Aubrey de Grey: Rejuvenation Technology — Will “Age” Soon Cease to Mean “Aging”?

Around the world, peo­ple are liv­ing longer — not just be­cause child mor­tal­ity is drop­ping, but also be­cause we’re stay­ing healthy for more years as we age. In the fu­ture, re­gen­er­a­tive medicine and other new de­vel­op­ments may help most peo­ple re­main youth­ful much longer than they do to­day. In this talk, Aubrey de Grey, Chief Science Officer at the SENS Re­search Foun­da­tion, dis­cusses the biol­ogy and so­ciol­ogy of what could be a mas­sive shift in the way we live.

Below is a tran­script of Aubrey’s talk, which we have lightly ed­ited for clar­ity. You may watch it on YouTube or read it on effec­tivealtru­ism.org.

The Talk

I am delighted to be here. This is the first time in five or six years that I have spo­ken at an EA [effec­tive al­tru­ism] event, and I am very im­pressed by how rapidly and how far the EA move­ment has grown.

What I’m go­ing to do to­day is try to ex­plain why I be­lieve it makes sense for effec­tive al­tru­ists to pri­ori­tize the is­sue of ag­ing. To make that case, there are a num­ber of ques­tions that need to be an­swered in the af­fir­ma­tive.


Slide02

First, is ag­ing a re­ally big prob­lem? I be­lieve that it is, by a good dis­tance, the world’s biggest prob­lem. But I un­der­stand that this group thinks very care­fully about such state­ments, so I need to jus­tify my opinion.

The sec­ond ar­gu­ment I need to make is that we have a suffi­cient un­der­stand­ing to­day of what ag­ing is, and gen­er­ally how we might go about ad­dress­ing it. There­fore, if we throw money at this prob­lem, there’s a good chance of hav­ing a sig­nifi­cant im­pact. This is not triv­ial. Other times that I’ve spo­ken at EA events, I’ve re­ceived a lot of push­back. [Many EAs be­lieve] we un­der­stand so lit­tle about ag­ing that what we do [at the SENS Re­search Foun­da­tion] is es­sen­tially ran­dom, and there­fore [spend­ing money on it is un­jus­tified].

The third ar­gu­ment I need to make is very new. It’s re­ally only arisen over the past few years, and it is this: Philan­thropy [is still] crit­i­cal, [even though] pri­vate in­vest­ment [in the study of ag­ing] has ex­ploded.

To ad­dress the first point — why ag­ing is im­por­tant — I’m just go­ing to tell you why I think that is clearly true. To me, it’s just a fact that ag­ing causes far more suffer­ing than any­thing else in the world to­day or in the fore­see­able fu­ture. It’s not just the death part. We’re talk­ing about effec­tive al­tru­ism here, and al­tru­ism means wor­ry­ing about other peo­ple. Peo­ple dy­ing makes other peo­ple un­happy. That’s not ar­guable.

But what might be much more im­por­tant is that when peo­ple die of ag­ing, they do it slowly. They do it as a con­se­quence of a chronic, pro­gres­sive ac­cu­mu­la­tion of dam­age in the body, a de­cline in men­tal and phys­i­cal func­tion. That’s a lot of suffer­ing, too — for the peo­ple who are ac­tu­ally ag­ing and for the loved ones of the peo­ple who are ag­ing. So, to me, it’s [self-ev­i­dent] that ag­ing is, by far, the source of the largest amount of suffer­ing in the world to­day. You could even ar­gue that it was true a long time ago.

I also want to em­pha­size that this is not only about the in­dus­tri­al­ized world. Some­thing that we of­ten over­look is that the de­vel­op­ing world is catch­ing up in terms of longevity, and there­fore, in terms of how much they ex­pe­rience the health prob­lems of late life. In the World Health Or­ga­ni­za­tion’s most re­cent statis­tics, there wasn’t a sin­gle coun­try in the world with an av­er­age lifes­pan lower than 50. Out­side of Sub-Sa­haran Africa, there wasn’t a sin­gle coun­try that had one lower than 60. So we can see that the is­sue of ag­ing is not just a first-world prob­lem. It is an ab­solutely fun­da­men­tal prob­lem for the en­tire world.

Now I’m go­ing to ad­dress the sec­ond ques­tion of whether we ac­tu­ally un­der­stand ag­ing well enough [to en­sure that fund­ing it will have] a sig­nifi­cant im­pact. In or­der to do that, I’m go­ing to fill in a lot of back­ground in­for­ma­tion.

