Cloning researchers in Pittsburgh have been awarded a federal grant to continue to look for ways to produce genetic copies of monkeys and other nonhuman primates.
The National Institutes of Health awarded a $6.4 million, five-year grant to the Pittsburgh Development Center, which is part of the Magee-Womens Research Institute and directed by cloning expert Gerald Schatten.
"It's nice to know our peers in the field feel that the work we're doing here in Pittsburgh is worthy of such significant support," he said.
Creating genetically identical monkeys -- clones -- would provide an important new tool for medical research, Schatten said. Before new treatments can be tested in people, they must first be rigorously checked in animal models. Lab mice have been bred so that each strain of animals has certain genes in exactly the same place on their chromosomes.
But monkeys, like humans, have far greater genetic diversity, and that means scientists must test a relatively large number of monkeys to get a more accurate picture of how humans might respond to an experimental therapy.
Schatten said that testing sets of genetically identical monkeys will allow researchers to find better answers to medical problems more quickly and that ultimately, testing could be done in fewer animals.
But the techniques that were successful in cloning Dolly the sheep, mice and other animals don't work in nonhuman primates and are not likely to work in humans, either, Schatten said.
His team has attempted conventional cloning methods with more than 700 eggs from rhesus macaques and has transferred 33 early embryos into surrogate mothers, but never achieved a pregnancy. The researchers reviewed those disappointing findings in an April issue of the journal Science and explained that the problem rests in improper distribution of genetic material during cell division.
In the first steps of cloning, the DNA-containing nucleus is removed from the egg and is replaced with the nucleus of an adult cell. That works fine in some species, but in monkeys the removal of the egg nucleus also removes what Schatten called "molecular motors" that are responsible for separating chomosomes during cell division.
Instead, "the chromosomes scatter in a helter-skelter fashion," he explained. "The cells that result after those cell divisions all have the wrong number of chromosomes."
One strategy he and co-investigators Calvin Simerly, Christopher Navara and Laura Hewitson are trying is to insert the adult cell nucleus before the egg's nucleus is removed. After a few hours, some of the molecular motors transfer their attachment to the adult nucleus. Then the egg's own nucleus can be taken out.
"It's showing promise," Schatten said. But "we don't have any cute-named monkeys yet."
Another approach is to split embryos so they become genetically identical twins, triplets or quadruplets, and then implant individuals in surrogate mothers to gestate. Schatten pioneered that "low-tech" method to produce a rhesus monkey, called Tetra, in 2000.
His new goal is to develop at least eight sets of identical twins this way.
Schatten said that in addition to developing better animal models of disease for testing new therapies, the research could also teach scientists about the potential for generating embryonic stem cells, which some hope will create treatments for Parkinson's disease, diabetes and many other disorders.
As he put it, "Knowing what works and doesn't work in nonhuman primates gives this controversial conversation at least some kind of scientific footing on which to evaluate it."