What’s the Future of Gene Editing?
One of the most surprising and remarkable discoveries in recent scientific history has been CRISPR.
近代科学史上最令人惊讶、最引人注目的发现之一就是 CRISPR。
Short for Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR is a form of immune system that evolved in bacteria more than a billion years ago to defend against persistent viral threats.
CRISPR 是成簇规则间隔短回文重复序列的缩写，是十亿多年前在细菌中进化出来的一种免疫系统形式，用于防御持续的病毒威胁。
Under attack, bacteria can snip a small fragment of a virus’s DNA, store it in the CRISPR region of their genome, and then use it to recognize and destroy the same virus if it returns.
受到攻击时，细菌可以剪下病毒 DNA 的一小段，将其存储在基因组的 CRISPR 区域中，然后在病毒卷土重来时用它来识别并消灭它。
The CRISPR-Cas9 system, to give it its longer name, consists of a short strand of guide RNA that identifies where to cut the DNA and a protein that acts as the molecular scissors.
CRISPR-Cas9 系统（其名称更长）由一条引导 RNA 短链（识别 DNA 切割位置）和充当分子剪刀的蛋白质组成。
What made this system truly revolutionary was the demonstration in 2012 that it could be reprogrammed with different pieces of guide RNA to edit virtually any genome in any species, and at a level of precision and ease that far surpassed existing gene-editing tools.
使该系统真正具有革命性的是，2012 年的演示表明，它可以用不同的向导 RNA 片段进行重新编程，以编辑任何物种的几乎任何基因组，并且其精确度和易用性远远超过现有的基因编辑工具。
Since then, the editing capability of CRISPR has been tested on everything from developing disease treatments to engineering drought-resistant crops to resurrecting genes of extinct species.
从那时起，CRISPR 的编辑能力已经在从开发疾病治疗方法到改造抗旱作物，再到复活灭绝物种的基因等各个方面进行了测试。
The possibilities have expanded so rapidly that researchers, ethicists, and regulators have found themselves struggling to keep up.
这种可能性的扩展如此之快，以至于研究人员、伦理学家和监管机构发现自己很难跟上。
One person acutely aware of the power of CRISPR is Jennifer Doudna , co-developer of the technology.
该技术的联合开发者 Jennifer Doudna 是一位敏锐地意识到 CRISPR 力量的人。
Doudna, who received the Nobel Prize in Chemistry in 2020 with Emmanuelle Charpentier for this pioneering work, has been a prominent voice not only for its vast potential but also for its responsible and ethical use.
杜德纳 (Doudna) 因这项开创性工作与埃曼纽尔·卡彭蒂耶 (Emmanuelle Charpentier) 一起获得了 2020 年诺贝尔化学奖，她不仅因其巨大的潜力，而且因其负责任和合乎道德的使用而成为知名人士。
In this episode of The Joy of Why , Doudna tells co-host Janna Levin how her early, “rebellious,” decision to study RNA led her on a serendipitous path to one of biology’s most transformative discoveries.
在《The Joy of Why》的这一集中，杜德娜告诉联合主持人詹娜·莱文 (Janna Levin)，她早期“叛逆”的研究 RNA 的决定如何让她走上了一条偶然的道路，获得了生物学上最具变革性的发现之一。
They also discuss the breakthroughs, barriers, and frontiers that will define CRISPR’s true impact.
他们还讨论了将定义 CRISPR 真正影响的突破、障碍和前沿。
Listen on Apple Podcasts , Spotify , TuneIn or your favorite podcasting app, or you can stream it from Quanta .
在 Apple 播客、Spotify、TuneIn 或您最喜爱的播客应用程序上收听，或者您也可以从 Quanta 进行流式传输。
All episodes Your browser does not support the audio element.
所有剧集 您的浏览器不支持音频元素。
00:00 / 51:27 APPLE SPOTIFY
00:00 / 51:27 苹果 Spotify
Okay, here we go.
好的，我们开始吧。
I’m Janna Levin.
我是詹娜·莱文。
And I’m Steve Strogatz.
我是史蒂夫·斯特罗加茨。
And this is The Joy of Why .
这就是“为什么的喜悦”。
A podcast from Quanta Magazine , where we discuss some of the biggest unanswered questions in math and science today.
来自《Quanta》杂志的播客，我们在其中讨论当今数学和科学中一些尚未解答的最大问题。
Hi, Steve.
嗨，史蒂夫。
Here we are.
我们到了。
Hi, Janna.
嗨，詹娜。
It’s a new season.
这是一个新的季节。
I know, this is fun.
我知道，这很有趣。
Season Five.
第五季。
I’m pretty excited to talk to you about CRISPR today.
我很高兴今天能和大家谈论 CRISPR。
Have we ever had this conversation?
我们曾经有过这样的谈话吗？
Do you remember first learning about the CRISPR mechanism for gene editing?
您还记得第一次了解基因编辑的 CRISPR 机制吗？
Well, I, I have heard of CRISPR, but I barely know anything about it.
嗯,我,我听说过CRISPR,但是我对它几乎一无所知。
Should I think of it as some kind of molecular scissors that can do chopping of bacterial DNA by the bacterium itself?
我是否应该将其视为某种分子剪刀，可以通过细菌本身来切割细菌 DNA？
Yeah, gosh, now you’re going to be challenging me, but yes.
是的，天哪，现在你要挑战我了，但是是的。
CRISPR, it’s a mechanism that can chop the DNA and then insert it.
CRISPR，它是一种可以切割 DNA 然后将其插入的机制。
So it’s a combination of a cut and a paste.
所以它是剪切和粘贴的组合。
And, I so distinctly remember hearing someone describe to me that there was a naturally occurring mechanism in bacteria which indicated they could edit their own genome and splice in the DNA of an invading virus, for instance, and store it for later so that it was more effective as an immune system if that same virus attacks.
而且，我清楚地记得听到有人向我描述，细菌中有一种自然发生的机制，表明它们可以编辑自己的基因组并剪接入侵病毒的 DNA，并将其存储起来以供日后使用，以便在相同病毒攻击时作为免疫系统更有效。
It’s a really cool idea in itself.
这本身就是一个很酷的想法。
I mean, aside from any applications it might have, I think I remember from high school biology that bacteria don’t have any immune system.
我的意思是，除了它可能有的任何应用之外，我想我记得高中生物学中细菌没有任何免疫系统。
Yeah.
是的。
I mean, pretty simple organism.
我的意思是，非常简单的有机体。
I think about this also, if you just imagine its molecules acting as prescribed, right?
我也想到了这一点，如果你想象它的分子按照规定发挥作用，对吗？
Just moving around.
只是四处走动。
When you hear it from this perspective, it sounds like a stroke of genius.
当你从这个角度听到它时，这听起来像是天才之举。
Yet, there’s really nobody doing the thinking.
然而，确实没有人思考。
It’s just molecules responding.
这只是分子的反应。
You know, thank you for saying that.
你知道，谢谢你这么说。
Because it’s so easy when you hear biologists talk about this or that mechanism.
因为当你听到生物学家谈论这个或那个机制时，这很容易。
It’s good to remember there’s nobody home.
最好记住家里没人。
This is, this is molecules.
这是，这是分子。
Yeah.
是的。
It’s just a little bit of positive charge making it move a little bit towards this.
只是一点点正电荷让它朝这个方向移动一点点。
It is incredible that through this kind of iterative steps of just very simple application of basically electrical attraction that something this sophisticated could emerge, and is essential to the survival of an organism, and even the definition of an organism.
令人难以置信的是，通过这种非常简单的基本电吸引力应用的迭代步骤，就可以出现如此复杂的东西，并且对于有机体的生存，甚至有机体的定义至关重要。
Absolutely fascinating.
绝对令人着迷。
Of course, this is our history.
当然，这是我们的历史。
We come from very simple organisms ultimately all the way back down, and yet we don’t have a CRISPR mechanism.
我们来自非常简单的有机体，最终一路回归，但我们没有 CRISPR 机制。
So, let me tell you about our guest.
那么，让我向您介绍一下我们的客人。
Jennifer Doudna is a professor of biochemistry, biophysics, and structural biology.
Jennifer Doudna 是生物化学、生物物理学和结构生物学教授。
She shared the 2020 Nobel Prize for her incredible pioneering work on CRISPR.
她因其在 CRISPR 方面令人难以置信的开创性工作而分享了 2020 年诺贝尔奖。
First time two women have won the Nobel Prize together, I believe, by the way.
顺便说一句，我相信这是第一次有两位女性一起获得诺贝尔奖。
She’s at UC Berkeley, and she leads the Innovative Genomics Institute and does so much beyond that.
她在加州大学伯克利分校领导创新基因组学研究所，并做了很多其他的事情。
And I’ve been wanting to speak to her for many years because I find the work so fascinating, and she’s an incredibly productive and prolific scientist.
多年来我一直想和她交谈，因为我发现这项工作非常有趣，而且她是一位非常多产和多产的科学家。
Really incredible person.
真是不可思议的人。
If you will, here is Jennifer Doudna.
如果你愿意的话，请听詹妮弗·杜德娜的报道。
Welcome to The Joy of Why , Jennifer, it’s such a pleasure to have you.
欢迎来到“为什么的喜悦”，詹妮弗，很高兴有你。
I’m delighted to be here, Janna.
我很高兴来到这里，詹娜。
Thanks for joining us.
感谢您加入我们。
I was saying I’m a big fan of your work.
我是说我非常喜欢你的作品。
I’ve been following it for years as much as I can.
多年来我一直尽可能地关注它。
For you, you have had such an unbelievably storied career.
对于您来说，您的职业生涯令人难以置信。
You’re so accomplished, incredibly productive, both in academia and outside in industry.
无论是在学术界还是在工业界，您都非常有成就，非常高效。
You literally discovered a means to rewrite the code of life.
你确实发现了一种重写生命代码的方法。
It’s a discovery of almost unfathomable ramifications.
这是一个几乎难以估量的后果的发现。
I think everyone wants to know the secret of your success, or at least what drew you to your subject?
我想每个人都想知道你成功的秘诀，或者至少是什么吸引你进入你的学科？
How did you know you were such a natural match for this subject?
你怎么知道你很适合这个科目？
Well, Janna, I’ll start by saying I certainly did not know that I was a natural match for my subject area.
