Regenerative medicine: the promises and perils of a Promethean task

Apparently, ancient Greeks somehow learned that human liver could regenerate after damage. This information was connected in their intuition with their most powerful ability, that to produce fire. What is less often remembered is that in Hesiod’s version of Prometheus’ myth, after he has stolen the fire, Zeus also sent Pandora, the first woman, to all-male human beings in retaliation, counting on their greed as their greatest weakness. Despite Prometheus’ warning, human beings accepted Pandora’s jar as a gift from the gods, from which were released ‘evils, harsh pain and troublesome diseases which give men death’ (of note, again a medical connotation). Eventually, Pandora shut the lid of the jar, too late to contain the evils that escaped, and what remained inside was the hope. Thus, not only the evils were unlashed, but even hope became inaccessible: an allusion to the subjective effects of disease? It is largely assumed that the focus of the myth was on the punishment that the Gods inflicted on Prometheus, for his sacrilegious courage. If so, the only positive information, that on liver regeneration, would have remained at the periphery of the legend. But let’s try another reading of this myth, by bringing the surprisingly advanced medical knowledge to the centre: maybe these genial Greeks wanted to create a story grandiose enough, to be commensurate with the depth of their biological discovery, and have imagined a punishment ferocious enough to highlight by comparison the power of this organ repair. They came up to link the genealogical sin of the humankind – in their version – to this astonishing ability of at least a part of a living body to resist, be it momentarily, destruction and death. Thus the dream, if not the goal, of regenerative medicine was defined in this beautiful, ∼3000 years old myth. Nowadays, humankind seems to re-enact this tragedy (in the Antique meaning of the word), at another level: after taming the atomic fire, with new courage and ambition, but also with our perennial greed for goods, we now re-discover the power of tissue regeneration and that of the driven, medically justified, tissue repair or even de novo creation by ‘tissue engineering’. Thus, stem cells became the next revolution in biology. Most likely, soon there will be no organ spared from our attempt of intentional repair using these miraculous cells. But what are the stem cells anyway? What are the stem cells of the adult organism? What about cell plasticity and trans-differentiation? How do these cells naturally contribute to cell turnover and organ maintenance, and how do they change in aging? Could these cells be determined to a reversed differentiation (in fact, de-differentiation) pathway for resuming their journey to another phenotypic destination? How efficient is tissue engineering likely to be? And (thinking of Pandora), what are the bioethical implications of this regenerative medicine?…. Based on the often sad lessons of the past, there is little reason to believe that with these great gifts evils would not also come, and once released these evils could be ever brought back into Pandora’s jar. This new Progress in Regenerative Medicine Reviews series will address these and related questions in the following issues of the Journal. We are inviting the pioneers of this exploding field to share with our readers the essence of their exciting discoveries, to express their opinions about the current state and to forecast the future. By design, less emphasis will be placed on an exhaustive covering of the topics, already populated by expert reviews. Symbolically, the opening of the series is entrusted to Dr. Darwin Prockop, Director of the Institute of Regenerative Medicine in Temple, TX, member of National Academy of Sciences and of the Institute of Medicine, who is a pioneer in mesenchymal stem cells research. Besides a succinct discussion of the classical interpretations of their roles, he brings forth arguments for a new paradigm to explain the beneficial effects of these cells, namely that of formation of transient ‘quasi-niches’via inter-cellular communication of the more primitive, healthier cells with the injured tissue. In conclusion, accepting Pandora’s last gift, we hope that this new Reviews series is going to be not only a source of solid information about the latest progress in the field, but also a forum for courageous debate about the promises and perils of the Promethean tasks, which lay ahead of Regenerative Medicine.