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

譯者: 審譯者: Helen Chang

蜗牛是怎么抓到鱼的？

毕竟蜗牛爬行很慢

鱼却一点儿也不慢。

How does a sea snail catch a fish?

但是，蜗牛确实抓到鱼了。

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

躯壳藏在沙子底下，

and the fish is not.

你会看到像舌头一样橙色的东西，

我们称之为鼻子。

But yet, this happens.

用鼻子跟踪并吸引这些毫无防备的鱼。

Hidden under the sand is a cone snail.

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

在这些诱饵的作用下，

We call it a proboscis.

这些显然不是你花园里各种各样的蜗牛，

It uses that to track and subdue this unsuspecting fish.

这些是海洋里的刺客。

In this predator-prey interaction,

它们的武器是毒液，

these are clearly not your garden variety escargots.

像你知道的毒蛇和蝎子一样的毒液。

These are assassins of the sea.

这些海螺用它们的毒液抑制鱼、蠕虫

And their weapon of choice is venom.

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

还有其他海螺。

这些海螺的毒液

不是只有一种，

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

实际上，有毒液体的混合物

装在叫做牙板的假牙里输送。

and other snails.

And the venom of these snails,

it's not just one thing,

it's actually a cocktail of toxic molecules

你可以称牙板叫皮下注射针。

现在不用担心海螺习惯练习好的针法，

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

因为每颗假牙只能用一次。

You can think of the radulas as hypodermic needles.

现在你知道了关于有毒液体的生物，

Now, no need to worry,

给你们看让你们夜不能寐的殺鱼视频，

these snails are practicing good needle habits,

because each radula is only used once.

或許你认为这些毒液都是不好、危险的。

Now from your own knowledge about venomous organisms,

是和不是。

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

一種更準確的理解毒液的方式

是把它同時看作 超級壞蛋和超級英雄。

you might think that venom is dangerous and all bad.

Well, yes and no.

在我的實驗室中，我們研究了 這些海螺毒液作為一種有益的力量，

A more accurate way of thinking of venom

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

聽起來有點誇大，或甚至像蛇油，

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

但，其實，雖然有涉及到蛇， 但這產品是合法的。

as a force for good.

毒液產品如此成功的原因之一

Sounds like a stretch,

是因為它會把身體的交戰

or maybe even snake oil,

but actually,

while there are snakes involved, the product is legit.

轉變成生物化學的交戰。

通常捕食者與獵物的互動是用蠻力，

One reason the venom product is so successful

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

毒液則把它帶入分子的規模。

重點不是大小，

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

而是將你的武器軍火庫做混合。

武器軍火庫中的毒素的化學性質

venom takes it to a molecular scale.

正是讓大衛能夠制服歌利亞， 以小搏大的關鍵。

And it's not size that matters,

but the mixture of your venom arsenal.

在我們的情境當中， 很明顯大衛就是海螺。

The chemistry of the toxins in your arsenal

毒液能如此成功的另一個特色

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

在於毒素的精準度不亞於瑞士刀。

And in our scenario, David is clearly the snail.

所以，這些毒素會針對

Another feature of venom that makes it so successful

協助生物運作的堡壘來進攻。

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

所以它們的目標包括 血液、頭腦，及薄膜。

And so these toxins,

不論是海螺毒液或蛇毒液，

they come for strongholds that help an organism to function.

它們都有些成份，能做到

So they target blood, brain and membranes.

比如讓你的血液凝固，

我們稱之為「血毒素」。

Whether it's snail venom or snake venom,

或者會造成大腦神經元 無法正常運作，

they each have components that can do things

like cause your blood to clot,

這是「神經毒素」。

或者它們會有某些毒素， 能在你的細胞膜上戳洞，

what we call "hemotoxic."

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

讓細胞破裂，基本上，就是爆炸，

what we call "neurotoxic."

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

我們稱之為「細胞毒」。

細胞爆炸，各位。

如果這還稱不上是神級， 就沒什麼稱得上了。

causing them to rupture and, basically, explode,

what we call "cytotoxic."

現在介紹一下我自己， 以及我為什麼這麼迷毒液。

Cellular explosion, people.

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

我在紐約市長大，

被迫要去參觀自然歷史博物館。

nothing is.

Now a little about me,

我說「被迫參觀」 是因為家中有五個孩子，

and why I'm so obsessed with venom.

我父母會把博物館 當作一種托兒的形式。

I grew up in New York City

with forced access to the Natural History Museum.

