Fight Aging!

Once SENS-sponsored research creates a therapy that:

- Apparently works
- Gets reported in the news (even if it's only in the clinical-trial stage)

I daresay that the cash trickle will become a flood and that SENS will literally get more money than it knows how to handle, as long as the news mentions that it's sponsored by SENS.

From a PR perspective, it doesn't particularly matter what the therapy actually is, nor if one of the seven targets is hit first, as long as it demonstratably reverses an aspect of aging. I urge Aubrey to consider some practical cynicism here and focus the most effort on the lowest-hanging fruit.

I think the SENS foundation is focusing on the lowest hanging fruit by focusing on removing oxidized Low Density Lippoprotein (7KC) from foam cells at Rice university. witness the recent multi-billion dollar race between drugs that can inhibit PCSK9 lowering blood cholesterol with fewer side effects than Statins.

An enzyme removing 7KC from foam cells could be even safer... and would have a decent chance of getting picked up by a large biotech or pharma company for clinical trials.

Aubrey's list is not exhaustive, even though it was designed to be exhaustive by definition... for example classifying junk as either in cells or outside cells, which logically includes everything except perhaps junk in the cell membrane.

But it nevertheless leaves out obvious things like:
8. Osteoporosis
9. Persistent viruses

Other than that, it is a good talk.

Slicer is right and I have the same opinion. I mentioned couple times same thing: lack of pragmatism from SENS. Though I donated and support SENS, they act like aging can be solved just "on paper", but doesn't have to be in real life. Their ideas must be brought from "paper" to "lab" into "humans" the whole cycle, not just "initiate" them.

Just imagine how much money can be donated to SENS from rich personalities from the movie industry, if there is simple proof that their theories are working.

That will solve all the funding issues that they have and super-accelerate the entire reverse aging science. With what we donated as community, they can move a thing here and there but will not do much.

Osteoporosis is a cell-loss problem (category 1) and can be solved with stem cells. https://www.fightaging.org/archives/2013/07/a-view-of-current-options-for-treating-osteoporosis.php Persistent viruses are not, strictly speaking, an aspect of aging.

If Rice University researchers manage to drain 7KC and cure the foam cells problem, SENS needs to immediately get on that and say "Our funds did this." Talking about accomplishments in the past tense as opposed to "we might be able to" is a tremendous boost to credibility and absolutely vital for big donations.

So, there's a lot here, of course ...

Posted by: Slicer at January 7, 2015 12:58 PM: If Rice University researchers manage to drain 7KC and cure the foam cells problem, SENS needs to immediately get on that and say "Our funds did this." Talking about accomplishments in the past tense as opposed to "we might be able to" is a tremendous boost to credibility and absolutely vital for big donations.

We absolutely agree, of course. We promote all of the research that we are doing even in its earliest phases across many channels today (our Chief Science Officer's Team and Research blogs, Annual Reports, reports in peer-reviewed scientific journals, in press releases, and at scientific conferences, including but not limited to the SENS Scientific Conferences in Cambridge and the new Rejuvenation Biotechnology conference series in the Bay Area), as well as important research done by others in the field of rejuvenation biotechnology.

You (Slicer) and Adrian are also absolutely right that advancing a therapy out of early-stage work in cell culture and animal models rightly increases credibility and interest substantially. Of course, we're working to do just that — but it simply takes time and money to conduct science. I assume that we all understand this, but there is a tone of criticism in most of these posts that I don't understand.

Slicer at January 6, 2015 7:51 PM: Once SENS-sponsored research creates a therapy that:

- Apparently works
- Gets reported in the news (even if it's only in the clinical-trial stage)

I daresay that the cash trickle will become a flood and that SENS will literally get more money than it knows how to handle, as long as the news mentions that it's sponsored by SENS.

From a PR perspective, it doesn't particularly matter what the therapy actually is, nor if one of the seven targets is hit first, as long as it demonstratably reverses an aspect of aging.

I don't think I'd go quite that far: if it were true that simply getting a therapy into clinical trials were enough to generate unlimited amounts of funding, then every pharmaceutical and biotech startup that got that far would be extremely well-funded, and Big Pharma would still be the darling of the investment community. But certainly, getting therapies into clinical trials will greatly lend credibility to the rest of the work we are doing; again, we are working toward that end, constrained by funding and the realities of conducting scientific research. Again, there seems to be a tone of criticism here rather than of simply stating the obvious that I don't understand.

This is even more evident in Adrian Crisan's comment, which seems to imply that we are intentionally holding back on doing late-stage work. Believe me, nothing would make me or any of SENS Research Foundation's principals happier than if some of our work were to already be in human clinical trials — but it isn't, because we've only existed for a few years, have a very small research budget, and are doing hard science.

Posted by: Slicer at January 6, 2015 7:51 PM: From a PR perspective, it doesn't particularly matter what the therapy actually is, nor if one of the seven targets is hit first, as long as it demonstratably reverses an aspect of aging.

I urge Aubrey to consider some practical cynicism here and focus the most effort on the lowest-hanging fruit.

What would that practical cynicism and going after the lowest-hanging fruit look like? And consider another important priority: to make the best use of our research funding to advance us toward true human rejuvenation. There are areas of research that have a strong promise of becoming therapies available on the market in the very near future, because they are finally reaping the fruits of a long track record of prior research and are now being aggressive supported by biotech VC, Big Pharma, and national health research institutes like the NIH and the MRC: in that context, SENS Research Foundation's investment would do very little to advance the needle, and would run a high risk of being redundant to others' efforts. It's exactly in relatively neglected areas of rejuvenation research that we have leverage (in the proper, non-buzzword sense) to make a disproportionate dollar-for-dollar impact with our investments.

