Within the first few years of his research, Mitalipov successfully used Thomson’s method to extract pluripotent stem cells from natural monkey embryos flushed from the uterus; then he figured out how to trigger those stem cells to grow into colonies known as cell lines. Somewhat akin to sourdough starter, these stem cell lines, provided with the right nutrients, can be kept alive indefinitely and used to produce ever more stem cells, which in turn can be coaxed into heart tissue or skin tissue or neurons as needed.
However, for reasons that were mysterious to him, Mitalipov couldn’t successfully clone an embryo from which to create those stem cell lines. Using an ATM-sized machine called a micromanipulator, he could suck the DNA out of a monkey egg; and employing Wilmut’s method, he could insert the DNA from another monkey’s skin cell into that egg. But he couldn’t get the egg to reprogram successfully and become an embryo.
Scientists at private labs who also had begun working with both monkey and human eggs were caught in the same snag. In a study that was published in the journal Science in April 2003, Gerald Schatten, a University of Pittsburgh developmental biologist who had worked at the ONPRC in the late 1990s, confirmed what many in the field had feared. After trying hundreds of times to clone monkey embryos, Schatten concluded that it was impossible.
“It is almost as if someone drew a sharp line between Old World primates—including people—and other animals, saying, ‘I’ll let you clone cattle, mice, sheep, even rabbits and cats, but monkeys and humans require something more,’” Schatten told Science.
But in his lab in Hillsboro, Mitalipov plodded on, and in 2006, he made a breakthrough.
“The primate egg is one of the most fragile and sensitive cells in nature, and here we were, putting it through hell,” says Mitalipov. “Something needed to change.” He began to suspect that the “something” had to do with the dye he’d been using. To guide the needle of his micromanipulator during the reprogramming process, Mitalipov had to stain the egg’s nucleus with a dye that glowed under ultraviolet light. The dye and light hadn’t harmed the eggs of any of the 15 other animal species that had been cloned thus far, but given the fragility of the primate egg, Mitalipov began to wonder if he had found the process’s Achilles’ heel. But without the dye, how would he be able to see the nucleus or extract the DNA?
Mitalipov had an idea. In 2006, he borrowed an Oosight Imaging System, a computer that uses polarized light to take digital pictures of microscopic structures inside eggs. But instead of using it to take pictures, Mitalipov used it as a video camera to help him remove genetic material. Eventually it worked: The egg survived the reprogramming process and matured into an embryo that reached the blastocyst stage, meaning it had produced stem cells. But it would take Mitalipov over 300 more tries, using as many eggs from 14 different monkeys, to refine the process. Finally, in January 2007, he was able to transform the stem cells from a successfully cloned embryo into a cell colony and get it to develop into heart tissue that matched the skin cell donor. Two weeks later, the heart tissue began to beat.
“I thought, This is a historic moment,” he recalls. “Finally, I knew we had solved all these problems.”
Eager to share his discovery, he rushed home and told his wife and children. The kids demanded to see the heart their daddy had made from the monkey’s ear. He obliged. Back in the lab, he lifted up his 8-year-old daughter, Nargiz, and then his 5-year-old son, Paul, to see the pulsing cells.
One week later, the scientific hero became a kind of exile.
You can hear their excitement in the video clip he shows during presentations.
“What is it, Daddy?” they both asked.
“This is magic,” he told his children. “This means we can cure lots of diseases and help millions of people, including Grandma.”
Mike Thomson and Wilmut before him, Mitalipov made the front page of the New York Times after he publicly announced his discovery in the journal Nature on November 15, 2007. In the Boston Globe, Reverend Thomas Berg, director of the Westchester Institute for Ethics and the Human Person, a Roman Catholic political think tank, warned that Mitalipov had eliminated the last barrier to cloning humans, an inevitability he deemed “one of humanity’s darkest endeavors.”