Moderna and Flagship Pioneering: Noubar Afeyan

当时彭博社就是把公开信息收集起来，加以整理、关联，再加一层自己的独家分析，最后通过终端以订阅方式卖出去。

So Bloomberg takes public information, at least they did back then, annotates it, interconnects it, adds some proprietary layers on it, and then sells it as a subscription, essentially, through terminals.

我们觉得生物学也能这么干。人类基因组计划测出的序列，就成了我们吸引用户来我们网站的基础——大家来了，就能用上这些基于原始数据的高级关联服务。

And we thought we could do the same thing with biology, and the Human Genome Project was a a kind of the the actual sequence became our way of actually trying to get people to come to our site in order to receive all these higher level connectivities from that baseline information.

所以这相当于给生物科技公司用的彭博终端。

So this would be like a Bloomberg terminal for biotech companies.

没错。

Absolutely.

这确实就是我们当初的愿景。

That was the that was absolutely the vision.

就像每家金融公司都配一台彭博终端一样。

The idea would be, like, every finance firm had a Bloomberg terminal.

每家生物科技公司也该有一台这样的终端，随时调取这些独家信息。

Every biotech company would have these terminals, and you could access this proprietary information.

我们当初就是冲着这个目标去做的。

That's what we set out to build.

我们得先把基因组测出来，一开始还觉得政府那边的项目大概就够了。

We needed to sequence the genome first, and we, at first, thought maybe the government can the government's effort at the time would suffice.

是的。

Yeah.

但进展实在太慢了。

But it was going fairly slowly.

于是我们启动了一个后来变成竞争性的项目，不过最初还真没打算跟他们对着干。

And so we launched a what became a competitive effort, although it wasn't fully intended to be competitive in the first instance.

因为人类基因组计划推进太慢，你们才决定自己干。

With the Human Genome Project, you started to compete with them because they weren't moving it wasn't moving fast enough.

确实太慢了。

It wasn't moving fast enough.

我们可等不了再拖两三年才拿到这些数据。

We weren't gonna wait two, three more years before this information could be available.

但当时这么一来，两边反而都干了件了不起的事——我们这边是为后续的内容服务铺路，他们那边则是为整个科研打下了基础。

But it definitely, at the time, allowed both sides to do something quite spectacular, which was to complete the sequencing of the genome, in our case, as a prelude to delivering this content business, in their case, as the basis for much of research going forward.

太惊人了，你现在已经参与了一年，投身于二十世纪最具突破性的项目之一——绘制人类基因组图谱，你当时肯定知道这会对医学产生巨大影响。

It's amazing because you you are now you've now spent a year being involved in one of the most groundbreaking projects in, I think, the twentieth century, mapping the human genome, which clearly you knew was going to have a huge impact on medicine.

这段经历有没有再次让你脑子里冒出念头：这背后是不是藏着属于我的机会？

Did that experience kind of, once again, kinda get the gears turning in your head thinking there's an opportunity from this for me to pursue?

是的。

Yes.

当然了，非常强烈。

Very much so.

但这个机会的意义，不只在于市场潜力，更是一次内部创业的尝试——也就是公司内部孵化出一家新公司。

But in in a different context than just the market opportunity, it was actually a foray into intrapreneurship, which is when a company creates a company.

对。

Right.

我以前从没想过，一个母公司居然能从内部孕育出一个全新的项目，一步步把它养大，再独立出去，而我们恰恰就这么做了。

And I'd never thought of that as a as an activity before where you literally can have a parent entity conceive of one thing and really develop it internally and then spin it out, which is what we did.

当然，身处这场公众舆论风暴的中心，虽然整体上是积极的、充满期待的，但也让我们清楚意识到，我们正迈入分子生物学的一个新时代。

That actually was equally interesting, of course, being in the middle of this whole kind of public storm, if you will, in the in many ways, positive sensitive word and excitement, also pointed out the fact that this we were entering a new era in molecular biology.

那真的特别让人兴奋。

So that was exciting.

没错。

Definitely.

稍后回来，聊聊这个分子生物学的新时代，怎么恰好和诺巴尔打造全新生物技术公司的想法不谋而合。

When we come back in just a moment, how the new era of molecular biology just happened to match up with Noubar's idea for an entirely new type of biotech company.

别走开。

Stay with us.

我是盖·拉兹，欢迎收听NPR的《我是如何打造这一切的》。

I'm Guy Raz, and you're listening to how I built this from NPR.

嘿。

Hey.

欢迎回到《我是如何打造这一切的》。

Welcome back to How I Built This.

我是盖·拉兹。

I'm Guy Raj.

那是九十年代末，诺巴·阿费扬在一家叫Aplara的生物技术公司工作，参与了多个不同项目。

So it's the late nineteen nineties, and Noubar Afeyan is working at a biotech company called Aplara, and he's involved in lots of different projects.

但随着时间推移，诺巴越来越感兴趣于推动一系列新兴的分子生物学研究，这些研究未必有立竿见影的商业价值。

But over time, Noubar is getting more and more interested in promoting a whole range of new promising molecular biology, research that doesn't necessarily have immediate commercial value.

于是他最终离开了Aplara，想重新思考生物科技公司的创立方式。

And so eventually, he leaves Uplara to try to reimagine the way biotech companies are created.

他的想法是，那时候大家都特别着迷于连续创业者，一个接一个地创业。

The idea was, you know, everybody was all fascinated with serial entrepreneurs and and you go from one to the other.

但我当时特别好奇一个问题——说不上来为啥，就是能不能同时做多个？

But the question that I got intrigued by, I'm not exactly sure why, is could you actually do this at the same time?

能不能同时启动好几个项目？

Could you have multiple of these things?

我一直对风投圈很好奇，他们虽然不亲自创办公司，但一直在投这些公司。

And and I was always curious about the venture capital community, which while they weren't starting these companies, they were investing in them.

而他们早就把这种并行运作玩得很溜了。

And they had this parallelism down.

他们可以同时参与不同的治疗型公司，有的搞心血管，有的搞癌症之类的。

They could be involved in therapeutic companies, some in cardiovascular, some in, you know, cancer.

这些项目彼此之间根本互不干扰。

Does that didn't one didn't seem to interfere with the other.

我就想，为什么创业者就不能这么干呢？

And I thought, well, why can't you do that as an entrepreneur?

为什么创新者就不能同时推进多个项目呢？

Why can't you do that as an innovator?

于是我们搞了个挺特别的机构，叫Nukegen，意思是‘新公司生成’，简称‘新创’。

And so we started an otherwise unusual entity, which was called Nukegen, and it stood for new company generation, new cogen.

这个叫Nukegen的机构，后来改名叫Flagship Ventures，再后来成了Flagship Pioneering。

That business, Nukegen is the entity that later became called Flagship Ventures and then Flagship Pioneering.

我们投了大概六千万美元。

We put up about $60,000,000.

我们这个公司，专门去孵化别的公司，这就是我们起步的方式。

It was a company that would create companies, and and that's how we started.

前四个或五个项目，我们本来就有了一些想法，但基因组领域的热潮确实给了我们很大推动。

The initial four or five projects, we already had some ideas what to pursue, but it was definitely buoyed by the excitement around the genome.

明白了。

Alright.

所以，Flagship Ventures——也就是现在说的Flagship Pioneering——你是在2000年左右真正启动的，对吧？

So this was so Flagship Ventures, now called Flagship Pioneering, this is what you kind of really launch in 2000.

而且得说清楚，这跟一般的孵化器完全不一样，到现在还是不一样。

And this was to be clear, I mean, this was very different from and still is very different from what incubators are.

