162 replies to this topic

[reason]

Heinlein: the 60k figure is cash in hand. The 425k figure is pledges. The idea behind building a large figure in pledges is for it to act as bait for larger donors. It's good psychology.

I think the fly prize idea has a lot going for it if it were funded - even a 100k prize would get competitors, given the economics involved. However, I'm extremely dubious that one could pull off the same sort of public funding methodology as the Mouse Prize is trying; you'd need a large philanthropic at the start.

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

[jaydfox]

Only a minor technical note: The 425k figure is cash and pledges, rounded to the nearest 25k. There's only currently 375k in pledges, 25k each for 15 people.

Reason,

I agree that the Fly prize wouldn't need to be nearly as large as the Mouse prizes for it to be effective. The current 3:1 ratio for the RP to the PP would apply well for a ratio for the Mouse Prizes to a Fly Prize, if one were created.

This would even work out fairly well: the Fly prize, given that fewer non-scientists would be convinced by its efficacy, would probably not be as well funded. So, in that respect, it wouldn't draw a lot of funds away from the Mouse prize, one of the major concerns here.

On the flip side, the limited funding it did get would probably be just as effective as the larger Mouse prizes in spurring research, because of the lower costs involved in performing the fly research.

Would those two points (minimal impact on funding the Mouse prize, plus higher rate of return on research [regardless of rate of return on PR]) affect anyone's vote on creating a Fly prize?

Also keep in mind that rather than a 25 year pledge, the Fly prize would probably be quite effective with only 15 year pledges.

Jay Fox

[apocalypse]

Maybe they do know and just don't care. If so, how can we help them to care?

Ideas, anyone?

I'd say it wouldn't hurt to put a % genome comparison, and several quotes from prestigious researchers showing the relevance of such work. IF the laymen realize the relevance to humans of work in mice, they'll pay attention.

[jaydfox]

So rather than the comparison of 25 years pledge for mouse versus 15 years for the fly is should be more like 5 years only for the fly.

Prometheus,

In straight research time, yes, the comparable pledge length would be 5 years. But I think the 25 year pledge for the Mouse prizes is considerably longer than the research time involved. We're essentially hedging our bets here. We're not just looking to reach a "significant" life extension in a model species, award a prize, and then stop. We're looking for incremental improvements, with more and more prize money being awarded, and more and more publicity being developed. I'm actually optimistic that 10 years would be sufficient for a Fly prize, but, I can't guess how many people will sign up to pledge in the next year or two to get serious research going. So I figured, hedge my bet, and set it to 15 years. If after 8 years we get dramatic results, and a billionaire philanthropist comes along, then those who wished to be released from their remaining pledges probably could be with negligible impact; their work is done.

At any rate, even 10 years is still useful. New pledges would continue to come in for several years, so that the money would be spread out over the 12-15 years it might take if the prize were created today. That said, I agree that 10 years is probably better, for this and other reasons (see below).

Also, given the smaller monetary requirement of the Fly prize (measured in hundreds of thousands to millions, versus millions to tens of millions for the Mouse prizes), the minimum annual amount for a Fly pledge could be a lot smaller, perhaps $500 or $200 dollars.

There could be a separate "300" just for the fly prize! If we got 300 people pledging $500/year over 10 years, it'd bring in $5000 per person in pledges. At $42/month, that's within reach of a few more people than $85/month is. If we got 300 people pledging $250/year over 10 years, it'd bring in $2500 per person in pledges. At $21/month, that's within reach of a lot more people than $85/month.

It'd only bring in 1/5th or 1/10th of the pledges of the Mouse "300", but in a shorter timeframe, bringing more results, more press, and hopefully more funding to the Mouse prizes (rather than pulling donations away from the MMP).

Also, keeping the pledge period shorter (at 10 years) would help us to realize that this is just a short term project to help make the Mouse prize successful earlier. We could even stipulate that at the end of 8-12 years (the exact time could be voted on by the Foundation or the Fly "300" themselves), we could just declare the Fly Prize a success (assuming it was), and consolidate the remaining prize money and pledges into the Mouse Prize.

After all, the Mouse Prize isn't an end unto itself, but a means to realizing a better end: extending human lifespans.

Jay Fox

[jaydfox]

I was feeling a little uneducated today (I always know that I'm uneducated, but I was *feeling* it a little more strongly today), so I did some snooping around at the MMP website. I came across the list of advisors, both scientific and non-scientific.

