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Should a Methuselah Fly Prize exist?


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Poll: Would you favor the creation of a Methuselah Fly Prize? (50 member(s) have cast votes)

Would you favor the creation of a Methuselah Fly Prize?

  1. Yes, a Methuselah Fly Prize should be created. (25 votes [54.35%])

    Percentage of vote: 54.35%

  2. No, the Methuselah Mouse Prize is sufficient. (21 votes [45.65%])

    Percentage of vote: 45.65%

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#1 jaydfox

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Posted 30 July 2004 - 04:36 AM


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?

I would also ask you to explain your position. For example, you might vote no because you think it will pull donations away from the two current Mouse prizes. Or you might vote no because you feel the results would be irrelevant (and explain why...).

On the other hand, you might vote yes because you think that it will draw more attention and result in more donations than would otherwise have been given. Or you might vote yes because you feel that the results will be available so soon as to make future Mouse prizes more meaningful.

Jay Fox

#2 reason

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Posted 30 July 2004 - 05:10 AM

I see one pro, two cons.

Pro: you can get much more done with flies in a given time period.

Con #1: flie studies are nowhere near as applicable to humans as mice studies are

Con #2: flies are not cute, and the short life span and lack of distinctive characteristics prevents you making media personalities out of them. One Yoda is worth any number of scientific pronouncements.

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#3 jaydfox

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Posted 30 July 2004 - 05:54 AM

Reason,

I accept both your cons, and I should point out that I made both objections to Prometheus a few days ago. (I was going to try to provide a link to the post I made those objections in, but it seems that links to individual comments aren't working properly; it just links to the start of the topic.)

Con #1: flie studies are nowhere near as applicable to humans as mice studies are


My biggest concern was that cancer was not a leading cause of death for flies (to my knowledge), so clearly the underlying evolutionary pressures of various aging (and anti-aging) mechanisms must have differences. The question is, how big are those differences? And could we at least use flies to narrow down our list of "suspects" for further investigation in mice?

Con #2: flies are not cute, and the short life span and lack of distinctive characteristics prevents you making media personalities out of them. One Yoda is worth any number of scientific pronouncements.


Yes, flies are not cute, and they aren't mammals. Making a fly live 20 times longer than average, as incredible a feat as that might be, might not spark as much interest as a mouse that lives 6 years. However, when combined with the awarding of a prize, does the PR value increase? Fly prizes would probably be awarded much more often, and the experiments are repeatable much more quickly, and in larger numbers than is possible with mice.

I'm not criticizing; I'm just looking to flush more issues out into the open. I was against a Fly prize at first, mainly out of concern that it would draw donations away from the Reversal Prize (I wouldn't care if it drew donations away from the Postponement Prize, though that prize is already seriously underfunded in comparison to the RP). I'm currently in favor of it; however, most of my reasons for supporting it are based on discussions with Prometheus, and I want a broader range of opinions (from other biologists, if possible) for my own benefit, as well as every one else's here.

Jay Fox

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#4 reason

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Posted 30 July 2004 - 08:12 AM

Dave Gobel has some ideas for the next prize in line after the Mouse Prize is well funded and established; he might share some of them here if prodded.

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#5 apocalypse

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Posted 30 July 2004 - 02:16 PM

I voted no, because of the complications(as explained by others, not sure to which it applies) with extending fly lifespans, as they've states that can significantly alter their lifespans.

Also many even some in the know, don't even fully understand how close all organisms truly are, and say "a mouse, oh how good, that's nothing to do with us, until done in humans I don't care", much less a fly.

Still, given that I've heard the fruitfly genome and proteome are available. They should indeed be an area with some strong research dedicated to it. Our understanding of biological systems, and the nature of aging would improve substantially.

Though, I would personally prefer a prize for elucidating differences in genes and the mechanisms involved betweeb negligible senescence species and short-lived ones of the same genus. It could be called something like" Prize for discovery of the nature of species that seem non-aging, ageless".

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Posted 30 July 2004 - 03:42 PM

According to the NIH,

Drosophila melanogaster is an extraordinarily attractive model organism owing to a combination of its easy to manipulate genetic system, relatively low cost, and biological complexity comparable to that of a mammal. Many organ systems in mammals have well-conserved homologues in Drosophila, and Drosophila research has already led the way in providing new insights into cancer, neurodegenerative diseases, behavior, immunity, aging, multigenic inheritance, and development. Indeed, analysis of the Celera-BDGP genomic sequence of Drosophila melanogaster provided enormous evidence on the value of the fly as a model for human disease, with about 2/3 of human disease genes having a clear cognate in Drosophila.

