18 minutes is an absolutely brutal time limit, so I'm going to dive straight in, right at the point where I get this thing to work. Here we go. I'm going to talk about five different things. I'm going to talk about why defeating aging is desirable. I'm going to talk about why we have to get our shit together, and actually talk about this a bit more than we do. I'm going to talk about feasibility as well, of course. I'm going to talk about why we are so fatalistic about doing anything about aging. And then I'm going spend perhaps the second half of the talk talking about, you know, how we might actually be able to prove that fatalism is wrong, namely, by actually doing something about it.
18 minute e o limita de timp absolut neomeneasca, astfel incat voi trece direct la subiect, la partea unde reusesc sa fac chestia asta sa mearga. Sa incepem. Voi vorbi despre cinci lucruri diferite. Voi vorbi despre motivul pentru care invingerea imbatranirii este de dorit. Voi vorbi despre motivul pentru care trebuie sa ne revenim si sa dezbatem acest subiect ceva mai mult. Voi vorbi si despre fezabilitate, desigur. Voi vorbi despre motivul pentru care suntem atat de fatalisti cand vine vorba sa facem ceva in legatura cu imbatranirea. Apoi probabil voi petrece a doua jumatate a conferintei vorbind, stiti, despre cum am putea dovedi realmente ca fatalismul este gresit, si anume chiar facand ceva in legatura cu acest lucru.
I'm going to do that in two steps. The first one I'm going to talk about is how to get from a relatively modest amount of life extension -- which I'm going to define as 30 years, applied to people who are already in middle-age when you start -- to a point which can genuinely be called defeating aging. Namely, essentially an elimination of the relationship between how old you are and how likely you are to die in the next year -- or indeed, to get sick in the first place. And of course, the last thing I'm going to talk about is how to reach that intermediate step, that point of maybe 30 years life extension.
Voi face asta in doi pasi. Primul pas despre care voi vorbi este cum sa ajungem de la o prelungire relativ modesta a duratei vietii, pe care o voi defini ca fiind de 30 de ani, in cazul oamenilor care sunt deja de varsta mijlocie cand incep, pana la ceea ce poate fi cu adevarat numit infrangerea imbatranirii. Altfel spus, este vorba despre eliminarea relatiei dintre cat de batran esti, si cat de probabil este sa mori in cursul anului viitor -- sau doar sa te imbolnavesti. Si desigur, ultimul lucru despre care voi vorbi este despre cum sa ajungem la acel pas intermediar, acel punct de lungire a vietii chiar si cu 30 de ani.
So I'm going to start with why we should. Now, I want to ask a question. Hands up: anyone in the audience who is in favor of malaria? That was easy. OK. OK. Hands up: anyone in the audience who's not sure whether malaria is a good thing or a bad thing? OK. So we all think malaria is a bad thing. That's very good news, because I thought that was what the answer would be. Now the thing is, I would like to put it to you that the main reason why we think that malaria is a bad thing is because of a characteristic of malaria that it shares with aging. And here is that characteristic. The only real difference is that aging kills considerably more people than malaria does.
Deci voi incepe cu de ce ar trebui. Vreau acum sa adresez o intrebare. Mana sus: este cineva din audienta in favoarea malariei? A fost usor. OK. OK. Mana sus, cine din audienta nu este sigur daca malaria e un lucru bun sau un lucru rau? OK. Deci cu totii credem ca malaria e un lucru rau. Este foarte bine, pentru ca ma asteptam ca asta sa fie raspunsul. Acum as vrea sa va spun ca motivul principal pentru care credem ca malaria e un lucru rau este pentru ca malaria are o caracteristica in comun cu imbatranirea. Si acea caracteristica este urmatoarea. Singura diferenta adevarata este ca imbatranirea ucide considerabil mai multe persoane decat malaria.
Now, I like in an audience, in Britain especially, to talk about the comparison with foxhunting, which is something that was banned after a long struggle, by the government not very many months ago. I mean, I know I'm with a sympathetic audience here, but, as we know, a lot of people are not entirely persuaded by this logic. And this is actually a rather good comparison, it seems to me. You know, a lot of people said, "Well, you know, city boys have no business telling us rural types what to do with our time. It's a traditional part of the way of life, and we should be allowed to carry on doing it. It's ecologically sound; it stops the population explosion of foxes." But ultimately, the government prevailed in the end, because the majority of the British public, and certainly the majority of members of Parliament, came to the conclusion that it was really something that should not be tolerated in a civilized society.
Acum, mie imi place ca mai ales in fata unei audiente din Marea Britanie, sa vorbesc despre comparatia cu vanatoarea de vulpi, activitate care a fost interzisa dupa o lupta de lunga durata, de catre guvern, nu cu multe luni in urma. Vreau sa spun, imi dau seama ca am o audienta intelegatoare acum, dar, dupa cum stim, multi oameni nu sunt complet convinsi de aceasta logica. Si mi se pare ca e o comparatie destul de buna. Stiti, multi oameni au spus "Ei bine, pe oraseni nu ii priveste ce facem noi, cei din mediul rural, cu timpul nostru. Face parte din modul traditional de viata, si ar trebui sa putem sa continuam in aceeasi maniera. E practic din punct de vedere ecologic; opreste explozia populatiei de vulpi." Dar in cele din urma, guvernul a triumfat, deoarece majoritatea populatiei britanice, si cu siguranta majoritatea membrilor din Parlament, au ajuns la concluzia ca era ceva ce nu ar trebui tolerat intr-o societate civilizata.
And I think that human aging shares all of these characteristics in spades. What part of this do people not understand? It's not just about life, of course -- (Laughter) -- it's about healthy life, you know -- getting frail and miserable and dependent is no fun, whether or not dying may be fun. So really, this is how I would like to describe it. It's a global trance. These are the sorts of unbelievable excuses that people give for aging. And, I mean, OK, I'm not actually saying that these excuses are completely valueless. There are some good points to be made here, things that we ought to be thinking about, forward planning so that nothing goes too -- well, so that we minimize the turbulence when we actually figure out how to fix aging.
