Susan Solomon: The promise of research with stem cells

Translator: Joseph Geni Reviewer: Morton Bast

翻译人员: Cat Qin 校对人员: xueling Sun

So, embryonic stem cells

胚胎干细胞

are really incredible cells.

非常神奇，

They are our body's own repair kits,

它们像是人体自带的修理包。

and they're pluripotent, which means they can morph into

胚胎干细胞具有多向分化的特性，也就是说，

all of the cells in our bodies.

它们可以变成人体中的各种细胞。

Soon, we actually will be able to use stem cells

其实我们很快就能使用干细胞

to replace cells that are damaged or diseased.

替代坏死或发生病变的细胞，

But that's not what I want to talk to you about,

但这不是我今天演讲的内容。

because right now there are some really

我们正在就干细胞开展

extraordinary things that we are doing with stem cells

非同寻常的研究工作，

that are completely changing

其结果将彻底转变

the way we look and model disease,

我们对于疾病的看法、建模的方式、

our ability to understand why we get sick,

对于疾病起因的理解

and even develop drugs.

以及我们开发药物的能力。

I truly believe that stem cell research is going to allow

我坚信，干细胞研究能使我们的下一代

our children to look at Alzheimer's and diabetes

应对老年痴呆症、糖尿病等重大疾病

and other major diseases the way we view polio today,

就像我们现在应对小儿麻痹症一样，

which is as a preventable disease.

可以找到预防之道。

So here we have this incredible field, which has

干细胞研究这个神奇的领域

enormous hope for humanity,

对人类而言，蕴涵着无限的希望。

but much like IVF over 35 years ago,

但是干细胞研究正如35年前的体外授精技术，

until the birth of a healthy baby, Louise,

在第一例试管婴儿Louise诞生之前，

this field has been under siege politically and financially.

体外授精一直遭受政治和资金方面的压力。

Critical research is being challenged instead of supported,

目前，干细胞方面的关键性研究缺少支持，面临挑战，

and we saw that it was really essential to have

我们意识到必须建立私密安全的实验室

private safe haven laboratories where this work

继续开展这项工作，

could be advanced without interference.

使之不受干扰。

And so, in 2005,

因此，我们在2005年

we started the New York Stem Cell Foundation Laboratory

建立了纽约干细胞基金会实验室，

so that we would have a small organization that could

使得我们可以有一个小小的组织

do this work and support it.

进行相关研究，对其提供支持。

What we saw very quickly is the world of both medical

我们很快意识到，医学研究

research, but also developing drugs and treatments,

以及药物和疗法的开发，

is dominated by, as you would expect, large organizations,

正如你所想，都是被大机构主导的。

but in a new field, sometimes large organizations

但是大机构在涉足新领域时，

really have trouble getting out of their own way,

有时很难跳出其固有模式，

and sometimes they can't ask the right questions,

因而看不清事情的重点。

and there is an enormous gap that's just gotten larger

与此同时，学术研究与

between academic research on the one hand

制药公司和生物技术之间的鸿沟

and pharmaceutical companies and biotechs

却仍在扩大。

that are responsible for delivering all of our drugs

但是，要想将所有药物以及很多疗法付诸应用，

and many of our treatments, and so we knew that

恰恰要靠制药公司和生物科技，因此我们意识到，

to really accelerate cures and therapies, we were going

要想加快疾病的治愈和治疗，

to have to address this with two things:

我们必须解决两个问题：

new technologies and also a new research model.

新技术和新的研究模式。

Because if you don't close that gap, you really are

因为如果不填补这一鸿沟，

exactly where we are today.

我们永远都会原地踏步。

And that's what I want to focus on.

这是我今天要讲的内容。

We've spent the last couple of years pondering this,

几年来，我们一直都在思考这一问题，

making a list of the different things that we had to do,

并且列出了一个任务清单，

and so we developed a new technology,

还发展了一项新技术，

It's software and hardware,

这是一种软硬件，

that actually can generate thousands and thousands of

能够生成数以百万计的干细胞系，

genetically diverse stem cell lines to create

涵盖全球各种基因阵列，

a global array, essentially avatars of ourselves.

