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分鐘的時間限制真是苛刻, 那麼我將直切入核心主題, 等我把這機器弄好。 好了。我會分別談到五個話題。 我會講為什麼戰勝衰老是可取的。 我會講為什麼我們得"痛改前非" 在這方面得要比現在討論更多一點。 當然,我也會講可行性。 我會談談為何我們會認為對於衰老 做任何努力都是徒勞的宿命論。 接下來我會用演講後半段 來談談如何證明這宿命主義是錯誤的, 即,我們可以通過行動來改變它。
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.
我會分兩步來談。 第一部份要講的是, 如何從一個較保守的壽命延長年數 --- 我定義為30年,並針對於 已步入中年才開始抗老化的人 ---- 讓他們達到一個真正可稱為戰勝衰老的境界。 本質上來說,即是徹底地消除 你的年齡與接下來一年內死亡機率 -- 或在那之前得病的機率,這兩者之間的關係。 當然,最後我會講的題目 是如何達到這個中間階段, 即延長壽命大約三十年。
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.
那麼,我從為什麼應該抗衰老開始。 現在,我想問你們一個問題。 請舉手: 現場觀眾誰贊同瘧疾? 這個簡單。好。 好。請舉手,現場觀眾 誰不確定瘧疾是件好事還是件壞事? 好。那麼我們都認為瘧疾是件壞事。 那太好了,因為我也想這應該是你們會回答的答案。 現在我想向你們提出 使我們認定瘧疾是件壞事的主要原因, 是因為瘧疾和衰老共有的一個特徵。 那就是… (問:為何我們要治癒衰老?答:因為衰老是殺人狂!) 唯一真正不同的地方是衰老所弒殺人數遠超於瘧疾。
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.
那麼,我想向觀眾,尤其是英國觀眾, 講下衰老與獵殺狐狸的對比, 獵狐在英國是經過了長期鬥爭 才終於在近幾個月前被政府正式禁止的。 雖然我知道這裡的觀眾是有同情心的, 但,大家都知道,有許多人對此邏輯不盡認同。 而就這點讓我覺得這是個不錯的比喻。 有許多人表示, "那些 城裡人憑什麼對我們郊區鄉民指點怎麼用我們的時間? 這是生活傳統的一部份, 我們不該被禁止繼續做這件事 (對比表:獵狐vs.人類老化) 這對自然生態有益;這是在防止狐狸繁殖氾濫。” 但最終政府還是佔了上風, 因為大多數的英國民眾 尤其是大多數的國會議員, 達到的共識是,這真的 不該為一個文明社會所容許。
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.
而我認為人類的衰老與獵狐 在所有這些共同特質上都極為契合。 哪方面是令人無法理解的呢? 當然,不僅是為了生命---- (笑聲) (為什麼不確定? 左:有趣 右:不好玩) 這更是為了健康的生命 ---- 我們都知道 變得悴弱,愁苦,依賴,都不好玩, 無論死亡是否好玩。 講真的,這就是我想表達的。 對衰老的看法是一種全球性麻木 (會很無聊;我們沒法付養老金;) 這些就是各種滑稽的藉口 (非洲飢荒怎辦;獨裁暴君會活太久) 人們用這些藉口給衰老做辦解。 我的意思是,好吧,我並不是說 這些藉口是完全沒有價值的。 這裡的確是有幾點不錯。 譬如一些我們本該思量和預備的事, 以免… 我是說,當我們解決了抗衰老問題之後, 可以讓我們把因此而造成的動盪最小化。
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)
但這些真的很瞎掰 --- 一旦你 記起尺長寸短的話。 你知道的,這些是議論辯詞,這些是 理應關心的事情。 但問題是,這些真有那麼危險嗎? --- 這些對抗老化的風險 --- 會比不對抗老化——即對老化不聞不問帶來的 缺點更嚴重嗎? 這些風險比 每天對十萬人判決無謂的早死更嚴重嗎? 要知道,若是沒比這更有力的理由, 那麼就別浪費我的時間了。 (笑聲)
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.