Trans-NIH Fly Initiative

It's very sad but more importantly, ethically irresponsible when proclamations such as there are made,

fly studies are nowhere near as applicable to humans as mice studies are


that discourage the support of such vital research and the enormous benefit that it can bring for achieving the goal of delivering human interventions for aging.

This sort of statement is the result of a fundamental lack of knowledge on the genetic principles and the design of experimental method using model organisms.

In Annual Reviews of Genomics and Human Genetics 2003, issue 4 in, "The Drosophila melanogaster genome.", the authors say, Drosophila's importance as a model organism made it an obvious choice to be among the first genomes sequenced

In FEBS letters 2004 Jun 1 in "Of flies and men; p53, a tumour suppressor", the authors say. "The completion of the Drosophila genome sequencing project [Science 287 (2000) 2185] has reconfirmed the fruit fly as a model organism to study human disease. Comparison studies have shown that two thirds of genes implicated in human cancers have counterparts in the fly [Curr. Opin. Genet. Dev. 11 (2001) 274; J. Cell Biol. 150 (2000) F23], including the tumour suppressor, p53.

#7 reason

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Posted 31 July 2004 - 05:57 AM

Hmm. I was under the impression that no medical research jumps from fly model to human studies. If you have something in the fly model, you go next to a mammal model, e.g. mice.

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#8 jaydfox

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Posted 31 July 2004 - 06:52 AM

Well, what do we have that we're testing in mice right now? Damaged IGF-1? Damaged insulin receptors in fat cells? I don't see anyone attempting a mouse version of SENS at the moment.

These are neat from an academic perspective. But we've identified hundreds of genes affected by CR, and certainly several of those have already been implicated to affect DNA repair, through up- and down-regulating Ku70, FOXO3, PPAR, or other proteins. We need to figure out which genes will really have a big impact. Short of implementing SENS, we need genetic therapies and better CR-mimetics.

And for genetic therapies, we need to figure out which genes to study. Unless someone wants to run massively parallel experiments, tweaking all the genes found involved with aging. Tweaking them singly is probably doable, but in pairs, it would yield tens of thousands of combinations.

Of course, we could do a "genetic approach" to this problem of genetics. Test all the genes singly, and identify the best 5 or 10 genes. Then pair those 5 or 10 with all the other genes, and find the best 5, 10, or 20 combinations of two genes. Take those, and throw in a third gene, and find the best combination of three genes. Repeat until you reach a point of diminishing returns that you're satisfied with.

At any rate, I expect this process to take a very long time in mice. It's not just a problem of creating all those mice. Then you have to take care of them for four or five or six years. At least with the flies, you're only looking at a few weeks for the genes that were irrelevant, and a few months for the few genes that really get the job done. If you're unlucky enough to have to care for a batch of flies for a year, well, I guess that's the price of science.

Of course, an argument that could come into play here is that biologists on top of their game will be able to use reasoning, deduction, to cull the list of genes to test. Thus, the lack of avenues being studied might not be a sign of a lack of serious effort or thoroughness. I'm not a biologist, so I can't really argue that point. But from the outside, it sure looks like there's a lot more to be done.

Jay Fox

#9 lightowl

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Posted 31 July 2004 - 07:16 AM

I don't se why contestants of the Mouse Prize can not use fly studies as a preliminary effort, and then transfer the knowledge to a mouse test. That would take the best of both worlds and still leave us with only one prize containing all the funds.

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#10

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Posted 31 July 2004 - 07:58 AM

Because contestants who may be able to enter using drosophila as the model organism may not have the resources to then duplicate those results in mice. Those investigators that are only able to use drosophila should also be rewarded. Don't lose sight of the real objective - which is to drive research - not merely to award a prize for a long lived mouse.

#11

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Posted 31 July 2004 - 08:05 AM

Pros:

Opens the contest to far more participants resulting in more investigations and broader scope of strategies
Data can be acquired within months instead of years

Cons:

Methuselah Foundation needs to re-think position.

:)

#12 lightowl

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Posted 31 July 2004 - 08:19 AM

So I take it that it is possible for contestants to use fly studies as a base, which is the answer to my question. I think focusing only on fly studies would make the PR efforts much more difficult. I am definitely not loosing sight of the real objective, and PR is a big part of achieving that objective.

Another objective is to break the deathmeme and make real interventions available to the public by convincing the private sector to invest in massive research and development programs.