好吧，詹娜，我首先要说的是，我当然不知道我是我的学科领域的天然匹配者。
I happened to be growing up on a rural island in Hawaii.
我碰巧在夏威夷的一个乡村岛屿上长大。
I got fascinated by chemistry in high school.
我在高中时就对化学着迷。
I had a great chemistry teacher and I was amazed at the variety of life I saw on the island there.
我有一位很棒的化学老师，我对在岛上看到的多种多样的生活感到惊讶。
And I guess I put all of that together and said, “I wanna understand the chemistry of all of that, of how life evolves.”
我想我把所有这些放在一起说，“我想了解所有这些的化学原理，了解生命如何进化。”
And I didn’t really know about that from a chemical perspective until I read The Double Helix by James Watson.
直到我读了詹姆斯·沃森的《双螺旋》，我才真正从化学角度了解这一点。
And I think it was the realization that science is a process of discovery.
我认为这是认识到科学是一个发现的过程。
It’s not about memorizing a bunch of facts.
这不是要记住一堆事实。
It’s about figuring things out.
这是关于弄清楚事情。
I remember thinking clearly when I was in high school that it would be a really fun career to be paid to figure things out, and I think that’s what I’ve always pursued.
我记得在高中时就清楚地思考过，如果能靠解决问题而获得报酬，那将是一个非常有趣的职业，我认为这就是我一直追求的目标。
Now The Double Helix is a fascinating story of discovery.
现在，《双螺旋》是一个引人入胜的发现故事。
It really is a great classic book.
这确实是一本很棒的经典书。
How they go from chemistry to life is so exciting.
它们如何从化学走向生活是如此令人兴奋。
I feel that a lot when I read about your work.
当我读到你的作品时，我有很多这样的感觉。
It’s really descriptions of molecules and bonds and enzymes and protein folding.
它实际上是对分子、键、酶和蛋白质折叠的描述。
How you get from there to life just seems to still be tremendously elusive.
如何从那里走向生活似乎仍然非常难以捉摸。
And is that still a huge source of curiosity for you?
这对你来说仍然是一个巨大的好奇心吗？
It is a source of curiosity.
这是好奇心的来源。
My line of work is biochemistry.
我的工作方向是生物化学。
We’ve always worked with purified molecules and tried to figure out how they function, what they’re doing inside of cells.
我们一直在研究纯化的分子，并试图弄清楚它们如何发挥作用，以及它们在细胞内的作用。
But taking knowledge like that and trying to weave it into a story that explains evolution or even just explains biology as we experience it in our own bodies and in our world.
但是，尝试将这样的知识编织成一个故事，解释进化论，甚至只是解释我们在自己的身体和世界中所经历的生物学。
That’s a big stretch.
这是一个很大的延伸。
So, we’re still working on that one.
所以，我们仍在研究这一问题。
Yeah, fascinating.
是啊，迷人。
When you were doing your PhD work, it was in the mid-’80s, and your work went on around the time the Human Genome Project started to become a really viable possibility and was grabbing a lot of people’s attention…
当您攻读博士学位时，那是在 80 年代中期，您的工作大约在人类基因组计划开始成为真正可行的可能性并吸引了很多人的注意力的时候进行……
all of this work on DNA.
所有这些都在 DNA 上进行。
But you took the direction to study RNA.
但你选择了研究RNA的方向。
And you’ve even described that yourself as a kind of bold and risky move.
您甚至将自己描述为一种大胆而冒险的举动。
Why was it that you were motivated to move away from where the crowd was going and to look at RNA instead, even knowing that it was risky?
为什么你有动力离开人群去研究 RNA，即使知道它有风险？
Well, it felt just a little bit rebellious, I guess.
嗯，我想这感觉有点叛逆。
If I’m honest, that’s part of the reason.
如果我说实话，这就是部分原因。
But I guess I feel that when you go to graduate school and I was, you know, very young, I was in my early 20s, I didn’t know anything and I had the really good fortune to work with an amazing mentor, Jack Szostak, who was a yeast geneticist.
但我想我觉得，当你进入研究生院时，我非常年轻，20岁出头，我什么都不知道，而且我非常幸运能够与一位出色的导师杰克·绍斯塔克（Jack Szostak）一起工作，他是一位酵母遗传学家。
So he studied how chromosomes divide in yeast cells.
因此他研究了酵母细胞中染色体如何分裂。
Sounds kind of esoteric, but actually a lot of fundamental discoveries were made from that system that ended up relating to things like how human chromosomes go awry and give rise to cancer.
听起来有点深奥，但实际上，许多基本发现都是从该系统中得出的，这些发现最终与人类染色体如何出错并引发癌症等问题有关。
So that’s been an interesting line of work for sure.
所以这肯定是一项有趣的工作。
However, when I arrived in Szostak’s lab, he said, “Actually, I’m changing my field of research because I’ve gotten very interested in evolution and specifically in the origin of life.”
然而，当我到达绍斯塔克的实验室时，他说：“实际上，我正在改变我的研究领域，因为我对进化，特别是生命的起源非常感兴趣。”
And I thought, wow, I can’t think of a bigger question than that.
我想，哇，我想不出比这更大的问题了。
And not only that, but he had a very specific experimental path to discovery there.
不仅如此，他还有一条非常具体的实验路径来发现。
He was curious about how RNA molecules might have, in fact, given rise to modern life by preexisting DNA being around on our planet before there was DNA, and that perhaps RNA could have played an original role as a self-replicating form of genetic material.
事实上，他很好奇 RNA 分子是如何通过在 DNA 出现之前就存在于我们星球上的 DNA 产生现代生命的，并且也许 RNA 作为一种自我复制形式的遗传物质发挥了原始作用。
So, you know, I didn’t know, again, anything about that, but it certainly sounded amazing, and that’s how I got into the field in the first place, was really through his encouragement and my ability to jump onto a seemingly kind of rebellious project at a time when nobody else, for the most part, was working in that space.
所以，你知道，我对此一无所知，但这听起来确实令人惊奇，这就是我进入这个领域的方式，实际上是通过他的鼓励和我的能力，在大多数情况下没有其他人在这个领域工作的时候，我能够跳入一个看似叛逆的项目。
Yeah, RNA was highly underrated at the time.
是的，RNA 在当时被严重低估了。
I mean, here he proposed this suggestion that seems quite grand, but that wasn’t really a popular thought about RNA at the time, was it?
我的意思是，他在这里提出了这个看起来很宏伟的建议，但这在当时并不是一个关于 RNA 的流行想法，不是吗？
I mean, RNA was kind of underrated.
我的意思是，RNA 被低估了。
It was an amazing example of how when you do fundamental research, it leads in unexpected directions.
这是一个令人惊奇的例子，说明当你进行基础研究时，它会导向意想不到的方向。
Well, to be fair, there were a few visionaries who were absolutely thinking about that.
好吧，公平地说，有一些有远见的人绝对在考虑这个问题。
Tom Cech is one of them.
汤姆·切赫就是其中之一。
He, with Sid Altman, won the Nobel Prize in 1989 for their discovery of catalytic RNA, RNA that could function like an enzyme.
他与 Sid Altman 因发现催化 RNA（可以像酶一样发挥作用的 RNA）而获得 1989 年诺贝尔奖。
And then there were quite an interesting collection of people who were also very interested in questions about the origin of life and were investigating curious examples of RNA molecules that have either catalytic properties, they can function like enzymes, or seem to play other very interesting roles in biology.
然后还有一群非常有趣的人，他们也对生命起源的问题非常感兴趣，并且正在研究 RNA 分子的奇怪例子，这些分子要么具有催化特性，要么可以像酶一样发挥作用，或者似乎在生物学中发挥着其他非常有趣的作用。
For example, serving as the genetic material of viruses.
例如，作为病毒的遗传物质。
For me, it was really those colleagues, my superiors really, but it was that whole generation of scientists who were interested in these questions that were not really in the mainstream at the time, who had a huge influence on me.
对我来说，确实是那些同事，确实是我的上级，但对我产生巨大影响的是那些对这些当时并不真正主流的问题感兴趣的整整一代科学家。
And in particular, a scientific conference that I went to when I was a second-year graduate student in 1987, where I had the chance to see a number of those folks giving lectures and meeting them for the first time, hugely influential on my decisions for the future of my career.
特别是 1987 年，当我还是一名研究生二年级学生时，我参加了一次科学会议，在那里我有机会看到其中一些人发表演讲并第一次与他们见面，这对我未来职业生涯的决定产生了巨大影响。
And how did it play out?
结果如何？
Does RNA have that role of possibly preceding DNA in the emergence of life in evolution?
在生命的进化过程中，RNA 是否具有可能先于 DNA 的作用？
Is that a question we can answer?
这是我们可以回答的问题吗？
Well, it’s hard to answer it definitively because unless we build a time machine, we can’t really go back and check, you know?
好吧，很难明确回答这个问题，因为除非我们建造一台时间机器，否则我们无法真正回去检查，你知道吗？
But I think what’s fascinating is that over the years, I think there’s only been increasing evidence that that theory is probably correct, or at least that’s an important piece of the story of evolution on the planet.
但我认为令人着迷的是，多年来，我认为只有越来越多的证据表明该理论可能是正确的，或者至少这是地球进化故事的重要组成部分。
Where RNA came from in the beginning is still debated.
RNA最初从何而来仍存在争议。
You know, did it arise here on the planet, or did it come from somewhere else in the universe and arrive on our planet as a seed?
你知道，它是在地球上出现的，还是来自宇宙的其他地方并作为种子到达我们的星球？
People still debate that kind of thing.
人们仍然在争论这类事情。
It’s an interesting speculation, but there’s a lot of evidence that RNA was probably the first kind of self-replicating biological molecule that gave rise to life on the planet.
这是一个有趣的推测，但有大量证据表明 RNA 可能是第一种在地球上产生生命的自我复制生物分子。
Hmm, I mean, the idea of a panspermia is fascinating, but it also just sort of kicks the question down the road.
嗯，我的意思是，有生源论的想法很有趣，但它也只是把这个问题抛到了一边。
It emerged somewhere.
它出现在某个地方。
But it is a fascinating possibility.
但这是一个令人着迷的可能性。
So here you are, you’re trying to understand these deep questions.
所以你在这里，你正试图理解这些深刻的问题。
How does that lead you to the CRISPR story?
