TEDxBoston
Geraldine Hamilton: Body parts on a chip
洁拉尔丁·汉密尔顿: 芯片上的人体部位
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构思一种新的药物、一个针对疾病的更好地药方相对容易。难的是测试它，测试过程可能会推迟有效新药上市若干年。在这个通俗易懂的演讲中，杰拉尔丁·汉密尔顿将向您解释她所在的实验室是怎样在芯片上创造人体器官和部位的，芯片具有简单的结构，所有的部件都对测试新药效果举足轻重 -- 甚至能为个人量身定做治疗方法。（TEDxBoston摄制）
Geraldine Hamilton - Bio researcher
Geraldine Hamilton builds organs and body parts on a chip -- to test new, custom cures. Full bio
Geraldine Hamilton builds organs and body parts on a chip -- to test new, custom cures. Full bio
Double-click the English transcript below to play the video.
00:12
We have a global health challenge
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我们面临全球性的医疗挑战
00:14
in our hands today,
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今时今日，
00:16
and that is that the way we currently
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我们目前发现并开发
00:19
discover and develop new drugs
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新药物的方式
00:22
is too costly, takes far too long,
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太昂贵，耗时太长
00:26
and it fails more often than it succeeds.
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研究结果失败多而成功少
00:30
It really just isn't working, and that means
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很多情况下完全无用，这意味着
00:33
that patients that badly need new therapies
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当病人急切地需要新的疗法时
00:36
are not getting them,
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却无法获得药物，
00:38
and diseases are going untreated.
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疾病也无从治疗。
00:41
We seem to be spending more and more money.
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似乎我们花的钱也越来越多。
00:44
So for every billion dollars we spend in R&D,
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在研究中我们每花费十亿美元，
00:48
we're getting less drugs approved into the market.
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而获准在市场上销售的新药却更少了。
00:52
More money, less drugs. Hmm.
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花更多的钱，研究出更少的新药。嗯。
00:55
So what's going on here?
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那么到底问题在哪？
00:57
Well, there's a multitude of factors at play,
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好，这里有一系列影响因素，
01:00
but I think one of the key factors
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但我认为主因之一是
01:02
is that the tools that we currently have
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我们目前的工具，
01:04
available to test whether a drug is going to work,
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测试新药是否可用，
01:08
whether it has efficacy,
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是否有疗效，
01:10
or whether it's going to be safe
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是否是安全的药品，
01:12
before we get it into human clinical trials,
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在开展人体临床试验之前，
01:15
are failing us. They're not predicting
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这些工具都无法满足我们的要求。这些工具
01:17
what's going to happen in humans.
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不能预测药物将对人体产生何种作用。
01:21
And we have two main tools available
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我们有两大主要工具
01:23
at our disposal.
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可供使用。
01:25
They are cells in dishes and animal testing.
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它们是培养皿和动物实验。
01:29
Now let's talk about the first one, cells in dishes.
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首先让我们讨论一下第一种工具，培养皿中的细胞。
01:33
So, cells are happily functioning in our bodies.
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一般，细胞在我们体内快乐的工作。
01:36
We take them and rip them out
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我们取出细胞，将它们从原生环境中
01:38
of their native environment,
throw them in one of these dishes,
throw them in one of these dishes,
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剥离出来，放进一个培养皿中，
01:41
and expect them to work.
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并希望它们能照常工作。
01:42
Guess what. They don't.
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猜怎么着。它们不工作了。
01:45
They don't like that environment
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它们不喜欢新环境
01:46
because it's nothing like
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因为新环境
01:48
what they have in the body.
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和它们生长的身体环境大不相同。
01:51
What about animal testing?
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至于动物实验呢？
01:53
Well, animals do and can provide
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好，动物们确实可以提供
01:55
extremely useful information.
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十分有用的信息。
01:58
They teach us about what happens
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它们使我们明白
01:59
in the complex organism.
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在复杂的有机体中药物如何作用。
02:02
We learn more about the biology itself.
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我们学到更多关于生物学本身的信息。
02:05
However, more often than not,
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但是往往，
02:08
animal models fail to predict
what will happen in humans
what will happen in humans
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动物体实验不能预测人类
02:12
when they're treated with a particular drug.
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在使用特定药物时会发生的情况。
02:15
So we need better tools.
