in our hands today,

我們现在正面臨全球人們健康的挑戰

and that is that the way we currently

而目前尋找以及研發新藥 太過昂貴、耗時

discover and develop new drugs

且大多以失敗收場

is too costly, takes far too long,

這樣的方式是無效的

and it fails more often than it succeeds.

也代表迫切需要新式療法的病人得不到治療

It really just isn't working, and that means

疾病也就無法被醫治

that patients that badly need new therapies

我們似乎花越來越多的金錢

are not getting them,

花在研發的每一個十億美元

and diseases are going untreated.

都得到更少成功上市的藥

We seem to be spending more and more money.

更多的錢，更少的藥。嗯

So for every billion dollars we spend in R&D,

到底發生了什麼事？

we're getting less drugs approved into the market.

嗯，有多種因素牽扯其中

More money, less drugs. Hmm.

但我認為最重要的原因是

So what's going on here?

在進入人體臨床試驗之前

Well, there's a multitude of factors at play,

目前用來測試藥物是否有效 或是否安全所使用的工具讓我們相當失望

but I think one of the key factors

它們無法預測在人體內會發生的事

is that the tools that we currently have

目前有兩種主要的工具

available to test whether a drug is going to work,

那就是細胞培養以及動物試驗

whether it has efficacy,

我們先來說說第一種，細胞培養

or whether it's going to be safe

好，細胞在我們的身體裡面快樂地工作著

before we get it into human clinical trials,

我們把它們從正常生長環境中取出來

are failing us. They're not predicting

並丟到這些培養皿的其中之一

what's going to happen in humans.

希望它們依然能夠運作

And we have two main tools available

結果並不意外 它們不能

at our disposal.

它們不喜歡那樣的環境

They are cells in dishes and animal testing.

因為這跟身體裡面的環境完全不同

Now let's talk about the first one, cells in dishes.

動物試驗呢？

So, cells are happily functioning in our bodies.

的確，動物能夠提供有用的訊息 牠們告訴我們在複雜器官結構中細胞的變化

We take them and rip them out

我們學到了很多生物學的相關知識

of their native environment, throw them in one of these dishes,

但是通常來說

and expect them to work.

動物模型並無法預測使用某種特定藥物時 在人體內發生的事

Guess what. They don't.

所以我們需要更好的工具

They don't like that environment

我們需要人體細胞

because it's nothing like

但是我們要找到讓它們 在體外也能「快樂」的方法

what they have in the body.

我們的身體是個動態的環境

What about animal testing?

一直在活動著

Well, animals do and can provide

我們的細胞也是這樣

extremely useful information.

它們也處於動態的環境、感受持續的作用力

They teach us about what happens

因次如果我們想讓細胞「快樂」的在體外生活

in the complex organism.

我們就得成為細胞建築師

We learn more about the biology itself.

去設計、建造、監控細胞們的另外一個家

However, more often than not,

在維斯研究所（Wyss Institute），我們已經做到了

animal models fail to predict what will happen in humans

我們把它叫做晶片上的器官

when they're treated with a particular drug.

我這裡正好有一個

So we need better tools.

它真美，對吧？ 但卻是如此地不可思議

We need human cells,

在我手上的是一個在晶片上 會呼吸、活生生的人類的肺

but we need to find a way to keep them happy

它不只是美

outside the body.

它能做強大到令人驚歎的事

Our bodies are dynamic environments.

在晶片上的細胞是活的

We're in constant motion.

且處於動態環境

Our cells experience that.

能夠和不同種類的細胞交互作用

They're in dynamic environments in our body.

有很多人嘗試過在實驗室裡培養細胞

They're under constant mechanical forces.

他們試過很多種方法

So if we want to make cells happy

他們甚至試過在實驗室裡培養迷你的器官

outside our bodies,

我們並不那麼做

we need to become cell architects.

我們只是在這小小的晶片上 創造了最小的功能單位

We need to design, build and engineer

這些單位代表了細胞在我們體內所經歷的 生化反應、作用機能和機械應變

a home away from home for the cells.