Si cred ca imbatranirea umana are si ea aceste caracteristici din belsug. Ce anume nu inteleg oamenii? Nu e vorba numai despre viata, desigur -- (Rasete) e vorba despre o viata sanatoasa, stiti -- sa ajungi firav si mizerabil si dependent nu e distractiv, indiferent daca moartea e sau nu distractiva. De fapt, asa imi place sa descriu acest lucru. E o hipnoza globala. Acestea sunt tipurile de scuze incredibile pe care oamenii le dau pentru imbatranire. Bine acum, nu vreau sa spun ca aceste scuze sunt fara nici o valoare. Sunt cateva chestiuni bune care pot fi punctate aici. Chestiuni la care ar trebui sa ne gandim, sa planificam asa incat sa nu mearga lucrurile prea... in fine, ca sa reducem la minim turbulentele atunci cand gasim o rezolvare pentru problema imbatranirii.
But these are completely crazy, when you actually remember your sense of proportion. You know, these are arguments; these are things that would be legitimate to be concerned about. But the question is, are they so dangerous -- these risks of doing something about aging -- that they outweigh the downside of doing the opposite, namely, leaving aging as it is? Are these so bad that they outweigh condemning 100,000 people a day to an unnecessarily early death? You know, if you haven't got an argument that's that strong, then just don't waste my time, is what I say. (Laughter)
Dar sunt totusi in totalitate nebunesti, daca pastrezi proportiile. Stiti, acestea sunt argumente, chestiuni in legatura cu care e normal sa ne ingrijoram. Dar intrebarea e, sunt ele atat de periculoase -- aceste riscuri de a face ceva in legatura cu imbatranirea -- incat sa depaseasca dezavantajul de a face exact opusul, adica de a lasa imbatranirea asa cum este? Sunt ele mai grave decat condamnarea a 100,000 de oameni pe zi la o moarte prematura? Daca nu aveti un argument care e destul de bun, atunci eu zic sa nu-mi irositi timpul. (Rasete)
Now, there is one argument that some people do think really is that strong, and here it is. People worry about overpopulation; they say, "Well, if we fix aging, no one's going to die to speak of, or at least the death toll is going to be much lower, only from crossing St. Giles carelessly. And therefore, we're not going to be able to have many kids, and kids are really important to most people." And that's true. And you know, a lot of people try to fudge this question, and give answers like this. I don't agree with those answers. I think they basically don't work. I think it's true, that we will face a dilemma in this respect. We will have to decide whether to have a low birth rate, or a high death rate. A high death rate will, of course, arise from simply rejecting these therapies, in favor of carrying on having a lot of kids.
Exista totusi un argument pe care oamenii il cred ca fiind atat de bun. Oamenii sunt ingrijorati in privinta suprapopularii, isi spun "Pai daca rezolvam imbatranirea, nimeni n-o sa mai moara sau oricum numarul mortilor va fi mult mai mic, vor fi doar cei care traverseaza St. Giles fara sa fie atenti. Asa ca nu vom mai putea avea multi copii si copiii sunt foarte importanti pentru cei mai multi dintre noi." Si asta e adevarat. Si stiti, multi oameni incearca sa ignore aceasta intrebare si sa dea raspunsuri de felul acesta. Nu sunt de acord cu aceste raspunsuri. Cred ca ele pur si simplu nu functioneaza. Cred ca intr-adevar vom avea o dilema in privinta asta. O sa trebuiasca sa hotaram daca vrem natalitate scazuta sau mortalitate ridicata. Mortalitatea ridicata va fi datorata, desigur, refuzului de a urma aceste terapii pentru continua sa avem multi copii.
And, I say that that's fine -- the future of humanity is entitled to make that choice. What's not fine is for us to make that choice on behalf of the future. If we vacillate, hesitate, and do not actually develop these therapies, then we are condemning a whole cohort of people -- who would have been young enough and healthy enough to benefit from those therapies, but will not be, because we haven't developed them as quickly as we could -- we'll be denying those people an indefinite life span, and I consider that that is immoral. That's my answer to the overpopulation question.
Iar eu spun ca asta e bine, viitorul umanitatii are dreptul de a face aceasta alegere. Ce nu e in regula este ca noi sa facem alegerea in numele viitorului. Daca vom oscila, ezita, si nu vom dezvolta cu adevarat aceste terapii, atunci vom condamna o intreaga cohorta de oameni, care ar fi fost destul de tineri si de sanatosi incat sa beneficieze de terapii dar nu vor putea pentru ca noi nu le-am dezvoltat atat de rapid pe cat am fi putut, le vom nega dreptul acestor oameni la o viata fara sfarsit, iar eu consider ca asta este imoral. Acesta este raspunsul meu la problema suprapopularii.
Right. So the next thing is, now why should we get a little bit more active on this? And the fundamental answer is that the pro-aging trance is not as dumb as it looks. It's actually a sensible way of coping with the inevitability of aging. Aging is ghastly, but it's inevitable, so, you know, we've got to find some way to put it out of our minds, and it's rational to do anything that we might want to do, to do that. Like, for example, making up these ridiculous reasons why aging is actually a good thing after all. But of course, that only works when we have both of these components. And as soon as the inevitability bit becomes a little bit unclear -- and we might be in range of doing something about aging -- this becomes part of the problem. This pro-aging trance is what stops us from agitating about these things. And that's why we have to really talk about this a lot -- evangelize, I will go so far as to say, quite a lot -- in order to get people's attention, and make people realize that they are in a trance in this regard. So that's all I'm going to say about that.
