TED2015
Siddhartha Mukherjee: Soon we'll cure diseases with a cell, not a pill
悉达多．穆克吉: 忘记药丸吧，细胞疗法即将到来
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现代医学治疗手段可以用6个（英文）单词概括：生病，吃药，杀死（某些东西）。但是悉达多．穆克吉（Siddhartha Mukherjee）医生向我们表示，未来的治疗手段将会出现很大的变革。
Siddhartha Mukherjee - Cancer physician and writer
When he’s not ferreting out the links between stem cells and malignant blood disease, Siddhartha Mukherjee writes and lectures on the history (and future) of medicine. Full bio
When he’s not ferreting out the links between stem cells and malignant blood disease, Siddhartha Mukherjee writes and lectures on the history (and future) of medicine. Full bio
Double-click the English transcript below to play the video.
00:12
I want to talk to you
about the future of medicine.
about the future of medicine.
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我想跟各位聊聊未来的药物。
00:16
But before I do that, I want to talk
a little bit about the past.
a little bit about the past.
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在聊未来之前，
我想稍稍回顾一下过去。
我想稍稍回顾一下过去。
00:21
Now, throughout much
of the recent history of medicine,
of the recent history of medicine,
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纵观医疗药物的历史，
00:24
we've thought about illness and treatment
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我们对于疾病和药物治疗的观念
00:28
in terms of a profoundly simple model.
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还停留在一个非常简单的模型上。
00:31
In fact, the model is so simple
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事实上这个模型简单到
00:34
that you could summarize it in six words:
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可以用六个英语单词概括：
00:37
have disease, take pill, kill something.
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生病，吃药，杀死一些东西。
00:43
Now, the reason
for the dominance of this model
for the dominance of this model
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这个简单的模型占据主导地位
00:47
is of course the antibiotic revolution.
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原因显然是由于抗生素革命带来的。
00:50
Many of you might not know this,
but we happen to be celebrating
but we happen to be celebrating
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可能很少有人知道，
我们前不久
我们前不久
00:53
the hundredth year of the introduction
of antibiotics into the United States.
of antibiotics into the United States.
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刚刚庆祝了抗生素
进入美国一百周年。
进入美国一百周年。
00:57
But what you do know
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但你们一定知道，
00:59
is that that introduction
was nothing short of transformative.
was nothing short of transformative.
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抗生素的引入简直是个重大变革。
你拿到的化学制剂，
不管是从自然提取的
不管是从自然提取的
01:04
Here you had a chemical,
either from the natural world
either from the natural world
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01:08
or artificially synthesized
in the laboratory,
in the laboratory,
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还是从实验室人工合成的，
01:11
and it would course through your body,
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服用之后它会遍布至你的全身
01:14
it would find its target,
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找到它的目标
01:17
lock into its target --
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然后锁定目标——
01:19
a microbe or some part of a microbe --
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一种微生物或者它的一部分——
01:21
and then turn off a lock and a key
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通过非常精巧和特别的手段
关闭目标的某一个功能。
01:25
with exquisite deftness,
exquisite specificity.
exquisite specificity.
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01:29
And you would end up taking
a previously fatal, lethal disease --
a previously fatal, lethal disease --
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结果就是当你感染了
过去的不治之症——
过去的不治之症——
01:33
a pneumonia, syphilis, tuberculosis --
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例如肺炎，梅毒，肺结核——
01:37
and transforming that
into a curable, or treatable illness.
into a curable, or treatable illness.
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变成可以治愈的疾病。
如果你感染了肺炎，
01:42
You have a pneumonia,
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你可以服用盘尼西林，
01:44
you take penicillin,
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01:45
you kill the microbe
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你杀死了微生物，
01:47
and you cure the disease.
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你治好了疾病。
01:49
So seductive was this idea,
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多么美妙的想法，
01:52
so potent the metaphor of lock and key
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钥匙、锁的比喻多么贴切
01:56
and killing something,
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还有杀死一些东西的归纳，
01:58
that it really swept through biology.
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横扫了生物医学。
02:00
It was a transformation like no other.
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这种转变是史无前例的。
而过去100年间
02:04
And we've really spent the last 100 years
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02:07
trying to replicate that model
over and over again
over and over again
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我们一直不停的尝试复制这个模型
02:10
in noninfectious diseases,
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想要用到非感染导致的疾病上，
02:12
in chronic diseases like diabetes
and hypertension and heart disease.
and hypertension and heart disease.
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像是糖尿病、高血压、
心脏病之类的慢性病。
心脏病之类的慢性病。
02:17
And it's worked,
but it's only worked partly.
but it's only worked partly.
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有些管用，有些不行。
让我来详细说明。
02:21
Let me show you.
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02:22
You know, if you take the entire universe
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现在如果把你体内
02:25
of all chemical reactions
in the human body,
in the human body,
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所有可能的化学反应
02:29
every chemical reaction
that your body is capable of,
that your body is capable of,
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都列举出来组成一个大集合
02:32
most people think that that number
is on the order of a million.
is on the order of a million.
