The new year opens with one of the greatest breakthroughs in medical science since Ian Wilmut used cells from an adult sheep to clone Dolly the lamb in 1996. Human stem cells, which for all intents and purposes are identical to the highly prized but controversial ones harvested from human embryos, now can be made from adult skin, without using embryos or eggs. Separate research groups headed by Shinya Yamanaka of Kyoto University and James Thomson of the University of Wisconsin unveiled the technique in late November. A third group, from Harvard, confirmed that work barely a month later. It seems the path to curing diseases like diabetes, Parkinson's, and many inherited disorders has a shortcut. In fact, stem cell pioneer Rudolf Jaenisch of the Whitehead Institute in Cambridge, Mass., just showed that a mouse version of these cells cures mice with sickle cell anemia.
Known by the rather clunky name "induced pluripotent stem cells," the new creations look and behave like embryonic stem cells taken from seven-day-old embryos; both are able to turn into any type of cell in the body—skin, heart, liver, nerve, you name it. Even better, iPS cells' DNA matches that of the person who provides the skin, which is crucial if the cells are to be used to replace that person's own destroyed or damaged tissue. To date, intense efforts in the United States and around the world to make such genetically matched stem cells through cloning, an alternative approach, have failed miserably.
Transformation. Even cloning of an animal embryo, like the one that led to Dolly, is a laborious process involving "nuclear transfer," in which an adult cell's nucleus and its payload of DNA are teased out and placed into a donated unfertilized egg that has been stripped of its own DNA. In a small fraction of transfers, the egg almost magically reprograms the adult nucleus to orchestrate the development of an embryo—as if it were in a fertilized egg. Cloning embryos from adult animals has been successful in many species other than sheep, including cows, cats, pigs, and mice. But as one ascends the evolutionary tree, this gets more difficult. Only last year, the first-ever primate stem cells were made from a cloned monkey embryo.
Difficulties aside, making human stem cells by nuclear transfer invariably requires creating and destroying a human embryo, which raises ethical issues. But the broader lesson of Dolly—that DNA from adults can be reprogrammed to an earlier stage of development—paved the way for making stem cells without embryos. In this new approach, inserted genes reprogram an adult cell directly. To do this, scientists needed to know the many genes that are active in stem cells and are turned off as cells mature. What's so remarkable is that only three or four inserted genes accomplish the transformation.
Although Dolly laid the intellectual groundwork, Wilmut says the feat of creating iPS cells may be more important than his own because it's so practical. The technique not only spares embryos; it doesn't even use eggs. Extracting eggs from young women volunteers brings ethical and medical concerns of its own that even now limit research. Also, gene-driven reprogramming is easier and faster and could be adapted to routine clinical use. As Wilmut says, a researcher can "sprinkle stardust on cells in a dish" and return three weeks later to find colonies of embryonic-like stem cells. Sure, there are hurdles. Many thousands of cells get "sprinkled" for each one that transforms. And the virus that carries genes into the cells, or the gene reprogramming itself, could be risky to humans. But most scientists I've spoken with predict these problems are not insurmountable.
Meanwhile, in an immediate windfall, scientists can put human disease in a test tube by having patients serve up a bit of skin. From that, researchers will be able to generate an unlimited supply of specialized cells prone to a particular disease and get an idea, for example, of how different patients respond to certain drugs. This brings a whole new dimension to personalized medicine.