通常来说，孵化器就是孵化器，风投就是风投，两码事。

Usually, incubators are incubators and venture capital is venture capital.

但我们的想法不一样。

And the this idea was different.

我们的想法是，所有事情都放在一个屋檐下完成。

I mean, the idea was that everything would happen under one roof.

没错。

Exactly.

研究、开发、团队、业务，全都像麻省理工媒体实验室那样整合在一起，只不过这是个私营企业。

The research, the development, the teams, the businesses, like, almost like like a like an MIT Media Lab, but that was a private business.

这说法挺有意思的。

Well, it's an interesting way of putting it.

说实话，我们当初想做的，就是把通常分开的三个要素拧到一块儿，打造一个成功的初创公司。

I'll tell you, you know, that what we set out to do is to combine the typically three separate inputs into a successful startup.

也就是：科学创意——一般来自学术界，创业人才，还有资金——来源多样，有风投、早期投资，后来还会引入后期资本。

That is the scientific ideas, usually comes from academia, the entrepreneurial talent, and then capital, which is always multiple sources, venture capital, early stage, and then eventually some later stage.

这些资源全来自不同地方。

They all come from different places.

各自的目标也不一样。

They have different interests.

你可以想象，这中间摩擦肯定少不了，对吧。

And so you could imagine there's a lot of friction between all these different Sure.

各个部分之间。

Different components.

我们当时想的是，要是这三样东西本来就存在于同一个实体里呢？

What we thought is what if all three of those things preexisted in the same entity?

对。

Yeah.

因为如果你要搞点特别超前的东西，按传统做法，你得先说服别人跟你干。

Because if you wanna propose doing something that is way out there, if you will, if you're doing it the traditional way, you have to convince other people to join you.

而且不管怎样，你还得说服投资人给你投钱。

And in any case, you have to convince investors to fund you.

是啊。

Yeah.

可他们最关心的，就是把风险压到最低。

And all they care about is to minimize the risk.

所以我们真正找到突破口的地方，就是利用这三样东西都在自己手里这个优势， pushes 自己走得比别人敢想的还远。

And so that's where we really found our footing is to say, can we take that advantage of having all three under one roof and apply it to propel ourselves beyond where people are comfortable going?

Noubar，到你创办Flagship的时候，你已经是个有头有脸的人物了。

Noubar, obviously, by this point, when you started Flagship, you were a known entity.

大家都知道你以前创业的故事。

People knew the story of, you know, your previous businesses.

但你是怎么招到人才，让他们愿意加入Flagship，相信你们会撑住他们？

But how did you recruit talent to come to come to Flagship and to take that leap that you guys would would have their back?

说实话，这花了挺长时间。

Well, I would say it took quite a while.

一开始最大的挑战是为我们的公司招到高管，因为咱们自己的团队没必要扩太多，但咱们孵化的公司得吸引得了顶尖人才。

So the first battle was hiring leadership into our companies because our own team size didn't have to grow very much, but the companies we were forming needed to attract leadership.

那时候我们才开始系统地想：什么样的人能顺利过渡过来？

And that was where we started really thinking more systematically what kind of people could make the transition.

跟软件行业不一样，现在互联网公司或者App领域，很多人干过好几家公司了。

Unlike the software field and for that matter, these days, Internet based companies or apps, you know, there's a lot of people who've done multiple companies.

但在生物科技领域，一家公司平均能活个十年、十五年。

In biotech, these companies have a half life or a life cycle of, say, ten years, fifteen years.

所以没人能一家接一家地连续创业。

So people don't do one company after another after another after another.

如果他们干了一家公司，十到十五年后成功了，就收手不干了。

If they do one company after ten, fifteen years and they succeed, they stop doing it.

所以你得自己培养人才。

So you have to create the talent.

你得去打造人才，还要让不同背景的人互相激发。

You have to create and and cross fertilize.

我们早期公司的领导层，全都是Flagship Pioneering自己人。

And so the early leadership of our companies is all Flagship Pioneering.

但这并不意味着他们就一定更优秀。

And, you know, that what that does is it doesn't mean that they're any better.

只是他们更靠谱，我们更了解他们。

It just means that they're more experienced, we're more familiar with them.

你们有个巨大优势，毕竟你们在世界生物技术中心之一——波士顿地区。

You had a a huge advantage in that you were in one of the biotech capitals of the world, which is the Boston area.

但我猜你们也在招那些很有潜力的研究生和科学家。

But I imagine you were recruiting probably promising graduate students and scientists.

我理解得对吗？你们其实是把他们和能帮他们打理业务的人配对？

Do I have this right that you would basically pair them up with people who could help to navigate their businesses?

也就是那些有科学背景、但也能搞定商业运作的人？

So presumably people with science backgrounds, but who could do the business side of it?

早些年，这事儿更像是一种摸索尝试。

In the earlier days, it it was a more of experimental, if you will.

我当时干了不少这类事，因为我积累了不少经验。

I I did a lot of that just because I had quite a bit of experience by

到那时候了。

this time.

就是这家公司跑跑，那家公司帮帮，顺手带一带。

Just go from little company to company and kinda help them out and help guide them.

是的。

Yeah.

十年前，我那时候同时在十五个董事会里，真是在满世界跑。

There was a time back a decade ago when I'm when I would have been on 15 different boards and literally literally was was kind of running around trying.

我有个同事叫道格·科尔，现在是我们这里的合作合伙人。

I had a colleague, Doug Cole, who's who's who's with us now as a managed partner.

那会儿是1978年2月，刚起步的时候。

So it was just early days in 02/1978.

我们当时就在摸索，哪些东西能标准化，哪些不能，哪些事得靠团队，哪些不用。

We were figuring out what can be systematized and what cannot, and what is a team sport and what is not.

创业圈里头流传着不少传说，总爱把个人英雄主义捧上天。

You know, there's a lot of folklore in the startup world, which I'd say emphasizes the role of the individual.

总爱塑造那种逆风翻盘的孤胆英雄形象。

There's a hero kind of notion that's created, you know, against all odds.

可我们偏偏说，创办、打造、壮大公司，本身就可以当成一门正经生意来干。

And and here we were claiming that conceiving, creating, growing companies could be the object of a company.

讲究方法、注重学习、目标明确、责任清晰，而不是那种随性、浪漫、乱糟糟的创业老套路。

Very methodical, very learning oriented, responsible to certain goals or accountable, let's say, versus kind of improvisational, romantic, chaotic, all the things that come to mind when you think of startups.

过去二十年，我和这儿的同事们一直在努力证明，那些花里胡哨的东西其实根本没必要。

I've spent the last twenty years together with my colleagues here trying to show that most of that is unneeded.

不过有些部分还是有必要的。

Some of that may be needed.

有些人可能就是这么干的，但这绝不是唯一的方式。

Some of that may be how people decide to do it, but that's not like that's the only way you can do it.

我明白一下，你们当时孵化和创立的那些公司，主要都是做生物医学研究的吗？

And just to be clear, most of these companies that you were hatching and forming, they were focused on biomedical research mainly?

它们主要聚焦在生物医学研究，或者生命科学在可持续发展中的应用。

They were focused on biomedical research or applications of life science in sustainability.

明白了。

Got it.

其实关于mRNA研究，有很多起源故事，可以追溯到七八十年代。

So so there's a there are a lot of stories, like origin stories around mRNA research that that go back to the seventies and the eighties.

鲍勃·兰格是全球顶尖的生物技术专家之一，后来成了莫德纳的联合创始人。

And Bob Langer, who is he's one of the best biotechnologists in the world, and he would go on to become a a Moderna cofounder.

他当时做了各种各样的研究。

He was doing all kinds of research.

