If James Thompson and Shinya Yamanaka are right, presidential hopefuls will soon have one less "war" to talk about.
The two molecular biologists and their teams at the University of Wisconsin-Madison and Japan's Kyoto University, respectively, announced last Tuesday they had reprogrammed regular human skin cells to mimic stem cells, sidestepping the usual ethically-charged process of destroying human embryos.
"It is earth-shattering," said Professor of Biology Ken Miller '70 P'02, who also commented on the news for PBS NewsHour. "The barriers of cost, technology and getting regulatory approval have now dropped by an order of magnitude."
Stem cells are found in developing organisms and have the unique ability to transform into any other cell type the organism needs - in humans, this amounts to over 200 cell types, including heart muscle, insulin-secreting cells of the pancreas and even neurons in the brain. In the last decade, these blank slates of development have been targeted for therapeutic use, with hopes that stem cells could one day repair damaged tissue or even grow organs for transplant.
But stem cell research has been met with as much controversy as promise. The traditional method of harvesting stem cells has been to destroy embryos - potential human lives - sparking concern in churches and even the White House over the ethical treatment of potential life.
That is, until now. By reprogramming skin cells to behave as stem cells, neologized as "induced pluripotent stem cells" or iPS cells, no embryo must be destroyed to obtain stem cells - the Kyoto research was done with skin from a middle-aged woman's face.
"It's really hard to find an ethical problem with this process," said Professor of Medical Science Michael Lysaght, who has worked with stem cells in the past. "I think we'll see the floodgates opening here in terms of research."
The ground-breaking results are based on previous research in mice. In a paper published in the summer of last year, Yamanaka determined which genes are responsible for stem cells' fascinating behavior. Beginning his search with a pool of 24 candidate genes, he and his team meticulously knocked out small groups of genes and then looked to see if the cells could still function as stem cells. Yamanaka narrowed the pool down to just four essential genes which, when expressed, give the stem cell its special properties.
"That paper didn't attract a lot of public attention, but in the cell biology world, it was a real eye-opener," Miller said. "The reaction we all had was, 'It can't be that simple.' "
The next step was to see if those four genes, when introduced into a regular mouse skin cell, could make the cell exhibit stem-cell-like characteristics. After giving the cells a virus that carried the genetic information - a process called transfection - the cells began to behave like stem cells, to the delight of molecular biologists keeping keen eyes on the research.
"We were stunned - it is that simple," Miller said. "But that research left one very important question open: 'Will this work in humans?' "
The recent breakthroughs - published in the prestigious scientific journals "Science" and "Cell" - repeated the process by introducing the human analogues of the mouse genes into human skin cells, answering that question with an emphatic yes.
"Skin cells are at the end of the road of the developmental trip and do not have the capacity to evolve into anything else but a skin cell," Lysaght said. "This research fundamentally ran the tape backwards to the very beginning."
Though iPS cells are far from ready for therapeutic use, one future advantage could be compatibility with patients, since iPS cells can be made from a patient's own cells.
"The cells that were created were immunologically identical to that of the donor," Lysaght said. "So they could, for therapeutic purposes, be transplanted back into the donor without immunosuppression."
The days-old news has already turned heads outside the world of cellular and molecular biology. The breakthrough has been given the thumbs-up by President Bush, who this summer vetoed legislation to expand federally funded embryonic stem cell research.
"President Bush is very pleased to see the important advances in ethical stem cell research," said a White House press release issued last Tuesday. "By avoiding techniques that destroy life, while vigorously supporting alternative approaches, President Bush is encouraging scientific advancement within ethical boundaries."
But numerous challenges still face researchers interested in IPS cells. Yamanaka's 2006 study with mice reported an increase in cancer, probably because one of the four essential genes is also known to cause tumors in certain circumstances, Miller said.
A second problem involves the use of a viral promoter to insert the genes into the cells. Viruses can have unwanted side effects, and the method of transfection does not specify the location on the genome that the inserted DNA will occupy, which could have unpredictable consequences.
"We've got to figure out how to use these four genes to make a stem cell without using a viral promoter," Miller said. "It makes you nervous, using a potential disease-causing method."
Another problem involves the age of iPS cells. When stem cells are harvested from embryos, they have undergone very few divisions and have yet to face potentially damaging genetic mutations, Lysaght said. Cells taken from a middle-aged woman's face have undergone years of mutations, and reprogramming them into iPS cells doesn't reverse the process of aging.
"The cells that they picked out probably have an accumulated set of genetic mutations," Lysaght said. "When you clone, for example, those things seem to get reset, but that doesn't seem to happen in this process."
Finally, biologists still do not know what instruction needs to be given to a stem cell, induced or embryonic, to move it along the desired path to a specific cell type.
"There's still a lot of work left to do," said Professor of Medical Science Edward Hawrot. "Even though these stem cells in theory can become any cell type, we still don't know what signals to send."
Because of all of these limitations, it could be years before therapeutic treatments are developed.
"These problems mean you don't have something that's clinically ready for prime time," Lysaght said.
Still, the advance opens the door to new research opportunities and has ignited a fire under an already hot field. Though no Brown researchers currently study stem cells, Lysaght predicted that interest in stem cells would rise in light of the recent development.
Lysaght, who conducts research on diabetes, previously studied stem cells as a possible treatment for the disease but wasn't able to produce effective results.
"This is really the first olive out of the jar," he said. "Whether or not we'll go back and take a fresh look at this, we'll have to see."
