SENS and the Polarization of Aging-Related Researc

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#1

Lurker
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Posted 28 April 2006 - 04:16 PM

Sci. Aging Knowl. Environ., Vol. 2006, Issue 7, pp. pe8, 5 April 2006
[DOI: 10.1126/sageke.2006.7.pe8]

SENS and the Polarization of Aging-Related Research

Douglas A. Gray and Alexander Bürkle
Douglas A. Gray is at the Ottawa Health Research Institute, Ottawa K1H 8L6, Canada. Alexander Bürkle is in the Department of Biology, University of Konstanz, D-78457 Konstanz, Germany. E-mail: dgray@ohri.ca (D.A.G.)

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Document URL: http://sageke.scienc...full/2006/7/pe8

Key words: strategies for engineered negligible senescence • Aubrey de Grey • life extension • rejuvenative medicine • SENS challenge • Methuselah mouse prize

In its original conception, what follows would have been a rather conventional meeting report on "Strategies for Engineered Negligible Senescence (SENS), Second Conference" which took place in Cambridge, United Kingdom, in September of 2005. There is nothing at all conventional about SENS (the concept or the meeting of the same name), and a greater purpose may be served by addressing the deepening controversy that SENS has generated, something a conventional meeting report would surely fail to capture. What follows, therefore, are the thoughts of two SENS II conference participants, one (D.A.G.) who is still relatively new to the field and was eager to hear from the leading lights, and the other (A.B.) who has a long-standing interest in biogerontology and who gave a short talk at SENS II.

The author of the SENS concept is Aubrey de Grey, who has organized the SENS meetings to promote his life-extension program in both the scientific and public relations sense. de Grey's argument is that age-related pathology can be attributed to seven types of damage, ranging from DNA mutations to the accumulation of intracellular junk. For each of these types of damage, he has proposed a strategy of molecular or cellular redress (see de Grey Viewpoint). These strategies range from the seemingly plausible (the enzymatic or chemical removal of advanced glycation end products) to the wildly ambitious [the whole-body interdiction of lengthening of telomeres (WILT) strategy of eliminating telomerase and the alternative pathway of telomere lengthening from all mitotic cells as a means of precluding cancer cell proliferation]. It would be fair to say that de Grey recognizes the inherent difficulty of some aspects of SENS, but he appears adamant that all components are possible. Indeed, in collaboration with Technology Review (TR), he has offered a sizable cash reward to anyone who can demonstrate that collectively they are not possible. More about that later.

Like SENS I (the subject of a previous SAGE KE meeting report; see Gray Perspective), the SENS II conference offered a stellar lineup of speakers, many of whom would be considered leading authorities in aspects of what can be loosely categorized as rejuvenative medicine. A partial list of topics discussed at the meeting includes (i) tissue engineering (with presentations from Tony Atala and Buddy Ratner), (ii) nuclear gene engineering (Matthew Porteus), (iii) manipulation of the mitochondrial genome (Bob Lightowlers, Takao Yagi, Rafal Smigrodski, and Henry Weiner), (iv) dealing with cellular aggregates (Bruce Rittman, Janet Sparrow, Jay Jerome, Wendy Jessup, David Rubinsztein, Ralph Nixon, Ana Maria Cuervo, and Roscoe Brady), and so forth. One session dealt with stem cell strategies and featured a spectacular presentation by Woo Suk Hwang, the South Korean cloning expert whose work on human stem cells has subsequently been shown to be fraudulent. The atmosphere in the room was of history in the making (a feeling reinforced by the subsequent and largely political talk given by Gerald Schatten praising Hwang, a collaborator with whom he has since severed relations). Altering the course of history is very much within Aubrey de Grey's own purview (could human immortality be considered anything less?), and the inclusion of Hwang at his very zenith must have been deeply satisfying to de Grey at the time and deeply troubling thereafter. If de Grey is to succeed in his quest to draw in substantial funding for SENS (1), he must deflect any suspicion of the charlatanism that has plagued aging-related research. The sensitivity of legitimate biogerontology researchers to this problem is evident from a position statement saying that "anti-aging" products do not exist and should be considered pseudoscience, signed by 52 eminent researchers (2). On the issue of immortality, the position statement reads as follows: "The prospect of humans living forever is as unlikely today as it has always been, and discussions of such an impossible scenario have no place in a scientific discourse." Surprisingly, Aubrey de Grey was a signatory to this statement.

