Francis Collins: We need better drugs -- now

Translator: Joseph Geni Reviewer: Morton Bast

譯者: Ivan Che 審譯者: 文进 肖

So let me ask for a show of hands.

請用舉手的方式回答我。

How many people here are over the age of 48?

多少人超過48歲？

Well, there do seem to be a few.

看來並不多。

Well, congratulations,

恭喜大家，

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

因為如果當你看到這張幻燈片上 美國人的預期壽命，

you are now in excess of the average life span

現在各位的壽命都超過

of somebody who was born in 1900.

1900 年出生的一些人。

But look what happened in the course of that century.

但看看在這個世紀裏發生了什麼事。

If you follow that curve,

如果各位沿著這條曲線，

you'll see that it starts way down there.

可以看到它從這下降了。

There's that dip there for the 1918 flu.

那就是因爲 1918 年大流感。

And here we are at 2010,

這是 2010 年的數據，

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

這一年出生的小孩，預估平均壽命為 79 歲，

and we are not done yet.

而且還會繼續增長。

Now, that's the good news.

目前，這是個好消息。

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

但還有很多工作要做。

So, for instance, if you ask,

舉例來說，如果你問，

how many diseases do we now know

我們現在到底知道多少疾病的

the exact molecular basis?

精確的分子基礎？

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

說穿了大概就是 4,000 種，這是非常了不起的，

because most of those molecular discoveries

而且發現這些分子大部分都是

have just happened in the last little while.

最近前發生的。

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

從已知的觀點，很興奮可以看到這樣的結果，

but how many of those 4,000 diseases

但是 4000 種疾病中，有多少疾病

now have treatments available?

現在有治療方法？

Only about 250.

大概祇有 250 種。

So we have this huge challenge, this huge gap.

所以我們面對著非常巨大的挑戰，巨大的差距。

You would think this wouldn't be too hard,

您可能會想這件事也不會太困難，

that we would simply have the ability

我們很容易就能

to take this fundamental information that we're learning

獲取基本資訊，

about how it is that basic biology teaches us

關於基礎生物學是如何告訴我們的

about the causes of disease

關於疾病的生成原因

and build a bridge across this yawning gap

以及在一條大壕溝的上面蓋一座橋樑，

between what we've learned about basic science

一邊是我們學到的基礎科學，

and its application,

另外一邊是它的應用。

a bridge that would look maybe something like this,

一座橋，看起來也許像這樣，

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

我們必須建一條優良的康莊大道

to get from one side to the other.

從一側連結到另一側。

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

嗯，是不是如果這麼簡單就太好了?

Unfortunately, it's not.

不幸的是，事與願違。

In reality, trying to go from fundamental knowledge

在現實中，試圖從基礎知識

to its application is more like this.

走向該知識的實際應用，更像是這樣。

There are no shiny bridges.

沒有閃亮的橋樑。

You sort of place your bets.

如同你在下賭注。

Maybe you've got a swimmer and a rowboat

也許你會得到一位泳將和划艇

and a sailboat and a tugboat

一艘拖船和一艘帆船

and you set them off on their way,

然後你開始給他們方向，

and the rains come and the lightning flashes,

開始下雨、雷電交加

and oh my gosh, there are sharks in the water

唉呦喂呀，水中還有鯊魚

and the swimmer gets into trouble,

你的泳將陷入大麻煩，

and, uh oh, the swimmer drowned

喔哦，你的泳將溺水了

and the sailboat capsized,

帆船翻船了，

and that tugboat, well, it hit the rocks,

這艘拖船，撞到大石頭，

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

如果你幸運的話，剛好有人要過去。

Well, what does this really look like?

事實上這樣看起來像什麼？

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

到底什麼東西可以有療效?

What's a drug? A drug is made up

藥是什麼? 藥是由

of a small molecule of hydrogen, carbon,

氫分子、碳分子、

oxygen, nitrogen, and a few other atoms

氧分子、 氮分子、 和其它幾個原子

all cobbled together in a shape,

組合而成的特定形狀，

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

正是靠這些形狀，事實上，

that particular drug is going to hit its target.

決定是否某種特定的藥物可擊中目標。

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

它會到達它應該去的地方嗎?