Thus, I both agree and disagree with a comment by Jim that you (Slicer) seemed to agree with:

Posted by: Jim at January 6, 2015 9:43 PM: I think the SENS foundation is focusing on the lowest hanging fruit by focusing on removing oxidized Low Density Lippoprotein (7KC) from foam cells at Rice university. witness the recent multi-billion dollar race between drugs that can inhibit PCSK9 lowering blood cholesterol with fewer side effects than Statins.

An enzyme removing 7KC from foam cells could be even safer... and would have a decent chance of getting picked up by a large biotech or pharma company for clinical trials.

I agree with everything Jim says here about the great promise — both therapeutically, and in terms of generating interest and excitement — of our work targeting clearance of lysosomal oxysterols from arterial foam cells as a way to postpone, arrest, and ultimately reverse the core lesion in atherosclerosis, and its obvious safety and efficacy advantages over approaches based on mere modulation of lipoprotein metabolism. However, it isn't particularly "low-hanging fruit" in the sense to being unusually easy work to do, or already in advanced stages, or likely to generate great near-term dividends as Slicer seems to intend here — nor should it. We're investing in this area not only because of its obvious therapeutic potential, but in substantial part precisely because no one else is doing it.

Posted by: Carl at January 7, 2015 10:39 AM: Aubrey's list is not exhaustive, even though it was designed to be exhaustive by definition... for example classifying junk as either in cells or outside cells, which logically includes everything except perhaps junk in the cell membrane.

That wasn't quite the tautology you seem to imply ... the division of aging damage into seven categories was based on the fact that there are extant examples of each class in aging bodies (e.g., β-amyloid plaque or aggregated transthyretin outside or the cell; α-synuclein and pathogenic tau species inside the cell), and that in general terms the same therapeutic strategies can be used to remove, repair, replace, or render harmless the more specific aging lesions that are classified within the category (immunotherapeutic clearance and novel lysosomal hydrolases, respectively).

Posted by: Carl at January 7, 2015 10:39 AM: But it nevertheless leaves out obvious things like:
8. Osteoporosis
9. Persistent viruses

Other than that, it is a good talk.

Osteoporosis is an indication of high risk of bone fracture due to varying degrees to low bone mineral density and loss of microarchitectural integrity, which like most specific diseases of aging emerges from the accumulation of several different forms of aging damage rather than being, itself, simply a form of aging damage. As Slicer notes, cell loss (the gradual loss of bone-forming osteoblasts) are one component of this; the relatively sudden onset and rapid  progression of osteoporosis in menopausal women is in large part driven by the fall in estrogen production, and there are several approaches that look promising for reversing menopause using rejuvenation biotechnologies; there is some evidence for crosslinking of collagen as well, and of course the degradation of trabecular structure can be targeted directly as well.

Whether or not persistent viruses are properly categorized as aging lesions is a somewhat semantic point, since they are not, themselves, damage to the body's own structures, but the colonization of those structures by a foreign infectious agent. The key practical question is what to do about them. One approach is to develop agents to eliminate the virus itself; another is to prevent them from leading to pathological consequences, by repair, removal, or replacement of those consequences of persistent infection that unambiguously are aging damage, such as eliminating anergic killer T-cells and cell replacement therapy for cells killed by infectious agents or the immune system's reaction to them. And in at least some cases, the rejuvenation of the immune system (via the aforementioned anergic T-cell clearance as well as engineering new thymus tissue and possibly other damage-repair strategies for immune rejuvenation.

As I've said before,

I must say that despite minimal funding (far less than will be required to succeed in three decades), we have really made quite remarkable progress in those few short years. No cures for age-related diseases or debilities, of course, but no one in pharma would expect to start from zero and have something in medical use in five years, even if one had GSK's resources behind one. ... [In that short time] we have made substantial progress (such as this recent SENS Research Foundation-funded research on catalytic antibodies that cleave transthyretin amyloid).

I certainly share your frustration with the slow pace of progress. If you want to help the work go faster, there's plenty you can do to help advance rejuvenation research. But do understand that the question is not whether we'll have new therapies in the next five years, but whether we will have them in the next twenty-five, or the next fifty, or the next hundred — or at all. Whether they will come for us, or our children, or our great-grandchildren, or whether humanity will continue to suffer the slow and terrible decline into disease, dementia, debility, and death, generation upon generation, world without end. That's going to be determined in part by the science itself, and to a much greater degree by what each of us does to make it go faster.

Thanks for the reply Michael. I guess part of the problem is the typical "supporter cycle" expectations. People start reading blogs like this one and get hyped, then realize after a few years that nothing seems to have happened (even if it has). Yes this expecation of progress in a few years is silly, but people are used to the yearly product refresh cycles of electronic products.

Michael, thanks for taking the time to respond.

I criticize because I believe that SENS is trying to boil too many pots with too little cash for each one. (You've got seven categories, and you still need public five-figure donation drives!) To a degree, this is wholly understandable; you can't really know what's going to work until you've already researched it and tested it in humans.

Some research has to be more immediately likely to generate results than other research, doesn't it? We're here guessing on that forum as to what that research is (it's not 7KC? Okay, thanks for telling us), but you ought to have some idea as to the answer. If the most promising research for immediate short-term results got fast-tracked to get done *now* and the other pots were put on the back burner, I believe that large donors would be more willing to donate a few orders of magnitude over what you're currently receiving- particularly if they, themselves, had their [insert aging-caused symptom here] ameliorated with it.

