Geraldine Hamilton: Body parts on a chip

譯者: NAN-KUN WU 審譯者: Shi Tan

We have a global health challenge

我們现在正面臨全球人們健康的挑戰

in our hands today,

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

is too costly, takes far too long,

and it fails more often than it succeeds.

且大多以失敗收場

It really just isn't working, and that means

這樣的方式是無效的

也代表迫切需要新式療法的病人得不到治療

that patients that badly need new therapies

are not getting them,

and diseases are going untreated.

疾病也就無法被醫治

We seem to be spending more and more money.

我們似乎花越來越多的金錢

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

花在研發的每一個十億美元

we're getting less drugs approved into the market.

都得到更少成功上市的藥

More money, less drugs. Hmm.

更多的錢，更少的藥。嗯

So what's going on here?

到底發生了什麼事？

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

嗯，有多種因素牽扯其中

but I think one of the key factors

但我認為最重要的原因是

is that the tools that we currently have

在進入人體臨床試驗之前

available to test whether a drug is going to work,

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

whether it has efficacy,

or whether it's going to be safe

before we get it into human clinical trials,

are failing us. They're not predicting

它們無法預測在人體內會發生的事

what's going to happen in humans.

And we have two main tools available

目前有兩種主要的工具

at our disposal.

They are cells in dishes and animal testing.

那就是細胞培養以及動物試驗

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

我們先來說說第一種，細胞培養

So, cells are happily functioning in our bodies.

好，細胞在我們的身體裡面快樂地工作著

We take them and rip them out

我們把它們從正常生長環境中取出來

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

並丟到這些培養皿的其中之一

and expect them to work.

希望它們依然能夠運作

Guess what. They don't.

結果並不意外 它們不能

They don't like that environment

它們不喜歡那樣的環境

because it's nothing like

因為這跟身體裡面的環境完全不同

what they have in the body.

What about animal testing?

動物試驗呢？

Well, animals do and can provide

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

extremely useful information.

They teach us about what happens

in the complex organism.

我們學到了很多生物學的相關知識

We learn more about the biology itself.

However, more often than not,

但是通常來說

animal models fail to predict what will happen in humans

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

when they're treated with a particular drug.

So we need better tools.

所以我們需要更好的工具

We need human cells,

我們需要人體細胞

but we need to find a way to keep them happy

但是我們要找到讓它們 在體外也能「快樂」的方法

outside the body.

Our bodies are dynamic environments.

我們的身體是個動態的環境

We're in constant motion.

一直在活動著

Our cells experience that.

我們的細胞也是這樣

They're in dynamic environments in our body.

它們也處於動態的環境、感受持續的作用力

They're under constant mechanical forces.

So if we want to make cells happy

因次如果我們想讓細胞「快樂」的在體外生活

outside our bodies,

we need to become cell architects.

我們就得成為細胞建築師

We need to design, build and engineer

去設計、建造、監控細胞們的另外一個家

a home away from home for the cells.

And at the Wyss Institute,

在維斯研究所（Wyss Institute），我們已經做到了

we've done just that.

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

我們把它叫做晶片上的器官

And I have one right here.

我這裡正好有一個

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

它真美，對吧？ 但卻是如此地不可思議

Right here in my hand is a breathing, living

在我手上的是一個在晶片上 會呼吸、活生生的人類的肺

human lung on a chip.

And it's not just beautiful.

它不只是美

It can do a tremendous amount of things.

它能做強大到令人驚歎的事

We have living cells in that little chip,

在晶片上的細胞是活的

cells that are in a dynamic environment

且處於動態環境

interacting with different cell types.

能夠和不同種類的細胞交互作用

There's been many people

有很多人嘗試過在實驗室裡培養細胞

trying to grow cells in the lab.

They've tried many different approaches.

他們試過很多種方法

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

他們甚至試過在實驗室裡培養迷你的器官

We're not trying to do that here.

