Francis Collins: We need better drugs -- now

Translator: Joseph Geni Reviewer: Morton Bast

翻译人员: Celine Kan 校对人员: Dong Mao

So let me ask for a show of hands.

请大家举手告诉我，

How many people here are over the age of 48?

这里有多少人已经超过48岁了？

Well, there do seem to be a few.

哦，看起来的确有一些。

Well, congratulations,

那么，恭喜，

because if you look at this particular slide of U.S. life expectancy,

因为如果你们看看这张关于美国人寿命期望的幻灯片，

you are now in excess of the average life span

你们现在已经超过了1900年生人的

of somebody who was born in 1900.

寿命的平均值。

But look what happened in the course of that century.

但是看看这个世纪发生的事情，

If you follow that curve,

看这条曲线，

you'll see that it starts way down there.

你会发现在这里开始下降了。

There's that dip there for the 1918 flu.

那是因为1918年的流感

And here we are at 2010,

这里是2010年的数据

average life expectancy of a child born today, age 79,

这一年出生的婴儿的平均寿命期望是79岁，

and we are not done yet.

而且这一数值还在继续增长。

Now, that's the good news.

这当然是个好消息。

But there's still a lot of work to do.

但是我们仍有很多事情可以做。

So, for instance, if you ask,

例如，如果你问，

how many diseases do we now know

我们已经发现了多少种

the exact molecular basis?

由分子层面引起的疾病？

Turns out it's about 4,000, which is pretty amazing,

结果是大约4000种，这真的很惊人。

because most of those molecular discoveries

因为这些疾病中的大多数，

have just happened in the last little while.

都是在最近才被发现的。

It's exciting to see that in terms of what we've learned,

对于迄今为止的成果我们当然很兴奋

but how many of those 4,000 diseases

但是这4000种疾病中，

now have treatments available?

现在有多少种可以被有效治疗？

Only about 250.

大概只有250种。

So we have this huge challenge, this huge gap.

所以我们面临着巨大的挑战，这是个很可观的差距。

You would think this wouldn't be too hard,

你可能认为这不会很难，

that we would simply have the ability

我们应该有能力

to take this fundamental information that we're learning

运用我们学到的

about how it is that basic biology teaches us

基础生物学知识

about the causes of disease

去搞明白这些疾病的成因

and build a bridge across this yawning gap

然后把差距的两端用一座“桥”连接起来

between what we've learned about basic science

一端是我们所学的基础科学，

and its application,

一端是这些理论的实际应用。

a bridge that would look maybe something like this,

这个桥看起来可能是这样的，

where you'd have to put together a nice shiny way

一条光辉的康庄大道，

to get from one side to the other.

从这一端连接到另一端。

Well, wouldn't it be nice if it was that easy?

嗯，如果真的这么简单就好了。

Unfortunately, it's not.

很不幸的，没那么简单。

In reality, trying to go from fundamental knowledge

在现实中，从基础的知识到实际应用的连接

to its application is more like this.

看起来更像这样：

There are no shiny bridges.

根本没有光辉的的桥梁。

You sort of place your bets.

你只能近似于盲目地把宝押在不同的途径上

Maybe you've got a swimmer and a rowboat

可能你有一名游泳选手，一艘划艇，

and a sailboat and a tugboat

一艘帆船和一艘拖船。

and you set them off on their way,

你让他们各自出发。

and the rains come and the lightning flashes,

暴风雨来了，电闪雷鸣。

and oh my gosh, there are sharks in the water

噢天哪，水里还有鲨鱼，

and the swimmer gets into trouble,

游泳的人遇到了麻烦

and, uh oh, the swimmer drowned

糟糕，你的游泳选手淹死了。

and the sailboat capsized,

帆船翻了，

and that tugboat, well, it hit the rocks,

拖船撞到了岩石，

and maybe if you're lucky, somebody gets across.

如果你运气好，有人可能刚好路过。

Well, what does this really look like?

好，真实情况看起来是怎样？

Well, what is it to make a therapeutic, anyway?

