Journal Club with Dr. Peter Attia | Effects of Light & Dark on Mental Health & Treatments for Cancer

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。

Today marks the second episode in our Journal Club series with myself and Dr. Peter Attia.

今天是我和彼得·阿提亚博士的日记俱乐部系列的第二集。

Dr. Peter Attia, as many of you know, is a medical doctor who is a world expert in all things health span and lifespan.

众所周知，彼得·阿提亚博士是一位医生，是健康和寿命领域的世界专家。

He is the author of the bestselling book "Outlive," as well as the host of his own terrific podcast, "The Drive." For today's episode, Peter and I each select a different paper to share with you.

他是畅销书《Outlive》的作者，也是他自己精彩的播客《The Drive》的主持人。在今天的节目中，彼得和我各自选择了一篇不同的论文与大家分享。

We selected these papers because we feel they are both extremely interesting and extremely actionable.

我们选择这些论文是因为我们觉得它们非常有趣并且非常具有可操作性。

First, I present a paper that is about how light exposure during the morning and daytime, as well as dark exposure at night, each have independent and positive effects on mental health, as well as the ability to reduce the symptoms of many different mental health disorders.

First, I present a paper that is about how light exposure during the morning and daytime, as well as dark exposure at night, each have independent and positive effects on mental health, as well as the ability to reduce the symptoms of many different mental health disorders.

Now, I've talked before on this podcast and elsewhere about the key importance of seeing morning sunlight, as well as trying to be in dim light at night.

Now, I've talked before on this podcast and elsewhere about the key importance of seeing morning sunlight, as well as trying to be in dim light at night.

However, the data presented in the paper today really expands on that by identifying the key importance of not just morning sunlight, but getting bright light in one's eyes as much as is safely possible throughout the entire day, and a separate additive effect of being in as much darkness at night as possible.

However, the data presented in the paper today really expands on that by identifying the key importance of not just morning sunlight, but getting bright light in one's eyes as much as is safely possible throughout the entire day, and a separate additive effect of being in as much darkness at night as possible.

I describe the data in a lot of detail, although you do not need a background in biology in order to understand that discussion.

我详细描述了这些数据，尽管您不需要生物学背景来理解该讨论。

And there's a key takeaway, which is that if you can't get enough light in your eyes during the daytime, you would be well advised to get as much darkness exposure at night.

And there's a key takeaway, which is that if you can't get enough light in your eyes during the daytime, you would be well advised to get as much darkness exposure at night.

In other words, light and dark have independent and additive effects on mental health.

换句话说，光明和黑暗对心理健康具有独立和相加的影响。

And during today's discussion, you'll learn exactly how to apply light exposure and dark exposure in order to get those benefits.

在今天的讨论中，您将准确了解如何应用亮曝光和暗曝光以获得这些好处。

Then Peter presents a paper about novel treatments for cancer.

然后彼得发表了一篇关于癌症新疗法的论文。

I must say, it's an extremely important conversation that everybody, regardless of whether or not you may have had cancer or know somebody who's had cancer, ought to listen to.

I must say, it's an extremely important conversation that everybody, regardless of whether or not you may have had cancer or know somebody who's had cancer, ought to listen to.

He highlights the current technology of cancer treatments, as well as the future technology of cancer treatments, and the key role that the immune system and the autoimmune system play in treatments for cancer.

He highlights the current technology of cancer treatments, as well as the future technology of cancer treatments, and the key role that the immune system and the autoimmune system play in treatments for cancer.

I assure you that by the end of today's Journal Club episode, you will have learned a ton of new information about light and dark and mental health, as well as cancer and the immune system, and treatments for curing cancer.

I assure you that by the end of today's Journal Club episode, you will have learned a ton of new information about light and dark and mental health, as well as cancer and the immune system, and treatments for curing cancer.

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, I'd like to thank the sponsors of today's podcast.

为了与这个主题保持一致，我要感谢今天播客的赞助商。

And now for my discussion with Dr. Peter Attia.

现在我与 Peter Attia 博士进行讨论。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Andrew, great to have you here for Journal Club number two.

安德鲁，很高兴您来到这里参加第二期期刊俱乐部。

I'm already confident this is going to become a regular for us.

我已经相信这将成为我们的常客。

Andrew Huberman:

安德鲁·休伯曼：

I'm excited.

我很兴奋。

I really enjoy this because I get to pick papers I'm really excited about.

我真的很喜欢这个，因为我可以挑选我真正兴奋的论文。

I get to hear papers that you're excited about, and we get to sharpen our skills at reading and sharing data, and people listening can do that as well.

I get to hear papers that you're excited about, and we get to sharpen our skills at reading and sharing data, and people listening can do that as well.

Dr. Peter Attia:

彼得·阿蒂亚博士：

So last time I went first, so I think I'm going to put you in the hot seat first and have you go first, then I'll follow you.

所以上次我先走，所以我想我会先让你陷入困境并让你先走，然后我会跟着你。

Andrew Huberman:

安德鲁·休伯曼：

Okay.

好的。

Well, I'm really excited about this paper for a number of reasons.

嗯，出于多种原因，我对这篇论文感到非常兴奋。

First of all, it, at least by my read, is a very powerful paper in the sense that it examined light exposure behavior as well as dark exposure behavior, and that's going to be an important point in more than 85,000 people as part of this cohort in the UK.

First of all, it, at least by my read, is a very powerful paper in the sense that it examined light exposure behavior as well as dark exposure behavior, and that's going to be an important point in more than 85,000 people as part of this cohort in the UK.

I'll just mention a couple of things to give people background, and I'll keep this relatively brief.

我只想提几件事来向人们提供背景知识，并且我会保持相对简短。

First of all, there's a long-standing interest in the relationship between light and mental health and physical health, and we can throw up some very well agreed upon bullet points.

First of all, there's a long-standing interest in the relationship between light and mental health and physical health, and we can throw up some very well agreed upon bullet points.

First of all, there is such a thing as seasonal affective disorder.

首先，有一种叫做季节性情感障碍的东西。

It doesn't just impact people living at really northern locations, but basically, there's a correlation between day length and mood and mental health, such that for many people, not all, but for many people, when days are longer in the spring and summer, they feel better.

It doesn't just impact people living at really northern locations, but basically, there's a correlation between day length and mood and mental health, such that for many people, not all, but for many people, when days are longer in the spring and summer, they feel better.

They report fewer depressive symptoms.

他们报告的抑郁症状较少。

And conversely, when days are shorter, significantly more people report feeling lower mood and affect.

相反，当白天较短时，更多的人表示情绪和情感较低。

Okay?

好的？

So there's a long-standing treatment for seasonal affective disorder, which is to give people exposure to very bright light, especially in the morning.

So there's a long-standing treatment for seasonal affective disorder, which is to give people exposure to very bright light, especially in the morning.

The way that that's normally accomplished is with these SAD lamps, seasonal affective disorder lamps, and those lamps are basically bright, meaning more than 10,000 lux lights that they place on their kitchen counter or at their table in the morning or in their office, so they're getting a lot of bright light.

The way that that's normally accomplished is with these SAD lamps, seasonal affective disorder lamps, and those lamps are basically bright, meaning more than 10,000 lux lights that they place on their kitchen counter or at their table in the morning or in their office, so they're getting a lot of bright light.

That has proven to be fairly effective for the treatment of seasonal affective disorder.

事实证明，这对于治疗季节性情感障碍相当有效。

What's less understood is how light exposure in the middle of the night can negatively impact mood and health.

人们不太了解的是，半夜的光线照射会对情绪和健康产生负面影响。

And so where we are headed with this is that there seems to be, based on the conclusions of this new study, a powerful and independent role of both daytime light exposure and nighttime dark exposure for mental health.

因此，根据这项新研究的结论，我们的研究方向是，白天接触光线和夜间黑暗接触似乎对心理健康都具有强大而独立的作用。

Now, a couple of other key points.

现在，还有其他几个关键点。

The biological mechanisms for all this are really well established.

所有这一切的生物学机制已经非常明确。

There's a set of cells in the neural retina, which aligns the back of your eye.

神经视网膜中有一组细胞，它们负责排列眼睛的后部。

They're sometimes called intrinsically photosensitive retinal ganglion cells, or sometimes called melanopsin retinal ganglion cells.

它们有时被称为本质光敏视网膜神经节细胞，有时被称为黑视蛋白视网膜神经节细胞。

We'll talk about those in a bit of detail in a moment.

我们稍后将详细讨论这些内容。

It's well known that those cells are the ones that respond to two different types of light input.

众所周知，这些细胞对两种不同类型的光输入做出反应。

Not one, but two different types of light input and send information to the hypothalamus where your master circadian clock resides, and then your master circadian clock sends out secretory signals, so peptides, hormones, but also neural signals to the brain and body and say, "Hey, now it's daytime.

Not one, but two different types of light input and send information to the hypothalamus where your master circadian clock resides, and then your master circadian clock sends out secretory signals, so peptides, hormones, but also neural signals to the brain and body and say, "Hey, now it's daytime.

Now it's nighttime.

现在已经是晚上了。

Be awake, be asleep." But it goes way beyond that.

醒了，睡着了。”但它的意义远不止于此。

These melanopsin intrinsically photosensitive retinal ganglion cells we know also project to areas of the brain like the habenula, which can trigger negative affect, negative mood.

These melanopsin intrinsically photosensitive retinal ganglion cells we know also project to areas of the brain like the habenula, which can trigger negative affect, negative mood.

They can trigger the release of dopamine or the suppression of dopamine, the release of serotonin, the suppression of serotonin.

它们可以触发多巴胺的释放或多巴胺的抑制，血清素的释放，血清素的抑制。

And so they're not just cells for setting your circadian clock.

因此，它们不仅仅是设置生物钟的细胞。

They also have a direct line, literally one synapse away into the structures of the brain that we know powerfully control mood.

它们还有一条直接的线路，实际上是一个突触，连接到我们知道可以强有力地控制情绪的大脑结构。

So the mechanistic basis for all this is there.

所以这一切的机械基础就在那里。

So there's just a couple of other key points to understand for people to really be able to digest the data in this paper fully.

因此，为了让人们真正能够充分理解本文中的数据，还需要理解其他几个关键点。

There are basically two types of stimuli that these cells respond to.

这些细胞基本上对两种类型的刺激做出反应。

One is very bright light, as we just talked about.

一种是非常明亮的光，正如我们刚才谈到的。

That's why getting a lot of daytime sunlight is correlated with elevated mood.

这就是为什么白天获得大量阳光与情绪高涨有关。

That's why looking at a 10,000 lux artificial lamp can offset seasonal affective disorder.

这就是为什么看着 10,000 勒克斯的人造灯可以抵消季节性情感障碍。

Dr. Peter Attia:

彼得·阿蒂亚博士：

By the way, just a couple questions on that.

顺便说一下，有几个问题。

How many lux does the sun provide on a sunny day at noon?

晴天中午的太阳光强度是多少勒克斯？

Andrew Huberman:

安德鲁·休伯曼：

Okay, great question.

好的，很好的问题。

So if you're out in the sun with no cloud cover or minimal cloud cover in the middle of the day at noon, chances are it's over 100,000 lux.

因此，如果您中午在阳光下、没有云层或云层很少的情况下，光照度很可能会超过 100,000 勒克斯。

On a really bright day, could be 300,000 lux.

在阳光明媚的日子里，亮度可能为 300,000 勒克斯。

Okay?

好的？

Most indoor environments, even though they might seem very bright, I like to think of your department store with the bright lights.

大多数室内环境，尽管看起来很明亮，但我喜欢想象你们的百货商店，灯光明亮。

Believe it or not, that's probably only closer to 6,000 lux maximum and probably more like 4,000 lux.

不管您是否相信，这可能仅接近 6,000 勒克斯最大值，并且可能更接近 4,000 勒克斯。

Most brightly lit indoor environments are not that bright when it comes down to total photon energy.

当谈到总光子能量时，大多数明亮的室内环境并不那么明亮。

Now, here's the interesting thing.

现在，这是有趣的事情。

On a cloudy day, when you're outside, it can be as bright as an average of 100,000 lux, but it won't seem that bright because you don't, quote-unquote, "see the sun." But it's also because when there's cloud cover, a lot of those long wavelengths of light, such as orange and red light, aren't coming through.

在阴天，当你在室外时，它的亮度可能达到平均 100,000 勒克斯，但它看起来不会那么亮，因为你看不到，引用不引用，“看到太阳”。但这也是因为当有云层覆盖时，许多长波长的光（例如橙色光和红色光）无法透过。

However, and this is so important, the circadian clock, the suprachiasmatic nucleus, it sums photons.

然而，这非常重要，生物钟，视交叉上核，它对光子进行求和。

It's a photon summing system.

这是一个光子求和系统。

So basically, if you're outside in 8,000 lux, very overcast UK winter day, and you're walking around, hopefully without sunglasses, because sunglasses are going to filter a lot of those photons out, your circadian clock is summing the photons.

所以基本上，如果你在 8,000 勒克斯、阴沉的英国冬日外面，你四处走动，希望没有戴太阳镜，因为太阳镜会过滤掉很多光子，你的生物钟正在对光子进行求和。

So it's an integration mechanism.

所以这是一个整合机制。

It's not triggered in a moment.

不是一瞬间就触发的。

And actually, the experiments of recording from these cells first done by David Berson at Brown were historic in the field of visual neuroscience when shown bright light on these intrinsically photosensitive cells.

事实上，布朗大学的戴维·伯森（David Berson）首次对这些细胞进行记录的实验在视觉神经科学领域具有历史意义，当时这些实验在这些本质上感光的细胞上显示了强光。

You could crank up the intensity of the light, and the neurons would ramp up their membrane potential and then start spiking, firing action potentials, long trains of action potentials that have been shown to go on for hours.

你可以提高光的强度，神经元会提高它们的膜电位，然后开始尖峰放电，激发动作电位，一长串的动作电位已被证明会持续几个小时。

And so that's the signal that's propagating into the whole brain and body.

这就是传播到整个大脑和身体的信号。

Okay, so the important thing to understand is this is not a quick switch.

好吧，重要的是要理解这不是一个快速切换。

That's why I suggest on non-cloudy days, we'll call them, that people get 10 minutes or so of sunlight in their eyes in the early part of the day, another 10 minimum in the later part of the day.

这就是为什么我建议在非阴天（我们这样称呼它们）时，人们在一天的早些时候让眼睛接受 10 分钟左右的阳光照射，在一天的晚些时候再接受至少 10 分钟的阳光照射。

As much sunlight in their eyes as they safely can throughout the day, but since you're a physician, I should just-- and you had a guest on talking about this recently.

全天尽可能多的阳光照射到他们的眼睛，但既然你是一名医生，我应该——最近有一位客人谈到了这个问题。

When the sun is low in the sky, low solar angle sunlight, that's really the key time for reasons we'll talk about in a moment.

当太阳在天空中位置较低、太阳光角度较低时，这确实是关键时刻，原因我们稍后会讨论。

And when the sun is low in the sky, you run very little risk of inducing cataract by looking in the general direction of the sun.

当太阳在天空中位置较低时，通过看太阳的大致方向，诱发白内障的风险很小。

You should still blink as needed to protect the eyes.

您仍应根据需要眨眼以保护眼睛。

It's when the sun is overhead and there's all those photons coming in quickly in a short period of time that you do have to be concerned about cataract and macular degeneration if you're getting too much daytime sunlight.

当太阳在头顶上并且所有光子在短时间内快速进入时，如果您白天接受太多阳光，您确实必须担心白内障和黄斑变性。

So the idea is sunglasses in the middle of the day are fine, but you really should avoid using them in the early and later part of the day, unless you're driving into the sun and you need to for safety reasons.

因此，我们的想法是，在中午戴太阳镜是可以的，但你真的应该避免在一天的早些时候和晚些时候使用它们，除非你在阳光下开车并且出于安全原因需要这样做。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Another question, Andrew.

还有一个问题，安德鲁。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

If the person is indoors, but they have large windows, so they're getting tons of sunlight into their space.

如果这个人在室内，但他们有大窗户，那么他们就会让大量的阳光进入他们的空间。

They don't even need ambient indoor light.

他们甚至不需要室内环境光。

How much of the photons are making it through the glass, and how does that compare to this effect?

有多少光子穿过玻璃，这与这种效应相比如何？

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

In general, unless the light is coming directly through the window, most of the relevant wavelengths are filtered out.

一般来说，除非光直接穿过窗户，否则大多数相关波长都会被滤掉。

Dr. Peter Attia:

彼得·阿蒂亚博士：

In other words, if you can't see the sun through the window, even if sufficient light is being provided, that's insufficient to trigger this phenomenon?

换句话说，如果透过窗户看不到阳光，即使有足够的光线，也不足以引发这种现象？

Andrew Huberman:

安德鲁·休伯曼：

That's right.

没错。

However, if you have windows on your roof, which some people do, skylights, that makes the situation much better.

然而，如果你的屋顶上有窗户（有些人这样做，天窗），情况就会好得多。

In fact, the neurons in the eye that signal to the circadian clock and these mood centers in the brain reside mainly in the bottom two-thirds of the neural retina and are responsible for looking up, basically.

事实上，眼睛中向生物钟发出信号的神经元和大脑中的这些情绪中心主要位于神经视网膜的底部三分之二，基本上负责向上看。

They're gathering light from above.

他们正在从上方收集光线。

These cells are also very low resolution, so think of them as big pixels.

这些单元的分辨率也非常低，因此可以将它们视为大像素。

They're not interested in patterns and edges and movement.

他们对图案、边缘和运动不感兴趣。

They're interested in how much ambient light there happens to be.

他们对环境光的强度感兴趣。

Now, keep in mind that this mechanism is perhaps the most well-conserved mechanism in cellular organisms.

现在，请记住，这种机制可能是细胞生物中最保守的机制。

And I'll use that as a way to frame up the four types of light that one needs to see every 24 hours for optimal health.

我将用它来构建四种类型的光，人们需要每 24 小时看到这些光才能获得最佳健康。

And when I say optimal health, I really mean mental health and physical health, but we're going to talk about mental health mainly today in this paper.

当我说最佳健康时，我真正指的是心理健康和身体健康，但今天我们将在本文中主要讨论心理健康。

There's an absolutely beautiful evolutionary story whereby single-cell organisms all the way to humans, dogs, rabbits, and everything in between have at least two cone opsins.

有一个绝对美丽的进化故事，单细胞生物一直到人类、狗、兔子以及介于两者之间的所有生物都至少有两个视锥细胞视蛋白。

One that responds to short wavelength light, AKA blue light, and another one that responds to longer wavelength light, orange and red.

一种对短波长光（又称蓝光）做出反应，另一种对较长波长的光（橙色和红色）作出反应。

So your dogs have this.

所以你的狗有这个。

We have this.

我们有这个。

And it's a comparison mechanism in these cells of the eye, these neurons of the eye.

这是眼睛细胞、眼睛神经元中的一种比较机制。

They compare contrast between blues and orange, or sometimes blues and reds and pinks, which are also all long wavelength light.

他们比较蓝色和橙色的对比度，或者有时比较蓝色、红色和粉色的对比度，这些也都是长波长光。

There are two times of day when the sky is enriched with blues, oranges, pinks, and reds, and that's low solar angle sunlight at sunrise and in the evening.

一天中有两个时间天空充满蓝色、橙色、粉红色和红色，即日出和傍晚的低太阳角阳光。

These cells are uniquely available to trigger the existence of those wavelengths of light early in the day and in the evening, not in the middle of the day.

这些细胞具有独特的能力，可以在白天早些时候和晚上（而不是在中午）触发这些波长的光的存在。

So these cells have these two cone photopigments, and they say how much blue light is there, how much red light is there, or orange light?

那么这些细胞有这两种视锥细胞感光色素，它们会说有多少蓝光、多少红光或橙光？

And the subtraction between those two triggers the signal for them to fire this signal off to the circadian clock of the brain, and that's why I say look at low solar angle sunlight early in the day.

两者之间的减法会触发信号，让它们向大脑的生物钟发射该信号，这就是为什么我说在一天早些时候观察低太阳角阳光。

What that does is it, what we call it, is phase advances the clock.

它的作用是，我们称之为时钟相位超前。

This can get a little technical, and we don't want to get too technical here, but think about pushing your kid on a swing.

这可能有点技术性，我们不想在这里太技术性，但考虑一下推着你的孩子荡秋千。

The period of that swing, the duration of that swing, is a little bit longer than 12 hours.

那个摆动的周期，那个摆动的持续时间，比12小时要长一些。

Okay?

好的？

So when you stand closer to the kid, so your kid swings back and you give it a push, you're shortening the period, right?

所以当你站得离孩子更近时，你的孩子向后摆动，你推它一下，你就缩短了这个时间，对吗？

You're not allowing the swing to come all the way up.

你不允许秋千一直向上。

That's what happens when you look at morning sunlight.

这就是当你看到早晨的阳光时会发生的情况。

You're advancing your circadian clock.

您正在推进您的生物钟。

Translated to English or non-nerd speak, you're making it such that you will want to go to bed a little bit earlier and wake up a little bit earlier the next day.

翻译成英语或非书呆子的语言，你会让你想早点睡觉，第二天早点起床。

In the evening, when you view low solar angle sunlight, so in the afternoon setting sun or evening setting sun, you do the exact opposite.

在晚上，当您观看低太阳角阳光时，因此在下午的夕阳或傍晚的夕阳中，您会做完全相反的事情。

You're phase delaying the clock.

你正在延迟时钟的相位。

It's the equivalent of your kid being at the very top of the arc, and so it's gone maybe 12 and a half hour.

这相当于你的孩子处于弧线的最顶端，所以可能已经过去了 12 个半小时。

Let's say 12 and a half hours is the duration of that swing, and you run up and you push them from behind and give them a little more push.

假设这次秋千的持续时间是 12 个半小时，你跑上去，从后面推他们，再给他们多一点推力。

That's the equivalent of making yourself stay up a little later and wake up a little later.

这相当于让自己晚睡一会儿起床。

These two signals average so that your clock stays stable.

这两个信号进行平均，以便您的时钟保持稳定。

You don't drift, meaning you're not waking up earlier every single day or going to sleep later every single day.

你不会随波逐流，这意味着你不会每天早起或晚睡。

This is why it's important to view low solar angle sunlight in the morning and again in the evening as often as possible.

这就是为什么在早上和晚上尽可能多地观察低太阳角阳光很重要。

And it's done by that readout of those two photopigments.

这是通过读出这两种感光颜料来完成的。

Now, midday sun, which contains, it's bright light, but you see it as white light, contains all of those wavelengths at equal intensity.

现在，正午的太阳包含明亮的光，但你将其视为白光，包含相同强度的所有这些波长。

So the middle of the day is the so-called circadian dead zone.

所以中午就是所谓的昼夜节律死区。

In the middle of the day, bright light triggers the activation of the other opsin, the melanopsin, which increases mood, increases feelings of wellbeing, has some other consequences, but you can't shift your circadian clock by viewing the sun in the middle of the day because it's in the circadian dead zone.

在中午，明亮的光线会触发另一种视蛋白（黑视蛋白）的激活，它会增加情绪，增加幸福感，还会产生其他一些后果，但你不能通过在中午观看太阳来改变你的生物钟，因为它处于昼夜节律死区。

It's the equivalent of pushing your kid on the swing when they're at the bottom of the arc.

这相当于当你的孩子处于弧线底部时推着他们荡秋千。

You can get a little bit more, but not much, and in biological terms, you get nothing.

你可以得到更多一点，但不会太多，从生物学角度来说，你什么也得不到。

So this is why looking at sunlight in the middle of the day is great, but it's not going to help anchor your sleep/wake cycle.

这就是为什么在中午看阳光固然很棒，但它无助于稳定你的睡眠/觉醒周期。

And if you think about it, this is incredible, right?

如果你仔细想想，这太不可思议了，对吧？

Every organism, from single cells to us, has this mechanism to know when the sun is rising and when the sun is setting, and it's a color comparison mechanism, which tells us that actually color vision evolved first not for pattern vision, not for seeing beautiful sunsets and recognizing that's beautiful or paintings or things of that sort, but rather for setting the circadian clock.

每个有机体，从单细胞到我们，都有这种机制来知道太阳何时升起和太阳何时落下，这是一种颜色比较机制，它告诉我们，实际上色觉首先不是为了图案视觉而进化的，不是为了看到美丽的日落并识别美丽或绘画或类似的东西，而是为了设置生物钟。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Now, what if you only do one of these, Andrew?

现在，如果你只做其中一项怎么办，安德鲁？

So what if you've got constant exposure to low morning light, but your job prevents you from doing the same in the evening or vice versa?

那么，如果您在早晨经常暴露在微弱的光线下，但您的工作不允许您在晚上做同样的事情，反之亦然，该怎么办？

Andrew Huberman:

安德鲁·休伯曼：

Yeah, a great question.

是的，一个很好的问题。

Better to get the morning light, because if you have to pick between low solar angle light early or later in the day.

最好获得早晨的光线，因为如果您必须在一天的早些时候或晚些时候在低太阳角光线之间进行选择。

And keep in mind, if you miss a day, no big deal.

请记住，如果您错过一天，也没什么大不了的。

It's a slow integrative mechanism averaging across the previous two or three days.

这是一种缓慢的整合机制，平均过去两三天。

But if you miss a day, you'll want to get twice as much light in your eyes that next morning.

但如果您错过了一天，第二天早上您会希望眼睛里有两倍的光线。

The reason it's better to do in the morning as opposed to the evening, although best would be to do both, is that most people are getting some artificial light exposure in the evening anyway.

早上做比晚上做更好的原因是，尽管最好是两者都做，但大多数人无论如何都会在晚上接受一些人造光照射。

And here's the diabolical thing.

这就是邪恶的事情。

Your retina is very insensitive to light early in the day.

清晨，您的视网膜对光线非常不敏感。

You need a lot of photons to trigger this mechanism early in the day.

您需要大量光子才能在一天早些时候触发此机制。

As the day goes on, retinal sensitivity increases, and it takes very little light to shift your circadian clock late in the day.

随着时间的推移，视网膜的敏感性会增加，并且只需要很少的光就能在一天中晚些时候改变你的生物钟。

Keep in mind also that if you do see afternoon and evening sunlight, there's a beautiful study published in "Science Reports" two years ago showing that that can partially offset the negative effects of artificial light exposure at night.

还要记住，如果您确实看到下午和晚上的阳光，两年前《科学报告》上发表的一项精彩研究表明，这可以部分抵消夜间人造光照射的负面影响。

I think of this as your Netflix inoculation.

我认为这是你在 Netflix 上的一剂疫苗。

The amount of melatonin suppression from nighttime light exposure is halved by viewing evening setting sun.

通过观看傍晚的落日，夜间光照所产生的褪黑激素抑制量会减半。

Now, keep in mind, you don't need to see the sun cross the horizon.

现在，请记住，您不需要看到太阳穿过地平线。

It can just be when it's low solar angle.

它可能只是在太阳角度较低时发生。

So you're looking for those yellow-blue or blue-pink, blue-red contrasts.

所以你正在寻找那些黄蓝色或蓝粉色、蓝红色的对比。

And on cloudy days, believe it or not, they're still there, just you don't perceive as much of it coming through.

在阴天，不管你信不信，它们仍然在那里，只是你感觉不到那么多。

So that's three things that we should all strive to do.

这是我们都应该努力去做的三件事。

View low solar angle sunlight early in the day, view solar angle sunlight later in the day, and get as much bright light in our eyes as we safely can, ideally from sunlight, throughout the day.

在一天的早些时候观察低太阳角阳光，在当天晚些时候观察太阳角阳光，并在我们的眼睛中安全地获得尽可能多的明亮光线，最好是全天来自阳光。

And if you can't do that, perhaps invest in one of these sad lights, although they can be a bit expensive.

如果你做不到这一点，也许可以投资购买其中一盏悲伤的灯，尽管它们可能有点贵。

There are a couple companies that are starting to design sunrise simulators and evening simulators that are actually good, that actually work.

有几家公司开始设计日出模拟器和夜间模拟器，这些模拟器实际上很好，而且确实有效。

But right now, my read is that aside from one company out there, which by the way I have no relationship to, it's called the Tuo Light, T-U-O.

但现在，我的解读是，除了一家公司（顺便说一句，我与这家公司没有任何关系）之外，它的名字叫 Tuo Light，T-U-O。

And that light bulb was developed by the biologists at the University of Washington who basically discovered these color opponent mechanisms.

那个灯泡是由华盛顿大学的生物学家开发的，他们基本上发现了这些颜色对手机制。

Those lights are not particularly expensive, but they do seem to work.

这些灯并不是特别昂贵，但它们似乎确实有效。

In fact, the study that is emerging, again, unpublished data, seems to indicate that if you look at it for more than five or six minutes, it can induce a mild euphoria.

事实上，这项正在出现的研究，同样是未发表的数据，似乎表明，如果你看它超过五六分钟，它会引起轻微的欣快感。

That's how powerful this contrast is.

这就是这种对比的强烈程度。

And what they did there in that light, I'll just tell you the mechanism is, they figured out that when most people look at low solar angle sunlight in the morning, they're getting 19 reversals of blue orange per second.

他们在那里做了什么，我只是告诉你其机制是，他们发现，当大多数人在早上观看低太阳角阳光时，他们每秒会看到 19 次蓝橙色反转。

So when you look at this light, it looks like a barely flashing white light, but it's reversals of orange and blue, orange and red and blue, and it's happening very fast.

所以当你看这个光时，它看起来就像是几乎不闪烁的白光，但它是橙色和蓝色、橙色、红色和蓝色的反转，而且发生得非常快。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And so what does the person looking at it perceive?

那么看着它的人会感知到什么呢？

Andrew Huberman:

安德鲁·休伯曼：

Well, I've used one of these.

嗯，我用过其中之一。

It just looks like a flickering light, and of course there's always the potential of a placebo effect, but-

它看起来就像闪烁的光，当然总有安慰剂效应的潜力，但是——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Well, that's what I was going to say.

嗯，这就是我想说的。

Is there a way to control for that by having something that looks the same to the user-

有没有一种方法可以通过让用户看起来相同的东西来控制这一点-

Andrew Huberman:

安德鲁·休伯曼：

Yeah

是啊

Dr. Peter Attia:

彼得·阿蒂亚博士：

...

...

but of course is not producing the same photo effect?

但当然不是产生相同的照片效果吗？

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Well, they've done that with the 10,000 lux sad lamps, and which most people use to try and induce sunrise simulation in their home.

好吧，他们已经用 10,000 勒克斯的悲伤灯做到了这一点，大多数人都用它来尝试在家里模拟日出。

But keep in mind that sunrise gives you this comparison of short and long wavelength light.

但请记住，日出可以让您对短波长光和长波长光进行比较。

Just a bright 10,000 lux light triggers one of the opsins, but it won't set your circadian clock.

只要一束明亮的 10,000 勒克斯光就会触发其中一个视蛋白，但它不会设置您的生物钟。

So most of the sad lamps that are out there are activating only one of the mechanisms in these cells that's relevant, and not the one that's most relevant.

因此，大多数悲伤的灯只激活这些细胞中相关的机制之一，而不是最相关的机制。

So I'm excited about what Tuo is doing.

所以我对 Tuo 所做的事情感到很兴奋。

And again, I have no relation to them except that I know the biologists who do the work that provide the mechanistic logic for that engineering.

再说一遍，我与他们没有任何关系，只是我认识从事为该工程提供机械逻辑工作的生物学家。

I still think we're in the really early days of this stuff.

我仍然认为我们还处于这方面的早期阶段。

What should be done is to have this stuff built into your laptop, right?

应该做的就是把这个东西内置到你的笔记本电脑中，对吗？

It should be built into your phone, and hopefully it will be.

它应该内置于您的手机中，希望如此。

Now, I mentioned this color contrast thing in sunrise and sunset.

现在，我提到了日出和日落时的颜色对比。

I mentioned the bright light throughout the day.

我提到了一整天的明亮光线。

But there's a fourth light stimulus that turns out to be really important, and this will provide the segue into the paper.

但事实证明，第四种光刺激非常重要，这将为本文提供线索。

Turns out that dark exposure at night, independent of light exposure during the day, is important for mental health outcomes.

事实证明，夜间的黑暗暴露（与白天的光照无关）对于心理健康结果很重要。

Now, most people think dark exposure, how do I think about that?

现在，大多数人都认为黑暗曝光，我对此有何看法？

Well, it is dark, yes.

嗯，天黑了，是的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Absence of light exposure?

没有光照？

Andrew Huberman:

安德鲁·休伯曼：

It's the absence of light, but what this paper really drives home is that people who make it a point to get dark exposure at night, AKA the absence of light at night, actually benefit even if they're not getting enough sunlight during the day.

这是因为缺乏光线，但这篇论文真正要说明的是，那些注重在夜间接受黑暗照射的人，也就是夜间缺乏光线的人，即使他们在白天没有获得足够的阳光，实际上也会受益。

And this is especially true for people with certain mental health issues.

