Mina Bissell: Experiments that point to a new understanding of cancer

Translator: Morton Bast Reviewer: Thu-Huong Ha

翻译人员: Jasmine Wang 校对人员: chen jh

Now, I don't usually like cartoons,

通常我不喜欢漫画，

I don't think many of them are funny,

我觉得很多漫画并不有趣，

I find them weird. But I love this cartoon from the New Yorker.

我觉得它们很怪。但是我喜欢这幅纽约客的漫画。

(Text: Never, ever think outside the box.) (Laughter)

（文字：永远别想跳出箱子（常规）思考）（笑声）

So, the guy is telling the cat,

所以，这人在对这只猫说，

don't you dare think outside the box.

别想要跳出这个箱子，

Well, I'm afraid I used to be the cat.

好吧，恐怕我曾经是那只猫。

I always wanted to be outside the box.

我总想身处箱子之外。

And it's partly because I came to this field

这部分是因为我的背景吧，

from a different background, chemist and a bacterial geneticist.

涉足该领域前，我是化学家和细菌基因学家。

So, what people were saying to me

那么，人们会对我说的

about the cause of cancer, sources of cancer,

有关癌症的起因，来源，

or, for that matter, why you are who you are,

或者，就此而言，你为什么会进入这一领域，你是哪个领域的专家，

didn't make sense.

根本没有意义。

So, let me quickly try and tell you why I thought that

所以，请让我迅速地告诉你为什么我会这么想

and how I went about it.

和我是怎么知道这些的。

So, to begin with, however,

好的，可是一开始

I have to give you a very, very quick lesson

我需要给你们上一个非常非常短的

in developmental biology,

有关生物生长的课程，

with apologies to those of you who know some biology.

同时我对你们之中有生物知识背景的人表示歉意。

So, when your mom and dad met,

好的。当我爸爸妈妈的精子卵子相遇时，

there is a fertilized egg,

受精卵出现了，

that round thing with that little blip.

那个圆圆的有个小光点的东西。

It grows and then it grows,

然后他生长啊生长啊，

and then it makes this handsome man.

然后它长了一名帅哥。

(Applause)

（掌声）

So, this guy, with all the cells in his body,

所以，这个人，体内的所有细胞，

all have the same genetic information.

拥有相同的基因信息。

So how did his nose become his nose, his elbow his elbow,

为什么他的鼻子会变成鼻子，手肘变成手肘，

and why doesn't he get up one morning

还有为什么他某天起床

and have his nose turn into his foot?

他的鼻子不会变成脚呢？

It could. It has the genetic information.

这是应该是可能发生的，那些鼻子上的细胞有那套基因信息。

You all remember, dolly,

孩子们，你们都记住了，

it came from a single mammary cell.

这都是从一个干细胞开始的。

So, why doesn't it do it?

那么，为什么这一切没有发生呢？

So, have a guess of how many cells he has in his body.

猜猜看他的体内有多少的细胞？

Somewhere between 10 trillion to 70 trillion cells in his body.

大约在10万亿到70万亿之间存在于他身体里。

Trillion!

几十万亿！

Now, how did these cells, all with the same genetic material,

现在，所有这些含有相同基因的细胞，

make all those tissues?

是怎么形成那么多的组织呢？

And so, the question I raised before

所以，我之前提得问题

becomes even more interesting if you thought about

会更加有趣了，如果你在想

the enormity of this in every one of your bodies.

你的身体里有如此多的细胞。

Now, the dominant cancer theory would say

现在，主流肿瘤理论会说

that there is a single oncogene

一个癌细胞里面里

in a single cancer cell, and it would make you

的一个致癌基因

a cancer victim.

会让你变成癌症患者。

Well, this did not make sense to me.

好吧，这个对我来说不科学。

Do you even know how a trillion looks?

你知道一万亿是怎么样的么？

Now, let's look at it.

现在让我们看看。

There it comes, these zeroes after zeroes after zeroes.

来了，这些0一个接着一个。

Now, if .0001 of these cells got mutated,

现在，如果，0.01%的细胞突变了，

and .00001 got cancer, you will be a lump of cancer.

现在是0.001%的细胞致癌了，你会变成一大块癌细胞。

You will have cancer all over you. And you're not.

你会全身都是癌细胞。但是你不是。

Why not?

为什么没有呢？

So, I decided over the years,

所以，我通过多年来

because of a series of experiments

一系列的实验

that this is because of context and architecture.

说明这是由于环境和体系的原因。

And let me quickly tell you

让我简略地告诉你

some crucial experiment that was able to actually show this.