Sometimes, I think that SENS forgets, or maybe intentionally doesn't remember, the value of what it offers. Very few people, poor or rich, actually look forward to hideously agonizing and prolonged deaths, and it's an extremely safe assumption that they'd spend quite a lot of money not to suffer this fate- but nobody wants to buy snake oil. Therefore, you must offer conclusive proof that you're the ones who can prevent them from being tortured to death, and generating that proof, in whatever form, ought to be priority one. Two-Foot Beard Man can be in all the symposia he wants in front of like-minded people, and he can be as detailed and as convincing as he likes, but none of his speeches could ever match "I was suffering from this problem, and now I'm not."

"And consider another important priority: to make the best use of our research funding to advance us toward true human rejuvenation"

Here's where the practical cynicism comes in. Your immediate priority should be to make the best use of your research funding to advance rejuvenation research that will generate more research funding. Ultimately, this advances true human regeneration more quickly, as you then have the money to do so.

I genuinely want to be told that I'm wrong in this criticism. Please, please tell me how.

I agree with slicer sens should focus on one thing and obtain that proof that will bring the funding in once there is proof of concept. Removing plaques is a good area to begin both artery based and in the brain. These are huge killers and would bring in the support fast if it works in humans.

@Slicer - I think Michael Rae has already answered your questions somewhat:

1 ~ Getting into a clinical trial will not generate much more funding (except for that narrow technology):

"if it were true that simply getting a therapy into clinical trials were enough to generate unlimited amounts of funding, then every pharmaceutical and biotech startup that got that far would be extremely well-funded, and Big Pharma would still be the darling of the investment community."

Think about a type of rejuvenation biotechnology that is already in the clinic, CAR T cells for cancer. If SENS had been involved in this and raised 400 million in a spun off company, I don't think the VCs or other investors would be particularly happy if the CEO then announced he was going to spend a chunk of the capital on a completely unrelated lysosomal storage disease like 7KC.

A clinical trial would generate some PR, but I'm guessing from Michael's comments that it would not be a panacea, and focusing on one area would leave other un-researched technologies languishing for decades.

2 ~ The low hanging fruit is already being dealt with by other people:

"And consider another important priority: to make the best use of our research funding to advance us toward true human rejuvenation. There are areas of research that have a strong promise of becoming therapies available on the market in the very near future, because they are finally reaping the fruits of a long track record of prior research and are now being aggressive supported by biotech VC, Big Pharma, and national health research institutes like the NIH and the MRC: in that context, SENS Research Foundation's investment would do very little to advance the needle, and would run a high risk of being redundant to others' efforts. It's exactly in relatively neglected areas of rejuvenation research that we have leverage (in the proper, non-buzzword sense) to make a disproportionate dollar-for-dollar impact with our investments."

3 ~ Even in areas of low hanging fruit, millions per annum and a decade or more are still required to get from a proposal to an in animal demostration and then a clinic trial:

"However, it [7KC] isn't particularly "low-hanging fruit" in the sense to being unusually easy work to do, or already in advanced stages, or likely to generate great near-term dividends as Slicer seems to intend here — nor should it. We're investing in this area not only because of its obvious therapeutic potential, but in substantial part precisely because no one else is doing it."

I've read SENS' tax returns; it's a 501(c)(3) after all. Except for de Grey's trust, the organization generally takes in something around a million and a half a year. In 2012, it granted money to several universities and research organizations, none for more than a quarter million that year (to an European organization; the highest U.S. cash grant listed was for $190k)

Each project takes millions per annum to get to humans, so how can an organization without millions to spend on each project try to fund them all? Is SENS' goal just to complete enough basic research that the projects might get picked up by someone with deeper pockets?

I get that focusing on one area leaves the other areas hanging out to dry, but when the CEO himself comes in here and says that we might not have therapies within our lifetimes because there's no money, aren't they all hanging out to dry?

Doesn't SENS' reach vastly exceed its grasp?

Hi again Slicer,

I don't know that there's any particular point on which you're strongly wrong, but I do think there are a couple of misconceptions embedded in your putting these points as "criticism" of the Foundation at all, rather than existential rage about the nature of science or the chicken-and-egg problems of human psychology:

"Some research has to be more immediately likely to generate results than other research, doesn't it?"

Yes, certainly: again:

There are areas of research that have a strong promise of becoming therapies available on the market in the very near future, because they are finally reaping the fruits of a long track record of prior research and are now being aggressive supported by biotech VC, Big Pharma, and national health research institutes like the NIH and the MRC: in that context, SENS Research Foundation's investment would do very little to advance the needle, and would run a high risk of being redundant to others' efforts. It's exactly in relatively neglected areas of rejuvenation research that we have leverage (in the proper, non-buzzword sense) to make a disproportionate dollar-for-dollar impact with our investments.

If you're asking whether some of the early-stage, underfunded work on which we're strategically focused is more likely to be ready for proof-of-concept animal studies and then clinical trials faster than other areas, I expect that many of the scientific staff at SENS Research Foundation and extramural scientists we fund will have their individual opinions on this, but the process is inherently going to be time-consuming for any of them, and I don't think there is any strong reason to put so much more expectation the marginal differences on timescales for one as to makeit worth the disadvantages of putting all of our eggs in one basket. Early-stage work is early-stage work: you inherently have less understanding of what technical challenges you'll encounter or the relative ease of overcoming them, nor of at what stage it might happen (free culture to cell models to basic animal work to proof-of-concept animal work to Phase I, II, and III trials, followed (even granted favorable regulatory reforms) by regulatory review and negotiation).