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

看看這張照片 -- 各位的周遭都有很多這種形狀在跳舞。

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

現在你需要做什麼，如果你想要探索

a new treatment for autism

自閉症的新治療法

or Alzheimer's disease or cancer

或阿茲海默症、或癌症

is to find the right shape in that mix

是在混和之中找到正確的形狀，

that will ultimately provide benefit and will be safe.

最終會帶來好處，而且很安全。

And when you look at what happens to that pipeline,

當你觀察這些管線，

you start out maybe with thousands,

你也許從成千上萬，

tens of thousands of compounds.

上億的化合物開始。

You weed down through various steps

你釐清各個的步驟

that cause many of these to fail.

這導致許多失敗。

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

最終，也許您可以對其中的 4~5 項做臨床試驗，

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

如果一切順利，在你開始14 年後，

you will get one approval.

你得到一個批准。

And it will cost you upwards of a billion dollars

它將花費超過 10 億美金

for that one success.

就為了一次成功。

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

所以我們必須用一種工程師的思維看看這條管線，

and say, "How can we do better?"

並說，"可以做得更好嗎?"

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

這就是今天早上要對各位說的主題。

How can we make this go faster?

如何讓整件事進行得更快?

How can we make it more successful?

我們如何讓它更成功？

Well, let me tell you about a few examples

讓我告訴你幾個例子

where this has actually worked.

實際有效的例子。

One that has just happened in the last few months

一個案例是幾個月前才發生的事情

is the successful approval of a drug for cystic fibrosis.

一項針對 "囊狀纖維化" 的藥物成功取得審批。

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

但是已經花了很長一段時間才得到。

Cystic fibrosis had its molecular cause discovered in 1989

"囊狀纖維化" 已於1989 年發現其分子層的成因。

by my group working with another group in Toronto,

經由我的團隊與位於多倫多的團隊一起合作

discovering what the mutation was in a particular gene

發現一個特定的基因突變

on chromosome 7.

在7 號染色體。

That picture you see there?

看到的那幅畫了嗎？

Here it is. That's the same kid.

是的。這就是同一的孩子。

That's Danny Bessette, 23 years later,

他叫丹尼班賽特，23 年之後，

because this is the year,

就是這一年

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

也是在丹尼結婚的一年

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

我們第一次通過 FDA 批准

of a drug that precisely targets the defect in cystic fibrosis

一種藥物可精確地修復"囊狀纖維化"的缺陷

based upon all this molecular understanding.

基於所有對分子的認識的基礎上。

That's the good news.

這是個好消息。

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

壞消息是，這種藥物並不真的 可以治療所有的 "囊狀纖維化"

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

對丹尼就無效，然而我們仍然在等待

for that next generation to help him.

希望下一代可以幫助到他。

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

但歷經了 23 年才到這邊。實在太長太久。

How do we go faster?

我們如何加速?

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

嗯，一種加速方式是利用科技，

and a very important technology that we depend on

一種我們非常看重的技術

for all of this is the human genome,

適用於全人類的基因組，

the ability to be able to look at a chromosome,

能够看到一對染色體，

to unzip it, to pull out all the DNA,

解開它，並拔出所有的 DNA，

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

然後能夠解讀該 DNA 代碼中的密码子

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

A、 C、 G 的和 T 的

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

這是我們人類的指令書 和一切生物的建構組成指導書，

and the cost of doing this,

做到這一點的成本

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

曾經需要好幾億美元

has in the course of the last 10 years

在過去 10 年中

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

下降的速度已超越摩爾定律，

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

今天做一份你我的基因體定序已經低於一萬美元

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

我們正快速朝向1,000 美元基因體定序前進。

Well, that's exciting.

嗯，真令人興奮。

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

應用於疾病的觀點，這件事是如何演變的?

I want to tell you about another disorder.

我要告訴你另一個障礙。

This one is a disorder which is quite rare.

這是非常罕見的一種紊亂。

It's called Hutchinson-Gilford progeria,

它被稱為哈欽森-吉爾福德（早衰症），

and it is the most dramatic form of premature aging.

