Craig Venter’s Legacy: The Most Influential Geneticist Since Watson and Crick

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In the eighteen hundreds, the railways, then telecom, fiber optic, and now?

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今天，我们想聊聊遗传学家克雷格·文特尔。

Today, we want to talk about Craig Venter, the geneticist.

他刚刚以79岁的年龄去世了。

He's died at the age of 79.

文特尔最出名的就是他在人类基因组测序项目中扮演的关键角色。

Now, Venter's most famous for the leading role he played in sequencing the human genome.

我觉得，他可以说是自沃森和克里克以来最有影响力的遗传学家。

There's a case to be made, I think, that he's the most influential geneticist since Watson and Crick.

你觉得呢？

What do you think?

没错。

Definitely.

确实有这个说法。

There's a

值得这么讲。

case to make.

今天我们在《世界、宇宙与天文新科学家》节目中就要聊这个。

That's what we're getting into today on The World, The Universe, and Astral New Scientist.

我是罗文·胡珀博士。

I'm Doctor Rowan Hooper.

我是佩妮·萨谢特博士。

And I'm Doctor Penny Sarchet.

克雷格·文特尔影响力这么大，这么多年来《新科学家》一直没少报道他的工作。

Now it is a mark of Craig Venter's influence that we've written so much about his work over the years at New Scientist.

为了深入聊聊这个，我们请来了两位前《新科学家》的记者。

So to get into this, we're joined by two former New Scientist journalists.

一位是作家迈克尔·马歇尔，另一位是前主编罗杰·海菲尔德，现在他是伦敦科学博物馆的科学总监。

We've got writer Michael Marshall and former editor Roger Highfield, now science director at the Science Museum in London.

罗杰，你跟克雷格很熟吧。

And, Roger, you knew Craig very well.

你还帮他编辑过自传。

You edited his memoir.

没错，是这样的。

That's right.

我想想啊，整个九十年代我就时不时采访克雷格，后来突然接到一通电话的时候我还挺意外的。电话那头说，你看啊。

I mean, I interviewed Craig on and off during the nineties, and then I was a bit shocked to get a phone call saying, look.

是纽约的企鹅出版社那边彻底乱套了，因为克雷格把他的基因自传写好交稿了——毕竟他是第一个测出自己完整基因序列的人。

You know, it was Penguin in New York was having a bit of a meltdown because Craig had delivered his genetic autobiography because he was the first to sequence his own genetic code.

结果那稿子攒了足足二十五万字，都是很随性的加州口语风格，篇幅实在太长了。

And it was basically a quarter of a million words of Californian, and it was way too long.

结果他们根本不敢接手这个工作

And they didn't dare touch it.

你懂吧？

You know?

出版社的人都挺敬重他的

He was kind of revered by the by the publisher.

所以我就被拉来顶上了

So I was drafted in

是的

Yeah.

去干那些脏活累活。

To To do the dirty work.

对。

Yes.

没错。

That's right.

事实上，我们还做了他的另一本书，对吧？

And and in fact, we did another right?

我们又帮他出了一本书。

We did another of his books.

没错。

Mhmm.

但这样确实让我对克雷格这个人有了很深刻的认识，也直接跟他合作过，打交道过。

But, obviously, got a vivid insight into Craig the man and also worked with him, you know, dealt with him.

而且你知道，他经常被妖魔化。

And I you know, he's often demonized.

在遗传学家当中，他是个极具争议的人物。

He's a very polarizing figure among geneticists.

事实上，如果你看关于人类基因组测序竞赛的官方记录，嗯，

And in fact, if you see official accounts of the race to the human genome Mhmm.

他常常被完全忽略，我觉得这简直太荒唐了。

Quite often, he's not mentioned, which I think is scandalous

是的。

Yeah.

实际上，

Actually.

没错。

Yeah.

但他影响巨大，而且坚决不肯退休。

But hugely influential and refused to retire.

我的意思是，就在几个月前，他还成立了另一家公司。

I mean, only a a few months ago, he was, I think he set up another company.

他简直就是个连续创业者。

So he was kind of serial entrepreneur.

对。

Mhmm.

他还给我发邮件，想跟我一起做另一个项目。

He was emailing me about doing another project together.

其实我知道他又被诊断出得了另一种癌症，但我觉得他好像永远不会倒下。

So I was actually really I I knew he'd been diagnosed with with yet another cancer, but he just felt like he was gonna go on forever.

今天真是个令人难过的日子。

So it's a sad day.

从此以后，这个世界明显变得灰暗、无聊、乏味了。

The world's got definitely got rather gray and boring and beige now as a result.

我觉得他最出名的，还是他在人类基因组测序竞赛中的角色。

I I think most of all, he's famous for his role in the race to sequence the human genome.

