In breakthroughs that burst like bombshells in biology's hottest field, rival scientists in Japan and the United States announced yesterday they have successfully turned human skin into cells that behave like embryonic stem cells - avoiding the controversial creation and destruction of embryos.
The accomplishment seems certain to dramatically speed the pace and alter the face of stem cell research, and perhaps end the acrimonious public debate over a science that - even conservative foes of some of its methods have long conceded - promises to be a powerful weapon against disease.
By using a simple recipe of four genes to reprogram ordinary adult cells into stem cells, the new approach appears to bypass the ethical, religious, and political objections that have blocked government funding for research on stem cells culled from human embryos.
Embryonic stem cells have been likened to blank slates because they replicate themselves endlessly and can form any of the 220 cell types in the body, including blood, bone, organs, and nerves.
The work at Japan's Kyoto University and the University of Wisconsin seemed likely to spur the Bush administration, which has banned funding for virtually all embryonic stem cell research, to open money spigots to researchers working on the "embryonic-like" stem cell lines.
The greater availability of money might lead researchers away from us ing frozen embryos from fertility clinics and cloned embryos as sources of stem cells.
White House spokeswoman Dana Perino said the president regarded yesterday's developments as "important advances in ethical stem cell research."
Stem cell scientists around the world hailed the new research as revolutionary, but many said it is premature to drop efforts, so far unsuccessful, to extract stem cells from cloned human embryos, until now most scientists' favored approach for generating stem cells.
"It's a bit like learning how to turn lead into gold," Robert Lanza, chief scientific officer for the Massachusetts-based research firm Advanced Cell Technology, said of the technique. "If perfected, there will no longer be any need for human eggs [in stem cell research], or any of the controversy associated with destroying embryos."
He stressed, however, that "this is early stage research, and we should not abandon other areas of stem cell research."
There remain wrinkles in the new research: Scientists have not yet shown conclusively that the new cells have all the capabilities of stem cells from embryos, and some of the genes used to reprogram skin cells are associated with cancer, though that problem can probably be remedied by using other genes.
But religious activists were proclaiming near-victory in their struggle against embryonic cloning.
"This is the breakthrough everyone's been waiting for," said the Rev. Tadeusz Pacholczyk, director of education for the National Catholic
In the Japanese work, described yesterday in the journal Cell, scientist Shinya Yamanaka used a potent cocktail of four genes inserted into human skin cells to turn back the clock and cause the tissue to regress to a stem cell stage, capable of becoming any type of tissue. In the research, Yamanaka's team transformed the stem cells into neurons and other human cell types, including thumping clumps of heart muscle. The Kyoto researcher earlier this year triggered a tsunami of excitement by forging functional embryonic-like stem cells from the tails of lab mice, a feat that many scientists predicted could not easily be replicated using human tissue.
Almost no one expected human results so quickly.
"We felt we were going in the right direction, but it was very hard, the hours were very long, and there was not the certainty of success," Yamanaka said by phone from Kyoto. "We were very surprised."
The University of Wisconsin scientists announced their results in a near dead-heat finish with Yamanaka's team. They used a process similar to Yamanaka's, but employed a different combination of genes. In both teams' work, the genes, once inside a skin cell's nucleus, produce "transcription factors," proteins that control the activity of other genes, and reprogram the adult human tissue into embryonic-like stem cells.
The Wisconsin results, which strongly buttressed Yamanka's findings because they were produced independently, will be published tomorrow by the journal Science.
"The world has changed," said James Thomson, head of the University of Wisconsin lab where scientist Junying Yu led the effort to form the new cells, called induced pluripotent stem cells.
"It is the beginning of the end of the controversy that has surrounded this field," Thomson told a news conference. "Over time, these [induced] cells will be used in more and more labs. And human embryo stem cell research will be abandoned by more and more labs."
The Wisconsin research was funded by the private Charlotte Geyer Foundation and to a lesser extent by the federal National Institutes of Health. Japan imposes no restriction on government funding for embryonic stem cell research.
The research drew loud hurrahs. But you could also almost hear the frustrated gnashing of teeth in top research centers in Cambridge, Boston, and beyond, where teams of scientists had been furiously closing on similar results.
"There's been a real race, and the competition has been intense, and this research represents a huge 'first' in a critically important area," said Leonard I. Zon, head of the stem cell research program at Children's Hospital Boston. "This is work of tremendous significance that is going open a lot of doors in biology and medicine.
"But it doesn't mean the larger race is over," Zon said. "Enormous new discoveries are waiting in the field."
Proof that embryonic-like stem cells can be engineered from adult tissue could eventually spell doom for the controversial research at Harvard and other top centers that focuses on creating stem cell lines from cloned embryos. This is the path that most scientists until now thought was most obvious and most likely to succeed.
"There was a prejudice, now shown to be wrong, against the very idea that you could take an adult cell and reprogram it back into an embryonic-like state," said Douglas A. Melton, co-director of the Harvard Stem Cell Institute.
Still, he stressed in an interview, these are early days, and there remain potential pitfalls.
It may prove in the long term, for example, that creating stem cells through embryo cloning yields purer, more "natural" stem cells than those engineered from adult cells.
Moreover, many scientists noted, the process used by Yamanaka uses cancer-causing genes inserted into cells with the aid of retroviruses. That's no hindrance to lab research, but could never pass muster for human therapy.
"What patients need is the fastest, most effective way forward," said Melton, whose lab produced most of the embryonic stem cell lines now being used by researchers around the world. "Until the alternative [approach] is shown to produce the same kind of extremely versatile, normal cells that we derive from previously frozen human blastocysts, it would be unfair to patients to renounce" use of embryonic clones for stem cell research, he said.
Embryonic cloning research at Harvard and elsewhere has been hampered as much by difficulty in procuring human eggs - women have been unwilling to undergo the uncomfortable, slightly risky process - and technical hurdles as by the objections of religious conservatives.
Thus, Melton agreed, the new research "removes the ethical complications, should make stem cells easier to obtain, and, certainly not least of all, could make embryonic stem cell work eligible for federal funding."
Embryonic stem cells are thought to hold extraordinary potential for medical research and eventual therapies for an array of lethal ailments, ranging from Parkinson's disease to severed spinal cords. Stem cells made from a patient's own body might be used to create new genetically identical tissue - heart cells, nerve cells, liver cells, and so on - to repair, say, diseased hearts or the ravages of juvenile diabetes.
Genetically matched cells might eventually be used to make direct repairs to ailing hearts, livers, kidneys, or lungs. They might be used to regrow shattered spines. More immediately, study of stem cells could help scientists better understand the underlying mechanisms of disease and allow for safer, more efficient screening of new drugs.
Yamanaka's and Thomson's simple approach sent shock waves through biological laboratories in North America, Europe, Asia, and Australia.
In perhaps the most dramatic reaction, Scottish stem cell pioneer Ian Wilmut, who led the team that in 1997 cloned Dolly the sheep, announced that his University of Edinburgh laboratory will abandon embryonic cloning in favor of reprogramming.
Wilmut, in remarks to journalists, said he is motivated not by ethical concerns, but by the conviction that Yamanaka's approach holds better chances for near-term scientific research and long-term medical therapies and cures.
"The technique of changing cells directly from a patient into stem cells, without the step of making a clone, has better potential," he said. "Plus, it's socially more acceptable. This is the way the science is going."
Colin Nickerson can be reached at nickerson@globe.com.