Innovation or Stagnation:  Challenge and Opportunity on the Critical Path to New Medical Products

To get medical advances to patients, product developers must successfully progress along a multidimensional critical path that leads from discovery or design concept to commercial marketing.

Currently, a striking feature of this path is the difficulty, at any point, of predicting ultimate success with a novel candidate. For example, a new medicinal compound entering Phase 1 testing, often representing the culmination of upwards of a decade of preclinical screening and evaluation, is estimated to have only an 8 percent chance of reaching the market. [...]

the current drug discovery process, based as it is on in vitro screening techniques and animal models of (often) poorly understood clinical relevance, is fundamentally unable to identify candidates with a high probability of effectiveness. The current scientific understanding of both physiology and pathophysiologic processes is of necessity reductionistic (e.g., is knowledge at the gene, gene expression or pathway level) and does not constitute knowledge at the level of the systems biology of the cell, organ, or whole organism, and certainly does not reach a systems understanding of the pathophysiology of particular diseases. ...

The main causes of failure in the clinic include safety problems and lack of effectiveness: inability to predict these failures before human testing or early in clinical trials dramatically escalates costs. For example, for a pharmaceutical, a 10-percent improvement in predicting failures before clinical trials could save $100 million in development costs per drug.

Now, before anyone freaks out in the opposite direction ;) , let me hasten to add that there are several reasons to think that rejuvenation biotechnologies should exhibit a better success rate than the recent record of the industry. One is part of the very nature of regenerative medicine-based solutions. Because these therapies do not work by interfering with basic metabolic pathways in the body, but instead directly repair, replace, remove, or render harmless cellular and molecular damage that is disabling normal function of a tissue, rejuvenation biotechnologies carry an inherently lower risk of side-effects (and particularly, unexpected side-effects) than conventional drug therapies — and thus, a lower risk of failure due to unacceptable risk profiles. Indeed, the concern that for conventional drug therapy  "scientific understanding of both physiology and pathophysiologic processes  ... is knowledge at the gene, gene expression or pathway level and does not constitute knowledge at the level of the systems biology of the cell, organ, or whole organism" is a problem exactly because safe and effective manipulation these of these pathways is the only basis on which candidate medicines that rely on this approach are  proposed to work, whereas "damage-repair" therapies work only to restore the original structure of the youthful, healthy organism.

Another is that we are working on tools (and, happily, so are others) to ensure that animal models in which future proof-of-concept work is carried out more accurately reflect the clinical state of future patients (an issue highlighted in "Innovation or Stagnation," and in more detail this report). In particular, as this story emphasizes, too often therapies that are inteded to treat people who have already undergone substantial degenerative aging are instead tested in young animals subjected to extreme and completely artificial insults to mimic some aspect of a disease of aging. The development of the Maximally-Modifiable Mouse will make it much faster and less expensive to routinely test candidate therapies in "pre-aged" organisms (see also the somewhat more up-to-date but more abbreviated discussion in our latest Annual Report), and our project on heterochronic plasmapheresis (also see the Annual Report) will give us insight to allow us to both better predict such problems, and to avoid them by making the systemic environment in aged tissues more "youthful" and receptive to accepting and recovering from regenerative therapies.

But what these tools and heuristic advantages will allow is for us to maximize the odds of success of all candidate rejuvenation biotechnologies — not to predict which of our candidates has a greater odds of rapid progress in the earliest stage of research. And again, although I agree with your general point about the increased excitement and opportunities to accelerate funding that would flow from successful movement of one of our therapies into clinical testing, there are still good reasons to intentionally take on difficult projects, to be humble about our ability to predict success of individual candidates or projects, and to not put all of our chips on one square on the Roulette table.

Again, thank you for your reply.

So you can't effectively prioritize based on time-to-completion at all. Making predictions would, itself, be difficult and expensive. Ouch.

You should edit and publish your responses to my criticism somewhere, if it's not already; I can't possibly be the only one who's thought along those lines. It is definitely a psychology thing; people, in general, want results, or a credible path to results, or at least some idea when results will happen, or a good explanation as to why they haven't got the previous three.

I hope that the tools are completed soon and widely adopted; even if the general public never understands their value, at least people in the community will be able to say "This is something that SENS money did."

Which goes back to my fundamental point: credibility. Telling anyone "There's people working on making it so you don't die of old age, ever" is generally met with outright incredulity, even if I don't offer any expectations of success. If the Foundation is ever going to get the kind of money it needs to fully fund every appropriate project, you absolutely need to convince people that it's possible and that you're the right ones to finance it. I don't know exactly what that'd take, but since past-tense "we did things" isn't feasible in the short term, you might want to talk to a marketing consultant (not outreach, *marketing*) who has experience with nonprofits and might bring in twenty times what you pay him.

Remember, people give away money to all kinds of stupid things, causes, and people who should not be receiving money. Having people donate money to researching ways of avoiding their own impending doom should not be so terribly difficult!

@Slicer:
This is a classic case of tight budget allocation.

Putting the few eggs in one basket or dispatching them one by one in each area of interest? There's no simple answer.

To take the case of another health-related foundation that I'm following, the American Tinnitus Association (ATA), it's the "dispatch" approach that has been chosen. A meager research budget funding several complementary aspects of the issue, with up to 50k USD per project per year. That is, almost nothing, so to speak.

Yet, I feel this is the right thing to do. Advancing slowly on all identified fronts - wich is not the same as funding randomly here and there in hope of finding a lead.
Financing all supposed key issues allows to keep a relatively even pace between all aspects of the problem, and as progress is made, could potentially allow for better inferences and help keep the whole project on track.

