The power of venom -- and how it could one day save your life | Mandë Holford

翻译人员: Siyu Zhu 校对人员: Yolanda Zhang

How does a sea snail catch a fish?

海螺如何捕捞一条鱼？

I mean, it's a snail, so it's slow,

我的意思是， 它很像蜗牛，所以它很慢，

and the fish is not.

鱼的速度却很快。

But yet, this happens.

但是呢，这件事发生了。

Hidden under the sand is a cone snail.

鸡心螺藏在沙的下面。

And that orange thing you see is kind of like a tongue.

你看见的橙色东西像一个舌头，

We call it a proboscis.

我们称它为长鼻。

It uses that to track and subdue this unsuspecting fish.

用来跟踪和制服 这条毫无防备的鱼。

In this predator-prey interaction,

在这种捕食者与猎物的互动中，

these are clearly not your garden variety escargots.

这些软体动物显然不如 你花园里的各种田螺那般和善，

These are assassins of the sea.

它们可是大海里的刺客，

And their weapon of choice is venom.

它们选择的武器是毒液。

Venom, like the venom you find in venomous snakes and scorpions,

就像毒蛇和蝎子体内的毒液，

these sea snails, they use their venom to subdue fish, worms

这些海螺也用毒液 制服鱼类、蠕虫

and other snails.

和其他海螺。

And the venom of these snails,

这些蜗牛的毒液

it's not just one thing,

不只是单一成分的物质，

it's actually a cocktail of toxic molecules

实际上是一种有毒分子的混合物，

that are packaged and delivered through a false tooth called a radula.

由一颗叫做“齿舌”的伪齿 携带并释放。

You can think of the radulas as hypodermic needles.

你可以把齿舌 想成皮下注射针头。

Now, no need to worry,

不过不用担心，

these snails are practicing good needle habits,

这些海螺正在练习 良好的注射习惯，

because each radula is only used once.

因为每一个齿舌只能用一次。

Now from your own knowledge about venomous organisms,

基于你对有毒生物的认知，

and the keep-you-up-at-night fish-killing video that I just showed you,

还有刚刚播放的 那段令人不寒而栗的杀鱼视频，

you might think that venom is dangerous and all bad.

你可能会认为毒液 是危险的，有害无利。

Well, yes and no.

是，也不是。

A more accurate way of thinking of venom

一种更准确的理解毒液的方式

is to think of it as both a supervillain and a superhero.

是把它同时看作 超级坏蛋和超级英雄。

In my lab, we study the evolution of venom in these sea snails

在我的实验室中，我们研究了 这些海螺毒液作为一种有益的力量，

as a force for good.

是如何进化的。

Sounds like a stretch,

听起来有点夸张，

or maybe even snake oil,

甚至可能做成蛇油，

but actually,

但实际上，

while there are snakes involved, the product is legit.

虽然有涉及到蛇， 该产品本身是合法的。

One reason the venom product is so successful

基于毒液的产品 如此成功的原因之一，

is that it transforms a physical warfare into a biochemical one.

是因为它把一个物理战争， 变成了生物战。

Where usually the predator-prey interaction is one of brute force,

通常，捕食者和被捕食者之间的 相互作用是一种蛮力，

venom takes it to a molecular scale.

而毒液将其带入了分子层面。

And it's not size that matters,

而且重要的并不是 生物体本身的尺寸，

but the mixture of your venom arsenal.

而是毒液混合物的成分。

The chemistry of the toxins in your arsenal

在你的武器库中 毒素的化学成分，

is what's going to enable David to conquer Goliath.

就是你制胜强敌的秘诀。

And in our scenario, David is clearly the snail.

在我们的研究领域中， 弱势的一方显然就是海螺。

Another feature of venom that makes it so successful

毒液如此成功的另一个特点，

is that the toxins work with the precision of a Swiss Army knife.

就是其效用精度堪比瑞士军刀。

And so these toxins,

这些毒素

they come for strongholds that help an organism to function.