这其实就是创造了我们自身的阿凡达，也就是化身。

And we did this because we think that it's actually going

我们开发这一技术的原因在于，

to allow us to realize the potential, the promise,

我们认为这能发挥人类基金组测序成果的潜能，

of all of the sequencing of the human genome,

使其蕴涵的希望转变为现实，

but it's going to allow us, in doing that,

而且通过这一过程，我们可以在试验皿中

to actually do clinical trials in a dish with human cells,

对人体细胞而不是动物细胞进行临床试验，

not animal cells, to generate drugs and treatments

从而使我们开发的药物和疗法

that are much more effective, much safer,

效果更好、安全性更高、

much faster, and at a much lower cost.

见效更快、成本更低。

So let me put that in perspective for you

我想给大家介绍一下相关的背景，

and give you some context.

帮助大家了解来龙去脉。

This is an extremely new field.

这是一个非常前沿的领域。

In 1998, human embryonic stem cells

1998年，人类首次发现胚胎干细胞。

were first identified, and just nine years later,

仅仅9年之后，

a group of scientists in Japan were able to take skin cells

日本的一个研究小组就成功地采集皮肤细胞，

and reprogram them with very powerful viruses

植入强力病毒，对其进行基因重组，

to create a kind of pluripotent stem cell

将其转变成一种多能干细胞，

called an induced pluripotent stem cell,

这种干细胞被称为诱导性多能干细胞，

or what we refer to as an IPS cell.

也就是俗称的IPS干细胞。

This was really an extraordinary advance, because

这项进展极为重要，

although these cells are not human embryonic stem cells,

因为这种干细胞虽然达不到

which still remain the gold standard,

人类胚胎干细胞的“金本位”标准，

they are terrific to use for modeling disease

但是对疾病建模有极大帮助，

and potentially for drug discovery.

对药物发现可能也会有很大意义。

So a few months later, in 2008, one of our scientists

于是，几个月之后，在2008年，

built on that research. He took skin biopsies,

我们的一位科学家在此基础上，

this time from people who had a disease,

采集了渐冻人症，也就是英国所说的

ALS, or as you call it in the U.K., motor neuron disease.

运动神经元疾病患者的皮肤活组织，

He turned them into the IPS cells

将其变成了IPS干细胞，

that I've just told you about, and then he turned those

也就是我刚才说过的那种干细胞，

IPS cells into the motor neurons that actually

随后，他将这些IPS干细胞变成了运动神经元，

were dying in the disease.

也就是在渐冻人症中逐渐死亡的细胞。

So basically what he did was to take a healthy cell

因此简单说来，他取了一个健康细胞，

and turn it into a sick cell,

将其变成一个病变细胞，

and he recapitulated the disease over and over again

并且在培养皿中反复再现这一病变过程。

in the dish, and this was extraordinary,

这非常了不起，

because it was the first time that we had a model

因为这是我们第一次使用活人细胞

of a disease from a living patient in living human cells.

对疾病进行建模。

And as he watched the disease unfold, he was able

而且，这位科学家在观察病变过程时发现，

to discover that actually the motor neurons were dying

在这种疾病中，运动神经元的死亡过程

in the disease in a different way than the field

与此前学术界推想的情况并不相同。

had previously thought. There was another kind of cell

其实是有另一种细胞

that actually was sending out a toxin

释放出一种毒素，

and contributing to the death of these motor neurons,

促使运动神经元死亡。

and you simply couldn't see it

之前无法发现这一点，

until you had the human model.

是因为还没有使用人体细胞建模。

So you could really say that

所以真的可以说，

researchers trying to understand the cause of disease

研究人员试图理解疾病起因、

without being able to have human stem cell models

却没有人类干细胞模型，

were much like investigators trying to figure out

就像是调查人员试图查明

what had gone terribly wrong in a plane crash

坠机事故原因、

without having a black box, or a flight recorder.

却找不到黑匣子或飞行记录仪，

They could hypothesize about what had gone wrong,

他们可以就事故原因提出假设，

but they really had no way of knowing what led

但真的没有办法断定

to the terrible events.

惨剧究竟是怎么发生的。

And stem cells really have given us the black box

而干细胞就像是一个研究疾病的黑匣子，

for diseases, and it's an unprecedented window.