对于有某些心理健康问题的人来说尤其如此。

So, I don't think we can overstate the value of accurately timed light exposure to the eyes in the context of mental health.

因此，我认为我们不能夸大在心理健康方面准确定时的光线照射眼睛的价值。

I think there's so much data by now.

我想现在已经有这么多数据了。

I will say, however, that some people seem more resilient to these light effects than others.

然而，我要说的是，有些人似乎比其他人更能适应这些光效果。

Meaning some people also don't suffer from jet lag too much.

这意味着有些人也不会受到太多时差的影响。

Some people can stay up late, get a lot of bright light exposure in the middle of the night, and during the day, they've got their sunglasses on all day, and they're in a great mood all the time.

有些人可以熬夜，半夜受到大量强光照射，而白天却整天戴着墨镜，心情一直很好。

Other people are more susceptible to these sorts of things, and we don't know whether or not genetic polymorphisms underlie that.

其他人更容易受到这类事情的影响，但我们不知道遗传多态性是否是造成这种情况的原因。

I personally am very sensitive to sunlight in the sense that if I don't get enough sunlight, I don't feel well after a couple of days.

我个人对阳光非常敏感，如果我没有得到足够的阳光，几天后我就会感觉不舒服。

But I'm less sensitive to light exposure at night, for instance.

但例如，我对夜间的光线不太敏感。

But I think it is perhaps, this is a big statement, but is perhaps the most fundamental environmental stimulus for levels of arousal and alertness, which correlate with all sorts of neuromodulator and hormone outputs.

但我认为这也许是一个重要的陈述，但也许是唤醒和警觉水平的最基本的环境刺激，这与各种神经调节剂和激素的输出相关。

And so none of this should come as any surprise.

因此，这一切都不足为奇。

I will mention one last thing.

我要提到最后一件事。

There was a study published, gosh, over 10 years ago now, from Chuck Czeisler's lab at Harvard Medical School.

哈佛医学院 Chuck Czeisler 实验室发表了一项研究，天哪，十多年前了。

It was a phenomenal lab exploring circadian human health behavior.

这是一个探索人类昼夜健康行为的非凡实验室。

He's just considered a, no pun, a luminary in the field.

他只是被认为是该领域的杰出人物。

But there wasn't a study that was in error where they had published in Science magazine that light shone behind the knee could shift circadian rhythms.

但他们在《科学》杂志上发表的一项研究并没有错误，即光线照射在膝盖后面可以改变昼夜节律。

And that paper was retracted, and a lot of people don't know that it was retracted.

那篇论文被撤回了，很多人不知道它被撤回了。

Light exposure to the eyes is what's relevant here.

这里与眼睛的光照有关。

And as far as we know, the color of one's eyes, the darkness or lightness of one's eyes, bears no relevance on their sensitivity to these types of mechanisms, and on and on.

据我们所知，一个人眼睛的颜色，一个人眼睛的黑暗或明亮，与他们对这些类型的机制的敏感性无关，等等。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So one question-

那么一个问题——

Andrew Huberman:

安德鲁·休伯曼：

Yeah

是啊

Dr. Peter Attia:

彼得·阿蒂亚博士：

...

...

one comment.

一条评论。

The question again is going back to the morning/evening light, and I spend a lot of time looking at those types of skies, for example, just because of the nature of my hobbies.

问题又回到了早晨/傍晚的光线，例如，我花了很多时间观察这些类型的天空，只是因为我的爱好的本质。

Andrew Huberman:

安德鲁·休伯曼：

Great.

太棒了。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Right?

对吗？

Because I'm always doing archery in the morning and rucking in the afternoon, so it's not uncommon that I'm seeing both of those.

因为我总是早上射箭，下午射箭，所以我同时看到这两种情况并不罕见。

How relevant is it that the sun be above the horizon?

太阳位于地平线上方有多重要？

So for example, it begins to get light about in 30 minutes before sunrise.

例如，日出前 30 分钟左右开始出现光照。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And then, so if sunrise is at 7:30, first light is 7:00, and then sort of 7:15 to 7:30 is actually quite bright.

然后，如果日出是在 7:30，第一道光是 7:00，然后 7:15 到 7:30 实际上相当亮。

You can see anything and everything, and the same is true at sunset.

你可以看到任何东西，日落时也是如此。

So does that 30 minutes pre or when sun is beneath the horizon constitute part of that 10 minutes?

那么，太阳在地平线以下之前或之后的 30 分钟是否构成这 10 分钟的一部分？

Andrew Huberman:

安德鲁·休伯曼：

It does.

确实如此。

In an ideal circumstance, you'd get outside and see the sunrise every day, and you'd see the sunset every day, even on cloudy days.

在理想的情况下，你每天都能走到户外看到日出，每天都能看到日落，即使是在阴天。

Some people, like myself, wake up before the sun comes up.

有些人，就像我一样，在太阳升起之前醒来。

And I get this question all the time.

我一直被问到这个问题。

Well, in the absence of powers to make the sunrise faster, which I'm not aware anyone has, certainly not me, I think the best thing to do is simply to turn on as many bright lights as you can indoors to trigger that melanopsin mechanism if you want to be awake.

好吧，在没有让日出更快的能力的情况下（我不知道任何人，当然不是我），我认为最好的办法就是在室内打开尽可能多的明亮灯光，以触发黑视素机制，如果你想保持清醒的话。

If you want to stay asleep or sleepy, then keep them dim.

如果您想保持睡眠或困倦，请将它们保持昏暗。

And then get outside once the sun is starting to come out.

一旦太阳开始出来，就出去。

Some people wake up after the sun has risen, right?

有些人是在太阳升起后醒来的，对吗？

In which case, get what you can.

在这种情况下，尽你所能。

And some people wake up 10:00 a.m.

有些人早上 10:00 就起床。

or noon, in which case you can still get the bright light exposure, but you won't shift your circadian clock.

或中午，在这种情况下，您仍然可以获得明亮的光线，但不会改变您的生物钟。

Now, in the evening, especially in the winter months, it's important to look west and try and get some sunlight in your eyes in the evening.

现在，在晚上，尤其是在冬季，重要的是向西看，尝试在晚上让阳光照射到眼睛里。

If you've ever gone into the clinic, for instance, at 2:00 in the afternoon after lunch, and then in the winter, and then come out and it's dark when you walk into your car, it's a kind of eerie feeling.

如果你曾经去过诊所，比如说，午饭后的下午2:00，然后是冬天，然后出来时，当你走进车里时，天已经黑了，那是一种怪异的感觉。

That sort of eerie feeling may correlate with the fact that you missed a signal.

这种怪异的感觉可能与您错过了信号有关。

Your brain is trying to orient your brain and body in time, and that's what all of this is, right?

你的大脑正试图及时调整你的大脑和身体的方向，这就是所有这一切的原因，对吗？

It's trying to orient in time.

它试图及时确定方向。

And again, some people are more susceptible to that than others.

再说一遍，有些人比其他人更容易受到这种影响。

Some people might like that feeling of, oh, I went in when it was bright, and I come out when it's dark.

有些人可能喜欢那种感觉，哦，天亮我进去，天黑我出来。

But the vast majority of people feel better when they're getting this morning and evening sunlight exposure.

但绝大多数人在早上和晚上接受阳光照射时会感觉更好。

And this is especially important in kids.

这对于孩子来说尤其重要。

All right?

好的？

This is one of the things that this paper points out, and there are good data, that people are spending approximately 90% of their time indoors nowadays.

这是本文指出的事情之一，并且有可靠的数据表明，如今人们大约 90% 的时间都在室内度过。

Daytime time indoors.

白天在室内。

And those indoor environments are simply not bright enough.

而那些室内环境根本就不够明亮。

You think, oh, there's all these bright lights.

你想，哦，有这么多明亮的灯光。

And some people are putting blue blockers on in the middle of the day, which is the worst thing you could possibly do.

有些人在中午戴上蓝色阻滞剂，这是你可能做的最糟糕的事情。

If you're going to wear blue blockers, and I don't think they're necessary, but if you're going to wear them, you'd want to wear them at night.

如果你要穿蓝色阻滞剂，我认为它们没有必要，但如果你要穿它们，你会想在晚上穿它们。

And in the evening, you don't need to wear blue blockers, you just simply should dim the lights and ideally have lights that are set a little bit lower in your environment, which the Scandinavians have been doing for a long time.

到了晚上，你不需要戴蓝色阻挡器，你只需要把灯光调暗，最好将环境中的灯光设置得稍微低一点，斯堪的纳维亚人长期以来一直这样做。

So, kill the overhead lights.

所以，关掉头顶的灯。

And don't obsess about bright light exposure in the middle of the night.

并且不要沉迷于半夜的强光照射。

In fact, for a long time, I and some other people were saying, oh, even just a brief flash of light in the middle of the night can quash your melatonin.

事实上，很长一段时间，我和其他一些人都在说，哦，即使只是半夜的短暂闪光也会消除你的褪黑激素。

That's true.

这是真的。

But the other time in which you're in this, quote-unquote, circadian dead zone is in the middle of the night.

但另一次你处于昼夜节律死区的时间是在半夜。

You can't shift your circadian clock in the middle of the night.

你无法在半夜改变你的生物钟。

But all of this gets down to interweaving rhythms of light sensitivity, temperature, hormone output, cortisol.

但所有这一切都归结为光敏感性、温度、激素分泌和皮质醇的交织节奏。

There's a whole landscape of circadian biology.

这是昼夜节律生物学的全貌。

This paper, which was published in a new journal I'm really excited about called "Nature Mental Health," this journal was just launched recently, is entitled "Day and Night Light Exposure are Associated with Psychiatric Disorders in Objective Light Study in More Than 85,000 People." Now, I have to say that I think the title of this paper is terrible.

这篇论文发表在一本我非常兴奋的新期刊《自然心理健康》上，该期刊最近刚刚推出，题为“在超过 85,000 人的客观光研究中，白天和夜间的光暴露与精神疾病有关”。现在，我不得不说，我认为这篇论文的标题很糟糕。

Sorry, folks at Nature Mental Health.

抱歉，《自然心理健康》的各位。

Because if one just read the title, it sounds like day and night light exposure are associated with psychiatric disorders, right?

因为如果光看标题，听起来白天和晚上的光线照射都与精神疾病有关，对吗？

If this were a newspaper headline, you'd be like, "Oh my goodness, well, what are you supposed to do?" Right?

如果这是报纸头条，你会说，“哦，天哪，那么，你该怎么办？”正确的？

But that's not the conclusion.

但这还不是结论。

The conclusion is that getting a lot of sunlight exposure during the day and getting a lot of dark exposure at night is immensely beneficial for psychiatric health and in a number of ways.

结论是，白天接触大量阳光，晚上接触大量黑暗，在很多方面对精神健康都非常有益。

Now, I'm not one to bring up another paper unannounced, but I will say that this paper built off a previous study entitled "Time Spent in Outdoor Light is Associated with Mood, Sleep, and Circadian Rhythm-Related Outcomes," and that was a cross-sectional longitudinal study in 400,000 biobank participants.

现在，我不是一个未经宣布就提出另一篇论文的人，但我要说的是，这篇论文建立在之前一项题为“在户外光线中度过的时间与情绪、睡眠和昼夜节律相关结果相关”的研究的基础上，这是一项针对 400,000 名生物样本库参与者的横断面纵向研究。

So this UK Biobank is an incredibly valuable resource, and there are now multiple studies establishing that one's pattern of light exposure is extremely important.

因此，这个英国生物银行是一个非常宝贵的资源，现在有多项研究证实一个人的光照模式极其重要。

Now, the previous study in 400,000 participants basically nailed home the idea that the more time you spend outdoors, the better is your mood, the better is your sleep, the better is the rhythmicity of your sleep-wake cycles, and on and on.

现在，之前对 400,000 名参与者进行的研究基本上明确了这样一个观点：你花在户外的时间越多，你的心情就越好，你的睡眠就越好，你的睡眠-觉醒周期的节奏就越好，等等。

Something that I think, even though people say we've known that for thousands of years, needed scientific substantiation.

我认为，尽管人们说我们已经知道了数千年，但仍然需要科学证实。

This new study essentially looked at the relative contributions of daytime light exposure and nighttime dark exposure, and they did that on a background of looking, in particular, at people who had major depressive disorder, generalized anxiety, PTSD, bipolar disorder.

这项新研究主要考察了白天光照和夜间黑暗暴露的相对贡献，他们特别关注患有重度抑郁症、广泛性焦虑症、创伤后应激障碍（PTSD）和双相情感障碍的人。

Here's the basic takeaway, and I'll quote them here, and then I'll tell you my interpretation.

这是基本要点，我将在这里引用它们，然后我会告诉你我的解释。

Here I'm quoting, "Avoiding night at light and seeking light during the day," I love that word, seeking, "may be a simple and effective non-pharmacologic means for broadly improving mental health." So that's a pretty bold statement, right?

在这里我引用，“避免夜间有光，白天寻求光明”，我喜欢这个词，寻求“可能是广泛改善心理健康的简单而有效的非药物手段。”所以这是一个非常大胆的声明，对吧？

And I love that they say seeking because it implies that people aren't reflexively getting the light exposure that they need, that this needs to be a practice, much like zone two cardio or resistance training.

我喜欢他们说“寻求”，因为这意味着人们没有本能地获得他们需要的光照，这需要成为一种练习，就像第二区有氧运动或阻力训练一样。

Okay, so what did they do in this study?

好吧，那么他们在这项研究中做了什么？

So basically, they gathered up 100,000 people or so.

所以基本上，他们聚集了10万人左右。

It eventually was pared down to about 86,000 participants because some just didn't qualify or didn't report their data back.

最终参与者人数减少到约 86,000 名，因为有些人不符合资格或没有报告他们的数据。

They equipped them with accelerometers on their wrist, and those wrist devices also could measure ambient light.

他们在手腕上配备了加速计，这些手腕设备还可以测量环境光。

Now, that's not a perfect tool because what you'd love to do is measure ambient light at the level of the eyes.

现在，这不是一个完美的工具，因为您想做的是测量眼睛水平的环境光。

By the way, will somebody design an eyeglass frame that changes color when you've gotten sufficient light from sunlight during the day, and then at night is a different color, and then if you're getting too much light exposure, will go to a different color frame?

顺便问一下，有人会设计一种眼镜框，当你白天从阳光中获得足够的光线时，它会改变颜色，然后在晚上会变成不同的颜色，然后如果你受到太多的光线照射，会选择不同颜色的镜框吗？

This has to be possible so that you don't have to wonder if you got enough light during the day.

这必须是可能的，这样您就不必怀疑白天是否有足够的光线。

And of course, if it's at the level of the eyes, then you know that's what's landing at the eyes.

当然，如果它在眼睛的水平，那么你就知道那是什么落在了眼睛上。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

That's what I was going to ask you about that.

这就是我要问你的问题。

Do these wrist-based devices potentially get covered by clothing in some-

这些腕式设备在某些情况下是否可能被衣服覆盖？

Andrew Huberman:

安德鲁·休伯曼：

Yep.

是的。

Turned over

翻了

Dr. Peter Attia:

彼得·阿蒂亚博士：

...

...

You have your sleeves down.

你已经放下袖子了。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

I have my sleeves up.

我已经挽起袖子了。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

They had it on the outside of the sleeve, but they asked that people just keep it on their dominant hand.

他们把它放在袖子的外面，但他们要求人们把它放在惯用手上。

It's not perfect, but in some ways, it's kind of nice that it's not perfect.

它并不完美，但从某些方面来说，它不完美也很好。

We could turn that disadvantage into advantage by thinking when the person is out and about, they're not often looking right at the sun.

我们可以通过思考当人外出时，他们不经常直视太阳，从而将这种劣势转化为优势。

If you're talking to a colleague under an overhang, for instance.

例如，如果您正在与悬挑下的同事交谈。

So it's not perfect.

所以它并不完美。

Dr. Peter Attia:

彼得·阿蒂亚博士：

It's directionally.

是有方向性的。

Andrew Huberman:

安德鲁·休伯曼：

It's directionally right.

方向是对的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

Okay.

好的。

And then they had two hypotheses, two primary hypotheses.

然后他们有两个假设，两个主要假设。

One, that greater light exposure in the day is associated with lower risk for psychiatric disorders, and two Second hypothesis, greater light exposure at night is associated with higher risk for psychiatric disorders and poorer mood.

第一，白天接触更多的光与精神疾病的风险较低有关，第二个假设，夜间接触更多的光与精神疾病和较差情绪的风险更高。

This is oh so relevant for the way we live now, people on screens and tablets in the middle of the night.

这与我们现在的生活方式非常相关，人们在半夜使用屏幕和平板电脑。

Okay.

好的。

Then they collected information about how much light exposure people were getting, as well as their sleep and their activity and so on.

然后他们收集了有关人们接受多少光照、睡眠和活动等的信息。

I should mention this was done in males and females.

我应该提到的是，这是在男性和女性中进行的。

It was a slightly older cohort than one is used to seeing, people in their 50s and 60s.

这是一个比人们通常看到的年龄稍大的群体，年龄在 50 多岁和 60 多岁。

They had psychiatric diagnosis information, and then they divided people into essentially two groups, but they had a lower, so a Q1 and a Q2, a lower quartile.

他们有精神病学诊断信息，然后他们将人们基本上分为两组，但他们有一个较低的组，即 Q1 和 Q2，即较低的四分位数。

That meant people that were getting less daytime light as opposed to the third and fourth quartile, more daytime light.

这意味着，与第三和第四四分位数的人相比，白天获得的光照较少的人获得的光照较多。

They also had a nighttime light exposure evaluation, and they had people in the low Q1 and Q2, so these people are getting less nighttime light versus Q3, Q4, more nighttime light.

他们还进行了夜间光暴露评估，其中 Q1 和 Q2 较低，因此这些人获得的夜间光较少，而 Q3、Q4 获得的夜间光较多。

Nicely, they also looked at sleep duration, and they looked at photoperiod, meaning how long the days were for those individuals, how active they were, 10 hours a day, 14 hours a day, because the more active you are, the more opportunity for light exposure you have during the day or night, for instance.

很好的是，他们还研究了睡眠持续时间和光周期，这意味着这些人的白天有多长，他们的活跃程度，每天 10 小时，每天 14 小时，因为你越活跃，你在白天或晚上接触光线的机会就越多。

Okay.

好的。

So they had, I would say, fairly complete data sets.

所以我想说，他们拥有相当完整的数据集。

Then, and I'm just going to kind of hit the top contour of what they did in each.

然后，我将简单介绍一下他们在每个项目中所做的事情。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And sorry, sleep duration, sleep efficiency, et cetera-

抱歉，睡眠时间、睡眠效率等等——

Andrew Huberman:

安德鲁·休伯曼：

Yep

是的

Dr. Peter Attia:

彼得·阿蒂亚博士：

...

...

was determined off the accelerometer?

是通过加速度计确定的吗？

Andrew Huberman:

安德鲁·休伯曼：

That's right, as well as self-report.

没错，还有自我报告。

Yeah.

是的。

Not ideal.

不理想。

You'd love for people to be wearing a Whoop band or a ring or something of that sort, but this was initiated some time ago, so they either didn't have access to that technology or, for whatever reason, didn't select it.

你希望人们佩戴 Whoop 乐队或戒指或类似的东西，但这是不久前发起的，所以他们要么无法使用该技术，要么出于某种原因没有选择它。

Then what they did is they have information on who has major depressive disorder, who has PTSD, generalized anxiety, bipolar, psychosis, et cetera, and then they ran three models.

然后他们所做的是获得关于谁患有重度抑郁症、谁患有创伤后应激障碍、广泛性焦虑症、双相情感障碍、精神病等的信息，然后他们运行了三个模型。

And you can tell me what you think about the power of these models, but as somebody who thinks about the mechanistic aspect of all of this a lot but not somebody who's ever run this type of study, I'd be really curious.

你可以告诉我你对这些模型的力量的看法，但作为一个经常思考所有这一切的机械方面但没有进行过此类研究的人，我真的很好奇。

Model one examined the unadjusted association between day and nighttime light exposure and psychiatric outcome.

模型一检查了白天和夜间光照与精神结果之间未经调整的关联。

So just basically asking, is there a relationship between how much light you get during the day and how much light you get at night, and how bad your depression is or anxiety is, et cetera?

所以基本上问一下，您白天获得的光照量和晚上获得的光照量与您的抑郁或焦虑程度等之间是否存在关系？

Looking at just a standard ratio of the probability that you have a certain symptom or set of symptoms versus you don't, given a certain amount of light exposure.

在一定量的光照下，仅查看您出现某种症状或一组症状与不出现某种症状的概率的标准比率。

Model two adjusted for the age of the person, their sex and ethnicity, and photoperiod.

模型二根据人的年龄、性别、种族以及光周期进行调整。

So they looked at how long the days were in that given person's region of the world.

因此，他们研究了该人所在地区的白天有多长。

And then model three also-

然后模型三也-

Dr. Peter Attia:

彼得·阿蒂亚博士：

These people were all in the UK, or were they around the world?

这些人都在英国，还是在世界各地？

Andrew Huberman:

安德鲁·休伯曼：

They were all in the UK.

他们都在英国。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Okay.

好的。

All right.

好的。

Andrew Huberman:

安德鲁·休伯曼：

As far as I know.

据我所知。

And then model three adjusted for employment, so employed versus unemployed, which, if you think about it, is pretty important.

然后根据就业情况调整模型三，即就业与失业，如果你仔细想想，这非常重要。

You say, well, an unemployed person has a lot more time to control these variables, but an employed person who's doing shift work does not.

你说，失业者有更多的时间来控制这些变量，但轮班工作的就业者却没有。

And they incorporated information about employed versus unemployed physical activity, which turns out to be very important, and then things like shift work, et cetera.

他们纳入了有关就业与失业体力活动的信息，事实证明这非常重要，然后是轮班工作等。

And so what we can say very safely is that the outcomes with each of these models, the results were very similar.

因此，我们可以非常有把握地说，每个模型的结果都非常相似。

So we don't want to discard the differences between those models entirely, but my read is, in every figure of the paper, it doesn't seem like model one, two, or three differ from one another in terms of total outcome.

因此，我们不想完全放弃这些模型之间的差异，但我的理解是，在论文的每个图中，模型一、二或三在总体结果方面似乎并没有彼此不同。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

That's an unusual aspect of this paper.

这是本文的一个不寻常的方面。

So these adjustments are very standard, right?

所以这些调整是非常标准的，对吧？

Andrew Huberman:

安德鲁·休伯曼：

Okay.

好的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So this is a classic tool that's used in most epidemiology because you don't have randomization.

所以这是大多数流行病学中使用的经典工具，因为没有随机化。

So once randomization is out the window, so for example, the paper I'm going to present is based on an RCT.

因此，一旦随机化被排除在外，例如，我将要介绍的论文就是基于随机对照试验。

There will be no models.

不会有模型。

It's just, here are the data.

只是，这是数据。

Andrew Huberman:

安德鲁·休伯曼：

Right.

对。

Yeah.

是的。

Here they're asking people, "What do you do?

他们在这里问人们：“你做什么？

Report back to us.

向我们报告。

We're going to measure your light exposure." But no one was assigned to any groups or swapped.

我们将测量你的曝光量。”但没有人被分配到任何组或交换。

Dr. Peter Attia:

彼得·阿蒂亚博士：

That's right.

没错。

Andrew Huberman:

安德鲁·休伯曼：

Whatever quote unquote controls are there, they're really not there.

无论存在什么引用非引用控件，它们实际上都不存在。

It's just comparisons between groups.

这只是群体之间的比较。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So what is interesting to me is that it's exactly as you said, and we'll make all these figures available in addition to the papers.

所以我感兴趣的是，正如你所说，除了论文之外，我们还将提供所有这些数据。

But it's very unusual that there's no difference between the unadjusted and the adjusted models.

但很不寻常的是，未调整的模型和调整后的模型之间没有差异。

And as you say, there's probably two places out of 30 when you look at all the different quartile comparisons where you might creep from statistically significant just out of it or just into it.

正如你所说，当你查看所有不同的四分位数比较时，30 个地方中可能有两个地方你可能会从统计显着性中脱颖而出或刚刚进入其中。

But yeah, you could simplify this figure two completely by just showing one of the models, and you would be getting 95% of the information.

但是，是的，您可以通过仅显示其中一个模型来完全简化图二，并且您将获得 95% 的信息。

I think in one way, that suggests that there's less dependency on those variables.

我认为在某种程度上，这表明对这些变量的依赖性较小。

Of course, it still doesn't address probably the greatest question I have here, which I'm sure we'll get to at some point as you continue.

当然，它仍然没有解决我在这里遇到的最大问题，我相信我们会在您继续阅读时在某个时候解决这个问题。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

So I'm very curious what that question is, but I'll suppress my curiosity for the moment.

所以我很好奇这个问题是什么，但我暂时压制住我的好奇心。

So if we look at figure two of this paper, and I realize a lot of people are listening and they're not able to look at this, although we have posted the figures on the YouTube versions of this.

因此，如果我们看一下本文的图二，我意识到很多人都在听，但他们无法查看此图，尽管我们已将这些图发布在 YouTube 版本上。

Just want to make clear what's going on, just for those that are listening.

只是想向那些正在倾听的人澄清正在发生的事情。

Essentially what they're looking at is what they call the odds ratio, which is the probability of something happening in one group divided by the probability of something happening in another group.

本质上，他们关注的是所谓的优势比，即一组中发生某事的概率除以另一组中发生某事的概率。

I guess would a By way of example would be, if you were going to look at the odds ratio of the probability of somebody getting lung cancer if they smoke versus probability of somebody getting lung cancer if they don't smoke.

我想举个例子，如果你要看看一个人吸烟时患肺癌的概率与不吸烟时患肺癌的概率的比值比。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So odds ratios and hazard ratios are often confused.

因此优势比和风险比经常被混淆。

They're very similar, and odds ratios generally refer to a lifetime exposure, whereas a hazard ratio is defined over a specific period of time.

它们非常相似，优势比通常指的是终生暴露，而风险比是在特定时间段内定义的。

But the math is still effectively the same.

但数学实际上仍然是相同的。

And using the example you gave, if you took the odds ratio of death, so let's talk all-cause mortality for a smoker versus a non-smoker, and the answer were 1.78, I'm making that up, but that's directionally correct.

使用你给出的例子，如果你采用死亡比值比，那么让我们来谈谈吸烟者与非吸烟者的全因死亡率，答案是 1.78，这是我编造的，但这在方向上是正确的。

1.78 as an odds ratio means there's a 78% chance greater of the outcome of interest, in this case, death by any cause in the affected group, which would be the smokers.

优势比 1.78 意味着感兴趣的结果的可能性更大，在本例中，受影响群体（即吸烟者）因任何原因死亡。

So a odds ratio of two is 100%, an odds ratio of three is 200%.

因此，优势比为 2 时为 100%，优势比为 3 时为 200%。

So the math is take the number, subtract one, and that's the percent.

所以数学就是把数字减一，这就是百分比。

Andrew Huberman:

安德鲁·休伯曼：

Figure two of this paper is one of the key take homes.

本文的图二是关键内容之一。

They essentially look at the odds ratio of people who are in the, let's just look at the nighttime light exposure.

他们本质上是看人们所处的比值比，让我们看看夜间的光照情况。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And just remind me, Andrew, because and everybody else watching, every one of these is showing second, third, fourth as your X-axis.

请提醒我，安德鲁，因为其他人都在观看，其中每一个都显示第二、第三、第四作为你的 X 轴。

Andrew Huberman:

安德鲁·休伯曼：

Right.

对。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Meaning they're all being compared to the first quartile.

这意味着它们都与第一个四分位数进行比较。

Andrew Huberman:

安德鲁·休伯曼：

That's right.

没错。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And the first quartile is lowest light exposure or highest light exposure?

第一个四分位数是最低曝光量还是最高曝光量？

Andrew Huberman:

安德鲁·休伯曼：

That's right.

没错。

Lowest.

最低。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Okay.

好的。

Andrew Huberman:

安德鲁·休伯曼：

Well, we have to--

好吧，我们必须——

Dr. Peter Attia:

彼得·阿蒂亚博士：

We could differentiate between day and night.

我们可以区分白天和黑夜。

Andrew Huberman:

安德鲁·休伯曼：

That's right.

没错。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Okay.

好的。

So restate it.

所以重申一下。

Andrew Huberman:

安德鲁·休伯曼：

Sure.

当然。

So if we look at what is your risk of a psychiatric challenge, broadly speaking.

因此，如果我们从广义上看您面临精神挑战的风险有多大。

Well, panel A is major depressive disorder.

嗯，A 组是重度抑郁症。

If you are in the second quartile, third quartile, or fourth quartile of nighttime light exposure.

如果您处于夜间光照的第二个四分位、第三个四分位或第四个四分位。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yep.

是的。

Andrew Huberman:

安德鲁·休伯曼：

So second being the least amount of nighttime light exposure, third being more nighttime light exposure, and fourth, the most nighttime light exposure relative to the first quartile.

因此，第二个是最少的夜间光暴露量，第三个是更多的夜间光暴露量，第四个是相对于第一个四分位数的最多的夜间光暴露量。

Dr. Peter Attia:

彼得·阿蒂亚博士：

This is just a stupid thing.

这只是一件愚蠢的事情。

Like if I were doing this figure, if you were doing this in a lecture-

就像如果我在做这个图，如果你在讲座中做这个——

Andrew Huberman:

安德鲁·休伯曼：

Yeah

是啊

Dr. Peter Attia:

彼得·阿蒂亚博士：

...

...

you know what you would do to make it so easy?

你知道你会做什么来让它变得如此简单吗？

You would draw arrows on it that say, increasing light exposure at night-

你会在上面画箭头，表示增加夜间的光照-

Andrew Huberman:

安德鲁·休伯曼：

Right.

对。

Yep

是的

Dr. Peter Attia:

彼得·阿蒂亚博士：

...

...

decreasing light exposure in the day.

减少白天的光照。

Andrew Huberman:

安德鲁·休伯曼：

Yep.

是的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

It's the same information.

这是相同的信息。

It just makes it easier for the reader to understand.

它只是让读者更容易理解。

Andrew Huberman:

安德鲁·休伯曼：

Absolutely.

绝对的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And then maybe the teaching point, I think, is for people when they review articles, don't be afraid to do that and just kind of like, "Wait, what is this?"

我认为，也许教学点是让人们在审阅文章时，不要害怕这样做，只是想，“等等，这是什么？”

Andrew Huberman:

安德鲁·休伯曼：

Oh, I've got scribble all over this.

噢，我已经把这一切都乱写乱画了。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah, exactly.

是的，完全正确。

Andrew Huberman:

安德鲁·休伯曼：

Right.

对。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So it's like I draw the arrow.

就像我画箭头一样。

That's increasing light, that's decreasing light, and that's how I can pay attention to what's actually happening.

这是增加光线，这是减少光线，这就是我可以关注实际发生的事情的方式。

Andrew Huberman:

安德鲁·休伯曼：

Right.

对。

And I'm actually in touch with the editorial staff at Nature Mental Health, although they don't know that I'm covering this paper until after this comes out.

事实上，我与《自然心理健康》的编辑人员保持着联系，尽管他们直到这篇论文发表后才知道我正在报道这篇论文。

I think one thing that scientific journals really, really need to do is start making the readability of the articles better for non-experts.

我认为科学期刊真正需要做的一件事就是开始提高文章对非专家的可读性。

Chances are, if you can't understand a graph, and this is true for everybody, chances are there's a problem with the way it's presented.

如果您无法理解图表（每个人都是如此），那么很可能它的呈现方式存在问题。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

Put it on them.

把它放在他们身上。

But then, of course, try and parse it because rarely, if ever, is it all spelled out clearly.

但是，当然，请尝试解析它，因为很少（如果有的话）将其全部阐明清楚。

But anyway, that's what we're trying to do here.

但无论如何，这就是我们在这里尝试做的事情。

So yeah, the way I would have done it is say second quartile is low amounts of nighttime light exposure and define what that is.

所以，是的，我的做法是说第二个四分位数是夜间光照量较低，并定义它是什么。

Third quartile is more light exposure, and then fourth maximum amount of light exposure at night.

第三个四分位是更多的光照量，然后是第四个最大的夜间光照量。

And basically what you see is that the probability of having worse major depressive symptoms linearly increases as you go from the second to third to fourth quartile.

基本上你看到的是，随着你从第二个四分位到第三个四分位到第四个四分位，出现更严重的严重抑郁症状的概率线性增加。

So more nighttime light exposure, worse for you, and there's a dose response, if you will, of the effect.

因此，更多的夜间光照对你来说更糟糕，而且如果你愿意的话，这种效应会产生剂量反应。

Now, we can march through or describe figure two pretty quickly by saying the same thing is true.

现在，我们可以通过说同样的事情是正确的来快速地浏览或描述图二。

Now we're just talking about nighttime light exposure for generalized anxiety disorder, so that's panel C.

