What I'd like to do is just drag us all down into the gutter, and actually all the way down into the sewer because I want to talk about diarrhea. And in particular, I want to talk about the design of diarrhea. And when evolutionary biologists talk about design, they really mean design by natural selection. And that brings me to the title of the talk, "Using Evolution to Design Disease Organisms Intelligently." And I also have a little bit of a sort of smartass subtitle to this. But I'm not just doing this to be cute. I really think that this subtitle explains what somebody like me, who's sort of a Darwin wannabe, how they actually look at one's role in sort of coming into this field of health sciences and medicine. It's really not a very friendly field for evolutionary biologists. You actually see a great potential, but you see a lot of people who are sort of defending their turf, and may actually be very resistant, when one tries to introduce ideas.
我想做的仅仅是将大家拽下排水沟, 并且实际上,一路下到下水道里 因为我想谈谈痢疾。 而且特别是,我想谈谈 痢疾的设计。 当进化生物学家谈起设计的时候 他们实际上表示的自然选择的设计。 这就引出了我这次演讲的题目, “通过进化来巧妙地设计病菌”。 并且我也有一个稍显聪明一些的副标题。 但我这么说不是为了引人注目。 我确实认为这个副标题说明了 像我这样的达尔文的崇拜者, 他们事实上是如何看待一个人在 健康科学和医学领域中的角色。 对进化生物学家们来说这真不是个友好的领域。 你确实看到了巨大的潜力, 但你也会看到许多人固步自封, 实际上这些人在他人试图 提出新观点时也许会非常的抗拒。
So, all of the talk today is going to deal with two general questions. One is that, why are some disease organisms more harmful? And a very closely related question, which is, how can we take control of this situation once we understand the answer to the first question? How can we make the harmful organisms more mild? And I'm going to be talking, to begin with, as I said, about diarrheal disease organisms. And the focus when I'm talking about the diarrheal organisms, as well as the focus when I'm talking about any organisms that cause acute infectious disease, is to think about the problem from a germ's point of view, germ's-eye view. And in particular, to think about a fundamental idea which I think makes sense out of a tremendous amount of variation in the harmfulness of disease organisms. And that idea is that from the germ's-eye point of view, disease organisms have to get from one host to another, and often they have to rely on the well-being of the host to move them to another host.
因此,今天所有的讨论都是为了解决两个普通的问题。 一个是,为什么一些病菌更有害, 而一个与之关系非常密切的问题是, 一旦我们有了第一个问题的答案, 我们如何才能控制这种情况? 我们如何才能使这些有害病菌的危害变得更轻微些? 而我将要谈论的,正如我所说,首先从 痢疾病菌开始。 并且,当我谈论痢疾病菌时, 同样,当我谈论任何 导致急性传染病的病菌时, 重点是从细菌的角度来思考这类问题。 细菌的视角。 尤其是考虑一个基本的观点, 我认为在有害的病菌中出现 大量的变异是合理的。 这一观点是从细菌的角度来看的, 病菌不得不从一个宿主迁移到另一个宿主, 并且它们通常不得不依赖于健康的宿主 把它们迁移到另一个宿主上。
But not always. Sometimes, you get disease organisms that don't rely on host mobility at all for transmission. And when you have that, then evolutionary theory tells us that natural selection will favor the more exploitative, more predator-like organisms. So, natural selection will favor organisms that are more likely to cause damage. If instead transmission to another host requires host mobility, then we expect that the winners of the competition will be the milder organisms. So, if the pathogen doesn't need the host to be healthy and active, and actual selection favors pathogens that take advantage of those hosts, the winners in the competition are those that exploit the hosts for their own reproductive success. But if the host needs to be mobile in order to transmit the pathogen, then it's the benign ones that tend to be the winners.
