D-Dad
11-20-2007, 01:49 PM
The new discovery was preceded by work in mice. Last year, Dr. Yamanaka published a paper showing that he could add four genes to mouse cells and turn them into mouse embryonic stem cells.
He even completed the ultimate test to show that the resulting stem cells could become any type of mouse cell. He used them to create new mice, whose every cell came from one of those stem cells. Twenty percent of those mice, though, developed cancer, illustrating the risk of using retroviruses and a cancer gene to make cells for replacement parts.
Scientists were electrified by the reprogramming discovery, Dr. Melton said. “Once it worked, I hit my forehead and said, ‘it’s so obvious,’ ”he said. “But it’s not obvious until it’s done.”
Some were skeptical about Dr. Yamanaka’s work and questioned whether such an approach would ever work in humans.
“They said, ‘That’s very good with mice. But let’s see if you can do it with a human,”’ Dr. Zon recalled.
But others set off in what became an international race to repeat the work with human cells.
“Dozens, if not hundreds of labs, have been attempting to do this,” said Dr. George Daley, associate director of the stem cell program at Children’s Hospital.
Few expected Dr. Yamanka would succeed so soon. Nor did they expect that the same four genes would reprogram human cells.
“This shows it’s not an esoteric thing that happened in the mouse,” said Rudolf Jaenisch, a stem cell researcher at M.I.T.
Ever since the birth of Dolly the sheep, scientists knew that adult cells could, in theory, turn into embryonic stem cells. But they had no idea how to do it without cloning, the way Dolly was created.
With cloning, researchers put an adult cell’s chromosomes into an unfertilized egg whose genetic material was removed. The egg, by some mysterious process, then does all the work. It reprograms the adult cell’s chromosomes, bringing them back to the state they were in just after the egg was fertilized. Those reprogrammed genes then direct the development of an embryo. A few days later, a ball of stem cells emerges in the embryo. Since the embryo’s chromosomes came from the adult cell, every cell of the embryo, including its stem cells, are exact genetic matches of the adult.
The abiding question, though, was, How did the egg reprogram the adult cell’s chromosomes? Would it be possible to reprogram an adult cell without using an egg?
About four years ago, Dr. Yamanaka and Dr. Thomson independently hit upon the same idea. They would search for genes that are being used in an embryonic stem cell that are not being used in an adult cell. Then they would see if those genes would reprogram an adult cell.
Dr. Yamanaka worked with mouse cells and Dr. Thomson worked with human cells from foreskins.
The researchers found more than 1,000 candidate genes. So both groups took educated guesses, trying to whittle down the genes to the few dozen they thought might be the crucial ones and then asking whether any combinations of those genes could turn a skin cell into a stem cell.
It was laborious work, with no guarantee of a payoff.
“The number of factors could have been one or ten or 100 or more,” Dr. Yamanaka said in a telephone interview from his lab in Japan.
If many genes were required, the experiments would have failed, Dr. Thomson said, because it would be impossible to test all the gene combinations.
The mouse work went more quickly than Dr. Thomson’s work with human cells. As soon as Dr. Yamanaka saw that the mouse experiments succeeded, he began trying the same brute force method in human skin cells that he ordered from a commercial laboratory. Some were face cells from a 36 year old white woman and others were connective tissue cells from joints of a 69 year old white man.
Dr. Yamanaka said he thought it would take a few years to find the right genes and the right conditions to make the human experiments work. Feeling the hot breath of competitors on his neck, he was in his lab every day for 12 to 14 hours a day, he said.
A few months later, he succeeded.
“We did work very hard,” Dr. Yamanaka said. “But we were very surprised.”
He even completed the ultimate test to show that the resulting stem cells could become any type of mouse cell. He used them to create new mice, whose every cell came from one of those stem cells. Twenty percent of those mice, though, developed cancer, illustrating the risk of using retroviruses and a cancer gene to make cells for replacement parts.
Scientists were electrified by the reprogramming discovery, Dr. Melton said. “Once it worked, I hit my forehead and said, ‘it’s so obvious,’ ”he said. “But it’s not obvious until it’s done.”
Some were skeptical about Dr. Yamanaka’s work and questioned whether such an approach would ever work in humans.
“They said, ‘That’s very good with mice. But let’s see if you can do it with a human,”’ Dr. Zon recalled.
But others set off in what became an international race to repeat the work with human cells.
“Dozens, if not hundreds of labs, have been attempting to do this,” said Dr. George Daley, associate director of the stem cell program at Children’s Hospital.
Few expected Dr. Yamanka would succeed so soon. Nor did they expect that the same four genes would reprogram human cells.
“This shows it’s not an esoteric thing that happened in the mouse,” said Rudolf Jaenisch, a stem cell researcher at M.I.T.
Ever since the birth of Dolly the sheep, scientists knew that adult cells could, in theory, turn into embryonic stem cells. But they had no idea how to do it without cloning, the way Dolly was created.
With cloning, researchers put an adult cell’s chromosomes into an unfertilized egg whose genetic material was removed. The egg, by some mysterious process, then does all the work. It reprograms the adult cell’s chromosomes, bringing them back to the state they were in just after the egg was fertilized. Those reprogrammed genes then direct the development of an embryo. A few days later, a ball of stem cells emerges in the embryo. Since the embryo’s chromosomes came from the adult cell, every cell of the embryo, including its stem cells, are exact genetic matches of the adult.
The abiding question, though, was, How did the egg reprogram the adult cell’s chromosomes? Would it be possible to reprogram an adult cell without using an egg?
About four years ago, Dr. Yamanaka and Dr. Thomson independently hit upon the same idea. They would search for genes that are being used in an embryonic stem cell that are not being used in an adult cell. Then they would see if those genes would reprogram an adult cell.
Dr. Yamanaka worked with mouse cells and Dr. Thomson worked with human cells from foreskins.
The researchers found more than 1,000 candidate genes. So both groups took educated guesses, trying to whittle down the genes to the few dozen they thought might be the crucial ones and then asking whether any combinations of those genes could turn a skin cell into a stem cell.
It was laborious work, with no guarantee of a payoff.
“The number of factors could have been one or ten or 100 or more,” Dr. Yamanaka said in a telephone interview from his lab in Japan.
If many genes were required, the experiments would have failed, Dr. Thomson said, because it would be impossible to test all the gene combinations.
The mouse work went more quickly than Dr. Thomson’s work with human cells. As soon as Dr. Yamanaka saw that the mouse experiments succeeded, he began trying the same brute force method in human skin cells that he ordered from a commercial laboratory. Some were face cells from a 36 year old white woman and others were connective tissue cells from joints of a 69 year old white man.
Dr. Yamanaka said he thought it would take a few years to find the right genes and the right conditions to make the human experiments work. Feeling the hot breath of competitors on his neck, he was in his lab every day for 12 to 14 hours a day, he said.
A few months later, he succeeded.
“We did work very hard,” Dr. Yamanaka said. “But we were very surprised.”