First primate cloned in U.S.

Ore. scientists split embryo to produce rhesus named Tetra

A step toward humans

Genetically identical monkeys could help research on diseases

January 14, 2000|By Frank D. Roylance | Frank D. Roylance,Sun Staff

Scientists in Oregon have announced the birth of a cloned rhesus monkey that could be the first of many genetically identical primates raised for conscription into the fight against human disease.

The monkey, named Tetra, was one of a set of quadruplets created by splitting a rhesus embryo that had grown to eight cells. The identical quads were then implanted in the wombs of two surrogate mothers. It is a technique used before in mice and farm animals, but never in a primate.

The breakthrough would appear to bring science a step closer to the skills needed to clone another primate -- humans. But the Oregon scientists say they support the federal moratorium on such experiments on humans.

"My laboratory's focus and expertise is on molecular medicine, with the goal of improving the state of human health," said Gerald Schatten, a member of the research team at Oregon Health Sciences University in Portland.

Schatten said the genetically identical mice now used in medical laboratories around the world simply aren't enough like humans. They don't get many human illnesses and can't provide the best data on the effectiveness and safety of medical therapies.

"It is a huge leap from a mouse to a patient," he said. "The [cloned] monkeys could fill that scientific gap."

Rhesus, macaque and other monkeys are used by medical researchers because they are more like humans biologically. But they are not genetically identical to each other. And that variety introduces potential genetic influences and uncertainties into experiment results.

"Any time you do an experiment ... you need to diminish the number of scientific variables as much as you can," said Dr. John D. Strandberg, a veterinarian and director of comparative medicine at the National Centers of Research Resources at the National Institutes of Health. He was not involved in the Oregon research.

With genetically identical monkeys, researchers could be more confident that any effects they see are caused by the test animals' environment, or are the results of the experimental therapy.

The Oregon team's work is reported in today's issue of the journal Science. The study team was led by OHSU staff scientist Anthony W.S. Chan and coordinated by Schatten, a professor of obstetrics and gynecology, cell and developmental biology.

Although Tetra is referred to as a clone, she is not the same sort of clone as Dolly, the sheep produced by Scottish researchers in 1997, or the cattle, mice or goats cloned by the same methods since then.

Dolly was created by taking genetic material from a breast cell of an adult sheep and inserting it into a sheep egg from which the original nucleus had been removed. The egg was then implanted in the womb of a surrogate mother sheep.

Tetra, on the other hand, is the sole survivor of four embryos created in the lab by splitting a single, normal monkey embryo that had been allowed to develop to eight cells. That produced what were, in effect, genetically identical quadruplets.

The two-cell embryos were then implanted in the wombs of two surrogate mother monkeys. Two failed to develop, but each mother became pregnant with single fetuses. One of them later miscarried, but Tetra survived and was born healthy.

What's new in the Oregon work, Strandberg said, was the successful application of the embryo-splitting technique to a primate.

Embryo-splitting is already being used to produce genetically identical farm animals, he said. It has also worked with mice, although most laboratory mice are made genetically uniform -- or nearly so -- through selective inbreeding, or by cloning embryonic stem cells, the ancestral cells from which all organs and tissue grow during gestation.

Embryo-splitting offers several potential advantages over the procedures that produced Dolly.

The report in Science notes that attempts to duplicate the success with Dolly have resulted in many fetal deaths and miscarriages. Some of the clones have proven to be "chimeras" -- animals that carry DNA from two ge

netically different animals, in this case the donors of the breast-cell nucleus and the denucleated egg.

There is also evidence that DNA taken from adult animals carries with it the genetic wear and tear that is expressed as the familiar symptoms of aging. The newborns, in effect, are born genetically old and don't fare well.

Strandberg said the application of embryo-splitting to monkeys could help researchers cut the number of animals they need for their work. For example, he said, AIDS researchers know there is a tremendous variety in the response of monkeys to HIV, the virus that causes acquired immune deficiency syndrome.

"Some will get sick rapidly; another group may not get sick at all, or only after a long time," he said. "To determine the effect of a drug, it would be very helpful to have animals that all respond the same."

Fewer animals would be needed to gauge the effect of the therapy, with beneficial effects on costs, scientific effort and the experimenters' ethical concerns.

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