The conclusion I came to is that they have a few heavyweights advising them on this, which makes me feel a little smaller, and it makes me wonder... To what degree could I or anyone else here affect the goals of the Methuselah Foundation? I ask this, because the more we debate the concept of creating a Methuselah Fly prize, the more I am in favor of it--and the more I want to know what the debate looks like to the insiders at the Foundation. (I haven't heard much from them lately. It seems like Dr. de Grey and Dave Gobel were active here a few weeks ago... But much thanks to Reason and others who are still commenting on this topic.)

For each argument against a Fly prize, I can pick out subtle details that only make me favor it more. I started out against it (for the PR reasons, as well as fears it would draw funds from the Mouse prize). Now I see it as a tool to advance the science, and actually help bring more funds to the Mouse prize.

You could even lay out a framework for how progress could be made (sort of like the research timetables that Prometheus often lays out, though I'd use more pessimistic time ranges just to cover our bases).

For example (I'm not an expert in prize administration, so these would need to be tweaked):

Step 1) Short term goals (4-12 years)
Fly Prize - Try to get 300 $2,500 pledges (divided over 10 years)*, plus donations. Over 10-12 years, this could gross $800,000-$1,000,000** in donations and pledges. If significant progress is made here***, a supermajority vote of the Foundation and/or pledgers could decide to phase out the Fly Prize in favor of the Mouse prize(s)****.

Step 2) Mid-term goals (10-25 years)
Mouse Prize(s) - The existing prize structure***** - Try to get 300 $25,000 pledges (divided over 25 year), plus donations. Over 25-30 years, this could gross $8M-$12M or more in donations and pledges. Rapid advances in Fly prize could help bring more donations******.

Step 3) Long-term goals (15-50 years)
Other prizes? Creation of an institute focused on systematic accomplishment of the goals of SENS, per the vision of Dr. Aubrey de Grey?

Explanatory notes:
* Those who think they understand the dynamics of the transhuman/anti-aging community could probably come up with a better system, given that the Fly prize will probably never appeal to the "general" public. Perhaps we could try for 150 pledges of $5,000, with $500 a year for 10 years. Or, we could try for 160 pledges of $4,500, with $300 a year ($25 a month) for 15 years. I'm aiming for a pledge goal 1/10th of the Mouse prize (i.e. $750,000). We could be more ambitious than this (I'd be in favor of a goal of 1/5th the Mouse prize), but I'm trying to appease those who see a Fly prize as pulling much-needed funding from the Mouse prizes.

** As some have pointed out, the prize will probably be small. However, there is still doubt that it could be funded:

However, I'm extremely dubious that one could pull off the same sort of public funding methodology as the Mouse Prize is trying; you'd need a large philanthropic at the start.

However, the Fly prize can be successful in spite of being an order of magnitude smaller than the Mouse Prize, for at least a couple reasons:
1) The funding required to run the experiments will be smaller, requiring a smaller incentive/reward/award.
2) Given the nature of the fruit fly lifespan, and using past precedents (not always a good idea, but humor me), I expect that incremental winners will win substantional percentages of the award at any given stage. I.e., a 20%-50% increase over the current recordholder seems easier to accomplish than a similar percentage increase in mice. So even though the prize is smaller, we could still see large payouts. If the Fly prize were at $250,000, and someone broke the record by 30%, they'd get $75,000. If the Mouse prize were $2,500,000, and someone broke the record by 10%, they'd get $250,000. Given the costs of running the experiments, these prizes could be adequately proportionate.

*** "Significant" need not be a function of % life extension. In other words, rather than focusing on the goal of a fly that lives 4 months, 6 months, 8 months, or a year, we could focus on what has been learned, and how well it could apply to mice and humans. If we are able to identify a dozen, two dozen, or "all" ("all" to our satisfaction) key genes, and how over/under-expressing them to various degrees affects lifespan, and if several/all of those genes have well-preserved analogues (orthologues? What's the right term?) in mice (and humans, preferably), would we consider this significant? Where do we draw the line and say we're seeing diminishing returns in terms of indentifying target genes?

**** Since Fly research will be ongoing, and will probably continue to be valuable even after it has made its most "significant" progress, we probably wouldn't want to end the prize outright. But, we could freeze the account, so to speak. Prevent further donations (encouraging donations to the Mouse prize, of course), and gives pledgers the choice to end their pledge, or direct the remaining money into the Mouse prize(s). Allow the Fly prize to still be awarded, until it is depleted sufficiently and is awarded infrequently enough to justify ending it and transferring the remaining funds to the Mouse prize.

