cron-web.org

[A1CR]

[Posted on behalf of MR]

All:

> CRONie_AP wrote:
> Ideas regarding how life may be extended in years of Dr. de Grey are being
> challenged in a competition.
>
> Random Samples
> Science 14 April 2006: 171
> AGING BET
>
> A scientific competition between Jason Pontin, editor in chief of the
> Massachusetts Institute of Technology's (MIT's) Technology Review, and
> biogerontologist Aubrey de Grey of Cambridge University in the U.K. is
> heating up with the announcement last month of the panel of judges.
>
> Pontin is challenging de Grey's prescription for extending the useful human
> life span ... Frustrated by scientists' reluctance to criticize it in
> public, he proposed a contest last July. The $20,000 prize will go to the
> submission that best demonstrates SENS "so wrong that it is unworthy of
> learned debate," says Pontin. ... The original prize fund of $10,000
> donated by the magazine doubled
> when The Methuselah Foundation, de Grey's organization, tossed in an
> additional $10,000.

[And see:

http://www.technologyreview.com/BioTech-Genomics/wtr_16593,312,p1.html

CRONie_NB wrote:

> Kidding, of course. What kind of competition is this?
> It is sort of like a religious group having a competition for
> the best essay to prove evolution is wrong. With a forgone
> conclusion someone will win the $20,000.

The _Science_ strory makes it sound that way, but it's not really, first because the judgees are an independent panel vetted by both sides, and second because at this point, despite what the Science story says, Pontin's position is significantly more nuanced. Pontin originally wrote an unbelievably vicious editorial attack on de Grey (1) and published a feature on him that hand-wavingly dismissed the platform without credibly engaging the science and indeed by saying that it will inevitbaly fail because of the perils of doing the one thing that SENS (unlike more conventional proposals for interventional biogerontology) does NOT do: perturbing metabolism (2). Pontin felt justified in doing so, not because he had himself undertaken a detailed study & assessment of SENS, but because he had done what reasonably passes for a proper assessment amongst journalists: gone around, polled a few gerontologists, and foudn that they dismissed his ideas out of hand. Crucially, however, they all did so ANONYMOUSLY and without detail: none were quoted by name, as in so many previous pop press stories in which unnamed biogerontologiests are said to say that SENS is a fantasy.

The readership absolutely lambasted them for these articles, and so Pontin went back to ask some of thse folks to step forward with their rebuttals. With the exception of a weak effort by Pete Estep of Longenity (an occasional, and generally quite insightful, poster on CR Society; his group at least WAS working on CR mimetics -- the leading proposed anti-aging interventioin).

Surprise: none of the scientists they'd previously contacted was willing
to go on the record. Pontin contacted Cynthia Kenyon, and even announced on his blog prematurely that she'd accepted the challenge (3) -- but she bowed out (4). This became an increasingly intense source of irritation & embarrasment to Pontin, and also an increasing burden on his intellectual honesty, and he expressed "sorrow and contrition" about the whole sordid affair.

Thus, the TechRev prize was likely in part still an attempt by Pontin to shore up his original critique, but it's also at this point something more:

----------
In my reply to our readers, whilst conceding nothing, I [Pontin] promised to find a working biogerontologist who would take on de Grey’s ideas. But while a number of biologists have criticized SENS to me privately, none have been willing to do so in public.

This silence is puzzling (de Grey, less charitably, calls it catatonia”). If de Grey is so wrong, why won't any biogerontologists say why he is wrong? If he is totally nuts, it shouldn't be so hard to explain the faults in his science, surely?

One possible explanation for the silence of biogerontologists is that criticizing SENS would require time and effort—and that working scientists are too busy to waste time on something so silly. Another explanation (one obviously preferred by de Grey) is that biogerontologists reject SENS out of hand without examining its details.

Technology Review thinks it would be useful to determine which of the two explanations is correct. If SENS has some validity, then we should take it seriously. Because if we can significantly extend healthy life, we will have to ask — should we?

