Discovery finally puts end to stem cell debate

STEM CELL BREAKTHROUGHS:Advances in stem cell research easily rank as the most innovative scientific discoveries of 2007. Aside from representing remarkable science, these breakthroughs have the potential to deliver powerful new treatments for formerly intractable diseases.

Eyes have come to glaze over at the very mention of stem cells, however. They represent a difficult concept to understand for many people and too frequently have been in the news for all the wrong reasons as people haggled over the ethical conundrums that surrounded them.

Yet stem cells are going to change medical practice in a fundamental way and everyone should understand what they are and what they can do. This is doubly true given the import of the latest discoveries, and the fact that in a single stroke they have swept away all of the ethical concerns voiced about stem cells.

The most important research announcements have coincidentally been clustered together towards the end of this year. The most recent, released last Friday, December 6 th, described how stem cells were used to reverse a blood disorder in lab mice. Mice and humans are miles apart but the mouse work does represent a proof of concept that without doubt will in time be repeated in humans.

Stem cells and the ethical controversy that has dogged their study from the start impacted on the public in 1998 when Prof James Thomson of the University of Wisconsin first harvested them from an early stage human embryo. The embryo was destroyed in the procedure, something that immediately incensed conservative and religious groups who viewed it as the murder of potential human life.

Yet medical researchers persisted with the work because of what these same stem cells could do. Life is triggered by the fusing of just two cells, and these divide a number of times before stem cells start to emerge. These same stem cells in turn have the potential to turn into any of the 200 plus cell types found in the body, a capacity that allows them to be described as pluripotent.

It is their pluripotency that so attracted the researchers. If they could learn the biochemical processes that turned a stem cell into say a muscle cell or a nerve cell then perhaps large numbers of these same cells could be used to reverse the damage caused by a heart attack, stroke, multiple sclerosis or Parkinson's disease.

The scientists continued their studies even as the ethical issues were politicized by lobbies opposed to the destruction of embryos. This reached its zenith several years ago when President Bush froze federal funding for some aspects of stem cell research.

The issues became further confused with research announcements related to cloning. Dolly the cloned sheep was announced in 1996 and other species were cloned soon after. Those working with stem cells also began using these and other cloning techniques to find a way to clone embryos rather than destroy fertilized human embryos.

Researchers had been using "left over" frozen embryos donated by couples attending fertility clinics, but then cloned embryos began to appear and from them self perpetuating stem cell lines. These were studied to understand the mix of growth factors and other substances needed to make them change into specific cell types.

Yet even these approaches were shunned by conservative thinkers who argued that the toll was too high if even one embryo was sacrificed to produce stem cell lines that might cure diseases.

Then in November the first of three major stem cell papers was published. A research group in Oregon announced it had used adult monkey skin cells and eggs to produce a Dolly-type clone, in effect an artificial embryo.

Even as the ethicists were considering whether this clone still represented potential life making it wrong to destroy it, the second paper emerged. It was actually a pair of papers published on November 20th and announcing a startling breakthrough.

Thomson's group in Wisconsin and another led by Shinya Yamanaka at Kyoto University in Japan had both found a way to take adult human cells and "reprogramme" them to become stem cells. Their astounding announcements finally destroyed the decade old ethical issues related to embryos. There was no embryo, these stem cells had come directly from adult cells, and were converted into stem cells that in tests so far seem indistinguishable from and just as pluripotent as stem cells taken from embryos.

This news had hardly sunk in when the third paper from collaborators in Massachusetts and Alabama was released by the journal Science on December 6th. Jacob Hanna and colleagues took skin cells from adult mice suffering from a form of sickle cell anemia. These cells were reprogrammed to become pluripotent stem cells and then techniques were used to repair the damaged gene known to cause the disease.

These "corrected" stem cells were cultured to become blood cells and these new cells, now free from disease, were then transferred into the mice. "Our results provide proof of principle for using reprogramming combined with gene and cell therapy for disease treatment in mice," the authors write.

It will be some time before researchers are confident enough to attempt such treatments in humans, but from now on the research can advance on a very wide front. The reprogramming techniques are relatively simple, much more so than cloning, and the ethical constraints are now gone.

Now, labs all around the world, including in Ireland, can now join in a research effort that will in time see diseases overcome using pluripotent human stem cells that have the benefit of being a perfect genetic match given the cell donor will also be the cell recipient.