#13

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Posted 31 July 2004 - 08:33 AM

Well then, Lightowl, you have to look at the benefits between a prize strategy that opens the competition to a whole lot more investigators and guarantees a more rapid result versus convincing a few private sector companies who will not give a damn unless they can slap a patent on it to invest in "massive research and development programs".

Why so much emphasis on "massive" R&D? We're not building a new type of atomic bomb or a staging an expedition to Mars - we're looking to isolate the genes that are the responsible for regulating aging. Believe me, it's not rocket science - its just doing the work - select gene:underexpress and observe, overexpress and observe. Very simple stuff actually.

It's either a matter of going through all the logical permutations using the brute force approach or you can be more elegant and think a bit more and reduce the total number of studies. Either way, it's a numbers game - numbers of studies that is.

#14 lightowl

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Posted 31 July 2004 - 09:06 AM

Well then, Prometheus,

Remembers, this is a public discussion. My comments are meant for the general content of this discussion, not as directed at you or anyone else. If you ask me a question, please do so politely. :)

#15 lightowl

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Posted 31 July 2004 - 09:27 AM

I don't se the Methuselah Foundations ultimate objective as only to discover a few genes related to aging. I se it as an effort to make interventions that eventually can rejuvenate the body and the mind. If you think that is a simple thing, I think you are on the wrong track. It is obvious that the foundation can not fund the development of such treatments with public donations alone. The private sector has to have a role in completing this task. I agree that many contestants is desirable, but if those contestants don't have the means to convince the private sector of the feasibility of real life-extension and rejuvenation, it will be a futile attempt indeed.

Now, I don't dispute that fly studies are needed, I am just questioning the wisdom in only focusing on fly studies. I think that a fly prize could have a positive effect, but in the long run we need a prize that can convince the public of the feasibility.

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Posted 31 July 2004 - 01:45 PM

Glad to see you agree with everything.

#17 Mind

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Posted 31 July 2004 - 01:47 PM

If also a fly prize, why not other animals? Why just flies and mice? If opening up the contest to fly researchers adds competition and creativeness why not open it up to all animals?

Why not? Because it may become a free-for-all that loses focus and applicability.

If there is a fly prize it should be seperate from the mouse prize altogether. MMP has done a good job getting donations and publicity so far. I think they are building momentum. I wouldn't want to ruin it by changing the rules in mid-stream.

#18 lightowl

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Posted 31 July 2004 - 02:07 PM

Yes, momentum has been build and is continuing to build. It is encouraging to se that the prize has hit $60.000 and is only 3 ThreeHundred members from the $½ MILLION mark. It will be exciting to se what that announcement will do to publicity.

#19 jaydfox

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Posted 31 July 2004 - 05:09 PM

The prize is growing, but recent trends don't really point at "momentum". There were more donations in the last 3½ months of 2003 than there have been in the 8 months since then! There has been some good "momentum" in the last two months, but I see that as mostly attributable to the slashdot article on June 2nd.

And if an extra dozen donations in two months is the best that the slashdot effect can do for the cause, then we're in trouble. I have this horrible vision of tens of thousands of nerds visiting the Methuselah Mouse Prize homepage, saying, "Hmm, that's a neat idea...", and then leaving to look at something else. And maybe one in a thousand decided it was worth it to donate.

Clearly, PR is a big problem right now. If we can't convince the nerds--the ones who should have a strong enough technical background to realize that an engineering approach is possible--the ones who were cheering on the X-Prize and all it stands for--then we're in trouble. We must do something more than what we're doing now. Sitting back and watching the prize grow a couple thousand dollars a month is painful.

And to be honest, I don't have the answers. But I'm willing to brainstorm here with the rest of you. Because we all have a stake in this. Some of us understand human nature better than others. I clearly don't understand it, because I'm so disappointed in my fellow nerds right now.

Maybe it's the Malthusian arguments. Maybe it's the Tithonus error. Maybe they don't feel like they can make a difference.

The number of donations is currently small. Only about 130 to 140. So donating any amount, even a tiny $5 or $10, will at least show support in the growing number of people that support this. At this point, I think the number of donations is more important than the size. Given that the average donation size is close to $400, I'm wondering if people are intimidated by that and just walk away, so to speak.

I do agree with others that once the prize reaches half a million in donations and pledges, the PR should increase. And once the prize reaches an even million, or the outright donations make it to 6 figures, then we should expect to see some momentum start to build.

But we need to do something to hook our fellow nerds. Perhaps it's the MMP website. Perhaps it's the perceived lack of an anti-aging community; I know I was quite surprised by the number of news sites and blogs dedicated to anti-aging and transhumanism.

