David Liu与Stuart Schreiber谈科学：激励人心、引人入胜，揭示人类本质

我当时完全不知所措。我之前从未接触过有机化学。所以在斯图尔特讲完关于椅式船式环己烷构象异构体的讲座后，我课后去找他问了一个问题。我记得那是个表述得很糟糕的问题，因为我真正想说的是：我完全不知道你在讲什么。

I was in way over my head. I'd never seen organic chemistry before. And so after a lecture by Stuart on chair boat cyclohexane conformers, I went up to him afterwards and asked him a question. And I remember it was a very poorly formed question because what I was really trying to say was, I have no idea what you're talking about.

您正在收听《立体化学》。我是主持人凯莉·詹森。

You're listening to Stereochemistry. I'm your host, Carrie Jansen.

我是阿托耶·罗德里格斯·贝尼特斯。

And I'm Atoye Rodriguez Benitez.

如果您收听了我们的季前预告，就已经知道阿塔贝将作为联合主持人加入本季《立体化学》。

If you listened to our season preview, you already know that Atabe will be joining us as a cohost for this season of Stereochemistry.

大家好。

Hi, everyone.

如果您还没听预告也没关系，我们会为您补上进度。

If you didn't listen to the preview yet, that's okay. We'll catch you up.

在本季《立体化学》中，我们将呈现一系列杰出化学家之间的对话。

In this season of Stereochemistry, we are featuring a lineup of sensational chemists in conversation with each other.

每期节目将邀请两位化学家对话，探讨他们的科学研究、灵感来源以及各自领域的未来。这是本系列四期节目中的第一期。想了解更多后续节目详情，请查看季前预告。

Each episode will pair up two chemists for a conversation about their science, their inspirations, and the future of their fields. This is the first of four episodes in the series. For more detail on the other episodes we have coming up, go check out that season preview.

我对这期节目特别兴奋，因为今天我们将呈现来自我所在化学生物学领域的两位科学家——大卫·刘和斯图尔特·施赖弗的对话。节目开头您听到的就是大卫，他回忆了早期接触有机化学的经历。

I'm so excited for this episode because today we are featuring a conversation between two scientists from my own field of chemical biology, David Liu and Stuart Shriver. That was David you heard at the beginning of the episode, remembering an early encounter with organic chemistry.

是啊，可以说他现在肯定不再是当初那个不知所措的新手了。

Yeah, think it's safe to say he's no longer in over his head.

没错。许多人会将化学生物学领域的创立归功于斯图尔特。

Right. And many will credit Stewart with helping to found the field of chemical biology.

CNN执行编辑丽莎·贾维斯最近与大卫和斯图尔特进行了一次相当广泛的访谈，我们将在本期节目中分享更多对话内容。丽莎现在正通过虚拟演播室与我们连线。

CNN executive editor Lisa Jarvis recently sat down with David and Stewart for a pretty wide ranging interview, and we're gonna be sharing more of that conversation with you in this episode. Lisa is here in the Stereochemistry Virtual Studio with us now.

谢谢卡丽。阿塔贝说得对，斯图尔特是化学生物学的先驱，稍后我们会详细讨论这个领域的定义。现在暂且称之为：开发化学工具来解答生物学问题的领域。

Thanks, Carrie. Yes, Atabay is right. Stuart is a pioneer of chemical biology, and later, we'll get into exactly what that means. But for right now, let's call it a field that develops chemical tools to answer biological questions.

好的，我们继续听你说。

Okay, we're with you.

斯图尔特和大卫都开发了不同的方法来扩展生物活性小分子的领域。斯图尔特帮助人类理解了众多重要生物通路并开发潜在药物，而大卫的技术成果更是遍布多个领域。近期备受关注的是名为碱基编辑的基因编辑技术，它能在核苷酸层面修复基因组，比如将腺嘌呤变为鸟嘌呤。若应用于人类，可能治疗甚至治愈许多遗传性疾病。

Stuart and David both have developed different ways of trying to expand the universe of bioactive small molecules. There's a long list of important biological pathways that Stuart has helped us to understand, as well as develop potential drugs for, and David's fingerprints are all over a long list of technologies. The one that's grabbing headlines these days is a type of gene editing called base editing. It allows fixes to the genome at the nucleotide level, say, changing an adenine to a guanine. And if it works in humans, it could lead to treatments or even cures from many genetic diseases.

他们还共同创立了众多生物技术公司（多到无法一一列举），相似之处不止于此。两人都是哈佛大学教授，在布罗德研究所设有实验室——这个研究所实际上是由斯图尔特协助创立的。

They've both founded many, many biotech companies, too many for me to list here, and his similarities don't stop there. They're both professors at Harvard, and they both have labs at the Broad Institute, which Stuart actually helped to found.

看来我们都清楚这两位对科学界做出了不少贡献。

Okay. So I think we're getting the point that these two have made a few contributions to science.

从即将播出的访谈中我能感受到，这两位科学家私交也非常好。

And I got the sense from the upcoming interview that these two scientists are really good friends as well.

确实如此。本期节目我们将领略他们亦师亦友的关系，重点了解他们的科学思维模式、探索新研究领域的动力、关注的前沿科学，以及在这个新冠疫情时代对科学与社会关系的思考。最让我感动的是他们相识于大卫的少年时期。现在让我们回到节目开头大卫的故事——当他带着那个不成熟的有机化学问题站在斯图尔特面前时，也听听斯图尔特的反应。

Yeah, definitely. So in this episode, we'll get a taste of their relationship as colleagues and friends, and spend a lot of our time learning about how they think about science, what motivates them to explore a new area of research, what science grabs their attention, and in this COVID era, what they think of the relationship between science and society. One thing I love about these two is that they've known each other since, well, David was a teenager. Let's go back to David's story from the beginning of the episode when he found himself standing before Stuart with that poorly formed organic chemistry question and also hear Stuart's reaction.