到了2000年初，我读到一篇报道，说宾夕法尼亚大学的一些研究者在mRNA领域做了特别前沿的工作。

And in the early two thousands, I read a story about some researchers from from University of Pennsylvania who were doing some pretty groundbreaking work around mRNA.

他们去参加一个科学会议，那时候——都二十年前了——科学界几乎没人当真。

They went to a scientific conference, almost nobody, this is twenty years ago, almost nobody in the scientific community was taking this seriously.

你是什么时候第一次听说mRNA研究的？

When did you first when did mRNA research first come onto your radar?

我先跟你讲个事儿：五年前，根本没人认真看待mRNA研究。

Let me answer that by first pointing out to you that five years ago, nobody was taking mRNA research seriously.

这事儿挺有意思的。

That's kind of an interesting thing.

但2010年5月的一天，我接到了Bob Langer的电话，他跟我说：嘿。

But back in 2010, May 2010, got a call from Bob Langer one day, and he said to me, hey.

你听好了。

Look.

我刚见了一个哈佛的年轻教授，他来找我。

I just met with a junior faculty member at Harvard who approached me.

于是我过去见了他，还有那位研究员德里克·罗斯基，他给我展示了他们实验室做的那些研究。

And so I went over and met with him and met with the faculty member, Derek Rossi, and he showed some of the scientific work that this lab had done.

他们 basically 是把 mRNA 和四个叫‘山中因子’的基因代码结合起来。

Essentially, what they had done is they'd taken mRNA and used the codes for the four what's called Yamanaka factors.

山中因子其实就是转录因子。

Yamanaka factors are transcription factors.

你可以把它们想象成一些能跟人类基因组互动、决定哪些基因表达、哪些基因沉默的蛋白质。

Think of these as proteins that interact with the human genome and control what genes get made and what genes don't get made.

他当时展示的就是这些，而且觉得这在生物医学研究领域可能有实际应用价值。

And that's what he was presenting, and he was interested in that as potentially the basis of something useful in the biomedical research field.

我当场就来了兴趣。

I got interested on the spot.

你想啊，要是咱们能把这个用到人体里，让自己的细胞直接生产药物，会怎么样？

You know, what if we could do this to introduce it into the body and have our own cells make drugs out of it?

所以我在跟鲍勃开会的时候，就问了这个问题。

And so I asked that question in the meeting with Bob.

他当时说，你瞧，

We kind of he said, look.

我觉得咱们不妨试试看，

I don't I don't know why we couldn't try.

于是我们达成一致，我回去后就在Flagship启动一个项目，专门探索这个想法：能不能开发一种分子，只要注入体内，就能让身体自行生产任何我们想要的蛋白质——根本不用管技术上能不能实现，先大胆想想行不行，

And so what ended up happening is we agreed that I would go back and initiate a project within Flagship to start exploring whether that could be something of interest and use without any regard to whether we could technically do it or how we could do it, but rather more just explore, could we think about a molecule that when introduced to the body could cause the body to make any protein we wanted?

这事儿就这么成了我们旅程的起点，

And that's how the journey started for us.

后来，这就发展成了Moderna，

That's what became Moderna.

太不可思议了，

It's amazing.

我的意思是，当时的想法就是，能不能造出一种药，打进去之后，让身体自己生产出对抗疾病所需的蛋白质？

I mean, the the idea was that you had was, could we basically, you know could you could you make medicines where you inject them in order for the body to develop the proteins, right, to to combat the the ailment or whatever it is?

那时候大家问的，就是这个问题吧？

That that was the question that was being asked at the time?

这个问题正是我们展开探索的初衷。

That was the question that we asked as the impetus for an exploration.

而对这个问题的普遍回答是：不可能。

And the answer to that question in general was, no.

这太荒谬了。

That's ridiculous.

差不多就是这么个情况，对吧？

Is that is that right, more or less?

当时觉得这想法荒谬，是因为从来没人证明过它行得通。

Well, the premonition was that it was ridiculous because it had never really been shown to be viable.

但正因为我们提出了这个问题，才让自己有底气去搞清楚：为什么没人做成？

And we you know, by asking the question, we gave ourselves the permission to go find out why it is Mhmm.

是因为根本没人试过，还是大家都觉得根本不可能？

That either nobody had done it or nobody believed it could be done.

我们很快发现，八十年代就有人试过，结果细胞出现了很强的免疫反应。

And we quickly found out that people had tried it in the eighties, and they had caused pretty significant immune response in cells.

所以早前就有人有这个想法了。

So people had this idea earlier.

但结果发现，这事儿不光是mRNA和免疫学那么简单。

But it turns out it's not just the mRNA and the immunology.

你还得搞清楚，到底哪些细胞会吸收这些物质。

You then have to figure out which cells are gonna take these up.

对。

Yeah.

细胞得吸收多少，才能让治疗剂量进入血液循环？

How much do they have to take up to make therapeutic doses available in your circulation?

你怎么知道产生的蛋白真的是对的那一个？

How do you know if the protein is actually the right protein?

我的意思是，它能不能正确折叠？

Meaning, will it fold correctly?

能不能正确分泌出来？

Will it secrete correctly?

我的意思是，你本质上是在往里头注入一小段新软件，不是改硬件——你没碰基因组这个硬件，你改的是软件，就为了在每天每纳秒都生成成千上万种蛋白的环境里，做出你想要的那一种。

I mean, you're basically going in and introducing a tiny new piece of software, not hardware, you're not messing with the hardware, the genome, but the software, to make a particular protein in a sea of thousands of other proteins being made every nanosecond of the day.

对。

Yeah.

所以你得精准切入，做出你想要的蛋白，达到你想要的效果。

So so you gotta get in precisely, make the protein you want, have the effect you want.

你懂的。

You know?

作为工程师，当时有太多未知数了，但我们能列出来，然后去问很多人：你觉得这事为啥做不成？

So there was a lot of as an engineer, there was a lot of unknowns, but we could list them, and we could start asking a lot of people out there what makes you think it can't be done?

障碍到底在哪？

What are the impediments?

以前试过啥？

What has been tried?

我们很多创新都是倒着来的——从一个设定好的目标反推。

That's how we do much of our innovation is that we kinda work backwards from a an asserted destination.

我们希望能做到这一点，然后把它和当下联系起来。

We wanna be able to do this and then try to tie it to the present.

我想问问你关于怀疑的事。

I wanted to ask you about about doubt.

我的意思是，我知道Flagship本来就是干这个的——专门挑那些高风险、有点怪的项目，当时科学界压根儿没共识。

I mean, I understand that Flagship was really designed to do exactly this kind of work, to to take on something risky and kind of weird, and maybe the the scientific consensus was kind of not.

根本没人达成一致。

There was no consensus.

整个领域对这项研究都持怀疑态度。

The community was skeptical of this research.

我知道Flagship成立的目的，就是专门去赌那些可能失败的风险项目。

I understand that Flagship was designed for this very reason in order to to take some risks that might fail.

但我很好奇。

But I'm curious.

我的意思是，这事儿得砸钱、耗时，还充满不确定性。

I mean, this was going to require a lot of money, a lot of time, and and a lot of uncertainty.

而且说实话，你们当时有那么优秀的研究员和科学家。

And and and most I mean, you had great researchers and scientists.

我的意思是，你们在Flagship内部就没一个人跟你说过：这事儿咱们不该干？

I mean, didn't anybody in Flagship that you talked to say, this is not what we should pursue?

真没人提出过反对意见吗？

Didn't didn't anybody push back?

你自己就没怀疑过吗？

Didn't you have doubts?

