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