它也创造了空前的机遇。

It really is extraordinary, because you can recapitulate

干细胞真的意义非凡，

many, many diseases in a dish, you can see

因为我们可以在培养皿中再现多种疾病，

what begins to go wrong in the cellular conversation

可以看到细胞互相接触时出现问题的过程，

well before you would ever see

其时点可以远远早于

symptoms appear in a patient.

患者出现症状。

And this opens up the ability,

这也赋予了我们一种能力，

which hopefully will become something that

一种有望在近期内

is routine in the near term,

发展成为常规操作的能力，

of using human cells to test for drugs.

那就是在药物测试中使用人体细胞。

Right now, the way we test for drugs is pretty problematic.

现在的药物测试法相当麻烦，

To bring a successful drug to market, it takes, on average,

要想将一种成功开发的药物推向市场，

13 years — that's one drug —

平均需要13年，这还仅仅是一种药物，

with a sunk cost of 4 billion dollars,

此外还会产生40亿美元的沉没成本。

and only one percent of the drugs that start down that road

而且计划通过这一流程投放市场的药物中，

are actually going to get there.

只有百分之一能够完成这一目标。

You can't imagine other businesses

你很难想像还有哪个行业，

that you would think of going into

是你愿意涉足的，

that have these kind of numbers.

却有这么高的失败率。

It's a terrible business model.

这种商业模式非常糟糕，

But it is really a worse social model because of

但它作为一个社会模式的危害可能更大，

what's involved and the cost to all of us.

因为它牵涉面广，给所有各方都带来很大成本。

So the way we develop drugs now

因为，我们现在开发药物时，

is by testing promising compounds on --

测试有望成功的合成物时是使用⋯⋯

We didn't have disease modeling with human cells,

我们以前没有使用人体细胞建模，

so we'd been testing them on cells of mice

因此我们一直使用老鼠细胞进行测试，

or other creatures or cells that we engineer,

或者使用其它生物细胞，或者是我们改造的细胞。

but they don't have the characteristics of the diseases

但是我们想要治愈的疾病

that we're actually trying to cure.

在这些细胞上未必会显现出来。

You know, we're not mice, and you can't go into

大家知道，我们不是老鼠，

a living person with an illness

但也不能随便找一位活着的患者，

and just pull out a few brain cells or cardiac cells

简简单单地取出几个脑细胞或心脏细胞，

and then start fooling around in a lab to test

然后就到实验室里胡来，

for, you know, a promising drug.

测试一种有望成功的药物。

But what you can do with human stem cells, now,

但是现在有了人类干细胞，

is actually create avatars, and you can create the cells,

我们就可以为患者创造阿凡达，创造细胞，

whether it's the live motor neurons

不管是活态的运动神经元细胞，

or the beating cardiac cells or liver cells

是跳动着的心脏细胞，还是肝细胞，

or other kinds of cells, and you can test for drugs,

或者其他类型的细胞，

promising compounds, on the actual cells

都可以造来测试药物或有希望的复合物，

that you're trying to affect, and this is now,

测试的对象就是你想要改变的细胞，

and it's absolutely extraordinary,

这一点现在就可以做到，绝对意义非凡。

and you're going to know at the beginning,

而且你从一开始，

the very early stages of doing your assay development

从检测的非常早期的阶段就能知道结果，

and your testing, you're not going to have to wait 13 years

不会出现等了13年，

until you've brought a drug to market, only to find out

终于将一种药物推向市场，结果却发现

that actually it doesn't work, or even worse, harms people.

这种药物根本没用，甚至对人体有害的情况。

But it isn't really enough just to look at

但是仅仅观察

the cells from a few people or a small group of people,

几个人或者一小组人的细胞还不够，

because we have to step back.

因为我们需要退后一步，

We've got to look at the big picture.

综合考虑。

Look around this room. We are all different,

环顾四周，大家就会发现，我们各不相同，

and a disease that I might have,

我可能患上的疾病，

if I had Alzheimer's disease or Parkinson's disease,

例如老年痴呆症或者帕金森氏症，

it probably would affect me differently than if

对我的影响很可能不同于同一疾病

one of you had that disease,

对你的影响。

and if we both had Parkinson's disease,

况且，如果我们都患上了帕金森氏症，

and we took the same medication,

使用同样的药物，

but we had different genetic makeup,

但由于我们的基因构成不同，

we probably would have a different result,

我们的治疗结果很可能也不相同。

and it could well be that a drug that worked wonderfully

很有可能一种对我非常见效的药物

for me was actually ineffective for you,

对你却毫无效果，反过来，

and similarly, it could be that a drug that is harmful for you

也有可能一种对你有害的药物对我却很安全。

is safe for me, and, you know, this seems totally obvious,

这一点似乎显而易见，

but unfortunately it is not the way

但很遗憾，这却不是

that the pharmaceutical industry has been developing drugs

制药行业一贯用以开发药物的指导思想。

because, until now, it hasn't had the tools.