The potential damage of SENS to mainstream research was recently highlighted by one of the leading figures in biogerontology, Tom Kirkwood. In a Nature book review (3) he wrote: "why is there a pervasive sense that advocates of life extension must make preposterous claims about imminent longevity claims if they are to gain public notice?" and referred to a specific example reported by the BBC, the "laughable claim that the first human who will live to 1000 years is 60 already." The author of that claim was Aubrey de Grey, who in support of the claim referred to the TR "SENS Challenge" in a response posted on the SAGE KE Bulletin Board.

The legitimacy of the SENS approach and the media-friendly face provided by its originator came under attack once again in a multiauthored critique in EMBO Reports (4). Positing that the SENS agenda is "so far from plausible that it commands no respect at all within the informed scientific community," these authors wish to "dissociate themselves from the cadre of those impressed by de Grey's ideas in their present state." This statement is both forceful and ambiguous. It can be read as the relatively benign wish to be placed in a nonoverlapping circle on the Venn diagram of who believes what in aging-related research, or it 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? It could not be attendance at one SENS conference, for some of the signatories have attended. Would attendance at both suffice? 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? The objective of eliminating insoluble cellular waste using a bioremediation approach (5) is novel and may have merit in ameliorating the undesirable consequences of aging. The strategy is of interest to one of the authors (D.A.G.; see Gray and Woulfe Review)--could he not endorse this component of SENS, for example, without buying into the whole program, including the possibility and/or advisability of immortality? 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.

The TR SENS Challenge is frequently mentioned by Aubrey de Grey (indeed he has devoted an editorial to it in Rejuvenation Research (6), the journal of which he is editor). Half of the wager on offer in the $20,000 TR SENS Challenge derives from the Methuselah Mouse Foundation (which de Grey chairs), and whereas the TR Challenge and the Methuselah Mouse Prize (see "Rewarding Research") both offer cash prizes drawn from a common source, that is where the similarity would appear to end. They are both public relations gambits, but the mouse prize was designed to be won, the TR Challenge to be lost (where the definition of "lost," as determined by de Grey, would encompass situations in which the SENS concept withstood a scientific critique or was simply left uncontested). The mouse prize is without question a clever way of attracting public interest to aging-related research, and by extending the mouse life span its winner will have made a contribution to knowledge. The TR Challenge serves no purpose but to attract attention to Aubrey de Grey and the increasingly bitter dispute with his detractors. Although it allows him to taunt them (baselessly, given the way in which the criteria have been set), it is hard to imagine how this could be a positive thing for future SENS conferences, which are likely to become increasingly populated by media in search of controversial sound bites from its organizer. From all indications, they are likely to come away satisfied. Whether the same will still be said for attending scientists remains to be seen.

April 5, 2006

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Comment on Article

References

1. A. D. de Grey, Resistance to debate on how to postpone ageing is delaying progress and costing lives. Open discussions in the biogerontology community would attract public interest and influence funding policy. EMBO Rep. 6 Spec. No. , S49-S53 (2005).[CrossRef][Medline]
2. S. J. Olshansky, L. Hayflick, B. A. Carnes, Position statement on human aging. J. Gerontol. A Biol. Sci. Med. Sci. 57, B292-B297 (2002).[Abstract/Free Full Text]
3. T. Kirkwood, Live longer and prosper. Nature 436, 915-916 (2005).[CrossRef]
4. H. Warner, J. Anderson, S. Austad, E. Bergamini, D. Bredesen, R. Butler, B. A. Carnes, B. F. Clark, V. Cristofalo, J. Faulkner et al., Science fact and the SENS agenda. What can we reasonably expect from ageing research? EMBO Rep. 6, 1006-1008 (2005).[CrossRef][Medline]
5. A. D. de Grey, P. J. Alvarez, R. O. Brady, A. M. Cuervo, W. G. Jerome, P. L. McCarty, R. A. Nixon, B. E. Rittmann, J. R. Sparrow, Medical bioremediation: Prospects for the application of microbial catabolic diversity to aging and several major age-related diseases. Ageing Res. Rev. 4, 315-338 (2005).[CrossRef][Medline]
6. A. D. de Grey, The SENS challenge: 20,000 US dollars says the foreseeable defeat of aging is not laughable. Rejuvenation Res. 8, 207-210 (2005).[CrossRef][Medline]