Asa. Urmatoarea chestiune este de ce ar trebui sa devenim mai activi in aceasta privinta? Iar raspunsul fundamental este ca hipnoza pro-imbatranire nu este atat de prosteasca pe cat pare. De fapt, este o metoda de bun simt pentru a face fata iminentei imbatranirii. Imbatranirea este infricosatoare dar inevitabila, asa ca, stiti, trebuie sa gasim o cale prin care sa ne-o scoatem din minte si este rational sa facem orice ne trece prin cap ca sa reusim asta. De exemplu, sa fabricam toate motivele alea ridicole pentru care imbatranirea este pana la urma un lucru bun. Dar desigur, asta functioneaza numai cand avem ambele componente. Si imediat ce partea cu inevitabilul devine putin mai neclara si ne gasim in situatia de a face ceva in privinta imbatranirii, ea devine parte a problemei. Aceasa hipnoza pro-imbatranire este ceea ce ne face sa nu ne agitam in legatura cu asemenea lucruri. Iar din acest motiv, vorbim foarte mult despre acest subiect, il propovaduim, as indrazni sa spun, in speranta ca vom atrage atentia oamenilor si ii vom face sa inteleaga ca sunt hipnotizati in aceasta privinta. Asta este tot ce voi spune despre acest subiect.
I'm now going to talk about feasibility. And the fundamental reason, I think, why we feel that aging is inevitable is summed up in a definition of aging that I'm giving here. A very simple definition. Aging is a side effect of being alive in the first place, which is to say, metabolism. This is not a completely tautological statement; it's a reasonable statement. Aging is basically a process that happens to inanimate objects like cars, and it also happens to us, despite the fact that we have a lot of clever self-repair mechanisms, because those self-repair mechanisms are not perfect.
Acum voi vorbi despre fezabilitate. Si motivul fundamental, cred eu, pentru care consideram imbatranirea inevitabila este rezumat intr-o definitie a imbatranirii pe care o voi da eu acum. O definitie foarte simpla. Imbatranirea este efectul secundar al vietii, mai precis al metabolismului. Aceasta nu este o afirmatie complet tautologica, este o afirmatie rationala. Imbatranirea este practic un proces care se petrece si cand vine vorba de obiecte, ca de exemplu masinile, si cand vine vorba de noi, cu toate ca avem o multime de mecanisme de auto-reparare pentru ca aceste mecanisme nu sunt perfecte.
So basically, metabolism, which is defined as basically everything that keeps us alive from one day to the next, has side effects. Those side effects accumulate and eventually cause pathology. That's a fine definition. So we can put it this way: we can say that, you know, we have this chain of events. And there are really two games in town, according to most people, with regard to postponing aging. They're what I'm calling here the "gerontology approach" and the "geriatrics approach." The geriatrician will intervene late in the day, when pathology is becoming evident, and the geriatrician will try and hold back the sands of time, and stop the accumulation of side effects from causing the pathology quite so soon. Of course, it's a very short-term-ist strategy; it's a losing battle, because the things that are causing the pathology are becoming more abundant as time goes on.
De fapt, metabolismul, care este alcatuit din tot ce e necesar ca sa ramanem in viata de la o zi la alta, are efecte secundare. Aceste efecte secundare se acumuleaza si cauzeaza pana la urma patologii. Este o definitie buna. Asa ca o putem exprima astfel: putem spune ca, stiti, avem aceasta insiruire de evenimente. Si nu exista decat doua variante, in opinia majoritatii oamenilor, in ce priveste amanarea imbatranirii. Ele sunt ceea ce eu voi numi aici abordarea gerontologica si abordarea geriatrica. Geriatrul va interveni tarziu, cand patologia devine deja evidenta, iar el va incerca sa incetineasca scurgerea vietii si sa opreasca acumularea de efecte secundare care cauzeaza patologia atat de repede. Desigur ca aceasta este o strategie pe termen scurt, este o batalie pierduta pentru ca lucrurile care cauzeaza patologia se inmultesc pe masura ce trece timpul.
The gerontology approach looks much more promising on the surface, because, you know, prevention is better than cure. But unfortunately the thing is that we don't understand metabolism very well. In fact, we have a pitifully poor understanding of how organisms work -- even cells we're not really too good on yet. We've discovered things like, for example, RNA interference only a few years ago, and this is a really fundamental component of how cells work. Basically, gerontology is a fine approach in the end, but it is not an approach whose time has come when we're talking about intervention. So then, what do we do about that? I mean, that's a fine logic, that sounds pretty convincing, pretty ironclad, doesn't it?
Abordarea gerontologica pare mult mai promitatoare la suprafata pentru ca, stiti, e mai bine sa previi decat sa tratezi. Dar, din nefericire, nu intelegem metabolismul prea bine. La momentul actual intelegem chiar foarte putin din modul de functionare al organismelor, chiar si din cel al celulelor. Am descoperit de exemplu lucruri ca interferenta ARN-ului abia acum cativa ani, iar aceasta este un element absolut fundamental in functionarea celulelor. De fapt, gerontologia este o abordare buna pana la urma, dar nu una al carei timp a venit, daca vorbim despre interventii. Asa ca pana la urma ce facem in privinta asta? Este o logica buna, nu neg, si care suna destul de convingator, e destul de solida, nu?
But it isn't. Before I tell you why it isn't, I'm going to go a little bit into what I'm calling step two. Just suppose, as I said, that we do acquire -- let's say we do it today for the sake of argument -- the ability to confer 30 extra years of healthy life on people who are already in middle age, let's say 55. I'm going to call that "robust human rejuvenation." OK. What would that actually mean for how long people of various ages today -- or equivalently, of various ages at the time that these therapies arrive -- would actually live? In order to answer that question -- you might think it's simple, but it's not simple. We can't just say, "Well, if they're young enough to benefit from these therapies, then they'll live 30 years longer." That's the wrong answer. And the reason it's the wrong answer is because of progress.
Dar nu este asa. Inainte sa va spun de ce nu este, voi intra putin in ceea ce numesc pasul al doilea. Presupuneti, cum am spus, ca am avea posibilitatea, sa zicem chiar in ziua de azi, de dragul discutiei, sa oferim inca 30 de ani de viata sanatoasa oamenilor care au ajuns deja la varsta mijlocie, sa zicem 55 de ani. Voi numi asta intinerirea omului robust. OK. Ce ar insemna acest lucru de fapt? Cat de mult ar reusi oamenii de varste diferite azi, si echivalent, de diferite varste in momentul in care ar aparea terapiile, sa traiasca? A raspunde acestei intrebari, ati putea crede ca e simplu, dar nu este. Nu putem spune pur si simplu "Pai daca sunt destul de tineri incat sa beneficieze de aceste terapii, atunci vor trai cu 30 de ani mai mult." Acesta este raspunsul gresit. Iar motivul pentru care este gresit este progresul.