但并不总是这样。 有时你染上的病菌 根本不依赖于宿主的移动性来传播。 而当你染上他们后,进化论告诉我们 自然选择会倾向于更会取巧的, 更有侵略性的细菌。 所以,自然选择会倾向于 更能造成破坏的细菌。 如果传播至另一宿主依靠原宿主的移动性, 那么我们可以预料竞争的胜利者 将是那些温和的细菌。 不过,如果病菌不需要宿主保持健康和活力 而且实际上自然选择倾向于选择 从宿主获利的细菌, 竞争的胜利者就是那些为了繁殖成功 而剥削宿主的病菌。 但是,如果需要宿主移动来传播病菌, 那么那些温和的病菌往往会成为胜利者。
So, I'm going to begin by applying this idea to diarrheal diseases. Diarrheal disease organisms get transmitted in basically three ways. They can be transmitted from person-to-person contact, person-to-food-then-to-person contact, when somebody eats contaminated food, or they can be transmitted through the water. And when they're transmitted through the water, unlike the first two modes of transmission, these pathogens don't rely on a healthy host for transmission. A person can be sick in bed and still infect tens, even hundreds of other individuals. To sort of illustrate that, this diagram emphasizes that if you've got a sick person in bed, somebody's going to be taking out the contaminated materials. They're going to wash those contaminated materials, and then the water may move into sources of drinking water. People will come in to those places where you've got contaminated drinking water, bring things back to the family, may drink right at that point. The whole point is that a person who can't move can still infect many other individuals.
所以,我将从把这些观点应用于痢疾病菌作为(我的演讲的)开始。 痢疾病菌有三种基本的传播途径。 它们能够通过人与人间的接触传播, 当某人吃了被污染的食物时, 会发生从人到食物再到人的传播。 或者它们能通过水进行传播。 当他们通过水传播时, 不像前两种传播方式, 这些病菌并不依赖于健康的宿主进行传播。 一个卧病在床的人仍能传染数以十计,甚至数以百计的 其他人。 为了说明这些,这个图表表明, 如果有一个卧床的病人, 总得有人来处理那些被污染的物品。 他们将清洗这些被污染的物品, 然后用于清洗的水可能会流至饮用的水源。 人们将到这些水源处取用 这些被污染的饮用水, 带着他们回到家中, 他们也许在那儿就会喝一些水。 重点是,一个不能移动的人 仍会传染其他许多人。
And so, the theory tells us that when diarrheal disease organisms are transported by water, we expect them to be more predator-like, more harmful. And you can test these ideas. So, one way you can test is just look at all diarrheal bacteria, and see whether or not the ones that tend to be more transmitted by water, tend to be more harmful. And the answer is -- yep, they are. Now I put those names in there just for the bacteria buffs, but the main point here is that -- (Laughter) there's a lot of them here, I can tell -- the main point here is that those data points all show a very strong, positive association between the degree to which a disease organism is transmitted by water, and how harmful they are, how much death they cause per untreated infection. So this suggests we're on the right track. But this, to me, suggests that we really need to ask some additional questions.
因此,这理论告诉我们 当痢疾病菌通过水进行传播时, 我们认为它们会变得更有侵略性,更加有害。 你可以测试一下这些观点。 测试它的一个方法就是,仅仅等着看这些痢疾病菌 看看它们是不是更倾向于 通过水进行传播,更加的有害。 答案是 —— 是的,的确是的。 现在我把这些名字放在这儿,仅仅为了细菌迷们, 但是要点是-- (笑声) 这儿有许多(细菌迷),我得说-- 要点是,这些数据点 显示了在两件事之间有很强的正向联系: 那就是这些病菌对水传播的依赖性, 和它们(对人)的危害, 也就是在未治疗的情况下感染它们导致死亡的人数。 因此这表明我们的思路是正确的。 但是,对我而言,这表明我们的确需要 问一些附加的问题。
Remember the second question that I raised at the outset was, how can we use this knowledge to make disease organisms evolve to be mild? Now, this suggests that if you could just block waterborne transmission, you could cause disease organisms to shift from the right-hand side of that graph to the left-hand side of the graph. But it doesn't tell you how long. I mean, if this would require thousands of years, then it's worthless in terms of controlling of these pathogens. But if it could occur in just a few years, then it might be a very important way to control some of the nasty problems that we haven't been able to control. In other words, this suggests that we could domesticate these organisms. We could make them evolve to be not so harmful to us.