究竟什么东西有疗效？

What's a drug? A drug is made up

药是什么？药是由

of a small molecule of hydrogen, carbon,

氢分子，碳分子

oxygen, nitrogen, and a few other atoms

氧分子，氮分子和一些其他原子

all cobbled together in a shape,

联结成特定形状的物体，

and it's those shapes that determine whether, in fact,

事实上正是这些形状决定

that particular drug is going to hit its target.

特定的药能够达到疗效。

Is it going to land where it's supposed to?

会到达它该去的地方吗？

So look at this picture here -- a lot of shapes dancing around for you.

所以，看看这幅图片——很多不同的形状在你周围跳动。

Now what you need to do, if you're trying to develop

现在你要做的是，如果你试着开发，

a new treatment for autism

自闭症，老年痴呆症，

or Alzheimer's disease or cancer

或者癌症的治愈方法，

is to find the right shape in that mix

就是在那些杂乱中找到对的形状，

that will ultimately provide benefit and will be safe.

哪个能最终带来疗效并且安全的形状。

And when you look at what happens to that pipeline,

我们来看看这个过滤管形状的的图示，

you start out maybe with thousands,

刚开始时可能有上千种

tens of thousands of compounds.

甚至上万种的化合物，

You weed down through various steps

需要很多步的过滤

that cause many of these to fail.

可能很多会失败

Ultimately, maybe you can run a clinical trial with four or five of these,

最终，其中的四五种药可能可以用于临床试验

and if all goes well, 14 years after you started,

如果一切顺利，14年后

you will get one approval.

其中一个会获得批准。

And it will cost you upwards of a billion dollars

这可能花费10亿多的美金

for that one success.

就为了这么一个成功。

So we have to look at this pipeline the way an engineer would,

所以我们必须以工程师的方式看着这个过程

and say, "How can we do better?"

然后发问，“要怎么做才能做得更好呢？”

And that's the main theme of what I want to say to you this morning.

这就是今天早上我想说的主题，

How can we make this go faster?

怎样让这个过程进展更快？

How can we make it more successful?

怎样让这个过程的结果更成功？

Well, let me tell you about a few examples

让我告诉你们几个例子，

where this has actually worked.

几个其实还真管用的例子。

One that has just happened in the last few months

一个是几个月前刚发生的，

is the successful approval of a drug for cystic fibrosis.

一种治疗囊性纤维化的药物成功通过了审批。

But it's taken a long time to get there.

它花了很长的时间才最终到达这一步。

Cystic fibrosis had its molecular cause discovered in 1989

囊性纤维化的分子层面的成因在1989年被

by my group working with another group in Toronto,

我的小组和另一个在多伦多的小组一起合作发现，

discovering what the mutation was in a particular gene

我们发现突变发生在7号染色体上的。

on chromosome 7.

一个特定基因上

That picture you see there?

看到那张照片了吗？

Here it is. That's the same kid.

看这里，他们是同一个人。

That's Danny Bessette, 23 years later,

那是23年后的Danny Bessette。

because this is the year,

在这一年

and it's also the year where Danny got married,

这也是Danny结婚的一年

where we have, for the first time, the approval by the FDA

我们第一次获得FDA的批准，

of a drug that precisely targets the defect in cystic fibrosis

一种药物可基于对所有这些分子的理解

based upon all this molecular understanding.

精准修复囊性纤维化的缺陷。

That's the good news.

这是好消息。

The bad news is, this drug doesn't actually treat all cases of cystic fibrosis,

坏消息是这个药并不能真正治疗所有的囊性纤维化

and it won't work for Danny, and we're still waiting

它对Danny也无效，我们仍然在等待

for that next generation to help him.

能够真正帮助他的下一代产品。

But it took 23 years to get this far. That's too long.

这经历23年才有这样的成效，非常久的时间。

How do we go faster?