Sometimes I feel it's better to have a superficial knowledge of many things, rather than a deeper knowledge of a select topics. That way you increase the number of "known unknowns" and get more perspective on what you're working on.

@Slicer - I think you are thinking that a really good explaination like the one Michael just gave you would help. But... I don't think the more general public care for the fine details of funding science. Yes things could always be marketed better, but diminishing returns set in at some point. Plus I think a certain member of the SENS foundation already has a ridiculous interview schedule. And I think others such as Reason are already doing all they can.

It would be nice to have a detailed FAQ for those that want to dig into the details. But most of the pyblic just work on trusting people they know or have dececided to respect, usually because a large proportion of the public already does. Can you name the complete policy document of the last political party that you voted for?

I don't know what exactly a marketing guru would do to resolve these challenges?

Jim: The thing is to gain the public's respect. It's not that the general public really cares about the details; some of the public just wants to know that the details are there, that if they donate, their money will be spent wisely.

But a lot of the public, as in the "Everyone Else" public, just needs to be convinced that the organization exists, is reputable, is funding something important, and needs money. This is the difference between outreach and marketing. Interviews, conferences, lectures, etc etc- that's all small-scale outreach. Marketing is a different beast. Marketing is the reason the Pink Ribbon of Breast Cancer (Susan G. Komen foundation) is so ubiquitous. Marketing is the Ice Bucket Challenge. Marketing is the reason Invisible Children got so much cash for its (pointless) KONY 2012 campaign. Could it backfire? Potentially, if it was done wrong and made the wrong promises. But what's the alternative? Going another underfunded decade?

First, I want to thank everyone engaged in this thread for intelligent, thoughtful, and well-argued posts.

One loose end, and a comment in response to Slicer's last post above:

Each project takes millions per annum to get to humans, so how can an organization without millions to spend on each project try to fund them all? Is SENS' goal just to complete enough basic research that the projects might get picked up by someone with deeper pockets?

That's certainly one route to doing it. Indeed, as I'm sure you're at least vaguely aware, this is the way most innovative new therapies get developed today: a small biotech startup with very little funding is established to work on some promising approach (often coming out of the principals' academic work), and as its work gets increasingly promising-sounding it first invites angel-investor and then VC funding, and is finally scooped up by Big Pharma, who have both the sheer cash reserves and the non-monetary resources and experience (regulatory, legal, clinical, networks of researchers, in-house researchers, experience in recruitment for trials, etc) to take it into human testing, or sometimes beyond Phase I testing. We certainly have considered some kind of licensing agreement as one way to graduate our early-stage work into clinical trials and eventual therapies, while generating a funding stream that would allow us to reinvest in other existing or newly-launched research projects.

It's also possible that we might "simply" get more funding — because of attracting the support of a small number of new wealthy donors, greater investment from our existing donor base, or converting the many people who still cheer our work from the sidelines without putting any skin in the game, or by a change in public attitudes and perceptions that led to an influx of people newly convinced of the value and feasibility of putting an end to the horror that is the ongoing degenerative aging and death of hundreds of thousands of people during the course of each and every year.

Indeed, while (as I've said) I completely acknowledge that having something in human clinical trials would very reasonably be thought to increase donations, the real sticking block to unlocking the truly massive amount of funding that is potentially available for our work (as can be seen from the budgets of the NIH, the UK's Medical Research Council and Wellcome Trust, the Canada Foundation for Innovation, the Australian National Health and Medical Research Council, etc), as well as to multiple disease-specific medical charities) is not likely SENS Research Foundation's current record of punching above our weight in turning donor funds into key research, or our still-unrealized aim to turn that research into actual medical therapies available to the public. Rather, it is the prior problems of widespread disbelief that aging is biomedically tractable at all, or acknowledgement that successful intervention is desirable — is, in fact, the central humanitarian and economic challenge of our time. I'm sure you're familiar with the problem.

Second:
Marketing is the reason the Pink Ribbon of Breast Cancer (Susan G. Komen foundation) is so ubiquitous. Marketing is the Ice Bucket Challenge. Marketing is the reason Invisible Children got so much cash for its (pointless) KONY 2012 campaign.

It's interesting that you would cite these two particular organizations. Komen has indeed been extremely successful, but I think if you were to ask the great majority of their donors and participants what exactly Komen has accomplished, they'd have a hard time naming anything in terms of actually working toward a cure. Rather, they mostly just feel good about the organization, and would also point to their work in raising awareness and increasing the level of participation in mammographic screening. Indeed, while this is mostly laudable work, the truth is that they really do very little research, and the share of it in their total activity was quite low for a long time (and eventually rose in large part due to external pressure).

And did more than a fraction of a percent of participants in the Ice Bucket Challenge have any clue what exactly the ‎ALS Association did — on the research front, or anywhere else? And no one can have had much idea what Invisible Children was doing or would do with donor funds, or of the serious criticism to which the group had been subjected?

I would, of course, be delighted if funds started rolling in from any source and for any (above-board) reason. Whatever we do to earn those investments on the marketing and PR front will best and most sustainably be firmly grounded in patient, ongoing investment in research strategically selected to advance us on the critical path toward comprehensive human rejuvenation; helping to train up the first wave of rejuvenation biotechnologists; and raising awareness both of our own work and of progress in the wide field of rejuvenation biotechnologies.

Michael, I understand that you want to generate all your funding without resorting to crass psychological manipulation of the general public. This is laudable and virtuous.

