Primum non nocere!
The Web is rife with news stories regarding a paper just published in PLOS Medicine about a benign tumor that arose in a child treated with fetal neural “stem cell” therapy for ataxia telangiectasia in a Moscow clinic. Most of the reports are total crap, showing typical journalistic dilettantism, and spreading “stem cells are BAD” FUD. Just about the best news story I was able to find on the subject is (not surprisingly) on The Scientist website. The discussion that follows is also pretty interesting, so if you have a subscrption, be sure to check it out. There are a few points, however, I would like to elaborate on a bit further.
- There doesn’t seem to be any indication that the “stem cell” transplant had any chance of success at curing the disease. At this point stem cell transplants often result in restoration of functional neural circuits in animals, but only in very well defined types of lesions (rat or mouse models of Parkinson’s disease and Alzheimer’s for example). AT on the other hand is a very complex disease (for review see for example here or here) involving, among other symptoms, neurodegeneration, immune deficiency, and cancer susceptibility. Most knowledgeable commenters seem puzzled as to why the Russian team even decided to go through with it. Material gains? Slim chance of fame if by some miraculous coincidence it panned out? Genuine, although clearly misguided, hope to help? It is a mystery.
- How legal was the procedure? Most countries have very strict guidelines as to what treatments can or cannot be administered to patients and in what circumstances (clinical trial etc.). There doesn’t seem to be any indication of the procedure following any such guidelines. We could even go so far as to claim that it was experimentation on human subject, which is a serious crime pretty much everywhere in the civilized world. Related to the legal concerns are ethical ones. Were the parents aware of the risks and of the very dubious nature of the potential benefits? Even if they were, did the surgeons have the moral right to perform the procedure that they probably knew was not likely to produce any improvement in the patient?
- From a scientific point of view, there are several outstanding questions that the authors of the papers did not or could not answer, but which are very important if we are to consider human stem cell therapy for any disease:
- How frequently do such cases of tumorigenesis occur after stem cell transplantation? The question would probably best be answered by experimenting with non-human primates, since I presume that stem cells will behave very differently depending on the species. Also, did the stem cells in the tumor show any signs of malignant transformation or genomic instability or was the tumor entirely caused by the cells being in the wrong place at the wrong time?
- What role does immunodeficiency play in tumor generation from stem cell grafts? The patient had an impaired immune system. Did that matter? Did it promote successful engraftment? We might expect that at least some stem cell transplants will involve taking immunosupressants. How will that influence the potential of these cells to generate tumors?
- How good of a source of therapeutic neural stem cells are aborted fetuses anyway? Leaving the ethical question of abortion aside, maybe fetuses are simply not the best source available. Questions about immunological incompatibility, purification feasibility, and heterogeneity are among the most important.
- Perhaps the most crucial point is what effect is all that, predominantly negative, publicity going to have on stem cell research. The news of the first-ever FDA approved stem cell clinical trial are still fresh and already stem cells are getting all this bad rap because a few half-wits decided to go ahead and play around with injecting mashed-up fetal brains into a sick kid’s spinal cord. The non-scientific crowd is not going to dig into the difference between adult, fetal, and embryonic, stem cells. They will not care if the tumor was benign or cancerous. They will just hear “stem cells give tumor to a child” and that will be enough for them to form a skeptical opinion of stem cell research as a whole. On one hand, this may mean diminished funding for stem cell-based therapies, and loss of public and political support for CIRM-like initiatives. But maybe it will not turn out to be such a bad thing after all. Stem cells have been all the rage for about a decade now, and it is time we started to ask ourselves questions about whether the billions of dollars poured into this field was money well spent. Maybe it is also time we focused more on the safety of these highly invasive methods and the benefit/risk ratio. Overall, I am optimistic that in the long run this unfortunate experiment will serve as a warning sign for those who want to move too fast to bring untested therapies to the bedside to the detriment of the patients. Remember this, it will say: Primum non nocere!
Entry filed under: Biomedical research, Conduct of science, New and cool in biomed, Philosophy of science. Tags: abortion, ataxia telangiectasia, human research, neurodegeneration, PLOS Medicine, science, stem cell, stem cell research, transplantation, tumor.