怎么样才能更快？

Well, one way to go faster is to take advantage of technology,

一种方法是用利用技术。

and a very important technology that we depend on

其中一个我们非常重要的技术

for all of this is the human genome,

就是人类基因组，

the ability to be able to look at a chromosome,

能够找出一条染色体，

to unzip it, to pull out all the DNA,

解密它，分离所有的DNA，

and to be able to then read out the letters in that DNA code,

并能够解读出其中的DNA密码的能力

the A's, C's, G's and T's

那些A，C，G 和 T 核苷酸

that are our instruction book and the instruction book for all living things,

这是人体说明书，也是所有有生命物体的说明书。

and the cost of doing this,

这项工作的花费，

which used to be in the hundreds of millions of dollars,

曾经需要几亿美元。

has in the course of the last 10 years

但在过去的十年里，

fallen faster than Moore's Law, down to the point

它以比摩尔定律更快的速度下降，

where it is less than 10,000 dollars today to have your genome sequenced, or mine,

现在用不到一万美元就能做一份关于你我的基因组的测定

and we're headed for the $1,000 genome fairly soon.

并且这个价格很快就能降低到一千美元。

Well, that's exciting.

的确很振奋人心。

How does that play out in terms of application to a disease?

那么如果应用到疾病治疗中呢？

I want to tell you about another disorder.

我想告诉你们另外一种疾病。

This one is a disorder which is quite rare.

一种非常罕见的紊乱症。

It's called Hutchinson-Gilford progeria,

它被称作早年综合衰老症（Hutchinson-Gilford progeria）

and it is the most dramatic form of premature aging.

这是早衰的最戏剧性方式。

Only about one in every four million kids has this disease,

大概四百万分之一的小孩会得这种疾病。

and in a simple way, what happens is,

简单说来，其实实际情况就是：

because of a mutation in a particular gene,

因为某个特定的基因突变，

a protein is made that's toxic to the cell

产生一种对细胞有害的蛋白质，

and it causes these individuals to age

这对蛋白质造成这些个体衰老。

at about seven times the normal rate.

速度大概是正常衰老速度的七倍。

Let me show you a video of what that does to the cell.

让我用一段影片告诉你们细胞发生了什么。

The normal cell, if you looked at it under the microscope,

这个正常的细胞，如果你们在显微镜下看，

would have a nucleus sitting in the middle of the cell,

会看到细胞中间有细胞核。

which is nice and round and smooth in its boundaries

漂亮的圆形，边缘光滑。

and it looks kind of like that.

它看起来就像这样。

A progeria cell, on the other hand,

而另一方面，一个衰老的细胞，

because of this toxic protein called progerin,

因为这种叫做丙羟木栓酮的有害蛋白质

has these lumps and bumps in it.

会在细胞内产生肿块，凸凹不平。

So what we would like to do after discovering this

在发现这一现象以后，我们想要做的

back in 2003

从2003年开始，

is to come up with a way to try to correct that.

就是想要找出一个方法试着修正它。

Well again, by knowing something about the molecular pathways,

恩再一次的，通过了解分子途径的某些知识，

it was possible to pick

我们是有可能

one of those many, many compounds that might have been useful

从成千上万的化合物中找出一种或许有用的，

and try it out.

然后进行尝试治疗。

In an experiment done in cell culture

培养细胞时的一个实验，

and shown here in a cartoon,

这里用一段卡通来展示。

if you take that particular compound

如果你把特定的化合物，

and you add it to that cell that has progeria,

加入有早衰症的细胞，

and you watch to see what happened,

看看会发生什么事情。

in just 72 hours, that cell becomes,

仅仅在72小时内，那个细胞变得，

for all purposes that we can determine,

我们可以确定，各个方面，

almost like a normal cell.

几乎是一个正常的细胞。

Well that was exciting, but would it actually work in a real human being?

这挺让人振奋的，但实际在人体上有效吗？

This has led, in the space of only four years

这项研究只花了四年

from the time the gene was discovered to the start of a clinical trial,

就从基因被发现到开始临床研究，

to a test of that very compound.

再到非常复杂的测试。

And the kids that you see here

你在这看到的这些小孩，

all volunteered to be part of this,

都是参与研究的志愿者

28 of them,

28个孩子，

and you can see as soon as the picture comes up

从照片上你们能看出来

that they are in fact a remarkable group of young people

事实上他们是一群非常优秀的年轻人，

all afflicted by this disease,

但都被这一疾病侵袭。

all looking quite similar to each other.

