162 replies to this topic

[Da55id]

Hi - Sorry for the confusion...

the text highlighted in red is not a correct statement... "Of course it is irrelevant that it is the most popular platform to study aging on (something the Methuselah Foundation keep on ignoring)."

I would be very glad if you would presume the following out of general good will...

1) We really care about what we're doing
2) We are carefully looking at your posts
3) We are ridiculously busy on dozens of efforts in addition to following your developing and well reasoned positions/arguments
4) We consider your ideas to be in the spirit of furthering the mission and we are not antagonistists or antagonistic toward them

Cheers,
Dave

[jaydfox]

I would be very glad if you would presume the following out of general good will...

Can do... In fact, I've decided to throttle back on both the number and length of posts for the next few days, to let everyone (myself included) catch their breath and have time to get out of the "defend my own position" mode. I think it will be more productive in the long run if I not feel so compelled to respond at length to everyone's posts, on a point by point basis...

Jay Fox

PS: Dave, thank you for your continuing consideration!

[lightowl]

I will dare to make some comments.

You must know that I am still reading all the posts in this thread and others about the same subject. I have stopped short of making comments because I don't like the tone used against people who oppose or have doubts about a fly prize. That may be one reason more people are not entering the debate. Another is probably that few have time to enter late and read this book of a thread.

I have previously stated that I think PR is very important and I think it is being ignored in favor of scientific viability. Now, don't get me wrong. I understand that the science is very important and it is science that is going to make radical longevity possible, but it is the people who are going to pay for it. So it is very important to get the PR right firstly. When a good deal of momentum has been build, effective research can be conducted and more PR can be made... and so on. PR is also a powerful tool for getting rid of the deathmeme. As many people as possible must be convinced that death is a conquerable foe. It is the main purpose of the Immortality Institute as far as I know.

I am not opposing a fly prize, but I am opposing that the Methuselah Foundation (MF) should create such a prize. At least for now. I am all for others creating a fly prize. The reason I think the MF should not create a fly prize is because I am convinced that if the layman had a choice between mouse and fly, they would choose the mouse most of the times, leaving little to the fly. Also, I personally think it would be great to have as many organizations as possible offering as many prizes as possible. That would show the public that allot is going on. I don't se prizes as competing entities since they have the same objective and would draw together more people to the cause. The MF should not begin to offer fly prizes, because it would probably make to much confusion about the focus of the MF. That would of course be different if the fund was $1+ MILLION because that would give the MF credibility in size.

Someone previously stated that he thought that research in long lived animals should be promoted, but he was ridiculed with sarcastic remarks. I think he was right. Research in long lived animals should be done and will probably be a valuable tool in figuring out what aging is all about. That said, I also agree that it would not be effective to conduct experiments like those proposed here on long lived animals. It would just take to long, and the results would not be as interesting since the animals already are long lived. What is interesting is why they live so long.

I see great value in combining research in flies and mice. A way to do that could be to let multiple scientists receive the MMP. That is, if a scientist doing work on mice asked a scientist doing work on flies to make some preliminary tests, both scientists could be awarded the prize whenever their work resulted in a prize mouse. Of course it could be the other way around with the fly researcher offering his results to a mouse researcher in a collaboration to win the MMP. The same could be done if someone won the fly prize.

If a fly prize is created, I think the name of the prize should not contain Methuselah. Since it would seem like the prize is awarded by the MF. That would effectively create confusion that could result in damage to the MF because of the previously stated focus concern of mine.

Finally I think the value of research in mice is being downplayed. Mice is being used in countless research facilities to conduct tests on potential medicine for humans. I know that this debate is about promoting fly research, but in the spirit of doing so, the importance of the Methuselah Mouse Prize (MMP) is being unfairly attacked. I think you are all supporters of the MMP so please try not to damage the cause.

That's my five cents for now, hope they are well received.

Thor.

[jaydfox]

I did the fly/human lifespan correlation in advance to formulate my question about 2 1/2 years...to see if a potentially powerful/wonderful PR "spike the football" goal was within the realm of possibility...a TRUE Methuselah Fly (969 years equivalent human years).