However, I offer a counterpoint: if organizations both honest and unsavory can receive massive donations from the general public through organized, widespread, viral campaigns, even in situations where the public really doesn't have any idea what the organizations actually do, why can't you, particularly since you actually plan on offering something that the donators might eventually receive in return?

"A change in public attitudes and perceptions" is pretty much the raison d' etre of marketing. Try to find a firm that can bring in more money than you pay it; it's obviously possible and worth your time.

@Slicer - You seem to be asking why SENS or Fightaging.org can't come up with a viral marketing campaign. The simple answer is that these are very difficult to create. "Hiring a marketing guru" won't be any panacea, as they probably won't be able to come up with one.

"if organizations both honest and unsavory can receive massive donations from the general public through organized, widespread, viral campaigns, even in situations where the public really doesn't have any idea what the organizations actually do, why can't you, particularly since you actually plan on offering something that the donators might eventually receive in return?"

Again you seem to think that if only the public understood what SENS and related organizations were about, money would flow in, given that viral marketing campaigns sometimes raise money for more nebulous causes. I think most of the public will never understand the value of this, until the day their doctor and friends tell them that treatments already exist to make them biologically younger and healthier.

What is more important is finding the people who are interested, and getting them to donate and create growing noise until some or all areas of research reach the angel investor phase.

Yes it sucks that we can't just have an 'ice bucket challenge for biomedical rejuvenation" and get this done in 10 years rather than 25 or 50, but that is the way the world is.

There are things you could try. How about creating a blog like fightaging? Or creating some CGI animations of the SENS proposed technologies? Communication isn't just about coming up with one perfect pitch to solve everything, it is an ongoing conversation between loads of people.

First of all, seems like SENS needs to have a continuous dialogue with its root base. The long discussions in this post are the proof of that. So either SENS open up a special section on their web site or they do it in a different manner, but I think that continuously open dialogue is a must.

@ Michael Rae – thanks for keep answering our questions, but do please transform these posts into a continuous dialogue with this community. It is very clear that we support SENS and we want SENS to succeed. But we want to happen faster and more transparent for us the laymen.

I have couple comments to make, complementary or totally independent from previous discussions. Some of these ideas I mentioned before – or similar ideas were mentioned by others in this blog.

1. About SENS web site:
It need to be easy to navigate and simple. As of now there are two blogs, like they are different entities. In general a blog is an interactive area where readers can post back questions, comments, idea. Right now the blog is just to inform the readers.

Front page of SENS is not giving any clear message of what SENS does. I had medical professionals visiting the site and they got back to me with not convincing comments.

So make it simple with high impact so in couple seconds the message is sent to visitors.

A bold and simple statement about who and what with the vision and mission of SENS. Maybe something like this:

“SENS Foundation
We develop medical technologies that SLOW, STOP and REVERSE AGING”

2. When pitch for donations, try to be a hero without going overboard, state simple things like:

“One of our generation duty is to stop and reverse aging, and SENS is deeply involved in this process”.

People love heroes, and if the hero is real and it brings me back to 18, then even better. They will follow you and support you. But in turn, you have to prove that you CAN do that, and is not just a slogan to attract followers!

Information needs to be presented in a simple way, easy to read. The lengthy explanations in the blog post are ok, but for busy professionals like us, you have to have a first page with a bi-weekly progress bar/chart of most important projects that you undergo. Something like a live update.

3. SENS needs to show and prove that actually is using a disruptive and genuine stop/reverse aging process. Easy to say, hard to do, but HAS to be done shortly. Otherwise we are keep talking and argues pros and cons. SENS needs to identify the easiest pathway that can be implemented to show real results and “go for it!”. Too many discussions, too many articles. But a simple proof brings legacy.

4. Open Source research. If you look at the Open Source packages developed in the software world, you will see that many of them matured quickly and became the backbone for many processes: Linux, GIMP, Inkscape, Blender, etc. I think SESN should create an Open Source software platform that read vast information from literature (web), compile it and creates logical vectors. As a result offer clues on what works, what doesn't, links between facts and what is the current status of research relative to rejuvenation pathways.
Let researchers (and laymen) run the software and use the data. There are millions of briliant mind in this world, ready to help this process, why not using that huge resource?
I'm sure that will accelerate tremendously the reverse aging process.

You can even create a portable version similar to SETI@home, that search for extraterrestrial life.
Such software can be created by the large community of Open Source volunteer programmers around the world. Give them a mission to cure age, and people will be proud to participate as much as they can. Also students that do internship can help with creating such software package. Try to post on universities and ask for such help, you will see how many volunteers will help. Just make sure you have a task group inside of SENS that organize the process, so it will come to a fruition.

5. Funding projects that run couple months to one-two years using crowdfunding.
There are tons of discussions if GDF-11, NAD+, C60, TA-65, MitoQ, Sk1Q, etc. actually work or not.
Why SENS doesn't step into and create “pet projects” with crowdfunding and clarify these discussions?
People will love to donate small sums to finally see a clear result. Better than that, if things work, then there will be good data that suggest some pathways actually work in rejuvenation. If doesn't work, subject is closed from SENS perspective.

Let's say you have experiments done couple years ago by Ronald DePinho claiming that telomerase activation reversed aging in mice. Start a study by trying to replicate that. How much cost? 100K?, OK post that and see how people will donate. Then make it live: create a live web cams that shows mice in real time, show data numbers, etc. Sounds like “reality show”, but this is serious science and this community here would love to see real results concerning these big questions. Why wait?

6. Whatever cannot be solved by SENS try to outsource it. Let's say you cannot figure out how to solve
moving from step A to step B in one of your technologies. Create an RFP (Request for Proposals) and post it on SENS web site.
Fees will depend on the complexity of the solution requested. Do not have the money to support that RFP, try crowfunding.