现在我们只是讨论夜间光照对广泛性焦虑症的影响，这就是 C 组。

Bipolar disorder, although the difference between the second and the third quartile in bipolar disorder isn't as dramatic.

双相情感障碍，尽管双相情感障碍的第二和第三四分位之间的差异并不那么显着。

Once you get up to the fourth quartile, bipolar symptoms get much worse when people are getting nighttime light exposure.

一旦达到第四个四分位，当人们接受夜间光照时，躁郁症症状就会变得更严重。

I really want to emphasize that point because they go on in the discussion of this paper to reemphasize that point several times.

我真的很想强调这一点，因为他们在本文的讨论中多次重新强调了这一点。

In fact, they say that while light exposure during the day, of course, we will go into the data, is beneficial for mental health.

事实上，他们说，虽然白天暴露在光线下，当然，我们会研究数据，对心理健康是有益的。

For people with bipolar disorder, it seems that light exposure at night is especially problematic independent of how much sunlight they're getting during the day.

对于双相情感障碍患者来说，无论白天接受多少阳光，夜间的光照似乎尤其成问题。

So the person with bipolar disorder who's struggling with either a manic or a depressive episode, who's making it a point to get sunlight during the day, who's also getting light exposure at night, is making their symptoms worse.

因此，患有躁郁症或抑郁症的双相情感障碍患者，白天必须接受阳光照射，晚上也接受光线照射，这会使他们的症状变得更糟。

And keep in mind, they couldn't completely control this, but this is largely independent of things like sleep duration.

请记住，他们无法完全控制这一点，但这在很大程度上与睡眠时间等因素无关。

So that doesn't necessarily mean that the person's sleeping less, although in a manic episode, presumably they are.

因此，这并不一定意味着这个人的睡眠时间减少了，尽管在躁狂发作期间，他们大概是这样。

It's independent of exercise.

它与运动无关。

It's independent of a bunch of other things because any logical person will hear this and say, "Okay, well, they're getting more light at night because they're doing a bunch of other things." But it's largely independent of those other things.

它独立于许多其他事情，因为任何有逻辑的人都会听到这个并说，“好吧，好吧，他们在晚上得到更多的光，因为他们正在做很多其他事情。”但它在很大程度上独立于其他事情。

Likewise, the symptomology of PTSD gets far worse with increasing light exposure at night.

同样，随着夜间光照的增加，创伤后应激障碍的症状会变得更加严重。

Self-harm really takes a leap from being fairly, I don't want to say minimal at the second and third quartile, so low and let's say medium.

自残确实比公平有一个飞跃，我不想说第二和第三四分位数是最小的，这么低，可以说是中等。

I'm taking some liberties here, but low and medium amounts of artificial light exposure at night.

我在这里有一些自由，但夜间的人造光暴露量较低和中等。

Then for people who get quite a lot of nighttime light exposure, self-harm goes up, and probability of psychotic episodes goes up, or psychotic symptoms.

那么，对于那些在夜间接触大量光线的人来说，自残行为会增加，精神病发作或精神病症状的可能性也会增加。

Now, what's nice about the data is that the exact inverse is basically true for daytime light exposure.

现在，数据的优点在于，对于白天的光照来说，精确的反演基本上是正确的。

Although not across the board, we can generally say that for major depressive disorder generalized anxiety, bipolar symptoms there it's a little more scattered, PTSD, and self-harm, the more daytime light exposure, ideally from sunlight because that's actually what's being measured in most cases, we could talk about how we know that, is going to approximately linearly drop the probability or the severity of these symptoms.

虽然不是一刀切，但我们一般可以说，对于重度抑郁症、广泛性焦虑症、双相情感障碍症状，它更加分散，创伤后应激障碍和自残，更多的白天暴露在阳光下，最好是阳光，因为这实际上是大多数情况下测量的，我们可以谈论我们如何知道，这些症状的概率或严重程度会近似线性下降。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And we could just explain again that the odds ratios now seem to be going down.

我们可以再次解释一下，优势比现在似乎正在下降。

So an odds ratio of 0.7 now refers to a 30% reduction in the variable of interest here.

因此，优势比 0.7 现在表示感兴趣的变量减少了 30%。

Andrew Huberman:

安德鲁·休伯曼：

Exactly.

正是如此。

Now, the psychosis, panel F, which focuses on psychosis, I think is also worth mentioning in a bit more detail.

现在，精神病，F 组，重点关注精神病，我认为也值得更详细地提及。

There's a fairly dramatic reduction in psychotic symptoms as one gets more daytime light exposure, independent of nighttime light exposure.

当一个人在白天接触更多的光（与夜间的光接触无关）时，精神病症状会显着减少。

There's a well-known phenomenon called ICU psychosis, which is that people come into the hospital for a broken leg or a car accident.

有一种众所周知的现象，称为 ICU 精神病，即人们因腿部骨折或车祸而进入医院。

Maybe they were getting surgery from Peter back when for something totally independent.

也许他们当时正在为完全独立的事情接受彼得的手术。

They're housed in the hospital, and as anyone who's ever been in a hospital as a patient or visitor knows, the lighting environment of the hospital is absolutely dreadful for health.

他们被安置在医院里，任何曾经作为病人或访客去过医院的人都知道，医院的照明环境对健康来说绝对是可怕的。

Just dreadful.

太可怕了。

People often complain about the food in the cafeterias being unhealthy.

人们经常抱怨食堂的食物不健康。

That's often not always true.

这通常并不总是正确的。

But the lighting environments in hospitals is absolutely counter to health.

但医院的照明环境绝对是与健康背道而驰的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Especially in the intensive care unit.

尤其是在重症监护室。

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

Right.

对。

So the-

所以——

Dr. Peter Attia:

彼得·阿蒂亚博士：

I think the intensive care unit at Hopkins, the main one, the main SICU, didn't have windows

我认为霍普金斯大学的重症监护室，主要的重症监护病房，没有窗户

Andrew Huberman:

安德鲁·休伯曼：

People who go into the hospital with a brain injury or with a stroke or something, I get contacted all the time, even though I'm not a clinician.

尽管我不是临床医生，但我总是会联系那些因脑损伤或中风或其他原因而住院的人。

What should I do for my kid, my parent?

我应该为我的孩子、我的父母做些什么？

I always say, get them near a window and start to the best of your abilities controlling their sleep-wake cycle.

我总是说，让他们靠近窗户，开始尽最大努力控制他们的睡眠-觉醒周期。

Now, oftentimes, there's nurses coming in and taking blood tests and measuring pulses in the middle of the night.

现在，经常有护士在半夜进来进行血液检查和测量脉搏。

That's disruptive.

这是破坏性的。

There's bright light, not just blue light.

有明亮的光，而不仅仅是蓝光。

That's disruptive.

这是破坏性的。

It's noisy.

太吵了。

That's disruptive.

这是破坏性的。

ICU psychosis is when non-psychotic individuals start having psychotic episodes in the hospital because of nighttime light exposure and, in some cases, lack of daytime sunlight.

ICU 精神病是指非精神病患者由于夜间光照以及在某些情况下缺乏白天阳光而在医院开始出现精神病发作。

We can say that with some degree of confidence because when those people go home, even though sometimes their symptoms for what brought them to the hospital in the first place get worse, their psychosis goes away.

我们可以有一定程度的信心地说，因为当这些人回家后，即使有时他们最初去医院的症状变得更糟，他们的精神病也会消失。

Now, and it's independent of medication.

现在，它与药物无关。

So let's just be really direct.

所以我们就直接说吧。

There is a possibility that we are all socially jet lagged, that we are all disrupting these mood regulation systems by not getting enough daytime light and by getting too much nighttime light.

有可能我们都患有社交时差，我们都因为白天没有获得足够的光照而夜间光照过多而扰乱了这些情绪调节系统。

If we want to look at just some of the bullet points of the takeaways, and Peter, thank you, you highlighted a few of these, but-

如果我们只想看一些要点，彼得，谢谢你，你强调了其中的一些，但是-

Dr. Peter Attia:

彼得·阿蒂亚博士：

Can we just go back to this figure two for a second?

我们可以回到图二吗？

Andrew Huberman:

安德鲁·休伯曼：

Oh, yeah.

哦，是的。

Sure.

当然。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Because there's a handful of things that really jump out.

因为有一些事情真的很突出。

Andrew Huberman:

安德鲁·休伯曼：

I had a feeling Peter was going to want to dig in the data more.

我有一种感觉，彼得想要更多地挖掘数据。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

Let's do it.

让我们开始吧。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And again, I normally wouldn't make so much hay out of this except for the fact that they're so tight.

再说一遍，我通常不会用这个做那么多干草，除非它们太紧了。

But there are a few that really stand out.

但有一些确实很突出。

And again, I love this figure.

再说一次，我喜欢这个人物。

I would have labeled it a little differently to make it completely user-friendly.

我会对它进行稍微不同的标记，以使其完全用户友好。

But nevertheless, the increasing light at night and the impact on depression-

但尽管如此，夜间光线的增加以及对抑郁症的影响——

Andrew Huberman:

安德鲁·休伯曼：

Panel A.

面板 A。

Mm-hmm

嗯嗯

Dr. Peter Attia:

彼得·阿蒂亚博士：

...

...

or let me be really technical in what I say, and the relationship or correlation to depression is very strong.

或者让我说得更专业一些，它与抑郁症的关系或相关性非常强。

The relationship to light and self-harm in the upper quartile, so when you take those 25% of people with the most nighttime light, that relationship to self-harm is interesting and completely uncoupled from the other 75%.

光和自残的关系位于上四分位数，因此当你选取夜间光线最多的 25% 的人时，这种与自残的关系很有趣，并且与其他 75% 的人完全脱节。

That's interesting.

那很有意思。

Andrew Huberman:

安德鲁·休伯曼：

By uncoupled, you mean that at the lower levels of light exposure at night, you're not seeing an increase in self-harm.

所谓“脱钩”，是指在夜间较低的光照水平下，你不会看到自残的增加。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Not whatsoever.

不是什么。

Andrew Huberman:

安德鲁·休伯曼：

And then once you get to that fourth quartile-

然后一旦你到达第四个四分位数 -

Dr. Peter Attia:

彼得·阿蒂亚博士：

It's a big step

这是一大步

Andrew Huberman:

安德鲁·休伯曼：

...

...

it's at, like, a 30% greater risk of self-harm.

自残的风险会增加 30%。

Dr. Peter Attia:

彼得·阿蒂亚博士：

That's right.

没错。

Yeah, so it's totally flat.

是的，所以它是完全平坦的。

The first, second, third quartile, no different, and then fourth, big jump.

第一、第二、第三四分位，没有什么不同，然后是第四个，大跳跃。

And then the inverse relationship, right?

然后是反比关系，对吗？

As light increases during the daytime, you see this reduction in self-harm.

随着白天光线的增加，你会发现自残的情况有所减少。

Interesting.

有趣的。

The PTSD relationship based on nighttime light and the psychosis relationship based on daytime light.

基于夜间光的 PTSD 关系和基于白天光的精神病关系。

Those are the ones that really jumped out to me.

这些才是真正让我震惊的。

I think anxiety relatively less impressive here.

我认为焦虑在这里相对不那么令人印象深刻。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Yep.

是的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And bipolar disorder didn't seem as strong-

双相情感障碍似乎并没有那么严重——

Andrew Huberman:

安德鲁·休伯曼：

Right

右

Dr. Peter Attia:

彼得·阿蒂亚博士：

...

...

as well.

以及。

So I think those are the big ones that-

所以我认为这些是最重要的——

Andrew Huberman:

安德鲁·休伯曼：

I agree

我同意

Dr. Peter Attia:

彼得·阿蒂亚博士：

...

...

that jumped out to me.

我突然想到了这一点。

Andrew Huberman:

安德鲁·休伯曼：

Yeah, I agree.

是的，我同意。

There's a bit more scatter on generalized anxiety, and the degree of significant change is not as robust.

广泛性焦虑的分散程度更高，而且显着变化的程度也不那么明显。

In other words, getting a lot of daytime light, ideally from sunlight, is not necessarily going to reduce your levels of anxiety.

换句话说，白天获得大量光线（最好是阳光）并不一定会降低您的焦虑程度。

Getting a lot of nighttime light exposure is not increasing nighttime anxiety that much, although 20% is not nothing for nighttime light exposure.

夜间接触大量光线并不会增加夜间焦虑，尽管 20% 对于夜间光线照射来说并不是什么。

But yeah, the psychosis, major depression, and self-harm are really-- they leap out.

但是，是的，精神病、重度抑郁症和自残确实——它们跳出来了。

Actually, maybe we even just drill a little bit deeper on major depression, and basically when you go from the second to third quartile of nighttime light exposure, so more nighttime light exposure, you basically go from no significant increase to almost a 20% increase.

事实上，也许我们甚至只是对重度抑郁症进行更深入的研究，基本上当你从夜间光照的第二个四分位数到第三个四分位时，所以更多的夜间光照，你基本上会从没有显着增加到几乎增加 20%。

And then as you get up to the fourth quartile, so the most nighttime light exposure, you're at about 25% increase in-

然后，当你到达第四个四分位数时，也就是夜间光照最多的时候，你的--增加了大约 25%

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah

是啊

Andrew Huberman:

安德鲁·休伯曼：

...

...

major depressive symptoms.

主要抑郁症状。

That's no joke.

这可不是开玩笑。

And I think that if we were to-- We don't have the data right here, but if we were to look at standard SSRI treatment for major depression, people debate this pretty actively, but light is a very potent stimulus, and the timing of light is critical because the inverse is also true.

我认为，如果我们——我们这里没有数据，但如果我们要看看标准的 SSRI 治疗重度抑郁症的方法，人们会非常积极地争论这一点，但光是一种非常有效的刺激，光的时机至关重要，因为反之亦然。

As you get to the fourth quartile of daytime light exposure, you get about a 20% reduction in major depressive disorder.

当白天光照达到第四个四分位时，重度抑郁症的发病率会降低约 20%。

Dr. Peter Attia:

彼得·阿蒂亚博士：

What I like about a study like this is that it puts the error bars so easy to see on the data.

我喜欢这样的研究，因为它使误差线在数据上很容易看到。

And why is that interesting?

为什么这很有趣？

Well, there's a belief that bigger is always better in sample size, and we often talk about that through the lens of power analysis, right?

嗯，人们相信样本量越大越好，我们经常通过功效分析的角度来谈论这一点，对吗？

So how many subjects do we need to reach a conclusion that is powered to this level?

那么，我们需要多少受试者才能得出如此有力的结论呢？

And that's true, but what I don't think gets discussed as often is the opposite of that, which is what if you overpower a study?

确实如此，但我认为人们不常讨论的恰恰是相反的情况，即如果你压倒了一项研究怎么办？

In other words, what if the power analysis says to have a level of power at 90%, you need 1,000 subjects, and you say, "Great, we're going to do 10,000 subjects." Well, you're clearly powered for it, but you might be overpowered, and people might say, "Well, why would that be a bad thing?" It could be a bad thing because it means you are very likely to reach statistical significance in things that might not be actually significant.

换句话说，如果功效分析显示功效水平为 90%，您需要 1,000 个受试者，然后您说：“太好了，我们要做 10,000 个受试者。”好吧，你显然有能力做到这一点，但你可能会被压倒，人们可能会说，“好吧，为什么那是一件坏事呢？”这可能是一件坏事，因为这意味着您很可能在实际上并不重要的事情上达到统计显着性。

And so one thing about this study that is just a quick and dirty way to tell that it's probably not overpowered is that you have varying lengths of error bars.

因此，这项研究的一件事是，你有不同长度的误差线，这是一种快速而肮脏的方式来判断它可能没有被压倒。

And what that tells me is that, and again, this is not a formal statistical analysis, it's just a back of the envelope statistical analysis.

这再次告诉我，这不是正式的统计分析，而只是粗略的统计分析。

If you look, for example, at self-harm in the top quartile, you actually have pretty big error bars.

例如，如果你观察前四分之一的自残行为，你会发现实际上有相当大的误差线。

In fact, all the self-harm have slightly bigger error bars.

事实上，所有的自残都有稍大的误差线。

And yet when you look at, for example, the depression, even though the error bars aren't all the same size, they're tighter.

然而，例如，当您观察抑郁症时，即使误差线的大小并不相同，但它们会更紧。

In fact, when you look at the relationship between depression and daytime light, the error bars are really, really small.

事实上，当你观察抑郁症和白天光线之间的关系时，你会发现误差线真的非常小。

So that just gives me confidence that there is variability in this, which paradoxically you kind of want to see because it tells me that this wasn't just done-- I think you said 8,000 subjects were in this, and I realized-

所以这让我相信这其中存在可变性，矛盾的是你有点想看到这一点，因为它告诉我这不仅仅是完成的——我想你说有 8,000 名受试者参与其中，我意识到——

Andrew Huberman:

安德鲁·休伯曼：

More than 86,000.

超过86,000。

Dr. Peter Attia:

彼得·阿蒂亚博士：

86,000, sorry.

86,000，抱歉。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

86,000.

86,000。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah, you realize that it wasn't that, oh, this should've been done with a tenth of that or a half of that.

是的，你意识到这不是那个，哦，这应该用十分之一或一半来完成。

And we're picking up signal that is statistically relevant but clinically irrelevant.

我们正在收集统计相关但临床无关的信号。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Yeah, thanks for that point that I didn't pay attention to that.

是的，谢谢你的这一点，我没有注意到这一点。

I paid attention to the error bars, but I didn't know that.

我注意了误差线，但我不知道。

So thank you.

所以谢谢你。

I'm learning, too.

我也正在学习呢

And I suppose for people that are listening, we can just give them a sense of what the error bar ranges are.

我想对于正在倾听的人来说，我们可以让他们了解误差线范围是多少。

For self-harm, they're running at as much as 20% either side of the mean, the average.

在自残方面，他们的自残率比平均值高出 20%。

And for major depression, it looks like it's more like, let's say eight to 10%.

对于重度抑郁症，看起来更像是 8% 到 10%。

Dr. Peter Attia:

彼得·阿蒂亚博士：

If that, yeah.

如果是这样，是的。

Andrew Huberman:

安德鲁·休伯曼：

If that.

如果那样的话。

Maybe more like five, right?

也许更像是五个，对吧？

So, yeah, I see what you're saying.

所以，是的，我明白你在说什么。

So when you get a very large sample size, you're going to have some outliers in there, and you can mask those outliers just by having so many data points, right?

因此，当您获得非常大的样本量时，就会有一些异常值，并且您可以通过拥有如此多的数据点来掩盖这些异常值，对吧？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah, because these error bars directly tell you whether or not you're statistically significant.

是的，因为这些误差线直接告诉你你是否具有统计显着性。

So what's really nice about this type of graph, and there's going to be a graph in my paper where you see the same analysis.

那么这种类型的图表到底有什么好处，在我的论文中将会有一个图表，您可以在其中看到相同的分析。

They're always drawing the 95% confidence interval on the data point.

他们总是在数据点上绘制 95% 的置信区间。

And if the 95% confidence interval does not touch the line of unity, which in this case is the odds ratio of 1.0 or the x-axis, then you know it's statistically significant to the confidence interval they've defined, which is almost assuredly 95%.

如果 95% 置信区间没有触及统一线（在本例中为 1.0 或 x 轴的优势比），那么您就知道它对于他们定义的置信区间具有统计显着性，几乎可以肯定为 95%。

Sometimes they'll make it tighter at 99.

有时他们会在 99 时把它弄得更紧。

And so that's why you can just look right at these and go, "Oh, look, in depression, the second quartile didn't reach statistical significance because the error bars are touching the line," just as the case for the second and third quartile for self-harm.

这就是为什么你可以直接看这些，然后说，“哦，看，在抑郁症中，第二个四分位数没有达到统计显着性，因为误差线已经触及界限”，就像第二个和第三个四分位数的自残情况一样。

But when you look at the fourth quartile, you can see that the lower tip of the error bars isn't anywhere near unity, and so we know without having to look up the P-value that it's smaller than either .05 or .1, however they've defined it.

但是，当您查看第四个四分位数时，您会发现误差线的下端并不接近统一，因此我们无需查找 P 值就知道它小于 0.05 或 0.1，无论他们如何定义它。

And it's really amazing when you see these overpowered studies, which are easier to do epidemiologically, where the P-value ends up being microscopic.

当你看到这些强有力的研究时，你会感到非常惊讶，这些研究从流行病学角度来说更容易进行，但 P 值最终却是微观的。

They can drive their P-values down to anything low because sample size can be infinite.

他们可以将 P 值降低到任意低的水平，因为样本量可以是无限的。

But you can see that the error bar is just skimming above the unity line, but it's so tight.

但您可以看到误差线只是略过统一线，但它非常紧。

Andrew Huberman:

安德鲁·休伯曼：

One thing that I hope people are taking away from this study is that imagine you're somebody who has a very sensitive circadian mood system.

我希望人们从这项研究中学到的一件事是，想象你是一个拥有非常敏感的昼夜节律情绪系统的人。

Well, that would mean you need less daytime light exposure to feel good or less bad, but it also means that you might need very little light at night in order to negatively impact your mood systems.

好吧，这意味着您需要较少的白天接触光来感觉良好或不那么糟糕，但这也意味着您在晚上可能需要很少的光才能对您的情绪系统产生负面影响。

And in fact, they make this argument in the discussion as an interesting point that I think is worth mentioning.

事实上，他们在讨论中将这一论点作为一个有趣的观点，我认为值得一提。

Because here, again, what I like about this study is that they've separated day and nighttime light exposure.

因为在这里，我再次喜欢这项研究，因为他们将白天和夜间的光照分开。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

It turns out that many of the drugs that are used to treat bipolar disorder are effective, perhaps in part because they reduce the sensitivity of the light-sensing circadian apparati.

事实证明，许多用于治疗双相情感障碍的药物都是有效的，部分原因可能是它们降低了光传感昼夜节律装置的敏感性。

Now, that's interesting, right?

现在，这很有趣，对吧？

If you think about this, okay, so these are drugs that can ameliorate some of the symptoms of bipolar, perhaps in part by reducing the extent to which nighttime light exposure can exacerbate bipolar symptoms.

如果你想一想，好吧，这些药物可以改善躁郁症的一些症状，也许部分是通过减少夜间光线照射加剧躁郁症症状的程度来实现的。

Conversely, there's evidence that people who take certain antidepressants may suppress the ability for daytime light-

相反，有证据表明服用某些抗抑郁药的人可能会抑制白天接受光线的能力——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Mm

毫米

Andrew Huberman:

安德鲁·休伯曼：

...

...

to positively impact the mood systems of the brain.

对大脑的情绪系统产生积极影响。

Now, of course, we don't want people halting their medication on the basis of that statement alone.

当然，现在我们不希望人们仅仅因为这一声明就停止用药。

Please don't.

请不要。

Talk to your psychiatrist.

和你的精神科医生谈谈。

But if we know one thing for sure, it's that if you want a significant outcome and a paper as a scientist Give a drug, any drug, and look at the amount of rapid eye movement sleep or the circadian cycle.

但如果我们确定一件事，那就是如果你想要一个显着的结果和一篇作为科学家的论文，给予一种药物，任何药物，并观察快速眼动睡眠的量或昼夜节律周期。

Pretty much any drug alters the circadian rhythm, for better or worse.

几乎任何药物都会改变昼夜节律，无论好坏。

But if we start to think about which medications might adjust our overall sensitivity to light, sometimes this could be a good thing.

但如果我们开始考虑哪些药物可以调整我们对光的整体敏感性，有时这可能是一件好事。

You think less sensitivity to light.

你认为对光的敏感性较低。

Well, for people who have bipolar disorder, the amount of daytime light exposure isn't that important for their overall mood regulation, but the amount of nighttime light exposure really is.

对于双相情感障碍患者来说，白天的光照量对于他们的整体情绪调节并不那么重要，但夜间的光照量确实很重要。

In other words, darkness for eight hours every night should be viewed, in my opinion, as a treatment for bipolar disorder.

换句话说，在我看来，每晚八小时的黑暗应该被视为治疗双相情感障碍的方法。

Not the only treatment.

不是唯一的治疗方法。

But it's also clear that we should all be avoiding extensive really bright nighttime light exposure.

但同样清楚的是，我们都应该避免大量的真正明亮的夜间光线照射。

If anything, my takeaway from this study is that darkness at night is the fourth key light stimulus.

如果说有什么不同的话，我从这项研究中得出的结论是，夜间的黑暗是第四个关键的光刺激。

Now, a couple of things.

现在，有几件事。

Very bright moonlight, very bright candlelight, is probably only like, gosh, three to 50 lux.

非常明亮的月光，非常明亮的烛光，可能只有，天哪，三到50勒克斯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

What?

什么？

Andrew Huberman:

安德鲁·休伯曼：

When you go outside on a brightly lit full moon night-- I encourage people to download this free app, I have no relationship to it, called Light Meter, and it gives you a pretty good read of what the lux are in that environment.

当你在灯火通明的满月之夜外出时——我鼓励人们下载这个免费的应用程序，我与它没有任何关系，它被称为照度计，它可以让你很好地了解该环境中的勒克斯情况。

By the way, a lot of people don't realize this.

顺便说一句，很多人没有意识到这一点。

They think you just tap the button, and then it tells you how many lux.

他们认为你只需点击按钮，然后它就会告诉你有多少勒克斯。

You hold it down.

你按住它。

It's kind of fun.

这很有趣。

You can scan around the room and see how many lux are on average coming from that location or outside.

您可以扫描房间周围，看看来自该位置或外部的平均勒克斯数。

Go out on a really bright moonlit night.

在一个非常明亮的月夜出去。

Dr. Peter Attia:

彼得·阿蒂亚博士：

We should have a full moon tonight.

今晚我们应该有满月。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Let's do it.

我们开始做吧。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

You're not going to get above 100 lux.

你不会达到 100 勒克斯以上。

Dr. Peter Attia:

彼得·阿蒂亚博士：

That's incredible.

这太不可思议了。

Andrew Huberman:

安德鲁·休伯曼：

You're sitting at a candlelight dinner with your spouse or with friends, and it's clearly bright enough to see them.

您正与配偶或朋友坐在烛光晚餐上，显然光线足够亮，可以看到他们。

Put that lux meter right up, not too close to the flame.

将勒克斯计放在正上方，不要太靠近火焰。

Fifty to 200 lux.

50 至 200 勒克斯。

Maybe 400 lux.

也许 400 勒克斯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

I had an interesting experience a couple of months ago on an elk hunt, where it was a full moon, which actually makes the hunting not so great.

几个月前，我在狩猎麋鹿时经历了一次有趣的经历，当时正值满月，这实际上让狩猎变得不太顺利。

But it was the first time I've ever noticed my shadow in relation to the moon.

但这是我第一次注意到我的影子与月亮的关系。

That's how bright it seemed the light was, but-

光看上去就是这么亮，但是——

Andrew Huberman:

安德鲁·休伯曼：

This is Halloween appropriate.

这很适合万圣节。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

Since we're recording this close to Halloween.

因为我们是在万圣节前夕录制的。

Yeah, it's remarkable.

是的，这很了不起。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So super interesting to think it could be that dim.

想到它可能这么暗真是太有趣了。

Andrew Huberman:

安德鲁·休伯曼：

Campfire-

篝火-

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah

是啊

Andrew Huberman:

安德鲁·休伯曼：

...

...

and firelight.

和火光。

You think, okay, gathering around a campfire.

你想，好吧，聚集在篝火旁。

Well, then okay, everyone's circadian rhythm must've been disrupted for ages before the development of electricity.

好吧，那么好吧，在电力发展之前，每个人的昼夜节律肯定已经被打乱了很长时间。

No. Those campfires are extremely bright, but they're not that bright compared to a very densely overcast day.

不。那些篝火非常明亮，但与浓密的阴天相比，它们并没有那么明亮。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And what is your phone, if you don't use any sort of light mitigating tech on it?

如果你不使用任何减光技术，你的手机是什么？

Andrew Huberman:

安德鲁·休伯曼：

Well, distance matters.

嗯，距离很重要。

But-

但是——

Dr. Peter Attia:

彼得·阿蒂亚博士：

But at the distance we're holding it.

但在远处，我们握着它。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

So with all the wavelengths cranked up.

因此，所有波长都调高了。

There is a nice feature intrinsic to the phone where you can eliminate the blues at night or this kind of thing.

这款手机有一个很好的固有功能，可以消除夜间的忧郁或类似的情况。

But if you crank it up to maximum light intensity, probably something like 500 to 1,000 lux.

但如果将其调至最大光强度，可能约为 500 至 1,000 勒克斯。

Now, keep in mind, though, it's additive, right?

但现在请记住，它是累加的，对吗​​？

So it's over time.

所以时间已经过去了。

So lux is a measure of, I think it relates back to candelas.

所以勒克斯是一种衡量标准，我认为它与坎德拉有关。

It's the amount of light shown, and I think it's one meter away, and there's a squaring and a falling off of distance.

这是所显示的光量，我认为在一米之外，距离有平方和下降。

We can look it up.

我们可以查一下。

These are old school measurements converted to lux.

这些是转换为勒克斯的老式测量值。

But keep in mind that if you're looking at your phone or tablet at 800 lux or 500 lux in the evening, and you do that for two hours, well, you're summing quite a lot of photons.

但请记住，如果您在晚上在 800 勒克斯或 500 勒克斯的光照条件下查看手机或平板电脑，并且持续两个小时，那么您就会汇总相当多的光子。

Now, it is true, and I do want to be fair to the biology, and it'd be dishonest to say anything different.

现在，这是真的，我确实想公平地对待生物学，说任何不同的话都是不诚实的。

We've hammered on people about not shifting their circadian rhythm with light at night.

我们一直敦促人们不要在夜间用光改变他们的昼夜节律。

But we know that the middle of the day and the middle of the night are circadian dead zones.

但我们知道，中午和半夜是昼夜节律死区。

You can't shift your circadian rhythm that well in the middle of the day and the middle of the night.

你无法在白天和半夜很好地改变你的昼夜节律。

But you can provide a wake-up signal for your body and brain.

但你可以为你的身体和大脑提供唤醒信号。

It's really that sunrise and sunset that are critical.

真正至关重要的是日出和日落。

That's why I said there are four things.

所以我说有四件事。

See sunrise or sun rising.

看到日出或太阳升起。

You don't need to see it cross the horizon.

你不需要看到它越过地平线。

Sunset, bright light during the day, minimize light exposure at night.

日落时，白天光线明亮，夜间尽量减少光照。

And you don't need pitch black.

而且你不需要漆黑一片。

In fact, pitch black probably just increases the frequency of injury.

事实上，漆黑可能只会增加受伤的频率。

I get up in the middle of the night to use the bathroom probably once.

我可能半夜起床去一次卫生间。

I think that's normal.

我认为这很正常。

I go back to sleep.

我回去睡觉了。

If it were pitch black, I'd probably injure myself.

如果周围漆黑一片，我可能会受伤。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

So just dim it down.

所以只要把它调暗一点就可以了。

Some people use red lights.

有些人使用红灯。

Our friend Rick Rubin.

我们的朋友里克·鲁宾。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Our mutual friend.

我们共同的朋友。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Rick Rubin is lights-

里克·鲁宾 (Rick Rubin) 很亮——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Can we tell a funny story about Rick?

我们能讲一个关于瑞克的有趣故事吗？

Andrew Huberman:

安德鲁·休伯曼：

Yeah, of course.

是的，当然。

Dr. Peter Attia:

彼得·阿蒂亚博士：

You know this story, but just in case Rick's listening, he'll appreciate this.

你知道这个故事，但万一瑞克在听，他会很感激的。

When Rick was here staying last summer, he's up in our guest house, and he came down after the first night, and he was like, "Unacceptable." You know what I'm talking about, right?

去年夏天里克在这里住宿时，他在我们的宾馆里，第一晚后他就下来了，他说，“不可接受。”你知道我在说什么，对吧？

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Unacceptable accommodations.

无法接受的住宿条件。

Dr. Peter Attia:

彼得·阿蒂亚博士：

What did he do?

他做了什么？

Andrew Huberman:

安德鲁·休伯曼：

He removed all the lighting that existed in that room and replaced it with red light bulbs, which I later used when I stayed here, and then later stole when I left.

他把那个房间里的所有照明灯都拆掉了，换上了红色灯泡，后来我住在这里的时候用了它，后来我离开的时候又偷了。

The teenage me, I took them.

十几岁的我，我带走了它们。

That's why Derek, when he stayed here, or Lane, or anyone else who stayed here, Conti or anyone else, didn't have those.

这就是为什么德里克，当他留在这里时，或者莱恩，或者任何留在这里的人，康蒂或者其他人，都没有这些。

I took them.

我拿走了它们。

I love them.

我爱他们。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So funny.

太有趣了。

Jill is like, "You know Rick changed every light in the guest house to red?" I'm like, "Yeah.