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大部分人都会觉得至少得上百万种反应。
02:35
Let's call it a million.
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我们假设是100万种。
02:36
And now you ask the question,
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现在你会问，
02:38
what number or fraction of reactions
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在所有药物的医学化学反应中
02:41
can actually be targeted
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有多少部分是真正能够有效锁定的?
02:43
by the entire pharmacopoeia,
all of medicinal chemistry?
all of medicinal chemistry?
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02:48
That number is 250.
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答案是250个。
其他是未知的化学领域。
02:51
The rest is chemical darkness.
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02:54
In other words, 0.025 percent
of all chemical reactions in your body
of all chemical reactions in your body
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换句话说
你体内只有 0.025% 的化学反应
03:00
are actually targetable
by this lock and key mechanism.
by this lock and key mechanism.
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适用于现在的钥匙和锁的机制。
如果你将人体生理学
03:05
You know, if you think
about human physiology
about human physiology
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03:08
as a vast global telephone network
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看成是一个巨大的全球的电话网络，
03:12
with interacting nodes
and interacting pieces,
and interacting pieces,
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有着相互作用的节点和部分，
那么我们所有的化学药物加起来
03:16
then all of our medicinal chemistry
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03:19
is operating on one tiny corner
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也只是占据了
03:22
at the edge, the outer edge,
of that network.
of that network.
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这个巨大网络的一个小小边角。
03:24
It's like all of our
pharmaceutical chemistry
pharmaceutical chemistry
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我们现有的药物加起来就像是
03:28
is a pole operator in Wichita, Kansas
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堪萨斯州州威奇托市的一个小小接线员
03:32
who is tinkering with about
10 or 15 telephone lines.
10 or 15 telephone lines.
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在笨拙地处理10条或15条电话线。
所以现在我们应该怎么办？
03:36
So what do we do about this idea?
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03:40
What if we reorganized this approach?
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我们是否能够重新组织现有的方式？
03:44
In fact, it turns out
that the natural world
that the natural world
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事实上，我们发现自然界
03:47
gives us a sense of how one
might think about illness
might think about illness
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为我们提供了一个完全不一样的视角
去看待疾病。
03:52
in a radically different way,
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03:54
rather than disease, medicine, target.
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跟“疾病，药物，目标”模式不同。
自然界是自下向上的
一层一层发展起来的，
一层一层发展起来的，
03:59
In fact, the natural world
is organized hierarchically upwards,
is organized hierarchically upwards,
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04:02
not downwards, but upwards,
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不是自上向下，而是自下而上。
04:04
and we begin with a self-regulating,
semi-autonomous unit called a cell.
semi-autonomous unit called a cell.
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我们首先有了一些能够自我控制、
半自主的单位，称为细胞。
半自主的单位，称为细胞。
这些基本的单元
04:11
These self-regulating,
semi-autonomous units
semi-autonomous units
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04:14
give rise to self-regulating,
semi-autonomous units called organs,
semi-autonomous units called organs,
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结合在一起组成了器官，
04:19
and these organs coalesce
to form things called humans,
to form things called humans,
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这些器官有机地组合在一起，构成了人
这最终构造了这个丰富的生态系统。
04:23
and these organisms
ultimately live in environments,
ultimately live in environments,
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04:27
which are partly self-regulating
and partly semi-autonomous.
and partly semi-autonomous.
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这个系统也是能够自我约束，
是半自主的。
是半自主的。
这种层次化的模式的好处在于，
04:32
What's nice about this scheme,
this hierarchical scheme
this hierarchical scheme
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04:35
building upwards rather than downwards,
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相对于自上向下的模式而言，
04:38
is that it allows us
to think about illness as well
to think about illness as well
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它带给了我们一个完全不同的视角
04:41
in a somewhat different way.
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去看待疾病。
拿癌症作为例子。
04:44
Take a disease like cancer.
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自从1950年代以来，
04:48
Since the 1950s,
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04:49
we've tried rather desperately to apply
this lock and key model to cancer.
this lock and key model to cancer.
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我们竭尽全力用锁和钥匙的模型去攻克癌症。
04:54
We've tried to kill cells
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我们用了大量的靶向疗法
04:57
using a variety of chemotherapies
or targeted therapies,
or targeted therapies,
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和放化疗手段去杀死细胞，
05:02
and as most of us know, that's worked.
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我们都知道这取得了一些效果。
05:04
It's worked for diseases like leukemia.
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对于白血病这样的疾病有效。
05:06
It's worked for some forms
of breast cancer,
of breast cancer,
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对于某些类型的乳腺癌有效，
05:09
but eventually you run
to the ceiling of that approach.
to the ceiling of that approach.
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但是最终你走到了这条路的尽头。
05:12
And it's only in the last 10 years or so
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直到近10年前左右
05:15
that we've begun to think
about using the immune system,
about using the immune system,
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我们开始考虑利用自身的免疫系统，
05:18
remembering that in fact the cancer cell
doesn't grow in a vacuum.
doesn't grow in a vacuum.