Regardless of which explanation is correct, biogerontologists apparently
need an incentive to consider SENS. To that end, Technology Review is announcing a prize for any molecular biologist working in the field of aging who is willing to take up the challenge: submit an intellectually serious argument that SENS is so wrong that it is unworthy of learned debate, and you will be paid $20,000 if it convinces independent referees.

http://pontin.trblogs.com/archives/2005/07/the_sens_challe.html

------------

The Methuselah Foundation is now in on it, precisely because they (or rather, "we": I'm Aubrey's research assistant, as most folks know, and funding for my position comes thru' MF -- but not, I emphasize, thru' funds donated to the MPrize for breakthrough anti-aging interventions in mice <http://www.MPrize.org> , all donations to which go DIRECTLY into the Prize) feel justified confidence that no one can, in fact, mount a really credible rebuttal, and the bigger the prize for such and the longer it goes without successful rebuttal (esp if there are many FAILED rebuttals) in the judgement of an independent and even possibly hostile jury of de Grey's scientific peers, the more obvious it will become that the faceless whisperers don't know what they're talking about.

I've reviewed the first 3 submissions. One is credible-sounding on its face, but in fact falls short; one fundamentally misunderstands the whole project; one is a truly pathetic ad hominem attack, almost entirely void of scientific content and making statements that the authors KNOW are untrue or misleading (and not just eg disagreements of judgement about the evidence and its implications) because the particular errors/misrepresentations have been pointed out to them before.

I predict that they're all going to be judged failures, and the competition will continue.

CRONie_CB wrote:

> What will they do
> with the $20,000 if no one makes a convincing case?

Contrary to the implication of the _Science_ story, there is in fact no deadline. The challenge will stand open until it's won, or TechRev and MF decide that it's no longer worth their engagement.

> Why did The
> Methuselah Foundation, de Grey's organization, double the original
> $10,000 prize money? Was it to have a chance to debunk the debunkers or
> to see if it is possible to learn something from the nay sayers, or to
> encourage more thinking by more qualified scientists in this area?

Both, but primarily for the reasons given above. It's also, generally, to stimulate serios scientific debate of SENS -- which some of its most prominent (and now openly-avowed) critics) have openly adamitted, in print, they are trying to simply shut down (5). (Note that many of these authors are distinguished scientists, including many biogerontologists and indeed many biogerontologists that I personally greatly respect & admire for their contributions to the field (Warner, Austad, Kirkwood, Miller, Masoro; to a lesser extent, Perls and Richardson) and who, despite their (evidently ignorant (I use the word precisely), based on the contents of (5)) dismissal of SENS, are sincerely in favor of anti-aging biomedicine: ie, their opposition to SENS is NOT dismissable in the way, eg, Hayflick's or Nuland's is, on the grounds that they (a) really don't know the science in the first place and (b) are actually opposed to the whole project to the point that appears to seriously cloud thier ability to reason (14). That doesn't absolve them of intellectual laziness & dishonesty on *this particular issue* ).

CRONie_MB wrote:

>>Why did The Methuselah Foundation, de Grey's organization, double
>>the original $10,000 prize money?
>
>
> Basically a publicity stunt. :-/

That too

> But I am not saying that is necessarily a bad thing...

I'd say it's a very good thing -- not for Aubrey's ego, but for the advancement of real anti-aging biomedicine; I suggest that this is so even if SENS is wrong.

> I think the money is safe. It is practically impossible to prove a
> negative (that SENS is not worthy consideration). So, I would be
> surprised if there will be any attempts to claim the prize.

This isn't proving a negative: that would be proving that SENS is actually wrong, which isn't required. The problem with proving a negative really only exists where you say eg "Prove that advanced extraterrestrial civilizations don't exist:" as an empirical questioin (unlike eg the existence of a Theist-type God, disproval of which can readily be accomplished on *logical* grounds), you can never REALLY disprove this as there is alwys going to be one more placae you haven't looked (the universe is a big place), and IAC a really advanced civilization might well elude our detectioin for reasons of their own (Prime Directive, anyone ).

The Challenge isn't like this, & indeed sets the bar a great deal lower than actually proving SENS *wrong*, which is done pretty handily in science: theories DO get falsified qite often, despite the fact that some may continue to hold them after they have in fact been disproved.

No, all that's being demanded here is to refute the thesis, "SENS is worthy of serious consideration." Strong improbability is plenty to refute this, without a slam-dunk falsification.

CRONie_RSB wrote:
> The whole thing is down right silly.
>
> It's equivalent to having an essay contest where the goal is to prove
> that a pink elephant will never stride down 5th Avenue or that some UFOs
> cannot be extraterestrial.

See above.
>
> The realm of the logically possible is extremely large as modern
> philosophers have noted - indeed, no one has ever solved the problem of
> induction so the logically possible is lot larger set than the so-called
> 'laws of science'.