会攻击协助生物体 发挥功能的关键组织。

So they target blood, brain and membranes.

因此，它们的作用目标 是血液、大脑和膜质。

Whether it's snail venom or snake venom,

不管是海螺毒素还是蛇毒，

they each have components that can do things

其中都含有

可以使你的血液凝结的成分，

like cause your blood to clot,

what we call "hemotoxic."

我们称之为“血液毒性”。

Or they cause neurons in your brains to not function normally,

或者它们会导致你大脑中的 神经元无法正常工作，

what we call "neurotoxic."

我们称之为“神经毒性”。

Or they have toxins that will poke holes into the membranes of your cells,

或者它们含有的毒素会在 你的细胞膜上戳出小孔，

causing them to rupture and, basically, explode,

导致它们破裂， 基本上是爆开了，

what we call "cytotoxic."

这是我们所谓的“细胞毒性”。

Cellular explosion, people.

细胞爆炸了！

Now, if that is not all powerful and all present,

没有什么比这种特性

nothing is.

更强大的了。

Now a little about me,

现在，我想谈谈我自己的经历，

and why I'm so obsessed with venom.

以及为什么我如此痴迷毒液。

I grew up in New York City

我在纽约市长大，

with forced access to the Natural History Museum.

经常“被迫前往” 自然历史博物馆参观。

I say "forced access,"

我说“被迫前往”，

because I'm one of five kids,

是因为我们家有五个孩子，

and my parents used museums as a form of childcare.

我父母用参观博物馆 作为一种育儿方式。

There were two rules:

他们有两条规则：

Don't lose anybody

不要让任何人走丢，

and meet Mom and Dad at the African elephants

在下午 5 点半博物馆关门的时候，

at 5:30, when the museum closes.

在非洲大象那里和爸爸妈妈会合。

Those totally unsupervised days running through the halls of the museum

那些在博物馆大厅里 无拘无束的日子

were full of adventure and exploration.

充满了冒险和探索。

And that's how I feel when I'm studying venom.

那也是我研究毒液时的感受。

It's a scientific adventure.

这是一次科学冒险。

We're boldly exploring this entity that connects nature and humanity.

我们正在大胆探索 这种连接自然与人类的物质。

Another reason that I'm obsessed with venom

我沉迷于毒液的另一个原因

is because of its duality.

是因为它的双重特性。

When you inject the components of a venom arsenal into an organism,

当你把毒液库的成分注射到 一个有机体中，

it can kill or it can cure.

它可以杀死， 也可以治愈这个有机体。

At a molecular level, several things can happen.

在分子水平， 可能会有几种不同的结果。

You saw one thing, paralysis in the fish.

你可以看到，鱼瘫痪了。

Now that was happening because the toxins in the venom

之所以会发生这种情况， 是因为毒液中的毒素

were attacking how the fish's cells communicate with each other,

攻击了鱼的细胞之间的交流，

preventing it from swimming away.

让它丧失了游开的能力。

Are there other things that I would like to use venom to attack?

还有其他我想 用毒液攻击的东西吗？

For sure.

当然。

And one of those is cancer.

其中之一就是癌症。

Cancer tumors are cells.

癌症肿瘤也是由细胞构成的。

And like all cells,

就像所有细胞一样，

they communicate with themselves and their environment around them.

肿瘤细胞也会在彼此之间 以及与周围的环境沟通。

So we would like to find venom components

所以我们想要找到

that are very good at disrupting how the tumor cells communicate.

能够扰乱肿瘤细胞通讯的毒液成分。

Similar to how the venom disrupted how the fish cells communicated

就像毒液扰乱了 鱼体内的细胞交流，

and the fish couldn't swim away.

因此鱼不会游走一样。

In my lab, we study cancer as a channelopathy.

在我的实验室里，我们把癌症 当作一种通道病来研究。

What this means is, basically, we're looking for venom components

基本上，这就意味着 我们正在寻找毒液成分，

that will target channels that are overexpressed in tumor cells

它会定位肿瘤细胞中过表达的通道，

versus normal cells.