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毕竟癌细胞并不是长在真空里的。
05:21
It actually grows in a human organism.
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癌细胞确实是长在人体器官里的。
05:23
And could you use the organismal capacity,
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你可以用器官自身的机制来防御。
05:25
the fact that human beings
have an immune system, to attack cancer?
have an immune system, to attack cancer?
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所以能够借用人类自身的
免疫系统去攻击癌细胞？
免疫系统去攻击癌细胞？
05:29
In fact, it's led to the some of the most
spectacular new medicines in cancer.
spectacular new medicines in cancer.
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事实上这个思维转变诞生了
一些非常令人瞩目的新药物。
一些非常令人瞩目的新药物。
最后还有环境级别的问题，不是么？
05:34
And finally there's the level
of the environment, isn't there?
of the environment, isn't there?
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05:38
You know, we don't think of cancer
as altering the environment.
as altering the environment.
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当我们改变环境的时候，
没想过癌症的问题
没想过癌症的问题
05:41
But let me give you an example
of a profoundly carcinogenic environment.
of a profoundly carcinogenic environment.
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但是让我来给你展示一个
高度致癌物环境。
高度致癌物环境。
05:46
It's called a prison.
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称之为「囚禁」。
05:48
You take loneliness, you take depression,
you take confinement,
you take confinement,
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你拿来孤独，你加上沮丧，
再加上约束，
再加上约束，
05:53
and you add to that,
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都加上，
05:55
rolled up in a little
white sheet of paper,
white sheet of paper,
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放在一张白纸上卷起来，
05:59
one of the most potent neurostimulants
that we know, called nicotine,
that we know, called nicotine,
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加上一种最为有效的
神经刺激物，尼古丁，
神经刺激物，尼古丁，
06:02
and you add to that one of the most potent
addictive substances that you know,
addictive substances that you know,
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你把这种最容易成瘾的
致癌成分放进来，
致癌成分放进来，
06:07
and you have
a pro-carcinogenic environment.
a pro-carcinogenic environment.
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你就有了一个容易
引发癌症的环境。
引发癌症的环境。
06:11
But you can have anti-carcinogenic
environments too.
environments too.
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但是你也可以拥有抗癌症环境。
06:14
There are attempts to create milieus,
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可以尝试自己创造一个小环境，
06:16
change the hormonal milieu
for breast cancer, for instance.
for breast cancer, for instance.
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例如为了预防乳腺癌
而改变荷尔蒙环境。
而改变荷尔蒙环境。
06:20
We're trying to change the metabolic
milieu for other forms of cancer.
milieu for other forms of cancer.
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我们正在尝试为其它癌症
而改变新陈代谢环境。
而改变新陈代谢环境。
06:23
Or take another disease, like depression.
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或者像是抑郁这样的疾病。
06:26
Again, working upwards,
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再次重申，自下向上地，
06:29
since the 1960s and 1970s,
we've tried, again, desperately
we've tried, again, desperately
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从1960和1970年代开始，
我们当时还是竭力地
我们当时还是竭力地
06:33
to turn off molecules
that operate between nerve cells --
that operate between nerve cells --
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尝试去关闭神经细胞
之间运行的分子
之间运行的分子
06:37
serotonin, dopamine --
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如血清素、多巴胺
06:39
and tried to cure depression that way,
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尝试从这个角度治疗抑郁。
06:41
and that's worked,
but then that reached the limit.
but then that reached the limit.
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一开始有一些进展，
但是很快就走到了尽头。
但是很快就走到了尽头。
06:45
And we now know that what you
really probably need to do
really probably need to do
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现在我们知道，更好的方式
06:47
is to change the physiology
of the organ, the brain,
of the organ, the brain,
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或许是改变组织的生理状况，
也就是大脑的结构
也就是大脑的结构
06:50
rewire it, remodel it,
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改变大脑的结构和连接，
06:52
and that, of course,
we know study upon study has shown
we know study upon study has shown
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而且，理所当然的，我们注意到
06:55
that talk therapy does exactly that,
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谈话疗法能够有效的做到这一点，
06:57
and study upon study
has shown that talk therapy
has shown that talk therapy
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并且后续的研究也表明
06:59
combined with medicines, pills,
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谈话疗法和药物质量的结合
07:02
really is much more effective
than either one alone.
than either one alone.
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要比单独使用任何一种方法
都要更加有效。
都要更加有效。
我们能否构想出一种
能够改变抑郁的浸入式的环境？
能够改变抑郁的浸入式的环境？
07:05
Can we imagine a more immersive
environment that will change depression?
environment that will change depression?
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07:09
Can you lock out the signals
that elicit depression?
that elicit depression?
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你能够完全隔绝抑郁
发出的刺激信号吗？
发出的刺激信号吗？
07:13
Again, moving upwards along this
hierarchical chain of organization.
hierarchical chain of organization.
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再次重申，需要顺着组织构成的
层次自下向上地考虑。
层次自下向上地考虑。
07:19
What's really at stake perhaps here
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在这里最重要的事情，
07:22
is not the medicine itself but a metaphor.