好,那麼現在是有這麼一個觀點 有些人的確覺得它非常有理,那就是 "我們擔心人口氾濫," 他們說。 "我們治好衰老的話,就沒有人會死了, 死亡人數至少會大幅減少, 除了那些過馬路不小心的。 這樣一來,我們就不能多生小孩, 而小孩對大部分人來說又很重要。” 說的對。 要知道,很多人都想把這個問題蒙混過去, 給些這樣的答覆。 我不同意這些說法。我覺得這些說法基本上是不通的。 我想,我們是得面對這方面的兩難問題。 我們將必須決定,是要選擇生育率低, 還是死亡率高。 死亡率高,可以簡單地由拒絕接受這些治療來達成, 要偏好繼續多生小孩的話。
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.
我說那也可以 ---- 未來的人類是有權做這個選擇的。 但,不應該的是由我們來代替未來人作此決定。 我們要是舉棋不定,優柔寡斷, 然後不好好著手研發這些治療技術的話, 那我們即是判了一大幫人的死刑 -- 他們原可在夠年輕夠健康的時候 得益于接受治療,但沒機會了, 就因我們沒盡責儘速研究開發這些治療技術 --- 我們等於是剝奪了那些人的無限壽命, 我認為那是不道德的。 這就是我對於人口氾濫這個問題的答案。
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.
好,那下一個題目是, 我們為什麼得在這方面更積極呢? 而我的主要答案是 麻木接受衰老並非如其表面看來那麼傻。 這其實是一種合理方法,用來應付衰老的必然性。 衰老是恐怖的,但又是必然的,那,只好 得找個方法來讓我們別去想它, 而且不論用什麼方式來不想它都合理。 就像,舉例,編出這麼些無稽的理由, 要辯解說衰老退化最終還是件好事。 不過,那也當然是只有在這兩項因素都成立的前提下才行得通。 一旦必然性方面不再那麼清楚,變得有點模糊, 那我們也許就在對衰老問題能有所行動了, 這又成為問題的一部份。 接受衰老為宿命的麻木認同正是阻止我們對此些事著急的原因。 而那也正是為什麼我們需要多提此事 --- 像傳福音一樣,我會甚至這樣比喻 --- 為了讓人關注,讓人醒悟 原來在這方面他們一直逃避於麻木中。 那麼這些就是我對這方面所有要講的內容了。
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.
現在我要講可行性。 我想基本上,我們為何感到老化是無法避免的 可以綜述於我下面要解說的,對老化的定義。 一個非常簡單的定義。 老化,是從生命一開始就有的副作用。 也就是說,新陳代謝。 這不是全然同義重覆的說詞; 而是合理的說法。 老化基本上是一個發生在沒有生命的物件如汽車上的過程, 也在我們身上發生, 雖然我們有很多精巧的自我修復機制, 但還是因為那些自我修復機制不完美。
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.
所以簡單講,新陳代謝,即定義為 基本上所有維持我們日復一日活命的每件事, 都有副作用。 那些副作用經年累月累積成病變。 那是個不錯的定義。所以我們可以這樣說: 我們可以說,這是一串互連的作用。 在延緩老化這個領域, 大多數人所知,有兩種方式。 在這裡我分別稱他們為:老年學方式和老人醫學方式。 老人醫學家在時日為晚之際才做干涉介入性治療, 在病變情況趨於明顯時, 老人醫學家會試圖阻撓病魔拖延時間漏沙, 並致力阻止副作用的持續累積 來阻止過早引發病變。 當然這是一種非常短期主義的策略,在打敗仗, 因為那些致病因素 會不斷的隨時間氾濫為患。
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?
