it's great to be here of course um so i just thought i'd start by saying that uh some of you may have heard perhaps of a complication that's going on in my life right now um so i just wanted to say that there is an independent investigation which was started at the beginning of july and is still ongoing and that of course means a couple of things first of all it means that i am on administrative leave which means that i am not representing sense research foundation here today officially i am here in a personal capacity um i should mention that i just noticed i have the sense research foundation logo at the bottom of all my slides so please pretend that that isn't there um uh apart from that i can't say anything more at all about what's going on and of course this would be the wrong place anyway so i just want to say how overwhelmed i am for all the love and support that i've received from hundreds and hundreds of people and uh it shouldn't be long now so you know watch this space so having said all that let me just share my screen so i thought i would talk today about the changing priorities that i see that we have in this field at the moment because it's very easy to get very you know optimistic and excited about how things are going no question things are moving much faster than they were even a few years ago but i believe that those of us here who are really at the forefront of this crusade need to be absolutely clear that there is an awful lot still to do and i thought i would start in kind of illustrating that by um using some of the sides that you're very familiar with but with different titles than you may have seen so of course you know all about this it's the um increase in life expectancy that has happened over the past couple of centuries and uh of course that's a wonderful thing it is the result of progress that we have made initially in the elimination or virtual elimination of infant mortality from things like tuberculosis and um subsequently as we've gone on uh the reduction in mortality rates at older ages which has been absolutely wonderful and it has certainly resulted in greater quantity of life and quality of life but as we all know the result is that more and more people are reaching ages at which they suffer from the chronic progressive health problems of late life and as usual i'm just putting up this slide showing the economic uh um outcome of that which is completely catastrophic in terms of the rate at which we are having to increase the proportion of the economy that is allocated to medical care it's completely terrifying and something better be done about it and of course that is very much in the minds of people across the board policy makers you know the private sector and so on um but what to do about it is something that of course there is rather less consensus on as things stand so i mention all that because it kind of illustrates how priorities change that when you identify a particular problem a particular bottleneck um and you make progress on it other ones pop up um in their place and so if we look at the maintenance approach the damage repair approach that of course i pioneered more than 20 years ago now and that have become very much the focus or one of the major focuses of the anti-aging research field uh we can see that potentially there is a bit of an issue because there are lots of different types of damage that we have to go after and of course the whole reason why geriatric medicine was originally seen to be a non-starter that would never really have all that much effect on the health span of the human race was because of that precise problem that there are so many things you have to fix the maintenance problem the maintenance approach um kinda sidesteps that it makes the divide and conquer problem more manageable in ways that i've talked about many times and i won't reiterate now um but still it's a divide and conquer problem and that means that we have to make quite sure that the most difficult parts of that divide and conquer approach are not left behind and neglected now of course since research foundation was set up more than a decade ago with exactly that in mind we set it up as a an independent charity an independent non-profit funded almost entirely by philanthropy and we did that precisely in order to avoid the constraints that force both industry and mainstream academia into short-termism and into focusing on low-hanging fruit and neglecting the harder but equally important problems that otherwise they might work on so of course the um first decade of work that we and others have done has had great successes and certainly some of those successes constitute progress in the most difficult areas of damage repair for example in the area of mitochondrial mutations in the area of extracellular matrix lessening these are areas which were completely stalled when we started and they're not stalled anymore but they're still nowhere near as far along as getting into clinical trials for example so we've got to make absolutely sure that that does not persist that these things are continuing to be pushed forward and that's where emerging challenge number one is it is extraordinarily hard to get most people to not focus on the low-hanging fruit in industry of course we know that people who want to make money they want to make it soon and therefore they are going to pressure to put pressure on to cause that to happen some of you who have long memories may um recall a company called elixir pharmaceuticals which was founded by two absolute demigods of gerontology cynthia kenyon and lenny garante and the reason why those of you with short memories will probably not remember elixir is because it ended up being a complete waste of time and that was why they took the wrong money they got pressured into doing stuff that