Roger Stein: A bold new way to fund drug research

翻译人员: Shi Tan 校对人员: Jing Peng

So this is a picture of my dad and me, at the beach in Far Rockaway,

这张照片是我和我爸爸

在Far Rockaway的海滩上

或叫Rockaway公园

or actually Rockaway Park.

I'm the one with the blond hair.

我是金头发的那个,

My dad's the guy with the cigarette.

那个拿着烟的是我爸爸

It was the 60's.

那是在六十年代，很多人吸烟

A lot of people smoked back then.

在二零零九年的夏天

In the summer of 2009, my dad was diagnosed with lung cancer.

我爸被诊断出了肺癌

Cancer is one of those things that actually touches everybody.

癌症听上去让每个人难过

如果你是一名美国男性

If you're a man in the US,

you've got about a one in two chance

在你的一生中，会有二分之一的机会

of being diagnosed with cancer during your lifetime.

被诊断出癌症

If you're a woman, you've got about a one in three chance

如果你是一名女性，那么你有三分之一的机会

of being diagnosed with cancer.

被诊断是癌症

每个人的身边都会有人

Everybody knows somebody who's been diagnosed with cancer.

被诊断出癌症

Now, my dad's doing better today,

现在，我爸爸好了很多

and part of the reason for that is that he was able to participate in the trial

有一部分原因是

他参与了一种新药

of an experimental new drug that happened to be specially formulated

的尝试

那药是用特别配方做成的

and very good for his particular kind of cancer.

对他那种癌症很有效

世界上有两百多种癌症

There are over 200 kinds of cancer.

And what I want to talk about today

那么我今天的主题就是

is how we can help more people like my dad,

为了帮助像我爸爸那些癌症患者,

because we have to change the way we think about raising money

我们必须改变

to fund cancer research.

为癌症筹资的方式

So a while after my dad was diagnosed,

在我爸爸被诊断出癌症后不久

I was having coffee with my friend Andrew Lo.

我和我的朋友Andrew Lo在一起喝咖啡

He's the head of the Laboratory for Financial Engineering at MIT,

他是MIT金融工程实验室的头

where I also have a position,

我也是实验室的一员

and we were talking about cancer.

当时我们在谈论癌症

Andrew一直在做各种研究

And Andrew had been doing his own bits of research,

and one of the things that he had been told

有人告诉过他一个问题

and that he'd learned from studying the literature

他也从文献中得知

was that there's actually a big bottleneck.

研究新药的过程中会遇到瓶颈

It's very difficult to develop new drugs,

导致研究新药非常困难

and the reason it's difficult to develop new drugs

而困难的原因在于

is because in the early stages of drug development,

新药研究的早期阶段

研究药品投资风险大,

the drugs are very risky, and they're very expensive.

而且十分昂贵

So Andrew asked me if I'd want to maybe work with him a bit,

Andrew问我是否想要

和他合作

work on some of the math and the analytics

在数学分析方面

看看我们能做些什么

and see if we could figure out something we could do.

我不是一个科学家

Now I'm not a scientist.

You know, I don't know how to build a drug.

我不懂怎样制药

And none of my coauthors, Andrew Lo or Jose-Maria Fernandez or David Fagnan --

我的合作者Andrew Lo

Jose Maria Fernandez和David Fagnan

none of those guys are scientists either.

所有人都不是科学家

We don't know the first thing about how to make a cancer drug.

我们甚至不知道制药第一步该干什么

But we know a little bit about risk mitigation

但我们略知如何降低风险

和一点儿金融工程,

and a little bit about financial engineering,

所以我们开始想，我们能干嘛呢

and so we started thinking, what could we do?

我要告诉你们的是

I'm going to tell you about some work

we've been doing over the last couple years

我们这几年做的工作

从本质上改变了

that we think could fundamentally change the way

癌症研究和其他事物的做法

research for cancer and lots of other things gets done.

We want to let the research drive the funding,

我们想让研究促进筹资

not the other way around.

而不是资金赞助研究

So in order to get started,

那么现在，我就告诉你们

let me tell you how you get a drug financed.

怎样让新药研究得到资助

Imagine that you're in your lab -- you're a scientist, you're not like me --

想象你在你的实验室里

不像我，你是个科学家

你发明了一种

and you've developed a new compound

你认为能

that you think might be therapeutic for somebody with cancer.

对某些癌症起作用的化合物

Well, what you do is, you test in animals, you test in test tubes,

那么下一步是在动物身上测试

在试管里测试

but there's this notion of going from the bench to the bedside,

这里有一个贯例，是让这种药从实验室

应用到临床

and in order to get from the bench, the lab, to the bedside, to the patients,

为了让这种药从实验室

应用到临床, 到病人,

you've got to get the drug tested.