***** As with the Fly prize, we (the Foundation and/or the relevant pledgers) could vote to phase out the Postponement Prize, once it has accomplished its PR goals and highly effective somatic gene therapy techniques (or other techniques) make germline research less useful and slower. Keep the prize operational, but prevent further donations, and direct remaining pledge money to the Reversal Prize.

***** The Fly prize will have affects on the Mouse prize in many ways, and I cannot predict the end result. However, I speculate that if the Fly prize's funding goals are small enough compared to the Mouse prize, then it will pull away only very limited funding from the Mouse prize. It could also be argued that, assuming the prizes reach "adequate" levels, a dollar spent on the Fly prize will encourage more teams and more avenues of research than a dollar spent on the Mouse prize.

The Fly prize could possibly hurt the "reputability" of the Methuselah Foundation, and by extension, the Methuselah Mouse Prize. So this could be another source of donation-drain.

However, the Fly prize could be generating more frequent winners, and more substantial percentage gains in lifespan. The PR value of this could help the fence-sitting nerds be more willing to donate to the Mouse prize (i.e. the prize that will more directly lead to human interventions). So in the short run (perhaps the first six months, or the first 3 years) after creating a Fly prize, I see a small net decrease in the donations that the Mouse Prize might otherwise have achieved. However, in the long term, I see a net increase in the donations. It could bring the PR value of the MMP to the "general" public (as opposed to the focused attention it has now) much sooner.

Jay Fox

[Da55id]

Hi Jay et al...you make interesting points. The main science that will establish effective rejuvenation is the science and art of human motivation. I am extremely focused on this science. I've devoted much of my life to it. I still have much to learn.

with no offense intended in the least, here's my bottom line on flies - They're not cute, and they seem so far removed from the human species that regular civilians with money to donate are likely to be repulsed at the idea of keeping the little buggers alive. Also, until we become more widely know and financially supported it will most likely be suicide to add another prize. The press will think we're bonkers and dismiss us. No more Fortune articles etc.

I'm like you. I want to run faster. However, I'm now on my 11th startup and have learned that focus and persistence are King. (pronounce that little dot out loud ...as PERIOD!)

What would be extremely interesting to me however is the idea of a prize to completely and accurately simulate biosystems (even flies) such that interventions in the real world totally and exactly match the outcomes from the simulation...the advantage of the simulation being that it can run thousands of generations in terahertz time using grid computing techniques free on swarms of donated computer cycles. This would further allow the free use and investigation of multifactor interventions.

So, the advantage of flies is that experiments are an order of magnitude faster than mice. I propose that we should be looking for a method by which we can gain 5 or more orders of magnitude improvement in experimental cycle time without having to concern ourselves with sourcing, feeding, care or the ethics of experiments on living creatures. (for those of you who would like to now argue that perfect simulations are alive, feel free...just don't expect me to join you :-)

dg

[reason]

As I say here:

http://www.fightagin...ives/000195.php

I'd be all for a group starting up a Fly Prize and working to prove me wrong on the publicity angle.

This strikes me as an Imminst-sized project, for example. There's a guy out there who runs hobbyist-level fly experiments on life extension who posts to various transhumanist lists. If he can do it...

If Imminst can write a book and organize a documentary, it can certainly run a prize for long-lived flies...

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

[jaydfox]

Reason,

Thank you for honoring this topic on Fight Aging! Only 8 people have voted in this topic (though many have posted), so perhaps this will draw more attention to the question. I really would like to see 20 or 30 votes on this issue.

And I suppose you're right that a prize of this modest size might be doable outside of the Methuselah Foundation should they decide not to pursue it.

To All,

With that in mind, perhaps this poll shouldn't merely be about whether or not a fly prize should exist. Perhaps the "Yes" and "No" options should be split:

Yes, a fly prize should be created; the Methuselah Foundation should create it.
Yes, a fly prize should be created; another group should create it.
Yes, a fly prize should be created; I'm a rich philanthropist, and I will create it.
No, a fly prize is not necessary.
No, a fly prize would not be successful.
No, a fly prize would do more harm that good to the goals of the mouse prize.

Are there enough people still interested in seeing this resolved to create a new poll? If there are, would you agree to my choices of options? Should we have a poll about creating a new poll? (Okay, now I'm just being silly...)