In that light, I take back my "bogus" comment. A "TRUE Methuselah Fly" really would be something which, in PR terms, could not be ignored by every moderately intelligent person in the world. A politically-backed "War on Aging" would be a likely outcome.

While I don't foresee a 2.5-year-old fly even being born in the next five years, let alone reaching the 2.5-year mark (though still a remote possibility), I do foresee that we could get there in 10-15 years, IF it's possible. (In the end, it might be harder to ridiculously extend fly lifespan than human lifespan, since organ replacement/rejuvenation via stem cells, and other such "manual" interventions, would be quite difficult to perform on something only a few millimeters long. And even if it could be done, it wouldn't be cost-effective in light of the vast numbers of flies that we would otherwise be dealing with in longevity studies...)

And just for fun, a true Methuselah Mouse would be almost 30 years old, beyond the timeframe of even the 25-year pledge period of the MMP. So, for those who think the 25-year pledge period is too long, consider that!

Jay Fox

[jaydfox]

That's my five cents for now, hope they are well received.

Indeed they were. You are correct that I have been becoming overly sarcastic of late. I apologize. (Sorry, bradbury!) Pride has a way of doing that...

And I appreciate your comments, especially about considering the fly prize valid. And to a degree, I agree that if sponsored by a separate organization, with a name that isn't easily confused or associated with the MMP or the MF, there will be certain benefits not as easily obtained by having the fly prize under the MF.

Also, I personally think it would be great to have as many organizations as possible offering as many prizes as possible. That would show the public that allot is going on.

Indeed, the number of organizations can be as important as the size of the organizations. It has been proposed that the Immortality Institute sponsor the prize. If this happened, I assume that a separate non-profit entity would be created and have its own corporate name and board of directors, and it would be a wholly- or majority-owned subsidiary of the Immortality Institute. In other words, another organization.

Putting the fly prize under the Methuselah Foundation would be easier, so that's why I was trying for that route. If there is enough support here to handle the complexities of creating a new organization, and if the folks at the MF would be willing to advise us, donate resources, and get us on our feet, then that might be better in the long run, even if it is a lot harder. I guess for something this important, the best way to do it should be done, not the easiest way (though ease is a factor in determining what's best). But I'm not a natural leader--in fact, I'm not even a mediocre leader--so I was trying to avoid putting myself in a leadership position.

Jay Fox

[Da55id]

Just for the record, no decisions have been made pro or con by MF about mounting a fly prize at some point. I very much like the "cheap/fast turnover/experimentation" features of fly research. I very much dislike flies as a populist PR vehicle. But if a great goal can be devised that would resonate with the public and initial seed funding of $50k were secured at initiation, then it would be worth taking a hard look at it. There was some earlier discussion about seed funding by a poster. If that was a bona fide donation offer, then there's something to talk about. If not, then a fly prize is something we'll need to look at in concert with dozens of other priorities down the road.

Fund raising is excrutiatingly hard and thankless work (stop the violins please ). I think that adding another prize outside the venue of the Foundation will diffuse resources and attention, cause public confusion and generate a net reduction in momentum toward our shared goals/mission. That's my personal judgement. But, it's a free country.

The whole point of discussion is to expose alternatives - and the work done by all has been great here. Jay et al, I really appreciate your willingness to lighten the "tone" of discourse.

Thanks!
Dave

[lightowl]

But, it's a free country.

I would hope it is a free world

About the many prizes issue. In the beginning of the aviation revolution many prizes where offered for various different goals. Although only a few is famous the rest of them where certainly good for the overall progress of aviation technology. Of course we may live in very different times, so one big prize for one goal could be the best way to go, but I don't think so. I could envision prizes for other goals with other subjects that would give momentum to each other.

For example, an organ preservation prize would be much more easily sold to the public but could eventually help convince many people that cryonics is feasible. Another example is space travel. I am assuming everyone knows about the X-Prize. Well, the success of the X-Prize is robbing off on NASA and they are preparing to offer prizes of their own. I suppose there may be negative aspects in having many publicly funded prizes, but I think the positives outweigh the negatives. Also, many public prizes might pull some rich philanthropists to offer a prize of their own. It may even be possible that donors to one publicly funded prize could be convinced to donate to others there by extending the donor network.