你必须测试药性

And the way the drug gets tested

测试药性需要进行一系列,大量的

is through a series of, basically, experiments,

试验

通过这些大量的试验,

through these large, they're called trials,

来确定药是否安全

that they do to determine whether the drug is safe

and whether it works and all these things.

以及它是否有用等等

So the FDA has a very specific protocol.

所以美国食品和药物管理局有一套特定的标准

In the first phase of this testing,

在测试的第一阶段

which is called testing for toxicity, it's called Phase I.

是测试药物的毒性

被称作为第一阶段

In the first phase, you give the drug to healthy people

在第一阶段，把药分发给健康的人群

and you see if it actually makes them sick.

来测试药物是否让他们生病

In other words, are the side effects just so severe

换句话说，如果副作用

that no matter how much good it does,

大于药品有效性, 不管药多好,

也不值得研发

it's not going to be worth it?

药物是否会引起人们的心脏病发作，让人死亡，

Does it cause heart attacks, kill people, liver failure?

肝功能衰竭，诸如此类

结果表明，这一阶级是一个巨大的障碍

And it turns out, that's a pretty high hurdle.

三分之一的药物在此阶段被淘汰

About a third of all drugs drop out at that point.

In the next phase, you test to see if the drug's effective,

下一阶段，是测试药物有效性

and you give it to people with cancer

这一阶段是给那些罹患癌症的病人服用此药,

and you see if it makes them better.

看疗效如何

这又是一个巨大障碍，很多病人不愿参与

And that's also a higher hurdle. People drop out.

在第三阶段, 把药用于大量人群

And in the third phase, you test it on a very large sample,

来确定用药量，

and you're trying to determine what the right dose is,

同时和现有药品有效性做比较,

is it better than what's available today? If not, then why build it?

如果不如意,干嘛要生产它

When you're done with all that,

当完成了所有步骤,

what you have is a very small percentage of drugs

只有一小部分药物

that start the process actually come out the other side.

通过了测试

So those blue bottles -- those blue bottles save lives,

所以，就只有这些蓝瓶的能救人

他们价值几十亿

and they're also worth billions, sometimes billions a year.

有时候甚至每年几十亿

So now here's a question:

问题出来了

if I were to ask you, for example,

如果我问你，例如

to make a one-time investment of, say, 200 million dollars

做一次性的投资

两亿美元

to buy one of those bottles,

买其中的一瓶药

so 200 million dollars up front, one time, to buy one of those bottles,

初始投资两亿，一次性

买其中一瓶

I won't tell you which one it is,

我不会告诉你是哪一瓶

and in 10 years, I'll tell you whether you have one of the blue ones.

十年后，我会告诉你,你买的是否是蓝瓶的.

Does that sound like a good deal for anybody?

对大家来说，这听上去划算吗？

No. No, right?

不是，对吧

And of course, it's a very, very risky trial position,

而事实上这是一种风险很大的投资

这就是药物研究很难得到资助的原因

and that's why it's very hard to get funding,

但是就概算来说

but to a first approximation, that's actually the proposal.

这确实是这个提议

你必须从早期开始投资

You have to fund these things from the early stages on.

而且花很长的时间

It takes a long time.

So Andrew said to me, he said,

所以Andrew对我说

"What if we stop thinking about these as drugs?

“如果我们不把这种产品当做药物来看呢？”

如果我们把这种投资当做是其他的金融资产来看待

What if we start thinking about them as financial assets?"

They've got really weird payoff structures and all that,

他们只是有一个很反常的收益结构而已

那么利用我们知道的

but let's throw everything we know about financial engineering at them.

所有关于金融工程的知识,

通过市场交易的计巧,

Let's see if we can use all the tricks of the trade

把研发这些药物

to figure out how to make these drugs work as financial assets.

视作金融产物

Let's create a giant fund.

我们先创建一个巨额基金

在金融界，我们知道

In finance, we know what to do with assets that are risky.

怎样处理高风险资产:

把它们放在投资组合中

You put them in a portfolio and you try to smooth out the returns.

试着增加平稳的回报

我们做了一些数学分析，结果

So we did some math, and it turned out you could make this work,

可行, 但是真正运作起来,

but in order to make it work, you need about 80 to 150 drugs.

需要八十到一百五十种新药

Now the good news is, there's plenty of drugs

但是现在有个好消息，市面上有大量新药

that are waiting to be tested.

等待测试

我们被告知

We've been told that there's a backlog of about 20 years of drugs

大概有积压了20年的药品

that are waiting to be tested but can't be funded.

