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这位科学家通过研究古老的昆虫来助力抗击疟疾 | 盖茨笔记

Bill Gates 比尔盖茨 2023-12-20

Of all the things I thought would help fight malaria, 100-year-old mosquitoes would not have been high on the list. Then I learned about the work of Dr. Mara Lawniczak.

在我想到有助于抗击疟疾的所有探索中,研究百岁高龄的蚊子并不是优先项。直到我了解到了玛拉·劳尼查克博士的研究工作。

An evolutionary geneticist at the Wellcome Sanger Institute in the United Kingdom, Mara has spent much of her career trying to understand how the genomes of various mosquito species have changed in response to humans’ attempts to kill them. When, where, and how fast has it happened? What does that say about how they might evolve in the future?

作为英国威康桑格研究所的进化遗传学家,玛拉在她的职业生涯中大部分时间都在致力于理解不同蚊子物种的基因组在人类试图消灭它们的过程中如何发生变化——何时、何地以及变化的速度有多快,而这对于预测它们将来可能如何进化有何影响。

In recent years, genetics has become an increasingly important tool for fighting malaria. Because mosquitoes breed so fast (a female can lay thousands of eggs in her lifespan of a couple of weeks), they evolve rapidly, at least compared to humans. By studying their genes, researchers are able to understand things like how they develop resistance to insecticides, crucial information that helps humans stay one step ahead.

近年来,基因学已经成为抗击疟疾的日益重要的工具。因为蚊子繁殖速度极快(雌蚊在它几周的寿命内可以产千百只卵),它们进化也相当迅速,至少与人类相比如此。通过研究它们的基因,研究人员能够了解诸如它们如何对杀虫剂产生抗性等问题,这些关键信息有助于人类保持领先一步。

After a few years of studying mosquitoes’ genomes, Mara had grown frustrated by the fact that the only insects available for study were ones that had been captured recently. Without DNA from their ancestors, there was no way to know how their genomes had responded to decades of human attacks. “We were often saying, ‘If only we could look into the past,’” Mara says. “And then it suddenly struck me: I'm sure there are historical collections of mosquitoes around.”

经过几年研究蚊子的基因组后,玛拉开始对目前只能研究最近捕获的昆虫感到沮丧。没有来自它们祖先的DNA,就无法了解它们的基因组在数十年的人类攻击中发生了什么样的变化。“我们经常会说,如果我们能够回到过去就好了”,玛拉说道,“突然有一天我恍然大悟:肯定存在着有关蚊子的历史样本。”

She was right. The Natural History Museum in London has a collection of 34 million insects from all over the world, carefully collected and preserved. Among the collection is a large sample of mosquitoes dating from 1936, when a British entomologist named H.S. Leeson spent a year in East Africa capturing and cataloguing the insects in the hope of learning more about malaria. Leeson didn’t know it at the time—DNA wouldn’t be discovered until the 1950s—but his collection of mosquitoes would become a vast source of genetic material that someone like Mara could study.

她是对的。伦敦自然史博物馆收藏了来自世界各地的3,400万只昆虫标本,这些昆虫经过精心采集和保存。在这些收藏中,有一大批蚊子样本,可以追溯到1936年,当时英国昆虫学家H.S.·利森在东非度过了一年的时间,捕捉并记录这些昆虫,希望能更多地了解关于疟疾的信息。利森当时并不知道(直到20世纪50年代才发现DNA的存在)他的蚊子收藏将成为像玛拉这样的研究人员可以研究的丰富的基因材料来源。

Mara reached out to the museum’s curators. They wanted to help, but there was a problem: Extracting DNA from the insects would require Mara to grind them up. Since the museum’s mission is to preserve its collection for future generations, they couldn’t let her do that.

玛拉与博物馆馆长取得联系。他们愿意提供帮助,但出现了一个问题:从昆虫中提取DNA需要玛拉将它们研磨成粉末。由于博物馆的使命是为了将这些收藏保存给未来的世代,他们不能允许她这样做。

So Mara and her colleagues invented a way around the problem. Working with the museum’s team, they developed a novel way to extract DNA from mosquitoes without damaging the specimen.