吉尔说：“你知道瑞克把宾馆里的每一盏灯都变成了红色吗？”我想，“是啊。

No, I didn't know that, but I'm not surprised."

不，我不知道，但我并不感到惊讶。”

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Well, in his place, he has mostly either no lighting or red lighting.

好吧，在他的位置上，他要么没有灯光，要么有红色灯光。

So during the day, he just goes by ambient light, and then red light in the evening, or candlelight.

因此，白天他只依靠环境光，然后在晚上使用红光或烛光。

And it's great.

这很棒。

And people hear red lights, and they think they have to buy these expensive red light units.

人们听到红灯，他们认为必须购买这些昂贵的红灯装置。

But that's not what we're talking about.

但这不是我们要讨论的。

You can literally buy red party lights or just a red bulb.

您实际上可以购买红色派对灯或仅购买红色灯泡。

Some people say, "Well, can I just use a red film, or can I put a T-shirt over the lamp?" I worry about people putting T-shirts over lamps because of the fire hazard.

有人说：“那么，我可以只使用红色胶片吗？或者我可以在灯上放一件 T 恤吗？”我担心人们把 T 恤放在灯上，因为存在火灾危险。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah, that starts to get bad.

是的，情况开始变得糟糕。

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

But I'll be honest, I dim the lights in my home at night.

但说实话，晚上我会把家里的灯调暗。

When I travel, sometimes I will bring one of the stolen from Rick Rubin red lights.

当我旅行时，有时我会带上一盏从 Rick Rubin 偷来的红灯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

The Rick Rubin stuff.

里克·鲁宾的事。

Here's something where I've sort of softened my tune.

这是我稍微软化了我的语气的地方。

So I used to be kind of a hardliner, no blue light in the evening guy.

所以我曾经是一个强硬派，晚上没有蓝光。

Everything was red light at night as far as my phone, using f.lux on the computer, whatever it was.

晚上，就我的手机而言，一切都是红灯，在电脑上使用 f.lux，无论是什么。

I suspect that that matters somewhat, but I think what matters more is the stimulation that may come from those things.

我怀疑这有点重要，但我认为更重要的是这些事情可能带来的刺激。

And what I've come to realize, at least in me, which means it probably is true in others as well, in at least some others, is that what I'm doing on my phone matters more than how bright my phone is.

我逐渐意识到，至少对我来说，这意味着对其他人来说可能也是如此，至少对其他一些人来说，我在手机上所做的事情比我的手机有多亮更重要。

In other words, if I've got the best blue light filter in the world on my phone, but I'm doom scrolling social media and getting lit up on email, that's way worse for me than if I've got my phone on maximum light and I'm watching YouTube videos of F1 cars and driving around having fun.

换句话说，如果我的手机上有世界上最好的蓝光过滤器，但我却注定要滚动社交媒体并被电子邮件点亮，这对我来说比我将手机开到最大亮度并观看 F1 赛车的 YouTube 视频并四处驾驶乐趣更糟糕。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Oh.

哦。

Dr. Peter Attia:

彼得·阿蒂亚博士：

It's a totally different experience.

这是一种完全不同的体验。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So the context matters and I think for that reason, I would want people to be mindful of the whole picture.

因此，背景很重要，我认为出于这个原因，我希望人们能够关注整个情况。

Going to bed under a period of intense duress brought on by something, that's an equally dangerous component to all of this that's distinct from what we're talking about.

在某种事物带来的强烈胁迫下上床睡觉，这对于所有这一切来说都是同样危险的组成部分，这与我们正在谈论的不同。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

But I want people to be able to think of this in the context of everything.

但我希望人们能够在一切事物的背景下思考这一点。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

It's a really important point.

这是非常重要的一点。

One thing I'll say is that if you're going to stay up past your normal bedtime, if you're going to get a lot of light in your eyes, I would hope that it would be for fun reasons and for reasons you enjoy.

我要说的一件事是，如果你要熬夜超过正常的就寝时间，如果你要让眼睛里充满阳光，我希望这是出于有趣的原因和你喜欢的原因。

You should definitely spend some nights out.

你绝对应该出去玩几个晚上。

You should definitely do some all-nighters studying if it's going to help you get the grade that's permanent, right?

如果能帮助你获得永久的成绩，你绝对应该通宵学习，对吗？

I'd certainly have done all-nighters studying and grant writing for years.

我肯定会多年来通宵学习和撰写资助论文。

There are going to be the inevitable all-nighters due to, God forbid, a trip to the hospital, or you heard something on the news that really amped you up, or you just simply can't sleep.

由于去医院，或者你在新闻中听到了一些真正让你兴奋的事情，或者你只是无法入睡，所以不可避免地会通宵达旦。

That stuff is going to happen.

那件事将会发生。

So I think the goal should be to minimize light exposure at night.

所以我认为目标应该是尽量减少夜间的光照。

And I think what you just said is especially true because we don't know-- For instance, people talk about the negative impact of social media.

我认为你刚才所说的尤其正确，因为我们不知道——例如，人们谈论社交媒体的负面影响。

Is it the fact that people are looking at this little box for so many hours per day?

难道是因为人们每天花这么多时间盯着这个小盒子吗？

Is it all the things they're not doing?

难道这一切都是他们没有做的事情吗？

Is it what they're looking at per se?

这是他们本身所关注的吗？

All of those things interact and are really important.

所有这些事情相互作用并且非常重要。

We know based on studies from the Stanford Sleep Lab that if you wake up in the middle of the night, looking at what time it is can be very disruptive to your ability to fall back asleep and to your sense the next day, it's a placebo effect, but it's a powerful one, of how tired you are the next day.

根据斯坦福睡眠实验室的研究，我们知道，如果你半夜醒来，看看现在是什么时间，可能会对你重新入睡的能力和第二天的感觉产生很大的干扰，这是一种安慰剂效应，但它是一种强大的效应，可以让你知道第二天你有多累。

They've done this where they wake people up in the middle of the night and then they say it's 4:00 a.m.

他们会在半夜叫醒人们，然后说现在是凌晨 4:00。

versus 2:00 a.m.

与凌晨 2:00 相比

versus 6:00 a.m.

与上午 6:00 相比

And people's perceived levels of energy during the day in some ways correlate with what they think, how much sleep they think they got.

人们在白天感知到的精力水平在某种程度上与他们的想法以及他们认为自己获得了多少睡眠有关。

Likewise, and this is one of the potential concerns with sleep trackers.

同样，这是睡眠追踪器的潜在问题之一。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yep.

是的。

Andrew Huberman:

安德鲁·休伯曼：

Ali Crum talked about this when she came on our podcast.

Ali Crum 在参加我们的播客时谈到了这一点。

If people see a poor sleep score, they often feel worse than if they see a good sleep score.

如果人们看到较差的睡眠分数，他们通常会比看到良好的睡眠分数时感觉更糟。

Now, of course, physiology matters.

当然，现在生理学很重要。

You can't lie to yourself and say you got a great night's sleep simply by virtue of a sleep score.

您不能对自己撒谎，仅仅凭借睡眠分数就说自己睡得很好。

But I worry more about the false-- Well, if it's a false negative that we don't want to put valence on this.

但我更担心错误——好吧，如果这是一个假阴性，我们不想对此进行定价。

Seeing a bad sleep score and then deciding that you're going to have a terrible day.

看到糟糕的睡眠分数，然后决定您将度过糟糕的一天。

I think a bad sleep score is an indication that you might need to dial some things in a bit better.

我认为糟糕的睡眠分数表明您可能需要更好地调整一些事情。

Getting a great sleep score is an indication that you might be doing a number of things right and start looking at these things as averages.

获得良好的睡眠分数表明您可能做对了很多事情，并开始将这些事情视为平均值。

Would you agree?

你同意吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah, completely.

是的，完全如此。

I don't think it's that different from CGM, right?

我觉得这和CGM没什么区别吧？

I think that CGM is an amazing tool to provide insight, and you pretty much know the insights after a relatively short period of time.

我认为 CGM 是一个提供洞察力的神奇工具，并且在相对较短的时间内你就几乎了解了这些洞察力。

30 days, maybe at the outside 90 for a person with a very complicated life, and you know all you need to know about how the inputs affect the output.

30天，对于一个生活非常复杂的人来说，也许在外面的90天，你就知道了所有你需要知道的关于输入如何影响输出的信息。

Thereafter, if you choose to use it, it's a behavioral tool.

此后，如果您选择使用它，它就是一种行为工具。

In other words, you're using this to build in a Hawthorne effect.

换句话说，您正在使用它来构建霍桑效果。

I think the same is largely true with sleep trackers.

我认为睡眠追踪器基本上也是如此。

Most people have this profound sense of learning when they first encounter one of these things.

大多数人在第一次遇到这些事情时都会有这种深刻的学习意识。

And it's, again, you've heard it all 100 times.

再说一遍，这句话你已经听过 100 遍了。

"Oh my God, I can't believe what alcohol does to my sleep."

“天哪，我简直不敢相信酒精对我的睡眠有什么影响。”

Andrew Huberman:

安德鲁·休伯曼：

Right.

对。

Or caloric trackers.

或热量追踪器。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Exactly.

正是如此。

Andrew Huberman:

安德鲁·休伯曼：

I think Layne Norton's app Carbon, I have no financial relationship to it.

我认为 Layne Norton 的应用程序 Carbon，我与它没有任何财务关系。

I use it, and it's taught me, wow, I consume a lot of calories in the form of certain things at certain times of day, and there's just a lot of good learning in that.

我使用它，它教会了我，哇，我在一天中的某些时间以某些东西的形式消耗了大量的卡路里，这里面有很多很好的学习。

Dr. Peter Attia:

彼得·阿蒂亚博士：

But it's the act of tracking that helps you manage it, and similarly, I think it's the act of knowing you're going to be looking at that score that gamifies it, that kind of helps people do the right things.

但跟踪行为可以帮助你管理它，同样，我认为知道你将查看分数的行为可以将其游戏化，这可以帮助人们做正确的事情。

"Oh, you know what?

“哦，你知道吗？

I'm not going to have that drink tonight," or, "I'm not going to eat that snack before bed because I've now been conditioned to see how that impacts score." That said, I think that recovery scores and things like that are just notoriously poor at predicting performance, and I think there's a reason that serious athletes would never use things like that.

我今晚不会喝那种饮料，”或者，“我不会在睡觉前吃那种零食，因为我现在已经习惯了看看这对分数有何影响。”也就是说，我认为恢复分数和类似的东西在预测表现方面是出了名的差，而且我认为严肃的运动员永远不会使用这样的东西是有原因的。

They would tend to rely on the more tried and true methods of predicting behavior, such as heart rate, maybe heart rate variability, but morning resting heart rate probably more predictive than anything else.

他们倾向于依赖更可靠的方法来预测行为，例如心率，也许是心率变异性，但早晨静息心率可能比其他任何方法都更具预测性。

And then in-workout things such as heart rate, heart rate recovery, lactate threshold, things like that.

然后是锻炼中的心率、心率恢复、乳酸阈值等。

So yeah, I agree.

所以是的，我同意。

I think we have to, and I say this as a guy who's generally perceived to be the most pro device guy in the world, people would be surprised how sparingly I use things like that.

我认为我们必须这样做，而且我这么说是因为我是一个被普遍认为是世界上最专业的设备人士，人们会惊讶于我很少使用这样的东西。

Andrew Huberman:

安德鲁·休伯曼：

I do some tracking, not as much as you.

我做了一些跟踪，但没有你那么多。

I love things that seem to work the first time and every time in terms of our natural biology based on a couple of criteria.

我喜欢那些在我们的自然生物学方面基于几个标准似乎第一次和每次都有效的东西。

There's an established mechanism.

有既定机制。

It's been explored in the context of pathology, like mental health disorders, as well as pro-health in healthy individuals, that it make really good sense at the level of kind of wellness and let's just say ancient health.

人们在病理学的背景下进行了探索，比如精神健康障碍，以及健康个体的促进健康，它在健康水平上非常有意义，我们就说古代健康。

When you're talking about getting a lot of sunlight during the day, a lot of people say, "Well, of course.

当你谈论白天获得大量阳光时，很多人会说：“嗯，当然。

Get outside and play." Not getting too much light at night.

出去玩吧。”晚上不要接受太多光线。

Of course, this is just quote-unquote good old-fashioned advice.

当然，这只是一个不加引用的老式建议。

People spend 90% of their time indoors now.

现在人们90%的时间都在室内度过。

Their daytime environments are too dim.

他们白天的环境太暗了。

Their nighttime environments are too bright.

他们的夜间环境太亮了。

And this kind of misleading aspect of artificial light, that when you see a bright bulb, you think, "I'm getting a lot of photons," is part of the problem.

人造光的这种误导性，当你看到一个明亮的灯泡时，你会想，“我得到了很多光子”，这是问题的一部分。

And the fact that when you're out on an overcast day, and you think the sun, quote-unquote, "isn't out," well, it's hidden by cloud cover.

事实上，当你在阴天外出时，你会认为太阳“没有出来”，好吧，它被云层遮住了。

But just think about how well you can navigate that environment without a flashlight-

但想想看，在没有手电筒的情况下，你能在那个环境中导航得有多好——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah

是啊

Andrew Huberman:

安德鲁·休伯曼：

...

...

versus at night, where you would require a flashlight.

而在晚上，你需要手电筒。

We evolved under this dramatic difference in day-night availability of photons, independent of whether or not you can, quote, "see the sun." And it's just very clear that all the mechanisms in our brain and body that regulate mood are just powerfully regulated by this stuff.

我们是在光子的昼夜可用性的巨大差异下进化的，无论你是否可以引用“看到太阳”。很明显，我们大脑和身体中调节情绪的所有机制都受到这些东西的有力调节。

So I've made it a point to really reduce the amount of nighttime light that I'm getting, but I am less concerned about flipping on the light switch to use the bathroom as I used to be.

因此，我确实减少了夜间的光线量，但我不太担心像以前那样打开灯开关使用浴室。

I used to think, "Oh, I'm quashing all my melatonin.

我曾经想，“哦，我正在耗尽我所有的褪黑激素。

This is terrible." I know I can't shift my circadian clock then.

这太可怕了。”我知道我无法改变我的生物钟。

I know that that light, yes, while it's bright, if it's brief, I'm not going to worry about it too much.

我知道那道光，是的，虽然它很亮，但如果它很短暂，我就不会太担心。

Would it be better to have a dim light on as opposed to a bright light?

开着昏暗的灯会比开着明亮的灯更好吗？

Sure.

当然。

But I'm not going to stress it in a hotel bathroom or something.

但我不会在酒店浴室或其他地方强调这一点。

I'm not going to walk around shielding my eyes.

我不会遮着眼睛走来走去。

People sometimes ask me, by the way, is it different to look at the phone directly versus if you tilt the phone away?

顺便说一句，人们有时会问我，直视手机与倾斜手机有什么不同吗？

Well, it absolutely is.

嗯，确实如此。

Think about a flashlight shone on the ground in front of you.

想象一下手电筒照在你面前的地面上。

Very few photons getting in your eyes versus shone directly into your eyes.

与直接照射到您的眼睛相比，很少有光子进入您的眼睛。

Think about ambient light from the sun going everywhere versus looking in the general direction of the sun.

考虑一下来自太阳的环境光无处不在，而不是朝着太阳的大致方向看。

So east in the morning, west in the afternoon, of course.

当然，早上向东，下午向西。

The directionality of the light matters.

光的方向性很重要。

So I'm not saying that you need to peek at your phone as if you're looking over the edge of a bowl or something into it.

所以我并不是说你需要像从碗边或其他东西往里面看一样看手机。

But my friend, Samer Hattar, who's head of the chronobiology unit at the National Institutes of Mental Health, we used to room together at meetings.

但我的朋友萨默·哈塔尔（Samer Hattar）是美国国立心理健康研究所时间生物学部门的负责人，我们过去经常在会议上住在一起。

We stopped because he's a terrible snorer.

我们停下来是因为他打呼噜很厉害。

There were a few times when I considered suffocating him in the middle of the night, since he was already suffocating himself.

有几次我在半夜考虑让他窒息，因为他已经窒息了。

Now we don't stay in the same rooms anymore.

现在我们不再住在同一个房间了。

We're no longer post-docs.

我们不再是博士后了。

But I caught him looking at his phone in the middle of the night, and he would tilt it away like he's holding a platter, for those that are just listening, and kind of looking over at the screen there.

但我发现他在半夜看手机，他会把手机倾斜起来，就像拿着一个盘子一样，对于那些只是听着、看着屏幕的人来说。

I'm like, "What are you doing?

我说：“你在做什么？

This is ridiculous." And he said, "I'm trying not to get so much light in my eyes." That's a little extreme, but I think it illustrates the point, which is how much direct light exposure you get at night matters.

这太荒谬了。”他说：“我正在努力不让太多的光线进入我的眼睛。”这有点极端，但我认为它说明了这一点，即夜间接受多少直接光照很重要。

How much direct sunlight exposure you get, especially early morning, late afternoon, and throughout the day, it really matters.

您接受多少直射阳光照射，尤其是清晨、傍晚和全天，这确实很重要。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Now remind me, Andrew, what is the wavelength of sunlight?

现在提醒我，安德鲁，阳光的波长是多少？

Andrew Huberman:

安德鲁·休伯曼：

Great.

太棒了。

So sunlight is going to include all visible spectra, right?

那么阳光将包括所有可见光谱，对吧？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Which runs from how many nanometers to what?

从多少纳米到多少纳米？

Andrew Huberman:

安德鲁·休伯曼：

We can answer two questions there.

我们可以在那里回答两个问题。

This wrist sensor detected 470 nanometer to 650 nanometer light.

该手腕传感器检测到 470 纳米至 650 纳米的光。

So that's going to be blue and ultraviolet.

所以这将是蓝色和紫外线。

Ultraviolet's kind of high threes.

紫外线的那种三声欢呼。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah, that's kind of like blue to orange.

是的，这有点像蓝色到橙色。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Blue to orange.

蓝色到橙色。

That's what this was measuring.

这就是这个测量的内容。

So red light is going to be more like 680.

所以红光会更像680。

Far-red is getting out to 700, 720, and up, upwards of that.

远红光正在达到 700、720 甚至更高。

Blue light is going to fall somewhere in the low fours.

蓝色的光将会落在四肢下方的某个地方。

Ultraviolet is getting down into the high threes and lower.

紫外线正在下降到高三和更低。

And so these spectra of light.

这些光谱也是如此。

So during the day, midday light, you're getting what looks like white light.

因此，在白天，正午的光线下，您会看到看起来像白光的光。

You'll see, oh, the sky is blue and the sun is bright white light.

你会看到，哦，天空是蓝色的，太阳是明亮的白光。

It's not even yellow to your eye.

在你看来它甚至不是黄色的。

And of course, don't stare at it, especially in the middle of the day.

当然，不要盯着它看，尤其是在中午。

You're getting all visible spectra, so you're getting everything from UV all the way out to red light.

您将获得所有可见光谱，因此您将获得从紫外线到红光的所有光谱。

It's just coming in at equal intensities.

它只是以相同的强度出现。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So is that a potential limitation of this study, in that it didn't have a sensor that could pick up the full spectrum of light?

那么，这是否是这项研究的潜在限制，因为它没有可以拾取全光谱的传感器？

Andrew Huberman:

安德鲁·休伯曼：

Potentially, especially since we don't think of humans as UV capable.

有潜力，特别是因为我们不认为人类具有紫外线能力。

We can't perceive UV light.

我们无法感知紫外线。

Like a ground squirrel, for instance, has UV sensors in its eyes.

例如，地松鼠的眼睛里有紫外线传感器。

Turns out, you know why they use this?

事实证明，你知道他们为什么用这个吗？

It's crazy.

太疯狂了。

When the ground squirrels sit up on their haunches, they're actually signaling one another.

当地松鼠用臀部坐起来时，它们实际上是在互相发出信号。

They rub urine on their belly, and it reflects UV.

他们将尿液擦在腹部，尿液会反射紫外线。

The New York Times, for some reason, has been running a series of papers, or articles rather, about naturally occurring fluorescence at night in all sorts of species.

出于某种原因，《纽约时报》刊登了一系列关于各种物种在夜间自然产生的荧光的论文，或者更确切地说是文章。

Scorpions and monotremes, like the platypus.

蝎子和单孔目动物，如鸭嘴兽。

No one really knows the reason for these odd wavelength of light emissions for all these animals.

没有人真正知道所有这些动物发出这些奇怪波长的光的原因。

But we view things in the blue, violet, and up to red, and we're not pit vipers.

但我们看待事物的方式是蓝色、紫色、甚至红色，而我们并不是毒蛇。

We can't see far-red.

我们看不到远红光。

But we can see lower than 470 nanometers, and we can see higher than 650.

但是低于470纳米我们可以看到，高于650纳米我们可以看到。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Is there a technology reason why they had such a narrow band in these sensors?

是否存在技术原因导致这些传感器的频带如此窄？

Is it not possible that they could have used a wrist sensor that was wider?

难道他们不可能使用更宽的手腕传感器吗？

Andrew Huberman:

安德鲁·休伯曼：

This study was initiated in 2013.

这项研究于 2013 年启动。

The tech was probably far worse than it is now.

当时的技术可能比现在差得多。

Again, I would love for somebody to design an eyeglass where it's measuring how many photons you're getting across the day.

再说一次，我希望有人能设计一款眼镜，它可以测量你一天中接收到的光子数量。

I'm not a big fan of having everything be app-ified, so I would love it if the frame would just shift color across the morning.

我不太喜欢把所有东西都应用到应用程序中，所以如果框架能在早上改变颜色，我会很高兴。

You go outside on a cloudy day, you wear these glasses and-- By the way, it's fine to wear eyeglasses or contacts for sunlight viewing, for setting your circadian rhythm.

你在阴天外出，戴上这些眼镜——顺便说一句，戴眼镜或隐形眼镜观看阳光是可以的，可以设定你的昼夜节律。

People always say, "Well, why is that okay and a window's not?" Well, corrective lenses are actually focusing the light onto your retina.

人们总是说：“好吧，为什么那可以，而窗户不行呢？”嗯，矫正镜片实际上是将光线聚焦到视网膜上。

The windows and windshields are scattering the light and filtering it.

窗户和挡风玻璃会散射并过滤光线。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And how much are sunglasses filtering this out?

太阳镜能过滤掉多少这种物质？

Andrew Huberman:

安德鲁·休伯曼：

Way too much.

太多了。

We can safely say way too much.

我们可以放心地说得太多了。

Probably causing a tenfold decrement in the total lux count that's landing on your retina.

可能会导致落在您视网膜上的总勒克斯数减少十倍。

But of course, sunglasses are important driving into sun, and some people have very sensitive eyes.

当然，在阳光下开车时，太阳镜很重要，而且有些人的眼睛非常敏感。

I can't sit at a cafe with a brightly reflective table in the afternoon.

下午我不能坐在一张桌子反光明亮的咖啡馆里。

I just squint like crazy.

我只是疯狂地眯着眼睛。

I can't do it.

我做不到。

My dad who's darker-eyed and he's South American descent, he can just sit there just fine.

我爸爸的眼睛颜色较深，是南美血统，他可以坐在那里就好了。

My mom, who's got light eyes like me, we're like, "Oh, it's really tough." We just have a terrible time.

我妈妈和我一样有着明亮的眼睛，我们就像，“哦，这真的很难。”我们只是度过了一段糟糕的时光。

People differ in their light sensitivity.

人们对光的敏感度不同。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So there's one other macro question I have here, and it's not answerable because without randomization, we can't know it.

所以我这里还有另一个宏观问题，它无法回答，因为如果没有随机化，我们就无法知道它。

But it's the question of how much reverse causality can exist in these observations.

但问题是这些观察结果中可以存在多少反向因果关系。

So again, these observations demonstrate very tight correlations, very strong associations, especially in the five areas that we highlighted.

因此，这些观察结果再次证明了非常紧密的相关性和很强的关联性，特别是在我们强调的五个领域。

But it's possible that part of what we're seeing is reverse causality brought on by both the treatments, which you've already kind of alluded to, and also the condition itself.

但我们所看到的部分情况可能是由您已经提到过的治疗方法以及病情本身带来的反向因果关系。

Andrew Huberman:

安德鲁·休伯曼：

Do you want to explain reverse causality for people?

你想给人们解释一下逆向因果关系吗？

And maybe could you mention, for those that missed, "The Hawthorne Effect?" Just because you-

也许您可以为那些错过的人提一下“霍桑效应”吗？只因为你——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yes

是的

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

"The Hawthorne Effect" is an effect that is named after an observation of what took place in a factory where they were actually studying worker productivity with light, of all things.

“霍桑效应”是一种因观察工厂中发生的情况而得名的效应，他们实际上是在用光研究工人的生产力。

But what it refers to is the idea that people will change their behavior when they are observed.

但它所指的是人们在被观察时会改变自己的行为的想法。

So if I said, "Well, I really want to know what a day in the life is like for Andrew Huberman, I'm going to follow him around for a day," it's very unlikely that his behavior that day will be exactly as it was if I wasn't there.

因此，如果我说：“嗯，我真的想知道安德鲁·胡伯曼生活中的一天是什么样的，我要跟随他一天”，如果我不在场，他那天的行为就不太可能完全一样。

And so the reason-

所以原因是——

Andrew Huberman:

安德鲁·休伯曼：

Which is why you probably will never see a day in the life of Andrew Huberman.

这就是为什么你可能永远不会在安德鲁·胡伯曼的一生中见到他。

Although it's pretty scripted unless I'm traveling.

虽然除非我去旅行，否则它的脚本很漂亮。

It's morning sunlight, hydration, and some cardio or weight training, and then a lot of time reading papers.

早晨的阳光、水分和一些有氧运动或举重训练，然后是大量的时间阅读论文。

It'd be the most boring video in the world because it'd be mostly me reading and underlining things.

这将是世界上最无聊的视频，因为它主要是我在阅读和强调内容。

Dr. Peter Attia:

彼得·阿蒂亚博士：

But it's why gamifying things can be beneficial, right?

但这就是为什么游戏化是有益的，对吗？

It's why a CGM can be beneficial because it's sort of like somebody's watching you, and you're going to modify what you eat in response to it, or why tracking can really be an effective way to reduce input because there's a sense of being monitored by doing that, especially if someone literally monitors it.

这就是为什么 CGM 是有益的，因为它有点像有人在看着你，你会根据它改变你吃的东西，或者为什么跟踪确实是减少输入的有效方法，因为这样做有一种被监视的感觉，特别是如果有人真正监视它。

In other words, you can set up an accountability partner where your health coach or someone is actually seeing the data.

换句话说，您可以建立一个责任合作伙伴，让您的健康教练或某人实际查看数据。

So that's what it is.

就是这样。

Now, as far as reverse causality, when you look at variables, so let's just pick a common one that's unrelated to this.

现在，就反向因果关系而言，当您查看变量时，让我们选择一个与此无关的常见变量。

So there's an association that more diet soda consumption is associated with greater obesity.

因此，饮用更多的无糖汽水与更严重的肥胖有关。

It's a bit paradoxical, right?

这有点矛盾，对吧？

Andrew Huberman:

安德鲁·休伯曼：

Is that true?

这是真的吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

It is.

是的。

Yeah.

是的。

It's been demonstrated in many series that the greater the consumption of diet soda, the greater the prevalence of obesity.

许多系列研究表明，无糖汽水的消耗量越大，肥胖的患病率就越高。

And that has been postulated by some to suggest that non-nutritive sweeteners, such as aspartame or sucralose or things like that, are actually part of what's causing obesity.

一些人推测，非营养性甜味剂，如阿斯巴甜或三氯蔗糖或类似物质，实际上是导致肥胖的部分原因。

And while there are probably some arguments you could make around the impact that those things might have on the gut microbiome, and maybe there's some way and that's happening, it's also equally likely, if not probably more likely, that there's reverse causality there.

虽然你可能会围绕这些东西可能对肠道微生物组产生的影响提出一些论点，也许有某种方式并且这种情况正在发生，但同样有可能（如果不是更有可能）存在反向因果关系。

That a person who is obese is therefore contemplating how much they're eating or thinking, "Hey, what's an easy way that I can reduce calories?

因此，肥胖的人会考虑自己吃了多少，或者在想，“嘿，有什么简单的方法可以减少卡路里摄入量？

How about instead of drinking a Coke, I drink a Diet Coke?" And so there, the causality which you would impute to mean the drink is causing the obesity, it might be, no, the obesity is causing the choice of drink.

我不喝可乐，而是喝健怡可乐怎么样？”因此，你认为是饮料导致肥胖的因果关系，可能是，不，肥胖导致了饮料的选择。

So here the question is, how much of the effect we're seeing is a result of the condition that's being studied, right?

所以这里的问题是，我们看到的效果有多少是由正在研究的条件造成的，对吗？

How much of the disruption in both day and night light exposure is the result of the depression?

白天和夜间光照的破坏有多少是由抑郁症造成的？

It's dysregulating the sleep.

这是睡眠失调。

Maybe they're sleeping more during the day and more awake at night because of depression.

也许因为抑郁症，他们白天睡得更多，晚上更清醒。

Again, you can't know this.

再说一次，你不可能知道这一点。

This is where epidemiology never allows us to determine this.

这是流行病学永远不允许我们确定这一点的地方。

And sadly, these questions can only be answered through either direct randomization or Mendelian randomization.

遗憾的是，这些问题只能通过直接随机化或孟德尔随机化来回答。

Which, by the way, I was going to also ask you, do you know if anyone has examined this from a Mendelian standpoint?

顺便说一句，我还想问你，你知道是否有人从孟德尔的角度研究过这个问题？

That would be very interesting, because I have to believe-- Well, it would be interesting.

那会很有趣，因为我必须相信——嗯，这会很有趣。

I don't know enough about the biology to know what SNPs would be studiable, but that would be interesting.

我对生物学了解不够，不知道哪些 SNP 可以研究，但这会很有趣。

Andrew Huberman:

安德鲁·休伯曼：

What Peter's saying is if you knew something about the genomes of these people, you would be in a great position to perhaps even link up light susceptibility genes or light sensitivity-

彼得的意思是，如果你对这些人的基因组有所了解，你甚至可以将光敏感性基因或光敏感性联系起来——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Right

右

Andrew Huberman:

安德鲁·休伯曼：

...

...

genes with genes for pathways involved in major depression, bipolar.

具有与重度抑郁症、双相情感障碍相关的通路基因的基因。

Getting to this issue of reverse causality, I think it's very straightforward to imagine that the person who's experiencing a manic episode is going to be up for two weeks at a time, sadly, and getting a lot of nighttime light exposure.

谈到这个反向因果关系的问题，我认为很容易想象，经历躁狂发作的人将一次连续两周不睡觉，不幸的是，并且会受到大量夜间光线照射。

Now, nighttime dark exposure as a treatment for bipolar is something that people are starting to talk about.

现在，人们开始谈论夜间黑暗暴露作为双相情感障碍的治疗方法。

So making sure that even if those people are awake, that they're at least blue blocking at night, reducing their online activities.

因此，要确保即使这些人醒着，他们也至少在夜间屏蔽蓝光，从而减少他们的在线活动。

But people with severe manic episodes have a hard time regulating their own behavior, of course.

但患有严重躁狂发作的人当然很难调节自己的行为。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And it's not one or the other.

这不是一个或另一个。

I don't want the question to come across to the listener that it has to be one or the other.

我不想让听众觉得这个问题必须是其中之一。

It's only A can cause B or B can cause A.

只有A可以导致B或者B可以导致A。

No, it's actually a lot of times these things feed off each other.

不，实际上很多时候这些东西是相互影响的。

Going back to the soda example, I actually think there's a bit of both, right?

回到苏打水的例子，我实际上认为两者都有，对吗？

I actually think there's a real clear body habitus dictates beverage choice, but I also am starting to think that in susceptible individuals, non-nutritive sweeteners will alter the gut biome, and that alters metabolism.

事实上，我认为有一个真正明确的身体习惯决定了饮料的选择，但我也开始认为，在易受影响的个体中，非营养性甜味剂会改变肠道生物群落，从而改变新陈代谢。

Andrew Huberman:

安德鲁·休伯曼：

What about just hunger?

如果只是饥饿呢？

I remember Lane telling me, and I've seen at least one of the studies that water is probably better for us than diet soda, but that for some people, diet soda is a great tool for reducing caloric intake.

我记得莱恩告诉我，我至少看过一项研究，水可能比无糖汽水对我们更好，但对于某些人来说，无糖汽水是减少热量摄入的好工具。

I also know some individuals, not me, who drink diet soda.

我也认识一些人，但不是我，也喝无糖汽水。

I drink diet soda from time to time, mainly stevia-sweetened sodas.

我时常喝无糖汽水，主要是甜菊糖汽水。

But what I'm referring to here are people besides myself who drink diet soda, and it seems to stimulate their appetite.