老年學方式表面上看來前景似乎樂觀許多, 因為,大家都知道預防勝於治療。 但很遺憾的我們對新陳代謝瞭解不多。 甚至可以說,我們對生物體如何工作所知少得可憐 --- 我們連細胞都還沒能算是真正的弄懂。 我們所發現的東西,例如, RNA核糖核酸干擾現象,僅僅是近幾年來的事, 而且這是一個細胞如何運行的非常基礎的部分。 本質上,老年學方式還算是個不錯的途徑, 不過它不適用於那些時日已至的人, 若我們講的是介入性的醫療手法。 那麼,我們對這個要怎麼辦? 我是說,這邏輯不錯,聽起來是足以令人信服地, 穩紮鐵定,是不是?
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.
但並非也。 我在告訴你為什麼它不是之前,要首先進入 我稱之為第二步驟的話題。 假設,如我所說過的,我們真能得到 --- 今天這麼做就算是為了方便討論吧 ---- 有能力將額外三十年的健康生命附加予 已入中年的人,我們說55歲好了。 我將稱之為人類健康回春 。好的。 這有什麼實質上的意義呢 對於現今各種不同歲數的人們來說 --- 或相當於,在這些療法來臨之際的各個年齡層的人們--- 真正可以活多久? 為了要回答這個問題… 也許你覺得這很簡單, 但其實它不簡單。 我們不能就說: “那麼,若他們在足夠年輕的時候從這些療法中受益, 那他們就會再活多個三十年。” 這是錯的答案。 答錯的原因呢,是因為技術的進步。
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.
科技進展可以分為兩種 以此話題來講。 有基礎級的重要突破, 另有在那些突破基礎上逐步的精修改良。 那麼,在對時間框架的預估上, 這兩種科技進步區別很大。 基礎性突破: 非常難預測需要多久時間 才能達成一個基礎性突破 我們從很久以前,就已經認定飛翔會很有趣, 然後我們拖到1903年才發明出實踐方法。 但在那之後,一切就滿穩定滿按部就班的了。 我想在動力飛行技術發展過程中, 這個是合理的事件發生順序。 我們可以把這想成是,每一步都似乎是 超越前項發明者的想像力 這漸階式進步是在 某樣非漸階式即突破性發展的基礎上產生的。
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.
那是在基礎性大突破之後才會看見的發展。 而且你會在各種各樣的科學技術裡發現這樣的情況。 電腦發展的時間線和飛機差不多, 當然發生時間是稍晚些。 你可以看醫療保健,如個人衛生,疫苗,抗生素 -- 你看,其發展過程是同類型的時間結構。 所以我想事實上第二步驟,我剛剛稱之為步驟的 根本不是個步驟。 這些人,若他夠年輕還來得及 從第一代治療技術中獲益, 得到這適量的延壽年數, 即使那些人在治療技術來臨時已屆中年 他們會處於某種先鋒期優勢。 他們大多會活得足夠久以接受更進步的治療 而可額外延續30或也許50年的壽命。 也就是說,他們會一直保持領先。 那些治療技術的進步會快於 治療技術殘留缺點追趕上我們壽命的速度。
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.
這是我要特別強調的重點。 因為,大部分人一聽到 我預估說有很多今天活著的人將活到一千歲以上 他們就以為我講的是,我們會在幾十年內發明 能徹底消除老化現象的治療技術, 以使我們活到一千歲以上。 我根本不是這麼說。 我說的是速率,光靠這些技術進步的速度 就夠了。 它們永遠不會完美,但我們能在還沒有人活到兩百歲之前, 先解決那些導致兩百歲人的死亡原因。 依此類推,到三百,四百... 等等。 我給這起了個小名 叫做 "延壽用逃逸速度" (笑聲) 反正,大概就是這個意思。
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.
那麼,這幾曲綫基本代表我們期望人們活多久, 以剩餘壽命期望值而計, 照他們健康狀況來衡量, 以這些技術問世時他們當時的年齡為準。 若你已經一百歲了,或甚至你是八十歲 ---- 那麼,一個平常的八十歲的人 用這些治療技術大概幫不了你什麼 因為你已經離死亡的大門太近了 這種剛萌芽的實驗期療法對你而言效果會不夠好。 你會無法承受它們。 但若你只有五十歲,那就有一線希望 你也許能從生命的俯衝線抽脫,然後 --- (笑聲) 終究熬過這關。 然後開始在生理上真正地變得更加年輕, 在身體和心理兩方面都變得更加年輕, 還有因年老相關的死亡風險也會降低。 若你比這還年輕一點, 那你甚至永遠不會 衰弱到會死於老年相關的死因。
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.