See above.
>
> The burden should be on De Grey to show that his technological solutions
> work and will be achieved within the horizon he has claimed.

His assertioin is, of course, that he has already done so with his many peer-reviewed publications on the subject (notably, (6-12)); I actually think that his timescales are quite overoptimistic -- but primarily for sociological, psychological, ethical, and legal reasons, rather than scientific ones. But IAC, the challenge doesn't relate to timescales, but to the once-whispered and now open assertion by the critics that , not only is the SENS agenda "so far from plausible that it commands no respect at all within the informed scientific community" (5) (a patent falsehood), but that SENS is SO flawed that even debate amongst scientists should be quashed: "Why not simply debate with de Grey and let the most convincing arguments win? It is, however, our opinion that pretending that such a collection of ill-founded speculations is a useful topic for debate, let alone a serious guide to research planning, does more harm than good both for science and for society" (5).

The chilling effect of this on serious scientists is being widely felt; see, eg, the recent meeting report on the SENS2 conference (13), in which Alexander Bürkle (who has done a lot of reserach on genome instability and PARP activity in aging) and Douglas A. Gray (works on lipofuscin -- and states that "the strategy ... of eliminating insoluble cellular waste using a bioremediation approach [citing my (12) below] ... is novel and may have merit in ameliorating the undesirable consequences of aging") suggest that (5) "can be read as a more sinister threat of shunning the apostates. If the authors intended the latter, what are the requirements for admission into the shunned cadre? ... Further, is it not possible to express interest in or contribute to some of the scientific objectives of SENS without being judged a SENS acolyte? ... [Could one] not endorse this component of SENS, for example, without buying into the whole program ...? Actually, one of the authors (A.B.) did not consider speaking at the SENS conference to be an endorsement of the SENS program but instead an active participation in an unconventional conference on aging-related research featuring a number of speakers outside mainstream biogerontology who were bringing in very interesting and inspiring experimental data. Apparently, the same motivation was shared by a number of other SENS speakers and conference participants at large, who were attracted by the novel scientific data they expected to see at the conference, irrespective of the prospects for SENS in life extension." (13)

It's a sad state of affairs when well-estaablihsed sicentists hesitate to simply PRESENT AT A SCIENTIFIC CONFERENCE, with extremely prestigious presenters and proceedings published in 2 peer-reviewed scientific journals, for fear of being shunned by the biogerontology establishment.

> That's the intellectually honest approach - if you believe in X, you're
> obligated to justify X.

Right -- and again, Aubrey has done this. The intellecutally honesat approach for his critics is to either present a counterargument, or admit that they don't understand SENS well enough to have an opinion on the subject and keep silence until they do. I get sick of people on the CR Society list repeatedly dismissing SENS or de Grey's specific MiFRA when evidently they aren't even vaguely familiar with the details thereof; I don't expect to see it in scientists who are otherwise of such calibre -- let alone an active attempt to shut down debate and isolate scientists whose work might be perceived as somehow supporting de Grey's program or agenda, which latter I find offensive even when the targets are eg. Holocaust deniers or unreformed Creation "Scientists," let alone a researcher whose platform I happen to know from intimate familiarity is very well-grounded in science and logic.

> It is not intellectually honest to say prove that X is impossible
> because possibility is not the issue, the issue is plausibility.

... which is, again, the basis of the SENS challenge: not DISPROVE it, but merely show that it is not worthy of scientific debate, as its critics (5) clearly claim.

CRONie_G wrote:
> CRONie_RSB wrote:
>>The burden [of proof] should be on De Grey...

> That's exactly the point- deGrey *believes* that it is possible. When one
> believes then one makes a *leap* of faith and that is ok so long that one
> is aware of it and is honest enough to admit it.

It APPEARS that you're using "belief" here to mean something SYNONYMOUS with "leap of faith." Yet one can of course *believe* something on rock-solid empirical, experimental, or logical grounds, and again, I submit that de Grey has such for SENS.

> Using scientific terms in
> Cambridgian English doesn't make it less of a belief.

No, but neither does having solid science behind it -- which, I say again, Aubrey has. There is no lack of detail or scientific documentation (5-12) -- and, as I've noted before, even expert assent (as demonstrated by collaboration and coathorship on key papers (8,11,12), including on the MOST CHALLENGING proposals in the platform (11,12)) -- to de Grey's proposals.