There are two sorts of technological progress really, for this purpose. There are fundamental, major breakthroughs, and there are incremental refinements of those breakthroughs. Now, they differ a great deal in terms of the predictability of time frames. Fundamental breakthroughs: very hard to predict how long it's going to take to make a fundamental breakthrough. It was a very long time ago that we decided that flying would be fun, and it took us until 1903 to actually work out how to do it. But after that, things were pretty steady and pretty uniform. I think this is a reasonable sequence of events that happened in the progression of the technology of powered flight. We can think, really, that each one is sort of beyond the imagination of the inventor of the previous one, if you like. The incremental advances have added up to something which is not incremental anymore.
Exista doar doua forme de progres tehnologic pentru acest scop. Exista descoperiri fundamentale, majore, si exista finisaje incrementale ale acestor descoperiri. Acum, ele difera foarte mult in termeni de previzionare a intervalelor de timp. Descoperiri fundamentale: foarte greu de prevazut cat va dura sa apara o descoperire fundamentala. Acum foarte mult timp ne-am hotarat ca ar fi amuzant sa zburam, dar abia in 1903 am inteles cum se poate face asta. Insa mai apoi lucrurile au evoluat destul de stabil si de uniform. Cred ca aceasta este o secventa rezonabila de evenimente care s-au petrecut in progresul tehnologiei de zbor cu propulsie. Putem considera chiar ca fiecare dintre ele este oarecum dincolo de imaginatia inventatorilor celei precedente, daca vreti. Avansurile incrementale au dus la ceva care nu mai este incremental.
This is the sort of thing you see after a fundamental breakthrough. And you see it in all sorts of technologies. Computers: you can look at a more or less parallel time line, happening of course a bit later. You can look at medical care. I mean, hygiene, vaccines, antibiotics -- you know, the same sort of time frame. So I think that actually step two, that I called a step a moment ago, isn't a step at all. That in fact, the people who are young enough to benefit from these first therapies that give this moderate amount of life extension, even though those people are already middle-aged when the therapies arrive, will be at some sort of cusp. They will mostly survive long enough to receive improved treatments that will give them a further 30 or maybe 50 years. In other words, they will be staying ahead of the game. The therapies will be improving faster than the remaining imperfections in the therapies are catching up with us.
Este genul de lucru care se vede dupa o descoperire fundamentala. Si se vede in tot felul de tehnologii. Computerele, putem urmari o axa temporala oarecum paralela, care, desigur, a inceput ceva mai tarziu. Putem privi ingrijirea medicala. Ma refer la igiena, vaccinuri, antibiotice, stiti, acelasi fel de interval temporar. Deci eu cred ca de fapt pasul doi, pe care l-am numit pas acum cateva clipe, nu este deloc un pas. Cred ca de fapt oamenii care sunt destul de tineri incat sa beneficieze de pe urma acestor terapii initiale care dau o prelungire moderata a vietii, chiar daca vor fi la varsta de mijloc cand apar terapiile, se vor gasi la un fel de cotitura. In mare parte vor supravietui destul incat sa primeasca tratamente imbunatatite care le vor oferi 30 sau 50 de ani in plus. Cu alte cuvinte, vor fi pionieri. Terapiile se vor imbunatati mai repede decat vor veni din urma imperfectiunile lor.
This is a very important point for me to get across. Because, you know, most people, when they hear that I predict that a lot of people alive today are going to live to 1,000 or more, they think that I'm saying that we're going to invent therapies in the next few decades that are so thoroughly eliminating aging that those therapies will let us live to 1,000 or more. I'm not saying that at all. I'm saying that the rate of improvement of those therapies will be enough. They'll never be perfect, but we'll be able to fix the things that 200-year-olds die of, before we have any 200-year-olds. And the same for 300 and 400 and so on. I decided to give this a little name, which is "longevity escape velocity." (Laughter) Well, it seems to get the point across.
Aceasta este o idee pe care mi se pare important s-o transmit. Pentru ca, stiti, cei mai multi oameni care aud ca prezic durate ale vietii de 1000 de ani sau mai mult pentru multi dintre oamenii in viata astazi, cred ca eu sustin ca vom crea terapii in urmatorii zeci de ani care vor elimina definitiv imbatranirea si ne vor permite sa traim pana la varsta de 1000 de ani si peste. Nu spun asta deloc. Ceea ce spun este ca imbunatatirea acelor terapii va fi de ajuns. Nu vor fi niciodata perfecte, dar vom fi capabili sa inlaturam motivele pentru care ar muri oamenii de 200 de ani, inainte sa existe oameni de 200 de ani. La fel pentru cei de 300, 400 de ani si asa mai departe. M-am decis sa dau acestui lucru un mic nume asa ca i-am spus "viteza de evadare a longevitatii". (Rasete) Pare sa transmita bine ideea de baza.
So, these trajectories here are basically how we would expect people to live, in terms of remaining life expectancy, as measured by their health, for given ages that they were at the time that these therapies arrive. If you're already 100, or even if you're 80 -- and an average 80-year-old, we probably can't do a lot for you with these therapies, because you're too close to death's door for the really initial, experimental therapies to be good enough for you. You won't be able to withstand them. But if you're only 50, then there's a chance that you might be able to pull out of the dive and, you know -- (Laughter) -- eventually get through this and start becoming biologically younger in a meaningful sense, in terms of your youthfulness, both physical and mental, and in terms of your risk of death from age-related causes. And of course, if you're a bit younger than that, then you're never really even going to get near to being fragile enough to die of age-related causes.