所以,我得出的這個結論是真實可靠的:第一位150歲的人 ---- 我們不知道那個人現今是幾歲, 因為我們不知道要多久 才會有這些第一代治療技術。 但無關於他是幾歲 我斷言第一位活到一千歲的人 --- 當然這會受像世界大浩劫等影響 --- 是極有可能只比第一位150歲的人年輕個十歲左右。 這是值得好好思索的。
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.
好,那我接下來終於要用 我最後的這七分半鐘,講第一步驟: 就是,我們要怎麼來適度增長壽命 使我們可抵達逃逸速度? 為此我必須講一點點白鼠。 我對人類強健回春設立了相應的里程碑。 我叫它老鼠強健回春,沒什麼想像力。 那就是這樣。 我說,我們用一隻長壽品種的老鼠, 通常平均壽命是大約三年。 我們完全不碰牠們,直到他們已兩歲後。 屆時我們就對牠們做許多實驗, 且經由這些治療技術讓牠們活到 平均來說,第五歲生日時。 也就是說,我們加了兩年 --- 將牠們餘壽增至三倍 從我們開始治療的時間點算起。
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.
問題是,這對我之前談到關於人類的里程碑而言, 在我們到達它之前,意味著什麽? 如我已經解釋過的,現在我們可同樣稱其為 人類強健回春或延壽用逃逸速度。 第二,這會如何影響大眾觀念,就是 由測試白鼠時開始算起, 我們還要多久才能達到這些目標呢? 第三,問題是,這能夠怎樣影響 人們對此渴求的程度? 在我看來第一個問題 純粹是生物學上的問題, 而且極難回答。 要做許多不切實的理論性猜測, 那我很多同事會警告我們別做這種推論, 要我們最好是別出聲,知道得多點再說。
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.
我說那是無稽之談。 我認為對此避口不提才絕對是不負責任。 我們應盡所能做最佳猜測,提出一個理論性的時間範圍, 讓人們至少能對此大體衡量下, 好讓他們可以自己做評估。 我說,我們有50:50的機率 從達到老鼠強健回春算起 在十五年以內, 達到這個RHR (人類強健回春) 的里程碑。 在那隻健全不朽老鼠成功後十五年即可。 大眾觀點可能比這還要樂觀一些。 民眾通常傾向于低估科學研究的艱難程度。 所以他們可能會想成是五年後。 雖然他們會錯,但是那其實不太重要。 當然,最後我想可以這麼說, 導致目前民眾們對於衰老意見矛盾的一大原因 是我先前提到的對衰老的全球性麻木狀態,那種應付策略。 屆時將成為歷史, 因為人們不再可能繼續相信人類的老化是必然的, 因為屆時在白鼠上會已取得非常有效地延遲作用。 這樣一來民眾的觀點應該會有極大的轉變, 這當然有極重要的含意。
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.
為了說明我們要如何在這些白鼠上實驗, 我對衰退老化現象加了一個形容用詞。 我要使用 "損害" 這個詞 來代表新陳代謝所引起的這些過渡性的東西, 其最終引起病變。 因為這個關鍵的地方是 就算這些損害只是最終才造成病變, 這個損害本身是持續性地發生,在我們出生前就已開始。 但它並不是新陳代謝過程的一部份。 那麼,這點變得很有用。 因為這樣一來我們就可以將原來的機理重新設計。 可以說,基本上,老年學和老年醫學的差別 是老年學試圖抑制 新陳代謝造成損害的速度。 我稍後會清楚說明 "損害" 在具體生物學來講到底是什麼。 那麼,老人醫學家試圖通過阻止損害轉成病變 來抵抗時間的漏沙。 這將會失敗的原因 是因為損害持續累積增加。
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.