回想一下我在开始提出的问题中的第二个问题, 我们怎样才能利用这些知识 来使得病菌进化的更加温和? 现在这表明,如果你能阻止水媒传播, 那么就能使病菌从 从这图表的右边转移到左边。 但是图中并没有表明这需要多久。 我是说,如果这需要数千年的话, 就控制这些病菌而言就没有意义了。 但如果这能在仅仅几年中就奏效 那么它也许就是一个非常重要的控制途径, 来控制那些我们没有控制住的严重的问题。 换句话说,这表明我们能够 驯化这些病菌。 我们能让它们进化的对我们不是那么有害。
And so, as I was thinking about this, I focused on this organism, which is the El Tor biotype of the organism called Vibrio cholerae. And that is the species of organism that is responsible for causing cholera. And the reason I thought this is a really great organism to look at is that we understand why it's so harmful. It's harmful because it produces a toxin, and that toxin is released when the organism gets into our intestinal tract. It causes fluid to flow from the cells that line our intestine into the lumen, the internal chamber of our intestine, and then that fluid goes the only way it can, which is out the other end. And it flushes out thousands of different other competitors that would otherwise make life difficult for the Vibrios.
而且,如我所回想起的我所关注的一种病菌, 一种被称为霍乱弧菌的埃尔托生物型细菌。 这种类型的细菌 导致了霍乱。 而我认为这种病菌是个好例子的原因, 是因为我们理解了为什么它如此有害。 它有害的原因是它产生一种毒素, 并且,当这些病菌在肠道中时 会释放这些毒素。 这导致了体液从肠细胞流至 肠腔内--肠内部的空间, 然后这些液体去了他们唯一能去的地方,排出体外。 这一过程冲走了数以千计的那些可能会使弧菌生存困难的 各种其他竞争者。
So what happens, if you've got an organism, it produces a lot of toxin. After a few days of infection you end up having -- the fecal material really isn't so disgusting as we might imagine. It's sort of cloudy water. And if you took a drop of that water, you might find a million diarrheal organisms. If the organism produced a lot of toxin, you might find 10 million, or 100 million. If it didn't produce a lot of this toxin, then you might find a smaller number. So the task is to try to figure out how to determine whether or not you could get an organism like this to evolve towards mildness by blocking waterborne transmission, thereby allowing the organism only to be transmitted by person-to-person contact, or person-food-person contact -- both of which would really require that people be mobile and fairly healthy for transmission.
所以,如果你感染了一个病菌,会发生什么 它会产生许多毒素。 感染后的几天的最终结果-- 排泄物实际上并不像我们想象的那么恶心。 它是一种浑浊的液体。 如果你去一滴这样的液体 你也许能找到一百万只痢疾病菌。 如果病菌产生了很多毒素, 你也许会找到一千万或是一亿只。 如果它们没有产生很多毒素 那么你也许会找到较少数量的病菌。 所以,我们的任务是试着发现 如何来确定我们是否能通过阻止水媒传播 使得这样的病菌朝着更温和的方向进化。 也就是只允许病菌通过 人与人之间的接触传播, 或者人-食物-人的接触传播。 这两种方式实际上都需要人们 能移动和有适当的健康来进行传播。
Now, I can think of some possible experiments. One would be to take a lot of different strains of this organism -- some that produce a lot of toxins, some that produce a little -- and take those strains and spew them out in different countries. Some countries that might have clean water supplies, so that you can't get waterborne transmission: you expect the organism to evolve to mildness there. Other countries, in which you've got a lot of waterborne transmission, there you expect these organisms to evolve towards a high level of harmfulness, right? There's a little ethical problem in this experiment. I was hoping to hear a few gasps at least. That makes me worry a little bit.