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所以我们需要更好的工具。
02:17
We need human cells,
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我们确实需要人类细胞，
02:19
but we need to find a way to keep them happy
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但是我们需要找到一个方式在体外
02:22
outside the body.
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保持细胞活性。
02:24
Our bodies are dynamic environments.
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人类身体有着动态的环境。
02:26
We're in constant motion.
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我们在不断的运动中。
02:28
Our cells experience that.
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细胞也是如此。
02:31
They're in dynamic environments in our body.
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细胞生活在身体的动态环境中。
02:33
They're under constant mechanical forces.
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细胞经受长期的机械力。
02:36
So if we want to make cells happy
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所以如果想让细胞，
02:39
outside our bodies,
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在身体外存活，
02:40
we need to become cell architects.
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我们就必须成为细胞建筑师。
02:42
We need to design, build and engineer
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我们需要设计、 策划和建造
02:47
a home away from home for the cells.
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细胞在身体以外的家。
02:50
And at the Wyss Institute,
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而在哈佛大学维斯研究所（Wyss Institute），
02:52
we've done just that.
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我们已经这样做了。
02:54
We call it an organ-on-a-chip.
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我们叫它芯片上的器官。
02:57
And I have one right here.
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我这里有一个。
02:58
It's beautiful, isn't it?
But it's pretty incredible.
But it's pretty incredible.
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它很美丽，不是吗？但它是相当令人难以置信。
03:01
Right here in my hand is a breathing, living
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就在我的手中，细胞就在这里呼吸生活，
03:06
human lung on a chip.
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一个生活在芯片上的人类肺细胞。
03:08
And it's not just beautiful.
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它并不只是美丽。
03:11
It can do a tremendous amount of things.
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它可以做大量的事情。
03:13
We have living cells in that little chip,
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我们将活细胞放入那个小小的芯片，
03:17
cells that are in a dynamic environment
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在动态环境之中的细胞
03:19
interacting with different cell types.
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与不同的细胞类型进行交互。
03:22
There's been many people
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有很多人
03:24
trying to grow cells in the lab.
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尝试在实验室里培养细胞。
03:26
They've tried many different approaches.
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他们尝试了许多不同的方法。
03:29
They've even tried to grow
little mini-organs in the lab.
little mini-organs in the lab.
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甚至试图在实验室里培育小型迷你器官。
03:32
We're not trying to do that here.
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但这不是我们想做的。
03:33
We're simply trying to recreate
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我们只想在这个小小的芯片里
03:35
in this tiny chip
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重新创建
03:37
the smallest functional unit
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一个最小的功能单位
03:40
that represents the biochemistry,
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它能模拟细胞的生物化学环境，
03:43
the function and the mechanical strain
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功能和在身体中经历的
03:46
that the cells experience in our bodies.
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机械拉力。
03:49
So how does it work? Let me show you.
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它是如何工作的？让我展示给你看。
03:52
We use techniques from the computer chip
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我们使用芯片技术
03:55
manufacturing industry
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和制造技术
03:56
to make these structures at a scale
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按照细胞及其环境情况
03:59
relevant to both the cells and their environment.
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建造具有相应规模的结构。
04:02
We have three fluidic channels.
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我们有三个流体通道。
04:04
In the center, we have a porous, flexible membrane
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在芯片中心，我们有一个多孔的、 可渗透的膜
04:07
on which we can add human cells
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在膜上，我们可以添加人体细胞
04:09
from, say, our lungs,
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比如说说，人类的肺细胞，
04:11
and then underneath, they had capillary cells,
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然后在肺细胞下，加入毛细血管细胞，
04:13
the cells in our blood vessels.
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一种我们的血管中的细胞。
04:15
And we can then apply mechanical forces to the chip
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我们然后可以对芯片施以机械力
04:19
that stretch and contract the membrane,
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来伸展和收缩膜，
04:22
so the cells experience the same mechanical forces
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所以细胞能受到与我们呼吸时
04:25
that they did when we breathe.
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感受的相同机械力。
04:28
And they experience them how they did in the body.
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细胞经历着与在身体中相同的环境。
04:31
There's air flowing through the top channel,
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顶部通道有空气流过，
04:34
and then we flow a liquid that contains nutrients
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然后使含有的营养物质的液体
04:37
through the blood channel.
