Bonnie Bassler: The secret, social lives of bacteria

298,101 views ・ 2009-04-08

TED


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譯者: Bill Hsiung 審譯者: Katherine Liu
細菌是地球上最古老的生命體。
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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它們已經存在數十億年了,
00:23
and what they are are single-celled microscopic organisms.
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它們是單細胞微生物。
00:27
So they're one cell
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它們只有一個細胞,而且還有個特徵
00:29
and they have this special property that they only have one piece of DNA.
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就是只有一份 DNA。
00:32
So they have very few genes and genetic information
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擁有極少的基因
及遺傳資訊,來儲存所有它們表現的特徵。
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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細菌賴以生存的方法是
從環境中吸取養分,
00:42
from the environment,
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00:43
they grow to twice their size,
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成長兩倍後,從中分開,
00:45
they cut themselves down in the middle,
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一分為二,二分為四,如此一直下去。
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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它們不停生長、分裂,然後再生長、分裂 — 有點無趣的生活,
00:53
except that what I would argue is that you have an amazing interaction
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但是我會說你與這些生物
擁有驚人的互動關係。
00:57
with these critters.
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00:58
I know you guys think of yourself as humans,
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我知道你們自認是人類,而這大概是我如何看待你們的。
01:00
and this is sort of how I think of you.
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這個人是代表
01:02
This man is supposed to represent a generic human being,
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一般的人類,
01:05
and all of the circles in that man are all the cells that make up your body.
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那些人體內的圈圈,代表組成人體的細胞。
01:09
There's about a trillion human cells that make each one of us who we are
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每個人大約是由一兆個人體細胞所組成,
讓我們能完成各式各樣的事
01:13
and able to do all the things that we do.
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但是你一生中任何時刻
01:16
But you have 10 trillion bacterial cells in you or on you
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都有大約十兆個細菌細胞在你身上或體內。
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,在一個人身上
有人體細胞數十倍的細菌細胞。
01:25
And, of course, it's the DNA that counts,
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當然,DNA 組成比細胞數重要,
01:27
so here's all the A, T, Gs and Cs that make up your genetic code
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所以這裡是組成你遺傳密碼的
所有 A, T, G, C,它們產生了你專屬的迷人特徵。
01:30
and give you all your charming characteristics.
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你有大約三萬個基因。
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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但事實上,你身上的細菌基因是你本身基因的一百多倍!
在你的身上或體內扮演著某些腳色。
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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最多最多,你只是 10% 的人類,
其實更有可能只是 1% 的人類,
01:46
depending on which of these metrics you like.
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端看你喜歡哪一種度量方法。
01:48
I know you think of yourself as human beings,
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我知道你認為你自己是人類,
但在我眼中你是 90% 或 99% 的細菌。
01:51
but I think of you as 90 or 99 percent bacterial.
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01:54
(Laughter)
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(笑聲)
01:55
And these bacteria are not passive riders.
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這些細菌不只是被動的乘客而已,
01:58
These are incredibly important; they keep us alive.
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它們非常地重要,它們維持我們的生命。
02:01
They cover us in an invisible body armor
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它們將我們保護在一層看不見的鎧甲中,
02:04
that keeps environmental insults out so that we stay healthy.
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隔絕環境刺激,
因此我們能保持健康。
02:08
They digest our food, they make our vitamins,
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它們消化我們的食物,製造我們所需的維他命,
02:10
they actually educate your immune system to keep bad microbes out.
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它們還教育你的免疫系統
將惡性微生物阻擋於體外。
它們做了這些了不起的事,
02:15
So they do all these amazing things
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幫助我們,是我們賴以為生的關鍵,
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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但細菌從來沒有因為這些好事上過媒體
02:22
But they get a lot of press because they do a lot of terrible things as well.
