and actually all the way down into the sewer

我想要做的就是把大家都拖到排水溝裡，

because I want to talk about diarrhea.

其實是一路滑下到下水道，

And in particular, I want to talk about

因為我想談的是有關於腹瀉。

the design of diarrhea.

更具體而言,我想談談

And when evolutionary biologists talk about design,

腹瀉的設計圖譜

they really mean design by natural selection.

當生物進化學家們談論設計時

And that brings me to the title of the talk,

真正指的是經由自然選擇的設計，

"Using Evolution to Design Disease Organisms Intelligently."

這也就是我的演講標題

And I also have a little bit of a sort of smartass subtitle to this.

“聰明巧妙的使用生物進化去設計病菌."

But I'm not just doing this to be cute.

我也有加上有一點自負的副標題,

I really think that this subtitle explains

但這樣做不是要譁眾取寵.

what somebody like me, who's sort of a Darwin wannabe,

我真的認為這副標題幫這些像我一樣

how they actually look at one's role in

想要成為達爾文第二的人闡述了心聲

sort of coming into this field of health sciences and medicine.

表達他們是如何真正看待自己

It's really not a very friendly field for evolutionary biologists.

在健康科學和醫學領域裡的角色。

You actually see a great potential,

對進化生物學家來說這實在不是一個很友好的領域。

but you see a lot of people who are sort of defending their turf,

雖然具有強大潛力，

and may actually be very resistant, when one tries

但你也會看到很多人固步自封，

to introduce ideas.

有時當試圖引進這些想法時

So, all of the talk today is going to deal with two general questions.

會被強烈排斥。

One is that, why are some disease organisms more harmful?

今天演講的主題是要針對兩個很普通的問題.

And a very closely related question, which is,

一個是，為什麼有些病菌比較有殺傷力

how can we take control of this situation once we understand

而一個非常密切相關的問題是:

the answer to the first question?

一旦我們知道第一個問題的答案後,

How can we make the harmful organisms more mild?

我們如何才能控制這種情況？

And I'm going to be talking, to begin with, as I said,

如何使殺傷力強的病菌變成比較溫和呢？

about diarrheal disease organisms.

而我將討論的,正如我所說，

And the focus when I'm talking about the diarrheal organisms,

首先關於腹瀉疾病的病菌。

as well as the focus when I'm talking about any organisms

我的焦點不僅僅是討論各種腹瀉的病菌

that cause acute infectious disease,

而且還包括當談論任何病菌

is to think about the problem from a germ's point of view,

造成急性傳染病時

germ's-eye view.

用病菌的角度來思考問題.

And in particular, to think about a fundamental idea

病菌的觀點.

which I think makes sense out of a tremendous amount of variation

用這方法來思考探究一個根本的想法,

in the harmfulness of disease organisms.

我覺得很合理, 尤其是面對殺傷力強

And that idea is that from the germ's-eye point of view,

且具有大量變異性的病源體時.

disease organisms have to get from one host to another,

從細菌的角度來看世界,

and often they have to rely on the well-being of the host

通常病菌必須從一個宿主轉移到另一個宿主,

to move them to another host.

他們往往必需要依靠還算健康的宿主

But not always.

來傳染疾病到另一個宿主.

Sometimes, you get disease organisms

但並非總是如此。

that don't rely on host mobility at all for transmission.

有時候,讓人得到疾病的病源體

And when you have that, then evolutionary theory tells us

不依賴宿主的活動力來傳播疾病。

that natural selection will favor the more exploitative,

這情形下,進化理論告訴我們，

more predator-like organisms.

自然選擇將有利於比較兇猛，

So, natural selection will favor organisms

更具侵略性的病源體，

that are more likely to cause damage.

也就是自然選擇將有利

If instead transmission to another host requires host mobility,

於殺傷力強的病源體，

then we expect that the winners of the competition

相反的,如果需要依賴宿主的活動性來傳播疾病,

will be the milder organisms.

我們可以預料競爭中的贏家

So, if the pathogen doesn't need the host to be healthy and active,

將是溫和的菌種.

and actual selection favors pathogens

所以,如果病源體不需要健康活動的宿主來傳播疾病,

that take advantage of those hosts,

那實際上自然選擇的病源體,

the winners in the competition are those that exploit the hosts

是有利於會佔盡宿主的便宜,摧殘宿主的菌種,

for their own reproductive success.

所以競爭中的贏家是那些剝削宿主

But if the host needs to be mobile in order to transmit the pathogen,

來繁殖自己的病源體.

then it's the benign ones that tend to be the winners.

但是,如果需要宿主的活動力來傳播疾病

So, I'm going to begin by applying this idea to diarrheal diseases.