我們並不那麼做

We're simply trying to recreate

我們只是在這小小的晶片上 創造了最小的功能單位

in this tiny chip

the smallest functional unit

that represents the biochemistry,

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

the function and the mechanical strain

that the cells experience in our bodies.

So how does it work? Let me show you.

它們怎麼運作呢？讓我告訴你們

We use techniques from the computer chip

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

manufacturing industry

to make these structures at a scale

relevant to both the cells and their environment.

We have three fluidic channels.

其中有三條液體通道

In the center, we have a porous, flexible membrane

在中間部分有兼具通透性以及彈性的膜

on which we can add human cells

在這些膜上我們可以放上人體細胞 例如肺部細胞

from, say, our lungs,

and then underneath, they had capillary cells,

下層則有微血管細胞

the cells in our blood vessels.

And we can then apply mechanical forces to the chip

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

that stretch and contract the membrane,

so the cells experience the same mechanical forces

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

that they did when we breathe.

And they experience them how they did in the body.

就如同在我們體內的時候一樣

There's air flowing through the top channel,

最上方的通道有氣流流過

and then we flow a liquid that contains nutrients

然後帶有養分的液體會流過血液通道

through the blood channel.

Now the chip is really beautiful,

晶片是很漂亮，但是我們要怎麼利用呢？

but what can we do with it?

We can get incredible functionality

這些小小的晶片具有相當不可思議的功能

inside these little chips.

Let me show you.

讓我告訴你們吧

We could, for example, mimic infection,

例如，加入細菌細胞就能夠模擬肺部感染

where we add bacterial cells into the lung.

then we can add human white blood cells.

然後加入人類白血球

White blood cells are our body's defense

白血球在我們體內 扮演抵抗細菌入侵的角色

against bacterial invaders,

and when they sense this inflammation due to infection,

當它們接受到因感染而引起的發炎反應時

they will enter from the blood into the lung

就會經由血管進入肺部並吞嗜細菌

and engulf the bacteria.

Well now you're going to see this happening

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

live in an actual human lung on a chip.

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

我們標記了白血球 所以你們能夠看到它們正常流過

and when they detect that infection,

當它們偵測到感染時，就會開始黏附（細菌）

they begin to stick.

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

黏附之後，就會試著從血管這一側進入肺部

side from blood channel.

And you can see here, we can actually visualize

如你所見，我們能夠 捕捉到單一一顆白血球

a single white blood cell.

It sticks, it wiggles its way through

黏附、擺動著穿越細胞層、細胞核

between the cell layers, through the pore,

comes out on the other side of the membrane,

到達膜的另外一側

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

就在這裡，白血球將會 吞噬擁有綠色標記的細菌

labeled in green.

In that tiny chip, you just witnessed

在小小的晶片上，你見到了我們身體 對感染的最基礎反應

one of the most fundamental responses

our body has to an infection.

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

這就是所謂的免疫反應

It's pretty exciting.

相當令人興奮

Now I want to share this picture with you,

現在我想分享這張圖片

not just because it's so beautiful,

不只是因為它很美

but because it tells us an enormous amount of information

也因為它告訴了我們 很多細胞在晶片上所發生的事

about what the cells are doing within the chips.

It tells us that these cells

它告訴我們這些 來自肺部細小氣管中的細胞

from the small airways in our lungs,

actually have these hairlike structures

其實有著你能夠想像得到的毛髮狀結構

that you would expect to see in the lung.

These structures are called cilia,

這些構造稱為纖毛

and they actually move the mucus out of the lung.

它們的作用是把黏液掃出肺部

Yeah. Mucus. Yuck.

對。黏液。真噁心

But mucus is actually very important.

但是黏液其實非常重要

Mucus traps particulates, viruses,

黏液會抓住顆粒、病毒、潛在過敏原

potential allergens,

and these little cilia move

而這些纖毛會將黏液清出肺部

and clear the mucus out.