Asa, aceste traiectorii sunt, de fapt, modul in care ne asteptam sa traiasca oamenii in termeni de speranta de viata ramasa, masurata prin sanatatea lor, in functie de varsta pe care o aveau in momentul aparitiei acestor terapii. Daca ai deja 100 de ani, sau chiar daca ai 80, si un om obisnuit de 80 de ani, probabil nu vom putea face prea multe pentru tine prin aceste terapii pentru ca esti prea aproape de usa mortii pentru ca terapiile cu adevarat initiale, experimentale, sa fie destul pentru tine. Nu le-ai putea suporta. Dar daca ai doar 50 de ani, exista o sansa ca tu sa fii capabil sa iti revii din cadere si sa...stii... (Rasete) sa treci pana la urma peste asta. Si sa incepi sa devii cu adevarat mai tanar din punct de vedere biologic, in termeni de intinerire fizica si mentala, dar si in ce priveste riscul mortii tale din cauze legate de imbatranire. Bineinteles, daca vei fi ceva mai tanar de atat, nici macar nu vei ajunge sa fii atat de fragil incat sa mori din cauze legate de imbatranire.
So this is a genuine conclusion that I come to, that the first 150-year-old -- we don't know how old that person is today, because we don't know how long it's going to take to get these first-generation therapies. But irrespective of that age, I'm claiming that the first person to live to 1,000 -- subject of course, to, you know, global catastrophes -- is actually, probably, only about 10 years younger than the first 150-year-old. And that's quite a thought.
Asa ca la concluzia aceasta am ajuns eu, ca primul om de 150 de ani, nu stim ce varsta are acel om astazi pentru ca nu stim cat va dura pana vor exista aceste terapii de prima-generatie. Dar fara a avea legatura cu varsta respectivului , eu sustin ca prima persoana care va trai pana la varsta de 1000 de ani influentat, stiti, si de catastrofele naturale, are acum, probabil, doar cu vreo 10 ani mai putin decat primul om de 150 de ani. Iar asta e chiar un gand interesant.
Alright, so finally I'm going to spend the rest of the talk, my last seven-and-a-half minutes, on step one; namely, how do we actually get to this moderate amount of life extension that will allow us to get to escape velocity? And in order to do that, I need to talk about mice a little bit. I have a corresponding milestone to robust human rejuvenation. I'm calling it "robust mouse rejuvenation," not very imaginatively. And this is what it is. I say we're going to take a long-lived strain of mouse, which basically means mice that live about three years on average. We do exactly nothing to them until they're already two years old. And then we do a whole bunch of stuff to them, and with those therapies, we get them to live, on average, to their fifth birthday. So, in other words, we add two years -- we treble their remaining lifespan, starting from the point that we started the therapies.
Asa, in sfarsit am sa dedic restul acestei discutii, ultimele mele 7 minute si jumatate, primului pas, cu alte cuvinte: cum obtinem de fapt aceasta extindere moderata a duratei de viata care ne va permite sa evadam? Iar ca sa facem asta, trebuie sa vorbesc putin despre soareci. Am un reper corespondent intineririi omului robust. Il numesc intinerirea soarecelui robust, fara prea multa imaginatie. El suna asa. Eu zic sa luam o generatie de soareci care traiesc mult, adica unii care supravietuiesc in medie pana la trei ani. Nu le facem absolut nimic pana la varsta de doi ani. Apoi le facem o multime de chestii, si prin aceste terapii, ii facem sa traiasca, in medie, pana implinesc cinci ani. Cu alte cuvinte, adaugam doi ani le triplam anii de viata ramasi din momentul in care incepem terapiile.
The question then is, what would that actually mean for the time frame until we get to the milestone I talked about earlier for humans? Which we can now, as I've explained, equivalently call either robust human rejuvenation or longevity escape velocity. Secondly, what does it mean for the public's perception of how long it's going to take for us to get to those things, starting from the time we get the mice? And thirdly, the question is, what will it do to actually how much people want it? And it seems to me that the first question is entirely a biology question, and it's extremely hard to answer. One has to be very speculative, and many of my colleagues would say that we should not do this speculation, that we should simply keep our counsel until we know more.
Apoi vine intrebarea: ce ar insemna asta pentru intervalul de timp pana ajungem la punctul de reper despre care am vorbit mai devreme, in cazul oamenilor? Acela pe care il putem numi acum, asa cum am explicat, in mod echivalent, fie intinerirea omului robust, fie viteza de evadare a longevitatii. Pe de alta parte, ce importanta are asta in ce priveste perceptia publicului asupra timpului care o sa treaca pana vom obtine aceste lucruri, incepand din momentul in care avem soarecii? Si in al treilea rand, se pune mai intrebarea: cat de mult va face asta oamenii sa si le doreasca? Si mi se pare ca prima intrebare este una pur biologica si cu un raspuns foarte greu de dat. Trebuie sa speculezi mult si multi dintre colegii mei ar spune ca nu trebuie sa facem aceste speculatii, ci ar trebui sa le tinem pentru noi pana stim mai multe.
I say that's nonsense. I say we absolutely are irresponsible if we stay silent on this. We need to give our best guess as to the time frame, in order to give people a sense of proportion so that they can assess their priorities. So, I say that we have a 50/50 chance of reaching this RHR milestone, robust human rejuvenation, within 15 years from the point that we get to robust mouse rejuvenation. 15 years from the robust mouse. The public's perception will probably be somewhat better than that. The public tends to underestimate how difficult scientific things are. So they'll probably think it's five years away. They'll be wrong, but that actually won't matter too much. And finally, of course, I think it's fair to say that a large part of the reason why the public is so ambivalent about aging now is the global trance I spoke about earlier, the coping strategy. That will be history at this point, because it will no longer be possible to believe that aging is inevitable in humans, since it's been postponed so very effectively in mice. So we're likely to end up with a very strong change in people's attitudes, and of course that has enormous implications.
