TED2009
Bonnie Bassler: How bacteria "talk"
Bonnie Bassler 談細菌如何溝通
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Bonnie Bassler 發現細菌能彼此「對話」，它們利用化學語言來協調防禦與發動攻擊。此發現震驚了醫學界和工業界，及我們原有的自我認知。
Bonnie Bassler - Molecular biologist
Bonnie Bassler studies how bacteria can communicate with one another, through chemical signals, to act as a unit. Her work could pave the way for new, more potent medicine. Full bio
Bonnie Bassler studies how bacteria can communicate with one another, through chemical signals, to act as a unit. Her work could pave the way for new, more potent medicine. Full bio
Double-click the English transcript below to play the video.
00:18
Bacteria are the oldest living organisms on the earth.
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細菌是地球上最古老的生命體。
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 are one cell and they have this special property
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它們只有一個細胞，而且還有個特徵
00:30
that they only have one piece of DNA.
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就是只有一份 DNA。
00:32
They have very few genes,
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擁有極少的基因
00:34
and genetic information to encode all of the traits that they carry out.
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及遺傳資訊，來儲存所有它們表現的特徵。
00:38
And the way bacteria make a living
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細菌賴以生存的方法是
00:40
is that they consume nutrients from the environment,
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從環境中吸取養分，
00:43
they grow to twice their size, they cut themselves down in the middle,
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成長兩倍後，從中分開，
00:46
and one cell becomes two, and so on and so on.
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一分為二，二分為四，如此一直下去。
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
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但是我會說你與這些生物
00:55
an amazing interaction with these critters.
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擁有驚人的互動關係。
00:58
I know you guys think of yourself as humans, and this is sort of how I think of you.
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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。
01:01
This man is supposed to represent
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這個人是代表
01:03
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 of 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 is about a trillion human cells that make each one of us
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每個人大約是由一兆個人體細胞所組成，
01:12
who we are and able to do all the things that we do,
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讓我們能完成各式各樣的事
01:15
but you have 10 trillion bacterial cells
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但是你一生中任何時刻
01:18
in you or on you at any moment in your life.
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都有大約十兆個細菌細胞在你身上或體內。
01:20
So, 10 times more bacterial cells
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所以，在一個人身上
01:22
than human cells on a human being.
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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
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所以這裡是組成你遺傳密碼的
01:29
that make up your genetic code, and give you all your charming characteristics.
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所有 A, T, G, C，它們產生了你專屬的迷人特徵。
01:32
You have about 30,000 genes.
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你有大約三萬個基因。
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!
01:37
playing a role in you or on you all of your life.
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在你的身上或體內扮演著某些腳色。
01:41
At the best, you're 10 percent human,
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最多最多，你只是 10% 的人類，
01:44
but more likely about one percent human,
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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，
01:50
but I think of you as 90 or 99 percent bacterial.
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但在我眼中你是 90% 或 99% 的細菌。
01:54
(Laughter)
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（笑聲）
01:55
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
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隔絕環境刺激，
02:06
so that we stay healthy.
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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
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它們還教育你的免疫系統
02:12
to keep bad microbes out.
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將惡性微生物阻擋於體外。
02:14
So they do all these amazing things
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它們做了這些了不起的事，
02:16
that help us and are vital for keeping us alive,
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幫助我們，是我們賴以為生的關鍵，
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
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倒是常常因為它們也能導致許多可怕的後果
02:24
terrible things as well.
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而登上各大版面
02:26
So, there's all kinds of bacteria on the Earth
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地球上有各式各樣的細菌
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
02:32
and if they are, they make you incredibly sick.
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如果有，它們會讓你極端難受。
02:36
And so, the question for my lab is whether you want to think about all the
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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
02:39
good things that bacteria do, or all the bad things that bacteria do.
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或是所有細菌做的壞事。
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？
02:45
I mean they're incredibly small,
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畢竟它們十分的小，
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 are just too small to have an impact
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所以對我們來說，它們實在是
03:00
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
And so we wanted to think if there couldn't be a different
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所以我們想探討，
03:06
way that bacteria live.