Slide03

First, why is it that ag­ing is a prob­lem at all? Why has it re­sisted the med­i­cal ad­vances that have been so suc­cess­ful against most in­fec­tious dis­eases?

Slide04

Over the past 200 years, we’ve brought in­fant mor­tal­ity down from some­thing like 40% (which is where it was 200 years ago, even in the wealthiest coun­tries in the world) to nearly zero. And we did it through ridicu­lously sim­ple mea­sures, like figur­ing out that hy­giene is a good idea.

So, what is the prob­lem? Most peo­ple would say it’s that there’s so much that goes wrong with us late in life — and it all goes wrong at the same time, so these things in­ter­act with one an­other.

Slide05

It’s the com­plex­ity. And that’s part of the an­swer. But it’s by no means the whole an­swer.

In or­der to ex­plain the whole an­swer, I need to define ag­ing, which is crazy. How on earth could we not yet have a good un­der­stand­ing of the pro­cess that has pre­oc­cu­pied hu­man­ity since the dawn of civ­i­liza­tion? But if you ask peo­ple what ag­ing is, you will not get the same an­swer from ev­ery­body. I’m go­ing to use a very sim­ple defi­ni­tion.

Slide06

Aging is the com­bi­na­tion of two pro­cesses [metabolism and dam­age, which to­gether re­sult in pathol­ogy]. Metabolism goes on through­out life, start­ing be­fore we’re even born. A net­work of pro­cesses keeps us al­ive — that’s what metabolism means — [and, over time,] gen­er­ates dam­age.

“Da­m­age” is the right word to be us­ing for the var­i­ous changes to the molec­u­lar and cel­lu­lar struc­ture of the body that are brought about by metabolism, be­cause the body is only set up to tol­er­ate a cer­tain amount of change. After that, the body starts to func­tion less well, both men­tally and phys­i­cally. And that, of course, [leads to] the late-life emer­gence and pro­gres­sion of the patholo­gies of ag­ing.

Cur­rently, the over­whelming ma­jor­ity of money and effort spent to pre­vent the patholo­gies of late life is spent wrongly. It is spent on try­ing to break the link be­tween dam­age and pathol­ogy.

Slide07

That is in­sanely stupid. Da­m­age, by defi­ni­tion, is ac­cu­mu­lat­ing, which means that efforts to stop it from caus­ing pathol­ogy are bound to be­come pro­gres­sively less effec­tive as some­one gets older. It’s ob­vi­ous.

The next ques­tion we have to ask our­selves is: Why has hu­man­ity been so wed­ded to this in­sanely quix­otic ap­proach? One might say that per­haps there are no al­ter­na­tives. (We’ll see shortly that that’s not true.) Another an­swer is sim­ply that we have mis­defined ag­ing. And in­deed, that is the case.

If you ask most peo­ple, “In what ways can peo­ple be sick?”, they’ll say, “There are com­mu­ni­ca­ble, in­fec­tious dis­eases. There are ge­netic dis­eases that a few peo­ple get. And there are the chronic, pro­gres­sive dis­eases of late life, like Alzheimer’s and most can­cers.” And then they would say that there’s this com­pletely differ­ent phe­nomenon called ag­ing, which con­sists of rather poorly defined phe­nom­ena like frailty.

Slide08

The per­cep­tion is that ag­ing is so differ­ent from the dis­eases in this com­mon tax­on­omy that it’s es­sen­tially off-limits to medicine.

It’s a shame that we would think that. The cor­rect view of the tax­on­omy of sick­ness is what I’m show­ing [in this next slide], which is ex­actly the same as the pre­vi­ous slide, in terms of the columns.

Slide09

The only differ­ence is where the black line is. That’s key for two rea­sons. First, the health is­sues in the third column [Alzheimer’s, can­cer, etc.] are com­pletely un­like those in the first column [malaria, HIV, and other com­mu­ni­ca­ble dis­eases]. There is no way that we would ex­pect to be able to ad­dress [Alzheimer’s, can­cer, or atheroscle­ro­sis] with the same kinds of medicine for [tu­ber­cu­lo­sis, malaria, HIV].

But [in my view of the cor­rect tax­on­omy,] there is no differ­ence be­tween [dis­eases like Alzheimer’s can­cer, etc.] and [frailty, sar­cope­nia, etc. — the ail­ments tra­di­tion­ally as­so­ci­ated with ag­ing]. It’s just se­man­tics. The is­sues in the third column are just the as­pects of ag­ing that we’ve cho­sen to give dis­ease-like names to. That’s a re­ally im­por­tant thing to take into ac­count. It helps us see that we should be adopt­ing a more pre­ven­ta­tive ap­proach to the elimi­na­tion of patholo­gies in late life.

