A new superweapon in the fight against cancer | Paula Hammond

譯者: Sophie Wu 審譯者: 易帆 余

Cancer affects all of us --

癌症會影響所有人--

especially the ones that come back over and over again,

尤其是那些反覆發作，

the highly invasive and drug-resistant ones,

具高入侵性、抗藥性的癌症，

即使我們給病患做最好的治療，

the ones that defy medical treatment,

even when we throw our best drugs at them.

病況也毫無起色。

Engineering at the molecular level,

分子工程

working at the smallest of scales,

在極微小的尺度運作，

can provide exciting new ways

可以提供令人振奮的新方法

to fight the most aggressive forms of cancer.

來跟最具攻擊性的癌症搏鬥。

Cancer is a very clever disease.

癌症是一種非常聰明的疾病。

There are some forms of cancer,

很幸運的，我們能運用現有的藥物和手術 來有效地治療ㄧ些癌症。

which, fortunately, we've learned how to address relatively well

with known and established drugs and surgery.

But there are some forms of cancer

但是針對其他的癌症，

that don't respond to these approaches,

這些治療完全無效，

and the tumor survives or comes back,

腫瘤仍舊會繼續生存或者再度復發。

even after an onslaught of drugs.

即使我們持續投放最強烈的藥物。

We can think of these very aggressive forms of cancer

我們可以把那些 非常具攻擊性的癌症，

as kind of supervillains in a comic book.

想像成漫畫書中的超級壞蛋。

They're clever, they're adaptable,

它們既聰明， 又善於適應環境，

and they're very good at staying alive.

而且擅長求生。

And, like most supervillains these days,

而且就像現今的超級壞蛋一樣，

their superpowers come from a genetic mutation.

它們的超能力來自基因突變。

The genes that are modified inside these tumor cells

那些腫瘤細胞內變異的基因

can enable and encode for new and unimagined modes of survival,

能夠編譯出一種嶄新、 令人難以想像的生存模式，

allowing the cancer cell to live through

使癌細胞在歷經最好的化療之後

even our best chemotherapy treatments.

仍然能夠存活下來。

One example is a trick in which a gene allows a cell,

例如，癌細胞有一種基因

even as the drug approaches the cell,

能夠在藥物接近細胞還沒發揮作用之前， 讓細胞把藥物推走。

to push the drug out,

before the drug can have any effect.

Imagine -- the cell effectively spits out the drug.

你可以把它想像成 細胞成功地把藥物吐出來。

This is just one example of the many genetic tricks

這只是超級壞蛋--癌症

in the bag of our supervillain, cancer.

眾多基因把戲中的一個例子而已。

All due to mutant genes.

原因皆是突變基因。

So, we have a supervillain with incredible superpowers.

當我們面對一個擁有 驚人能力的超級壞蛋，

And we need a new and powerful mode of attack.

我們需要一種 嶄新而強勁的攻擊模式。

Actually, we can turn off a gene.

實際上，我們可以讓基因無法運作。

The key is a set of molecules known as siRNA.

其關鍵是一種 被稱為siRNA的組分子，

siRNA are short sequences of genetic code

它是一種短遺傳密碼序列，

that guide a cell to block a certain gene.

它能使細胞阻斷某個特定基因。

Each siRNA molecule can turn off a specific gene

每個 siRNA 分子可以關閉

inside the cell.

細胞內一個特定的基因。

For many years since its discovery,

自從發現它後，多年來科學家們 都對基因阻斷器在醫療方面的應用很感興趣。

scientists have been very excited

about how we can apply these gene blockers in medicine.

But, there is a problem.

但是有一個問題：

siRNA works well inside the cell.

siRNA 在細胞裡運作良好，

But if it gets exposed to the enzymes

但是如果它接觸到

that reside in our bloodstream or our tissues,

存在於我們的血液或者 身體組織中的酵素，

it degrades within seconds.

它就會在瞬間降解。

It has to be packaged, protected through its journey through the body

它在身體運行的旅途上 需要被包裝，受到保護

on its way to the final target inside the cancer cell.

直到抵達最終目標 --癌細胞裡面。

So, here's our strategy.

所以這是我們的策略：

First, we'll dose the cancer cell with siRNA, the gene blocker,

我們給癌細胞一劑 siRNA， 也就是基因阻斷器，

and silence those survival genes,

來抑制讓癌細胞存活的基因的表現， 接著利用化學藥物把癌細胞擊垮。

and then we'll whop it with a chemo drug.

But how do we carry that out?

但是我們怎樣進行呢？

Using molecular engineering,

運用分子工程，

we can actually design a superweapon

我們可以設計出一種能在血液中 自由游走的超級武器，

that can travel through the bloodstream.

It has to be tiny enough to get through the bloodstream,

它要小得可以穿過血流，

it's got to be small enough to penetrate the tumor tissue,

穿過腫瘤組織，

and it's got to be tiny enough to be taken up inside the cancer cell.

