Dr Aubrey de Grey - Changing Priorities in Rejuvenation Technologies - Lifespan io

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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

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