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倒是常常因為它們也能導致許多可怕的後果
而登上各大版面
地球上有各式各樣的細菌
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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有些絕不應該出現在你身上或體內
如果有,它們會讓你極端難受。
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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因此,我實驗室的研究主題是,所有你想得到細菌做的好事
02:38
is whether you want to think about all the good things that bacteria do
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或是所有細菌做的壞事。
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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並且探討,它們是如何辦到的?
畢竟它們十分的小,
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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你必須在顯微鏡底下才能觀察到它們。
02:49
They live this sort of boring life where they grow and divide,
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它們的生活如此無趣,只是成長與分裂,
02:52
and they've always been considered to be these asocial, reclusive organisms.
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而且它們總被認為是無社會行為的獨行俠
02:57
And so it seemed to us that they're just too small
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所以對我們來說,它們實在是
03:00
to have an impact on the environment
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微小到無法對環境產生任何影響
03:02
if they simply act as individuals.
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尤其它們只是單獨行動的話。
03:04
So we wanted to think if there couldn't be a different way that bacteria live.
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所以我們想探討,
細菌是不是其實用別種方式生存?
這個問題的線索,來自一種海洋細菌,
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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叫做費氏弧菌 (Vibrio fischeri) 。
03:15
What you're looking at on this slide is just a person from my lab
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你們在這張投影片看到的,是我實驗室的一個人
03:18
holding a flask of a liquid culture of a bacterium,
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握著一瓶裝滿這種細菌的培養液
一種來自海洋,美麗且無害的細菌,
03:22
a harmless, beautiful bacterium that comes from the ocean,
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名為費氏弧菌 (Vibrio fischeri)。
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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這種細菌的特性是會發光,
它會發出生物螢光,
03:30
so it makes bioluminescence,
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03:31
like fireflies make light.
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就如同螢火蟲發出的光。
03:33
We're not doing anything to the cells here,
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我們沒有對這些細胞做任何事。
03:35
we just took the picture by turning the lights off in the room,
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我們只是把房間燈關了,然後照了這張照片,
這是我們所見到的情形。
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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我們尤其感興趣的
不是細菌會發光這件事,
03:43
but when the bacteria made light.
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而是細菌何時發光。
03:45
What we noticed is when the bacteria were alone,
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我們注意到當細菌處於單獨環境中,
03:48
so when they were in dilute suspension,
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也就是當它們被稀釋,且懸浮在培養液中時,它們不會發光。
03:50
they made no light.
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但是當它們成長至一定數量後,
03:52
But when they grew to a certain cell number,
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所有細菌會同時開始發光。
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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我們疑惑的是,像細菌這麼原始的生物,
03:59
How can bacteria, these primitive organisms,
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如何能夠分辨它們現在是單獨
04:02
tell the difference from times when they're alone
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還是處於群體中
04:04
and times when they're in a community,
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然後能夠一起開始從事某種行為。
04:06
and then all do something together?
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我們已經發現,這是因為細菌能夠彼此「對談」
04:09
And what we figured out is that the way they do that is they talk to each other,
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它們說的是化學語言
04:13
and they talk with a chemical language.
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假設這個是我的細菌。
04:15
So this is now supposed to be my bacterial cell.
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當它獨處時,不會發出任何光線。
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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但是它會製造與分泌化學小分子,
04:24
that you can think of like hormones,
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你可以將它想成荷爾蒙,
04:26
and these are the red triangles.
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這邊以紅色三角形代表,當細菌獨處的時候,
04:28
And when the bacteria are alone, the molecules just float away,
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這些分子都擴散開來,因此沒有發光。
04:31
and so, no light.
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04:32
But when the bacteria grow and double
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但是當這些細菌成長倍增後,
04:34
and they're all participating in making these molecules,
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它們全都一起製造這些分子,
這些細胞外分子的含量,
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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隨著細胞數的增加而增加。
04:44
And when the molecule hits a certain amount
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等這個分子累積到一定的量之後,
04:46
that tells the bacteria how many neighbors there are,
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它告訴了細菌,它周圍有多少鄰居,
04:49
they recognize that molecule
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它們都認識這個分子,
04:51
and all of the bacteria turn on light in synchrony.
