PHILADELPHIA, May 14 (UPI) -- A single gene may determine whether cloned animals will develop successfully or not, which may be a good reason to avoid cloning humans for reproductive purposes, scientists reported Tuesday.
The single gene lends support to the concept of therapeutic cloning, however, scientists said.
The gene, called Oct4, "is essential" to successful development, Hans R. Scholer, principal author and director of University of Pennsylvania's Center for Animal Transgenesis and Germ Cell Research, told United Press International.
"If the gene is not expressed, then the embryos die early in development," he added.
Scholer's team studied cloned mouse embryos and found the Oct4 gene is expressed at levels adequate for correct development in only 10 percent of the animals.
There is only a "very narrow window" for Oct4 levels at which correct development can proceed, Scholer said, so if the gene is overexpressed or underexpressed -- its levels are too high or too low -- the embryo will not survive. To make the process even more exacting, the gene must be expressed in the right place in the developing embryo at exactly the right time.
"This is an argument against reproductive cloning," Scholer said. This is "not something we should try to pursue, because if you're having a problem at the very beginning, we know that this is a problem that can be maintained through the later stages."
The research, reported in the journal Genes and Development, "definitely speaks loudly that we need to investigate this ... before we can even think of applying this to humans," Robert Lanza, vice president of medical and scientific development at Advanced Cell Technology, told UPI. Lanza's company, which was not involved in Scholer's research, is developing cloned animals to be used for cell and organ transplants.
Ever since Dolly the sheep was successfully cloned -- transferring DNA from a single cell into an egg cell and creating a relatively exact copy of that organism -- the possibility of cloning a human has become a contentious issue.
Some fear it could be used merely as a way of reproducing, while others see therapeutic cloning's promise, wherein the technology could be used to create embryonic stem cells with the potential to cure diseases ranging from diabetes to Alzheimer's.
"The danger (in reproductive cloning) is that since we know that levels of Oct4 are so important for development, certain parts of embryos may be wrong in their development and so could have a specific problem later on," Scholer said.
He also noted, "There's no known relationship between Oct4 and specific problems later."
Although the findings raise doubts about the ethics of cloning humans for reproductive purposes, Scholer maintained "they support therapeutic cloning" because viable embryonic stem cells could be harvested from clones, even if Oct4 expression is not perfect.
"It has to be really perfect, perfect if you want a normal embryo, but it doesn't have to be exactly perfect to pull out embryonic stem cells," he said.
The stringent requirements of Oct4 expression also help explain why cloning is such an inefficient process despite researchers' success with sheep, cows, mice and cats. For every successful clone, there are 30 or more failures.
"Cloning at this point is as much an art as it is a science," said Lanza. "I think this will allow us to turn it into more of a science."
Lanza's company is repeating the experiment in cows to see if it holds true in that species. If successful, cloning could become a more efficient process and the technology could become commercially viable for purposes such as agriculture, he said.
The Oct4 gene "can explain more than 90 percent of cloning failures," Scholer said. Animal cloners "were so surprised that their embryos failed so early ... and now we can say no wonder they failed -- Oct4 was not expressed properly."
Scholer said, "That does not mean that there are not other factors" that may cause a clone to fail. It's just that if you don't have Oct4, that's it, that's the end of the story."
(Reported by Steve Mitchell, UPI Medical and Health Correspondent, in Washington)