我觉得我得先把这个背景说清楚。

I think we I should try to put it in context.

关键是要明白，我们公司本来就是干这个的——专门做那些突破边界的创新。

An important thing to realize is that we are set up to make innovation leaps that are beyond adjacencies.

比如说‘邻近领域’这个概念，你要是拿张纸画个圈，把某个领域里所有已知的东西都圈起来——

So, you know, this the the notion of adjacency, if you just simply on a piece of paper said in any given field, in any given endeavor of activity, I could draw a circle and let that circle represent everything that's known

对。

Yeah.

或者说是所有已经存在的东西。

Or everything that exists.

然后我在那个圈外面再画一圈，代表那些还没发生、但接下来一定会出现的各种可能性。

And then I draw another ring around that circle that represents all sorts of things that have not yet been done, but are gonna be done next.

你可以想象，时间之箭就这样从一个圈向外推到下一个圈。

So imagine a sense of the arrow of time going, you know, outward from one circle to the next ring.

没错。

Sure.

对我来说，这就是一个简单直观的模型，用来理解创新、科学和市场上的产品是怎么产生的。

And that's kind of, for me, a simplistic mental model of how innovation, science, products in the marketplace occur.

那这个‘相邻领域’的边界到底由什么决定？

Now what defines the size of that adjacency?

就是看人们愿意往前走多远，直到觉得某件事不再靠谱、不再值得去碰。

It's how far people are willing to go before they stop thinking that something is reasonable to work on.

对。

Yeah.

所以问题来了，我们什么时候才能突破这个边界呢？

So the question is, when will we ever work beyond that adjacency?

通常来说，时候到了，自然就到了。

And in the ordinary course, you get there when you get there.

所以你得先等等看。

So you wait for a while.

等一些新情况出现，慢慢地，那些以前觉得太疯狂的事，现在看起来也没那么离谱了。

You some new things happen, and then eventually, you start working on what would have been too far out before, but now it's not so far out.

所以我们的任务就是，看看今天能不能直接突破这些边界。

So our job is to see if we could work beyond the adjacencies today.

但我一直想弄明白的是，Noubar，这件事本来完全可能走上另一条路。

But what I'm trying to understand, Noubar, is this could have been a very different story.

对吧？

Right?

Moderna 的故事，本来完全可能变成一场笑话——一群资金充裕的科学家，把钱全烧光了，最后惨败收场。

The story of Moderna could have been a story of folly of a bunch of, you know, well funded scientists who just spent all of this money, and it was a disaster.

我们本来也可能在商学院里讲这个故事，说它是个失败案例。

And we could have been telling this store that story at business schools.

对吧？

Right?

我的意思是，这种结局本来完全有可能发生。

I mean, there's always a possibility that would have been the story.

而你们决定支持Moderna，肯定得权衡过一些关键因素。

And by greenlighting Moderna, you had to consider certain factors.

但如果当时大多数科学界的人都说这事不值得做，你们和团队怎么就看法不一样呢？

But if if most of the scientific community was saying, this is not worth doing, why did you and your team think differently?

你这个问题啊，其实是在特定背景下提的。

So you're asking the question in a and, again, in in a context.

这问题问得很有道理，但你这是把事情单独拎出来看了。

It's a very valid question, but I wanna say you're asking the question in isolation.

是的。

Yeah.

我还想告诉你，就在我们为Moderna打基础的那一年，我们同时启动了另外四个项目，每个都是独立的平台，瞄准生物医学领域不同的机会，每个都像Moderna一样大胆，一样充满质疑。

Let me also just tell you that in the exact same year that we did the foundation laying for what became Moderna, we also started four other projects that were each platforms in their own right going after different aspects of biomedical opportunity space, each with as big a leap, each with as much doubt.

前一年我们这么干过，之后十一年里我们一直这么干。

And we did that the year before, and we've done that for the eleven years since.

没错。

Yeah.

我以前也说过这一点，我觉得特别重要，得让大家明白。

So in fact, I've described this before, and I think it's really important to understand.

我们并没有专门‘发明’Moderna。

We didn't conceive of Moderna.

我们发明了一百个‘可能的Moderna’。

We conceived of a 100 different Moderna's.

对。

Right.

真正发生的是——这也是我看待这件事的方式——是实验、现实和执行决定了这上百个‘Moderna’里，哪个能活下来，哪个得被淘汰。

And what's happened is, and this is very much how I look at this, is that experiments and reality and and execution have dictated which of those Moderna's got to live and which of those Moderna's got to die.

那些其他的‘Moderna’，有多少没成功？

How how many of those other, quote, Moderna's didn't make it?

你说你们搞了一百个啊。

You said we launched a 100.

很多。

A lot.

多得去了。

A lot.

我们可没真启动一百个。

We didn't launch a 100.

我们只是想象了一百个。

We imagined a 100.

对。

Right.

所以我想说的是，你能不能准确猜中哪个能成，根本没那么重要。

And so the point I'm making is the accuracy with which you have to guess what's gonna work is not at all important.

因为我们踏入的是全新的领域，所以哪里有价值完全不清楚，对吧？

Because we get into these brand new areas, it's wide open to find where value lies, right?

要是我们像别人那样等个三四年，甚至像mRNA那样等上十年，会怎么样？

Imagine if we waited three, four years as people did, or ten years in the case of mRNA.

那时候别人一进来，早就满地都是专利了，各种东西都被人做过了。

Now all of a sudden, they'd go into the space and there's hundreds of patents and there's tons of different things that have already been done.

这完全是另一种竞争方式。

That's a very different competitive approach.

我们通常会说：嘿，不如这样——

What we tend to do is say, you know what?

我们干脆赌一把，就算最后一点价值都没有也认了。

We'll risk the possibility that there's absolutely no value to be had.

对。

Yeah.

所以关键不是你非得精准踩中那个点不可。

So it's not that you have to get it dead right where you land.

你只需要进入一个模糊的领域，然后开始摸索哪里可能有价值。

You just have to be in a rough space where you now start searching for where value might be.

是送到肝脏，还是皮肤？

Is it delivering it into the liver or skin?

是做疫苗，还是心血管药物？

Is it delivering you know, doing vaccines or cardiovascular drugs?

这些变量，至少对我来说，代表了不同的成功路径——我不需要所有都成功。

You saw all of those variables, at least for me, represent alternative success versions of which I don't need everyone to succeed.

我只需要有一个成功就够了。

I just need one succeed.

稍后回来，我们会讲到Noubar没料到的一种成功：Moderna在关键时刻，以惊人的速度开发出了一种关键疫苗。

When we come back in just a moment, one version of success that Noubar did not anticipate was how Moderna would develop a critical vaccine at a critical time and do it unbelievably fast.

请继续关注。

Stay with us.

我是盖伊·拉兹，您正在收听NPR的《我是如何打造这一切的》。

I'm Guy Raz, and you're listening to how I built this from NPR.

嘿。

Hey.

欢迎回到《我是如何打造的》。

Welcome back to How I Built This.

我是盖·拉兹。

I'm Guy Raz.

现在故事要进入关键部分了——Moderna 从一家你可能根本没听说过的生物技术公司，一跃成为数千万人耳熟能详的名字。

So we're getting to the part of the story where Moderna will go from being a biotech company you probably never heard of to a household name for tens of millions of people.

别忘了，这家公司2010年刚成立时，目标只是找到mRNA新技术最合适的用途。

And it's easy to forget that when the company launched in 2010, the idea was to find the best use for the new research around mRNA.

那时候，根本没人能确定，最合适的应用会是疫苗。

And at that time, it wasn't at all clear that the best use would be a vaccine.

