Bonnie Bassler: The secret, social lives of bacteria

296,679 views ・ 2009-04-08

TED


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翻译人员: Zhenyu Zhou 校对人员: elyse lin
细菌是地球上最古老的生物.
00:19
Bacteria are the oldest living organisms on the earth.
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00:21
They've been here for billions of years,
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它们已经存在数十亿年了
00:23
and what they are are single-celled microscopic organisms.
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它们是单细胞微生物
00:27
So they're one cell
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它们特征是只有一个细胞
00:29
and they have this special property that they only have one piece of DNA.
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还有就是它们只有一份DNA
00:32
So they have very few genes and genetic information
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它们只有少量基因,
和遗传信息来编码它们表达的特性。
00:35
to encode all of the traits that they carry out.
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00:38
And the way bacteria make a living is that they consume nutrients
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细菌生存的方法
是不断从环境中吸取养分©
00:42
from the environment,
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00:43
they grow to twice their size,
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在成长到两倍的体积后,它们从中一分为二
00:45
they cut themselves down in the middle,
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分裂为两个细胞,如此循环
00:47
and one cell becomes two, and so on and so on.
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00:49
They just grow and divide and grow and divide -- so a kind of boring life,
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它们不停得生长、分裂,然后再生长、再分裂—过着有点乏味的生活。
00:53
except that what I would argue is that you have an amazing interaction
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但是,今天我想告诉你
你与这些细菌有着惊人的互动关系
00:57
with these critters.
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00:58
I know you guys think of yourself as humans,
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我知道你认为你自己是人类,而这可能也是我如何看你们的
01:00
and this is sort of how I think of you.
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在这里的是
01:02
This man is supposed to represent a generic human being,
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一个一般人类的代表
01:05
and all of the circles in that man are all the cells that make up your body.
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在他身上所有的圆圈代表着各个组成人体的细胞
01:09
There's about a trillion human cells that make each one of us who we are
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每个人体大约是由一兆个人体细胞所组成
它们让我们能完成各种各样我们想做的事情
01:13
and able to do all the things that we do.
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但是,你一生中的每时每刻,
01:16
But you have 10 trillion bacterial cells in you or on you
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有大约十兆个细菌细胞生活在你的体内体表。
01:19
at any moment in your life.
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01:20
So, 10 times more bacterial cells than human cells on a human being.
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所以,有十倍于人体细胞的细菌细胞
生活在一个人身上
01:25
And, of course, it's the DNA that counts,
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同理, 我们要算一下DNA
01:27
so here's all the A, T, Gs and Cs that make up your genetic code
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这是所有的 A, T, G 和 C (腺嘌呤, 胸腺嘧啶, 鸟嘌呤, 胞嘧啶)
组成你的基因密码, 赋予你所有的魅力特征.
01:30
and give you all your charming characteristics.
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你有3万左右的遗传基因,
01:33
You have about 30,000 genes.
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01:34
Well, it turns out you have 100 times more bacterial genes
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而围绕你的细菌的遗传基因数量是你自己的100倍
它们在你的身体内部和表面上中始终扮演着重要的角色。
01:38
playing a role in you or on you all of your life.
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01:41
So at the best, you're 10 percent human; more likely, about one percent human,
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最乐观的看法是: 你只是"10分之1人",
事实上"100分之一人"更准确,
01:46
depending on which of these metrics you like.
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取决于你更喜欢用哪个尺度来衡量.
01:48
I know you think of yourself as human beings,
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我知道你自认为是一个"人类",
但在我眼里你是90%~99%的细菌.
01:51
but I think of you as 90 or 99 percent bacterial.
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01:54
(Laughter)
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(笑)
01:55
And these bacteria are not passive riders.
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这些细菌不是顺从的乘客,
01:58
These are incredibly important; they keep us alive.
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他们难以置信得重要, 他们让我们活着.
02:01
They cover us in an invisible body armor
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它们是我们身上的无形盔甲
02:04
that keeps environmental insults out so that we stay healthy.
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阻断来之环境的伤害
保持我们的健康.
02:08
They digest our food, they make our vitamins,
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它们消化食物, 制造维他命,
02:10
they actually educate your immune system to keep bad microbes out.
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它们还指导你的免疫系统
将有害微生物阻挡在体外。
它们尽心尽职干活
02:15
So they do all these amazing things
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帮助我们,维护我们的生命。
02:17
that help us and are vital for keeping us alive,
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02:20
and they never get any press for that.
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却从没有因此得到过报道.
02:22
But they get a lot of press because they do a lot of terrible things as well.
