I finally broke down and set aside an hour and a half to read Estep's submission, de Grey's rebuttal, and Estep's response.
Intense shitfight, if you ask me. de Grey doesn't sink as low, but the implied (as opposed to Estep's explicit) ad hominems still run thick. Overall, I think de Grey wins for style, but I suppose I can't say I'm unbiased.
As for content, I'd have to read all the supplementary material and references, which of course I'm not going to do.
But based on the arguments Estep et al. put up, here's my take:
The only points they made any traction on were nDNA mutations and (especially) epimutations, and WILT.
Before I address these, I'd like to point out that their arguments against allotopic expression and bioremediation were poor at best. de Grey handily answered these points in his rebuttal, so I'll move on to the response.
Estep et al.'s response to de Grey is even more puzzling. They basically admit that their statement:
even if accomplished, there is insufficient evidence to conclude that mitochondrial genome decay limits cellular or organismal life span more than other molecular pathologies within these same cells, e.g. non-oncogenic decay of the nuclear genome or epigenome
was basically there to fill space, as it certainly wasn't an argument. They then proceed to more hand-waving about how difficult the problem is, without explaining why it's so difficult. "It's just hard. We say so."
They then move on to microbial hydrolases. It's hard to judge here, because they dive into technical territory I haven't yet ventured. But it sounds like they're just saying it's hard again, not that it's impossible. By way of example, they're saying that it's the kind of "difficulty" an engineer would have in designing a rocket to go to Mars using only chemical propellants (i.e., no "nuclear" shortcuts, etc.), as opposed to the kind of difficulty of designing a
single-stage rocket to go to Mars. The latter is clearly much more difficult and borders on impossible for scientific reasons (simple math, really, the amount of fuel needed would be tremendous, and the structure would have to be so light that it would be impractically fragile). The former is simply difficult from an engineering perspective (witness the gigantic effort it took to get to the Moon in the 1960's, let alone trying to get to Mars), but not obviously ruled out by our current scientific knowledge.
de Grey isn't proposing something obviously nearly impossible (e.g., single stage to Mars with chemical propellants). He's proposing an engineering problem that's very difficult (e.g., a rocket [perhaps three stages] to Mars with chemical propellants).
But where Estep et al. made some traction was on nDNA damage and WILT. Mind you, it's not that they pointed out anything new to us. It's just a helpful reminder that SENS as currently constructed faces the grave risk that nDNA damage will be demonstrated beyond a reasonable doubt to matter to aging, perhaps even sufficiently to warrant a change in stance from de Grey. But does that mean that SENS, as a model or prototype of a way of adding decades to human lifespan, is useless in its present form? Surely it couldn't be that difficult to add a strand to SENS to deal properly with nDNA damage. If the goal for effecting escape velocity is to add, say, two decades to lifespan, then isn't it fair to say that even a moderate improvement in nDNA health—say from the nDNA profile of an 80-year-old to the nDNA profile of a 60-year-old—would be sufficient to help out in this regard? Remember, the strands of SENS have never been claimed by de Grey to cure aging: they simply buy enough time to allow the next generation of biotechnology to add even more decades, ad nauseam. They don't need to be perfect; they just need to be good enough.
On WILT, they rightly point out that there are complications with removing telomerase. On one front, they suggest an increased frequency of certain cancer types, which is hardly surprising. What they fail to grasp is that, while the number of such cancers might increase, none of the tumors should survive long enough to become life threatening. What's life-threatening to a mouse isn't relevant to what's life-threatening in an organism 10,000 times bigger. For one, cancers don't need to metastasize in mice to become life-threatening; in humans, metastasis is the norm for life-threatening cancers.
On another front, they point out that one of the subunits of telomerase has non-telomere-regulating functions, and deleting it could compromise stem cell health. I believe de Grey has covered that one before as well, somewhere in our SENS archives, but I've lost count of the number of uses for telomerase: telomere lengthening, stem cell mobilization,
DNA repair enhancer,
apoptosis inducer,
etc.,
etc.Actually, in looking back, I suppose they didn't make as much traction on WILT as I thought. It sounded impressive, but it's nothing new. At any rate, I don't actually expect WILT to be used in mainstream medicine, but if, 20 years from now, it becomes clear that it's the only available way to deal with cancer, then at least it'll have been pondered over and researched.