现在,我可以考虑一些可能的实验。 一个实验需要许多不同株这类病菌-- 一些会产生许多毒素,一些产生很少毒素-- 然后把这些株放至不同的国家。 一些国家有清洁的水源供应, 因此不能进行水媒传播, 在那儿,病菌可能会进化的更加温和。 在另一些国家会有很多水媒传播, 这些病菌会朝着 更有害的方向进化,对么? 这个实验会有些道德问题。 我(原本)以为至少会听到一些人抽冷气。 (你们这么容易就接受了这个实验计划,)这倒让我有点担心。
(Laughter)
(笑声)
But anyhow, the laughter makes me feel a little bit better. And this ethical problem's a big problem. Just to emphasize this, this is what we're really talking about. Here's a girl who's almost dead. She got rehydration therapy, she perked up, within a few days she was looking like a completely different person. So, we don't want to run an experiment like that. But interestingly, just that thing happened in 1991. In 1991, this cholera organism got into Lima, Peru, and within two months it had spread to the neighboring areas. Now, I don't know how that happened, and I didn't have anything to do with it, I promise you. I don't think anybody knows, but I'm not averse to, once that's happened, to see whether or not the prediction that we would make, that I did make before, actually holds up. Did the organism evolve to mildness in a place like Chile, which has some of the most well protected water supplies in Latin America? And did it evolve to be more harmful in a place like Ecuador, which has some of the least well protected? And Peru's got something sort of in between.
但无论如何,笑声让我感觉更好了点。 但是这个道德问题是个大问题。 只是为了强调,这是我们所谓的(道德问题)。 这是个差点死去的女孩。 她进行了补水治疗,她重新活泼起来, 在几天内她看起来像完全另外一个人。 所以我们并不想进行这样的一个实验。 但是有趣地是,这些事在1991年发生了。 1991年,在秘鲁的利马爆发了霍乱, 在两个月内病毒就传播至邻国。 我现在都不知道这是如何发生的, 而且我也与此无关,我保证。 我不认为有人知道(这是怎么发生的), 但是我并不反对,一旦一切已经发生, 看看我们做的预测, 我之前做的预测,是不是对的。 病菌会在像智利那样 有拉美保护得最好的水源供应的地方 进化的更温和么? 它会在那些水源保护的最差的地方,比如厄瓜多尔, 进化的更有害么? 而秘鲁的水源供应保护在这两种情况之间,处于中等保护程度。
And so, with funding from the Bosack-Kruger Foundation, I got a lot of strains from these different countries and we measured their toxin production in the lab. And we found that in Chile -- within two months of the invasion of Peru you had strains entering Chile -- and when you look at those strains, in the very far left-hand side of this graph, you see a lot of variation in the toxin production. Each dot corresponds to an islet from a different person -- a lot of variation on which natural selection can act. But the interesting point is, if you look over the 1990s, within a few years the organisms evolved to be more mild. They evolved to produce less toxin. And to just give you a sense of how important this might be, if we look in 1995, we find that there's only one case of cholera, on average, reported from Chile every two years.
因此,由波扎克-克鲁格基金会提供资金支持, 我从不同国家得到了许多菌株 并且,我们在实验室中仔细测量了毒素的生产。 我们发现在智利--在病毒入侵秘鲁后的两个月内 就会在智利发现菌株。 当留心观察这些菌株, 在这幅图的很靠左侧的地方, 你会看到毒素生产中的许多变异。 每个点对应着来自不同人的一个样本。 自然选择会导致许多的变异。 但是有趣的地方时,如果你仔细看看90年代, 仅仅几年病菌就进化的更温和。 它们进化的会产生更少毒素。 为了让你们对这有多重要有个感觉, 注意一下1995年起,在智利平均每两年 我们只发现一例霍乱。
So, it's controlled. That's how much we have in America, cholera that's acquired endemically, and we don't think we've got a problem here. They didn't -- they solved the problem in Chile. But, before we get too confident, we'd better look at some of those other countries, and make sure that this organism doesn't just always evolve toward mildness. Well, in Peru it didn't. And in Ecuador -- remember, this is the place where it has the highest potential waterborne transmission -- it looked like it got more harmful. In every case there's a lot of variation, but something about the environment the people are living in, and I think the only realistic explanation is that it's the degree of waterborne transmission, favored the harmful strains in one place, and mild strains in another.
