Avoiding, Treating & Curing Cancer With the Immune System | Dr. Alex Marson
Dr. Alex Marson:
亚历克斯·马森博士：
We're living in this amazing moment of biology where we can put a gene that encodes something on the surface of T cells that will make them programmed to search and destroy for cancer cells.
我们生活在生物学的这个令人惊叹的时刻，我们可以将编码某些东西的基因放在T细胞表面，使它们被编程为搜索和摧毁癌细胞。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
Now, this is largely known as CAR T cells, chimeric antigen receptor.
现在，这被广泛称为 CAR T 细胞，即嵌合抗原受体。
This is a receptor that was designed in a lab, does not exist in nature.
这是一种在实验室设计的受体，自然界中不存在。
When those T cells get reinfused into a patient the way that you get a blood transfusion, those CARs are directed to go against cancers.
当这些 T 细胞像输血一样重新输入患者体内时，这些 CAR 就会被用来对抗癌症。
Andrew Huberman:
安德鲁·休伯曼：
Welcome to the Huberman Lab podcast, where we discuss science and science-based tools for everyday life.
欢迎来到休伯曼实验室播客，我们在这里讨论科学和基于科学的日常生活工具。
I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine.
我是安德鲁·胡伯曼，斯坦福大学医学院神经生物学和眼科教授。
My guest today is Dr. Alex Marson.
今天我的客人是亚历克斯·马森博士。
Dr. Alex Marson is a medical doctor and scientist at the University of California, San Francisco.
亚历克斯·马森博士是加州大学旧金山分校的医生和科学家。
He is developing new ways to reprogram the immune system to cure cancers.
他正在开发重新编程免疫系统以治愈癌症的新方法。
Today, we discuss how your immune system works, how autoimmunity works, and how gene editing and other new technologies can be successfully leveraged to defeat childhood and adult cancers.
今天，我们讨论免疫系统如何工作、自身免疫如何工作，以及如何成功利用基因编辑和其他新技术来战胜儿童和成人癌症。
Dr. Marson is truly one-of-a-kind in his understanding of the clinical aspects of cancer treatment, the science of the immune system, and, as you'll soon hear, in explaining the things that genuinely increase your cancer risk, many of which are surprising, and the actionable steps that we can all take to reduce our probability of getting cancer.
马森博士对癌症治疗的临床方面、免疫系统科学的理解确实是独一无二的，而且您很快就会听到，他解释了真正增加癌症风险的因素（其中许多是令人惊讶的），以及我们都可以采取的降低患癌症概率的可行步骤。
In addition to the usual factors, smoking, UV light, and environmental toxins such as pesticides, we discuss the actual cancer risks that come from things like eating charred meats, airport scanners, and food additives, and how to gauge your individual level of risk.
除了吸烟、紫外线和杀虫剂等环境毒素等常见因素外，我们还讨论了吃烧焦的肉、机场扫描仪和食品添加剂等因素带来的实际癌症风险，以及如何衡量个人风险水平。
We also explore gene editing for reversing diseases, which until recently was science fiction, but now is a reality.
我们还探索基因编辑来逆转疾病，这直到最近还是科幻小说，但现在已成为现实。
By the end of today's episode, thanks to Dr. Marson, you'll have the most up-to-date understanding of the state-of-the-art science for cancer prevention and treatment, knowledge that is certain to impact you or a close friend or family member in your lifetime.
在今天的节目结束时，感谢马森博士，您将对癌症预防和治疗的最先进科学有最新的了解，这些知识肯定会影响您或您的亲密朋友或家人的一生。
Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford.
在开始之前，我想强调一下，这个播客与我在斯坦福大学的教学和研究角色是分开的。
It is, however, part of my desire and effort to bring zero cost to consumer information about science and science-related tools to the general public.
然而，我的愿望和努力的一部分是向公众提供有关科学和科学相关工具的零成本消费者信息。
In keeping with that theme, today's episode does include sponsors.
为了与这个主题保持一致，今天的节目确实有赞助商。
And now for my discussion with Dr. Alex Marson.
现在我与亚历克斯·马森博士进行讨论。
Dr. Alex Marson, welcome.
亚历克斯·马森博士，欢迎光临。
Dr. Alex Marson:
亚历克斯·马森博士：
Andrew.
安德鲁.
Andrew Huberman:
安德鲁·休伯曼：
This is the first time that we're going to have a serious discussion about the immune system, cancer, and gene editing technologies on this podcast.
这是我们第一次在这个播客上认真讨论免疫系统、癌症和基因编辑技术。
So I'm delighted that you're here.
所以我很高兴你在这里。
It's also great to see you again.
很高兴再次见到你。
Dr. Alex Marson:
亚历克斯·马森博士：
Thank you for having me.
谢谢你有我。
Really, really good to see you.
真的，真的很高兴见到你。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, it's been a while.
是的，已经有一段时间了。
Let's start off with the big picture.
让我们从大局开始。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
How are we doing?
我们怎么样？
How's biology looking?
生物学看起来怎么样？
How's medicine looking?
医学看起来怎么样？
Are we on the fast track to much better things?
我们是否正走在通往更好事物的快车道上？
Are we going to slog along for another 10 years before we have cures to the many concerns that people have about cancer, Alzheimer's, and the rest, or are you encouraged by what's happening right now?
我们是否还要再苦苦挣扎 10 年才能治愈人们对癌症、阿尔茨海默氏症和其他疾病的许多担忧，或者您对现在发生的事情感到鼓舞吗？
Dr. Alex Marson:
亚历克斯·马森博士：
I think maybe the general public doesn't quite know how excited biologists are about what's possible.
我想也许公众不太了解生物学家对可能性有多么兴奋。
And maybe we've overpromised.
也许我们承诺过多了。
Maybe in the past, we've said we're on the brink of curing disease and people haven't seen it.
也许在过去，我们说过我们正处于治愈疾病的边缘，但人们还没有看到它。
But something is materially different right now, and there is a convergence of so many different ways of understanding biology, but then not having that stop at understanding, but to actually intervene at the root causes of disease.
但现在情况有所不同，许多不同的生物学理解方式趋同，但并不仅仅停留在理解上，而是实际干预疾病的根源。
And over the course of this conversation, I imagine we're going to talk about DNA sequencing, understanding cells, but going all the way to rewriting specific DNA sequences inside of the cells of our immune system, doing this not one at a time, but testing every gene and understanding pieces of DNA throughout our entire genome to understand what controls our cells.
在这次谈话的过程中，我想我们将讨论 DNA 测序、理解细胞，但会一直重写我们免疫系统细胞内的特定 DNA 序列，不是一次一个，而是测试每个基因并了解整个基因组中的 DNA 片段，以了解控制我们细胞的因素。
And then being able to take that information and actually do something about it to boost our immune system to go after cancer, to balance it for inflammation and autoimmunity.
然后能够获取这些信息并实际采取一些措施来增强我们的免疫系统来对抗癌症，平衡炎症和自身免疫。
And that doesn't just have to be sort of searching for a pill.
这不仅仅需要寻找药丸。
All of a sudden, we can actually talk to our own cells and give them instructions in the language of DNA and the language of molecular biology.
突然之间，我们实际上可以与自己的细胞对话，并用 DNA 语言和分子生物学语言向它们发出指令。
And in some instances, this is being done with CRISPR, but it's also being done with lipid nanoparticles and vaccines.
在某些情况下，这是通过 CRISPR 完成的，但也可以通过脂质纳米颗粒和疫苗来完成。
And we're still inventing new ways of giving these instructions, but all of a sudden, medicine is programming the behavior of cells in a way that's much more directed than was ever conceivable before.
我们仍在发明发出这些指令的新方法，但突然之间，医学正在以一种比以前想象的更有针对性的方式对细胞的行为进行编程。
There's really a step function in what's imaginable and achievable in medicine.
医学上的可想象和可实现确实存在阶梯函数。
Andrew Huberman:
安德鲁·休伯曼：
Super exciting.
超级刺激。
Do you think that molecular biology and genetic engineering and/or AI are the reasons that things are on this accelerated timeline?
您认为分子生物学、基因工程和/或人工智能是事情加速发展的原因吗？
Dr. Alex Marson:
亚历克斯·马森博士：
Yes is the answer.
答案是肯定的。
All of those things.
所有这些事情。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
I think we can do experiments at a different level of scale.
我认为我们可以在不同规模上进行实验。
We can generate data, and then we have the computational tools, including AI, but we have computational sophistication to actually extract insights from massive amounts of data.
我们可以生成数据，然后我们拥有包括人工智能在内的计算工具，但我们拥有计算的复杂性，可以真正从大量数据中提取见解。
And I think historically, biology, it was an observational science.
我认为从历史上看，生物学是一门观察科学。
Especially if you wanted to study things in humans, there wasn't a way to intervene.
尤其是如果你想研究人类的东西，就没有办法干预。
Now all of a sudden, we're taking human cells, we're taking them into the lab and making genetic changes and reading out the consequences and directly being able to observe the effect.
现在突然间，我们将人类细胞带入实验室，进行基因改变，读出结果并直接观察效果。
And we have tools to do this with imaging.
我们有工具可以通过成像来做到这一点。
We have the tools to do this with DNA sequencing, and we can take this all the way into clinical trials and see what are the consequences when we actually go after targeted DNA sequences and make our cells better at treating disease.
我们拥有通过 DNA 测序来做到这一点的工具，我们可以将其一直带入临床试验，看看当我们真正追求目标 DNA 序列并使我们的细胞更好地治疗疾病时会产生什么后果。
Andrew Huberman:
安德鲁·休伯曼：
Would you mind educating us about the immune system a bit?
您介意向我们介绍一下免疫系统吗？
The adaptive and the innate immune system, some of the major cell types, because I think those are going to form the building blocks of our discussions about cancer and other things today.
适应性和先天免疫系统，一些主要的细胞类型，因为我认为这些将构成我们今天讨论癌症和其他事物的基石。
Dr. Alex Marson:
亚历克斯·马森博士：
Our immune system permeates almost every aspect of our health and disease.
我们的免疫系统几乎渗透到我们健康和疾病的各个方面。
It is a system, really, in the sense of it's involved in every part of our body that has evolved to protect us.
从某种意义上说，它实际上是一个系统，涉及我们身体的每个部分，这些部分都是为了保护我们而进化的。
Largely to protect us against infections, viruses, bacteria, fungus, all sorts of foreign invasions.
主要是为了保护我们免受感染、病毒、细菌、真菌和各种外来入侵。
And our immune system has developed a balance that, when it's working properly, doesn't recognize the cells that are supposed to be in the body, but is finely tuned to recognize signs of things that shouldn't be in the body and to eliminate them.
我们的免疫系统已经形成了一种平衡，当它正常工作时，它不会识别应该存在于体内的细胞，但会进行微调以识别不应该存在于体内的事物的迹象并消除它们。
I mean, at its core, that's the basic job of the immune system.
我的意思是，从本质上讲，这是免疫系统的基本工作。
Andrew Huberman:
安德鲁·休伯曼：
To recognize us versus non-us.
识别我们与非我们。
Dr. Alex Marson:
亚历克斯·马森博士：
Exactly.
正是如此。
And you talked about the innate versus the adaptive immune system.
您谈到了先天免疫系统与适应性免疫系统。
Largely what we're talking about are white blood cells.
我们谈论的主要是白细胞。
We're talking about different types of white blood cells that are either inside of tissues or circulating in our bloodstream that go around and play coordinated and specialized roles in sensing when something comes in that is not us, that's foreign, that shouldn't be there.
我们谈论的是不同类型的白细胞，它们要么在组织内部，要么在我们的血液中循环，它们四处走动，在感知不属于我们、外来的、不应该存在的东西时发挥协调和专门的作用。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
The innate immune system is thought of as the first alarm system that something's wrong.
先天免疫系统被认为是出现问题的第一个警报系统。
And with the innate immune system, which consists of cells like dendritic cells, macrophages, these are cells that are going around and they're looking for patterns of things that just generally aren't in human cells.
先天免疫系统由树突状细胞、巨噬细胞等细胞组成，这些细胞四处活动，寻找人类细胞中通常不存在的模式。
Some signs of damage, some signs of things that shouldn't be there in a generic way in a healthy human.
一些损伤的迹象，一些不应该以一般方式出现在健康人身上的迹象。
When those first alarm systems get triggered, all of a sudden, these innate immune systems start releasing things.
当第一个警报系统被触发时，这些先天免疫系统突然开始释放物质。
They change their state, and they send off an alarm to other cells in the immune system.
它们改变自己的状态，并向免疫系统中的其他细胞发出警报。
And then they often recruit in the second arm of the immune system that you mentioned, the adaptive immune system.
然后他们经常招募你提到的免疫系统的第二臂，即适应性免疫系统。
We'll talk a lot about the adaptive immune system today.
今天我们将详细讨论适应性免疫系统。
And the major players in the adaptive immune system are a group of white blood cells that are collectively known as lymphocytes.
适应性免疫系统的主要参与者是一组统称为淋巴细胞的白细胞。
But we'll talk about B cells and T cells in particular, which are major groups of lymphocytes.
但我们将特别讨论 B 细胞和 T 细胞，它们是淋巴细胞的主要群体。
We've been focused heavily on T cells.
我们一直非常关注 T 细胞。
T cells play a central role in coordinating the fine-tuning of the immune response.
T 细胞在协调免疫反应的微调方面发挥着核心作用。
One of the amazing things about the T cells is that each T cell naturally in our body, it's one of the few places where each cell will actually have a different piece of DNA that's not inherited in our germline sequence.
T 细胞令人惊奇的事情之一是，我们体内的每个 T 细胞都是自然存在的，它是每个细胞实际上都具有不同 DNA 片段的少数地方之一，这些 DNA 片段不是在我们的种系序列中遗传的。
Each T cell will make its own receptor that is generated largely at random to go and sense something, and those sensors that get put on the surface of T cells are there to engage.
每个 T 细胞都会产生自己的受体，该受体很大程度上是随机生成的，用于感知某些东西，而那些放置在 T 细胞表面的传感器则可以参与其中。
And if they're engaged, it's a sign that something has been recognized as foreign.
如果他们订婚了，那就表明某些东西被认为是外国的。
And so we have this incredible diversity of different T cell receptors that have developed on our T cells.
因此，我们的 T 细胞上形成了令人难以置信的不同 T 细胞受体多样性。
Each one will have a different unique receptor on its surface.
每一种的表面都有不同的独特受体。
Each cell will have a different receptor on its surface.
每个细胞的表面都有不同的受体。
And the way to think about these receptors is that they're sensors.
考虑这些受体的方式是它们是传感器。
When they're engaged, they send a signal to the T cell that, okay, we found something that you've been programmed to recognize, and programmed as recognized as foreign, if the immune system is working properly.
当它们参与时，它们会向 T 细胞发送信号，好吧，我们发现了一些你已被编程识别的东西，并且如果免疫系统正常工作，则被编程为识别为外来物。
Andrew Huberman:
安德鲁·休伯曼：
And are the genes that these T cells make as these receptors are those based on experience of the organism?
这些T细胞作为这些受体产生的基因是基于生物体的经验吗？
Because you said that it doesn't come from the germline.
因为你说它不是来自种系。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But we should clarify that the germline is not about infectious germs in this context.
但我们应该澄清，在这种情况下，种系与传染性细菌无关。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
The germline DNA is from the sperm and egg-
种系 DNA 来自精子和卵子
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
that were your parents.
那是你的父母。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
It became you.
它变成了你。
There's recombination of those genes, and then there's you, all, each and all.
这些基因会重组，然后就是你，所有人，每一个和所有人。
And the T cells are making genes that neither of your parents necessarily expressed, nor that you were expected to express, except based on what?
T 细胞正在制造你父母都不一定表达的基因，你也不一定会表达这些基因，除非基于什么？
Exposure to particular pathogens?
接触特定病原体？
Why do they make certain receptors and not others?
为什么它们会产生某些受体而不是其他受体？
Dr. Alex Marson:
亚历克斯·马森博士：
Largely random.
很大程度上是随机的。
The pieces of DNA at this part of the DNA actually recombine and get pasted together in unique ways.
这部分 DNA 的 DNA 片段实际上会以独特的方式重新组合并粘贴在一起。
Andrew Huberman:
安德鲁·休伯曼：
So it's probabilistic.
所以这是概率性的。
Dr. Alex Marson:
亚历克斯·马森博士：
It's probabilistic, and that's what allows us to have cells lying there and waiting for things that we've never encountered.
它是概率性的，这使得我们能够让细胞躺在那里等待我们从未遇到过的事情。
If a bacteria might come into existence or a virus might come into existence that doesn't even exist now in nature, but we might have T cells lying there waiting that could be engaged by those proteins on the surface that viruses would introduce.
如果细菌可能存在，或者病毒可能存在，但现在自然界中甚至不存在，但我们可能会有 T 细胞躺在那里等待，它们可能会被病毒引入的表面蛋白质所结合。
Andrew Huberman:
安德鲁·休伯曼：
That's incredible.
这太不可思议了。
Would you mind mentioning the role of the thymus?
您介意提一下胸腺的作用吗？
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
These days I'm hearing more and more about we have a thymus-
这些天我越来越多地听到我们有胸腺——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and we lose a thymus.
我们失去了胸腺。
Would it be beneficial if we could keep our thymus around?
如果我们能保留胸腺，会有好处吗？
Dr. Alex Marson:
亚历克斯·马森博士：
So thymus is actually the reason that T cells are called T cells is the T stands for thymus.
所以胸腺实际上就是T细胞被称为T细胞的原因，T代表胸腺。
And the thymus is an organ that it does sort of shrink as we age, but at least in childhood, it sort of lies by your heart.
胸腺是一个随着年龄的增长而萎缩的器官，但至少在童年时期，它就位于你的心脏旁边。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
And it is the place where T cells go and a key place of their education.
它是T细胞的去向和教育的关键场所。
So they are making these sensors largely at random.
所以他们很大程度上是随机制造这些传感器的。
And in the thymus, they get culled.
在胸腺中，它们被剔除。
They get selected, and the ones that by accident are generated that recognize something that is supposed to be in your body, if the T cell engages a natural target in the thymus, those cells will die.
它们被选中，并且偶然生成的细胞能够识别您体内应该存在的东西，如果 T 细胞与胸腺中的天然目标结合，这些细胞就会死亡。
And so what emerges from the thymus should be, and this is not perfect process, but should be things that have emerged at random but then are selected to remove things that recognize your own body targets.
所以从胸腺中出现的东西应该是，这不是完美的过程，但应该是随机出现的东西，然后被选择去除识别你自己身体目标的东西。
Andrew Huberman:
安德鲁·休伯曼：
There's sort of a negative selection-
有一种负面选择——
Dr. Alex Marson:
亚历克斯·马森博士：
There's a negative selection
存在负选择
Andrew Huberman:
安德鲁·休伯曼：
...
...
of the stuff that's you, so that your immune system doesn't attack you, and it knows you from non-you.
就是你的东西，这样你的免疫系统就不会攻击你，并且它可以区分你和非你。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
That's exactly right.
完全正确。
There's actually both a positive selection and a negative selection.
实际上有正选择和负选择。
That's exactly the right way to think of it.
这正是正确的思考方式。
The cells get Will only emerge from the thymus that if they have a receptor on their surface that's there, so that's one positive selection.
细胞只有在表面有受体的情况下才会从胸腺中出现，所以这是一种正选择。
But if it engages with a self-target in the thymus, it gets negatively selected.
但如果它与胸腺中的自我目标发生作用，它就会被负面选择。
So what comes out are T cells that are there with sensors in place to recognize things that shouldn't be there.
因此，T 细胞就会出现，其中带有传感器，可以识别不应该存在的东西。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So your thymus and your T cells get educated-
这样你的胸腺和 T 细胞就会得到教育——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
in childhood.
在童年。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And that's what you're working with, except that the immune system can adapt and make antibodies to things it doesn't recognize.
这就是你正在处理的事情，只不过免疫系统可以适应并针对它无法识别的东西产生抗体。
Dr. Alex Marson:
亚历克斯·马森博士：
The antibodies come from the other type of lymphocytes.
抗体来自其他类型的淋巴细胞。
So now we can talk about the B cells.
现在我们可以谈谈 B 细胞。
B cells are this other type of lymphocyte that work in coordination with T cells, and they're the antibody-producing cells.
B 细胞是另一种类型的淋巴细胞，与 T 细胞协同工作，它们是产生抗体的细胞。
So they actually have a similar process where they're generating different antibodies at random through a similar kind of recombination event.
因此，他们实际上有一个类似的过程，通过类似的重组事件随机生成不同的抗体。
They have their own form of selection that they go through.
他们有自己的选择形式。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
And then those antibodies can then be released into the bloodstream and are the basis for protection against infections after we get them.
然后这些抗体可以释放到血液中，成为我们感染后预防感染的基础。
Andrew Huberman:
安德鲁·休伯曼：
I'd like to take a quick break and acknowledge our sponsor, BetterHelp.
我想稍微休息一下并感谢我们的赞助商 BetterHelp。
BetterHelp offers professional therapy with a licensed therapist carried out entirely online.
BetterHelp 提供由持证治疗师完全在线进行的专业治疗。
Now, I've been doing therapy for a very long time, and I can tell you that it's a lot like physical workouts.
现在，我已经进行治疗很长时间了，我可以告诉你，这很像体育锻炼。
There are days when I want to do it, and there are days when I don't want to do it.
有想做的日子，也有不想做的日子。
But when I finish a therapy session, every single time, I come away feeling better and knowing that the time was well spent.
但当我完成一次治疗后，每一次，我都会感觉好多了，并且知道我的时间花得很值。
And typically, when I finish a therapy session, I come away with a valuable insight or some new perspective on something that I've been working through, whether or not that's with work, with relationships, my personal life, or simply my relationship with myself.
通常，当我完成一次治疗时，我会对我一直在努力解决的事情产生宝贵的见解或一些新的观点，无论是工作、人际关系、我的个人生活，还是仅仅是我与自己的关系。
There's just so much benefit that comes through effective therapy, and that's not just my personal experience.
有效的治疗可以带来很多好处，这不仅仅是我个人的经历。
There are loads and loads of clinical studies to support that.
有大量的临床研究可以支持这一点。
With BetterHelp, they make it very easy to find an expert therapist who can help provide the benefits that come through effective therapy.
通过 BetterHelp，他们可以很容易地找到一位专家治疗师，他可以帮助提供通过有效治疗带来的好处。
They have a short questionnaire to help match you to the ideal therapist for you.
他们有一份简短的调查问卷，可以帮助您找到最适合您的治疗师。
And while BetterHelp has an industry-leading match rate, if you aren't happy with your match, you can switch to a different therapist anytime.
虽然 BetterHelp 拥有行业领先的匹配率，但如果您对匹配不满意，您可以随时更换为其他治疗师。
Also, because BetterHelp is done entirely online, it's extremely time efficient.
此外，由于 BetterHelp 完全在线完成，因此非常省时。
You simply log on and have your session.
您只需登录并进行会话即可。
If you would like to try BetterHelp, go to betterhelp.com/huberman to get 10% off your first month.
如果您想尝试 BetterHelp，请访问 betterhelp.com/huberman，第一个月可享受 10% 的折扣。
Again, that's betterhelp.com/huberman.
再说一次，这是 betterhelp.com/huberman。
Today's episode is also brought to us by Helix Sleep.
今天的节目也是由 Helix Sleep 为我们带来的。
Helix Sleep makes mattresses and pillows that are customized to your unique sleep needs.
Helix Sleep 生产根据您独特的睡眠需求定制的床垫和枕头。
Now, I've spoken many times before on this and on other podcasts about the fact that getting a great night's sleep is the foundation of mental health, physical health, and performance.
现在，我之前曾多次在这个播客和其他播客上谈到这样一个事实：睡个好觉是心理健康、身体健康和表现的基础。
When we aren't getting great sleep on a consistent basis, everything suffers.
当我们不能持续获得良好的睡眠时，一切都会受到影响。
And when we are sleeping well and enough, our mental health, physical health, and performance in all endeavors improve markedly.
当我们睡眠充足且良好时，我们的心理健康、身体健康和所有努力的表现都会显着改善。
Now, the mattress you sleep on makes a huge difference in the quality of sleep that you get each night.
现在，您所睡的床垫会对您每晚的睡眠质量产生巨大影响。
How soft it is or how firm it is all play into your comfort and need to be tailored to your unique sleep needs.
它的柔软度或硬度都会影响您的舒适度，并且需要根据您独特的睡眠需求进行定制。
If you go to the Helix website, you can take a brief two-minute quiz, and it will ask you questions such as, do you sleep on your back, your side, or your stomach?
如果你访问 Helix 网站，你可以做一个两分钟的简短测验，它会问你一些问题，比如你是仰卧、侧卧还是俯卧？
Maybe you know, maybe you don't.
也许你知道，也许你不知道。
Do you tend to run hot or cold during the night?
你晚上容易感到热还是冷？
Things of that sort.
诸如此类的事情。
You answer those questions, and Helix will match you to the ideal mattress for you.
您回答这些问题，Helix 将为您匹配理想的床垫。
For me, that turned out to be the Dusk, D-U-S-K, mattress.
对我来说，这就是 Dusk、D-U-S-K 床垫。
I've been sleeping on a Dusk mattress for more than four years now, and it's been far and away the best sleep that I've ever had.
我已经在 Dusk 床垫上睡了四年多了，这无疑是我睡过的最好的睡眠。
If you'd like to try Helix, you can go to helixsleep.com/huberman, take that two-minute sleep quiz, and Helix will match you to a mattress that's customized for you.
如果您想尝试 Helix，可以访问 helixsleep.com/huberman，参加两分钟的睡眠测验，Helix 将为您匹配专为您定制的床垫。
Right now, Helix is giving up to 27% off their entire site.
目前，Helix 整个网站提供高达 27% 的折扣。
Helix has also teamed up with TrueMed, which allows you to use your HSA, FSA dollars to shop Helix's award-winning mattresses.
Helix 还与 TrueMed 合作，允许您使用 HSA、FSA 美元购买 Helix 屡获殊荣的床垫。
Again, that's helixsleep.com/huberman to get up to 27% off.
再次强调，helixsleep.com/huberman 提供高达 27% 的折扣。
What underlies the sort of efficiency and functioning of the immune system?
免疫系统的效率和功能的基础是什么？
I know I and many people are thinking, okay, we hear our immune system gets activated-
我知道我和很多人都在想，好吧，我们听说我们的免疫系统被激活了——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
or our immune system is impaired.
或者我们的免疫系统受损。
The one thing that I'm certain supports the immune system is great sleep.
我确信支持免疫系统的一件事就是良好的睡眠。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Right?
对吗？
We just know this.
我们只知道这一点。
If we don't sleep well or enough, we get sick.
如果我们睡眠不好或睡眠不足，我们就会生病。
Is that because there's a known impairment of the immune system?
这是因为已知免疫系统受损吗？
Dr. Alex Marson:
亚历克斯·马森博士：
I wonder about this too.
我也想知道这个问题。
I agree.
我同意。
Anecdotally, I've experienced that so many times of being run down and then experiencing that I'm susceptible to infection, but I don't actually know the basis of that.
有趣的是，我经历过很多次的沮丧，然后经历了我很容易被感染，但我实际上不知道其基础。
It's kind of amazing how much we don't know about these determinants of immune health, largely because they're often variables that are left out of the mouse studies that we're doing, where we're studying largely steady-state immune responses in mice, and I would say we haven't done a full exploration yet of all the types of ways that general health impinges on the immune system.
令人惊讶的是，我们对这些免疫健康的决定因素知之甚少，很大程度上是因为它们通常是我们正在进行的小鼠研究中遗漏的变量，我们正在研究小鼠的稳态免疫反应，我想说的是，我们还没有对一般健康影响免疫系统的所有类型的方式进行全面的探索。
I had someone in my lab, a postdoc named Sagar Bapat, who came to my lab with an interest in metabolic health and wanted to study the effect of metabolic health on T cells.
我的实验室里有一位博士后，名叫 Sagar Bapat，他来到我的实验室，对代谢健康感兴趣，想要研究代谢健康对 T 细胞的影响。
And there's some growing stuff on this.
这方面还有一些不断增长的东西。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
But it's another like, what are the determinants of it?
但这是另一个问题，它的决定因素是什么？
He did experiments in my lab where he exposed an allergen, something that irritated the skin and caused an allergic-type reaction in the skin of mice.
他在我的实验室做了实验，暴露了一种过敏原，这种过敏原会刺激皮肤并引起小鼠皮肤的过敏型反应。
He did it in mice that were eating a normal mouse diet versus a high-fat diet that caused obesity.
他在吃正常老鼠饮食的老鼠和吃导致肥胖的高脂肪饮食的老鼠身上进行了实验。
And what we saw was that it was actually not just a quantitative difference in the immune system, but actually a qualitative difference.
我们看到的是，这实际上不仅仅是免疫系统的量的差异，而是质的差异。
Andrew Huberman:
安德鲁·休伯曼：
Mm.
嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
The actual type of inflammation, the cell responses were different in the mice eating a high-fat diet.
吃高脂肪饮食的小鼠的实际炎症类型和细胞反应是不同的。
And I think we haven't done enough studies like that where we actually start playing with the variables of life-
我认为我们还没有做足够的研究来真正开始研究生活的变量——
Andrew Huberman:
安德鲁·休伯曼：
Mm
毫米
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
and test them in a mechanistic way to isolate individual variants.