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細菌是不是其實用別種方式生存？
03:08
The clue to this came from another marine bacterium,
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這個問題的線索，來自一種海洋細菌，
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
03:21
a harmless beautiful bacterium that comes from the ocean,
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一種來自海洋，美麗且無害的細菌，
03:24
named Vibrio fischeri.
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名為費氏弧菌 (Vibrio fischeri)。
03:26
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，
03:29
so it makes bioluminescence,
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它會發出生物螢光，
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，
03:37
and this is what we see.
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這是我們所見到的情形。
03:39
What was actually interesting to us
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我們尤其感興趣的
03:41
was not that the bacteria made light,
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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, they made no light.
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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。
03:51
But when they grew to a certain cell number
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但是當它們成長至一定數量後，
03:53
all the bacteria turned on light simultaneously.
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所有細菌會同時開始發光。
03:57
The question that we had is how can bacteria, these primitive organisms,
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我們疑惑的是，像細菌這麼原始的生物，
04:01
tell the difference from times when they're alone,
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如何能夠分辨它們現在是單獨
04:03
and times when they're in a community,
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還是處於群體中
04:05
and then all do something together.
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然後能夠一起開始從事某種行為。
04:08
What we've figured out is that the way that they do that is that they talk to each other,
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我們已經發現，這是因為細菌能夠彼此「對談」
04:12
and they talk with a chemical language.
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它們說的是化學語言
04:14
This is now supposed to be my bacterial cell.
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假設這個是我的細菌。
04:17
When it's alone it doesn't make any light.
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當它獨處時，不會發出任何光線。
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, and when the bacteria is alone
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這邊以紅色三角形代表，當細菌獨處的時候，
04:29
the molecules just float away and so no light.
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這些分子都擴散開來，因此沒有發光。
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，
04:37
the molecule -- the extracellular amount of that molecule
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這些細胞外分子的含量，
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
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。
04:58
The reason that Vibrio fischeri is doing that comes from the biology.
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費式弧菌的發光現象有它生物學上的原因
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，
05:05
Vibrio fischeri lives in this squid.
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費式弧菌住在這種烏賊體內
05:08
What you are 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，
05:10
and it's been turned on its back,
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這是牠的腹側，
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
and 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。
05:22
The reason the squid is willing to put up with these shenanigans
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這烏賊之所以願意忍受這些胡鬧行為的原因是，
05:25
is because it wants that light.
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牠想要這些光線。
05:27
The way that this symbiosis works
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這個共生行為建立的基礎是
05:29
is that this little squid lives just off the coast of Hawaii,
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因為這個小烏賊居住在夏威夷的海岸邊，
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
The squid is nocturnal, so during the day
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這烏賊是夜行性的，因此白天
05:38
it buries itself in the sand and sleeps,
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牠把牠自己埋藏在沙中睡覺，
05:40
but then at night it has to come out to hunt.
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但是到了晚上，牠必須出來獵食。
05:43
On bright nights when there is lots of starlight or moonlight
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在有許多星光與月光點綴的明亮夜晚，
05:45
that light can penetrate the depth of the water
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這些光線可以穿透烏賊所住的地方
05:48
the squid lives in, since it's just in those couple feet of water.
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因為這裡的海水只有數呎深而已。
05:51
What the squid has developed is a shutter
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這烏賊發展出了一種活葉遮板，
05:54
that can open and close over this specialized light organ housing the bacteria.
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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
05:58
Then it has detectors on its back
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加上這烏賊背上有一些感光裝置，
06:00
so it can sense how much starlight or moonlight is hitting 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。
06:04
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
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 anti-predation device
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當成是牠匿蹤裝置中，模擬背景光線的來源，
06:20
so predators can't see its shadow,
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因此獵食者無法看見牠的陰影，
06:22
calculate its trajectory, and eat it.
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計算牠的動向，然後吃了牠。
06:24
This is like the stealth bomber of the ocean.