每个人看起来都很相像。

And instead of telling you more about it,

不再赘言，

I'm going to invite one of them, Sam Berns from Boston,

我将邀请其中一位，波士顿来的Sam Berns

who's here this morning, to come up on the stage

早上来刚到，马上要来到讲台上

and tell us about his experience

和大家分享有关他

as a child affected with progeria.

早衰症的经历

Sam is 15 years old. His parents, Scott Berns and Leslie Gordon,

Sam现年15岁。他的父母，Scott Berns和Leslie Gordon,.

both physicians, are here with us this morning as well.

都是医生，今天也在这里。

Sam, please have a seat.

Sam，请坐。

(Applause)

（掌声）

So Sam, why don't you tell these folks

Sam，你能不能告诉大家

what it's like being affected with this condition called progeria?

身为早衰症患者是什么样的？

Sam Burns: Well, progeria limits me in some ways.

Sam Burns：嗯，早衰症在某些方面限制了我。

I cannot play sports or do physical activities,

我不能运动，不能参加体育活动。

but I have been able to take interest in things

但我还能对事物保持兴趣，

that progeria, luckily, does not limit.

很幸运，早衰症没有限制这个。

But when there is something that I really do want to do

但当我真正想做一些会被早衰症影响的事情的时候，

that progeria gets in the way of, like marching band

比如加入军乐队或者当裁判的时候，

or umpiring, we always find a way to do it,

我们也总能找到方法去做，

and that just shows that progeria isn't in control of my life.

只是想告诉大家我的人生并没有被早衰症掌控。

(Applause)

（掌声）

Francis Collins: So what would you like to say to researchers

Francis Collins: 那么你想对今天在这里的

here in the auditorium and others listening to this?

研究者以及其他观众说些什么吗？

What would you say to them both about research on progeria

你有什么关于早衰症研究的话想对他们说的吗，

and maybe about other conditions as well?

或者针对其他的病症的也可以？

SB: Well, research on progeria has come so far

SB：关于早衰症的研究到目前为止

in less than 15 years,

已经有快15年了，

and that just shows the drive that researchers can have

能走到今天，说明研究人员真的有很强的动力

to get this far, and it really means a lot

这不管对我还是对其他的患者来说

to myself and other kids with progeria,

都是很有意义的

and it shows that if that drive exists,

它也表明只要我们有动力

anybody can cure any disease,

没有不能治愈的疾病

and hopefully progeria can be cured in the near future,

我也希望早衰症也能在不久的将来也可以被治愈。

and so we can eliminate those 4,000 diseases

这样我们我们就能治愈刚才Francis提到的

that Francis was talking about.

4000种疾病

FC: Excellent. So Sam took the day off from school today

FC：好极了。Sam今天是翘了一天课

to be here, and he is — (Applause) --

来这的，他—（掌声）—

He is, by the way, a straight-A+ student in the ninth grade

顺便说一下，他在他波士顿的学校

in his school in Boston.

是九年级全A+优等生

Please join me in thanking and welcoming Sam.

请跟我一起来谢谢Sam并且再次欢迎他来这里。

SB: Thank you very much. FC: Well done. Well done, buddy.

SB：非常谢谢你们。FC：棒极了。棒极了伙计。

(Applause)

（掌声）

So I just want to say a couple more things

关于这个特别的故事，

about that particular story, and then try to generalize

我想再多说几句，然后试着总结一下

how could we have stories of success

我们怎样才能听到

all over the place for these diseases, as Sam says,

更多战胜疾病的故事，就像Sam所说的，

these 4,000 that are waiting for answers.

还有4000个疾病在等待答案。

You might have noticed that the drug

你们可能已经注意到这些对早衰症

that is now in clinical trial for progeria

做临床试验的药品

is not a drug that was designed for that.

并不是专为早衰症设计的

It's such a rare disease, it would be hard for a company

这是如此罕见的疾病，对公司来说一个很难

to justify spending hundreds of millions of dollars to generate a drug.