这说明它被控制住了。 这就是我们在美洲所了解到的。 霍乱是地方性的。 而我们不认为这儿有问题。 没有--在智利他们解决了这个问题。 但在我们变得过于自信之前,我们最好看看其他一些国家的情况。 并确认这一病菌并不总是朝着更温和的方向进化。 好吧,在秘鲁它不是的。 而且在厄瓜多尔--别忘了这是 最可能通过水媒进行传播的地方-- 看起来,它变得更加有害了。 在每个病例中都有许多的变异, 但这与那儿的人们所居住的环境有关, 而且我认为水媒传播程度 是唯一正确的解释。 在一个地方对有害的菌株有利,而另一个地方则对温和的菌株有利。
So, this is very encouraging, it suggests that something that we might want to do anyhow, if we had enough money, could actually give us a much bigger bang for the buck. It would make these organisms evolve to mildness, so that even though people might be getting infected, they'd be infected with mild strains. It wouldn't be causing severe disease. But there's another really interesting aspect of this, and this is that if you could control the evolution of virulence, evolution of harmfulness, then you should be able to control antibiotic resistance. And the idea is very simple. If you've got a harmful organism, a high proportion of the people are going to be symptomatic, a high proportion of the people are going to be going to get antibiotics. You've got a lot of pressure favoring antibiotic resistance, so you get increased virulence leading to the evolution of increased antibiotic resistance. And once you get increased antibiotic resistance, the antibiotics aren't knocking out the harmful strains anymore. So, you've got a higher level of virulence.
这非常让人振奋, 这个结果表明我们应该,其实无论如何我们都应该, 如果我们有足够的资金,我们可以取得更大的进展, 我们可以使得这些病菌进化的更温和, 以便人们即使感染了病毒, 他们也是被温和的菌株所感染。 这不会导致严重的疾病。 但这有另一个真实而有趣的方面, 就是说如果你能控制致病力的进化, 危害性的进化, 然后你就有能力控制抗生素抗药性了。 这个想法很简单。 如果你有一个有害的病菌, 高比例的人会出现症状, 高比例的人会有抗体。 在对抗生素的抗药性的促进上有很大的压力。 因此增强的毒性导致了 (病菌对)抗生素的抗药性增强的进化。 并且,一旦(病菌)对抗生素的抗药性增强, 那么抗生素就不在能消灭有害的菌株了。 因此,你得到了更高级别的毒性。
So, you get this vicious cycle. The goal is to turn this around. If you could cause an evolutionary decrease in virulence by cleaning up the water supply, you should be able to get an evolutionary decrease in antibiotic resistance. So, we can go to the same countries and look and see. Did Chile avoid the problem of antibiotic resistance, whereas did Ecuador actually have the beginnings of the problem? If we look in the beginning of the 1990s, we see, again, a lot of variation. In this case, on the Y-axis, we've just got a measure of antibiotic sensitivity -- and I won't go into that. But we've got a lot of variation in antibiotic sensitivity in Chile, Peru and Ecuador, and no trend across the years. But if we look at the end of the 1990s, just half a decade later, we see that in Ecuador they started having a resistance problem. Antibiotic sensitivity was going down. And in Chile, you still had antibiotic sensitivity.
这是个危险的循环。 我们的目标是使这种情况得到扭转。 如果你能通过清洁水源供应来促进 毒性进化的衰减。 那你就应该能使它们对抗生素的抗药性 的进化衰减。 因此我们能去同样的国家,看一看。 智利避免了抗生素的抗药性的问题么? 而厄瓜多尔实际上只是处于这一问题的初始阶段? 如果我们看看九十年代初, 我们会又一次看到许多的变异。 在这种情况下,在Y轴上我们会得到一个对抗生素敏感性的衡量。 我不准备详谈这些。 但在智利,我们发现了许多抗生素敏感性的变异。 秘鲁和厄瓜多尔,没有跨越数年的趋势。 但如果我们看看90年代末,仅仅五年后, 我们看到在厄瓜多尔,开始有抗药性的问题了。 抗生素的敏感性在下降。 而在智利仍有抗生素敏感性。
So, it looks like Chile dodged two bullets. They got the organism to evolve to mildness, and they got no development of antibiotic resistance. Now, these ideas should apply across the board, as long as you can figure out why some organisms evolved to virulence. And I want to give you just one more example, because we've talked a little bit about malaria. And the example I want to deal with is, or the idea I want to deal with, the question is, what can we do to try to get the malarial organism to evolve to mildness? Now, malaria's transmitted by a mosquito, and normally if you're infected with malaria, and you're feeling sick, it makes it even easier for the mosquito to bite you.