这确实是个挺复杂的遗产，对吧？

And it's a complicated legacy there, isn't it?

迈克，要不你先讲讲那个著名的竞速故事？就是争夺率先完成基因组测序的那段历史？

Mike, do you wanna start us off really by by talking about that story, that iconic story of the race to to to get it done?

其实这是一场双向竞赛。

So it was kind of a a two way race, really.

官方的人类基因组计划是1990年启动的，由政府出资支持。

So the the official human genome project kicked off in 1990, and that was a a publicly funded thing.

当时全球一大批研究团队，美国、英国，还有世界各地的机构联手合作，目标是完整读出人类DNA的全部序列——那时候这简直是件难以想象的大工程。

It was this huge consortium of researchers in The US, The UK, sort of all around the world working together to, yeah, read the entire human DNA sequence from beginning to end, which is, you know, at the time an absolutely gargantuan endeavor.

我记得最后花了大约30亿美元。

I think it cost something like $3,000,000,000 Yeah.

到他们完成的时候。

By the time they'd finished it.

整整花了十年时间。

It took them essentially a decade.

基因组草图在2000年就发布了。

The sort of the the first draft of it was published in 2000.

但与此同时，当时还在美国国立卫生研究院工作的文特尔，觉得官方这套方法实在太慢了。

But meanwhile, Venter had been sort of working away at the National Institutes of Health in The US, and he had sort of got the idea that the way that they were doing it was just too slow.

他压根不认可那套做法。

And he was just like, no.

完全不认可。

No.

不行

No.

咱们得赶紧把这事儿搞定，不能再拖了

We need to we need to hurry this the hell up.

于是他在1998年成立了自己的公司塞雷拉，放话要抢先完成测序，抢在官方项目前面

And so he founded his own company, Celera, in 1998 and just said, I'm gonna beat them to it.

不过最后他没能如愿

And he didn't.

其实就是平局。

It was a tie, essentially.

他们俩几乎同时发布了各自的基因组草图。

And that both of them published their draft genomes sort of essentially at the same time.

那是因为他们最后和解了，联手合作了。

That that's because they sort of came together at the end and made peace.

是的。

Did.

他们确实这么做了。

They did.

这事儿太复杂了，因为克雷格本人其实一直想跟政府资助的项目合作。

I it's such a Mike, it's such a complicated story because Craig himself, you know, he tried hard to work with the the government funded program.

我记得他通过吉姆·沃森提交过好几份提案，但每次都碰壁，特别挫败。

I think he put in some of that four proposals through Jim Watson and was endlessly frustrated.

后来他想出了一个特别巧妙的办法，叫表达序列标签，来定位基因。

Then he came up with this very nifty way to find genes, express sequence tags.

其实是NIH想为这些序列申请专利，主要是为了给制药行业一个明确的说法。

And it was the NIH that wanted to patent them really to get clarity about what it meant for for pharma.

这根本不是克雷格在推动。

It wasn't Craig driving this.

对。

Mhmm.

但这件事后来被歪曲成了一个说法，说他是个贪婪的资本家，想用廉价又粗糙的方式完成基因组测序，好像这事儿非得这么干不可似的。

But this got sort of twisted into a narrative that he was a kind of rapacious capitalist and that he was trying to do a kind of cheap and dirty version of the genome when you had to do it, a kind of

詹姆斯·沃森当时就说，这活儿随便哪个猴子都能干。

grinding James Watson said any monkey could do it.

没错，就是这样。

Well, exactly.

当时……

At

一开始，双方矛盾特别尖锐。

first, they were there was this tension between Huge tension.

他大概心想：有人想抢我这年轻气盛、势头正猛的美国人的风头？

Probably thought, oh, is someone stealing my crown as the young, brash, up and coming American.

他清楚Craig在搞什么，那会儿他是在国会委员会面前——记不清是哪个了——故意作秀。

Knew all about what Craig was up to, and it was a bit of grandstanding in front of, I can't remember, congressional committee or something like that.

我觉得赛拉那帮人第二天真穿上了大猩猩服装，站在序列图旁边拍照取乐。

I think the Salera guys actually donned a gorilla suit the next day and posed next to the sequence for for a bit of fun.

但说实话，这倒也挺有帮助的。

But, actually, it was a useful adjunct.

我觉得Craig从来没把这当成正经事，只当是做完整个人类基因组计划的辅助手段。

I don't think Craig ever saw anything more than an adjunct to doing the serious genome.

我觉得最后他发现，私人资金能让他随心所欲地做事。

And I think what happened was that ultimately he found that private money could let him do what he wanted to do.

于是他搞了个非营利机构，叫Tiger。

And he set up this non for profit outfit, Tiger.