这如何引导您了解 CRISPR 的故事？
It was a circuitous route, if I’m honest, and this has really been my experience more generally in science, is that I think you start off in one direction, and if you are open to interesting ideas and results that come up along the way, the path is never straight.
老实说，这是一条迂回的路线，这确实是我在科学领域更广泛的经验，我认为你从一个方向开始，如果你对沿途出现的有趣的想法和结果持开放态度，那么这条路永远不会是笔直的。
In my case, that was through a process where initially we investigated catalytic RNAs and, in particular, understanding their molecular structures to try to find out how they could actually function in an enzymatic way, which was a very interesting question.
就我而言，这是通过一个过程，我们最初研究催化RNA，特别是了解它们的分子结构，试图找出它们如何以酶促方式实际发挥作用，这是一个非常有趣的问题。
Still is, frankly.
坦率地说，仍然是。
And then we started to look into how RNA molecules control the way that gene expression works, and that simply means control the levels of proteins that are made in different kinds of cells.
然后我们开始研究 RNA 分子如何控制基因表达的工作方式，这意味着控制不同种类细胞中产生的蛋白质水平。
It turns out that that’s something that is very fundamental to all of life.
事实证明，这是所有生命中非常基础的东西。
It probably influences not only organismal behaviors, but also the way that certain tissues form, the way that viruses function, of course.
它可能不仅影响有机体行为，还影响某些组织的形成方式，当然还有病毒的功能方式。
Fascinating aspects of gene regulation that really boil down to understanding the levels of proteins that are made at any given time.
基因调控的迷人方面实际上可以归结为了解在任何特定时间产生的蛋白质水平。
There’s a lot of evidence that RNA molecules in different ways are a very important part of that story.
有大量证据表明，RNA 分子以不同的方式是这个故事中非常重要的一部分。
They help control those expression levels of genes.
它们有助于控制基因的表达水平。
And so we were investigating this in viruses and in different types of cells.
因此，我们正在病毒和不同类型的细胞中研究这一点。
And at that point I had started my career at Yale.
那时我在耶鲁大学开始了我的职业生涯。
I moved my lab to UC Berkeley in 2002.
2002 年，我将实验室搬到了加州大学伯克利分校。
And I was fascinated to make the acquaintance of Jill Banfield here at Berkeley, who had discovered evidence at a computational level of an adaptive RNA-guided immune system in bacteria.
我很高兴结识了伯克利分校的吉尔·班菲尔德 (Jill Banfield)，她在计算水平上发现了细菌中适应性 RNA 引导免疫系统的证据。
So this was, for me, yet another fascinating example of RNA molecules controlling the expression of genes, and we wondered, how does that work?
所以，对我来说，这是另一个令人着迷的 RNA 分子控制基因表达的例子，我们想知道，它是如何工作的？
And that was really my entrée into the CRISPR system and all of the CRISPR biology that came from that.
这确实是我进入 CRISPR 系统以及由此产生的所有 CRISPR 生物学的入口。
Wow.
哇。
Now CRISPR is an absolutely fascinating, I guess I would say mechanism.
现在，我想我会说 CRISPR 是一种绝对令人着迷的机制。
How would you, how would you best describe CRISPR?
您会如何、如何最好地描述 CRISPR？
I mean, maybe it would be fair to the uninitiated to tell us what the acronym stands for.
我的意思是，也许对于外行来说，告诉我们这个缩写词代表什么是公平的。
Uh, let’s see if I can pull it out.
呃，我看看能不能把它拉出来。
Clusters of Regularly Interspaced Short Palindromic Repeats.
规则间隔的短回文重复簇。
Ooh!
哦！
Don’t ask me to do that again!
别再要求我这样做了！
Yeah, it’s a bit of a mouthful!
是啊，就是有点拗口！
I had a little cheat sheet somewhere if I had to look it up.
如果我必须查找的话，我在某处有一个小备忘单。
It’s part of the genome of bacteria, is that right?
它是细菌基因组的一部分，对吗？
That’s right.
这是正确的。
It’s in the genome of bacteria, and it’s a very special part of the genome because it actually allows bacteria to create a genetic vaccination card.
它位于细菌的基因组中，是基因组中非常特殊的部分，因为它实际上允许细菌创建基因疫苗接种卡。
They capture little pieces of DNA from viruses and insert them into this special place in the genome called the CRISPR locus that stores that information from viruses over time.
他们从病毒中捕获小段 DNA，并将其插入基因组中称为 CRISPR 位点的特殊位置，该位点会随着时间的推移存储来自病毒的信息。
It, it makes an amazing, you know, recording really in real time of infections that are happening.
它确实实时记录了正在发生的感染，令人惊叹。
And not only that, it’s not sort of dead information, it’s actually information that gets reused in the form of RNA molecules that are produced from those little templates in the DNA to make molecules of RNA that can go out and search for matching sequences in DNA.
不仅如此，这并不是一种死信息，它实际上是以 RNA 分子的形式被重复使用的信息，这些 RNA 分子是由 DNA 中的小模板产生的，从而形成可以出去寻找 DNA 中匹配序列的 RNA 分子。
When those matches are found, they recruit proteins that can come in and snip the viral DNA and protect the cell.
当找到这些匹配时，它们会招募蛋白质，这些蛋白质可以进入并剪切病毒 DNA 并保护细胞。
That’s just unbelievable actually, right?
这实际上令人难以置信，对吧？
So the RNA is playing a really active role going out and then annihilating the virus that it might previously have contracted.
因此，RNA 发挥着非常积极的作用，它走出去，然后消灭它之前可能感染的病毒。
But it’s hard to imagine that all of this is just molecules interacting electromagnetically.
但很难想象这一切只是分子的电磁相互作用。
It’s, it really is such a sophisticated mechanism.
确实，这确实是一个非常复杂的机制。
I think one of the interesting questions is, why did humans not develop this amazing vaccination system?
我认为有趣的问题之一是，为什么人类没有开发出这种令人惊奇的疫苗接种系统？
Well, it’s hard to say, you know, why something doesn’t exist, or at least as far as we know.
好吧，你知道，很难说为什么某些东西不存在，或者至少据我们所知。
But I guess what I would say is that humans have other ways of defending against viruses that are in some ways more advanced, in the sense that they are protein-based and they allow very sophisticated defenses against viruses that themselves have clever ways of trying to avoid immunity.
但我想我想说的是，人类还有其他防御病毒的方法，这些方法在某些方面更先进，因为它们是基于蛋白质的，并且它们可以对病毒进行非常复杂的防御，而病毒本身有巧妙的方法来试图避免免疫。
We could use exactly the same protein to manipulate genes in wheat, rice, human liver cells, the brain, you name it.
我们可以使用完全相同的蛋白质来操纵小麦、水稻、人类肝细胞、大脑等等的基因。
And I think what we see with CRISPR systems is that because they’re based on direct recognition of a viral DNA sequence, it means that viruses can avoid being detected by simply mutating their DNA sequences.
我认为我们在 CRISPR 系统中看到的是，因为它们基于对病毒 DNA 序列的直接识别，这意味着病毒可以通过简单地突变其 DNA 序列来避免被检测到。
And this is probably one of the reasons why we see so many different types of CRISPR systems in biology.
这可能是我们在生物学中看到如此多不同类型的 CRISPR 系统的原因之一。
There’s a lot of active evolution of those systems going on over time.
随着时间的推移，这些系统正在发生许多积极的演变。
They have to keep ahead.
他们必须保持领先。
They have to keep ahead.
他们必须保持领先。
Right?
正确的？
Yeah.
是的。
And so I think when you have rapidly growing cells, like bacteria that are reproducing on a scale that is very similar to the rate at which viruses are reproducing, that kind of works.
所以我认为，当细胞快速生长时，比如细菌的繁殖规模与病毒的繁殖速度非常相似，这种情况就会起作用。
But when you have viruses that reproduce much faster than the cells they’re infecting, like in us, I suspect that kind of a mechanism just can’t keep up if it’s a CRISPR system.
但是，当病毒的繁殖速度比它们感染的细胞快得多时（就像我们体内的病毒一样），我怀疑如果是 CRISPR 系统，这种机制就无法跟上。
And so we evolved other ways of being able to defend against viruses that avoid those immediate escape mechanisms in viruses.
因此，我们进化出了其他防御病毒的方法，避免了病毒的直接逃逸机制。
Now, because the CRISPR mechanism also involves cutting the DNA of the host, it introduces the potential to damage the host as well.
现在，由于 CRISPR 机制还涉及切割宿主的 DNA，因此它也有可能损害宿主。
And so how does a repair mechanism get involved to make sure that it’s not a more damaging system than it is protective?
那么修复机制如何参与以确保它不是一个破坏性大于保护性的系统呢？
Well, in bacteria, of course, that’s kind of the point, right?
嗯，当然，在细菌中，这就是重点，对吧？
The cutting is the way that the immune system functions, so it helps the cell to find and then cut up viral DNA sequences.
切割是免疫系统发挥作用的方式，因此它可以帮助细胞找到并切割病毒 DNA 序列。
But what’s very interesting is that it turns out that in animal and plant cells, these cells respond to DNA cutting differently.
但非常有趣的是，事实证明，在动物和植物细胞中，这些细胞对 DNA 切割的反应不同。
They detect cuts in DNA, and they tend to try to fix them, and they can fix them because they have time, and that’s, again, because the cells are dividing much slower than if the cell is a bacterial cell.
他们检测到 DNA 中的切口，他们倾向于尝试修复它们，他们之所以能够修复它们，是因为他们有时间，而这又是因为细胞的分裂速度比细菌细胞慢得多。
And as a result, when there’s an insult to the DNA, like, say, a double-stranded break that gets introduced, for example, by CRISPR, cells can find the break and fix it.
因此，当 DNA 受到损伤时，例如通过 CRISPR 引入的双链断裂，细胞可以找到断裂并修复它。
And when they fix it, as you just said, that’s an opportunity to also introduce a change to the DNA sequence, and that’s fundamentally how CRISPR works to induce gene editing.
当他们修复它时，正如你刚才所说，这也是一个对 DNA 序列进行改变的机会，这就是 CRISPR 诱导基因编辑的根本原理。
Now, here you’re studying this esoteric mechanism in bacteria, might be relevant for evolution.
现在，您正在研究细菌中的这种深奥机制，可能与进化有关。
Clearly really fascinating.