是的，我想听完这个故事的后半部分。

Yeah. I wanna hear the rest of that story.

我真正想说的是，我完全不知道你在说什么。但我想我当时是想表达我正在非常努力地试图理解他在说什么。以斯图尔特典型的风格，他停下来，全神贯注地看着我，并用非常得体、清晰、冷静的斯图尔特式语言告诉我，他很难理解我在说什么。他说了些类似这样的话：这些是你将永远铭记的记忆。他还说了类似：我能看出你真的在努力理解这些内容。

What I was really trying to say was, I have no idea what you're talking about. But I think I was trying to convey that I was investing great effort into trying to figure out what he was talking about. In true Stuart style, he stopped, gave me his full attention and said in very tactful, clear, dispassionate Stuart like language, basically that he was having difficulty understanding what I was talking about. He said something like, These are the memories that you live with sort of forever. He said something like, I can see you're really trying to understand this material.

如果你能更清楚地说明你遇到的困难是什么，那将对我有很大帮助。所以我记住了那一刻，并且会终生铭记。但这给我留下了深刻印象：一位处于事业巅峰的著名有机化学家，竟然停下来帮助一个迷茫的大一新生弄清楚方向。

And it would really help me if you could convey more clearly, what is the difficulty that you're having? So I remember that moment and will for the rest of my life. But it made this great impression that here was a very famous organic chemist in the prime of his career who was stopping to help a lost freshman undergraduate figure out which way was up.

我真希望我能记得那个特别的插曲。我不记得了，但我对自己早期认识戴维的日子有着鲜明的记忆。

I wish I could remember that particular incident. I don't, I have my own vivid memories of the early days of getting to know David.

戴维，我相信知道你在有机化学上也曾有点挣扎，会让很多学生感觉好受些。

I'm sure it will make a lot of students feel good to know that you struggled a little bit in organic chemistry, David.

我在第一次有机化学考试后非常害怕，那是我大学里的第一场考试。那也是我第一次离开家生活，等等。我记得我打电话给我父母说：嗯，这里的每个人都比我聪明。我想我仍然能学到很多东西。但是，你知道，名列前茅的日子已经结束了。

I was so scared after my first organic chemistry exam, which is my first exam in college. And it's also the first time I lived away from home, etcetera. I remember calling my parents saying, Well, everyone here is smarter than I am. I think I'll still learn a lot. But, you know, the days of of being at the top of my class are are over.

剧透警告，戴维名列前茅的日子并没有结束。他后来以班级第一的成绩从哈佛毕业，并在化学界留下了深刻印象，无论是在本科期间在化学诺贝尔奖得主E.J.科里的实验室做研究，还是后来作为研究生。年轻的戴维·刘开始在彼得·舒尔茨的实验室工作，当时实验室在加州大学伯克利分校。斯图尔特对戴维的记忆就是从那里开始的。

Spoiler alert, David's days as being at the top of his class were not over. He went on to graduate first in his class at Harvard and made a big impression within the chemistry community, both as an undergrad doing research in chemistry Nobelist EJ Corey's lab and later as a graduate student. The young David Lu started working in Peter Schultz's lab, which at the time was at UC Berkeley. That's where Stuart's memories of David began.

嗯，我认识戴维的记忆非常鲜明，实际上始于与皮特·舒尔茨的一次谈话。皮特对他实验室里的一位年轻研究生说了一些非常了不起的事情。当皮特给出那样的建议时，你往往会倾听，因为他是一个深思熟虑且有批判性的人。然而我当时听到的简直太出色了。所以我上楼去和E.J.科里谈，E.J.说：我认识戴维·刘，戴维曾在我的实验室待过。

Well, my memories of getting to know David are pretty vivid and they start actually with a conversation with Pete Schultz. Pete had some really remarkable things to say about a young graduate student in his lab. And when Pete has advice like that, you tend to listen because he's a thoughtful and critical person. And yet what I was hearing was just remarkable. So I went up stairs to talk to EJ Corey and EJ said, I know David Liu, David was in my lab.

于是我第二次听到了一系列关于戴维的非凡评价。我想那时候，戴维，你好像是研究生三年级。

And I heard for the second time, a series of remarkable statements about David. And I think at that time, David, you were like a third year graduate student.

是的，我是。

Yeah, I was.

E.J.和我几乎当场就说，好吧，让我们把这个人招到哈佛化学系来。我不记得我们两人之间有哪怕一刻是那种更标准的想法，比如‘他还很年轻’，或者‘他做到了吗？他应该做博士后吗？’没有，想法就像是，你知道，那样的人才不常出现，所以我们就去招他吧。

EJ and I pretty much on the spot said, okay, let's recruit this guy to Harvard chemistry department. I don't recall there being a single moment between the two of us of sort of the more standard thinking, well, he's very young and like, has he done it? Should he do a postdoc? No, was like, you know, talents like that don't come along very often, so let's just go get him.

他们确实这么做了。

And so they did.

这是哈佛典型的招聘策略吗？让一个刚毕业的研究生掌管自己的实验室？

Is that Harvard's typical hiring strategy? Give someone just out of graduate school the keys to their own lab?

绝对不是。这说明他们认为大卫有多么特别。他告诉我们，他甚至没有意识到自己被招募，也不确定自己独立实验室的研究方向。然而，他的第一个项目——一种利用DNA序列生成非天然生物活性化合物库的方法——帮助推动了一个研究领域的发展。

Definitely not. That tells you how special they thought David was. He told us that he didn't even realize he was being recruited and wasn't even sure what direction he wanted to take an independent lab. And yet, his very first project, a method of using DNA sequences to generate libraries of non natural bioactive compounds, helped spur a field of research.

这个工具很好地展示了化学如何启发生物学，而生物学又能帮助拓展化学的可能性。所以，没错，化学生物学确实很酷。

And that tool is such a good example of how chemistry can inform biology, which can help expand the possibilities of chemistry. So yeah, chemical biology is pretty cool.