wasn't useful and nobody remembers them at all it's of course exactly the same in academia that short-termism arises from the need to publish or perish and um same result worst of it is that it's quite easy in biology in general and certainly in our field to identify areas that where you can make quick progress and make a big splash and get a terribly interesting paper on the front page of science magazine and unfortunately it doesn't go anywhere because there is no actual way to take it forward to something that would have clinical relevance in the long run and the final problem that the final aspect of this problem is that most of the real visionaries who have money are actually capitalists they are people who made their money in the private sector and they believe in that kind of way of doing things and many of them simply do not believe in philanthropy or in charity in general now some of those people have been visionary enough to recognize that they have to bite that bullet of course the person who gets the greatest credit for that in our world is peter thiel who started funding the methizola foundation back in 2006. but the fact is now that they these people have the opportunity to invest rather than to donate they are very very tempted to do exactly that so we absolutely need to be vigilant in making sure that the most difficult components of the damage repair portfolio are not neglected so then there's the problem or another problem arising from the divide and conquer nature of damage repair which is that there are lots and lots and lots of different type of damage you know some people often oversimplify what i say and they say well he's saying there's only seven types of damage that's nonsense of course that's not what i'm saying what i'm saying is that there are seven types of damage repair and within each of these categories there are many examples like different types of stem cell therapy that were needed for different types of cell loss in different issues for example so what this means from the point of view of those of us who are developing these therapies is that it's absolutely critical to find out as soon as possible what bad things might happen when we simultaneously administer a bunch of different damage repair therapies to the same people at the same time and that is something that is very hard to get anybody to do because the fact is it's antithetical to the way that medicine is normally done medics just like to keep things simple because they understand that unforeseen interactions are really hard to anticipate um but it's worse than that because the thing is it's boring in other words it does not fit the incentive structure of other groups we have more or less the same problem i talked about before in terms of low fruits but perhaps even more so in this case because in industry you know everyone's got their own intellectual property and they want to try and make money out of that and there is not much of an incentive to actually work together there are of course eventually incentives of that nature so as to you know bring therapies together and do cross-licensing and such like but it takes a hell of a long time to put that kind of structure in place so there is a huge barrier to this absolutely essential component of our mission when we look at industry and unfortunately the same is true in academia basically you know if you have a therapy that in mice for example causes them to live a bit longer and you have another therapy that also does so then you'll get really good papers publishing each of those things but you sure as i won't get a good high profile paper just putting the two things together and finding out that yes everything's okay that's just they're just you're inducing to the people who make the decisions about what papers get published in high-profile places and that is a problem that we this community need to be very very serious about and to compensate for so at the foundation there is now a very nascent effort to do that we are putting together a program to put just two therapies together a stem cell therapy and a synalitic therapy and there's going to be a lot more of that i believe that one of the biggest consequences of the enormous windfall that some of you may know we received recently is that there'll be a very big expansion of work at sense research foundation on combining therapies it may end up in fact being our main focus over the next few years but we shall see um now i want to talk a little bit about the um steps that companies make there's been a huge emphasis of course over the past few years in our world on startups and there's literally hundreds of them now and that is absolutely wonderful no question i mean half a dozen of them were spun out of sense research foundation but the numbers that have sprung up independently but doing very much damage repair work it's just breathtaking and that's wonderful but the thing is the reason why these companies exist is because they got investment and the reason they got investment was because the investors were looking ahead to the point where they could get their money back which of course happens as a consequence of things like ipos and acquisitions and such like and that is all very well but the thing is that when those things happen you are talking about different kinds of investors coming in and that is a problem because those different kinds of investors are far less mission focused than the angels and seed investors who get these companies going in the first place i'm sure all of you are familiar with many of the many of the main people who have made these investments and who are absolute heroes who have saved the most enormous number of lives you know in the future as a result of accelerating research by putting that money in but the fact is when you go