因为直到现在，相关的工具才到位。

And so we need to move away

因此，我们需要跳出

from this one-size-fits-all model.

这种一刀切的思维模式，

The way we've been developing drugs is essentially

我们一直以来开发药物的方法

like going into a shoe store,

就像是走进一家鞋店时，

no one asks you what size you are, or

没有人问我们穿多大号，

if you're going dancing or hiking.

买鞋是为了跳舞还是爬山，

They just say, "Well, you have feet, here are your shoes."

只知道说：“哦，你们有脚啊，那给你们鞋。”

It doesn't work with shoes, and our bodies are

这样买鞋是行不通的，而我们的身体

many times more complicated than just our feet.

又比我们的脚要复杂很多倍。

So we really have to change this.

所以我们必须改变这一做法。

There was a very sad example of this in the last decade.

在这方面，本世纪初有一个非常悲伤的事例。

There's a wonderful drug, and a class of drugs actually,

当时有一种效果很好的药物，其实是有一类药物，

but the particular drug was Vioxx, and

但其中我要讲的是Vioxx，

for people who were suffering from severe arthritis pain,

对那些因为关节炎而遭受剧烈疼痛的患者来说，

the drug was an absolute lifesaver,

这种药物绝对是根救命稻草，

but unfortunately, for another subset of those people,

但很不幸的是，对于另外一个亚型的患者，

they suffered pretty severe heart side effects,

这种药物却会引起心脏方面的严重副作用，

and for a subset of those people, the side effects were

有些患者的副作用非常严重，

so severe, the cardiac side effects, that they were fatal.

并最终死于这种副作用。

But imagine a different scenario,

但是我们来设想一下另一种情形，

where we could have had an array, a genetically diverse array,

如果我们之前能有心脏细胞的各种基因阵列，

of cardiac cells, and we could have actually tested

并且已经实际测试过这种药物，

that drug, Vioxx, in petri dishes, and figured out,

在培养皿中实际测试过Vioxx，

well, okay, people with this genetic type are going to have

知道某一种遗传类型的人会出现

cardiac side effects, people with these genetic subgroups

心脏方面的副作用，而另一些遗传亚型

or genetic shoes sizes, about 25,000 of them,

或遗传“鞋号“的人——大约有2万5千个，

are not going to have any problems.

不会出现任何问题。

The people for whom it was a lifesaver

这样的话，那些将Vioxx视为救命稻草的患者

could have still taken their medicine.

本可以继续使用，

The people for whom it was a disaster, or fatal,

而那些会因Vioxx发生事故甚至丧命的患者，

would never have been given it, and

永远也不会拿到Vioxx的药方。

you can imagine a very different outcome for the company,

不难想像，制药公司本来也可以有很不一样的结局，

who had to withdraw the drug.

不需要将Vioxx撤出市场。

So that is terrific,

由此可见，干细胞技术真的意义非凡，

and we thought, all right,

我们觉得，好吧，

as we're trying to solve this problem,

我们要想解决这个问题，

clearly we have to think about genetics,

显然需要考虑遗传学的问题，

we have to think about human testing,

需要考虑人体细胞测试。

but there's a fundamental problem,

但是，有一个基本问题，

because right now, stem cell lines,

因为现在干细胞系

as extraordinary as they are,

尽管非同寻常，

and lines are just groups of cells,

究其实质仍然只是成组的细胞，

they are made by hand, one at a time,

是靠手工逐个完成的，

and it takes a couple of months.