你知道吗？他在九十年代中期就完成了第一个非生命体的基因组测序。

You know, he did the first genome of a pre living organism in in the mid nineties.

就像迈克说的，他真觉得，我能比那些公共项目的人快得多、轻松得多把基因组做出来。

And, you know, as Mike said, he really felt, look, I I can do the genome much more quickly and more easily than the public guys.

我觉得他简直把人惹毛了——Craig 绝对拿不到年度外交官奖。

I think he completely enraged I mean, Craig would never win diplomat of the year award.

他动不动就说：‘我来搞定人类基因组。’

He would say things like, I'll do the human.

你们干嘛不赶紧去弄小鼠啊，之类的？

Why don't you guys rush off and do the mouse or something like that?

这样咱们就不重叠了。

And then we're not overlapping.

对啊。

Yeah.

但你说得对，Rowan，说到白宫那场协议，背后早就乱得一塌糊涂了。

But you're right, Rowan, that when it came to that White House agreement, it had all got completely ridiculous behind the scenes.

我觉得是跟 Craig 一起工作的阿里·佩特里诺斯当了和事佬，那场合作可是精心排练过的。

I think it was Ari Petrinos who worked with Craig who kind of act as a peacemaker, and it was a highly choreographed joint Yeah.

宣布一下。

Announcement.

对啊。

Yeah.

我跟约翰·索尔斯塔德聊过，你知道的，他总被塑造成那种‘反物质厨师’、‘反厨师’的角色。

But I talked to John Solstad, you know, who's always portrayed as the kind of it was a bit like the anti matter matter cook and anti cook.

你想想，约翰·索尔斯塔德，牧师的儿子，穿凉鞋，对比那个坏透了的越战老兵克雷格·文特尔。

You know, you're John Solstad, son of a vicar, you know, wore sandals versus this evil Vietnam vet, Craig Venter.

嗯，那个无神论者——

Well, the atheist

当然，另一边的领导者弗朗西斯·柯林斯是个虔诚的基督徒。

and Francis Collins, of course, the leader of the on the other side being a devout Christian.

没错。

Very

确实非常虔诚。

devout indeed.

但约翰说过，克雷格把基因组第一版的完成时间提前了整整三年。

But John had said, look, Craig accelerated the the first draft of the genome by about three years.

不过我说了，他现在却被从遗传学的历史里悄悄抹去了，这真有点可惜。

But as I say, he is sort of being airbrushed out of genetics history now, which is a bit of a shame.

我觉得是这样。

I think.

但我还想说，没错，他确实把进度提前了三年。

But I'd also suggest that, okay, he's he sped it up by three years.

但更大的贡献，难道不是鸟枪法测序吗？

Isn't the bigger legacy shotgun sequencing?

因为确实如此。

Because Yeah.

当时很多人瞧不起这方法，说它又快又粗糙。

There was this snobbishness about it's quick and dirty.

但你看看现在我们做遗传学和生物学的方式——这么多物种的基因组数据，我们能研究这么多东西，全靠鸟枪法测序。

But if you look at how we do genetics and biology today, the vast number of genomes we have for all these species that we can now study, that's shotgun sequencing.

能便宜地测很多人基因组，而不只是一个人的，这靠的就是鸟枪法测序。

The ability to cheaply sequence many people's genome, not just one person, that's shotgun sequencing.

你觉得呢，迈克？

Would you agree, Mike?

是的，没错。

Oh, yeah.

当然了。

Absolutely.

鸟枪法就是把基因组彻底随机打碎成一堆小片段，分别测序，再用电脑重新拼起来。

Shotgun sequencing, which is where you sort of break up a a genome completely at random into all these little chunks and then sequence all them individually and then use a computer to put it all back together.

这比先绘图再测序快多了。

It's so much faster than the other way, which is to map the genome first.

过去二三十年里最了不起的发现之一，我觉得就是阿斯加德古菌——那些单细胞微生物，很可能是所有动物、植物和复杂细胞的祖先。

I mean, one of the sort of biggest discoveries of the last sort of couple of decades, think, is Asgard Archaea, which are these Archaea, these, like, single celled microbes that are probably the ancestors of all animals, plants, and complex cells.

它们是通过宏基因组学发现的，直接从海底捞点沉积物，把里面所有DNA都读一遍，再重新拼出来。

They're found by metagenomics by literally just scooping up some sediment from the bottom of the sea, reading all the DNA in it, and then putting it back together.

我觉得，这正是大规模应用 shotgun metagenomics 的成果，它发现了二十一世纪最重要的生物学发现之一。

And that, I'm fairly sure, is shotgun metagenomics done on a massive scale, and it's and it discovered one of the most important biological finds of the of the twenty first century.

用其他方法，根本不可能发现这个。

There's no way that that would have turned up, I think, by the other methods.

是的。

Yeah.