它是最具戲劇性的過早老化現象。

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

大約每個 400 萬孩子中只有 1位有這種疾病，

and in a simple way, what happens is,

一種簡單的方式發生，發生的情況是，

because of a mutation in a particular gene,

因為在一個特定的基因突變

a protein is made that's toxic to the cell

產生一種對細胞有毒的蛋白質

and it causes these individuals to age

造成這些人老化

at about seven times the normal rate.

老化的速度比一般人快 7 倍。

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

透過一段影片說明這個突變對細胞做了什麼事。

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

正常的細胞，如果你在顯微鏡下看它是這樣

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

會有一個核心在細胞中央，

which is nice and round and smooth in its boundaries

邊緣是是漂亮、圓潤、平滑

and it looks kind of like that.

和它看上去有點像。

A progeria cell, on the other hand,

另一方面，早衰症細胞

because of this toxic protein called progerin,

因為這種有毒蛋白質，稱為 "早衰蛋白" (progerin)，

has these lumps and bumps in it.

有這些腫塊與凹凸不平整。

So what we would like to do after discovering this

發見這件事後，最想做的事

back in 2003

早在 2003 年

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

就是找出修正它的方法。

Well again, by knowing something about the molecular pathways,

同樣，透過瞭解分子途徑，

it was possible to pick

是有可能

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

從許多化合物中找出有用的一個

and try it out.

然後試試看。

In an experiment done in cell culture

培養細胞時做的一個實驗

and shown here in a cartoon,

在此以動畫方式秀出來，

if you take that particular compound

如果把特定化合物

and you add it to that cell that has progeria,

將其加到具有早衰症的細胞，

and you watch to see what happened,

你看發生什麼事，

in just 72 hours, that cell becomes,

在短短 72 小時內，那個細胞變成

for all purposes that we can determine,

可由我們控制的所有目標。

almost like a normal cell.

幾乎就是一個正常細胞。

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

真令人興奮，但在實際人體中是否也有效?

This has led, in the space of only four years

僅四年的空間裡

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

從發現基因到臨床實驗測試

to a test of that very compound.

到測試那個非常複合物。

And the kids that you see here

然後看到這些孩子

all volunteered to be part of this,

全部都是自願參加的，

28 of them,

一共有28位，

and you can see as soon as the picture comes up

从照片上可以看出

that they are in fact a remarkable group of young people

他們事實上是一群非常突出的年輕人。

all afflicted by this disease,

他们都患有這種疾病，

all looking quite similar to each other.

每個人都很相似。

And instead of telling you more about it,

與其告訴你更多資訊，

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

不如邀請其中之一， 從波士頓來的 山姆· 伯恩斯

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

他早上來到這裡，站上這舞台

and tell us about his experience

告訴我們他的經歷。

as a child affected with progeria.

身為早衰症的患童。

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

山姆現在15 歲。他的父母， 斯科特 · 伯恩斯和萊斯利 · 戈登

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

和兩位醫生早上也都和我們在一起。

Sam, please have a seat.

山姆，請坐。

(Applause)

（掌聲）

So Sam, why don't you tell these folks

山姆，你何不告訴大家

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

身受早衰症所苦的的感覺是什麼?

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

山姆伯恩斯： 嗯，早衰症限制我某些發展。

I cannot play sports or do physical activities,

我不能運動或肢體活動

but I have been able to take interest in things

但是我一直可以對事物感到興趣

that progeria, luckily, does not limit.

幸運的是，早衰症並不侷限我的興趣。

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

但當我真正想做某件事

that progeria gets in the way of, like marching band

早衰症有點像鼓號樂隊般介入

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

或像主審，我們總是找方法去做，

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

只是要說明早衰症並沒有控制我的人生。

(Applause)

（掌聲）

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

法蘭西斯 · 柯林斯： 所以，您想要對研究人員說什麼

here in the auditorium and others listening to this?

在這個禮堂及所有聆聽的人？

What would you say to them both about research on progeria

你會針對早衰症的研究說什麼

and maybe about other conditions as well?

也許其他有關的狀況說時麼?