ipo and such like you've got people coming in who are only interested in the money and they really don't have much interest at all in the um in the longevity crusade unfortunately what has already happened a few times is errors of judgment well in hindsight anyway of um you know when to go and how to go public or to do something like that uh you know i'm sure many of you are familiar with the company ajax which is headed by uh the absolute granddaddy of private sector longevity work mike west they've had a very very tough time then there's restore bio which collapsed completely and ended up you know um just disappearing off the face of the earth basically uh as a result of one uh you know negative clinical trial and it wasn't even really their fault you know they kind of had the goalposts moved under their feet um you know it was it was it was enough to cover now i of course am in no way pretending to be any kind of uh you know knowledgeable person let alone guru in terms of investment judgments and such things i know nothing about that kind of world really but this is what i see so you know don't shoot the messenger but this is what has been happening so those of you who are in a position to um you know to influence the timing and the structure of the subs of the later stages of growth of these startup companies this is what i want everybody to be thinking about and being aware of and alert to we could end up having things slow down and go you know less rapidly than they could if we allow too many companies to make this kind of mistake i want to talk a bit more about thought leadership especially now thought leadership from the scientific community because here we also have a difficulty um let me first of all draw your attention to the line immediately under the red one uh in 2003 when i ran my first conference in cambridge uk i gave two talks excuse me and one of them was a kind of um call to action kind of talk and the title was something like gerontologists have a duty to make time frame predictions publicly that was focused on the principle that if the thought leaders especially the small minority of thought leaders who are willing to do a whole bunch of um public out outward facing stuff talking to the general public and such like um if those people are too cautious in talking about time frames they are going by by omission to leave their audience with the assumption that nothing is ever going to be to be doable about aging which of course is an assumption based on thousands of years of failure to do anything about aging and therefore it's rather deep seated you know i understand very strongly that scientists hate making time frame predictions across the whole of science and i understand why scientists do not want to over promise and under deliver they think it's going to hurt their funding in the future and so on but it's our duty we have no choice if we do not stick our necks out and you know take risks for peace if someone said then we will suffer really badly in terms of the enthusiasm the credibility that we have uh as a result as a um in the sense of time frames that the public sees and you know things won't happen now of course we know that there are now some examples of other thought leaders following the lead that i've been giving all these years and coming out and saying pretty optimistic things i often highlight the title that david sinclair gave to his book just two years ago why we age and why we don't have to but of course that's just one illustration there are a few other people saying the same kind of thing these days but we must say it louder louder and louder because that's the only way that people are going to really get the message that now we really are on the brink of bringing aging under comprehensive medical control so um let me talk about well my fourth emerging challenge it comes down to the regulatory environment so you all know what tame is the um clinical trial for metformin against aging and the uh and i'm sure that all of you or at least most of you will be familiar with the enormous amount of work that had to be done several years ago now to actually get the fda to say yeah this trial sounds like a good trial if you do this trial then um you know we will recognize the results and all that the difficulty of course was that in order to create a clinical trial they had to define a very clear crisp clinical endpoint and they wanted the clinical endpoint to be aging and everybody had their own personal definition of aging so it was a complete you know it was a complete non-starter so an enormous amount of work was done by near basel and a few colleagues in conversation with the fda to gravitate to a definition of the clinical endpoint for tame that in from the general intelligence perspective was synonymous with aging in orbit name but from the fda standpoint was crisp enough to actually be a you know genuinely binary thing that the child would either succeed or fail at so that was massive i mean like there is no overstating what how massive that regulatory breakthrough was there was a bit of a problem however which was that because metformin was off pattern since before most of us were born um there was no way that anyone from the private sector was going to pay for this trial it had to be paid for from other sources a lot of the money was pledged by a foundation but it also required other money and the nih rejected the proposal twice i am um perhaps the first person to actually name names in that regard there is one person who at least behind the scenes has received most of the program that i have heard for the reason why that um that trial was never funded by the nih but anyway here we are the trial is so i gather very likely to be funded this year however we cannot ignore the fact that it should have started years