这正是他的遗产之一。

So that's part of his legacy.

遗产。

Legacy.

没错。

Yeah.

克雷格意识到，这本质上是个计算问题。

And Craig realized it was really a computational challenge.

而不是化学问题。

It wasn't a chemistry challenge.

所以他们花了大量精力开发软件，把那些海量的数据片段重新拼回原样。

So they they put a lot of effort into the software to put all those gazillions of bits back together again.

而且，这方法早就已经公开了。

And, also, it had been out there.

你知道吗？他曾经收到过一封弗雷德·桑格的亲笔信，桑格是他非常敬重的人，信里说他喜欢霰弹枪测序法，但他的同事觉得这方法有点怪，甚至有点土。

You know, he's got a lovely letter or he had a lovely letter from Fred Sanger, who he revered, saying he liked shotgun sequencing, but his colleagues thought it was a bit off and a bit naff.

因为桑格测序法是那种慢工出细活、严谨又干净的方法。

Because Sanger sequencing was the the slow, careful, clean method there.

是啊。

Yeah.

没错。

Yeah.

他们最后不是用桑格法复核过吗？

And didn't they double check it using Sanger eventually?

他们先用霰弹枪法快速拼出初稿，后来再用桑格法逐字核对，结果发现——嗯，他真的搞对了。

They they did they did the rough draft with mostly shotgun and then it eventually they went through it with this this sort of more thorough Sanger sequencing and found, yeah, basically, it's the he got it right.

是的。

Yeah.

够用了。

Good enough.

对。

Yeah.

那时候大家可吵翻了，争谁的基因组更靠谱啊之类的。

I mean, there was there was huge argument at the time about whose genome was better, etcetera, etcetera.

不过话说回来，克雷格后来还干了别的不少事呢。

But, of course, the thing is, you know, Craig went on to do other stuff as well.

他可不只是搞了个人类基因组。

So it wasn't just him and the human genome.

他影响可大了，确实如此。

You know, he's hugely influential Yeah.

在好多其他领域都是如此。

In in loads of other ways.

不过我想稍后聊聊这些，咱们先倒回去说说，他当年可是个冲浪混子。

Well, I wanna get into some of that in a bit, but let's let's rewind because he was a surf bum.

对啊。

Yep.

后来他被征召入伍，去了越南。

He went and then he went to Vietnam to he was called up.

他去打了越战，这事儿真把他的人生给彻底改变了，对吧？

He went to the war in Vietnam and that really changed his life, didn't it?

其实是往好的方向转变的。

In in in for the positive, actually.

是的。

Yeah.

我的意思是，他当时已经彻底崩溃了，他在自传里说过，那时候就想着一直游啊游，直到累死算了。

I mean, he well, he he was completely at the end of his tether and he, you know, he described in his autobiography how he just wanted to keep on swimming until he died.

结果他碰上了一条鲨鱼，这一下子把他给激醒了，拼命地游了起来。

And then he encountered a shark and that sort of shopped him back into then he swam furiously.

不是。

No.

恰恰相反。

I don't The opposite direction.

不是被鲨鱼逼的。

Not by shark.

我觉得他当时是，我觉得……

And I think he was I I think

他在岘港的医疗单位亲眼看着几百人死去，是的。

he saw hundreds of men die Yeah.

在岘港的医疗单位工作时，他总是对一些事感到惊讶——比如有些人伤得那么重，却凭着一股顽强的意志撑了下来，而有些人却撑不住。

In the Da Nang Medical Unit where he worked and was always sort of amazed by things like how some people with impossible injuries seem to, by sheer power of will, keep on going and others couldn't.

我觉得正是这段经历让他明白了要活在当下，于是他回了大学，后来在加州大学圣地亚哥分校拿到了博士学位。

And I think he gave him a kind of seize the day attitude, then went back to college, did his doctorate at UC San Diego.

这为他后来的职业道路打下了基础，最终进了NIH，参与了早期的测序工作，那时候他特别严谨，用的都是那些不靠谱的老序列。

And that really set him on the career to get to the NIH and then do some very early sequencing where he was very meticulous about using these dodgy old sequences.

很多人根本搞不定这些设备，只好退回来。

A lot of people just couldn't get the things to work and sent them back.

但克雷格呢，说实话，让我想起了吉姆·洛夫洛克，他也说过类似的话——根本不信实验室里的纯度检测。

But Craig, you know, actually kind of reminded me strange ly of Jim Lovelock who say the same thing that he didn't trust lab purity measurements.

他一定要亲自搞清楚每一种化学试剂，确保自己完全了解、完全掌握。

He had to make sure every single chemical going into the sequence that he understood and he'd characterized.

是的。

Yeah.

结果他做出了超棒的成果。

And he got brilliant results.