它們怎麼運作呢？讓我告訴你們

And at the Wyss Institute,

我們運用了電腦晶片的技術來創造 這些規模和細胞以及生長環境相仿的結構

we've done just that.

其中有三條液體通道

We call it an organ-on-a-chip.

在中間部分有兼具通透性以及彈性的膜

And I have one right here.

在這些膜上我們可以放上人體細胞 例如肺部細胞

It's beautiful, isn't it? But it's pretty incredible.

下層則有微血管細胞

Right here in my hand is a breathing, living

然後我們就可以對晶片施加 伸展以及收縮這些膜的作用力

human lung on a chip.

而在中間的細胞就會受到 在我們呼吸的時候所承受的作用力

And it's not just beautiful.

就如同在我們體內的時候一樣

It can do a tremendous amount of things.

最上方的通道有氣流流過

We have living cells in that little chip,

然後帶有養分的液體會流過血液通道

cells that are in a dynamic environment

晶片是很漂亮，但是我們要怎麼利用呢？

interacting with different cell types.

這些小小的晶片具有相當不可思議的功能

There's been many people

讓我告訴你們吧

trying to grow cells in the lab.

例如，加入細菌細胞就能夠模擬肺部感染

They've tried many different approaches.

然後加入人類白血球

They've even tried to grow little mini-organs in the lab.

白血球在我們體內 扮演抵抗細菌入侵的角色

We're not trying to do that here.

當它們接受到因感染而引起的發炎反應時

We're simply trying to recreate

就會經由血管進入肺部並吞嗜細菌

in this tiny chip

你們將會看到這個在真正的人類肺部發生的過程 發生在這片晶片上

the smallest functional unit

我們標記了白血球 所以你們能夠看到它們正常流過

that represents the biochemistry,

當它們偵測到感染時，就會開始黏附（細菌）

the function and the mechanical strain

黏附之後，就會試著從血管這一側進入肺部

that the cells experience in our bodies.

如你所見，我們能夠 捕捉到單一一顆白血球

So how does it work? Let me show you.

黏附、擺動著穿越細胞層、細胞核

We use techniques from the computer chip

到達膜的另外一側

manufacturing industry

就在這裡，白血球將會 吞噬擁有綠色標記的細菌

to make these structures at a scale

在小小的晶片上，你見到了我們身體 對感染的最基礎反應

relevant to both the cells and their environment.

這就是所謂的免疫反應

We have three fluidic channels.

相當令人興奮

In the center, we have a porous, flexible membrane

現在我想分享這張圖片

on which we can add human cells

不只是因為它很美

from, say, our lungs,

也因為它告訴了我們 很多細胞在晶片上所發生的事

and then underneath, they had capillary cells,

它告訴我們這些 來自肺部細小氣管中的細胞

the cells in our blood vessels.

其實有著你能夠想像得到的毛髮狀結構

And we can then apply mechanical forces to the chip

這些構造稱為纖毛

that stretch and contract the membrane,

它們的作用是把黏液掃出肺部

so the cells experience the same mechanical forces

對。黏液。真噁心

that they did when we breathe.

但是黏液其實非常重要

And they experience them how they did in the body.

黏液會抓住顆粒、病毒、潛在過敏原

There's air flowing through the top channel,

而這些纖毛會將黏液清出肺部

and then we flow a liquid that contains nutrients

當它們被例如香菸等等破壞的時候

through the blood channel.

就沒辦法正常作用，也就無法將黏液清掉

Now the chip is really beautiful,

這會導致支氣管炎之類的疾病

but what can we do with it?

纖毛以及黏液的清除 也和囊性纖維化等嚴重疾病有關

We can get incredible functionality

但是有了這些晶片的功能

inside these little chips.

我們就能夠著手尋找新的治療方法

Let me show you.

這些晶片並不侷限於肺

We could, for example, mimic infection,

我們也有了腸道晶片

where we add bacterial cells into the lung.

就是這個

then we can add human white blood cells.

我們將人類小腸細胞放進腸道晶片中

White blood cells are our body's defense

它們會持續蠕動並傳導到所有的細胞

against bacterial invaders,

因此我們能夠模擬許多功能

and when they sense this inflammation due to infection,

就如同你在人類小腸所見的一般

they will enter from the blood into the lung

現在我們可以開始建立腸燥症的模型了

and engulf the bacteria.