因此,看起来智利避免了两个问题。 他们使病菌进化的更温和, 而且他们没有让病菌的抗药性进一步恶化。 现在这些观点应该被全面的应用。 只要你能弄明白为什么一些病菌进化的更具毒性。 我想仅仅再给出一个例子, 因为我们已经谈论了一下痢疾。 而我想要给出的例子是, 或者说我想提出的想法,问题是, 为了使痢疾病菌进化的更加温和,我们能做什么? 现在,痢疾通过蚊子进行传播, 通常,如果你感染了痢疾,你会觉得不舒服, 这使得蚊子更容易叮你。
And you can show, just by looking at data from literature, that vector-borne diseases are more harmful than non-vector-borne diseases. But I think there's a really fascinating example of what one can do experimentally to try to actually demonstrate this. In the case of waterborne transmission, we'd like to clean up the water supplies, see whether or not we can get those organisms to evolve towards mildness. In the case of malaria, what we'd like to do is mosquito-proof houses. And the logic's a little more subtle here. If you mosquito-proof houses, when people get sick, they're sitting in bed -- or in mosquito-proof hospitals, they're sitting in a hospital bed -- and the mosquitoes can't get to them.
而且,仅仅通过查看文献中的数据,你就会发现 通过虫媒传播的疾病比那些 通过非虫媒传播的疾病更加有害。 但我想有个真实的迷人的例子, 人们可以做实验来尝试实际的去论证这些。 就水媒传播而言, 我们想通过清理水源供应, 来看看是否能使得这些病菌朝着温和的方向进化。 就痢疾而言,我们想做的是建造防蚊的房屋。 这儿的逻辑有点更微妙了。 如果在防蚊的房屋里, 当人们生病了,坐在床上时, 或者在防蚊的医院中,人们坐在医院的床上时, 蚊子没法去叮咬他们。
So, if you're a harmful variant in a place where you've got mosquito-proof housing, then you're a loser. The only pathogens that get transmitted are the ones that are infecting people that feel healthy enough to walk outside and get mosquito bites. So, if you were to mosquito proof houses, you should be able to get these organisms to evolve to mildness. And there's a really wonderful experiment that was done that suggests that we really should go ahead and do this. And that experiment was done in Northern Alabama. Just to give you a little perspective on this, I've given you a star at the intellectual center of the United States, which is right there in Louisville, Kentucky. And this really cool experiment was done about 200 miles south of there, in Northern Alabama, by the Tennessee Valley Authority. They had dammed up the Tennessee River. They'd caused the water to back up, they needed electric, hydroelectric power. And when you get stagnant water, you get mosquitoes. They found in the late '30s -- 10 years after they'd made these dams -- that the people in Northern Alabama were infected with malaria, about a third to half of them were infected with malaria.