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反而却因为它们同时做的许多
坏事而时常见报。
地球上有无数种细菌
02:27
So there's all kinds of bacteria on the earth
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02:29
that have no business being in you or on you at any time,
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它们有些在任何时候都绝对不应该出现在你的体内体表,
然而假如你不幸遇到了, 那你一定会病得很厉害。
02:33
and if they are, they make you incredibly sick.
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02:36
And so the question for my lab
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所以, 我们实验室研究的问题是, 正是你想知道的
02:38
is whether you want to think about all the good things that bacteria do
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细菌做的所有好事或者细菌做的所有坏事。
02:41
or all the bad things that bacteria do.
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02:43
The question we had is: How could they do anything at all?
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我们曾经提出一个疑问: 它们究竟是怎么做到的?
我指的是, 它们是那么细微,
02:46
I mean, they're incredibly small.
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02:47
You have to have a microscope to see one.
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用显微镜才能看到一个。
02:49
They live this sort of boring life where they grow and divide,
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它们的生活好像只是单调乏味的成长与分裂,
02:52
and they've always been considered to be these asocial, reclusive organisms.
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而且长久以来被认为是不善社交的隐居生命体。
02:57
And so it seemed to us that they're just too small
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所以在我们看来, 它们实在是太渺小,
03:00
to have an impact on the environment
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如果单枪匹马
03:02
if they simply act as individuals.
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根本到无法对环境产生任何影响。
03:04
So we wanted to think if there couldn't be a different way that bacteria live.
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所以我们正在探讨
细菌是不是有着特殊的生存方式。
解答这个问题的线索
03:09
And the clue to this came from another marine bacterium,
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03:12
and it's a bacterium called "Vibrio fischeri."
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来自一种叫做费氏弧菌的海洋细菌。
03:15
What you're looking at on this slide is just a person from my lab
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你们在这张幻灯看到的,是我实验室的一个工作人员
03:18
holding a flask of a liquid culture of a bacterium,
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握着一瓶装满这种细菌的培养液,
这是一种来自海洋的,美丽而且无害的细菌:
03:22
a harmless, beautiful bacterium that comes from the ocean,
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"费氏弧菌".
03:25
named Vibrio fischeri.
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03:26
And this bacterium has the special property that it makes light,
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这种细菌的特性是会发光,
产生生物荧光,
03:30
so it makes bioluminescence,
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03:31
like fireflies make light.
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像萤火虫一样。
03:33
We're not doing anything to the cells here,
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我们没有对这些细胞做任何处理。
03:35
we just took the picture by turning the lights off in the room,
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我们只是把房间灯关了,然后照了这张照片,
这是我们所见到的情形。
03:38
and this is what we see.
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03:39
And what's actually interesting to us was not that the bacteria made light
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事实上, 我们感兴趣的部分
并不是细菌会不会发光,
03:43
but when the bacteria made light.
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而是细菌何时发光。
03:45
What we noticed is when the bacteria were alone,
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我们发现, 当细菌独立存在,
03:48
so when they were in dilute suspension,
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经稀释后进行悬浮培养时, 它们不发光。
03:50
they made no light.
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但一旦它们增长到一个特定数量之后
03:52
But when they grew to a certain cell number,
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所有的细菌同时发光。
03:54
all the bacteria turned on light simultaneously.
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03:57
So the question that we had is:
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于是我们想, 这些原始生物,
03:59
How can bacteria, these primitive organisms,
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到底如何得知自己是处于孤立的状态,
04:02
tell the difference from times when they're alone
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还是处在一个群体里,
04:04
and times when they're in a community,
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并且同时一起做同一件事情。
04:06
and then all do something together?
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然后我们发现了这是因为细菌能够彼此交谈,
04:09
And what we figured out is that the way they do that is they talk to each other,
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它们用的是化学语言。
04:13
and they talk with a chemical language.
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假设这是我的细菌。
04:15
So this is now supposed to be my bacterial cell.
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当它独处时, 丝毫不会发光。
04:18
When it's alone, it doesn't make any light.
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04:20
But what it does do is to make and secrete small molecules
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但是它们会制造分泌小化学分子
04:24
that you can think of like hormones,
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你可以把他想象成荷尔蒙,
04:26
and these are the red triangles.
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这里的红色三角形代表这些小分子, 当细菌独处时,
04:28
And when the bacteria are alone, the molecules just float away,
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分泌的小分子游离开来,所以不发光。
04:31
and so, no light.
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04:32
But when the bacteria grow and double
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随着这些细菌成倍增长,
04:34
and they're all participating in making these molecules,
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且全部一起制造这些分子,
这些细胞外分子的含量
04:38
the molecule, the extracellular amount of that molecule,
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04:41
increases in proportion to cell number.