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可能不是有药物本身，
而是比喻的说法
而是比喻的说法
07:25
Rather than killing something,
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相比于现在的“杀死某些东西”，
07:27
in the case of the great
chronic degenerative diseases --
chronic degenerative diseases --
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对于大量的慢性退行性疾病——
07:31
kidney failure, diabetes,
hypertension, osteoarthritis --
hypertension, osteoarthritis --
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肾衰竭、糖尿病、高血压、关节炎
07:35
maybe what we really need to do is change
the metaphor to growing something.
the metaphor to growing something.
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或许我们要做的反而
应该是“培养一些东西”。
应该是“培养一些东西”。
07:38
And that's the key, perhaps,
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而这之中的关键，
07:40
to reframing our thinking about medicine.
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可能就是重塑我们的药物观。
07:43
Now, this idea of changing,
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这个想法，
07:46
of creating a perceptual
shift, as it were,
shift, as it were,
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即感知认识上的转变，
07:49
came home to me to roost in a very
personal manner about 10 years ago.
personal manner about 10 years ago.
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来自我10年前一次个人经历。
07:52
About 10 years ago --
I've been a runner most of my life --
I've been a runner most of my life --
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大概10年前——我常年跑步——
07:55
I went for a run, a Saturday morning run,
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我在周六早上照常跑了一会儿，
07:57
I came back and woke up
and I basically couldn't move.
and I basically couldn't move.
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回来后从床上醒来时
发现腿动不了了。
发现腿动不了了。
07:59
My right knee was swollen up,
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我的右膝盖肿得厉害
08:01
and you could hear that ominous crunch
of bone against bone.
of bone against bone.
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而且能够听见骨头跟骨头摩擦的声音。
08:06
And one of the perks of being a physician
is that you get to order your own MRIs.
is that you get to order your own MRIs.
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做医生有一样好处，
便是可以自己预约MRI扫描。
便是可以自己预约MRI扫描。
08:11
And I had an MRI the next week,
and it looked like that.
and it looked like that.
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第二周我做了MRI扫描，
结果就像展示的那样
结果就像展示的那样
08:15
Essentially, the meniscus of cartilage
that is between bone
that is between bone
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简单的说，
骨头之间的半月型软骨层
骨头之间的半月型软骨层
08:19
had been completely torn
and the bone itself had been shattered.
and the bone itself had been shattered.
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已经被彻底的磨掉了，
骨头也受损了。
骨头也受损了。
08:22
Now, if you're looking at me
and feeling sorry,
and feeling sorry,
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现在，如果你为我感到难过，
08:25
let me tell you a few facts.
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那么让我来告诉你一些信息。
08:27
If I was to take an MRI
of every person in this audience,
of every person in this audience,
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如果给在做的所有人都做一次MRI，
08:31
60 percent of you would show signs
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在座各位中60%以上的人
08:33
of bone degeneration
and cartilage degeneration like this.
and cartilage degeneration like this.
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会看到跟我一样的
骨头和软骨退化的迹象。
骨头和软骨退化的迹象。
08:36
85 percent of all women by the age of 70
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70岁以上女性中有85%的人
08:40
would show moderate to severe
cartilage degeneration.
cartilage degeneration.
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会出现中度或重度的软骨退化。
08:43
50 to 60 percent
of the men in this audience
of the men in this audience
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在座的男性中有50%到60%
08:45
would also have such signs.
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已经出现了这种症状。
08:47
So this is a very common disease.
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所以这是非常常见的疾病。
08:48
Well, the second perk of being a physician
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作为医生的第二个好处
08:51
is that you can get
to experiment on your own ailments.
to experiment on your own ailments.
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是你可以自己给自己治病。
08:54
So about 10 years ago we began,
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所以大约10年前，我们开始着手，
08:56
we brought this process
into the laboratory,
into the laboratory,
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把这些方法带到实验室。
08:58
and we began to do simple experiments,
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并且开始做一些简单的实验，
09:00
mechanically trying
to fix this degeneration.
to fix this degeneration.
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呆板地想解决退化的问题。
09:03
We tried to inject chemicals
into the knee spaces of animals
into the knee spaces of animals
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我们尝试了将一些化学成分
注入动物的关节囊
注入动物的关节囊
09:08
to try to reverse cartilage degeneration,
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尝试反转退化现象，
09:10
and to put a short summary
on a very long and painful process,
on a very long and painful process,
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经过了痛苦而漫长的尝试，
结果简单概括就是，
结果简单概括就是，
09:15
essentially it came to naught.
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基本上没有任何效果。
09:17
Nothing happened.
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一点用都没有，什么都没发生。
09:18
And then about seven years ago,
we had a research student from Australia.
we had a research student from Australia.
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直到大概7年前，
我们来了个澳大利亚研究生。
我们来了个澳大利亚研究生。
09:23
The nice thing about Australians
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澳洲人的优点
09:25
is that they're habitually used to
looking at the world upside down.
looking at the world upside down.