那些重要的实验是如何证明这些的。

To begin with, I came to work with this virus

首先，我进行病毒的研究工作

that causes that ugly tumor in the chicken.

涉及鸡身体里的恶心的肿瘤。

Rous discovered this in 1911.

Rous在1911年发现了这个。

It was the first cancer virus discovered,

那是第一个被发现的肿瘤病毒，

and when I call it "oncogene," meaning "cancer gene."

当我称它为“致癌基因”，就是说“导致癌症的基因”。

So, he made a filtrate, he took this filter

所以他设计了一个过滤装置，并用它

which was the liquid after he passed the tumor through a filter,

过滤了肿瘤后得到一种液体，

and he injected it to another chicken, and he got another tumor.

并把这种液体注射到另一只鸡体内，他就得到了另一个肿瘤。

So, scientists were very excited,

于是，科学家当时很兴奋，

and they said, a single oncogene can do it.

它们就认为，一个致癌基因就可以导致肿瘤。

All you need is a single oncogene.

你只需要一个致癌基因。

So, they put the cells in cultures, chicken cells,

所以，他们培养了那些鸡的细胞，

dumped the virus on it,

并倒入一些病毒，

and it would pile up,

它们就会堆积起来，

and they would say, this is malignant and this is normal.

然后他们就说这些是恶性肿瘤，这些是良性肿瘤。

And again this didn't make sense to me.

这个对我来说也不科学。

So for various reasons, we took this oncogene,

所以由于多种原因，我们把这些致癌基因，

attached it to a blue marker,

用蓝色标记物标记了，

and we injected it into the embryos.

并把它们注射到胚胎中。

Now look at that. There is that beautiful feather in the embryo.

现在来看看这个，这个胚胎里美丽的羽毛。

Every one of those blue cells are a cancer gene

这些蓝色的就是致癌基因

inside a cancer cell, and they're part of the feather.

都在一个癌细胞中，这些就是它羽毛的一部分。

So, when we dissociated the feather and put it in a dish,

所以，当我们分离这些羽毛并把它们放进一个培养皿里，

we got a mass of blue cells.

我们就得到了一堆蓝色细胞。

So, in the chicken you get a tumor,

所以你可以在鸡里得到肿瘤，

in the embryo you don't,

在鸡胚胎里却不能。

you dissociate, you put it in a dish, you get another tumor.

你分离了它们，并把它们放到一个培养皿里你得到的是一个肿瘤。

What does that mean?

这说明了什么？

That means that microenvironment

说明了在微环境中

and the context which surrounds those cells

环绕它们的细胞

actually are telling the cancer gene and the cancer cell what to do.

在告诉致癌基因和癌细胞该怎么做。

Now, let's take a normal example.

现在，我们举个正常例子，

The normal example, let's take the human mammary gland.

关于乳腺的例子。

I work on breast cancer.

我研究了乳腺癌。

So, here is a lovely human breast.

这个是个可爱的人类乳房。

And many of you know how it looks,

你们中的很多人都知道它看上去是什么样，

except that inside that breast, there are all these

但是它里面是什么样却没有多少人知道了，这些是

pretty, developing, tree-like structures.

所有的可爱的，正在生长的，树状结构的组织。

So, we decided that what we like to do

那么，我们决定将要做的

is take just a bit of that mammary gland,

就是取一些乳腺，

which is called an "acinus,"

这叫做“腺泡”

where there are all these little things inside the breast

乳房里都是这些东西

where the milk goes, and the end of the nipple

母乳便是在此生成的，在乳头末端

comes through that little tube when the baby sucks.

是一根根细小的微管，婴儿可以从此吸到母乳。

And we said, wonderful! Look at this pretty structure.

我们不得说，这太棒了！看看这些可爱的结构。

We want to make this a structure, and ask the question,

我们想要制造出这样一个结构，并问个问题：

how do the cells do that?

细胞是怎么做到那些的？

So, we took the red cells --

那么，我们取得了红细胞--

you see the red cells are surrounded by blue,

你们可以看到红细胞被蓝色的细胞围着，

other cells that squeeze them, and behind it

蓝色的细胞将红细胞挤得紧紧的，在它们后面

is material that people thought was mainly inert,

是人们通常认为的惰性物质，

and it was just having a structure to keep the shape,

它只是为了维持某种形状，

and so we first photographed it

所以我们在多年前利用电子显微镜

with the electron microscope years and years ago,

首先给它做了一个快照，

and you see this cell is actually quite pretty.

