162 replies to this topic

[jaydfox]

I credit this finding to the longevity meme which drew my attention to it in the first place.

I was going to post this same article from the Longevity Meme, though I focused on this quote:

While this work studied calorie restriction in yeast, it would seem to indicate that the comparable mechanisms in higher life forms are also a little more complex than was first thought.

There are some here, including some with prominent positions in the field of aging research, that have completely discounted the remaining benefits of studying flies. And yet the lowly *yeast*, at least a couple major steps further back on the evolutionary ladder, is still providing important insights.

Enough said.

Jay Fox

[jaydfox]

There have been arguments for and against the fly prize, and opinions on boths sides are slow to change. I was planning a reply to Dr. de Grey's comment that "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." However, in preparing my reply, I began to think about the mission statement of the Methuselah Mouse Prize.

The Methuselah Mouse Prize is the premier effort of the Methuselah Foundation. It is a contest designed to accelerate progress towards real longevity-enhancing medicine, promote public interest and involvement in research on healthy life extension, and encourage more such research by providing a financial incentive to researchers.

I have some comments to make, and I want to collect some feedback from the critics of the mouse prize.

Let's start with the first sentence.

The Methuselah Mouse Prize is the premier effort of the Methuselah Foundation.

The premier effort, as far as I can tell, is actually the Reversal Prize. But that's beside the point. A fly prize, if instituted under the Methuselah Foundation, would not take the place of the Mouse prize. In fact, it would not even need to become more prominent. The Reversal Prize, or the Mouse Prize when taken as both mouse prizes, would still be the premier effort.

It is a contest designed to accelerate progress towards real longevity-enhancing medicine

Arguably, the fly prize would actually be more successful in accelerating progress, though that depends on your definition of progress. It also depends on whether you believe that fly research will provide meaningful results that can be applied towards future RP mice competitors. Nevertheless, a dollar spent on the fly prize will more likely help initiate research projects where achieving maximum longevity is the focus, and results will be realized much sooner.

promote public interest and involvement in research on healthy life extension

By itself, I do not dispute that the fly prize would not be as successful as the mouse prize would on this point. While it might be more successful per dollar, in the absence of the mouse prize I see a problem in maintaining any useful level of donations. In that regards, the mouse prize has set a nice precedent for funding a longevity prize, and one which I am hoping I am not seen as belittling.

When taken together, the two prizes help set up an argument for us:

Dramatic life extension in flies can be demonstrated much sooner, and it will draw media attention. Perhaps limited media attention, but attention nonetheless.

Then, life extension in mice follows a few years thereafter, and in some ways was made possible by the fly research. More attention is drawn.

And a logical connection is made in people's minds (where this connection is not made, properly prepared public statements will allow us to help people to make that connection). Flies, then mice, have succumbed to the miracle of modern genetics and bioengineering. A precedent is set, a progression of species closer and closer to humans is made. It becomes quite plausible that similar accomplishments in humans are possible. Which leads us back to accelerating progress: this will best be accomplished when the public is begging the scientific community to get off their... Well, you know what I mean.

More importantly, we can begin making this connection in the next couple years, instead of five or ten years from now. We get results in flies, and we award the prize. (Possibly quite frequently in relation to the Postponement Prize, by the way.) As pointed out, flies aren't cute and fuzzy, so the results are not as dramatic as they would have been in mice. But, media attention is drawn, and we point the way to the mouse prize. Now, people are waiting for the mouse prize to be awarded, instead of not ever hearing about it until it is finally awarded, 5+ years from now. More suspense means more donations to the Mouse Prize, and more importantly, more willing competitors.

The Postponement Prize fills this role to a limited extent, and this has been one of the main arguments in support of keeping the Postponement Prize instead of just having the one prize: the Reversal Prize.

But wouldn't the fly prize serve nearly as well in this capacity? It draws media attention, and it demonstrates valid science which can then be applied to the RP competitors.

And it gets even better! If we have both the fly prize and the Postponement Prize fulfilling this role, then the public will be in even more suspense, awaiting the first competitor to win the Reversal Prize. After all, as we've pointed out, short of a statistical fluke, the RP will not be awarded until someone comes up with an intervention that at least doubles remaining lifespan. And given how high the record has currently been set, by one such statistical fluke, it will probably even require quite a bit more than being able to double remaining lifespan.