他在NIH的实验室在测序方面干得特别出色，沃森都特别佩服。

And he you know, his lab in the NIH was doing great things in terms of sequencing, and Watson was very impressed.

可后来政治插了一脚，剩下的就是历史了。

But then politics got in the way, and the rest is history.

你提到了洛夫洛克，我也想到他，不过是从另一个角度——他是个独立科学家。

Well, you mentioned Lovelock, and I I also thought of him in a different way though that being an independent scientist

是的。

Yeah.

像洛夫洛克那样有收入，就能随心所欲地做研究，不用看别人脸色。

Being like Lovelock's income allowed him to basically do what he wanted Yeah.

也不用去申请经费。

And without having to apply for grants.

克雷格·文特尔也是这样。

Craig Venter was also able to do that.

这让我想到马斯克，他也是那种独立行事的人——有钱就能自己说了算。至于到底有多少科学含量，咱可以争论，但确实，这些有钱人就能甩开膀子干自己想干的事。

It also made me think of Elon Musk actually as another sort of independently well, he can do what he wants and, you know, you can argue how much science there is, but in the same way, there there is that these men with with big chunks of money that can go off and do what they want.

没错。

Definitely.

大家总把克雷格说成是贪婪的资本家海盗，其实完全搞反了。

And and, you know, people always characterize Craig as this rapacious, buccaneering capitalist, but I think they got it exactly wrong.

他很穷吗？

Poor, was he?

他根本不穷。

He wasn't poor.

他赚了整整一大笔钱。

He made a shed load of money.

而且他甚至

And he even

那钱是从哪儿来的？

Where did that money come from?

嗯，是来自Salaire的。

Well, it was it was from his from Salaire.

贪婪的资本主义。

Rapaceous capitalism.

他的贪婪资本主义。

His rapacious capitalism.

但你知道，他真正的动力一直都是科学。

But, you know, his driving force was always a science.

我的意思是，真的就是这个意思，好吧。

That's what really I mean, okay.

还有航海，这也是他生命中另一大热爱。

Maybe sailing as well as the other his great love of his life.

他每天早上起床，可没想着‘今天我要赚一亿美金’。

But he wasn't sort of getting out of bed in the morning thinking, hey, I'm gonna make a $100,000,000 today.

他想的是：‘我要把一个基因组移植到另一个生物里’，或者‘我要让某种细菌合成出前所未有的东西’。

It was like, I'm I'm gonna transplant a genome between organisms, or I'm gonna get a bug to make something that's never been made before.

对。

Yeah.

所以他根本停不下来，干脆一路当上了连续创业者，就为了做那些——像你说的——酷到不行的事。

So he was completely irrepressible, and he just became a serial entrepreneur to do, as you say, the cool stuff he wanted to do.

不过咱们再回头看看当年人类基因组计划时期，大家对他的那种说法。

But just to revisit that sort of narrative that was around the time of the the human genome project.

有些人真把他描绘成了反派角色。

He really was, by some, painted as, like, a villain.

如果我们不抢在他前面，他就要把整个人类基因组都申请专利，那就不属于我们了。

And if we didn't beat him, then he was going to patent the whole human genome and it wouldn't belong to us anymore.

而且你知道，如果我们以后想用基因技术治病，他都要抽成。

And, you know, if we ever wanted to use genetics for medicine, he'd get a cut.

真有这回事吗？

Was that true?

现在都过去二十五年了，我们能不能更全面地看待这个说法？他当时真的是这个打算吗？

Is that is that, you know, with twenty five years on, can we look at that narrative with more nuance, or is that actually what he was trying to do?

嗯，我觉得……

Well, I

我的意思是，Solara 公司确实一开始藏了一部分数据，就是为了拿去卖。

mean, I mean, Solara did, like, hold back a chunk of their data, at least at first, so that they could sell it.

这确实是事实。

That is straightforwardly true.

而人类基因组计划因为是公共资助的科研项目，就把所有数据都免费公开在网上，谁都能下载，谁都能用。

Whereas the human genome project, because it was a publicly funded bit of research, just put everything out freely available online to anyone that anyone anyone who who wanted it and anyone who could download it.

关于这个伦理问题，咱们能吵到天荒地老。

And we can sort of fight about the ethics of that until the cows come out.

我总觉得，数据免费开放共享的证据和它带来的好处实在太庞大了，从实际效果来看，人类基因组计划那帮人确实是对的，这么做能带来更大的社会收益。

I sort of tend to think that the evidence for free and open sharing of data and the for the benefits of that is so enormous that I do think that essentially the human genome project guys were right on the sort of practical level that you will get more societal benefits that way.