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随着细胞数量的增加而增加,
04:44
And when the molecule hits a certain amount
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当这些个分子累积到一定的量之后,
04:46
that tells the bacteria how many neighbors there are,
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它们会告诉了细菌,它们周围有多少邻居,
04:49
they recognize that molecule
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细菌接受到这些信息后,
04:51
and all of the bacteria turn on light in synchrony.
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所有的细菌,同时开始发光。
04:54
And so that's how bioluminescence works --
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生物光就是这样运作的 --
04:56
they're talking with these chemical words.
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它们籍由上述的化学语言交流。
费氏弧菌的发光现象来自生物学上的原因。
04:59
The reason Vibrio fischeri is doing that comes from the biology --
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05:02
again, another plug for the animals in the ocean.
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接下来,我们再来看一个海洋生物:
费式弧菌寄生在这种乌贼的体内。
05:06
Vibrio fischeri lives in this squid.
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05:08
What you're looking at is the Hawaiian bobtail squid.
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你们现在看到的是夏威夷截尾乌贼,
这是它的腹侧,
05:11
It's been turned on its back,
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05:12
and what I hope you can see are these two glowing lobes.
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我希望你们看得到,那两个发着光的叶状突起,
05:15
These house the Vibrio fischeri cells.
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这里是费式弧菌的寄生之处,
05:18
They live in there, at high cell number.
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他们居住在这里面。
05:20
That molecule is there, and they're making light.
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他们分泌的小分子也在这里面,所以它们能够发光。
这种乌贼之所以愿意接受它们在里面胡作非为
05:23
And the reason the squid is willing to put up with these shenanigans
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是因为它需要这些亮光。
05:26
is because it wants that light.
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这种共存行为的建立基础
05:28
The way that this symbiosis works
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是因为这种小乌贼生活在夏威夷的海岸,
05:30
is that this little squid lives just off the coast of Hawaii,
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05:33
just in sort of shallow knee-deep water.
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大概只有膝盖一般深的水里。
05:35
And the squid is nocturnal,
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这种乌贼是夜行性的,
05:37
so during the day, it buries itself in the sand and sleeps.
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因此在白天它们藏在沙子里睡觉,
但是到了晚上,它们必须出来猎食。
05:41
But then at night, it has to come out to hunt.
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05:43
So on bright nights
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在有着许多星光与月光的明亮夜晚,
05:44
when there's lots of starlight or moonlight,
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这些光线可以照透乌贼所生活的地方
05:46
that light can penetrate the depth of the water the squid lives in,
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因为这里的海水只有数尺深而已
05:50
since it's just in those couple feet of water.
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这种乌贼演化出了一种活叶瓣,
05:52
What the squid has developed is a shutter that can open and close
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可以打开或关闭细菌所寄生的发光器官。
05:55
over the specialized light organ housing the bacteria.
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这种乌贼背上有一些感光装置,
05:59
And then it has detectors on its back
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可以测量有多少月光或星光照在它背上,
06:01
so it can sense how much starlight or moonlight is hitting its back.
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06:04
And it opens and closes the shutter
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然后调节它的活叶瓣。
06:06
so the amount of light coming out of the bottom,
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使从它腹部所放出的光
06:08
which is made by the bacterium,
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细菌产生的光
06:10
exactly matches how much light hits the squid's back,
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完全符合照射在乌贼背上的光强度
06:12
so the squid doesn't make a shadow.
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因此这乌贼就不会产生任何影子。
06:14
So it actually uses the light from the bacteria
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它们使用来自细菌的光,
06:17
to counter-illuminate itself in an antipredation device,
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不断调节光线,就像穿上隐身衣,
使猎食者无法看见它的阴影,
06:21
so predators can't see its shadow,
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计算它的动向,然后吃了它。
06:23
calculate its trajectory and eat it.
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就像是大海中的隐形轰炸机一般。
06:25
So this is like the stealth bomber of the ocean.
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06:27
(Laughter)
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(笑声)
06:28
But then if you think about it, this squid has this terrible problem,
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但是如果你再深入地想一下,这乌贼会有一个可怕的问题
因为在它的体内,这些黏稠的细菌会不断的增长,死亡,
06:32
because it's got this dying, thick culture of bacteria,
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06:34
and it can't sustain that.
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乌贼无法无限地维持这种状态。
06:36
And so what happens is, every morning when the sun comes up,
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因此每天早上太阳升起后,
它将自己埋藏在沙子里睡觉,
06:39
the squid goes back to sleep, it buries itself in the sand,
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它有一个与日夜周期同步的活泵
06:42
and it's got a pump that's attached to its circadian rhythm.
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当太阳升起时,它将大约95%的细菌排出体外。
06:45
And when the sun comes up, it pumps out, like, 95 percent of the bacteria.