這種疾病困擾了很多人

Well now you're going to see this happening

它讓人變得虛弱 而且好的治療方法不多

live in an actual human lung on a chip.

現在我們正在實驗室裡 研發一系列不同的器官晶片

We've labeled the white blood cells so you can see them flowing through,

然而，這項技術的真正強大之處

and when they detect that infection,

在於我們能夠用液體使它們產生連結

they begin to stick.

細胞之間有液體流通 因此我們可以把多個晶片連結在一起

They stick, and then they try to go into the lung

形成一個所謂的「人類晶片」

side from blood channel.

我們真的很興奮

And you can see here, we can actually visualize

我們並不會過度重製人類

a single white blood cell.

我們的目標是再造足夠的功能性

It sticks, it wiggles its way through

讓我們得以更好的預測體內會發生的事

between the cell layers, through the pore,

舉例來說，我們已經可以去探索 使用了噴劑藥物後所發生的事

comes out on the other side of the membrane,

氣喘病人使用吸入劑之後

and right there, it's going to engulf the bacteria

我們可以探尋藥物是如何進入肺部、身體

labeled in green.

會影響哪些器官，例如心臟

In that tiny chip, you just witnessed

它會改變心跳嗎？

one of the most fundamental responses

他有毒性嗎？

our body has to an infection.

他會經由肝臟清除嗎？

It's the way we respond to -- an immune response.

他會經由肝臟代謝嗎？

It's pretty exciting.

它會經由腎臟排泄嗎？

Now I want to share this picture with you,

我們可以開始研究藥物在體內的動態反應

not just because it's so beautiful,

這將會是革命性的改變

but because it tells us an enormous amount of information

不僅僅是針對製藥工業，也會影響很多不同的產業 包括化妝品工業

about what the cells are doing within the chips.

未來將可以利用我們 正在實驗室裡研發的皮膚晶片

It tells us that these cells

在不需要動物試驗的情況下來測試 這些產品裡的成分對皮膚是否安全

from the small airways in our lungs,

我們可以測試每天都會 接觸到的化學製品是否安全

actually have these hairlike structures

例如家庭清潔劑裡面的成分

that you would expect to see in the lung.

我們也可以將器官晶片利用在 生物恐怖主義以及輻射暴露方面

These structures are called cilia,

我們可以將它們用在伊波拉病毒 或是其他致命性疾病 例如SARS

and they actually move the mucus out of the lung.

器官晶片也得以改變未來的臨床試驗方式

Yeah. Mucus. Yuck.

目前，平均來說臨床試驗的對象都太單一了

But mucus is actually very important.

通常是中年、通常是女性

Mucus traps particulates, viruses,

你不會看到臨床試驗的對象有孩童

potential allergens,

但是我們每天都會餵孩子吃藥

and these little cilia move

而我們所擁有的安全性資料都來自於成人

and clear the mucus out.

孩童並不是成人

When they get damaged, say,

他們可能會有不同於成人的反應

by cigarette smoke for example,

人群和人群之間也會有遺傳差異 這可能會導致有負面藥物反應的危險族群

they don't work properly, and they can't clear that mucus out.

想像我們可以把彼此有差異的 族群細胞取出並放在晶片上

And that can lead to diseases such as bronchitis.

並創造一個族群晶片

Cilia and the clearance of mucus

這絕對會改變臨床試驗的做法

are also involved in awful diseases like cystic fibrosis.

而這正是研究團隊正在努力的方向

But now, with the functionality that we get in these chips,

工程師、細胞生物學家、醫師 所有人正通力合作

we can begin to look

現在 Wyss Institute 已經有了相當不可思議的成果了

for potential new treatments.

它集合了各方的大成

We didn't stop with the lung on a chip.

生物學影響了工程以及建造的定義

We have a gut on a chip.

這真是令人興奮

You can see one right here.