Perhaps it would do as much good to promote the rest of the anti-aging community to slashdot, rather than just pushing the MMP. Get people interested in the whole concept of the using 21st century technology to truly fight aging. Then, once they're interested, the MMP becomes more than just a "neat idea".

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

Ideas, anyone?

Jay Fox

#20 lightowl

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Posted 31 July 2004 - 05:56 PM

I think it is important to remember that the X-Prize also was just a neat idea when it was conceived. The X-Prize has been in effect in almost 10 years now. It took several years before it had gathered some degree of momentum. I think the size of the prize is an important PR value. As soon as the word MILLION enters the media, it will be much easier to get peoples attention. ( at least I hope so )

The Methuselah Foundation has a group of volunteers that are working to improve the website and the media coverage. There has been some brainstorms and a lot of suggestions are under consideration and implementation. I have been making suggestions to the foundation for some months now, and I am encouraged by the media progress that has been made recently.

The job of the immortalist communities is a tough one. We are fighting the deathmeme. The notion that death is inevitable. It is a powerful conviction that is hard to dispel.

Jay,

I noticed you have expressed your intend to join TheThreeHundred. As a current member, I am grateful to have people like you who are willing to put your money where your mouth is. I am optimistic about the future of the prize, and patience is a virtue. All to often do people raise up and throw out multiple suggestions and nag about them not being implemented fast enough, only to give up and loose interest. It is encouraging that already 15 people have pledged $25.000 to the prize over 25 years. It is a major commitment that can only be fulfilled by patient and dedicated people.

#21 Mind

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Posted 31 July 2004 - 09:12 PM

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


The interest of the nerd/tech community is directly proportional to the "coolness" factor. They are interested in the latest chip offerings by AMD and Intel because they can do cool things with them immediately. The latest DVD format is always "cooler" than the last. The newest flatscreen tv's and new holographic projectors are cool. Conquering aging is a long term project that will not produce immediate "cool" results. It is more a process than an event. I don't think a lot of "young" nerds will ever be interested in anti-aging research. Unless we can make anti-aging research more "sexy" and "cool" we should point most advertising efforts toward the baby-boomer nerds, who may feel more of a need to fund the MMP - given their age.

#22 jaydfox

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Posted 01 August 2004 - 12:48 AM

Unless we can make anti-aging research more "sexy" and "cool" we should point most advertising efforts toward the baby-boomer nerds, who may feel more of a need to fund the MMP - given their age.


Ahh, good point. I'm 26, and I have to admit that I don't feel a lot of personal pressure. Whether the MMP starts building significant momentum in five or eight years, or in the next one or two, I'm convinced that scientific progress will be sufficient that I won't have to worry about aging. I've got 40 years for us to figure out how to dramatically slow aging, or repair/replace age-damaged organs; from there, another 30-40 years for us to figure out how to stop aging. Beyond that, well, I've got all the time in the world.

But my parents, and my wife's parents, and a few other people out in the world, are in their 50's or 60's or older. It's for them that I seek to push this as quickly as possible. It is for their sake that I consider this research so urgent. I can wait. A lot of them can't. If we can't help them reach actuarial escape velocity, we should at least try to give them a couple extra decades, if we can.

And yes, I do realize that a certain degree of patience is necessary. From a PR perspective, the MMP will have fulfilled its job once a mouse has had the last third of its lifespan extended by a factor of [3 according to de Grey, but I speculate at least 4]. However, once its PR role is completed, its scientific goals will just be reaching their stride. And I suppose that as long as new mice continue to break the records, the PR value will be important to keep the pressure up on the scientists and the politicians.

So I realize we're in this for the long haul, and I'm willing to dedicate myself to this cause for 25 years. That's why I'm not too disappointed in the number of people that have signed up for The Three Hundred so far.

Having said that, I still feel the urgency. As many have pointed out, every year sooner that we bring a cure to aging, we "save" 50 million people. Given the incremental advances in age retardation that we'll probably have to make along the way, I figure the actual number will be far lower, perhaps 10 million people. But that's still a hell of a lot of people. Every day sooner that we have the cure, we save 30,000 to 150,000 people.

In my own family, that urgency is expressed as heart-felt advice about health. My dad finally has his diabetes, cholesterol, and blood pressure under control. He's exercising more (his body fat is down from 25% to 18%), taking his prescriptions, and using appropriate supplements (like CoQ10 to counter the side effects of his Zocor). CR would help even more, but I'll settle for getting him to stop damaging himself further.