但我这里指的是除了我自己之外喝无糖汽水的人，而且它似乎能刺激他们的食欲。

There's something about the perception of sweet as driving hunger, whereas not eating or drinking anything with any sweetness doesn't seem to.

有人认为甜食会让人产生饥饿感，但不吃或喝任何带甜味的东西似乎却并非如此。

This is one of the things I wonder if it impacts why some people like intermittent fasting, because for some people, just even the perception.

这是我想知道它是否会影响为什么有些人喜欢间歇性禁食的事情之一，因为对于某些人来说，甚至只是一种看法。

I wonder if the perception of sweetness or even just the smell of food we know can stimulate appetite.

我想知道对甜味的感知，甚至只是我们所知道的食物的气味是否可以刺激食欲。

So you can imagine the perception of sweetness in the mouth, even if there's no calories there.

所以你可以想象口中甜味的感觉，即使那里没有卡路里。

I don't think it necessarily makes people hypoglycemic, but perhaps it makes them think about sweet means food.

我不认为它一定会让人们低血糖，但也许它会让他们想到甜食。

For instance, for years, I loved the combination of a Diet Coke and a slice of pizza whenever I was in New York.

例如，多年来，每当我在纽约时，我都喜欢喝健怡可乐和一片披萨。

Ideally, two slices of pizza.

理想情况下，两片披萨。

So now every time I have a Diet Coke, which isn't that often, but I like Diet Coke, especially with a little bit of lemon in it.

所以现在每次我喝健怡可乐时，虽然不常见，但我喜欢健怡可乐，尤其是里面加了一点柠檬。

I just think about a slice of cheese or mushroom or pepperoni pizza.

我只想一片奶酪、蘑菇或意大利辣香肠披萨。

It's like I want it.

就好像我想要它一样。

I crave it more.

我更渴望它。

So there's a paired association there that I think is real, and we know based on Dana Small's lab at Yale that there's this paired association between the sweetness from sucralose and that there's an insulin response.

因此，我认为存在真实的配对关联，而且根据耶鲁大学 Dana Small 的实验室，我们知道三氯蔗糖的甜味与胰岛素反应之间存在配对关联。

They actually had to cease the study in kids because they were becoming pre-diabetic, which unfortunately meant the study was never published.

事实上，他们不得不停止对儿童的研究，因为他们正处于糖尿病前期，不幸的是，这意味着这项研究从未发表。

Have you talked to Dana on this podcast?

你在这个播客上和达纳谈过吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

No. We wrote a premium newsletter on this several months ago.

不。几个月前我们就此写了一篇高级时事通讯。

It's got to be like, I don't know, 10 to 20,000 words on all things related to sugar substitutes.

我不知道，关于与糖替代品相关的所有事情，必须有 10 到 20,000 个单词。

Andrew Huberman:

安德鲁·休伯曼：

Okay.

好的。

I'll read that.

我会读一下。

I need to read that.

我需要读一下。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So yeah.

所以是的。

Andrew Huberman:

安德鲁·休伯曼：

I'm behind.

我落后了。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Folks who are interested in this topic, I would refer them to the premium newsletter on sugar substitutes.

对这个话题感兴趣的人们，我会推荐他们阅读有关糖替代品的优质时事通讯。

I think it was our September edition.

我想这是我们的九月版。

The short of it is the data are a little bit noisy.

缺点是数据有点嘈杂。

But there is indeed some sweeteners in some studies do result in that phenomenon you described, the cephalic insulin response.

但在一些研究中确实有一些甜味剂确实会导致你所描述的现象，即头部胰岛素反应。

And I came away from the research that went into that, which was Herculean effort on the part of the team, a little bit more confused than when I went in, but being even more cautious around artificial sweeteners than I was going in.

我从团队的艰巨努力中结束了这项研究，比我刚开始时更加困惑，但对人工甜味剂的态度比我刚开始时更加谨慎。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And not for the reasons that I don't necessarily-- I didn't find any evidence that these things are cancer-causing, right?

并不是因为我不确定的原因——我没有发现任何证据表明这些东西会致癌，对吗？

So that's the headline stuff people worry about.

这就是人们担心的头条新闻。

Oh, aspartame causes-

哦，阿斯巴甜会导致——

Andrew Huberman:

安德鲁·休伯曼：

You have to ingest like 10 grams or something crazy like that.

你必须摄入大约 10 克或类似的疯狂东西。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

I came away more confident that from a long-term safety perspective in terms of cancer and catastrophic outcomes like that, that wasn't the issue.

我更加确信，从癌症和类似灾难性后果的长期安全角度来看，这不是问题。

But I came away much more cautious around these things can really be mucking around with both your brain chemistry and your gut chemistry, which can pertain to your metabolism.

但我对这些事情更加谨慎，这些事情确实会扰乱你的大脑化学物质和肠道化学物质，这可能与你的新陈代谢有关。

And therefore, my takeaway was buyer beware.

因此，我的结论是买家要小心。

Use limited amounts only.

仅使用有限的数量。

The one, by the way, that still emerged to me as a reasonable one, it's the only one that I use, and I've talked about it a lot, is xylitol.

顺便说一句，对我来说，木糖醇仍然是一种合理的，它是我唯一使用的，而且我已经谈论过很多次了，那就是木糖醇。

Xylitol is the-- Pardon me, I shouldn't say that.

木糖醇是——请原谅，我不应该这么说。

Xylitol for chewing, so for gum, and allulose as an additive.

木糖醇用于咀嚼，因此用于口香糖，而阿洛酮糖作为添加剂。

So those were the-

所以那些是-

Andrew Huberman:

安德鲁·休伯曼：

Safer, you're saying?

你是说更安全？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yes.

是的。

Those are basically the only two I will consume.

这些基本上是我唯一会消费的两个。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

I'll drink a Diet Coke every now and again if I'm on a plane or something.

如果我在飞机上或其他什么地方，我会时不时地喝一杯健怡可乐。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

You know this law that got passed a few years ago that you couldn't bring liquids of your own into the airport and onto the plane.

你知道几年前通过的这条法律规定你不能携带自己的液体进入机场和飞机。

Like what a great-

就像多么伟大的——

Dr. Peter Attia:

彼得·阿蒂亚博士：

A few years ago.

几年前。

Andrew Huberman:

安德鲁·休伯曼：

What a great scheme to get people to buy overpriced fluids in the airport.

让人们在机场购买价格过高的液体真是一个很棒的计划。

There are more important issues in the world, but this one really gets me.

世界上还有更重要的问题，但这一个确实让我着迷。

But yeah, I drink things with a little bit of stevia in it, the occasional Diet Coke.

但是，是的，我喝一些含有一点甜叶菊的东西，偶尔喝健怡可乐。

And I generally avoid sucralose.

我通常避免使用三氯蔗糖。

I don't like the way it tastes.

我不喜欢它的味道。

Monk fruit's too sweet.

和尚果太甜了

But yeah.

但是是的。

Maybe we'll do a podcast on that in the future.

也许我们将来会就此做一个播客。

Okay.

好的。

So I think we can wrap this paper because I really-

所以我想我们可以把这张纸包起来，因为我真的-

Dr. Peter Attia:

彼得·阿蒂亚博士：

Well, but tell me what you think about that point, Andrew.

好吧，但请告诉我你对这一点的看法，安德鲁。

You know more about this stuff than I do, but if you had to just lay on your judgment, right?

你对这件事的了解比我多，但如果你不得不做出自己的判断，对吗？

So if it were 100 to zero, you would say the light is 100% causal in the effects we're seeing.

因此，如果是 100 比 0，你会说光与我们所看到的效果有 100% 的因果关系。

If it were zero to 100, you'd say, nope, the behavior is 100% causal of the exposure to light.

如果它是 0 到 100，你会说，不，这种行为 100% 是暴露在光下的原因。

Where do you-- Again, you can't know it.

你在哪里——再说一遍，你不可能知道。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

But what does your intuition tell you?

但你的直觉告诉你什么？

Andrew Huberman:

安德鲁·休伯曼：

Okay.

好的。

There's my intuition, and then there's my recognition of my own bias.

这是我的直觉，然后是我对自己偏见的认识。

Because I started working on these circadian pathways originating in the eye back in '98 as a graduate student at Berkeley.

因为早在 98 年，作为伯克利分校的一名研究生，我就开始研究这些源自眼睛的昼夜节律通路。

The cells, these melanopsin intrinsically sensitive retinal ganglion cells, were discovered in the early 2000s by a guy named Iggy Provencio, Dave Berson, Samer Hattar, Sachin Panda, and others.

这些细胞，即对黑视蛋白本质敏感的视网膜神经节细胞，是由 Iggy Provencio、Dave Berson、Samer Hattar、Sachin Panda 等人在 2000 年代初发现的。

And it was one of the most important discoveries in all of biology, clearly.

显然，这是整个生物学中最重要的发现之一。

So I've been very excited about these systems.

所以我对这些系统感到非常兴奋。

But if I set that aside, so bias disclosure made I think 65% to 75% of the effects are likely due to light directly.

但如果我把这一点放在一边，那么偏见披露让我认为 65% 到 75% 的影响可能是直接由光造成的。

Now, it's impossible to tease those apart, as you mentioned, but to play devil's advocate against myself, you could imagine that the depressed individual is laying around indoors with the curtains drawn.

现在，正如你所提到的，不可能将它们分开，但是为了对我自己唱反调，你可以想象那个抑郁的人躺在室内，窗帘拉着。

They didn't sleep well the night before, which gives you a photosensitivity that isn't pleasant.

他们前一天晚上没有睡好，这会让你产生一种不愉快的光敏感性。

It sucks to have bright light in your eyes first thing in the morning, especially if you didn't sleep well.

早上第一件事就是让明亮的光线进入你的眼睛，这很糟糕，尤其是在你睡得不好的情况下。

And then they're making their coffee in a dimly lit, what they think is brightly lit environment, and then they're looking at their phone and the state of the world sucks, and their state of their internal landscape is rough.

然后他们在昏暗的灯光下煮咖啡，他们认为是明亮的环境，然后他们看着手机，世界的状况很糟糕，他们的内部景观的状况很糟糕。

And maybe they're dealing with a pain or an injury or something, and their likelihood of getting outside is low, and when they do get outside, they're going to shuffle.

也许他们正在处理疼痛或受伤或其他什么问题，他们出去的可能性很低，当他们出去时，他们会拖着脚步。

So I could see how the behaviors could really limit the amount of light exposure.

所以我可以看到这些行为如何真正限制光照量。

And then evening rolls around, they've been tired all day, and a common symptom of depression, you fall asleep, and then 2:00 or 3:00 in the morning, they're wide awake.

然后夜幕降临，他们一整天都很累，这是抑郁症的常见症状，你睡着了，然后凌晨 2:00 或 3:00，他们就完全清醒了。

What are you going to do at 2:00 or 3:00 when you're wide awake, sit in the dark?

2:00 或 3:00 当你完全清醒时，坐在黑暗中，你会做什么？

No. You're going to get online.

不，你要上网。

You're going to listen to things.

你会听到一些事情。

You might have, I'm not recommending this, but an alcoholic drink in order to try and fall asleep.

我不建议你这样做，但你可能会喝点酒精饮料来尝试入睡。

This is the pattern.

这就是模式。

And so, shaking up that pattern is really what so much of my public health work these days is about and trying to get people onto a more natural daylight-night dark rhythm.

因此，改变这种模式确实是我这些天的公共卫生工作的目的，并试图让人们进入更自然的昼夜黑暗节奏。

But yeah, it's impossible to tease apart.

但是，是的，不可能将其分开。

We do know this, and this is really serious.

我们确实知道这一点，而且这确实很严重。

We know that in almost every instance, almost every psychopathology report of suicide, in the weeks, but especially in the days preceding suicide, that person's circadian rhythms looked almost inverted from their normal patterns.

我们知道，在几乎每一个实例中，几乎每一份自杀的精神病理学报告中，在几周内，尤其是在自杀前的几天里，该人的昼夜节律看起来几乎与正常模式相反。

And that's true of non-bipolar individuals as well.

对于非躁郁症患者来说也是如此。

Circadian disruption and disruption in psychiatric health are inextricable.

昼夜节律的紊乱和精神健康的紊乱是不可避免的。

Conversely, positive mood and affect and circadian behavior seem very correlated.

相反，积极的情绪和情感与昼夜节律行为似乎非常相关。

I think it's clear that if you want to become an early riser, get light in your eyes and get activity in your body early in the day.

我认为很明显，如果您想成为早起者，请在一天的早些时候让眼睛明亮并让身体活动起来。

You entrain to those rhythms so that you start to anticipate that morning workout, you start to anticipate the morning sunlight.

你跟随这些节奏，这样你就开始期待早晨的锻炼，你开始期待早晨的阳光。

Just one more scientific point.

只是多了一个科学点。

We know that when you view bright sunlight in the morning, or just sunlight that's illuminating your environment, as you said, you don't even have to see the sun itself, that there's a 50%, 5-0, percent increase in the amplitude of the morning cortisol spike, which is a good thing.

我们知道，当你在早上看到明亮的阳光，或者只是照亮你的环境的阳光时，正如你所说，你甚至不必看到太阳本身，早上皮质醇峰值的幅度会增加 50%、5-0%，这是一件好事。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Right.

对。

That's where you want it.

这就是你想要的地方。

Andrew Huberman:

安德鲁·休伯曼：

Because the amplitude of the morning cortisol spike is inversely related to the amplitude of the evening cortisol spike, and high evening cortisol is associated with middle-of-the-night waking, and on and on.

因为早晨皮质醇峰值的幅度与晚上皮质醇峰值的幅度成反比，而晚上皮质醇高则与半夜醒来有关，等等。

So, I'm very bullish on these mechanisms.

所以，我非常看好这些机制。

I also love that they're so deeply woven into our evolutionary history, that we share with single-cell organisms.

我还喜欢它们如此深入地融入我们的进化历史，以至于我们与单细胞生物体共享。

It's so wild.

太狂野了。

But of course, there's going to be a bidirectionality there, and it's impossible to see where one thing starts and the other one stops.

但当然，那里会存在双向性，不可能看出一件事从哪里开始，另一件事从哪里停止。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Here's my take, Andrew.

这是我的看法，安德鲁。

First of all, I actually, with far less authority than you, agree with your assessment and might even be a little bit more bullish, might even put it at 80/20.

首先，实际上，我的权威远不如你，同意你的评估，甚至可能更乐观一些，甚至可能把它定为80/20。

And here, I'll give you my explanations which stem more from my fastidious battles with epidemiology in general.

在这里，我将向您提供我的解释，这些解释更多地源于我与流行病学的严格斗争。

Because so much of the world that I live in still has to rely on epidemiologic data.

因为我所生活的世界大部分地区仍然必须依赖流行病学数据。

And so how do you make sense of it?

那么你如何理解它呢？

And the truth of it is most of it is really pretty bad.

事实上，大部分情况都非常糟糕。

But I tend to find myself looking at the Austin Bradford Hill criteria all the time.

但我发现自己一直在关注奥斯汀·布拉德福德·希尔的标准。

And for folks who don't know, he was a statistician who basically proposed a set of criteria, believe there are eight of them, and I can't believe I don't know every one of them off by heart.

对于那些不知道的人来说，他是一位统计学家，他基本上提出了一套标准，相信有八个标准，我不敢相信我不熟记其中的每一个。

I certainly used to.

我当然曾经这样做过。

But the more of these criteria that are met within your correlations, the more likelihood you will find causality.

但是，相关性中满足的这些标准越多，找到因果关系的可能性就越大。

So when I think of your data here, the data in this paper, I'll tell you what makes these correlations seem to have causality within them in the direction that's being proposed.

因此，当我想到这里的数据，即本文中的数据时，我将告诉您是什么使这些相关性在所提出的方向上似乎具有因果关系。

Look at the dose effect.

看剂量效应。

So dose effect matters, and this is done in quartiles, and that's a very elegant thing.

所以剂量效应很重要，这是以四分位数完成的，这是一件非常优雅的事情。

If they just did it as on/off, it would be harder.

如果他们只是按开/关方式进行操作，那就更难了。

Andrew Huberman:

安德鲁·休伯曼：

High/low.

高/低。

Dr. Peter Attia:

彼得·阿蒂亚博士：

That's right.

没错。

But the fact that they did it in quartiles allows you to see that every example in figure two, I don't believe there is an exception to this.

但他们以四分位数进行的事实让您可以看到图二中的每个示例，我不认为有例外。

Andrew Huberman:

安德鲁·休伯曼：

No, and I think also in the other figure-

不，我认为在另一个图中也是如此——

Dr. Peter Attia:

彼得·阿蒂亚博士：

There's only one exception to what I'm about to say.

我要说的只有一个例外。

Sorry, two out of God knows how many.

抱歉，天知道有多少个。

They're all monotonically increasing and decreasing.

它们都是单调递增和递减的。

In other words, the dose effect is always present.

换句话说，剂量效应始终存在。

Another thing is biologic plausibility.

另一件事是生物学的合理性。

You've spoken at length about that today.

今天你已经详细地谈到了这一点。

So in other words, sometimes you have to look at epidemiology and ask, is there a biologic explanation?

换句话说，有时你必须看看流行病学并问，是否有生物学上的解释？

And here there is.

就在这里。

You've added another one, which is evolutionary conservation to the biologic plausibility.

您还添加了另一项，即生物合理性的进化守恒。

Then you can talk about animal models or experiments in humans over short durations that generally support these findings.

然后你可以谈论通常支持这些发现的动物模型或短期人体实验。

And so those are just a couple of the Bradford Hill criteria that lead to my belief that, yeah, there's reverse causality here, but it's not the full explanation, and that more of the explanation is probably the direction that's being proposed.

因此，这些只是布拉德福德希尔标准中的几个，这些标准使我相信，是的，这里存在反向因果关系，但这不是完整的解释，更多的解释可能是正在提出的方向。

And if that's true, because then at the end of the day, what's the purpose of the discussion?

如果这是真的，那么最终讨论的目的是什么？

The purpose of the discussion is if you are under the influence of any of these psychiatric conditions, in addition to the treatments you're doing now, what else can you do?

讨论的目的是，如果您受到任何这些精神疾病的影响，除了现在正在做的治疗之外，您还能做什么？

And to me, the takeaway is ...

对我来说，要点是......

follow these light behaviors.

遵循这些轻微的行为。

It's a relatively low lift-

这是一个相对较低的升力

Andrew Huberman:

安德鲁·休伯曼：

Yeah

是啊

Dr. Peter Attia:

彼得·阿蒂亚博士：

...

...

when you consider some of the other things.

当你考虑其他一些事情时。

I'm over here asking people to do zone two for three hours a week, and VO2 max workouts, and all this other stuff, and I think all those things matter for mental health as much as physical health, but this strikes me as on the spectrum of low asks.

我在这里要求人们每周进行三小时的第二区锻炼，以及最大摄氧量锻炼，以及所有其他的东西，我认为所有这些事情对于心理健康和身体健康都很重要，但这让我印象深刻，因为它属于低要求范围。

If it's only even 30% causality, 70% reverse causality, I'll take those.

如果只有 30% 的因果关系，70% 的反向因果关系，我也会接受。

I would still instate that.

我仍然会这么说。

Andrew Huberman:

安德鲁·休伯曼：

Yeah, and it's taking your coffee on the balcony, and people will often say, "Well, how do you do this with kids?" The kids should be doing it, too.

是的，当你在阳台上喝咖啡时，人们经常会说，“那么，你怎么和孩子们一起做这个呢？”孩子们也应该这样做。

It means popping your sunglasses off.

这意味着摘掉你的太阳镜。

It means getting out for just a few minutes.

这意味着出去几分钟。

And the fact that it's additive, that these photon counting mechanisms, they sum, is great.

事实上，它是可加的，这些光子计数机制，他们总结起来，是伟大的。

And look, this paper also says, and I should've stated this earlier, if you missed your daytime light ration, get your nighttime dark ration.

看，本文还说，我应该早点说明这一点，如果您错过了白天的光配给，请获取夜间的黑暗配给。

They are independent and additive.

它们是独立且相加的。

So that's really something.

所以这真的很重要。

But of course, ideally, you get both.

但当然，理想情况下，你两者都能得到。

But I appreciate your take on it, and thanks for your expertise in parsing epidemiology.

但我很欣赏你的看法，也感谢你在解析流行病学方面的专业知识。

I look at fewer studies of that sort, but I learned from you, and that's one of the reasons I love doing these journal clubs is I learn.

我看的这类研究较少，但我从你那里学到了东西，这就是我喜欢参加这些期刊俱乐部的原因之一就是我学习。

So along those lines, tell us about the paper you selected.

因此，请按照这些思路，告诉我们您选择的论文。

I'm really eager to learn more.

我真的很渴望了解更多。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Well, I wanted to pick a paper that was kind of interesting as a paper, and this paper, I think, is interesting in that it is kind of the landmark study of a class of drugs.

嗯，我想选一篇有趣的论文，我认为这篇论文很有趣，因为它是一类药物的里程碑式研究。

But in the same way that you picked a paper that I think has a much broader overarching importance, the reason I picked this paper, which is from "The New England Journal of Medicine," it's about 10 years old-- no, correction, 13 years old-- is because it is kind of the landmark study in a class of drugs that I believe are the most relevant class of drugs we've seen so far in cancer therapy.

但就像你选择了一篇我认为具有更广泛的总体重要性的论文一样，我选择这篇论文的原因是，它来自《新英格兰医学杂志》，它已经有大约 10 年的历史了——不，更正，13 年前——是因为它是一类药物的里程碑式研究，我认为这是我们迄今为止在癌症治疗中看到的最相关的一类药物。

And even though the net effect of these drugs has only served to reduce mortality by maybe 8% to 10%, which is not a huge amount, it's the manner in which they've done it that gives me great hope for the future, even if it's through other means.

尽管这些药物的净效果仅使死亡率降低了 8% 到 10%，这并不是一个很大的数字，但它们的作用方式给了我对未来的巨大希望，即使是通过其他方式。

So I'll take a step back before we go into the paper for, again, just the context and background.

因此，在我们进入本文之前，我将退后一步，再次了解上下文和背景。

So the human immune system is kind of a remarkable thing.

所以人类的免疫系统是一个了不起的东西。

It's hard when you're sort of trying to imagine what's the most amazing part of the human system, and maybe it's my bias as well, because just as you spent your time in the light system, in the photosensing system, I spent my time in the immunology world.

当你试图想象人类系统中最令人惊奇的部分是什么时，这是很困难的，也许这也是我的偏见，因为就像你花时间在光系统、光传感系统中一样，我也花时间在免疫学世界中。

But it is remarkable to me how our immune system's evolved.

但对我来说，我们的免疫系统是如何进化的却是值得注意的。

And they have this really brutal task, which is how can they be tuned to detect any foreign pathogen that is harmful without knowing a priori what that could be, while at the same-- so in other words, how can you tune a system to be so aggressive that it can eradicate any virus or bacteria billions of years into the future without knowing what it's going to be, but at the same time, it has to be so forgiving of the self that it doesn't turn around and attack the self?

他们面临着一项非常残酷的任务，那就是如何调整它们来检测任何有害的外来病原体，而不知道它可能是什么，同时——换句话说，你如何才能将一个系统调整得如此具有攻击性，以至于它可以在数十亿年后消灭任何病毒或细菌，而不知道它会是什么，但与此同时，它必须如此宽容自我，以至于它不会转身攻击自我？

It's remarkable.

这很了不起。

And of course, we can always think of the exceptions.

当然，我们总是可以想到例外的情况。

There are things called autoimmune conditions, so clearly the system fails, and the immune system turns around and attacks the self.

有些东西被称为自身免疫性疾病，很明显，系统出现故障，免疫系统会反过来攻击自身。

If you see a person with vitiligo, I have a little bit of vitiligo on my back, a couple of spots.

如果你看到一个患有白癜风的人，我的背上有一点白癜风，有几个斑点。

Clearly, the immune system is attacking something there and destroying some of the pigment.

显然，免疫系统正在攻击那里的某些东西并破坏一些色素。

Andrew Huberman:

安德鲁·休伯曼：

I didn't realize vitiligo was autoimmune.

我没有意识到白癜风是自身免疫性疾病。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

So there are lots of more serious autoimmune conditions, of course, somebody that has lupus or where the immune system can be attacking the kidney, the immune system can be attacking anywhere.

当然，还有很多更严重的自身免疫性疾病，患有狼疮的人或者免疫系统可以攻击肾脏的人，免疫系统可以攻击任何地方。

Autoimmune conditions can be deadly, but fortunately, they are very rare, and for the most part, this immune system works remarkably well.

自身免疫性疾病可能是致命的，但幸运的是，这种情况非常罕见，而且在大多数情况下，这种免疫系统运行得非常好。

So how does it work, and why is it that cancer seems to evade it virtually all of the time?

那么它是如何发挥作用的，为什么癌症似乎总是逃避它呢？

This is the question.

这就是问题所在。

Now, let's first of all talk about how it works, and then when I tell you how it works, you'll say, "That sounds amazing.

现在，让我们首先谈谈它是如何工作的，然后当我告诉你它是如何工作的时，你会说，“这听起来棒极了。

Clearly, it should be able to destroy cancer." I'm going to simplify it by only talking about one system, which is how T cells recognize and get activated, how T cells recognize antigens.

显然，它应该能够消灭癌症。”我将通过仅讨论一个系统来简化它，即 T 细胞如何识别并被激活，T 细胞如何识别抗原。

So we have something called an antigen.

所以我们有一种叫做抗原的东西。

So an antigen is an antibody-generating peptide.

因此，抗原是一种产生抗体的肽。

So it's a protein, almost always a protein.

所以它是一种蛋白质，几乎总是一种蛋白质。

They can be carbohydrates, but they're almost always proteins, and they're very, very small peptides.

它们可以是碳水化合物，但它们几乎总是蛋白质，而且是非常非常小的肽。

We're talking as little as nine amino acids, maybe up to 20 amino acids, so teeny, tiny, little peptides.

我们谈论的是少至 9 个氨基酸，可能多达 20 个氨基酸，所以是非常微小的肽。

But it's amazing that in such a short peptide, the body can recognize if that's Andrew or not Andrew.

但令人惊奇的是，在如此短的肽中，身体可以识别那是不是安德鲁。

Again, we talk about proteins in kilodaltons.

我们再次讨论以千道尔顿为单位的蛋白质。

We're talking about proteins in terms of thousands of amino acids that make up every protein in your body, and yet, if it samples a protein and sees that, "Hey, this little nine, 10, 15 peptide amino acid is not part of you, I know it's bad, and therefore, I'm going to generate an immune response to it." So we have what are called antigen-presenting cells.

我们谈论的是由数千种氨基酸组成的蛋白质，这些氨基酸构成了你体内的每种蛋白质，然而，如果它对蛋白质进行采样并发现，“嘿，这个小小的 9、10、15 肽氨基酸不是你的一部分，我知道它是不好的，因此，我将对它产生免疫反应。”所以我们有所谓的抗原呈递细胞。

You have cells that go around sampling peptides, and they will On these things called MHC class receptors, bring the peptide up to the surface and serve it up to the T cell.

你有一些细胞在采样肽，它们会在这些称为 MHC 类受体的东西上，将肽带到表面并将其提供给 T 细胞。

There are two types of these.

有两种类型。

There's MHC class 1 and MHC class 2.

有 MHC 1 类和 MHC 2 类。

I only bring them-

我只带它们——

Andrew Huberman:

安德鲁·休伯曼：

So this is major histocompatibility complex

所以这是主要的组织相容性复合体

Dr. Peter Attia:

彼得·阿蒂亚博士：

...

...

compatibility.

兼容性。

That's correct.

这是正确的。

And we refer to them that way because of the context in which they were discovered, which was for organ rejection.

我们这样称呼它们是因为它们被发现的背景，即器官排斥。

So not surprisingly, when you need to put a kidney into another person, if that kidney is deemed foreign, it will not last long.

因此，毫不奇怪，当您需要将肾脏移植到另一个人体内时，如果该肾脏被视为异物，则它不会持续很长时间。

And the early days of organ transplantation were rife with immediate rejections.

器官移植的早期充斥着立即排斥反应。

And the immediates are the ABO incompatibilities, but the sort of next layer of incompatibility was MHC incompatibility, which would lead to, within weeks, the organ is gone as opposed to within hours.

最直接的后果是 ABO 不相容，但下一层不相容是 MHC 不相容，这将导致器官在几周内消失，而不是几小时内。

So you have these two classes of MHC.

所以你有这两类 MHC。

You have class 1 and class 2.

你有班级 1 和班级 2。

Class 1 is what we call endogenous.

第 1 类就是我们所说的内生性。

So this is basically what happens when a protein or an antigen is coming from inside the cell.

这基本上就是当蛋白质或抗原来自细胞内部时发生的情况。

So let's consider the flu.

那么让我们考虑一下流感。

So if you get the flu, the influenza virus infects the respiratory epithelium of your larynx, and that virus as folks listening might remember from our days of talking about COVID, viruses can't replicate on their own.

因此，如果你得了流感，流感病毒会感染你喉部的呼吸道上皮，而人们可能还记得，从我们谈论新冠病毒的日子里，病毒就无法自行复制。

What they do is they hijack the replication machinery of the host, and they use that either to insert their RNA or DNA to replicate.

它们所做的就是劫持宿主的复制机制，并利用它插入 RNA 或 DNA 进行复制。

And in the process, proteins are being made.

在此过程中，蛋白质被制造出来。

Well, those proteins are the proteins of the virus, not of us.

嗯，这些蛋白质是病毒的蛋白质，而不是我们的蛋白质。

So some of those peptides get launched onto these MHC class 1 glove, basically.

因此，基本上，其中一些肽会被发射到这些 MHC 1 类手套上。

The glove comes up to the surface, and a T cell comes along.

手套浮到表面，T 细胞随之出现。

And in the case of MHC class 1, it's a CD8 T cell.

对于 1 类 MHC，它是 CD8 T 细胞。

These are what are called the killer T cells, right?

这些就是所谓的杀伤性 T 细胞，对吧？

And so this cell comes along, and with its T cell receptor, the T cell receptor meets the MHC class 1 receptor with the antigen in it, and if that's a lock, it realizes, "That's my target." And it begins to replicate and proliferate and target those.

所以这个细胞出现了，它的 T 细胞受体，T 细胞受体遇到了含有抗原的 MHC 1 类受体，如果这是一把锁，它就会意识到，“那就是我的目标。”它开始复制、扩散并瞄准这些目标。

And that creates the immune response.

这会产生免疫反应。

And by the way, that's how it works when you vaccinate somebody.

顺便说一下，这就是给某人接种疫苗的原理。

You're basically pre-building that thing up.

你基本上是在预先构建那个东西。

Andrew Huberman:

安德鲁·休伯曼：

So would this fall under the adaptive immune response or the innate immune response?

那么这属于适应性免疫反应还是先天免疫反应呢？

Dr. Peter Attia:

彼得·阿蒂亚博士：

No, this is adaptive, yep.

不，这是自适应的，是的。

Innate is just the pure antibody response on the B cell side.

先天性只是 B 细胞侧的纯抗体反应。

I won't get into that for the purpose of this discussion.

为了本次讨论的目的，我不会深入讨论这一点。

The other example is MHC class 2, and that's also part of the adaptive system or the innate system, which is more what we call the exogenous form.

另一个例子是 MHC 2 类，它也是适应性系统或先天系统的一部分，更多的是我们所说的外源形式。

So these are peptides that are usually coming from outside the cell.

所以这些肽通常来自细胞外。

So we're going to focus more on the MHC class 1 because this is peptides that come from inside the cell.

因此，我们将更多地关注 MHC 1 类，因为这是来自细胞内部的肽。

Okay, so just keep in the back of your mind, if a foreign protein gets presented from inside a cell to outside a cell, the T cells recognize that, and they will mount a foreign response.

好吧，所以请记住，如果外来蛋白质从细胞内部呈现到细胞外，T 细胞会识别到这一点，并且它们会发起外来反应。

And by the way, that's why we basically can beat any virus.

顺便说一句，这就是为什么我们基本上可以击败任何病毒。

If you consider how many viruses are around us, the fact that we almost never die from a viral infection is a remarkable achievement of how well this immune system works.

如果你考虑一下我们周围有多少病毒，我们几乎从未死于病毒感染，这一事实是免疫系统运作良好的一项了不起的成就。

And by-

并通过-

Andrew Huberman:

安德鲁·休伯曼：

We're constantly combating these viruses.

我们一直在与这些病毒作斗争。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Constantly, and by the way, we don't really have very effective antiviral agents.

顺便说一句，我们一直没有真正有效的抗病毒药物。

It's not like antibiotics.

它不像抗生素。

We have antibiotics up the wazoo.

我们有抗生素。

We're way better at fighting viruses than bacteria.

我们对抗病毒的能力比对抗细菌的能力要强得多。

Andrew Huberman:

安德鲁·休伯曼：

Can I just ask one question?

我可以只问一个问题吗？

I've always wondered about this.