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流过血液通道。
04:40
Now the chip is really beautiful,
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现在，这张芯片是真的很美，
04:42
but what can we do with it?
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但它能做什么呢？
04:44
We can get incredible functionality
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我们可以使用这些小芯片
04:47
inside these little chips.
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获得惊人的功能。
04:49
Let me show you.
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让我来展示下。
04:50
We could, for example, mimic infection,
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比如说，我们可以模仿感染，
04:53
where we add bacterial cells into the lung.
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将细菌细胞添加到肺细胞上
04:56
then we can add human white blood cells.
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然后再添加人类白细胞。
04:59
White blood cells are our body's defense
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白细胞是人类身体的防御者
05:02
against bacterial invaders,
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专门针对细菌入侵者，
05:03
and when they sense this
inflammation due to infection,
inflammation due to infection,
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当白细胞感觉到这种炎症感染，
05:06
they will enter from the blood into the lung
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它们将从血液进入肺
05:09
and engulf the bacteria.
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并吞噬细菌。
05:11
Well now you're going to see this happening
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现在你能通过芯片上的活生生的人类肺细胞
05:13
live in an actual human lung on a chip.
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观测到这种情况的发生。
05:17
We've labeled the white blood cells
so you can see them flowing through,
so you can see them flowing through,
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我们已经标记过这些白细胞，所以你可以看到它们流过，
05:20
and when they detect that infection,
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当白细胞发现感染，
05:22
they begin to stick.
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就会粘在细胞壁上。
05:24
They stick, and then they try to go into the lung
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白细胞聚集在感染处，然后试着从血液通道一侧
05:28
side from blood channel.
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进入肺细胞一侧。
05:29
And you can see here, we can actually visualize
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你可以看到，我们其实使每个白细胞
05:33
a single white blood cell.
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可视化了。
05:37
It sticks, it wiggles its way through
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这个白细胞粘住后，扭动并通过
05:39
between the cell layers, through the pore,
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细胞层，通过孔洞，
05:41
comes out on the other side of the membrane,
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从膜的另一边出来
05:44
and right there, it's going to engulf the bacteria
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而在膜的这边，它将会去吞噬
05:47
labeled in green.
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标记为绿色的细菌。
05:49
In that tiny chip, you just witnessed
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在那小小的芯片里，你刚刚目睹了
05:52
one of the most fundamental responses
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当我们的身体受到感染时做出的
05:55
our body has to an infection.
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一种最基本的反应。
05:57
It's the way we respond to -- an immune response.
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这就是我们身体回应的方式 — — 免疫反应。
06:01
It's pretty exciting.
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这是很令人兴奋的。
06:03
Now I want to share this picture with you,
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现在我想跟你们分享这张照片，
06:06
not just because it's so beautiful,
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不只是因为它特别美丽，
06:08
but because it tells us an enormous
amount of information
amount of information
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而是因为它告诉了我们大量的
06:11
about what the cells are doing within the chips.
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关于细胞在芯片中活动的信息。
06:14
It tells us that these cells
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它告诉我们，这些
06:16
from the small airways in our lungs,
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从我们的肺气道里提取的细胞
06:19
actually have these hairlike structures
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其实有一些绒毛般的结构
06:20
that you would expect to see in the lung.
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就像人们常常在肺里看到绒毛一样。
06:22
These structures are called cilia,
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这些结构被称为纤毛，
06:24
and they actually move the mucus out of the lung.
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它们的作用是将肺里的痰清除出来。
06:27
Yeah. Mucus. Yuck.
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是这样的。痰。恶心。
06:28
But mucus is actually very important.
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但痰其实是非常重要的。
06:31
Mucus traps particulates, viruses,
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痰液捕获大气尘、 病毒、
06:33
potential allergens,
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潜在过敏原，
06:35
and these little cilia move
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这些小纤毛移动
06:36
and clear the mucus out.
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并将痰液清除。
06:39
When they get damaged, say,
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当纤毛被损坏时，比如说
06:41
by cigarette smoke for example,
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被香烟烟雾损坏时，
06:43
they don't work properly,
and they can't clear that mucus out.
and they can't clear that mucus out.
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它们就停止正常工作，也不能清除痰液。
06:46
And that can lead to diseases such as bronchitis.
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就会导致支气管炎等疾病。
06:50
Cilia and the clearance of mucus
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纤毛和痰液清除
06:52
are also involved in awful diseases like cystic fibrosis.