在我当记者之前，曾在剑桥郊外的桑格中心工作过几年，那里正是人类基因组计划的重要据点之一。

Before I was a journalist, I worked for a few years at the Sanger Center in just outside Cambridge, which is where a chunk of the human genome project was on there.

那儿有个房间，里面全是排成阵列的测序仪。

There there was a room you could go into that just had these arrays of sequencing machines.

那确实是人类基因组计划里非常关键的一部分。

If that was a really important chunk of the human genome program.

对。

Yeah.

极其重要。

Hugely important.

我那时候是2005、2006年在那儿。

I was there in, like, 2005, 2006.

如果你提到文特尔这个名字，大家

And if you said the word Venter, you would

基本上都会立刻炸毛

basically you would basically get this sort of piss

然后可能还会比个十字架的手势。

and then possibly a a sign of a cross.

他当时被普遍看作是极其不道德的人。

Like, he was sort of widely despised as as just like profoundly unethical.

我对这事其实挺矛盾的，一方面觉得他确实推动了进展，但另一方面，我也挺反感那种充满雄性激素的科研风格——吉姆·沃森其实也一样，就是那种‘我就是要往前冲，管你谁被冒犯、谁的生活被掀翻’的做派。

I sort of go back and forth over it because I do think that he did sort of kick things along, but I I do also sort of have a mild annoyance with that whole like testosterone driven style of science, which I think Jim Watson, to be fair, was also incredibly guilty on that sort of I'm just gonna push ahead, and I don't care who I offend or, like, who whose lives I sort of overturn along the way.

罗杰，你觉得克雷格自己怎么看待他被当成反派和贪婪资本家的角色？

Roger, do you have an idea of how, Craig felt about being the villain and the rapacious capitalist?

我觉得吧，说白了，

I think he got well, you know, look.

他自尊心强得不得了。

He had a giant ego.

但他做的那些了不起的事，确实配得上他这么大的架子。

But, you know, I think he'd done enough, impressive things to sort of earn his giant ego.

我觉得特别能说明问题的是，我读完他写的那厚厚一摞手稿后，跟他说：‘克雷格，我得找人核实一下这些内容，你懂的，我需要第二个信源。’

What I thought was really telling was when I when I waded through this vast manuscript he'd produced, I said to him, look, Craig, I've got to be at a second source all of this, you know, or whatever I want a second source.

他对此一点不担心。

And he had no worries about that.

其实有本特别棒的书，叫《基因战争》之类的，作者是杰米·史瑞夫，书里写得简直像他住在世外桃源一样。

And in fact, there's an amazing book by Jamie Shrieve, I think, The Genome War or something like that, where it almost sounds like he was living in Salera.

我的意思是，他认识所有人，想见谁都能见到。

I mean, he had, like, access to everybody.

对。

Mhmm.

我觉得克雷格本人其实特别坦率，挺好打交道的。

And I think Craig was actually very open and straightforward to deal with.

还有件挺有意思的事，我本来想提一提的，因为讲出来故事会更精彩，可惜现在不能说。

And what I found funny and, actually, I wish I could have mentioned them because it makes it a much better story, but I can't really.

但有一个非常重要、众所周知的机构，是公共基因组计划的核心。

But there is a major, very well known organization that was central to the publicly funded genome.

我说：‘你看，克雷格说开过一次关键会议’，我还跟那边的公关人员聊过，整个故事的核心就是搞定文特尔。

And when I said, look, I've got Craig saying there was this key meeting and, in fact, I talked to a press officer who's there and that the whole narrative was get Venter, basically.

能把会议记录给我看看吗？

Can I see your minutes?

就像迈克说的，这个机构一直嚷嚷着说所有东西都会公开，全部免费。

And and this is an organization that, as Mike said, went on and on about it's all gonna be publicly available, everything.

他们当时说：‘没问题啊。’

They said, oh, fine.

会议记录、所有资料，你尽管拿去好了。

You can have all the minutes, everything.

是的。

Mhmm.

可六个月后，他们又说：‘实在不好意思。’

And then after six months, they said, oh, terribly sorry.

我们的档案乱七八糟的。

Our archives are in disarray.

你们可以拿走那些新闻稿和赛事相关的剪报。

You can have the press releasing press releases and the cuttings from the race.

是的。

Yeah.

我觉得这其实挺能说明问题的。

I thought that was pretty telling, actually.

对。

Yeah.

我的意思是，就像我说的，他走向商业化的过程，远比人们通常说的要复杂得多。

I mean, I I I think that, as I say, the story about how he became commercial was much more complicated than often portrayed.

没错。

Mhmm.

他根本不是冲着赚钱去的。

And it wasn't his motor to make money.

是的

Yeah.

他的目标是做科学。

It was to do the science.

好的。

Okay.

迈克，咱们聊聊另一个重大突破，它们其实是有重叠的。

Mike, let's talk about the other major breakthrough, and they do overlap.