我一直想知道这个问题。

To what extent is our ability to ward off viruses on a day-to-day basis as an adult reliant on us having been exposed to that virus during development?

作为成年人，我们日常抵御病毒的能力在多大程度上依赖于我们在发育过程中接触过该病毒？

As I walk around today, maybe I'll be exposed to 100,000 different viruses.

当我今天四处走动时，也许我会接触到 100,000 种不同的病毒。

Would you say that half of those I've already got antibodies to because I was exposed to them at some prior portion of my life?

你会说我已经有一半的抗体是因为我在生命的前一段时间接触过它们吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah, hard for me to quantify.

是的，我很难量化。

Andrew Huberman:

安德鲁·休伯曼：

And the other ones, I'm just building up antibodies.

至于其他的，我只是在建立抗体。

I was on a plane last night.

昨晚我在飞机上。

Someone was coughing, so I was hiding.

有人咳嗽，所以我躲了起来。

And I had COVID a little while ago, so I wasn't too worried about that, and I feel great today.

不久前我得了新冠病毒，所以我并不太担心，今天我感觉很好。

But I just assume that on that plane, I'm in a swamp of viruses no matter what, and that most of them I've already been exposed to since I was a little kid.

但我只是假设，在那架飞机上，无论如何，我都处于病毒的沼泽中，而且我从小就已经接触过其中的大多数病毒。

So I've got all the antibodies, and they're just fighting it back, binding up those viruses and destroying them.

所以我已经有了所有的抗体，它们只是反击，结合那些病毒并消灭它们。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah, I think it's part that, and I also think it's part of them that our body can destroy without mounting much of an immune response, so therefore, your immune system is doing the work, and yet it's not mounting a systemic inflammatory response that you're not sensing.

是的，我认为这是其中的一部分，而且我也认为我们的身体可以在不产生大量免疫反应的情况下摧毁它们的一部分，因此，您的免疫系统正在发挥作用，但它并没有产生您没有感觉到的全身炎症反应。

Andrew Huberman:

安德鲁·休伯曼：

So is it also a physical trapping in my nasal epithelium?

那么它是否也是我鼻上皮的物理陷阱？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

It's a virus-

这是一种病毒——

Dr. Peter Attia:

彼得·阿蒂亚博士：

So yeah.

所以是的。

You have huge barriers, right?

你有很大的障碍，对吗？

So the skin, the hairs in your nose, all of these things are huge barriers, but assuming that still a bunch of them are getting in, at least the respiratory ones.

因此，皮肤、鼻子里的毛发，所有这些东西都是巨大的障碍，但假设仍然有一堆东西进入，至少是呼吸道的障碍。

That's the other thing to keep in mind, right?

这是另一件事要记住，对吧？

There are certain viruses that are totally useless floating around the air, right?

空气中漂浮着某些完全无用的病毒，对吧？

There are certain viruses, the viruses that most people are really afraid of, Hep C, Hep B, HIV, well, if they're sitting on a table or floating around the air, they're of no threat to you.

有某些病毒，大多数人真正害怕的病毒，丙型肝炎、乙型肝炎、艾滋病毒，好吧，如果它们坐在桌子上或漂浮在空气中，它们对您没有威胁。

They have to be sort of transmitted through the barrier.

它们必须通过屏障传播。

But again, some of these viruses you're going to defeat without an enormous response.

但同样，其中一些病毒无需做出巨大反应即可被击败。

And then some of them, why is influenza, quote unquote, "such a bad virus," whereas the common respiratory cold kind of sidelines you for a day?

然后他们中的一些人，为什么流感是“如此糟糕的病毒”，而普通的呼吸道感冒却让你缺席一天？

It's the immune response that you're feeling.

这是您感受到的免疫反应。

The bigger the immune response to the virus, the more you're feeling that.

对病毒的免疫反应越大，你的感觉就越强烈。

You feel your immune system going crazy, right?

你感觉你的免疫系统发疯了，对吗？

The interleukins that are spiking, the third spacing that occurs to get more and more of the immune cells there, the spike of your temperature as your body basically tries to cook the virus.

白细胞介素激增，第三次间隔出现，以获得越来越多的免疫细胞，当你的身体基本上试图煮病毒时，你的体温会飙升。

All of that stuff is your body doing this.

所有这些都是你的身体在做的。

Andrew Huberman:

安德鲁·休伯曼：

The fatigue.

疲劳。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yep.

是的。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

You're being drained in all this happening.

这一切的发生让你精疲力竭。

So One more point I'll mention just to close the loop on the autoimmunity.

因此，我还要提一点，以关闭自身免疫的循环。

How is it that we learn not to attack ourselves?

我们如何学会不攻击自己？

That's something called thymic selection that occurs in infancy.

这就是发生在婴儿期的所谓胸腺选择。

So you and I have a no-good-for-nothing, tiny little thymus that would be-- It's almost impossible to see these things.

所以你和我都有一个一无是处的、微小的胸腺——几乎不可能看到这些东西。

When we used to operate on people, the thymus is barely visible in a healthy adult, outside of thymic tumors.

当我们过去对人进行手术时，除了胸腺肿瘤之外，健康成年人的胸腺几乎看不见。

But in a child, the thymus is quite large, and the purpose of the thymus is to educate T cells and basically show the T cells what self is, and any T cell that doesn't immediately recognize it gets killed.

但在儿童中，胸腺相当大，胸腺的目的是教育 T 细胞，基本上向 T 细胞展示自我是什么，任何不能立即识别它的 T 细胞都会被杀死。

So it's a really clever system where we basically teach you to recognize self at a very early age, and if you can't do that, you're weeded out.

所以这是一个非常聪明的系统，我们基本上教你在很小的时候就认识自我，如果你做不到，你就会被淘汰。

And then the thymus involutes thereafter because it's sort of served its purpose.

然后胸腺就会退化，因为它已经达到了它的目的。

Okay, now let's talk about cancer.

好吧，现在我们来谈谈癌症。

So what do we know about cancer?

那么我们对癌症了解多少呢？

So we know that, again, cancer is a genetic disease in the sense that every cancer has genetic mutations.

所以我们再次知道，癌症是一种遗传性疾病，因为每种癌症都有基因突变。

Most of those mutations are somatic, which means most of those mutations are mutations that occur during the course of our life.

大多数突变是体细胞突变，这意味着大多数突变是在我们生命过程中发生的突变。

They're not germline mutations.

它们不是种系突变。

Andrew Huberman:

安德鲁·休伯曼：

The germline being the eggs and sperm, right?

生殖系是卵子和精子，对吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Right.

对。

Andrew Huberman:

安德鲁·休伯曼：

So it's all other cells.

所以都是其他细胞。

And I love that you pointed out that cancer can be genetic but isn't necessarily inherited, right?

我喜欢你指出癌症可以是遗传性的，但不一定是遗传的，对吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

In fact, it's rarely inherited.

事实上，它很少被遗传。

Andrew Huberman:

安德鲁·休伯曼：

People hear genetic and they think inherited, right?

人们听到遗传就认为遗传，对吧？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yes.

是的。

Andrew Huberman:

安德鲁·休伯曼：

Inherited is always genetic to some extent, but genetic isn't always inherited.

遗传在某种程度上总是遗传的，但遗传并不总是遗传的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

So there are a handful of cancers that are derived from inherited mutations.

因此，有少数癌症是由遗传突变引起的。

So Lynch syndrome is an example of that.

林奇综合症就是一个例子。

Hereditary polyposis is an example of that, where you have a gene that gets passed through the germline, and that gene codes for a protein, like all genes do, and it's either you have too much of a gene or too little of a gene.

遗传性息肉病就是一个例子，你有一个基因通过种系传递，并且该基因编码蛋白质，就像所有基因一样，要么你的基因太多，要么你的基因太少。

So it's either a gene that promotes cancer and you have too much of that, or it's a gene that prevents cancer and you have too little of it, or a dysfunctional version of it.

因此，它要么是一种促进癌症的基因，而你的基因过多，要么是一种预防癌症的基因，但你的基因太少，或者是它的功能失调版本。

Right?

正确的？

So BRCA is an example of that.

BRCA 就是一个例子。

BRCA is hereditary.

BRCA 具有遗传性。

BRCA codes for a protein, and the women and men, but mostly the women that we think about who have a BRCA mutation that, in some cases, almost guarantees breast cancer, it's because of a defective copy.

BRCA 编码一种蛋白质，我们认为女性和男性，但主要是女性，都患有 BRCA 突变，在某些情况下，几乎肯定会患乳腺癌，这是因为有缺陷的拷贝。

So it's like they don't get the protein that they need to protect them from breast cancer.

所以就好像他们没有获得保护自己免受乳腺癌侵害所需的蛋白质一样。

So what do we know?

那么我们知道什么呢？

Well, we know that, and this is probably one of the most remarkable things I've ever learned, and it still blows my mind every time.

好吧，我们知道这一点，这可能是我学到的最了不起的事情之一，它每次仍然让我震惊。

Well, actually, before I get to that point, I want to make another point.

嗯，实际上，在讲到这一点之前，我想再说一点。

Okay, so you might think, so our cells become cancerous, but they're clearly hijacked because they have these mutations, and as a result of these mutations, they make proteins that allow cancers to behave differently.

好吧，你可能会想，所以我们的细胞会癌变，但它们显然被劫持了，因为它们有这些突变，并且由于这些突变，它们产生了使癌症表现不同的蛋白质。

And cancers behave differently from non-cancers in two very critical ways.

癌症与非癌症的表现在两个非常关键的方面有所不同。

The first way is that they do not respond to cell cycle signaling.

第一种方式是它们不响应细胞周期信号传导。

So if you cut your skin, it heals, but how does it know to heal just right and not to keep growing and growing and growing and growing and growing?

所以，如果你割伤你的皮肤，它会愈合，但它怎么知道愈合得恰到好处，而不是继续生长、生长、生长、生长、生长呢？

Well, it knows that because there are cell cycle signals that tell it time to grow, time to stop.

嗯，它知道这一点，因为有细胞周期信号告诉它该生长，该停止。

If, believe it or not, this is an extreme example, if you donated to me half of your liver, which I know you would-

不管你信不信，这是一个极端的例子，如果你把你的一半肝脏捐给我，我知道你会——

Andrew Huberman:

安德鲁·休伯曼：

Absolutely.

绝对的。

I'd give you more than half of my liver.

我愿意把我一半以上的肝脏给你。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Well, you'd only need to give me half.

好吧，你只需要给我一半就可以了。

Andrew Huberman:

安德鲁·休伯曼：

If it meant that we could keep doing these journal clubs, right?

如果这意味着我们可以继续举办这些期刊俱乐部，对吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Within months, you would regenerate a full liver.

几个月之内，你就会再生出完整的肝脏。

Andrew Huberman:

安德鲁·休伯曼：

That's so wild.

那太狂野了。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Isn't that amazing?

这不是很神奇吗？

Andrew Huberman:

安德鲁·休伯曼：

That's so wild.

那太狂野了。

It's like a salamander.

它就像蝾螈一样。

You cut off a salamander limb, and please don't do that experiment because other people are doing it anyway, and it grows back.

你切断了蝾螈的肢体，请不要做这个实验，因为无论如何其他人也在这样做，而且它会长回来。

It's a stem cell.

这是干细胞。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah, and it knows how much to grow back.

是的，它知道要恢复多少。

Andrew Huberman:

安德鲁·休伯曼：

It's so wild.

太狂野了。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So when a cell is perfectly functioning, it knows how much to grow, and it's simple.

因此，当细胞功能完美时，它知道要生长多少，而且很简单。

Cancer loses that ability.

癌症失去了这种能力。

That is one of the hallmarks of cancer.

这是癌症的特征之一。

It just keeps growing.

它只是不断增长。

It doesn't grow faster, by the way.

顺便说一句，它的增长速度并不快。

That's a misnomer.

这是用词不当。

People think cancers grow faster than non-cancers.

人们认为癌症比非癌症生长得更快。

There's no real evidence that that's the case.

没有真正的证据表明情况确实如此。

They just don't stop growing.

他们只是不会停止成长。

The second property of cancer is the capacity to leave the site of origin, go someplace else, and take up residence.

癌症的第二个特性是能够离开原发地、前往其他地方并定居。

Andrew Huberman:

安德鲁·休伯曼：

So that's metastasis.

这就是转移。

Dr. Peter Attia:

彼得·阿蒂亚博士：

That's the metastasis component.

这就是转移成分。

So if you think about it for a minute, a cell that never stops replicating and has the capacity to up and leave and move and take up residence is clearly different from the cell itself, right?

因此，如果你想一想，一个永远不会停止复制、有能力向上、离开、移动和定居的细胞显然与细胞本身不同，对吗？

So if I have a cell of colonic epithelium, the cell that lines the inside of my colon, it's clearly got a set of proteins in it.

因此，如果我有一个结肠上皮细胞（排列在结肠内部的细胞），那么它显然含有一组蛋白质。

But if all of a sudden that thing can grow, grow, grow, grow, grow, not stop, not stop, not listen to the signal, and then somehow wind its way into the liver and just keep growing and growing and growing, it must have different proteins.

但如果那个东西突然能够生长、生长、生长、生长、生长，不停歇，不停歇，不听信号，然后以某种方式蜿蜒进入肝脏，继续生长、生长、生长，那么它一定有不同的蛋白质。

So the question then becomes, why does cancer even exist?

那么问题就变成了，为什么癌症会存在？

How has our immune system not figured out a way to just silence this and eradicate it the way it does to virtually every virus you encounter?

我们的免疫系统怎么没有找到一种方法来沉默并根除它，就像对待你遇到的几乎所有病毒一样？

And to me, this is one of the most interesting questions in all of biology, and it really comes down to how clever cancer is, unfortunately, how evolutionarily clever it is.

对我来说，这是所有生物学中最有趣的问题之一，这实际上取决于癌症的聪明程度，不幸的是，它在进化上是多么聪明。

It basically does a lot of things to trick the immune system.

它基本上做了很多事情来欺骗免疫系统。

So it has its own secretory factors that tamp down the immune system.

因此它有自己的分泌因子来抑制免疫系统。

It grows in an environment because of its nature.

它生长在一个环境中，是因为它的本质。

So one of the things that's long understood about cancer is it's heavily glycolytic, and when something is heavily glycolytic, it's going glucose to pyruvate to lactate nonstop.

因此，人们长期以来对癌症的了解之一是它具有严重的糖酵解作用，当某些物质具有严重的糖酵解作用时，它就会不停地从葡萄糖转变为丙酮酸，再转变为乳酸。

There are lots of reasons for that.

原因有很多。

I think there's more than one.

我认为不止一个。

Andrew Huberman:

安德鲁·休伯曼：

What does that afford it?

这有什么用处呢？

Does that-

是不是——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Well, so it's interesting

嗯，所以这很有趣

Andrew Huberman:

安德鲁·休伯曼：

...

...

does that afford it a migratory potential?

这是否赋予它迁移的潜力？

Dr. Peter Attia:

彼得·阿蒂亚博士：

No, so it's super interesting.

不，所以这非常有趣。

So that's the effect, what I just described is called the Warburg effect.

这就是效应，我刚才描述的叫做瓦尔堡效应。

And when Warburg proposed this, which, God, was probably in the 1920s, it was before World War II, he proposed it because he thought the mitochondria of cancer cells were defective.

当瓦尔堡提出这个的时候，天哪，可能是在 20 年代，也就是第二次世界大战之前，他提出这个是因为他认为癌细胞的线粒体有缺陷。

So he proposed that the cancer cells' mitochondria don't work, hence they have to undergo glycolysis.

因此他提出癌细胞的线粒体不起作用，因此它们必须进行糖酵解。

They can't undergo aerobic metabolism.

它们不能进行有氧代谢。

We now know that that's not the case.

我们现在知道事实并非如此。

So we now know that the Warburg effect, or the Warburg effect, if I'll refer to him correctly by his name, almost assuredly does not have to do with defective mitochondria.

所以我们现在知道，瓦尔堡效应，或者说瓦尔堡效应，如果我正确地称呼他的名字的话，几乎可以肯定与有缺陷的线粒体无关。

Others have proposed several mechanisms.

其他人提出了几种机制。

I think there's probably more than one thing going on.

我想可能不止一件事正在发生。

So a paper that came out in 2009, very influential paper, by a guy named Matt Vander Heiden and Craig Thompson and Lou Cantley, proposed that the reason that cancer cells do the Warburg effect is that they're not optimizing for energy, they're optimizing for cellular building blocks.

因此，2009 年发表的一篇非常有影响力的论文，作者是马特·范德·海登 (Matt Vander Heiden)、克雷格·汤普森 (Craig Thompson) 和卢·坎特利 (Lou Cantley)，提出癌细胞产生瓦伯格效应的原因是它们没有优化能量，而是优化了细胞构建模块。

And if you do the mass balance, it completely makes sense.

如果你进行质量平衡，那就完全有道理了。

Dividing cells need building blocks more than energy, and glycolysis, while very inefficient for generating ATP, is much more efficient at generating substrate to make more cells.

分裂细胞需要的构建模块比能量还多，而糖酵解虽然生成 ATP 的效率非常低，但在生成底物以制造更多细胞方面却要有效得多。

But another proposed mechanism is exactly at this one.

但另一种提议的机制正是于此。

Glycolysis lowers the surrounding pH because of lactate.

由于乳酸，糖酵解会降低周围的 pH 值。

Lactate attracts hydrogen, pH goes down, and guess what that does to the immune system?

乳酸吸引氢，pH 值下降，猜猜这对免疫系统有何影响？

Detracts the immune system.

损害免疫系统。

So it's also a way to hide from the immune system.

所以这也是躲避免疫系统的一种方法。

Andrew Huberman:

安德鲁·休伯曼：

So there's a pH cloaking.

所以存在 pH 隐形。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yes.

是的。

Andrew Huberman:

安德鲁·休伯曼：

You leveraging pH to cloak-

您利用 pH 值来隐藏-

Dr. Peter Attia:

彼得·阿蒂亚博士：

That's right

没错

Andrew Huberman:

安德鲁·休伯曼：

...

...

the signal that the immune system would otherwise see.

否则免疫系统会看到的信号。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yep.

是的。

And then when you layer on top of that, that it knows how to secrete things like IL-10, TGF-beta, all of these other secretory factors that also inhibit the immune system, basically, it's figured out a way to kind of hide itself from the immune system.

然后当你进一步了解它时，它知道如何分泌IL-10、TGF-β等物质，所有这些其他也会抑制免疫系统的分泌因子，基本上，它找到了一种隐藏自己免受免疫系统攻击的方法。

Andrew Huberman:

安德鲁·休伯曼：

The way you describe it, cancer sounds like a virus.

按照你的描述，癌症听起来像一种病毒。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yes.

是的。

Andrew Huberman:

安德鲁·休伯曼：

It sounds a lot like a virus.

听起来很像病毒。

And that leads me to ask, are there any examples of contagious cancers?

这让我想问，有传染性癌症的例子吗？

I recall seeing some studies about these little critters down in Australia, Tasmanian devils, that they'd scratch each other and fight, as Tasmanian devils do.

我记得在澳大利亚看到过一些关于这些小动物的研究，塔斯马尼亚恶魔，它们会互相抓伤并打架，就像塔斯马尼亚恶魔一样。

They're actually quite cute.

它们其实很可爱。

And they would get cancers and tumors growing on their faces.

他们的脸上会长出癌症和肿瘤。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yes.

是的。

Andrew Huberman:

安德鲁·休伯曼：

And so it was like a literal physical interaction that could transmit cancer from one animal to the next.

因此，这就像一种真正的物理相互作用，可以将癌症从一种动物传播到另一种动物。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So it's less that.

所以它更少。

There are viruses that cause cancer.

有些病毒会导致癌症。

So in that sense, you could argue yes, there are contagious cancers.

所以从这个意义上说，你可以说是的，存在传染性癌症。

Andrew Huberman:

安德鲁·休伯曼：

Well, HPV.

嗯，HPV。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Sure, yeah.

当然，是的。

HPV, hep B, hep C, but there are even cancers like cutaneous cancers that arise from viruses.

HPV、乙型肝炎、丙型肝炎，甚至还有由病毒引起的癌症，例如皮肤癌。

But I don't know if that's quite the same as what you're saying.

但不知道和你说的是不是一样。

Andrew Huberman:

安德鲁·休伯曼：

No, no, what you're saying is an important point.

不不不，你说的是很重要的一点。

We don't want to go down the rabbit hole of HPV, but right, that's increasing susceptibility to cervical cancer.

我们不想陷入 HPV 的陷阱，但确实，这会增加宫颈癌的易感性。

Now there's a vaccine against HPV, right?

现在有针对 HPV 的疫苗，对吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yep.

是的。

Andrew Huberman:

安德鲁·休伯曼：

There wasn't when we were in college, as we all knew.

我们都知道，我们上大学的时候没有。

There was no vaccine.

没有疫苗。

But yeah, direct transmission of cancers from one organism to the next, more rare.

但是，癌症从一种生物体直接传播到另一种生物体的情况更为罕见。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yes.

是的。

Okay, so now a moment ago, I said there's this really incredible thing about cancer that blows my mind, and about our immune system, which is that at least 80% of solid organ tumors, and we're going to mostly talk about solid organ tumors, because that's where the field of oncology has made very little progress.

好的，刚才我说过，关于癌症和我们的免疫系统，有一件非常令人难以置信的事情让我大吃一惊，免疫系统至少占实体器官肿瘤的 80%，我们将主要讨论实体器官肿瘤，因为这是肿瘤学领域取得很少进展的领域。

So if you go back 50 years, where has oncology made huge progress?

那么，如果回顾 50 年前，肿瘤学在哪些方面取得了巨大进步？

It's made great progress in blood tumors, leukemias, and some kinds of lymphomas.

它在血液肿瘤、白血病和某些淋巴瘤方面取得了巨大进展。

In fact, there's two kinds of lymphomas where the progress has been remarkable.

事实上，有两种淋巴瘤的进展非常显着。

One has been in Hodgkin's lymphoma, and the other has also been in immunotherapy, has been in a type of B-cell lymphoma, where that B-cell demonstrates or presents something called a CD19 receptor.

一个是霍奇金淋巴瘤，另一个也接受了免疫治疗，是一种 B 细胞淋巴瘤，其中 B 细胞表现出或呈现出一种称为 CD19 受体的东西。

So in B-cell lymphomas with CD19, there's a very unique niche immunotherapy, we won't talk about that today, called CAR T therapy that has got rid of those guys, and then leukemias have also been pretty good.

所以在带有CD19的B细胞淋巴瘤中，有一个非常独特的利基免疫疗法，我们今天不讲这个，叫做CAR T疗法，它已经摆脱了这些家伙，然后白血病也已经很好了。

But in solid organ tumors, there have been only two real breakthroughs in the last 50 years.

但在实体器官肿瘤方面，过去50年只有两次真正的突破。

One has been the therapy for a certain type of testicular cancer, and it's really just a chemotherapy cocktail that has been found to work really well, and the other has been in this really rare kind of gastric cancer called the GI stromal tumor, which happens to result from one mutation in a kinase pathway, and there's one drug that can now target that, and it works.

一种是治疗某种类型睾丸癌的疗法，它实际上只是一种化疗鸡尾酒，被发现效果非常好，另一种是治疗一种非常罕见的胃癌，称为胃肠道间质瘤，它恰好是由激酶途径中的一个突变引起的，现在有一种药物可以针对它，并且它有效。

It's kind of amazing.

这真是太神奇了。

Andrew Huberman:

安德鲁·休伯曼：

Cures that cancer.

治愈癌症。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Cures that.

可以治愈这个。

What I'm talking about are the cancers that kill virtually everybody else.

我所说的是几乎杀死所有人的癌症。

This is when you sort of line up what are the big causes of cancer death, let's start at the top.

当你列出癌症死亡的主要原因时，让我们从头开始。

It's lung, it's then breast and prostate in men and women, it's colorectal, it's pancreas.

是肺，然后是男性和女性的乳房和前列腺，是结直肠癌，是胰腺。

Those are the big five.

这就是五巨头。

They kill more than 50% of Americans, cancer-wise, not-- Sorry, let me restate that.

他们杀死了超过 50% 的美国人，就癌症而言，不是——抱歉，让我重申一下。

More than 50% of cancer deaths in Americans come from those five.

美国人 50% 以上的癌症死亡病例来自这五种疾病。

These are what we call the solid epithelial tumors, and you can march down the list, and most cancers that most people are thinking of are those cancers.

这些就是我们所说的实体上皮肿瘤，你可以顺着清单往下看，大多数人想到的大多数癌症都是这些癌症。

Well, here's the thing.

嗯，事情是这样的。

More than 80% of those cancers have antigens that are recognized by the host's immune system.

超过 80% 的癌症具有可被宿主免疫系统识别的抗原。

I will state it again because it is so profound.

我再说一遍，因为它太深刻了。

80%, at least, of those cancers actually generate an antigen, meaning a little peptide in that cell gets presented to the T cell, and it is recognizable.

至少 80% 的癌症实际上会产生抗原，这意味着细胞中的一点肽被呈递给 T 细胞，并且可以被识别。

And now the question is, why is that not sufficient to induce remission?

现在的问题是，为什么这不足以诱导缓解？

And the short answer is there are not enough T cells that are able to act and/or they are being sufficiently inhibited from acting, which gets me to the point of this paper.

简而言之，没有足够的 T 细胞能够发挥作用和/或它们的作用被充分抑制，这就是我这篇论文的重点。

One of the ways in which the body inhibits the immune system, which we should remind ourselves is an important thing, is something called a checkpoint inhibitor.

我们应该提醒自己，身体抑制免疫系统的方式之一是检查点抑制剂，这一点很重要。

Okay.

好的。

So go back to that idea that I talked about before.

那么回到我之前谈到的那个想法。

You have an antigen-presenting cell.

你有一个抗原呈递细胞。

It brings up an MHC receptor with a peptide on it, and there is a T cell that is coming.

它会产生一个带有肽的 MHC 受体，并且有一个 T 细胞即将到来。

And I actually brought a diagram, which I'm going to link to this because I don't want to make this too complicated, but I really think that this figure is helpful to understand how these drugs work.

我实际上带来了一个图表，我将链接到这个图表，因为我不想让这变得太复杂，但我真的认为这个图表有助于理解这些药物是如何发挥作用的。

So the MHC receptor with the peptide is sitting there, and it binds to the T cell receptor on the T cell, but there is another receptor on the T cell, a CTLA-4 receptor.

因此，带有肽的 MHC 受体就在那里，它与 T 细胞上的 T 细胞受体结合，但 T 细胞上还有另一个受体，即 CTLA-4 受体。

And that binds to a receptor that I won't bother naming now, because the names don't matter, but there's another receptor on the antigen-presenting cell that binds to that, and that acts as the brakes in the reaction.

它与一个受体结合，我现在不想命名它，因为名称并不重要，但抗原呈递细胞上还有另一个受体与其结合，并充当反应的刹车。

So CTLA-4, which is on the T cell, binds to another CD receptor on the antigen-presenting cell, and it says, "Tamp down the response." And the reason for that is we want to keep our immune system in check.

因此，T 细胞上的 CTLA-4 与抗原呈递细胞上的另一个 CD 受体结合，它会说“抑制反应”。原因是我们想要控制我们的免疫系统。

This basically is a way of asking the immune system, because remember, when the immune system sees that antigen, it wants to go nuts.

这基本上是询问免疫系统的一种方式，因为记住，当免疫系统看到该抗原时，它会发疯。

It wants to start replicating and killing.

它想要开始复制和杀戮。

This is a CD8 T cell.

这是 CD8 T 细胞。

It is a targeted killer T cell.

它是一种靶向杀伤性 T 细胞。

The checkpoint says, "Let's double-check that.

检查站说：“让我们仔细检查一下。

Let's be sure.

让我们确定一下。

Let's tamp down the response." And as a result of that, a thought experiment emerged, which was, what if we block CTLA-4?

让我们压低回应。”结果，出现了一个思想实验，那就是，如果我们阻断 CTLA-4 会怎样？

What if we block the checkpoint?

如果我们封锁检查站怎么办？

Could we unleash the immune system a little bit more?

我们能更多地释放免疫系统吗？

And I will say this, at the time it was proposed, it seemed a bit far-fetched.

我要说的是，在它提出的时候，这似乎有点牵强。

Because of the complexity of the immune system, it seemed a little far-fetched that simply blocking the checkpoint would have any effect.

由于免疫系统的复杂性，简单地阻断检查点就会产生任何效果，这似乎有点牵强。

It's also worth noting that prior to this, one immunotherapy had found some efficacy, which was trying the exact opposite strategy.

还值得注意的是，在此之前，一种免疫疗法已经发现了一些疗效，但它正在尝试完全相反的策略。

Rather than blocking the inhibitor, it was throwing more accelerant at the fire, which was giving something called interleukin-2.

它没有阻断抑制剂，而是向火中投入更多的助燃剂，从而产生一种叫做白介素-2 的物质。

So interleukin-2 is, for lack of a better word, candy and fuel for T cells.

因此，没有更好的词来形容，白细胞介素 2 就是 T 细胞的糖果和燃料。

So the idea was, if we have T cells that innately recognize a cancer antigen, can we just give high doses of interleukin-2 and have them undergo proliferation and response?

所以我们的想法是，如果我们有天生识别癌症抗原的 T 细胞，我们是否可以只给予高剂量的 IL-2 并让它们进行增殖和反应？

And the answer turned out to be yes, but only in two cancers, melanoma and kidney cancer, and only at very small levels.

答案是肯定的，但仅限于黑色素瘤和肾癌这两种癌症，而且水平非常小。

About 10% of the population would respond to these things.

大约 10% 的人会对这些事情做出反应。

Now, look, that's 10% of people who were going to be dead within six months, because these are devastating cancers, and once they spread, there are no treatments that have any efficacy whatsoever.

现在，你看，有 10% 的人将在六个月内死亡，因为这些是毁灭性的癌症，一旦扩散，就没有任何有效的治疗方法。

In fact, I think median survival for metastatic melanoma at the time was probably four months.

事实上，我认为当时转移性黑色素瘤的中位生存期可能是四个月。

So this was a very grim death sentence.

所以这是一个非常严厉的死刑判决。

But the idea now was, what about doing the exact opposite approach?

但现在的想法是，采取完全相反的方法怎么样？

Instead of trying to throw more fire at the T cell, what if we can take its brakes down?

与其试图向 T 细胞投入更多的火力，不如我们能够降低它的制动效果呢？

Instead of giving more gas, let's give less brakes.

让我们减少刹车，而不是增加油门。

And there were some phase one studies that demonstrated efficacy, phase two, and the paper I'm going to talk about today is the phase three study that compared the first version of these.

有一些第一阶段的研究证明了疗效，第二阶段的研究，我今天要讨论的论文是比较这些研究的第一个版本的第三阶段研究。

So the drug we're going to talk about today is an anti-CTLA-4 drug called ipilimumab.

那么我们今天要讲的药物是一种抗CTLA-4的药物，叫做ipilimumab。

There is another drug out there that came along shortly thereafter that is an anti-PD-1 drug.

此后不久又出现了另一种药物，那就是抗 PD-1 药物。

So PD-1 turns out to be another one of these checkpoints on T cells.

因此，PD-1 是 T 细胞上的另一个检查点。

And the Nobel Prize, by the way, I think it was 2018 or 2019, in medicine or physiology, was actually awarded to the two scientists who discovered CTLA-4 and PD-1.

顺便说一句，我认为是2018年或2019年的诺贝尔奖，无论是医学还是生理学，实际上是颁发给发现CTLA-4和PD-1的两位科学家的。

So I believe this is the only Nobel Prize in medicine for immunotherapy.

所以我相信这是免疫疗法领域唯一的诺贝尔医学奖。

It's a very big deal.

这是一件大事。

So this study sought to compare the effect of anti-CTLA-4 to a placebo, and the placebo in this case was not a real placebo.

因此，这项研究试图比较抗 CTLA-4 与安慰剂的效果，而本例中的安慰剂并不是真正的安慰剂。

It was a peptide vaccine called GP-100, to ask the question, in patients with metastatic melanoma, what would be the impact on median survival and overall survival?

这是一种名为GP-100的肽疫苗，请问，对于转移性黑色素瘤患者，对中位生存期和总生存期有何影响？

So let's talk a little bit about the paper.

那么让我们来谈谈这篇论文。

So again, one of the funny things about this is I used to read these papers a lot, Andrew.

再说一次，有趣的事情之一是我曾经经常阅读这些论文，安德鲁。

These used to be my bread-and-butter papers.

这些曾经是我的面包和黄油文件。

So reading these, it's my hobby.

所以阅读这些是我的爱好。

And I don't read them that much anymore, so it was kind of amazing how long it took me to remind myself of stuff I used to remember.

我不再读它们了，所以我花了很长时间才提醒自己以前记得的东西，这有点令人惊讶。

But you do have to kind of go back and read the methods and figure out who were the patients in this?