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也会与可怕的疾病有关，比如囊胞性纤维症。
06:57
But now, with the functionality
that we get in these chips,
that we get in these chips,
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但现在，通过使用这些芯片的功能，
07:00
we can begin to look
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我们可以开始探索
07:02
for potential new treatments.
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潜在的新疗法。
07:05
We didn't stop with the lung on a chip.
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我们并没有止步于芯片上的肺细胞。
07:07
We have a gut on a chip.
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我们有肠细胞芯片。
07:08
You can see one right here.
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大家可以看到我这里就有一个。
07:10
And we've put intestinal human cells
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我们已经把人类肠道中的细胞
07:14
in a gut on a chip,
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放在在芯片上，
07:16
and they're under constant peristaltic motion,
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它们生活在不断的肠道蠕动下
07:18
this trickling flow through the cells,
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有条滴流通过肠细胞，
07:22
and we can mimic many of the functions
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我们可以模仿许多
07:24
that you actually would expect to see
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大家能想到的
07:26
in the human intestine.
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在发生在人体肠道内的身体功能。
07:28
Now we can begin to create models of diseases
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现在我们可以开始创建疾病的模型
07:32
such as irritable bowel syndrome.
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如肠易激综合症。
07:34
This is a disease that affects
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这是一种疾病，
07:36
a large number of individuals.
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影响许多病患。
07:38
It's really debilitating,
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此病会使人衰弱，
07:40
and there aren't really many good treatments for it.
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确实还没有很多好的治疗方法。
07:44
Now we have a whole pipeline
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现在，我们研发出了一整套
07:46
of different organ chips
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不同器官的芯片，
07:49
that we are currently working on in our labs.
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用在实验室中对该疾病进行研究。
07:52
Now, the true power of this technology, however,
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这项技术的真正力量
07:56
really comes from the fact
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是从这一事实衍生而来：
07:58
that we can fluidically link them.
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我们可以将细胞通过液体连接起来。
08:00
There's fluid flowing across these cells,
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有流体流过这些细胞，
08:02
so we can begin to interconnect
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然后我们可以开始互连
08:04
multiple different chips together
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多个不同芯片
08:07
to form what we call a virtual human on a chip.
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以形成我们称之为虚拟的芯片人体。
08:12
Now we're really getting excited.
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现在我们真的很兴奋。
08:15
We're not going to ever recreate
a whole human in these chips,
a whole human in these chips,
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我们并不会建造一个芯片人体，
08:19
but what our goal is is to be able to recreate
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我们的目标是要能够重新创建
08:23
sufficient functionality
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足够的细胞功能
08:25
so that we can make better predictions
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使我们能够更好的预测
08:27
of what's going to happen in humans.
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人体反应。
08:29
For example, now we can begin to explore
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例如，现在我们可以开始探索
08:32
what happens when we put
a drug like an aerosol drug.
a drug like an aerosol drug.
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当我们使用气雾剂药物时，身体将如何反应。
08:36
Those of you like me who have asthma,
when you take your inhaler,
when you take your inhaler,
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那些像我一样有哮喘的人，使用吸入器时
08:39
we can explore how that drug comes into your lungs,
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我们可以研究药物如何进入肺细胞，
08:42
how it enters the body,
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如何进入人体，
08:43
how it might affect, say, your heart.
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如何影响，比如说，心脏。
08:45
Does it change the beating of your heart?
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它会改变心脏的跳动吗？
08:47
Does it have a toxicity?
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有没有毒性吗？
08:49
Does it get cleared by the liver?
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会被肝脏清除吗？
08:51
Is it metabolized in the liver?
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它是通过肝脏代谢吗？
08:53
Is it excreted in your kidneys?
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它是通过肾脏排泄吗？
08:55
We can begin to study the dynamic
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我们可以开始研究
08:57
response of the body to a drug.
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药物对身体的动态反应。
09:00
This could really revolutionize
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这是一项创举，
09:01
and be a game changer
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并将改变游戏规则，
09:03
for not only the pharmaceutical industry,
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不管是制药业，
09:06
but a whole host of different industries,
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还是其他不同的许多行业，
09:08
including the cosmetics industry.