你们可以看到这个细胞看起来十分的可爱。

It has a bottom, it has a top,

它有底有顶，

it is secreting gobs and gobs of milk,

它正在分泌大量的乳汁,

because it just came from an early pregnant mouse.

因为它是刚从怀孕初期的老鼠身上取得的。

You take these cells, you put them in a dish,

你取得了这些细胞，并把它放在一个培养皿中，

and within three days, they look like that.

三天后，它们看起来就是那样的。

They completely forget.

它们完全忘记了自己原来是乳腺细胞。

So you take them out, you put them in a dish,

你把它们再取出，放入一个培养皿，

they don't make milk. They completely forget.

它们不会再产出乳汁。它们忘记了自己是乳腺细胞。

For example, here is a lovely yellow droplet of milk

例如，这儿，左边是一滴可爱的乳黄色的乳汁

on the left, there is nothing on the right.

而右边什么也没有。

Look at the nuclei. The nuclei in the cell on the left

看这些“细胞核”。这些在左边的细胞中的细胞核

is in the animal, the one on the right is in a dish.

是在动物体中的，右边的则是从培养皿出来的。

They are completely different from each other.

它们完全不一样。

So, what does this tell you?

那么，这说明什么？

This tells you that here also, context overrides.

这说明这儿有环境影响。

In different contexts, cells do different things.

在不同的环境下，细胞做不同的事。

But how does context signal?

但是环境是怎样影响的呢？

So, Einstein said that

爱因斯坦曾说过，

"For an idea that does not first seem insane, there is no hope."

“如果一个想法一上来就不疯狂，那么这个想法便毫无用处。”

So, you can imagine the amount of skepticism

那么，你们可以想象一上来我受到

I received -- couldn't get money,

多大的怀疑--那样做没有前途，

couldn't do a whole lot of other things,

那样做一点用也没有，

but I'm so glad it all worked out.

但是我很高兴我这样做出来了。

So, we made a section of the mammary gland of the mouse,

那么，我们做了老鼠乳腺的切片，

and all those lovely acini are there,

所有可爱的腺泡都在那儿，

every one of those with the red around them are an acinus,

每一个被红颜色围绕的东西都是一个腺泡,

and we said okay, we are going to try and make this,

我们知道一切正常，我们将尝试制造这一切，

and I said, maybe that red stuff

然后我说，也许那堆红色的物质

around the acinus that people think there's just a structural scaffold,

就是围绕的腺泡的那堆物质，人们会认为那只是一个结构支架

maybe it has information,

也许它承载着信息，

maybe it tells the cells what to do, maybe it tells the nucleus what to do.

也许它告诉细胞该做什么，也许它告诉细胞核该做什么。

So I said, extracellular matrix, which is this stuff

然后我说，细胞外基质，也是就这堆物质

called ECM, signals and actually tells the cells what to do.

叫做ECM，发出信号并告诉细胞该做什么。

So, we decided to make things that would look like that.

所以，我们决定照着那个样子开始着手制造。

We found some gooey material

我们发现了一些黏稠的物质

that had the right extracellular matrix in it,

这些黏稠的中有着正确的细胞外基质，

we put the cells in it, and lo and behold,

我们把细胞放进去，然后等，

in about four days, they got reorganized

大约四天后，它们重组了。

and on the right, is what we can make in culture.

右边的就是我们在培养皿中培养出的。

On the left is what's inside the animal, we call it in vivo,

左边的是动物体内的，我们称之为活体培养

and the one in culture was full of milk,

培养出来的已满是乳汁，

the lovely red there is full of milk.

那些可爱的红色物质，已满是乳汁。

So, we Got Milk, for the American audience.

那么，我们制造出了乳汁，欢呼吧，美国人。

All right. And here is this beautiful human cell,

完全正确。这些是美丽人类细胞，

and you can imagine that here also, context goes.

然后你们可以想象到，这儿是环境。

So, what do we do now?

那么，我们要做什么？

I made a radical hypothesis.

我做了一个发散性设想。

I said, if it's true that architecture is dominant,

我说，如果架构具有决定性作用是正确的话，

architecture restored to a cancer cell

癌变细胞的架构

should make the cancer cell think it's normal.

应该是让该癌变细胞认为自己是正常的。

Could this be done?

这有可能吗？

So, we tried it.

于是，我们开始尝试。

In order to do that, however,

然而，为了实现它，

we needed to have a method of distinguishing normal from malignant,

我们需要找到分辨正常与异常的方法。

and on the left is the single normal cell,

左边的是单个正常细胞，

human breast, put in three-dimensional gooey gel

人类乳房细胞，放置在有细胞外基质

that has extracellular matrix, it makes all these beautiful structures.