SB: Well, research on progeria has come so far

SB： 嗯，研究早衰症至今

in less than 15 years,

不少於15年，

and that just shows the drive that researchers can have

只要研究者有一條路

to get this far, and it really means a lot

撐到目前為止，有非常的意義

to myself and other kids with progeria,

對我自己和所有早衰症的孩子們，

and it shows that if that drive exists,

只要還有一條路，

anybody can cure any disease,

任何人都可以治癒任何疾病，

and hopefully progeria can be cured in the near future,

期望早衰症在不久的將來是可以被治癒的，

and so we can eliminate those 4,000 diseases

因此，我們可以消除這 4,000 種疾病

that Francis was talking about.

這就是法蘭西斯所言。

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

FC: 很棒。山姆今天向學校請假一天。

to be here, and he is — (Applause) --

來到這裡，他是 -- (掌聲) --

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

順便說明，他是成绩一直優等的九年級學生

in his school in Boston.

在他的學校在波士頓。

Please join me in thanking and welcoming Sam.

請和我一起感謝並歡迎山姆。

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

SB： 非常感謝你。FC: 非常好。非常好，朋友。

(Applause)

（掌聲）

So I just want to say a couple more things

我想要再講一、兩件事，

about that particular story, and then try to generalize

關於特別的故事，進而希望推廣

how could we have stories of success

我們如何能有成功的故事呢

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

如同山姆所說，這些疾病片佈各地，

these 4,000 that are waiting for answers.

這4,000種疾病在等待解答。

You might have noticed that the drug

您可能已經注意到這個藥物

that is now in clinical trial for progeria

正在做早衰症的臨床試驗

is not a drug that was designed for that.

並不是為了這個目的而製成的藥。

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

這麼罕見的疾病，很難找到公司

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

願意花上億美元研發藥物。

This is a drug that was developed for cancer.

這是一種治療癌症的藥物。

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

事實證明，這藥對癌症沒有很有效，

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

但是這藥有完全相同的屬性與形狀

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

對早衰症有效，就是這麼回事。

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

如果我們能更有系統地這樣做，不是很棒嗎？

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

事實上，我們可以鼓勵所有市場上的公司

that have drugs in their freezers

公司冷凍櫃中的藥物

that are known to be safe in humans

只要是對人類是安全的

but have never actually succeeded in terms

但從來沒有真正成功地

of being effective for the treatments they were tried for?

有效治療他們原來被試驗的目的？

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

現在我們正在學習這些新的分子途徑 --

some of those could be repositioned or repurposed,

其中一些這種藥物可以被重新定位或改變用途，

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

若用你想要用的字眼用在新的應用上，

basically teaching old drugs new tricks.

就是讓老藥玩新把戲。

That could be a phenomenal, valuable activity.

有可能變成非常驚人的、有價值的活動。

We have many discussions now between NIH and companies

我們目前對美國國家衛生研究院和藥廠之間有很多討論，

about doing this that are looking very promising.

認為往此方向前進非常有前途。

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

你可以對此滿懷期望。

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

任何人都可以說出一堆成功的故事

about how this has led to major advances.

有關這種方法已經引起的重大進展。

The first drug for HIV/AIDS

愛滋病毒/愛滋病的第一款藥物

was not developed for HIV/AIDS.

並不是為愛滋病毒/愛滋病所發展。

It was developed for cancer. It was AZT.

是為了癌症而研發的藥物。它就是AZT。

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

當時對癌症並不有效，但成為

the first successful antiretroviral,

但卻首次成功對 "抗反轉病毒" 有效，

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

您可以從表格中看到還有很多其他案例。

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

所以我們實際上如何讓這種方法更普及而努力？

Well, we have to come up with a partnership

嗯，我們必須拿出一種夥伴關係

between academia, government, the private sector,

學術界、 政府、 私營部門之間

and patient organizations to make that so.

及病人組織，成為夥伴。

At NIH, we have started this new

在美國國家衛生研究院，我們已經開始

National Center for Advancing Translational Sciences.

新的國家推進轉化科學研究中心。

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

去年 12 月剛開始，其目標之一就是今日討論的概念。

Let me tell you another thing we could do.

讓我告訴你另一件我們能做的事。

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

能做藥物測試不是很好嗎?

to see if it's effective and safe

看看它是否有效和安全

without having to put patients at risk,

而無需置病人於風險之中，

because that first time you're never quite sure?