等着被测试但是沒有得到资金

In fact, that early stage of the funding process,

事实上，初始阶段的筹资,

如第一阶段和临床前测试,

that Phase I and preclinical stuff,

that's actually, in the industry, called the Valley of Death

在这个行业里被称为"死亡之谷"

因为这些阶段就是药物被淘汱的主要时期

because it's where drugs go to die.

It's very hard to for them to get through there,

对新药来说很难通过这些阶段

当然，如果不能通过这些阶段，也就不能进入下一阶段

and of course, if you can't get through there,

you can't get to the later stages.

所以我们做了数学分析，我们发现,

So we did this math, and we figured out, OK,

需要八十到一百五十种新药,

well, you need about 80 to, say, 150, or something like that, drugs.

或者类似那样的东西，

然后我们做了进一步分析,

And then we did a little more math, and we said, OK,

大概需要融资

well, that's a fund of about three to 15 billion dollars.

三十亿到一百五十亿

So we kind of created a new problem by solving the old one.

所以我们又从一个怪圈

跳进另一个怪圈

We got rid of the risk, but now we need a lot of capital,

我们可以解决风险问题，但是我们现在需要大量资金

只有一个地方可以获得如此多的资金

and you can only get that kind of capital in the capital markets.

即"资本市场"

Venture capitalists and philanthropies don't have it.

风险投资家没有那么多资金，慈善家也没有

我们得想办法让那些在金融市场中

But we have to figure out how to get people in the capital markets,

通常不热衷投资此类项目的人们

who traditionally don't invest in this, to want to invest in this stuff.

甘愿对此进行投资

再一次金融工程起到很大作用

So again, financial engineering was helpful here.

想象一下, 这个宠大的基金本身并无价值,

Imagine the megafund starts empty,

and what it does is it issues some debt and some equity,

它做的只是发售债券

和股票,

and that generates cash flow.

来产生现金流量

That cash flow is used, then, to buy that big portfolio of drugs that you need,

当有了现金以后，买进

所需的药物投资组合

and those drugs start working their way through that approval process,

然后药物就可以如期

通过测试阶段,

每一次他们抵达下一阶段

and each time they go through a phase of approval,

他们的价值得到提升

大部分做不到

they gain value.

Most of them don't make it, but a few of them do,

只有少数能做到

那些增值的药物可以出售,

and with the ones that gain value, you can sell some,

此时,

and when you sell them,

获得的利润可以付利息,

you have money to pay the interest on those bonds,

而且有余钱进行下一阶段的测试

but also to fund the next round of trials.

几乎是财政自给.

It's almost self-funding.

如此循环下去,

You do that for the course of the transaction,

and when you're done, you liquidate the portfolio,

当一切完成了，清算这组投资组合,

清偿债务, 发放股息,

pay back the bonds, and you can give the equity holders a nice return.

给了股东很好的收益

但那只是个理论,我们也谈论了一段时间,

That was the theory, and we talked about it,

做了一些实验,

we did a bunch of experiments,

我们很想把它付诸于实际

and then we said, let's really try to test it.

We spent the next two years doing research.

我们用了两年时间做市场调研,

We talked to hundreds of experts in drug financing and venture capital.

我们的团队和上百个药物金融和风险投资的

专家谈过

We talked to people who have developed drugs.

我们和发明药物的科学家谈过

We talked to pharmaceutical companies.

我们也和药物公司谈过

We actually looked at the data for drugs,

实际上我们研究了药物的数据

over 2,000 drugs that had been approved or denied or withdrawn,

超过两千种被通过或淘汰

或放弃的

and we also ran millions of simulations.

我们进行了几百万的数据模拟

当然花费了大量时间

And all that actually took a lot of time.

But when we were done, we found something that was sort of surprising.

当我们完成时,我们发现结果令人吃惊,

实际上我们的想法是可行的

It was feasible to structure that fund

such that when you were done structuring it,

这个基金模式

能产生出低风险的债券

you could actually produce low-risk bonds that would be attractive to bond holders,

对于债券持有者来说很有吸引力

投资收益在百分之五到八

that would give you yields of about five to eight percent,

and you could produce equity

对于股票，

股东可获得百分之十二的投资收益

that would give equity holders about a 12 percent return.

但是对风险投资者来说

Now those returns aren't going to be attractive to a venture capitalist.

回报还不够

风险投资者是那些压的赌注很大

They want to make those big bets

and get those billion dollar payoffs.

并且得到几十亿回报的人

But it turns out there are lots of other folks that would be interested.

但结果表明，仍然有很多人对药物投资兴趣浓厚

对退休基金和退休福利计划来说

That's right in the investment sweet spot of pension funds and 401(k) plans

以及其他

这是最佳的投资计划

and all this other stuff.

So we published some articles in the academic press,

因此我们在学术刊物上发表了一些文章

在医学期刊上发表文章

in medical journals, in finance journals.