从第一天起，我们就研究了各种疾病，比如心血管病、癌症，疫苗也是我们考虑的方向之一。

We worked from day one on any number of diseases, cardiovascular disease, cancer, and and vaccines were a part of our thinking process.

但说真的，我们是全盘都试了。

But indeed, what we did do is we went after everything.

对。

Right.

我说的就是这100个不同版本的Moderna。

That's the 100 versions of Moderna that I'm referring to.

我们从来没觉得自己聪明到能提前知道这平台该用在哪儿。

We did not think for a minute that we were smart enough to anticipate what we should actually apply the platform to.

还有一件事，我觉得也值得提一下。

And this is something else that probably is worth pointing out.

这些年，在我们的Flagship Labs里，我们慢慢意识到，与其去发明具体技术，不如去打造平台。

We have, over the years, in our Flagship Labs, kind of realized that rather than inventing technologies, we really ought to invent platforms.

在生物科技领域，平台这种东西其实挺少见的，不像科技行业，那儿已经有太多成功的平台了，比如苹果的iOS，或者亚马逊的。

And a platform is a relatively rare thing in biotechnology, unlike in the tech sector, where we've seen phenomenal examples of platforms, whether it's the iOS, you know, Apple's platform or Amazon's.

就是那种能支撑无数产品开发或接入的技术框架。

That whole idea of a technological suite upon which many, many products could be developed or attached.

到2010年，还没成立Moderna之前，我们就已经围绕这个想法创办了好多家公司了。

By 2010, before we even started Moderna, that is something that we had started many, many companies around that notion.

所以，Moderna 从一开始就是个平台，它的核心就是用代码驱动的分子，在人体内制造蛋白质，不管用在哪儿都一样。

And so Moderna only ever was going to be a platform that enabled a code based molecule to make proteins in the subjects, no matter what application it was.

而这个平台的关键在于，要不断尝试各种不同的应用场景。

And a key discipline of that is to say, try many, many applications.

没错。

Yeah.

等到新冠来袭的时候，我们已经测试了九种，甚至可能十种不同的人用疫苗，每一种都成功诱导出了中和抗体。

And so we had by the time this coronavirus came along, we had tested nine, maybe even 10 different human vaccines in every single case showing neutralizing antibodies.

另外，我们还有九个项目在开发针对人类疾病的治疗药物。

And we had also another nine programs that were going after human therapeutics.

所以说，这个平台早就打下了相当广泛的基础。

So it was a fairly broad platform that had already been developed.

为了打造这个平台，我们已经投入了大约20亿美元的研发资金。

About $2,000,000,000 of research had gone into developing the platform.

对。

Yeah.

你们2018年就上市了。

You you went public in in 2018.

那时候你们其实还没卖过任何产品。

You still hadn't sold any products, really.

你们当年的运营亏损接近四亿美元。

You had an operating loss of almost $400,000,000.

2019年了，这都已经是Moderna成立的第九年了。

2019, still, you this is nine years in to Moderna.

我记得你们那时候还没卖出去任何东西，亏损都快到十亿美金了。

You had not I believe you had not sold anything yet, and you had almost half $1,000,000,000 in losses.

但这些事儿压根没影响到你和团队，一点都没。

But none of that seems like like, none of that seemed to to phase you or the team at all.

根本不是你们担心的事儿。

Like, that was not even a concern.

是的。

Yeah.

所以这很正常。

So it's not.

事实上，盖伊，我在这行干了三十四年，可以告诉你，2010年成立的生物技术公司，绝大多数都没能在那时候产生收入，可能一百家里才有一家能做到。

And in fact, Guy, what I can tell you, having spent the last thirty four years in the biotechnology field, is that there is no biotech company that was started in 2010 with rare, rare exceptions, maybe one in a 100, that had revenues by that time.

没错。

Right.

所以这根本不是技术出了问题，而是行业常态。

And so it's par for the course in the sense that that's not because of the failing of the technology.

这需要时间，你知道的。

That's because it takes Yeah.

在我们这行，开发一个产品通常得花五到十年。

Five to ten years to actually develop a product in our field.

这就跟说我想开家新飞机公司，结果十年还没推出飞机，就大惊小怪一样。

So it's a little bit like saying, you know, I wanna start a new airplane company, and then I'm surprised that I don't have an airplane on the market in the first ten years.

实际上，造一架飞机得花十四年呢。

Well, it takes fourteen years.

是的

Yeah.

真正让人意外的，反而是我们没能让产品进入临床试验。

Now what would have been surprising is if we didn't have products in clinical testing.

临床试验。

Trial.

这一点完全被忽略了，因为在任何新冠疫苗投入测试之前，我们已经让两千多人接种了我们的mRNA。

And and that's something that was completely missed because before a single vaccine for coronavirus that we tested, we had already 2,000 people who had received mRNA from us.

对。

Yeah.

我们当时在多种mRNA技术上都远远领先——涉及疫苗、非疫苗用途等等，正因如此，我们才坚信自己在这个领域一定能取得突破。

And so we were far, far advanced in actually many, many different mRNAs for different activities, vaccines, nonvaccines, and that's what allowed us to have the conviction that what we would do in this space could be quite productive.

明白了。

Okay.

咱们先回过头来看看时间线吧，整个过程简直像一部惊悚片一样上演。

Let's let's go back to to the timeline for a moment because it's almost like it plays out like a like a movie, like a thriller.

据我了解，应该是2020年1月6日吧。

And from what I understand, I think it was, like, 01/06/2020.

Moderna的CEO斯特凡·布塞尔，最早得知中国出现了这种病毒，而且很可能是一种冠状病毒。

Stephane Bunsell, who's the CEO of Moderna, he found out about this virus in China and that it was probably a coronavirus.

几天后，中国正式公布了首例死亡病例。

And I I think a few days later, the first death was publicly announced in China.

到了那时候，也就是2020年1月11日左右，美国几乎没人认真讨论这件事，更别说大规模关注了。

And at at that point, I think that's 01/11/2020, almost no one in The US was was talking about this seriously or in a big way.

我的意思是，可能有几个人知道，但绝大多数人都没当回事。

I mean, probably a few people, but almost nobody.

你记得那时候这事儿是啥时候引起你注意的吗？

Do you remember this story coming onto your radar around that time?

今年一月初，我们就已经开始互相发邮件、传文章，主要都是关于武汉那边的情况。

Well, in the very early parts of January, we were exchanging emails and and articles that were, you know, kind of appearing largely around the Wuhan situation initially.

当时大家以为就是流感加肺炎，直到1月23号——我记得特别清楚，因为那天是我女儿的生日之一，那天我正和她在剑桥吃饭，离MIT不远。

It was thought to be a flu like thing and pneumonia, and it wasn't until January 23, which I remember quite clearly, partly because it was my daughter's one of my daughter's birthdays, and and and so I I was out at dinner with her in Cambridge, close to MIT.

我确实接到了Stephane的电话，他当时在达沃斯。

I actually got a call from Stephane, who was in Davos.

当时情况的紧张程度已经升级了。

The situation had increased in terms of intensity.

没人说得清这事儿最后会变成什么样。

It was not clear what this would become.

那时候还不叫大流行。

It was not a pandemic.

根本没人这么看，但至少已经开始觉得它可能构成威胁了。

It was not at all viewed that way, but but that it could become a threat was beginning to at least appear.

有意思的是，我们的讨论有两个方向。

And our discussion, interestingly, was twofold.

第一，我们其实别无选择，只能先迈出第一步，不然以后反应就来不及了。

One, we probably didn't have any choice but to at least do the first steps of this work because if we didn't, then we'd be late reacting to it later on.