中，就是这块黏稠的凝胶中，它组成了这所有美丽的结构。

On the right, you see it looks very ugly,

右边，你们可以看到它看上去很丑，

the cells continue to grow,

这些细胞还在生长，

the normal ones stop.

而正常的已经停止生长了。

And you see here in higher magnification

这儿你们可以看到高倍放大的图片

the normal acinus and the ugly tumor.

正常的腺泡和极丑的肿瘤。

So we said, what is on the surface of these ugly tumors?

那么我们要问，什么东西在那些极丑无比的肿瘤的表面上？

Could we calm them down --

我们能让它们停止吗？

they were signaling like crazy and they have pathways all messed up --

--它们正在疯狂地发出信号，它们把所有的信道弄得乱七八糟，

and make them to the level of the normal?

我们能让它们恢复到正常水平吗？

Well, it was wonderful. Boggles my mind.

额，这想法很奇妙。它使我灵感大发。

This is what we got.

这是我们获得的成果。

We can revert the malignant phenotype.

我们可以扭转这恶性外显物质

(Applause)

（掌声）

And in order to show you that the malignant phenotype

为了向大家展示这个恶性外显物质

I didn't just choose one,

我没有使用照片

here are little movies, sort of fuzzy,

而是带来了一个小短片，有点模糊，

but you see that on the left are the malignant cells,

但是大家可以看到左边的是恶性细胞，

all of them are malignant,

它们全都是恶性的，

we add one single inhibitor in the beginning,

我们一开始加入了单个制约因素，

and look what happens, they all look like that.

看看发生了什么，它们看上去都是那样的。

We inject them into the mouse, the ones on the right,

我们将其注射到老鼠体内，右边那群，

and none of them would make tumors.

没有一只老鼠得癌症。

We inject the other ones in the mouse, 100 percent tumors.

我们将另一种细胞注射进老鼠体内，百分之百患癌症。

So, it's a new way of thinking about cancer,

那么，对于研究癌症，这是一种全新的方法，

it's a hopeful way of thinking about cancer.

这是一种满是希望的方法。

We should be able to be dealing with these things at this level,

我们能够在这个层级上对事物进行操作，

and these conclusions say that growth and malignant behavior

实验结论表明利用相关方法，细胞的增殖和恶性行为

is regulated at the level of tissue organization

在组织层级上恢复了正常。

and that the tissue organization is dependent

而且组织结构是独立于

on the extracellular matrix and the microenvironment.

细胞外基质和微部环境的。

All right, thus form and function interact dynamically and reciprocally.

那么， 这儿结构及功能不断地动态交互作用。

And here is another five seconds of repose,

现在休息5秒钟，

is my mantra. Form and function.

这是我的口头禅，结构及功能。

And of course, we now ask, where do we go now?

当然，我们要问，下一步做什么？

We'd like to take this kind of thinking into the clinic.

我们希望将这个想法用于临床治疗。

But before we do that, I'd like you to think

但在那之前，我需要你们想一想，

that at any given time when you're sitting there,

你们坐在这儿的每一分每一秒，

in your 70 trillion cells,

你们体内那700亿细胞中的

the extracellular matrix signaling to your nucleus,

细胞外基质正向细胞核发出信号，

the nucleus is signaling to your extracellular matrix

细胞核也想细胞外基质发出信号回应，

and this is how your balance is kept and restored.

由此你们的机体保持平衡。

We have made a lot of discoveries,

我们发现了很多现象，

we have shown that extracellular matrix talks to chromatin.

我们刚像大家展示了细胞外基质与染色质相互交流。

We have shown that there's little pieces of DNA

我们展示了乳腺细胞某段

on the specific genes of the mammary gland

有特殊功能的基因的DNA片段，

that actually respond to extracellular matrix.

就是它回应细胞外基质的。

It has taken many years, but it has been very rewarding.

我们做了很多年试验，才发现这些，这些努力是值得的。

And before I get to the next slide, I have to tell you

在看下一张幻灯片之前，我需要告诉你们

that there are so many additional discoveries to be made.

仍然有很多不断增加的谜团等待我们去解开。

There is so much mystery we don't know.

未解之谜浩瀚如星。

And I always say to the students and post-docs I lecture to,

我总是对我的学生和博士后说，

don't be arrogant, because arrogance kills curiosity.

不能骄傲，骄傲与好奇为敌。

Curiosity and passion.

好奇心和热情。

You need to always think, what else needs to be discovered?