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就是他们习惯把世界倒转来看。
09:28
(Laughter)
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（笑声）
09:29
And so Dan suggested to me, "You know,
maybe it isn't a mechanical problem.
maybe it isn't a mechanical problem.
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这个名叫丹的学生跟我说，
“或许这不是机能问题，”
“或许这不是机能问题，”
09:33
Maybe it isn't a chemical problem.
Maybe it's a stem cell problem."
Maybe it's a stem cell problem."
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“或许也不是化学问题，
或许是干细胞问题。”
或许是干细胞问题。”
换句话说，他有两个假想：
09:39
In other words, he had two hypotheses.
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09:41
Number one, there is such a thing
as a skeletal stem cell --
as a skeletal stem cell --
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第一，假設真有这样的骨干细胞--
09:45
a skeletal stem cell that builds up
the entire vertebrate skeleton,
the entire vertebrate skeleton,
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构造了整个脊椎骨架，
09:49
bone, cartilage and the fibrous
elements of skeleton,
elements of skeleton,
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骨头、软骨组织、
以及骨架周边的支持物，
以及骨架周边的支持物，
09:51
just like there's a stem cell in blood,
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就像是血液中的造血干细胞，
09:53
just like there's a stem cell
in the nervous system.
in the nervous system.
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就像是神进系统中的神经干细胞。
09:55
And two, that maybe that, the degeneration
or dysfunction of this stem cell
or dysfunction of this stem cell
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假设二，可能是因为
骨干细胞的退化或失能，
骨干细胞的退化或失能，
09:59
is what's causing osteochondral arthritis,
a very common ailment.
a very common ailment.
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导致了关节炎这种常见的疾病。
10:03
So really the question was,
were we looking for a pill
were we looking for a pill
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所以问题根源可能在于
我们一直在找治疗药物
我们一直在找治疗药物
10:06
when we should have really
been looking for a cell.
been looking for a cell.
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但是实际上我们应该寻找的是这种细胞。
10:08
So we switched our models,
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于是我们换用了新模型，
10:11
and now we began
to look for skeletal stem cells.
to look for skeletal stem cells.
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开始寻找这种骨干细胞。
长话短说，
10:15
And to cut again a long story short,
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10:18
about five years ago,
we found these cells.
we found these cells.
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大概五年前我们终于找到了。
10:21
They live inside the skeleton.
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它们存在于骨架内部。
10:24
Here's a schematic and then
a real photograph of one of them.
a real photograph of one of them.
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图上是原理图和真实的骨头
10:27
The white stuff is bone,
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白色的是骨头，
10:29
and these red columns that you see
and the yellow cells
and the yellow cells
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你看到的红色管狀的，黄色的细胞
10:32
are cells that have arisen
from one single skeletal stem cell --
from one single skeletal stem cell --
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都是由一个单独的
干细胞生长而来的——
干细胞生长而来的——
10:35
columns of cartilage, columns of bone
coming out of a single cell.
coming out of a single cell.
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软骨、骨组织都来自同一个干细胞，
10:38
These cells are fascinating.
They have four properties.
They have four properties.
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这些细胞太神奇了，
它们有四个特点。
它们有四个特点。
10:42
Number one is that they live
where they're expected to live.
where they're expected to live.
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第一，它们就存在于
我们预期的位置。
我们预期的位置。
10:45
They live just underneath
the surface of the bone,
the surface of the bone,
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它们就存在于骨头表面之下，
10:48
underneath cartilage.
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存在于软骨组织下面。
10:49
You know, in biology,
it's location, location, location.
it's location, location, location.
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你或许知道在生物学上，
位置是很重要的，
位置是很重要的，
10:52
And they move into the appropriate areas
and form bone and cartilage.
and form bone and cartilage.
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所以这些干细胞移动到了
合适的位置方便生成骨和软骨。
合适的位置方便生成骨和软骨。
10:56
That's one.
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这是第一个特点。
10:58
Here's an interesting property.
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还有一个有意思的特点。
10:59
You can take them out
of the vertebrate skeleton,
of the vertebrate skeleton,
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你可以将这些细胞从
脊椎动物骨架中分离出来
脊椎动物骨架中分离出来
11:02
you can culture them
in petri dishes in the laboratory,
in petri dishes in the laboratory,
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放在实验室的培养皿中，
11:04
and they are dying to form cartilage.
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它们会拼命的构造软骨组织。
11:06
Remember how we couldn't
form cartilage for love or money?
form cartilage for love or money?
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要知道我们无论用多少钱和
爱都没办法生成软骨。
爱都没办法生成软骨。
11:09
These cells are dying to form cartilage.
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它们会拼命的构造软骨组织。
11:11
They form their own furls
of cartilage around themselves.
of cartilage around themselves.
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它们通过构造软骨组织把自己卷起来。
11:14
They're also, number three,
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第三点，
11:16
the most efficient repairers
of fractures that we've ever encountered.
of fractures that we've ever encountered.