第二，这对我们来说是个难得的机会，能第一次真正检验这个平台最原始的优势——它能实现超快响应。

But then second, it was an interesting opportunity for us to test the platform in one of its earliest, at least, imagined advantages that we could never test in any other time, which was that it would be a very rapid response technology.

这项技术从一开始就有个天然优势：一旦需要快速行动，我们真能飞快推进，因为它本质上就只是一个基因序列。

This technology had this innate advantage we knew from day one that if you ever needed to go quickly, we could really go quickly because it was so it's just a code molecule.

你只要把DNA序列测出来就行。

You just sequence put the sequence in for the DNA.

下一步直接合成RNA。

You make the RNA in one step.

再把它放进脂质纳米颗粒里，搞定。

You put it in LMP in a second step, and you're done.

我这说得有点简化，但也没夸张多少。

I mean, it's I'm simplifying, but not by much.

所以我们特别兴奋，心想：得趁这机会测试下咱们平台的快速响应能力，但当时真没意识到这优势有多关键。

And so what was exciting to us was that we said we wanna test our platform's ability to demonstrate very rapid capability to respond, and and we did not know how what a what an advantage that was.

说真的，你和斯特凡几乎是连夜就决定要干这事，赶紧把疫苗造出来。

I mean, I think virtually overnight, you and and Stefan decided to pursue this, to try and do this, to manufacture the vaccine.

没错。

Absolutely.

这事儿看着就该做，也让我们看到了一点进展，心里特别踏实，立马就投入了。

It looked like the right thing to do and an incremental proof point for us that we were happy to jump into.

但说实话，没过几天，可能也就两三周吧，这件事的重要性一下子就翻天覆地了。

Now I must say within days, probably a couple of weeks, the whole thing changed in its importance and significance.

我们特别庆幸当初下手早，要不是这样，到三月份根本不可能这么快就进人体试验、拿到数据。

And we were quite happy that we had jumped in so early on because that's the only way that by already March, we could enter the first humans and get data.

你们拿到疫苗原型花了多久？

How long before you had a a prototype for the vaccine?

我记得以前最快的疫苗研发上市记录，好像是麻疹疫苗，就是小时候打的那种。

Because from from what I understand, the fastest time it took to get a vaccine from development to market was, I think, the MMR, one of one of the one of these childhood thing

麻疹。

Measles.

麻疹。

Measles.

对。

Yeah.

大概五年左右吧。

It was, like, five years or something.

那这次你们多快就做出原型了？

So in this case, how quickly were you able to to develop a prototype?

从拿到序列到我们做出

From the time we had the sequence to the time we had The

新冠病毒的序列。

sequence of the of the coronavirus.

新冠病毒的序列。

Of the coronavirus.

就用了

It was

好像是中国那边公布的，我记得。

the Chinese published, I think.

对吧？

Right?

他们把数据公开了。

They made that available.

对。

Yep.

从拿到序列到生成出RNA的计算机序列，也就是现在的mRNA-1273，只用了两天。

And and to the time when we had the computer generated sequence of the RNA that is essentially today mRNA twelve seventy three was two days.

从公布数据到……

Two two days from

数据一公布，你们就马上有了疫苗的计算机模型。

the time that it was published, you basically had had a a computer model of a vaccine.

基本上，就是用计算机模拟出一段mRNA序列，只要注入人体，就能产生足够的S蛋白，触发免疫反应。

Basically, a computer model of the sequence of mRNA that would essentially, when introduced into a human, would produce the s protein sufficient to generate an immune response.

那时候，你们有没有想过，只要进入临床试验，它很快就会被证明有效？

I mean, at the time, did you know that if it just got into clinical trials, it would be it it would quickly be shown to be effective?

你们从计算机模型里就能预见到这一点吗？

Like, did you know that from the computer models?

我们之前在其他人体蛋白上都成功诱导出中和抗体，这点我们是清楚的。

Well, we knew that in every other protein that we had used in humans before, we could generate neutralizing antibodies.

这一点我们心里有数。

That much we knew.

真正不确定的是：能不能快速生产出足够多的量？更别说做三万人规模的临床试验了——这事儿我们以前连想都不敢想。

Whether we could make enough of it quickly enough, let alone to be able to do a 30,000, you know, subject trial, which we'd never ever done or dreamt of before, that was the unknown.

最大的疑问就是：到底能不能生产出足够的量？

The unknown was, can you make enough of it?

是的。

Yeah.

我们当时也在纠结该选多大的剂量。

And we had some questions as to what dose we should choose.

但总的来说，很多事都还不清楚，只能凭当时最好的信息，拍板试试看。

But, essentially, there was a lot unknown, and we just had to kind of decide based on the best information what to try.

我们就这么试了。

We tried it.

到2020年5月，我们已经拿到了第一批人体数据，显示能产生很强的抗体反应。

And by May 2020, we had already the first human data that showed that we could generate robust antibody levels.

2020年3月，你们就和国立卫生研究院启动了临床试验。

In in March 2020, you began clinical trials with the NIH.

我记得，第一位受试者是个西雅图的护士。

It was it was a, I think, a nurse in Seattle.

就在同一个月，2020年3月，你岳父因新冠去世了。

That same month, March 2020, your father-in-law died of COVID.

是四月。

April.

对。

Yeah.

他是四月份走的。

April is when he passed away.

对。

Yeah.

在瑞典。

In Sweden.

是的。

Yeah.

复活节期间。

In Easter.

我的意思是，

I mean,

这影响了我们每一个人。

this was affecting all of us.

说实话，每个人身边都有人要么重病，要么死于这个病毒。

I mean, everybody knows somebody who was either severely ill or or was killed by this.

那真让人崩溃，因为他的妻子和岳母也都病得很重，我们以为她也会挺不过去。

I was devastating because his wife and mother-in-law also got quite sick, and we thought we're gonna lose her as well.

她们俩都快九十岁了。

They were both in their early nineties.

所以那段时间特别艰难，因为我们每天都在打一场硬仗。

So it was it was very, very tough also because, you know, we were engaged in this day to day battle.

一方面，我为咱们能做到的事感到振奋。

And on the one hand, I was excited by what we were able to do.

但另一方面，看到他最终还是没能挺过去，说实话，这事对我个人来说特别沉重。

And on the other hand, when you see, you know, in his case, ultimately a life lost, you know, it's it's a anyway, it's it was quite personal to me.

我想说，我这辈子还没在iPhone时代失去过亲人，但我可以告诉你，眼睁睁看着亲近的人在FaceTime里离世，那种滋味，真的太痛苦了。

Let me just say that I have not lost a family member during the time of of iPhones, and and I can tell you that being on a FaceTime with somebody close to you when they're dying is a miserable, miserable experience.

那段日子太难熬了，也让我彻底看清了这一切意味着什么。

It was very tough, and it it certainly made brought into sharp focus what this was all about.

确实，很多人因此失去了生命，还有更多人至今仍在承受这场疫情的后遗症。

Certainly, many, many people lost lives, and many more are suffering yet today with the downstream effects of this disease.

Noubar，你从第一次临床试验就知道结果不错，一期数据挺好的，但还得走完后面两期。

Noubar, you knew already from that first clinical trial that the news was good, that the initial results from from phase one were good, but but you had to go through two more phases.

而我们公众，因为各种原因，根本无从得知这些信息。

And we, the public, were not privy to that information for a variety of reasons.

对吧？

Right?

你根本不能突然跑出来说：嘿。

You can't you could not come out and say, hey.

一期结果很不错。

Phase one looks great.

这就是数据。

These are the results.

因为有规定不允许这么做。

Is that there are rules against that.