你需要不断想，还有什么没被发现？

And maybe my discovery needs to be added to

也许我应该发现更多，

or maybe it needs to be changed.

也许我应该换个角度思考。

So, we have now made an amazing discovery,

那么，现在我们有了一个惊人的发现后，

a post-doc in the lab who is a physicist asked me,

实验室里的一个物理学博士后问我，

what do the cells do when you put them in?

你把细胞放进去后，它们在做什么？

What do they do in the beginning when they do?

它们在一开始的时候再做什么？

I said, I don't know, we couldn't look at them.

我说，我不知道，我们不能一直看着它们。

We didn't have high images in the old days.

过去，我们并未充分利用我们的想象力。

So she, being an imager and a physicist,

然后她，一个充满想象力的物理学家，

did this incredible thing.

做了这件不可思议的事。

This is a single human breast cell in three dimensions.

这是一个人类乳细胞的三维图。

Look at it. It's constantly doing this.

看看它，它经常做这些。

Has a coherent movement.

一系列的连贯动作。

You put the cancer cells there, and they do go all over,

你把细胞都放在这儿，它们就开始动了，

they do this. They don't do this.

这些这样做，那些那样做。

And when we revert the cancer cell, it again does this.

当我们还原这些癌症细胞后，它们也有如此反应。

Absolutely boggles my mind.

这不得不使我惊奇。

So the cell acts like an embryo. What an exciting thing.

这些细胞就像胎儿一样，多么神奇啊。

So I'd like to finish with a poem.

我想以一首诗来总结。

Well I used to love English literature,

我相当喜欢英国文学，

and I debated in college, which one should I do?

我曾在大学选课时犹豫不决，该选哪一个？

And unfortunately or fortunately, chemistry won.

不知是幸运抑或不幸，我选了化学。

But here is a poem from Yeats. I'll just read you the last two lines.

不过叶芝有一首诗极符合目前情景，我就念一下最后两行。

It's called "Among the School Children."

诗名叫做“学童之中”。

"O body swayed to music / O brightening glance /

“哦，曼姿随乐起舞； 哦，青睐湛湛灼灼

How [can we know] the dancer from the dance?"

起舞之时才是舞者的人生。”

And here is Merce Cunningham,

这是梅西·坎宁汉，

I was fortunate to dance with him when I was younger,

我有幸在年轻时与他共舞，

and here he is a dancer,

他是一名舞者，

and while he is dancing, he is both the dancer and the dance.

当其为舞，人与舞皆可叹止。

The minute he stops, we have neither.

舞随乐停，心犹醉不可醒。

So it's like form and function.

那么，这就像是结构及功能。

Now, I'd like to show you a current picture of my group.

这是我们组现有成员的合照。

I have been fortunate to have had these magnificant

能有这些优秀的学生和博士后，

students and post-docs who have taught me so much,

我真是异常幸运，与他们交流我受益匪浅。

and I have had many of these groups come and go.

我的组员流动性很大。

They are the future and I try to make them not be afraid

他们是未来，我尝试告诉他们

of being the cat and being told,

成为那只猫

don't think outside the box.

或被告知不要想箱子外的世界时，不要害怕。

And I'd like to leave you with this thought.

并且，我想留给大家思考一个问题。

On the left is water coming through the shore,

左边是岸上潺潺流水，

taken from a NASA satellite.

NASA的卫星拍摄到的。

On the right, there is a coral.

右边是一片珊瑚。

Now if you take the mammary gland and spread it

现在如果你取得乳腺细胞并培养它

and take the fat away, on a dish it looks like that.

抽取它的脂肪，它看上去会是这样的。

Do they look the same? Do they have the same patterns?

他们看上去一样吗？他们是否有相同的图案？

Why is it that nature keeps doing that over and over again?

为什么自然一遍又一遍的画着这幅图？

And I'd like to submit to you

这就是我要问大家的问题。

that we have sequenced the human genome,

我们给人类基因组排了序，

we know everything about the sequence of the gene,

我们知道基因序列的一切，

the language of the gene, the alphabet of the gene,

语言基因，字母基因，

But we know nothing, but nothing,

但是我们却一点也不清楚

about the language and alphabet of form.

架构好的语言与字母。

So, it's a wonderful new horizon,

这是一条令人激动的新地平线，

it's a wonderful thing to discover for the young

这对年轻人来说是一件激动人心的挑战，

and the passionate old, and that's me.

对于满是激情的老人，比如我，也一样，

So go to it!

那么，着手去发现它！

(Applause)

（掌声）