决定花上亿的钱去研发一种药物来对付它。

This is a drug that was developed for cancer.

这种药物本来是研发来对抗癌症的。

Turned out, it didn't work very well for cancer,

结果它对癌症疗效并不太好，

but it has exactly the right properties, the right shape,

但它有正确的特性和形状

to work for progeria, and that's what's happened.

用来治疗早衰症，所以我们也算误打误撞。

Wouldn't it be great if we could do that more systematically?

如果我们能更系统地操作，那不是很棒吗？

Could we, in fact, encourage all the companies that are out there

实际上，如果我们能鼓励外那些

that have drugs in their freezers

有新型药品的公司

that are known to be safe in humans

使用这些已知对人体安全，

but have never actually succeeded in terms

但从未真正成功

of being effective for the treatments they were tried for?

治愈他们打算治疗的疾病的药品

Now we're learning about all these new molecular pathways --

现在我们来看看这些新的分子途径——

some of those could be repositioned or repurposed,

有些能被重新定位或被重新利用

or whatever word you want to use, for new applications,

不管你想用什么词来定义它，总之进行各种新的应用

basically teaching old drugs new tricks.

基本上是旧药新用。

That could be a phenomenal, valuable activity.

那会是一项惊人的，有价值的活动。

We have many discussions now between NIH and companies

我们同国家卫生研究所（NIH）和药厂讨论过很多次

about doing this that are looking very promising.

这一议题，这看起来非常有前景。

And you could expect quite a lot to come from this.

这项计划真的值得你期待

There are quite a number of success stories one can point to

我们可以列举大量的成功案例

about how this has led to major advances.

关于它如何带来重大发展

The first drug for HIV/AIDS

比如治疗艾滋病的药物

was not developed for HIV/AIDS.

一开始并非为艾滋病研发的

It was developed for cancer. It was AZT.

它是为癌症研发的，叫做AZT。

It didn't work very well for cancer, but became

它对癌症效果不是很好，但成为

the first successful antiretroviral,

首个成功的抗逆转录病毒的药物

and you can see from the table there are others as well.

然后你们也能在表格中看到其他的一些例子

So how do we actually make that a more generalizable effort?

那么我们究竟该如何努力推广普及呢？

Well, we have to come up with a partnership

嗯，我们必须让学术界

between academia, government, the private sector,

政府，私营部门以及病人组织

and patient organizations to make that so.

合伙干这件事

At NIH, we have started this new

在国家卫生研究所（NIH），我们已经建立了一个新的

National Center for Advancing Translational Sciences.

国家医学转化中心

It just started last December, and this is one of its goals.

它刚刚在去年十二月成立，刚刚谈到的就是它的一个新目标。

Let me tell you another thing we could do.

让我告诉你们另一件我们能做的事情。

Wouldn't it be nice to be able to a test a drug

如果我们不用在人体上进行试验

to see if it's effective and safe

来检测一项药物是否安全有效

without having to put patients at risk,

那岂不是很棒？

because that first time you're never quite sure?

因为第一次总会有风险

How do we know, for instance, whether drugs are safe

我们如何知道，在我们把它拿给病人之前，

before we give them to people? We test them on animals.

药品是否安全？我们进行动物试验。

And it's not all that reliable, and it's costly,

然而它不是完全可靠，而且所费不赀

and it's time-consuming.

并且费时

Suppose we could do this instead on human cells.

想象一下如果我们能在人体细胞上进行试验

You probably know, if you've been paying attention

如果你留意过一些科学文献的话

to some of the science literature

你可能会知道

that you can now take a skin cell

你可以用一个皮肤细胞，

and encourage it to become a liver cell

培养成一个肝脏细胞，

or a heart cell or a kidney cell or a brain cell for any of us.

或者心脏细胞，肾脏细胞，脑细胞

So what if you used those cells as your test

那如果你用这些细胞试验

for whether a drug is going to work and whether it's going to be safe?

某种药品是否有效或者是否安全会怎么样呢

Here you see a picture of a lung on a chip.