对吧？

Right?

其实我们五月确实公开说过，初步结果挺鼓舞人心的，结果立马招来一堆批评，说我们搞‘新闻稿式科研’之类的。

Well, we indeed in May, we indeed did come out and say at a very high level that we had some encouraging results, and people attacked us every which way for having said that because they basically said, well, that's doing science by press release and many other things.

但现实是，当一场大流行爆发，你又是一家上市公司，手握重大数据时，我们觉得至少得先给大家一个大致的交代。

And and the reality is when you have a pandemic and you're a public company and you've got material data, our sense was that we at least needed to, at a high level, put that out there.

我们学到的一点是，因为以前没人经历过这种情况，所以不管我们怎么做，都会挨骂。

So one of the things we learned, because none of us have been in this situation before, and was that we were gonna get criticized no matter what we did.

所以我们只能做自认为对的事，做决定，然后解释清楚。

And so we just had to do what we thought was right, make some calls, you know, explain ourselves.

我们就这么做了。

And and so we did that.

最后，我们把数据公开发表了。

We we ultimately published the data.

美国国立卫生研究院也公布了他们的数据。

The NIH came out and presented their data.

我们挺惊讶的，居然有人质疑 NIH 自己的临床研究。

We were quite surprised that people were questioning the NIH's own clinical clinical research.

临床工作不是我们做的。

We didn't do the clinical work.

是他们做的。

They did.

是的。

Yeah.

到第三期试验结束，也就是十一月的时候，你们宣布初步数据显示有效率达到了百分之九十四。

By the end of the third trial, phase three November, and you announced that the preliminary data showed that the efficacy rate was ninety four percent.

这个结果连你都没想到吗？

Did that that surprise you, even you?

我确实没想到，但从科学角度来说，我又不觉得意外。

It did surprise me, and it didn't surprise me scientifically.

到那时候，我已经把预期降得挺低了，因为听太多人说这事有多难了。

It surprisingly, by that time, I had lowered my expectations largely by having heard so much about how difficult all this would be.

你看看传统疫苗是怎么做的，无非是把病毒的某些蛋白片段拿过来，人工合成，再加点佐剂，刺激免疫系统发火。

If you look at how vaccines are made, they either take, you know, bits and pieces of proteins and they make them artificially and they combine them and they put adjuvants that kind of get your immune system to get angry.

现在的疫苗技术根本不是分子层面的创新。

There's nothing molecular about the current approaches.

而我们呢，只是把一个单一的蛋白，用已知的方式，精准地送到特定细胞里。

Here we were putting in a single protein delivered in known way to specific cells.

所以我们其实是在给免疫系统做准备，但当时根本没人觉得能到90%以上。

And so we were really priming the immune system, but still there was no basis to believe that we could do 90 anything.

疫苗领域从来没人一上来就做到94%，更别说用的是全新技术了。

It's not at all typical in vaccines, let alone with a new technology, let alone out of the gates that you start at 94.

是的。

Yeah.

我们当时想，只要能超过50%，就算赢了，至少能打一场仗，之后还能不断改进。

We thought if we were well above fifty percent, at least we will start putting up a fight, and maybe we can make a better and better version.

与此同时，你们肯定还得赶紧扩大疫苗的生产能力吧。

And in parallel to the testing, presumably, you had to ramp up your ability to produce this vaccine.

没错。

Yes.

那才是真正的壮举——我们根本没想到第一年就能生产十亿剂，而前一年，我们可能连一千剂都产不出来。

And that and that was really the the massive heroism that I think of all the things that we could not imagine that we could make, you know, a billion doses the first year of production up from probably making, you know, a thousand doses the year before of anything.

你们是怎么做到的？

How did you do that?

你们是怎么在不到一年的时间里，从年产几千甚至几万剂，直接跃升到十亿剂的？

How did you go from the capacity to make a thousand or 10,000 to a billion in less than a year?

说到底，这一切都离不开人。

Well, first of all, all these things start with people.

我们特别幸运，遇到了一位叫胡安·安德雷斯的先生，他负责我们整个技术运营、生产和质控，之前在诺华制药当过同样的职位，经历过上一代流感疫苗的大规模扩产，简直是领导人才的典范。

We had the great fortune of having a gentleman named Juan Andres, who as head of our whole technical operations, manufacturing, quality, the whole field, previously held that role at Novartis, one of the largest pharmaceutical companies, had gone through previous flu epidemic kind of scale up of vaccines of that generation, and just is a phenomenal leader of people.

他对我们来说简直是天降神兵。

And he was really a godsend to us.

在快速规划、迅速响应、组织协调、招聘人员这些事上，他从不接受‘这不可能’这种说法，不管时间多紧、规模多大，他都硬是给办成了。

And when it came to planning rapidly, responding, organizing, hiring people, and just not taking that's not possible for an answer for just about anything that they that they did in terms of either time frames or scale.

几个月后，我们就开始量产数百万剂，后来是几千万、上亿剂。

And several months later, we started producing millions of doses and then and then eventually tens of millions and hundreds of millions of doses.

那现在这意味着什么？

What does this mean now?

我的意思是，这对其他疫苗或疗法的研发意味着什么？

I mean, what what does what does it mean for the development of other vaccines or other treatments?

我的意思是，这对科学界来说，是不是证明了我们真的有可能研发出长效流感疫苗、疟疾疫苗或者艾滋病疫苗？

I mean, has this, at least to the scientific community, proved that you can really maybe develop a long lasting flu vaccine or a malaria vaccine or an HIV vaccine?

我的意思是，这事儿靠谱吗？有戏吗？

Like, is that is that within the realm of possibility?

你这一个问题里其实问了两个事儿。

Well, you asked me two two questions in one.

第一个是：这能证明吗？

One was, has it proved that?

答案是不能。

The answer is no.

但它是不是暗示了这种可能性？确实是的。

But does it suggest that that's possible That's right.

而且值不值得去研究？

And perhaps wise to work on?

答案是值得。

The answer is yes.

这个问题问得更好。

A better question.

谢谢。

Thank you.

我们正在做这方面的研究。

We are working on it.

不行。

No.

还不行。

No.

我之所以这么说，是因为我早就明白，像托马斯·库恩这些人讲过，科学的本质就是有组织的怀疑精神。

And and and I'm only saying it because, look, I learned long ago, Thomas Kuhn and all these guys who've written on on these things that, you know, the scientific process is one of organized skepticism.

对。

Yeah.

这种怀疑精神其实很好，它让你不断去寻找证据。

And that organized skepticism is a good thing because it keeps you constantly looking for proof.

我觉得，mRNA 有可能成为一种全新的药物形式，这个想法更有说服力。

I would say that there's there's a slightly greater reason to believe that mRNA could actually be a new drug modality.

但回到 Flagship 一直在做的事，这一点也再次说明，真正颠覆性的突破，往往源自看似不靠谱的起点。

But the other thing it does, just to come back more broadly to what it is that we've been doing at Flagship, is that it illustrates that, yet again, completely transformative things could come out of unreasonable beginnings.

没错。

Yeah.

如果你只盯着那些看起来合理的东西，那大概永远也找不到真正的突破。

And that if all you do is look for reasonable beginnings, you're probably not gonna find breakthroughs.

现在年轻人可能觉得不可思议，就在没多久以前，每个人小时候都出过水痘，可现在孩子都不再得这病了，因为有了疫苗。

It's probably remarkable to young younger people today that that everybody had their chickenpox not that long ago, and no kids don't get it anymore because there's a vaccine.

未来会不会有一天，季节性流感也彻底成为历史？

Is there a potential future where there's no such thing as seasonal flu?