So how do we fill the media void between now and then? The Postponement Prize can, to an extent, and this is one of the reasons that even the founders have put forth in support of keeping it. However, when combined with the fly prize, we now can be even more successful in filling the media void, and in keeping "momentum" going in attracting new donors and competitors.

encourage more such research by providing a financial incentive to researchers

Hands down the fly prize wins, dollar for dollar. However, it has been argued that the fly prize will never achieve the same level of donations as the mouse prize, and I fully concur. However, if the fly prize need only award 1/10th of what the mouse prize would in order to justify a research project, then achieving only 1/10th the level of donations of the mouse prize would suffice. Of course, given the accelerated rate at which we foresee fly research being conducted, the prize would probably need closer to 1/5th the donations to be "successful", and closer to half the donations to be greatly successful. But I'd settle for 10%-20% of the donation level that the Mouse Prize is receiving.

And I don't particularly see why donations to one prize automatically pull from the same pool of willing donations that might have been made to the mouse prizes in the same timeframe. More press means more support, which means hopefully a larger donation pool. Were the fly prize to be funded at 20% of the level of the mouse prize, I doubt that even 10% of the potential donations of the mouse prize would be lost, and I can even foresee that once the fly prize starts getting awarded, the Mouse prize will benefit from a net increase in donations.

The point, if it has been lost on everyone here, isn't so much that I'm asking the Methuselah Foundation to reconsider taking on the fly prize. Even as a separate entity, all the points I've discussed are just as valid. Cooperation (in both directions) with the MMP should be encouraged from the start, and I don't see the Fly prize as a being a parasitic organization, but a symbiotic one, with respect to the Mouse prize.

However, I am wondering if those who have been against the prize still hold to that opinion, and if so, for the same reasons? If you feel public relations is the issue, please explain why. If you feel that scientific credibility is an issue, please explain why. If you think that the fly prize will hurt the Mouse prize in some way, please explain why. And keep in mind that all of these points have been well addressed by myself or Prometheus, so let us know where we're wrong, so that we can either fix our assumptions, or perhaps come to see things as you do. Progress cannot be adequately made without feedback from our critics.

Thank you.

Jay Fox

[kevin]

From my own personal opinion,

I wholeheartedly agree with Reason that diversity in concordance with friendly competition is much healthier and effective than a perceived 'monopoly'. The more the merrier. What is required is flag waving and the more flags from different corners the more impact.

One has only to look at the 3 billion dollar bond Californians are willing to put up in order to accelerate stem cell research to know that we are arriving at a cusp and soon we might see many developments which will have a paradigm shifting quality beyond the expectations of the Methuselah Foundation. If this were to happen I would be only too pleased.

Still, there is many a slip 'twixt the cup and the lip and to take progress for granted is not wise when many opponents can play upon the irrationalities of our genome.

I think the most scarce resource, as any activist knows, is time, I hope there is a lot more of it coming from those who have it who are interested in extending it.

[johncumbers]

slightly off topic, but I had an idea for a number of different front ends to the prize, to target different groups. I think older people would want to give to the site, and younger people too. but the type of websites that would appeal to each group and make them donate would be different.

a bit like how a business might licence it's product to people to allow them to market it how they want, but at the end of the day, it's still the same product being sold.

just an idea,
John

[bodebliss]

Hi All,

Hey, Immortality is unobtainable by humans because it implies a being can't be kill or die by any means. I guess Everlasting Life Institute or Everlasting Health Institute must have been taken or sounded too woos.

As to the main topic, I think they should stay in the Order Mammalia. My thought is they should use or have a separate category for non-germline altered shrews as shrews have much shorter lives(1 year, not much more) and are animal protein eaters like most of us. I think the use of germline altered mice skews the result unless it can be shown the germline alteration can be introduced into non-germline altered mice. In that case, the use of this altered shrew or mouse would be considered time-saving expediency.

Bode Bliss

ps: If shrews were the size of people, guess who would be ruling the world?

[lightowl]

"unobtainable" Hmmm... Sounds allot like Impossible, which is very hard to prove.

Some examples of immortality.
- Mind uploading.
- Cloning with mind transferring.
- Molecular rebuilding from snapshot.
etc...

[bodebliss]

lightowl,
Those may someday be valid, well and good, but they won't keep you from being hit by a 10 mile wide asteroid traveling at 70,000 miles an hour, or you'll never achieve the ability to take a direct hit from a 10 megaton nuke in the chest and survive.

Now that would be Immortality!

Immortality means not killable.

Bode

Edited by bodebliss, 05 September 2004 - 01:20 PM.