那麼那些較溫和的病源體,往往會成為贏家.

Diarrheal disease organisms get transmitted in basically three ways.

所以我將開始應用這一想法到腹瀉的疾病上。

They can be transmitted from person-to-person contact,

腹瀉的病菌基本是以三種方式傳播。

person-to-food-then-to-person contact,

它們可以由人接觸傳染到另一人，

when somebody eats contaminated food,

(人-食物-人)

or they can be transmitted through the water.

人吃下被污染的食物而傳染

And when they're transmitted through the water,

或者通過水傳播。(水媒)

unlike the first two modes of transmission,

如果通過水傳播，

these pathogens don't rely on a healthy host for transmission.

那就不像前兩種模式傳染，

A person can be sick in bed and still infect tens, even hundreds

這些病源體不依賴於一個健康的宿主傳播病源體。

of other individuals.

一個人可以是重病在床,仍然感染其他人，

To sort of illustrate that, this diagram emphasizes that

甚至數百個人。

if you've got a sick person in bed,

這附圖可說明更清楚,這圖強調，

somebody's going to be taking out the contaminated materials.

如果有一個生病的人在床上，

They're going to wash those contaminated materials,

有人需要處理被污染的器皿,

and then the water may move into sources of drinking water.

他們將清洗這些受污染的器具.

People will come in to those places where you've got

然後髒水可能進入飲用水源中,

contaminated drinking water,

人們會去在那些地方取水,

bring things back to the family,

而這些是被污染的飲用水.

may drink right at that point.

他們會把水帶回家,

The whole point is that a person who can't move

有時就在水源處喝上幾口.

can still infect many other individuals.

整個的重點是:一個人即使沒有活動力

And so, the theory tells us that

仍然可以感染許多其他個人。

when diarrheal disease organisms are transported by water,

所以,理論告訴我們，

we expect them to be more predator-like, more harmful.

當腹瀉的病菌是經由水傳播，

And you can test these ideas.

我們可預料病源體更凶狠,更有害的。

So, one way you can test is just look at all diarrheal bacteria,

而且,您可以測試這些推論。

and see whether or not the ones that tend to be

只需看看所有腹瀉細菌們，

more transmitted by water, tend to be more harmful.

看是否那些更趨向於利用水傳播

And the answer is -- yep, they are.

的病源體,往往更有殺傷力?

Now I put those names in there just for the bacteria buffs,

答案是-沒錯，它們是。

but the main point here is that --

現在我為細菌迷把很多病菌名字列在此，

(Laughter)

但主要的一點是 -

there's a lot of them here, I can tell --

（眾笑）

the main point here is that those data points

我敢說,這裡很多是細菌迷-

all show a very strong, positive association between

重點是，這些數據點

the degree to which a disease organism is transmitted by water,

均表現出非常強烈的正向關聯:

and how harmful they are,

越是依賴水傳播疾病的病菌,

how much death they cause per untreated infection.

殺傷力越強.

So this suggests we're on the right track.

以及如果未經治療的死亡率.

But this, to me, suggests that we really need

因此,這表示我們的推論是正確的,

to ask some additional questions.

我建議我們真的需要

Remember the second question that I raised at the outset was,

深入探討這現象.

how can we use this knowledge

記得我在一開始就提出了的第2個問題嗎:

to make disease organisms evolve to be mild?

我們如何用這些知識，

Now, this suggests that if you could just block waterborne transmission,

使病源體進化成較溫和的細菌呢？

you could cause disease organisms to shift from

所以現在假設如果你能阻止水媒傳播,

the right-hand side of that graph to the left-hand side of the graph.

那表明就能把這種細菌們的

But it doesn't tell you how long.

進化從圖中的右邊推向到左邊去.

I mean, if this would require thousands of years,

但是我們不知要多久,進化才能完成.

then it's worthless in terms of controlling of these pathogens.

我的意思是,如果這將需要數千年,

But if it could occur in just a few years,

那不值得去試控制這些病源體。

then it might be a very important way to control

但如果它可能發生在短短幾年內,

some of the nasty problems that we haven't been able to control.

那麼它可能是一個非常重要的方式,來控制

In other words, this suggests that we could

那些我們以前沒法控制,難纏困難的問題.

domesticate these organisms.

換言之,這表明我們可以

We could make them evolve to be not so harmful to us.

馴養這些細菌們,

And so, as I was thinking about this, I focused on this organism,

使他們進化成較溫和的細菌.

which is the El Tor biotype of the organism called Vibrio cholerae.

所以,當我在作研究時我把重心放在這個EL Tor(埃爾托)

And that is the species of organism that is responsible

生物型的細菌上,也就是被稱為霍亂弧菌的菌種.

for causing cholera.