有兩條規則：別讓任何人走失，

I say "forced access,"

because I'm one of five kids,

五點三十分博物館要關門時，

and my parents used museums as a form of childcare.

在非洲象那裡和爸媽碰面。

那些沒人管的日子，

There were two rules:

Don't lose anybody

and meet Mom and Dad at the African elephants

在博物館各廳間穿梭，

滿滿都是冒險和探索。

at 5:30, when the museum closes.

Those totally unsupervised days running through the halls of the museum

我在研究毒液時也有這種感受。

那是場科學冒險。

我們大膽地探索這種連結 大自然和人類的實體。

were full of adventure and exploration.

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

我很迷毒液的另一個原因，

It's a scientific adventure.

是因為它的二元性。

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

當你把毒液軍火庫中的元素 注射到生物體內，

可能會殺死它或治癒它。

Another reason that I'm obsessed with venom

is because of its duality.

在分子層級，會發生好幾個現象。

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

剛才已經看到了一種，魚會癱瘓。

it can kill or it can cure.

會發生那種現象， 是因為毒液中的毒素

At a molecular level, several things can happen.

在攻擊魚類細胞彼此溝通的方式，

You saw one thing, paralysis in the fish.

讓牠無法游走。

我會想用毒液攻擊其他東西嗎？

Now that was happening because the toxins in the venom

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

絕對會。其中之一是癌症。

preventing it from swimming away.

癌症腫瘤是細胞。

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

和所有細胞一樣，它們會彼此溝通，

也會和它們周圍的環境溝通。

For sure.

And one of those is cancer.

我們想要找出非常擅長

Cancer tumors are cells.

打斷腫瘤細胞溝通的毒液元素。

And like all cells,

they communicate with themselves and their environment around them.

就類似毒液打斷魚細胞溝通的方式，

So we would like to find venom components

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

讓魚無法游走。

在我的實驗室中，我們把癌症 當作一種通道病來研究。

Similar to how the venom disrupted how the fish cells communicated

基本上，意思就是 我們要找的毒液元素

and the fish couldn't swim away.

會攻擊腫瘤細胞中相對於正常細胞

In my lab, we study cancer as a channelopathy.

顯得過度表現的通道。

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

我們目前把焦點放在肝癌。

that will target channels that are overexpressed in tumor cells

那是因為，從八○年代到現在，

肝癌的死亡率已經加倍，

versus normal cells.

The cancer that we're most focused on right now

它是美國的新興威脅。

is liver cancer.

在一項分析中，我們比較子宮頸癌、

And that's because since the 1980s,

神經母細胞癌、 前列腺癌，及肝癌細胞，

the death rate of liver cancer has doubled,

and it's an emerging threat in the US.

發現來自一種筍螺的化合物

In a screen in which we had cervical,

似乎會去攻擊肝癌細胞，

neuroblastoma, prostate and liver cancer cells,

且只攻擊肝癌細胞，實驗中的 其他幾種癌細胞都沒被攻擊。

we found a compound from a terebrid snail

接著，我們把這種化合物注射到

that seems to attack liver cancer cells,

有肝癌細胞的小鼠身上，

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

它很明顯抑制了腫瘤的成長。

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

我們還不確定這背後的原理，

我們仍然在研究這個機制，

that were expressing liver cancer cells,

以及要如何讓這種化合物更有效，

it significantly inhibited the growth of the tumors.

所以，你不能衝去藥房

We're not quite sure how this works yet,

訂購殺手螺肝癌治療法。

we're still investigating the mechanism

and how we can make this compound more effective,

還不能。

基本上，我們認為

so you can't rush out to the pharmacy

是這種化合物阻斷了特定的通道，

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

抑制了特定化學物質的傳輸，

Not yet.

Basically, what we think is happening

這種化學物質會導致讓腫瘤增長

is that the compound is blocking a specific channel,

並將血液引向腫瘤的下游訊號。

prohibiting the transmission of a specific chemical

我們在研究毒液元素以期

that leads to downstream signaling

能為人類疾病找出治療方式的做法

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

並不是新做法，

它就是我們所謂的 天然產物新藥探索，

What we're doing in studying the components of venom

已經存在數世紀，

to find treatments for human diseases and disorders,

全世界各地的文化中都有。

is not new,

毒液不僅能給我們很酷的新化合物，

it's what we call natural products drug discovery,

它們也能給我們新的思考方式，

and it's been happening for centuries,

思考如何治療人類疾病。

and in cultures all over the world.