7. Somebody mentioned recent ModeRNA landing a $450 mil contract. How they can do it and SENS cannot? They are a start-up too (founded in 2011), with a portfolio that is less impressive than what SENS has to offer. Why they can seal a deal like that? Simple, they focus on achievable targets that are couple years away, focusing on deliverable “in human” solutions that will in turn bring lots of revenues. Those revenues will help develop other solutions. The vicious circle that needs to be cut by SENS (like many others said here in this blog) is the funding vs real life proof, and that can be done by focusing on few things that can deliver a proof, then that will bring revenues and legacy that allow SENS to develop seriously all the other pathways. Yes, SENS needs to break the ice in one spot first and then can catch large fish, otherwise will be many, many decades before something happen for real. And we do not want that for sure.

9. Push on the end of Artificial Intelligence, or whatever can be available right now. I know people on this blog don't like Calico's approach. But make no mistake, they ride the technology and they have the funds. I'm pretty much sure that they will re-calibrate their efforts and will leapfrog many others. Everything in this Universe is a database, and who can read and make intelligent connections between database sets, will move fast ahead of others. As of now, Calico has that ability to crunch and make intelligent connections in this large database that is human aging and reverse aging.

10. Reinvent SENS at every couple months. Show that progress is made in your crusade against aging. If it was me, I was renaming the Foundation something like “SENS 0.18” - which means, as of now we are 18% complete in our effort to reverse aging. In two months or so, based on research developments, I'll have renamed it to SENS 0.24. That will give people real time signals that things are moving in the right direction. As opposed of what is now seen, or not: if you look at the web site, shows pretty much same thing like two years ago. You have to “dig” into to find out about the progress made – or receive the newsletter. But we are busy professionals and do not have always time to dig into, so as simple supporters we need a simple and efficient interface to tell us that things are progressing.

Again thanks for your work and hopefully SENS listen to its base root and recalibrate improving and speeding up the reverse aging process. We are here to help.

@Adrian - regarding redesigning the SENS website, you are free to take the content and do this yourself. We can't just say "do better marketing and outreach" without suggesting how.

I think part of the problem is that this is scientific research, not an engineering project. No one actually knows how long any research project will take. If they did it wouldn't be called research.

I do think the "how long" question is a problem though. It would be nice if there was a project timeline for each technology with supposed milestones, a marker showing where the project is for each task, and perhaps resources and personel working on each task. Then maybe have kickstarter type goals such as "raise 100k to hire one more researcher for one year on task x of project y". Creating a webpage/site like that would probably not be cheap though? But it would offer a landing page on which people could drop in to view the latest news and internal and external blog posts on various subjects and projects.

Jim, please stop saying "hire a guru" - I'm not talking about employing a "guru" who sits on the SENS payroll, I'm talking about actually contracting with a firm that handles marketing for other nonprofits. Sloganeering is what these companies do.

Adrian, as for #4, there already is a "monkeys on typewriters" project for proteins; it's called Foldit and has plenty of highly experienced monkeys, but that approach is simply not appropriate for most of what SENS-funded researchers do. #7, that one's a for-profit funded by investors. #9, not even gonna comment.

@Slicer - as for#9 -you are not going to comment about AI, Calico, database or all together?
Just curious why?
As for #4 I'm thinking of something much more complex that will evolve in next releases. It will connect all available info and run parallel algorithms that highlight clear results as well as potential pathways. Yes a tool that slice huge databases and extract meaningful results. In time will evolve to AI. And I do believe it will accelerate SENS research a lot.

So, there's an awful lot here, and I'm not even going to attempt to cover it all. I do first and foremost want to clear up a pretty serious misunderstanding:

Slicer at January 10, 2015 9:34 PM: Michael, I understand that you want to generate all your funding without resorting to crass psychological manipulation of the general public. This is laudable and virtuous.

However, I offer a counterpoint: if organizations both honest and unsavory can receive massive donations from the general public through organized, widespread, viral campaigns, even in situations where the public really doesn't have any idea what the organizations actually do, why can't you, particularly since you actually plan on offering something that the donators might eventually receive in return?

I can somewhat see how my comments would have led you to thinking that I thought that viral fundraising appeals were somehow crass, but I can assure you that such is not my view and it was not my intention to suggest that they were. Believe me, if an "Ice Bucket Rejuvenation" challenge raised $41.8 million (or even $$41.8 thousand) for rejuvenation research, I would be quite ecstatic and have no ethical compunctions about the gimmick whatsoever!

I am guessing that I accidentally gave you this impression by not explicitly looping back from your comments about viral marketing to our earlier discussion about shooting for clinical trials as a way to ensure increased funding. What I intended to convey was that these campaigns illustrate that the success of these organizations and campaigns illustrate that fundraising success doesn't simply flow in a linear way from the organization's track record as an effective organization, or the public's awareness of that track record.

And I was saying that whatever we do to raise funds — ice bucket challenges, celebrity dinners, Reason and collaborators' amazing challenge grants, one-off crowdfunding campaigns, or just straight-up appeals for funding for the importance of our work — we have to continue making core research allocations based above all on their scientific merit in advancing us toward a comprehensive panel of rejuvenation biomedicines, rather than trying to make those decisions according to which might for other reasons have a "hook" that draws in more donations. Both for our own integrity and the long-term, sustainable support of our donors hang on it. (Here's one cautionary tale — from ALS research, no less).