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它们是我们见过的最神速的修补匠。
11:20
This is a little bone,
a mouse bone that we fractured
a mouse bone that we fractured
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这是一个老鼠的骨头
被我们掰断了
被我们掰断了
11:23
and then let it heal by itself.
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然后任由其自然恢复。
11:25
These stem cells have come in
and repaired, in yellow, the bone,
and repaired, in yellow, the bone,
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骨干细胞出现
修复了骨头（黄色部分）
修复了骨头（黄色部分）
11:28
in white, the cartilage,
almost completely.
almost completely.
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修复了软骨（白色部分）
基本上完好如初。
基本上完好如初。
11:31
So much so that if you label them
with a fluorescent dye
with a fluorescent dye
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所以基本上
如果你给这些细胞染上颜色
如果你给这些细胞染上颜色
11:34
you can see them like some kind
of peculiar cellular glue
of peculiar cellular glue
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你就能够看到
它们就像是某种细胞胶水
它们就像是某种细胞胶水
11:38
coming into the area of a fracture,
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填充到骨折的地方，
11:40
fixing it locally
and then stopping their work.
and then stopping their work.
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修复好，然后收工。
11:43
Now, the fourth one is the most ominous,
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现在，第四点也是最不好的，
11:45
and that is that their numbers
decline precipitously,
decline precipitously,
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这些细胞的数量
下降地出乎意料的快，
下降地出乎意料的快，
11:49
precipitously, tenfold,
fiftyfold, as you age.
fiftyfold, as you age.
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随着你的年龄
十倍或者十五倍的减少。
十倍或者十五倍的减少。
11:54
And so what had happened, really,
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这里最重要的，
11:56
is that we found ourselves
in a perceptual shift.
in a perceptual shift.
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是我们发现自己的观念转变了。
11:59
We had gone hunting for pills
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我们一开始是为了寻找药物而努力
12:01
but we ended up finding theories.
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最后却发现了新的理论。
12:04
And in some ways
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从某个角度看，
12:05
we had hooked ourselves
back onto this idea:
back onto this idea:
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我们回到了一开始的想法上：
12:08
cells, organisms, environments,
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细胞，组织，环境，
12:11
because we were now thinking
about bone stem cells,
about bone stem cells,
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现在我们从骨干细胞的角度出发
12:13
we were thinking about arthritis
in terms of a cellular disease.
in terms of a cellular disease.
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我们开始将关节炎
当作是细胞疾病来看待。
当作是细胞疾病来看待。
接下来的问题就是
那么器官级别的呢？
那么器官级别的呢？
12:17
And then the next question was,
are there organs?
are there organs?
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12:20
Can you build this
as an organ outside the body?
as an organ outside the body?
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我们能在体外培育这样的器官么？
12:22
Can you implant cartilage
into areas of trauma?
into areas of trauma?
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我们能够在磨损的位置直接植入软骨么？
12:26
And perhaps most interestingly,
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还有更加有趣的，
12:28
can you ascend right up
and create environments?
and create environments?
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我们能否继续向上
创造出适宜的环境？
创造出适宜的环境？
12:30
You know, we know
that exercise remodels bone,
that exercise remodels bone,
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当然，我们都知道运动可以重塑骨骼，
12:33
but come on, none of us
is going to exercise.
is going to exercise.
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但是得了吧，没人愿意运动。
12:36
So could you imagine ways of passively
loading and unloading bone
loading and unloading bone
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所以你想过有一天
你能把骨头拆下来再装回去
你能把骨头拆下来再装回去
12:41
so that you can recreate
or regenerate degenerating cartilage?
or regenerate degenerating cartilage?
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这样你就可以重塑
已经退化的软骨组织了？
已经退化的软骨组织了？
12:46
And perhaps more interesting,
and more importantly,
and more importantly,
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最有意思、也是最重要的，
12:48
the question is, can you apply this model
more globally outside medicine?
more globally outside medicine?
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这个模型能否
更加广泛的在医疗界推广？
更加广泛的在医疗界推广？
12:52
What's at stake, as I said before,
is not killing something,
is not killing something,
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重要的是，如我之前所言，
不是杀死什么
不是杀死什么
12:56
but growing something.
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而是培育什么
12:58
And it raises a series of, I think,
some of the most interesting questions
some of the most interesting questions
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这进一步的引发了
一系列有趣的问题，
一系列有趣的问题，
13:03
about how we think
about medicine in the future.
about medicine in the future.
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影响到我们未来对于药物观念。
13:07
Could your medicine
be a cell and not a pill?
be a cell and not a pill?
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（未来）你的药物有没有可能
不是药片而是细胞？
不是药片而是细胞？
13:10
How would we grow these cells?
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我们如何培育这些细胞？
13:13
What we would we do to stop
the malignant growth of these cells?
the malignant growth of these cells?
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我们如何阻止这些细胞的恶性增殖？
13:16
We heard about the problems
of unleashing growth.
of unleashing growth.