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06:49
So now the bacteria are dilute,
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当细菌被稀释了,这些小荷尔蒙分子也随之消失,
06:51
that little hormone molecule is gone, so they're not making light.
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因此它们就不发光了,
06:54
But, of course, the squid doesn't care, it's asleep in the sand.
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但这时乌贼完全不在乎,因为它正在沙子里睡觉呢。
当白天过去,这些细菌持续分裂增长,
06:57
And as the day goes by, the bacteria double,
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它们释放出足够的这些小分子,然后又开始在晚上发光,
06:59
they release the molecule, and then light comes on at night,
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这时正好又是乌贼需要光线的时候。
07:02
exactly when the squid wants it.
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07:04
So first, we figured out how this bacterium does this,
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我们首先了解了这些细菌为什么会有这种现象,
07:07
but then we brought the tools of molecular biology to this
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然后我们使用分子生物学的方法
07:10
to figure out, really, what's the mechanism.
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来研究这种现象的真正的机理。
07:12
And what we found -- so this is now supposed to be my bacterial cell --
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我们发现了:比如这是我的费氏弧菌
07:16
is that Vibrio fischeri has a protein.
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它有一种蛋白质-
07:18
That's the red box --
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就是这个红色的方块—它是一种催化剂,
07:20
it's an enzyme that makes that little hormone molecule,
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是它制造的这种小荷尔蒙分子,就是这红色三角形。
07:23
the red triangle.
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07:24
And then as the cells grow,
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当细胞生长时,他们全都释放这个种分子到环境中,
07:25
they're all releasing that molecule into the environment,
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因此周围环境中有大量的这种分子。
07:28
so there's lots of molecule there.
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这些细菌的细胞表面,存在一种受体,
07:30
And the bacteria also have a receptor on their cell surface
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07:33
that fits like a lock and key with that molecule.
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它与小分子的构造就如同锁与钥匙一般的吻合。
07:36
These are just like the receptors on the surfaces of your cells.
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它们就如同你我身体细胞表面上的受体一般。
当这些分子增加到一定的量时—
07:40
So when the molecule increases to a certain amount,
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07:42
which says something about the number of cells,
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这也意味着这些细胞的数量增加到一定的量
07:44
it locks down into that receptor
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荷尔蒙小分子与受器相结合,
07:46
and information comes into the cells
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讯息开始向细胞内部传递,
这个讯息会告诉这些细胞
07:49
that tells the cells to turn on this collective behavior of making light.
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开始集体发光的行为。
07:53
Why this is interesting is because in the past decade,
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这个发现之所以有趣,是因为在过去十年间
07:56
we have found that this is not just some anomaly
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我们发现这种现象,
07:58
of this ridiculous, glow-in-the-dark bacterium that lives in the ocean --
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不只局限在这种住在大海中,古怪的、会在黑暗中发光的细菌,
而是所有的细菌都有类似的系统。
08:02
all bacteria have systems like this.
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08:04
So now what we understand is that all bacteria can talk to each other.
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由此,我们发现所有细菌都是可以彼此交谈的。
08:07
They make chemical words, they recognize those words,
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它们制造化学文字,同时也能够辨认这些文字,
08:10
and they turn on group behaviors
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然后表现
08:12
that are only successful when all of the cells participate in unison.
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只有当所有细胞齐心协力才能成功的集体行为。
08:17
So now we have a fancy name for this: we call it "quorum sensing."
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我们为这种行为取了一个新潮的名字,称作:聚量感应。
08:20
They vote with these chemical votes,
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就象用化学物质投票,
08:22
the vote gets counted, and then everybody responds to the vote.
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再对票量加以统计,然后 所有细胞都要服从最后的投票结果。
08:26
What's important for today's talk is we know there are hundreds of behaviors
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今天演讲最重要的一点是,
我们已经知道细菌有数百种以上的这种
08:30
that bacteria carry out in these collective fashions.
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集体行为。
08:33
But the one that's probably the most important to you is virulence.
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其中对大家来说,最关心的应该还是细菌的致病性。
并不是说少量细菌进入你体内后
08:37
It's not like a couple bacteria get in you and start secreting some toxins --
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就马上开始分泌毒素。
08:41
you're enormous; that would have no effect on you, you're huge.
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相对它们来说,你是个庞然大物,少量细菌对你不会有任何的影响。
我们发现,
08:45
But what they do, we now understand,
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08:47
is they get in you, they wait, they start growing,
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它们是先进入你的体内,然后等待,开始不断复制增长,
08:50
they count themselves with these little molecules,
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它们由统计小分子的数目来估计自身的实力,
08:52
and they recognize when they have the right cell number
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当确定有足够的细胞数后,
所有细菌一起发动致病攻击,
08:55
that if all of the bacteria launch their virulence attack together,
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08:58
they're going to be successful at overcoming an enormous host.