ago and that the delay in actually doing the trial has also delayed the recognition of tame's significance uh in the wider world and especially in big farmer and of course the significance i'm talking about here is the regulatory breakthrough because we are all very well aware that for the longest time big pharma has been extremely uninterested in developing therapies that will have broad-based impact on the health problems of late life and the reason they have is because they did not see a path through the fda to actually get something approved so that they could make money out of it the 10 trial as it currently stands before it has been actually done just because of the nature of that clinical endpoint has to a very large extent solved that problem but getting people decision makers in big pharma to actually recognize that while tame is still actually just a twinkle in the eye of the people who are supposed to be getting on and doing it you know that's really tough decision making in big pharma in this inherently has serious inertia just as it just says would be the case in any industry so this is hugely problematic sooner we get 10 going the better but even before we get tame going we've really got to drill into the decision makers in big pharma that now is the time to be putting really proper money into investing in anti-aging therapies um so i haven't got much more to say actually i've just got one breakthrough that i want to talk about again but i'm going to talk about it at some length um the last emerging challenge is at the level of policy and here i don't just mean regulatory i mean beyond that and uh so i've mentioned in the past i may even have mentioned a year ago at this meeting that uh covert is a bit of an opportunity in the sense that it has hit the elderly extraordinarily preferentially the um as we know most infectious diseases are worse for the elderly than for young adults but it's particularly extreme in the case of covid what we have not i believe said nearly loudly enough and focused policymakers nearly strongly enough on is the fact that among all of the damage repair rejuvenation technologies that we're interested in rejuvenating the immune system is really going rather well it's one of the ones that's furthest along all of us are familiar i'm sure with the trim trial led by greg fay um even if you can't pronounce fae uh the immune rejuvenation is doing really well cyanide rejuvenation especially and other parts so if policymakers were to understand that really not very much additional you know public money thrown at this kind of area could have a significant impact on the immune function of the elderly and thus could have a very significant impact on the likelihood let alone the severity of any future pandemic then we would be in a better position than what we are now so what this fundamentally means because of course policymakers ultimately care about the economy more than anything else what this ultimately means is that we need a really aggressive revival right now of that thing that came along best part of 20 years ago originally led by jail chansky and a few other people called the longevity dividend this was a really aggressive and articulate initiative uh trying to drill home into policy makers minds the fact that even a really modest postponement of the health problems of late life would have the most indescribable astronomical impact on the economy and um you know it was coming from really authoritative people or four of the people the authors of the original longevity dividend initiative were very very you know um mainstream grandees of the field biologists an economist a sociologist a lobbyist you know these are the right people to have done that and the impact of that initiative was exactly zero of course i don't really need to explain to you why the impact was zero it was zero because it was not accompanied by what do you know any time frame predictions from the biologists so it was all received terribly courteously as an appeal for more money that would be poured down the drain so it is a revival now because progress has been made in all the laboratories around the world and of course uh that progress uh you know could accelerate with more money and the good news is that it is being revived a british economist named andrew scott has led a new uh study that was published quite recently um in which he explores the economic benefits of progress against aging and unlike the original longevity dividend andrew has gone as far as to incorporate rejuvenation as an actual part of the um the study in other words one of the scenarios that might actually occur in the foreseeable future and he's given this wonderful name he's called it the wolverine scenario i think that will catch people's attention um now a very cool thing about this is that it's only the start andrew's paper looks at an extremely half-hearted version of the wolverine scenario in which people at some point in the relatively near future receive rejuvenation therapies at the age of i think 60 but they only receive them once and then they just age and die anyway so of course that's the absolute ultra minimal minimal um version of actual rejuvenation and he knows it perfectly well so right now there is of course follow-up work going on to you know to broaden this and to look at other variations on the wolverine theme and i believe that this is the way that we are going to get policymakers attention really seriously but you know he's just one guy one research group this is not enough we have to be all of us out there in our own ways with our own communities our own networks our own areas of influence telling people listen this is really coming and you can make it come faster and you will get votes for it because people will be wealthier as a result you
2021-09-21