显然真的很迷人。
But then there’s a big step forward, which is to contemplate how you might alter this mechanism to allow editing for, for the human genome.
但接下来还有一大步，那就是思考如何改变这种机制，以允许对人类基因组进行编辑。
Was that something you intentionally sought out, or was it kind of an accidental realization that this was possible?
这是你有意寻找的东西，还是偶然意识到这是可能的？
Well, it certainly wasn’t something that was the motivation for the project in the beginning.
嗯，这肯定不是该项目一开始的动机。
The project was designed to ask and answer a question about how bacterial adaptive immunity was operating.
该项目旨在提出并回答有关细菌适应性免疫如何运作的问题。
However, as soon as we understood the chemistry of that RNA-guided DNA-cutting activity of a protein known as Cas9.
然而，一旦我们了解了一种名为 Cas9 的蛋白质的 RNA 引导 DNA 切割活性的化学原理。
It was, you know, an amazing example of how when you do fundamental research, it leads in unexpected directions.
你知道，这是一个令人惊奇的例子，说明当你进行基础研究时，它会导致意想不到的方向。
That understanding of the chemistry of RNA-guided DNA cutting immediately suggested a very interesting application of that activity, namely to induce precision editing in cells like ours, or like plants and animal cells, that have this capacity to repair double-stranded DNA breaks.
对 RNA 引导 DNA 切割化学的了解立即表明了该活动的一个非常有趣的应用，即在像我们这样的细胞或像植物和动物细胞中诱导精确编辑，这些细胞具有修复双链 DNA 断裂的能力。
You mentioned the Cas protein.
你提到了Cas蛋白。
What was so important about the Cas protein specifically.
Cas 蛋白有何特别重要之处？
Proteins abound in these systems.
这些系统中富含蛋白质。
So what was so important?
那么什么如此重要呢？
Why is it often paired, CRISPR-Cas9?
为什么它经常配对，CRISPR-Cas9？
Well, it turns out to be the real engine of gene editing, and the reason is that it’s the enzyme that does the DNA cutting.
事实证明，它才是基因编辑的真正引擎，原因是它是进行 DNA 切割的酶。
It uses the RNA molecule that comes from the CRISPR sequence as the zip code.
它使用来自 CRISPR 序列的 RNA 分子作为邮政编码。
It’s the molecular guide that tells that protein where to go and where to cut DNA.
它是告诉蛋白质去哪里以及在哪里切割 DNA 的分子指南。
But Cas9 is the actual machine that does the cutting.
但 Cas9 才是真正进行切割的机器。
And so you really need both together and the two together provide a very powerful tool for programmable gene editing in different kinds of cells.
因此，您确实需要将两者结合在一起，并且两者一起提供了一个非常强大的工具，可以在不同类型的细胞中进行可编程基因编辑。
Once you’re editing genes, you immediately realize that you have the potential to radically alter life on Earth, to participate in the process of evolution.
一旦你编辑基因，你就会立即意识到你有潜力从根本上改变地球上的生命，参与进化过程。
But there were other gene-editing tools also at the time.
但当时还有其他基因编辑工具。
What was so special about this gene-editing tool that really made it transcendent and ubiquitous in a way that the other gene-editing tools didn’t really take on?
这种基因编辑工具有什么特别之处，真正使其超越并普遍存在，而其他基因编辑工具却没有真正做到这一点？
Well, you bring up an important point because you’re right, that there had been a fairly long-standing effort among molecular biologists to figure out how to manipulate genes in a precise way.
嗯，你提出了一个重要的观点，因为你是对的，分子生物学家长期以来一直在努力找出如何以精确的方式操纵基因。
There were a whole series of discoveries that were made that were instrumental to that capability.
一系列的发现对这种能力发挥了重要作用。
Partly it was the understanding of how double-stranded DNA-break repair works in cells, and the other was figuring out how to introduce a double-stranded DNA break in the first place, especially at a place that you might want to induce a gene-editing event.
部分是为了了解双链 DNA 断裂修复如何在细胞中发挥作用，另一个是弄清楚如何首先引入双链 DNA 断裂，特别是在你可能想要诱导基因编辑事件的地方。
And so because that knowledge was preexisting, I think it created a very nice path for CRISPR because what CRISPR offers is an easy way to generate double-stranded breaks.
因此，因为这些知识是预先存在的，我认为它为 CRISPR 创造了一条非常好的道路，因为 CRISPR 提供的是一种产生双链断裂的简单方法。
And not only that, back to the role of this Cas9 protein, what’s really interesting and kind of crazy about the CRISPR technology is that we can use exactly the same protein to manipulate genes in wheat, rice, human liver cells, the brain, you name it, right?
不仅如此，回到Cas9蛋白的作用，CRISPR技术真正有趣和有点疯狂的是，我们可以使用完全相同的蛋白来操纵小麦、水稻、人类肝细胞、大脑中的基因，凡是你能想到的，对吧？
It’s the same enzyme.
这是同一种酶。
And the reason that works is because we can simply change the guide RNA that tells it where to go, and we can redirect its activity to a gene of interest in any cell type.
之所以有效，是因为我们可以简单地改变引导RNA，告诉它去哪里，并且我们可以将其活性重定向到任何细胞类型中感兴趣的基因。
Because of that, it just makes it a very easy technology to deploy, and that’s really what we saw in the field.
正因为如此，它使它成为一种非常容易部署的技术，这正是我们在该领域所看到的。
As soon as that original article with my collaborator Emmanuelle Charpentier was published in the summer of 2012, immediately there were many labs that started using it and testing it for gene editing in different systems.
2012 年夏天，我与合作者 Emmanuelle Charpentier 发表的原创文章一发表，许多实验室立即开始使用它并在不同系统中测试它的基因编辑功能。
And that set off an enormous race, and then of course a trajectory of many labs adopting the technology for all kinds of applications.
这引发了一场巨大的竞赛，当然，随后许多实验室也开始采用该技术进行各种应用。
I mean, this is the discovery of a lifetime.
我的意思是，这是一生的发现。
I mean, it really is.
我的意思是，确实如此。
You described, in response to receiving the Nobel Prize with Emmanuelle Charpentier, that this was a joyous time of discovery, as though it was singular, as it stood out.
您在与埃曼纽尔·夏彭蒂埃 (Emmanuelle Charpentier) 一起获得诺贝尔奖时描述说，这是一个发现的快乐时光，就好像它是独一无二的，因为它脱颖而出。
And I guess I’m wondering, would you describe it as a moment of a realization or was it more the process of the discovery?
我想我想知道，你会把它描述为一个实现的时刻，还是更多的是一个发现的过程？
It was possible to create a therapy — I don’t know if anyone’s ever created a therapy that quickly tested it and delivered it to a patient.
创造一种疗法是可能的——我不知道是否有人曾经创造过一种可以快速测试并将其交付给患者的疗法。
Well, it wasn’t instantaneous, but it was pretty fast actually.
嗯，虽然不是瞬时的，但实际上很快。
Because, you know, and that, that’s sort of been my experience in science over the years is that, you know, when you discover something that is of real import you kind of know it right away in a sense.
因为，你知道，这是我多年来在科学领域的经验，你知道，当你发现一些真正重要的东西时，你在某种意义上立刻就知道了它。
With CRISPR it’s not as though we could foresee everything that was to come, of course, from the technology.
当然，对于 CRISPR，我们并不能预见该技术将带来的一切。
But we could really pretty immediately see how this could be a very powerful tool because of the ease of deployment, how easy it was to alter this RNA molecule and send Cas9 to different places in a genome.
但我们真的可以立即看到它如何成为一个非常强大的工具，因为它易于部署，改变这个 RNA 分子并将 Cas9 发送到基因组中的不同位置是多么容易。
And all of the potential uses of that kind of technology.
以及此类技术的所有潜在用途。
It was just very exciting to think about and contemplate and imagine what could be possible.
思考、沉思和想象什么是可能的，真是令人兴奋。
So, has the technology changed significantly?
那么，技术是否发生了重大变化？
And what do you think the most impactful technological advances have been since its discovery?
您认为自发现以来最具影响力的技术进步是什么？
Well, since the discovery of CRISPR, what’s happened is that it’s become a whole toolbox, and the way that’s happened is that it’s been possible to take advantage of, again, the fundamental chemistry of the way the CRISPR system functions as an RNA-guided mechanism of recognizing and cutting DNA.
嗯，自从 CRISPR 被发现以来，发生的事情是它已经成为一个完整的工具箱，而发生的方式是，我们可以再次利用 CRISPR 系统作为识别和切割 DNA 的 RNA 引导机制的基本化学原理。
It’s been possible to change that into a mechanism of recognizing and changing DNA in different ways.
有可能将其转变为一种以不同方式识别和改变 DNA 的机制。
And so that’s really made it an incredibly versatile technology that can now be used for all kinds of different types of genetic manipulations.
因此，这确实使其成为一种令人难以置信的多功能技术，现在可用于各种不同类型的基因操作。
And I think that I’m just excited about all of those, to be honest, because I think that it gives scientists a very rich set of technologies that can be deployed as they’re needed in different settings, and it’s only gonna continue.
说实话，我认为我对所有这些感到兴奋，因为我认为它为科学家提供了一套非常丰富的技术，可以根据不同环境的需要进行部署，而且这种情况只会继续下去。
I mean, every time I go to a meeting about CRISPR, I’m continually blown away by you know, by that expansion of the toolbox.
我的意思是，每次我参加有关 CRISPR 的会议时，我都会不断地被工具箱的扩展所震撼。
And so I just think it continues to get better and better and better.
所以我认为它会继续变得越来越好。
Wow, this is making me try to remember some of my biology classes because, for instance, the phrase double-stranded break.
哇，这让我试图记住我的一些生物课，因为例如“双链断裂”这个词。
I’m not sure I fully appreciate what’s going on here.
我不确定我是否完全理解这里发生的事情。
So let’s just remember, maybe you can correct me if I’m getting this wrong.
所以让我们记住，如果我错了，也许你可以纠正我。
DNA is a double helix, we all learned that.
DNA是双螺旋，我们都知道。
It has these two strands, and you can break one strand and leave the other strand intact.
它有这两股，你可以折断一根，而另一股完好无损。
There are enzymes that do single-stranded breaks, and that’s not super dangerous from the point of view of the integrity of the DNA molecule or the gene because you’ve still got one intact strand.