每个干细胞系都会耗时好几个月，

This is not scalable, and also when you do things by hand,

无法批量操作，而且由于是靠手工完成，

even in the best laboratories,

即使是在最好的实验室，

you have variations in techniques,

操作技术也不可能完全稳定。

and you need to know, if you're making a drug,

此外，从事制药工作的人必须知道，

that the Aspirin you're going to take out of the bottle

预备周一从瓶子中取出来的阿司匹林

on Monday is the same as the Aspirin

和预备周三取出来的阿司匹林，

that's going to come out of the bottle on Wednesday.

必须是一样的。

So we looked at this, and we thought, okay,

我们明白这一点，我们想，好吧，

artisanal is wonderful in, you know, your clothing

手工制作有时候是件好事，

and your bread and crafts, but

例如在制作服装、面包和工艺品的时候，

artisanal really isn't going to work in stem cells,

但对于干细胞来说，手工制作实在不适合，

so we have to deal with this.

我们必须解决这一问题。

But even with that, there still was another big hurdle,

但即便如此，还有一个很大的障碍，

and that actually brings us back to

这就还得说回到

the mapping of the human genome, because

人类基因组测序这一话题，

we're all different.

因为我们各不相同，

We know from the sequencing of the human genome

而人类基因组测序工作

that it's shown us all of the A's, C's, G's and T's

已经揭示出构成人类基因代码的

that make up our genetic code,

A、C、G、T全部四种碱基序列。

but that code, by itself, our DNA,

但是这种代码本身，也就是我们的DNA，

is like looking at the ones and zeroes of the computer code

就像计算机代码中的1和0 一样，

without having a computer that can read it.

必须使用电脑加以识别，

It's like having an app without having a smartphone.

否则就像下载了app应用程序，却还没有智能手机，

We needed to have a way of bringing the biology

我们必须想办法运用生物知识，

to that incredible data,

解读这种神奇的数据，

and the way to do that was to find

而其方法就是

a stand-in, a biological stand-in,

找一个替身，一个生物替身，

that could contain all of the genetic information,

替身必须包含所有遗传信息，

but have it be arrayed in such a way

但它的基因序列必须排列得

as it could be read together

能够整体解读，

and actually create this incredible avatar.

这样就建立了一个神奇的阿凡达。

We need to have stem cells from all the genetic sub-types

我们需要收集所有遗传亚型的干细胞，

that represent who we are.

代表我们特性的干细胞。

So this is what we've built.

这就是我们迄今的工作成果，

It's an automated robotic technology.

这是一项自动的技术，

It has the capacity to produce thousands and thousands

能够生成数以百万计的干细胞系。

of stem cell lines. It's genetically arrayed.

按基因阵列排列，

It has massively parallel processing capability,

具备强大的平行处理能力。

and it's going to change the way drugs are discovered,

我们希望这将改变我们发现药物的方式，

we hope, and I think eventually what's going to happen

而且我认为其最终结果是

is that we're going to want to re-screen drugs,

我们会希望对药物进行再次筛选，

on arrays like this, that already exist,

按照已有的这种基因阵列筛选

all of the drugs that currently exist,

目前已有的全部药物。

and in the future, you're going to be taking drugs

将来，人们服用的药物

and treatments that have been tested for side effects

和接受的治疗都将是经过副作用测试的，

on all of the relevant cells,

测试将涵盖所有相关细胞，

on brain cells and heart cells and liver cells.

包括脑细胞、心脏细胞和干细胞。

It really has brought us to the threshold

干细胞技术真的已经使我们

of personalized medicine.

离药物个性化技术近在咫尺。

It's here now, and in our family,

这种技术已经进入了我们的生活。

my son has type 1 diabetes,

我的儿子患有I型糖尿病，

which is still an incurable disease,

这仍然是一种绝症。

and I lost my parents to heart disease and cancer,

我的父母死于心脏病与癌症，

but I think that my story probably sounds familiar to you,

可是我想，你们可能会觉得我的遭遇听起来有些耳熟，

because probably a version of it is your story.

因为你可能也有过类似的经历。

At some point in our lives, all of us,

在我们生命的某些时刻，我们所有人，

or people we care about, become patients,

或者我们所关心的人，都会患上疾病，

and that's why I think that stem cell research

正是因为如此，我认为，干细胞研究

is incredibly important for all of us.

对我们所有人来说都极其重要。

Thank you. (Applause)

谢谢。（掌声）

(Applause)

（掌声）