我們正和業界進行重要的合作

And we've put intestinal human cells

例如一家專精於大規模數位製造的公司

in a gut on a chip,

他們將會協助我們製造不止一個 而是數以百萬計的晶片

and they're under constant peristaltic motion,

讓我們得以將晶片交給盡可能多的研究人員

this trickling flow through the cells,

而這就是這項科技潛力的關鍵

and we can mimic many of the functions

現在，讓我來介紹我們的儀器

that you actually would expect to see

這台儀器是我們目前實驗室裡的原型

in the human intestine.

它能提供我們連結十個 或更多的晶片所需要的工程控制

Now we can begin to create models of diseases

此外，它也能辦到其它很重要的工作

such as irritable bowel syndrome.

它擁有很簡單的使用介面

This is a disease that affects

因此一個像我一樣的細胞生物學家 也可以進到實驗室

a large number of individuals.

把一片晶片放進 像這台一般的原型機卡匣中

It's really debilitating,

然後把卡匣放進機器裡，就像放 CD 一樣

and there aren't really many good treatments for it.

插上電並播放。輕鬆容易

Now we have a whole pipeline

現在，讓我們來想像一下 未來可能發生的事情

of different organ chips

假設我能把你的幹細胞放進晶片裡

that we are currently working on in our labs.

這就像是你個人的晶片

Now, the true power of this technology, however,

現在在這裡的每個人都是獨立個體

really comes from the fact

個體差異代表我們對藥物 可能有天差地遠或無法預測的反應

that we can fluidically link them.

我個人在幾年前有很嚴重的頭痛

There's fluid flowing across these cells,

完全沒辦法搖頭、思考 「好吧，我要嘗試些其它方法」

so we can begin to interconnect

我吃了一些Advil。十五分鐘以後我就因為嚴重氣喘發作而在前往急診室的路上了

multiple different chips together

很明顯地，我並沒有死

to form what we call a virtual human on a chip.

但是很不幸地，有些藥物的負面反應是致命的

Now we're really getting excited.

那我們要怎麼避免呢？

We're not going to ever recreate a whole human in these chips,

嗯，可預見的是有一天將出現

but what our goal is is to be able to recreate

Geraldine 晶片

sufficient functionality

Danielle 晶片

so that we can make better predictions

你的晶片

of what's going to happen in humans.

個人化醫療。謝謝

For example, now we can begin to explore

（掌聲）

what happens when we put a drug like an aerosol drug.

Those of you like me who have asthma, when you take your inhaler,

we can explore how that drug comes into your lungs,

how it enters the body,

how it might affect, say, your heart.

Does it change the beating of your heart?

Does it have a toxicity?

Does it get cleared by the liver?

Is it metabolized in the liver?

Is it excreted in your kidneys?

We can begin to study the dynamic

response of the body to a drug.

This could really revolutionize

and be a game changer

for not only the pharmaceutical industry,

but a whole host of different industries,

including the cosmetics industry.

We can potentially use the skin on a chip

that we're currently developing in the lab

to test whether the ingredients in those products

that you're using are actually safe to put on your skin

without the need for animal testing.

We could test the safety

of chemicals that we are exposed to

on a daily basis in our environment,

such as chemicals in regular household cleaners.

We could also use the organs on chips

for applications in bioterrorism

or radiation exposure.

We could use them to learn more about

diseases such as ebola

or other deadly diseases such as SARS.

Organs on chips could also change

the way we do clinical trials in the future.

Right now, the average participant

in a clinical trial is that: average.

Tends to be middle aged, tends to be female.

You won't find many clinical trials

in which children are involved,

yet every day, we give children medications,

and the only safety data we have on that drug

is one that we obtained from adults.

Children are not adults.

They may not respond in the same way adults do.

There are other things like genetic differences

in populations

that may lead to at-risk populations

that are at risk of having an adverse drug reaction.

Now imagine if we could take cells from all those different populations,

put them on chips,

and create populations on a chip.

This could really change the way

we do clinical trials.

And this is the team and the people that are doing this.

We have engineers, we have cell biologists,

we have clinicians, all working together.

We're really seeing something quite incredible

at the Wyss Institute.

It's really a convergence of disciplines,

where biology is influencing the way we design,

the way we engineer, the way we build.

It's pretty exciting.