而不是正常细胞。

The cancer that we're most focused on right now

现在我们的研究最关注的是

is liver cancer.

肝癌。

And that's because since the 1980s,

那是因为自 1980 年代以来，

the death rate of liver cancer has doubled,

肝癌死亡率增加了一倍，

and it's an emerging threat in the US.

成为了美国的一个新的威胁。

In a screen in which we had cervical,

在对宫颈癌、神经母细胞瘤、

neuroblastoma, prostate and liver cancer cells,

前列腺癌和肝癌细胞的筛查中，

we found a compound from a terebrid snail

我们发现了一种 来自特瑞布里蜗牛的化合物，

that seems to attack liver cancer cells,

它似乎可以攻击，

and only liver cancer cells, and none of the others that were tested.

且只攻击肝癌细胞， 而非其他被测试的细胞。

And then, when we took this compound and we injected it into mouse models

然后，当我们使用这种化合物， 并将其注射到

that were expressing liver cancer cells,

表达肝癌细胞的小鼠模型中，

it significantly inhibited the growth of the tumors.

它显著地抑制了肿瘤的生长。

We're not quite sure how this works yet,

我们尚无法确定其背后的原因，

we're still investigating the mechanism

仍在调查其背后的作用机理，

and how we can make this compound more effective,

以及我们如何可以 让这种化合物更有效，

so you can't rush out to the pharmacy

所以目前，我们还无法

and order up a killer snail liver-cancer therapy treatment.

在药房直接买到一只杀手海螺， 并用于肝癌治疗。

Not yet.

现在还不行。

Basically, what we think is happening

那么我们目前的推测是，

is that the compound is blocking a specific channel,

这种化合物阻断了 一个特定的通道，

prohibiting the transmission of a specific chemical

阻止了一种特定化学物质的传递，

that leads to downstream signaling

这种化学物质促成了 下游信号的传递，

that enables the tumor to multiply and draw blood to itself.

使得肿瘤能够繁殖 并引导血液进入自身体内。

What we're doing in studying the components of venom

我们通过研究毒液的成分

to find treatments for human diseases and disorders,

来寻找治疗人类疾病和失调的方法，

is not new,

这并不是什么新鲜事，

it's what we call natural products drug discovery,

而是我们所谓的 “天然产物药物发现”，

and it's been happening for centuries,

几个世纪以前 就已经出现在了

and in cultures all over the world.

在世界各地的文化中。

Venoms are not only giving us cool new compounds,

毒液不仅为我们提供了 神奇的新型化合物，

but they're also giving us new ways of thinking

也为我们提供了

治疗人类疾病和生理失调的 新思考方式。

about how we treat human diseases and disorders.

And I'll give you three examples.

我想举三个例子。

The first is from killer snails, of course.

首先，当然是杀手海螺。

And so the first drug from these snails that is on the market

市场上第一种 从这些海螺身上提取的药物

is called ziconotide, or Prialt,

叫做 ziconotide， 或齐考诺肽（Prialt），

and it's used to treat chronic pain in HIV and cancer patients.

用以治疗艾滋病 和癌症患者的慢性疼痛。

Prialt is a nonaddictive pain therapy.

齐考诺肽是一种非成瘾的疼痛疗法。

Three magic words when you think about how we're treating pain currently.

想到我们现在是如何治疗疼痛的， 就不得不想到三个神奇的词。

We're using things that have a huge cost of addiction.

我们目前的治疗手段 是以高成瘾性为代价的。

So think of morphine

想想吗啡，

or think of any of your favorite opioid out there.

或任何你喜欢的阿片类药物。

What the snails have done

而海螺向我们展示了

is they've shown us a way to treat pain without the addiction,

一种治疗疼痛而不会导致

which is huge.

严重上瘾的方法。

The next example comes from the Brazilian pit viper.

下一个例子， 是来自巴西的响尾蛇。

From these snakes, we've derived a compound called captopril.