并以机械的方式测试它们以隔离各个变体。
What was interesting there was that The allergic reaction actually looked totally different in the obese mice.
有趣的是，肥胖小鼠的过敏反应实际上看起来完全不同。
And if we used surrogates that are for the types of drugs that are being used now to treat severe allergy, so we gave antibodies that block allergic responses, the normal diet mice would respond favorably to these.
如果我们使用现在用于治疗严重过敏的药物类型的替代品，因此我们给予阻止过敏反应的抗体，那么正常饮食的小鼠会对这些药物产生良好的反应。
They didn't help the mice that had the obese, high-fat diet response to inflammation.
他们并没有帮助那些肥胖、高脂肪饮食的小鼠对炎症的反应。
And in some cases, it actually maybe made it worse.
在某些情况下，这实际上可能会让情况变得更糟。
Andrew Huberman:
安德鲁·休伯曼：
Interesting.
有趣。
Dr. Alex Marson:
亚历克斯·马森博士：
So I think that there are these systemic ways.
所以我认为有这些系统性的方法。
Clearly, our intuition tells us this strongly, that systemic health can feed into our immune responses.
显然，我们的直觉强烈地告诉我们，全身健康可以促进我们的免疫反应。
But I think it's still been underexplored in rigorous ways.
但我认为它仍然没有得到严格的探索。
Andrew Huberman:
安德鲁·休伯曼：
I realize I'm asking very top contour type questions for which there probably aren't specific answers, but we all know people that get sick all the time.
我意识到我问的是非常重要的轮廓类型问题，这些问题可能没有具体的答案，但我们都知道人们总是生病。
And we know people who never seem to catch the bugs that everyone else seems to catch.
我们知道有些人似乎从来没有发现其他人似乎都能发现的错误。
Is there any understanding of what a more robust immune system is at the level?
是否了解什么是更强大的免疫系统？
Is it more T cells?
是不是T细胞更多了？
Are the B cells engaged more quickly so they can generate antibodies more quickly?
B 细胞是否能更快地参与反应，从而更快地产生抗体？
What is it?
它是什么？
Dr. Alex Marson:
亚历克斯·马森博士：
These are great questions that I don't think have full answers.
这些都是很好的问题，但我认为还没有完整的答案。
There's been a lot of work on genetic determinants, and there's extreme cases where people have a genetic gap in their immune system where they're really susceptible to something that healthy people should not be susceptible to.
关于遗传决定因素已经做了很多工作，在极端的情况下，人们的免疫系统存在遗传缺口，他们确实很容易受到健康人不应该敏感的东西的影响。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
And you see that there are certain types of infections that either happen or happen with a different type of severity in people with genetic deficits in certain branches of their immune system.
您会看到，在免疫系统某些分支有遗传缺陷的人身上，某些类型的感染要么发生，要么发生的严重程度不同。
And in some cases, you can pinpoint that we just talked about the innate immune response, the adaptive immune response.
在某些情况下，您可以指出我们刚刚谈到了先天免疫反应，即适应性免疫反应。
You can see that certain genetic mutations that people inherit could influence one or multiple branches of that immune responses and the consequences that manifests itself with different types of infection.
您可以看到，人们遗传的某些基因突变可能会影响免疫反应的一个或多个分支，以及不同类型感染所表现出来的后果。
And I suspect that there's some spectrum of that, that you can diagnose the really strong genetic consequences, and then there might be a long tail of more subtle genetic that might be multigenic that we don't fully understand.
我怀疑其中有一些范围，你可以诊断出真正强烈的遗传后果，然后可能会有一个更微妙的遗传长尾，可能是我们不完全理解的多基因。
And then I'm sure that there's other determinants of health that are just multifactorial.
然后我确信健康还有其他多因素的决定因素。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
And it also becomes this interplay between the health and then what you get exposed to by your environment.
它还成为健康与您所接触的环境之间的相互作用。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, speaking of which, I'm familiar with some studies from Stanford, I believe, where kids that have no exposure to peanuts get peanut allergies.
是的，说到这里，我相信斯坦福大学的一些研究表明，没有接触过花生的孩子会出现花生过敏。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And careful, subtle increasing exposure to peanuts essentially protects them against peanut allergies.
小心、微妙地增加对花生的接触基本上可以保护他们免受花生过敏。
So is it true that when we're young, that exposure to pathogens and different foods gives us a more robust immune system?
那么，当我们年轻时，接触病原体和不同的食物真的能让我们拥有更强大的免疫系统吗？
Dr. Alex Marson:
亚历克斯·马森博士：
I think that what we're exposed to and what we develop tolerance for is critically important during, there's some windows of early life that I think we're particularly susceptible to becoming tolerant.
我认为，在生命早期的某些时期，我们所接触的事物以及我们所产生的耐受性至关重要，我认为我们特别容易变得宽容。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
And I think if we don't get the proper exposure to certain things, all of a sudden our body can start to be hypersensitive to them, which manifests as allergies.
我认为，如果我们没有正确接触某些东西，我们的身体会突然开始对它们过敏，表现为过敏。
Now there's this balancing act.
现在有这种平衡行为。
I think the fear of allergies makes people more hesitant to expose kids, and I think it can get into these dangerous zones of you don't want to expose kids who are going to have a dangerous allergic response.
我认为对过敏的恐惧使人们更加犹豫是否要让孩子接触，而且我认为这可能会进入这些危险区域，因为你不想让孩子接触，因为他们会产生危险的过敏反应。
But on the other hand, critical early exposure is part of how tolerance is maintained.
但另一方面，关键的早期暴露是维持耐受性的一部分。
And I think peanut allergies, there is strong evidence that exposure to peanuts can be beneficial in people who are not yet allergic.
我认为花生过敏，有强有力的证据表明接触花生对尚未过敏的人是有益的。
Andrew Huberman:
安德鲁·休伯曼：
What's going on with autoimmune conditions?
自身免疫性疾病是怎么回事？
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Is this that the B cells and T cells are at a probabilistic level, the T cells developed some reaction, so to speak, a binding to cells that we naturally make that they shouldn't have, that it's just like it happens?
B细胞和T细胞是否处于概率水平，T细胞产生了一些反应，可以说，与我们自然产生的细胞的结合，它们不应该有，就像它发生一样？
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I've always been intrigued by the idea that when the immune system is really ramped up, people will experience autoimmune-like symptoms.
我一直对这样的想法很感兴趣：当免疫系统真正增强时，人们会经历类似自身免疫的症状。
I experienced that as a master's student.
我作为硕士生就经历过这一点。
I was working so much and probably not eating enough and drinking so much caffeine back then that I got some kind of funky skin lesion things.
那时我工作太多，可能吃得不够，喝了太多咖啡因，所以我得了一些奇怪的皮肤病变。
I went to the doctor, and like, "Oh, you're starting to get some attack of the deeper layers of your skin.
我去看医生，说：“哦，你的皮肤深层开始受到攻击。
You just need to work a little less." And sure enough, did that and-
你只需要少工作一点。”果然，我做到了并且——
Dr. Alex Marson:
亚历克斯·马森博士：
That did the trick?
就这样成功了？
Andrew Huberman:
安德鲁·休伯曼：
It did the trick.
它成功了。
It made me so keenly aware of how the immune system will, for lack of a better word, adapt to conditions, and it was trying to keep me healthy.
它让我如此敏锐地意识到免疫系统将如何适应条件，因为没有更好的词来形容，并且它正在努力保持我的健康。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And it overshot the mark, basically.
基本上，它超出了标准。
Dr. Alex Marson:
亚历克斯·马森博士：
I sort of walked you through at a first principle, how things are supposed to work.
我向您介绍了首要原则，即事情应该如何运作。
I told you, okay, there's this process of generating receptors on the surface of T cells.
我告诉过你，好吧，T 细胞表面有一个生成受体的过程。
Antibodies get generated on B cells, that they go through this positive selection and negative selection.
B 细胞上产生抗体，并经历正选择和负选择。
That's a delicate balancing act, and it doesn't actually work that way in practice.
这是一种微妙的平衡行为，但在实践中实际上并非如此。
In practice, T cells escape from the thymus that do recognize our own self-antigens.
实际上，T 细胞会从识别我们自身抗原的胸腺中逃脱。
And there's actually secondary mechanisms to block that, but autoimmune diseases emerge when those normal checks fail.
实际上有一些辅助机制可以阻止这种情况，但是当这些正常检查失败时，就会出现自身免疫性疾病。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
And I think it's a consequence that the immune system has two major responsibilities.
我认为这是免疫系统承担两个主要职责的结果。
It has to be primed to protect us from infections, which would be fatal, and be strong and recognize this incredible diversity of potential foreign dangerous things that we might experience.
它必须做好准备，保护我们免受致命的感染，并且必须坚强，并认识到我们可能遇到的潜在外国危险事物的令人难以置信的多样性。
But it also has to not recognize our own cells, and it can miss the mark in both ways.
但它也必须不识别我们自己的细胞，而且它可能会在这两个方面失去目标。
And so autoimmune disease manifests in different tissues.
因此，自身免疫性疾病表现在不同的组织中。
If your immune system starts recognizing targets in your joints, it can cause rheumatoid arthritis.
如果您的免疫系统开始识别关节中的目标，则可能会导致类风湿性关节炎。
If it's in the cells that produce insulin in the pancreas, it causes type 1 or childhood diabetes.
如果它存在于胰腺中产生胰岛素的细胞中，就会导致 1 型糖尿病或儿童糖尿病。
If it's the myelinated cells in the brain, it's multiple sclerosis.
如果是大脑中的有髓鞘细胞，那就是多发性硬化症。
So this is autoimmunity and inflammation of different kinds Cause their own pathology.
所以这是自身免疫和不同种类的炎症引起它们自己的病理。
So the immune system is always these sort of two sides of the coin, making sure that we're having strong responses to infection.
因此，免疫系统始终是硬币的两面，确保我们对感染有强烈的反应。
We'll talk about cancer-
我们来谈谈癌症——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
where we want to also strengthen our responses, but for autoimmunity, inflammation, allergies, our goal therapeutically with drugs is to make sure that we make the immune system under control.
我们也想加强我们的反应，但对于自身免疫、炎症、过敏，我们药物治疗的目标是确保我们控制免疫系统。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
And ideally do it in a targeted way so that you don't have to turn off the whole immune system with blanket immunosuppression, but to do it in a way that just makes you tolerant or not reactive against the things that are being inappropriately targeted by the immune system.
理想情况下，以有针对性的方式进行，这样您就不必通过全面免疫抑制来关闭整个免疫系统，而是以一种让您能够耐受或不对免疫系统不当针对的事物做出反应的方式进行。
Andrew Huberman:
安德鲁·休伯曼：
Two things that I'd love to understand about the immune system is, how is it that an immune response, let's say, to a cold virus, is systemic?
关于免疫系统，我想了解的两件事是，比如说，对感冒病毒的免疫反应是如何具有系统性的？
Where is the sort of master controller?
那种主控制器在哪里？
Or maybe it's a distributed system that says, "Okay, we need to launch a body-wide response-"
或者也许是一个分布式系统说：“好吧，我们需要发起全身响应——”
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
as opposed to a localized response.
而不是局部响应。
I can imagine with a splinter, of course-
当然，我可以用碎片想象——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
you're going to get a localized response.
您将得到本地化的回复。
It's a little piece of wood or metal.
它是一小块木头或金属。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And so you're going to get the innate response, and you're going to get some pus around it, and it'll kind of localize the wound.
所以你会得到固有的反应，你会在它周围出现一些脓液，它会定位伤口。
But when it comes to an invasive virus like the cold virus, it overtakes us, right?
但当谈到像感冒病毒这样的侵入性病毒时，它就会超越我们，对吗？
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
The production of mucus.
粘液的产生。
We get the headache.
我们很头疼。
And I think it's the systemic effect that intrigues me so much.
我认为这是系统性的影响让我如此着迷。
Where is the signal to launch a systemic versus a localized response in the immune system?
免疫系统中启动全身反应与局部反应的信号在哪里？
How does it determine that?
它是如何确定的呢？
Dr. Alex Marson:
亚历克斯·马森博士：
I think some of it depends on what virus we're talking about, how systemically invasive the different viruses can be.
我认为这在一定程度上取决于我们所讨论的病毒是什么，以及不同病毒的系统性侵入性如何。
And some of it can be that the immune system has different levels of it can have a local response, but the cells that we talked about in the immune system, one of their jobs can actually be to secrete things into the bloodstream, things that are essentially chemical signals that something is wrong.
其中一些可能是免疫系统有不同程度的局部反应，但我们在免疫系统中谈到的细胞，它们的工作之一实际上可能是将物质分泌到血液中，这些物质本质上是表明出现问题的化学信号。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
Major ones are called cytokines.
主要的称为细胞因子。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
And they can act locally, but they can also have more distributed effects.
它们可以在本地发挥作用，但也可以产生更分散的影响。
And some of the things that the cytokines can do can influence what can cause the development of fever.
细胞因子的一些作用可能会影响导致发烧的原因。
Right?
正确的？
So you can have these sort of cascading effects of something being recognized at a particular site in the body, then sending distributed signals to the blood that will make us feel sick.
因此，你可以在身体的特定部位识别某些东西，从而产生级联效应，然后向血液发送分布式信号，让我们感到恶心。
And in some cases, there's, again, this balancing act of maybe the fever gives us some edge in fighting some types of infection, but it also makes us feel lousy.
在某些情况下，发烧的这种平衡行为可能给我们在对抗某些类型的感染方面带来了一些优势，但它也让我们感觉很糟糕。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
And so the immune system is always walking.
所以免疫系统总是在行走。
I think sometimes the immune system response to infections is too strong.
我认为有时免疫系统对感染的反应太强烈。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
And a lot of the negative consequence of what we experience is the immune system going too far and having to come back as an infection gets under control.
我们所经历的许多负面后果是免疫系统走得太远，并且在感染得到控制后不得不回来。
Andrew Huberman:
安德鲁·休伯曼：
Thank you.
谢谢你。
One of the reasons I ask that is, well, I hate being sick.
我问这个问题的原因之一是，我讨厌生病。
Fortunately, I don't get sick too often if I take good care, which I think is like most people.
幸运的是，如果我照顾得好，我就不会经常生病，我想这就像大多数人一样。
I think about antibiotics, for instance.
例如，我想到抗生素。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Antibiotics are amazing.
抗生素是神奇的。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I've had a few things where I was like, "Oh, this thing's bothering me," and I had this sinus infection a few years back, and I was like, "Oh, this is definitely not a cold." And then they tell you it's not a sinus infection unless...
我曾经经历过一些事情，“哦，这件事让我很困扰”，几年前我得了鼻窦感染，我当时想，“哦，这绝对不是感冒。”然后他们告诉你这不是鼻窦感染，除非......
I was like, I have a feeling.
我当时想，我有一种感觉。
Now, I'm not a physician, of course, but it got really bad, and I took antibiotics, and within a day, I was feeling substantially better.
当然，现在我不是医生，但情况变得非常糟糕，我服用了抗生素，一天之内，我感觉好多了。
That's great.
那太棒了。
Many people have such experiences with antibiotics.
很多人都有这样的使用抗生素的经历。
I realize they can be over-prescribed, and you-
我意识到它们可能会被过度处方，而你-
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
can end up with antibiotic-resistant infections.
最终可能会导致抗生素耐药性感染。
That's a concern for sure.
这肯定是一个令人担忧的问题。
But what is the sort of inherent danger of using things like antibiotics the way I described, like not in a life or death situation, to mitigate the duration or the intensity of some sort of infection?
但是，按照我所描述的方式使用抗生素等药物来减轻某种感染的持续时间或强度，而不是在生死存亡的情况下，其固有的危险是什么？
Because surely, you're short-circuiting your immune system's ability to eventually just fight that thing off.
因为毫无疑问，你正在削弱你的免疫系统最终抵抗这种东西的能力。
Is part of building a robust immune system across your lifespan allowing your immune system to do the work and going through the misery of being really sick and infected?
在您的一生中建立强大的免疫系统是否是让您的免疫系统发挥作用并经历真正生病和感染的痛苦的一部分？
Dr. Alex Marson:
亚历克斯·马森博士：
I don't think so.
我不这么认为。
Andrew Huberman:
安德鲁·休伯曼：
Great.
太棒了。
Okay.
好的。
Fantastic.
极好的。
Love that answer.
喜欢这个答案。
Love that answer.
喜欢这个答案。
Dr. Alex Marson:
亚历克斯·马森博士：
I think you probably were exposed and had an immune response.
我认为您可能已暴露并产生了免疫反应。
The antibiotics, when they're used for bacterial infections that are susceptible to them, are a miracle.
当抗生素用于治疗对其敏感的细菌感染时，这是一个奇迹。
And we live in this amazing sliver of human history where we have antibiotics that can cure disease.
我们生活在人类历史的这一令人惊奇的时期，我们拥有可以治愈疾病的抗生素。
I think many of us have had bacterial infections of different kinds, cuts, and wounds that would have been deadly in other generations, and we're the beneficiaries of having antibiotics that work.
我认为我们中的许多人都曾遭受过不同种类的细菌感染、割伤和伤口，这些在其他几代人中可能是致命的，而我们是有效抗生素的受益者。
We are at some risk that if we overuse them, that window of human history might come to an end if we don't continue to replenish new antibiotics, but we gain more and more bacteria that are resistant to antibiotics.
我们面临着一些风险，如果我们过度使用它们，如果我们不继续补充新的抗生素，人类历史的窗口可能会结束，但我们会获得越来越多的对抗生素有抗药性的细菌。
Andrew Huberman:
安德鲁·休伯曼：
Are people developing new antibiotics?
人们正在开发新的抗生素吗？
Dr. Alex Marson:
亚历克斯·马森博士：
It's an underfunded area of medicine.
这是一个资金不足的医学领域。
Andrew Huberman:
安德鲁·休伯曼：
Because I just hear amoxicillin, penicillin.
因为我只听到阿莫西林、青霉素。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I have a friend over in the UK who's been having some eye symptoms that from what I'm learning, or still learning, is likely an infection-
我在英国有一个朋友，他出现了一些眼部症状，据我所知或仍在了解，很可能是感染——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
near the posterior chamber, which just simply means his vision is potentially at risk.
靠近后房，这仅仅意味着他的视力可能面临风险。
Systemic antibiotics are very likely going to save his vision.
全身抗生素很可能会挽救他的视力。
Dr. Alex Marson:
亚历克斯·马森博士：
Mm.
嗯。
Andrew Huberman:
安德鲁·休伯曼：
And so people say, "Well, antibiotics are bad."
所以人们说：“嗯，抗生素不好。”
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
100 years ago, they would've just enucleated the eye.
100年前，他们会把眼睛剜出。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Which is be blind, right?
哪个是盲目的，对吗？
So I think they're a spectacularly good tool, but it seems like there's just a kit of maybe, what, five to a dozen very commonly prescribed ones.
所以我认为它们是一个非常好的工具，但似乎只有一套可能，什么，五到十几个非常常用的处方工具。
Why aren't people developing better, new generation antibiotics?
为什么人们不开发更好的新一代抗生素？
Seems like it would be a, if for no other reason, a trillion-dollar industry, but also save a lot of lives.
看起来，如果没有其他原因，这将是一个价值数万亿美元的产业，而且还能拯救很多生命。
Dr. Alex Marson:
亚历克斯·马森博士：
I don't know whether there's a business reason for that or it's a-
我不知道这是否有商业原因，或者是-
Andrew Huberman:
安德鲁·休伯曼：
Hmm
嗯
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
but it is an underfunded area.
但这是一个资金不足的领域。
It's not where medicine has turned enough attention, and I do think it's a genuine risk.
这并不是医学界给予足够重视的地方，我确实认为这是一个真正的风险。
Andrew Huberman:
安德鲁·休伯曼：
Hmm.
嗯。
All right.
好的。
Well, some entrepreneurial-
嗯，一些创业者——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
young guy or gal or both will launch into it.
年轻人或女孩或两者都会投入其中。
I want to understand the relationship between the immune system and cancer.
我想了解免疫系统和癌症之间的关系。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But perhaps first we should talk about cancer-
但也许我们首先应该谈谈癌症——
Dr. Alex Marson:
亚历克斯·马森博士：
Okay
好的
Andrew Huberman:
安德鲁·休伯曼：
...
...
what it is and what it isn't.
它是什么，它不是什么。
I think there's a lot of misunderstanding out there that cancer did not exist in our not-so-distant past.
我认为人们存在很多误解，认为癌症在我们不远的过去并不存在。
You hear this.
你听到这个。
People say, "Oh, cancer is a new thing because of the advent of all these devices with EMFs and radiation." That's certainly not what I believe.
人们说，“哦，癌症是一个新事物，因为所有这些带有电磁场和辐射的设备的出现。”这当然不是我所相信的。
Has cancer been around a very, very long time?
癌症已经存在了非常非常长的时间了吗？
Do we have evidence for that?
我们有证据吗？
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
If anyone's really interested, I would highly recommend this book, "The Emperor of All Maladies"-
如果有人真的感兴趣，我强烈推荐这本书，《万病之王》——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
which is really a biography of cancer as a disease-
这实际上是一本关于癌症作为一种疾病的传记——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
and talk about the long history of going back as far as there's records of tumors of various kinds and the misery associated with that.
并谈论追溯到各种肿瘤记录的悠久历史以及与之相关的痛苦。
We have a very different understanding of cancer right now, right?
我们现在对癌症的理解非常不同，对吧？
And I think cancer is where we have one of the most sophisticated genetic understandings of disease.
我认为癌症是我们对疾病拥有最复杂的遗传理解的领域之一。
Doesn't mean we can always do things about it, but now we can understand mutations that accumulate in cells and all of a sudden-- So the DNA inside of a healthy cell is there programming.
这并不意味着我们总能对此采取行动，但现在我们可以理解细胞中突然积累的突变——所以健康细胞内的 DNA 正在编程。
So if you have a skin cell, your DNA is programming your skin cell to be a skin cell.
因此，如果您有皮肤细胞，您的 DNA 就会将您的皮肤细胞编程为皮肤细胞。
In cancer, all of a sudden, some combination of mutations emerge in that cell that lose its normal regulation.
在癌症中，细胞中突然出现一些突变组合，失去了正常的调节。
The skin cell is no longer getting the proper signals from its DNA to stay in the right place, and it goes and switches into a mode where it's dividing out of control.
皮肤细胞不再从其 DNA 获得正确的信号来保持在正确的位置，并且它会进入一种分裂失控的模式。
And the result is that those cells will then transform into cancer cells.
结果是这些细胞将转化为癌细胞。
They'll start dividing.
他们将开始分裂。
They'll lose the normal architecture.
他们将失去正常的架构。
The risk is that they can disrupt things in the tissue where they are, or that further mutations can accumulate, and they can actually start spreading into distant sites in the body, and that's metastasis, when a cancer goes from one local site to another part of the body.
风险在于，它们可能会破坏所在组织中的物质，或者进一步积累突变，并且它们实际上可能开始扩散到身体的远处部位，当癌症从一个局部部位转移到身体的另一部位时，这就是转移。
And as that happens, it's really an evolutionary process where those cancerous cells have acquired new genetics that are focused on their well-being.
当这种情况发生时，这实际上是一个进化过程，这些癌细胞获得了关注其健康的新遗传学。
Those cells are dividing, they're growing out of control, and they're taking the resources.
这些细胞正在分裂，它们正在失控地生长，并且它们正在夺取资源。
They're growing at the expense of the normal coordination of the human body.
它们的生长是以牺牲人体的正常协调为代价的。
And that's really, at its core, what cancer is.
从本质上讲，这确实是癌症的本质。
It's a genetic disease where cells lose their normal regulation and are dividing out of control in various tissues.
这是一种遗传性疾病，细胞失去正常调节并在各种组织中分裂失控。
Andrew Huberman:
安德鲁·休伯曼：
I can see the picture in my mind where an otherwise healthy cell gets a mutation, we can talk about how mutations arise-
我可以在脑海中看到一个原本健康的细胞发生突变的画面，我们可以讨论突变是如何产生的-
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and then starts spitting off daughter cells-
然后开始吐出子细胞-
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
as it's referred to.
正如它所提到的。
Dr. Alex Marson:
亚历克斯·马森博士：
Yep.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Why would the daughter cells inherit the mutation necessarily to then create more cells?
为什么子细胞必然继承突变以产生更多细胞？
Because that's the proliferation of the tumor.
因为那是肿瘤的增殖。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Certainly, cells propagate their DNA into their daughter cells, but I could imagine a situation where every day some of our cells get a mutation, spit off a couple daughter cells, and then those daughter cells are terminal, as we say, right?
当然，细胞将它们的DNA复制到它们的子细胞中，但我可以想象这样一种情况：每天我们的一些细胞都会发生突变，吐出几个子细胞，然后这些子细胞就终止了，正如我们所说的，对吗？
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And they don't create more cells.
而且它们不会产生更多的细胞。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Is that happening all over the body every day?
全身上下每天都会出现这样的情况吗？
So how is it that the DNA that creates the further propagation gets passed from one cell to the next?
那么，产生进一步繁殖的 DNA 是如何从一个细胞传递到下一个细胞的呢？
Dr. Alex Marson:
亚历克斯·马森博士：
I do think this is happening constantly.
我确实认为这种情况正在不断发生。
It's a process that every time a cell is around, especially as it's dividing, there is some imperfection in how the DNA, inside each of our cells, if that cell's going to replicate, the DNA has to replicate itself.
这是一个过程，每次细胞存在时，尤其是在分裂时，我们每个细胞内部的 DNA 都会存在一些缺陷，如果该细胞要复制，DNA 就必须自我复制。
So you end up with two copies of DNA that should be the same-
所以你最终会得到两个应该是相同的 DNA 副本——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
each one being passed on to the two daughter cells of that dividing cell.
每一个都被传递给该分裂细胞的两个子细胞。
That process of DNA replication is imperfect, and if there's any kind of damage during that process, one of those two copies might end up different than the other one, in which case you end up with a mutation now in one daughter cell and not the other.
DNA复制的过程是不完美的，如果在这个过程中出现任何类型的损伤，这两个拷贝中的一个最终可能会与另一个不同，在这种情况下，你最终会在一个子细胞中出现突变，而不是在另一个子细胞中。
If that is deleterious or if it's damaging, which probably most mutations are, those cells might start to die off.
如果这是有害的或具有破坏性的（大多数突变可能都是如此），那么这些细胞可能会开始死亡。
Okay, the DNA got messed up.
好吧，DNA 被搞乱了。
Those cells that are carrying that DNA die.
那些携带该 DNA 的细胞就会死亡。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, they can't take up glucose.
是的，他们不能吸收葡萄糖。
They just can't do cell stuff.
他们只是不能做细胞的事情。
Dr. Alex Marson:
亚历克斯·马森博士：
And there's a lot of control mechanisms in the cell that say, "If something's wrong, let's send a programmed cell death signal to that cell," and cells will kind of implode with various processes when something's wrong, and that happens most of the time.
细胞中有很多控制机制，“如果出现问题，让我们向该细胞发送程序性细胞死亡信号”，当出现问题时，细胞会通过各种过程发生内爆，而这种情况大多数时候都会发生。
The problem is if that change all of a sudden starts to not be damaging but to actually be a signal, okay, now the cell is growing more.
问题是，如果这种变化突然开始不再具有破坏性，而是实际上成为一个信号，好吧，现在细胞生长得更多了。
It has some benefit that it's accumulated as a result of that mutation.
它有一些好处，因为它是由于突变而积累的。
Now that cell will start to divide more, and that cell that's carrying that first mutation might start dividing more.
现在，该细胞将开始更多分裂，而携带第一个突变的细胞可能会开始更多分裂。
Both of its daughters now will pass on this mutation that's made it divide more.
它的两个女儿现在都会遗传这种使其分裂更多的突变。
And if in subsequent rounds, it gets a second hit, the combination may go from just cells that are dividing a little bit more to cells that take off and become full-blown cancer.
如果在接下来的几轮中，它受到第二次打击，这种组合可能会从仅分裂更多的细胞转变为起飞并成为全面癌症的细胞。
Now, there's certain processes that will accelerate that.
现在，某些流程将加速这一过程。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
One was exposure to things that cause DNA damage.
其中之一是接触会导致 DNA 损伤的物质。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
Right?
对吗？
The major one is smoking.
其中最主要的就是吸烟。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
When smoking causes chemicals to go into your lungs, the lung cells get exposed to these chemicals that then cause higher amounts of DNA damage, more mutations, and just as you have more mutations at a higher frequency, you're more likely to accumulate a set of mutations that will gradually go on to cause the generation of cancer.
当吸烟导致化学物质进入您的肺部时，肺细胞就会接触到这些化学物质，从而导致更多的 DNA 损伤和更多的突变，正如您以更高的频率产生更多突变一样，您更有可能积累一组突变，这些突变将逐渐导致癌症的产生。
Another way that this process can be accelerated is that some people carry an underlying genetic predisposition to cancer.
加速这一过程的另一种方式是，有些人具有潜在的癌症遗传倾向。
So people will likely have heard of the BRCA or the B-R-C-A genes, which predispose to breast cancer and other types of cancer.
因此，人们可能听说过 BRCA 或 B-R-C-A 基因，它们容易患乳腺癌和其他类型的癌症。
There, people start with one copy that's already Setting them on a road to higher risk of mutations accumulating, and the whole process happens with a higher frequency.