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我们已经听说了不受控的细胞增殖。
13:20
Could we implant
suicide genes into these cells
suicide genes into these cells
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我们能否在细胞中植入一些自杀基因
13:23
to stop them from growing?
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来阻止它们的增长？
13:25
Could your medicine be an organ
that's created outside the body
that's created outside the body
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未来你的药物有没有可能
就是一个身体器官
就是一个身体器官
13:29
and then implanted into the body?
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在体外培育然后植入体内？
13:30
Could that stop some of the degeneration?
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这样能否阻止器官的老化？
13:33
What if the organ needed to have memory?
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如果这些器官需要记忆呢？
13:35
In cases of diseases of the nervous system
some of those organs had memory.
some of those organs had memory.
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例如神经系统中的一些器官保存了记忆。
13:40
How could we implant
those memories back in?
those memories back in?
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我们怎么把这些记忆移植回来？
13:42
Could we store these organs?
258
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我们能保存这些器官么？
13:44
Would each organ have to be developed
for an individual human being
for an individual human being
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这些器官能否根据
患者的不同而分别培育
患者的不同而分别培育
13:47
and put back?
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然后再移植回去？
13:50
And perhaps most puzzlingly,
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最后可能是最令人困惑的，
13:53
could your medicine be an environment?
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你的药物可以是环境么？
13:56
Could you patent an environment?
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治疗的环境能否
（像药物一样）申请专利？
（像药物一样）申请专利？
13:57
You know, in every culture,
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每个人类文化里
14:01
shamans have been using
environments as medicines.
environments as medicines.
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都有巫师这样的角色，
将环境视为治疗的药物。
将环境视为治疗的药物。
14:04
Could we imagine that for our future?
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你能想象我们未来是那样的么？
14:08
I've talked a lot about models.
I began this talk with models.
I began this talk with models.
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我们聊了很多模型，
也是从模型开始说起的。
也是从模型开始说起的。
14:11
So let me end with some thoughts
about model building.
about model building.
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让我在结束的时候
再聊一聊如何构造模型。
再聊一聊如何构造模型。
14:14
That's what we do as scientists.
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我们科学家就是做这个的。
14:16
You know, when an architect
builds a model,
builds a model,
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你知道，当建筑师建造一个模型，
14:19
he or she is trying to show you
a world in miniature.
a world in miniature.
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他（她）会尝试用微型图
向你展示想象的世界
向你展示想象的世界
14:22
But when a scientist is building a model,
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但是当一个科学家构造模型的时候，
14:25
he or she is trying to show you
the world in metaphor.
the world in metaphor.
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他（她）给你展示的是世界的隐喻。
14:29
He or she is trying to create
a new way of seeing.
a new way of seeing.
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他（她）尝试从新的角度看这个世界。
14:33
The former is a scale shift.
The latter is a perceptual shift.
The latter is a perceptual shift.
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前者是比例的变化，
后者是观念的变化。
后者是观念的变化。
14:38
Now, antibiotics created
such a perceptual shift
such a perceptual shift
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现在，抗生素创造了观念的变化
14:43
in our way of thinking about medicine
that it really colored, distorted,
that it really colored, distorted,
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非常成功地改变了过去
百年来我们对药物的看法
百年来我们对药物的看法
14:47
very successfully, the way we've thought
about medicine for the last hundred years.
about medicine for the last hundred years.
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以前的看法是过度夸张和歪曲事实。
14:52
But we need new models
to think about medicine in the future.
to think about medicine in the future.
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但是未来我们需要新的模型。
14:56
That's what's at stake.
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这是最重要的。
14:59
You know, there's
a popular trope out there
a popular trope out there
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你知道的，现在有种论调很流行
15:02
that the reason we haven't had
the transformative impact
the transformative impact
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说我们之所以在疾病的治疗上
15:06
on the treatment of illness
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没有改革性的影响
15:08
is because we don't have
powerful-enough drugs,
powerful-enough drugs,
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是因为我们还没有找到足够强大的药物，
15:11
and that's partly true.
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这倒说对了一半。
15:14
But perhaps the real reason is
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但是可能真正的原因是
15:15
that we don't have powerful-enough
ways of thinking about medicines.
ways of thinking about medicines.
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我们对药物没有足够强大的思维模式。
15:20
It's certainly true that
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有一点是肯定的
15:23
it would be lovely to have new medicines.
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有新的药物自然是令人喜悦的。
15:26
But perhaps what's really at stake
are three more intangible M's:
are three more intangible M's:
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但是可能当前最紧要的
还是这三个难以理解的" Ｍ "
还是这三个难以理解的" Ｍ "
15:31
mechanisms, models, metaphors.
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机制、模型、隐喻。
15:35
Thank you.
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感谢大家。
15:36
(Applause)
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（掌声）
Chris Anderson：我真的喜欢这种隐喻方法。
15:45
Chris Anderson:
I really like this metaphor.
I really like this metaphor.
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15:49
How does it link in?