Remember, I am not an expert on prizes, I am only stating my guesses on self learned information. Also, I am only speaking on behalf of myself.

[jaydfox]

I could envision prizes for other goals with other subjects that would give momentum to each other.
...
I suppose there may be negative aspects in having many publicly funded prizes, but I think the positives outweigh the negatives. It may even be possible that donors to one publicly funded prize could be convinced to donate to others there by extending the donor network.

Actually, you should check out the "Prometheus" prize. It's actually a concept of keeping a prize for 10 important aging related goals at any given time, and retiring goals when they are met and creating a new prize to replace the ones that are retired. I don't have a weblink, but perhaps someone else here does? I think I actually got the link from Dave Gobel once in another topic, but I could be wrong...

Jay Fox

[lightowl]

Found it

http://research.medn.../Agingprize.htm

I think the MMP is a good roundup of all the issues addressed by "The Prometheus Prize (TPP)". One difference is that TPP is looking for one individual donor and not like the MMP multiple donors. Multiple donors is in my opinion a much better approach.

"Fall 1999 – The search for a donor begins."

This tells a bit about the success of the MMP. I think the TPP website has allot of good points that could be used by the MMP and other potential prizes.

[lightowl]

Another more updated page I think
http://research.arc2...ts/agingprz.htm

And a BetterHumans Article about the Prizes.
http://www.betterhum...ID=2003-06-03-4

[ag24]

Sorry for the extended silence. My thoughts on recent posts:

1) PR versus science. Prometheus wrote:

> Now it's quite obvious that I was correct in my initial assertion that
> the Methuselah Foundation places more value on PR than good science,
> despite Aubrey's statement to the contrary.

I'm not sure what you're referring to here. I have always said that the
main value of the MMP is PR. The only area in which the science is more
important than the PR is where the PR depends absolutely on the science,
such as in not instituting a prize that is rather easy to win in ways
that are scientifically uninteresting and hence which would not be made
into conspicuous news items by the awed quotes of biogerontologists. A
prominent example of this is the diapause state in flies, which as far
as I know has never even been tested for maximal length (in contrast to
the dauer state in nematodes -- though that has only been tested rather
perfunctorily in my view and I'm on record as predicting that the usual
duration quoted, 3 months, can probably be doubled with care). I would
be very surprised if it were other than trivial to keep flies alive for
over 180 days, even in a state that wasn't precisely diapause, just by
genetically predisposing them to some of the genetic pathways that are
activated in diapause (similar to the worm situation -- the long-lived
alleles of daf-2, for example, are partial loss-of-function mutations
of genes for which total loss causes constitutive, permanent entry to
the dauer state).

If a fly prize can be devised that I'm confident can't be won boringly,
I am generally in favour of it. I don't have strong views on details
such as what the threshold winning age should be. I have long felt,
and said, that we're probably some way past the point where flies will
tell us anything much about mammalian aging that we don't already know,
but I could certainly be wrong about that and the speed and cheapness
of fly work definitely mean that a low likelihood of utility (even if
most gerontologists agreed with me about that, which plenty claim not
to, albeit possibly for research-inertia reasons) is no argument not
to try.

Prometheus Prize: Yes, Greg Stock was heavily involved in the original
discussions that led to the MMP idea (see our Acknowledgements page).

Who should run any fly prize: I tend to agree with lightowl that one
run by the MMP would be unlikely to succeed, because the competition
with the mouse prizes would be too overt.

Aubrey de Grey

[reason]

Prometheus: I'd say gather some volunteers and go for it. Do the groundwork and planning out in the open here where people will help, make some scientific contacts for advisory matters, and then just get on and launch it. You'll certainly find volunteers here to help with much of the initial work.

Reason
Founder, Longevity Meme
reason@longevitymeme.org
http://www.longevitymeme.org

[ag24]

Hi again all,

I want to start by clarifying that the last sentence of my previous
post was not, repeat not, a statement of the MF position on whether
or not MF should launch a fly prize, but rather merely my personal
view at this point (which, I stress, I may change). No decision
on this matter has been made by MF and I don't see a decision being
made all that soon, as several important issues relating to it are
still being actively and productively discussed here.