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然後所有細菌,協同一致地開始發光。
04:54
And so that's how bioluminescence works --
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這就是它們如何一起發光—
04:56
they're talking with these chemical words.
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它們藉由這些化學語言交談著。
費式弧菌的發光現象有它生物學上的原因
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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再一次地,又連結到海洋裡的生物,
費式弧菌住在這種烏賊體內
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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你們現在看到的是,夏威夷截尾烏賊,
這是牠的腹側,
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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我希望你們看得到,那兩個發著光的葉狀突起,
05:15
These house the Vibrio fischeri cells.
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它們內部儲藏著這些費式弧菌
05:18
They live in there, at high cell number.
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它們就以非常高的數量,居住在那裡面,
05:20
That molecule is there, and they're making light.
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這個分子也在那,所以它們發著光。
這烏賊之所以願意忍受這些胡鬧行為的原因是,
05:23
And the reason the squid is willing to put up with these shenanigans
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牠想要這些光線。
05:26
is because it wants that light.
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這個共生行為建立的基礎是
05:28
The way that this symbiosis works
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因為這個小烏賊居住在夏威夷的海岸邊,
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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牠們生活的海域,大概只有膝蓋一般的深度。
05:35
And the squid is nocturnal,
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這烏賊是夜行性的,因此白天
05:37
so during the day, it buries itself in the sand and sleeps.
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牠把牠自己埋藏在沙中睡覺,
但是到了晚上,牠必須出來獵食。
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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在有許多星光與月光點綴的明亮夜晚,
05:44
when there's lots of starlight or moonlight,
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這些光線可以穿透烏賊所住的地方
05:46
that light can penetrate the depth of the water the squid lives in,
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因為這裡的海水只有數呎深而已。
05:50
since it's just in those couple feet of water.
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這烏賊發展出了一種活葉遮板,
05:52
What the squid has developed is a shutter that can open and close
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可以打開或遮蔽由特化發光器官裡的細菌所發出的光線
05:55
over the specialized light organ housing the bacteria.
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加上這烏賊背上有一些感光裝置,
05:59
And then it has detectors on its back
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可以用來偵測有多少月光或星光照在牠背上。
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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然後牠隨之調節遮板的開關,
06:06
so the amount of light coming out of the bottom,
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因此從牠腹部所放出的光 —
06:08
which is made by the bacterium,
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是由細菌產生的
06:10
exactly matches how much light hits the squid's back,
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完全符合照射在這烏賊背部上的光強度,
06:12
so the squid doesn't make a shadow.
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因此這烏賊不會產生任何影子。
06:14
So it actually uses the light from the bacteria
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牠使用來自細菌的光,
06:17
to counter-illuminate itself in an antipredation device,
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當成是牠匿蹤裝置中,模擬背景光線的來源,
因此獵食者無法看見牠的陰影,
06:21
so predators can't see its shadow,
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計算牠的動向,然後吃了牠。
06:23
calculate its trajectory and eat it.
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就像是大海中的隱形轟炸機一般。
06:25
So this is like the stealth bomber of the ocean.
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06:27
(Laughter)
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(笑聲)
06:28
But then if you think about it, this squid has this terrible problem,
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但是如果你深入去思考,這烏賊會有一個可怕的問題,
因為在牠體內,這些黏稠的細菌液正在逐漸死亡,
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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牠無法維持這些細菌的生長。
06:36
And so what happens is, every morning when the sun comes up,
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因此每天早上當太陽升起後,
牠將自己埋藏在沙中,進入睡眠,
06:39
the squid goes back to sleep, it buries itself in the sand,
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而且牠有一個與日夜週期同步的幫浦,
06:42
and it's got a pump that's attached to its circadian rhythm.