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就像是大海中的隱形轟炸機一般。
06:27
(Laughter)
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（笑聲）
06:28
But then if you think about it, the 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，
06:31
because it's got this dying, thick culture of bacteria
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因為在牠體內，這些黏稠的細菌液正在逐漸死亡，
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，
06:38
the squid goes back to sleep, it buries itself in the sand,
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牠將自己埋藏在沙中，進入睡眠，
06:41
and it's got a pump that's attached to its circadian rhythm,
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而且牠有一個與日夜週期同步的幫浦，
06:44
and when the sun comes up it pumps out like 95 percent of the bacteria.
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當太陽升起時，它將大約 95% 的細菌排出體外。
06:49
Now the bacteria are dilute, that little hormone molecule is gone,
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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，
06:52
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。
06:56
And as the day goes by the bacteria double,
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當一天過去，這些細菌持續分裂生長，
06:58
they release the molecule, and then light comes on
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牠們釋放出這些分子，然後又開始在晚上發光，
07:01
at night, exactly when the squid wants it.
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剛好就是烏賊需要光線的時候。
07:04
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, again, 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 -- it's an enzyme that makes
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這個紅色的方塊 — 它是製造這
07:21
that little hormone molecule, the red triangle.
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小荷爾蒙分子（紅三角形）的酵素。
07:24
And then as the cells grow, they're all releasing that molecule
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當細胞生長時，他們全都釋放這個分子
07:26
into the environment, so there's lots of molecule there.
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到環境中，因此環境裡有一堆這種分子。
07:29
And the bacteria also have a receptor on their cell surface
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這些細菌的細胞表面，同時還有一種受器，
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。
07:39
When the molecule increases to a certain amount --
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當這些分子增加到一定的量時 —
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，
07:48
that tells the cells to turn on
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這個訊息告訴這些細胞開始
07:50
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，
08:01
all bacteria have systems like this.
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所以的細菌都有類似的系統。
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
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
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今天演講最重要的一點是
08:28
is that we know that there are hundreds of behaviors
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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。
08:36
It's not like a couple bacteria get in you
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並不是說一些細菌進入你體內後
08:39
and they 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。
08:44
What they do, we now understand,
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我們現在了解，它們是
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，
08:54
that if all of the bacteria launch their virulence attack together,
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一旦這些細菌一起發動致病攻擊，
08:58
they are 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
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。
09:06
That's how it works.
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這就是它們運作的原理。
09:08
We also then went to look at what are these molecules --
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我們同時也研究了這些分子，
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
So 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。
09:23
What I hope you can see
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我希望你們看得出來
09:25
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 in every single species.
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但是右半部則因不同的菌種而有些許的不同。
09:36
What that does is to confer
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這個發現證實了
09:38
exquisite species specificities to these languages.
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細菌的語言有高度的專一性。
09:42
Each molecule fits into its partner receptor and no other.
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每一種分子只能與其相對受器結合，非常專一。
09:46
So these are private, secret conversations.
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所以這些交談是私下的、秘密的
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。
10:01
Once we got that far we thought
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一旦我們了解這些，
10:03
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。
10:06
But what we were really thinking about is that most of the time
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但我們真正思考的問題是，多數時間裡，
10:09
bacteria don't live by themselves, they live in incredible mixtures,
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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，
10:12
with hundreds or thousands of other species of bacteria.
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跟其它千百種以上的細菌同處一室。
10:16
And that's depicted on this slide. This is your skin.
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這張投影片說明了這個情形。這是你的皮膚。
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，
10:24
and what I hope you can see is that there's all kinds of bacteria there.
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我希望你能看出，這裡有各種不同的細菌。
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
10:37
There has to be a way to take a census
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它們一定有某種方法
10:39
of the rest of the bacteria in the population.
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能跟其他種細菌達成共識。
10:42
So we went back to molecular biology
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所以我們回到分子生物學的領域，
10:44
and started studying different bacteria,
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開始研究不同的細菌，
10:46
and what we've found now is that
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我們現在已經發現，
10:48
in fact, bacteria are multilingual.