这是一张在片型的肺部细胞的照片

This is something created by the Wyss Institute in Boston,

这是波士顿的韦斯研究机构（Wyss Institute ）制造的模型。

and what they have done here, if we can run the little video,

他们所做的，我们继续看下去，

is to take cells from an individual,

是从个体中提取细胞，

turn them into the kinds of cells that are present in the lung,

把它们变成肺脏中出现的细胞的类型，

and determine what would happen

然后他们他们添加各种药物化合物

if you added to this various drug compounds

看会发生什么

to see if they are toxic or safe.

检测是有害，还是安全。

You can see this chip even breathes.

你可以看到这块方片甚至会呼吸

It has an air channel. It has a blood channel.

它有空气通道和有血液通道

And it has cells in between

中间有细胞

that allow you to see what happens when you add a compound.

让你能看到加入一种复合物后会发生的变化

Are those cells happy or not?

看看这些细胞状态如何

You can do this same kind of chip technology

你可以把同样的芯片技术，

for kidneys, for hearts, for muscles,

应用在肾脏，心脏，肌肉上，

all the places where you want to see whether a drug

以及任何地方，或者你想知道一种药物，

is going to be a problem, for the liver.

是否对肝脏有影响

And ultimately, because you can do this for the individual,

最终，因为我们就可以对个体进行试验了，

we could even see this moving to the point

我们还可以得到这样的观点，

where the ability to develop and test medicines

我们完全可以在一个在小方片上的“你”身上“

will be you on a chip, what we're trying to say here is

进行药物开发与实验。我们想说明的是，

the individualizing of the process of developing drugs

药品研发的过程，

and testing their safety.

和测试安全性的过程被个人化了

So let me sum up.

让我总结一下

We are in a remarkable moment here.

我们现在正经历一个非凡的时刻。

For me, at NIH now for almost 20 years,

对我而言，在国家卫生研究院已经快20年了，

there has never been a time where there was more excitement

从来没有一个时刻比现在更让人振奋。

about the potential that lies in front of us.

我们面对着无穷的潜力。

We have made all these discoveries

世界各地的实验室

pouring out of laboratories across the world.

做出了不计其数的新发现

What do we need to capitalize on this? First of all, we need resources.

我们该如何利用它？首先，我们需要资源。

This is research that's high-risk, sometimes high-cost.

这是高风险，高花费的研究。

The payoff is enormous, both in terms of health

但回报是巨大的，不管是在健康事业，

and in terms of economic growth. We need to support that.

还是在经济效益上。我们要支持它。

Second, we need new kinds of partnerships

其次，我们需要新型的合作关系

between academia and government and the private sector

在学术界，政府，私有部门

and patient organizations, just like the one I've been describing here,

以及病人组织间，跟我刚才提到的一样

in terms of the way in which we could go after repurposing new compounds.

然后利用这种关系进行药物再定位

And third, and maybe most important, we need talent.

第三，也是最重要的一点，我们需要人才。

We need the best and the brightest

我们需要最好的，最有智慧的人才

from many different disciplines to come and join this effort --

从不同领域加入我们，

all ages, all different groups --

不分年龄，族群

because this is the time, folks.

因为现在就是关键时刻，诸位。

This is the 21st-century biology that you've been waiting for,

这是你们在等待的21世纪生物学

and we have the chance to take that

我们可以抓住机会

and turn it into something which will, in fact,

让它成为某种，事实上

knock out disease. That's my goal.

打败疾病的东西。那是我的目标。

I hope that's your goal.

我希望这也是你们的目标

I think it'll be the goal of the poets and the muppets

我想它也会是诗人和芝麻街居民的目标

and the surfers and the bankers

冲浪者和银行家的目标

and all the other people who join this stage

其他所有人的目标

and think about what we're trying to do here

想想我们试着在做的事情，

and why it matters.

以及为什么它如此重要。

It matters for now. It matters as soon as possible.

现在就很重要， 简直迫在眉睫

If you don't believe me, just ask Sam.

如果你们不相信我，问问Sam。

Thank you all very much.

非常感谢。

(Applause)

（掌声）