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它们怎么联系起来的？
15:50
There's a lot of talk in technologyland
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科技领域有很多的讨论
15:53
about the personalization of medicine,
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都提到了个体化医疗，
15:55
that we have all this data
and that medical treatments of the future
and that medical treatments of the future
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说我们汇集所有的数据，然后
15:59
will be for you specifically,
your genome, your current context.
your genome, your current context.
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未来的药物会基于你的基因组
和所处环境量身定做
和所处环境量身定做
16:03
Does that apply to this model
you've got here?
you've got here?
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这种说法跟你提到的模型是契合的吗？
16:07
Siddhartha Mukherjee:
It's a very interesting question.
It's a very interesting question.
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SM：这个问题很有意思。
16:10
We've thought about
personalization of medicine
personalization of medicine
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我们已经从基因角度考虑个体化医疗
16:12
very much in terms of genomics.
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有一段时间了。
16:14
That's because the gene
is such a dominant metaphor,
is such a dominant metaphor,
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那是因为基因本身就是主流的隐喻，
16:16
again, to use that same word,
in medicine today,
in medicine today,
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同样也是这个词，在今天的医疗界
16:19
that we think the genome will drive
the personalization of medicine.
the personalization of medicine.
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我们认为基因组会主导
个体化医疗的进展。
个体化医疗的进展。
16:23
But of course the genome
is just the bottom
is just the bottom
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但是显然的，基因组这个概念
16:26
of a long chain of being, as it were.
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只是这个链条最基础的部分。
16:30
That chain of being, really the first
organized unit of that, is the cell.
organized unit of that, is the cell.
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这个链条最开始真正有
组织的单元是“细胞”。
组织的单元是“细胞”。
16:34
So, if we are really going to deliver
in medicine in this way,
in medicine in this way,
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所以如果我们真的要开始个体化医疗了，
16:37
we have to think of personalizing
cellular therapies,
cellular therapies,
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我们需要考虑的是个性化的" 细胞疗法 "，
16:40
and then personalizing
organ or organismal therapies,
organ or organismal therapies,
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然后是个性化的组织和器官疗法，
16:43
and ultimately personalizing
immersion therapies for the environment.
immersion therapies for the environment.
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最后的最后是个性化的
浸入式的环境疗法。
浸入式的环境疗法。
16:47
So I think at every stage, you know --
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我觉得現在每个阶段...你知道
16:50
there's that metaphor,
there's turtles all the way.
there's turtles all the way.
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用一个比喻可以形容 -“龟速”。
16:52
Well, in this, there's
personalization all the way.
personalization all the way.
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也因如此，才可以做到醫療个性化。
16:55
CA: So when you say
medicine could be a cell
medicine could be a cell
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CA：所以当你说未来的药物是细胞
16:58
and not a pill,
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而不是药物的时候
17:00
you're talking about
potentially your own cells.
potentially your own cells.
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你说的是有可能是自己的细胞？
17:02
SM: Absolutely.
CA: So converted to stem cells,
CA: So converted to stem cells,
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SM：绝对地。
CA：转换成干细胞，
CA：转换成干细胞，
17:04
perhaps tested against all kinds
of drugs or something, and prepared.
of drugs or something, and prepared.
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可能还会跟各种药物或者
别的东西做测试，然后准备好。
别的东西做测试，然后准备好。
17:09
SM: And there's no perhaps.
This is what we're doing.
This is what we're doing.
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SM：这不是可能。我们现在就在做。
17:11
This is what's happening,
and in fact, we're slowly moving,
and in fact, we're slowly moving,
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这是正在发生的事情，
实际上，我们正在慢慢取得进展。
实际上，我们正在慢慢取得进展。
17:15
not away from genomics,
but incorporating genomics
but incorporating genomics
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并没有脱离基因组，
而是跟基因组结合
而是跟基因组结合
17:19
into what we call multi-order,
semi-autonomous, self-regulating systems,
semi-autonomous, self-regulating systems,
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我们称之为多层级、半自动、自制系统，
17:24
like cells, like organs,
like environments.
like environments.
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像是细胞、器官、环境。
17:26
CA: Thank you so much.
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CA：非常感谢。
17:28
SM: Pleasure. Thanks.
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SM：很荣幸。谢谢。
ABOUT THE SPEAKER
Siddhartha Mukherjee - Cancer physician and writerWhen he’s not ferreting out the links between stem cells and malignant blood disease, Siddhartha Mukherjee writes and lectures on the history (and future) of medicine.
Why you should listen
While discussing a diagnosis with a patient, Siddhartha Mukherjee realized that there were no easy answers to the question, “What is cancer?” Faced with his hesitation, Mukherjee decided to do something about it.
Over the next six years, Mukherjee wrote the influential, Pulitzer-winning The Emperor of All Maladies, a 4,000-year “biography” of cancer. He collaborated with Ken Burns on a six-hour documentary for PBS based on his book, updating the story with recent discoveries in oncology.
In his new TED Book, The Laws of Medicine, he examines the three principles that govern modern medicine -- and every profession that confronts uncertainty and wonder.
Siddhartha Mukherjee | Speaker | TED.com