[bodebliss]

Hi Prometheus,

Sorry to hear that shrews are not sequenced yet. I at least find them quite interesting. 'Change nothing' , seems to be ahead. I still think using germline altered mice skews the results. The fact that a researcher uses germline altered mice w/o first proving the alteration can be introduced in non-germline altered mice, does not help you or I to achieve everlasting health.

Bode

Edited by bodebliss, 05 September 2004 - 09:36 PM.

[lightowl]

bodebliss,

My point is, the fact that your original body is destroyed does not necessarily mean that you are dead. Also, the fact that the earth is destroyed does not necessarily mean that the human race is gone. But to take your argument to the extreme. You could argue that nothing could survive the destruction of the universe, so Immortality is impossible. If that is your argument, then I agree with you. Unless of course there are multiple universes... And so on....

Well.. Anyway, this is not the thread to discuss this in, so I'll leave it at that.

[jaydfox]

As to the main topic, I think they should stay in the Order Mammalia. My thought is they should use or have a separate category for non-germline altered shrews as shrews have much shorter lives(1 year, not much more) and are animal protein eaters like most of us. I think the use of germline altered mice skews the result unless it can be shown the germline alteration can be introduced into non-germline altered mice. In that case, the use of this altered shrew or mouse would be considered time-saving expediency.

I agree with the idea of using shrews, and I proposed something similar before. I am not sure how a prize would fit in with shrews, as they are not a very well-researched species to begin with. Flies, on the other hand, are well-researched, and it gives us a good starting point, especially in the "speed" department.

However, once the fly prize is rolling and I have more free time (or before the fly prize gets started; the point is, I would need more free time), I'd be interested in advocating more research into a shorter-lived species than mice. We have to examine the tradeoffs of how long ago we diverged from the species and how long the species lives.

I don't know exactly how long shrews live, though I had figured it was on the order of about a year, as you said. Certainly that would allow research to be conducted about twice as fast as with mice, and probably at about a third or a fourth of the cost.

The Nothobranchius furzeri (an African fish) lives about 12 weeks, but is several hundred million years further removed genetically. A lot better than flies, but not nearly as good as the shrew.

In a perfect world, I would say research them both. For now, it seems likely that neither will be researched much, let alone both, so if ImmInst wanted to try to influence some research decisions, we would probably want to pick one additional species ("additional" to the current yeasts, C. Elegans, Drosophila Melanogaster, and Mus Musculus), and concentrate our efforts there. However, I would not want such an effort to pull resources away from the Fly Prize until it is well on its way to being realized.

Hi Bode, shrews haven't yet had the honor of having their genome sequenced so it makes it a less attractive model to the research community.

I've asked this question before, either here or in the Google sci.life-extension group. How long would it take to sequence a new species, if we started today, and how much would it cost? I know it's significantly less than the human genome project. What though? Six months? Three? One? How much would it cost? Five million? A million? Half a million? A hundred thousand?

I still think using germline altered mice skews the results. The fact that a researcher uses germline altered mice w/o first proving the alteration can be introduced in non-germline altered mice, does not help you or I to achieve everlasting health.

I think that germline research is still important. If nothing else, it helps us understand aging better, both genetically and chemically. Also, if we wait until we know that we can adequately move over the genetic changes, we'll have lost many years that we could have been researching in germline experiments. So germline research is still valid, in my opinion (and Dr. de Grey seems to agree).

Of course, it's happening anyway, so we at ImmInst don't need to be advocating germline research. We *do* need to be advocating alternative experimental techniques though. The current paradigm, so far as I can tell as an outsider, is to test one gene at a time. I know of only a handful of experiments that have tried to explore the cumulative effects of combining genetic and/or pharmacological interventions.

And it's important to note that most such experiments find no cumulative effect, or a small cumulative effect at best. I can only think of one recent study that found good cumulative effects, involving the Sir2 protein (gene?) and the FOB1 protein (I could have protein names a little off, I'm going from memory). Dwarfism and Calorie Restriction are only partially cumulative. Calorie Restriction and resveratrol (a CR mimetic) are actually antogonistic, at least in some studies. We need much more of this type of research.

And of course, we need to be advocating the use of the best models. Progress is too rapid, and our knowledge far too lacking, to be working in organisms as long-lived as mice, let alone longer-lived models like dogs or primates. Given the degree of preservation of genetic mechanisms, it would seem the most logical to pursue the relatively rapid and inexpensive route of experimenting in yeast, nematodes, and flies, and then taking the *best* results and moving them forward into mice (and fish and shrews). Sort of like a modified genetic algorithm (no pun intended). Find the best therapies, and refine them and test again. But the first few generations of therapies can be better explored in flies than in the relatively long-lived mice. We'll eventually exhaust any further benefit of studying flies, but recent press releases indicate to me that we are far from exhausting the potential benefits of studying flies (and lower organisms, for that matter).