对于这里的非化学生物学背景的人（比如我），我们能稍微退一步吗？你告诉我们化学生物学是关于制造化学工具来回答生物学问题，但能详细说说吗？化学生物学到底是什么？

For the non chemical biologists here, me, can we back up a second? You told us chemical biology is about making chemical tools to answer biological questions, but can we expand on that? What exactly is chemical biology?

哦，我很高兴你问这个，Carrie，因为我确实认为这对领域外的人来说很困惑。事实上，我请Stuart和David谈谈这一点。我想我们是否可以首先讨论一下化学生物学的现状，因为当我试图让作家们对这些话题更感兴趣时，我觉得我们都对它有不同的理解。所以我想听听你们每个人是如何看待它的，你们自己是如何定义的？

Oh, I'm glad you asked, Carrie, because I really do think it's confusing to anyone outside of the field. And in fact, I asked Stuart and David to talk about that. I wondered if we could first just talk about the state of chemical biology because when I try to get writers to get a little more interested in writing on those topics, think we all think of it as different things. And so I wondered if I could hear from each of you, how you think of it, how do you define it to yourselves?

Lisa，你说得对，‘化学生物学’这个词对不同的人意味着不同的东西。但我认为这正是这个领域的独特之处和成功之处。我认为它比许多其他规定性很强的领域更具包容性。而且，尽管许多人可能做着非常不同的事情，但他们仍自认为是化学生物学家。我认为这是这个领域的一个真正优点。

I think you're right, Lisa, that the word chemical biology means different things to different people. But I actually think that's part of the specialness of the field and its success. It has been, I think more inclusive than many other fields, which tends to be very prescriptive. And I think the fact that just a lot of people identify themselves as chemical biologists, even though maybe they do very different things. So I think that's a real plus of the field.

我并不担心定义是什么。在我自己看来，反映我自己的兴趣，我认为化学生物学，对我来说一个关键问题是，作为一个对机制（包括生物学机制）感兴趣的人，在科学中区分相关性和因果性存在诸多挑战。我认为化学生物学是一种扰动系统的手段，只有通过扰动，我们才能区分相关性和因果性？我给学生们举过例子，其中一个就像是，如果你开车上班时看到一个闪烁的街道标志，写着‘前方事故’，你会感到沮丧，因为你知道你可能会迟到。但我们凭直觉知道，不应该下车去拔掉那个标志。

I'm not worried about like, what is the definition? I think in my own mind, just reflecting my own interests, I think of chemical biology, I think a really key issue for me is as someone who's interested in mechanism, including biological mechanism and in science where there's so many challenges distinguishing correlations from causality. And I think of chemical biology as this means to perturb systems and only through perturbation can we ever distinguish correlation and causality? I give the example to my students or a number of examples, but one is like, if you're driving into work and you see a flashing street sign that says accident ahead, you get frustrated because you know you're probably gonna be late. But we intuitively know not to get out of our car and unplug the street sign.

那不会有任何区别，对吧？但那就是一个实验。一个扰动实验。

It's not gonna have any any difference. Right? But that's an experiment. That's a perturbational experiment.

Stuart提供了一个更具体的例子，说明为什么拥有工具来测试这种相关性与因果关系的问题很重要，即好胆固醇和坏胆固醇的案例。几十年来，我们已经知道高水平的LDL（坏胆固醇）与心脏病风险增加有关，而较高水平的HDL（好胆固醇）与预防心脏病有关。但经过多年测试要么降低坏胆固醇、要么提高好胆固醇的药物，才证明LDL是导致疾病的原因，而HDL仅仅是与疾病相关。

Stuart offered a more concrete example of why it's important to have tools to test this correlation causation question, the case of good and bad cholesterol. We've known for decades that high levels of LDL or bad cholesterol are associated with an increased risk of heart disease, and higher levels of HDL are associated with protection from heart disease. But it took years of testing drugs that either lower bad cholesterol or raise good cholesterol to prove LDL causes the disease, whereas HDL is simply correlated with it.

那是因为它是一种生物标志物，与心血管疾病存在相关性。所以化学生物学正好提供了各种神奇的工具，以这种方式来探究生物系统。

That's because it's a biomarker. It's a correlation of cardiovascular disease. So chemical biology just provides these amazing tools of all sorts to interrogate biological systems in that way.

是的，斯图尔特说得非常好。我完全同意他的观点。你知道吗，我认为我们确实受益于仍然保持的社群感——尽管如今的化学生物学已经涵盖了从用化学阐释生物学、利用生物学方面推进化学、到在基因组上实施化学等方方面面，但我们仍然都享受并受到所有这些领域、所有这些方法的激励，对利用生命启示探索生物学充满好奇。对我来说，这真正体现了化学生物学的特别之处。它更像是一种哲学，而非一套具体问题。

Yeah, Stuart said it beautifully. I totally agree with him. And you know what, I think we do benefit from still feeling like a community in that despite the fact that chemical biology these days has come to include everything from using chemistry to illuminate biology, to using aspects of biology, to advanced chemistry, to performing chemistry on the genome that we all still enjoy and are stimulated by, are very curious about all of these fields, all of these approaches to using lessons from life, to exploring biology. And to me, that's really what makes chemical biology special. It feels more like a philosophy than it does a set of problems.

作为一名化学生物学家，我对此深有共鸣，因为我们确实运用化学来解答一系列生物学问题。这个领域已经产生了许多非常有用的工具，比如能让你研究细胞并在其原始环境中进行反应的探针。

This really resonates with me as a chemical biologist because we do use chemistry to answer a bunch of biological questions. And a lot of really useful tools have come out of this field, like probes that allow you to study cells and do reactions in their original environment.