但整个合成生物学的事儿，确实是从1995年他测出第一个自由生活生物的基因组开始的。

But the the whole synthetic biology thing, they overlap because it was in '95 where he sequenced the first genome of a of a free living organism.

就是那种细菌，之后他就以此为基础，展开了所有合成生物学的研究。

It was that bacterium, and then he took it from there with all this synthetic biology stuff.

对。

Yeah.

没错。

That's right.

所以，在人类基因组计划完成后的几年里，文特尔决定尝试制造一种合成细胞。

So after, you know, within a few years of, like, the human genome project finishing, Venter decided that what he was gonna do is to try to create a sort of synthetic cell.

但这并不是说他从零开始，一分子一分子地构建整个活细胞。

Now what that that doesn't mean that he was building an entire living cell, like, completely from scratch molecule by molecule.

他其实是拿了一个现有的细菌——一种相对简单的、会感染山羊的病原体。

What he did was to take an existing bike bacterium, a relatively simple one that it's it's like a pathogen that infects goats.

对。

Yeah.

它的基因组比较小，所以更容易操作。

And it has a relatively small genome, so it was kinda easy to work with.

他们做的是，完全人工合成了一份基因组。

And what they did was to create a completely artificial version of the genome.

也就是说，他们先读取了原有的基因组，然后在实验室里重新合成了一份全新的。

So that, yeah, they they had read it and then they built their own version of it in the lab.

接着，他们选了一个近缘的单细胞细菌，把它的原有DNA全部取出，换上了他们合成的基因组。

And then they took a cell of a related species, know, another single cell bacterium, took all its DNA out of it, and inserted their synthetic genome into it.

结果这个细胞活下来了，根本没像你想象的那样炸掉。

And the cell lived and did did not immediately explode as you might expect.

对啊。

Yeah.

本来以为会出事的。

Expect to happen.

这事儿真够怪的。

It's a weird thing.

从大多数角度来说，这确实算是一种人造生命。

It it is a kind of synthetic life for most yeah.

这个细胞的全部成分都是天然的，唯独它的基因组是电脑设计出来的。

The entire cell is natural except for the fact that its entire genome has been built by a computer.

某种程度上，它没有生物意义上的祖先。

And in some sense, it doesn't have a biological ancestor.

严格说它还是有祖先的，只不过那一整段基因是人工合成的。

You know, it it kind of does except except for this whole chunk of it that's that's artificial.

我记得还加了个水印。

Including a watermark, I seem to remember.

对。

Yes.

团队里大概四十多人把自己的名字签在了基因组里，还藏了几句名言。

They about 40 something of the team sort of signed their names in the genome, and then there's also a few quotes.

好像有句詹姆斯·乔伊斯的，我还特别喜欢那句来自《美国的普罗米修斯》——奥本海默的传记——的话，选得真贴切。

I think there's a quote from James Joyce, and I rather like this actually a quote from American Prometheus the biography of Robert Oppenheimer which is apt choice.

是啊。

Yeah.

那句‘不要看事物本来的样子，而要看它可能成为的样子’，就是奥本海默说的。

That that one is see things not as they are but as they might be was what Oppenheimer said.

他还说过费曼那句‘我造不出来的东西，我就算不上真正懂’。

He he also had Richard Feynman What I cannot build, cannot understand.

他挺爱这种气派的，对吧？

He liked his sense of grandeur, didn't he?

是啊，他确实如此。

Yeah, he did.

他确实做到了。

He did.

至于詹姆斯·乔伊斯那句，是‘活着，跌倒，崛起，从生命中再造生命’。

And the James Joyce one was To live to to fall, to triumph, to recreate life out of life.

选 quote 真有眼光！

Good eye for a quote!

迈克，

Mike,

你知道，合成细胞最大的亮点在于，虽然它的框架可能不算完全人造，但你完全可以对基因组进行编程。

you know, big excitement with the synthetic cell is that, okay, you you can argue that the scaffolding of it is not synthetic, but you can then program the genome.

他好几次提到，他真正想做的，是造出一种能吸收二氧化碳的生物——虽然这是很久以前的事了，但他那时候就已经在说，咱们得把大气里的二氧化碳清掉，这能帮我们摆脱化石燃料。

And I you know, a few times he said that what he really dreamt of doing was making an organism that could then draw down carbon dioxide and, you know, and this was a long time ago, but he was already talking about, you know, we need to get CO2 out of the atmosphere and this is gonna help us get off fossil fuels.

但到现在我们还没实现，事实上，合成生物学比想象中复杂多了。

We haven't done that yet, and actually synthetic biology has been turned out to be much more complicated.

你知道，这基本上就是原因吗？

You know, what is that basically the reason?