在那里，人们从一个副本开始，这个副本已经让他们走上了更高的突变积累风险的道路，整个过程发生的频率更高。
And so this march towards cancer cells is more likely to occur in people with that type of predisposition.
因此，这种向癌细胞的进军更有可能发生在具有这种倾向的人身上。
Andrew Huberman:
安德鲁·休伯曼：
How common is the BRCA mutation?
BRCA 突变有多常见？
Is it equally distributed in men and women?
它在男性和女性中的分布是否均等？
Yeah, what can you tell us?
是的，你能告诉我们什么？
And should everyone get tested for BRCA?
每个人都应该接受 BRCA 检测吗？
And there's a lot of questions here.
这里有很多问题。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I'll ask them again one by one, and then, of course, we'll talk about things that could be protective, but certainly avoiding smoking-
我会一一再问他们，然后，当然，我们会讨论一些可以起到保护作用的事情，但肯定要避免吸烟——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
would be paramount.
将是最重要的。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So how common is BRCA?
那么 BRCA 有多常见？
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah, so in terms of mutagens, the big ones are smoking-
是的，所以就诱变剂而言，最大的诱变剂是吸烟-
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
sun exposure for melanoma.
阳光照射可预防黑色素瘤。
I know the balancing features of sun exposure, but-
我知道阳光照射的平衡特征，但是-
Andrew Huberman:
安德鲁·休伯曼：
Yeah, we can talk about that
是的，我们可以谈谈这个
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
But clearly UV is a risk factor for DNA damage in the skin.
但显然，紫外线是皮肤 DNA 损伤的一个危险因素。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
I'm perfectly happy going on record.
我很高兴能记录下来。
The things I've said around sunlight have been contorted so many different ways.
我所说的关于阳光的事情已经被许多不同的方式扭曲了。
It's like a pretzel twist now.
现在就像椒盐卷饼一样。
No, it's more like one of those balloon animals at a party, but it's a mess.
不，它更像是聚会上的气球动物，但一团糟。
Too much UV is bad- ...
太多的紫外线是不好的——...
for skin cells.
对于皮肤细胞。
It's just bad.
这太糟糕了。
You need some, but too much is bad.
你需要一些，但太多不好。
Long wavelength light is great-
长波长光很棒——
Dr. Alex Marson:
亚历克斯·马森博士：
Yes
是的
Andrew Huberman:
安德鲁·休伯曼：
...
...
and therein lies the challenge.
这就是挑战。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But yeah, love sunlight, but you don't want excessive UV.
但是，是的，你喜欢阳光，但你不想要过多的紫外线。
Avoid getting sunburn, folks.
避免晒伤，伙计们。
Yeah.
是的。
Thank you.
谢谢。
So yeah, the BRCA mutation, I have a personal relationship to this because I lost both my graduate advisor and my postdoctoral advisor to BRCA mutation-related cancers, 50 and just a little bit older than 60 in the other, and brutal, especially when one of them, I know their kids.
所以，是的，BRCA 突变，我与此有个人关系，因为我因 BRCA 突变相关癌症而失去了我的研究生导师和博士后导师，一个 50 岁，另一个比 60 岁稍大一点，这是残酷的，特别是当他们中的一个，我了解他们的孩子时。
And just for young people getting cancer, and I know there are childhood cancers, but BRCA seems pretty common.
对于患癌症的年轻人来说，我知道也有儿童癌症，但 BRCA 似乎很常见。
Dr. Alex Marson:
亚历克斯·马森博士：
I don't know the numbers off the top of my head.
我不知道我脑子里的数字。
They're not the major numerical causes of cancer.
从数量上看，它们并不是癌症的主要原因。
In the scheme of cancers that develop, it's a minority.
在发生的癌症中，它只占少数。
It's a relatively small set number of the full set of cancers.
它是全套癌症中相对较小的一组。
The problem is if you inherit a BRCA mutation, as an individual, you have a very high risk of developing cancer.
问题是，如果您继承了 BRCA 突变，作为一个个体，您患癌症的风险非常高。
So as an individual, your risk goes way, way up, and of certain types of cancer in particular.
因此，作为个人，您的风险会不断上升，尤其是某些类型的癌症。
Andrew Huberman:
安德鲁·休伯曼：
And we can all get tested for it now pretty cheaply, right?
现在我们都可以非常便宜地接受检测，对吧？
Dr. Alex Marson:
亚历克斯·马森博士：
Yes.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
That's certainly recommended if there's a family history of cancer for BRCA mutations and a couple of other ones.
如果有 BRCA 突变和其他一些癌症家族史，那么当然建议这样做。
But you're right, the tests are available.
但你是对的，测试是可用的。
And you asked about men and women.
你还问了关于男人和女人的问题。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
Actually, it was men were some of the ways that those BRCA genes were identified.
事实上，BRCA 基因的一些识别方式是男性。
Andrew Huberman:
安德鲁·休伯曼：
Mm.
嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
Because it's so rare for men to develop breast cancer, the ones who did develop it, there was a thought, well, maybe there's an underlying genetic predisposition, and that helped identify those genes.
因为男性患乳腺癌的情况非常罕见，所以对于那些确实患乳腺癌的人来说，人们有一种想法，好吧，也许存在潜在的遗传倾向，这有助于识别这些基因。
Andrew Huberman:
安德鲁·休伯曼：
Interesting.
有趣。
Everyone, get tested for BRCA, because there are lifestyle factors that can-
每个人都接受 BRCA 检测，因为生活方式因素可能会-
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
reduce your cancer risk.
降低患癌症的风险。
I'd like to talk about mutagens.
我想谈谈诱变剂。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Smoking, bad.
抽烟，不好。
I'll go on record saying vaping, bad.
我会公开表示，电子烟不好。
Perhaps not as bad as smoking, but still way, way worse than not vaping.
也许不像吸烟那么糟糕，但仍然比不吸烟更糟糕。
The battle to sort of protect vaping is beyond me.
保护电子烟的斗争超出了我的能力范围。
But okay, to each their own.
但好吧，每个人都有自己的。
Environmental and workplace hazards, like known mutagens.
环境和工作场所危害，如已知的诱变剂。
If you work in a laboratory-
如果你在实验室工作——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
you're working with mutagens.
你正在使用诱变剂。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Right?
对吗？
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
You're working with things that literally pull DNA apart.
你正在研究那些实际上会分裂 DNA 的东西。
Dr. Alex Marson:
亚历克斯·马森博士：
Yes.
是的。
Andrew Huberman:
安德鲁·休伯曼：
This always worried me, working in a laboratory.
在实验室工作的我总是担心这一点。
There are a lot of carcinogenic chemicals in a laboratory.
实验室里有很多致癌化学物质。
Dr. Alex Marson:
亚历克斯·马森博士：
For good reason, yeah.
有充分的理由，是的。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
Dr. Alex Marson:
亚历克斯·马森博士：
We're trying to study cancer, but we're certainly working around a lot of things that could cause cancer.
我们正在努力研究癌症，但我们确实正在解决许多可能导致癌症的问题。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Alex Marson:
亚历克斯·马森博士：
Chemicals-
化学品-
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
radiation.
辐射。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
I don't know about you, I did a lot of experiments, radiolabeling cells.
我不了解你，我做了很多实验，对细胞进行放射性标记。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Well, fortunately, we worked with radio tagged amino acids with radiation that was, we were told, and I do believe was not as dangerous as some of the others.
好吧，幸运的是，我们用放射性标记的氨基酸进行了研究，我们被告知，我确实相信它不像其他一些氨基酸那么危险。
But yeah, so chemical exposures are a big one.
但是，是的，化学物质暴露是一个很大的问题。
Dr. Alex Marson:
亚历克斯·马森博士：
Yep.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And so those labels on paints and thinners and stuff in the garage, that's real.
所以那些油漆、稀释剂和车库里的东西上的标签是真实的。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
That's a real thing.
这是真实的事情。
They mutate cells.
它们使细胞发生突变。
Dr. Alex Marson:
亚历克斯·马森博士：
And there's some spectrum of-
还有一些范围-
Andrew Huberman:
安德鲁·休伯曼：
Sure
当然可以
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
stronger and less strong ones.
较强的和较弱的。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
And I think oftentimes we're operating in an absence of great data, but I think a lot of things are implicated as potential mutagens.
我认为我们经常在缺乏大量数据的情况下进行操作，但我认为很多事情都被认为是潜在的诱变剂。
Andrew Huberman:
安德鲁·休伯曼：
Pesticides.
农药。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
You look at cancer rates in rural areas near where crops are dusted with pesticides, and Shanna Swan came on here and she's like, "Listen, the cancer risks, the endocrine disruptor risks, we think of big cities as dirty and dangerous," and they are for certain reasons, but she said, "If you really see the spikes in these cancers related to environmental factors, it's less so bus exhaust than it is pesticides."
你看看农作物喷洒杀虫剂的农村地区的癌症发病率，莎娜·斯旺来到这里，她说，“听着，癌症风险、内分泌干扰物风险，我们认为大城市又脏又危险，”这是有一定原因的，但她说，“如果你真的看到这些癌症的激增与环境因素有关，那么与杀虫剂相比，公共汽车尾气的影响更小。”
Dr. Alex Marson:
亚历克斯·马森博士：
It is not evenly or fairly distributed.
它的分布不均匀或不公平。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
Some people get exposed way more to these things.
有些人更多地接触这些东西。
And we haven't studied them enough.
我们对它们的研究还不够。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
We need way more study to really be able to answer, okay.
我们需要更多的研究才能真正能够回答，好吧。
This is me just speaking, it's kind of amazing to me how much we're left on our own to be figuring out what the risk of individual products is, and I think it's a place where we should be investing a lot more to get clarity on where the real risks are.
这只是我的发言，令我感到惊讶的是，我们需要依靠自己的力量来弄清楚个别产品的风险是什么，我认为我们应该在这个领域进行更多投资，以弄清楚真正的风险在哪里。
Andrew Huberman:
安德鲁·休伯曼：
As many of you know, I've been taking AG1 for nearly 15 years now.
你们很多人都知道，我服用 AG1 已有近 15 年了。
I discovered it way back in 2012, long before I ever had a podcast, and I've been taking it every day since.
我早在 2012 年就发现了它，那时我还没有播客，从那时起我就每天都在听它。
The reason I started taking it, and the reason I still take it, is because AG1 is, to my knowledge, the highest quality and most comprehensive of the foundational nutritional supplements on the market.
我开始服用它的原因，以及我仍然服用它的原因，是因为据我所知，AG1是市场上质量最高、最全面的基础营养补充剂。
It combines vitamins, minerals, prebiotics, probiotics, and adaptogens into a single scoop that's easy to drink and it tastes great It's designed to support things like gut health, immune health, and overall energy, and it does so by helping to fill any gaps you might have in your daily nutrition.
它将维生素、矿物质、益生元、益生菌和适应原结合到一勺中，易于饮用，味道极佳。它旨在支持肠道健康、免疫健康和整体能量等，并通过帮助填补您日常营养中可能存在的任何缺口来实现这一目标。
Now, of course, everyone should strive to eat nutritious whole foods.
当然，现在每个人都应该努力吃有营养的天然食品。
I certainly do that every day.
我当然每天都这样做。
But I'm often asked, "If you could take just one supplement, what would that supplement be?" And my answer is always AG1, because it has just been so critical to supporting all aspects of my physical health, mental health, and performance.
但我经常被问到，“如果你只能服用一种补充剂，你会选择什么补充剂？”我的答案始终是 AG1，因为它对于支持我的身体健康、心理健康和表现的各个方面都非常重要。
I know this from my own experience with AG1, and I continually hear this from other people who use AG1 daily.
我从自己使用 AG1 的经验中了解到这一点，并且我不断从其他每天使用 AG1 的人那里听到这一点。
If you would like to try AG1, you can go to drinkag1.com/huberman to get a special offer.
如果您想尝试 AG1，可以访问 Drinkag1.com/huberman 以获得特别优惠。
For a limited time, AG1 is giving away six free travel packs of AG1 and a bottle of vitamin D3 K2 with your subscription.
限时订阅后，AG1 将赠送 6 个免费 AG1 旅行包和一瓶维生素 D3 K2。
Again, that's drinkag1, with the numeral one, .com/huberman to get six free travel packs and a bottle of vitamin D3 K2 with your subscription.
同样，这是 Drinkag1，通过数字 1 .com/huberman 订阅即可获得六个免费旅行包和一瓶维生素 D3 K2。
I get X-rays at the dentist now and again.
我时常去看牙医，拍 X 光片。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But I prefer not to get them.
但我宁愿不得到它们。
X-rays cause mutations.
X射线会导致突变。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Again, there's a trade-off in-
再说一遍，这里有一个权衡——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
the dose and-
剂量和-
Andrew Huberman:
安德鲁·休伯曼：
Sure
当然可以
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
I, when you need an X-ray, you need an X-ray.
我，当你需要X光检查时，你就需要X光检查。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
But I wouldn't do them for fun.
但我不会为了好玩而做这些事。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
I have colleagues who-
我有一些同事——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
prefer to do the slower manual pat-down at the airport-
更喜欢在机场进行较慢的手动搜身 -
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
to going through the scanner.
通过扫描仪。
It's a low level of radiation-
辐射水平很低——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
is what they tell me.
他们是这么告诉我的。
But if you're traveling a lot, you're getting multiple low-level exposures.
但如果您经常旅行，您就会受到多次低水平的暴露。
And we know pilots, and this is for other reasons-
我们了解飞行员，这是出于其他原因-
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
because they're, you can tell us, but atmospherically they're exposed to more radiation.
因为它们，你可以告诉我们，但在大气中它们暴露在更多的辐射下。
Cancer rates are higher in pilots.
飞行员的癌症发病率更高。
Now, they're sitting a lot, too.
现在，他们也坐了很多时间。
Prostate cancer.
前列腺癌。
Okay, there's a bunch of things there.
好吧，那里有很多东西。
But do you yourself avoid the scanner at the airport?
但您自己会避开机场的扫描仪吗？
Dr. Alex Marson:
亚历克斯·马森博士：
Honestly, I do, but I can't say that there's data for that.
老实说，我知道，但我不能说有这方面的数据。
I feel the same way as you.
我和你有同样的感觉。
If I can avoid it I try to minimize.
如果可以避免，我会尽量减少。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
But that's not based on some inside knowledge I have, but I have the same-
但这并不是基于我所拥有的一些内部知识，但我也有同样的——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
bias of-
偏向-
Andrew Huberman:
安德鲁·休伯曼：
Sure.
当然。
Yeah
是啊
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
less seems better.
更少似乎更好。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
I'm not out to get the scanner industry.
我并不是要进入扫描仪行业。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I think it's useful for people to hear that, that one can have no formal data-
我认为人们听到这样的话很有用，一个人可以没有正式的数据——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
but an understanding of mechanism that leads them to hedge.
而是对引导他们进行对冲的机制的理解。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
It's good to know.
很高兴知道。
Are there any mutagens and...
是否有任何诱变剂以及...
Well, is a carcinogen and a mutagen the same thing?
那么，致癌物和诱变剂是同一种东西吗？
Dr. Alex Marson:
亚历克斯·马森博士：
So they're closely related.
所以它们是密切相关的。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
Mutagen, I think, means that you're mutating, that you're changing the DNA in the cell.
我认为，诱变剂意味着你正在发生突变，你正在改变细胞中的 DNA。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
That's the idea.
就是这个想法。
Those mutations may or may not be linked to cancer, but by virtue of the fact that you're causing more mutations, almost inevitably you're also increasing the risk of cancer, and carcinogens are things that increase the rate of cancer.
这些突变可能与癌症有关，也可能无关，但由于你引起了更多的突变，几乎不可避免地你也会增加患癌症的风险，而致癌物会增加癌症的发病率。
Andrew Huberman:
安德鲁·休伯曼：
I love barbecued meat.
我喜欢烤肉。
I don't like barbecue sauce- ...
我不喜欢烧烤酱-...
because it's sweet, but I like meat with a char.
因为它很甜，但我喜欢带炭的肉。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Is the char bad?
炭是坏的吗？
Dr. Alex Marson:
亚历克斯·马森博士：
I think so.
我想是的。
I like it, too, but yeah.
我也喜欢，但是是的。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Again, these are balancing decisions in life.
同样，这些都是生活中的平衡决定。
Andrew Huberman:
安德鲁·休伯曼：
Sure.
当然。
Dr. Alex Marson:
亚历克斯·马森博士：
But yes.
但是是的。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Alex Marson:
亚历克斯·马森博士：
There's some...
有一些...
Meat, in general, has been implicated as a potential carcinogen-
一般来说，肉类被认为是一种潜在的致癌物质——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
especially in colorectal cancer.
尤其是结直肠癌。
There's some data around that.
有一些相关数据。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Yeah, my read of those data, not the char data-
是的，我读取的是这些数据，而不是字符数据-
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
but the meat data, is it's tricky.
但肉类数据却很棘手。
This is just my standpoint.
这只是我的立场。
I want to make sure I put-
我想确保我把-
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
brackets around this, that this is my read of the literature, is that many of the studies that looked at red meat-rich diets versus plant-based diets, the problem is, a lot of times, the red meat-enriched diets had a bunch of other things in them.
围绕这一点的括号，这是我读到的文献，许多研究都着眼于富含红肉的饮食与植物性饮食，问题是，很多时候，富含红肉的饮食中还含有很多其他东西。
Like sourcing wasn't considered.
就像没有考虑采购一样。
There was also a lot of starches.
还有很多淀粉。
Because nowadays, you find people who seem to at least feel better, who knows about the longevity aspect-
因为现在，你会发现人们至少感觉好多了，他们知道长寿的方面——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
but feel better eating red meat, fruits, and vegetables-
但吃红肉、水果和蔬菜会感觉更好-
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
limited amounts of starches.
淀粉的量有限。
So I feel like the nutrition studies are a mess.
所以我觉得营养研究一团糟。
They're kind of a disaster.
他们有点像一场灾难。
Dr. Alex Marson:
亚历克斯·马森博士：
I certainly-
我当然——
Andrew Huberman:
安德鲁·休伯曼：
Yeah
是啊
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
don't have clarity on this.
对此不清楚。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, it's possible.
是的，这是可能的。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
And it seems like it changes-
而且好像又变了——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
the direction.
方向。
I think some things we have pretty good common sense intuition about.
我认为我们对某些事情有很好的常识直觉。
Andrew Huberman:
安德鲁·休伯曼：
Fiber.
纤维。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Ultra-processed foods are probably bad.
超加工食品可能不好。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
But I think the balance of exactly what whole foods we're eating probably still needs to be worked out.
但我认为我们所吃的天然食品的确切平衡可能仍然需要解决。
Andrew Huberman:
安德鲁·休伯曼：
How do you think about the data on, for instance, food dyes, this is very timely-
您如何看待有关食品染料等数据，这是非常及时的-
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
where a certain food dye-
其中某种食用染料-
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
at a very high concentration in laboratory animals-
在实验动物中浓度非常高-
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
creates a significantly higher incidence of tumors and cancers in those animals.
使这些动物的肿瘤和癌症发病率显着升高。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But then the amount of food dye that's in the human food-
但人类食物中的食用色素含量——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
is a tiny fraction of that.
只是其中的一小部分。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I'm not trying to get political here.
我并不是想在这里涉及政治。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I just think as a framework for people to think about, there are many carcinogens, I'm sure, right in this environment.
我只是认为作为人们思考的一个框架，我确信，在这个环境中存在很多致癌物质。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I don't doubt that the lacquer on this table-
我毫不怀疑这张桌子上的漆——
Dr. Alex Marson:
亚历克斯·马森博士：
Mm-hmm
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
in fact, if that's even what they used, if ingested, could cause cancer.
事实上，即使他们使用的是这种物质，如果摄入的话，也可能会导致癌症。
I don't doubt that, right?
我对此并不怀疑，对吧？
But I don't know that in its form here, being near it for many hours a day does that.
但我不知道以这里的形式，每天靠近它几个小时会起到这样的作用。
I doubt it.
我对此表示怀疑。
We're not inhaling the table.
我们不会吸入桌子。
Dr. Alex Marson:
亚历克斯·马森博士：
This is what I mean by this level of confusion.
这就是我所说的这种程度的混乱的意思。
I think we all live with this background confusion of some study has been published in, like you said, high concentrations, exposure doesn't mean anything in our lives.
我认为我们都生活在这种背景混乱之中，就像你说的，一些研究已经发表，高浓度，暴露在我们的生活中没有任何意义。
What's the relative risk?
相对风险是多少？
So that's why I start with smoking-
这就是为什么我从吸烟开始——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
sunlight, and then say there's a tail, and I don't think we know fully what that distribution is yet.
阳光，然后说有一条尾巴，我认为我们还没有完全知道这个分布是什么。
I'm sure there are some combination of things that are increasing our risk of cancer.
我确信某些因素的结合会增加我们患癌症的风险。
Andrew Huberman:
安德鲁·休伯曼：
We don't really know how to weigh duration and amount of exposure, and this is why I think it's really scary to people.
我们真的不知道如何权衡暴露的持续时间和数量，这就是为什么我认为这对人们来说真的很可怕。
People don't know.
人们不知道。
They know smokers who don't get lung cancer.
他们认识没有患肺癌的吸烟者。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
And non-smokers who do.
以及不吸烟的人。
Andrew Huberman:
安德鲁·休伯曼：
And non-smokers who do.
以及不吸烟的人。
And so I think people go, well, it actually has caused, I believe, a lot of damage in the faith in medicine, unfortunately, because the messaging is all mixed up.
所以我认为人们会说，不幸的是，我相信它实际上对医学信仰造成了很大的损害，因为信息都是混乱的。
Yeah, I think that nowadays people are trying to do what they can to protect themselves.
是的，我认为现在人们正在尽力保护自己。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But people still get cancer.
但人们仍然会患癌症。
You can do everything right-
你可以把一切都做对-
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and still get cancer.
仍然会得癌症。
Is that Even if you don't have a BRCA mutation.
即使您没有 BRCA 突变。
Dr. Alex Marson:
亚历克斯·马森博士：
Absolutely.
绝对的。
I think the last thing you ever want to do is attribute someone's actions to cancer.
我认为你最不想做的事情就是将某人的行为归因于癌症。
It is a probabilistic disease where some set of mutations occur that cause a really devastating disease.
这是一种概率疾病，其中发生的某些突变会导致真正具有破坏性的疾病。
And so, yeah, we don't know the answers, and I think we have to be humble about that.
所以，是的，我们不知道答案，我认为我们必须对此保持谦虚。
Now, what I think we can also talk about is, well, how do we handle, how do we treat cancer when it comes up?
现在，我认为我们还可以讨论的是，当癌症出现时，我们如何处理、如何治疗？
And this is where these two conversations that we've been having really come together of when talking about the immune system.
这就是我们在谈论免疫系统时所进行的两次对话真正结合在一起的地方。
Actually, we went through a lot of sort of detailed mechanism, thinking about the different cell constituents of our immune system.
事实上，我们经历了很多详细的机制，思考我们免疫系统的不同细胞成分。
I will tell you that when I went to medical school, which wasn't that long ago, I graduated in 2010, the dogma was, "Don't waste time thinking about cancer immunology.
我会告诉你，当我上医学院时，就在不久前，我于 2010 年毕业，教条是：“不要浪费时间思考癌症免疫学。
Cancer immunology is a field that's going nowhere."
癌症免疫学是一个没有前途的领域。”
Andrew Huberman:
安德鲁·休伯曼：
Hmm.
嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
I was in Boston, and I think maybe there was some local bias in that direction, but this was not the mainstream of thinking about how we would treat cancer.
我当时在波士顿，我认为在这个方向上可能存在一些当地偏见，但这并不是我们如何治疗癌症的主流思考方式。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
At that point, the way that cancer was being treated was chemotherapy, which is something that's been around for decades, and it's basically give toxins to the body that will be more toxic to the cancer cells than to the healthy cells and ask people to endure all the side effects because they have to, to get rid of the cancer cells, and that's still the mainstay of cancer treatment.
那时，治疗癌症的方法是化疗，这种方法已经存在了几十年，它基本上是向身体提供毒素，对癌细胞的毒性比对健康细胞的毒性更大，并要求人们忍受所有的副作用，因为他们必须这样做，以消除癌细胞，而这仍然是癌症治疗的支柱。
We all want to do better than that.
我们都希望做得更好。
Andrew Huberman:
安德鲁·休伯曼：
It's very unpleasant.
这是非常不愉快的。
Very, very unpleasant.
非常非常不愉快。
Dr. Alex Marson:
亚历克斯·马森博士：
Unpleasant, and worse.
不愉快，甚至更糟。
We put people through horrific things because it's the best we can do.
我们让人们经历可怕的事情，因为这是我们能做的最好的事情。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
And then there was a wave of thinking, okay, well, let's try to make drugs that are targeted to the mutations that we talked about.
然后出现了一波想法，好吧，好吧，让我们尝试制造针对我们谈到的突变的药物。
And that was the hot thing.
这就是最热门的事情。
That was the promising avenue when I was in medical school of, okay, now we've really measured, these are mutations that accumulate inside of cancer cells.
当我在医学院时，这是一条很有希望的途径，好吧，现在我们已经真正测量到了，这些是癌细胞内部积累的突变。
This is what's causing cancer.
这就是导致癌症的原因。
Let's make drugs that go after those things.
让我们制造针对这些东西的药物。
And it turned out that although a lot of good has come from that, people have extended lives, cancer has a way of working around that.
事实证明，尽管这带来了很多好处，人们的寿命也延长了，但癌症有办法解决这个问题。
Andrew Huberman:
安德鲁·休伯曼：
So these are cell cycle inhibitors?
那么这些是细胞周期抑制剂吗？
Dr. Alex Marson:
亚历克斯·马森博士：
Signaling-
信令-
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
various mutations affect these growth properties of cells, and there's targeted drugs that have been designed to go after some of those pathways that are making the cells divide out of control.
各种突变会影响细胞的这些生长特性，并且有针对性的药物被设计来追踪某些使细胞分裂失控的途径。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
I think that benefit has come, but cancer has ways of mutating around that and can be developing resistance, the same way we talked about resistance in bacteria to antibiotics.
我认为这种好处已经到来，但癌症有办法围绕它进行突变，并且可能产生耐药性，就像我们谈论细菌对抗生素的耐药性一样。
Cancer cells can evolve quickly and can become resistant to these targeted modifications.
癌细胞可以快速进化，并且可以对这些有针对性的修饰产生抵抗力。
What has emerged as a whole new way of thinking about going after cancer is using the power of the immune system that we talked about at the beginning and redirecting that against cancer targets.
一种全新的治疗癌症的思维方式出现了，那就是利用我们一开始谈到的免疫系统的力量，并将其重新定向到癌症目标上。
This has changed how we think about cancer treatment.
这改变了我们对癌症治疗的看法。
The hope is that, all of us have this immune system that goes through every organ in our body.
希望我们所有人都有这种免疫系统，遍布我们身体的每个器官。
It circulates.
它循环流动。
We have white blood cells that are constantly going around and looking for things that shouldn't be there.
我们的白细胞不断地四处走动，寻找不应该存在的东西。
Can we unleash that immune system against cancer?
我们可以释放免疫系统来对抗癌症吗？
And the hope would be that the cells of our immune system, we talked about how they're really exquisitely evolved-
希望我们的免疫系统细胞，我们讨论了它们是如何真正精致地进化的——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
to make a determination of this is a healthy cell, this is not a healthy cell.
来判断这是一个健康的细胞，这是一个不健康的细胞。
This cell should be here, this should not.
这个单元格应该在这里，这个不应该在这里。
If we could get that level of precision where we could have a durable immune response that gets rid of the cancer cells but leaves the healthy cells intact, that is what we want.
如果我们能够达到这样的精确度，我们可以产生持久的免疫反应，消除癌细胞，但保持健康细胞完好无损，这就是我们想要的。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
Now, that is not science fiction and is now approved and used to treat a number of different cancers.
现在，这不是科幻小说，现已被批准并用于治疗多种不同的癌症。
The first place where this happened was in a class of medicines called checkpoint inhibitors-
最先发生这种情况的是一类叫做检查点抑制剂的药物——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
or immunotherapy drugs.
或免疫治疗药物。
A lot of people will have heard of these things.
这些事情很多人都会听说过。
PD-1, CTLA-4 are some targets where there are drugs that get infused that hit these things that are on the surface of T cells, and they actually are natural breaks to the T cells.
PD-1、CTLA-4 是一些靶标，注射药物会击中 T 细胞表面的这些物质，它们实际上是 T 细胞的自然断裂。
T cells might be in our body there, but turned off or not turned on enough to be strong enough against cancer.
T 细胞可能就在我们体内，但处于关闭状态或未开启到足以抵抗癌症的程度。
And for certain types of cancer, it's been absolutely miraculous that if you make a drug that hits the brake on the T cells, the T cells go stronger, and they can be unleashed against cancer just by taking the brakes off of them.
对于某些类型的癌症来说，如果你制造出一种能够抑制 T 细胞的药物，T 细胞就会变得更强，只要松开它们的刹车，它们就能释放出来对抗癌症，这绝对是奇迹。
Andrew Huberman:
安德鲁·休伯曼：
What sorts of cancers has it been successful for?
它对哪些类型的癌症已取得成功？
Dr. Alex Marson:
亚历克斯·马森博士：
The poster child for this has been melanoma.