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當太陽升起時,它將大約 95% 的細菌排出體外。
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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既然細菌被稀釋了,這些小荷爾蒙分子也隨之消失,
06:51
that little hormone molecule is gone, so they're not making light.
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因此牠們不發光了,
06:54
But, of course, the squid doesn't care, it's asleep in the sand.
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但烏賊當然不在意。牠正在沙中睡覺呢。
當一天過去,這些細菌持續分裂生長,
06:57
And as the day goes by, the bacteria double,
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牠們釋放出這些分子,然後又開始在晚上發光,
06:59
they release the molecule, and then light comes on at night,
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剛好就是烏賊需要光線的時候。
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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我們先瞭解這些細菌為什麼會有這種現象,
07:07
but then we brought the tools of molecular biology to this
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然後我們使用分子生物學的方法來研究
07:10
to figure out, really, what's the mechanism.
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這個現象下,真正的分子機制為何?
07:12
And what we found -- so this is now supposed to be my bacterial cell --
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我們發現了 — 再一次,想像這是我的細菌 —
07:16
is that Vibrio fischeri has a protein.
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費氏弧菌有一種蛋白質
07:18
That's the red box --
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這個紅色的方塊 — 它是製造這
07:20
it's an enzyme that makes that little hormone molecule,
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小荷爾蒙分子(紅三角形)的酵素。
07:23
the red triangle.
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07:24
And then as the cells grow,
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當細胞生長時,他們全都釋放這個分子
07:25
they're all releasing that molecule into the environment,
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到環境中,因此環境裡有一堆這種分子。
07:28
so there's lots of molecule there.
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這些細菌的細胞表面,同時還有一種受器,
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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與此分子的構造就如同鑰匙與鎖一般的吻合。
07:36
These are just like the receptors on the surfaces of your cells.
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它們就如同你身體細胞表面上的受器一般。
當這些分子增加到一定的量時 —
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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它也意味著這些細胞數量的增加 —
07:44
it locks down into that receptor
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荷爾蒙與受器相結合,
07:46
and information comes into the cells
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訊息開始向細胞內部傳遞,
這個訊息告訴這些細胞開始
07:49
that tells the cells to turn on this collective behavior of making light.
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表現此集體行為,並開始發光。
07:53
Why this is interesting is because in the past decade,
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這個發現之所以有趣,是因為在過去十年間,
07:56
we have found that this is not just some anomaly
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我們發現這個現象,不只侷限在這些住在大海中,
07:58
of this ridiculous, glow-in-the-dark bacterium that lives in the ocean --
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滑稽的、會在黑暗中發光的細菌,
所以的細菌都有類似的系統。
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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所以現在,我們了解所有細菌都可以彼此交談。
08:07
They make chemical words, they recognize those words,
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它們製造化學文字,也能夠辨認這些文字,
08:10
and they turn on group behaviors
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然後表現集體行為,
08:12
that are only successful when all of the cells participate in unison.
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只有當所有細胞一起同心協力才能成功。
08:17
So now we have a fancy name for this: we call it "quorum sensing."
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我們為這種行為取了一個新潮的名字,稱作:聚量感應。
08:20
They vote with these chemical votes,
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取決於這些化學物質的數量
08:22
the vote gets counted, and then everybody responds to the vote.
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加以統計後,所有細胞都要服從最後的結果。
08:26
What's important for today's talk is we know there are hundreds of behaviors
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今天演講最重要的一點是
我們已經知道有數百種以上的
08:30
that bacteria carry out in these collective fashions.
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這種細菌的集體行為。
08:33
But the one that's probably the most important to you is virulence.
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但對你們來說,最關心的應該還是致病性的問題。
並不是說一些細菌進入你體內後
08:37
It's not like a couple bacteria get in you and start secreting some toxins --
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就馬上開始分泌致病毒素,
08:41
you're enormous; that would have no effect on you, you're huge.