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这样它们就能成功攻陷巨大的宿主。
09:02
So bacteria always control pathogenicity with quorum sensing.
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细菌总是以「聚量感应」来控制其致病性
这就是它们运作的原理。
09:07
So that's how it works.
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我们同时也研究了这些小分子,
09:09
We also then went to look at what are these molecules.
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09:11
These were the red triangles on my slides before.
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这些就是我刚才幻灯上的小红三角形。
09:14
This is the Vibrio fischeri molecule.
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这个是费氏弧菌的小分子。
09:16
This is the word that it talks with.
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也就是它们用以交谈的文字。
09:18
And then we started to look at other bacteria,
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我们开始研究其他细菌,
09:20
and these are just a smattering of the molecules that we've discovered.
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这些是部份我们已发现小分子
我希望你们看得出来
09:24
What I hope you can see is that the molecules are related.
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这些分子之间是有关联性的。
09:27
The left-hand part of the molecule is identical
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每种细菌,
09:29
in every single species of bacteria.
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它们的小分子的左半部都是完全相同的。
09:32
But the right-hand part of the molecule is a little bit different
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只是在右半部则因菌种的不同而有少许的不同。
09:35
in every single species.
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这个发现证实
09:37
What that does is to confer exquisite species specificities to these languages.
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细菌的语言有高度的专一性。
09:42
So each molecule fits into its partner receptor
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每一种分子只能与其相对受器结合,非常专一。
09:45
and no other.
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所以这些交谈是私下的、秘密的。
09:47
So these are private, secret conversations.
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09:49
These conversations are for intraspecies communication.
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这种交流是只限于同种族内部的沟通。
09:53
Each bacteria uses a particular molecule that's its language
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每一种细菌使用其特殊分子代表它的语言,
09:57
that allows it to count its own siblings.
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让它能够计算同类的数量。
一旦我们了解这些,
10:02
Once we got that far,
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10:03
we thought we were starting to understand that bacteria have these social behaviors.
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我们也开始了解细菌有所谓的社交行为。
但我们真正思考的问题是,
10:07
But what we were really thinking about is that most of the time,
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在多数情况下,细菌并不是单独生活的,它们居住的地方是鱼龙混杂的,
10:10
bacteria don't live by themselves, they live in incredible mixtures,
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它们跟其它成百上千种的细菌同居一处。
10:13
with hundreds or thousands of other species of bacteria.
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10:16
And that's depicted on this slide.
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这张幻灯可以说明这个情形:这是你的皮肤。
10:18
This is your skin.
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10:19
So this is just a picture -- a micrograph of your skin.
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这是一张照片,是你皮肤的显微照片。
10:22
Anywhere on your body, it looks pretty much like this.
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在你身体的任何地方,看上去都会和这差不多。
我希望你能看出,这里有各种不同的细菌。
10:25
What I hope you can see
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10:26
is that there's all kinds of bacteria there.
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10:28
And so we started to think, if this really is about communication in bacteria,
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因此我们开始思考,如果这真的是细菌间的交流
10:32
and it's about counting your neighbors,
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计算与之相邻的同种细菌的数量,
10:34
it's not enough to be able to only talk within your species.
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只跟同种细菌沟通是不够的,
它们一定有某种
10:38
There has to be a way to take a census
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跟周围其他种细菌和平共处的方法。
10:40
of the rest of the bacteria in the population.
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所以我们回到分子生物学的方法,
10:43
So we went back to molecular biology
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开始研究不同的细菌。
10:45
and started studying different bacteria.
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我们现在已经发现,
10:47
And what we've found now is that, in fact, bacteria are multilingual.
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事实上,细菌可以讲多国种语言。
它们都有一个菌种特别识别系统,
10:51
They all have a species-specific system,
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用特别分子来辨别同类。
10:54
they have a molecule that says "me."
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10:55
But then running in parallel to that is a second system
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但是,我们发现,
10:58
that we've discovered, that's generic.
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它们同时还有另一种系统,那是一个通用的系统。
11:00
So they have a second enzyme that makes a second signal,
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因此,它们有另一种催化剂,能产生第二种信号,
11:03
and it has its own receptor,
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这种信号也有自己的受体,
11:05
and this molecule is the trade language of bacteria.
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这种分子是细菌们的公共语言。
它被所有不同的细菌所公共使用,
11:09
It's used by all different bacteria,
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是一种菌种间沟通的语言。
11:11
and it's the language of interspecies communication.