让我印象深刻的一点是，如今大型制药公司喜欢谈论他们如何建立了化学生物学专业能力。这在我看来是一种转变，很可能是由大卫和斯图尔特等实验室产出的许多变革性工具推动的。这两位科学家都对该领域做出了巨大贡献，成为许多生物技术公司的基础。所以我想知道，这一切对他们实验室的学生意味着什么？你们是否觉得这个领域如今有了不同的形象？

One thing that strikes me is that big drug companies now like to talk about how they've built up chemical biology expertise. That feels like a shift to me, probably one driven by the many transformational tools coming out of labs like David and Stuart's. Both of these scientists have made huge contributions to the field that have been the basis of many, many biotech companies. So I wondered what all this has meant for the students in their labs. Does it feel to you like there's the field has a a different kind of profile now?

你们发现学生比过去更频繁地被工业界追求吗？

Do you find your students being more often pursued by industry than in the past?

是的，也许我先来回答这个问题，因为斯图尔特可能太谦虚而不愿说一些我会说的话。我认为，化学生物学的突出地位以及将其学生视为不仅是生物技术公司，还有制药公司真正优选招聘对象的转变，在我看来，确实始于一些杰出的化学生物学家，即斯图尔特·施赖伯、彼得·舒尔茨及其同代人，开始培养那些在智力和奉献精神上都非常出色的学生。制药和生物技术公司最初可能认为雇佣他们是在冒险，但很快意识到这些学生最终成为了公司的明星。领导层迅速充满了来自这些实验室的受训者。我认为，文化变革源于这些实验室证明，分子科学产业中一些最具创造力和生产力的贡献者来自化学生物学实验室。我完全同意你所说的，过去加入化学生物学实验室的学生可能有一种不安全感，担心他们比那些在传统合成有机化学实验室受训的人更难被工业界雇佣。

Yeah, maybe I'll take this one first because Stuart may be too modest to say a few things that I'll say, which is, I think it's largely the prominence of chemical biology and the transition in viewing chemical biology students as really choice recruits for not only biotech companies, but pharmaceutical companies, really, in my opinion, began when some of the luminary chemical biologists, namely Stuart Schreiber, Peter Schultz, and their contemporaries, began training students who were so incredible in their intellect and their dedication that I think pharma companies and biotech companies that initially might've been viewed as taking a risk hiring them quickly realized those students ended up becoming stars at the companies. And the leadership ranks were populated quickly with trainees from those labs. And the culture change, I think, grew out of those labs demonstrating that some of the most creative and productive contributors to the molecular science industries came from chemical biology labs. And I definitely agree with what you're saying, that it used to be that students who joined chemical biology labs, I think, had an insecurity that perhaps they would be less hireable by industry than those who trained in traditional synthetic organic chemistry labs.

而现在我看到一个彻底的巨变，化学生物学的学生毫无困难地被各种各样的工业界雇佣，也被各种各样的学术部门聘用。

And now I see a complete sea change that chemical biology students have no problem getting hired by a large variety industries, to a large variety of academic departments as well.

我会说这个转变是缓慢的，跨越了几十年，但确实正如大卫所描述的那样。我认为我们的学生不再那么担心这个问题了，而曾有一段时间，学生可能会觉得如果他们从事化学生物学，就必须极力强调他们工作中合成有机化学的部分。我认为他们现在没有人再那样想了。我认为他们大多数人更关心的是能否证明自己是真正优秀的解决问题者。他们知道如何应对并解决难题，对吧？

I would say that the transition was slow and it's been over decades, but it is exactly as David describes. I don't think our students think so much anymore about this issue, whereas there was a period of time when students might feel that if they were in chemical biology, they had to really stress the synthetic organic chemistry elements of their chemical biology. I don't think any of them think that way now. I think most of them are more concerned whether they can show that they are really good problem solvers. They know how to tackle a difficult problem and solve it, right?

而这将是评判他们的标准。

And that that's how they'll be judged.

说到解决难题，一个目前仍在每个人心头的重要问题就是结束全球大流行。事实证明，化学生物学家也在其中扮演角色。斯图尔特和大卫都是一个名为‘科学家阻止COVID-19’的非正式团体的成员，该团体在幕后充当政府官员的过滤器，因为他们试图解析BioArchive等预印本服务器上涌现的大量COVID研究。基本上，他们试图从海量选项中——无论是潜在的治疗方法还是疫苗技术——提炼出最有可能成功的那些。他们还就口罩佩戴和检测提供了指导，斯图尔特和大卫惋惜这些建议未被遵循。

Speaking of solving difficult problems, one big problem that is still front of mind for everyone right now is ending the global pandemic. And it turns out that's one that chemical biologists are playing a role in too. Stuart and David were both part of an informal group called Scientists to Stop COVID nineteen that, behind the scenes, acted as a filter for government officials as they tried to parse the flood of COVID research popping up on preprint servers like BioArchive. Basically, they were trying to distill down the massive options, whether potential treatments or vaccine technologies, to the ones most likely to succeed. And then they also offered guidance on masking and testing, which Stuart and David lament was not followed.

他们分享了这段经历让他们对科学与政治之间棘手的交集有了怎样的认识。

They shared what the experience taught them about the tricky intersection of science and politics.

但大卫和斯图尔特是如何加入这个团体的呢？

But how did David and Stuart get involved in this group?

嗯，这始于一位风险投资界的成员邀请了几位他认为愿意抛开政治因素参加视频会议的知名科学家。我会让斯图尔特来描述。

Well, it began with a member of the venture capital community asking a few prominent scientists, ones he felt would be willing to put politics aside to hop on a video conference. I'll let Stuart describe it.