因為你對第一次永遠不敢確保無事？

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

例如，我們怎麼知道藥物在我們

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

給人們使用之前是否安全？我們在動物上測試它們。

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

並不完全可靠，而且代價很高，

and it's time-consuming.

而且很耗時。

Suppose we could do this instead on human cells.

假設我們可以在人體細胞上做試驗。

You probably know, if you've been paying attention

如果你很關注，您可能已經知道，

to some of the science literature

對一些科學文獻

that you can now take a skin cell

您現在可以採一個皮膚細胞

and encourage it to become a liver cell

並培養成為肝細胞

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

或一個心臟細胞、腎細胞、或腦細胞給我們任何一個人。

So what if you used those cells as your test

所以如果您使用這些細胞作為您的測試，對

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

一種藥物是否會有效?和安全?

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

這裡您看到一張照片，肺在一個晶片上。

This is something created by the Wyss Institute in Boston,

這是由 Wyss 研究所(在波士頓)所創造的

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

他們在這裡完成了什麼，如果我們播放這短片，

is to take cells from an individual,

從一個人身上取得細胞，

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

把他們變成類似肺裡面出現的細胞

and determine what would happen

並控制可能的結果

if you added to this various drug compounds

如果您添加到這各種藥物化合物

to see if they are toxic or safe.

以查看它們是否有毒或安全。

You can see this chip even breathes.

您可以看到這晶片甚至會呼吸。

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

它具有空氣通道。它有一個血通道。

And it has cells in between

細胞在中間

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

這使您可以看到當您添加一種化合物時會發生什麼反應。

Are those cells happy or not?

這些細胞開心嗎?

You can do this same kind of chip technology

你可以做這種晶片技術

for kidneys, for hearts, for muscles,

給腎臟、 心臟、 肌肉、

all the places where you want to see whether a drug

和所有你想要知道的地方，是否某種藥物

is going to be a problem, for the liver.

對肝臟而言會是一個問題。

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

最終，您可以為個人這麼做

we could even see this moving to the point

我們甚至可以看見一個重點

where the ability to develop and test medicines

在開發和測試藥物的能力上

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

你就在晶片上，我們要說的是

the individualizing of the process of developing drugs

"個人化"的藥品開發過程

and testing their safety.

以及"個人化"的測試安全性。

So let me sum up.

所以讓我總結一下。

We are in a remarkable moment here.

我們正處於一個重要的時刻。

For me, at NIH now for almost 20 years,

對我來說，在美國國家衛生研究院將近20年

there has never been a time where there was more excitement

對於位於前面我們的潛力

about the potential that lies in front of us.

從來沒有更興奮過。

We have made all these discoveries

我們讓這些發現

pouring out of laboratories across the world.

走出實驗室到世界各地。

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

我們需要利用什麼？首先，我們需要的資源。

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

這是高風險、 有時高成本的研究。

The payoff is enormous, both in terms of health

為了巨大的回報，可以從健康的角度和

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

經濟增長的角度。我們都需要支持。

Second, we need new kinds of partnerships

第二，我們需要各種新的夥伴關係

between academia and government and the private sector

學術界、政府、私營部門之間

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

、病人組織，就像我剛剛說明的一

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

用一種我們能去重新提出新化合物的方法。

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

第三，可能是最重要的，我們需要人才。

We need the best and the brightest

我們需要最好和最聰明的人

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

從許多不同的學科來參加這項工作 --

all ages, all different groups --

來自所有年齡、 所有不同群體 --

because this is the time, folks.

因為現在正是時候，夥伴。

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

這是 21 世紀您一直在等待的生物學，

and we have the chance to take that

我們有機會得到

and turn it into something which will, in fact,

並把它變成某東西，事實上

knock out disease. That's my goal.

殲滅疾病。這就是我的目標。

I hope that's your goal.

我希望這也是你的目標。

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

我想它也會是詩人和木偶的目標

and the surfers and the bankers

衝浪者者和銀行家們

and all the other people who join this stage

和所有其他的人加入這舞台

and think about what we're trying to do here

想想我們可以試著做些什麼

and why it matters.

和為什麼它很重要。

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

它現在很重要。它馬上就很重要

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

如果你不相信我，問問山姆吧。

Thank you all very much.

感謝大家。

(Applause)

（掌聲）