This research becomes more urgent when there's a human face attached to it, and it's hard to suppress that urgency and take the patient road. I know that I need to work on my patience. But I feel that an infectious sense of urgency will help keep us all motivated.

That sense of urgency is expressed in the idea of the Methuselah Fly prize. Whether that urgency will help or hinder the Mouse prize, I can only speculate. That's why I'm looking for feedback, and I appreciate the feedback I've gotten so far.

Jay Fox

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#23

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Posted 01 August 2004 - 01:35 AM

Yes it does help to be over 30 which is when one begins to notice the beginnings of the body's inability to keep up with damage, although on a molecular level this has started far, far earlier.

One neglected point to longevity enhancement which is not being mentioned is that such an intervention would also have positive effects in people in their teens and 20's. Supposing the interventional strategy had to do with DNA repair, the benefits would include accelerated regenerative capacity and an abundance of energy. For athletes, that would mean greater recovery between training sessions, and for students and executives greater energy and endurance resulting in increased performance academically or in the workplace. Also the incidence of diseases like cancer would virtually disappear.

Furthermore, parallel to this type of genomic intervention, it would not be inconceivable that other enhancements such as specifically targeted transcription factors also be incorporated that would enable every recipient of this treatment to also be given access to the best that our collective gene pool has to offer.

Consequently participation in the Olympics of the future should no longer be a question of who your parents were (genetics). Therefore the benefits provided would be found in all age groups, not just those ravaged by aging and disease.

#24

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Posted 01 August 2004 - 02:03 AM

If also a fly prize, why not other animals? Why just flies and mice? If opening up the contest to fly researchers adds competition and creativeness why not open it up to all animals?

Why not? Because it may become a free-for-all that loses focus and applicability.

If there is a fly prize it should be seperate from the mouse prize altogether. MMP has done a good job getting donations and publicity so far. I think they are building momentum. I wouldn't want to ruin it by changing the rules in mid-stream.


Ouch! I don't often encounter this degree of ignorance. Do you have any idea about the basis for which model organisms are chosen for research?

Have you not read the threads in this forum? Drosophila is the best organism by far for PP type research.

When the organizers of the prize chose the mouse as the model organism to back for the prize they did so on the basis of a number of factors that they deemed appropriate at the time. Perhaps they thought mouse research would take off like a rocket in labs all over the world or perhaps they thought researchers would trip over themselves to enter this competition. Maybe they placed too much emphasis on the PR side of things because they thought a long lived mouse would make a better impression in the news than a long lived fly or worm.

Well, we have mice today, which are living the equivalent of 150 human years. I don't see Fox News reporting it. We have mice today that are impervious to cancer. It never made the news.

When the fundamental discovery is made that creates a paradigm shift in the way we view the process of aging, it will be reported irrespective of whether the investigative platform was a mouse or a fly. What will matter is that a breakthrough will have been achieved. Credible, legitimate scientists will advocate and the meme will promulgate through the media.

#25 kevin

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Posted 01 August 2004 - 02:57 AM

Ouch! I don't often encounter this degree of ignorance. Do you have any idea about the basis for which model organisms are chosen for research?


what a way with words you have prometheus.

#26 Mind

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Posted 01 August 2004 - 02:58 AM

Well, we have mice today, which are living the equivalent of 150 human years. I don't see Fox News reporting it. We have mice today that are impervious to cancer. It never made the news.


If we had human equivalent 150 year-old flies and cancer resistant flies, do you think news organizations would be tripping over themselves to report it?

Prometheus, I think you missed my point altogether. My fear is splitting up donations between prizes, and splitting up the focus. No one is stopping anyone from creating a "fly prize". I just think the MMP is on its way (I am sure quite a few projects are underway), and it shouldn't be fiddled with.

Ouch! I don't often encounter this degree of ignorance. Do you have any idea about the basis for which model organisms are chosen for research?


I am aware of some advantages and disadvantages of different organisms. I don't claim to be an expert.

#27 heinlein

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Posted 01 August 2004 - 10:31 AM

Can somebody explain the difference between the $60K prize money and the $425K in contributions?

#28 heinlein

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Posted 01 August 2004 - 10:47 AM

How do you donate to fly prize?

#29 heinlein

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Posted 01 August 2004 - 10:55 AM

Too bad. Ill hold off donating until the flu comes.

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#30

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Posted 01 August 2004 - 03:48 PM

... hilarious ... [lol] [lol] [lol]




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