這種病源體是造成

And the reason I thought this is a really great organism to look at

霍亂的原因。

is that we understand why it's so harmful.

而我之所以認為研究這菌種是很棒的題材,

It's harmful because it produces a toxin,

是因為我們已知道它為什麼如此有殺傷力。

and that toxin is released when the organism

它的有害,是因為它會產生一種毒素.

gets into our intestinal tract.

當霍亂弧菌進入我們的腸道的時候,

It causes fluid to flow from the cells that line our intestine

毒素會被釋放出來.

into the lumen, the internal chamber of our intestine,

這會使體液從腸壁細胞流入腸道(腔)中

and then that fluid goes the only way it can, which is out the other end.

--就是腸子中間的內在管腔.

And it flushes out thousands of different other competitors

然後，這液體流向唯一可去的另一端,排出人體外.

that would otherwise make life difficult for the Vibrios.

經由這過程沖刷走數以千計不同種腸道內競爭菌種,

So what happens, if you've got an organism,

使霍亂弧菌可以容易生存繁殖下來.

it produces a lot of toxin.

然後呢?如果有一種病源體在體內,

After a few days of infection you end up having --

它產生大量的毒素.

the fecal material really isn't so disgusting as we might imagine.

經過幾天後最終的結果是--

It's sort of cloudy water.

糞便排洩物並不像我們想的那麼噁心.

And if you took a drop of that water,

只是一灘混濁的水.

you might find a million diarrheal organisms.

如果你從中取一滴的水,

If the organism produced a lot of toxin,

你會發現一百萬腹瀉病源體在其中.

you might find 10 million, or 100 million.

如果病源體產生了大量的毒素,

If it didn't produce a lot of this toxin,

你可能會找到1千萬或1億個病源體.

then you might find a smaller number.

但如果病源體沒有產生了大量的毒素,

So the task is to try to figure out

可能只會被發現較少量的病源體.

how to determine whether or not you could get an organism like this

因此,主要的任務是設法弄清楚

to evolve towards mildness by blocking waterborne transmission,

如何能確定是否經由阻斷它們的水媒介傳播途徑,

thereby allowing the organism only to be transmitted

可以使這種殺傷力強的病源體進化成較溫和的病源體

by person-to-person contact,

從而使傳播途徑只有

or person-food-person contact --

人對人直接接觸,

both of which would really require that people be

或人-食物-人的接觸感染.

mobile and fairly healthy for transmission.

而此二種都是需要有

Now, I can think of some possible experiments.

足夠活動力或還算健康的人來傳播.

One would be to take a lot of different strains of this organism --

於是,我能想到一些可能的實驗。

some that produce a lot of toxins, some that produce a little --

其中之一是採取了很多同種病菌的不同菌株(不同亞型)

and take those strains and spew them out in different countries.

一些會產生大量的毒素，一些只產生少數的毒素-

Some countries that might have clean water supplies,

把這些不同菌株，散播在不同的國家。

so that you can't get waterborne transmission:

有些國家有清潔食水供應

you expect the organism to evolve to mildness there.

所以不能利用水來傳播，

Other countries, in which you've got a lot of waterborne transmission,

您可以預期在那裡病菌的進化會更溫和。

there you expect these organisms to evolve

但有些國家,有很多水媒傳播機會，

towards a high level of harmfulness, right?

所以你預期這些病菌的生物進化,

There's a little ethical problem in this experiment.

會邁向更有殺傷力的方向,對不對？

I was hoping to hear a few gasps at least.

這實驗會面臨一個道德問題。

That makes me worry a little bit.

我以為會聽到一些人(驚嚇的)倒抽一口氣。

(Laughter)

這就會使我有點擔心。

But anyhow, the laughter makes me feel a little bit better.

笑聲

And this ethical problem's a big problem.

不過,無論如何,笑聲讓我覺得好一點。

Just to emphasize this, this is what we're really talking about.

而這種道德問題是一個大問題。

Here's a girl who's almost dead.

為了強調這一點,也這就是我們真正談論的。

She got rehydration therapy, she perked up,

看這女孩差一點死了。

within a few days she was looking like a completely different person.

她得到了支持性補充體液療法,才恢復起來，

So, we don't want to run an experiment like that.

幾天之內,她看上去像一個完全不同的人。

But interestingly, just that thing happened in 1991.

因此,我們不希望進行這樣的實驗。

In 1991, this cholera organism got into Lima, Peru,

但有意思的是,類似的狀況發生在1991年。

and within two months it had spread to the neighboring areas.