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相對它們來說非常巨大,這點量對你不會有太大的影響。
我們現在了解,它們是
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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先進入你的身體,等待,開始複製成長,
08:50
they count themselves with these little molecules,
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它們藉由計算這些小分子的數目來估計自身的數量,
08:52
and they recognize when they have the right cell number
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直到確定有足夠的細胞數為止,
一旦這些細菌一起發動致病攻擊,
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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它們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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細菌一向是以「聚量感應」來控制其致病性。
這就是它們運作的原理。
09:07
So that's how it works.
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我們同時也研究了這些分子,
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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這些就是我之前投影片上的小紅三角形。
09:14
This is the Vibrio fischeri molecule.
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這個是費氏弧菌的分子。
09:16
This is the word that it talks with.
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這就是它們用以交談的文字。
09:18
And then we started to look at other bacteria,
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我們開始研究其他細菌,
09:20
and these are just a smattering of the molecules that we've discovered.
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這些是我們已發現分子中的一小部份。
我希望你們看得出來
09:24
What I hope you can see is that the molecules are related.
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這些分子之間是有關聯性的。
09:27
The left-hand part of the molecule is identical
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就算是不同的菌種
09:29
in every single species of bacteria.
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它們分子的左半部都是相同的
09:32
But the right-hand part of the molecule is a little bit different
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但是右半部則因不同的菌種而有些許的不同。
09:35
in every single species.
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這個發現證實了
09:37
What that does is to confer exquisite species specificities to these languages.
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細菌的語言有高度的專一性。
09:42
So each molecule fits into its partner receptor
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每一種分子只能與其相對受器結合,非常專一。
09:45
and no other.
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所以這些交談是私下的、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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只給同種族內溝通交流。
09:53
Each bacteria uses a particular molecule that's its language
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每一種細菌使用一種特殊分子代表它的語言,
09:57
that allows it to count its own siblings.
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讓它能夠計算同類的數量。
一旦我們了解這些,
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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我們也開始了解細菌有所謂的社交行為。
但我們真正思考的問題是,多數時間裡,
10:07
But what we were really thinking about is that most of the time,
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細菌並不是單獨生活的,它們居住的地方龍蛇雜處,
10:10
bacteria don't live by themselves, they live in incredible mixtures,
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跟其它千百種以上的細菌同處一室。
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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這張投影片說明了這個情形。這是你的皮膚。
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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這只是一張照片,你皮膚的顯微照片。
10:22
Anywhere on your body, it looks pretty much like this.
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不論在你身體何處,看起來差不多就是這個樣子,
我希望你能看出,這裡有各種不同的細菌。
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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因此我們開始思考,這會不會也跟細菌間的溝通有關,
10:32
and it's about counting your neighbors,
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跟計算你鄰居的數量有關,
10:34
it's not enough to be able to only talk within your species.
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只跟自己人溝通是不夠的
它們一定有某種方法
10:38
There has to be a way to take a census
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能跟其他種細菌達成共識。
10:40
of the rest of the bacteria in the population.
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所以我們回到分子生物學的領域,
10:43
So we went back to molecular biology
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開始研究不同的細菌,
10:45
and started studying different bacteria.
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我們現在已經發現,
10:47
And what we've found now is that, in fact, bacteria are multilingual.
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事實上,細菌可以講很多種語言。
它們都有一個菌種專一的系統,
10:51
They all have a species-specific system,
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並用特定分子來辨別同類
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,我們已經發現,它們同時還有第二種系統,
10:58
that we've discovered, that's generic.
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那是一個通用的系統。
11:00
So they have a second enzyme that makes a second signal,
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因此,它們有另一個酵素能產生第二種訊號,
11:03
and it has its own receptor,
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這訊號也有自己的受器,
11:05
and this molecule is the trade language of bacteria.
