Stem Cells’ Self-Renewal or Cell Biologists’ Self-Cheating?

In a commentary published in October 2005 I predicted that the discovery of animal stem cells might be awarded with a Nobel Prize (Liu, 2005e). I appraised McCulloch and Till for their pioneering work in that discovery and wished them to be the recipients for the award if it happens.

Today, I still believe that the discovery of animal stem cell is a major breakthrough in biomedical research. However, I must say that a fundamental conceptual mistake on stem cells has obscured the stem cell research and possibly delayed the advancement of a correct knowledge on stem cells. As the first people who proposed that misconception McCulloch and Till should take at least some scientific responsibility.

That misconception is that stem cells can “self-renew”, i.e., generating a new daughter cell identical or similar to the mother cell. This so-called “unique” feature of stem cell was described very early in the discovery of animal stem cells (McCulloch and Till, 1964; Siminovitch et al., 1963). Since then the capacity of “self-renewal” has been regarded as one of the two essential defining properties of stem cells (McCulloch and Till, 2005). Indeed, “self-renewal” has become such a popular terminology that is in fact inseparable from stem cell research. A quick search for this term in PubMed in the title field alone yielded 400 “matches” (performed on December 17, 2006). Many of these matches appeared in the very “top” scientific journals such as Science, Nature, Cell, PNAS, Blood, and Stem Cells with 6, 6, 12, 30, 25 and 24 records for each journal respectively. As stem cell research becomes trendy and trendier, self-renewal will no doubt become a hot and hotter phrase in “top” scientific journals as well as mass media.

Then why would I call “self-renewal” a misconception?

Firstly and the easiest, it has now been shown in many cases that “self-renewal” in fact is not unique for the stem cells. The “self-renewal” phenomenon has been report for many other non-stem cells in the later stages of cell differentiation hierarchy (McCulloch et al., 1991; Okubo et al., 2000; Takakura et al., 1997). So “self-renewal”, even if it is a true process or correct term, should not be regarded as a defining feature for stem cells. Using this non-specific (artificial) feature to describing a specific (real) cell population has added only confusion to the stem cell research.

Secondly and more mind-torturing, “self-renewal” is logically impossible if a mother cell “dies” because it “divides” into two daughter cells. In the common sense or by the conventional wisdom, “renewal” means the quality or state of an object being renewed. “Self-renewal” thus should mean something renews to its own previous quality or state. But for the object to renew itself, it must keep its existence. For a life to renew itself, this means that it must remain alive so that it can renew to its original new state after it becomes some old different state. However, if a mother cell dies or simply disappears in the “division” process, how could it renew itself? The dead cell has to be resuscitated and that “resuscitation” has to be done by other.

Thus, from both objective observations and subjective reasoning, “self-renewal” should not be regarded as a unique or a logical feature for stem cells. Then why would stem cell biologists continue to play the “self-renewing” tune for stem cells?

I believe, besides the lack of any real correct knowledge on stem cells, a strong motivation for (at least some) stem cell biologists to continue an incorrect knowledge is that “self-renewing” concept serves better for their money-seeking research careers.

“Self-renewal” is a very good selling point for grant application and/or fund-raising because it just touches the very nerve of human being’s wish to live longer if not forever. Interestingly, the revitalization of the long-dead hope for immortal human life has been largely the result of recent success in stem cell research. The magic effect of stem cell replacement in treating some diseases has made stem cells the much demanded commodities in regenerative medicine or, even further, anti-aging treatment. In this modern version of the immortality dream, stem cells can give hope for immortality because they can be “self-renewed” indefinitely. Thus, when a multicellular organism can be given such “immortal” cells to replace its damaged or worn out cells, its life span can be extended indefinitely.

That is the catch point played now and played well by many especially those very successful stem cell biologists. In fact, if one read just the mainstream scientific literature especially those in the “top” journals, one may feel that possibility of longer human life is not only very likely but also very close. Why? because The Fountain (the name of a new film) for “The quest for immortality” (the title of a Nature article) (Marris, 2006) has been discovered and “the waters of the fountain of youth may include ingredients that among other things preserve numbers of “high quality” stem cells” (Van Zant et al., 1997).

However, as I clearly stated in a series of articles that are all rejected by the “top” journals (Liu, 2005f, 2006a, c), no cell including stem cells can be immortal because all cells will age and die (Liu, 1999, 2000a, 2004a; Liu, 2005a). The so-called “self-renewal” of stem cells is an illusion of stem cell biologists for a normal process of cell reproduction that is common for all types of cells including the so-called “immortal” bacteria (Liu, 1999, 2004b; Liu, 2005a; Liu and Zhang, 2004a, b).

Thus, while I do believe that stem cells have some unique properties and may even be more valuable than other non-stem cells for biomedicine. I denounce the continued cheating of playing the “self-renewal” concept, especially solely for the purpose of attracting money for one’s “scientific” career by touching the immortality nerve of a human being.

Instead of sticking to some fictional features of stem cells I strongly encourage stem cell researchers to correct some wrong definitions assigned to stem cells. It is time to put the immortality claim (not just for stem cells but also for any other cells) to death (Liu, 2006a, j). I appeal cell biologists to endorse those “odd” but objective scientific observations (Liu, 1999, 2004b; Liu, 2005a; Liu and Zhang, 2004a, b) and “unconventional” but truly logical reasoning (Liu, 2000a, b, 2004a; Liu, 2005b, c, k) and denouncing those superficial/artificial findings (Stewart et al., 2005; Watve et al., 2006) that comply only to out-of-touch dogmas (Liu, 2005c; Liu, 2005g; Liu, 2006b, e). Stem cell biologists as well as all other kinds of cell biologists including microbiologists should open their minds (Liu, 2006g, h; Liu, 2006k; Liu, 2006m, n, p) to appreciate some alternative views (Liu, 2005d, j; Liu, 2006l) and take these different insights into evaluation and interpretation of their experimental observations and/or theoretical thinking (Liu, 2005i, 2006d, f, h, i, p). Instead of wasting one’s finite life span to search for the non-existing immortality ingredients in the fictional “fountain of youth”, I suggest cell biologists look hard for the real cause of aging and death not just for the multicellular organisms but also for the unicellular organisms (Liu, 2005h, 2006o).

“Self-renewal” is a wrong concept for stem cells or any other kinds of cells. Let’s do not cheat ourselves by continuing this pseudo-scientific theme of futile search and research.

References

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* This manuscript was submitted to Nature Medicine on December 18, 2006. Nature Medicine rejected it the next day on the ground that “it would not be well suited to Nature Medicine”. It was then submitted to Cell on December 19, 2006 but it was rejected, too. The publication here contains the exact content as submitted to Cell except for the added highlight and keywords.

*Logical Biology* 6 (4): 106-109, 2006	COMMENTARY
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