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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,
the ones that defy medical treatment,
即使我們給病患做最好的治療,
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
但是針對其他的癌症,
with known and established drugs and surgery.
這些治療完全無效,
But there are some forms of cancer
腫瘤仍舊會繼續生存或者再度復發。
that don't respond to these approaches,
即使我們持續投放最強烈的藥物。
and the tumor survives or comes back,
我們可以把那些 非常具攻擊性的癌症,
even after an onslaught of drugs.
想像成漫畫書中的超級壞蛋。
We can think of these very aggressive forms of cancer
它們既聰明, 又善於適應環境,
as kind of supervillains in a comic book.
而且擅長求生。
They're clever, they're adaptable,
而且就像現今的超級壞蛋一樣,
and they're very good at staying alive.
它們的超能力來自基因突變。
And, like most supervillains these days,
那些腫瘤細胞內變異的基因
their superpowers come from a genetic mutation.
能夠編譯出一種嶄新、 令人難以想像的生存模式,
The genes that are modified inside these tumor cells
使癌細胞在歷經最好的化療之後
can enable and encode for new and unimagined modes of survival,
仍然能夠存活下來。
allowing the cancer cell to live through
例如,癌細胞有一種基因
even our best chemotherapy treatments.
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。
One example is a trick in which a gene allows a cell,
你可以把它想像成 細胞成功地把藥物吐出來。
even as the drug approaches the cell,
這只是超級壞蛋--癌症
to push the drug out,
眾多基因把戲中的一個例子而已。
before the drug can have any effect.
原因皆是突變基因。
Imagine -- the cell effectively spits out the drug.
當我們面對一個擁有 驚人能力的超級壞蛋,
This is just one example of the many genetic tricks
我們需要一種 嶄新而強勁的攻擊模式。
in the bag of our supervillain, cancer.
實際上,我們可以讓基因無法運作。
All due to mutant genes.
其關鍵是一種 被稱為siRNA的組分子,
So, we have a supervillain with incredible superpowers.
它是一種短遺傳密碼序列,
And we need a new and powerful mode of attack.
它能使細胞阻斷某個特定基因。
Actually, we can turn off a gene.
每個 siRNA 分子可以關閉
The key is a set of molecules known as siRNA.
細胞內一個特定的基因。
siRNA are short sequences of genetic code
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。
that guide a cell to block a certain gene.
但是有一個問題:
Each siRNA molecule can turn off a specific gene
siRNA 在細胞裡運作良好,
inside the cell.
但是如果它接觸到
For many years since its discovery,
存在於我們的血液或者 身體組織中的酵素,
scientists have been very excited
它就會在瞬間降解。
about how we can apply these gene blockers in medicine.
它在身體運行的旅途上 需要被包裝,受到保護
But, there is a problem.
直到抵達最終目標 --癌細胞裡面。
siRNA works well inside the cell.
所以這是我們的策略:
But if it gets exposed to the enzymes
我們給癌細胞一劑 siRNA, 也就是基因阻斷器,
that reside in our bloodstream or our tissues,
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。
it degrades within seconds.
但是我們怎樣進行呢?
It has to be packaged, protected through its journey through the body
運用分子工程,
on its way to the final target inside the cancer cell.
我們可以設計出一種能在血液中 自由游走的超級武器,
So, here's our strategy.
它要小得可以穿過血流,
First, we'll dose the cancer cell with siRNA, the gene blocker,
穿過腫瘤組織,
and silence those survival genes,
微小得可以留在癌細胞內。
and then we'll whop it with a chemo drug.
為了順利完成這個任務,
But how do we carry that out?
它的大小必須是 人類頭髮的百分之一。
Using molecular engineering,
現在請近距離看看我們 如何製造這個奈米粒子。
we can actually design a superweapon
首先由奈米粒子的核心開始。
that can travel through the bloodstream.
它是一只含有化療藥物 的細小膠囊。
It has to be tiny enough to get through the bloodstream,
那是一種真正能結束 癌細胞生命的毒藥。
it's got to be small enough to penetrate the tumor tissue,
我們將會在這顆核心的周圍
and it's got to be tiny enough to be taken up inside the cancer cell.
包裹一層非常薄的 siRNA 奈米膜。
To do this job well,
這是我們的基因阻斷器。
it has to be about one one-hundredth the size of a human hair.
因為 siRNA 是強力負極電荷,
Let's take a closer look at how we can build this nanoparticle.
所以我們可以利用一層 正極的聚合物保護膜來保護siRNA。
First, let's start with the nanoparticle core.