Citation: D. A. Gray, A. Bürkle, SENS and the Polarization of Aging-Related Research. Sci. Aging Knowl. Environ. 2006 (7), pe8 (2006).

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SENS's detractors should not intimidate aging-related scientists
Aubrey D.N.J. de Grey
SAGE KE, 13 Apr 2006 [Full text]
Shunned cadres - a clarification
Rich Miller
SAGE KE, 21 Apr 2006 [Full text]

Copyright © 2006 by the American Association for the Advancement of Science.

#2

Lurker
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Posted 28 April 2006 - 04:20 PM

Electronic letters published:

SENS's detractors should not intimidate aging-related scientists
(13 April 2006)
Shunned cadres - a clarification
(21 April 2006)
SENS's detractors should not intimidate aging-related scientists 13 April 2006
Aubrey D.N.J. de Grey,
Research Scientist
University of Cambridge
Enter response to this comment:
Re: SENS's detractors should not intimidate aging-related scientists

E-mail Aubrey D.N.J. de Grey

Gray and Buerkle's commentary [1] on SENS's evaluation by scientists is most welcome, not only for what it gets right but also for the serious factual errors that it contains. These errors are probably widespread in the biogerontology community, because they result from misleading statements that have been made, both in print and off the record, by others. I am therefore grateful to Gray and Buerkle for giving me this opportunity to correct those errors.
First, I have never remotely suggested that participation in my SENS conferences constitutes tacit agreement with me as to SENS's feasibility. (It is not clear from Gray and Buerkle's text whether they think I have been doing this, but a reader might easily form such an impression.) That would be a ludicrous inference, given that I am on abundant record as knowing full well how radical SENS is, and also that I have repeatedly taken a decidedly more established approach when I seek to determine whether other scientists support a component of SENS, namely, first to expose them to it for a whole day and then to ask them to co-author a paper on it [2-5]. (It is notable that only one of my co-authors on any of these papers signed Warner et al.'s recent denunciation of SENS [6]; one can draw one's own conclusions from the fact that her name was mis-spelled in the list of authors.) There is no reason whatever for a SENS conference participant to be concerned that his or her opinions regarding SENS will be misrepresented either by me or by any other SENS advocate. If some of my more energetic detractors seek to make such a link, it is those detractors who should be condemned for impugning the reputations of eminent scientists in an attempt to marginalise me, and if anything, scientists should resist that intimidation by attending SENS conferences in greater numbers than ever. Perhaps this was Gray and Buerkle's point, but if so, I fear that some readers might have missed it.

The converse point also merits a slight correction. While attendance at the SENS conferences means nothing about support for SENS, it does confer at least circumstantial authority to opine on the matters that were presented there. Gray and Buerkle point out that some of the 28 signatories to the recent denunciation of SENS [6] attended, but this may give an exaggerated impression; in fact, and as I pointed out in my response to Warner et al. [7], not one of them attended SENS 2 and only five attended its altogether less SENS-centric predecessor, IABG10, in 2003 (when SENS had less notoriety).

Gray and Buerkle quote the "Position Statement on Human Aging" [8] out of context: the comment there about humans living forever referred to literally that, i.e. no death from age-independent causes either. My agreement with that paper's main thrust, the present non-existence of any true life- extending products, is the reason I endorsed it. I and some other endorsers lobbied the authors vigorously to remove assertions about the probability of such products arriving within our lifetime, but without success; but that was not the paper's main theme, so I judged that an endorsement was still appropriate.