I'd be happy to be able to engineer a viral video campaign; of course, so would every other nonprofit on the planet ;) . Really having the "secret sauce" to make this happen — and to have it rise over the noise of everyone else competing to push their meme to the top — is a very substantial challenge. Notably, the "Ice Bucket Challenge" did not come either out of a strategy carefully developed by ALS Association (either an in-house "guru" or external consulting agency in social media), but out of a long organic process that (according to Wikipedia) came out of previous low-profile use of similar gimmicks, particular patient-donors adopting it for their own social circles, small and major TV hosts taking it up for different causes, before finally somehow gelling around the ALS campaign:

The origins of the idea of dumping cold water on one's head to raise money for charity are unclear and have been attributed to multiple sources. The most commonly accepted origin credits [two friends with ALS] ...

From mid-2013 to early 2014, a challenge of unknown origin often called the "Cold Water Challenge" became popular on social media in areas of the Northern United States. The task usually involved the option of either donating money to cancer research or having to jump into cold water. According to the Wall Street Journal, the Ice Bucket Challenge was begun by professional golfers as means to support various pet charities.

One version of the challenge, which took place in Salem, Indiana as early as May 15, 2014, involved dousing participants with cold water and then donating to a charity, for example a local child diagnosed with an inoperable brain tumor. In another version, the Auckland Division of the Cancer Society of New Zealand was the beneficiary. [Several other historical antecedents documented] ...

Shifting focus to ALS

The challenge first received increased the media attention in the United States on June 30, 2014, when personalities of the program Morning Drive, which airs weekdays on Golf Channel, televised the social-media phenomenon, and performed a live, on-air Ice Bucket Challenge. Soon after, the challenge was brought to mainstream audiences when television anchor Matt Lauer did the Ice Bucket Challenge on July 15, 2014 on NBC's The Today Show at Greg Norman's challenge.

On the same day, golfer Chris Kennedy did the challenge, then challenged his cousin Jeanette Senerchia of Pelham, New York, whose husband, Anthony, had ALS for 11 years. Kennedy's challenge was the first documented instance of the challenge being connected with ALS. At this time, the challenge was not connected directly with ALS. Participants would donate to a charity of their choice. [Etc]

As you can see, a lot of twists and turns and serendipity led into the eventual ALS Association breakout.

Adrian: there's much merit in many of your suggestions. I can assure you that some variation on most of them have been suggested and discussed internally, and continue to be taken under advisement. I also promise to pass your specific suggestions to key decision-makers within the Foundation. I should address two in particular directly:

Adrian Crisan at January 11, 2015 8:38 AM: A bold and simple statement about who and what with the vision and mission of SENS. Maybe something like this:

“SENS Foundation
We develop medical technologies that SLOW, STOP and REVERSE AGING”

Hm. I think we're doing that, with several different angles/"takes" on the theme and the ways we're doing it, in the five-part slideshow on the upper left-hand side of the home page. For several years now, we've chosen to be explicit about our target being the disease and disability driven by aging rather than simply talking about "aging" because of the fuzziness and different associations that the word "aging" alone elicits in the general public, but I think that the various taglines given in the slideshow make the point I know you want to make (and that the people in this thread would all understand immediately without explicating what we're talking about).

Adrian Crisan at January 11, 2015 8:38 AM: I think SESN should create an Open Source software platform that read vast information from literature (web), compile it and creates logical vectors. As a result offer clues on what works, what doesn't, links between facts and what is the current status of research relative to rejuvenation pathways.

While it's being developed in-house at this stage rather than on a truly Open Source model, we are actually working on a relational database project whose ultimate aim is to be able to do what you're envisioning: mine through the vast troves of biomedical research that is being published today (happily almost all of it online, with or without print), with particular but non-exclusive emphasis on a curated subset, and ultimately derive novel information from associations amongst widely-scattered data points that may be too complex for a single human mind (or even a small group of expert minds) to grasp.

Adrian said:

"4. Open Source research. If you look at the Open Source packages developed in the software world, you will see that many of them matured quickly and became the backbone for many processes: Linux, GIMP, Inkscape, Blender, etc. I think SESN should create an Open Source software platform that read vast information from literature (web), compile it and creates logical vectors. As a result offer clues on what works, what doesn't, links between facts and what is the current status of research relative to rejuvenation pathways."

I partially agree with you. I think it isn't a matter of open source software but open information.

I don't understand why the "Ending Aging" book has a restrictive license. If it's purpose is outreach, why it's prohibited to share it? If it's purpose is funding SENS, I think it's a very bad way to obtain funding (how people will fund something they don't know about?) and SENS surely is already obtaining much more money from donations than from selling the book.

I also don't understand why the scientific journal Aubrey created for rejuvenation research has also a restrictive license. I can understand that a publishing company wants a monopoly for its journal, but why an organization whose purpose is research and outreach would want to close their papers so that only a few people can read them? There are already open journals like PLOS Biology. They certainly know them.

I talked about these two issues with Michael Rae some time ago and didn't got convincing answers. He said they wanted to obtain funding from the book and that the publishing company of the journal wanted it to be closed to make money. I still don't understand the rationale behind these two decisions. I think they only can be harmful for research and outreach.

Why not use crowdfunding sites like kickstarter and experiment to raise funds for anti-aging research. Every medical project on experiment I saw had full funding. That included one project that had to do with aging. Depending on the current amount of money needed for each research project you are looking at funding you could most likely fund most of the research you want to fund that way.Particularly if you are only looking at funding each project with less than 1 million dollars. Help the scientists whose work you want to support connect with the general public on platforms like http://www.kickstarter.com and http://www.experiment.com . I would bet a lot of money that many people don't know you exist.