当时的情况是我们答应了。而且我们每天都在阅读bioRxiv，关注所有关于这个话题的新论文。他说预计会有大约30人参加。但第一次会议就有数百人，甚至可能接近一千人参加。令我们惊讶的是，我们注意到有很多来自白宫的知名人士、州长、国会议员、市长、娱乐界人士、NBA、PGA、NHL、美国职业棒球大联盟等等。

What happened was we said, sure. And we'd all been reading bioRxiv every day, every paper coming out on this topic. And so he said, there'll be about 30 people will show up. And that very first meeting, many hundreds, maybe reaching a thousand people showed up. And to our surprise, we noticed that there were a lot of well known people from the White House, governors, members of Congress, mayors, members of the entertainment industry, NBA, PGA, NHL, Major League Baseball, etcetera.

然后我想之后我们说，我们需要认真对待这件事。如果这种草根理念有机会将科学与政策制定者结合起来。我知道我是为自己说话，认为大卫也一样。有九个月或更长时间，我想这是我们做的大部分事情。我们几乎把其他一切都放在一边，不断投入。而且这种情况一直持续到今天。

And then I think after that we said, we need to get real serious about this. If this sort of grassroots notion and an opportunity to integrate science with policymakers. I know I speak for myself, think David is the same. There was a nine month period or more where I think it was the vast majority of everything we did. It just sort of put everything else aside and we were constantly And it does continue to this day.

我的意思是，我知道那个世界的人会联系我。

I mean, I know I'm contacted by members of that world.

在2020年，当世界显然将发生重大变化时，每个人都在尽力贡献自己的力量。科学家们，我认为，认识到我们有能力帮助梳理由信息共享技术、社交媒体和预印本服务器的进步所带来的海量信息，而公众和政策制定者将面临真正的挑战，去区分良莠，甚至理解即使10项精心设计的研究也可能得出不同的结论，但你可以从中汲取经验以达成共识意见。

In this 2020, when it became apparent that the world was going to change in a major way, everybody was trying to do their part. Scientists, I think, recognize that we're in a position to be able to help sort through the massive amount of information enabled by advances in information sharing technologies and social media, in preprint servers, and that the public and policymakers were going to have a real challenge to separate the wheat from the chaff, to even understand that even 10 well designed studies can come to different conclusions, but you can extract the lessons to arrive at consensus opinions.

我认为我们预见到的那场‘火车失事’是，可能性实在太多了。因此我们会花很多时间在一起，以理清思路。

The train wreck I think we saw coming was that there were just so many possibilities out there. And so we would spend a lot of time together to get clear ideas.

我想我们认识到一个现实：那些后勤挑战虽然可以克服，但当政治介入到使每个决策都陷入瘫痪的程度时，实际上就变得不可逾越了。这对我们来说是一个真正的教训，一个悬而未决的问题，也是我们为未来应对大流行病需要努力改进的一课。

I think we learned the reality that those logistical challenges while surmountable, become, in effect, insurmountable when politics are introduced at a level that makes every decision paralyzed. It's a real lesson for us, unresolved problem and a lesson for us to work on for the future pandemics.

我想知道过去这两年，稍微短一点，让你们对公众如何看待科学是如何进行的有了怎样的认识？

I wondered what the last two years, a little less, has taught you about just sort of the public's perception of how science is done?

首先，我认为询问科学家对科学认知的看法总是危险的，因为我们并非无偏见的群体，甚至我们与周围人的经历也是经过高度筛选的。我们生活在非代表性的社区中，既不代表整个国家，也不代表整个世界。但我愿意希望，并且乐观的一面认为，至少这场疫情提醒了公众，我们面临和将要面临的一些最大挑战最终都将归结于科学，而潜在的解决方案也将来自科学。至少这是我的希望。

Well, first, it's always, I think, dangerous to ask scientists about their view of the perception of science because we're not an unbiased party and what we, even the experiences we have with the people around us are highly filtered. We live in non representative communities, non representative of the entire country, non representative of the entire world. But I'd like to hope and the optimistic side of me thinks that if nothing else, the pandemic served as a reminder to the general public that some of the biggest challenges that we face and will face ultimately will boil down to science and the potential solutions will come from science. At least that's what I hope.

我认同大卫的希望。理应如此，但当然最终结果尚未定论。我们正处于一个社会层面的奇怪时期。我认为，我们必须真正努力让世界其他地方继续理解科学的价值。我们不能认为这是理所当然的。

I share David's hope. It ought to be that way, but of course the verdict is still out. We're at a strange time societally. And I think, we have to really work hard to continue to get the rest of the world to understand the value of science. We can't take it for granted.

我们将短暂休息一下。回来后，我们将聆听大卫和斯图尔特讲述哪些研究吸引着他们，以及他们的科学工作如何让他们更了解自己。

We're going to take a short break. And when we come back, we'll hear from David and Stuart about what research captivates them and how their science teaches them about themselves.

大家好，我是吉娜·维塔莱，CNEN的助理编辑。我来提醒大家一个了解化学与化学工程领域最新动态的好方法——我们的每周通讯。这份通讯每周将CNEN的精华内容直接送达您的收件箱。您将获得最重要的研究发现、需要了解的新兴趋势以保持领先，还有最新的职位和职业见解，以及一些非常酷的讲座内容，比如与科学插画网站Compound Interest合作的周期图形，或者展示中心科学之美的“图片中的化学”。

Hi, everyone. Gina Vitale here. I'm an assistant editor at CNEN, and I'm here to remind you about a great way to stay up to date with the latest news from the world of chemistry and chemical engineering, our weekly newsletter. The newsletter delivers the best of CNEN to your inbox every week. You'll get the most important research findings, the emerging trends you need to know to get ahead, plus the latest jobs and career insights, and also some really cool lecture content, like periodic graphics in collaboration with the science illustration website Compound Interest, or chemistry in pictures, which showcases the beauty of the central science.

您可以在 bit.lychemnewsletter 注册我们的通讯。只需将我们指向您的收件箱，剩下的交给我们。再次说明，链接是 bit.ly/chemnewsletter。现在回到节目。

You can sign up for our newsletter at bit.lychemnewsletter. Just point us to your inbox, and we'll take it from there. Again, that link is bit.ly/chemnewsletter. And now back to the show.