I'm guessing (pure speculation) that the Fly Prize will serve its purpose well for about the next 5-8 years, beyond which the genetic differences will be to great to extract any further useful information. From a financial perspective, studying flies doesn't pull much away from the aging research community. It will pull away researchers, who I assume are in high demand in this field at the moment (mostly due to lack of funding ). So it's a mixed bag. Even if we learned nothing (which I *highly* doubt), we'll have wasted very little money. We will have lost precious man-hours by qualified researchers, but since they aren't using up as much of the available funds as the mouse researchers, there's more to go around, and hence more researchers will be able to enter the field. So I don't see that we have much to lose, and we have *so much* to possibly gain.

At any rate, if we could push to have the African fish or the shrews sequenced (perhaps it might take a couple years, including the time to advocate the new species), then they should be sequenced and ready in time to start testing the second or third generation of therapies researched in flies. By the time the flies have exhausted their usefulness, we could expect second and third generation therapies to have been tested in the new intermediate model, and ready for testing in mice. If the shrew is indeed the next model, then we could be very hopeful that the therapies will provide dramatic results in mice.

Of course, this assumes we could influence enough *influential* researchers to get shrews (or fish) sequenced and preliminarily studied in the context of an aging model.

Even without the shrews, I suspect that going straight from flies to mice will still be useful.

Jay Fox

[bodebliss]

lightowl,
Have you ever thought about the benefits of exteriorization?

I don't mean traumatic exteriorization caused by near-death. I mean self-exteriorization caused by conscious effort.

http://www.rememberi...7.html#comments
http://freezoneameri...oads/files.html
http://www.ronstech.org/
http://freezoneameri...chapter_11.html
http://www.etext.org...ook/ch4222.html


Or Goooogle : Exteriorization

[jaydfox]

Gentlemen, and ladies, I think this is getting a little off topic. Bodebliss, you may want to pursue this further in the What is Immortality? topic. There we can discuss not only what immortality is, but what we believe is achievable, and if you want, whether it is even worth trying for.

The point of the current thread is not about who would want immortality. It's not even about immortality, per se. It's about what is the best/fastest way to significantly slow the aging process. It's a stepping stone towards immortality, but it's also a worthy goal in its own right. We could even get into a debate about that assertion (that it's a worthy goal), but nevertheless, that debate wouldn't belong here either.

Here we are focused specifically on whether a Fly Prize has merit, and more generally on what is the fastest, most efficient way to make a serious dent in the aging process.

Thank you everyone.

Jay Fox

[lightowl]

Heh, Sorry about that Jay, I just needed to respond.

I started the "What is Immortality" thread for the same reason.

Edited by lightowl, 06 September 2004 - 12:41 AM.

[bodebliss]

Jay,
I was working up a worthy response to your great post. When the op to enlighten lightowl to the possibility of a greater reality knocked. Sorry.

Little money didn't stop the Wright brothers. We can do something right here and now. Start a Folding@Home Team for the Immortality Institute.Links:
http://folding.stanford.edu/
http://folding.stanford.edu/faq.html
Team sign-up:
http://vspx27.stanfo...n/createteam.pl

Then you just start a new Topic on the Immortality Folding@Home Team.

Here is a very good gene therapy that I can't wait to see come out as it would slow aging.
Link:
http://www.uphs.upen.../jan04/MSRA.htm

I emailed the main researcher and was told it will be at least 6-8 years before they'll be ready for human trials.

What is needed is more breakthroughs along these lines.

Your logic on the idea of a fly prize is very good. I like it.

Bode

[jaydfox]

We can do something right here and now. Start a Folding@Home Team for the Immortality Institute.

An excellent idea!! A little off topic, but I'll indulge. If there isn't currently a team, we should definitely create one. Does anyone know if we have a team?

Your logic on the idea of a fly prize is very good. I like it.

By chance, have you voted yet in this poll? The poll results seem to be pretty static lately, and you seem to be joining the debate at a late stage.

But it's good to see more support, because the idea initially met quite a bit of resistance. I think some people are warming to the idea, but there's still a lot of work to do to see this through. If you're at all interested in helping out, there's a topic where I'm Looking for volunteers...

I by no means see the Fly Prize as a final project, just a good start. Other projects will follow, once the Fly Prize is on its own two feet, or six ).