When they get damaged, say,

當它們被例如香菸等等破壞的時候

by cigarette smoke for example,

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

就沒辦法正常作用，也就無法將黏液清掉

And that can lead to diseases such as bronchitis.

這會導致支氣管炎之類的疾病

Cilia and the clearance of mucus

纖毛以及黏液的清除 也和囊性纖維化等嚴重疾病有關

are also involved in awful diseases like cystic fibrosis.

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

但是有了這些晶片的功能

we can begin to look

我們就能夠著手尋找新的治療方法

for potential new treatments.

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

這些晶片並不侷限於肺

We have a gut on a chip.

我們也有了腸道晶片

You can see one right here.

就是這個

And we've put intestinal human cells

我們將人類小腸細胞放進腸道晶片中

in a gut on a chip,

and they're under constant peristaltic motion,

它們會持續蠕動並傳導到所有的細胞

this trickling flow through the cells,

and we can mimic many of the functions

因此我們能夠模擬許多功能

that you actually would expect to see

就如同你在人類小腸所見的一般

in the human intestine.

Now we can begin to create models of diseases

現在我們可以開始建立腸燥症的模型了

such as irritable bowel syndrome.

This is a disease that affects

這種疾病困擾了很多人

a large number of individuals.

It's really debilitating,

它讓人變得虛弱 而且好的治療方法不多

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

Now we have a whole pipeline

現在我們正在實驗室裡 研發一系列不同的器官晶片

of different organ chips

that we are currently working on in our labs.

Now, the true power of this technology, however,

然而，這項技術的真正強大之處

really comes from the fact

在於我們能夠用液體使它們產生連結

that we can fluidically link them.

There's fluid flowing across these cells,

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

so we can begin to interconnect

multiple different chips together

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

形成一個所謂的「人類晶片」

Now we're really getting excited.

我們真的很興奮

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

我們並不會過度重製人類

but what our goal is is to be able to recreate

我們的目標是再造足夠的功能性

sufficient functionality

so that we can make better predictions

讓我們得以更好的預測體內會發生的事

of what's going to happen in humans.

For example, now we can begin to explore

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

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

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

氣喘病人使用吸入劑之後

we can explore how that drug comes into your lungs,

我們可以探尋藥物是如何進入肺部、身體

how it enters the body,

how it might affect, say, your heart.

會影響哪些器官，例如心臟

Does it change the beating of your heart?

它會改變心跳嗎？

Does it have a toxicity?

他有毒性嗎？

Does it get cleared by the liver?

他會經由肝臟清除嗎？

Is it metabolized in the liver?

他會經由肝臟代謝嗎？

Is it excreted in your kidneys?

它會經由腎臟排泄嗎？

We can begin to study the dynamic

我們可以開始研究藥物在體內的動態反應

response of the body to a drug.

This could really revolutionize

這將會是革命性的改變

and be a game changer

for not only the pharmaceutical industry,

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

but a whole host of different industries,

including the cosmetics industry.

We can potentially use the skin on a chip

未來將可以利用我們 正在實驗室裡研發的皮膚晶片

that we're currently developing in the lab

to test whether the ingredients in those products

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

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

without the need for animal testing.

We could test the safety

我們可以測試每天都會 接觸到的化學製品是否安全

of chemicals that we are exposed to

on a daily basis in our environment,

such as chemicals in regular household cleaners.

例如家庭清潔劑裡面的成分

We could also use the organs on chips

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

for applications in bioterrorism

or radiation exposure.

We could use them to learn more about

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

diseases such as ebola

or other deadly diseases such as SARS.

Organs on chips could also change

器官晶片也得以改變未來的臨床試驗方式

the way we do clinical trials in the future.

Right now, the average participant

目前，平均來說臨床試驗的對象都太單一了

in a clinical trial is that: average.

Tends to be middle aged, tends to be female.