有些酶可以进行单链断裂，从 DNA 分子或基因完整性的角度来看，这并不是非常危险，因为你仍然有一条完整的链。
There’s still all the base pairing along the whole double-stranded structure.
整个双链结构中仍然存在所有碱基配对。
You put a snip in one strand, but you haven’t broken the back of the molecule.
你在一根链上剪了一个剪刀，但你并没有折断分子的背面。
A double-stranded break is literally chopping the molecule, DNA in half.
双链断裂实际上是将 DNA 分子切成两半。
Really very dramatic move.
真是非常戏剧性的举动。
Right.
正确的。
In principle, it should be very damaging to the cell.
原则上，它对细胞的损害应该很大。
Yeah, and so to be able to have access to genetic machinery that can not only do these double-stranded breaks, but do it in a manageable way, and this is the part that got me, it’s like it’s a sort of universal scissors.
是的，因此能够获得遗传机制，不仅可以实现这些双链断裂，而且可以以可管理的方式进行，这就是让我着迷的部分，它就像一种万能剪刀。
It can work in any organism.
它可以在任何有机体中发挥作用。
And you can just guide it to any place.
你可以引导它到任何地方。
Right?
正确的？
Like, in the old days, there were enzymes that they’re good at snipping one strand, but only if the sequence was such and such, you know, like much more restricted kinds of scissors.
就像，在过去，有一些酶擅长剪断一根链，但前提是序列是这样那样的，你知道，就像更受限制的剪刀一样。
This is like a really magnificent all-purpose gadget.
这就像一个非常华丽的多用途小工具。
I think she really says it well when she says, “It was just so easy to deploy.” And you saw it right away in use in other labs immediately.
我认为她说得很好，“部署起来太容易了。”您立即看到它在其他实验室中得到使用。
There was very little barrier to its application.
其应用几乎没有障碍。
I think this point about the double-strand breaking is a single-strand breaking, as I understand, is more easily repaired.
我认为关于双链断裂的这一点是单链断裂的，据我了解，更容易修复。
Yeah.
是的。
And you can, but you don’t, in principle, change the DNA.
你可以，但原则上你不能改变 DNA。
But if you double break, you can now insert new base pairs.
但如果你双重断裂，你现在可以插入新的碱基对。
And that’s really what CRISPR is doing.
这正是 CRISPR 正在做的事情。
It’s, for instance, taking the DNA from an invading virus.
例如，它从入侵病毒中获取 DNA。
It’s cutting its own DNA and putting the viral DNA in its own strands.
它正在切割自己的 DNA，并将病毒 DNA 放入自己的链中。
It’s inserting the base pairs, and you need the double break to do that.
它正在插入碱基对，你需要双断点才能做到这一点。
And the reason why that’s interesting is you’ve essentially made an immunization card, a record of your own ability to immunize against that invader.
这很有趣的原因是你本质上制作了一张免疫卡，记录了你自己对入侵者进行免疫的能力。
At least that’s the case for bacteria.
至少对于细菌来说是这样。
So here now we can adapt this from the bacterial toolkit and implement it in human beings, and fundamentally change the genetic material.
所以现在我们可以从细菌工具包中改编并将其应用到人类身上，从根本上改变遗传物质。
It’s pretty incredible.
这太不可思议了。
It’s, it’s not the biology I ever learned, and I guess the real experts are just as shocked, right?
这不是我学过的生物学，我想真正的专家也同样震惊吧？
It was a really monumental discovery.
这确实是一个具有里程碑意义的发现。
I’ve got to say, this sort of excitement over CRISPR, I think, is among the most fascinating scientific discoveries that I’ve ever heard of, and it has the potential to change fundamentally the human blueprint.
我不得不说，我认为这种对 CRISPR 的兴奋是我听过的最令人着迷的科学发现之一，它有可能从根本上改变人类的蓝图。
It’s just astonishing now what’s possible.
现在的可能性真是令人惊讶。
But it sounds like it’s been discovered in the laboratory, tested in the laboratory.
但听起来它是在实验室里发现的、在实验室里测试过的。
Is it making its way to the bedside, to the clinic?
它是否正在走向床边、走向诊所？
Is it helping real people?
它对现实的人有帮助吗？
Yeah, exactly.
是的，完全正确。
Jennifer discussed cases, real patients, living human beings who are alive precisely because of CRISPR therapies.
Jennifer 讨论了病例、真实的患者、活生生的人类，这些人正是因为 CRISPR 疗法才得以生存。
So, we’re gonna get right into that after the break.
所以，我们将在休息后立即开始讨论。
It’s just an extraordinary story of teamwork.
这是一个非凡的团队合作故事。
It’s an extraordinary story of using off-the-shelf technology.
这是一个使用现成技术的非凡故事。
No new research had to be done.
无需进行新的研究。
We could use existing versions of CRISPR and a delivery tool that had been developed originally for the COVID vaccine.
我们可以使用现有版本的 CRISPR 和最初为新冠疫苗开发的递送工具。
Welcome back to The Joy of Why .
欢迎回到“为什么的喜悦”。
We’ve got biochemist Jennifer Doudna with us here today to discuss CRISPR and the future of gene editing.
今天，生物化学家 Jennifer Doudna 与我们一起讨论 CRISPR 和基因编辑的未来。
It’s not quite 20 years, but we are living in the time where there’s these really impactful technological advances.
虽然还不到 20 年，但我们生活在一个真正有影响力的技术进步的时代。
You have this work with Baby KJ.
你和 Baby KJ 一起完成了这部作品。
Why don’t we talk about Baby KJ?
我们为什么不谈谈宝贝KJ呢？
Maybe you could tell us, it’s a very concrete example of what’s actually being done therapeutically.
也许你可以告诉我们，这是一个非常具体的例子，说明了实际的治疗效果。
Well, Baby KJ was born in August of 2024 and he had a rare metabolic disease that was diagnosed right away after he was born.
那么，KJ宝宝出生于2024年8月，他患有一种罕见的代谢疾病，出生后立即被诊断出来。
He couldn’t digest protein properly, meaning that he was extremely sick.
他无法正常消化蛋白质，这意味着他病得很重。
He couldn’t eat a normal diet.
他无法正常饮食。
He wasn’t gaining weight.
他的体重没有增加。
He was in the neonatal intensive care unit.
他在新生儿重症监护室。
You can imagine that his parents were distraught and, you know, desperate to do something to help their boy.
你可以想象他的父母心烦意乱，并且不顾一切地想要做点什么来帮助他们的孩子。
Fortunately, his clinical team at the Children’s Hospital of Philadelphia realized that he probably had a rare genetic disorder and were able to quickly get a sample and sequence the DNA.
幸运的是，他在费城儿童医院的临床团队意识到他可能患有一种罕见的遗传性疾病，并且能够快速获取样本并对 DNA 进行测序。
They figured out that this boy had mutations in both copies of a gene encoding an essential enzyme required for protein digestion.
他们发现这个男孩的两个基因拷贝都发生了突变，该基因编码蛋白质消化所需的必需酶。
And not only that, they realized that this was a type of mutation that could in principle be fixed using a version of CRISPR that would have that capability.
不仅如此，他们意识到这种突变原则上可以使用具有这种能力的 CRISPR 版本来修复。
And so they reached out to a number of groups, including the Innovative Genomics Institute out here in California, about helping them to create a version of CRISPR that could treat this boy.
因此，他们联系了包括加州创新基因组研究所在内的多个团体，希望帮助他们创建一种可以治疗这个男孩的 CRISPR 版本。
And incredibly, incredibly, I still can’t really believe it, but it did happen in an eight-month time period.
令人难以置信，令人难以置信，我仍然不敢相信，但这确实在八个月的时间内发生了。
And the baby was treated and today he seems to be thriving, which is absolutely wonderful.
孩子接受了治疗，今天他看起来正在茁壮成长，这绝对是美妙的。
So, you know, it’s just an extraordinary story of teamwork.
所以，你知道，这只是一个非凡的团队合作故事。
It’s an extraordinary story of using off-the-shelf technology.
这是一个使用现成技术的非凡故事。
No new research had to be done.
无需进行新的研究。
We could use existing versions of CRISPR and a delivery tool that had been developed originally for the COVID vaccine, actually.
实际上，我们可以使用现有版本的 CRISPR 和最初为新冠疫苗开发的递送工具。
And using that in the patient, it was possible to create a therapy I don’t know if anyone’s ever created a therapy that quickly tested it and delivered it to a patient.
在患者身上使用它，就有可能创建一种疗法，我不知道是否有人曾经创建过一种可以快速测试并将其交付给患者的疗法。
But now we know it can happen, which is really exciting.
但现在我们知道这可能会发生，这真的很令人兴奋。
It’s fascinating.
这很有趣。
I have so many questions, but when you deliver this kind of a therapy, since it’s a gene editing therapy, is it a one time you deliver it?
我有很多问题，但是当你提供这种疗法时，既然是基因编辑疗法，那么你提供的是一次性的吗？
The genome is edited?
基因组被编辑了？
Or is it a therapy that has to be re-administer over time?
还是随着时间的推移必须重新进行治疗？
Well, in this case it was a little of both in the sense that it was three times into the patient, but not since then.
好吧，在这种情况下，两者兼而有之，因为它三次进入患者体内，但从那以后就没有了。
And I think the hope is that sufficient editing of that patient’s cells in his liver, that are essentially repopulating his liver over time, have been edited such that he now has a normal functioning liver that’s producing the kind of digestive enzymes that are needed for his health.
我认为希望的是，对该患者肝脏中的细胞进行充分的编辑，随着时间的推移，这些细胞基本上会重新填充他的肝脏，这样他现在就有一个功能正常的肝脏，可以产生他的健康所需的消化酶。
That will just have to be monitored, of course, over time.
当然，随着时间的推移，这只需要进行监控。
And because it’s a one patient situation, we don’t have any way of actually testing whether and how much editing occurred in his liver.
而且因为这是一个病人的情况，我们没有任何方法来实际测试他的肝脏是否发生了编辑以及有多少编辑发生。
It’s just, looking at his physiological properties now and trying to assess what his health is.
只是，现在看看他的生理特性并试图评估他的健康状况。
But it is quite impressive that it took just this, you know, kind-of very succinct delivery.
但令人印象深刻的是，它的表达方式非常简洁。
It doesn’t require treating the patient every day or every month.
