A cluster of recently published papers details the progress that is being made engineering stem cells. It is simultaneously bolstering the critics of Bush’s embryonic stem cell ban by showing the potential of this technology, and also bolstering Bush’s supporters by showing that harvesting ES cells from fertilized embryos may not be necessary. The progress is further ironically based upon research with ES cells – so scientists have used ES cells in research that hast the potential to render ES cells obsolete.

Regardless of the ethical and political twists – the developments are very cool and are likely to pull us out of this political morass (but also likely to throw us into others).

The first paper is authored by Shinya Yamanaka of Kyoto University in Japan and is published in Nature, the second is by Rudolf Jaenisch at the Massachusetts Institute of Technology and is also published in Nature, and the third is by Konrad Hochedlinger at Harvard and is published in Cell Stem Cell. (Here is a summary of the three papers.)

What makes a stem cell a stem cell is that it is pluripotent – which means that it can differentiate into different kinds of cells. ES cells can turn into any kind of cell in the body (a necessity since one ES cell can become an adult) – so they are maximally pluripotent, also called totipotent.

The researchers took a fibroblast – a basic connective tissue cell – from a mouse fetus and then used a retrovirus to insert four genes that are known to be associated with pluripotency. These genes reverted the fetal fibroblasts into pluripotent cells – so called induced pluripotent stem cells, or iPS cells. To test the extent of their pluripotency they injected labeled iPS cells into a an early mouse embryo. When the embryo developed into a fully developed mouse, they checked and found that labeled descendents of the iPS cells were found in every tissue.

The next step was to inject iPS cells into a tetraploid embryo – an embryo created by the fusion of two embryos and incapable of developing on their own. Therefore the iPS cells would have to be able to form into every kind of cell if order for a mouse to develop, and this is what happened. This is really the exciting part of the breakthrough, as it shows these iPS cells have the same potential as ES cells.

As exciting as this is, there is still some work to do before we can declare ES cells obsolete. First, using retroviruses to insert genes is still tricky business. Evidence of this is that 20% of the mice grown from iPS cells developed tumors, likely because the retroviruses also turned on cancer forming genes. So this technology needs to be tweaked or alternative found.

The second major limitation is that fetal mice cells were used in these studies – the use of fetal tissue will not save us from the political barriers to this technology. The researchers are confident that they can replicate this work using adult mouse fibroblasts – but they still need to prove it. Once this is done then they need to replicate the technology with human cells.

So while there is still work to do, and unforeseen problems may crop up, the technology is incredibly promising and these advances definitely take us a huge step closer to the fantastic promises of stem cells. The specific application that this type of technology points to is patient specific stem cells – in other words, making stem cells that have your own DNA. This is crucial because then any tissue grown from such cells for implantation will be you – there will be no risk for rejection. This, of course, could revolutionize organ transplantation. It could lead to growing replacement organs to be transplanted, or even developing patient specific cells that can be injected into failing organs to regrow them from within – eliminating the need for surgery altogether.

It will also be interesting to witness the political battles that will surround this technology. It is likely to be heated, and there are intense emotions on both sides. On the one hand we are dealing with cells that have the potential to be people and we are attempting to control the basic machinery of life. I have no personal problem with any of this, as long as the technology (like any technology) is used ethically. But many will recoil from this out of either traditionalism or just moral queasiness.

On the other side, the technology has the potential to save lives and cure the worst diseases that afflict humanity. Stopping or even hampering such research therefore may come with an enormous human cost.

Although the current ethical battles seem to be slipping away as the technology advances, new ones are likely to take their place. I think the best outcome will occur if we continue the ethical conversation in a very serious and open-minded manner, while letting the scientists get on with the research.