黑色素瘤就是这种现象的典型代表。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
One of the big success cases was Jimmy Carter, who had a melanoma, which is a skin cell, aggressive skin cancer that had already gone to his brain, which was thought of as a death sentence, and he got treated with checkpoint inhibitors and basically was cured.
其中一个巨大的成功案例是吉米·卡特，他患有黑色素瘤，这是一种皮肤细胞，侵袭性皮肤癌已经转移到他的大脑，这被认为是死刑，他接受了检查点抑制剂治疗，基本上被治愈了。
Andrew Huberman:
安德鲁·休伯曼：
Amazing.
太棒了。
Dr. Alex Marson:
亚历克斯·马森博士：
And so, you saw these tumors just shrink away.
所以，你看到这些肿瘤就缩小了。
And not just him, but a large fraction of melanoma patients now respond to these.
不仅是他，很大一部分黑色素瘤患者现在都对这些做出了反应。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
And so that has changed how melanoma is treated, and other cancers to varying degrees because some types of cancers can respond to this.
因此，这在不同程度上改变了黑色素瘤和其他癌症的治疗方式，因为某些类型的癌症可以对此做出反应。
That's taking a drug that unleashes the T cells that are already in our body.
即服用一种药物来释放我们体内已有的 T 细胞。
The focus of my research then is, well, the first thing I said was we're living in this amazing moment of biology where we can do things to cells in our body with incredible precision, and we're often just limited by our imagination.
我的研究重点是，嗯，我说的第一件事是，我们生活在生物学的这个令人惊叹的时刻，我们可以以令人难以置信的精确度对我们体内的细胞做一些事情，而我们往往只是受到我们的想象力的限制。
And what we can see now is that we don't actually have to just be limited to the T cells that are naturally in our body that already have this random distribution of sensors.
我们现在可以看到的是，我们实际上不必仅仅局限于我们体内自然存在的 T 细胞，它们已经具有这种随机分布的传感器。
We can actually genetically make one of these sensors for T cells and put it into T cells.
实际上，我们可以通过基因技术制造一种 T 细胞传感器，并将其放入 T 细胞中。
We can put a gene that encodes something on the surface of T cells That will make them programmed to search and destroy for cancer cells.
我们可以在 T 细胞表面放置一个编码某些东西的基因，这将使它们被编程为搜索和摧毁癌细胞。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
Now, this is largely known as chimeric antigen receptor T cells.
现在，这主要被称为嵌合抗原受体 T 细胞。
That's a long term.
这是一个长期的过程。
They're known for short as CAR T cells, chimeric antigen receptor.
它们简称为 CAR T 细胞，即嵌合抗原受体。
And what that means, chimeric, is that these are stitched together.
这意味着，嵌合，这些是缝合在一起的。
This is a receptor that was designed in a lab, does not exist in nature, but can be put into a piece of DNA, delivered into a T cell, and when that DNA goes into the genetic code of the T cell, all of a sudden the T cell will start making proteins that go on its surface and act as these artificial sensors.
这是一种在实验室设计的受体，自然界中不存在，但可以放入一段 DNA 中，传递到 T 细胞中，当该 DNA 进入 T 细胞的遗传密码时，T 细胞会突然开始制造位于其表面的蛋白质，并充当这些人工传感器。
And those CARs then, when those T cells get reinfused into a patient the way that you get a blood transfusion, those CARs are directed to go against cancers.
然后，当这些 T 细胞像输血一样被重新注入患者体内时，这些 CAR 就会被用来对抗癌症。
This has been done for certain types of leukemia and lymphoma, and there's been these amazing success stories.
这已经针对某些类型的白血病和淋巴瘤进行了，并且已经有了这些惊人的成功案例。
Andrew Huberman:
安德鲁·休伯曼：
Mm.
嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
The thing that woke up me and the world was, in 2012, there was a young girl who was the first pediatric patient to be treated with a CAR T cell for cancer.
让我和全世界警醒的是，2012 年，一名年轻女孩成为第一个接受 CAR T 细胞治疗癌症的儿科患者。
So she's become a heroic figure.
于是她就成为了英雄人物。
Emily Whitehead.
艾米莉·怀特海德。
She was, I think, eight at the time, and she had a form of leukemia that, for some reason, whatever reason, it failed all the treatments, and nothing worked.
我想她当时八岁，患有一种白血病，由于某种原因，无论什么原因，所有的治疗都失败了，没有任何效果。
She was going to be sent home on hospice.
她将被送回家接受临终关怀。
She had exhausted all the possibilities at the age of eight.
八岁时她已经用尽了所有的可能性。
And she got enrolled in a, at that time, highly experimental treatment to get these CAR T cells.
当时，她参加了一项高度实验性的治疗，以获得这些 CAR T 细胞。
So her blood cells were taken out in a big blood donation.
于是，她的血细胞在一次大献血中被取出了。
Her own T cells were genetically modified, and we could talk about how that was done.
她自己的 T 细胞经过了基因改造，我们可以讨论这是如何完成的。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
It was actually done with a pretty crude technique that's been around.
它实际上是用一种已经存在的相当粗糙的技术完成的。
Actually used viruses, lentiviruses, these are sort of modified HIV viruses, to deliver this extra piece of DNA that encoded the CAR.
实际上使用了病毒、慢病毒，这些是经过改造的 HIV 病毒，来传递编码 CAR 的额外 DNA 片段。
This was done on her cells, and then after that extra gene was put into the T cells, the T cells were reinfused into her body.
这是在她的细胞上完成的，然后将额外的基因放入 T 细胞中后，T 细胞被重新注入她的体内。
And it was not a straightforward course.
这并不是一个简单的过程。
She ended up in the ICU.
她最终住进了重症监护室。
In real time, people had to figure out how to control the immune systems and the side effects.
人们必须实时弄清楚如何控制免疫系统和副作用。
But as that was controlled, all of a sudden, her cancer cells disappeared.
但随着病情得到控制，她的癌细胞突然消失了。
Andrew Huberman:
安德鲁·休伯曼：
Amazing.
太棒了。
And the lentivirus itself didn't spark an immune reaction that was-
慢病毒本身并没有引发免疫反应，那就是——
Dr. Alex Marson:
亚历克斯·马森博士：
No
否
Andrew Huberman:
安德鲁·休伯曼：
...
...
that outweighed the benefits of the cargo.
这超过了货物的好处。
Dr. Alex Marson:
亚历克斯·马森博士：
No. Amazingly, it really hasn't.
不，令人惊讶的是，事实确实如此。
There's been some discussion about the risks of using these lentiviruses.
关于使用这些慢病毒的风险存在一些讨论。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
And we'll talk in a second about how we could do better now.
稍后我们将讨论如何做得更好。
But-
但是——
Andrew Huberman:
安德鲁·休伯曼：
Yeah, people are going to hear putting viruses into cells and putting them into humans, and a bunch of people will freak out.
是的，人们会听到将病毒放入细胞中并放入人体中，很多人会吓坏了。
But I promise you that things like adeno, which is like a cold virus, or lenti, which is similar to HIV, and of course, they didn't give her HIV, they changed the virus-
但我向你保证，像腺病毒这样的东西，就像感冒病毒，或者慢病毒，类似于艾滋病毒，当然，他们没有给她带来艾滋病毒，他们改变了病毒——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
so they're not delivering HIV.
所以他们不会传播艾滋病毒。
These viruses are incredible because they can create long-lasting expression of genes that you deliberately put into them.
这些病毒令人难以置信，因为它们可以使您故意放入其中的基因产生持久的表达。
They're a shuttle.
他们是班车。
Dr. Alex Marson:
亚历克斯·马森博士：
It's an amazing application of biological understanding, right?
这是生物学理解的惊人应用，对吧？
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
That all of a sudden, we've been studying viruses because of the risk that they have-
突然间，我们开始研究病毒，因为它们具有——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
but we've learned that viruses have evolved to be very good shuttles-
但我们了解到病毒已经进化成为非常好的航天飞机-
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
and to deliver their genetic material into cells.
并将其遗传物质传递到细胞中。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
The way I think of it is the viruses have evolved to take advantage of our biology and our genes.
我的想法是，病毒的进化是为了利用我们的生物学和基因。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And so we did the ultimate touché in these instances.
因此，我们在这些情况下做了最终的处理。
You're so good at hijacking our cells' DNA and proliferating, all right, we'll leverage you-
你非常擅长劫持我们细胞的 DNA 并进行增殖，好吧，我们会利用你——
Dr. Alex Marson:
亚历克斯·马森博士：
Exactly
正是如此
Andrew Huberman:
安德鲁·休伯曼：
...
...
to help us as opposed to hurt us, right?
帮助我们而不是伤害我们，对吗？
Dr. Alex Marson:
亚历克斯·马森博士：
That's exactly right.
完全正确。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
And so that was done in 2012.
这就是 2012 年完成的。
Emily Whitehead was eight.
艾米莉·怀特海德八岁。
It was done as an experimental treatment at the University of Pennsylvania, and the story now is that now, all these years later, Emily Whitehead is not only cured of her leukemia, she's pre-med at the University of Pennsylvania.
这是宾夕法尼亚大学的一项实验性治疗，现在的故事是，这么多年过去了，艾米莉·怀特海德不仅治愈了她的白血病，而且还在宾夕法尼亚大学完成了医学预科课程。
Andrew Huberman:
安德鲁·休伯曼：
So awesome.
太棒了。
So awesome.
太棒了。
Dr. Alex Marson:
亚历克斯·马森博士：
And so no one could ignore that.
所以没有人可以忽视这一点。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
This was just all of a sudden this dogma that I had just been taught a couple of years earlier in medical school that we should ignore cancer immunotherapy.
几年前我在医学院才被教导我们应该忽视癌症免疫疗法，这突然成为了我的教条。
We were just wrong.
我们只是错了。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
And all of a sudden, the field woke up and said, "Okay, the immune system is not just limited to protecting us from viruses and bacteria.
突然间，田野醒了过来，说道：“好吧，免疫系统不仅仅局限于保护我们免受病毒和细菌的侵害。
The immune system can be exploited and potentially re-engineered to protect us from cancer and maybe other diseases." So that was 2012.
免疫系统可以被利用并有可能被重新设计，以保护我们免受癌症和其他疾病的侵害。”那是2012年。
2012 also was the year that a paper got published in "Science" by Emmanuelle Charpentier and Jennifer Doudna that introduced this new technology called CRISPR.
2012 年，Emmanuelle Charpentier 和 Jennifer Doudna 在《Science》杂志上发表了一篇论文，介绍了 CRISPR 新技术。
And we'll talk about this, but CRISPR fundamentally is a tool to rewrite DNA sequences.
我们将讨论这一点，但 CRISPR 从根本上来说是一种重写 DNA 序列的工具。
That came out in 2012.
那是在 2012 年问世的。
And on a personal level, 2012 was also the year that I moved to San Francisco to start a lab studying T cells and how genetics influences T cells.
就个人而言，2012 年也是我搬到旧金山建立一个实验室研究 T 细胞以及遗传学如何影响 T 细胞的一年。
I was looking around and trying to figure out what my lab would do, and all of a sudden, I was arriving with an empty lab space at exactly the same moment that the world was shown that T cells could cure cancer, and that we had a tool that could potentially rewrite DNA sequences and that we wouldn't be limited to these lentiviruses, which are kind of clunky, the best tools we had at the time, but pretty clunky and non-precise in how they insert genetic material.
我环顾四周，试图弄清楚我的实验室要做什么，突然间，我带着一个空的实验室空间来到了世界，同时世界也看到了 T 细胞可以治愈癌症，我们有一种可能重写 DNA 序列的工具，而且我们不会局限于这些慢病毒，它们有点笨重，是我们当时拥有的最好的工具，但在如何插入遗传物质方面相当笨重且不精确。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
All of a sudden, we could imagine that we could take T cells and use CRISPR to actually pick individual places in the genome and make targeted changes to program exactly how cells behave.
突然之间，我们可以想象我们可以利用 T 细胞并使用 CRISPR 来实际选择基因组中的各个位置，并进行有针对性的改变，以准确地编程细胞的行为方式。
And that is the basis for my ongoing work.
这是我正在进行的工作的基础。
We've put a lot of work over the years into being able to now take CRISPR technology, get it to work in T cells, to learn the rules about what are the genetic changes that will be most effective at making T cells into Into immunotherapies that cure patients with different diseases.
多年来，我们投入了大量的工作，现在能够采用 CRISPR 技术，让它在 T 细胞中发挥作用，了解哪些基因变化最有效地使 T 细胞进入免疫疗法，从而治愈患有不同疾病的患者。
Andrew Huberman:
安德鲁·休伯曼：
It's amazing.
太棒了。
Dr. Alex Marson:
亚历克斯·马森博士：
And then to go all the way and then actually use CRISPR to make T cells that can be input into patients with new levels of precision and power, and that's in clinical trials now.
然后一路走下去，然后实际使用 CRISPR 来制造 T 细胞，这些 T 细胞可以以新的精度和功率水平输入患者体内，现在正在进行临床试验。
We're now in clinical trials with these CRISPR engineered CAR T cells, and we're not just going after leukemias, where these CAR T cells have historically worked, but we're also thinking about can we make these work for the really common causes of cancer deaths, solid tumors.
我们现在正在进行这些 CRISPR 工程 CAR T 细胞的临床试验，我们不仅要研究这些 CAR T 细胞历来发挥作用的白血病，而且我们也在考虑是否可以让这些细胞对癌症死亡的真正常见原因——实体瘤——发挥作用。
And that's been a challenge, and we can talk about that, but getting T cells to find the right targets in tumors and then work inside of tumor environments, which are inherently immunosuppressive, requires figuring out additional gene edits that are now possible with CRISPR to try to beat the cancer at its own game.
这是一个挑战，我们可以谈论这个，但是让 T 细胞在肿瘤中找到正确的靶标，然后在肿瘤环境中工作，肿瘤环境本质上是免疫抑制的，需要找出额外的基因编辑，现在可以使用 CRISPR 来尝试以自己的方式击败癌症。
If cancer is evolving to make itself cloaked from the immune system, now with CRISPR, we can think about getting one step ahead and making T cells that are able to resist all the tricks that cancers throw at it.
如果癌症正在进化，使其能够躲避免疫系统的攻击，现在有了 CRISPR，我们可以考虑领先一步，制造出能够抵抗癌症攻击的所有诡计的 T 细胞。
I think we're on the brink of having precise CRISPR engineered cells that will, I hope, start to melt away cancers without the side effects of chemotherapy.
我认为我们即将拥有精确的 CRISPR 工程细胞，我希望这些细胞能够在没有化疗副作用的情况下开始消除癌症。
Andrew Huberman:
安德鲁·休伯曼：
Amazing.
太棒了。
Just amazing.
太棒了。
And the story of this young woman is spectacular.
这位年轻女子的故事非常精彩。
I have two questions before we talk about CRISPR technology.
在我们谈论 CRISPR 技术之前我有两个问题。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
The first one is, is it true, I believe it is, but is it true that cancer risk goes up as we get older?
第一个是，这是真的吗？我相信是的，但是癌症风险随着年龄的增长而增加，这是真的吗？
And if so, why?
如果是这样，为什么？
So that's the first question.
这是第一个问题。
And then the other question has to do with how the immunotherapy that you described was able to target the cancer and not cause problems elsewhere-
然后另一个问题与你所描述的免疫疗法如何能够靶向癌症而不在其他地方引起问题有关-
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
which is kind of the major issue of chemo and radiation therapy.
这是化疗和放射治疗的主要问题。
But the first question, again, was why more mutations as we get older?
但第一个问题又是，为什么随着年龄的增长，突变会增多？
Dr. Alex Marson:
亚历克斯·马森博士：
So I think there's a few cancers that peak in childhood, and there's risk as the body's developing of certain cancer, childhood cancers, and there's childhood leukemias, for example, like the one we talk about, Emily Whitehead.
所以我认为有一些癌症在儿童时期达到顶峰，随着身体发展某些癌症，儿童癌症，还有儿童白血病，例如我们谈论的艾米莉·怀特黑德（Emily Whitehead），这是有风险的。
But most cancers, as you said, exactly as you said, that there's this sort of increase, and they're largely disease of later stages of life.
但大多数癌症，正如你所说，正如你所说，有这种增加，而且它们很大程度上是生命后期的疾病。
I think that the reason for that is, remember when we talked about what causes cancer, it's this evolution where cells start to accumulate mutations.
我认为原因是，记住当我们谈论导致癌症的原因时，正是这种进化使细胞开始积累突变。
Numerically, a lot of those cells that have the mutations will die off, and it's just a game that unfolds over time.
从数字上看，许多具有突变的细胞将会死亡，这只是一场随着时间的推移而展开的游戏。
And the more time you have cells dividing and sticking around in the body, they're accumulating more damage, and eventually, you're more likely that that damage would actually transform the cells into a cancer cell.
细胞分裂并在体内停留的时间越长，它们就会积累更多的损伤，最终，这种损伤更有可能将细胞转化为癌细胞。
So time is a big factor here.
所以时间在这里是一个重要因素。
Time and just accumulated damage.
时间和刚刚累积的伤害。
Andrew Huberman:
安德鲁·休伯曼：
And the other question was, how is it that the lentivirus knows to, the lentiviral cargo-carrying T cells know to attack the cancer and not something else?
另一个问题是，慢病毒如何知道携带慢病毒货物的 T 细胞知道攻击癌症而不是其他东西？
Dr. Alex Marson:
亚历克斯·马森博士：
So this is a key question for the field, right?
所以这是该领域的一个关键问题，对吧？
And I think one of the things that worked incredibly well was a brilliant choice by a group of scientists in a few different places that converged on the target that was used in the first CAR T cell.
我认为其中一个非常有效的方法是来自几个不同地方的一组科学家做出的明智选择，他们集中在第一个 CAR T 细胞中使用的目标上。
And the target is a protein called CD19.
目标是一种名为 CD19 的蛋白质。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
That's just the name of this thing that's found on a lot of different types of B cells.
这只是在许多不同类型的 B 细胞上发现的东西的名称。
So this brings us back to this discussion.
这让我们回到了这个讨论。
The leukemias themselves are a cancer of the immune cells, so they're a cancer of B cells, and CD19 is found on the surface of a large number of different types of B cell leukemias and lymphomas.
白血病本身是免疫细胞的癌症，所以它们是B细胞的癌症，CD19存在于大量不同类型的B细胞白血病和淋巴瘤的表面。
Andrew Huberman:
安德鲁·休伯曼：
I see.
我明白了。
Dr. Alex Marson:
亚历克斯·马森博士：
I think one of the things that turns out to be serendipitous here is that B cells themselves, healthy B cells actually also have CD19 on their surface.
我认为这里偶然发现的一件事是 B 细胞本身，健康的 B 细胞实际上在其表面也有 CD19。
What just turns out to be serendipitous is that the body can tolerate those cells going away.
偶然发现的是，身体可以容忍这些细胞的消失。
And so what has made this a particularly effective and safe and relatively well-tolerated treatment for cancer is that the collateral damage is actually not that damaging.
因此，这种疗法之所以成为一种特别有效、安全且耐受性相对良好的癌症治疗方法，是因为其附带损害实际上并没有那么大。
That T cells, in this case, are not strictly distinguishing between cancer and health.
在这种情况下，T 细胞并不能严格区分癌症和健康。
They're not just getting the leukemia cells.
他们不仅仅获得白血病细胞。
They are getting collateral B cells.
他们正在获得附带的 B 细胞。
But by and large, to a first approximation, people can live without those cells, and so that side effect has just been tolerable.
但总的来说，初步估计，人们可以在没有这些细胞的情况下生存，因此副作用是可以忍受的。
Finding that balance gets harder and harder for more cancers, right?
对于更多的癌症来说，找到这种平衡变得越来越难，对吧？
If you start to think about pancreatic cancer or brain cancer, finding targets that if you hit the healthy pancreas or the healthy brain are not toxic, it's harder and harder.
如果你开始考虑胰腺癌或脑癌，找到击中健康胰腺或健康大脑不会有毒的目标，那就越来越难了。
So people are thinking about more and more sophisticated ways to look for these targets that are selectively found on the cancer cell and not on the healthy cell, or to think about ways that you might actually make the cell depend on recognizing multiple features so that you can have what's sometimes talked about as like a two-factor authentication.
因此，人们正在考虑越来越复杂的方法来寻找在癌细胞上而不是在健康细胞上选择性发现的这些目标，或者考虑实际上可以使细胞依赖于识别多个特征的方法，以便您可以获得有时所说的双因素身份验证。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
Like the T cell will only kill cancer if it finds this and this.
就像 T 细胞只有找到这个和这个才会杀死癌症一样。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
And that combination of things are not found on healthy cells, even if one or the other might be.
健康细胞上并没有发现这种组合，即使其中一个可能存在。
So people are thinking about how do we get more sophisticated about building these discrimination systems into T cells.
因此，人们正在思考如何将这些辨别系统更复杂地构建到 T 细胞中。
The building blocks are there, but the specifics for each cancer have to be invented.
构建模块已经存在，但每种癌症的具体细节还需要发明。
But we have the tools to do that.
但我们有工具可以做到这一点。
Andrew Huberman:
安德鲁·休伯曼：
Awesome.
太棒了。
Before we talk about CRISPR, there was one other question that I know many people will be thinking about.
在我们谈论 CRISPR 之前，我知道很多人都会考虑另一个问题。
A few years back, maybe five, 10 years back, there was a lot of discussion, maybe even some enthusiasm, about ketogenic diets to treat or prevent cancer.
几年前，也许五年、十年前，关于生酮饮食治疗或预防癌症有很多讨论，甚至可能有些热情。
And my understanding from looking at that literature was that for some cancers, it perhaps, I want to bold, underline, and capitalize perhaps might help, but for other cancers, it could make things worse.
通过查看这些文献，我的理解是，对于某些癌症，我想加粗、下划线和大写也许会有所帮助，但对于其他癌症，它可能会让事情变得更糟。
And then I also more recently started hearing about low glutamine diets.
然后我最近也开始听说低谷氨酰胺饮食。
Dr. Alex Marson:
亚历克斯·马森博士：
Mm.
嗯。
Andrew Huberman:
安德鲁·休伯曼：
And of course, this is the way the internet works.
当然，这就是互联网的运作方式。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But I did see some papers in some decent journals that at least were exploring this.
但我确实在一些不错的期刊上看到了一些论文，至少正在探索这一点。
So are low, let's call it what they are, ketogenic diets, have they been shown to be useful for treatment or avoidance of cancer?
那么，生酮饮食的含量很低，我们就这么称呼它吧，它们是否被证明对治疗或避免癌症有用？
Dr. Alex Marson:
亚历克斯·马森博士：
I have to defer to you.
我必须服从你。
I actually don't know the answer to that.
我其实不知道答案。
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
My guess is that people are still looking at this.
我的猜测是人们仍在关注这个问题。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But there was also the idea that they could be useful for certain forms of dementia.
但也有人认为它们可能对某些形式的痴呆症有用。
There was an effort to call dementia type three diabetes.
有人试图将痴呆症称为三型糖尿病。
Dr. Alex Marson:
亚历克斯·马森博士：
Mm.
嗯。
Andrew Huberman:
安德鲁·休伯曼：
But my understanding from talking to the experts in this is that it might help through indirect mechanisms, but that it's not going to solve the problem.
但通过与专家交谈，我的理解是，它可能通过间接机制有所帮助，但并不能解决问题。
Okay.
好的。
Well, thanks for entertaining that little- ...
好吧，谢谢你招待那个小-...
cul-de-sac that I created.
我创造的死胡同。
CRISPR.
CRISPR。
Tell us the story of CRISPR, because I think CRISPR is one of those funny things in biology and medicine that almost everybody has heard about in the general population.
告诉我们 CRISPR 的故事，因为我认为 CRISPR 是生物学和医学领域的有趣事物之一，几乎每个人都听说过普通人群。
Most people know it has something to do with changing genes, but it's sort of like AI.
大多数人都知道它与改变基因有关，但这有点像人工智能。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
It's here.
就在这里。
It's powerful.
它很强大。
It scares certain people.
它让某些人感到害怕。
It excites other people.
它让其他人兴奋。
But most people don't know how it works, because there's really no incentive to.
但大多数人不知道它是如何运作的，因为实际上没有动力去这样做。
But I think the story of CRISPR is actually also a story about how science works.
但我认为 CRISPR 的故事实际上也是一个关于科学如何运作的故事。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And that's important, too.
这也很重要。
Dr. Alex Marson:
亚历克斯·马森博士：
I think it's exactly true.
我认为这是千真万确的。
I think it is a perfect illustration of something where a discovery happened that no one was planning-
我认为这是一个完美的例证，说明了无人计划的发现的发生——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
but changed biology.
但改变了生物学。
Let me tell you this story in two separate arcs.
让我用两个不同的故事来告诉你这个故事。
One arc is the arc of understanding DNA.
一根弧线就是理解DNA的弧线。
If you go back to Watson and Crick, it's understanding the double helix-
如果你回到沃森和克里克，就会明白双螺旋——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
to understand the structure of what a DNA sequence is.
了解 DNA 序列的结构。
That matures.
那成熟了。
We've learned how to sequence, to understand, to be able to measure a row of A, Ts, and Cs and Gs that, in whatever combination they are, will start to be the building blocks for programming which proteins get made inside a cell.
我们已经学会了如何测序、理解、测量一排 A、T、C 和 G，无论它们以何种组合，都将开始成为编程细胞内生成哪些蛋白质的构建块。
And then around 2000, we get to the first draft of the human genome, which is this multibillion-dollar project across the world to come up with a draft of one human genome sequence, a milestone for biology and medicine.
然后在 2000 年左右，我们得到了人类基因组的第一份草图，这是一个耗资数十亿美元的全球项目，旨在绘制一个人类基因组序列的草图，这是生物学和医学的里程碑。
And then DNA sequencing technologies continue to improve and cost comes down, and we're getting to the point where we can start to measure big chunks of our DNA at increasingly affordable costs, and people were starting to understand the differences between people with DNA at the level of at least statistics.
然后 DNA 测序技术不断改进，成本下降，我们已经可以开始以越来越实惠的成本测量我们 DNA 的大块，人们开始至少在统计水平上了解 DNA 人之间的差异。
Okay, people with this disease are more likely to have this gene than that.
好吧，患有这种疾病的人更有可能拥有这种基因。
But we're getting to some limit of what we can do just by sequencing DNA.
但仅仅通过 DNA 测序我们的能力已经达到了一定的极限。
All of a sudden, you're observing the DNA sequence that's in someone's cells, but you don't really know what those effects are.
突然间，您观察某人细胞中的 DNA 序列，但您并不真正知道这些影响是什么。
Just as the sequencing world is maturing, we're desperately looking for a tool to say, "Well, as we have all the sequences, we want to be able to see what happens if you change a sequence." And people were stumbling around looking for different tools.
正如测序世界正在走向成熟，我们迫切需要一种工具来表达：“好吧，由于我们拥有所有序列，我们希望能够看到如果改变序列会发生什么。”人们四处寻找不同的工具。
There was a range of these things.
这些事情有很多。
There were zinc fingers.
有锌指。
Lentivirus was another one that we just talked about, with different degrees of efficiency, and people were trying to be able to change DNA sequences in cells, and it had been a longstanding effort.
慢病毒是我们刚才谈到的另一种病毒，具有不同程度的效率，人们试图能够改变细胞中的DNA序列，这是一项长期的努力。
Out of nowhere emerges CRISPR as the answer to this problem.
CRISPR 突然出现，成为解决这个问题的答案。
CRISPR was being studied as an interesting and unusual set of DNA sequences that were found in certain types of bacteria.
CRISPR 是在某些类型的细菌中发现的一组有趣且不寻常的 DNA 序列。
There were these repeated sequences, and no one knew what they were.
这些重复的序列，没有人知道它们是什么。
And people, out of real basic curiosity about what was happening in bacteria, started studying these repeat sequences and what they were doing.
人们出于对细菌中发生的事情的真正基本好奇，开始研究这些重复序列以及它们在做什么。
And little by little by little, it was worked out that these repeat sequences actually formed the basis of a kind of immune system for bacteria.
渐渐地，人们发现这些重复序列实际上构成了细菌免疫系统的基础。
Andrew Huberman:
安德鲁·休伯曼：
Mm.
嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
Now, we talked about the human immune system.
现在，我们谈论人体免疫系统。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
Bacteria are just an individual cell, but they're also susceptible to infections, which is sort of a strange idea.
细菌只是一个单独的细胞，但它们也容易受到感染，这是一个奇怪的想法。
Bacteria cause infections in us, but there's this arms race between organisms, right?
细菌会导致我们感染，但生物体之间存在军备竞赛，对吧？
Andrew Huberman:
安德鲁·休伯曼：
Everyone's trying to kill everyone else.
每个人都试图杀死其他人。
Dr. Alex Marson:
亚历克斯·马森博士：
And so bacteria are constantly being bombarded by certain types of viruses.
因此，细菌不断受到某些类型病毒的轰炸。
They're called bacteriophage viruses.
它们被称为噬菌体病毒。
Bacteria have evolved a series of defense mechanisms to protect themselves from these viruses.
细菌进化出了一系列防御机制来保护自己免受这些病毒的侵害。
CRISPR turns out to be a bacterial defense mechanism against viruses, which is kind of amazing that this-
CRISPR 被证明是一种针对病毒的细菌防御机制，这有点令人惊讶——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
thing that has entered into popular culture is-
已经进入流行文化的是——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
a bacteria protection against bacteriophage.