Prometheus wrote:

> 1. accelerate progress towards real longevity-enhancing medicine,
> 2. promote public interest and involvement in research on healthy
> life extension, and
> 3. encourage more such research by providing a financial incentive
> to researchers
> ....
> It seems to me that either you have shifted position or that my
> definition of what objective (1) is in contrast to objective (2) is
> not the same as yours.

I think your latter interpretation is correct -- we see the relation
between (1) and (2) differently. All my activities, of which the MF
is just one facet, are focused on objective 1 and are purely means
to that end. I view the MMP's PR potential as the main way in which
it can contribute to objective 1, and specifically I view objective 2
as the main component of the MMP's PR potential. I do not, in other
words, think that objective 1 is something that the MMP will greatly
contribute to unless it does well on objective 2, because without a
high public profile it will be ignored by researchers and will make
no difference to what research is done.

I hope that's clearer. Feel free to come back on this if not.

> I think that you are saying that an element that is crucial to the
> success of the prize is that the science behind the winning effort must
> be interesting to the biogerontological community. Is that right?

Yes.

> If so can you explain what you mean by interesting - for example are
> there certain approaches that biogerontologists would find more
> spectacular than others?

Probably, but that's not what I meant by interesting -- I meant, that
biogerontologists would find more likely to be relevant to human life
extension.

> Aging mechanisms are highly conserved across the vast majority of
> multicellular, and single celled organisms.

Unfortunately this is much less true than we might wish. At the most
fundamental level there is a lot in common: flies and humans both use
oxygen, for example, with the same machinery (the mitochondria), which
have more or less the same structure. But we know those fundamental
things quite well now. One huge pitfall that gerontologists face is
that we are now trying to fill in details that are only sometimes the
same across all mammals, let alone all metazoans. For example, Sir2
does essentially the opposite to the cell cycle in mice versus worms,
probably because mice need to avoid dying of cancer and worms don't.
Mice express telomerase all over and have huge telomeres, so telomere-
driven cell senescence definitely doesn't happen in mice, but plenty
of people think it may both happen and matter in humans (and in some
tissues, especially cartilage, the evidence is strong); this is very
likely to be because telomere shortening couldn't stop a cancer fast
enough to help a mouse whereas it can for us.

> Death seems to be a universal consequence to the majority of life.

Sure, but because aging is (as Hayflick has so succinctly put it) a
consequence of evolutionary neglect, the mechanistic, genetic basis of
aging need not be particular conserved across aging organisms, unlike
processes that are evolutionarily selected (e.g., respiration).

> It would not be a wild
> flight of the imagination to consider that if a fly can be made to be
> semi-immortalized then the interventions that made that possible would
> also herald the existence of some some similar intervention in other
> species.

You are so right, and that exact flight has duly trapped most of my
colleagues into a decidedly sticky research cul-de-sac. I presume
you're familiar with my ongoing attempts to change this by pointing out
why it is not at all surprising that we can sextuple the longevity of
worms but not mice, and what that and lots of other data says about
the human life extension to be expected from manipulation of nutrient
sensing. My paper on this is in press.

> Also it would not be surprising that the implications of such
> a discovery would not only resonate in every laboratory in the world
> but in every newsroom as well.

Again true, and of course this has been the case every time Cynthia
Kenyon or whoever extends worm lifespan a bit more. However, and this
is the key point, work on serious mammalian life extension (especially
late-onset) has not resulted.

> On the "diapause problem": this has been covered before, and it was
> shown that it is easy to delineate diapause from non-diapause state
> using hormonal testing for validation purposes. Providing that the
> researchers entering the prize are made aware that any extension in the
> diapause period does not count towards life-extension and that their
> results would be subject to peer review what is the issue with
> diapause?