Slide10

This idea is not in any way origi­nal or my own. More than 100 years ago, peo­ple started think­ing this way. They in­vented geron­tol­ogy, which is in­spired by the ob­ser­va­tion that in na­ture we see a very big vari­a­tion in the rates of ag­ing across differ­ent species. Even within a species, we see differ­ences in in­di­vi­d­u­als. The idea was that if we stud­ied that vari­a­tion, we might be able to un­der­stand it well enough to make our metabolism run more cleanly, so that it gen­er­ates dam­age more slowly. That would be great, be­cause it would post­pone the point at which the dam­age reaches a level that causes patholo­gies.

But there’s a bit of a prob­lem with that [line of think­ing].

Slide11

Some of you may have writ­ten soft­ware in the past, and you may un­der­stand that this is the ul­ti­mate [ex­am­ple] of “spaghetti code.” There is no way that we’re ever go­ing to be able to ma­nipu­late this crazy net­work of pro­cesses that keep us al­ive in such a way as to stop it from do­ing the thing we don’t want it to do — the cre­ation of dam­age — with­out also stop­ping it from do­ing the things we need it to do to keep us al­ive. Not go­ing to hap­pen. And of course, this re­flects only what we un­der­stand about metabolism. What re­ally mat­ters is what we _don’t_ know about how the body works, let alone what we don’t even know that we don’t know.

Luck­ily, there is a com­pletely differ­ent ap­proach. Re­mem­ber: What we need to do is sep­a­rate metabolism from pathol­ogy. We want to carry on be­ing al­ive with­out hav­ing the side effect of get­ting sick late in life. I’ve shown that we can de­scribe the link be­tween metabolism and pathol­ogy as be­ing di­vided into two pro­cesses, and I’ve also shown that we can’t sever the link be­tween them by break­ing ei­ther pro­cess. But what we might be able to do is sep­a­rate the com­po­nent pro­cesses from each other. That’s the main­te­nance ap­proach — it’s dam­age re­pair. We might be able to pe­ri­od­i­cally re­pair some of the dam­age that metabolism gen­er­ates, so that even though it con­tinues to gen­er­ate it, the dam­age does not reach a level of abun­dance that’s bad for us. I think it is rea­son­able to call this the com­mon-sense al­ter­na­tive.

Slide12

In fact, we have already ob­served that it works. Take a sim­ple ma­chine, a car, that’s more than 100 years old.

Slide13

It did not reach that age by be­ing de­signed to last 100 years. It reached that age by be­ing de­signed to last maybe 10 years, but then, through own­ers who fell in love with it and did com­pre­hen­sive, pe­ri­odic, pre­ven­ta­tive main­te­nance. In other words, ag­ing is not a mys­tery. We already un­der­stand it well enough. It’s sim­ply the same thing as in a car. It’s not some kind of emer­gent phe­nomenon like con­scious­ness. And we already know, there­fore, that com­pre­hen­sive pre­ven­ta­tive main­te­nance works.

The body is, of course, a lot more com­pli­cated than a car. But how much more com­pli­cated? Not very much.

Slide14

Seven­teen years ago, I de­scribed the dam­age of ag­ing in only seven words, as seven types of dam­age [cell loss or at­ro­phy, di­vi­sion-ob­sessed cells, death-re­sis­tant cells, mi­to­chon­drial mu­ta­tions, in­tra­cel­lu­lar waste prod­ucts, ex­tra­cel­lu­lar waste prod­ucts, ex­tra­cel­lu­lar ma­trix stiffen­ing].

Slide15

What’s most im­por­tant is the fact that for each of these types of dam­age, we can de­scribe a generic ther­apy that could po­ten­tially rep­re­sent the main­te­nance ap­proach — the way to re­pair this type of dam­age.

Within each cat­e­gory, there are many, many ex­am­ples of sub­tly differ­ent types of dam­age in differ­ent tis­sues. But they can still be ad­dressed through slightly differ­ent ver­sions of the same ther­apy, which means that we can de­velop those ver­sions pretty quickly. (I don’t have time to go into that in any more de­tail right now.)

How­ever, one thing I want to em­pha­size is that I’m not the only one say­ing this any­more. Five or 10 years ago, this was an ar­gu­ment that still needed to be made. But now it has been made. As an illus­tra­tion, a pa­per came out only six years ago that is go­ing to be, by far, the most highly-cited pa­per this decade in the whole of the biol­ogy of ag­ing.