这个我没法确定，但我从来不会直接说‘不可能’。

That I cannot say, although I never wanna say no to that either.

对。

Right.

更广泛地说，我过去两年一直关注的一个重要议题，就是所谓的健康安全，或者说提前干预的医疗方式。

Because more broadly, by raising an issue, which which is important to me, and I've I've worked for the last two years, and that is broadly what I would view as health security or practicing medicine in a preemptive way.

没错。

Yep.

我的意思是，我们对疾病有了太多新认识，知道它不是非黑即白——不是突然发病才要应对，而是有一段漫长的酝酿期。如果我们能用新技术尽早发现这些早期信号，就能通过疫苗预防，或者至少延缓、减缓、甚至改变疾病的发展轨迹。

And what I mean by that is we've learned so much about disease that we realize that disease isn't just a switch that goes on and all of a sudden now you have it and you have to fight it, But that there are long ramps, kind of on ramps towards disease that if we could intervene long before the disease is manifest and we can find it now with with new techniques, then both to prevent it through vaccines, but also to delay it, slow it down, redirect it.

能做的事多着呢。

There's many things we can do.

我觉得，如果我们只等着疾病发展到严重了才动手，那代价——人命的损失、社会的成本——简直承受不起。

And I think unless we do those things, if all we do is wait for diseases to be good and advanced until we start treating them, the cost of that, the human loss, you know, as a result of that is just gonna be prohibitive.

同样地，我想象得到，有一天季节性流感也能被彻底控制住。

So in the same vein, I can imagine a time when seasonal flu is mastered and basically kept at bay.

为什么？

Why?

因为我们对免疫系统的理解越来越深，只要干预得够早、够广，就完全可能为流感、冠状病毒、引起普通感冒的鼻病毒，甚至艾滋病毒这类高度变异的病毒，打造一层持久的防护盾。

Because I think that we're learning enough about the immune system that if we intervene early enough and broadly enough, we may well create a shield, a protective shield against these hypervariable viruses like influenza, like corona, like rhinovirus that causes the common flu, like HIV.

我的意思是，这些威胁本身就很严重，而且还在疯狂扩散。

I mean, there's a lot of these threats that aren't just themselves threats, but they're hyper proliferating threats.

面对这些，只有我们的免疫系统能解决问题。

And for that, our immune system is the only answer.

诺布尔，当你回望自己的职业生涯和人生，还记得那次偶然遇见戴维·帕卡德吗？他让你开始想，也许该自己闯一番事业。

Noubar, when you think about the arc of your career and your life, you know, a chance meeting with David Packard who kind of inspires you to think about maybe starting your own thing.

你敢押注mRNA技术，结果催生了人类历史上最快的疫苗，如今Moderna成立已经十年了。

Taking a gamble on mRNA, which would lead to the fastest vaccine ever manufactured in history, to now, you know, Moderna was founded ten years ago.

我上次查的时候，它的市值快达到一千七百亿美元了。

I think its market cap, the last I checked, was almost a $170,000,000,000.

而这还只是你创办的其中一家公司。

And that's just one of the businesses you you started.

这真是个了不起的故事。

It's a pretty remarkable story.

你觉得你现在走到这一步，有多少是靠拼命努力，又有多少是运气使然？

How much of of your of where you are today do you attribute to how hard you worked, and how much do you think has to do with just luck?

我这么拼命，大概是因为作为移民，我从不把任何东西当成理所当然。

How hard I work is a function of probably the orientation that I had that as an immigrant, you don't really take much for granted.

我觉得没什么是该给我的，一切都有可能，但你得自己去争取。

You don't think much is owed to you, and everything is a possibility, and you have to go get it.

对我而言，真正的动力是想搞清楚：我们能不能用一种全新的方式去创新。

In my case, the motivator has been truly trying to figure out if we could innovate a new way to innovate.

是的。

Yeah.

所以，努力确实是关键。

So hard work, yes.

说到运气，说来也巧，你刚问这个问题，前几天正好有人给我发了条消息，我想回他，但没回，就说了一句：与其说幸运，不如说好运。我觉得，光指望运气，算不上什么策略。

In terms of luck, you know, it's it's ironic that you're that that you asked me that because somebody had written to me something the other day that I wanted to respond to, but I didn't by saying better, lucky, and good in the sense that I think that to some extent, counting on luck is not a strategy.

但不管多努力，机会不一定来，你也不一定能撑到成功之前不倒下。

But it is the case that no matter how hard you work, there's no guarantee that the opportunity will come up or that you will fail to fail long enough succeed.

对。

Yeah.

这些事儿，要非得说原因，也只能归结为运气了。

These are all things that otherwise can only be explained by chance.

但我真不知道该怎么应对这事儿，因为我没法指望它。

But I don't know what to do with that because I can't count on it.

我也召唤不来它。

I can't summon it.

要是能随时召唤出来，那倒挺爽，可我就是办不到。

If I could summon it anytime, that would be fun, but I can't.

所以它压根儿影响不了我的行动。

And so therefore, it doesn't roll doesn't play any role in in my actions.

它来的时候，自然就来了。

And and when it comes, it comes.

这是努巴尔·阿费扬。

That's Noubar Afeyan.

他是莫德纳的联合创始人兼董事长，也是Flagship Pioneering的创始人兼首席执行官。

He's cofounder and chairman of Moderna, and he's also the founder and CEO of Flagship Pioneering.

如今，Moderna大概是Noubar创办的最知名的生物科技公司了。

Today, Moderna is probably the most famous biotech company Noubar has developed.

但自从二十多年前成立起，Flagship Pioneering就已经帮助孵化了一百多家公司。

But since it was founded over twenty years ago, Flagship Pioneering has helped launch more than 100 other companies.

其中，已经有三十家成功上市了。

And of those, 30 are now publicly traded.

感谢大家本周收听本节目。

Thanks so much for listening to the show this week.

如果你还没订阅，欢迎在你常用的播客平台订阅我们。

If you're not yet a subscriber, please do subscribe wherever you get your podcasts.

想给我们发邮件的话，地址是 hibt@npr.org。

If you wanna write to us, our email address is hibt@npr.org.

想在Twitter上关注我们，可以搜 Guy Raz 或者 how I built this。

And if you wanna follow us on Twitter, we're at Guy Raz or at how I built this.

你也可以在Instagram上找到我们。

You can also find us on Instagram.

我的个人账号是 guy dot raz，关注我们请搜 how I built this n p r。

That's at how I built this n p r on my personal account at guy dot raz.

本期节目由凯西·赫尔曼制作，配乐由拉姆廷·阿拉布卢伊创作。

This episode was produced by Casey Herman with music composed by Ramtin Arablui.

本集由努巴尔·阿费扬剪辑，克莱尔·穆拉希马提供研究支持。

It was edited by Noubar Afeyan with research help from Claire Murashima.

我们的制作团队还包括：J.C. 霍华德、詹姆斯·德拉·胡西、蕾切尔·福尔克纳、莉兹·梅茨格、朱莉娅·卡尼、费拉赫·萨法里、伊莱恩·库茨、安妮莉丝·奥伯，以及哈里森和张志远。

Our production staff includes JC Howard, James Della Hussi, Rachel Faulkner, Liz Metzger, Julia Carney, Ferrah Safaree, Elaine Coates, Annalise Ober, and Harrison, Vijay Choi.

杰夫·罗杰斯是我们节目的执行制片人。

Jeff Rogers is our executive producer.

我是盖伊·拉兹，你正在收听的是《我是如何打造这一切的》。

I'm Guy Raz, and you've been listening to how I built this.

这是美国国家公共电台。

This is NPR.