I am perplexed at Gray and Buerkle's implication that I have in some way been tarred with the Hwang brush as a result of his participation in a conference that I organised. If I have, all I can say is that I am in very good company.

Finally, I must take sharp exception to Gray and Buerkle's assessment of the SENS Challenge. When scientists disagree as to the plausibility of a hypothesis or the feasibility of an experiment, they generally do so in cautious terms, and in such circumstances it is entirely proper to be able to express one's view without being required to justify it rigorously. When they express their opinion of a colleague's work using words like "fantasy" and "pretence," however, the object of their derision is entitled to ask for an explanation - and, if years pass with no explanation being forthcoming, to bring his critics' reticence to public notice. Gray and Buerkle say that the terms of the Challenge mean that it allows me to taunt my detractors "baselessly," but that is not true at all: rather, the conclusion that a submission must persuade a panel of independent experts of in order to win (namely, that SENS is so absurd that it should not be dignified with learned debate) is precisely the view that my critics have been expressing off the record for some years and more recently (though only after my strong criticism of their public silence [9]) in print. It is public knowledge [10] that Technology Review began the search for a mainstream gerontologist's demolition of SENS entirely on its own initiative, as a result of having been given a strongly negative but non- specific evaluation of it by experts whom they consulted during 2004, and that the SENS Challenge was begun (with input from the Methuselah Foundation, yes) only after a number of experts declined to write such an article and Technology Review began to wonder whether they had been misled. Thus, Gray and Buerkle are absolutely wrong to suggest that "[t]he TR Challenge serves no purpose but to attract attention to Aubrey de Grey and the increasingly bitter dispute with his detractors" -- rather, it serves the wholly legitimate purpose of testing the hypothesis that my detractors have formed their negative opinions of SENS without the attention to its details that their audience will tend to presume that they have paid. If Gray and Buerkle know of a better way to distinguish that hypothesis from the competing one, advanced by my detractors, that no such commentary has been written simply because experts are too busy to ridicule something so ridiculous, they should suggest it.

In conclusion, my high media profile results from the coherence of the SENS agenda and the incoherence of the criticism that SENS has so far received [7]. This is demonstrated by the fact that SENS has been accorded an almost uniformly positive media treatment (Technology Review's articles in February 2005 being almost the only exception). I am not a soundbite expert, nor am I fond of them. The SENS conferences will thus continue to bring together the world's best science in areas that I consider relevant to extreme life extension, and participants will continue to be able to make up their own minds as to whether that science adds up to a viable approach to greatly postponing aging.

1. D. A. Gray, A. Buerkle, SENS and the Polarization of Aging-Related Research. Sci. Aging Knowl. Environ. 2006 (7), pe8 (2006).

2. de Grey ADNJ, Ames BN, Andersen JK, Bartke A, Campisi J, Heward CB, McCarter RJM, Stock G. Time to talk SENS: critiquing the immutability of human aging. Annals NY Acad Sci 2002; 959:452-462.

3. de Grey ADNJ, Baynes JW, Berd D, Heward CB, Pawelec G, Stock G. Is human aging still mysterious enough to be left only to scientists? BioEssays 2002; 24(7):667-676.

4. de Grey ADNJ, Campbell FC, Dokal I, Fairbairn LJ, Graham GJ, Jahoda CAB, Porter ACG. Total deletion of in vivo telomere elongation capacity: an ambitious but possibly ultimate cure for all age-related human cancers. Annals NY Acad Sci 2004; 1019:147-170.

5. de Grey ADNJ, Alvarez PJJ, 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; 4(3):315-338.

6. H. Warner, J. Anderson, S. Austad, E. Bergamini, D. Bredesen, R. Butler, B. A. Carnes, B. F. Clark, V. Cristofalo, J. Faulkner et al., Science fact and the SENS agenda. What can we reasonably expect from ageing research? EMBO Rep. 6, 1006-1008 (2005).