它不需要每天或每月治疗患者。
He had three treatments with this therapy, and we hope that that’s sufficient to give him a normal lifespan with a normal outlook.
他接受了三次这种疗法的治疗，我们希望这足以让他拥有正常的寿命和正常的外表。
It’s incredible.
太不可思议了。
I mean, there are other areas in terms of human health therapeutics where you would see this kind of possibility, cardiovascular disease or, I dunno, altering the microbiome.
我的意思是，在人类健康治疗的其他领域，你会看到这种可能性，心血管疾病，或者，我不知道，改变微生物组。
Where do you see the most sort-of productive direction for thinking about gene therapies?
您认为基因疗法最有成效的方向在哪里？
Well, you just mentioned two big ones that we think about a lot.
嗯，你刚才提到了我们经常思考的两个大问题。
So I think, you know, the cardiovascular angle is fascinating.
所以我认为，你知道，心血管角度很有趣。
It might not be obvious to someone listening to this, you know, why would CRISPR be useful for treating heart disease?
对于听这个的人来说可能不太明显，你知道，为什么 CRISPR 对治疗心脏病有用？
And yet it is.
但事实确实如此。
And the reason is that many studies have shown that people that have a particular form of an enzyme in the liver that processes cholesterol differently than others have protection against cardiovascular disease because they don’t tend to accumulate plaques in their arteries over time.
原因是，许多研究表明，肝脏中存在一种特殊形式的酶的人，其处理胆固醇的方式与其他人不同，可以预防心血管疾病，因为随着时间的推移，他们的动脉中不会积聚斑块。
So, wouldn’t it be great if you could actually use CRISPR to give everybody that form of the gene?
那么，如果你真的可以使用 CRISPR 为每个人提供这种形式的基因，那不是很棒吗？
And that’s what the principle is for using CRISPR in that fashion.
这就是以这种方式使用 CRISPR 的原理。
And in fact, there was a company that was founded to do this, a company called Verve that has demonstrated enough potential for this approach that they were actually purchased by Eli Lilly last year.
事实上，有一家公司就是为了做到这一点而成立的，这家名为 Verve 的公司已经展示了这种方法的足够潜力，以至于去年他们被礼来公司 (Eli Lilly) 收购。
And so, you know, there’s a lot of interest on the part of even big pharmaceutical companies in pursuing a strategy that could give people an option that doesn’t involve taking a daily pill or getting, you know, frequent injections or something, or having to radically change their diet, but instead having a one-and-done therapy that just gives them a genetic fix to the problem of high cholesterol.
所以，你知道，即使是大型制药公司也对寻求一种策略很感兴趣，这种策略可以为人们提供一种选择，不需要每天服用药物或频繁注射或其他什么，或者必须从根本上改变他们的饮食，而是采用一种一次性疗法，只为他们提供基因修复高胆固醇问题的方法。
Now, this is the upside, the success stories.
现在，这就是好处，成功的故事。
But there are also barriers to developing these treatments at scale.
但大规模开发这些治疗方法也存在障碍。
What are the barriers?
有何障碍？
Are they all just financial barriers or getting FDA approval, or are there actual barriers to scaling up these kinds of treatments?
它们是否都只是财务障碍或获得 FDA 批准，还是在扩大此类治疗方面存在实际障碍？
Well, certainly the financial and barriers are there.
嗯，财务和障碍肯定是存在的。
What’s exciting about the case of Baby KJ in particular is that those barriers were overcome and that sort-of speaks to what’s possible.
Baby KJ 的案例尤其令人兴奋的是，这些障碍都被克服了，这说明了一切皆有可能。
On the flip side, we know that that strategy isn’t going to work for everybody.
另一方面，我们知道该策略并不适合所有人。
It’s very hard to scale that.
很难扩展这个规模。
For example, how would we replicate that particular path for other patients that have rare diseases?
例如，我们如何为其他患有罕见疾病的患者复制这一特定路径？
So, I think it’s worth really for the field to think about what are the approaches that could just radically reduce the cost and make it a lot easier for other patients to get access to this type of a therapeutic.
因此，我认为该领域确实值得思考什么方法可以从根本上降低成本并使其他患者更容易获得这种类型的治疗。
And so I think it’ll take not only getting creative with engineering and the way that these molecules are manufactured, and that’s already underway to try to reduce costs there.
因此，我认为不仅需要在工程和这些分子的制造方式上发挥创意，而且已经在努力降低成本。
But it also goes back to the science and the technology.
但这也可以追溯到科学和技术。
For example, you know, Baby KJ was lucky that his disease affected his liver, so it was possible to use an off-the-shelf delivery technology to introduce the CRISPR molecules to cells in his liver.
例如，你知道，Baby KJ 很幸运，他的疾病影响了他的肝脏，因此可以使用现成的递送技术将 CRISPR 分子引入他肝脏的细胞中。
But that’s not going to be helpful for people that have a lung disorder or a muscle disease or a brain disorder.
但这对于患有肺部疾病、肌肉疾病或大脑疾病的人没有帮助。
One of the real forefronts in the field right now is figuring out how to solve the delivery problem for all these other tissue types.
目前该领域真正的前沿之一是弄清楚如何解决所有这些其他组织类型的输送问题。
I think it’s gonna be solvable.
我想这是可以解决的。
I’m very bullish on this.
我对此非常看好。
But it’s gonna take real work.
但这需要真正的工作。
And so, one of the real forefronts in the field right now is figuring out how to solve the delivery problem for all these other tissue types.
因此，目前该领域真正的前沿之一是弄清楚如何解决所有其他组织类型的输送问题。
I think it’s gonna be solvable.
我想这是可以解决的。
You know, I’m very bullish on this.
你知道，我非常看好这一点。
But it’s gonna take real work.
但这需要真正的工作。
I mean, you know, it’s not going to just happen.
我的意思是，你知道，这不会轻易发生。
I think we have to really focus on it.
我认为我们必须真正关注它。
And fortunately, many people recognize that this is an important challenge.
幸运的是，许多人认识到这是一个重要的挑战。
And so we’re seeing more and more efforts in this regard.
因此，我们看到这方面的努力越来越多。
A lot of our young students that come in to the Innovative Genomics Institute here in California certainly are very motivated by this.
我们许多进入加州创新基因组学研究所的年轻学生肯定对此非常有动力。
They’re excited about it.
他们对此感到兴奋。
It’s a hard problem.
这是一个难题。
They wanna grapple with it.
他们想解决这个问题。
They wanna figure it out.
他们想弄清楚。
So, that’s the kind of energy and innovation that I think will solve a hard problem like delivery.
所以，我认为这种能量和创新将解决像交付这样的难题。
If you have a newborn baby with a terrible genetic disease, who is not going to have a long life prognosis, you can imagine risking anything to treat this child.
如果你的新生儿患有严重的遗传病，而且他的寿命不会很长，你可以想象冒着一切风险来治疗这个孩子。
But for somebody who has alternative therapies, how scared are people of doing something as radical as editing their genome?
但对于拥有替代疗法的人来说，人们有多害怕做像编辑基因组这样激进的事情呢？
And are there negative consequences?
是否有负面后果？
Are there possibilities of having mistakes in what’s edited, or how it’s edited, or immune response?
编辑内容、编辑方式或免疫反应是否有可能出现错误？
Yeah.
是的。
Well, you know, with any technology of course there’s always risk, right?
嗯，你知道，任何技术当然都存在风险，对吧？
And with gene editing in particular, you could imagine, right, you don’t wanna have something that’s not accurate, or editing sites that are unintended or even that are harmful.
尤其是基因编辑，你可以想象，是的，你不想得到不准确的东西，或者编辑无意的甚至有害的网站。
You certainly don’t want to be in a situation where you have consequences of editing that lead to undesired outcomes.
您当然不希望出现因编辑而导致不良结果的情况。
I think a good case in point is actually the situation with sickle cell disease, because that’s a disease where the presence of the sickle cell mutation in the human population is probably in part because it gives some protection against malaria infection.
我认为一个很好的例子实际上是镰状细胞病，因为在这种疾病中，人类中存在镰状细胞突变，部分原因可能是它可以提供一些针对疟疾感染的保护作用。
So, people that have one copy of the so-called sickle cell gene, phenotypically they’re normal, but they have some protection against malaria infection.
因此，拥有一份所谓镰状细胞基因拷贝的人，在表型上是正常的，但他们对疟疾感染有一定的保护作用。
So you could argue that for them a bit of an advantage to have that in parts of the world where malaria is endemic.
所以你可能会说，在世界上疟疾流行的地区，对他们来说有一点优势。
And so that’s just kind of a good reminder that our genetics are complex and genes, you know, aren’t necessarily good or bad.
所以这只是一个很好的提醒，我们的遗传学是复杂的，你知道，基因不一定是好是坏。
They could be a little of both depending on the situation.
根据具体情况，它们可能两者兼而有之。
So I think, gene editing just, we have to employ it cautiously because it does require a lot of knowledge about what effect a genetic change is going to have on a person over the course of their life.
所以我认为，就基因编辑而言，我们必须谨慎使用它，因为它确实需要大量关于基因变化将对一个人的一生产生什么影响的知识。
Yeah, you raised this fascinating possibility that a gene we think is simply harmful, actually has a protective purpose.
是的，你提出了一个令人着迷的可能性，即我们认为只是有害的基因实际上具有保护作用。
And we talk a lot about, you know, maybe myopic people also have some correlation with abilities, or you can’t fix one thing without possibly damaging another.
我们谈论了很多，你知道，也许近视的人也与能力有一定的相关性，或者你不可能在不损害另一件事的情况下解决一件事。
I think that’s just generally true about human beings.
我认为这对于人类来说通常都是正确的。
It also leads to some ethical questions, and I know you’ve thought a lot about the ethical questions.
这也会引发一些道德问题，我知道你对道德问题思考了很多。
I feel like we have to talk about the somewhat shocking case of the Chinese scientist in 2018 who used CRISPR to genetically alter human embryos, which seemed like it was really crossing a line, resulting in the birth of two twin girls.
我觉得我们必须谈谈 2018 年中国科学家使用 CRISPR 对人类胚胎进行基因改造的令人震惊的案例，这似乎真的越界了，导致了两个双胞胎女孩的诞生。
It’s my understanding that he was trying to make the babies resistant to HIV.