Jay Fox

[reason]

Prometheus; Bruce is going to be fairly busy and intermittantly online until the end of TV2004. A useful and constructive thing to do would be to lay out a proposed prize structure, rules, time cost of setup (build a website, corrall people, etc, etc) and management process for a Fly Prize so that the leadership here - since this is a board-run organization - can see how feasible it would be to put under the Imminst umbrella.

The most important thing is dedicated people with the time to drive this - there's no shortage of ideas, but a great shortage of people willing to put their backs behind them.

As I've said before, I think you're wrong about what can be done with public opinion regarding flies, but I'll be happy to see you try to prove me wrong on that score. The more diverse efforts there are by motivated people, the more successes we as a community will achieve.

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

[jaydfox]

Thank you for your response, Dave. I was wondering if we were talking to ourselves in here...

with no offense intended in the least, here's my bottom line on flies - They're not cute, and they seem so far removed from the human species that regular civilians with money to donate are likely to be repulsed at the idea of keeping the little buggers alive. Also, until we become more widely know and financially supported it will most likely be suicide to add another prize. The press will think we're bonkers and dismiss us. No more Fortune articles etc.

So... that would be a "no" vote? [tung]

What would be extremely interesting to me however is the idea of a prize to completely and accurately simulate biosystems (even flies) such that interventions in the real world totally and exactly match the outcomes from the simulation...

My prediction is that our knowledge of biological systems and our computer processing power would have to increase by at least one order of magnitude before we can even entertain the development of such systems.

Actually, computer processing power will most likely increase an order of magnitude every 5-6 years. If that's all it took, I'd say sponsor the biological simulation prize!

However, I think *several* orders of magnitude will need to be accomplished. Right now, the Folding@Home project is already using terahertz-level distributed processing power for weeks and weeks at a time to fold a single simple protein, a process measured in milliseconds (or was it microseconds?) in the real world. That should give you an idea of how many orders of magnitude we need. We'll probably have 8- to 10-year-old mice before we can even accurately simulate a yeast in anything resembling "real time". We'll probably have 12- to 15-year-old mice before we can simulate fruit-flies in real time. And another 3-6 years before those simulations run at 10 times normal speed. And another 3-6 years for another 10x speed improvement.

In the long-term, a biological simulator is our best hope! But that's more a function of Moore's law than of creating a prize.

Unless you're willing to cut corners on the accuracy--sacrificing moleculer-level accuracy to heuristics models--biological simulations won't tell us enough for decades to come. And we don't know enough about the biology yet to be able to fully trust the heuristics approach (unless someone would like to prove otherwise...).

Of course, when I laid out a set of "short"-, "mid"-, and "long"-term goals in my example timeline, perhaps a biological simulation would make a good long term goal? Perhaps a good complement to Dr. de Grey's proposed institute? Prometheus, would you agree?

On Reason's suggestion:

Why not? Are you in BJ? I'll cover the costs of incorporating a non-profit entity and pledge $5,000 towards the prize.

That's very generous! I'd be willing to "pledge" as well, though more along the lines of the ten- or fifteen-year pledges I suggested in a previous post.

While I'm at it, allow me to rehash an old quote by MethuselahMouse:

Relieve frustration by personal action...donation is a good outlet :-)

We started this effort with the full knowledge that it was likely that more than a billion people would die before it yielded clear results. We are likely to be blamed one day for some of these deaths. But the pure fact is - ANYONE - can start a prize...just look in the mirror and say like we did - "why not"?

A useful and constructive thing to do would be to lay out a proposed prize structure, rules, time cost of setup (build a website, corrall people, etc, etc) and management process for a Fly Prize so that the leadership here - since this is a board-run organization - can see how feasible it would be to put under the Imminst umbrella.

Prometheus, I say we not tread lightly into creating a new prize. However, we should at least begin planning its structure, rules, etc. (assuming BJ and others are interested). Those details will need to be resolved before the prize is created, whether the Methuselah Foundation ultimately hosts the fly prize or not. That gives more time for us to prove our point to the imminst community, and possibly the Methuselah Foundation. If--after working out the minimum necessary details--the Foundation still decides not to pursue this, then we could pursue a separate organization (though try to maintain good relations with the MF).

By educating the public, by offering incentives, by capturing people's interest and imagination, by showing that if we can make a fly live longer we can do the same to humans, by explaining that 24 hours in a fly's life is equal to 1 human year - that gives a real sense of excitement - each day that a fly lives longer for is an extra year of life! So many ways to market it. These are not big dirty, hairy, turd dwelling flies, these are tiny, delicate, dainty fruit flies. Thanks to these little creatures many medical advances have been made that have saved innumerable lives already and continue to be made by some of the worlds most prestigious investigators.

