A team of University of Pittsburgh scientists has produced the world's first cloned monkey embryos with the help of the South Korean scientists who created the first mature human cloned embryos.
But while the February announcement of cloned human embryos raised concerns that science had come a step closer to producing a cloned human baby, yesterday's report provided new evidence that reproductive cloning of both human and nonhuman primates will be difficult, if not impossible, to accomplish.
The team led by Gerald Schatten, director of the Pittsburgh Development Center at Magee-Womens Research Institute, produced 135 cloned embryos of rhesus macaques and transferred them to 25 surrogate mothers. But no viable pregnancies resulted.
"If you don't like reproductive cloning, it is certainly good news," said Ronald Cole-Turner, an ethicist at the Pittsburgh Theological Seminary who specializes in biomedical issues. "Nature itself seems to be saying to us that reproductive cloning is not going to be an easy step to take."
Calvin Simerly of the Pitt team reported yesterday at the American Society for Cell Biology meeting in Washington, D.C. that the team was successful in producing three blastocysts ---- embryos more than several days old that contain embryonic stem cells.
The researchers weren't able to isolate a stable stem cell line from any of the blastocysts, which were produced last spring. But Schatten expressed confidence that will be possible as more blastocysts are produced.
In the human cloning experiments in South Korea, he explained, researchers needed to create 30 blastocysts before they could isolate a single stable line of embryonic stem cells.
"We are working around the clock" to make more blastocysts, he said, noting that female monkeys are in their fertile period between October and April. "We're getting very encouraging results."
Schatten's group collaborated with Woo Suk Hwang and other researchers at Seoul National University for their study.
In addition to yesterday's announcement, the results also are being reported next week in the journal Developmental Biology.
Like most scientists, Schatten would just as soon find that reproductive cloning is impossible. But producing embryonic stem cell lines from monkey blastocysts would give scientists an opportunity to use monkeys to assess the potential for stem cell therapies without the ethical and moral concerns associated with human embryonic stem cells.
"This group is working toward that goal and deserves to be congratulated," said Jose Cibelli, a cloning expert and director of the Cellular Reprogramming Laboratory at Michigan State University.
Embryonic stem cells have been proposed as a possible cure for diabetes, Parkinson's disease and a host of disorders. But much remains to be learned about how to grow and evaluate embryonic stem cells in culture. And no one knows yet if the cells will be tolerated by a patient's immune system or whether the cells might give rise to cancers or other problems.
"The more we know about embryonic stem cells, the more fully convinced we are that we need animal models," Cibelli said. "You can't go straight from the mouse [experiments] to humans. ... If we get one failure [in humans], the whole field will be set back for years."
Among scientists, the Pitt findings are perhaps most notable because they provide the first confirmation of Hwang's cloning techniques, Cibelli noted.
Just last year, Schatten reported in the journal Science on his group's dismal results in monkey cloning using the techniques that produced Dolly, the cloned sheep, in 1997. He concluded that it was virtually impossible to produce clones of primates by that method.
Cloning involves removing the nucleus from an egg cell and replacing it with the DNA from an adult, non-reproductive cell, such as a skin cell. This results in an embryo with genes identical to those of the cell donor.
But drawing out the nucleus from an egg cell also removes surrounding cytoplasm that contains proteins essential for proper cell division, Schatten and his colleagues discovered. The South Koreans get around that problem by gently squeezing the nucleus out through a slit in the cell wall.
The Hwang team also used freshly donated eggs that are less mature than those used in the Dolly technique. That appears to be crucial, Schatten said, and raises questions about human cloning experiments in the United Kingdom.
U.K. officials issued the first license authorizing human cloning for embryonic stem cells this past summer, but limited the work to mature, aged eggs that have failed fertilization attempts at assisted reproduction clinics.
Those efforts may be doomed if the Pittsburgh and Seoul researchers are correct.
Though the Bush administration has pushed for a worldwide ban on all forms of human cloning, many scientists suspect that embryonic stem cells used for therapies will have to match the patient genetically. It thus might be necessary to produce a cloned embryo of the patient.
Great Britain has been aggressive in supporting this research and the South Korean team is using its cloning technique to study possible human embryonic stem cell therapies.
President Bush has limited federal funding of embryonic stem cell research to a few cell lines that existed before August 2001. Several privately financed research efforts have been launched to produce additional lines and California voters last month approved a $3 billion bond measure to finance embryonic stem cell research.
Pennsylvania is one of seven states that outlaw experiments involving human embryos. But Schatten, whose group received a $6.4 million National Institutes of Health grant last year to develop cloned monkeys, maintains that monkey experiments could settle many of the questions relating to stem cell therapy without harming human embryos.
"Certainly, the big step was taken with the research in Seoul," Cole-Turner said. Now, the whole therapeutic approach might be studied without involving humans, at least in the near term.
"To be able to test that in a primate model is a real gift," he added.