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包括化妆品行业。
09:11
We can potentially use the skin on a chip
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我们可能会使用皮肤细胞芯片，
09:14
that we're currently developing in the lab
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我们目前正在实验室中开发，
09:16
to test whether the ingredients in those products
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并测试您使用的化妆品中的成分
09:18
that you're using are actually
safe to put on your skin
safe to put on your skin
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是不是对皮肤安全，
09:21
without the need for animal testing.
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而无需动物试验。
09:24
We could test the safety
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我们可以测试我们接触到的
09:26
of chemicals that we are exposed to
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化学品的安全，
09:28
on a daily basis in our environment,
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比如基于我们的日常生活环境的，
09:30
such as chemicals in regular household cleaners.
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在普通家用清洁剂中使用的化学品。
09:34
We could also use the organs on chips
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我们也可将芯片器官
09:37
for applications in bioterrorism
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应用在生物反恐中
09:40
or radiation exposure.
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或测试辐射暴露上。
09:43
We could use them to learn more about
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我们可以用它们来了解更多关于
09:46
diseases such as ebola
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疾病的特点，比如埃博拉病毒，
09:49
or other deadly diseases such as SARS.
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或其他致命的疾病，如非典型肺炎(SARS)。
09:53
Organs on chips could also change
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芯片器官也可以改变
09:55
the way we do clinical trials in the future.
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我们在未来做临床试验的方式。
09:58
Right now, the average participant
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现在，一般参与
10:01
in a clinical trial is that: average.
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临床试验的被测者都是平均值。
10:04
Tends to be middle aged, tends to be female.
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往往是中年人，往往是女性。
10:07
You won't find many clinical trials
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临床试验并不多，
10:10
in which children are involved,
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特别是涉及到儿童，
10:11
yet every day, we give children medications,
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然而日常生活中，我们给孩子用药，
10:15
and the only safety data we have on that drug
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使用药物的安全数据
10:19
is one that we obtained from adults.
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却是从测试成年人时取得的。
10:22
Children are not adults.
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儿童不同于成人。
10:23
They may not respond in the same way adults do.
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儿童对药物的反应也可能与成人不同。
10:27
There are other things like genetic differences
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还有其他的影响因素，像不同人群间的
10:29
in populations
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遗传差异
10:30
that may lead to at-risk populations
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可能会导致一部分高危人群，
10:34
that are at risk of having an adverse drug reaction.
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承受药物不良反应的风险。
10:37
Now imagine if we could take cells
from all those different populations,
from all those different populations,
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现在想象一下，
我们是否可以从不同人群中提取细胞
我们是否可以从不同人群中提取细胞
10:40
put them on chips,
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把它们放上芯片，
10:42
and create populations on a chip.
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并在芯片上创建这些人群。
10:44
This could really change the way
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这真的可以改变
10:46
we do clinical trials.
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我们做临床试验的方式。
10:48
And this is the team and the people
that are doing this.
that are doing this.
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这正是我们团队和成员正在做的事。
10:51
We have engineers, we have cell biologists,
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我们中有工程师，有细胞生物学家，
10:54
we have clinicians, all working together.
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有临床医生在一起工作。
10:58
We're really seeing something quite incredible
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在 VIS 研究所我们确实观察到了
11:00
at the Wyss Institute.
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一些很不可思议的东西。
11:02
It's really a convergence of disciplines,
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这真是一门综合学科，
11:04
where biology is influencing the way we design,
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生物学正在影响我们设计的方式，
11:07
the way we engineer, the way we build.
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策划的方式，和建造的方式。
11:10
It's pretty exciting.
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这很令人兴奋。
11:12
We're establishing important industry collaborations
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我们要建立重要的产业合作
11:15
such as the one we have with a company
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比如我们已与一家熟知
11:18
that has expertise in large-scale
digital manufacturing.
digital manufacturing.
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大型数字化制造的公司合作。
11:22
They're going to help us make,
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他们会帮助我们制造，
11:24
instead of one of these,
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不是一枚，
11:26
millions of these chips,
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而是数以百万计的芯片，
11:27
so that we can get them into the hands
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这样，我们可以让尽可能多的研究人员
11:29
of as many researchers as possible.
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使用这些芯片。
11:32
And this is key to the potential of that technology.
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这是该技术至关重要的潜能。
11:36
Now let me show you our instrument.