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事實上，細菌可以講很多種語言。
10:50
They all have a species-specific system --
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它們都有一個菌種專一的系統，
10:53
they have a molecule that says "me."
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並用特定分子來辨別同類
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。
11:08
It's used by all different bacteria
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它被所有不同的細菌所使用，
11:10
and it's the language of interspecies communication.
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是一種菌種間溝通交流的語言。
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
11:17
how many of me and how many of you.
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同種與異種細菌的數量。
11:20
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，
11:24
depending on who's in the minority and who's in the majority
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它們的行為取決於在一個族群中，
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 turn 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。
11:40
What the important thing is that we learned
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重要的是，我們發現
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
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它們全都使用這個分子
11:50
for interspecies communication.
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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
Once we got that far, we started to learn
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一旦我們了解這個後，我們知道
11:58
that bacteria can talk to each other with this chemical language.
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細菌可以用這個分子來相互交流。
12:01
But what we started to think is that maybe there is something
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但是我們又開始思考，也許我們可以使用
12:03
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。
12:05
I've told you that bacteria do have all these social behaviors,
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我已經告訴過你，細菌間是有社交行為的，
12:08
they communicate with these molecules.
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它們使用這些分子溝通。
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
12:14
is to initiate pathogenicity using quorum sensing.
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它們使用聚量感應來啟動致病性。
12:17
We thought, what if we made these bacteria
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我們不禁想，如果我們讓這些細菌
12:19
so they can't talk or they can't hear?
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聾了或啞了，會怎麼樣?
12:22
Couldn't these be new kinds of antibiotics?
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這能不能成為一種新的抗生素？
12:25
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，
12:27
that we're running out of antibiotics.
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我們快要沒有有效的抗生素了。
12:29
Bacteria are incredibly multi-drug-resistant right now,
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現在的細菌都擁有，不可思議的多重抗藥性，
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
We thought, well 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，
12:57
and they don't know to launch virulence.
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它們就不知何時發起毒性攻擊。
13:00
And so that's exactly what we've done, and we've sort of taken two strategies.
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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。
13:03
The first one is we've targeted
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第一個，我們鎖定
13:05
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 --
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我們製造了一些看起來跟真的分子很像的分子，
13:11
which you saw -- but they're a little bit different.
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你在這邊可以看到，它們間有一點點的不同。
13:13
And so they lock into those receptors,
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因此，它們會鎖住這些受器，
13:15
and they jam recognition of the real thing.
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並且干擾辨識真正的分子。
13:18
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 to make
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我們可以製造的是
13:22
species-specific, or disease-specific, anti-quorum sensing molecules.
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針對菌種，或是針對疾病的「反聚量感應」分子。
13:27
We've also done the same thing with the pink system.
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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
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我們做了一些拮抗劑，
13:35
of the interspecies communication system.
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它們都是針對菌種間的通訊系統。
13:37
The hope is that these will be used as broad-spectrum antibiotics
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我們希望這些分子可以拿來當作廣效性抗生素，
13:42
that work against all bacteria.
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對所有細菌都有效。
13:44
To finish I'll just 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
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，
13:54
in this case, a mouse,
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以此為例，一隻老鼠，
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, it starts secreting
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它進入，開始增殖，開始分泌
14:01
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
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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，
14:07
and the animal dies.
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然後老鼠就死了。
14:09
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，
14:18
but they're a little bit different which I've depicted on this slide.
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但是，就如同我在投影片上指出的，它們之間有一點點不同。
14:21
What we now know is that if we treat the animal
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我們現在知道，如果使動物感染致病細菌
14:24
with a pathogenic bacterium -- a multi-drug-resistant pathogenic bacterium --
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即一種具有多重抗藥性的致病細菌
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
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，
14:45
they use chemicals as their words,
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它們使用化學物質當作文字，
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。
14:53
Of course what that allows bacteria to do
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當然，也因為這些語彙，使細菌得以
14:56
is to be multicellular.