因此如果你是一个有害的病菌, 结果不得不待在一个防蚊的房子里,你就输了。 那些唯一能传播的病原体 是通过那些感染了却觉得自己很健康的人进行传播的, 他们走到外面,被蚊子叮咬了。 那么,如果你在防蚊的房屋里, 你就能够使得这些病菌进化的更温和。 实际上我们已经作了一个非常棒的实验, 这实验说明我们应该来使用防蚊的房屋和医院。 这个实验室在北阿拉巴马进行的。 仅仅给你一个关于这一实验的小观点, 我告诉你一个位于肯塔基的路易斯维尔的 美国知识产权中心的明星。 这个非常酷的实验是由田纳西流域管理局作的, 实验地点是从这个中心向南大约200英里的地方, 就在北阿拉巴马。 他们阻塞了田纳西河。 他们把水蓄积起来, 他们需要电力,水电。 而当有一片死水的时候,就会出现蚊子。 他们发现在最近30年代后期--在建造了这些大坝后的十年内-- 北阿拉巴马的人们感染了疟疾。 大约三分之一到一半的人感染了疟疾。
This shows you the positions of some of these dams. OK, so the Tennessee Valley Authority was in a little bit of a bind. There wasn't DDT, there wasn't chloroquines: what do they do? Well, they decided to mosquito proof every house in Northern Alabama. So they did. They divided Northern Alabama into 11 zones, and within three years, about 100 dollars per house, they mosquito proofed every house. And these are the data. Every row across here represents one of those 11 zones. And the asterisks represent the time at which the mosquito proofing was complete. And so what you can see is that just the mosquito-proofed housing, and nothing else, caused the eradication of malaria. And this was, incidentally, published in 1949, in the leading textbook of malaria, called "Boyd's Malariology." But almost no malaria experts even know it exists. This is important, because it tells us that if you have moderate biting densities, you can eradicate malaria by mosquito proofing houses.
这里显示了这些水库的位置。 那好,田纳西流域管理局受到一点点限制。 在那儿不能用滴滴涕,不能用氯喹,那么人们该怎么办? 好吧,他们决定让北阿拉巴马的每所房屋都能够防蚊。 他们这么做了。他们把北阿拉巴马分成了11个区域, 并且在三年内,每所房子花费大约100美元, 他们对每所房子都进行了防蚊处理。 这儿是一些数据。 每个横跨这里的一行表示11个区域的其中之一。 这些星号表示防蚊措施实施 完成的时间。 那么你可以看到, 仅仅是进行了房屋的防蚊处理,没有做别的, 就根除了疟疾。 而且这在1949年,偶然地发表在 关于疟疾最重要的名为"博伊德的痢疾学"的教科书中。 但是几乎没有痢疾方面的专家知道它的存在。 这很重要, 因为它告诉我们,如果在中等的叮咬密度下, 你用防蚊的房屋就能消除疟疾。
Now, I would suggest that you could do this in a lot of places. Like, you know, just as you get into the malaria zone, sub-Saharan Africa. But as you move to really intense biting rate areas, like Nigeria, you're certainly not going to eradicate. But that's when you should be favoring evolution towards mildness. So to me, it's an experiment that's waiting to happen, and if it confirms the prediction, then we should have a very powerful tool. In a way, much more powerful than the kind of tools we're looking at, because most of what's being done today is to rely on things like anti-malarial drugs. And we know that, although it's great to make those anti-malarial drugs available at really low cost and high frequency, we know that when you make them highly available you're going to get resistance to those drugs. And so it's a short-term solution. This is a long-term solution.
现在,我建议可以在许多地方这么做。 比如,你知道,正如你进入疟疾区, 非洲的撒哈拉以南。 但是如果你去有十分强烈的叮咬率的区域,比如尼日利亚, 你肯定不能根除它。 但是你可以帮助它们变得更加温和。 因此对我而言,这是个等待发生的实验, 而如果它确认了预测的结果,那么 我们就会有了一个非常强有利的工具。 在某种程度上,它是比我们现在用的工具有力得多。 因为如今我们能做的就是 依赖于像抗疟疾药似的东西。 而我们知道,虽然这能让这些抗疟疾药 以实在的低价和高频率供应。 我们知道,当你不断用药时, 它们将对这些药产生抗药性。 所以这是个短期的解决方案。 这是个长期的解决方案。
What I'm suggesting here is that we could get evolution working in the direction we want it to go, rather than always having to battle evolution as a problem that stymies our efforts to control the pathogen, for example with anti-malarial drugs. So, this table I've given just to emphasize that I've only talked about two examples. But as I said earlier, this kind of logic applies across the board for infectious diseases, and it ought to. Because when we're dealing with infectious diseases, we're dealing with living systems. We're dealing with living systems; we're dealing with systems that evolve. And so if you do something with those systems, they're going to evolve one way or another. And all I'm saying is that we need to figure out how they'll evolve, so that -- we need to adjust our interventions to get the most bang for the intervention buck, so that we can get these organisms to evolve in the direction we want them to go.