在财经期刊上发表文章

但是直到

But it wasn't until we actually got the popular press interested in this

在一些主流媒体上发表了相关文章,

我们才真正开始得到一些关注

that we began to get some traction.

我们不只是想让人们意识到此问题,

We wanted to do more than just make people aware of it.

We wanted people to get involved.

而且想让人们参与到其中

所以我们把编程的计算机代码

So we took all of our computer code and made that available online

放在了网上

under an open-source license to anybody that wanted it.

我们申请了开放源代码的许可

这样大家就都能使用了

And you guys can download it today

大家现在就可以下载

if you want to run your own experiments to see if this would work.

来试试看这个模型是否可行

实际上它很有帮助，因为试用的人们

And that was really effective,

也许不相信我们的假设

because people that didn't believe our assumptions

但现在可以自己测验它的可行性

could try their own and see how it would work.

现在有一个显著的问题，那就是

Now there's an obvious problem, which is,

世界上有那么多钱来资助这些项目吗

is there enough money in the world to fund this?

我们已经知道我们有足够多的试验药物

I've told you there's enough drugs, but is there enough money?

但是有足够的钱吗

There's 100 trillion dollars of capital

我们有一百兆的资金

currently invested in fixed-income securities.

现在存在于固定收益证券中

That's a hundred thousand billion.

那可以是一百兆啊

There's plenty of money.

太多钱了

(Laughter)

笑声

但是我们意识到需要的不仅仅是钱

But we realized it's more than just money that's required.

We had to get people motivated, involved,

我们必须让大家有信心来参与进来

and get them to understand this.

大家也必须要懂得相关知识

And we started thinking about all the different things that could go wrong.

所以我们开始思考可能会出错的地方

在做的过程中会遇到什么挑战

What are all the challenges that might get in the way?

我们列了一张很长的单子

And we had a long list.

We assigned a bunch of people, including ourselves,

其中囊括很多人，包括我们自己

different pieces of this problem.

细化可能出现的问题

And we said, could you start a work stream on credit risk?

我们提出，能不能在信贷危机方面开展工作？

Could you start a work stream on the regulatory aspects?

能不能在监管调控下展开工作？

能不能

Could you start a work stream on how you would manage so many projects?

同时处理很多项目?

我们的专家在一起合计

And we had all these experts get together and do these different work streams,

并且分管不同工作

在今年夏天

and then we held a conference.

我们开了一个会

The conference was held over this past summer.

是一个只有邀请者才可参与的会议

It was an invitation-only conference.

会议是由美国癌症协会赞助的

It was sponsored by the American Cancer Society

由国家癌症学会

and done in collaboration with the National Cancer Institute.

协办

We had experts from every field we thought would be important,

我们汇集了各方精英，

including the government, and people that run research centers,

包括政府和

那些研究中心负责人等等,

and for two days they heard the reports

整整两天，我们坐在一起听取对五种工作研究的报告

他们还做了进一步探讨.

from those five work streams, and talked about it.

这是第一次

It was the first time the people who could make this happen

让这件事情成真的人们

坐在一起

sat across the table from each other and had these conversations.

讨论可行性

Now these conferences, it's typical to have a dinner,

会后有个常规晚宴

and at that dinner, you get to know each other,

在晚宴上

我们彼此了解,

sort of like what we're doing here.

就像我们现在在这儿一样

I happened to look out the window,

我恰好看了看窗外

and hand on my heart,

我是很真诚地说这番话，在晚宴当天

on the night of this conference -- it was the summertime --

我看了窗外，那还是夏天

我看到了叠虹

and that's what I saw, a double rainbow.

我想那是个好兆头

So I'd like to think it was a good sign.

Since the conference, we've got people working between Paris and San Francisco,

自从那次会议以后，在巴黎和旧金山的专家们

开始一起合作

lots of different folks working on this

很多人一起研究这个项目

看是否会成真

to try to see if we can really make it happen.

We're not looking to start a fund, but we want somebody else to do this.

我们不是在拉赞助

但是我们希望别人能这样做

因为，再次重申，我不是科学家

Because, again, I'm not a scientist.

I can't build a drug.

我不会制药

I'm never going to have enough money to fund even one of those trials.

我也没有那么多钱去

资助哪怕只是其中一个试验

But all of us together, with our 401(k)s,

但是我们在一起合作，用我们的养老金计划

with our 529 plans, with our pension plans,

用我们的529个方案，用我们的退休金

all of us together can actually fund hundreds of trials

我们大概能赞助几百个试验

and get paid well for doing it

也能收到很好回报

and save millions of lives like my dad.

然后拯救像我爸那样的许多病人

谢谢大家

Thank you.

(Applause)

掌声