> Besides, no serious scientist would agree to be distracted from his/her own
> scientific research for $20,000 not even in the spirit of sport. Creative
> scientists wake up with a theory/day that they would like to work on;-).

I think you don't spend enough time talking to serious scientists . Researchers bemoan the amount of time they have to waste digging up grant money already; a much shorter, less bureaucratized, and less formal effort (merely 750 words, tho' they are allowed much more for supplemental arguments if they want it), requiring merely that one show sufficient implausibility as to be unworthy of debate AS THEY ASSERT, ought to be easy if SENS is as wildly off-mark as they are claiming. They should either say WHY they think SENS is wrong, or not comment -- and either is fine, but to continue flatly asserting that SENS is totally beyond the scientific pale, in the absence of argumentation (& in most cases evidently even familiarity with its details), is intellectual laziness which ought to be beneath any of these folks. Again, I've seen the efforts to date; if indeed their rejection is entirely or even largely encapsulated by thehand-waving and misrepresentation of (5) and of the Tech Rev submissions to date, then they are simply dismissing SENS without bothering to actually understand the science or the argument.

CRONie_TT wrote:
> I only hope the money didn't come from the mprize funds!

Nope: again, all funds donated to the MPrize go DIRECTLY into the Prize fund itself. They got private, special funding for this, as with various other non-Prize MF projects (administration, my contractor's fees, etc). Ditto for $ going into the research side of MF.
>
> The "if it convinces independent referees" in the challenge is not
> very specific about how many of the referees have to be convinced.

The panel has to be convinced; I don't actually know whether majority rules or whether consensus sensu stricto is required, however.

> Looking at the referees, they include a robot builder, an
> ex-microsoft employee and the guy who runs nanobiosym.com -
> thoroughly geeky types, who are more likely than most to be on
> de Grey's side - I would have thought.

OTOH, Craig Venter's training & background is in quite conventional biology. IAC, even if the engineering types are more likely to share some aspects of sensibiity with Aubrey rather than (say) Richardson (nose-to-the-petri-dish benchwork) or Kirkwood (careful gedankenexperiment from theory), that doesn't mean that they'll necessarily favor de Grey's PARTICLAR engineering proposal.

CRBASICS wrote:
> How to prove SENS project is impossible, or at least
> illogical.
>
> Method: Use mathematics for modeling Stochastic Phenomena,
> based on Reliability Theory, Catastrophe Theory, Chaos Theory,
> etc.
>
> A stochastic computation based upon mutually agreeable
> premises can proved SENS is illogical and SENSeless.
>
> Example:
> Approach a living system as a network of interacting
> critical components harmonized by chaotic rhythms whose
> interactions result in homeostasis (life), where each
> component is subject to frailty and eventual deterioration
> over time.

This constitutes a fundamental misunderstanding of the nature of SENS. The above would present an argument as to why you can't build an organism that will, without further maintenance, last forever -- but that isn't what SENS purports to do (even restricting ourselves to aging, as vs eg asteroid strikes or catastrophic infection of the Ebola type). It is integral to SENS that the idea is to leave the organism's metabolic processes almost entirely as they are -- quite falliable and subject to entropic decay -- but to periodically REPAIR the damage at levels from the molecular, to the cellular, to tissue and organ and ultimately the grossly physiological level.

For SENS to work, the organism doesn't HAVE to be rebuilt to prevent it from being *intrinsically* no longer " subject to frailty and eventual deterioration over time:" we just have to be able to *fix* the deterioration before it reaches levels that actually lead to frailty . We accumulate molecular damage from the time sperm meets egg (those of us lucky and wise enough to have attended CR Conf IV will recall Caleb "Tuck" Finch's revelation that we can now detect early atherosclerotic lesioins in FOETUSES of IIRC 3 mo of development), but we remain at an almost unchanged level of actual risk of death from our early twenties until around 40 (and we can push this backward if we eliminate the stupid, risky behavior associated with adolescents' underdeveloped brains).

By way of analogy: we do not, and don't have to, build cars that can be driven forever without maintenance, even if our goal is to keep driving them indefinitely -- we just have to keep repairing the things as they fall apart. Many folks just let their cars die, but as any antique car collector can attest, this doesn't HAVE to be a car's fate.