对抗噬菌体的细菌保护。
Now, why has this caught the world of biology by storm?
那么，为什么这会席卷生物学界呢？
Well, what was realized was that the way that CRISPR works to protect bacteria from viruses is that it can recognize particular sequences of DNA, which are virus sequences, and discriminate whether it's a virus sequence or its own bacteria sequence.
人们意识到，CRISPR 保护细菌免受病毒侵害的方式是它可以识别特定的 DNA 序列（即病毒序列），并区分它是病毒序列还是其自身的细菌序列。
Andrew Huberman:
安德鲁·休伯曼：
Mm.
嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
And it actually does that by scanning across the DNA and finding something that's recognized as a virus target and not a bacteria target.
它实际上是通过扫描 DNA 并找到被识别为病毒目标而不是细菌目标的东西来实现这一点的。
And when it finds it, it makes a cut.
当它找到它时，它就会进行切割。
Okay?
好的？
Now, this sounds technical, obscure, but what was recognized, and this became the basis for a Nobel Prize with Jennifer Doudna and Emmanuelle Charpentier, many people around the world have contributed to this field.
现在，这听起来技术性、晦涩难懂，但却得到了认可，并且这成为了与 Jennifer Doudna 和 Emmanuelle Charpentier 一起获得诺贝尔奖的基础，世界各地的许多人都为这一领域做出了贡献。
What was realized was that this could be repurposed As a tool, if we take it out of bacteria, we could actually exploit this CRISPR system that had evolved to protect bacteria.
我们意识到，这可以重新用作一种工具，如果我们将其从细菌中取出，我们实际上可以利用这种为保护细菌而进化的 CRISPR 系统。
And the same rules that allowed bacteria to scan across DNA and find a virus sequence and cut it could be used to scan across any DNA and cut at a particular sequence.
允许细菌扫描 DNA 并找到病毒序列并切割它的相同规则也可以用于扫描任何 DNA 并切割特定序列。
That's the power of CRISPR.
这就是 CRISPR 的力量。
Now, why do we care so much about being able to cut a particular sequence?
现在，为什么我们如此关心能否剪切特定序列？
If you can cut, you can also start pasting.
如果可以剪切，也可以开始粘贴。
You can cut out genes that are limiting, that you don't want to be in a cell.
你可以切除那些你不希望存在于细胞中的限制性基因。
You can start pasting in sequences to replace mutations that cause disease.
您可以开始粘贴序列以替换导致疾病的突变。
We can start pasting in big sequences, like the sequence for CARs or other types of things that will make T cells more powerful.
我们可以开始粘贴大序列，例如 CAR 序列或其他类型的序列，这些序列将使 T 细胞变得更强大。
So I'm focused on T cells, but this is now in every aspect of biology.
所以我专注于 T 细胞，但这现在已经渗透到生物学的各个方面。
People are studying this in plants and to make crops that will be drought resistant.
人们正在植物中研究这一点，并培育抗旱作物。
People are studying this in every organ system to understand every type of disease and to build new types of molecular medicines.
人们正在每个器官系统中进行研究，以了解每种类型的疾病并开发新型分子药物。
There's one other feature of CRISPR that's really important in this story.
CRISPR 的另一个功能在这个故事中非常重要。
It's not just that this CRISPR can cut at a specific sequence, that it's evolved to cut at virus sequences.
这种 CRISPR 不仅可以切割特定序列，而且它已经进化到可以切割病毒序列。
It's the way that it cuts that has made it really catch on in a way that none of these earlier technologies do.
正是它的切割方式使其真正流行起来，而这些早期技术都没有做到这一点。
So CRISPR, if you think of it, it's an enzyme that can cut DNA, and it can cut essentially almost any sequence of DNA.
所以 CRISPR，如果你想一下的话，它是一种可以切割 DNA 的酶，它基本上可以切割任何 DNA 序列。
So how does it decide which sequence to cut?
那么它如何决定剪切哪个序列呢？
It does it by actually pairing with an RNA molecule.
它实际上是通过与 RNA 分子配对来实现的。
So CRISPR, sometimes called Cas9, which is a particular type of CRISPR system, is a combination of a protein, which is a scissor, and then an RNA that sticks to it, and the RNA is what actually programs where that scissor will cut.
因此，CRISPR，有时称为 Cas9，是一种特殊类型的 CRISPR 系统，是蛋白质（剪刀）和粘附在其上的 RNA 的组合，而 RNA 是实际编程剪刀将切割的位置的东西。
Okay?
好的？
And what's so special about that is that we actually know with near perfect precision the rules of how an RNA will recognize any DNA sequence.
其特别之处在于，我们实际上以近乎完美的精确度知道 RNA 如何识别任何 DNA 序列的规则。
There's a complementarity where you can match up and know exactly which RNA you want to design.
这是一种互补性，您可以匹配并准确地知道您想要设计哪种 RNA。
So you can now cut DNA sequences at will, and it's gotten to the point where now if we want to cut a piece of DNA, we order a piece of RNA off the internet.
所以你现在可以随意切割 DNA 序列，现在如果我们想切割一段 DNA，我们就从互联网上订购一段 RNA。
It shows up in the lab in a matter of days.
几天之内它就会出现在实验室中。
We mix it with Cas9 protein, and then that's going in T cells the next day, and we're able to introduce a cut into any DNA sequence.
我们将其与 Cas9 蛋白混合，然后第二天进入 T 细胞，我们就能够在任何 DNA 序列中引入切割。
So now you go back to the genome sequence that came out in 2010, and all of a sudden you can go on the internet, pick a place in the genome that you're interested in studying, order a piece of RNA, make your targeted CRISPR molecule, and make a cut or a cut and a paste at that particular site, and then in a very tangible way, read out the consequences.
所以现在你回到2010年发布的基因组序列，突然间你可以上网，在基因组中选择你感兴趣研究的一个位置，订购一段RNA，制作你的目标CRISPR分子，并在那个特定位点进行剪切或剪切和粘贴，然后以一种非常有形的方式读出结果。
You're going into the source code of DNA inside of a cell, and when you make that change, you can say, "What happens to the cell?
你要研究细胞内 DNA 的源代码，当你做出改变时，你可以说，“细胞会发生什么？
Is it a stronger response?
这是一个更强烈的反应吗？
Is it a different response?" We can test it in test tubes.
是不是有不同的反应？”我们可以在试管中测试它。
We can test it in models of disease.
我们可以在疾病模型中对其进行测试。
And then as we learn the rules, we can actually take those CRISPR-modified cells all the way and infuse them into patients.
然后，当我们了解规则时，我们实际上可以将这些 CRISPR 修饰的细胞一直注入患者体内。
Andrew Huberman:
安德鲁·休伯曼：
Incredible, and thank you for that incredibly clear and detailed explanation of the CRISPR-Cas9 system.
难以置信，感谢您对 CRISPR-Cas9 系统极其清晰和详细的解释。
A couple of questions.
有几个问题。
How precise is the cut?
切割的精度如何？
Are you damaging adjacent nucleotides, or can you home in exactly on the site that you want to cut?
您是否会破坏相邻的核苷酸，或者您能否准确定位到您想要切割的位点？
And then a related question is if you're going to introduce a gene sequence there, how do you ensure that there aren't downstream effects?
然后一个相关的问题是，如果你要在那里引入基因序列，你如何确保没有下游影响？
Dr. Alex Marson:
亚历克斯·马森博士：
I think what you're getting at with both of these questions are unintended consequences, and that's always present, right?
我认为你对这两个问题的理解都是意想不到的后果，而且这种后果总是存在的，对吗？
I think this has been a major concerted effort for the field of CRISPR, of how do you get more and more precise.
我认为这是 CRISPR 领域一项重大的共同努力，关于如何变得越来越精确。
And it's come a long way, but nothing's perfect, right?
虽然已经取得了很大的进步，但没有什么是完美的，对吧？
So I think the field has done a lot of work to test off targets, right?
所以我认为该领域已经做了很多工作来测试目标，对吧？
If you're programming to cut on one place on chromosome six, do you accidentally ever cut anywhere else?
如果您正在编程在六号染色体上的一个位置进行切割，您是否会意外地切割其他地方？
And there's a range.
并且有一个范围。
Sometimes some sequences are a little bit more promiscuous than others, but we've gotten quite good at getting more and more precise to say, "Okay, we're making these high-fidelity cuts at one place." There are still the second risks of bystander effects.
有时，某些序列比其他序列更加混乱，但我们已经非常擅长变得越来越精确地说，“好吧，我们正在一个地方进行这些高保真剪辑。”还存在旁观者效应的第二个风险。
Okay, you make a cut.
好吧，你剪一下吧。
Does the DNA get chewed back at the neighboring part?
DNA 是否会在邻近部分被咀嚼？
There's been, in some extreme places, pieces of chromosomes actually falling off.
在一些极端的地方，染色体碎片实际上已经脱落。
All of these things can happen, and I think we're at a place in a field where now we're thinking about, for each disease, a risk benefit of, okay, there's always a risk for any medicine of some unintended consequences.
所有这些事情都可能发生，我认为我们现在所处的领域是，对于每种疾病，风险收益，好吧，任何药物总是存在一些意想不到的后果的风险。
We have to be on the lookout for them.
我们必须留意他们。
We have to know what they are.
我们必须知道它们是什么。
Most cells, as we said, that get a mutation, don't have a problem.
正如我们所说，大多数发生突变的细胞都没有问题。
They just die off.
他们就死掉了。
So if you have an unintended consequence, most will die, but there is always the risk of the unintended consequences, and I think as a field, we have to be humble about that.
因此，如果出现意外后果，大多数人都会死亡，但意外后果的风险总是存在，我认为作为一个领域，我们必须对此保持谦虚。
That said, the CRISPR world is not static.
也就是说，CRISPR 世界并不是一成不变的。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
And the story I told you was the building block of CRISPR.
我告诉你的故事是 CRISPR 的基础。
It's a protein scissor that can be targeted to any piece of DNA with an RNA molecule.
它是一把蛋白质剪刀，可以用 RNA 分子靶向任何 DNA 片段。
People are appropriately thinking, "Well, scissors can cause damage.
人们会适当地思考：“嗯，剪刀会造成损坏。
Maybe that CRISPR molecule should actually be re-engineered not to be a scissor, but to do other things." And now people have started engineering it to say, "Well, let's not make it a scissor.
也许 CRISPR 分子实际上应该被重新设计，而不是成为一把剪刀，而是做其他事情。”现在人们开始设计它，说：“好吧，我们不要把它做成剪刀。
Let's make it a thing that just introduces a more predictable mutation at a site." David Liu at Harvard has created these things called CRISPR base editors that doesn't introduce a double-stranded break, but actually changes nucleotides in a more predictable way at that site by recruiting a deaminase domain, something that will change DNA nucleotides when it's recruited to a particular place, and you use CRISPR just to recruit that enzyme that makes that mutation at a targeted place.
让我们让它成为一个在某个位点引入更可预测的突变的东西。”哈佛大学的 David Liu 创造了一种叫做 CRISPR 碱基编辑器的东西，它不会引入双链断裂，而是实际上通过招募脱氨酶结构域以更可预测的方式在该位点改变核苷酸，当脱氨酶结构域被招募到特定位置时，它会改变 DNA 核苷酸，而你使用 CRISPR 只是为了招募在目标位置产生突变的酶。
Other people have actually started using epigenetic enzymes.
其他人实际上已经开始使用表观遗传酶。
The DNA doesn't just get enacted by DNA sequences, but pieces of it can be active or inactive, and this is called epigenetics, where there can be a stable program of things getting turned on or off without any change in the A's and T's and C's and G's.
DNA 不仅仅由 DNA 序列决定，而且它的各个部分可以是活跃的或不活跃的，这被称为表观遗传学，其中可以有一个稳定的程序来打开或关闭事物，而 A、T、C 和 G 不会发生任何变化。
And now we and others are using CRISPR-based epigenetic editing.
现在我们和其他人正在使用基于 CRISPR 的表观遗传编辑。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
It's called epi-editing, where we don't make any cut in the genome, but we just turn on or off, and it's in a large part to think about mitigating some of these risks that might come with the scissor function.
这被称为表观编辑，我们不对基因组进行任何切割，只是打开或关闭，这在很大程度上是为了考虑减轻剪刀功能可能带来的一些风险。
Instead, all of a sudden, we're thinking about we're using the same building block of recruiting an enzyme to a particular place in the DNA code, but using the full set of things that we might do at that DNA site to program cells in the most precise possible way.
相反，突然之间，我们开始思考我们正在使用相同的构建模块将酶招募到 DNA 代码中的特定位置，但使用我们可能在该 DNA 位点上执行的全套操作以最精确的方式对细胞进行编程。
Andrew Huberman:
安德鲁·休伯曼：
I'd like to take a quick break and acknowledge one of our sponsors, Element.
我想稍微休息一下并感谢我们的赞助商之一 Element。
Element is an electrolyte drink that has everything you need and nothing you don't.
Element 是一种电解质饮料，它拥有您需要的一切，却没有您不需要的东西。
That means the electrolytes, sodium, magnesium, and potassium, all in the correct ratios, but no sugar.
这意味着电解质、钠、镁和钾的比例都正确，但不含糖。
Proper hydration is critical for brain and body function.
适当的水合作用对于大脑和身体功能至关重要。
Even a slight degree of dehydration can diminish your cognitive and physical performance.
即使是轻微程度的脱水也会降低您的认知和身体表现。
It's also important that you get adequate electrolytes.
获得充足的电解质也很重要。
The electrolytes, sodium, magnesium, and potassium, are vital for the functioning of all cells in your body, especially your neurons or your nerve cells.
电解质（钠、镁和钾）对于体内所有细胞（尤其是神经元或神经细胞）的功能至关重要。
Drinking Element makes it very easy to ensure that you're getting adequate hydration and adequate electrolytes.
Drinking Element 可以轻松确保您获得足够的水分和电解质。
My days tend to start really fast, meaning I have to jump right into work or right into exercise.
我的日子往往开始得很快，这意味着我必须立即投入工作或立即锻炼。
So to make sure that I'm hydrated and I have sufficient electrolytes, when I first wake up in the morning, I drink 16 to 32 ounces of water with an Element packet dissolved in it.
因此，为了确保我有足够的水分和足够的电解质，当我早上第一次醒来时，我会喝 16 至 32 盎司的水，并溶解有 Element 包。
I also drink Element dissolved in water during any kind of physical exercise that I'm doing, especially on hot days when I'm sweating a lot and losing water and electrolytes.
我还在进行任何体育锻炼时饮用溶解在水中的元素，尤其是在炎热的日子里，当我大量出汗并失去水分和电解质时。
Element has a bunch of great-tasting flavors.
Element 有很多美味的口味。
In fact, I love them all.
事实上，我爱他们所有人。
I love the watermelon, the raspberry, the citrus, and I really love the lemonade flavor.
我喜欢西瓜、覆盆子、柑橘，而且我真的很喜欢柠檬水的味道。
So if you'd like to try Element, you can go to drinkelement.com/huberman to claim a free Element sample pack with any purchase.
因此，如果您想尝试 Element，可以访问 Drinkelement.com/huberman，购买任意产品即可领取免费的 Element 样品包。
Again, that's drinkelement.com/huberman to claim a free sample pack.
再次强调，请访问 Drinkelement.com/huberman 索取免费样品包。
I'm curious about getting CRISPR into the cells of interest.
我很好奇将 CRISPR 引入感兴趣的细胞中。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
The lentivirus example that you gave before, my understanding is it involved harvesting some T cells, introducing the lentivirus with the cargo that you want, putting that back into circulation, and the T cells know where to go and know what to do.
你之前举的慢病毒的例子，我的理解是，它涉及收获一些T细胞，将慢病毒与你想要的货物一起引入，然后将其放回到循环中，T细胞知道该去哪里，知道该做什么。
For a lot of cell types, like neurons in the brain-
对于许多细胞类型，例如大脑中的神经元 -
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
liver cells, pancreatic cells, I could imagine a surgery where you inject directly into those organs, but wouldn't it be wonderful if you could get the cells of interest without having to be so invasive?
肝细胞、胰腺细胞，我可以想象通过手术直接注射到这些器官中，但如果您无需如此侵入性就能获得感兴趣的细胞，那不是很棒吗？
So what's being done there in terms of trafficking CRISPR to appropriate cell types and/or organs, and then that sort of seeds another question that I'll hold off on about whether we should be banking cells for what's coming.
那么，在将 CRISPR 转移到适当的细胞类型和/或器官方面，我们正在做什么，然后这就引发了另一个问题，我将暂缓讨论我们是否应该为即将发生的事情储存细胞。
Dr. Alex Marson:
亚历克斯·马森博士：
First of all, I just want to pause.
首先，我想暂停一下。
This is great.
这太棒了。
I love this conversation.
我喜欢这次谈话。
Andrew Huberman:
安德鲁·休伯曼：
No, I do too.
不，我也一样。
You're taking us to the, I don't like the phrase bleeding edge, it sounds violent, but you're taking us to the cutting edge of molecular biology and medicine, and we are peering over into what's next.
你正在带我们到，我不喜欢“前沿”这个词，这听起来很暴力，但你正在带我们到分子生物学和医学的最前沿，我们正在凝视接下来会发生什么。
Like what your children and my children and probably our parents also will be able to benefit from in the next 10 years, maybe sooner.
就像你的孩子和我的孩子，或许还有我们的父母也将能够在未来 10 年（也许更早）中受益。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah, we're really talking about things that are happening now and happening at an accelerating rate.
是的，我们确实在谈论现在正在发生并且正在加速发生的事情。
So you asked, part of what just made me have that reaction is I think you asked one of the key questions for this field of how is this being delivered into cells.
所以你问，让我产生这种反应的部分原因是我认为你问了这个领域的关键问题之一，即如何将其传递到细胞中。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
So I told you, let me go backwards and then I'll go forward.
所以我告诉你，让我后退，然后我再前进。
I told you that in 2012, I sort of was sitting there thinking about I wanted to study T cells, the genetic control of T cells.
我告诉过你，2012 年，我坐在那里思考我想研究 T 细胞，即 T 细胞的遗传控制。
I saw the power of CAR T cells.
我看到了 CAR T 细胞的力量。
I saw the power of CRISPR, which at that time was being only used in highly artificial immortalized cell lines that grow easily in the lab.
我看到了 CRISPR 的力量，当时它仅用于在实验室中轻松生长的高度人工永生化细胞系。
And it just wasn't clear that there would be a way to get CRISPR to work in real T cells that you would take out of a human blood sample that are not immortalized, that can only stay in a dish for a short amount of time and still retain their function.
目前还不清楚是否有一种方法可以让 CRISPR 在真正的 T 细胞中发挥作用，这些 T 细胞是从人类血液样本中取出的，这些细胞不是永生化的，只能在培养皿中停留很短的时间，但仍然保留其功能。
And I sort of tripled down on this was what my lab was going to do, that we were going to figure out a way, and we went through a long list of different ways that we might deliver, and it wasn't obvious.
我在这方面投入了三倍的精力，这就是我的实验室要做的事情，我们要找出一种方法，我们列出了一长串我们可能提供的不同方法，但这并不明显。
Actually, a key collaboration early in my career was another serendipitous run-in.
事实上，我职业生涯早期的一次重要合作是另一次偶然的磨合。
I met Jennifer Doudna through some persistence of my own, and Jennifer Doudna and I sat down and started thinking about how could we team up to take her expertise in CRISPR biochemistry and get it to work in T cells.
我通过自己的坚持认识了 Jennifer Doudna，我和 Jennifer Doudna 坐下来开始思考我们如何合作，利用她在 CRISPR 生物化学方面的专业知识，并让它在 T 细胞中发挥作用。
And we settled on this thing that was not at the top of my list of things that would work, but ended up opening up the field.
我们决定做这个事情，它不在我的可行的事情清单的首位，但最终打开了这个领域。
We actually purified the CRISPR protein.
我们实际上纯化了 CRISPR 蛋白。
So we had protein and RNA that we could make in a test tube.
这样我们就有了可以在试管中制造的蛋白质和 RNA。
Now we order it off the internet.
现在我们从互联网上订购。
We can mix them together, and we could make these protein RNA complexes, and we could suspend that in liquid.
我们可以将它们混合在一起，我们可以制造这些蛋白质 RNA 复合物，我们可以将其悬浮在液体中。
And then what we did is we actually incubated T cells from a blood sample in that liquid.
然后我们所做的实际上是在该液体中培养来自血液样本的 T 细胞。
And then the question was how do you get these protein RNA complexes into the cells?
接下来的问题是如何让这些蛋白质 RNA 复合物进入细胞？
And we use this trick that's been around for a long time.
我们使用这个已经存在很长时间的技巧。
As long as it's been around, sounds magical, and no one quite understands how it works.
只要它存在，听起来就很神奇，但没有人完全理解它是如何工作的。
We put these cells into a device that gives a small electrical current to the T cells.
我们将这些细胞放入一个向 T 细胞提供小电流的装置中。
Andrew Huberman:
安德鲁·休伯曼：
Electroporation.
电穿孔。
Dr. Alex Marson:
亚历克斯·马森博士：
Electroporation.
电穿孔。
Andrew Huberman:
安德鲁·休伯曼：
Oh, man.
哦，伙计。
I During my graduate career, I electroporated a lot of...
在我的研究生生涯中，我电穿孔了很多...
Well, I can just say it now because I don't do it anymore.
好吧，我现在只能这么说，因为我不再这样做了。
Electroporated a lot of brains of intact animals.
对许多完整动物的大脑进行电穿孔。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
You inject DNA, it's floating around in the local tissue.
当你注射DNA时，它会漂浮在局部组织中。
You pass some square wave current.
您通过一些方波电流。
Dr. Alex Marson:
亚历克斯·马森博士：
Yep.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And the assumption is that it creates little transient pores in the cell membrane, and it gets in, and sometimes you end up with four cells transfected, and sometimes you end up with 40,000 cells transfected.
假设它会在细胞膜上产生短暂的小孔，然后它就会进入，有时最终会转染 4 个细胞，有时最终会转染 40,000 个细胞。
It's a wildly useful technique, but it's a little bit hit-or-miss.
这是一种非常有用的技术，但有点碰运气。
Dr. Alex Marson:
亚历克斯·马森博士：
That's a perfect description.
这是一个完美的描述。
And so my first postdoc in my lab, Katherine Schumann, sat there and tested different electroporation conditions, altering these little pulse widths.
因此，我实验室的第一位博士后凯瑟琳·舒曼 (Katherine Schumann) 坐在那里测试不同的电穿孔条件，改变这些小脉冲宽度。
Andrew Huberman:
安德鲁·休伯曼：
One pulse, 12 pulses, long pulses.
1 个脉冲、12 个脉冲、长脉冲。
You're taking me back to my graduate, and to some extent, my postdoctoral years.
你让我回到了我的研究生时代，在某种程度上，我回到了博士后时代。
It's unclear for given tissues, for given sequences, what's going to go into cells, what's going to not kill the cells.
对于给定的组织、给定的序列，尚不清楚什么会进入细胞，什么不会杀死细胞。
Dr. Alex Marson:
亚历克斯·马森博士：
We were walking this tightrope of how do you make this pore is big enough that CRISPR will get in, but that the cells don't die.
我们正在走钢丝，如何让这个孔足够大，让 CRISPR 能够进入，但细胞又不会死亡。
And we did it, and we've optimized this, and it was one of those things when it happens, you see it, and you just realize it's binary.
我们做到了，我们对此进行了优化，当它发生时，它就是其中之一，你看到它，你就会意识到它是二进制的。
Like all of a sudden you're editing DNA inside of T cells.
就像突然间你在 T 细胞内编辑 DNA 一样。
And we got our foot in the door with some level of efficiency.
我们以一定的效率迈出了第一步。
We've gone through the roof.
我们已经穿过屋顶了。
This is now used by labs widely, and it's incredibly efficient.
现在，它已被实验室广泛使用，而且非常高效。
And some cells die, but overwhelmingly, you end up with cells that are gene edited.
有些细胞会死亡，但绝大多数细胞最终都会经过基因编辑。
Andrew Huberman:
安德鲁·休伯曼：
She figured out the protocol.
她弄清楚了协议。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
She really did, and it's been optimized.
她确实做到了，而且已经优化了。
And then another grad student in my lab came in, this guy, amazing grad student, Theo Roth, and realized that he didn't have to stop there, that we thought we were limited to just putting CRISPR in and these very small pieces of DNA called oligonucleotides that would just change a couple of nucleotides at a time.
然后我实验室的另一位研究生进来了，这个家伙，令人惊叹的研究生，Theo Roth，他意识到他不必就此止步，我们认为我们只能将 CRISPR 和这些称为寡核苷酸的非常小的 DNA 片段放入其中，一次只会改变几个核苷酸。
Our mindset was like, maybe we can fix a mutation, an individual mutation.
我们的心态是，也许我们可以修复一个突变，一个个体突变。
Theo said, "Let's not stop there.
西奥说：“我们不要就此止步。
Let's put big pieces of DNA in." And we've pushed this boundary of being able to say, let's pick a site, make a cut, and introduce hundreds or up to thousands of different nucleotides to be able to really write a piece of DNA code that doesn't even have to exist in nature, but then we have the precision using CRISPR to put it into a particular place in the DNA.
让我们把大片段的 DNA 放进去。”我们已经突破了这样的界限：让我们选择一个位点，进行切割，并引入数百甚至数千种不同的核苷酸，以便能够真正编写一段甚至不必存在于自然界中的DNA代码，然后我们可以使用CRISPR精确地将其放入DNA中的特定位置。
We started a company when that technology worked, a company called Arsenal Biosciences that's now in clinical trials.
当这项技术发挥作用时，我们成立了一家公司，名为 Arsenal Biosciences，目前正处于临床试验阶段。
It's actually in its third clinical trial right now for solid tumors.
实际上，它现在正在进行针对实体瘤的第三次临床试验。
It's in a clinical trial for prostate cancer that's about to start enrolling patients.
这是一项针对前列腺癌的临床试验，即将开始招募患者。
And that company can now do this at industrial scale.
该公司现在可以在工业规模上做到这一点。
It takes patient cells, electroporates them, and has now written a long piece of 10,000 nucleotides of DNA code that put in a sequence of a combination of different receptors-
它获取患者细胞，对它们进行电穿孔，现在已经编写了一段长长的 10,000 个核苷酸的 DNA 代码，其中包含不同受体组合的序列 -
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
including a CAR, and additional gene enhancements that will make these T cells more powerful in a tumor microenvironment.
包括 CAR 和其他基因增强功能，使这些 T 细胞在肿瘤微环境中更加强大。
Andrew Huberman:
安德鲁·休伯曼：
And then they go into the bloodstream, they navigate to the prostate-
然后它们进入血液，导航到前列腺-
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
...
...
and they start fighting the cancer cells.
他们开始对抗癌细胞。
And I imagine you can also put, it sounds like you're putting some kind of resilience genes in there as well.
我想你也可以说，听起来你也把某种弹性基因放在那里。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
That's exactly right.
完全正确。
Andrew Huberman:
安德鲁·休伯曼：
To bolster the healthy cells.
增强健康细胞。
Dr. Alex Marson:
亚历克斯·马森博士：
To bolster the T cells that carry these receptors-
为了增强携带这些受体的 T 细胞 -
Andrew Huberman:
安德鲁·休伯曼：
Got it
明白了
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
to make them persist longer-
让他们坚持得更久——
Andrew Huberman:
安德鲁·休伯曼：
Better warriors
更好的战士
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
and be able to function.
并能够发挥作用。
Exactly.
确切地。
Andrew Huberman:
安德鲁·休伯曼：
Awesome.
太棒了。
Dr. Alex Marson:
亚历克斯·马森博士：
That's happening and the way that that happens is that a patient will be selected, will go in for a blood donation, give a rather large blood donation, but those cells are then shipped to a facility that Arsenal maintains.
这种情况正在发生，发生的方式是选择一名患者，进行献血，献血量相当大，然后将这些细胞运送到阿森纳维护的设施。
The electroporation happens in the centralized facilities.
电穿孔在集中设施中进行。
The cells get grown up for a couple of days and tested.
这些细胞会生长几天并进行测试。
They get frozen down and then sent back to the patient, where the cells are then thawed, and it's the equivalent of a blood transfusion.
它们被冷冻起来，然后被送回患者体内，然后细胞被解冻，这相当于输血。
Now their own cells have been supercharged to allow them to recognize cancer, but also to have, as you said, added resilience, added strength in that battle against cancer.
现在，他们自己的细胞已经被增强，使他们能够识别癌症，而且，正如你所说，在与癌症的斗争中，增加了韧性，增加了力量。
Andrew Huberman:
安德鲁·休伯曼：
The cells that have been modified by the CRISPR-Cas9, they're sitting in this bag.
经过 CRISPR-Cas9 修饰的细胞就放在这个袋子里。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
They get infused.
他们被注入。
Are they designed, is the CRISPR designed to only go after the prostate cancer cells?
它们是经过设计的吗？CRISPR 是否被设计为只针对前列腺癌细胞？
Or is there some version of this where you can inoculate against a number of different cancers?