但你确实必须回去阅读方法并弄清楚谁是其中的患者？

What was the eligibility criteria?

资格标准是什么？

Why did they do it this way?

他们为什么要这样做？

And of course, it all kind of came back to me, but it took a minute.

当然，我又想起来了，但花了一分钟的时间。

So the first thing is these are all patients who had progressed through every standard therapy.

因此，首先，这些都是通过每一种标准治疗取得进展的患者。

So these are patients for whom there were no other options.

因此，这些患者没有其他选择。

These patients either had very advanced stage three melanoma, which means it was local regional melanoma, but it couldn't be resected.

这些患者要么患有非常晚期的三期黑色素瘤，这意味着它是局部区域黑色素瘤，但无法切除。

So an example of that would be a cancer that was completely engulfing, let's say the primary site was the cheek, and it had completely grown into all of the surrounding soft tissue.

一个例子是完全吞噬的癌症，假设原发部位是脸颊，并且它已经完全生长到周围的所有软组织中。

It hadn't spread anywhere, but it was all the lymph nodes of the neck.

它没有扩散到任何地方，但扩散到了颈部的所有淋巴结。

And I've seen patients like this, and it's just completely disfiguring.

我也见过这样的病人，这简直就是毁容。

And they'd already been through the standard chemotherapy, and nothing was working, and the thing was growing.

他们已经接受了标准化疗，但没有任何作用，而且肿瘤还在生长。

And then it was mostly made up of patients with stage four cancer.

然后它主要由第四期癌症患者组成。

Now, melanoma has a very funny staging system.

现在，黑色素瘤有一个非常有趣的分期系统。

So in cancer, we typically talk about something called the TNM staging system.

因此，在癌症领域，我们通常会谈论一种称为 TNM 分期系统的东西。

It is the standard way that cancers are staged.

这是癌症分期的标准方法。

T refers to the tumor size, N refers to the lymph node status, and M refers to the presence or absence of metastases.

T指肿瘤大小，N指淋巴结状态，M指是否存在转移。

And for most cancers, it is a very simple system.

对于大多数癌症来说，这是一个非常简单的系统。

T is typically a number one, two, sometimes up to three and four, N is typically zero, one, or two, and M is zero or one.

T通常是数字一、二，有时高达三和四，N通常是零、一或二，并且M是零或一。

Either there's no mets or there are mets.

要么没有大都会，要么有大都会。

So for example, in colorectal cancer, the T staging determines the depth in the colon wall that it went.

例如，在结直肠癌中，T 分期决定了其进入结肠壁的深度。

N is did it go to mets, and I think in colon, I may be a little rusty on this, I think colon has N zero, one, or two, depending on how many lymph nodes.

N 是它是否去大都会，我认为在结肠中，我对此可能有点生疏，我认为结肠有 N 零、一个或两个，具体取决于有多少淋巴结。

And then M0, did it go to anything beyond that, like to the liver, lung, et cetera, or not?

然后M0，它是否到达了除此之外的任何地方，例如肝脏、肺等等？

Melanoma is a bit more complicated.

黑色素瘤有点复杂。

It has M0, meaning no mets, but it also has M1A, M1B, M1C, and M1D, and within each of those, it has a threshold for high and low lactate dehydrogenase, or LDH.

它有 M0，意味着没有代谢物，但它也有 M1A、M1B、M1C 和 M1D，并且在每一个中，它都有高和低乳酸脱氢酶 (LDH) 的阈值。

So it's both a staging based on imaging and biochemical.

所以它既是基于成像和生化的分期。

And the reason for that is LDH level is such a strong prognostic indicator of survival, in addition to M staging.

原因是除了 M 分期之外，LDH 水平也是一个强有力的生存预后指标。

Higher LDH levels tend to reflect more acidity, which we talked about why that's problematic, tends to reflect faster-growing tumors, higher turnover, higher metabolic activity.

较高的 LDH 水平往往反映出较高的酸度，这往往反映了肿瘤生长速度更快、周转率更高、代谢活动更高，这也是我们讨论过为什么会出现问题的原因。

M1A, let me see if I can remember this.

M1A，让我看看我是否还记得这个。

M1As are cancers that have metastasized to surrounding soft tissue or soft tissue anywhere in the body, so anywhere else on the skin.

M1As 是已经转移到周围软组织或身体任何部位软组织（即皮肤其他部位）的癌症。

And you might think, well, that's kind of crazy.

你可能会想，好吧，这有点疯狂。

How does that happen?

这是怎么发生的？

And it's really bizarre.

这真的很奇怪。

You can have a patient who had a melanoma that showed up in one part of their body, and then they have metastases on other parts of their skin.

一名患者的身体某一部位出现黑色素瘤，然后皮肤的其他部位出现转移。

M1B is, and I always get B and C confused.

M1B 是，但我总是把 B 和 C 搞混了。

I think B is the lung.

我认为B是肺。

So M1B is to the lung, M1C is to any internal organ, so liver, et cetera, and M1D is to the CNS.

因此，M1B 对应于肺，M1C 对应于任何内脏器官，例如肝脏等，而 M1D 对应于中枢神经系统。

And as those numbers increase, as those letters increase, the prognosis gets lower and lower and lower.

随着这些数字的增加，随着这些字母的增加，预后会变得越来越低。

So one of the first things I always look at when I look at a paper like this is, tell me about the patient population.

因此，当我看这样的论文时，我首先关注的事情之一就是告诉我有关患者群体的信息。

What was the breakdown of patients?

患者的病情到底是怎样的？

And in table one, so that's, again, in clinical papers like this, table one is always, always, always baseline characteristics.

在表一中，同样，在这样的临床论文中，表一始终、始终、始终是基线特征。

Oh, I should mention one other thing, Andrew.

哦，我应该提另一件事，安德鲁。

This was done as a three-to-one-to-one randomization.

这是以三对一的随机化方式完成的。

So again, in the simplest form, a study would have two groups.

因此，以最简单的形式，一项研究将分为两组。

We're going to just have a treatment group and a placebo group.

我们将只有一个治疗组和一个安慰剂组。

But in this arm, you had three groups, with one of them being the placebo.

但在这一组中，你分为三组，其中一组是安慰剂。

The placebo got just GP100, which is just a cancer vaccine.

安慰剂只有 GP100，这只是一种癌症疫苗。

By the way, this is a cancer vaccine that never showed any efficacy.

顺便说一下，这是一种从未表现出任何功效的癌症疫苗。

So it was a cancer vaccine that had been tested both with interleukin-2 directly and as an adjuvant for patients who had metastatic melanoma, or had, sorry, not metastatic melanoma, who had melanoma resected, who were tumor-free, and then given the vaccine as adjuvants to see did that have an effect on outcomes, and it didn't.

因此，这是一种癌症疫苗，直接用白介素-2 进行了测试，并作为佐剂用于患有转移性黑色素瘤的患者，或者抱歉，没有转移性黑色素瘤、切除了黑色素瘤、无肿瘤的患者，然后将疫苗作为佐剂注射，看看是否对结果有影响，结果没有。

So it's kind of a known placebo.

所以它是一种已知的安慰剂。

So you had that group, then you had the anti-CTLA-4 group, and then you had anti-CTLA-4 plus GP100 as-

所以你有那个组，然后你有抗 CTLA-4 组，然后你有抗 CTLA-4 加 GP100 作为-

Andrew Huberman:

安德鲁·休伯曼：

Yeah, what's the rationale of-

是啊，理由是什么——

Dr. Peter Attia:

彼得·阿蒂亚博士：

For the three-to-one-to-one, it's basically it increases statistical power.

对于三对一对一来说，基本上是提高了统计能力。

So this total study was a little under 700 people.

所以这项研究的总人数略低于 700 人。

They put 400 in the anti-CTLA-4 plus GP100 group, and then a little over 130 in each of the other two groups.

他们将 400 例放入抗 CTLA-4 加 GP100 组，然后将略多于 130 例放入其他两组。

So you're always going to be able to make these two comparisons.

所以你总是能够进行这两个比较。

What you can check by doing this is, is there any effective GP100 in this setting, which had never been done before.

通过这样做你可以检查的是，在这个设置中是否有任何有效的GP100，这是以前从未做过的。

So again, GP100 is a known protein expressed by melanoma, and all of these people were haplotyped to make sure that their immune system would recognize it.

再说一遍，GP100 是黑色素瘤表达的一种已知蛋白质，所有这些人都进行了单倍型分析，以确保他们的免疫系统能够识别它。

And the question was, would giving people anti-CTLA-4, i.e., taking the brakes off their immune system, with or without GP100 make a difference?

问题是，给予人们抗 CTLA-4，即停止免疫系统的制动，无论有或没有 GP100，都会有效果吗？

So going through this, you can see it sort of skews about 60% to 40% male to female.

综上所述，您可以看到男性与女性之间的比例大约为 60% 到 40%。

They talk about something called the ECOG performance status.

他们谈论的是“ECOG 表现状态”。

That refers to how healthy a patient is coming in.

这指的是病人进来时的健康状况。

So ECOG zero is no limitations whatsoever, which is kind of amazing when you really consider something.

因此，ECOG 零没有任何限制，当你真正考虑某件事时，这有点令人惊奇。

I think this speaks to just how devastating this disease is.

我认为这说明了这种疾病的破坏性有多大。

These are patients who all have six months to live.

这些患者的生命只有六个月。

A year max, and yet look at this, 58% to 60% of them have no limitation on their quality of life at this very moment.

最多一年，但看看这个，58%到60%的人此时此刻的生活质量没有受到限制。

That's going to change dramatically absent a cure here.

如果没有治愈方法，情况将会发生巨大变化。

And then ECOG 1 has some limitation, and you can see that ECOG 1 plus ECOG 0 is basically 98% of the population.

然后ECOG 1有一些局限性，你可以看到ECOG 1加上ECOG 0基本上是98%的人群。

You can see the staging there.

你可以看到那里的表演。

So again, very, very few of these patients are the M0 category.

同样，这些患者中属于 M0 类别的患者非常非常少。

M0s are people who have stage three disease that is so aggressive it can't be resected.

M0 是指患有第三阶段疾病的人，这种疾病非常严重，无法切除。

That's about 1%.

大约是1%。

But the majority of these people are the M1As, M1Bs, M1Cs.

但这些人中的大多数是 M1A、M1B、M1C。

So these are people with very aggressive cancers.

这些人患有非常侵袭性的癌症。

You can also see that about 10% to 15% of these people also have CNS metastases.

您还可以看到，这些人中大约有 10% 到 15% 也有 CNS 转移。

Again, the poorest prognosis of the poor.

再次强调，穷人的预后最差。

And then you can see about 40% of them have the LDH level above cutoff.

然后您可以看到大约 40% 的人的 LDH 水平高于临界值。

All of this is to say we're talking about a group of patients who have a very high likelihood of not surviving more than a year.

所有这一切都表明，我们正在谈论的是一群很可能无法存活超过一年的患者。

It would be very unlikely that many of these patients would survive more than a year.

这些患者中的许多人不太可能存活超过一年。

So basically, more than 70% of these people have visceral metastases, a third have high LDH, and more than 10% have brain mets.

所以基本上，这些人中70%以上有内脏转移，三分之一有高LDH，10%以上有脑转移。

They've also all progressed through standard therapy.

他们也都通过标准治疗取得了进展。

So-

所以——

Andrew Huberman:

安德鲁·休伯曼：

Radiation, chemo

放射、化疗

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

And the chemo for melanoma can be kind of a toxic chemo that really just doesn't really do anything.

黑色素瘤的化疗可能是一种有毒的化疗，实际上没有任何作用。

Andrew Huberman:

安德鲁·休伯曼：

So is it commonplace to use a treatment that failed in clinical trials as a placebo in these sorts of studies?

那么，在此类研究中使用临床试验失败的治疗方法作为安慰剂是否很常见？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah, it's interesting.

是的，这很有趣。

You're referring, obviously, to the GP100, and I think the thinking was, okay, it hasn't been effective in other treatments, for example, when combined with IL-2 or as an adjuvant, but never before has it been tried with a checkpoint inhibitor, which is the technical term for this type of drug.

显然，你指的是 GP100，我认为，好吧，它在其他治疗中没有效果，例如与 IL-2 联合使用或作为佐剂时，但以前从未尝试过与检查点抑制剂（这是此类药物的技术术语）一起使用。

I think there was also some belief that it would be easier to enroll patients.

我认为还有一些人认为招募患者会更容易。

I don't think they stated this, but that's often the case.

我不认为他们说过这一点，但情况经常如此。

It would be easier to enroll patients if they would know that even in the placebo arm, they're still getting an active agent.

如果患者知道即使在安慰剂组中，他们仍在服用活性药物，那么招募患者就会更容易。

Andrew Huberman:

安德鲁·休伯曼：

Got it.

明白了。

And I suppose there's always the possibility that the combination of the failed drug with a new drug would work, and then so you're increasing the probability for novel discovery.

我认为失败的药物与新药的组合总是有可能发挥作用，这样就增加了新发现的可能性。

Dr. Peter Attia:

彼得·阿蒂亚博士：

For sure, and again, if you go back to the randomization of three to one to one, it's really only one-fifth or 20% of the participants that would get just the GP100.

当然，如果你回到三比一比一的随机化，实际上只有五分之一或 20% 的参与者只会获得 GP100。

So in other words, you're basically telling people when they come into this study, there's an 80% chance you're going to get anti-CTLA-4.

换句话说，当人们参与这项研究时，你基本上是在告诉他们，你有 80% 的机会会感染 CTLA-4 抗体。

That's a much better set of odds than your typical study where you're going to be 50% likely to get the agent of interest.

这比您的典型研究（您有 50% 的可能性找到感兴趣的代理）的几率要高得多。

Andrew Huberman:

安德鲁·休伯曼：

Right, and people who are literally dying of cancer, they don't want to be in the control group.

是的，那些真正死于癌症的人，他们不想成为对照组。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Right.

对。

That's right.

这是正确的。

So the primary outcome for this study actually changed in the study.

因此，这项研究的主要结果实际上在研究中发生了变化。

Now, they have to get permission to do that.

现在，他们必须获得许可才能这样做。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So the original primary endpoint was the best overall response rate.

因此，最初的主要终点是最佳总体缓解率。

So I have to explain how response rates are measured.

所以我必须解释一下响应率是如何衡量的。

This is a bit complicated.

这有点复杂。

Remember, all of these patients, by definition, have measurable visible cancer, by visible either on the surface of their body, but more likely on an MRI or CT scan.

请记住，根据定义，所有这些患者都患有可测量的可见癌症，通过身体表面可见，但更有可能在 MRI 或 CT 扫描中可见。

So all of these patients had to be scanned head to toe within 12 weeks of enrollment.

因此，所有这些患者都必须在入组后 12 周内接受从头到脚的扫描。

Again, there's another thing I should point out here, which I know you understand, but it's always worth reminding people.

再次，我应该在这里指出另一件事，我知道你明白，但它总是值得提醒人们。

When a study like this takes place, it usually takes place over many years.

当进行这样的研究时，通常会持续很多年。

And so it's not the case that all 700 of these patients were enrolled on the same day and we finished observing them on the same day.

因此，这 700 名患者并不是在同一天全部入组，我们也不是在同一天完成对他们的观察。

No, no, this took place for a very long period of time.

不不，这已经发生了很长一段时间了。

This took place across tens of centers.

这发生在数十个中心。

I can't remember if this was just globally or across the world.

我不记得这是全球性的还是全世界的。

It might've been across the world.

它可能已经遍布世界各地。

And so every center really needs to adhere to a very strict protocol, and you have a central organization that is running this.

因此，每个中心确实需要遵守非常严格的协议，并且有一个中央组织来运行它。

So you have a drug company, I think this is Bristol Myers Squibb, that makes the drug.

所以你有一家制药公司，我想这就是百时美施贵宝，生产这种药物。

They provide the drug, and then you have a CRO, a clinical research organization, that is basically managing the trial, and the trial is being done at cancer centers all over the world or all over the country.

他们提供药物，然后有一个 CRO，一个临床研究组织，基本上负责管理试验，试验是在世界各地或全国各地的癌症中心进行的。

And enrollment, I think, began in 2008 for this.

我想，这个项目的招生是从 2008 年开始的。

No, no, I think it completed in 2008.

不不，我想它是在 2008 年完成的。

It probably started in about 2004, 2005, and therefore you had to kind of have real clear protocols around this.

它可能开始于 2004 年、2005 年左右，因此你必须对此有真正明确的协议。

So a complete response is the easier of these to understand.

因此，完整的响应是更容易理解的。

A complete response is everything vanishes completely.

完整的反应就是一切都完全消失。

That's very rare in cancer therapy.

这在癌症治疗中非常罕见。

So instead, what we kind of look for is a partial response.

因此，我们寻找的是部分回应。

A partial response, and there's really different ways to define this, there are different criteria, but this is the most common way you define a partial response.

部分响应，定义它的方法确实不同，有不同的标准，但这是定义部分响应的最常见方法。

A partial response is at least a 50% reduction by diameter, because remember, in this type of imaging, you're looking at 2D versus 3D.

部分响应是直径至少减少 50%，因为请记住，在这种类型的成像中，您看到的是 2D 与 3D。

So if you're looking at a lung lesion and it's this big, if it's two centimeters long, it has to go to at least one centimeter in diameter.

因此，如果您正在观察肺部病变，并且它有这么大，如果它有两厘米长，那么它的直径必须至少达到一厘米。

So it's a 50% reduction at least of every single lesion with no new lesions appearing and no lesions growing.

因此，每个病灶至少减少 50%，且不会出现新病灶，也不会生长病灶。

So it's very strict criteria.

所以这是非常严格的标准。

Again, CR means everything vanishes.

再说一遍，CR 意味着一切都消失了。

PR means at least a 50% by diameter, which by the way is a much bigger reduction in terms of tumor volume when you consider the linear versus the third power relationship of length and volume, of every single lesion with nothing new appearing, regardless of how small, and no lesion growing.

PR 意味着直径至少减少 50%，顺便说一句，当您考虑长度和体积的线性关系与三次方关系时，每个单个病灶没有新出现，无论病灶有多小，并且没有病灶生长，这对肿瘤体积而言是一个更大的减少。

So, that's a PR.

所以，这是一个公关。

So you basically have no response, progression, we talk about those together, and then partial response and complete response.

所以你基本上没有反应，进展，我们一起讨论这些，然后是部分反应和完全反应。

So initially, the authors of this study, the primary endpoint of this was going to be the best overall response rate.

因此，本研究的作者最初的主要终点是最佳总体缓解率。

So what was the proportion of patients that hit PR?

那么达到 PR 的患者比例是多少？

What was the proportion that hit a CR?

达到 CR 的比例是多少？

That's very common in this type of paper where the outcomes are typically so dire.

这在这类论文中很常见，其结果通常非常可怕。

I think I said that the study was-- I don't remember when the study ended, but the amendment was made to change the primary endpoint to overall survival at some point during the study.

我想我说过这项研究是——我不记得研究何时结束，但进行了修改，将主要终点更改为研究期间某个时刻的总体生存率。

And by the way, that tends to be the metric everybody cares most about.

顺便说一句，这往往是每个人最关心的指标。

So the overall survival for metastatic melanoma is zero, with the exception of people who respond to high-dose interleukin-2, and that will boost the overall survival rate to somewhere between 8% and 10%.

因此，转移性黑色素瘤的总体生存率为零，但对高剂量白细胞介素 2 有反应的人除外，这将使总体生存率提高到 8% 至 10% 之间。

Very low.

非常低。

These patients, many of whom had already taken and progressed through interleukin-2.

这些患者中的许多人已经服用了白介素-2，并且病情有所进展。

Let me refresh my memory on what percentage of those patients.

让我回忆一下这些患者的百分比。

About a quarter of these patients had already taken high dose interleukin-2, and by definition, the fact that they're in this study means they had already progressed through that.

这些患者中约有四分之一已经服用了高剂量的白细胞介素-2，根据定义，他们参与这项研究的事实意味着他们已经取得了进展。

That treatment had failed.

那次治疗失败了。

Just reiterate, just the state these patients are in.

只是重申一下，这些患者所处的状态。

So now let's look at figure one.

现在让我们看一下图一。

So again, I'll describe it because I realize many people are just listening to us.

再次，我会描述它，因为我意识到很多人只是在听我们说话。

All of this will be available both on the video, and then we'll link to the paper.

所有这些都可以在视频中找到，然后我们将链接到该论文。

So figure one is a figure that probably looks really familiar to people who look at any data that deal with survival.

因此，对于那些查看任何与生存相关的数据的人来说，图一可能看起来非常熟悉。

It's called a Kaplan-Meier survival curve.

这称为卡普兰-迈耶生存曲线。

So on the x-axis for this curve is time, and time here is shown in months.

因此，该曲线的 x 轴上是时间，这里的时间以月为单位显示。

And on the y-axis is the overall survival.

Y 轴是总体生存率。

At the very top, 100%, at the bottom, 0%.

在最顶部，100%，在底部，0%。

And it has three graphs or three curves that are superimposed on one another for each of the three groups.

对于三组中的每一组，它都有三个图表或三个曲线相互叠加。

Again, the control group, which is the GP100, the anti-CTLA-4 group by itself, and the anti-CTLA-4 plus GP100.

再次，对照组，即 GP100、抗 CTLA-4 组本身以及抗 CTLA-4 加 GP100。

And one of the characteristics of a Kaplan-Meier curve is, by definition, they have to be decreasing in a monotonic fashion because it's cumulative overall survival.

根据定义，卡普兰-迈耶曲线的特征之一是它们必须以单调方式减少，因为它是累积的总体生存率。

That just means it can't come down and go back up.

这只是意味着它无法下降并返回。

Nobody comes back to life.

没有人复活。

So once a person dies, they are censored from the study and the curve drops and drops.

因此，一旦一个人去世，他们就会被排除在研究之外，并且曲线会不断下降。

And you can see that they highlight, and I actually think it makes the graph a little harder to read when they put some of those marks on there.

你可以看到他们突出显示，我实际上认为当他们在那里放置一些标记时，这会使图表变得更难以阅读。

But what really becomes clear when you look at this is that there's a clear distinction between the curve for the placebo group, the GP100 group, and the other two, the two treatment groups.

但当您看到这一点时，真正清楚的是，安慰剂组（GP100 组）和另外两个（两个治疗组）的曲线之间存在明显区别。

Now, you'll note at the very end that the two treatment groups appear to separate a little bit.

现在，您会在最后注意到两个治疗组似乎有点分开。

I'll talk about that in a second.

我稍后会讨论这个问题。

So when I look at these, Andrew, the first thing I always turn my attention to, I can't resist, I have to look at the right-hand side of the graph, because what is that really telling me, right?

所以，当我看到这些时，安德鲁，我总是将注意力转向的第一件事，我无法抗拒，我必须看图表的右侧，因为它真正告诉我什么，对吗？

The tail of this is showing me the true overall survival.

这个尾巴向我展示了真正的总体生存率。

And I want to sort of figure out what is going on.

我想弄清楚到底发生了什么。

So in the GP100 group, which is the placebo group, it is kind of amazing to think that there is still one person who is alive at 44 months.

因此，在 GP100 组（即安慰剂组）中，想到还有一个人在 44 个月时还活着，真是令人惊讶。

It's amazing.

太棒了。

It's both sobering and amazing that one person made it to 44 months.

一个人能活到 44 个月，这既令人警醒又令人惊奇。

The next thing I ask myself is, well, how long did half of the people make it?

接下来我问自己，一半的人坚持了多长时间？

That's called median survival.

这就是所谓的中位生存期。

And to do that, you go up to the y-axis, and you draw a little line from the 50 over, and then you bring that down, and that's awfully low.

为此，你需要向上移动 y 轴，从 50 上方画一条小线，然后将其向下拉，这是非常低的。

In fact, the table will tell us exactly what that is, because I think it's really hard to eyeball that stuff.

事实上，表格会准确地告诉我们那是什么，因为我认为很难用肉眼观察到这些东西。

So there's always a table that will accompany these things, and let's pull up that table.

所以总有一张桌子会伴随这些东西，让我们把那张桌子拉起来。

I've got this paper spread out over so many things.

我把这篇论文分散到了很多事情上。

That's adverse events.

这就是不良事件。

Where's our survival table here?

我们的生存表在哪里？

Andrew Huberman:

安德鲁·休伯曼：

Figure two, subgroup analysis of overall survival.

图二，总生存期的亚组分析。

Dr. Peter Attia:

彼得·阿蒂亚博士：

It would probably be helpful if I stapled these things together because it would be easier.

如果我把这些东西钉在一起可能会有帮助，因为它会更容易。

Andrew Huberman:

安德鲁·休伯曼：

Well, this is always a trade-off.

嗯，这始终是一个权衡。

Actually, since this is a journal club episode, I will say that stapling helps, but it also prevents one from separating things out, writing in the margins.

实际上，由于这是期刊俱乐部的一集，我会说装订很有帮助，但它也会阻止人们将内容分开，在页边空白处书写。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

So I like these little mini clips.

所以我喜欢这些迷你小剪辑。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

No financial relationship to the mini clips either.

与迷你剪辑也没有经济关系。

Just have to state that because if you don't say that, people go, "Oh, you must have a stake in these mini clips." And I like these little mini clips.

只需要声明这一点，因为如果你不这么说，人们会说，“哦，你一定在这些迷你剪辑中占有一席之地。”我喜欢这些迷你小剪辑。

In fact, I'm such a nerd, I always have one of these Pilot V5, V7s on my pocket or my hip, and then my pockets are always filled with these little mini clips.

事实上，我是个书呆子，我的口袋或臀部总是有一个这样的 Pilot V5、V7，然后我的口袋里总是装满这些小迷你夹子。

But then again, I have a friend who's a musician, and he's always raining guitar picks.

但话又说回来，我有一个朋友是一位音乐家，他总是演奏吉他拨片。

So, as far as occupational hazards go of being a nerd, these mini clips are pretty-

所以，就成为书呆子的职业危害而言，这些迷你剪辑非常-

Dr. Peter Attia:

彼得·阿蒂亚博士：

No, I'm a big fan of the mini clips as well.

不，我也是迷你剪辑的忠实粉丝。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

But I went without it today.

但我今天没有带它。

All right.

好的。

So thank you.

所以谢谢你。

Yes, table two.

是的，表二。

All right.

好的。

So let's look at table two while looking at the Kaplan-Meier curve, because now this allows us to see a couple of things.

因此，让我们在查看卡普兰-迈耶曲线的同时查看表二，因为现在这让我们可以看到一些事情。

By the way, remember how I said there's that one person who Kind of is still alive in the treatment group.

顺便说一下，请记住我说过治疗组中有一个人还活着。

Well, you can tell that he's not a complete responder.

嗯，你可以看出他不是一个完全的回应者。

He or she is not a complete responder, because under evaluation of therapy in table two, it says best overall response, and it says complete responders, zero.

他或她不是完全反应者，因为在表二的治疗评估中，它显示最佳总体反应，而完全反应者为零。

So there were zero complete responders in the placebo.

因此，安慰剂组的完全反应者为零。

There were two partial responders.

有两个部分响应者。

Again, a partial responder is some lesions got smaller, some got bigger.

同样，部分反应是一些病变变小，一些病变变大。

Stable disease is it didn't really change that much, and progressive disease is obviously it went beyond.

稳定的疾病是指它并没有真正改变那么多，而进展性疾病则是指它明显超出了范围。

Not eval-

不评价-

Andrew Huberman:

安德鲁·休伯曼：

When you say a partial response, like lesions got smaller, are they literally just tracing the circumference of one of these skin lesions and saying-

当你说部分反应时，比如病变变小，他们实际上只是追踪其中一个皮肤病变的周长，然后说——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yep

是的

Andrew Huberman:

安德鲁·休伯曼：

...

...

okay, it got bigger or smaller?

好吧，它变大了还是变小了？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Literally, we'd had rulers in clinic.

从字面上看，我们在诊所里有尺子。

Andrew Huberman:

安德鲁·休伯曼：

Like just morphology.

就像形态学一样。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yep.

是的。

Andrew Huberman:

安德鲁·休伯曼：

Gosh.

天哪。

This feels so crude, I mean, it makes total sense, but in terms of modern medicine.

这感觉很粗糙，我的意思是，这完全有道理，但就现代医学而言。

Oh, your lesion grew from three millimeters to six millimeters.

哦，你的病变从三毫米长到了六毫米。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

And you're literally drawing little boundaries around little blotches on the skin.

你实际上是在皮肤上的小斑点周围画出小界限。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

You're putting a little measuring tape on them.

你在它们上面放了一根小卷尺。

Now again, most of these are happening in the radiology suite because most of the disease for these patients is inside the body.

现在，大部分这些都发生在放射科，因为这些患者的大部分疾病都发生在体内。

Remember, more than 70% of these patients had visceral metastases, so liver, soft tissue, lung, brain.

请记住，这些患者中 70% 以上有内脏转移，即肝脏、软组织、肺、脑。

In fact, if you include lung, liver, brain, and viscera, it's pretty much all the patients.

事实上，如果包括肺、肝、脑和内脏的话，几乎就是所有的病人了。

So most of this is looking at a CT scan or an MRI for the brain.

因此，其中大部分是针对大脑进行 CT 扫描或 MRI 检查。

Andrew Huberman:

安德鲁·休伯曼：

Got it.

明白了。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Okay, so that's kind of the first thing that comes up.

好的，这就是首先出现的问题。

The median response rate should be shown pretty prominently here.

中位响应率应该在此处非常显着地显示。

So I'm looking through this and da, da, da, da, da.

所以我正在研究这个，达，达，达，达，达。

Where is median response?

中位反应在哪里？

Maybe it's shown in a different table.

也许它显示在不同的表中。

Let's see.

让我们来看看。

Not disease control rate, time to progression.

不是疾病控制率，而是进展时间。

I remember it's about 10 months, but maybe that's just in the text.

我记得大约有10个月，但也许这只是在文字中。

Yeah, here it is.

是的，就是这里。

So I thought this would be in a table, but it's on page 715 of the paper.

所以我以为这会出现在表格中，但它出现在论文的第 715 页上。

It just reports it.

它只是报告它。

I'm sorry, I misspoke.

对不起，我说错了。

The 10 months was for the anti-CTLA-4 plus GP100, and 6.4 months for the GP100 alone.

抗 CTLA-4 加 GP100 为 10 个月，单独 GP100 为 6.4 个月。

That's the control.

这就是控制。

And then 10.1 for the anti-CTLA-4 alone.

然后是单独的抗CTLA-4的10.1。

Okay.

好的。

So again, and again, I'm just always doing this.

所以一次又一次，我总是这样做。

I'm kind of going back to the paper to be like, does that make sense?

我有点回到报纸上想，这有意义吗？

And yeah, you kind of called it, right?

是的，你这么称呼它，对吧？

You said median survival was about eight.

你说中位生存期约为八。

Well, it turns out it's actually six and change because it has that little ding in it.

好吧，事实证明它实际上是六个并且发生了变化，因为里面有那个小叮当声。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And it's out to a little past 10 on the two others.

另外两个的时间已经过了 10 点。

So the net takeaway here is, again, just to put that in English because it's so profound, 50% of the patients in the control group were dead in six months.

因此，这里的最终结论是，再次用英语表达，因为它是如此深刻，对照组中 50% 的患者在六个月内死亡。

50% of the patients in the treatment group, both treatment groups, were dead in 10 months.

治疗组（两个治疗组）都有 50% 的患者在 10 个月内死亡。

So what that means in cancer speak is these drugs extended median survival by four months.

因此，用癌症术语来说，这意味着这些药物将中位生存期延长了四个月。

Now, that's an important concept.

现在，这是一个重要的概念。

When we think about how has cancer therapy changed over the past 50 years, median survival for metastatic cancer has increased across the board.

当我们思考过去 50 年癌症治疗发生了怎样的变化时，转移性癌症的中位生存期全面提高。

So a person today with metastatic colorectal cancer, or a woman today with metastatic breast cancer, or a person with metastatic lung cancer, these people will live longer with those diseases today, thanks mostly to treatments.

因此，今天患有转移性结直肠癌的人，或者患有转移性乳腺癌的女性，或者患有转移性肺癌的人，这些人今天患有这些疾病时会活得更长，这主要归功于治疗。

This is not an early detection lead time bias issue.

这不是早期检测提前期偏差问题。

This is treatments are allowing people to live longer, and that's an important part of the story, but it's only half of the story, yet it often gets touted as the story.

这是治疗方法让人们活得更久，这是故事的重要部分，但这只是故事的一半，但它经常被吹捧为故事。

The other half of the story, and frankly the story that I think is more important, is what is overall survival doing?

故事的另一半，坦率地说，我认为更重要的故事是，整体生存在做什么？

And if you go back to those cancers, the answer is zero.

如果你回到那些癌症，答案是零。

So overall survival hasn't changed for solid epithelial tumors.