I thought I answered this but maybe I missed a post some time ago. The
problem is that it is NOT easy to delineate diapause from non-diapause
state, especially not when genetic manipulations are involved, because
one can arrange for an intermediate level of expression of genes that
are turned up or down in diapause, and this may confer plenty of life
extension, just as intermediate levels of dauer-specific genes confer
in worms. The second problem is that flies are too small to be tested
non-destructively for hormone levels, so any study in which there was a
high degree of heterogeneity of gene expression would necessarily have
outliers that would not be identified by testing other flies. There is
also no way to avoid this heterogeneity, because so much gene expression
is determined stochastically and epigenetically, and this seems to have
a profound effect on fly lifespan as demonstrated by several large-scale
studies over the years, such as the Carey and Curtsinger ones published
in Science in 1992. Curtsinger regularly saw 100-day-old Drosophila. In
principle one might be able to estimate the degree of heterogeneity by
statistical means and extrapolate to the expected diapauseness of the
most diapauseful fly in the experiment, but that helps not at all, because
winning experiments will be large and the answer to that calculation will
therefore be "very diapauseful indeed".

Aubrey de Grey

[treonsverdery]

Jaydfox writes It has been discussed in other topics (e.g., in the 3rd page of the "Methuselah Prize - You Decide" poll.) that we should create a Methuselah Fly Prize, as an extension of the Methuselah Foundation's goals. Would you support the creation of such a prize category
Id give an afternoons wages I think a differently named hyperlinked entity might keep things coherent


different JDF messageSitting back and watching the prize grow a couple thousand dollars a month is an opportunity to bring value to site visitors a coherent statement matters a bunch Ive thought that theres a clever way to finance 300 membership

Annuities pay funds with time
a 25k annuity 1k per year might have a NPValue near 9 or 11k at 3 pt
a 9k NPV annuity with 25k time value might be made a part of a bigger item typically the advantageous refinancing of a house

There is a way that the millions of scientist engineer homeowners might be motivated to remember the Mouse Prize while advantageously refinancing their houses I think that an online item attractive to these homeowners will generate donations

A minimal page mentioning these three things might increase donations

http://www.ofheo.gov...pdf/1q04hpi.pdf tells where property most appreciates
a site like http://www.bankrate.com that lists rates
a few words from the mouse prize saying the likes If you read this government listing you'll find areas near you where property values increase at well over 10 pt per year Adding just a few pt to your home financing will create an opportunity to endow the Mouse prize with a 25k annuity joining the 300 you know the way all those ads have happy family pictures well think on the future

[jaydfox]

I'm not the biologist, so I'll sit back and let Prometheus continue the debate from here. However, I must chime in on one statement, as its foundation is as much in reason (not Reason ) ) as it is in biology, and thus accessible to us non-biologists:

Sure, but because aging is (as Hayflick has so succinctly put it) a
consequence of evolutionary neglect, the mechanistic, genetic basis of
aging need not be particular conserved across aging organisms, unlike
processes that are evolutionarily selected (e.g., respiration).

(I apologize for the length of the post)
There are several well-supported and -reasoned arguments to the effect that evolution's creation of aging is not a case of neglect, but of increased fitness of the species. And bottom line has always been "Survival of the fittest", whatever "fittest" means.

Aging can be a good thing for the species, even if it unfortunately sucks for us individuals. Since many aspects of Evolution cannot be "tested" in the lab--I acknowledge that a LOT can still be theorized from inter-species (inter-genus, inter-family, etc.) genetic and biological comparison--we are left with several competing theories of Evolution, just as in physics we had several competing theories for how Relativity and Quantum Mechanics would mesh together (and we still have many, though strong candidates are emerging).

In Evolution's case, we can't even go so far as to say "the jury's still out"; we're still in the evidentiary phase right now. Evolution's hand in creating aging--or in neglecting it, depending on how you look at it--will not be decided for some time, probably not until we're a lot closer to actually having stopped the process; after all, such an understanding will help determine the future direction of anti-aging research.

If Evolution did have a hand in creating aging (or put another way, in not neglecting aging), then your statement that "the mechanistic, genetic basis of aging need not be particular conserved across aging organisms, unlike processes that are evolutionarily selected (e.g., respiration)." loses its merit.

Quite a bit will still be conserved across the species. Some of it won't, of course. New mechanisms for dealing with age-related problems have come along, with other new mechanisms to prevent those new mechanisms from extending life too much.

But that CR is so effective across a variety of species, indeed Kingdoms, (regardless of whether or not its benefits are absolute, which I would like to read your paper about, as from the abstracts you've posted the suggestion does seem flawed) indicates that at least this one mechanism, with its underlying genetic basis, has been preserved. Lazarus Long has taken issue with this claim, but on the flawed assumption that CR is only a situation of sub-optimal performance, which on the surface it may appear to be. However, that's neither conclusive, nor is it relevant to humans, for whom "optimal" has very little to do with the conditions that evolved us.