或者是否有某种版本可以让您针对多种不同的癌症进行接种？
In other words, if I'm understanding correctly, if there are sort of canonical mutation sequences-
换句话说，如果我理解正确的话，如果存在某种规范的突变序列-
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
that occur in all cancerous cells-
发生在所有癌细胞中的现象——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
is there a version of this where I give some blood-
有没有一个版本可以让我献血-
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
you or a company, probably a company, electroporates them with the CRISPR-Cas9 system, brings in resilience genes for the T cells, for my T cells, plus some attack genes, right?
你或者一家公司，可能是一家公司，用 CRISPR-Cas9 系统对它们进行电穿孔，为 T 细胞、我的 T 细胞引入弹性基因，再加上一些攻击基因，对吗？
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So that are going to destroy the cancer cells.
这样就会消灭癌细胞。
And then I get an infusion of these when I turn, well, I'm 50 now, so like 52.
然后当我转身时，我会得到这些的注入，好吧，我现在50岁了，所以就像52岁一样。
And then it protects against all cancers that probably are forming at multiple sites throughout my body.
然后它可以预防可能在我身体多个部位形成的所有癌症。
Little mutations here, little mutations there.
这里有一点突变，那里也有一点突变。
Hopefully, they don't proliferate, but is there a way to just short-circuit cancer body-wide?
希望它们不会扩散，但是有没有办法在全身范围内短路癌症呢？
Dr. Alex Marson:
亚历克斯·马森博士：
I think that's a hope that all of us have to some extent.
我认为这在某种程度上是我们所有人的希望。
I think these technologies get proven out in patients where the risk-benefit of an unproven technology is tolerated.
我认为这些技术在患者身上得到了验证，而未经证实的技术的风险收益是可以承受的。
And I think that in reality, that means that patients who have exhausted other treatment opportunities get treated, and often those are the sickest patients.
我认为，实际上，这意味着用尽其他治疗机会的患者会得到治疗，而且往往是病情最严重的患者。
And I think there's good reasons for ethics-
我认为道德上有充分的理由——
Andrew Huberman:
安德鲁·休伯曼：
Sure
当然可以
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
where that's where we start.
这就是我们开始的地方。
But our hope is that these technologies eventually will be proven to be safe, they'll get more and more precise.
但我们希望这些技术最终将被证明是安全的，它们将变得越来越精确。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
I hope the cost would go down.
我希望成本能下降。
And I don't know You talk about the other extreme of doing it preventatively, but at least we should start marching earlier and earlier in the course of diagnosis.
我不知道你是否谈论预防性的另一个极端，但至少我们应该在诊断过程中越来越早地开始前进。
And the hope is that we're already seeing improved tools for early diagnosis of cancer, where we're detecting the earlier signs of cancer.
希望我们已经看到了用于癌症早期诊断的改进工具，我们可以检测癌症的早期迹象。
It'd be nice if we have the ability to start treating those early cancers that might be the ones that are the most responsive to the immune system.
如果我们有能力开始治疗那些可能对免疫系统最敏感的早期癌症，那就太好了。
And then beyond that, preventative would be even better.
除此之外，预防措施会更好。
I think to get there, if we really want to scale up, I think we also have to think about, going back to your last question about delivery, maybe it's not always going to be these cells getting shipped to a centralized factory and electroporated.
我认为要实现这一目标，如果我们真的想扩大规模，我认为我们还必须考虑，回到你关于交付的最后一个问题，也许这些细胞并不总是被运送到集中工厂并进行电穿孔。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
Although that's been incredibly powerful and it's not stopping now, we're actually starting academically in an institute that I run, the Gladstone UCSF Institute of Genomic Immunology.
尽管这种力量非常强大，而且现在还没有停止，但我们实际上是在我管理的一个研究所——格拉德斯通加州大学旧金山分校基因组免疫学研究所——开始学术研究。
We're starting a philanthropically funded CRISPR trial for multiple myeloma, where we're using a different genetic program.
我们正在开始一项由慈善资助的针对多发性骨髓瘤的 CRISPR 试验，我们使用了不同的基因程序。
So there's a huge number of diseases where we are thinking about what can we do with existing technologies.
因此，我们正在思考如何利用现有技术应对大量疾病。
We're also starting to look for ways that the deliveries of the future will happen, and different people are coming up with different solutions.
我们也开始寻找未来交付的方式，不同的人正在提出不同的解决方案。
But one emerging trend is that rather than taking the cells out of the body and then exposing them to CRISPR in these targeted ways with electroporation, what if we could put CRISPR into the body and just send it and address it just to the cells that we want to modify?
但一个新兴趋势是，我们不是将细胞从体内取出，然后通过电穿孔以这些有针对性的方式将它们暴露于 CRISPR 之下，而是如果我们可以将 CRISPR 放入体内，然后将其发送到我们想要修改的细胞，会怎样呢？
We're interested in the T cells.
我们对 T 细胞感兴趣。
Someone else might be interested in modifying lung-
其他人可能对改变肺感兴趣
Andrew Huberman:
安德鲁·休伯曼：
Neurons
神经元
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
or heart or neurons, right?
或心脏或神经元，对吗？
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
For different diseases.
针对不同的疾病。
And that is a field that is now exploding-
这是一个正在爆炸式增长的领域——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
thinking about technologies.
思考技术。
It's another area where there's just tools that are happening so fast.
这是另一个领域，工具的发展速度如此之快。
Andrew Huberman:
安德鲁·休伯曼：
When I was a postdoc, it was all about, it seemed, for a few years, different ways to get genes into cells.
当我还是一名博士后时，几年来似乎一切都是关于将基因导入细胞的不同方法。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So there's electroporation-
于是就有了电穿孔——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
there are lentiviruses, there are adenoviruses-
有慢病毒，有腺病毒——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
there are calcium phosphate transfection, and on and on.
还有磷酸钙转染等等。
One of the things that was kind of interesting, but at the time didn't really go anywhere, was customized little liposomes.
其中一件很有趣的事情是定制的小脂质体，但当时并没有真正发挥任何作用。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Like little fatty bubbles-
就像小脂肪泡一样——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
because fatty stuff can get onto and through cell membranes, so it makes good sense.
因为脂肪物质可以进入并穿过细胞膜，所以这是有道理的。
But with some sort of zip coding so that you could inject these fatty bubbles or swallow them even, get them into the bloodstream, and then those fatty bubbles would go to the very specific type of liver cell or brain cell that you wanted.
但是通过某种邮政编码，您可以注射这些脂肪气泡，甚至吞下它们，将它们进入血液，然后这些脂肪气泡将进入您想要的特定类型的肝细胞或脑细胞。
Has that technology moved forward at all, the liposome technology?
脂质体技术到底有没有进步？
Dr. Alex Marson:
亚历克斯·马森博士：
Dramatically.
戏剧性地。
Andrew Huberman:
安德鲁·休伯曼：
Oh, great.
哦，太好了。
Dr. Alex Marson:
亚历克斯·马森博士：
Dramatically.
戏剧性地。
Andrew Huberman:
安德鲁·休伯曼：
Relieved to hear and relieved to hear I wasn't the one that had to do the work because I knew a lot of very frustrated people working on liposomes.
听到这个消息我松了口气，听到我不是那个必须做这项工作的人，我松了一口气，因为我认识很多从事脂质体研究的非常沮丧的人。
Fortunately for me, electroporation adenoviruses worked spectacularly well for my experiments, but a lot of people needed cell-type specific in transfection-
对我来说幸运的是，电穿孔腺病毒在我的实验中效果非常好，但是很多人在转染中需要特定的细胞类型-
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
through a vein injection.
通过静脉注射。
Dr. Alex Marson:
亚历克斯·马森博士：
So all of these things have gone under rapid progress.
所以所有这些事情都在快速进展。
Let's talk about the viruses.
我们来谈谈病毒。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
We talked about viruses as a tool, as a shuttle of DNA.
我们谈论病毒作为一种工具，作为DNA的穿梭机。
They naturally, each one will have some range of what cells it would infect.
当然，每个细胞都会有一定范围的感染细胞。
For a virus, this is called tropism.
对于病毒来说，这称为趋向性。
What cells are susceptible to infection with any virus?
哪些细胞容易受到病毒感染？
Those would be the cells that you would be able to deliver genetic material to with an engineered virus.
这些细胞可以通过工程病毒传递遗传物质。
People have really advanced engineered tropism, engineering what cells a virus will deliver material to, and that can be dialed in quite precisely now in a number of different ways.
人们拥有真正先进的工程趋向性，可以设计病毒将物质输送到哪些细胞，并且现在可以通过多种不同的方式非常精确地进行调节。
So people are working on-
所以人们正在努力——
Andrew Huberman:
安德鲁·休伯曼：
Right
右
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
engineered viruses.
工程病毒。
There's still problems.
还是有问题啊
They're trying to make sure that they don't trigger immune responses, but they're getting more and more precise, both viruses and things that have virus-like properties that are sometimes called virus-like particles-
他们试图确保它们不会触发免疫反应，但他们变得越来越精确，无论是病毒还是具有类似病毒特性的东西，有时被称为类病毒颗粒——
Andrew Huberman:
安德鲁·休伯曼：
Right
右
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
that are essentially viruses that can just deliver either DNA or protein to a cell that's specified by what that virus tropism is.
它们本质上是病毒，只能将 DNA 或蛋白质传递到由病毒向性所指定的细胞。
And people are working on engineering these tropisms with a lot of technologies.
人们正在努力利用大量技术来设计这些趋向性。
Andrew Huberman:
安德鲁·休伯曼：
Because you could put drugs in them, too.
因为你也可以在里面放毒品。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
We talk about SSRIs have all these side effects.
我们谈论 SSRIs 具有所有这些副作用。
Well, that's because you're getting serotonin increases at locations you don't want it.
嗯，那是因为你的血清素在你不想要的地方增加了。
You could imagine only getting drugs to certain cells.
你可以想象只将药物输送到某些细胞。
To me, it's super exciting and just seems so fundamental.
对我来说，这非常令人兴奋，而且似乎非常重要。
So I'm relieved to hear that there's progress being made.
因此，听到正在取得进展，我感到很欣慰。
Dr. Alex Marson:
亚历克斯·马森博士：
Anything that can be genetically encoded, you can start imagining these types of targeting.
任何可以基因编码的东西，你都可以开始想象这些类型的目标。
Now, you asked about liposomes.
现在，您询问了脂质体。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
Now, liposomes have kind of come up with our new name is lipid nanoparticles.
现在，脂质体已经有了我们的新名称：脂质纳米颗粒。
Andrew Huberman:
安德鲁·休伯曼：
Lipid nanoparticles.
脂质纳米粒子。
That kind of rolls off the tongue nicely.
这种感觉很好地从舌头上滚下来。
Dr. Alex Marson:
亚历克斯·马森博士：
And the abbreviation we use is LNPs, but a billion people around the world have now been injected with LNPs.
我们使用的缩写是LNP，但是现在全世界有10亿人注射了LNP。
LNPs are the technology that delivered mRNA vaccines.
LNP 是提供 mRNA 疫苗的技术。
Andrew Huberman:
安德鲁·休伯曼：
Ah, okay.
啊，好吧。
That'll raise some eyebrows.
这会引起一些人的注意。
Dr. Alex Marson:
亚历克斯·马森博士：
I-
我-
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
No, we're going to talk about vaccines.
不，我们要谈谈疫苗。
Listen, we're going into it all today.
听着，我们今天将详细讨论这一切。
They were liposome bound.
它们是脂质体结合的。
Dr. Alex Marson:
亚历克斯·马森博士：
Essentially, these are lipids that can deliver genetic material to cells, and this was done locally for the COVID vaccine, but people are now engineering them with the targeting molecules that you described so that they go to particular cells.
从本质上讲，这些脂质可以将遗传物质传递给细胞，这是在新冠疫苗中本地完成的，但人们现在正在用您描述的靶向分子对它们进行改造，以便它们进入特定的细胞。
If you inject them into the body, lipid nanoparticles naturally tend to go to the liver, so people are using these already to cure genetic diseases where the genetic burden is affecting the cells in the liver because you can deliver CRISPR to cells in the liver pretty robustly with these.
如果将它们注射到体内，脂质纳米颗粒自然会进入肝脏，因此人们已经在使用它们来治疗遗传疾病，其中遗传负担正在影响肝脏中的细胞，因为你可以用它们将 CRISPR 非常可靠地传递到肝脏中的细胞。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
I have my strong view on the COVID vaccine.
我对新冠疫苗有强烈的看法。
I think it was a miracle that we were able to develop something on a short timeline to address a pandemic that was killing people.
我认为我们能够在很短的时间内开发出一些东西来应对一场导致人类死亡的流行病，这真是一个奇迹。
But I understand there's controversy.
但我知道存在争议。
Leaving that aside, lipid nanoparticles are, it's amazing that we were able to do this, that we took something that was an idea Most people thought it would be an obscure technical thing, like you talked about, like would it ever work?
撇开这一点不说，脂质纳米颗粒是，我们能够做到这一点，我们采取了一些想法，这真是太神奇了。大多数人认为这将是一个晦涩的技术问题，就像你谈到的那样，就像它会起作用吗？
All of a sudden it could be manufactured at scale, could deliver a synthetic piece of mRNA to give a temporary instruction to cells to make a protein to protect us.
突然之间，它可以大规模生产，可以提供合成的 mRNA 片段，向细胞发出临时指令，制造蛋白质来保护我们。
And whether that's for COVID or for other things, all of a sudden, we're, again, I just keep coming back to this theme where there's more and more ways that we can not only understand biology, but that we can intervene in it to treat disease.
无论是针对新冠病毒还是其他事情，突然间，我们再次回到这个主题，我们不仅可以理解生物学，而且可以干预生物学来治疗疾病。
And so now we're talking about something totally different.
所以现在我们谈论的是完全不同的事情。
We're talking about delivering CRISPR, which is not an mRNA vaccine, but we're talking about how would we get CRISPR into cells, or how would we get extra pieces of genetic material, which might be an mRNA, so into a T cell.
我们谈论的是提供 CRISPR，它不是 mRNA 疫苗，但我们谈论的是我们如何将 CRISPR 引入细胞，或者我们如何将额外的遗传物质片段（可能是 mRNA）引入 T 细胞。
All of this can now be done even beyond the vaccine world with the same kind of building blocks of technologies like lipid nanoparticles.
现在，所有这一切甚至可以在疫苗领域之外使用脂质纳米颗粒等同类技术构建模块来完成。
Actually, there's a company out of the University of Pennsylvania that actually developed recently a technology to make lipid nanoparticles that could be injected into the bloodstream.
事实上，宾夕法尼亚大学的一家公司最近开发了一种技术，可以制造可以注射到血液中的脂质纳米颗粒。
Think of them as these little fat bubbles, exactly as you said.
正如您所说，将它们视为这些小脂肪气泡。
But in them, they included a protein that would recognize something on the surface of T cells, so that as these lipid bubbles were going through the blood, they would stick preferentially to T cells and deliver mRNA to T cells.
但它们中含有一种能够识别 T 细胞表面某些物质的蛋白质，因此当这些脂质气泡穿过血液时，它们会优先粘附在 T 细胞上，并将 mRNA 传递给 T 细胞。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
And you could actually put in an mRNA into T cells that would temporarily make a gene that it would encode a CAR, these artificial receptors against cancer.
实际上，你可以将 mRNA 放入 T 细胞中，T 细胞会暂时生成一个基因，编码 CAR，这些人工受体可以对抗癌症。
And they've done this now in testing in a number of models.
他们现在已经在多个模型中进行了测试。
They can actually make these CAR T cells by injecting lipid nanoparticles into the body without ever taking the T cells out of the bloodstream.
他们实际上可以通过将脂质纳米粒子注射到体内来制造这些 CAR T 细胞，而无需将 T 细胞从血液中取出。
And I think we're going to see more and more things like that from the pharm industry, is all of a sudden saying, "Okay, there's more ways that we can make drugs.
我认为我们会在制药行业看到越来越多类似的事情，突然说，“好吧，我们可以有更多的方法来制造药物。
Things don't have to just be pills anymore."
Things don't have to just be pills anymore."
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
They can be engineered proteins, or lipid nanoparticles, or viruses, or engineered cells, whatever is going to be most effective at getting to the root cause of disease.
它们可以是工程蛋白质、脂质纳米粒子、病毒或工程细胞，只要能最有效地找到疾病的根源即可。
Andrew Huberman:
安德鲁·休伯曼：
I want to just talk about the COVID vaccine briefly.
我想简单谈谈新冠疫苗。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Because in my role as a public health educator, I was exposed to a lot of voices.
因为作为一名公共卫生教育者，我接触到了很多声音。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And I can't speak for everybody-
我不能代表所有人——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
certainly, but I think that at least three of the things that caused a lot of divide around the mRNA vaccines were, first of all, the difference between mandates versus optionality.
当然，但我认为，至少有三个因素导致 mRNA 疫苗产生很大分歧，首先是强制性与选择性之间的差异。
We don't have to go there, but I think that-
我们不必去那里，但我认为-
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
that was a major player.
那是一个主要参与者。
People, especially Americans, don't like to be told what to do.
人们，尤其是美国人，不喜欢被告知该做什么。
That's just a-
那只是一个——
Dr. Alex Marson:
亚历克斯·马森博士：
I've noticed that.
我注意到了这一点。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Second of all, it was closely related to notions of the shutdown, which differentially impacted people.
其次，它与政府关门的概念密切相关，这对人们产生了不同的影响。
And that's an understatement.
这是轻描淡写的说法。
Some people maintained paychecks, some people didn't.
有些人保留了薪水，有些人则没有。
Some people could work, some people couldn't.
有些人可以工作，有些人则不能。
So there was that.
所以就是这样。
I'm not trying to soften anything here, but I think that the vaccines were nested in a bunch of other issues.
我并不是想软化任何问题，但我认为疫苗还包含着许多其他问题。
Again, at least three.
再说一次，至少三个。
This is not exhaustive.
这并不详尽。
And then the other one, and I actually had this concern myself, which was how is it that it gets turned off?
然后是另一个，我自己其实也有这样的担忧，那就是它怎么会被关闭？
I can imagine a situation where I would want to put an mRNA into me to do something biologically, but then I don't want it to continue to do that after a period of time.
我可以想象这样一种情况，我想将 mRNA 放入我体内以进行生物学上的某些操作，但在一段时间后我不希望它继续这样做。
So what in the design of that vaccine allowed it to be targeted to the cells of interest and then not continue to express in all other cells in perpetuity?
那么，该疫苗的设计是什么让它能够靶向感兴趣的细胞，然后不再继续在所有其他细胞中永久表达呢？
Dr. Alex Marson:
亚历克斯·马森博士：
I'll answer the specific question, but I think the context that you give is also a really important part of this, and I would take one second to talk about this.
我将回答具体问题，但我认为您提供的背景也是其中非常重要的一部分，我会花一点时间来讨论这个问题。
I think to answer your first question, we talked about DNA as the source code.
我想为了回答你的第一个问题，我们讨论了 DNA 作为源代码。
We talked about proteins as what the DNA is ultimately encoding.
我们讨论了 DNA 最终编码的蛋白质。
Let's just talk for a second about what mRNA is.
我们先来谈谈什么是 mRNA。
mRNA is the temporary intermediate between those things.
mRNA 是这些事物之间的临时中间体。
DNA will get what's called transcribed into mRNA, which is another nucleic acid, but doesn't stick around permanently.
DNA 会被转录成 mRNA，这是另一种核酸，但不会永久保留。
It is the temporary instruction, which will then go to the ribosome and become the template for a particular protein.
它是临时指令，然后将进入核糖体并成为特定蛋白质的模板。
The idea of an mRNA vaccine is that you're using this temporary template so that the cells that will take this up will make proteins from this temporary template for some period of time.
mRNA 疫苗的想法是，你使用这个临时模板，这样接受它的细胞就会在一段时间内利用这个临时模板制造蛋白质。
Now, you can always imagine the extreme outliers of ways that this could last longer or not, but fundamentally, you're putting in an mRNA that gives a temporary instruction to the cell to make a small part of the COVID vaccine.
现在，你总是可以想象这种情况可能会持续更长时间或不会持续的极端异常情况，但从根本上来说，你正在放入一个 mRNA，它向细胞发出临时指令，以制造一小部分新冠疫苗。
Now, of the COVID virus, a very small part.
现在，新冠病毒只是很小的一部分。
Now, just by comparison, if you get infected with COVID, you're also going to get COVID mRNA is transcribed in your cells.
现在，相比之下，如果您感染了新冠病毒，您的细胞中也会转录新冠病毒 mRNA。
And so we're talking about genetic material making mRNA either way, whether it's the mRNA from the COVID or a designed small part of that COVID genome that we're using as a vaccine.
因此，我们谈论的是以任何方式制造 mRNA 的遗传物质，无论是来自新冠病毒的 mRNA，还是我们用作疫苗的新冠病毒基因组的设计小部分。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
So I think it's important to think about the risks in the context of the virus versus what we're doing with a vaccine.
因此，我认为重要的是要考虑病毒的风险与我们使用疫苗所做的事情。
So I got the COVID vaccine enthusiastically, and actually, I think overwhelmingly, I know overwhelmingly my immunology colleagues did the same.
因此，我热情地接种了新冠疫苗，实际上，我认为绝大多数情况下，我知道绝大多数我的免疫学同事也做了同样的事情。
In people who live in this world of immunology, a great enthusiasm that this could be done and built.
生活在免疫学世界的人们对这一切的实现和建立抱有极大的热情。
Now That doesn't answer what you said about the cultural phenomenon.
这并不能回答你所说的文化现象。
I'm talking just as a person-
我只是以一个人的身份说话——
Andrew Huberman:
安德鲁·休伯曼：
Sure, yeah
当然，是的
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
not as an immunologist.
不是作为免疫学家。
Andrew Huberman:
安德鲁·休伯曼：
Please.
请。
Dr. Alex Marson:
亚历克斯·马森博士：
But I think we probably haven't done enough to talk about the trauma that we went through as a nation during COVID, of being fractured by people dying on one hand, and all the negative consequences, as you said, of shutdown.
但我认为我们可能还没有做足够的事情来谈论我们作为一个国家在新冠疫情期间所经历的创伤，一方面被人们的死亡所撕裂，以及正如你所说的关闭带来的所有负面后果。
Shutdown of economic life, shutdown of social life.
经济生活停摆，社会生活停摆。
I think it was a period of major dislocation and we're still feeling the trauma and the people's different relationships with things like vaccine, but of science even more generally, were dislodged or accentuated by this trauma that I think we all collectively went through and we don't talk enough about.
我认为那是一个严重混乱的时期，我们仍然感受到创伤和人们与疫苗等事物的不同关系，但更普遍的是，科学被这种创伤所取代或加剧，我认为我们都共同经历过这种创伤，但我们谈论得不够。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
I'll just give one anecdote.
我只讲一则轶事。
Well, I spent a lot of time isolated during COVID and was disheartened by the fact that on one hand, I was watching the scientific speed race.
好吧，在新冠疫情期间，我花了很多时间与世隔绝，一方面，我在观看科学速度竞赛，这让我感到沮丧。
That was actually, I think, one of the highlights of the first Trump administration, Operation Warp Speed, to streamline and get coordination, both on the science and the regulatory side, to get vaccines approved in an extraordinary timeline, taking advantage of a number of technologies and making them all.
我认为，这实际上是特朗普第一届政府“曲速行动”的亮点之一，旨在简化科学和监管方面的协调，在非常时期内获得疫苗批准，利用多种技术并制造它们。
So I was watching this science unfold with some optimism, but also watching the trust in science being eroded.
因此，我乐观地看着这门科学的展开，但也看到人们对科学的信任正在被侵蚀。
I developed a side hobby, which is I've gone back, I've been reading presidential biographies sequentially.
我养成了一个副业爱好，那就是我回去了，我一直在按顺序阅读总统传记。
This is just a side hobby.
这只是一个业余爱好。
Now, in thinking about this frustration with how science was tearing things apart, I found this strange relief in reading about early American history.
现在，在思考科学如何撕裂事物所带来的挫败感时，我在阅读美国早期历史时发现了这种奇怪的解脱。
In 1793, there was a yellow fever epidemic in Philadelphia, and actually, the early parties that were forming, the Federalists and the Democrats, actually took wildly dissenting views of how to deal with an epidemic.
1793年，费城爆发了黄热病疫情，实际上，早期组建的政党——联邦党和民主党——实际上对如何应对疫情持有截然不同的看法。
They had different views of what caused it, whether it was outside contagion or sanitation.
他们对于造成这种情况的原因有不同的看法，无论是外部传染还是卫生条件。
And the Democrats at that time, the Jeffersonian Democrats, were in favor of really extreme bloodletting techniques.
当时的民主党人，即杰斐逊派民主党人，赞成真正极端的放血技术。
And the Hamiltonians, the Federalists, had a totally different set of techniques of baths and more gentle treatments, and they just couldn't see eye to eye.
汉密尔顿派、联邦党人有一套完全不同的沐浴技术和更温和的治疗方法，但他们的看法却不一致。
Why am I saying all this?
我为什么要说这些？
I think it's not new territory, that these discussions of how we deal with infections, which are inherently societal diseases, unearth the societal tensions, and we deal with them in different ways, and we come at to them from different perspectives.
我认为这并不是什么新领域，这些关于我们如何处理感染的讨论，这些感染本质上是社会疾病，揭示了社会紧张局势，我们以不同的方式处理它们，我们从不同的角度来看待它们。
And there's a lot of things that are simultaneously being balanced in any decision of how we deal with thinking about the trade-offs that we're willing to make in the face of a pandemic or an epidemic.
在我们如何处理思考面对大流行病或流行病时愿意做出的权衡的任何决定中，有很多事情同时需要平衡。
Andrew Huberman:
安德鲁·休伯曼：
I really appreciate that, and I'm also impressed that you're reading these biographies.
我真的很感激，而且你正在阅读这些传记也给我留下了深刻的印象。
How do you know which biography to select?
How do you know which biography to select?
Because there are many of them, and unfortunately, Walter Isaacson hasn't written them all.
因为它们有很多，不幸的是，沃尔特·艾萨克森并没有把它们全部写出来。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I love his books.
我喜欢他的书。
So how do you select the author of each biography?
那么如何选择每本传记的作者呢？
Dr. Alex Marson:
亚历克斯·马森博士：
This is an ongoing-- This is a project that I spend a lot of time.
这是一个正在进行的项目，我花了很多时间。
Each one, I go through a period of indecision about which one I-
每一个，我都会经历一段犹豫不决的时期，对于哪一个我-
Andrew Huberman:
安德鲁·休伯曼：
Okay
好的
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
I should read.
我应该读书。
Andrew Huberman:
安德鲁·休伯曼：
Uh-huh.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
I can share my list.
我可以分享我的清单。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Dr. Alex Marson:
亚历克斯·马森博士：
I'm not done yet.
我还没说完。
This has been over several years.
这已经过去好几年了。
Andrew Huberman:
安德鲁·休伯曼：
Uh-huh.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
I'm now up to World War II.
我现在正准备参加第二次世界大战。
Andrew Huberman:
安德鲁·休伯曼：
You should do a podcast someday.
You should do a podcast someday.
Just know, in your copious amounts of spare time, not as a husband, father, running a giant lab, et cetera, and physician, you could do a podcast and teach us what you learn.
只要知道，在你大量的业余时间，而不是作为一个丈夫、父亲、经营一个巨大的实验室等等，或者医生，你可以做一个播客并教我们你学到的东西。
Anyway, awesome.
无论如何，太棒了。
I'd like to take a quick break and acknowledge one of our sponsors, Function.
我想稍微休息一下并感谢我们的赞助商之一 Function。
Last year, I became a Function member after searching for the most comprehensive approach to lab testing.
去年，在寻找最全面的实验室测试方法后，我成为了 Function 成员。
Function provides over 100 advanced lab tests that give you a key snapshot of your entire bodily health.
Function 提供 100 多项高级实验室测试，为您提供整个身体健康状况的关键快照。
This snapshot offers you with insights on your heart health, hormone health, immune functioning, nutrient levels, and much more.
此快照为您提供有关心脏健康、激素健康、免疫功能、营养水平等方面的见解。
They've also recently added tests for toxins, such as BPA exposure from harmful plastics, and tests for PFAS, or forever chemicals.
他们最近还增加了毒素测试，例如有害塑料中的 BPA 暴露，以及 PFAS 或永久化学物质的测试。
Function not only provides testing of over 100 biomarkers key to your physical and mental health, but it also analyzes these results and provides insights from top doctors who are expert in the relevant areas.
Function 不仅提供对您的身心健康至关重要的 100 多种生物标记物的测试，而且还分析这些结果并提供相关领域专家的顶级医生的见解。
For example, in one of my first tests with Function, I learned that I had elevated levels of mercury in my blood.
例如，在我第一次使用 Function 进行测试时，我发现我的血液中汞含量升高。
Function not only helped me detect that, but offered insights into how best to reduce my mercury levels, which included limiting my tuna consumption, I'd been eating a lot of tuna, while also making an effort to eat more leafy greens and supplementing with NAC, N-acetylcysteine, both of which can support glutathione production and detoxification.
功能不仅帮助我发现了这一点，还为我提供了如何最好地降低汞含量的见解，其中包括限制我的金枪鱼摄入量，我一直在吃大量金枪鱼，同时还努力多吃绿叶蔬菜并补充 NAC、N-乙酰半胱氨酸，这两者都可以支持谷胱甘肽的产生和解毒。
And I should say, by taking a second Function test, that approach worked.