微小得可以留在癌細胞內。

To do this job well,

為了順利完成這個任務，

it has to be about one one-hundredth the size of a human hair.

它的大小必須是 人類頭髮的百分之一。

Let's take a closer look at how we can build this nanoparticle.

現在請近距離看看我們 如何製造這個奈米粒子。

First, let's start with the nanoparticle core.

首先由奈米粒子的核心開始。

It's a tiny capsule that contains the chemotherapy drug.

它是一只含有化療藥物 的細小膠囊。

This is the poison that will actually end the tumor cell's life.

那是一種真正能結束 癌細胞生命的毒藥。

Around this core, we'll wrap a very thin,

我們將會在這顆核心的周圍

nanometers-thin blanket of siRNA.

包裹一層非常薄的 siRNA 奈米膜。

This is our gene blocker.

這是我們的基因阻斷器。

Because siRNA is strongly negatively charged,

因為 siRNA 是強力負極電荷，

we can protect it

所以我們可以利用一層 正極的聚合物保護膜來保護siRNA。

with a nice, protective layer of positively charged polymer.

The two oppositely charged molecules stick together

兩個異性電分子 因為互相吸引

through charge attraction,

繼而黏在一起，

and that provides us with a protective layer

並提供了一層保護層

that prevents the siRNA from degrading in the bloodstream.

防止 siRNA 在血流中降解。

We're almost done.

我們差不多完成了。

(Laughter)

（笑聲）

But there is one more big obstacle we have to think about.

但是我們還要 考慮到一個大障礙。

In fact, it may be the biggest obstacle of all.

其實可能是所有 障礙中最大的一個。

How do we deploy this superweapon?

我們怎樣善用這種超級武器呢？

I mean, every good weapon needs to be targeted,

每種優良的武器 都需要瞄準目標。

we have to target this superweapon to the supervillain cells

我們要把超級武器 瞄準腫瘤內的

that reside in the tumor.

超級壞蛋細胞。

But our bodies have a natural immune-defense system:

但是我們體內有一種 天然的免疫防衛系統：

cells that reside in the bloodstream

血流裡有一種細胞

and pick out things that don't belong,

能夠辨認出原本 不存在於身體的東西，

so that it can destroy or eliminate them.

繼而破壞或消滅它們。

And guess what? Our nanoparticle is considered a foreign object.

猜猜看怎麼了？我們的奈米粒子 被視為一種外來物。

We have to sneak our nanoparticle past the tumor defense system.

我們要把奈米粒子 偷渡過腫瘤防護系統時，

We have to get it past this mechanism of getting rid of the foreign object

必須掩飾它，讓它通過 身體排除外物的機制，

by disguising it.

So we add one more negatively charged layer

於是我們再增加 一層負極電膜，

around this nanoparticle,

包圍這個奈米粒子，

which serves two purposes.

這有兩個目的。

First, this outer layer is one of the naturally charged,

第一，外層是天然電荷，

highly hydrated polysaccharides that resides in our body.

那是人體內的高水合多醣。

It creates a cloud of water molecules around the nanoparticle

它可以在奈米粒子周圍 製造一層水分子。

that gives us an invisibility cloaking effect.

這有隱形斗蓬的效果。

This invisibility cloak allows the nanoparticle

這隱形斗篷讓奈米粒子

to travel through the bloodstream

能夠藉著血液的流動，

long and far enough to reach the tumor,

移動到足以到達腫瘤的距離，

without getting eliminated by the body.

而不會被身體消滅。

Second, this layer contains molecules

第二，這層高水合多醣含有

which bind specifically to our tumor cell.

可以和腫瘤細胞 結合的分子。

Once bound, the cancer cell takes up the nanoparticle,

一旦結合了，癌細胞 就會吸收奈米粒子。

and now we have our nanoparticle inside the cancer cell

現在奈米粒子就在 癌細胞的內部，

and ready to deploy.

準備展開行動了。

Alright! I feel the same way. Let's go!

好，我也有同感。出發吧！

(Applause)

（掌聲）

The siRNA is deployed first.

首先調動 siRNA。

It acts for hours,

它需要數小時才見效。

giving enough time to silence and block those survival genes.

因為要足夠的時間去抑制 癌細胞生存基因的表現，

We have now disabled those genetic superpowers.

我們現在已經使這些基因 的超能力無法運作。

What remains is a cancer cell with no special defenses.

剩下來的是沒有 特殊防禦的癌細胞。

Then, the chemotherapy drug comes out of the core

接下來，化療藥物 從核心釋放，

and destroys the tumor cell cleanly and efficiently.

徹底且有效率地 破壞腫瘤細胞。

With sufficient gene blockers,

只要我們有足夠的基因阻斷器，

we can address many different kinds of mutations,

就能對付不同種類的突變，

allowing the chance to sweep out tumors,

有機會能剿滅腫瘤，

without leaving behind any bad guys.

讓壞蛋一個也不剩地消失。

So, how does our strategy work?