通常是中年、通常是女性

You won't find many clinical trials

你不會看到臨床試驗的對象有孩童

in which children are involved,

yet every day, we give children medications,

但是我們每天都會餵孩子吃藥

and the only safety data we have on that drug

而我們所擁有的安全性資料都來自於成人

is one that we obtained from adults.

Children are not adults.

孩童並不是成人

They may not respond in the same way adults do.

他們可能會有不同於成人的反應

There are other things like genetic differences

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

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,

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

put them on chips,

and create populations on a chip.

並創造一個族群晶片

This could really change the way

這絕對會改變臨床試驗的做法

we do clinical trials.

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

而這正是研究團隊正在努力的方向

We have engineers, we have cell biologists,

工程師、細胞生物學家、醫師 所有人正通力合作

we have clinicians, all working together.

We're really seeing something quite incredible

現在 Wyss Institute 已經有了相當不可思議的成果了

at the Wyss Institute.

It's really a convergence of disciplines,

它集合了各方的大成

where biology is influencing the way we design,

生物學影響了工程以及建造的定義

the way we engineer, the way we build.

It's pretty exciting.

這真是令人興奮

We're establishing important industry collaborations

我們正和業界進行重要的合作

such as the one we have with a company

例如一家專精於大規模數位製造的公司

that has expertise in large-scale digital manufacturing.

They're going to help us make,

他們將會協助我們製造不止一個 而是數以百萬計的晶片

instead of one of these,

millions of these chips,

so that we can get them into the hands

讓我們得以將晶片交給盡可能多的研究人員

of as many researchers as possible.

And this is key to the potential of that technology.

而這就是這項科技潛力的關鍵

Now let me show you our instrument.

現在，讓我來介紹我們的儀器

This is an instrument that our engineers

這台儀器是我們目前實驗室裡的原型

are actually prototyping right now in the lab,

and this instrument is going to give us

它能提供我們連結十個 或更多的晶片所需要的工程控制

the engineering controls that we're going to require

in order to link 10 or more organ chips together.

It does something else that's very important.

此外，它也能辦到其它很重要的工作

It creates an easy user interface.

它擁有很簡單的使用介面

So a cell biologist like me can come in,

因此一個像我一樣的細胞生物學家 也可以進到實驗室

take a chip, put it in a cartridge

把一片晶片放進 像這台一般的原型機卡匣中

like the prototype you see there,

put the cartridge into the machine

然後把卡匣放進機器裡，就像放 CD 一樣

just like you would a C.D.,

and away you go.

Plug and play. Easy.

插上電並播放。輕鬆容易

Now, let's imagine a little bit

現在，讓我們來想像一下 未來可能發生的事情

what the future might look like

假設我能把你的幹細胞放進晶片裡

if I could take your stem cells

and put them on a chip,

or your stem cells and put them on a chip.

It would be a personalized chip just for you.

這就像是你個人的晶片

Now all of us in here are individuals,

現在在這裡的每個人都是獨立個體

and those individual differences mean

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 could react very differently

and sometimes in unpredictable ways to drugs.

I myself, a couple of years back, had a really bad headache,

我個人在幾年前有很嚴重的頭痛

just couldn't shake it, thought, "Well, I'll try something different."

完全沒辦法搖頭、思考 「好吧，我要嘗試些其它方法」

I took some Advil. Fifteen minutes later,

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

I was on my way to the emergency room

with a full-blown asthma attack.

Now, obviously it wasn't fatal,

很明顯地，我並沒有死

but unfortunately, some of these

但是很不幸地，有些藥物的負面反應是致命的

adverse drug reactions can be fatal.

So how do we prevent them?

那我們要怎麼避免呢？

Well, we could imagine one day

嗯，可預見的是有一天將出現

having Geraldine on a chip,

Geraldine 晶片

having Danielle on a chip,

Danielle 晶片

having you on a chip.

你的晶片

Personalized medicine. Thank you.

個人化醫療。謝謝

(Applause)

（掌聲）