兩個異性電分子 因為互相吸引
It's a tiny capsule that contains the chemotherapy drug.
繼而黏在一起,
This is the poison that will actually end the tumor cell's life.
並提供了一層保護層
Around this core, we'll wrap a very thin,
防止 siRNA 在血流中降解。
nanometers-thin blanket of siRNA.
我們差不多完成了。
This is our gene blocker.
(笑聲)
Because siRNA is strongly negatively charged,
但是我們還要 考慮到一個大障礙。
we can protect it
其實可能是所有 障礙中最大的一個。
with a nice, protective layer of positively charged polymer.
我們怎樣善用這種超級武器呢?
The two oppositely charged molecules stick together
每種優良的武器 都需要瞄準目標。
through charge attraction,
我們要把超級武器 瞄準腫瘤內的
and that provides us with a protective layer
超級壞蛋細胞。
that prevents the siRNA from degrading in the bloodstream.
但是我們體內有一種 天然的免疫防衛系統:
We're almost done.
血流裡有一種細胞
(Laughter)
能夠辨認出原本 不存在於身體的東西,
But there is one more big obstacle we have to think about.
繼而破壞或消滅它們。
In fact, it may be the biggest obstacle of all.
猜猜看怎麼了?我們的奈米粒子 被視為一種外來物。
How do we deploy this superweapon?
我們要把奈米粒子 偷渡過腫瘤防護系統時,
I mean, every good weapon needs to be targeted,
必須掩飾它,讓它通過 身體排除外物的機制,
we have to target this superweapon to the supervillain cells
於是我們再增加 一層負極電膜,
that reside in the tumor.
包圍這個奈米粒子,
But our bodies have a natural immune-defense system:
這有兩個目的。
cells that reside in the bloodstream
第一,外層是天然電荷,
and pick out things that don't belong,
那是人體內的高水合多醣。
so that it can destroy or eliminate them.
它可以在奈米粒子周圍 製造一層水分子。
And guess what? Our nanoparticle is considered a foreign object.
這有隱形斗蓬的效果。
We have to sneak our nanoparticle past the tumor defense system.
這隱形斗篷讓奈米粒子
We have to get it past this mechanism of getting rid of the foreign object
能夠藉著血液的流動,
by disguising it.
移動到足以到達腫瘤的距離,
So we add one more negatively charged layer
而不會被身體消滅。
around this nanoparticle,
第二,這層高水合多醣含有
which serves two purposes.
可以和腫瘤細胞 結合的分子。
First, this outer layer is one of the naturally charged,
一旦結合了,癌細胞 就會吸收奈米粒子。
highly hydrated polysaccharides that resides in our body.
現在奈米粒子就在 癌細胞的內部,
It creates a cloud of water molecules around the nanoparticle
準備展開行動了。
that gives us an invisibility cloaking effect.
好,我也有同感。出發吧!
This invisibility cloak allows the nanoparticle
(掌聲)
to travel through the bloodstream
首先調動 siRNA。
long and far enough to reach the tumor,
它需要數小時才見效。
without getting eliminated by the body.
因為要足夠的時間去抑制 癌細胞生存基因的表現,
Second, this layer contains molecules
我們現在已經使這些基因 的超能力無法運作。
which bind specifically to our tumor cell.
剩下來的是沒有 特殊防禦的癌細胞。
Once bound, the cancer cell takes up the nanoparticle,
接下來,化療藥物 從核心釋放,
and now we have our nanoparticle inside the cancer cell
徹底且有效率地 破壞腫瘤細胞。
and ready to deploy.
只要我們有足夠的基因阻斷器,
Alright! I feel the same way. Let's go!
就能對付不同種類的突變,
(Applause)
有機會能剿滅腫瘤,
The siRNA is deployed first.
讓壞蛋一個也不剩地消失。
It acts for hours,
所以我們的策略是如何進行的?
giving enough time to silence and block those survival genes.
我們利用動物測試 這些奈米結構粒子,
We have now disabled those genetic superpowers.
運用極具攻擊性的 三陰性乳腺癌做實驗。
What remains is a cancer cell with no special defenses.
三陰性乳腺癌的基因表現
Then, the chemotherapy drug comes out of the core
讓癌症藥物一接近它就被排除。
and destroys the tumor cell cleanly and efficiently.
通常,阿黴素是治療乳癌
With sufficient gene blockers,
第一線療程的藥物。
we can address many different kinds of mutations,
於是我們首先只投放 阿黴素來治療動物。
allowing the chance to sweep out tumors,
腫瘤生長速度減緩了,
without leaving behind any bad guys.
