Reply to Cheong et al.: Unicellular survival precludes Parrondo’s paradox

Parrondo’s paradox is a scenario in game theory in which a combination of two losing strategies (“losing” here defined as population decline) can result in a “winning” strategy (population persistence) when different strategies are used in different conditions (1). For example, hares that are constitutively either brown or white may suffer strong predation during the winter or summer, respectively, making both coat colors losing strategies. A hare that alternates between brown in the summer and white in the winter, however, can successfully avoid predation in both seasons. Cheong et al. (2) suggest that our model (3) fits Parrondo’s paradox, with unicellular and multicellular modes of existence as the two “strategies.” For Parrondo’s paradox to apply, three conditions must be met: (i) An exclusively multicellular life history strategy must be a losing strategy, (ii) an exclusively unicellular life history strategy must be a losing strategy, and (iii) switching between multicellularity and unicellularity must be a winning strategy. Here we take for granted that the third condition is true and examine the first two.

If a parent’s cellular degradation were inherited by offspring, multicellularity per se would be a globally losing strategy. However, germ–soma division provides a degree of protection from mutational degradation (4, 5), especially against the somatic amplification of mutations encoding potentially cancerous loss of cooperation. The paucity of examples of exclusively multicellularity organisms, that is, multicellular organisms that reproduce solely by budding or fragmentation without passing through a unicellular stage, suggests that exclusive multicellularity tends to be a losing strategy. However, with organisms like Hydra providing possible exceptions (6), we do not yet have a definitive answer.

In contrast, the falsity of the second requirement of the paradox, that exclusive unicellularity is a losing strategy, is unambiguous. While the unicellular stage in metazoans is typically brief and nonreplicative, exclusive unicellularity is a fantastically successful strategy employed by the majority of life on this planet. Therefore, our model does not fit the criteria for Parrondo’s paradox. Cheong et al. (2) seem to assume that alternation is the predominant strategy among species and ask how alternation between unicellular and multicellular stages allows life to persist. A more appropriate question is, Why attach such a dubious strategy as multicellularity to the tried-and-true winner that is unicellularity? with answers to be found via phylogenetic (7) and experimental (8) approaches. Our work (3) does not demonstrate any superiority of multicellularity but instead demonstrates the inevitability of aging via a mechanism that is specific to multicellular organisms.