Eu zic ca n-are niciun rost. Eu zic ca suntem absolut iresponsabili daca trecem asa ceva sub tacere. Trebuie sa estimam cat mai exact intervalul de timp pentru a da oamenilor proportii in functie de care sa isi evalueze prioritatile. Deci, eu cred ca avem 50% sanse sa atingem reperul IOR, intinerirea omului robust, in 15 ani de la momentul in care obtinem intinerirea la soareci. 15 ani de la soarecele robust. Perceptia publicului va fi oarecum mai favorabila decat atat. Publicul are tendinta sa subestimeze dificultatea actelor stiintifice. Asa ca probabil va considera ca mai sunt doar 5 ani. Se vor insela, dar nu va conta prea mult. Iar in final, desigur, cred ca e corect sa spun ca motivul principal pentru care publicul este atat de nehotarat in ce priveste imbatranirea acum il reprezinta hipnoza globala despre care am vorbit mai devreme, strategia de adaptare. Ea va fi uitata in acel moment, pentru ca va fi imposibil sa mai credem ca imbatranirea este inevitabila pentru oameni, avand in vedere ca deja a fost amanata pentru soareci. Asa ca ne vom alege cel mai probabil cu o provocare pentru atitudinea oamenilor, iar acest lucru are implicatii enorme, desigur.
So in order to tell you now how we're going to get these mice, I'm going to add a little bit to my description of aging. I'm going to use this word "damage" to denote these intermediate things that are caused by metabolism and that eventually cause pathology. Because the critical thing about this is that even though the damage only eventually causes pathology, the damage itself is caused ongoing-ly throughout life, starting before we're born. But it is not part of metabolism itself. And this turns out to be useful. Because we can re-draw our original diagram this way. We can say that, fundamentally, the difference between gerontology and geriatrics is that gerontology tries to inhibit the rate at which metabolism lays down this damage. And I'm going to explain exactly what damage is in concrete biological terms in a moment. And geriatricians try to hold back the sands of time by stopping the damage converting into pathology. And the reason it's a losing battle is because the damage is continuing to accumulate.
Ca sa va explic mai clar cum vom obtine acesti soareci, o sa mai adaug ceva descrierii fenomenului de imbatranire. Voi folosi cuvantul "daune" ca sa denumesc aceste evenimente intermediare cauzate de metabolism si care pana la urma cauzeaza patologii. Ce trebuie sa retinem este ca desi daunele cauzeaza patologii doar spre sfarsit, daunele insele se petrec pe tot parcursul vietii, incepand dinainte de nastere. Dar ele nu fac parte din metabolism. Ceea ce se dovedeste un lucru folositor. Pentru ca astfel ne putem redesena diagrama. Putem spune ca diferenta fundamentala intre gerontologie si geriatrie este ca gerontologia incearca sa incetineasca ritmul cu care metabolismul face aceste daune. Si voi explica imediat ce anume sunt daunele din punct de vedere biologic. Iar geriatrii incearca sa incetineasca scurgerea vietii impiedicand daunele sa se transforme in patologie. Motivul pentru care aceasta este o lupta pierduta este ca daunele continua sa se adune.
So there's a third approach, if we look at it this way. We can call it the "engineering approach," and I claim that the engineering approach is within range. The engineering approach does not intervene in any processes. It does not intervene in this process or this one. And that's good because it means that it's not a losing battle, and it's something that we are within range of being able to do, because it doesn't involve improving on evolution. The engineering approach simply says, "Let's go and periodically repair all of these various types of damage -- not necessarily repair them completely, but repair them quite a lot, so that we keep the level of damage down below the threshold that must exist, that causes it to be pathogenic." We know that this threshold exists, because we don't get age-related diseases until we're in middle age, even though the damage has been accumulating since before we were born.
Asa ca exista si o a treia abordare, daca privim din acest punct de vedere. O putem numi abordarea inginereasca, si eu sustin ca ne este accesibila. Abordarea inginereasca nu intervine in nici un proces. Nu intervine nici in acesta, nici in acesta. Iar asta e un lucru bun pentru ca inseamna ca nu e o lupta pierduta, este ceva ce suntem capabili sa realizam pentru ca nu implica o imbunatatire a evolutiei. Abordarea inginereasca spune doar "Hai sa reparam periodic toate aceste tipuri de daune, nu neaparat sa le reparam de tot, dar intr-o proportie destul de mare, asa incat sa mentinem nivelul daunelor sub cel normal, care trebuie sa existe si care le face sa fie patogene." Stim ca acest prag exista, pentru ca nu dezvoltam afectiuni ale batranetii pana nu ajungem la varsta mijlocie, cu toate ca daunele s-au tot acumulat inca dinainte sa ne nastem.
Why do I say that we're in range? Well, this is basically it. The point about this slide is actually the bottom. If we try to say which bits of metabolism are important for aging, we will be here all night, because basically all of metabolism is important for aging in one way or another. This list is just for illustration; it is incomplete. The list on the right is also incomplete. It's a list of types of pathology that are age-related, and it's just an incomplete list. But I would like to claim to you that this list in the middle is actually complete -- this is the list of types of thing that qualify as damage, side effects of metabolism that cause pathology in the end, or that might cause pathology. And there are only seven of them. They're categories of things, of course, but there's only seven of them. Cell loss, mutations in chromosomes, mutations in the mitochondria and so on.
De ce spun ca este realizabil? Pai, motivul ar fi urmatorul. Partea importanta a acestui slide este de fapt cea de jos. Daca incercam sa spunem care parti ale metabolismului sunt importante in procesul de imbatranire, stam aici toata noaptea, pentru ca practic tot metabolismul este important in procesul de imbatranire intr-un fel sau altul. Aceasta lista este doar demonstrativa, este incompleta. Lista din dreapta este de asemenea incompleta. Este o lista a tipurilor de patologii legate de imbatranire dar este una incompleta. Insa eu sustin in fata voastra ca lista din mijloc este chiar una completa, este lista tipurilor de lucruri care alcatuiesc daunele, efectele secundare ale metabolismului care duc la patologii sau care ar putea duce la patologii. Si sunt doar sapte. Sunt categorii, bineinteles, dar sunt doar sapte. Pierderea celulelor, mutatii in cromozomi, mutatii in mitocondrii si asa mai departe.