所以我們的策略是如何進行的？

We've tested these nanostructure particles in animals

我們利用動物測試 這些奈米結構粒子，

using a highly aggressive form of triple-negative breast cancer.

運用極具攻擊性的 三陰性乳腺癌做實驗。

This triple-negative breast cancer exhibits the gene

三陰性乳腺癌的基因表現

that spits out cancer drug as soon as it is delivered.

讓癌症藥物一接近它就被排除。

Usually, doxorubicin -- let's call it "dox" -- is the cancer drug

通常，阿黴素是治療乳癌

that is the first line of treatment for breast cancer.

第一線療程的藥物。

So, we first treated our animals with a dox core, dox only.

於是我們首先只投放 阿黴素來治療動物。

The tumor slowed their rate of growth,

腫瘤生長速度減緩了，

but they still grew rapidly,

但仍生長迅速，

doubling in size over a period of two weeks.

在兩週後，腫瘤的大小 就增加了一倍。

Then, we tried our combination superweapon.

接下來，我們試了 我們的綜合超級武器，

A nanolayer particle with siRNA against the chemo pump,

用化療泵注射 siRNA奈米粒子，

plus, we have the dox in the core.

加上，在內核放置阿黴素。

And look -- we found that not only did the tumors stop growing,

看！我們發現 腫瘤不僅停止生長

they actually decreased in size

而且還縮小，

and were eliminated in some cases.

有些腫瘤甚至完全消失

The tumors were actually regressing.

腫瘤真的復原了。

(Applause)

(掌聲)

What's great about this approach is that it can be personalized.

這個方法最棒的地方是 可以個人化。

We can add many different layers of siRNA

我們針對不同的突變和腫瘤的防護機制 添加不同層次的 siRNA，

to address different mutations and tumor defense mechanisms.

And we can put different drugs into the nanoparticle core.

我們也可以把不同的藥物 放進毫微粒核心。

As doctors learn how to test patients

當醫生學習如何替病人檢測

and understand certain tumor genetic types,

以及了解特定腫瘤的基因類型時，

they can help us determine which patients can benefit from this strategy

他們可以幫助我們 決定哪類病人

and which gene blockers we can use.

可以受惠於這個療法 和採用哪種基因阻斷器。

Ovarian cancer strikes a special chord with me.

卵巢癌對我而言 具有特別的意義。

It is a very aggressive cancer,

它是一種很具攻擊性的癌症，

in part because it's discovered at very late stages,

部分原因是因為它通常在 病症末期才被診斷出來，

when it's highly advanced

那時候癌細胞已經根深蒂固

and there are a number of genetic mutations.

而且它有多種基因突變。

After the first round of chemotherapy,

經過第一輪化療後，

this cancer comes back for 75 percent of patients.

有 75％ 的病人 會再次復發癌症。

And it usually comes back in a drug-resistant form.

而且它通常會以 抗藥性的型態回到身體。

High-grade ovarian cancer

惡性的卵巢癌

is one of the biggest supervillains out there.

是最壞的超級壞蛋之一。

And we're now directing our superweapon

我們現在要把我們的 超級武器瞄準它，

toward its defeat.

希望能夠將它擊潰。

As a researcher,

作為一個研究員，

I usually don't get to work with patients.

我通常不會替病患做臨床治療。

But I recently met a mother

但最近我遇見一位卵巢癌倖存者媽媽 Mimi和她的女兒Paige，

who is an ovarian cancer survivor, Mimi, and her daughter, Paige.

I was deeply inspired by the optimism and strength

我深受他們母女兩人的 樂觀和力量啟發，

that both mother and daughter displayed

and by their story of courage and support.

她們的故事展現了 勇氣和互相扶持。

At this event, we spoke about the different technologies

在活動中，我們談論關於

治療癌症的不同科技。

directed at cancer.

And Mimi was in tears

Mimi 的雙眼泛淚

as she explained how learning about these efforts

她說她了解我們 這些努力的成果

gives her hope for future generations,

可以讓她對下一代 充滿了希望，

including her own daughter.

包括她的親生女兒。

This really touched me.

這令我非常感動。

It's not just about building really elegant science.

我們不只是做 精密的科學研究，

It's about changing people's lives.

還能改變人們的人生。

It's about understanding the power of engineering

這是在分子尺度中

on the scale of molecules.

運用工程的力量。

I know that as students like Paige move forward in their careers,

我知道在像Paige 這樣的學生，在進入職涯後，

they'll open new possibilities

他們會開創很多 嶄新的可能性，

in addressing some of the big health problems in the world --

來解決世界上的 重大醫療衛生議題——

including ovarian cancer, neurological disorders, infectious disease --

包括卵巢癌、 精神疾病、傳染病

just as chemical engineering has found a way to open doors for me,

就像化學工程已 為我開了一扇門，

and has provided a way of engineering

提供我世上最小的分子規模工程， 來治癒世上大規模的人類。

on the tiniest scale, that of molecules,

to heal on the human scale.

Thank you.

謝謝

(Applause)

（掌聲）