因此,玛拉和她的同事们想出了解决这个问题的方法。与博物馆的团队合作,他们研发了一种新颖的方法,可以在不损害标本的情况下从蚊子身上提取DNA。

They affectionately call this work Project Neandersquito. It’s not because the mosquitoes date from the time of Neanderthals, some 40,000 years ago—this isn’t Jurassic Park, where they extract dinosaur DNA from a prehistoric mosquito trapped in amber. It’s because the mosquitoes they’re studying are 1,000 or 2,000 generations removed from modern ones, just as Neanderthals are more than 1,000 generations removed from modern humans.

他们亲切地将这项工作称为“尼安德特蚊计划”。这并非因为这些蚊子可以追溯到约40,000年前的尼安德特人时代——就像《侏罗纪公园》中从困在琥珀里的史前蚊子体内提取恐龙DNA那样。而是因为他们所研究的蚊子与现代蚊子相隔了大约1,000到2,000代,就像尼安德特人与现代人相隔超过1,000代一样。

Mara’s team has made some surprising finds. For example, because mosquitoes started developing resistance to the insecticide DDT in the 1950s, they expected to see genetic mutations for resistance appearing around the same time. But they didn’t. “We still don't see them even as late as the 1980s,” she says. “So the mosquitoes were somehow making themselves resistant to DDT in ways that we still don't really understand.”

玛拉的团队取得了一些令人惊讶的发现。例如,由于蚊子在20世纪50年代开始对杀虫剂DDT产生抗药性,按预期它们会在大约同一时间出现产生抗药性的遗传突变,但事实并非如此。玛拉说:“甚至到了20世纪80年代,我们仍然没有看到这些抗药性的遗传突变。所以这些蚊子以某种方式使自己对DDT产生了抗性,而我们对这种抗性方式仍然了解甚少。”

They also hope to get insight into what's coming. “How fast can mosquitoes evolve? And as we throw new control initiatives at them, how quickly are they going to get around them?” Other labs are now using the process devised by the Lawniczak Group to do their own research.

他们还希望能够洞察未来。“蚊子能够以多快的速度进化?当我们针对它们投入新的控制措施时,它们会以多快的速度适应?”其他实验室现在也在使用劳尼查克团队(Lawniczak Group)设计的此方法进行研究。

Project Neandersquito is just one of the ways Mara and her team are using genomics to advance the fight against malaria. A different project, the Malaria Cell Atlas, is providing new genetic data that could inform the effort to make better malaria drugs and vaccines. Another project is designed to make it easier and cheaper to identify a mosquito’s species using its DNA—it’s surprisingly hard to do just by looking—as well as whether it’s carrying the parasite that causes malaria, and even which species of the parasite it has. Ultimately, the project’s goal is to help governments get data that will help them get the most out of their anti-malaria efforts.

“尼安德特蚊计划”只是玛拉和她的团队利用基因组学推进抗击疟疾斗争的众多方式之一。另一个项目,即“疟疾细胞图谱”(Malaria Cell Atlas),提供了新的基因数据,可以为研发更好的抗疟药物和疫苗提供信息。另一个项目旨在通过利用蚊子的DNA,更简单易行、成本低廉地鉴定其物种——因为仅仅通过外观判断实际上难度极大——以及判断其是否携带引起疟疾的寄生虫,甚至是携带哪种寄生虫。最终,该项目的目标是帮助各国政府获得数据,以帮助它们更有效地开展抗击疟疾的工作。

Mara would be the first to say that these are just a few examples of the tools the world needs to eradicate malaria. It’s going to take global cooperation from governments, the private sector, and academia. And now we can add natural history museums to the list.

玛拉会毫不犹豫地说,这只是全球根除疟疾所需工具的几个例子而已。这需要政府、私营部门和学术界的全球合作。现在,我们还可以把自然历史博物馆列入到合作名单中。


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