First of all, I'd like to give you an argument for why that list is complete. Of course one can make a biological argument. One can say, "OK, what are we made of?" We're made of cells and stuff between cells. What can damage accumulate in? The answer is: long-lived molecules, because if a short-lived molecule undergoes damage, but then the molecule is destroyed -- like by a protein being destroyed by proteolysis -- then the damage is gone, too. It's got to be long-lived molecules. So, these seven things were all under discussion in gerontology a long time ago and that is pretty good news, because it means that, you know, we've come a long way in biology in these 20 years, so the fact that we haven't extended this list is a pretty good indication that there's no extension to be done. However, it's better than that; we actually know how to fix them all, in mice, in principle -- and what I mean by in principle is, we probably can actually implement these fixes within a decade. Some of them are partially implemented already, the ones at the top.
In primul rand, as vrea sa va dau un argument pentru care aceasta lista este una completa. Sigur ca am putea aduce argumentul biologic. Am putea spune "Bine, dar noi din ce suntem facuti?" Suntem facuti din celule si materia dintre celule. In ce se pot acumula daunele? Raspunsul este "In moleculele care traiesc mult" pentru ca daca o molecula care traieste putin este afectata, dar apoi este distrusa, asa cum o proteina este distrusa de proteoliza, atunci si daunele asupra ei sunt distruse. Trebuie sa fie vorba de molecule care traiesc mult. Toate aceste sapte lucruri erau discutate in gerontologie acum multa vreme, ceea ce reprezinta vesti destul de bune, pentru ca inseamna ca, stiti, am evoluat mult in biologie in acesti 20 de ani, deci faptul ca n-am extins aceasta lista ne arata destul de clar ca nu se pot face extensii. Totusi, e mai bine decat atat; stim cum sa le rezolvam pe toate la soareci, in principiu, si ce vreau sa spun prin "in principiu" este ca probabil putem implementa aceste solutii in decursul a zece ani. Unele dintre ele sunt deja partial implementate, cele de sus.
I haven't got time to go through them at all, but my conclusion is that, if we can actually get suitable funding for this, then we can probably develop robust mouse rejuvenation in only 10 years, but we do need to get serious about it. We do need to really start trying. So of course, there are some biologists in the audience, and I want to give some answers to some of the questions that you may have. You may have been dissatisfied with this talk, but fundamentally you have to go and read this stuff. I've published a great deal on this; I cite the experimental work on which my optimism is based, and there's quite a lot of detail there. The detail is what makes me confident of my rather aggressive time frames that I'm predicting here. So if you think that I'm wrong, you'd better damn well go and find out why you think I'm wrong.
Nu am timp sa trec prin toate, dar concluzia mea este ca, daca vom reusi sa gasim destule fonduri, vom putea implementa intinerirea masei robuste in doar zece ani, dar trebuie sa incepem sa o facem in mod serios. Trebuie sa incercam cu adevarat. Cu siguranta ca exista biologi in auditoriu si vreau sa raspund unora din intrebarile pe care le-ati putea avea. Se poate sa nu fi fost satisfacuti de aceasta prelegere, dar trebuie neaparat sa mergeti sa cititi lucrurile astea. Am publicat un volum mare de lucrari pe aceasta tema. Am citat experimentele pe care imi bazez optimismul asa ca veti gasi acolo multe detalii. Ceea ce ma face increzator in intervalele de timp destul de agresive pe care le-am enuntat aici. Asa ca daca va inchipuiti ca gresesc, ar trebui sa incercati serios sa vedeti de ce credeti ca gresesc.
And of course the main thing is that you shouldn't trust people who call themselves gerontologists because, as with any radical departure from previous thinking within a particular field, you know, you expect people in the mainstream to be a bit resistant and not really to take it seriously. So, you know, you've got to actually do your homework, in order to understand whether this is true.
Si desigur ca este vital sa nu aveti incredere in oamenii care se auto-intituleaza gerontologi pentru ca, asa cum se intampla de fiecare data cand ne indepartam de sistemul de gandire anterior dintr-un domeniu, stiti, ne asteptam ca oamenii care apartin de curent sa fie ceva mai potrivnici si sa nu ne ia in serios. Asa ca trebuie sa va faceti temele in mod serios ca sa puteti intelege daca toate astea sunt adevarate.
And we'll just end with a few things. One thing is, you know, you'll be hearing from a guy in the next session who said some time ago that he could sequence the human genome in half no time, and everyone said, "Well, it's obviously impossible." And you know what happened. So, you know, this does happen. We have various strategies -- there's the Methuselah Mouse Prize, which is basically an incentive to innovate, and to do what you think is going to work, and you get money for it if you win. There's a proposal to actually put together an institute. This is what's going to take a bit of money. But, I mean, look -- how long does it take to spend that on the war in Iraq? Not very long. OK. (Laughter) It's got to be philanthropic, because profits distract biotech, but it's basically got a 90 percent chance, I think, of succeeding in this. And I think we know how to do it. And I'll stop there. Thank you. (Applause)
Si vom incheia cu cateva lucruri. Primul este ca veti auzi un tip in urmatoarea sesiune care spunea acum ceva vreme ca vom putea reproduce secventa genomului uman in scurt timp si toata lumea a crezut ca asa ceva este, evident, imposibil. Si stiti ce s-a intamplat. Deci, stiti, lucrurile astea se intampla. Avem diverse strategii, printre care Premiul Methuselah Mouse, de fapt un stimulent al inovarii si al dorintei de a face ceea ce crezi ca ar functiona, si apoi primesti bani cand castigi. S-a propus chiar deschiderea unui institut. O sa fie nevoie de ceva bani. Dar ganditi-va, cat dureaza sa cheltuim suma respectiva pe razboiul din Irak? Nu prea mult. OK. (Rasete) Trebuie sa fie un act filantropic, pentru ca profiturile distrag atentia biotehnologilor, dar eu cred ca sunt sanse de 90% sa reusim. Si mai cred ca stiu cum s-o facem. Si ma voi opri aici. Va multumesc. (Aplauze)
Chris Anderson: OK. I don't know if there's going to be any questions but I thought I would give people the chance. Audience: Since you've been talking about aging and trying to defeat it, why is it that you make yourself appear like an old man? (Laughter)
OK. Nu stiu daca vor fi intrebari, dar m-am gandit sa ofer ocazia. Daca ati vorbit despre imbatranire si incercarea de a o combate, de ce aratati ca un om batran? (Rasete)
AG: Because I am an old man. I am actually 158. (Laughter) (Applause)
Pentru ca sunt un batran. Am 158 de ani. (Rasete) (Aplauze)
Audience: Species on this planet have evolved with immune systems to fight off all the diseases so that individuals live long enough to procreate. However, as far as I know, all the species have evolved to actually die, so when cells divide, the telomerase get shorter, and eventually species die. So, why does -- evolution has -- seems to have selected against immortality, when it is so advantageous, or is evolution just incomplete?
