Rebuttal of Estep et al . Submission by Aubrey de Grey

Estep et al.’s Challenge tactics centre on repeating the word “unscientific” as often as possible in the apparent hope that this will render the judges oblivious to the complete absence of substance in their submission. Particularly incongruous is their accusation that I use the media to skirt expert criticism, when the SENS Challenge itself is my most conspicuous effort to do just the reverse, exposing the public reticence of SENS’s off-the-record detractors and thereby forcing them to make their supposed case in print. Their summary consists entirely of claims of their own scientific infallibility, aspersions on my methods and credentials, and blurrings of the distinctions between the methods of science and of technology. Not wishing to descend to such tactics, I will ignore Estep et al.’s invective and instead summarise here my detailed enumeration [posted on the TR website] of the flaws in the specific criticisms given in their supplementary material [also posted there]. Estep et al. state that: “Any claim regarding extreme extension of life span in higher organisms must be regarded with extreme skepticism, and the evidentiary and logical support for such a claim must be as extraordinary as the claim itself.” This is correct for claims that such extension has been achieved, but not for claims that a particular plan for achieving it might (not would) succeed. Since human aging causes immense suffering and death, any plan that might dramatically postpone it merits detailed expert review; only if its chance of success can be evaluated as negligible should we ignore it. Similarly, their statement: “human aging is not well understood, and any prospective therapy or cure must be regarded as pure speculation... any claim of a cure for human aging prior to evidence of therapeutic efficacy, or prior to a scientifically supported mechanistic model of human aging, must be pseudoscience” forgets that, whereas science is about reducing our ignorance, technology is about sidestepping our ignorance. Estep et al. highlight the three most challenging of my seven categories of aging “damage” and scorn my preferred approaches to combating them. One such approach, allotopic expression (AE), has been pursued experimentally for 20 years. The others were each the focus of a full-day workshop, one of them NIA-sponsored, involving eight eminent experimentalists spanning all relevant disciplines, whose enthusiasm for the approach was demonstrated by coauthorship of the article arising from the respective workshop – 14 of 16 attendees signed and the others declined for reasons unrelated to their evaluation of the approach (see ref. 3’s acknowledgements). Faced with this evidence – rather stronger than mere attendance at conferences – that my proposals are wholly legitimate, Estep et al. simply omit it from their critique. The section of one of these articles that they deride as “pseudoscientific pretense” was contributed by Prof. Bruce Rittmann, who, as shown by his biography, cannot easily be dismissed for lacking relevant experimental expertise (as Estep et al. so blithely dismiss me). I reject experimentalists’ criticisms only when I have detailed, robust scientific arguments and the support of more appropriately specialised experimentalists. Estep et al. evidently overlook how thoroughly their diatribe fits their own definition of pseudoscience. In my interactions with experimentalists exemplified above, I always provide all the facts known to me that might help them to evaluate my proposals reliably. By contrast, Estep et al. repeatedly omit key facts that Estep certainly knows (though his coauthors may not). They lampoon my prediction from 2000 concerning AE, without mentioning that I made it assuming that Zullo et al.’s seminal breakthrough (which I presented at the time I made the bet) would be published imminently in Science (where it was then in review), stimulating effort to perfect this approach; in fact, followup effort remained negligible until it was finally published in 2005. Thus, it is grossly misleading to suggest that my overoptimism arose from underestimating how hard AE is – and I fully explained this recently in a reply to Estep on a well-known mailing list. Similarly, Estep et