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變得像多細胞。
14:58
So in the spirit of TED they're doing things together
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所以，就像 TED 的精神一樣， 它們彼此合作
15:01
because it makes a difference.
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因為這樣才能有一番作為。
15:03
What happens is that bacteria have these collective behaviors,
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細菌因為有這些集體行為，
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
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是它們本來永遠無法完成的，
15:11
if they simply acted as individuals.
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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
15:16
is that this is the invention of multicellularity.
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這就是多細胞生物的起源。
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
We think bacteria made the rules
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我們認為細菌制定了
15:27
for how multicellular organization works.
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多細胞的組織運作規則。
15:30
We think, by studying bacteria,
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我們認為，藉由研究細菌，
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
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，
15:41
the hope is that they will be applied
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這些規則也有希望能夠應用到
15:43
to other human diseases and human behaviors as well.
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其它人類疾病與行為上。
15:47
I hope that what you've learned
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我希望你們已經學到
15:49
is that bacteria can distinguish self from other.
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細菌可以區分敵我。
15:52
By using these two molecules they can say "me" and they can say "you."
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藉由使用這兩種分子，它們可以表達「我」和「別人」。
15:55
Again of course that's what we do,
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當然，再一次，這就是我們所做的，
15:57
both in a molecular way,
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不僅只在分子層面上，
15:59
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 your 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，
16:08
and that's because there's all of this chemistry going on,
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這是因為你體內有一堆化學反應一直在進行著，
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，
16:14
and what their tasks should be.
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還有它們所應該執行的任務。
16:16
Again, we think that bacteria invented that,
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再一次的，我們認為細菌發明了這個機制，
16:19
and you've just evolved a few more bells and whistles,
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你只不過是多演化出了一些鈴鐺與哨子而已，
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
The final thing is, again 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。
16:46
Remember you have these 10 times or more bacterial cells
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記得在你身上或體內，有超過你體細胞十倍的細菌，
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
16:55
of the bacteria that live as mutualists with you,
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和你之間的對談
16:58
in the hopes of making you more healthy,
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希望能夠讓你更健康，
17:00
making those conversations better,
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增進對談，
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。
17:12
Everything I told you about was discovered by someone in that picture.
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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。
17:16
I hope when you learn things,
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我希望當你們學到東西的同時，
17:18
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 get to 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，
17:26
it was done by a child.
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都是由孩子們完成的。
17:28
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。
17:30
All of those people are between 20 and 30 years old,
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所有這些二、三十歲的人們，
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。
17:38
It's a really lucky demographic to work with.
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能與這樣年齡層的人一起共事，真的是非常幸運。
17:41
I keep getting older and older and they're always the same age,
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我一直不斷地在變老，他們卻是始終不變，
17:44
and it's just a crazy delightful job.
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這真是一個美好得不像話的工作。
17:47
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）
ABOUT THE SPEAKER
Bonnie Bassler - Molecular biologistBonnie Bassler studies how bacteria can communicate with one another, through chemical signals, to act as a unit. Her work could pave the way for new, more potent medicine.
Why you should listen
In 2002, bearing her microscope on a microbe that lives in the gut of fish, Bonnie Bassler isolated an elusive molecule called AI-2, and uncovered the mechanism behind mysterious behavior called quorum sensing -- or bacterial communication. She showed that bacterial chatter is hardly exceptional or anomolous behavior, as was once thought -- and in fact, most bacteria do it, and most do it all the time. (She calls the signaling molecules "bacterial Esperanto.")
The discovery shows how cell populations use chemical powwows to stage attacks, evade immune systems and forge slimy defenses called biofilms. For that, she's won a MacArthur "genius" grant -- and is giving new hope to frustrated pharmacos seeking new weapons against drug-resistant superbugs.
Bassler teaches molecular biology at Princeton, where she continues her years-long study of V. harveyi, one such social microbe that is mainly responsible for glow-in-the-dark sushi. She also teaches aerobics at the YMCA.
Bonnie Bassler | Speaker | TED.com