那么，在本期节目的第一部分，我们听到了大卫和斯图尔特对科学和社会做出的一些贡献。他们的工作确实涵盖了非常广泛的领域。

So, in the first part of this episode, we hear about some of the contributions David and Stuart have made to science and society. Their work has really covered a lot of territory.

没错。帮助建立化学生物学这一新科学领域、发明新技术、发现药物、创办生物技术公司，并在疫情期间为政策制定者提供稳健的声音。

Right. Helping to establish a new field of science in chemical biology, inventing new technologies, discovering drugs, starting biotech companies, and pitching in to be steady voices to policymakers amid the pandemic.

这两位可真忙啊。

Those two sure are busy.

确实如此。并且希望很明显，大卫和斯图尔特一直在思考新的问题，这些问题常常开辟出全新的研究方向。我想听听这两位思想开阔的人是如何产生新想法的。比如，当你对这么多不同的事物都感到好奇时，你如何决定下一步做什么？你如何设定优先级？

Seriously. And hopefully, it's clear that David and Stuart are constantly pondering new questions, ones that very often open up whole new veins of research. I wanted to hear about how these two expansive minds come up with new ideas. Like, when you're someone who is curious about so many different things, how do you decide what to do next? How do you set your priorities?

结果发现，提出这个问题本身在我们的对话中也开辟了一个探索的新方向，一个变得非常个人化的方向。

It turns out that asking this question opened up its own vein of exploration in our conversation, one that became deeply personal.

作为一名学者的最大好处，或许也是成为学者的唯一真正理由——相比于在科学领域内外或智力追求等方面可能从事的许多其他事情——就是能够自由地与这些极具才华的受训者合作，共同研究我们集体感兴趣的领域问题。因此，就如何选择科学领域而言，对我而言，我猜对斯图尔特也是如此，这确实是由好奇心驱动的，我们认为哪里能取得最大进展，哪些是最有趣的问题。对我来说，这从来不是为了创办一家伟大的公司，因为如果你选择了一个真正有趣的问题，如果它最终产生了你所期望的那种影响，那么创办公司的机会往往会自然而然地出现。

The best part of being an academic and maybe the only real reason to be an academic, as opposed to many other things one could do in the sciences or outside of the sciences, in intellectual pursuits, etcetera, is to have the freedom to work with these incredibly talented trainees, but working on problems in areas that are of interest to us collectively. So with respect to how to choose science areas, for me, and I suspect for Stuart, it's really been driven by curiosity and where we think the biggest advances can be made, what the most interesting problems are. It's never been for me what would make a great company, because if you've chosen a really interesting problem, if it turns out to have the kind of impact that you were hoping, then the company creation opportunities tend to come naturally.

对我来说，它总是像在某个时候、某个地方，发生了某件事，然后你就会想，这太棒了。这太神奇了。比如这是怎么发生的？所以这是一种对神秘事物的兴奋感。此时此刻，最让我着迷的是那个我可能已经太老而无法再研究的问题。

For me, it's always been like somehow, somewhere along the way, something happens and you just think, that's awesome. That's amazing. Like how does that happen? So it's the excitement about a mystery. At this moment, the one that fascinates me is the one that I'm probably too old to ever study now.

但我终于知道了这个问题的答案，许多学生问我，如果你能重新开始，你会做什么？比如，有没有比意识是什么更引人入胜、更迷人的问题？我们是如何知道我们存在，我们有自我意识的？你知道，大脑里并没有一个小人在为我们放映电影。我的意思是，这是怎么发生的，对吧？

But I do know finally the answer to the question, which a lot of students ask me, if you were to start all over again, what would you do? Like, is there a problem more interesting and fascinating than the question of what is consciousness? How is it that we know that we are, you know, we have a self awareness? You know, there's not a little homunculus in the brain that's, you know, running a movie for us. I mean, like how does that happen, right?

所以总是类似这样的事情。然后问自己，我会如何回答这个问题？

So it's always something like that. And then asking, how would I answer that question?

我猜他开始在化学生物学中寻找答案了。

I have a hunch he got looking for answers in chemical biology.

我认为你绝对猜对了。不过，斯图尔特可能会声称自己太老了，无法彻底弄清意识的本质——顺便说一句，我绝不会低估他那颗好奇的心——但他花了很多时间思考这个关于什么造就了我们，嗯，我们自己的问题。这部分 preoccupation 源于他最近的一段非常个人化的经历。我问了他一个即兴的问题，关于他钦佩的研究，这让我们进一步深入了这个话题。我想知道，在你们自己的实验室之外，有哪些科学研究让你们感到真正兴奋。

I think you're definitely on the right track. Stuart might claim he's too old to get to the bottom of consciousness though, side note, I would never count that curious mind out but he spends a lot of time pondering this question of what makes us, well, us. Part of that preoccupation comes from a deeply personal experience he recently had. I asked him a sort of off the cuff question about what research he admires, and it took us further down that path. I'm wondering what science is going on outside of your own labs that you feel really excited about.

我可以立刻告诉你我想到的两个。一个是研究人类历史的能力，这来自于对古老人群基因组进行测序的能力，比如十万年前的骨骼，然后分析它们，发现我们与尼安德特人和丹尼索瓦人发生了基因渗入，并且我们获得了导致重症COVID的头号风险等位基因，这是一个渗入的尼安德特人基因。所以这些具有医学相关性，但在我看来更重要的是，它们告诉我们我们是谁，我们从哪里来。美洲人的起源是今年早些时候一篇《自然》论文的主题，看到这些发现真是绝对令人惊叹。我想我知道为什么它对我如此有吸引力。

I can tell you two that come to mind right away. So one is our ability to study the history of humans that comes from the ability to sequence archaic genomes, 100,000 year old bones and then to analyze them and to see that we introgressed with Neanderthals and Denisovans and that we picked up the number one risk allele for severe COVID, it's an introgressed Neanderthal gene. So these are medically relevant, but more important from my point of view, they tell us who we are, where we come from. The people of America's was a subject of a nature paper earlier this year, just absolutely astonishing to see. I think I know why it's so fascinating to me.