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這個分子是細菌們的貿易語言。
它被所有不同的細菌所使用,
11:09
It's used by all different bacteria,
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是一種菌種間溝通交流的語言。
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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細菌能夠計算並區分自己周遭
同種與異種細菌的數量。
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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它們傳遞這些訊息到胞內,
11:22
and they decide what tasks to carry out
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然後決定該怎麼做,
它們的行為取決於在一個族群中,
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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誰佔多數優勢,誰是少數弱勢。
11:30
Then, again, we turned to chemistry,
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又一次的,我們轉向使用化學方法,
11:32
and we figured out what this generic molecule is --
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我們搞清楚了這個通用分子的構造,
11:35
that was the pink ovals on my last slide, this is it.
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這通用分子就是我上一張投影片的粉紅色橢圓形。
11:38
It's a very small, five-carbon molecule.
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它是一個非常小的五碳分子。
重要的是,我們發現
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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每種細菌都有完全一樣的酵素,
11:46
and makes exactly the same molecule.
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可以製造一模一樣的分子。
11:48
So they're all using this molecule for interspecies communication.
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它們全都使用這個分子
作為菌種間溝通使用。
11:52
This is the bacterial Esperanto.
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這是細菌的世界語。
11:55
(Laughter)
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(笑聲)
11:56
So once we got that far,
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一旦我們了解這個後,我們知道
11:58
we started to learn that bacteria can talk to each other
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細菌可以用這個分子來相互交流。
12:00
with this chemical language.
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但是我們又開始思考,也許我們可以使用
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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這個發現做一些實質上的應用。
我已經告訴過你,細菌間是有社交行為的,
12:06
I've told you that bacteria have all these social behaviors,
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它們使用這些分子溝通。
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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當然,我也告訴過你,其中一件主要的事情就是
它們使用聚量感應來啟動致病性。
12:15
is to initiate pathogenicity using quorum sensing.
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我們不禁想,如果我們讓這些細菌
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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聾了或啞了,會怎麼樣?
這能不能成為一種新的抗生素?
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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當然,你才剛聽說過,而且你早就知道了,
我們快要沒有有效的抗生素了。
12:28
that we're running out of antibiotics.
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現在的細菌都擁有,不可思議的多重抗藥性,
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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而這都是因為,我們企圖用來殺死細菌的這些抗生素
12:36
They either pop the bacterial membrane,
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不是使細菌的細胞膜破裂,
12:38
they make the bacterium so it can't replicate its DNA.
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就是不讓細菌複製自己的 DNA。
12:41
We kill bacteria with traditional antibiotics,
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當我們用傳統抗生素來殺菌時
12:44
and that selects for resistant mutants.
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等於在篩選出有抗藥性的突變株。
12:46
And so now, of course, we have this global problem
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因此,現在我們當然有全球性的
12:49
in infectious diseases.
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感染病問題。
12:51
So we thought, what if we could sort of do behavior modifications,
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我們想,如果我們可以稍微更改這些細菌的行為,
12:54
just make these bacteria so they can't talk, they can't count,
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只要使這些細菌無法交談,無法計數,
它們就不知何時發起毒性攻擊。
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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這就是我們已經完成的實驗,我們使用了兩種不同策略。
13:02
and we've sort of taken two strategies.
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第一個,我們鎖定
13:04
The first one is, we've targeted the intraspecies communication system.
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菌種內通訊系統。
13:08
So we made molecules that look kind of like the real molecules, which you saw,
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我們製造了一些看起來跟真的分子很像的分子,
你在這邊可以看到,它們間有一點點的不同。
13:12
but they're a little bit different.
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因此,它們會鎖住這些受器,
13:14
And so they lock into those receptors,
287
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並且干擾辨識真正的分子。
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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藉由鎖定紅色的系統,
13:20
what we are able to do is make species-specific, or disease-specific,
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我們可以製造的是
針對菌種,或是針對疾病的「反聚量感應」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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2589
我們也對粉紅系統做了同樣的事情。
13:30
We've taken that universal molecule and turned it around a little bit
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我們使用那個通用分子,將之做了一些更改,
13:33
so that we've made antagonists of the interspecies communication system.