1991年,霍亂病菌侵襲秘魯首都利馬，

Now, I don't know how that happened,

並在兩個月內,蔓延到鄰近地區(國家)。

and I didn't have anything to do with it, I promise you.

即使是現在我也不知道為什麼發生那瘟疫，

I don't think anybody knows,

我向你們保證,那跟我沒有任何關係。

but I'm not averse to, once that's happened,

我不認為有人知道為什麼會發生，

to see whether or not the prediction that we would make,

一旦這發生了,我不反對，

that I did make before, actually holds up.

借由這機會來分析看看是否我們的推論是對的，

Did the organism evolve to mildness in a place like Chile,

就是我曾經提出過的理論,是否經得起考驗。

which has some of the most well protected water supplies

在智利是否霍亂病菌進化成較溫和的菌種,

in Latin America?

因為智利在拉丁美洲具有最為完善的

And did it evolve to be more harmful in a place like Ecuador,

水源保護系統?

which has some of the least well protected?

是否在厄瓜多爾霍亂病菌進化成殺傷力更強的菌種

And Peru's got something sort of in between.

因為厄瓜多爾的水源最不受保護?

And so, with funding from the Bosack-Kruger Foundation,

而秘魯對水源的保護程度是介在兩國之間.

I got a lot of strains from these different countries

因為有Bozack-Kruger基金會的財政協助,

and we measured their toxin production in the lab.

我們從這些國家得到了很多不同的菌株.(樣品)

And we found that in Chile -- within two months of the invasion of Peru

我們於是在實驗室測量它們產生的毒素.

you had strains entering Chile --

我們發現,在智利-霍亂入侵秘魯兩個月後,

and when you look at those strains,

霍亂病菌漫延入智利.

in the very far left-hand side of this graph,

仔細研究這些菌株(種),

you see a lot of variation in the toxin production.

在這個圖的最左邊,

Each dot corresponds to an islet from a different person --

毒素的生產量有很大的變異性(很多不同的菌株)

a lot of variation on which natural selection can act.

每個點或一個島形代表來自不同的個人

But the interesting point is, if you look over the 1990s,

自然選擇可以倒導致很多變化.

within a few years the organisms evolved to be more mild.

但有趣的一點是,如果你看整個1990年代,

They evolved to produce less toxin.

在幾年內霍亂病菌進化成較溫和的菌種.

And to just give you a sense of how important this might be,

它們發展成只會產生少量毒素的菌種.

if we look in 1995, we find that there's only one case of cholera,

更清楚的讓你們瞭解這個的重要性,

on average, reported from Chile every two years.

如果研究1995年只有一個霍亂病例,

So, it's controlled.

平均每二年只有一個霍亂病例.

That's how much we have in America,

所以,霍亂被控制住了.

cholera that's acquired endemically,

這跟在美國發生律一樣.

and we don't think we've got a problem here.

霍亂是一種區域性的瘟疫.

They didn't -- they solved the problem in Chile.

我不認為在美國我們有霍亂瘟疫的問題.

But, before we get too confident, we'd better look at some of those other countries,

它們不是問題--在智利他們解決了這個瘟疫問題.

and make sure that this organism doesn't just always evolve toward mildness.

但在我們過於自信前,我們最好看看其他的鄰近國家.

Well, in Peru it didn't.

並確認這些病菌(不是)只朝著更溫和的方向進化.

And in Ecuador -- remember, this is the place where it has

嗯,在秘魯病菌就不是變溫和。

the highest potential waterborne transmission --

而在厄瓜多爾-記得嗎這地方的

it looked like it got more harmful.

水媒傳輸可能性最高-

In every case there's a lot of variation,

-看起來病菌進化得更有殺傷力.

but something about the environment the people are living in,

每個例子都有很多變異性,

and I think the only realistic explanation is that it's

這是與人們居住的環境有關.

the degree of waterborne transmission,

我認為唯一真正的解釋是在於

favored the harmful strains in one place, and mild strains in another.

病菌水媒傳輸的程度.

So, this is very encouraging,

所以有些地區進化成殺傷力強的菌種.有些則進化成溫和菌種.

it suggests that something that we might want to do anyhow,

因此,這結果非常令人興奮，

if we had enough money, could actually give us a much bigger bang for the buck.

這代表有些事我們應該去做,

It would make these organisms evolve to mildness,

如果我們有足夠的錢，我們可更有效率的利用這錢來(控制瘟疫)

so that even though people might be getting infected,

使這些病菌進化成溫和菌種.

they'd be infected with mild strains.

所以,即使人們可能被感染，

It wouldn't be causing severe disease.

他們只會被溫和的菌種(株)感染

But there's another really interesting aspect of this,

不會引起嚴重的症狀.

and this is that if you could control the evolution of virulence,