The recent upsurge in interest on the national scene in stem cell biology comes as no surprise to hematologists. Both as individuals and as a community, we are used to thinking about hematopoietic stem cells and how they grow. We are also comfortable with both hematopoietic growth factors as pharmaceutical stem cell stimulants and signal transduction inhibitors as hematopoietic progenitor inhibitors. As a result, in a real sense, we're all puzzled at the non-hematologists' sudden simultaneous fascination and confusion over stem cells -- what they are, what they can do, and what is safe and ethical to do with them. After all, the science of stem cells has been around and developing, carefully and productively, for decades. So, what is the significance of the current interest surrounding stem cells among non-hematologists, and how should hematologists respond?
I believe the answers are: "everything" and "we should lead the way, at all levels." We are in the midst of a scientific "paradigm shift," in the sense described by Thomas Kuhn in "The Structure of Scientific Revolutions." As he intuited and described, our view of nature occasionally changes cataclysmically, often following many years of incremental advances, when sudden, sometimes sociologic events conspire to create a sense of "Aha, so that's how it works!" Our whole cosmologic world view changed when Copernicus pointed out that the data suggested that the earth might revolve around the sun, and not vice versa. When Einstein pointed out that solving Maxwell's Equations from the point of view of both moving magnets and moving wires implied E = mc2, the implications were even more staggering. Precisely this sort of transformation is now happening in biology, under the rubric of stem cells, as we now see adult organisms as 'simply' the continuous, orchestrated production, differentiation, and organization of stem cells, throughout life. Rather than the adult pattern of organs being set early in life, with gradual and partial turnover of mature cells, the entire organism is now seen as continually re-emerging and re-developing. These are lessons that we hematologists have appreciated ever since the first colony assays were presented, but when considered in their broadest contexts these ideas have universally profound implications.
The emergence of this paradigm radically changes the way in which we approach literally every aspect of physiology and the ways in which physiology interacts with its intellectual neighbors, including chemistry, engineering, and pharmacology. Producing and manipulating stem cells will lead to the creation of new tissues for implantation (tissue engineering), modifying these cells for infusion will lead to long-term correction of lost function (stem cell gene therapies), and treating the most important diseases will require targeting the tissue-specific stem cells from which they spring (stem cell pharmacology).The implication of this paradigm shift is that nearly everything we teach in medical school needs to be reinterpreted, as will the way in which we develop and evaluate new therapies. For example, if John Dick at the University of Toronto and Mike Clarke at Stanford are correct, the only cells that matter within a mass of tumor cells are the most immature subpopulation with self-renewal capacity, i.e. the tumor stem cells, because all the other cells are destined to die. It is these cells, not the whole tumor mass, that we must study by RNA expression array analyses to discover signal transduction pathways we can target to selectively kill. And the incredible thing -- what makes this concept so extraordinary -- is that it must be right, at some fundamental level. Once it is pointed out to us, how else could the system be organized? That's what's amazing about a revolutionary concept, a true shift in paradigms -- once it's been articulated, it is hard to imagine how we thought beforehand.
So if this Stem Cell Revolution is upon us in this unavoidable way, why is it so important that hematologists stand up and take the lead? I believe that the scientific and medical health of society requires that stem cell biology be explained and promulgated carefully, completely, and creatively. Pockets of resistance need to be illuminated and convinced, and no one is better positioned to do this than hematologists, who understand these issues implicitly, both at the levels of basic science and patient care. Medical schools need to reorganize how they teach physiology and connect it with embryology. Stem cell biology cannot merely be seen as another special interest area for intellectual investment and government funding, but as perhaps one of the central organizing principles around which all such activities occur.
Our leadership in the forthcoming debates and developments will be extremely beneficial. As just one example, many non-scientists wonder why human embryonic stem (ES) cells need to be studied. The thought of thousands or millions of ES cell lines for individualized tissue repair raises all sorts of ethical spectres in the minds of some. On the other hand, we hematologists realize that perhaps the strongest motivation to study human ES cells is to understand the molecular details of how they grow and differentiate, so that we can apply these lessons to post-natal stem cells, and to identify pathways involved in diseased stem cells in the adult. Having personally had the experience of explaining these ideas to responsible but concerned local legislators, I am convinced that the hematologist's experience and perspective makes a huge difference.
Thus, while we hematologists have long been implicit stem cell biologists, it is now time for us to make that belief explicit, and to lead the way in articulating this renaissance in our medical schools, research communities, and our practice. The Stem Cell Revolution is upon us, and we must be at the vanguard.