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我們做了一些拮抗劑,
它們都是針對菌種間的通訊系統。
我們希望這些分子可以拿來當作廣效性抗生素,
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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對所有細菌都有效。
13:44
And so to finish, I'll show you the strategy.
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為了在控制時間,我只跟你們說明策略。
13:47
In this one, I'm just using the interspecies molecule,
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在這個實驗中,我們只是使用跨菌種分子,
13:49
but the logic is exactly the same.
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但是思維邏輯是一模一樣的。
13:51
So what you know is that when that bacterium gets into the animal --
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如你們所知,當細菌進入動物體內,
以此為例,一隻老鼠,
13:55
in this case, a mouse --
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13:56
it doesn't initiate virulence right away.
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它並不會馬上起動致病機制。
13:58
It gets in, it starts growing,
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它進入,開始增殖,開始分泌
14:00
it starts secreting its quorum-sensing molecules.
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它的聚量感應分子。
14:03
It recognizes when it has enough bacteria
305
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當累積到足夠數量時,細菌能察覺
14:05
that now they're going to launch their attack,
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並開始發起攻擊,
然後老鼠就死了。
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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我們已能夠在給予這些致病感染的同時,
14:12
but we give them in conjunction with our anti-quorum-sensing molecules.
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也給予我們的「反聚量感應分子」,
14:16
So these are molecules that look kind of like the real thing,
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也就是看起來很像真的「聚量感應分子」的東西,
但是,就如同我在投影片上指出的,它們之間有一點點不同。
14:19
but they're a little different, which I've depicted on this slide.
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我們現在知道,如果使動物感染致病細菌
14:22
What we now know is that if we treat the animal with a pathogenic bacterium --
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即一種具有多重抗藥性的致病細菌
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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但是同時,我們施予「反聚量感應分子」治療,
14:32
in fact, the animal lives.
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事實上,實驗動物能夠存活。
14:34
And so we think that this is the next generation of antibiotics,
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我們認為這是下一世代的抗生素,
14:38
and it's going to get us around, at least initially,
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而且它將能夠帶我們避過,至少一開始,
14:40
this big problem of resistance.
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避過抗藥性的難題。
14:42
What I hope you think is that bacteria can talk to each other,
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我希望你們也能認為,細菌可以彼此交談,
它們使用化學物質當作文字,
14:46
they use chemicals as their words,
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14:48
they have an incredibly complicated chemical lexicon
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它們擁有極端複雜的化學語彙,
14:51
that we're just now starting to learn about.
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我們現在才剛剛要開始學習這些語彙。
當然,也因為這些語彙,使細菌得以
14:54
Of course, what that allows bacteria to do is to be multicellular.
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變得像多細胞。
14:58
So in the spirit of TED,
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所以,就像 TED 的精神一樣, 它們彼此合作
15:00
they're doing things together because it makes a difference.
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因為這樣才能有一番作為。
細菌因為有這些集體行為,
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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所以可以執行一些任務,
15:09
that they could never accomplish if they simply acted as individuals.
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是它們本來永遠無法完成的,
如果它們只是獨自行動的話。
15:13
What I would hope that I could further argue to you
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我希望能進一步地說服你
這就是多細胞生物的起源。
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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細菌已經生存在地球上數十億年了。
15:23
humans, couple hundred thousand.
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人類只有數十萬年而已。
15:25
So we think bacteria made the rules for how multicellular organization works.
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我們認為細菌制定了
多細胞的組織運作規則。
我們認為,藉由研究細菌,
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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我們將能夠對,人體內的多細胞系統,有更進一步的認識。
15:37
So we know that the principles and the rules,
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我們現在已經知道大原則跟規則了,
15:39
if we can figure them out in these sort of primitive organisms,
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如果我們可以在這些原始生命體上弄懂它們,
這些規則也有希望能夠應用到
15:42
the hope is that they will be applied
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其它人類疾病與行為上。
15:44
to other human diseases and human behaviors as well.
