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  • What I'd like to do is just drag us all down into the gutter,

    譯者: Inder Peng(彭) 審譯者: Shelley Krishna Tsang

  • 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,

    還有更有意思的另方面是:

  • evolution of harmfulness,

    如果我們可以控制病毒性的演變,

  • then you should be able to control antibiotic resistance.

    危害性的進化.

  • And the idea is very simple.

    那我們應該能夠控制抗生素的耐藥性

  • If you've got a harmful organism,

    原理非常簡單,

  • a high proportion of the people are going to be symptomatic,

    如果人們被殺傷力強的菌種感染,

  • a high proportion of the people are going to be going to get antibiotics.

    就會有高比例的人生病(症狀嚴重).

  • You've got a lot of pressure favoring antibiotic resistance,

    那大量抗生素將會被使用來控制病情,

  • so you get increased virulence leading to

    結果會有利於抗生素耐藥性的產生.

  • the evolution of increased antibiotic resistance.

    也就是增加導致毒性更強

  • And once you get increased antibiotic resistance,

    且對抗生素產生耐藥性的細菌增加.

  • the antibiotics aren't knocking out the harmful strains anymore.

    一旦耐藥性增強,

  • So, you've got a higher level of virulence.

    這種抗生素就不再對這菌種(株)產生作用.

  • So, you get this vicious cycle.

    那細菌的毒性會更強.

  • The goal is to turn this around.

    最後這是個惡性循環.

  • If you could cause an evolutionary decrease in virulence

    我們的目標是要扭轉這個局面。

  • by cleaning up the water supply,

    如果可以通過淨化水源來