这是另一个个人兴趣——基因谱系学的一个分支，它很幸运地给了我一生中最快乐的经历之一，去弄清楚我是谁，我来自哪里？我暗示过的另一个领域，虽然还处于早期阶段，但我们仍然不知道这团‘湿件’（指大脑）是如何创造的。并最终在人类中创造出意识。所以我觉得这非常迷人。因此，对我来说，这是一个惊人的领域，似乎已经成熟，适合现代方法去探索。

It is an offshoot of another personal interest of genetic genealogy, which happily gave me one of the most joyful experiences of my life and figuring out like, who am I and where do I come from? The other one I've kind of hinted at, it's still early days, but we still have no clue how this wetware creates. And then ultimately in humans creates consciousness. So I find this really fascinating. So to me, this is just an amazing area that is sort of ripe for modern approaches.

斯图尔特，你提到做过自己的基因谱系研究，在我们整个谈话过程中，感觉你多次暗示了一些吸引你、激励你去了解我们是谁的事情。也许你可以和我们简单谈谈你做自己基因组分析的经历。

Stuart, you referenced having done your own genealogy and throughout our conversation, it's felt like you've made a number of allusions to things that sort of captivate you, motivate you in terms of knowing who we are. Maybe you could tell us a little bit about doing your own genome.

我能说的是，我原以为我知道自己是谁、来自哪里。但这一切以多种方式被彻底颠覆了，不仅仅是我，还有我的母亲，她不知道她来自哪里、她是谁。所以，我将其描述为一个超现实的阶段，然后过渡到一个失去锚定的阶段。我觉得自己总体上是个很有根基的人，但在这个时期不是。

What I can say is that I thought I had a knowledge of who I am and where I come from. And it all got turned upside down in multiple ways and not just me, but my mother and not knowing where she came from and who she is. And so that is a, I described it as a surreal phase that moves in into an unmoored phase. And I feel like I'm a very moored person in general, but not at this period.

听起来这里发生了非常严重的事情。

It sounds like something very serious happened here.

是的，这是斯图尔特在各种场合写过并谈论过的事情。他母亲因阿尔茨海默病去世后，斯图尔特和他兄弟想知道自己是否具有更高的患病风险。于是他们做了我们许多人做过的事——购买了23andMe基因检测套件来测试DNA。当结果出来时，斯图尔特发现他原以为的生父其实并不是。他在哈佛校友杂志上发表了一篇非常个人化且深思熟虑的文章，讲述了自己的经历。

Yeah, this is something Stuart has written about and talked a bit about in various venues. After his mom died of Alzheimer's, Stuart and his brother wanted to know if they had a higher risk of getting the disease. So they did what a lot of us have done they bought 23andMe kits to test their DNA. When the results came back, Stuart learned that the man he thought was his biological father wasn't. He wrote a very personal and thoughtful article in Harvard's Alumni Magazine about his experience.

我们会在本期节目说明中附上这篇文章链接。文中，斯图尔特写道自己最初感到麻木，然后经历了深刻的情感动荡，最后对解开身世之谜产生了浓厚兴趣。他将科学家的问题解决能力转向了揭开家族真相。

We'll link to that article in this episode's show notes. In it, Stewart writes about at first feeling numb, then experiencing deep emotional turmoil, and then becoming intrigued by solving the mystery of his heritage. He turned his problem solving skills as a scientist to uncovering the truth of his family.

没错。最终，这帮助斯图尔特理解了许多关于他童年以及与抚养他长大的那位男士的关系。正如他告诉我们，这也打开了新大门，并进一步强化了对'我们人类是谁、来自何方'这个问题的迷恋。

Yes. And, ultimately, it helped Stuart understand a lot about his childhood and relationship with the man who raised him. And as he told us, it also opened doors and only reinforced this fascination with the question of who we humans are and where we come from.

于是我进行这些寻根之旅，与家人相见，充满喜悦。太不可思议了。我确实认为这自然延伸出一个问题：为什么要止步于此？我们现在拥有追溯所有人源流的技术。目前我们可以回溯十万年。

So I go on these pilgrimages, I meet family and it's just joyful. It's amazing. And I do think that this has just carried over to say, well, like why stop there? We now have the technology to know about all of us all the way back. Right now we can go a 100,000 back.

很快，我认为我们将能追溯到人类分化之初。我们正在了解多次走出非洲又返回非洲的迁徙浪潮。这是对自我认知的贪婪渴望。对我而言，虽然需要亲身经历才能体会，但这无疑将伴随我的余生。

Pretty soon, I think we'll go back to the split. We're learning about the multiple waves out of Africa, back into Africa. It's this voracious appetite for knowing who we are. And for me, it took something personal to get, but it'll be with me now the rest of my life, no doubt.

可惜听众看不到我脸上灿烂的笑容，因为每次听斯图尔特讲述这个故事——他的故事——都让我深受鼓舞，原因诸多。我想这提醒了我，提醒了我们所有人，也肯定提醒了斯图尔特，我们彼此是多么紧密相连。尽管当今社会轻易强调我们的差异，但我们在诸多方面如此相似。希望斯图尔特不介意我分享一个与他刚才叙述直接相关的故事。斯图尔特是个极其沉稳的人，99.99%的时间都是如此。

It's too bad your listeners can't see the huge grin on my face because every time I hear Stuart talk about the story, his story, it's just so inspiring to me for many reasons. I think it reminds me, reminds all of us, I'm sure reminds Stuart, how connected we all are. How despite the easy emphasis these days on our differences, that we're so similar in so many ways. And hopefully Stuart won't mind me sharing a story that directly interfaces with some of his recount just now. But Stuart is an incredibly moored person, 99.99% of the time.