Venoms are not only giving us cool new compounds,

讓我舉三個例子。

第一個當然就是殺手螺。

but they're also giving us new ways of thinking

市場上最早來自這些螺類的藥物

about how we treat human diseases and disorders.

And I'll give you three examples.

叫做辛抗寧，或阿坎酸，

The first is from killer snails, of course.

用來治療愛滋病 和癌症病人的慢性疼痛。

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

阿坎酸是不會成癮的疼痛治療法。

is called ziconotide, or Prialt,

想想我們目前怎麼治療疼痛， 它算是很神奇的。

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

我們現在使用的藥物 都有很巨大的成癮成本。

Prialt is a nonaddictive pain therapy.

想想嗎啡，或任何 你最喜歡的鴉片類藥物。

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

這些螺類所做的，是讓我們知道

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

有可以治療疼痛又不會成癮的方式，

So think of morphine

or think of any of your favorite opioid out there.

這是大事。

下一個例子，來自巴西蝰蛇。

What the snails have done

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

我們從這些蛇的身上取得一種化合物 叫做卡托普利。

which is huge.

卡托普利可以用來治療高血壓，

The next example comes from the Brazilian pit viper.

卡托普利是一種突破性的藥物。

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

但不僅是因為這個原因，

Captopril is used to treat high blood pressure,

也因為它讓一整個類別的藥物 都有所進展，

and captopril is a breakthrough drug.

這個類別就是 ACEI，

是治療高血壓與心臟衰竭

But not only in and of itself,

but because it advanced a whole class of drugs,

最常見的處方。

最後一個例子來自美國毒蜥。

what we know as ACE inhibitors,

which are the most commonly [prescribed] for treating hypertension

這個例子十分讓人興奮，

可以讓我們了解這些生物的生態，

and heart failure.

The last example is from the Gila monster.

再將之與有效的新藥探索搭配。

美國毒蜥是暴食者。

And this is a really exciting example of understanding the ecology

所以當牠們咬住大餐時，

of these organisms,

牠們的毒液中會釋放出某些東西 來降低血糖。

and pairing it with efficient drug discovery.

猜猜我們從美國毒蜥 製造出的藥物是什麼？

And Gila monsters are binge eaters.

So when they bite into a large meal,

幫助糖尿病病人降低血糖的化合物。

they release things in their venom that lower blood sugar.

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

這三個例子都很了不起，

但我們才略懂皮毛而已。

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

還有好多等著我們去研究的毒液。

事實上，我們認為，地球上 所有動物當中有 15% 有毒。

Now these are three marvelous examples,

but we've just scratched the surface.

我認為這個數字還是低估，

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

因為我們尚未調查完 地球上的所有動物。

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

但大自然似乎找到了它喜歡的東西，

are venomous.

And I think this is a low estimate,

一而再再而三地重覆它，

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

造成我們現在在身邊及生物譜系圖上

But nature seems to have found something that she likes,

所見到的各種動物。

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

所以，不論我們在談的 是我最愛的殺手螺，

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

或水母，

或蝴蝶及蛾的幼蟲，

and all throughout the tree of life.

或鴨嘴獸，或懶猴，

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

不論在海中、陸地上、天上，

or jellyfish,

or the larvae of butterflies and moths,

都一定會遇到有毒生物。

or platypus or slow lorises,

記得嗎，我剛才提過，

毒液既是超級英雄也是超級反派，

whether by sea, land or air,

you're sure to encounter a venomous creature.

你那時還懷疑我？嗯哼。

Remember when I told you

我們正在跟時間賽跑， 要在我們失去地球上

that venom can be both a superhero and a supervillain,

大部分動物之前， 好好利用這些毒液的益處。

and you doubted me?

這是一個完整的過程。

Mhm.

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

不可能只有治療而沒有動物。

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

若沒有動物的生態系統 就不會有動物。

It's a holistic process.

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

所以，對我及對海螺而言， 意思就是我們必須要拯救海洋。

因為各地都有有毒動物，

And you can't have the animals

without having their ecosystems.

基本上，我們必須要拯救地球。

So for me and the snails,

所以，如果你不想為了自己， 那就為了有毒動物而做吧。

what it means is we have to save the oceans.

And because venomous animals are found everywhere,

誰知道，說不定哪一天，

海螺毒液還會救你一命呢。

we basically have to save the planet.

So do it for the venomous animals,

謝謝。

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

And who knows,

some day, snail venom might just save your life.

Thank you.