据我了解，他试图让婴儿对艾滋病毒产生抵抗力。
Now, when you heard about that were you shocked, or did you feel it was inevitable that somebody would transgress across this unspoken ethical line?
现在，当你听到这个消息时，你是否感到震惊，或者你是否觉得有人不可避免地违反了这条不言而喻的道德界限？
It was shocking.
太令人震惊了。
No, it was definitely shocking.
不，这绝对是令人震惊的。
It had already been on my mind though that, you know, this was certainly a possibility.
我已经想到了，不过，你知道，这肯定是有可能的。
And this particular individual had been going around and attending meetings on gene editing, so he wasn’t unknown to the genome editing community.
这个人一直在四处走动并参加有关基因编辑的会议，因此他对基因组编辑界并不陌生。
But that all being said it was certainly shocking to find out that this wasn’t just chat, it was actual action that he had taken.
但话虽如此，当发现这不仅仅是聊天，而是他采取的实际行动时，确实令人震惊。
And once the details were revealed, it was pretty clear it was an extraordinarily unethical thing to have done for multiple reasons.
一旦细节被揭露，很明显，出于多种原因，这是一件极其不道德的事情。
You know, if there’s a silver lining to that story, it’s that I think internationally people recognized right away that this was wrong and they took a stand against it.
你知道，如果这个故事有一线希望的话，那就是我认为国际上的人们立即认识到这是错误的，并采取了反对的立场。
And in fact, that scientist was arrested and his lab was closed and he was jailed for a few years.
事实上，那位科学家被捕了，他的实验室被关闭，他被监禁了几年。
So, we’ll see what happens going forward, but I was pleased, I guess, that there was a very strong and concerted response by the international community about his action.
因此，我们将看看未来会发生什么，但我想，我很高兴国际社会对他的行动做出了非常强烈和一致的反应。
And the big issue being that it was in embryos, it was editing the germline.
最大的问题是它在胚胎中，它正在编辑种系。
So in other words, it could be passed down.
也就是说，它是可以传承下去的。
Was that the big line that was crossed versus another therapy?
这是与其他疗法相比所跨越的大界限吗？
Well, for me, even more than that was that it was first of all used in a way that was medically unnecessary because there were other proven ways to protect those babies from transmission of HIV during their development and birth.
嗯，对我来说，更重要的是，它首先以一种医学上不必要的方式使用，因为还有其他行之有效的方法可以保护这些婴儿在发育和出生期间免受艾滋病毒的传播。
Secondly, I don’t think from the evidence that I saw that the parents were aware particularly of what they were actually agreeing to, which is also very shocking.
其次，从我看到的证据来看，我认为父母并没有特别意识到他们实际上同意的是什么，这也非常令人震惊。
And then as you mentioned, the third piece is that this is a permanent technology.
正如您提到的，第三点是这是一项永久性技术。
And not only that, when you perform it in embryos, you are making changes that are heritable.
不仅如此，当你在胚胎中进行这种实验时，你正在做出可遗传的改变。
So those changes will now be passed to future generations, and we really don’t know what the impact of that will be.
因此，这些变化现在将传递给后代，我们真的不知道这会产生什么影响。
We have to employ it cautiously because it does require a lot of knowledge about what effect a genetic change is going to have on a person over the course of their life.
我们必须谨慎使用它，因为它确实需要大量关于基因变化将对人的一生产生什么影响的知识。
Do you think that there are others that are unscrupulously performing these kinds of experiments?
您认为还有人肆无忌惮地进行此类实验吗？
As you said, it’s an incredibly flexible, programmable, swift, and not terribly expensive technology, which also makes it kind of scary.
正如你所说，这是一种非常灵活、可编程、快速且不是非常昂贵的技术，这也使得它有点可怕。
You know, it’s possible.
你知道，这是可能的。
I think that my assessment is that the original perpetrator, I guess you could say of that germline application of CRISPR, a lot of his motivation I think was frankly for publicity.
我认为我的评估是，最初的肇事者，我想你可以说 CRISPR 的种系应用，我认为他的很多动机坦率地说是为了宣传。
And so I think that part of the deterrent now is the idea that publicity would be pretty negative for somebody forging ahead with something like that today.
所以我认为现在的部分威慑因素是这样的想法，即公众对今天推进类似事情的人来说是相当负面的。
And yet, you know, we do know of companies, for example, I’ve heard of a few around the country that are exploring again the possibility of germline editing and offering that as a service to people.
然而，你知道，我们确实知道一些公司，例如，我听说全国各地有一些公司正在再次探索种系编辑的可能性，并将其作为一项服务提供给人们。
So, it’s not as though this is off the table or no one’s thinking about it anymore.
所以，这并不是说这是不可能的，或者没有人再考虑它。
I think it’s still very much in the milieu and we’ll have to see what happens in the future.
我认为这仍然处于目前的环境中，我们必须看看未来会发生什么。
But it, to me, just underscores the continued importance of public engagement, of scientists being involved in the conversation around CRISPR and how it should be used.
但对我来说，这只是强调了公众参与、科学家参与围绕 CRISPR 及其应如何使用的对话的持续重要性。
There are implications for using this technology for climate, for plant life.
使用这项技术对气候和植物生命都有影响。
I mean possibly even food, to address food scarcity, or diseases like malaria, where you stop it at the level of the insect, not at the human-body level.
我的意思是甚至可能是食物，以解决食物短缺或疟疾等疾病，你可以在昆虫层面而不是在人体层面来阻止它。
How do you see those advances progressing?
您如何看待这些进展？
Is that an area that’s very active at the moment?
这是目前非常活跃的领域吗？
Yeah, it’s pretty active and I think there’s a real upswing in the applications of CRISPR for those kinds of things that we’re seeing right now.
是的，它非常活跃，我认为 CRISPR 在我们现在看到的这类事情上的应用确实在上升。
Especially for addressing challenges that are coming with the changing climate, both in terms of food security, how we ensure that we have plants that are robust with respect to drought, with respect to pests, that have improved nutritional value.
特别是为了应对气候变化带来的挑战，无论是在粮食安全方面，还是在我们如何确保我们的植物能够抵抗干旱和害虫、提高营养价值方面。
All of those things are interesting applications using CRISPR.
所有这些都是 CRISPR 的有趣应用。
And then the other is thinking directly about carbon release and applications that involve changing the microbiome in cattle to avoid the emission of methane.
然后另一个是直接考虑碳释放和涉及改变牛体内微生物组以避免甲烷排放的应用。
Cattle are one of the major sources of methane emissions around the world every year, and CRISPR in principle can dial that back by changing the genes in those bugs to reduce methane emissions potentially permanently.
牛是每年世界各地甲烷排放的主要来源之一，原则上，CRISPR 可以通过改变这些细菌的基因来扭转这一局面，从而潜在地永久减少甲烷排放。
So that’s, I think, something that I’m very excited about, and is an active program here at the Innovative Genomics Institute.
所以，我认为，这是我非常兴奋的事情，也是创新基因组研究所的一个活跃项目。
What do you see as a primary focus in your research in the coming decade?
您认为未来十年研究的主要重点是什么？
Do you see it as being more focused on industry and application, or back to exploration in the lab?
您认为它是更关注行业和应用，还是回到实验室的探索？
Well, it’s a little of both.
嗯，两者都有一点。
I think that, you know, in my own research lab, I continue to have folks that are doing fundamental discoveries, and there’s a lot of exciting work, frankly, coming out of that effort right now.
我认为，你知道，在我自己的研究实验室中，我继续有人在做基础性的发现，坦率地说，现在有很多令人兴奋的工作正在从这些努力中产生。
And then we also appreciate the value of figuring out this delivery challenge.
然后我们也意识到解决这一交付挑战的价值。
I think it’s a big challenge.
我认为这是一个很大的挑战。
We’re not engineers in the lab.
我们不是实验室里的工程师。
We love engineers, but I’m certainly not an engineer.
我们喜欢工程师，但我肯定不是工程师。
But the opportunity to understand fundamentally how cells take up new molecules, how these molecules can access specific kinds of cells.
但有机会从根本上了解细胞如何吸收新分子，这些分子如何进入特定类型的细胞。
There’s a mechanistic basis for a lot of that, that is something that we do love to dig into in a lab like mine.
其中很多都有其机械基础，这是我们喜欢在像我这样的实验室中深入研究的东西。
So those are gonna be two areas that we’re gonna focus in, for sure.
所以这肯定是我们要重点关注的两个领域。
Beyond that, I really want to continue to serve as a mentor.
除此之外，我真的很想继续担任导师。
I’m enjoying the fact that at the Institute here, we’ve been able to hire in a number of younger faculty who are kicking off exciting research programs of their own that align with the kind of overall goals and mission of the Institute.
我很高兴在研究所聘请了一些年轻的教师，他们正在启动自己的激动人心的研究项目，这些项目与研究所的总体目标和使命相一致。
These are folks that are here in large part because they love working on big, hard problems.
这些人来到这里很大程度上是因为他们喜欢解决重大难题。
They love doing that collaboratively.
他们喜欢合作做这件事。
They love doing it here in the Bay Area, where we have access to incredible resources of all types.
他们喜欢在湾区这样做，在这里我们可以获得各种类型的令人难以置信的资源。
We love being literally right across the bay from Silicon Valley.
我们喜欢与硅谷隔海湾相望的地方。
You know, as AI continues to advance and accelerate the pace of our work, we’re increasingly integrating that into what we’re doing.
你知道，随着人工智能不断进步并加快我们的工作节奏，我们越来越多地将其整合到我们正在做的事情中。
So that’s been really fun and I wanna do more of that.
所以这真的很有趣，我想做更多这样的事情。
So it’s a really exciting time, I would say.
所以我想说，这是一个非常激动人心的时刻。
When you were working on this originally, in the early days when you were making the transition from studying RNA to studying CRISPR to realizing its incredible power in terms of rewriting the code of life, so to speak.
当你最初从事这项工作时，在早期，当你从研究 RNA 过渡到研究 CRISPR 时，可以这么说，认识到它在重写生命密码方面的不可思议的力量。
When you look back at that time, is there a time that you miss of, you know, before all of this, before the success, the attention, and also seeing the impact it’s having on so many other researchers and so much other work?
当你回顾那段时光时，是否有一段时光是你怀念的，你知道，在这一切之前，在成功、关注之前，以及看到它对许多其他研究人员和许多其他工作产生的影响之前？
Well, yes, um, my life certainly changed dramatically right around 2012.