但仍生長迅速,
So, how does our strategy work?
在兩週後,腫瘤的大小 就增加了一倍。
We've tested these nanostructure particles in animals
接下來,我們試了 我們的綜合超級武器,
using a highly aggressive form of triple-negative breast cancer.
用化療泵注射 siRNA奈米粒子,
This triple-negative breast cancer exhibits the gene
加上,在內核放置阿黴素。
that spits out cancer drug as soon as it is delivered.
看!我們發現 腫瘤不僅停止生長
Usually, doxorubicin -- let's call it "dox" -- is the cancer drug
而且還縮小,
that is the first line of treatment for breast cancer.
有些腫瘤甚至完全消失
So, we first treated our animals with a dox core, dox only.
腫瘤真的復原了。
The tumor slowed their rate of growth,
(掌聲)
but they still grew rapidly,
這個方法最棒的地方是 可以個人化。
doubling in size over a period of two weeks.
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,
Then, we tried our combination superweapon.
我們也可以把不同的藥物 放進毫微粒核心。
A nanolayer particle with siRNA against the chemo pump,
當醫生學習如何替病人檢測
plus, we have the dox in the core.
以及了解特定腫瘤的基因類型時,
And look -- we found that not only did the tumors stop growing,
他們可以幫助我們 決定哪類病人
they actually decreased in size
可以受惠於這個療法 和採用哪種基因阻斷器。
and were eliminated in some cases.
卵巢癌對我而言 具有特別的意義。
The tumors were actually regressing.
它是一種很具攻擊性的癌症,
(Applause)
部分原因是因為它通常在 病症末期才被診斷出來,
What's great about this approach is that it can be personalized.
那時候癌細胞已經根深蒂固
We can add many different layers of siRNA
而且它有多種基因突變。
to address different mutations and tumor defense mechanisms.
經過第一輪化療後,
And we can put different drugs into the nanoparticle core.
有 75% 的病人 會再次復發癌症。
As doctors learn how to test patients
而且它通常會以 抗藥性的型態回到身體。
and understand certain tumor genetic types,
惡性的卵巢癌
they can help us determine which patients can benefit from this strategy
是最壞的超級壞蛋之一。
and which gene blockers we can use.
我們現在要把我們的 超級武器瞄準它,
Ovarian cancer strikes a special chord with me.
希望能夠將它擊潰。
It is a very aggressive cancer,
作為一個研究員,
in part because it's discovered at very late stages,
我通常不會替病患做臨床治療。
when it's highly advanced
但最近我遇見一位卵巢癌倖存者媽媽 Mimi和她的女兒Paige,
and there are a number of genetic mutations.
我深受他們母女兩人的 樂觀和力量啟發,
After the first round of chemotherapy,
她們的故事展現了 勇氣和互相扶持。
this cancer comes back for 75 percent of patients.
在活動中,我們談論關於
And it usually comes back in a drug-resistant form.
治療癌症的不同科技。
High-grade ovarian cancer
Mimi 的雙眼泛淚
is one of the biggest supervillains out there.
她說她了解我們 這些努力的成果
And we're now directing our superweapon
可以讓她對下一代 充滿了希望,
toward its defeat.
包括她的親生女兒。
As a researcher,
這令我非常感動。
I usually don't get to work with patients.
我們不只是做 精密的科學研究,
But I recently met a mother
還能改變人們的人生。
who is an ovarian cancer survivor, Mimi, and her daughter, Paige.
這是在分子尺度中
I was deeply inspired by the optimism and strength
運用工程的力量。
that both mother and daughter displayed
我知道在像Paige 這樣的學生,在進入職涯後,
and by their story of courage and support.
他們會開創很多 嶄新的可能性,
At this event, we spoke about the different technologies
來解決世界上的 重大醫療衛生議題——
directed at cancer.
包括卵巢癌、 精神疾病、傳染病
And Mimi was in tears
就像化學工程已 為我開了一扇門,
as she explained how learning about these efforts
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。
gives her hope for future generations,
謝謝
including her own daughter.
(掌聲)
This really touched me.
It's not just about building really elegant science.
It's about changing people's lives.
It's about understanding the power of engineering
on the scale of molecules.
I know that as students like Paige move forward in their careers,
they'll open new possibilities
in addressing some of the big health problems in the world --
including ovarian cancer, neurological disorders, infectious disease --
just as chemical engineering has found a way to open doors for me,
and has provided a way of engineering
on the tiniest scale, that of molecules,
to heal on the human scale.
Thank you.
(Applause)