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11:14
What happens is that bacteria are able to count
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细菌能够计算
并区分自己周围同种与异种细菌的数量。
11:18
how many of "me" and how many of "you."
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11:20
And they take that information inside,
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它们传递这些讯息到细胞内,
11:22
and they decide what tasks to carry out
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然后决定该怎么做,
它们的行动取决于在整个群体中
11:25
depending on who's in the minority and who's in the majority
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11:28
of any given population.
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谁占多数,谁占少数。
11:30
Then, again, we turned to chemistry,
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我们又使用化学方法
11:32
and we figured out what this generic molecule is --
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搞清了这个通用分子的构造-
11:35
that was the pink ovals on my last slide, this is it.
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通用分子就是我上一张幻灯的粉红色椭圆形。
11:38
It's a very small, five-carbon molecule.
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它是一个非常小的五碳分子。
重要的是,我们发现
11:41
And what the important thing is that we learned
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11:43
is that every bacterium has exactly the same enzyme
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每种细菌都有完全一样的催化剂,
11:46
and makes exactly the same molecule.
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可以制造一模一样的分子。
11:48
So they're all using this molecule for interspecies communication.
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它们都使用这个分子
作为菌种间交流的语言。
11:52
This is the bacterial Esperanto.
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这是细菌的世界语。
11:55
(Laughter)
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笑声
11:56
So once we got that far,
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一旦我们了解这个后,
11:58
we started to learn that bacteria can talk to each other
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我们知道细菌可以用这个分子来相互交流。
12:00
with this chemical language.
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但是我们又开始思考,
12:02
But we started to think
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12:03
that maybe there is something practical that we can do here as well.
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也许我们可以使用这个发现来做一些实质上的应用。
我已经告诉过你们,细菌间是有社交行为的,
12:06
I've told you that bacteria have all these social behaviors,
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它们是使用这些分子进行交流的。
12:09
that they communicate with these molecules.
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12:11
Of course, I've also told you that one of the important things they do
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当然,我也告诉过你,
其中一件主要的事情就是它们使用聚量感应来启动致病性。
12:15
is to initiate pathogenicity using quorum sensing.
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我们不禁想,我们是不是
12:18
So we thought:
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12:19
What if we made these bacteria so they can't talk or they can't hear?
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可以让这些细菌哑了或聋了?
这岂不是可以成为一种新的抗生素?
12:23
Couldn't these be new kinds of antibiotics?
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12:25
And of course, you've just heard and you already know
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当然,你一定听说过,而且你早就知道了
我们快要没有有效的抗生素了。
12:28
that we're running out of antibiotics.
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现在的细菌都拥有,不可思议的多重耐药性
12:30
Bacteria are incredibly multi-drug-resistant right now,
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12:32
and that's because all of the antibiotics that we use kill bacteria.
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而这都是因为,这些抗生素的工作原理都是杀死细菌。
12:36
They either pop the bacterial membrane,
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它们要么是使细菌的细胞膜破裂,
12:38
they make the bacterium so it can't replicate its DNA.
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就是不让细菌复制自己的DNA。
12:41
We kill bacteria with traditional antibiotics,
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当我们用传统抗生素来杀菌时,
12:44
and that selects for resistant mutants.
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会同时培养筛选出有耐药性的突变菌株。
12:46
And so now, of course, we have this global problem
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所以,我们有了全球性的
12:49
in infectious diseases.
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感染病问题。
12:51
So we thought, what if we could sort of do behavior modifications,
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我们想,如果我们可以稍微更改这些细菌的行为,
12:54
just make these bacteria so they can't talk, they can't count,
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只是让这些细菌无法交谈,无法计数,
它们就不知何时发起毒性攻击。
12:58
and they don't know to launch virulence?
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13:00
So that's exactly what we've done,
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这就是我们已经完成的实验,我们使用了两种不同策略:
13:02
and we've sort of taken two strategies.
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第一个,
13:04
The first one is, we've targeted the intraspecies communication system.
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我们锁定菌种内通讯系统。
13:08
So we made molecules that look kind of like the real molecules, which you saw,
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我们制造了一些看起来跟真的分子很像的分子,
你们可以看到,它们间只有一点点的不同。
13:12
but they're a little bit different.
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因此,它们会锁住这些受体,
13:14
And so they lock into those receptors,
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并且干扰受体辨识真正的分子。
13:16
and they jam recognition of the real thing.
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13:18
So by targeting the red system,
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既然锁定红色的系统,
13:20
what we are able to do is make species-specific, or disease-specific,
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我们就可以制造
针对菌种,或是针对疾病的「反聚量感应」分子。
13:25
anti-quorum-sensing molecules.