这比我们想象的复杂多了。

It's much more complicated than we thought.

部分是因为太复杂了，你看，细胞里那些相互作用的东西，哪怕在这么简单的细菌里，其网络也疯狂得吓人。

It's partly that it's wildly complicated because, yeah, the the the sort of the network of, like, interacting things within a cell turns out to be so ferocious even in something as simple as this little bacterium.

所以想让它们按你的想法做事，确实挺难的。

So it is it does prove quite difficult to sort of get them to do what you want.

我觉得，如果你真想改造一种细菌，比如让它吸收二氧化碳，或者生产药物这类有用的东西，其实没必要像克雷格那样大动干戈。

I think also if you want to, you know, engineer a bacterium that, like, draws down c o two or do or, you know, some other kind of useful thing like, like, make a medicine or something like that, You probably don't need to do anything quite as wholesale as what Craig was doing.

你根本不用把整个基因组都替换掉。

You you don't need to replace the entire genome.

你大概只需要调整几个小地方，比如加个六七个基因之类的。

You're probably gonna be tweaking a few little bits of it, like adding a half dozen genes, that sort of thing.

某种程度上，当时就有人说，合成生物学对社会最有用的成果，很可能来自比克雷格那套简单得多的实验。

And in some respects, I think that it was said at the time that probably some of the biggest benefits of synthetic biology in terms of, like like, societally useful things will probably come from much simpler experiments than what Craig was doing.

我觉得之后的发展也印证了这一点，因为确实如此。

And I think that's probably been born out since because we yeah.

我觉得现在有一种抗疟药叫青蒿素，是用基因改造的细胞生产的吧？

You can I think there's a there's an antimalarial drug called artemisinin that's now made by, like, engineered cells?

而且其实我们也没改多少基因，就动了那么一两个就搞定啦。

And and it's just a and I don't think it's very many genes at all that we've messed around with to do that.

我觉得文特尔那些实验真正探讨的，其实是更根本的生物学问题。

What I think Venter's experiments with these cells really sort of get at is more is really kind of fundamental biological questions.

我觉得这跟细胞工程、生产制造之类的东西关系其实不大。

They're actually not, I think, very much to do with, like, cellular engineering or, like, manufacturing or anything like that.

它们关注的是生命的本质——到底要什么条件细胞才算活着，生命能简单到什么地步。

They're to do with understanding, like, the the deeper nature of life and, like, what what it actually is required for a cell to be alive and how simple it's possible to to get it to be.

这些实验更偏向于探索这类深层的生物学问题，而不是追求什么立竿见影的实际应用。

They're they're much more to do with these sort of deep biological questions than they are to do really with anything that has any kind of immediate practical use.

是的。

Yeah.

他当时对这个最小基因组的想法特别着迷。

He he was he was really interested in this idea of a minimal genome.

是的。

Yeah.

要让一个东西活起来，最少需要多少个基因？

What's the least number of genes you can get away with for something to to live?

那时候，他们开发出合成大片DNA的技术，一次性搞出相当大的基因片段，简直是一次技术壮举。

And, you know, the the way that they develop new techniques to synthesize huge stretches, you know, relatively big chunks of of DNA at the time, you know, was was a kind of technical tour de force.

很多人争论，这到底算不算生命？

I mean, people coped a lot about, is it really life?

当然了，我们连‘生命’都定义不清。

Of course, we can't even define life Mhmm.

从科学角度来说，我觉得这事儿可以先放一放。

Scientifically, so I think we can park that.

但就像迈克说的，他看的不只是合成生物学的实用价值，比如让生物体干点酷炫的事儿。

But, you know, as Mike says, he he saw it not just in terms of the practical applications of synthetic biology and making organisms do really interesting things.

他其实也被这些更根本的问题所驱动。

He was driven by these more fundamental issues as well.

大概二十年前我去听过他的一场演讲，当时我对他很感兴趣，因为在我眼里，他可是这场竞赛里的反派角色。

I went to see him speak about twenty years ago, and I I was interested because this was this guy that I knew as the villain of the race.

结果我特别惊讶，他居然整个演讲都在讲他开着游艇环游世界的事。

And then I was very surprised that he he basically just gave a talk about traveling the world in his yachts Yeah.

收集海水，然后对里面的DNA进行测序。

Collecting seawater and sequencing the DNA.

迈克，你能跟我们说说这项工作吗？

Mike, could you tell us a bit about that work?

是的。

Yeah.

那其实是早期的宏基因组学研究。

So that that was an an early bit of metagenomics work.

简单说，就在他做完人类基因组计划后不久，他就弄了艘叫‘探索者二号’的游艇。

So essentially, yeah, a a few years after he'd finished his work on the human genome project, yeah, he he took this yacht, which is called the Sorcerer two.