从这些蛇中，我们得到了 一种称为卡托普利（captopril）的化合物，

Captopril is used to treat high blood pressure,

可用于治疗高血压，

and captopril is a breakthrough drug.

同时也是一种突破性药物。

But not only in and of itself,

但不仅如此，

but because it advanced a whole class of drugs,

因为还它推进了 一套药物的研发，

what we know as ACE inhibitors,

也就是所谓的 “ACE 抑制剂”，

which are the most commonly [prescribed] for treating hypertension

这是治疗高血压和心力衰竭

and heart failure.

最常见的（处方）。

The last example is from the Gila monster.

最后一个例子来自 毒蜥（Gila monster）。

And this is a really exciting example of understanding the ecology

从这些生物体的生态学研究，

和将其与有效的药物发现 相结合的角度来说，

of these organisms,

and pairing it with efficient drug discovery.

这是一个非常令人兴奋的例子，

And Gila monsters are binge eaters.

毒蜥是暴食者。

So when they bite into a large meal,

所以当它们大快朵颐时，

they release things in their venom that lower blood sugar.

会释放能够导致血糖降低的毒液。

So what's the drug that you think we found from the Gila monster?

那么你认为我们从毒蜥那里 找到了什么药物？

A compound that is used to lower the blood sugar in diabetic patients.

一种用来降低 糖尿病患者血糖的化合物。

Now these are three marvelous examples,

这些就是三个令人惊叹的例子，

but we've just scratched the surface.

但还只是冰山一角。

There's so much more venom out there for us to study.

还有更多毒液有待研究。

In fact, we think that 15 percent of all the animals on the planet

实际上，我们认为 地球上 15% 的动物

are venomous.

都是有毒的。

And I think this is a low estimate,

而且我认为只是 一个保守的估计，

given the fact that we haven't surveyed all the animals on the planet.

鉴于我们尚未触及到 地球上的所有动物。

But nature seems to have found something that she likes,

但是大自然似乎已经 找到了她喜欢的东西，

and she's repeated it over and over and over again,

并且不断地重复，

leading to the vast array of animals that we see around us

于是就诞生了 我们周围的大量动物，

and all throughout the tree of life.

以及整个生命之树。

So whether we're talking about my fave, killer snails,

所以，无论我们谈论的是 我的最爱——杀手海螺、

or jellyfish,

水母、

or the larvae of butterflies and moths,

蝴蝶和飞蛾的幼虫，

or platypus or slow lorises,

还是鸭嘴兽或懒猴，

whether by sea, land or air,

无论是在海上、陆地还是空中，

you're sure to encounter a venomous creature.

你一定会遇到有毒的生物。

Remember when I told you

还记得我刚才说过，

that venom can be both a superhero and a supervillain,

毒液可以同时是 超级英雄和超级坏蛋，

and you doubted me?

而你当时对此还表示怀疑吗？

Mhm.

再想想看？

We're in a race to harness all of this venom goodness

我们正趁着失去地球上 绝大多数动物之前，

before we lose the vast majority of animals on our planet.

进行一场搜集 所有这些毒液的竞赛。

It's a holistic process.

这是一个环环相扣的过程。

You can't have the therapeutic treatments without having the animals.

没有动物，就没有治疗方法。

And you can't have the animals

而没有这些动物 赖以生存的生态系统，

without having their ecosystems.

也就没有这些动物。

So for me and the snails,

所以对我和海螺来说，

what it means is we have to save the oceans.

这就意味着我们必须拯救海洋。

And because venomous animals are found everywhere,

而且因为有毒物种无处不在，

we basically have to save the planet.

我们就必须拯救整个星球。

So do it for the venomous animals,

所以即使不为了自己，

if you don't want to do it for yourself.

也要为了这些有毒生物 而保护地球。

And who knows,

谁知道呢，

some day, snail venom might just save your life.

也许某一天，海螺毒素 就可以挽救你的生命。

Thank you.

谢谢。