Many other such mechanisms, many stress-related, will also likely have been preserved (heat shock proteins come to mind). And there's a good chance that non-stress-related mechanisms will have been preserved as well; evolvability (which is sort of stress-related I admit) can be upregulated, which implies that it can be downregulated as well. If aging is a key to (both cause and effect of) evolvability, then certainly our bodies would not be designed for maximal lifespan when the evolvability mechanisms are functioning as "normal".

So while I agree that there's a possibility that extending life in flies will have no further relevance to humans, I see that possibility as remote (for now). Given the costs involved, not pursuing the fly route (in addition to the mouse route) would be unwise. I'm not saying that you have to do it, of course.

Jay Fox

[jaydfox]

treonsverdery:

Very interesting proposition about annuitizing the 300 membership pledge.

Perhaps the MMP website could incorporate information about this? You should go to the Giving the Methuselah Mouse Prize some jets topic in the Action & Reaching Out forum, and post the suggestion there. The directors of the Methuselah Foundation check in from time to time to look at the suggestions.

[Lazarus Long]

Lazarus Long has taken issue with this claim, but on the flawed assumption that CR is only a situation of sub-optimal performance, which on the surface it may appear to be. However, that's neither conclusive, nor is it relevant to humans, for whom "optimal" has very little to do with the conditions that evolved us.

I think this is an interesting and important debate aspect on evolution. I also think you are reading way too much into what CR does but I should add it is precisely the *universal* aspects of species that makes genetics and Evolutionary Biology areas well worth examining more closely. I should add that whereas an explanation of the phenomenon as a part of a back up strategy akin to sporification, hibernation, and as I like to identify it, *minimal demand* mode are all logical results of environmental adaptation from Natural Selection, none of these need to be explained by some *programmed necessity* for death.

I would appreciate if we take this debate back to the appropriate thread however as I suspect it will continue and *evolve* on its own for some time to come.
DNA, In My Opinion, Is The Cause Of Aging

Humans BTW carry many if not most of the genes (as well as additional successful mutations) acquired through the long process of evolution. It is this simple fact that makes cross species analysis very relevant, provides reason to reflect on why genes in C-Elegans are the *same* operative genes in humans, but more importantly understanding that we evolved by undergoing many similar adaptive stresses and overcame them through often very similar adaptive strategies. (Convergent adaptation)

Famine was and is one of the MOST common stresses to survival under any model of Natural Selection and as such I would suspect there are many genetic fall back strategies that have evolved to address this *threat*.

The three I mention are found across the entire spectrum of life from the bacterial to humans; sporification, hibernation, and an ability to metabolically slow down to extend life till opportunity returns. This last seems to accompany the more complex life forms at the top of food chains. An extreme instance of the reduced demand mode may have something even to do with hypothermia survival cases.

CR does not have to be understood as more complex than this and I think that we may sooner than you expect resolve the question as the map of the human genome continues to unfold leading us to greater understanding not only of how our biology functions but how (and why) it evolved the way it has.

I should add that *Optimal* for human physiology as we have evolved has everything to do with the problem both as you are assuming it to be based on your interpretation of evolution and from my differing one.

[jaydfox]

I would appreciate if we take this debate back to the appropriate thread...

Well, we've been debating it with respect to relevance of flies vs. mice, so I see it as appropriate here. However, having at least *raised the issue*, we could settle the issue there, as you suggest, and keep this topic clear from such clutter.

Jay Fox

[jaydfox]

Okay, there are a GREAT MANY issues here! It is becoming increasingly difficult to get a good debate going on the important details, especially when so many people are carrying on their own little debates, and Prometheus and Dr. de Grey are having their attention deflected to "asked-and-answered" types of questions and objections.

I have a proposal. I don't know if it's technically feasible, or how long it would take to set up, but...