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13:27
We've also done the same thing with the pink system.
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我们也对粉红色系统做了同样的事情。
13:30
We've taken that universal molecule and turned it around a little bit
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我们使用那种通用分子,将之做了一些更改
13:33
so that we've made antagonists of the interspecies communication system.
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我们做了一些拮抗剂,
它们都是针对菌种间的通讯系统。
我们希望这些分子可以用来作广谱抗生素,
13:38
The hope is that these will be used as broad-spectrum antibiotics
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13:42
that work against all bacteria.
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对所有细菌都有效。
13:44
And so to finish, I'll show you the strategy.
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最后,我只跟你们说一下战略。
13:47
In this one, I'm just using the interspecies molecule,
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在这个里,我们只是使用跨菌种分子,
13:49
but the logic is exactly the same.
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但是思维逻辑是一模一样的。
13:51
So what you know is that when that bacterium gets into the animal --
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你们都知道,当细菌进入动物体内,
以此为例,对这只老鼠,
13:55
in this case, a mouse --
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13:56
it doesn't initiate virulence right away.
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它并不会马上启动致病机制。
13:58
It gets in, it starts growing,
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它进入,开始增殖,
14:00
it starts secreting its quorum-sensing molecules.
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开始分泌它的聚量感应分子。
14:03
It recognizes when it has enough bacteria
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当累积到足够数量时,细菌能识别,
14:05
that now they're going to launch their attack,
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并开始发起攻击,
然后老鼠就死了。
14:08
and the animal dies.
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14:09
And so what we've been able to do is to give these virulent infections,
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我们所做的是在致病感染的同时,
14:12
but we give them in conjunction with our anti-quorum-sensing molecules.
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加入我们的「反聚量感应分子」,
14:16
So these are molecules that look kind of like the real thing,
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也就是看起来很像真的「聚量感应分子」的物质,
但是,正如同我在幻灯上指出的,它们之间有一点点不同。
14:19
but they're a little different, which I've depicted on this slide.
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我们现在发现,
14:22
What we now know is that if we treat the animal with a pathogenic bacterium --
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如果让实验动物感染一种具有多重耐药性的致病细菌,
14:26
a multi-drug-resistant pathogenic bacterium --
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14:28
in the same time we give our anti-quorum-sensing molecule,
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4024
但是同时, 我们施予「反聚量感应分子」治疗,
14:32
in fact, the animal lives.
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动物就能够存活。
14:34
And so we think that this is the next generation of antibiotics,
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我们认为这应该是下一代的抗生素,
14:38
and it's going to get us around, at least initially,
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它将能够让我们,至少在开始阶段,
14:40
this big problem of resistance.
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解决耐药性细菌的问题。
14:42
What I hope you think is that bacteria can talk to each other,
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我希望你们也能认为,细菌可以彼此交谈,
它们使用化学物质当作语言,
14:46
they use chemicals as their words,
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2150
14:48
they have an incredibly complicated chemical lexicon
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它们拥有极端复杂的化学语汇,
14:51
that we're just now starting to learn about.
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我们现在才刚刚要开始学习这些语汇。
当然,也因为这些语汇
14:54
Of course, what that allows bacteria to do is to be multicellular.
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使细菌得以变得像多细胞生物。
14:58
So in the spirit of TED,
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所以,就像TED的精神一样,它们彼此合作,
15:00
they're doing things together because it makes a difference.
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因为这样才能有一番作为。
细菌因为有这些集体行为,
15:04
What happens is that bacteria have these collective behaviors,
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15:07
and they can carry out tasks
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所以可以执行
15:09
that they could never accomplish if they simply acted as individuals.
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一些如果是单枪匹马
是永远无法完成的任务。
15:13
What I would hope that I could further argue to you
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我希望能进一步地说服你们的是
这就是多细胞生物的起源。
15:17
is that this is the invention of multicellularity.
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15:19
Bacteria have been on the earth for billions of years;
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细菌已经生存在地球上数十亿年了。
15:23
humans, couple hundred thousand.
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人类只有数十万年而已。
15:25
So we think bacteria made the rules for how multicellular organization works.
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我们认为细菌制定了
多细胞的组织运作规则。
我们认为,由研究细菌,
15:31
And we think by studying bacteria,
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15:33
we're going to be able to have insight about multicellularity in the human body.
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我们将能够对,人体内的多细胞系统,有更进一步的认识。
15:37
So we know that the principles and the rules,
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我们现在已经知道基本规则了,
15:39
if we can figure them out in these sort of primitive organisms,
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如果我们可以从这些原始生命体上进一步弄懂它们,
这些规则也有希望能够应用
15:42
the hope is that they will be applied
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到人类其它疾病与行为上。
15:44
to other human diseases and human behaviors as well.