我的建议是,我们能让进化 朝着我们希望的方向进行。 而不总是与进化做斗争。 这是个问题因为它妨碍了我们对控制病原体做出的努力, 例如抗疟疾药。 因此,我给出的这张表仅仅是为了强调, 我只是谈了两个例子。 但如我之前所说,这类的逻辑应用贯穿整个 传染病领域,应该这样。 由于当我们应对传染病时,我们是在应对生命系统。 我们在应对生命系统, 我们在应对一个可以进化的系统。 而如果你对这样的系统做了些什么, 它们将朝着这个或那个方向进化。 而所有我要说的是,我们需要弄明白它们如何进化, 以便于我们调整我们的干预措施, 来获得最大收益的干预措施, 以便于我们能使这些病菌朝着我们期望的方向进化。
So, I don't really have time to talk about those things, but I did want to put them up there, just to give you a sense that there really are solutions to controlling the evolution of harmfulness of some of the nasty pathogens that we're confronted with. And this links up with a lot of the other ideas that have been talked about. So, for example, earlier today there was discussion of, how do you really lower sexual transmission of HIV? What this emphasizes is that we need to figure out how it will work. Will it maybe get lowered if we alter the economy of the area? It may get lowered if we intervene in ways that encourage people to stay more faithful to partners, and so on.
所以,我真的没有时间来讨论这些事, 但我确实想要把它们放在这儿。 仅仅为了给你们一个感觉,我们确实有办法 来控制 一些我们所面对的有害的病菌的进化。 并且,这把许多之前讨论过的观点联系了起来。 那么,例如,今天早些时候的讨论, 如何真正降低艾滋病毒的性传播? 需要强调的是我们需要清楚它是如何造成危害的。 如果我们改变了这一区域的经济状况,它可能会降低么? 它可能会降低,如果我们的干预措施 鼓励人们对他们的伴侣更忠诚,等等。
But the key thing is to figure out how to lower it, because if we lower it, we'll get an evolutionary change in the virus. And the data really do support this: that you actually do get the virus evolving towards mildness. And that will just add to the effectiveness of our control efforts. So the other thing I really like about this, besides the fact that it brings a whole new dimension into the study of control of disease, is that often the kinds of interventions that you want, that it indicates should be done, are the kinds of interventions that people want anyhow. But people just haven't been able to justify the cost.
但关键是明白如何降低它。 因为如果我们降低它的话,我们将改变病毒的进化。 并且有数据的确实支持的, 如果你确实是让病毒朝着更加温和的方向进化。 并且这将增加我们的控制投入的效率。 因此,另一个我确实喜欢的部分是, 除了它会为疾病控制研究带来 一个全新的领域之外, 通常各种你想要的干预措施, 这些应该做的干预措施, 就是人们无论如何都想要的那些干预措施。 但人们只是不能判断出所需付出的代价。
So, this is the kind of thing I'm talking about. If we know that we're going to get extra bang for the buck from providing clean water, then I think that we can say, let's push the effort into that aspect of the control, so that we can actually solve the problem, even though, if you just look at the frequency of infection, you would suggest that you can't solve the problem well enough just by cleaning up water supply. Anyhow, I'll end that there, and thank you very much.
因此,我所谈论的这类事情, 如果我们知道我们将会从提供清洁的水源中获得额外的好处, 那么我想,我们会说, 让我们努力推进这方面的控制, 以便我们能真正的解决这个问题, 即使这样,如果你仅仅是看看这些感染的频率, 你可能会觉得这个问题无法仅仅通过清理水源供应 就可以很好的解决。 总之,我的演讲到此结束,非常感谢。
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