Just a sampling of the issues raised:
-Would a fly prize be able to raise "enough" money, and what is "enough"?
-Do flies have anything further to provide in terms of understanding mammalian, and specifically human, aging?
-To what degree is aging a factor of DNA, i.e. programmed in by Evolution?
-Regardless of whether Evolution programmed us with aging, to what degree can properly engineered DNA prevent aging beyond development to adulthood/reproductive maturity?
-Would a fly prize serve a better scientific role than the MMP's Postponement Prize in producing results which could then be tested in competitors for the MMP's Reversal Prize?
-When could we see results, and what kind of results could we expect, from the Mouse prize and from the Fly prize?
-What criteria would be used for determining who "wins"?
-Will diapause, or effects related to it, skew the results, and is there a way to detect this?
-How can we best ensure that--aside from the related issue of monitoring diapause--the winning competitor's results are valid?
-How much does the scientific community care about public opinion and public relations?
-Would a fly prize end up competing with the Methuselah Mouse Prize for donations (and for intellectual/management resources)?
-Would a fly prize best be hosted by the Methuselah Foundation?
-If not hosted by the MF, who will host/operate/own the fly prize?
-Why not other animals? Why not a whole slew of prizes?
-Why not, for that matter, incremental goals with associated prizes, much like one of the precepts of the Prometheus Prize?

If we are serious about settling this issue, and judging by the tone the debate has at times taken (I myself am guilty!), then this is just the tip of the iceberg! Some of these issues might be settled in the next couple weeks, and we'll move on, but if enough people are serious about this, then many issues will remain and will take a more "let's get it done" approach, rather than a debating approach. At any rate, how do we identify which topics and polls are related to creating the fly prize?

Support here is very split. Not including myself or Prometheus, about 60% of the votes have been against creating a fly prize. Many of these votes were cast before people even read the many good arguments for and against the prize (I'll admit there are good ones against, in case anyone has gotten the impression that I believe otherwise), so I don't know where the numbers really stand if we took a poll today. Perhaps a 50/50 split? (As an aside, we need a way to allow people to (anonymously) change their votes...)

The point is, regardless of however many people are against it, there is still a goodly proportion in favor of it. Reason has suggested that Prometheus et al. come up with a formal proposal, and perhaps go as far as creating the prize ourselves.

Before we take that plunge, here is the suggestion that I was taking my sweet time getting to:

Why not have a new forum added under the Focus or Projects section of the ImmInst forum? I don't care really what it's called: "Biotech Prizes", "Prizes and Research", etc. I wouldn't go as far as calling it "Creating a Fly Prize", although such a topic/poll should be one of the "pinned" topics, probably. This forum would have a lot to offer to the MMP (see e.g. Prometheus's topic about Giving the Methuselah Mouse Prize some jets), as well as to many future prizes that might come along.

If we do create such a forum, I wouldn't necessarily move all these topics over there. If we do, I would at least want to create a new poll for creating a fly prize, so that we can get fresh results, and pin that new poll. Make references of course to the old poll. Etc., etc.

What do you guys think? Bruce, is this possible? If not, what would you suggest so that this issue doesn't swamp the Biotech forum?

Jay Fox

[reason]

Jay (and others), groundwork done on the rest of the iceberg for a Fly/Small Living Thing Of Choice Prize is valuable work irrespective of other issues or resulting usage. It can be done by volunteers here and remain as a resource even if it is not immediately made use of.

I agree that a new forum for a wider and more coherently organized discussion is a good plan. You should PM/e-mail Bruce and make your case for it.

Reason
Founder, Longevity Meme
reason@longevitymeme.org
http://www.longevitymeme.org

[Bruce Klein]

Thanks, Jaydfox.

Good idea.

I've created a new "Life Extension Prizes" Forum under Projects Category. This forum will possibly be temporary or permanent depending on activity and participation.

I've moved some of the prize discussion topics under this new forum (including this thread).

Bruce

[ag24]

Prometheus wrote:

> Aubrey, I've never perceived researchers as being sufficiently
> concerned by public opinion to influence the direction of their
> investigations so I do not share your confidence that the primary
> objective of accelerating discovery would be best served by using
> the MF to generate public PR. I wish I were wrong, of course, as the
> world would be a different and better place if the establishment of
> scientific research direction could be 'democratized' by public
> opinion. If you see this differently, let us know.