You have to give people more credit than to think that they are so influenced by the model organism type they are donating to. Educate! Promote! Explain!

In that lights, the Fly prize would need a lot of education resources--accessible to the public in terms of science, history, and metaphors--available on a website. As Prometheus has pointed out, the website needs to cater to the needs of the layman, the competitors/scientists, and the press.


Before ending this post, I wanted to share an old quote, because I think it sums up my attitude about the people here:

I have been moved by the passion of the folks here at Imminst. They stand against the tide, sometimes grasping at straws, sometimes briefly glimpsing a tiny snippet of the grand design. Those without scientific training courageously fumble with concepts in their quest, and those with training, well.. there are not enough of those. It is up to us privileged to have the education and training to properly resource and guide the rest.

I'm in the first group--courageously fumbling...

Jay Fox

[jaydfox]

I think a Methuselah Fly would be a step backwards compared with a Methuselah Mouse, and would detract from that contest.

If the Methuselah Mouse prize could produce results at the same cost in the same timeframe as a Methuselah Fly prize, then yes, a fly prize would be a step backwards.

However, there are literally hundreds of possible genes to target that would have non-negligible positive impacts on life expectancy. Which ones to target (why not all?) is a big question. We could probably estimate the biochemical effects of quite a few of them using gene chip microarrays, etc. But how would these effects affect lifespan, either individually, or when combined.

For example, dwarf mice live a really long time. CR'd mice live a really long time. One could postulate that the effects would be additive. However, they are not. CR'd dwarf mice do not get the same absolute life extension, let alone the same relative life extension, that "normal" CR'd mice do.

Another example. Exercised mice live considerably longer than sedentary mice. However, exercised CR'd mice do not live considerably longer than sedentary CR'd mice. Again, the absolute benefit is smaller, and the relative benefit is much smaller.

If you look at the current situation, the scientists are busy testing one gene at a time. Progress is good. In some cases, the progress is very good.

But one gene at a time is too slow, especially when you have to wait 4-6 years to see the results.

Besides, even once we know the effects of several individual genes, we still won't know how they work together. Some may even conflict with each other. Some genes are just "squaring" the curve, reducing premature deaths relative to some "maximum lifespan" based on other factors. The net result is an increased life expectancy. However, multiple squarings of the curve result in diminishing returns. We need to find mechanisms that are truly additive in nature, at least in absolute timescales, if not relative.

Many of the genes in fruit flies that affect aging have related genes in mice. The effects should be similar, though the degree of life extension may not be. However, out of those several hundred relevant genes, a fly prize could help identify a couple dozen key genes. And not just the genes, but the mechanisms whereby those genes work--that way, if there isn't a directly analogous gene in mice, we'll know what the mechanism is. And not just the mechanisms involved, but which genes (and mechanisms) conflict, and which work well together.

In fact, fly studies could at the very least validate broad theories, such as the DNA-damage/repair theory that Prometheus advocates. What if a fly study disproved that theory, or at least showed that only modest improvements are possible with improved DNA repair alone? That would be extremely valuable information. On the other hand, it could "prove" such a theory, even if limited to the fly model. That information will help focus the search for the correct method(s) of extending the lifespans in mice.

I am in no way advocating that we do a fly prize instead of a mouse prize. The way I see it, the two prizes would have a certain synergy that we can tap into. If the fly prize helped mouse researchers develop a 7-year-old mouse a year earlier, then who's to say that the fly prize was a failure, even if it never becomes popular enough to be the subject of a 48 Hours, 20/20, or 60 Minutes show (which I believe the Mouse prize someday will accomplish).

The Mouse Prize is mostly about PR (I'm not saying this is a bad thing). The Fly prize wouldn't ignore PR, but it would focus so much more on the research from the moment of inception.

Jay Fox

[jaydfox]

Prometheus, and others interested in forming a Fly prize:

Between this topic and two or three others in which we have been debating a fly prize, there are a lot of true gems in terms of information about fruit fly relevance and how a prize could be structured to be successful (and to complement the Mouse prize).

I am planning to "collate" this information into a sort of "prospectus", because there are so many good points, as well as arguments and counter-arguments, that it would be beneficial to see it structured (rather than just a back and forth debate). I'm not planning to add much new information, just a summary of what's been discussed so far. We can then use this summary as a jumping point to create a more formal proposal to present to either the MF or imminst.

