Dogged Pursuit

First sheep, now a dog—what next? How a lab in South Korea perfected a cloning technique that is likely to transform medical research around the world

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But funding alone--Hwang intentionally keeps his budget lean, relying primarily on $2 million from the government annually--can't explain such resounding success in a country hardly known for its deep scientific roots. Hwang's theory: "Koreans use metal chopsticks, so I think we have good micromanipulation skills," he says. He's only half kidding: Hwang believes that thanks to years of corralling small grains of rice and other slippery foods with stainless-steel slivers, his researchers are especially well suited to squeezing and injecting individual cells under the microscope using fine instruments. He credits that delicate manipulation of cells as a key to his success in creating the first cloned human embryos and extracting a stable colony of stem cells from them in 2004.

That dexterity is the hallmark of the South Korean technique--that and the lab's nearly round-the-clock, seven-days-a-week schedule. "Stem cells do not know Saturday and Sunday," Hwang says. Encouraged by his success with the notoriously finicky human stem-cell lines, Hwang went to the dogs--a challenge even for a lab the caliber of his. Dogs have a limited breeding period; a female's eggs can be harvested for only a few weeks each year, when she is in heat. In addition, the eggs cannot be easily extracted from the ovaries, as they can with pigs and cows. "We failed so many times to get eggs from many egg-donating dogs," says Hwang. "So I studied and surveyed the reproductive cycle and reached a solution. If we try to get the egg not from the ovary but from the oviduct after ovulation, then maybe we would get good-quality eggs."

Hwang and his team began by doing what scientists do best: observe. They meticulously documented the temperature, hormone levels and vaginal cellular changes of potential canine egg donors through an entire ovulation cycle. On some days, they took readings two or three times a day. That way, they could pinpoint when an egg began its journey from the ovary into the oviduct.

The next steps were similar to the ones used in cloning human cells. First, they gently squeezed out the nucleus of each egg and replaced it with an entire ear cell from an adult dog. Then the egg and its new cargo were electrically stimulated and chemically fused in a series of steps that Hwang developed so that the egg would begin dividing and acting like a growing embryo. But the culture medium in which he had been growing his animal clones--even the one that had worked so well for his human stem-cell lines--turned out to be inhospitable to canine embryos. "It took almost two years to get this specific in vitro culture for the dog clones," Hwang says.

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