are limited and expensive. Some scientists hoped to solve this by substituting animal eggs for human.

Research on these hybrid embryos — as well as chimeric embryos, formed by mixing actual human and animal DNA — was approved last year in the United Kingdom. But that approval came after bitter public debate in which opponents raised the specter of sentient human-animal hybrids being used as biological parts factories.

The latest findings suggest that hybrids are incapable of growing to a medically useful stage, much less sentience. But both cloning and induced pluripotency — a recently-developed procedure in which adult cells are transformed into an embryo-like state — should work.

"Science has a way to go with both of these, but we will soon have a way to create a bank of stem cells to expand the range of stem cell therapies," said Lanza.

His team compared the gene expression of a human embryo produced through in vitro fertilization with clones that incorporated human, cow, rabbit and mouse eggs. Several thousand genes were active in the fully human clones, but almost completely silent in their counterparts, which stopped developing after several days.

Among these were the genetic targets stimulated during induced pluripotency, in which adult cells are returned to an embryo-like state. Their silence suggests that animal eggs will not be useful in making clones capable of generating embryonic stem cells, much less growing to adulthood.

"You can never say never," said Lanza, "but we've been at this a very long time, and despite literally thousands of these attempts, we've never seen one of these hybrids advance further than what we're reporting here. And though negative results don't often get reported, I know for a fact that other experts have had the same results."

But the fully human cloned embryos could produce stem cells and, if permitted, perhaps grow into a person.

"The DNA resembles the DNA of a normal human embryo, which raises the question of human reproductive cloning," said Lanza.

However, New York Medical College cell biologist Stuart Newman disagreed with Lanza's assessment. Though the paper "shows that interspecies SCNT is a bust," he said, there are still "substantial differences" between fully-human cloned and IVF embryos.

But even if Lanza's embryos cannot develop, other scientists may come up with a more effective process. And though reproductive cloning has not yet been attempted, some experts say it's inevitable.

The procedure is illegal in the United States, but a global ban proposed in the United Nations fell apart after the U.S. insisted that therapeutic cloning be banned as well.

"Virtually every country agreed, but President Bush held it hostage," said Lanza.

President Barack Obama has promised to overturn President Bush's moratorium on federal funding of most embryonic stem cell research. Lanza hopes he will abandon Bush's position at the U.N. as well.

"Reproductive cloning is unsafe and unethical," he said. "This raises the urgency that those laws need to be passed."

Citation: "Reprogramming of Human Somatic Cells Using Human and Animal Oocytes." By Young Chung, Colin E. Bishop, Nathan R. Treff, Stephen J. Walker, Vladislav M. Sandler, Sandy Becker, Irina Klimanskaya, Wan-Song Wun, Randall Dunn, Rebecca M. Hall, Jing Su, Shi-Jiang Lu, Marc Maserati, Young-Ho Choi, Richard Scott, Anthony Atala, Ralph Dittman and Robert Lanza. Cloning and Stem Cells, Vol. 11 No. 2, Feb. 1, 2009.

Image: Cloning and Stem Cells / Each top-and-bottom image is a pair; from left to right, a human-mouse embryo; human-cow; human-rabbit; human; and a human embryo produced through in vitro fertilization.