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我希望你们已经学到
15:48
I hope that what you've learned
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15:49
is that bacteria can distinguish self from other.
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细菌是可以区分你我,
15:52
So by using these two molecules,
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使用这两种分子,它们可以表达「我」和「你」。
15:53
they can say "me" and they can say "you."
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当然,这就是我们所做的
15:56
And again, of course, that's what we do,
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不仅只在分子层面上,
15:58
both in a molecular way, and also in an outward way,
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同样也在行为上,
16:01
but I think about the molecular stuff.
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只是我在分子层次上想的多一点。
16:03
This is exactly what happens in your body.
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这完全就是你们体内正在发生的事情。
16:05
It's not like your heart cells and kidney cells get all mixed up every day,
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你们的心脏和肾脏细胞不会每天混杂在一起,
这是因为你体内有一大堆化学反应不断地进行着,
16:09
and that's because there's all of this chemistry going on,
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16:11
these molecules that say who each of these groups of cells is
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这些分子能够区分不同的细胞群组,
还有它们所应该执行的任务。
16:15
and what their tasks should be.
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16:16
So again, we think bacteria invented that,
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再一次,我们认为细菌发明了这个机制,
你只不过是多演化出了一些铃铛与哨子而已,
16:20
and you've just evolved a few more bells and whistles,
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16:22
but all of the ideas are in these simple systems that we can study.
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但是所有的概念都包含在这个我们所研究的简单系统中。
16:26
And the final thing is, just to reiterate that there's this practical part,
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最后,只是再一次重申,这个研究的实际应用方面,
16:30
and so we've made these anti-quorum-sensing molecules
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是我们已经制造出了这些「反聚量感应分子」,
16:33
that are being developed as new kinds of therapeutics.
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它们正作为新一代的疗法被开发研究中。
16:36
But then, to finish with a plug for all the good and miraculous bacteria
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为了鼓励地球上生存的
16:39
that live on the earth,
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所有对人有益的细菌,
16:41
we've also made pro-quorum-sensing molecules.
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我们也制造了「强化聚量感应分子」。
16:43
So we've targeted those systems to make the molecules work better.
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因此,我们已经锁定了这些系统,让这些分子运作得更好。
请记得在你体内体表,有超过你自身细胞十倍的细菌,
16:47
So remember, you have these 10 times or more bacterial cells
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16:50
in you or on you, keeping you healthy.
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它们使你保持健康。
16:52
What we're also trying to do is to beef up the conversation
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我们也努力加强
你和你的共生的细菌之间交流,
16:56
of the bacteria that live as mutualists with you,
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16:58
in the hopes of making you more healthy,
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让你更健康,
让这种互动更有益。
17:01
making those conversations better,
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17:02
so bacteria can do things that we want them to do
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让细菌只做我们希望它们做的事情。
17:05
better than they would be on their own.
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防止细菌做我们不希望它们做的事情。
17:08
Finally, I wanted to show you --
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最后,我希望让你们看看
17:10
this is my gang at Princeton, New Jersey.
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我在新泽西,普林斯顿大学实验室的成员。
我今天所告诉你们的每一个发现,都是由照片中的某人所完成的。
17:13
Everything I told you about was discovered by someone in that picture.
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我希望当你们学到东西的同时
17:17
And I hope when you learn things, like about how the natural world works --
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比如:自然世界是怎样运作的,
17:20
I just want to say that whenever you read something in the newspaper
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我只是想说,任何时候,当你们在报纸上看到某事,
17:23
or you hear some talk about something ridiculous in the natural world,
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或是你们听到某些有关自然的,好玩事情的演讲,
都是由年轻人完成的。
17:27
it was done by a child.
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17:28
So science is done by that demographic.
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科学是由这种年龄层的人所造就的。
这些二、三十岁的年轻人
17:31
All of those people are between 20 and 30 years old,
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17:34
and they are the engine that drives scientific discovery in this country.
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他们是推动这个国家科学发现的引擎。
我真的是非常幸运能与这群年轻人一起共事。
17:39
And it's a really lucky demographic to work with.
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17:41
(Applause)
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我自己在不断地变老,但他们却是始终不变,
17:42
I keep getting older and older, and they're always the same age.
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这真是一个美好得不能再好的工作。
17:45
And it's just a crazy, delightful job.
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17:47
And I want to thank you for inviting me here,
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我要谢谢你们的邀请。
17:49
it's a big treat for me to get to come to this conference.
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非常荣幸能参加这个大会。
17:52
(Applause)
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掌声
17:57
Thanks.
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谢谢
17:58
(Applause)
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掌声
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