With TV2004 wrapping up in less than a week, I want to have something finished by Monday (though it probably won't take that long, since I'm just copying and pasting). Would you guys be willing to pick your favorite quotes, arguments, counter-arguments, etc., from the posts in the last two or three weeks, and PM them to me? For the longer quotes, perhaps just PM the link to that person's post, and a description of what subset(s) of that post you like.

Jay Fox

[reason]

From the topic on sci.life-extension:

http://groups.google....life-extension

--------------------------
> I'm of the opinion that it's a good plan technically and economically,
> but very hard to sell to the public. They like fuzzy long-lived mice,
> but are not going to go for flies.

Maybe you've not chosen the right insect: my suggestion is that you go for
the public's *all-time-favourite* insect -- the *ladybird* (US:
'ladybug'...?). People love them: you see them treating them almost like
*cats*...!

Hope that helps!

Philippic
-------------------------------------

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

[jaydfox]

From the topic on sci.life-extension:

http://groups.google....life-extension

Ahh, the debate rages elsewhere, and I wasn't invited! A disadvange to being new to the community, I suppose...

Hmm, interesting. How long would it take to sequence the ladybug genome? A big theme at futurepundit.com is that technology is improving exponentially, both in terms of capability and especially speed.. Where are we at in our ability to sequence new species? Six months? More? Less?

There's already a lot of science invested in the fruit fly, so I'd like to know where we are in using lady bugs as a model (or any other bugs).

While I do agree that ladybugs are in better public favor, I'm wondering what the best model is from the science point of view. We're going to have a hard enough time selling the public on bugs; choice of bug isn't going to matter much (I could be wrong, just my opinion). There's no point to sacrifice science for PR; our job is to educate the public on the science. The public shouldn't look at this as extending a bug's life to make that bug happier. It's to develop science to extend our lives.

CNN, USA Today, and many others have repeatedly covered Fruit Fly stories (e.g., the Indy gene), without coming across as "what's the point?" or "Eww, those pests!". This can be professionally handled.

Which is the best model from a science standpoint?



Methuselah Fly... Methuselah Ladybug...er, Ladybird... er... Hmm, the naming could be tricky.

Jay Fox

[reason]

I guess they aren't that well studied:

http://www.blackwell...id=llMHhWaqorfg

But "Ladybird Longevity Prize" or "Long Lived Ladybird Prize" works just as well as a prize name. The idea of using some beetle/insect/etc other than flies that is well studied but also well received by the public stands.

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

[jaydfox]

Prometheus, try to keep cool. Reason is skeptical of the fly prize, for now. If the fly prize is launched, I suspect he will become one of its biggest cheerleaders. It's okay to openly disagree with what Reason says, but try to tone down the sarcasm (I understand where you were coming from with that comment, and it was even a little funny, but...)

As you once said yourself (to Dr. de Grey, in fact):

It is a pity, you could not have left your previous post at the first two paragraphs so we could move along. Now I am compelled to clear the haze (we are all possessed of pride, but some of us choose not to trip over it):

Reason may also feel it necessary to clear the haze, when we should be moving along.

I think we need to step back and re-read the many arguments for and against a fly prize. I direct this comment especially to those who oppose it.

I did review this and a couple other topics today, and I remain ever convinced that the prize could work. PR is not as much of an issue, because the level of funding is not as much of an issue. ($5 million to $25 million would be nice, but not necessary.) Besides which, we don't have the luxury of time that the MMP has: we're looking to generate fast, targeted results. We don't have time to win over the greater public and convince them to donate. If we can find a way to bring them in, great. After all, we should aim high, and settle for success.

But the anti-aging community, as well as our circles of friends and family, can give this prize a great start. The MMP generated about $40,000 to $50,000 in funds in its first year (not including the seed money), and most of that from the anti-aging community. If a fly prize got only $20,000 in its first year (excluding seed money), it would be in a better position. And with the precedent that the MMP has already set, it would not be as much of an uphill battle as it would have been to create a fly prize a year ago. After all, the anti-aging community has grown in the last year, and has grown to accept the MMP and what it stands for.

I'm not a psychologist, an economist, nor a natural leader, so I can't say with any accuracy where we'll be a year from now. But the MMP is getting ready to reach 1/2 a million in donations and pledges. Its momentum has been slowing, but I suspect it is about to pick back up. I see the fly prize piggybacking on that momentum, not stealing it. I could see the fly prize generating $20,000 to $60,000 in the first year, and with a pledging system open to more of us (due to lower annual minimum donation, as well as a shorter pledge period), its initial growth should be both sustainable and increasable.