那還另有第三種途徑,我們來這樣看。 我們可以稱之為工程途徑, 我先聲明這工程途徑是在可實現範圍之內的。 工程途徑不介入任何過程中。 它不介入這個過程,或這個 而那也不錯,因為這樣就表示沒在打敗仗, 且它是在我們所能做到的範圍之內, 因為它不牽涉對生物進化過程作出改進。 工程途徑就是很簡單地說, “我們來定期的修補這些不同類型的損害 --- 並不一定全要修到好,但修補了算滿多, 讓我們將損害的程度維持在臨界值以下, 這個臨界值是必然存在的,即能剛好引起病變的損害。“ 我們知道這個臨界值是存在的, 因為我們在未到中年以前,不會得與年老相關的疾病, 就算是這些損害從我們在胎中就已經開始累積。
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.
我為什麼說我們在可實現範圍之內呢? 這個…基本上就是這樣。 這張幻燈片的要點其實是下面這個。 我們若試圖分辨新陳代謝的哪些是對老化有影響的, 那會要花整個晚上,因為基本上整個新陳代謝 都對衰老現象起這樣或那樣的作用。 這個列單僅是用來做個展示,它還不完整。 右邊的這列單也還不完整。 這個列單列出幾種與年老相關的疾病, 而且它不是完整的。 但我要指出,這個中間的列單確是完整的, 它列出那些可以算作是損害的種類的東西, 即新陳代謝的副作用,其最終將導致病變, 或可能導致病變。 一共只有七個。 當然,它們是按類別分的,但是僅有七個而已。 細胞損失、染色體突變、線粒體內突變等等。
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.
首先呢,我要告訴你們為何這列清單是完整的理由。 當然我們可以從生物學角度來討論。 我們可以問,好,那我們是什麼組成的? 我們是細胞和細胞之間的東西組成的。 損害可以在什麼地方累積? 答案是,壽命久的分子, 因為若要是一個短壽的分子受到損害,但隨後這個分子很快就消亡了 --- 就像一個蛋白質受到水解作用而分解 --- 那麼這個損害也沒了。 這麼來就一定是長壽分子。 其實,這七項很久前都曾在老年學中討論過, 這是個好消息,因為這表示, 你想,我們這二十年來在生物學上進步了很多, 而我們並未在這清單增加項目, 這一事實是個很好的跡象,意味著沒有需要增加的項目了。 不過,更好的消息是,我們甚至知道,理論上,在白鼠身上怎麼修復 所有這些項目 --- 而我所說的理論上的意思是, 我們可能在十年內能夠實踐這些補修措施。 這其中有些已經部分實施了,上面這些
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.
我不夠時間每項講完,但 我的結論是,如果我們真的可以為此得著適當的資金, 那我們很可能在僅僅十年內就研發出全民大眾強健回春, 但我們是需要對此事認真了。 我們是需要真的開始著手嘗試。 當然,觀眾之間有一些生物學家 讓我要回答一些你們可能會有的問題。 你也許對這演說不滿意, 但基本上這些是需要你去研讀的。 我在這方面有發表很多的文刊; 我舉引出那些實驗研究為我樂觀的依據基礎, 那裡面有滿多細節的。 這些細節正是讓我有信心做出 我這些算是滿激進的時間範圍預言。 所以要是你認為我錯了, 你最好好好找出為什麼你認為我是錯的。
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.
