Space travel has effects on planarian regeneration that cannot be explained by a null hypothesis.

We thank the editors of Regeneration for the opportunity to respond to the letter by Sluys and Stocchino (2017) (S&S), who take issue with our report of observations (Morokuma, Durant, & Williams, 2017) on planaria that spent several weeks aboard the International Space Station (ISS), in comparison with controls that stayed (similarly sealed) on Earth. First, we give a brief review of what we did and did not claim in the original study. Our paper describes what we observed in the “spaceexposed” animals upon return to Earth.We saw significant differences in behavior, water metabolite content, and microbiome composition. Moreover, one of the animals came back as a biaxial heteromorphosis (having heads on both ends of the main body axis). We did not claim to have determined which of the many aspects of the space travel experience (loss of gravitational field, reduced geomagnetic field, effects of highG-force or vibration during take-off and splashdown, etc.) induced these marked changes, nor did we claim to have identified the molecular mechanism by which the changes were induced. We were clear that this is (necessarily, given the logistics of space flight) a small pilot experiment and that many future experiments will be necessary to mechanistically understand the processes by which space travel interacts with biological systems. At the same time, our study reveals clear, statistically significant differences between space-exposed and Earthbound controls, which cannot be swept under the rugwithout rigorous argument. We now summarize the facts regarding the double-headed worm phenotype, which is the focus of S&S's critique. As far as we can tell, the argument by S&S is as stated at the end of their Abstract: “Double-headedworms have been amply documented as arising under experimental conditions as well as spontaneously in stock cultures of planarians.” The first part is a non-sequitur: certainly there are other experimental treatments that can cause the same phenotypeour laboratory showed that treating Dugesia japonica with gap junction blockers generates double-headed worms (Nogi & Levin, 2005; Oviedo, Morokuma, & Walentek, 2010). As we hope is clear from the text of our paper, we never claimed space travel to be the only way to induce double-headed worms or that double-headed worms had never been observed before. Regardless of the fact that a few other treatments can also induce this phenotype, such treatments were not present on the ISS and are quite irrelevant here. Moreover, the claim that double-headed worms arise spontaneously in stock cultures is misleading. Whilst a double-headed worm could form spontaneously, this is an extremely rare event; surely S&S are not suggesting that,