Simple-minded laymen may believe that scientists are on the verge of being able to manipulate stem cells. But some thoughtful biologists are questioning the very notion of what a stem cell is.

An opinion piece by Arthur Lander in the open-access Journal of Biology, argues that the idea of stem cells could be a dead end, much like the mysterious substance “phlogiston” which was sought by chemists in the 18th century. Before it was learned that matter burns by taking up oxygen, chemists explained combustion as the release of phlogiston. Only when it came to pinning down its distinctive physical properties did it become clear that phlogiston did not exist.

Professor Lander, Director of the Center for Complex Biological Systems at the University of California, Irvine, argues that neither of the two properties that define “stem cells” as they are popularly discussed, potency and self-renewal, can be ascribed an exclusive molecular basis, and that both are seen in cell types not usually described as stem cells.

He said, "It is curious that, after 45 years, we are unable to place the notion of 'stemness' on a purely molecular footing. Of course, the fact that a goal has not been achieved after a long time does not mean that the answer is not around the corner. But it does give one cause to wonder whether something we are doing needs to change, either in the question we are asking or the way we are approaching it".

Lander feels that “stemness” should be considered a property of systems, rather than individual cells. A system with stemness is one that can achieve a controlled size, maintain itself homeostatically, and regenerate when necessary. He argues that such behaviors naturally emerge as a consequence of basic engineering principles of feedback control.

One practical consequence of an inaccurate understanding of the precise nature of stem cells may be the assumption that targeting of “cancer stem cells” with chemotherapy will stop tumors.

In an interview in The Scientist, Professor Lander explained that like phologiston, “the concept [of stem cells] can have a perfectly good operational definition and still refer to nothing that actually exists”. It could be that if stem cells are taken out of their context, or “niche”, they may not behave the way that they do in a living organism.

What about the latest development, pluripotent stem cells created from skin cells by reprogramming 3 or 4 genes? Lander says that this could be a red herring. The unipotent skin cell certainly becomes pluripotent, but it may not be a genuine stem cell.

Lander is not arguing that work with stem cells is a waste of time. The notion of phlogiston was a conceptual breakthrough that helped chemists conduct experiments and share ideas and eventually led to the correct explanation. But his unconventional theory does suggest that regenerative medicine may still have a long way to go. ~ Journal of Biology, Sept 21; The Scientist, Sept 29