Jay Fox

[bodebliss]

Prometheus,
I have read all of alot of Hubbard. I could recommend the best of his writings,but I chose not to bias. Exteriorization appears throughout human history. It seems to be the highest state in martial arts, meditation, coping w/ daily life.

People reject it 'cause they don't understand it. To say I have it all worked out is to say I have decided to circumvent the present, which I can do, but haven't.


We need more breakthroughs like this.

Bode

[bodebliss]

Jay,
I have voted in the poll. I am very interested in science and would like to see longevity, especially eternal health, winout over the objections of the naysayers.

Bode

[bodebliss]

Prometheus,
I thought Jay explained it quite well. He didn't even use stats or research that showed the correlation betwixt humans and The Fly and yet I was totally cognizant of the possibilities of such research.

We need more breakthroughs like this.

Bode

[jaydfox]

If innovative ideas designed to promote research into the the aging problem encounter such resistance within a community that views that the day when aging will be treated as an affliction rather than as an inevitability is drawing near, I fear to think what the position of a less 'sophisticated' public would be.

You know, ironically enough, I think that Dr. de Grey nailed this one on the head. To wit:

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.

In this case, he was referring to the current paradigm of studying aging in terms of calorie restriction and other similar pathways, in the hopes of slowing aging down a little, with no hope of dramatically slowing, stopping, or reversing it.

However, it could equally well be applied to the paradigm that exists in some in this group: that radical techniques such as SENS, stem cell therapies, and research into long-lived species are much more cutting edge, and hold (at least in combination) much more promise for actually stopping or reversing the aging process.

It's a great paradigm, and not one I'm against. But those who stick to it too strongly are not taking into account the returns for the effort. Two or three decades, and hundreds of millions, if not billions, of dollars. With fly research, we may only help develop science that extends the human lifespan by 10-50 years, depending on how late the interventions are applied (well, technically, zero years for those on their death beds already) and on how successful the research is. And in the context of achieving actuarial escape velocity, it's a *huge* return on a relatively modest investment. Dr. de Grey stated:

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.

(my emphasis added)

(By the way, I emphasized the word "boringly", because Prometheus and I have been hashing out details on how to ensure just that: that the Fly Prize cannot be won "boringly". But that's another issue altogether...)

Sure, fly research is not nearly as *cool* as accomplishing SENS, and so there's this tendency to think that it will detract from SENS in some sense.

As far as I'm concerned, it will give SENS a real boost, because before people are willing to throw political support, and indeed, that all powerful *hope*, behind a War on Aging, they will need to have some sort of vague assurance that it will not be in vain.

The Methuselah Mouse Prize tries to accomplish this, and I myself have donated. But we can do more.

We don't need to be stuck in this mode of thinking, where the Fly Prize will be a distraction to the "real" work. For many scienitists, the Fly Prize does address the "real" work (more conventional, "old school" gerontologists). More importantly, more publicity, in an area this unknown to the public at large, is a *good* thing.

By the way, I'd like to go on another tangent, addressing old school versus new school. Reason likes to discuss this, and it's an interesting area. In general, old school seems to deal with supplements, and more recently CR mimetics, while new school focuses on cutting edge stuff: genetics, stem cells, SENS.

There's not really an "old school" and a "new school", in my opinion. It depends on where you stand. When I started, old school was supplements, and CR mimetics seemed cutting edge to me. I had my reasons for believing so, and they were good ones.

However, for many of us here, who have known about SENS for quite some time, or at least have studied it in depth, there's this tendency to view anything less than SENS (or stem cells, because they're in vogue) as being old school. This applies to genetics research into existing lifespan-altering genetic mechanisms. It's as if we've learned all there is to learn, and at this point further study is merely academic.

I'm not saying that genetic research isn't old school; perhaps it is. But I thought I'd share that point; it's how I see this debate shaping. Those opposed to the Fly Prize view genetics, at least certain aspects of it, as old school. When indeed the first discoveries into the genetics of calorie restriction have only just occured in past few years, and are ongoing. It might be old school compared to what we *think we know*, but it's still very new school compared to *what we know*. We should not lose sight of this fact, that supplements truly are old school (not that there's not a lot to learn from them), whereas CR studies, given the genetic aspect we are only recently discovering, are not old school, even if CR has been known for decades.

Anyway, just my two cents. And relevant I hope, since it seems to be influencing people's votes in this poll.

Jay Fox

[bodebliss]

On calorie restiction I read an article recently that touted the fact that as soon as the subject came off calorie restriction diet, the benefits were lost.

Bode