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现在让我给大家看看我们的仪器。
11:39
This is an instrument that our engineers
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这是一台我们的工程师
11:41
are actually prototyping right now in the lab,
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正在实验室中建造的样机，
11:43
and this instrument is going to give us
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这台仪器能使我们
11:45
the engineering controls that we're going to require
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工程控制需要实现的功能，
11:48
in order to link 10 or more organ chips together.
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那就是将 10 个或更多器官芯片连接在一起。
11:52
It does something else that's very important.
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这台机器做的事情是非常重要的。
11:54
It creates an easy user interface.
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它将创建一个简单的用户界面。
11:57
So a cell biologist like me can come in,
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所以像我这样的细胞生物学家可以来
12:00
take a chip, put it in a cartridge
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拿起一块芯片，把它放在盒子里
12:02
like the prototype you see there,
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像你看到的原型一样
12:04
put the cartridge into the machine
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将盒子放入机器里，
12:06
just like you would a C.D.,
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这就像你放 C.D.一样
12:08
and away you go.
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然后就好了。
12:09
Plug and play. Easy.
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即插即用。很容易。
12:12
Now, let's imagine a little bit
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现在，让我们想象一下
12:14
what the future might look like
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未来可能会是什么样子
12:15
if I could take your stem cells
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如果能把你的干细胞
12:18
and put them on a chip,
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放在芯片上，
12:19
or your stem cells and put them on a chip.
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或者把你的干细胞，放在一个芯片上。
12:22
It would be a personalized chip just for you.
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它将只为你一个人创造一枚个性化的芯片。
12:26
Now all of us in here are individuals,
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今天在座的各位都是单独个体，
12:29
and those individual differences mean
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而那些个体差异意味着
12:32
that we could react very differently
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我们对药物的反应方式有可能非常不同，
12:34
and sometimes in unpredictable ways to drugs.
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有时甚至无法预知身体反应的方式。
12:39
I myself, a couple of years back,
had a really bad headache,
had a really bad headache,
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就我自己来说，过去有两年，头痛得真的很厉害，
12:43
just couldn't shake it, thought,
"Well, I'll try something different."
"Well, I'll try something different."
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完全不能摆脱它，我当时想，"嗯，我要试点不同的药方"，
12:46
I took some Advil. Fifteen minutes later,
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我吃了几片雅维。十五分钟后，
12:48
I was on my way to the emergency room
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我就在去急救室的路上了，
12:50
with a full-blown asthma attack.
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哮喘全面发作。
12:52
Now, obviously it wasn't fatal,
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现在，当然没有致命，
12:53
but unfortunately, some of these
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但不幸的是，有些
12:57
adverse drug reactions can be fatal.
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药品的不良反应确是致命的。
13:00
So how do we prevent them?
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所以我们如何防范呢？
13:02
Well, we could imagine one day
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嗯，我们可以想象一下有一天
13:05
having Geraldine on a chip,
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在芯片上，载有杰拉尔丁细胞
13:07
having Danielle on a chip,
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在芯片上，载有丹妮细胞
13:09
having you on a chip.
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有你的细胞在芯片上。
13:10
Personalized medicine. Thank you.
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个体化用药。谢谢。
13:13
(Applause)
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（掌声）
ABOUT THE SPEAKER
Geraldine Hamilton - Bio researcherGeraldine Hamilton builds organs and body parts on a chip -- to test new, custom cures.
Why you should listen
Geraldine Hamilton’s career spans from academic research to biotech start-ups to pharma. Her research focus has been on the development and application of human-relevant in-vitro models for drug discovery. She was one of the founding scientists, VP of Scientific Operations and Director of Cell Products, in a start-up biotech company (CellzDirect), that successfully translated and commercialized technology from academic research to supply the pharmaceutical industry with hepatic cell products and services for safety assessment and drug-metabolism studies.
Hamilton received her Ph.D. in cell biology/toxicology from the University of Hertfordshire (England) in conjunction with GlaxoSmithkline, followed by a post-doctoral research fellowship at the University of North Carolina. Her current research interests and prior experience include: organs on-a-chip, toxicology and drug metabolism, liver cell biology, mechanisms regulating gene expression and differentiation, regulation of nuclear receptors and transcriptional activation in hepatocytes by xenobiotics, human cell isolation and cryopreservation techniques.
Geraldine Hamilton | Speaker | TED.com