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我希望你們已經學到
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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細菌可以區分敵我。
15:52
So by using these two molecules,
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藉由使用這兩種分子,它們可以表達「我」和「別人」。
15:53
they can say "me" and they can say "you."
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當然,再一次,這就是我們所做的,
15:56
And again, of course, that's what we do,
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不僅只在分子層面上,
15:58
both in a molecular way, and also in an outward way,
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同樣也在外顯行為上,
16:01
but I think about the molecular stuff.
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只是我習慣以分子層次思考。
16:03
This is exactly what happens in your body.
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這完全就是正在你們體內發生的事情。
16:05
It's not like your heart cells and kidney cells get all mixed up every day,
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你們的心臟和腎臟細胞不會每天混在一起,
這是因為你體內有一堆化學反應一直在進行著,
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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這些分子能夠區分不同的細胞群組,
還有它們所應該執行的任務。
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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再一次的,我們認為細菌發明了這個機制,
你只不過是多演化出了一些鈴鐺與哨子而已,
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這個我們研究的簡單系統中。
16:26
And the final thing is, just to reiterate that there's this practical part,
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最後一件事是,只是再一次重申,這個研究的實際應用面,
16:30
and so we've made these anti-quorum-sensing molecules
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就是我們已經製造出了這些「反聚量感應分子」,
16:33
that are being developed as new kinds of therapeutics.
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它們正在被當作新一代的療法研發中。
16:36
But then, to finish with a plug for all the good and miraculous bacteria
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帶是現在,我以替地球上生存的所有美好的、神奇的細菌
16:39
that live on the earth,
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宣傳做結尾,
16:41
we've also made pro-quorum-sensing molecules.
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我們也製造了「強化聚量感應分子」。
16:43
So we've targeted those systems to make the molecules work better.
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因此,我們已經鎖定了這些系統,讓這些分子運作得更好。
記得在你身上或體內,有超過你體細胞十倍的細菌,
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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它們使你保持健康。
16:52
What we're also trying to do is to beef up the conversation
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我們也試著促進,在你身上那些和你互利共生的細菌
和你之間的對談
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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希望能夠讓你更健康,
增進對談,
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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讓細菌做出我們希望它們做的事情,
17:05
better than they would be on their own.
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比它們單獨的時候做得更好。
17:08
Finally, I wanted to show you --
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最後,我希望讓你們看看,
17:10
this is my gang at Princeton, New Jersey.
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這是我在紐澤西,普林斯頓實驗室的成員。
每一件我所告訴你們的事情,都是由照片中的某人所發現的。
17:13
Everything I told you about was discovered by someone in that picture.
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我希望當你們學到東西的同時,
17:17
And I hope when you learn things, like about how the natural world works --
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例如:自然世界運作的原理,
17:20
I just want to say that whenever you read something in the newspaper
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我只是想說,不管何時,當你們在報紙上看到某事,
17:23
or you hear some talk about something ridiculous in the natural world,
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或是你們聽到某些,關於自然界好玩事情的演講,
都是由孩子們完成的。
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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科學是由這種年齡層的人所成就的。
所有這些二、三十歲的人們,
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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他們也是推動這個國家科學發現的引擎。
能與這樣年齡層的人一起共事,真的是非常幸運。
17:39
And it's a really lucky demographic to work with.
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17:41
(Applause)
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我一直不斷地在變老,他們卻是始終不變,
17:42
I keep getting older and older, and they're always the same age.
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這真是一個美好得不像話的工作。
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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我要謝謝你們邀請我來這邊演說。
17:49
it's a big treat for me to get to come to this conference.
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能參與這個大會,對我來說真是難得的樂事。
17:52
(Applause)
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(掌聲)
17:57
Thanks.
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謝謝
17:58
(Applause)
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(掌聲)
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