我应该说，通过进行第二次功能测试，这种方法奏效了。
Comprehensive blood testing is vitally important.
Comprehensive blood testing is vitally important.
There are so many things related to your mental and physical health that can only be detected in a blood test.
有很多与您的心理和身体健康相关的事情只能通过血液检查来检测。
The problem is blood testing has always been very expensive and complicated.
问题是血液检测一直非常昂贵且复杂。
In contrast, I've been super impressed by Function's simplicity and at the level of cost.
相比之下，Function 的简单性和成本水平给我留下了深刻的印象。
It is very affordable.
这是非常实惠的。
As a consequence, I decided to join their scientific advisory board, and I'm thrilled that they're sponsoring the podcast.
因此，我决定加入他们的科学顾问委员会，我很高兴他们赞助了这个播客。
If you'd like to try Function, you can go to functionhealth.com/huberman.
如果您想尝试 Function，可以访问 functionhealth.com/huberman。
Function currently has a wait list of over 250,000 people, but they're offering early access to Huberman Podcast listeners.
Function 目前有超过 250,000 人的等候名单，但他们正在为 Huberman 播客听众提供早期访问服务。
Again, that's functionhealth.com/huberman to get early access to Function.
同样，可以通过 functionhealth.com/huberman 提前访问 Function。
I have a question related to technologies to killing or altering cells that we didn't cover, but since we've touched on a number of them, the lipid nanoparticles, lentiviruses, since we're In a previous lifetime, I used in my experiments and I was excited by immunotoxins.
我有一个与杀死或改变细胞的技术有关的问题，我们没有涉及到，但由于我们已经接触过其中的一些技术，脂质纳米颗粒、慢病毒，因为我们在前世，我在实验中使用过，我对免疫毒素感到兴奋。
So an antibody against, you generally need a cell surface protein, and then you attach to it.
因此，针对的抗体，通常需要细胞表面蛋白，然后附着在其上。
In our case, we use sophorin toxin, which I think is most infamous because it was put on the tip of an umbrella and used to assassinate somebody on a bridge someplace in some sort of international spy warfare in the last 20 years or so.
在我们的案例中，我们使用槐角毒素，我认为这是最臭名昭著的，因为在过去 20 年左右的某种国际间谍战中，它被放在伞尖上并用于暗杀桥上的某人。
Sophorin will kill you if it goes systemic, but the idea there is that you take the sophorin toxin and you tether it to an antibody that then finds a cell surface protein and then kills that cell and only cell.
如果槐角素进入全身，就会杀死你，但这个想法是，你服用槐角素毒素，将其与抗体结合，然后抗体找到细胞表面蛋白，然后杀死该细胞，而且只杀死该细胞。
And it works remarkably well in experimental conditions if certain things are right.
如果某些事情是正确的，它在实验条件下会表现得非常好。
It doesn't always have the specificity you would like or the thoroughness.
它并不总是具有您想要的特异性或彻底性。
Has that been tried in cancer, directing toxins towards cancer cells?
是否已在癌症中尝试过将毒素导向癌细胞？
Dr. Alex Marson:
亚历克斯·马森博士：
The short answer is yes.
简短的回答是肯定的。
It's a really interesting area.
It's a really interesting area.
And what that toxin is can almost be thought of as modular, that you can think of it as two components.
这种毒素几乎可以被认为是模块化的，您可以将其视为两个组件。
You have a targeting component.
You have a targeting component.
You have an antibody as a natural one, where an antibody is evolved to recognize one particular type of protein.
您拥有一种天然抗体，其中抗体经过进化可以识别一种特定类型的蛋白质。
That can be the thing that targets something on the surface of cancer cells.
这可能是针对癌细胞表面某些东西的东西。
People have then developed what's called antibody drug conjugates, where basically a drug or something that's going to kill the cell gets appended to that antibody, and so it's selectively delivered.
然后，人们开发出了所谓的抗体药物偶联物，基本上将一种药物或某种能够杀死细胞的东西附加到抗体上，这样它就可以被选择性地递送。
You don't have to deliver the drug at systemic doses, but you can actually increase the local concentration by delivering it preferentially to the cancer cells that will be recognized by that antibody.
您不必以全身剂量输送药物，但实际上可以通过优先将药物输送到将被该抗体识别的癌细胞来增加局部浓度。
It doesn't have to be drugs.
It doesn't have to be drugs.
People are thinking about other things.
People are thinking about other things.
When people are now trying to attach radioactive isotopes, there's radioligand therapies that can be attached to these things.
当人们现在尝试附着放射性同位素时，可以将放射性配体疗法附着在这些东西上。
And I think in an extreme, that's essentially what we're doing with these T cell therapies, too.
我认为从极端的角度来看，这本质上也是我们对 T 细胞疗法所做的事情。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
When I've talked about this CAR, the chimeric antigen receptor, the outside of it, that is the sensor that's being used, is also a part of an antibody.
当我谈到这个CAR时，嵌合抗原受体，它的外部，即正在使用的传感器，也是抗体的一部分。
And so essentially what we're doing is now using the antibody to target, but instead of dragging along a drug, it's dragging along a cell.
And so essentially what we're doing is now using the antibody to target, but instead of dragging along a drug, it's dragging along a cell.
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
And so when that's engaged, the T cell is there and the T cell becomes the killing module.
因此，当它参与时，T 细胞就在那里，并且 T 细胞成为杀伤模块。
But the T cell not only kills the cancer cell, but could potentially be used to amplify that response, could release things and recruit other things.
但 T 细胞不仅可以杀死癌细胞，还可以用来放大这种反应，可以释放物质并招募其他物质。
So I think this general way of thinking about designing things to drag something to a cancer site is something that people are thinking a lot about.
所以我认为这种设计将某些东西拖到癌症部位的一般思考方式是人们正在思考的。
There's even another flavor of this that are called T cell engagers.
甚至还有另一种形式，称为 T 细胞接合者。
So I talked about, okay, we can genetically put an antibody fragment on a T cell and use that to direct a T cell to a cancer.
所以我谈到，好吧，我们可以通过基因方法将抗体片段置于 T 细胞上，并用它来引导 T 细胞治疗癌症。
People are also making antibodies that are antibodies on both ends.
人们也在制造两端都有抗体的抗体。
Okay, so this is sometimes, I think this is a proprietary term, but it can be called a bispecific or a BiTE.
好的，有时，我认为这是一个专有术语，但它可以称为双特异性或 BiTE。
The BiTE is a proprietary term.
The BiTE is a proprietary term.
But basically, these are two-headed antibodies.
但基本上，这些是双头抗体。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
One side will recognize a cancer cell and the other side will recognize a T cell and essentially bring these things together-
一侧将识别癌细胞，另一侧将识别 T 细胞，本质上将这些东西结合在一起 -
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
so that you get the T cell action locally to the cancer cell without having to do any genetic modification to the T cell.
这样您就可以在癌细胞局部发挥 T 细胞作用，而无需对 T 细胞进行任何基因改造。
You actually just take advantage of T cells that are already in the body.
实际上，您只是利用了体内已有的 T 细胞。
So all of these things are now under very active development, and some of them are approved, others are still in development.
所以所有这些事情现在都在非常积极的开发中，其中一些已经获得批准，其他一些仍在开发中。
Andrew Huberman:
安德鲁·休伯曼：
Very cool.
非常酷。
I'm sure people are catching on to this, but basically if you can understand the structure of things, including very, very small things, you can Lego them-
我确信人们已经明白了这一点，但基本上，如果你能理解事物的结构，包括非常非常小的事物，你就可以乐高它们——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and you can put all sorts of interesting cargos and play matchmaker between cells and it's kind of infinite what you can do once you start to understand things at that scale.
你可以放置各种有趣的货物，并在细胞之间扮演媒人的角色，一旦你开始了解这种规模的事物，你可以做的事情是无限的。
That's really what it's about.
这就是它的真正含义。
Dr. Alex Marson:
亚历克斯·马森博士：
I'll push it one step further.
我会更进一步。
I'm actually helping to organize a cancer immunotherapy conference here in LA.
实际上，我正在帮助在洛杉矶组织一场癌症免疫治疗会议。
I'm simultaneously here for this and for that.
我同时来这里是为了这个，也是为了那个。
I was at the conference yesterday and there was a talk by Amgen, big pharma company.
我昨天参加了会议，大型制药公司安进（Amgen）做了演讲。
I should disclose, I'm an advisor to Amgen.
我应该透露一下，我是安进的顾问。
And Amgen's been one of the leaders in these BiTEs.
安进 (Amgen) 一直是这些 BiTE 的领导者之一。
I think they actually trademarked this idea of bispecific T cell engager.
我认为他们实际上为双特异性 T 细胞接合器的想法注册了商标。
These are antibody fragments, but one of the leaders at Amgen talked yesterday about how looking forward, these aren't being used as just traditional antibodies that come out of animals, but they're actually being used as AI-designed protein engagers of any target you want.
这些是抗体片段，但安进公司的一位领导人昨天谈到了如何展望未来，这些片段不仅仅被用作来自动物的传统抗体，而且它们实际上被用作人工智能设计的任何你想要的目标的蛋白质接合剂。
So essentially now it's getting to the point where if you know that something's on the surface of a cancer cell, people are increasingly using AI models to design a synthetic protein that doesn't even exist in nature, that is designed to recognize and stick to something on the surface of cancer cell.
因此，现在基本上已经到了这样的地步：如果你知道癌细胞表面有什么东西，人们就会越来越多地使用人工智能模型来设计一种甚至在自然界中不存在的合成蛋白质，这种蛋白质旨在识别并粘附在癌细胞表面上的某些东西。
And that could be one of these Lego blocks for these modular, multifaceted T cell engagers or drug engagers or any of these other things.
这可能是这些模块化、多方面的 T 细胞接合器或药物接合器或任何其他东西的乐高积木之一。
So this is another area where the crosstalk between experimental capabilities and computational capabilities is further accelerating what's possible.
因此，这是实验能力和计算能力之间的串扰进一步加速可能性的另一个领域。
Andrew Huberman:
安德鲁·休伯曼：
Incredible.
难以置信。
Would you mind if I asked a couple of questions about the kind of science sociology and ethics around CRISPR?
您介意我问几个关于 CRISPR 的科学社会学和伦理学的问题吗？
Dr. Alex Marson:
亚历克斯·马森博士：
No, I would love it.
不，我会喜欢的。
Andrew Huberman:
安德鲁·休伯曼：
I'll keep this brief A few years back, we all learned, meaning the entire world learned, that a scientist in China had done a CRISPR-Cas experiment on babies.
我简单说一下几年前，我们都知道，也就是说全世界都知道，中国的一位科学家在婴儿身上进行了 CRISPR-Cas 实验。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I don't know when he did the modification.
不知道他什么时候修改的。
My guess is it was in utero.
我猜是在子宫里的。
You'll tell us what exactly he did.
你会告诉我们他到底做了什么。
This hit close to home for me because he and I were post-docs at the same time at Stanford, different labs.
这对我来说很重要，因为我和他同时在斯坦福大学的不同实验室担任博士后。
And the way the news hit the world was very interesting.
这个消息传遍世界的方式非常有趣。
One of the things I benefit from now as a podcaster and not just a professor is that I can talk about the stuff that perhaps pure professors wouldn't be willing to.
作为一名播客，而不仅仅是一名教授，我现在受益的一件事是，我可以谈论一些纯粹的教授可能不愿意谈论的事情。
So I'll say it.
所以我就这么说吧。
It was very interesting because the world kind of braced, but didn't make a decision as to whether or not they were upset that he had done this, like put him in front of an ethics board, maybe even throw him in a cell, or give him a Nobel Prize.
这很有趣，因为全世界都做好了准备，但没有决定是否对他的做法感到不安，比如把他放在道德委员会面前，甚至可能把他扔进牢房，或者授予他诺贝尔奖。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
It was like there was this kind of moment where no one really knew what to do.
就好像有这样一个时刻，没有人真正知道该怎么做。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Like, do you reward him?
比如，你奖励他吗？
Do you punish him?
你惩罚他吗？
Do you do nothing?
你什么都不做吗？
And it circulated back to Stanford because there was a question of what he had learned at Stanford, what was done at Stanford, and the stance, as I recall, was everyone just kind of waited to see how the world treated him.
它又传回了斯坦福大学，因为有人问他在斯坦福大学学到了什么，在斯坦福大学做了什么，而据我记得，每个人的立场都是在等着看世界如何对待他。
This is not a disparagement of any of my colleagues.
这并不是贬低我的任何同事。
I think we didn't understand how to react to this.
我认为我们不知道如何对此做出反应。
And then the decision was quickly made at large that he had done a bad thing.
然后大家很快就认定他做了一件坏事。
And that's kind of the last we ever heard about him or those kids.
这是我们最后一次听说他或那些孩子的消息。
The Chinese government condemned it publicly.
中国政府对此予以公开谴责。
I think they said he was going to be punished, but it wasn't clear if he was going to be punished by being put in a jail cell, being fined, or given a larger laboratory and more resources.
我认为他们说他会受到惩罚，但目前还不清楚他是否会受到监禁、罚款或给予更大的实验室和更多资源的惩罚。
It was very unclear.
事情很不清楚。
It's playing God-
这是在扮演上帝——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
at some level.
在某种程度上。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Right?
对吗？
It's not the same as deciding to not implant some embryos that were created through IVF because they carry an extra chromosome.
这与决定不植入一些通过体外受精产生的胚胎不同，因为它们带有额外的染色体。
It's different than that.
与此不同。
It's taking healthy children, in this case, and making a change to try and make them, quote unquote, super people.
在这种情况下，它需要健康的孩子，并做出改变，试图让他们（引用不引用的话）成为超级人。
So I would love your thoughts on that particular instance, your awareness, if any, that CRISPR in otherwise healthy humans has continued, and where you think this is all going.
因此，我希望了解您对这个特定实例的看法，您是否意识到 CRISPR 在健康人类中的应用仍在继续，以及您认为这一切的发展方向（如果有的话）。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah, I think you capture a lot of that moment.
是的，我认为你捕捉到了很多那个时刻。
I wasn't there, but there was an international CRISPR conference that was being held, I believe, in Hong Kong at the time.
我当时不在现场，但我相信当时在香港正在举行一场国际 CRISPR 会议。
And the scientist got up and announced with extraordinary pride in one of the sessions in this conference that he had done it, he had done genetic modification of embryos.
这位科学家站起来，在这次会议的一次会议上非常自豪地宣布他已经做到了，他已经完成了胚胎的基因改造。
And my understanding of what had happened was that there were two twins, there were parents who wanted to have kids, and the father was HIV positive.
我对所发生的事情的理解是，有两对双胞胎，有父母想要孩子，而父亲是艾滋病毒阳性。
And the modifications that they decided to try to make were to delete a gene that, if it's deleted, can confer resistance to HIV.
他们决定尝试进行的修改是删除一个基因，如果删除该基因，可以赋予对艾滋病毒的抵抗力。
Andrew Huberman:
安德鲁·休伯曼：
Mm.
嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
This is a gene called CCR5.
这是一个名为 CCR5 的基因。
There's people who naturally have a certain mutation in this at some frequency, and mutations in this gene confer resistance to HIV if they're naturally occurring.
有些人在这种情况下会以一定的频率自然地产生某种突变，如果这种基因的突变是自然发生的，就会赋予对艾滋病毒的抵抗力。
So that was the supposed rationale.
这就是所谓的理由。
Andrew Huberman:
安德鲁·休伯曼：
So there was a disease aspect to it.
所以这里面有一个疾病的方面。
Okay.
好的。
I wasn't aware of that.
我不知道这一点。
Thank you for that clarification.
谢谢你的澄清。
Dr. Alex Marson:
亚历克斯·马森博士：
It was a prophylaxis against this potential risk of HIV.
这是针对艾滋病毒这种潜在风险的预防措施。
Now, there were a lot of troublesome features from what I understand.
现在，据我了解，有很多麻烦的功能。
First of all, there's state-of-the-art methods to reduce the risk of HIV, through sperm washing and things that can be done that would, from my understanding, essentially reduce the risk to near zero of transmission from a father to an embryo.
首先，有最先进的方法可以降低艾滋病毒的风险，根据我的理解，通过精子清洗和可以做的事情，基本上可以将从父亲到胚胎的传播风险降低到接近零。
So I think it was a bit of a manufactured need, but there was the supposed justification.
所以我认为这有点是人为的需求，但有假定的理由。
Second of all, so they actually ended up generating two twins, and my understanding of how it was done, and I don't think that this was ever published, there was some publicity that was released, so I'm sort of piecing this together from what was public at that time, but I don't think any journal ever published this in any peer-reviewed context.
其次，他们实际上最终产生了两个双胞胎，我对它是如何完成的的理解，我认为这从未发表过，有一些宣传发布过，所以我是根据当时公开的内容将其拼凑在一起，但我认为没有任何期刊在任何同行评审的背景下发表过这篇文章。
They did this in concert with essentially IVF techniques.
他们这样做基本上是与体外受精技术相结合。
So they were fertilizing embryos with this father's sperm and the mother's eggs.
所以他们用父亲的精子和母亲的卵子使胚胎受精。
They created multiple embryos, and then they delivered CRISPR into these embryos and tried to create mutations in the CCR5 gene.
他们创造了多个胚胎，然后将 CRISPR 导入这些胚胎中，并试图在 CCR5 基因中产生突变。
There was some variability.
存在一些变化。
It was pretty early in days of CRISPR, and as I said, there's an unpredictability of what happens when you make a double-stranded break in the genome.
CRISPR 还处于早期阶段，正如我所说，当你在基因组中进行双链断裂时，会发生什么是不可预测的。
So it was a stretch to say, okay, they didn't exactly get the mutations that they wanted, but they proceeded nonetheless to implant these embryos.
所以说，好吧，他们并没有完全获得他们想要的突变，但他们仍然继续植入这些胚胎，这有些牵强。
And I know less about this, but there were also serious concerns about the way that consent was done on this.
我对此知之甚少，但也有人对同意的方式表示严重担忧。
So, like how much was informed about what the actual benefits would be to these patients.
所以，就像有多少人了解这些患者的实际好处是什么。
My understanding is that he got up, and I wasn't in the room, but I do think that there was some degree of immediate horror that this was being announced, and that it was unfolding in this way, and that it hadn't been considered, and it was not ready.
我的理解是，他站起来了，而我不在房间里，但我确实认为，这件事的宣布，以及它以这种方式展开，而且还没有被考虑到，而且还没有准备好，这让人们立即感到某种程度的恐惧。
In the wake of that, the Chinese government then announced that they were going to punish this, and I don't know the details, but I believe that he underwent some period of house arrest.
随后中国政府宣布要对此进行处罚，具体内容我不知道，但我相信他被软禁了一段时间。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
He was punished.
他受到了惩罚。
Dr. Alex Marson:
亚历克斯·马森博士：
I believe so.
我相信是这样。
I think after there was some degree of scientific outrage at this conference.
我认为在这次会议上引起了一定程度的科学愤怒。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, there was this pause moment that lasted maybe a week or two.
是的，这个停顿时刻可能持续了一两周。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Okay, well, you're clarifying a lot of the important details.
好吧，你正在澄清很多重要的细节。
Dr. Alex Marson:
亚历克斯·马森博士：
But my understanding Again, is that he's now free, and I think is restarting a lab.
但我的理解是，他现在自由了，我认为他正在重新启动一个实验室。
I don't think in China, I think somewhere else.
我不认为在中国，我认为在其他地方。
So the story might not be over yet.
所以故事可能还没有结束。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
So that's my understanding of the facts.
这就是我对事实的理解。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
I'll tell you now what I think.
我现在告诉你我的想法。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, please.
是的，请。
Dr. Alex Marson:
亚历克斯·马森博士：
I actually have a pretty hard line position on this, which I'm not sure all my colleagues would agree with, but I think that we should have a line in the sand where we do not introduce genetic edits that will be passed on to the next generation.
事实上，我对此持非常强硬的立场，我不确定我所有的同事都会同意这一点，但我认为我们应该有一条底线，即我们不引入将传递给下一代的基因编辑。
I told you I dedicated my life now to creating CRISPR technologies to engineer individual cells in the immune system, but these are what we call somatic edits.
我告诉过你，我现在毕生致力于创造 CRISPR 技术来改造免疫系统中的单个细胞，但这些就是我们所说的体细胞编辑。
These are making edits to the DNA in individual cells, where those genetic consequences will be passed on to the daughter cells, but not to the next generation of human, because we're not making genetic edits in sperm or in eggs.
它们对单个细胞中的 DNA 进行编辑，这些遗传结果将传递给子细胞，但不会传递给下一代人类，因为我们不会在精子或卵子中进行基因编辑。
If you do it in an embryo, all of a sudden every cell in the developing embryo will have it, including sperm and egg, and now you've not only made a genetic change to treat a disease or in this case, to prevent a disease.
如果你在胚胎中进行这项工作，突然之间，发育中的胚胎中的每个细胞都会拥有它，包括精子和卵子，现在你不仅进行了基因改变来治疗疾病，或者在这种情况下，预防疾病。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
As you said, in some cases, it'll be imagined to make an enhancement.
正如你所说，在某些情况下，会设想进行增强。
People have talked about maybe you want to add, we know genes that would make people be more muscular, or will there be a rush to-
人们已经讨论过也许你想补充一点，我们知道基因会让人们变得更加肌肉发达，或者是否会急于——
Andrew Huberman:
安德鲁·休伯曼：
Or enhanced memory.
或者增强记忆力。
Many years ago, there was a paper, it had some issues with replication down the line, but where I think it was Joe Cheng at Princeton, introduced maybe a mutant or an extra, I forget now, it's been a while.
很多年前，有一篇论文，它在复制方面存在一些问题，但我认为是普林斯顿大学的 Joe Cheng 引入了可能是突变体或额外的，我现在忘记了，已经有一段时间了。
A case in point, I clearly don't have this receptor- ...
举个例子，我显然没有这种受体——......
to the NMDA receptor, which is involved in plasticity in a sub-region of the hippocampus.
NMDA 受体参与海马亚区域的可塑性。
The idea was they were trying to make super smart mice.
他们的想法是试图制造超级聪明的老鼠。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
I remember that.
我记得。
That made quite a splash at the time.
这在当时引起了不小的轰动。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
I forget where that went.
我忘记那去了哪里。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Maybe Joe followed up on that, I don't know.
也许乔跟进了这一点，我不知道。
But that would be the sort of thing that people are both excited about and concerned about.
但这将是人们既兴奋又担心的事情。
Could you confer your offspring with better memory genes?
你能赋予你的后代更好的记忆基因吗？
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But of course, we have no idea if that's a good or a bad thing.
但当然，我们不知道这是好事还是坏事。
Forgetting certain things is very useful as well.
忘记某些事情也非常有用。
Dr. Alex Marson:
亚历克斯·马森博士：
I completely agree with you.
我完全同意你的观点。
And I think the point you made is a key one, that we do live in a world where people do IVF, and we do pre-implantation genetic testing, and people have the option to select not implant embryos that have certain mutations.
我认为你提出的观点很关键，我们确实生活在一个人们进行体外受精的世界，我们进行植入前基因测试，人们可以选择不植入具有某些突变的胚胎。
That's already a level of avoiding disease in a next generation if there's a severe mutation.
如果存在严重突变，这已经达到了避免下一代患病的水平。
I think it's a qualitatively different step to then not just select, but to actually make a genetic change.
我认为这是一个本质上不同的步骤，不仅是选择，而且是真正进行基因改变。
All of a sudden now you're really hampered.
突然之间，你真的受到了阻碍。
You have the ability to make some kind of mass-produced genetic edit in many embryos.
你有能力在许多胚胎中进行某种大规模生产的基因编辑。
I worry a lot about what this means for our offspring if they are designed rather than just born by chance.
我非常担心这对我们的后代意味着什么，如果他们是被设计的而不是偶然出生的。
I worry about fads.
我担心时尚。
When you think about the Pinterest culture that we live in, where people see something on Pinterest and want to follow on, I worry deeply about losing human diversity if we see fads in what genes are popular for our offspring, and people can order those in concert with IVF.
当你想到我们生活的 Pinterest 文化时，人们在 Pinterest 上看到一些东西并想要继续关注，我深感担心的是，如果我们看到哪些基因对我们的后代来说很流行，并且人们可以订购这些基因与 IVF 相一致，那么我会非常担心我们会失去人类的多样性。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
And I don't think we gain enough to come close to what we would lose as a society if we embark on that journey of editing offspring.
我认为，如果我们踏上编辑后代的旅程，我们所获得的收益还不足以弥补作为一个社会所失去的损失。
Andrew Huberman:
安德鲁·休伯曼：
Appreciate the clear stance and answer.
赞赏明确的立场和答案。
As long as we're there, I'd love your thoughts on some of the newer technologies that are only available to those that can afford them-
只要我们在那里，我很想听听您对一些新技术的想法，这些技术只有那些有能力负担得起的人才能使用——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
so that's an important caveat, for deep sequencing embryos from IVF.
因此，对于 IVF 胚胎的深度测序来说，这是一个重要的警告。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So typically with IVF-
所以通常通过 IVF-
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
check to see that they're chromosomally normal-
检查他们的染色体是否正常-
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
that they're euploid, as they say, and they'll do some sequencing of the parents, maybe of the embryos as well for certain mutations.
正如他们所说，它们是整倍体，并且他们会对父母进行一些测序，也许对胚胎以及某些突变进行测序。
But there's this whole other industry now.
但现在有另一个行业了。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I believe a company in the Bay Area, Orchid-
我相信湾区的一家公司，Orchid-
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
is probably the most popular one-
可能是最受欢迎的一个——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
or well-known one, where if you pay a certain amount of money, they'll deep sequence.
或者是知名的，如果你支付一定数量的钱，他们就会深度序列。
If you pay more, they'll deeper sequence.
如果你付更多的钱，他们会更深的序列。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And so you're getting some additional readout of potential disease genes in.
所以你会得到一些潜在疾病基因的额外读数。
And I've looked at that technology, and they're very clear that at some point they can't draw a causal relationship between, say, like a neuroligin mutation and autism.
我研究过这项技术，他们非常清楚，在某些时候他们无法得出神经连接蛋白突变和自闭症之间的因果关系。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But there are these implications based on the animal data.
但根据动物数据，存在这些影响。
And so it starts to become this, it's not gene editing-
所以它开始变成这样，这不是基因编辑——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
but it is deeper and deeper gene sequencing-based selection of embryos.
但它是基于基因测序的越来越深入的胚胎选择。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
First of all, I'm sympathetic to the idea, right?
首先，我很赞同这个想法，对吗？
We want to protect our kids from suffering and from disease, right?
我们希望保护我们的孩子免受痛苦和疾病的侵害，对吗？
And I understand the idea of doing pre-implantation genetic testing, if you want to avoid a mutation or a chromosomal abnormality that would really impair lifespan or quality of life for your offspring.
如果您想避免确实会损害后代寿命或生活质量的突变或染色体异常，我理解进行植入前基因检测的想法。
The impulse that we know that this sort of straightforward chromosomal testing that's done from the first level will miss a lot of mutations.
我们知道这种从第一级开始进行的直接染色体测试会错过很多突变。
So I understand the idea of trying to fill that in with more deep sequencing or comprehensive sequencing of the genome.
因此，我理解尝试通过更深入的基因组测序或全面的基因组测序来填补这一空白的想法。
The problem is there are some mutations that if we see them, we will know that they can cause severe disease, but there's a lot that become probabilistic and statistical, and I think we're overpromising what can be delivered.
问题是有一些突变，如果我们看到它们，我们就会知道它们会导致严重的疾病，但有很多突变变成概率和统计的，我认为我们过度承诺了可以提供的东西。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
So all of a sudden, you're using an algorithm to determine which embryos are more desirable than others.
所以突然之间，你使用一种算法来确定哪些胚胎比其他胚胎更受欢迎。
And I think the fact is, it's not an axis that actually exists.
我认为事实是，它并不是真正存在的轴。
There aren't Categorically more desirable or less desirable.
没有绝对更理想或更不理想的选择。
That we want diverse people.
我们想要多元化的人。
And how successful you're going to be is an interplay of how your genes come around and influence your community, your environment.
你的成功取决于你的基因如何相互作用并影响你的社区和环境。
Those are unknowable from just looking at a DNA sequence alone.
仅凭 DNA 序列是无法得知这些的。
So, I think that it introduces a false axis.
所以，我认为它引入了假轴。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
There's another book that I would recommend here that I read years ago, and I actually am probably overdue to go back and reread this.
我在这里推荐另一本书，我几年前读过，实际上我可能早就应该回去重读这本书了。
This predates CRISPR technology, but there's a Harvard philosopher, Michael Sandel, who years ago wrote a short book called "The Case Against Perfection." And it's a really beautiful meditation on what's lost when we enter into this illusion of thinking that we can engineer towards some axis of perfection, rather than embracing the beauty of chance and happenstance, which is a part of our relationship with our kids, with ourselves, of thinking, "Okay, this is the human experience of you're a product of some degree of chance and circumstance."
这早于 CRISPR 技术，但哈佛大学哲学家迈克尔·桑德尔 (Michael Sandel) 多年前写了一本名为《反对完美的案例》的短书。这是一个非常美丽的冥想，当我们陷入这种幻想时，我们会失去什么，我们可以朝着某种完美的方向进行设计，而不是拥抱机会和偶然的美丽，这是我们与孩子、与我们自己的关系的一部分，我们会思考，“好吧，这是人类的经验，你是某种程度的机会和环境的产物。”
Andrew Huberman:
安德鲁·休伯曼：
I'll definitely check out the book.
