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Of Adaptive Improvisation, self-stabilization of stressreduction, etc.) are driven by necessity. Quality of written English: Acceptable.Reviewers’ report 3: Dr. Itai YanaiThis reviewer provided no comments for publication.Abbreviations MGEs: Mobile genetic elements. Competing interests The authors declare that they have no competing interests. Authors’ contributions YS, MK and ME formulated the hypothesis and wrote the manuscript. All authors read and approved the manuscript. Acknowledgements We would like to acknowledge the inspiring and pioneering work of Prof. Erez Braun (Technion, Israel) and Prof. Shimon Marom (Technion, Israel), and the insightful research of Dr. Shay Stern and members of our lab. These studies were instrumental for developing a perspective which motivated and helped shaping these ideas. We thank Prof. Erez Braun (Technion, Israel), Prof. Naama Brenner (Technion, Israel), Prof. Eva Jablonka (Tel-Aviv University) and Prof. Shimon Marom (Technion, Israel) for ongoing discussions of this subject and related ideas. We would also like to thank Prof. Michael Walker (Weizmann Institute of Science, Israel), Prof. Yitzhak Rabin (Bar-Ilan Univ.), Prof. Denis Noble (University of Oxford, UK), Prof. Zvi Livneh (Weizmann Institute of Science, Israel), Prof. Eytan Domany (Weizmann Institute of Science, Israel), Prof. Nir Friedman (Weizmann Institute of Science, Israel) and Dr. Yael Heifetz (Hebrew University, Israel) for INK1117 site helpful discussions. We thank Prof. Moshe Szyf (McGill University, Canada) for helpful discussion of potential implications to cancer treatment. We also thank Profs. Michael Walker, Eva Jablonka, Denis Noble, Yosef Shaul, Eytan Domany and Dr. Idan Efroni (NYU, USA) for comments on the manuscript, and we thank Shira Holand for contribution to the preparation of the graphic presentations. This work was supported by the Sir John Templeton Foundation (grant ID: #40663) and the ISRAEL SCIENCE FOUNDATION (grant No.1860/13). Yoav Soen is Incumbent of the Daniel E. Koshland Sr. Career Development Chair at the Weizmann Institute. Received: 8 May 2015 Accepted: 18 NovemberReviewers’ comment I appreciate the extended response given by the authors to my comments. I must admit that the level of abstraction in this discussion remains largely above my head. Hopefully, other, theoretically better versed readers receive inspiration from this treatise. Quality of written English: Acceptable.Reviewers’ report 2: Dr. Yuri WolfSoen, Knafo and Elgart touch upon an important topic of the nature of adaptation to novel challenges. To me, however, this discussion seems to be a bit too vague and general. Quality of written English: Acceptable Authors’ response: As indicated above, we revised the manuscript (and its title) to provide a clearer description.Reviewers’ comment The authors improved the presentation, but the main problem remains – in my opinion it is impossible to criticize or embrace ideas, formulated in such a general terms. Even the very existence of a problem in need of solution is not entirely obvious – yes, none of the genericReferences 1. Curtin NJ. DNA repair dysregulation from cancer driver to therapeutic target. Nat Rev Cancer. 2012;12(12):801?7. 2. Fuchs Y, Steller H. Programmed cell death in animal development and PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28045099 disease. Cell. 2011;147(4):742?8. 3. Ouyang L, Shi Z, Zhao S, Wang FT, Zhou TT, Liu B, et al. Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis. Cell Prol.

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