SENS proposes to do the same with the human machine, beginning with a platform of existing or near-term foreseeable biotech under development that would fix organisms well enough to reverse or arrest aging significantly in the medium term ((6-12), and esp (6-8)) -- not enough to allow, in itself, for indefinite maintenance, but to do so ENOUGH to reach "actuarial escape velocity" (15), buying us enough time to survive until the putting us on a trajectory to catch successive waves of life-extending biotech, until we can consistently repair damage faster than it accumulates through successive repetitions & iterations of the emerging technologies, culminating in a mature anti-aging biotech that will keep us within a narrow range of physiological youth indefinitely.

1. Jason Pontin. Against Transcendence. Technology Review, Febuary 2005.
http://www.technologyreview.com/articles/05/02/issue/editor.asp

2. Sherwin Nuland. Do You Want to Live Forever? Technology Review, Febuary 2005
http://www.technologyreview.com/articles/05/02/issue/feature_aging.asp?p=0

3. http://pontin.trblogs.com/archives/2005/05/aubrey_de_grey_1.html

4. http://pontin.trblogs.com/archives/2005/05/cynthia_kenyon_1.html

5. Warner H, Anderson J, Austad S, et al.
Science fact and the SENS agenda. What can we reasonably expect from
ageing research?
EMBO Rep. 2005 Nov;6(11):1006-8. No abstract available.
PMID: 16264422 [PubMed - in process]

6. de Grey AD. An engineer's approach to the development of real anti-aging medicine. Sci Aging Knowledge Environ. 2003 Jan 8;2003(1):VP1. Review. PMID: 12844502 [PubMed - indexed for MEDLINE]
http://www.sens.org/focusPP.pdf

7. de Grey AD. Challenging but essential targets for genuine anti-ageing
drugs. Expert Opin Ther Targets. 2003 Feb;7(1):1-5. PMID: 12556198 [PubMed - as supplied by publisher]
http://www.sens.org/manu21.pdf

8. de Grey AD, Ames BN, Andersen JK, Bartke A, Campisi J, Heward CB, McCarter RJ, Stock G. Time to talk SENS: critiquing the immutability of human aging. Ann N Y Acad Sci. 2002 Apr;959:452-62; discussion 463-5. PMID: 11976218 [PubMed - indexed for MEDLINE]
http://www.sens.org/manu12.pdf

9. de Grey AD. Foreseeable pharmaceutical repair of age-related extracellular damage. Curr Drug Targets. 2005, in press.
http://www.sens.org/excellPP.pdf

10. de Grey AD. Appropriating microbial catabolism: A proposal to treat and prevent neurodegeneration. Neurobiol Aging. 2006 Apr;27(4):589-95. Epub 2005 Oct 3. PMID: 16207503 [PubMed - as supplied by publisher] http://www.sens.org/NBA-PP.pdf

11: de Grey AD, Campbell FC, Dokal I, Fairbairn LJ, Graham GJ, Jahoda CA, Porterg AC.
Total deletion of in vivo telomere elongation capacity: an ambitious but possibly ultimate cure for all age-related human cancers.
Ann N Y Acad Sci. 2004 Jun;1019:147-70. Review.
PMID: 15247008 [PubMed - indexed for MEDLINE]
http://www.sens.org/WILT.pdf

12: de Grey AD, Alvarez PJ, Brady RO, Cuervo AM, Jerome WG, McCarty PL, Nixon RA, Rittmann BE, Sparrow JR. Medical bioremediation: prospects for the application of microbial catabolic diversity to aging and several major age-related diseases. Ageing Res Rev. 2005 Aug;4(3):315-38. Review. PMID: 16040282 [PubMed - indexed for MEDLINE]
http://www.sens.org/medbioremPP.pdf

13: Gray DA, Burkle A.
SENS and the polarization of aging-related research.
Sci Aging Knowledge Environ. 2006 Apr 5;2006(7):pe8.
PMID: 16600918 [PubMed - indexed for MEDLINE]
http://sageke.sciencemag.org/cgi/content/full/2006/7/pe8

14: Rae MJ.
Anti-aging medicine: fallacies, realities, imperatives.
J Gerontol A Biol Sci Med Sci. 2005 Oct;60(10):1223-7; discussion 1228-32. No
abstract available.
PMID: 16282551 [PubMed - indexed for MEDLINE]

15. de Grey AD
Escape velocity: why the prospect of extreme human life extension
matters now.
PLoS Biol. 2004 Jun;2(6):723-6.
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=423155&blobtype=pdf