Speciile acestei planete au evoluat cu sisteme imunitare care sa indeparteze toate bolile in asa fel incat indivizii sa traiasca destul incat sa procreeze. Totusi, din cate stiu, toate speciile au evoluat astfel incat sa moara asa incat, cand celulele se divizeaza, telomerazele devin mai scurte si in final speciile mor. Deci, de ce evolutia pare sa fi selectat impotriva imortalitatii cand ea este atat de avantajoasa, sau cumva este evolutia incompleta?
AG: Brilliant. Thank you for asking a question that I can answer with an uncontroversial answer. I'm going to tell you the genuine mainstream answer to your question, which I happen to agree with, which is that, no, aging is not a product of selection, evolution; [aging] is simply a product of evolutionary neglect. In other words, we have aging because it's hard work not to have aging; you need more genetic pathways, more sophistication in your genes in order to age more slowly, and that carries on being true the longer you push it out. So, to the extent that evolution doesn't matter, doesn't care whether genes are passed on by individuals, living a long time or by procreation, there's a certain amount of modulation of that, which is why different species have different lifespans, but that's why there are no immortal species.
Genial. Multumesc pentru aceasta intrebare la care pot sa dau un raspuns care nu naste controverse. Iti voi da raspunsul general acceptat cu care, intamplator, sunt si eu de acord. Si anume ca nu, imbatranirea nu este rezultatul unei selectii, ci este un act de neglijenta evolutionara. Cu alte cuvinte, imbatranim pentru ca este foarte greu sa facem altfel, ai nevoie de mai multe conexiuni genetice, de gene mai sofisticate ca sa poti imbatrani mai greu, si nevoia creste pe masura ce imbatranesti. Altfel spus, evolutia nu conteaza si nu are importanta daca genele sunt transmise de invidizi care traiesc mult, sau prin procreere acest fenomen este modular, si din acest motiv diferitele specii au durate de viata diferite si nu exista nici una care sa traiasca infinit.
CA: The genes don't care but we do?
Genelor nu le pasa, doar noua?
AG: That's right.
Exact.
Audience: Hello. I read somewhere that in the last 20 years, the average lifespan of basically anyone on the planet has grown by 10 years. If I project that, that would make me think that I would live until 120 if I don't crash on my motorbike. That means that I'm one of your subjects to become a 1,000-year-old?
Buna. Am citit undeva ca in ultimii 20 de ani, durata medie de viata a oamenilor a crescut cu zece ani. Daca extrapolez, ajung la concluzia ca as trai pana la 120 de ani daca nu fac vreun accident cu motocicleta. Asta inseamna ca sunt unul din subiectii care vor putea trai 1000 de ani?
AG: If you lose a bit of weight. (Laughter) Your numbers are a bit out. The standard numbers are that lifespans have been growing at between one and two years per decade. So, it's not quite as good as you might think, you might hope. But I intend to move it up to one year per year as soon as possible.
Daca pierzi putin din greutate. (Rasete) Cifrele nu prea se potrivesc. Cifrele standard spun ca durata de viata a crescut cu intre unul si doi ani per decada. Deci nu e atat de bine pe cat ai crede, pe cat ai putea spera. Dar intentionez sa transform cresterea intr-una de un an in fiecare an.
Audience: I was told that many of the brain cells we have as adults are actually in the human embryo, and that the brain cells last 80 years or so. If that is indeed true, biologically are there implications in the world of rejuvenation? If there are cells in my body that live all 80 years, as opposed to a typical, you know, couple of months?
Mi s-a spus ca multe celule ale creierului unui adult exista inca din embrion si ca celulele cerebrale traiesc cam 80 de ani. Daca e adevarat, exista implicatii biologice in lumea intineririi? Daca exista celule in corpul meu care traiesc 80 de ani, comparativ cu unele tipice, care traiesc, stiti, cateva luni?
AG: There are technical implications certainly. Basically what we need to do is replace cells in those few areas of the brain that lose cells at a respectable rate, especially neurons, but we don't want to replace them any faster than that -- or not much faster anyway, because replacing them too fast would degrade cognitive function. What I said about there being no non-aging species earlier on was a little bit of an oversimplification. There are species that have no aging -- Hydra for example -- but they do it by not having a nervous system -- and not having any tissues in fact that rely for their function on very long-lived cells.
Exista implicatii tehnice, desigur. Practic ce trebuie sa facem este sa inlocuim celule in cele cateva zone ale creierului care le pierd intr-un ritm respectabil, in special in neuroni, dar fara sa le inlocuim mai rapid decat atat, sau nu cu mult mai rapid pentru ca daca le inlocuim prea rapid se degradeaza functiile cognitive. Ceea ce am zis mai devreme despre faptul ca nu exista specii care nu imbatranesc era oarecum prea simplificat. Exista specii care nu imbatranesc, cum este Hydra, dar secretul lor este ca nu au sistem nervos si nici vreun fel de tesut care sa se bazeze pentru a-si indeplini functiile pe celule care traiesc mult.