The fly prize should do as well as the MMP with a prize fund an order of magnitude smaller. That means it doesn't need to "steal" donations from the mouse prize. And if it did... Not to step on anyone's toes at the Methuselah Foundation, but if both prizes were adequately funded, a dollar spent on the fly prize would be better spent than a dollar on the mouse prize. At least for the next few years, until the RP starts getting awarded (other than the inaugural awarding, of course).

And if the Methuselah Foundation did take on the fly prize, then it would be one big happy family. No toes to step on...

Postscript: TV2004 officially starts tomorrow, so I suspect that there will be many who have been vocal in this debate who will not be heard from until Sunday night or Monday morning.

Jay Fox

[jaydfox]

By the way, there has been a debate in other locations about the the model organism to use for a prize to complement the Mouse prize. Other suggestions have been ladybugs (which live far too long, apparently) and a type of African fish that lives about 12 weeks at most, and has an age-dependent increase in mortality. I've asked for more suggestions, based on a set of criteria; we'll see what comes forth.

However, with the exception of the fish, none of the suggestions made so far has yet to show better promise than the fruit fly. I like the African fish at a casual glance, because of the age-dependent increase in mortality, and the fact that fish don't go through a larval stage. I'm also assuming these fish don't hibernate, or do any of the other things that have raised objections. Lastly, fish are not as objectionable as insects. (I still agree that this point should be more about education on our part than pandering to the masses, but we are a small group, after all...)

However, a casual amount of research on the internet suggests that these fish have long incubation periods before hatching, on the order of 3 months or more. As for the 12-week lifespan, casual research showed several dozen species or sub-species in the Nothobranchius genus, some of which apparently can live four to five months quite easily. Some species die quite suddenly, while others die of old age (i.e., they have an age-dependent increase in mortality). These factors complicate the choice of species, given how related these various species are. After all, the MMP chose an already relatively long-lived species of mice, to avoid such issues.

Also, these fish grow about 5-6 cm long, so maintenance costs will probably be a little higher per experimental group, and especially per fish (aquaria, water filters/tank cleaners, etc.). Experimental groups will necessarily have to be smaller.

Finally, as I have pointed out in the Google sci.life-extension group discussion, a relatively unstudied organism may have a steep learning curve. Oh yeah, and I can only assume that this species of fish has not been sequenced yet (its genome, that is...).

However, these negatives aside, these fish do pose a valid alternative to the fruit fly. Comments from either side of this debate?

(If you got the impression I was purposely making a stacked argument against using the fish, you're right! I'm not saying I don't agree with the fish; I do see their appeal on both the scientific, and especially the PR fronts. The whole concept of the fly prize is not that it is rooted in the use of fruit flies, but in the use of a cheap, short-lived species. If we change species now, none of the arguments made in favor of the fly prize is invalidated (assuming the change was not made strictly for PR reasons, but for scientific reasons as well). However, given the resistance met by the suggestion of using fruit flies, I'm putting the burden of proving the case for the fish back on those who would oppose the creation of a fly prize.)

By the way, Prometheus, would you agree with this statement?: If we change species now, none of the arguments made in favor of the fly prize is invalidated (assuming the change was not made strictly for PR reasons, but for scientific reasons as well).

Jay Fox

[jaydfox]

Whatever you are, Jay, you are bridge builder and a natural philosopher in the literal sense of the word (he who loves knowledge)

Prometheus, thank you for the compliment. If there is one thing that I can say about myself without reservation, it is that I love knowledge. There is nothing I enjoy more in life than learning. And not learning in the engineering sense, but in the scientific sense: I do not try to learn how to apply new formulae; I try to learn why the formulae work.

This unfortunately drives my wife crazy, because she can't understand why I can enjoy spending hours at a time in my head--philosophizing, analyzing, etc.

Jay put it more succinctly than I ever have

An ironic statement, given my unfortunately innate ability to say in a thousand words what could be said in a hundred. Just peruse my posts to see this flaw in action. [tung]

The comments on the prize name trivialize the fundamental importance of appropriate choice in model organism.

In all fairness, I started that... [wis]

Jay Fox

[jaydfox]

As promised here, I am trying to move a debate about the fly prize from another topic to this topic. Perhaps they'll follow my lead, perhaps not.