7. de Grey ADNJ. Like it or not, life extension research extends beyond biogerontology. EMBO Reports 2005; 6(11):1000.

8. S. J. Olshansky, L. Hayflick, B. A. Carnes, Position statement on human aging. J. Gerontol. A Biol. Sci. Med. Sci. 57, B292-B297 (2002).

9. de Grey ADNJ. Resistance to debate on how to postpone ageing is delaying progress and costing lives. EMBO Rep 2005; 6(S1):S49-S53.

10. Pontin J. Cynthia Kenyon declines. http://www.technologyreview.com/ Blogs/wtr_15021,291,p1.html (2005).

Shunned cadres - a clarification 21 April 2006
Rich Miller,
Biogerontologist
Enter response to this comment:
Re: Shunned cadres - a clarification

E-mail Rich Miller

Friday, April 21, 2006

Dear Dr. Gray and Dr. Bürkle:

I enjoyed your article in SAGE-KE about the recent SENS-II conference, which gave a nice overview of the meeting and the areas of controversy around Aubrey’s ideas and activities.

As one of the authors of the EMBO Reports article, I thought I ought to respond to your speculation about an area of apparent ambiguity. You write:

[quotation] Positing that the SENS agenda is 'so far from plausible that it commands no respect at all within the informed scientific community,' these authors wish to 'dissociate themselves from the cadre of those impressed by de Grey's ideas in their present state.' This statement is both forceful and ambiguous. It can be read as the relatively benign wish to be placed in a nonoverlapping circle on the Venn diagram of who believes what in aging-related research, or it 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? It could not be attendance at one SENS conference, for some of the signatories have attended. Would attendance at both suffice? 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? [end quotation]

I am very sorry that the article may have left the misimpression of its cosignators as sinister and threatening bullies, the kind of people who take attendance at meetings and make lists of evil-doers destined to be confined to some scientific Guantanamo, where they are denied access to their copies of Rejuvenation Research, and from which much-needed shipments of liquid nitrogen and telomerase are diverted to other purposes. It was intended, as you speculated, to express a fully benign wish, inviting comrades to see the light and step into the part of the Venn diagram where people support aging research, do some of it themselves, go to any conferences they want to attend, and talk to and be friendly with anyone they wish, but are careful to try to distinguish fact from speculation, and speculation from fantasy.

I don’t see any need to define a shunned cadre, with or without admission requirements. Nearly all of the scientific objectives on the SENS menu are interesting, and people working on them are likely to make discoveries of great importance. But when colleagues, like Aubrey, feel a need to exaggerate the speed with which biogerontology will produce practical advances, or exaggerate the likelihood that old people can be converted into spanking new ones, I think this is in general bad for society and harmful to the scientific enterprise. I think it’s important for scientists to do their part to help administrators, journalists, and interested laypersons distinguish strategy from wish-fulfillment, and critical thought from advertising. Your SAGE-KE article is, in my view anyway, a fine example of how to approach this kind of knotty issue.

Rich Miller

#3 Live Forever

Guest Recorder
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Location:Atlanta, GA USA

Posted 28 April 2006 - 04:34 PM

"The four stages of acceptance:
1) this is worthless nonsense
2) this is an interesting but perverse point of view
3) this is true, but quite unimportant
4) I always said so "
-J.B.S. Haldane

"New ideas pass through three periods:
1) It can't be done.
2) It probably can be done, but it's not worth doing.
3) I knew it was a good idea all along!"
-Arthur C. Clarke

I think we are about halfway between stages 1 & 2 of both statements at this point.

#4 Mind

Life Member, Director, Moderator, Treasurer
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Location:Wausau, WI
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Posted 28 April 2006 - 07:25 PM

I think one of the main problems is that the mainstream biogerontologists have to deal on a personal level with the sick/aged/dying on a daily basis. They know great medical advances are on the way. They know Aubrey has good ideas, but they can't say it because it is not useful with the people they are dealing with in the present. They can't dish out spoonfuls of hope to people with a year or two to live. They have to be very guarded with what they say in public.