I see it as you do for most of science, but gerontology is different.
I think the difference results mainly from the insatiable appetite that
the public demonstrate for what biogerontologists do, and the resulting
scale of the media attention that we get. If you divide the number of
national TV hours or newspaper column-inches devoted to biogerontology
by the number of its researchers, you get a very, very different number
than for any other field. Life extension is not understood by Congress
etc., so when Richard Hodes (head of NIA) gives his annual address to
Congress he sticks to safer topics such as "compression of morbidity".
Every gerontologist knows, deep down, that compression of morbidity is
a pipe-dream -- yet they meekly go along with this party line because
they're petrified of the funding agencies and the funding agencies are
petrified of the government. And the government are petrified of the
public, who ... take their cue from what biogerontologists say to the
media. Have a look at my web page http://www.gen.cam.a...ens/silence.htm
for a more detailed exposition of this "triangular logjam".

> What is intriguing, is that knowing as you do that your colleagues
> are entrenched in their 'cul de sac' thinking that you did not choose
> an intermediate approach using a less radical paradigm.

It's not that bad -- after all, there are plenty of mouse researchers.

> I would ask you to clarify your opinion on the conserved (or not)
> nature of aging across species.

OK. Certainly oxidative damage is a more-or-less universal mechanism
of aging, and has been for a very long time. Thus, the fundamentals
of how species protect themselves against it were evolved a very long
time ago and have been retained. What I was stressing was that the
less fundamental aspects are less conserved, partly because they've
been freer to vary during evolution, but mainly because their optimal
nature is more dependent on the details of the organism's physiology
than is the case for the fundamental things. Now, clearly the obvious
approach to mammalian life extension is to figure out the fundamentals
(using any old species, since they are conserved) and then apply our
knowledge. Unfortunately, we've been trying that ever since Harman
started feeding antioxidants to mice in the 1950s, and it's been a
complete flop. So, we have to get into the detailed mechanisms -- and
for those, we have to work with species closer to us.

Aubrey de Grey

[ag24]

Prometheus wrote:

> Aubrey, the degree of diapausal lifespan manipulation that you are
> suggesting would bring into doubt and possible disrepute every single
> study where adult organism longevity has been an experimental outcome
> using diapausal capable organisms.

Absolutely not, there's no issue of disrepute or fraud here, not at all.
I see I've omitted something: it's not just that diapause is impossible
to detect (let alone prevent) sufficiently accurately, it's that diapause
is not considered a problem so long as it's not wholehearted.

The issue is one of the PR value of a given result. When Cynthia Kenyon
discovered the daf-2 mutation that doubles worm lifespan (in 1993), that
gene was already known to be one in which a null mutation causes the worm
to enter a constitutive dauer state -- that's why it's called "daf", for
DAuer Formation. It had also been known, for nearly 20 years, that dauer
worms could be kept as dauers for three months -- much longer than daf-2
mutants live -- and revived and live a normal lifespan thereafter. This
being so, one may wonder why anyone was interested, since the argument
you give about diapause would seem to apply in spades here.

The reason people were interested is that they didn't care that the genes
involved were the same ones involved in dauer -- what mattered was the
bottom line that lifespan was doubled despite the worms not being in a
true dauer state. Morphologically and behaviorally they look normal.
Similarly, in flies, there is nothing at all wrong with life-extending
mutations that hijack the diapause pathway -- if the flies are getting
on with their lives in a normal way, rather than hunkering down in the
manner typical of diapause, it's still interesting, publishable, etc.

Up to a point.

And this is the key issue. Mammals do not have dauer and they do not
have diapause (though of course some have hibernation). It turns out,
not very surprisingly in retrospect, that the genetic pathways involved
in dauer and diapause are still present in mammals and are involved in
the life-extending action of caloric restriction. And sure enough, the
story just outlined for worms has happened in mammals: mutations have
been found that extend mouse lifespan, and they're mutations in the CR
pathways, but people have been very excited about them anyway, because
the life extension is what matters. But, this all *is* the prevailing
paradigm. One of the more miserable things about science is that it's
much easier to get a paper into Science or Nature that reinforces the
existing paradigm than one that shifts it.

Aubrey de Grey