當然主要是你不應相信那些 稱自己作老年學家的人因為 猶如在任何一個領域中徹底地脫離舊有思想的情況一樣, 你自然預期主流學派的那些人會有點排斥, 而並不把它當回事。 那麼,其實,你是必須得做該做的功課, 才能瞭解這個是不是真的。
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)
再下來我們即將以幾點做完結。 其中一點是,你下場會聽的是,一個之前曾聲稱 自己可以排列出人類基因組合的傢伙, 那時每個人都說,“那很明顯的是不可能的呀。” 你知道接下來發生了什麼。 所以這是會發生的。 我們有不同的策略 --- 有瑪士撒拉鼠標獎 就是基本上一個給創新發展的獎勵, 做你認為可行的項目, 若成功的話,你就會得獎金。 還有個提案是要正式的成立一間研究所。 這才是要花不少錢的地方。 但說真的 --- 同樣的錢花在伊拉克戰爭上夠用幾天? 沒幾天。好。 (笑聲) 那這必須是慈善性地,因為追求利潤會干擾生物科技的發展, 但我想,在這方面成功的機率,大致上有90%。 還有,我認為我們知道如何做到。那麼,我就在這裡結束。 謝謝你們。 (鼓掌)
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)
克立斯‧安德生:好,我不曉得會不會有任何問題 但我想應該給大家一個機會發問 觀眾:既然你談到衰老還有嘗試擊敗它 為什麼你把自己弄成老頭子的模樣? (笑聲)
AG: Because I am an old man. I am actually 158. (Laughter) (Applause)
AG:因為我是個老頭。我實際上已經158歲了 (笑聲) (掌聲)
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?
觀眾:這顆行星上的生物的免疫系統,在他們進化過程中, 幫助他們抵抗所有疾病,使個體能活得足夠久,以便繁衍後代。 不過,據我所知,所有的生物種類都是以死亡為目地衍變進化, 當細胞分裂時,端粒酶會縮短,最終生物滅亡。 那麼,為何自然進化看來是選擇反對永生不朽呢? 既然那麼有利的話。還是自然進化還未完善?
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.
AG: 太棒了。謝謝你提問的這個問題, 我可以用一個無爭議性的答案來回覆。 我對你的問題有個正統的主流答案, 恰是與我意見相同的。 那就是,不,老化不是自然選擇的產物; 進化簡單說是一個進化時疏忽的產物。 也就是說,我們會有老化是因為不老是件困難的事; 你需要更多遺傳途徑,更精密的基因, 才能老化得慢些, 而你想活得越久,上述的條件要求就越高。 在某種程度上可以這麼說,進化不介意, 也不管基因通過什麽方式被個體傳遞下去, 不管是通過長壽的方式還是生殖的方式, 進化在一定程度上對此有所調節, 這也是為什麼不同生物種類有不同的壽命, 但上述這些就是沒有長生不死的生物種類的緣故。
CA: The genes don't care but we do?
CA:基因不管,但我們管?
AG: That's right.
AG: 是的。
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?
觀眾:你好,我在某處讀到在過去20年 在地球上基本上任何人的平均壽命都已經增加10年 若我以這個做比例,那我會想說 如果我騎車摩托車不撞車的話,則我可以活到120歲。 那是不是意味著我成為你千歲人的研究對象之一嘍?
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.
AG:要是你減一點體重的話。 (笑聲) 你的數字有點過時了。 標準數據是,每十年 人的壽命延長一到兩年。 所以,沒有你想得那麼好,也許你會這麼期望。 但我的意願是,要儘快將這個數據每年增加一年。
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?
觀眾:有人告訴我說,我們成年人的許多腦細胞 早在胚胎期就存在了, 而這些腦細胞能維持80年左右。 若這是真的話, 從生物學的角度講,會否對新生抗老領域造成影響? 是否在我身體內也有細胞會活整整80年, 而非通常情況下,只活幾個月?
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.
AG: 那是確實有技術上的影響。 基本上我們需要做的是在大腦的少數部位 將一些消亡速度較快的細胞換成新的, 尤其是神經元細胞,但我們不想讓更換速度 超過消亡速度--- 或至少不能超過太快, 因為換新的速度太快會降低認知功能。 我之前說到有關沒有不老化的生物種類, 這個說法有點太簡單化了。 其實是有生物是不會老化的 --- 例如水螅 但它們做到這點是因為它們沒有神經系統, 並且沒有任何需要仰賴 長壽細胞才能夠運作的生物組織。