#5 Lazarus Long

Life Member, Guardian
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Location:Northern, Western Hemisphere of Earth, Usually of late, New York
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Posted 30 May 2006 - 05:34 AM

I think this article on the intentional polarization of the debate is fascinating in that it demonstrates applied scientific dialectics.

http://news.yahoo.co...onsgoheadtohead

Anti-Aging Competitions Go Head-to-Head
Ker Than LiveScience Staff Writer
LiveScience.com
Fri May 26, 12:00 PM ET

Anyone debating the scientific feasibility of extending the human life span will find that it's only a matter of time before the name "Aubrey de Grey" comes up.

The controversial Cambridge University researcher has been making news in recent years by claiming that humans could soon enjoy thousand-year lifetimes and by helping to establish two contests: one to spur anti-aging research and another to debunk his own audacious claims.

In 2003, de Grey helped establish the Methuselah Foundation and create the M-Prize, a $1.5 million award available to any scientist who can slow or reverse the effects of aging in mice.

Private donations made since 2003 have bumped the prize value up to nearly $3.5 million, according to the latest update on the Methuselah Foundation website.

Just getting started

About $100,000 of award is reserved for a "Longevity Prize" that focuses on extending total lifespan; the hefty remainder of the award is reserved for a "Rejuvenation Prize," which aims to reverse the effects of aging in the elderly.

The unequal distribution of the money between the two prizes reflects the wishes of the donors, says Methuselah Foundation director David Gobel.

"People who happen to be alive want to be fixed," Gobel said.

The M-Prize has been awarded three times to date, all in 2004:

The Longevity Prize went to Southern Illinois University researcher Andrzej Bartke for a mouse genetically modified mouse that lived for 1819 days, or nearly 5 years.
The Rejuvenation Prize was won by University of California, Riverside researcher Steve Spindler and colleagues for a mouse that lived for 1,356 days, or about 3.7 years, due to caloric restriction.
The Foundation also awarded a no-longer-active "Reversal Prize" to animal breeder Sandy Keith for "Charlie," a mouse that lived to 1551 days without any kind of genetic or dietary intervention.

None of these previous winners received any substantial cash award; rather, their efforts were used to set the standard that future entries had to beat, Gobel said.

Both Bartke and Keith received $500 for their accomplishments; Spindler received a "Methuselah of champagne."

The M-Prize was modeled after the Ansari X-Prize, a $10 million dollar award created to spur the creation of reusable manned spacecraft. The X-Prize prize was won in October 2004 by Burt Rutan's SpaceShipOne.

In addition to sponsoring M-Prize, de Grey has also put forward his own research proposal to slow the process of aging. Called "Strategies for Engineered Negligible," or SENS, de Grey's approach focuses on repairing the damage aging inflicts on our cells.

SENS is highly controversial among biogerontologists, or scientists who study aging. Many believe it is overly optimistic science fiction.

Prove me wrong

In response to the criticisms, de Grey teamed up with one of his detractors to create another contest—this time to debunk his own claims.

In July, 2005, de Grey and the MIT-affiliated magazine Technology Review announced the SENS Challenge, a $20,000 award for anyone who can show that SENS is scientifically impossible.

"It seems absurdly far-fetched to me…but the plan behind the SENS Challenge is to give de Grey's idea a chance," said Jason Pontin, Technology Review's editor-in-chief.

The competition is open to any molecular biologist with a Ph.D. from a recognized institution. Submissions will be judged by a distinguished five-person panel that includes Craig Venter, who led the private effort to decode the human genome, and Nathan Myhrvold, a former chief technologist at Microsoft.

The SENS Challenge "was designed to shine some very bright lights on what was basically behind-closed-doors badmouthing of the hypotheses Aubrey was putting out," Gobel told LiveScience. "The thought was 'If you want to say something is wrong, then you ought to put your name on it.'"

The SENS Challenge award will be paid by matching funds from both the Technology Review and the Methuselah Foundation. Pontin told LiveScience that numerous scientists have accepted the challenge and that the top submissions will be published in the magazine's July issue.