The following quote is an extract of comments made by Dr. de Grey in a post in the Methuselah Prize - You Decide poll/topic:

> I'm wondering if there are species we can use with shorter lifespans
> than mice, but that still get cancer

This would be nice. There is work now on some fish that appear to age
very quickly and live well under a year despite having a normal gradual
mortality rate increase (unlike salmon):

http://www.ncbi.nlm....t_uids=14667379

In general, the chance of flies telling us any more about mammalian aging
than they already have is rather low, in my view. Just too many things
are built differently, and too many things that go wrong in humans just
have no time to do so in flies (such as clonal expansion of mitochondrial
mutations). In particular:

> What makes you think you can't induce cancer in flies? Simplest way is
> just to knock out a tumor suppressor gene and they develop beautiful
> large tumors in various tissues with all the classic neoplastic
> characteristics. They die from it too.

No, not really. They get something called melanotic tumours, but these
are usually benign (as I understand it) and do not continue growing in
the adult, and moreover (as you say) they only get them when mutated.

> Fly Prize

The biggest problem here, which has not been addressed yet, is diapause.
Flies normally live only a few weeks in the lab, but in the wild they
do perfectly well right through the winter. It's a sort of hibernation,
without any of the morphological oddities seen in the dauer pathway in
worms or sporulation in yeast, but it still multiplies the lifespan by
a large factor (much more than can be explained by the low temperature:
indeed, some species do it when the hours of light per day are reduced
even if there is no change in temperature). It's very hard to see how
to run a prize that disallows diapause.

Aubrey de Grey

Here are Prometheus's replies:
1) His first reply is a list of studies where the lifespan of drosophila has recently been investigated.
2) His second reply is a survey of cancer studies using drosophila as the model organism over the last few months.
3) His third reply can be summarized by its first statement:

I do not believe Aubrey has as yet to make a case against using flies as a model organism with which to study aging.

Dr. de Grey responds, and, among other things, questions the credibility of awarding a fly prize to the longest-lived fly:

But if a single fly lives verifiably six months,
how are you going to show that it didn't spend a lot of that time in a diapause-like state?

Prometheus responds:

I am sure that any investigator would be looking to also publish or patent results and would consequently still need to be subjected to the scrutiny of the peer review process. Furthermore, engaging the competitors to participate in a daily reporting mechanism would provide content for the website as well as a means of monitoring the progress of the animals.

Finally, here's my reply to the comments made by both gentlemen.

Jay Fox

[Da55id]

Hi Jay - Just wanted to let you know that I'm reading everything carefully and appreciate the effort. More later.

[ag24]

This is a reply to the more recent posts on the previous thread (someone please insert
a hyperlink for me) that Jay has sensibly redirected to this thread (which I had in fact
not seen any of until temn minutes ag).

prometheus: your main question is:

> Aside from this concern of measuring efficacy of intervention in the context of a diapause > state, is there any other issue that you have with using drosophila?

No comparably severe issue, no. I see both sides of the various arguments that others
have raised re cuteness, perceived relevance to humans, etc, but ultimately the problem
of making a strong scientific case is what dominates my thinking (as you might expect).
Daily/weekly reporting is indeed straightfowrard if you're wiling to use data on flies that
will not be your record-breaker (because you sacrificed them in order to do the assay),
but unfortunately the role of epigenetics that I mentioned means that the assays on other
flies in the same expt privide no information at all for the record-breaker itself, however
much they may contribute to publishability.

Which brings me to Jay's point:

> we don't have to lock ourselves into the single subject paradigm

This is a much more promising avenue. It may also have merit in the mouse prize arena
-- and in fact Dave and I have been discussing this recently; more on this soon. But, then
the question is, how diapause-esque does a fly have to be before it's disqualified? I have
a bad feeling that this is a serious problem, as here is undoubtedly a continuum here, just
as with worms (the mutants that extend lifespan are typically hypomorphs of genes that
when amorphic -- totally non-expressing -- cause constituteive dauerism).

I have to quit now - lots to do tonight before leaving for TV04. Keep up the good work,
everyone... if only the rest of my work involved this much enthusiastic brainstorming!

Cheers, Aubrey

[jaydfox]

...this thread (which I had in fact not seen any of until [ten] minutes [ago]).

Hmmm.. There have been a lot of posts in this thread. I'm not sure how much of it is relevant to where the discussion is now, but it might be interesting if you go back to the beginning of this thread and get caught up. I suspect that traffic will be down here at imminst over the next few days (due to TV2004), so you have time...

That is, if the question at hand still has your interest...

Jay Fox