Slide16

It’s sim­ply a restate­ment of what I said more than a decade ear­lier. (I don’t care about get­ting credit — I get plenty.) The im­por­tant point is that a di­vide-and-con­quer, dam­age-re­pair ap­proach is now a com­pletely main­stream, or­tho­dox idea.

Slide17

The rele­vance of longevity is some­thing that’s worth talk­ing about. If you look me up in the me­dia, you will see that I get de­scribed as things like “the prophet of im­mor­tal­ity.” It’s a bit ir­ri­tat­ing, be­cause we don’t work on longevity, let alone im­mor­tal­ity.

Slide18

Longevity is a side effect of health. And yes, as I men­tioned ear­lier, when peo­ple die, it makes peo­ple sad. But I think that the suffer­ing be­fore death is more im­por­tant. There’s an awful lot of it, and that makes peo­ple sad, too, in­clud­ing the peo­ple who are ac­tu­ally ex­pe­rienc­ing it. So to me, we’re just do­ing medicine. There is a side effect that if we do medicine re­ally well for the el­derly, then on av­er­age, peo­ple are likely to live a lot longer. And I think that’s a good thing, but it’s still a side effect. So don’t be se­duced by [how the me­dia con­stantly frames the is­sue].

Of course, the me­dia harp on about it be­cause of the ease with which it is pos­si­ble to make a case against longevity.

Slide19

Peo­ple say, “Oh dear, where will we put all the peo­ple?”, “It’ll only be for the rich”, or “Won’t dic­ta­tors live for­ever?” Th­ese are very easy con­cerns to re­but. Last I heard, “dic­ta­tor” was fairly high on the list of risky jobs; not a lot of dic­ta­tors die of ag­ing, and the ones who do or­ga­nize their suc­ces­sion be­fore­hand, so it’s func­tional im­mor­tal­ity.

[As for the ar­gu­ment that we will be­come bored if we solve the prob­lem of ag­ing], would you pre­fer to get Alzheimer’s at the age of 80 or to be bored at the age of 150?

Even the con­cern of over­pop­u­la­tion [is easy to re­but]. This is a mean­ingful con­cern, but we know that the over­pop­u­la­tion prob­lem we have to­day that’s caus­ing cli­mate change is go­ing to go away, be­cause we’ve already got re­new­able en­ergy that’s cheaper than fos­sil fuels. The United King­dom, for the first time since the in­dus­trial rev­olu­tion, re­cently made more elec­tric­ity from re­new­ables than from fos­sil fuels. And that is some­thing that we all know is go­ing to con­tinue. And ar­tifi­cial meats, de­sal­i­na­tion, and other tech­nolo­gies are go­ing to raise the car­ry­ing ca­pac­ity of the planet far faster than the pop­u­la­tion could con­ceiv­ably in­crease, even if we com­pletely elimi­nated all death.

We should fo­cus on the fact that peo­ple do not like be­ing sick. And we should fo­cus on the fact that even if some of these prob­lems arise as a con­se­quence of solv­ing the prob­lem of ag­ing, there is no way to ar­gue that those prob­lems will be worse than the [ag­ing prob­lem] we have to­day.

Slide20

I’m go­ing to finish by ad­dress­ing the ques­tion of fea­si­bil­ity. It’s very im­por­tant for effec­tive al­tru­ists to know that their money is spent well and mak­ing a differ­ence. That’s im­por­tant to me, too, in terms of how I use my time.

About 10 years ago, it was un­clear whether we knew enough about ag­ing to know what to put money into. That’s no longer true. We’ve made sub­stan­tial progress — enough to be sure that we’re go­ing in the right di­rec­tion.

Slide21

Over the past few years, the SENS Re­search Foun­da­tion has pub­lished break­throughs in very high-pro­file jour­nals. But more than that, we’ve been able to con­vince in­vestors [of our progress] and spin out startup com­pa­nies that are pur­su­ing this is­sue with the benefit of con­sid­er­ably more money than what was available when re­search was only philan­throp­i­cally funded.

Slide22

And in ad­di­tion to the com­pa­nies that we’ve spun out, there are huge num­bers of emerg­ing com­pa­nies that are al­igned with us and do­ing other types of dam­age re­pair.

Slide23

One ex­am­ple is Unity Biotech­nol­ogy. They’ve been a poster child, be­cause they were able to raise the kind of money that a biotech com­pany would nor­mally raise in phase three — when the com­pany is [on the verge of re­ceiv­ing ap­proval to bring a money-mak­ing product to mar­ket]. Unity re­ceived a huge amount of fund­ing be­fore they had be­gun their first clini­cal trial. That’s good news.