嗯，是的，嗯，我的生活确实在 2012 年左右发生了巨大的变化。
And, I often joke…
而且，我经常开玩笑……
my husband’s also a professor here at UC Berkeley…
我丈夫也是加州大学伯克利分校的教授……
and I often, uh, joke to him that there was my life BC — before CRISPR — and then everything changed.
我经常，呃，对他开玩笑说，我的生活是公元前的——在 CRISPR 之前——然后一切都改变了。
And you know, do I miss it?
你知道吗，我想念它吗？
Well, yeah, some parts of it I definitely do.
嗯，是的，其中的某些部分我确实做到了。
I, you know, there’s a joy in just coming into the lab every day and spending time with my students.
我，你知道，每天来到实验室和我的学生们共度时光是一种快乐。
I try to do as much as that as I can, but, you know, I’m doing things like, this, which is fine, you know, but it’s different.
我尝试尽我所能，但是，你知道，我正在做这样的事情，这很好，你知道，但它是不同的。
And yeah, I love science so much.
是的，我非常热爱科学。
I love the process of discovery.
我喜欢发现的过程。
I love working with scientists who are just starting out in their careers, you know, and they’re creative.
我喜欢与刚刚开始职业生涯的科学家一起工作，你知道，他们很有创造力。
They’re fearless.
他们无所畏惧。
They want to figure things out.
他们想把事情弄清楚。
And it’s, you know, science is always a struggle, right?
你知道，科学总是一场斗争，对吗？
It’s always hard.
总是很难。
And so I do enjoy going through that struggle with them, and I don’t do that as much as I used to.
所以我确实喜欢和他们一起经历这场斗争，但我不像以前那样经常这样做了。
And I do miss it.
我确实很想念它。
I often joke…
我经常开玩笑...
that there was my life BC — before CRISPR — and then everything changed.
我的生活是公元前的——在 CRISPR 之前——然后一切都改变了。
All great stories have to have a struggle.
所有伟大的故事都必须经历斗争。
No great book was written without a struggle to drive the plot.
没有一部伟大的书是不经过努力推动情节而写成的。
Thank you so much, Jennifer.
非常感谢你，詹妮弗。
It really is such a mind-blowing topic.
这确实是一个令人兴奋的话题。
It’s so exciting to see it moving and that it’s happening and it’s actually happening fast.
看到它的移动、它正在发生，而且实际上发生得很快，真是令人兴奋。
We’re gonna live to see the implications of this.
我们会活着看到这的影响。
Thank you so much for joining us.
非常感谢您加入我们。
Thanks for having me, Janna.
谢谢你邀请我，詹娜。
Great to be here.
很高兴来到这里。
Wow, I’m hit by so many things as I listen to that.
哇，当我听到这个的时候，我被很多事情击中了。
The first is something that I think I heard Stephen Jay Gould, the old evolutionary biologist and writer, say when I was sitting in on a lecture of his one time, which was that it was the age of bacteria, it is the age of bacteria, and it will always be the age of bacteria.
第一个是我听老进化生物学家兼作家史蒂芬·杰伊·古尔德（Stephen Jay Gould）听他讲课时说的一句话，那就是，这是细菌的时代，这是细菌的时代，而且永远都是细菌的时代。
You know, we don’t, see them.
你知道，我们看不到他们。
We don’t think about them much.
我们不太考虑他们。
But they’re so important, and you can learn so much about life as Jennifer Doudna and her collaborators have done by focusing on bacteria.
但它们非常重要，你可以像詹妮弗·杜德纳（Jennifer Doudna）和她的合作者一样，通过关注细菌来了解更多关于生命的知识。
Yeah.
是的。
But it’s also fascinating to talk to someone who’s had such a direct impact on technology, therapies, the potential for improving the human condition, but that’s not really why she got started, and this is something people keep forgetting.
但与对技术、治疗、改善人类状况的潜力产生如此直接影响的人交谈也很有趣，但这并不是她开始的真正原因，而且这是人们一直忘记的事情。
It really was just curiosity-driven science, childlike enthusiasm that she maintained her whole life.
她一生都保持着好奇心驱动的科学和童心般的热情。
And how do we convince people that we need to encourage that to have the impact on humanity?
我们如何说服人们我们需要鼓励这一点才能对人类产生影响？
Hmm.
唔。
Well, it might help if we could convey the history of science in a way that was as engaging to people as it really is.
好吧，如果我们能够以一种真正吸引人们的方式来传达科学史，这可能会有所帮助。
You know?
你知道？
I mean, throughout the history of science, we hear about these stories of serendipity, where someone discovers something so important, and it’s often described as being by accident.
我的意思是，在整个科学史上，我们都听说过这些偶然的故事，即有人发现了如此重要的东西，而且通常被描述为偶然。
But it was pointed out in some place that I read that you shouldn’t think of it as exactly by accident.
但我在某个地方读到，你不应该认为它完全是偶然的。
Like in her case, she was really looking for something very focused and thinking about RNA in bacteria.
就像她的例子一样，她真正在寻找一些非常专注并思考细菌中 RNA 的东西。
But then she ended up finding something she wasn’t looking for and somehow putting your mind in that state where you’re curious and alert — I mean, it’s that old line about chance favoring only the prepared mind.
但后来她最终发现了一些她没有在寻找的东西，并以某种方式让你的头脑处于好奇和警觉的状态——我的意思是，这就是那句老话，机会只青睐有准备的头脑。
Mmm-hmm.
嗯嗯。
Oh, and you definitely get that in her story.
哦，你肯定在她的故事中明白了这一点。
“And then I met so and so, and then we talked about this.” So it’s not as though she simply sat down and it was just a matter of time.
“然后我遇到了某某人，然后我们谈论了这个。”所以她并不是简单地坐下来，这只是时间问题。
There is that serendipity.
有这样的机缘巧合。
There is that making decisions, choosing to be open to somebody, choosing to have a dialogue on something a little left of center of what you’re working on, and being open to pursuing that with everything that you brought to the table.
做出决定，选择对某人持开放态度，选择就你正在做的事情中心偏左的事情进行对话，并以开放的态度用你带到桌面上的一切来追求这一目标。
It’s something, too, that I think about as a scientist or a mathematician in the broader collective of our enterprise that will lightning strike for me personally?
作为我们企业更广泛集体中的科学家或数学家，我也认为这对我个人来说会是闪电般的事情吗？
You know, there’s ego in what we do.
你知道，我们所做的事情都是自负的。
And I sometimes have to remind myself that it doesn’t matter if it happens to me as long as it happens to somebody.
有时我必须提醒自己，只要它发生在别人身上，它是否发生在我身上并不重要。
Yeah, absolutely.
是的，绝对是。
Well, Steve, to be continued.
好吧，史蒂夫，待续。
Let’s both get back to our work.
让我们回到我们的工作上来吧。
All right.
好的。
Get to work, Janna.
开始工作吧，詹娜。
I’ll see you next time.
下次见。
Bye-bye.
再见。
[laughs]
[笑]
If you’re enjoying The Joy of Wh y and you’re not already subscribed, hit the subscribe or follow button wherever you’re listening.
如果您正在享受“为什么的乐趣”并且尚未订阅，请在您收听的任何地方点击“订阅”或“关注”按钮。
You can also leave a review for the show.
您还可以对节目发表评论。
It helps people find this podcast.
它可以帮助人们找到这个播客。
Find articles, newsletters, videos and more at Quanta Magazine [DOT] org.
在 Quanta Magazine [DOT] org 查找文章、时事通讯、视频等。
The Joy of Why is a podcast from Quanta Magazine , an editorially independent publication supported by the Simons Foundation.
《The Joy of Why》是来自《Quanta》杂志的播客，《Quanta》杂志是一份由西蒙斯基金会支持的独立编辑出版物。
Funding decisions by the Simons Foundation have no influence on the selection of topics, guests or other editorial decisions in this podcast or in Quanta Magazine .
西蒙斯基金会的资助决定不会影响本播客或广达杂志的主题选择、嘉宾或其他编辑决定。
The Joy of Why is produced by PRX Productions; the production team is Caitlin Faulds, Jade Abdul-Malik, Genevieve Sponsler, and Merritt Jacob.
《Joy of Why》由 PRX Productions 制作；制作团队包括 Caitlin Faulds、Jade Abdul-Malik、Genevieve Sponsler 和 Merritt Jacob。
The Executive Producer of PRX Productions is Jocelyn Gonzales.
PRX Productions 的执行制片人是 Jocelyn Gonzales。
Edwin Ochoa is our project manager.
埃德温·奥乔亚是我们的项目经理。
From Quanta Magazine , Simon Frantz and Samir Patel provided editorial guidance, with support from Samuel Velasco, Simone Barr, and Michael Kanyongolo.
《Quanta》杂志的 Simon Frantz 和 Samir Patel 提供了编辑指导，并得到了 Samuel Velasco、Simone Barr 和 Michael Kanyongolo 的支持。
Samir Patel is Quanta’s Editor-in-Chief.
萨米尔·帕特尔 (Samir Patel) 是广达的主编。
The episode art is by Chanelle Nibbelink and our logo is by Jaki King and Kristina Armitage.
剧集艺术由 Chanelle Nibbelink 创作，我们的徽标由 Jaki King 和 Kristina Armitage 创作。
Special thanks to Garth Avery at the Cornell Broadcast Studio.
特别感谢康奈尔广播工作室的 Garth Avery。
I’m your host, Janna Levin.
我是你们的主持人，詹娜·莱文。
If you have any questions or comments, please email us at [email protected] .
如果您有任何问题或意见，请发送电子邮件至 [email protected]。
Thanks for listening!
感谢您的聆听！
Get highlights of the most important news delivered to your email inbox
获取发送到您的电子邮件收件箱的最重要新闻的摘要
Quanta Magazine moderates comments to facilitate an informed, substantive, civil conversation.
《Quanta》杂志对评论进行审核，以促进知情、实质性、文明的对话。
Abusive, profane, self-promotional, misleading, incoherent or off-topic comments will be rejected.
辱骂、亵渎、自我推销、误导、语无伦次或偏离主题的评论将被拒绝。
Moderators are staffed during regular business hours (New York time) and can only accept comments written in English.
版主在正常工作时间（纽约时间）有工作人员，并且只能接受英文评论。