Advance in Stem-Cell Work Avoids Destroying Embryos By GAUTAM NAIK - The Wall Street Journal November 21, 2007; Page A1 The promise of using stem cells to treat disease has moved a tantalizing step closer to reality, without the ethical shackles that have long hindered its progress. In a compelling scientific feat, independent teams of researchers in Japan and the U.S. have created human embryonic stem cells without destroying any human embryos. Scientists said they "reprogrammed" mature human cells and returned them to a primordial, embryonic-like state in a laboratory dish. The hope is to someday convert those cells into fresh heart, nerve or other tissue and transplant it into a patient to treat diabetes, Parkinson's disease or other ailments. Because the transplanted tissue would be derived from the patient's own mature cells, it would share the same genetic makeup and wouldn't be rejected by the immune system. Previously, master stem cells that can turn into all other tissue types could only be obtained from embryos, in a process that destroyed them. Moreover, to provide freshly created tissue that wouldn't be rejected by a patient's body if implanted, the embryo had to be cloned from the patient. The new method would make both cloning and embryo destruction unnecessary. "This is going to be the way forward," predicted Sir Martin Evans, a British stem-cell pioneer who shared this year's Nobel Prize for Medicine. "We've all been waiting for this." Although practical medical applications are years away, the findings are likely to spark a wave of similar experiments by other researchers that could propel the science forward. The studies have already reignited a debate in Washington about funding of human embryo research, a subject sure to be an issue in the presidential contest. They are likely to bolster the cause of those who oppose embryo research, yet accelerate the pace of stem-cell research as scientists rush to build on the new approach. Since mid-2001, the Bush administration has decreed that federal funds may be used for research using only 60 or so stem-cell lines obtained from human embryos, lines that existed at that time. Many Bush supporters, especially on the religious right, would like that constraint to remain, and possibly be tightened. Sen. Sam Brownback, a Republican from Kansas and vociferous opponent of human embryo research, said the new experiments "identify a more promising embryonic-type stem-cell research method that also meets the ethical bar." Others saw it differently. "We applaud the breakthrough today but think it's one of many approaches that should be explored," said Democratic Rep. Diana DeGette of Colorado. She is the chief architect of legislation to expand federal funding for stem-cell research -- legislation twice passed and twice vetoed by Mr. Bush. Several states have moved to pay for stem-cell research themselves. California has pledged $3 billion over a decade. One of the new studies, published in the journal Cell, was led by Shinya Yamanaka of Kyoto University, a pioneer in the reprogramming field. A second was published in Science by researchers at the laboratory of James Thomson of the University of Wisconsin, who isolated the first human stem-cell line in 1998. Cell and Science are peer-reviewed journals. In both cases, scientists inserted several genes into mature human cells. For reasons no one can yet fully explain, doing so reset the molecular clock -- turning mature cells into embryonic-like cells. Even among researchers, the result has a touch of science fiction. "You have this extremely strong arrow of time, and it's going completely backwards," said Dr. Thomson. The two teams separately showed that the embryonic-like stem cells they had created could also become heart, nerve and other human tissue. A key step, not yet taken, would be to use freshly derived tissues to treat diseases in large mammals, such as monkeys, before attempting this in humans. There are plenty of hurdles. To ferry the genes into the cells, both teams had to use dangerous viruses as a transport mechanism. Unfortunately, the DNA of those viruses can get incorporated into the genetic structure of the cells, potentially causing cancer or other unwanted side effects. Dr. Yamanaka and others are now racing to find a benign virus that won't trigger those problems. Before this research, many stem-cell scientists were mainly focused on the cloning technique that was used to create Dolly the sheep in 1996. Back then, a sheep's egg was used to reprogram a mature sheep cell and return it to an embryonic state. However, the scientists didn't harvest the cloned embryo for fresh tissue. Instead, it was taken to term, yielding Dolly. Some researchers began to wonder whether they could avoid the use of both cloning and eggs and somehow reprogram a mature cell by introducing genes. In a breakthrough paper published in 2006, Dr. Yamanaka and a colleague showed how four specific genes could do exactly that in a mouse cell. What they couldn't do was implant the reprogrammed cells into other mouse embryos and have them accepted and incorporated into the mice that were later born -- an important test to see whether the embryonic cells were really viable. Then, this June, Dr. Yamanaka and two other research teams showed that they had surmounted this problem. Each team used the same four genes to reprogram a mouse cell and return it to its youthful, embryonic stage. When implanted into other mouse embryos, the cells produced healthy mice. That result set off a global race among scientists seeking to replicate the mouse results with human cells. Almost nobody predicted that the human barrier would fall quite so quickly. "We were very surprised because human and mouse embryonic cells are very different," said Dr. Yamanaka, who is also a senior investigator at the Gladstone Institute of Cardiovascular Disease in San Francisco. His discoveries have sparked a flurry of fresh research. Some scientists now are introducing different kinds of genes, in the hope of improving the reprogramming process. Douglas Melton, co-director of the Harvard Stem Cell Institute, says his colleagues want to see if they can pull off the same trick by using chemicals instead of genes. "You have to give Yamanaka enormous credit. Most people, including me, wouldn't have thought about using this approach," Dr. Melton said. Unlike cloning, "the wonderful thing about this approach is that it's easy. You're going to see lots and lots of labs give it a try," predicts Robert Blelloch, a stem-cell biologist at the University of California, San Francisco, who recently published his own reprogramming experiments based on Dr. Yamanaka's breakthroughs. Ian Wilmut, who cloned Dolly, has long been hoping to find a treatment for motor-neuron disease in people by using the same technology he used in his original sheep experiment. Now, he's so impressed with the latest discoveries, he's given up cloning in favor of the Yamanaka approach. "It seems we should all focus our efforts on reprogramming," says Prof. Wilmut. Cloning experiments still hold promise. Just last week, researchers in Oregon used the technique to create embryonic clones of monkeys. But such research on human cells is harder. Human eggs are in short supply, the technology is tricky and expensive, and funding isn't easily available. A major scandal has hurt, too. In 2005, a Korean researcher published a study that appeared to show how he'd used the Dolly approach to create human embryonic clones. The claim turned out to be fraudulent. By contrast, "any scientist with basic technology in molecular and cell biology can do reprogramming," Dr. Yamanaka said.