事实上，我唯一一次听到他声音颤抖是他给我打电话时。我突然接到电话，斯图尔特简单地说：'大卫，我现在感觉迷失了方向'——这是他的原话。他向我解释了发现的家族历史。我只记得当时百感交集，包括深受感动于斯图尔特愿意与我分享他即将踏上的探索之旅。我记得我的回应——至今仍强烈感受到——我说：'斯图尔特，我们多么幸运，你的生母和生父得以相遇并有机会孕育了你，让你、你的科学、由你工作衍生出的领域，以及你热情带来的社会福祉得以见到天日。'

In fact, the only time I've ever heard him have a sort of quiver in his voice was when he called me. I got a call out of the blue and Stuart said simply, David, I'm feeling unmoored right now, was the words he used. And he explained to me what he had learned about his family history. And I just remember being filled with all sorts of thoughts, including how touched I was that Stuart was sharing this adventure that he was about to embark on with me. And I remember my response to him, which I continue to feel very strongly to this day, which was, well, Stuart, how incredibly fortunate we all are that your biological mother and biological father met and had the opportunity to create you so that you, your science and the fields that have grown from your work and the societal benefits that have come from your passions could live to see the light of day.

谢谢你，大卫。你太客气了。

Thank you, David. You're very kind.

对我而言，斯图尔特以理性而富有同情心的方式处理这件事，在家族秘密中找到喜悦，并以此深入探索自我认同问题，这充分体现了斯图尔特作为科学家和人的本质。

To me, the cerebral compassionate way Stuart is processing this, finding joy in a family secret and using it to push further into these questions of self feels so indicative of who Stuart is as a scientist and a human.

我特别喜欢这个观点：科学，尤其是化学生物学，有如此多的方式告诉我们我们是谁，无论是意味着我们从哪里来，还是什么使我们成为人类。确实如此。

I love this idea that there are so many ways for science and for chemical biology in particular to tell us about who we are, whether that means where we came from or what make us human beings human. Indeed.

斯图尔特说如果可以重来一次，他会专注于这个领域，但我感觉仍有机会看到他的一些工作从个人生活转向实验室。

Stuart says he would focus on this area if he could do it all over again, but I have a feeling there's still a chance to see some of this work transitioned out of his personal life and into the lab.

或者也许一些年轻的化学生物学家会受到启发去探索这些问题。

Or maybe some young chemical biologist will be inspired to pursue those questions.

也许吧。说到质疑我们是谁，我将让斯图尔特留下一些思考，给那些担心自己在科学界的位置以及自我认知是否与他人对其科学家身份的看法一致的年轻科学家们。

Maybe. Speaking of questioning who we are, I'm going to let Stuart leave us with some thoughts for any young scientists out there worried about their place in the community and whether their sense of self aligns with how other people perceive them as scientists.

大卫和我可能都经历过的是，人们要么告诉我们因为未经培训或不懂而不能做某事，然后我们又会被评判是否对化学做出了贡献。我告诉过你我的想法。如果你是一名化学家，受过化学训练，你发现了激发你好奇心和热情的东西，并推动了知识进步，那么根据定义，这就是化学。化学在进化，它通过化学家的行动而进化。

Probably David and I both have experienced along the way is people either telling us that we can't do something because we are not trained or we don't know. And then also we become judged as to whether we're contributing to chemistry or not. I told you my thoughts on that one. If you're a chemist and you're trained in chemistry and you find something that strikes your curiosity and your passion and you advance knowledge, it's chemistry by definition. Chemistry evolves and it evolves through the actions of chemists.

如果你想从这些科学家那里听到更多好建议，一个好的起点是大卫在CNN 2018年“才华十二人”研讨会上的精彩主题演讲，他在那里谈到了他走向科学成功的道路，以及一路走来关于作为一名研究者和导师的所学。这是一个发人深省的演讲。我鼓励听众去听听看。你可以在CNN网站上找到他演讲的视频。

If you wanna hear more good advice from these scientists, a good place to start is David's brilliant keynote address at CNN's twenty eighteen Talented Twelve Symposium, where he talked about his path to scientific success and what he's learned along the way about being a researcher and mentor. It's a poignant talk. I'd encourage listeners to check it out. You can find a video of his talk on CNN's website.

CNN记者Ryan Cross也写了一篇关于大卫的精彩报道，你可以在我们对他多年来获得的众多奖项的报道中了解更多关于斯图尔特的生平和职业生涯。我们会在节目说明中链接所有这些报道。本集由Lisa Jarvis撰写，由我Carrie Jansen制作。故事编辑是Michael McCoy和Amanda Yarnell。制作协助来自Gina Vitale。

CNN reporter Ryan Cross also wrote a great profile of David, and you can learn more about Stewart's life and career in our coverage of the many awards he's received over the years. We'll link to all of those stories in the show notes. This episode was written by Lisa Jarvis and produced by me, Carrie Jansen. Story editing by Michael McCoy and Amanda Yarnell. Production assistance from Gina Vitale.

本集音乐是Anthony Lazaro的《Different Kind of Love》器乐版和《Something New》器乐版。宣传音乐是Kevin MacLeod的《Plain Loafer》。《立体化学》是《化学与工程新闻》的官方播客。CNN是由美国化学会出版的独立新闻媒体。

Music in this episode was Different Kind of Love, instrumental version, and Something New, instrumental version by Anthony Lazaro. The promo music was Plain Loafer by Kevin MacLeod. Stereochemistry is the official podcast of chemical and engineering news. CNN is an independent news outlet published by the American Chemical Society.

感谢收听。

Thanks for listening.