Slide24

But when Unity an­nounced a phase-one re­sult last week — and it was a re­ally good re­sult — they ex­pe­rienced a 20% de­cline in their share price. (Phase one is all about safety, but if you’re do­ing well, you look for effi­cacy as well, and they saw re­ally good effi­cacy.) That’s the prob­lem with the pri­vate sec­tor. It re­volves around peo­ple try­ing to make money, ir­re­spec­tive of how they make the money. I think [what hap­pened to Unity] demon­strates why we still need philan­thropy.

SENS Re­search Foun­da­tion views it­self these days as the en­g­ine room of the in­dus­try. We work on early-stage pro­jects for as long as it takes to es­tab­lish suffi­cient proof of con­cept to spin them out into startup com­pa­nies. We’re not the only ones. The Longevity Re­search In­sti­tute (LRI) is a new or­ga­ni­za­tion, also in the Bay Area, that’s work­ing in a more nar­rowly defined space. But they may grow, and, of course, there are go­ing to be other or­ga­ni­za­tions like this.

Philan­thropy mat­ters enor­mously in this. We be­lieve that we can get all — or at least al­most all — of the key tech­nolo­gies in re­ju­ve­na­tion biotech­nol­ogy into clini­cal tri­als within a few years. About three years ago, we started say­ing we’d do that by 2021, and that has not changed.

Slide25

But the key point here is that the things be­ing funded effec­tively by the pri­vate sec­tor are the low-hang­ing fruit. And dam­age re­pair is an in­her­ently di­vide-and-con­quer con­cept. You can’t just fo­cus on the low-hang­ing fruit. You’ve got to ad­dress all of the com­po­nents. It’s more im­por­tant than ever to make progress on the most difficult ar­eas, and that is still a goal for philan­thropy.

As some of you know, I wrote a book some time ago. Please read it if you want to know more about the biol­ogy.

Slide26

Moder­a­tor: When it comes to im­pact­ful ca­reers for bio­scien­tists, how would you rate study­ing ag­ing ver­sus pan­demic pre­ven­tion?

Aubrey: That’s tricky, be­cause pan­demic pre­ven­tion is cer­tainly a huge area. The ques­tion is: Are there already enough peo­ple work­ing in [pan­demic pre­ven­tion]? I hon­estly don’t know. Cer­tainly, there’s a huge amount be­ing done to build new tech­nolo­gies to de­velop an­tibiotics quickly, for ex­am­ple.

I think in or­der to an­swer that ques­tion, you need to look closely at the spe­cific area [you’re con­sid­er­ing go­ing into] — whose lab you would work in and things like that — and look at the de­tails of how much im­pact you could make. I don’t think there’s a sim­ple an­swer.

Moder­a­tor: Thank you. And what re­la­tion­ship do you see be­tween your work and tran­shu­man­ism?

Aubrey: I don’t see much of a link be­tween my work and tran­shu­man­ism. I don’t like to be called a tran­shu­man­ist. I do very much ap­prove of the work that peo­ple who call them­selves tran­shu­man­ists do, whether it’s work­ing on AGI [ar­tifi­cial gen­eral in­tel­li­gence], nan­otech­nol­ogy, molec­u­lar man­u­fac­tur­ing, or things like that. But I be­lieve that the word “tran­shu­man­ism” is a huge al­ba­tross. It makes the gen­eral pub­lic think that we’re all out to cre­ate a whole new species, rather than sim­ply em­pha­siz­ing the con­ti­nu­ity of tech­nolog­i­cal ad­vances that peo­ple are gen­er­ally happy with.

Au­di­ence Mem­ber: How much money do you es­ti­mate that we need to defeat ag­ing?

Aubrey: No one can an­swer that ques­tion in­stantly, be­cause the amount of money that one needs at the early stages to de­velop these tech­nolo­gies is much less than what is needed at the late stages. But the ease with which that money can be ob­tained is very differ­ent. Once [a treat­ment] has reached a clini­cal trial, then in­vest­ment money pours in, be­cause most of the de-risk­ing has already hap­pened.

So when I get asked that ques­tion and want to provide a head­line, I say tiny amounts — a half-billion dol­lars over a pe­riod of 10 years would be enough. It’s prob­a­bly even down now to about a quar­ter-billion dol­lars. It’s definitely still an or­der of mag­ni­tude more than what we have at the SENS Re­search Foun­da­tion (our bud­get is about $5 mil­lion per year), but it’s a pitifully small amount of money com­pared to what’s gen­er­ally spent on med­i­cal re­search.

Moder­a­tor: Thank you so much, Dr. de Grey.

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