我一定会看看这本书。
I know the whole point of life is not to be a quote, unquote "high performer," but I'll just say as an example, I know of no single very successful person that doesn't have some thing about themselves that initially they disliked or felt that they had to overcome, which led them to pursue certain things, hopefully in a healthy way, and that they eventually came to embrace, and are now grateful for.
我知道生活的全部意义不是成为一个引用，不引用“高绩效者”，但我只想说作为一个例子，我知道没有一个非常成功的人没有一些关于自己的东西，最初他们不喜欢或觉得他们必须克服，这导致他们追求某些东西，希望以一种健康的方式，他们最终拥抱，现在感激不尽。
I know of no exception to that.
据我所知，也不例外。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
It's the story of humans in many ways.
从很多方面来说，这都是人类的故事。
It's the story of humans.
这是人类的故事。
And in fact, people who perhaps are told that they're perfect in every dimension their entire lives, I can only imagine the amount of pressure they must feel.
事实上，那些可能被告知他们一生在各个方面都很完美的人，我只能想象他们必须感受到的压力有多大。
In fact, before today's discussion, we were talking about people that we knew that perhaps had been told that, and some of the fragility that that can introduce to the psyche.
事实上，在今天的讨论之前，我们谈论的是我们认识的人，他们可能被告知过这一点，以及这可能会给心灵带来的一些脆弱性。
Dr. Alex Marson:
亚历克斯·马森博士：
I think that's really well said.
我觉得这句话说得真好。
I think it goes both ways.
我认为这是双向的。
I think things that we think are hardships or disabilities often end up being the things that make us who we are and make us more sympathetic, give us added depth as humans.
我认为我们认为是困难或残疾的事情往往最终成为我们的身份，让我们更有同情心，让我们作为人类更有深度。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
And the things that we think are the things that make us perfect are the things that are really holding us back or creating all sorts of false ideas that limit us.
我们认为使我们变得完美的事物实际上是阻碍我们前进或产生各种限制我们的错误想法的事物。
Andrew Huberman:
安德鲁·休伯曼：
I couldn't agree more.
我完全同意。
I'd love to know what, right now, you're most excited about for your own intellectual enrichment and in your lab, and what you really feel is the thing that has the most electricity for you.
我很想知道，现在，您对自己的智力丰富和实验室中最感兴趣的是什么，以及您真正感受到的对您来说最有力量的东西。
And if you're willing to also give us a hint of what's just right over the edge in terms of what you think will be the next big therapeutic breakthrough that we can look forward to.
如果您愿意也给我们一些提示，您认为什么是我们可以期待的下一个重大治疗突破。
Dr. Alex Marson:
亚历克斯·马森博士：
Thanks for asking that.
谢谢你这么问。
So, I'm going to give a little bit of a long and-
所以，我要讲一点长话——
Andrew Huberman:
安德鲁·休伯曼：
Please
请
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
meandering answer that
蜿蜒的回答
Andrew Huberman:
安德鲁·休伯曼：
Listen, when it comes to me, succinct is not something that exists in my neural circuitry, although I try.
听着，对于我来说，简洁并不是我的神经回路中存在的东西，尽管我尝试过。
Dr. Alex Marson:
亚历克斯·马森博士：
So, I see this moment, I talked about clinical trials that are already filling me with hope.
所以，我看到这一刻，我谈到了已经让我充满希望的临床试验。
I talked about a biotech trial that I'm associated with for prostate cancer.
我谈到了一项与我有关的前列腺癌生物技术试验。
I talked about an academic trial that I've put a lot of work in with my colleagues over many years to open for multiple myeloma.
我谈到了一项学术试验，多年来我与同事们投入了大量精力，为多发性骨髓瘤开展了这项试验。
And we have a pipeline that we're developing.
我们正在开发一条管道。
We haven't fully talked yet about the idea of CAR T cells for autoimmunity.
我们还没有充分讨论 CAR T 细胞用于自身免疫的想法。
We left that open a little bit, but that's an amazing moment that we're at right now.
我们对此保留了一点开放的态度，但这是我们现在所处的一个令人惊奇的时刻。
That the same CAR T cells that are being used to get rid of B cell leukemias are also getting rid of B cells which are contributing to autoimmune disease.
用于消除 B 细胞白血病的 CAR T 细胞也可以消除导致自身免疫性疾病的 B 细胞。
So, without making any change, people are already starting to see incredible responses in the early trials for lupus and other autoimmune diseases with T cells engineered to eliminate B cells.
因此，在不做任何改变的情况下，人们已经开始在狼疮和其他自身免疫性疾病的早期试验中看到令人难以置信的反应，这些试验通过改造 T 细胞来消除 B 细胞。
Andrew Huberman:
安德鲁·休伯曼：
Oh, fantastic.
哦，太棒了。
Could you just mention a few other disease targets?
您能否提及一些其他疾病目标？
I know a few people with fibromyalgia.
我认识一些患有纤维肌痛的人。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
They suffer tremendously.
他们承受着巨大的痛苦。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Fibromyalgia is a disease that we just don't understand.
纤维肌痛是一种我们不了解的疾病。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
Talk about understudied diseases.
谈论未被充分研究的疾病。
I think fibromyalgia is something that gets bucketed in a certain way, and we just have not figured out what it really is, what causes it.
我认为纤维肌痛是一种以某种方式陷入困境的疾病，我们只是还没有弄清楚它到底是什么，是什么原因造成的。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Alex Marson:
亚历克斯·马森博士：
And so, that is its own thing.
所以，这是它自己的事。
But for autoimmune diseases, these are diseases where we do know that there are immune cells going after our own tissue in various ways.
但对于自身免疫性疾病，我们确实知道免疫细胞以各种方式攻击我们自己的组织。
Lupus, people are talking about various engineered T cell trials for rheumatoid arthritis, for childhood diabetes, for multiple sclerosis, and on and on.
狼疮，人们正在谈论针对类风湿性关节炎、儿童糖尿病、多发性硬化症等的各种工程 T 细胞试验。
But those are a number that people are thinking about different types of immunotherapies, including gene-edited T cells to treat these autoimmune diseases.
但人们正在考虑不同类型的免疫疗法，包括用于治疗这些自身免疫性疾病的基因编辑 T 细胞。
So, I guess what I'm saying is excited about the near future-
所以，我想我所说的是对不久的将来的兴奋——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Alex Marson:
亚历克斯·马森博士：
...
...
of things that have come out of decades of lab work from labs around the world, already starting to be assembled into things that are advancing through clinical pipelines.
来自世界各地的实验室数十年的实验室工作成果，已经开始组装成正在通过临床管道推进的产品。
But the next wave of what's coming up behind that is just as exciting, if not more.
但随之而来的下一波浪潮同样令人兴奋，甚至更令人兴奋。
So, I think that one of the things that makes me feel like I have one of the great jobs out there is, there's about 30 people in my lab.
所以，我认为让我感觉自己拥有一份很棒的工作的原因之一是，我的实验室里大约有 30 个人。
I get the joy of ideas bubbling up.
我得到了想法涌现的乐趣。
The ideas in the lab don't come top-down from me.
实验室的想法并不是我自上而下的。
They come from grad students and post-docs who have come filled with energy to bring their own ideas.
他们来自研究生和博士后，他们充满活力地提出自己的想法。
And progress is being made through this conversation of people in the lab reading papers, going to conferences, talking late at night in the lab.
通过实验室里的人们阅读论文、参加会议、在实验室深夜交谈的对话，正在取得进展。
And I can't believe the surprises that are coming.
我简直不敢相信即将到来的惊喜。
So I want to give you a couple of these.
所以我想给你几个。
So looking backwards to 2013, 2014, we were struggling to see if we could get CRISPR with electroporation to make one cut in a T cell.
因此，回顾 2013 年、2014 年，我们一直在努力研究是否可以通过电穿孔技术使用 CRISPR 对 T 细胞进行一次切割。
We could barely do it.
我们几乎做不到。
Now, if a grad student comes into my lab, within a month or two, they can routinely do a CRISPR experiment where we do CRISPR, where we deliver a set of thousands, up to tens of thousands or hundreds of thousands of different CRISPRs into a population of T cells from a blood sample.
现在，如果研究生进入我的实验室，一两个月内，他们就可以常规地进行 CRISPR 实验，我们进行 CRISPR，我们将一组数千、数万或数十万不同的 CRISPR 从血液样本中注入 T 细胞群中。
So each cell will get a different CRISPR modification.
因此每个细胞都会得到不同的 CRISPR 修饰。
And then we can essentially race these cells against each other.
然后我们基本上可以让这些细胞相互竞争。
So we can put them into a tumor environment and see which ones continue to grow, which ones have markers that seem like they're going to be favorable, and giving them characteristics that are going to be strong against cancer.
因此，我们可以将它们放入肿瘤环境中，看看哪些会继续生长，哪些具有看起来对它们有利的标记，并赋予它们强大的抗癌特性。
So we are able to do the type of genetics that was possible in fruit flies, but unimaginable in human cells.
因此，我们能够进行在果蝇中可行但在人类细胞中难以想象的遗传学类型。
We're doing directly in the human cells that will be the therapies of the future.
我们直接在人体细胞中进行研究，这将成为未来的疗法。
We're directly learning what are the genetic modifications that will make T cells do exactly what we want.
我们正在直接了解哪些基因修饰可以使 T 细胞完全按照我们的意愿行事。
And one of the things that we just made publicly available is that we used to do these experiments and race these cells against each other, and race them against each other for one characteristic, which ones would start to make one cytokine.
我们刚刚公开的一件事是，我们过去常做这些实验，让这些细胞相互竞争，并让它们相互竞争以获得一种特征，哪些细胞将开始产生一种细胞因子。
I talked about these signals that immune cells can make.
我谈到了免疫细胞可以发出的这些信号。
Now what we can do is, for each genetic modification, we can do a complete measurement of the state of each individual cell.
现在我们能做的是，对于每一个基因修饰，我们都可以对每个单独细胞的状态进行完整的测量。
This is a technology called single-cell RNA sequencing.
这是一种称为单细胞 RNA 测序的技术。
So we measure now simultaneously all of the RNA that's in that cell, giving us a snapshot of what that cell is now able to do.
因此，我们现在同时测量该细胞中的所有 RNA，让我们大致了解该细胞现在能够做什么。
And we can also simultaneously measure which CRISPR was put into that cell.
我们还可以同时测量哪些 CRISPR 被放入该细胞中。
And so now we can essentially inactivate every gene in the genome in T cells and read out the consequences on the overall state of the cells.
所以现在我们基本上可以灭活 T 细胞基因组中的每个基因，并读出对细胞整体状态的影响。
And this is technology that was developed by a number of labs around the world.
这是由世界各地的许多实验室开发的技术。
We've now deployed this at a massive scale directly in primary human immune cells.
我们现在已将其直接大规模部署在人类原代免疫细胞中。
We just released 22 million cells where each one has a different CRISPR gene inactivated, and we get a map of this.
我们刚刚释放了 2200 万个细胞，其中每个细胞都有不同的 CRISPR 基因失活，我们得到了一张图谱。
And I think of this, not just what we're doing in T cells, but what other labs are doing around the world, using CRISPR to read out the consequence of every gene in different cell types, in different conditions, as a sequel to the Genome Project.
我认为这不仅是我们在 T 细胞中所做的事情，也是世界各地其他实验室所做的事情，使用 CRISPR 读出不同细胞类型、不同条件下每个基因的结果，作为基因组计划的续集。
Mm-hmm.
嗯嗯。
We talked about the genome giving us this draft of the DNA sequence.
我们讨论了基因组，为我们提供了这份 DNA 序列草图。
Now we can actually read out the function of every gene and see how each gene contributes to the behavior of every cell.
现在我们实际上可以读出每个基因的功能，并了解每个基因如何影响每个细胞的行为。
And this is being used as a basis for massive computational analysis.
这被用作大规模计算分析的基础。
It's providing us a real roadmap of how cells are wired that will be the instruction manual for the next generation of T-cell immunotherapies.
它为我们提供了细胞如何连接的真实路线图，这将成为下一代 T 细胞免疫疗法的指导手册。
The lessons that we learn about how every gene behaves are now going to be actionable, and these are going to be genes that we tune or epigenetically edit or inactivate or add to genes that we will now have a recipe book for what do we want an immune cell to do?
我们学到的关于每个基因如何表现的经验教训现在将是可操作的，这些将是我们调整或表观遗传编辑或失活或添加到基因中的基因，我们现在将有一本关于我们希望免疫细胞做什么的食谱书？
What do we want it to recognize?
我们希望它识别什么？
Where do we want it to go?
我们想让它去哪里？
And we'll have a cheat sheet- Mm-hmm ...
我们会有一个备忘单 - 嗯嗯......
that tells us, okay, here's what we should be adding or subtracting from that cell genetically to endow it with the powers that will give it precision and endurance against some disease that we want to go after.
这告诉我们，好吧，我们应该从基因上添加或减去该细胞的内容，以赋予它力量，使其具有精确性和耐力，以对抗我们想要治疗的某些疾病。
Andrew Huberman:
安德鲁·休伯曼：
Amazing.
太棒了。
Truly amazing.
真是太神奇了。
Should I be banking T cells?
我应该储存 T 细胞吗？
Dr. Alex Marson:
亚历克斯·马森博士：
Well, I never know what the answer is to this.
好吧，我永远不知道这个问题的答案是什么。
I was going to say the good news is that we largely have T cells.
我想说好消息是我们大部分都有 T 细胞。
Now, are there exceptions to that?
现在，有例外吗？
Yes.
是的。
There are patients who are getting treated for certain types of cancer, and the chemotherapy that they're getting depletes their T cells.
有些患者正在接受某些类型癌症的治疗，而他们接受的化疗会耗尽他们的 T 细胞。
It's hard to know.
很难知道。
I guess I can't say that there would never be a use, but I think we're getting better and better at being able to take whatever T cells are there, and I hope reactivate them, endow them with powers.
我想我不能说它永远不会有用，但我认为我们在利用那里的任何 T 细胞方面做得越来越好，我希望重新激活它们，赋予它们力量。
I would be disappointed if in the future, we would need to go back and take the bank T cells and not be able to re-engineer cells that are already there.
如果将来我们需要返回并获取 T 细胞库并且无法重新设计已经存在的细胞，我会感到失望。
Are there edge cases where it might be?
是否存在可能出现的边缘情况？
But it's not something that I would tell people to go out and do.
但这不是我会告诉人们出去做的事情。
It's not something I'm doing.
这不是我在做的事情。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, I would only do it if you told me to.
是的，只有你告诉我我才会这么做。
A colleague of yours, Yamanaka-
你的同事山中伸——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
won a Nobel Prize for-
荣获诺贝尔奖——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
essentially showing that you can take a skin cell, put it in a dish, give it Yamanaka factors, as it were-
本质上表明你可以取出一个皮肤细胞，把它放在一个盘子里，给它山中因子，就像这样——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
for, in some cases, only three transcription factors-
在某些情况下，只有三个转录因子-
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and essentially revert that cell to a stem cell.
并基本上将该细胞恢复为干细胞。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And then give it some other transcription factors and turn it into, I don't know, a neuron or a pancreatic cell.
然后给它一些其他的转录因子，然后把它变成，我不知道，神经元或胰腺细胞。
Should we be banking fibroblasts and putting them into that ready state, reverting them to the stem cell state?
我们是否应该储存成纤维细胞并将它们置于准备状态，将它们恢复到干细胞状态？
In my mind, I always thought, well, if I ever need more cells of a given organ, I can always, assuming I'm alive-
在我看来，我总是想，好吧，如果我需要某个器官的更多细胞，我总是可以，假设我还活着——
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
they can take a skin cell, and they can do all that.
他们可以获取皮肤细胞，他们可以做到这一切。
But I could imagine that there would be use for a cell bank, not a tissue bank, where there are a bunch of these pluripotent-
但我可以想象，细胞库会有用，而不是组织库，那里有一堆这样的多能-
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
Huberman in my case, Marson in your case, obviously, cells that if, God forbid, I needed a bunch of pancreatic islet cells, boom-
胡伯曼（Huberman）就我而言，马森（Marson）就你而言，显然，这些细胞，如果上帝保佑，我需要一堆胰岛细胞，繁荣-
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
they could have those within a week.
他们可以在一周内得到这些。
Dr. Alex Marson:
亚历克斯·马森博士：
This field is something that's been amazing to watch.
这个领域令人惊叹不已。
There's been ups and downs of it, of this induced pluripotent stem cell field that Shinya Yamanaka opened up.
山中伸弥开辟的诱导多能干细胞领域经历了起起落落。
One of the interesting areas is actually imagining how these iPS cells could be made into T cells, which would essentially create a limitless supply of T cells, which would-
有趣的领域之一实际上是想象如何将这些 iPS 细胞制成 T 细胞，这实际上会产生无限量的 T 细胞供应，这将-
Andrew Huberman:
安德鲁·休伯曼：
That's what I was thinking.
我就是这么想的。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
You don't have to even draw blood.
您甚至不必抽血。
Dr. Alex Marson:
亚历克斯·马森博士：
Yeah, exactly.
是的，完全正确。
Which would negate the need for banking if you had your...
如果您有...，这将消除对银行业务的需求。
So I don't know.
所以我不知道。
Again, it's probably not something that would be cost-effective for everyone to have their iPS cells ready to go.
同样，对于每个人来说，准备好 iPS 细胞可能并不划算。
I understand, in conversation with Shinya Yamanaka, that one of the things that he's been involved with is actually building a bank of iPS cells that would be immune compatible with broad sets of different people, so that it could essentially be used as a transplant bank.
在与山中伸弥（Shinya Yamanaka）的交谈中，我了解到，他参与的其中一件事实际上是建立一个 iPS 细胞库，该细胞库与广泛的不同人群具有免疫相容性，因此它本质上可以用作移植库。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
Which might be a way to be an intermediate step, that there would be iPS cells available that could be transplanted with various degrees of ease into different people.
这可能是一个中间步骤，即存在可用的 iPS 细胞，可以以不同程度的轻松程度移植到不同的人身上。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
And then I do think that, I hope it gets easier and easier to make iPS cells that are matched to any patient when they're needed.
然后我确实认为，我希望制造出与任何需要的患者相匹配的 iPS 细胞变得越来越容易。
But again, these different threads of things, of being able to make endless supplies of any cell, direct them to any tissue type, and then being able to program them with the language of CRISPR.
但同样，这些不同的线索能够无限地供应任何细胞，将它们引导到任何组织类型，然后能够使用 CRISPR 语言对它们进行编程。
Actually, it's worth some moment.
事实上，值得花一些时间。
In 2020, I moved my lab from the main branch of UCSF to a separate research institute in San Francisco called the Gladstone Institutes.
2020 年，我将实验室从 UCSF 的主要分支机构搬到了旧金山的一个独立的研究所，名为 Gladstone Institutes。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Alex Marson:
亚历克斯·马森博士：
It's a non-profit research institute.
这是一个非营利性的研究机构。
My grad students still come from UCSF, University of California, San Francisco, but my lab's at Gladstone.
我的研究生仍然来自加州大学旧金山分校、加州大学旧金山分校，但我的实验室在格拉德斯通。
And one of the reasons that I moved my lab to Gladstone was a conversation when they were recruiting me.
我将实验室搬到格拉德斯通的原因之一是他们招募我时的一次谈话。
They brought me into the president's office, and in the president of Gladstone's office was Shinya Yamanaka, who maintains a lab at Gladstone, and Jennifer Doudna, who also maintains a lab at Gladstone.
他们把我带到总裁办公室，格莱斯顿办公室的总裁是山中伸弥（Shinya Yamanaka），他在格莱斯顿拥有一个实验室，还有詹妮弗·杜德纳（Jennifer Doudna），她也在格莱斯顿拥有一个实验室。
Andrew Huberman:
安德鲁·休伯曼：
You had to say yes.
你必须说是的。
They're very clever.
他们非常聪明。
You had some psychologist inform that they got your number, so to speak.
可以这么说，一些心理学家告诉你他们得到了你的电话号码。
Dr. Alex Marson:
亚历克斯·马森博士：
I describe this, and I think this is not just a cliche.
我描述了这一点，我认为这不仅仅是陈词滥调。
I actually remember that feeling of hair sticking up on the back of your head of like, oh, all of a sudden, these are the technologies that these two humans have made possible, and others.
我实际上记得那种头发在后脑勺上竖起来的感觉，就像，哦，突然之间，这些都是这两个人使之成为可能的技术，以及其他技术。
But we can now program what the epigenetic state of a cell is, thanks to the Yamanaka factors.
但由于山中因素，我们现在可以对细胞的表观遗传状态进行编程。
You can dial between skin and embryo and then back to anything else.
您可以在皮肤和胚胎之间切换，然后再返回到其他任何内容。
And then not only epigenetically program a cell, but take the power of CRISPR and genetically program.
然后不仅对细胞进行表观遗传编程，而且利用 CRISPR 的力量进行遗传编程。
And when you put these things together, all of a sudden, we have this ability to imagine programmable cells that we can dial in and direct their behavior to either regenerate or to, in the case of the immune system, survey the body and get to the root cause of disease.
当你把这些东西放在一起时，突然之间，我们就有了想象可编程细胞的能力，我们可以拨入这些细胞并指导它们的行为来再生，或者就免疫系统而言，调查身体并找出疾病的根本原因。
And my imagination still lies at that intersection of what's possible when we combine that with immunology.
我的想象力仍然在于当我们将其与免疫学相结合时可能发生的事情的交叉点。
Andrew Huberman:
安德鲁·休伯曼：
I love it.
我喜欢它。
One question I don't expect you to answer, but your enthusiasm for this is tangible.
我不希望你回答这个问题，但你对此的热情是显而易见的。
I'm excited.
我很兴奋。
I know people listening are.
我知道听的人是。
And the question is, how do you sleep at night?
问题是，你晚上怎么睡觉？
It's so exciting.
太令人兴奋了。
The tools, they're here.
工具，它们就在这里。
And mostly, I want to say thank you.
最重要的是，我想说谢谢。
Thank you for coming here today and giving us a absolute master class on the immune system, on cancer, on the technologies to improve the immune system, combat autoimmune diseases.
感谢您今天来到这里，为我们上了一堂关于免疫系统、癌症、改善免疫系统、对抗自身免疫性疾病的技术的绝对大师课。
We got into molecular biology with some considerable degree of depth, and thanks to you, it was incredibly clear.
我们对分子生物学有了相当深入的了解，多亏了你，一切都变得非常清晰。
I know people learned a ton.
我知道人们学到了很多东西。
I know I learned a ton, and I'm super excited about what you're doing.
我知道我学到了很多东西，而且我对你所做的事情感到非常兴奋。
Also, just the heart and soul.
而且，只是心灵和灵魂。
There are no other words, really.
真的，没有其他词了。
I think those are apt. The heart and soul that you put into your work is so clear, and you are definitely in the right job.
我认为这些都是恰当的。你对工作的投入是如此清晰，你绝对是在正确的岗位上。
So just one request is that you come back and talk to us again when the next advancements are made.
因此，只有一个请求是，当您取得下一个进展时，请回来再次与我们交谈。
We'd love to have you back.
我们很乐意让你回来。
Dr. Alex Marson:
亚历克斯·马森博士：
I'd be honored.
我将很荣幸。
And I just really want to thank you.
我真的很想感谢你。
There are not enough forums that are dedicated, really, to the depth to talk about science.
没有足够的论坛真正致力于深度讨论科学。
So much of the joy of science is in the details, and you do such a great job of letting those details really come through and sharing them broadly.
科学的大部分乐趣都在于细节，而您在让这些细节真正得以体现并广泛分享方面做得非常出色。
So it's an honor to be here.
所以很荣幸来到这里。
Andrew Huberman:
安德鲁·休伯曼：
Well, thank you.
嗯，谢谢。
It's a labor of love, and I've loved this.
这是一种爱的劳动，我很喜欢这个。
So come back again.
所以再回来吧。
Dr. Alex Marson:
亚历克斯·马森博士：
Thanks.
谢谢。
Andrew Huberman:
安德鲁·休伯曼：
Thank you for joining me for today's discussion with Dr. Alex Marson.
感谢您参加今天与 Alex Marson 博士的讨论。
To learn more about his work, please see the links in the show note captions.
要了解有关他的作品的更多信息，请参阅演出注释标题中的链接。
If you're learning from and/or enjoying this podcast, please subscribe to our YouTube channel.
如果您正在学习和/或喜欢此播客，请订阅我们的 YouTube 频道。
That's a terrific zero-cost way to support us.
这是支持我们的绝佳零成本方式。
In addition, please follow the podcast by clicking the follow button on both Spotify and Apple.
此外，请通过单击 Spotify 和 Apple 上的关注按钮来关注播客。
And on both Spotify and Apple, you can leave us up to a five-star review.
在 Spotify 和 Apple 上，您都可以给我们五星级的评价。
And you can now leave us comments at both Spotify and Apple.
您现在可以在 Spotify 和 Apple 上给我们留下评论。
Please also check out the sponsors mentioned at the beginning and throughout today's episode.
另请查看今天节目开头和整个节目中提到的赞助商。
That's the best way to support this podcast.
这是支持这个播客的最佳方式。
If you have questions for me or comments about the podcast or guests or topics that you'd like me to consider for the Huberman Lab Podcast, please put those in the comments section on YouTube.
如果您对我有疑问，或者对播客、嘉宾或您希望我考虑在 Huberman 实验室播客中讨论的主题有意见，请将这些意见放入 YouTube 的评论部分。
I do read all the comments.
我确实阅读了所有评论。
For those of you that haven't heard, I have a new book coming out.
对于那些还没有听说过的人，我即将出版一本新书。
It's my very first book.
这是我的第一本书。
It's entitled "Protocols: An Operating Manual for the Human Body." This is a book that I've been working on for more than five years, and that's based on more than 30 years of research and experience.
它的标题是“协议：人体操作手册”。这本书是我花了五年多时间编写的，它基于 30 多年的研究和经验。
And it covers protocols for everything from sleep, to exercise, to stress control, protocols related to focus and motivation, and of course, I provide the scientific substantiation for the protocols that are included.
它涵盖了从睡眠、锻炼、压力控制、与注意力和动机相关的各个方面的协议，当然，我还为所包含的协议提供了科学依据。
The book is now available by presale at protocolsbook.com.
该书现已在protocolbook.com 上预售。
There you can find links to various vendors.
在那里您可以找到各个供应商的链接。
You can pick the one that you like best.
您可以选择您最喜欢的一个。
Again, the book is called "Protocols: An Operating Manual for the Human Body." And if you're not already following me on social media, I am hubermanlab on all social media platforms.
同样，这本书的名字是“协议：人体操作手册”。如果您还没有在社交媒体上关注我，我是所有社交媒体平台上的 hubermanlab。
So that's Instagram, X, Threads, Facebook, and LinkedIn.
这就是 Instagram、X、Threads、Facebook 和 LinkedIn。
And on all those platforms, I discuss science and science-related tools, some of which overlaps with the content of the Huberman Lab Podcast, but much of which is distinct from the information on the Huberman Lab Podcast.
在所有这些平台上，我讨论科学和与科学相关的工具，其中一些与胡伯曼实验室播客的内容重叠，但其中大部分与胡伯曼实验室播客上的信息不同。
Again, it's hubermanlab on all social media platforms.
再说一遍，所有社交媒体平台上都是 hubermanlab。
And if you haven't already subscribed to our Neural Network Newsletter, the Neural Network Newsletter is a zero-cost monthly newsletter that includes podcast summaries, as well as what we call protocols in the form of one to three-page PDFs that cover everything from how to optimize your sleep, how to optimize dopamine, deliberate cold exposure.
如果您还没有订阅我们的神经网络时事通讯，神经网络时事通讯是一份零成本的月度时事通讯，其中包括播客摘要，以及我们所说的一到三页 PDF 形式的协议，涵盖从如何优化睡眠、如何优化多巴胺、故意冷暴露等所有内容。
We have a foundational fitness protocol that covers cardiovascular training and resistance training.
我们有一个基本的健身方案，涵盖心血管训练和阻力训练。
All of that is available completely zero cost.
所有这些都是完全零成本可用的。
You simply go to hubermanlab.com, go to the Menu tab in the top right corner, scroll down to Newsletter, and enter your email.
您只需访问 hubermanlab.com，转到右上角的“菜单”选项卡，向下滚动到新闻通讯，然后输入您的电子邮件即可。
And I should emphasize that we do not share your email with anybody.
我要强调的是，我们不会与任何人分享您的电子邮件。
Thank you once again for joining me for today's discussion with Dr. Alex Marson.
再次感谢您参加今天与 Alex Marson 博士的讨论。
And last but certainly not least, thank you for your interest in science.
最后但并非最不重要的一点是，感谢您对科学的兴趣。
Speaker 3:
演讲者3：
"I want to date with rules," Carty says.
“我想按规则约会，”卡蒂说。
"Rules?" Rucke asks.
“规则？”鲁克问道。
This is the love story of real Hinge couple Carty and Rucke, written and read by me, Nicola Dinan.
这是真实的铰链夫妇卡蒂和鲁克的爱情故事，由我尼古拉·迪南撰写和阅读。
Listen to the free audiobook now.
立即收听免费有声读物。