因此，实体上皮肿瘤的总体生存率没有改变。

It was 0% in 1970, and it's 0% today.

1970 年是 0%，今天也是 0%。

Andrew Huberman:

安德鲁·休伯曼：

Everyone dies.

每个人都会死。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Everyone dies from metastatic solid organ tumors.

每个人都会死于转移性实体器官肿瘤。

Now again, there's those niche examples I gave you.

现在，我再次给你提供了那些小众的例子。

Testicular cancer is now an exception.

睾丸癌现在是一个例外。

GI stromal tumors would be an exception, and I'm not including leukemias and lymphomas, where now there are exceptions.

胃肠道间质瘤是一个例外，我不包括白血病和淋巴瘤，但现在也有例外。

Andrew Huberman:

安德鲁·休伯曼：

Okay.

好的。

Not to try and be overly optimistic, but if I look at the graph in figure one, and I look out at the tail of the graph-

不要过于乐观，但如果我看一下图一中的图表，我会看到图表的尾部——

Dr. Peter Attia:

彼得·阿蒂亚博士：

That's right

没错

Andrew Huberman:

安德鲁·休伯曼：

...

...

and for those that are just listening, what I see, and I'm far less familiar with this type of work and analyzing these type of data, but what I see is that people in the placebo group, they're all dead except that one.

对于那些只是在听的人，我所看到的，我对这种类型的工作和分析这些类型的数据不太熟悉，但我看到的是安慰剂组的人，除了那个人之外，他们都死了。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yep.

是的。

Andrew Huberman:

安德鲁·休伯曼：

They're basically all dead at 44 months.

他们在 44 个月时基本上就全部死亡了。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yep.

是的。

Andrew Huberman:

安德鲁·休伯曼：

But when I look at the number, how long it takes for everyone to be dead in the treatment groups, it's like 50, looks like 53, 54 months or so.

但当我看一下这个数字时，治疗组中每个人死亡需要多长时间，大约有 50 个月，看起来大约是 53、54 个月左右。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Well, and they're not dead.

好吧，他们还没有死。

That's the point.

这就是重点。

Andrew Huberman:

安德鲁·休伯曼：

They're hanging in there, right?

他们就挂在那里，对吗？

As somebody who lost both of my scientific advisors, two of the three, the other one to suicide, we've talked about this before, but the other two to different cancers, both had the BRCA2 mutation, by the way.

作为一个失去了我的两位科学顾问的人，三名中的两位，另一位因自杀而去世，我们之前已经讨论过这一点，但顺便说一句，另外两位因不同的癌症而都有 BRCA2 突变。

An extra eight to 10 months with your kids or with your spouse or to quote unquote, "Get your affairs in order," is a big deal.

多花八到十个月的时间陪伴孩子或配偶，或者用原话来说，“让你的事务井井有条”，这是一件大事。

I mean, it's still depressing in the sense that nobody survives long-term, but an extra 10 months, as long as one is not miserable in that time, completely miserable, that's an extra 10 months of living, right?

我的意思是，没有人能够长期生存，这仍然是令人沮丧的，但是额外的10个月，只要一个人在那段时间不痛苦，完全痛苦，那就是额外的10个月的生活，对吧？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Well, and what's interesting here is the observation period stops, and some of these patients are still going.

有趣的是，观察期已经结束，但其中一些患者仍在继续观察。

So What you're highlighting is the point I want to make, which is overall survival is the most important metric, and it's the highest bar, make no mistake about it, and it's certainly not the bar any drug company is ever going to want to talk about for a cancer drug.

所以你强调的就是我想表达的观点，即总体生存率是最重要的指标，也是最高的标准，毫无疑问，这肯定不是任何制药公司想要谈论的抗癌药物的标准。

Andrew Huberman:

安德鲁·休伯曼：

But why not?

但为什么不呢？

Because-

因为——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Because none of them work, right?

因为它们都不起作用，对吗？

Andrew Huberman:

安德鲁·休伯曼：

They only want to talk about cures.

他们只想谈论治疗方法。

They don't want to talk about extending life.

他们不想谈论延长生命。

Dr. Peter Attia:

彼得·阿蒂亚博士：

No, they only want to talk about median survival.

不，他们只想谈论中位生存率。

They only want to talk about extending median survival.

他们只想谈论延长中位生存期。

And there are lots of people out there that are on this platform, I don't need to get onto it, but who will say, "Look, it's a real racket in oncology today, where drugs that are extending median survival by four weeks are being put on the market at a tune of $50,000 to $100,000 per treatment." That's not uncommon in oncology.

这个平台上有很多人，我不需要进入它，但谁会说，“看，这是当今肿瘤学领域的一个真正的喧嚣，将中位生存期延长四个星期的药物正在以每次治疗 50,000 至 100,000 美元的价格投放市场。”这在肿瘤学中并不罕见。

There was one drug that was approved for pancreatic cancer.

有一种药物被批准用于治疗胰腺癌。

I believe it extended median survival by nine days, and it cost $40,000.

我相信它可以将中位生存期延长 9 天，而且花费了 40,000 美元。

Andrew Huberman:

安德鲁·休伯曼：

And it's being advertised as significant-

它被宣传为重要的——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yes

是的

Andrew Huberman:

安德鲁·休伯曼：

...

...

extended survival.

延长生存期。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Because that was a statistical significant improvement in median survival.

因为这是中位生存率的统计显着改善。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So look, it's really understandable why people are very skeptical of the pharma industry, and I think a much more nuanced view is necessary.

所以看，人们对制药行业非常怀疑的原因确实可以理解，我认为有必要采取更细致的观点。

Clearly, I don't think pharma is all bad, but I really understand why people lose faith in pharma when these types of products somehow make regulatory approval.

显然，我不认为制药业全都是坏事，但我真的理解为什么当这些类型的产品以某种方式获得监管部门批准时，人们会对制药业失去信心。

Andrew Huberman:

安德鲁·休伯曼：

Does insurance cover these kinds of drugs?

保险承保这些药物吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

It can.

可以。

In fact, it often does.

事实上，经常如此。

It depends on the FDA approval, of course, and the indication, but a lot of times they do, right?

当然，这取决于 FDA 的批准和适应症，但很多时候他们确实这样做，对吗？

So yeah, there's a societal cost to these things.

所以，是的，这些事情会产生社会成本。

But there's also a patient cost, right?

但还有患者费用，对吗？

So a lot of times insurance doesn't fully cover it, and a patient has to bear the cost difference.

所以很多时候保险并不能完全覆盖，病人必须承担费用差额。

And on top of that, you alluded to this a second ago, which is what if your quality of life is dramatically compromised as a result of this treatment?

最重要的是，您刚才提到了这一点，如果您的生活质量因这种治疗而急剧下降怎么办？

And yes, statistically, you're going to live nine days longer or three weeks longer, but at what cost to your health in those final remaining days?

是的，从统计数据来看，你会多活九天或三周，但在最后剩下的日子里，你的健康会付出什么代价呢？

And by the way, you're potentially straddling your loved ones with enormous debt in your absence.

顺便说一句，当你不在的时候，你可能会让你所爱的人背上巨额债务。

So it's a super complicated topic.

所以这是一个超级复杂的话题。

Andrew Huberman:

安德鲁·休伯曼：

Yeah, there's a dignity component, too.

是的，还有尊严的成分。

I've seen this in people dying.

我在人们的死亡中看到过这种情况。

At some point they become such a diminished version of their former selves that they don't want to be seen by people that way.

在某些时候，他们会变成以前的自己的缩小版本，以至于他们不想被人们那样看待。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So what is exciting about this drug, although this paper is not the one that shows it.

那么这种药物有什么令人兴奋的地方，尽管这篇论文不是展示它的。

The reason I chose this paper, Andrew, is because it was the first approval.

安德鲁，我选择这篇论文的原因是因为它是第一次批准。

A second drug came along that is an anti-PD-1 drug.

另一种药物出现了，它是一种抗 PD-1 药物。

That drug is called Keytruda.

这种药物叫做Keytruda。

That drug turned out to be even better and has even a greater response rate, both in terms of median survival and overall survival.

事实证明，该药物效果更好，无论是在中位生存期还是总生存期方面，反应率都更高。

But this was the landmark paper.

但这是具有里程碑意义的论文。

I also have a slight bias here, and I'll disclose in a moment why.

我在这里也有一点偏见，稍后我会透露原因。

But I think it just talks about very interesting biology.

但我认为它只是谈论了非常有趣的生物学。

So let's talk about a couple things that stuck out to me in this paper.

那么让我们来谈谈这篇论文中让我印象深刻的几件事。

The first thing that stuck out to me, and the authors didn't comment on it, unless they did and I missed it, is look at figure two.

第一件让我印象深刻的事情是看图二，作者没有对此发表评论，除非他们发表了评论，但我错过了。

So figure two is the subgroup analyses where you're sort of showing a similar graph to the one you showed earlier, right?

图二是子组分析，其中显示的图表与之前显示的图表类似，对吗？

Where you show the response rate or the change in response between the groups, and then you put the error bars on it, and this is where we talk about how, well, it's a 95% confidence interval, so does it touch the unity line?

在其中显示各组之间的响应率或响应变化，然后在其上放置误差线，这就是我们讨论如何，嗯，它是 95% 置信区间，那么它是否触及统一线？

So these are called tornado plots, typically.

因此，这些通常被称为龙卷风图。

And what you'll notice is that in the top you're looking at, it's comparing the anti-CTLA-4 with GP100 versus the GP100, and in the bottom, you're looking at the anti-CTLA-4 versus the GP100.

您会注意到，在顶部，您看到的是抗 CTLA-4 与 GP100 与 GP100 的比较，而在底部，您看到的是抗 CTLA-4 与 GP100 的比较。

So at a glance, you can see GP100 is not doing anything.

所以乍一看，你可以看到 GP100 没有做任何事情。

That's the first takeaway of comparing A to B.

这是比较 A 和 B 的第一个要点。

What I find most interesting is look at the subgroup analysis of females.

我发现最有趣的是女性的亚组分析。

Notice that in females, while there's a trend towards risk reduction, and this is risk reduction for overall mortality.

请注意，在女性中，虽然存在风险降低的趋势，但这是总体死亡率风险的降低。

So again, I just want to restate that.

再说一遍，我只想重申这一点。

The primary outcome of this trial was changed to overall survival, which I think is the better outcome, by the way.

顺便说一句，该试验的主要结果更改为总体生存率，我认为这是更好的结果。

And overall, for all patients, when you compare anti-CTLA-4 plus placebo versus placebo, there was a 31% risk reduction in overall mortality.

总体而言，对于所有患者，当比较抗 CTLA-4 联合安慰剂与安慰剂时，总体死亡率风险降低了 31%。

That's the mathematical interpretation of what you're seeing at the tail end of that Kaplan-Meier curve.

这就是您在卡普兰-迈耶曲线尾部看到的内容的数学解释。

Andrew Huberman:

安德鲁·休伯曼：

So living longer.

所以寿命更长。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Living longer.

活得更久。

Andrew Huberman:

安德鲁·休伯曼：

And it sounds like a big difference.

听起来差别很大。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Sounds like a big difference.

听起来差别很大。

Andrew Huberman:

安德鲁·休伯曼：

In some sense, it is a big difference.

从某种意义上来说，这是一个很大的区别。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Well, it is for those people because you're really looking at basically 0% surviving in the placebo group versus 20% of people are still alive at 56 months in the treatment group.

嗯，这是针对这些人的，因为安慰剂组中的存活率基本上为 0%，而治疗组中 56 个月时仍有 20% 的存活率。

But look, that means 80% have died, right?

但是看，这意味着 80% 已经死亡，对吧？

But notice that, and sorry, when you just look at the anti-CTLA-4 plus GP100 in the subgroup B, that hazard ratio's even showing more compression.

但请注意，抱歉，当您只查看 B 组中的抗 CTLA-4 加上 GP100 时，该风险比甚至显示出更多的压缩。

It's a 36% reduction in risk of death.

死亡风险降低了 36%。

But notice that the females did not reach significance.

但请注意，雌性并未达到显着水平。

So in the first group, they barely do, and you can see that because the confidence interval runs from 0.55 to 0.92, and notice the error bar almost touches the line.

因此，在第一组中，他们几乎没有这样做，您可以看到，因为置信区间从 0.55 到 0.92，并且注意到误差条几乎触及该线。

And in the second one, it does not reach significance at all.

而在第二个中，它根本没有意义。

So I actually went and did a little reading on this after, and I said, "Hey, was this an outlier study?" And it turned out it wasn't.

所以我实际上去读了一点关于这个的内容，然后我说，“嘿，这是一项异常研究吗？”但事实证明并非如此。

And that about half the studies of anti-CTLA-4 did indeed find that the drug was less effective in women than men, which I found interesting.

大约一半的抗 CTLA-4 研究确实发现该药物对女性的疗效低于男性，我觉得这很有趣。

Now, I couldn't find any great explanation for it, but the most plausible explanations fit into two categories.

现在，我找不到任何很好的解释，但最合理的解释分为两类。

The first are maybe there are differences in the immune response to the drug if you're a man or a woman.

首先，男性和女性对药物的免疫反应可能存在差异。

The second comes down to dosing.

第二个归结为剂量。

I should've said this at the outset, but of course, these drugs are not like a pill, where it's like everybody gets 50 milligrams of this.

我一开始就应该这么说，但是当然，这些药物不像药丸，就像每个人都服用 50 毫克一样。

They're all dosed based on weight.

它们都是根据体重服用的。

So this study is dosed, I believe, at three milligrams per kilogram.

因此，我认为这项研究的剂量为每公斤三毫克。

And because most men are heavier than women, men are getting a higher dose than women.

由于大多数男性比女性重，因此男性接受的剂量高于女性。

And weight and body surface area and immune system, these things are not all perfectly linear.

而体重、体表面积和免疫系统，这些东西并不都是完全线性的。

So I kind of wonder if this difference is simply explained by men, on average, getting a higher dose than women.

所以我有点想知道这种差异是否可以简单地用男性平均比女性接受更高的剂量来解释。

Andrew Huberman:

安德鲁·休伯曼：

Interesting.

有趣。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Last thing I want to talk about here is in table three.

我想在这里谈论的最后一件事是表三。

So table three, always an important table to look at in any paper, is what are the adverse outcomes, right?

所以表三，在任何论文中始终是一个重要的表格，是不利的结果是什么，对吗？

What are the adverse effects of the drug?

该药物有哪些不良反应？

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

I spent a little bit of time with this, and I confess it, I definitely don't want cancer to the extent that I can avoid it, but this table made me wonder whether or not I would also want to just avoid cancer treatment given the life extension provided.

我花了一点时间在这上面，我承认，我绝对不希望癌症达到可以避免的程度，但这张表让我想知道，考虑到所提供的寿命延长，我是否也想避免癌症治疗。

These adverse events are pretty uncomfortable.

这些不良事件令人非常不舒服。

They sound like it.

他们听起来很像。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

So just to put in perspective, and you always have to kind of be mindful of how many of these adverse events are occurring in people just because their disease is progressing.

因此，从长远来看，您始终必须注意人们中发生了多少此类不良事件，只是因为他们的疾病正在进展。

So the first thing I always want to look at is total adverse events in all three groups.

因此，我总是想关注的第一件事是所有三组的不良事件总数。

So grade three and grade four are real toxicities, right?

那么三级和四级才是真正的毒性，对吗？

Grade four toxicity is life-threatening toxicity, by the way.

顺便说一下，四级毒性是危及生命的毒性。

Grade three is pretty significant toxicity.

三级是相当显着的毒性。

Grade one and two, that's not that severe, right?

一二年级，没那么严重吧？

The little rash, put some corticosteroids on it, it went away kind of thing.

小皮疹，涂点皮质类固醇，就消失了。

Okay, so in the treatment plus GP100 group, 98.4% of people reported some event.

好的，在治疗加 GP100 组中，98.4% 的人报告了一些事件。

So all but 1.6%.

所以只有 1.6% 除外。

In the anti-CTLA-4 group alone, it was 96.7%, so only 3.1% did not.

仅抗 CTLA-4 组中，这一比例为 96.7%，因此只有 3.1% 的人没有。

But in the placebo group, it's 97%.

但在安慰剂组中，这一比例为 97%。

So it's important to keep in mind, everybody's having some adverse effect.

因此，重要的是要记住，每个人都会产生一些不利影响。

Okay, well, what if you say, well, let's just limit it to the most severe events.

好吧，如果你说，好吧，让我们把它限制在最严重的事件上怎么办？

Well, let's just talk about grade four toxicities.

好吧，我们只讨论四级毒性。

There were 6.1% of those in the placebo group, 8.4% in the anti-CTLA4 group, and 6.8% in the combined group.

安慰剂组有 6.1%，抗 CTLA4 组有 8.4%，联合组有 6.8%。

So not a huge difference-

所以差别不大——

Andrew Huberman:

安德鲁·休伯曼：

No

否

Dr. Peter Attia:

彼得·阿蒂亚博士：

...

...

in grade four toxicity.

毒性为四级。

Andrew Huberman:

安德鲁·休伯曼：

Meaning that whatever adverse events are occurring may not be related to the treatment.

这意味着发生的任何不良事件可能与治疗无关。

Dr. Peter Attia:

彼得·阿蒂亚博士：

They may not be related to the treatment.

它们可能与治疗无关。

Again, if you think about it, and it's a very awful, sad, morbid thought to imagine, you're looking at the adverse responses of people more than 80% of whom died during the course of a very short study.

再说一次，如果你仔细想想，这是一个非常可怕、悲伤、病态的想法，你会看到80%以上的人在一项非常短暂的研究过程中死亡的人的不良反应。

And so, it's very difficult to disentangle what effects or what side effects a person is having just from that process as they are from the actual treatment.

因此，很难区分一个人在这个过程中所产生的影响或副作用，就像实际治疗中产生的影响或副作用一样。

But if there is an area where there's a really clear difference, it's down in the autoimmune category.

但如果有一个领域存在真正明显的差异，那么它就属于自身免疫类别。

So if you look at any immune-related events, you can see that in the anti-CTLA-4 plus GP100 group, it's about 60% in both of those treatment groups versus 30%.

因此，如果您观察任何免疫相关事件，您会发现在抗 CTLA-4 加 GP100 组中，这两个治疗组的发生率约为 60%，而对照组为 30%。

And if you look at the grade three and four toxicities, it's 10% in the anti-CTLA4, 15% in the anti-CTLA-4 alone group, and only 3% in the treatment.

如果你看一下三级和四级毒性，抗 CTLA4 组为 10%，单独抗 CTLA-4 组为 15%，而治疗组仅为 3%。

So that's a real difference.

所以这是一个真正的区别。

Andrew Huberman:

安德鲁·休伯曼：

Well, it makes sense that people getting this drug plus placebo or just the drug would have autoimmune issues because this is an immunotherapy.

好吧，服用这种药物加安慰剂或仅服用这种药物的人会出现自身免疫问题，这是有道理的，因为这是一种免疫疗法。

Dr. Peter Attia:

彼得·阿蒂亚博士：

It's an immunomodulator.

它是一种免疫调节剂。

In fact, what is it doing?

事实上，它在做什么？

It is taking the brakes off the immune system.

它正在解除免疫系统的刹车。

Andrew Huberman:

安德鲁·休伯曼：

But then again, the things that they list out, pruritus, is that a irritation of the skin?

但话又说回来，他们列出的东西，瘙痒，是皮肤刺激吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah, irritation of the skin.

是的，刺激皮肤。

Andrew Huberman:

安德鲁·休伯曼：

I'm not a physician, but I know that any itis is going to be like an inflammation.

我不是医生，但我知道任何炎症都会像炎症一样。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yep.

是的。

Andrew Huberman:

安德鲁·休伯曼：

And oma, unfortunately, likely a cancer or cell replication.

不幸的是，oma可能是癌症或细胞复制。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Look at the difference in vitiligo.

看看白癜风的区别。

Andrew Huberman:

安德鲁·休伯曼：

Rash and vitiligo.

皮疹和白癜风。

Wow.

哇。

Yeah.

是的。

So very little.

所以很少。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Or, sorry.

或者，对不起。

Look at the gastrointestinal differences.

看看胃肠道的差异。

Yeah.

是的。

And the vitiligo, right?

还有白癜风，对吧？

So 3.7%, 2.3%, 0.8%.

所以3.7%、2.3%、0.8%。

The GI stuff is the most common stuff you're going to see there.

GI 的东西是你在那里最常见的东西。

Those are the really big ones.

这些才是真正的大人物。

Now-

现在——

Andrew Huberman:

安德鲁·休伯曼：

And of course, there's diarrhea and there's diarrhea.

当然，还有腹泻，还有腹泻。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Oh, yeah, yeah.

哦，是啊，是啊。

Andrew Huberman:

安德鲁·休伯曼：

Like there's traveler's diarrhea, there's-

就像旅行者腹泻一样，有——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah, no, these-

是的，不，这些——

Andrew Huberman:

安德鲁·休伯曼：

...

...

ate an overly spicy-

吃了太辣的——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah, and these people, I mean some-

是的，还有这些人，我的意思是一些-

Andrew Huberman:

安德鲁·休伯曼：

...

...

large meal the night before diarrhea, and then there's can't really do anything besides make trips back and forth to the bathroom diarrhea.

腹泻前一天晚上吃了一顿大餐，然后除了来回上厕所腹泻之外，真的无能为力。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Well, put it this way.

好吧，这么说吧。

Colitis here is diarrhea so significant these patients require IV fluids.

这里的结肠炎是严重的腹泻，这些患者需要静脉输液。

Now, what you don't see here is how many of these patients actually required corticosteroids to reverse the autoimmunity.

现在，您在这里看不到的是这些患者中有多少实际上需要皮质类固醇来逆转自身免疫。

So a lot of times what'll happen here in these studies or with these drugs is the autoimmunity becomes so significant that you have to stop the drug and give corticosteroids.

因此，很多时候，在这些研究中或使用这些药物时，自身免疫会变得如此严重，以至于您必须停止用药并给予皮质类固醇。

Do the exact opposite.

做完全相反的事情。

You now have to shut the immune system down.

你现在必须关闭免疫系统。

So you just took the brakes off it with the drug, and now you need to shut it down with corticosteroids.

所以你刚刚用药物解除了它的刹车，现在你需要用皮质类固醇来关闭它。

When I was, was I in med school?

当我在的时候，我在医学院吗？

No. When I was in my fellowship, I wrote a paper about autoimmunity correlating with response rate in anti-CTLA4 early on.

不。当我在研究员期间，我很早就写了一篇关于自身免疫与抗 CTLA4 反应率相关的论文。

This was during the phase two work.

这是在第二阶段工作期间。

So the NCI was a very early adopter of participating in these trials, and It was observed that, or at least hypothesized, this is what the paper basically wrote about, which was: Is there any correlation between autoimmunity and response?

因此，NCI 是参与这些试验的早期采用者，据观察，或者至少假设，这就是该论文的基本内容，即：自身免疫和反应之间是否存在相关性？

And it turned out the answer was yes.

事实证明答案是肯定的。

There was a very strong correlation.

存在非常强的相关性。

So there was no difference in autoimmunity between the doses.

因此，不同剂量之间的自身免疫没有差异。

So the paper we wrote was two dosing schedules.

所以我们写的论文是两个给药方案。

So it was basically the full dose, the three milligrams per kilogram, versus a low dose, one milligram per kilogram.

所以基本上是全剂量，即每公斤三毫克，而低剂量，即每公斤一毫克。

This is a phase two trial.

这是第二阶段试验。

Those are your two arms.

那是你的两条手臂。

There turned out to be no difference in autoimmunity between them, but there was a big difference between the response rate that tied to autoimmunity.

事实证明，它们之间的自身免疫没有差异，但与自身免疫相关的反应率却存在很大差异。

In other words, autoimmunity predicted response.

换句话说，自身免疫可以预测反应。

Now, I think over time, these investigators, the doctors who administer these treatments, are getting better and better at catching these things earlier because these autoimmune conditions can actually be devastating.

现在，我认为随着时间的推移，这些研究人员、实施这些治疗的医生在更早地发现这些情况方面变得越来越好，因为这些自身免疫性疾病实际上可能是毁灭性的。

So on a very personal note, when Keytruda came out, I want to say it was around 2011.

因此，就我个人而言，当 Keytruda 推出时，我想说那是在 2011 年左右。

No, gosh, it must've been 2013, 2014, thereabouts.

不，天哪，那肯定是 2013 年、2014 年左右了。

Again, it was for treatment of metastatic melanoma.

同样，它是用于治疗转移性黑色素瘤。

I want to come back and explain why melanoma gets all of the attention in immunotherapy conditions.

我想回来解释为什么黑色素瘤在免疫治疗条件下受到所有关注。

I'll state that.

我会声明这一点。

But anyway, a friend of mine got pancreatic cancer, and he got the bad type of pancreatic cancer.

但无论如何，我的一个朋友得了胰腺癌，而且他得的是恶性胰腺癌。

So this is adenocarcinoma of the pancreas.

这是胰腺癌。

So this is a non-survivable type of cancer.

所以这是一种无法生存的癌症。

Furthermore, his was unresectable.

此外，他的手术是不可切除的。

Andrew Huberman:

安德鲁·休伯曼：

Can you explain what that is for me?

你能解释一下这对我来说意味着什么吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

So about 20% of people who have pancreatic cancer technically have it in a way where you could still take out the head of the pancreas.

因此，从技术上讲，大约 20% 的胰腺癌患者即使切除胰头也仍会罹患胰腺癌。

Andrew Huberman:

安德鲁·休伯曼：

Right, the Whipple procedure.

对，惠普尔手术。

Dr. Peter Attia:

彼得·阿蒂亚博士：

The Whipple procedure.

惠普尔手术。

Andrew Huberman:

安德鲁·休伯曼：

Right.

对。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Now, tragically, most of those patients will still recur.

现在，可悲的是，大多数患者仍然会复发。

Andrew Huberman:

安德鲁·休伯曼：

My understanding is that pancreatic cancer progresses from anterior to posterior in the pancreas, and that the Whipple is a removal of the front and the anterior.

我的理解是，胰腺癌是从胰腺的前部到后部进展的，而惠普尔手术就是切除前部和前部。

That's the Whipple procedure.

这就是惠普尔程序。

So if the cancer has progressed far enough caudal into the posterior pancreas, then there's nothing left to cut out, basically.

因此，如果癌症已经进展到足够远的尾部进入后胰腺，那么基本上就没有什么可以切除的了。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Well, I mean-

嗯，我的意思是——

Andrew Huberman:

安德鲁·休伯曼：

Can we survive without a pancreas for any amount of time?

没有胰腺我们能生存多久吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Oh, yeah, absolutely.

哦，是的，绝对是。

Andrew Huberman:

安德鲁·休伯曼：

So why don't they just remove the whole pancreas?

那么他们为什么不直接切除整个胰腺呢？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Oh, that's my point.

哦，这就是我的观点。

It's already micrometastasized.

它已经微转移了。

So the surgical procedure is not the challenge anymore.

因此，外科手术不再是挑战。

It used to be.

曾经是。

So at Johns Hopkins, which is one of the hospitals where this was pioneered, the 30-day mortality for a Whipple procedure was, I don't know, 80%.

因此，在约翰·霍普金斯大学（该医院是率先采用这一技术的医院之一），惠普尔手术的 30 天死亡率（我不知道）是 80%。

And the reason was to figure out how to suture a pancreas to the bowel without the-- So the pancreas is such an awful organ to operate on because its enzymes are designed to digest anything and everything.

原因是想弄清楚如何将胰腺缝合到肠道上，而无需--所以胰腺是一个非常难以操作的器官，因为它的酶被设计用来消化任何东西。

So imagine now you have to cut the pancreas in half, take out the head of the pancreas with the duodenum, and then somehow sew that open half of a raw pancreas to the end of the jejunum and not let it digest itself.

所以想象一下，现在你必须把胰腺切成两半，取出胰头和十二指肠，然后以某种方式将半个生胰腺缝到空肠末端，不让它自行消化。

Andrew Huberman:

安德鲁·休伯曼：

Someone at Hopkins figured this out?

霍普金斯大学有人发现了这一点吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

No, the first one was actually done by A.O.

不，第一个实际上是 A.O. 完成的。

Whipple.

惠普尔。

But yes, at Hopkins is where they figured out the way to put drains in, the surgical technique, how to do it in two layers, what type of stitches to use.

但是，是的，在霍普金斯大学，他们找到了放置引流管的方法、手术技术、如何分两层进行引流、使用什么类型的缝线。

All of the nuances of this were worked out in a few places, but I would say Hopkins more than any place else.

所有这些细微差别都是在几个地方解决的，但我会说霍普金斯比其他任何地方都多。

Andrew Huberman:

安德鲁·休伯曼：

And are there physicians who try this on non-human primates or something, or is this always just done on patients and you keep saying-

有没有医生在非人类灵长类动物身上尝试这个，或者这总是只在病人身上进行，而你一直说——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Well, nowadays, put it this way, even 25 years ago, at a major center like Hopkins, the mortality of that procedure was less than 1%.

嗯，现在这么说吧，即使是25年前，在霍普金斯这样的主要中心，这种手术的死亡率还不到1%。

Andrew Huberman:

安德鲁·休伯曼：

Amazing.

太棒了。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Total myth.

完全是神话。

Andrew Huberman:

安德鲁·休伯曼：

So there have been some victories.

所以已经取得了一些胜利。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Well, yes, but here's my point.

嗯，是的，但这就是我的观点。

That's no longer the bottleneck, right?

这不再是瓶颈了，对吧？

Taking out the pancreas safely, as complicated and challenging as that is, and if you need a Whipple procedure, you only want to have it done by someone who just does that night and day, because you don't want weekend warriors doing it.

安全地取出胰腺，虽然复杂且具有挑战性，但如果您需要惠普尔手术，您只想让一个日夜不停地做的人来完成，因为您不希望周末勇士来做这件事。

That's not why people are living or dying.

这不是人们生或死的原因。

They're dying because the cancer just comes back.

他们快要死了，因为癌症又复发了。

It was already spread to the liver by the time you did it, you just didn't realize it yet.

当你这样做的时候它已经扩散到肝脏了，只是你还没有意识到而已。

So whether you took out the whole pancreas or the head of the pancreas or the tail of the pancreas, the location of the tumor is predictive of survival only in the extent that it basically is a window into how soon did symptoms occur.

因此，无论你取出整个胰腺、胰头还是胰尾，肿瘤的位置只能预测生存期，因为它基本上是了解症状发生的时间的窗口。

So pancreatic cancers in the tail tend to be more fatal, even though they're way easier surgically to take out, because by the time you develop symptoms of a tail pancreas cancer, it's a big cancer.

因此，尾部胰腺癌往往更致命，尽管它们更容易通过手术切除，因为当您出现尾部胰腺癌的症状时，它已经是一种大癌症了。

Andrew Huberman:

安德鲁·休伯曼：

So I was going to ask this question later, but I'll just ask it now.

所以我本来打算稍后再问这个问题，但我现在才问。

Given the link between the immune system and these cancers, is there an idea in mind that people who are, let's say, 40 and older or 50 and older, who they're not diagnosed with any cancer, would periodically just stimulate their immune system to wipe out whatever early cancers might be cropping up.

考虑到免疫系统与这些癌症之间的联系，是否有一种想法，比如 40 岁以上或 50 岁以上的人，如果没有被诊断出患有任何癌症，会定期刺激他们的免疫系统，以消灭可能出现的任何早期癌症。

Just take a drug to just ramp up the immune system, even to the point where you start having a little diarrhea, maybe a few skin rashes, and then come off the drug.

只需服用药物来增强免疫系统，甚至到您开始出现轻微腹泻，可能出现一些皮疹，然后停止用药。

Just basically to fight back whatever little cell growths are starting to take place in skin or liver, maybe for three weeks out of each year.

基本上只是为了抵抗皮肤或肝脏中开始发生的任何小细胞生长，可能每年持续三周。

I mean, why not?

我的意思是，为什么不呢？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah, it's an interesting question.

是的，这是一个有趣的问题。

I've never thought of it through that lens.

我从来没有从那个角度思考过。

I suppose the question is, what can we do to keep our immune systems as healthy as possible as we age?

我想问题是，随着年龄的增长，我们能做些什么来保持我们的免疫系统尽可能健康？

Because-

因为——

Andrew Huberman:

安德鲁·休伯曼：

Stay on a normal circadian schedule.

保持正常的昼夜节律。

There's evidence for that.

有证据证明这一点。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Sure.

当然。

No, there's evidence that Certainly if it promotes sleep, anything that promotes better rest is going to promote immune health.

不，有证据表明，如果它能促进睡眠，那么任何促进更好休息的事物都将促进免疫健康。

Because if you ask the macro question, which is, why does the prevalence of cancer increase so dramatically with age?

因为如果你问一个宏观问题，即为什么癌症的患病率随着年龄的增长而急剧增加？

There are certain diseases where it's really obvious why the prevalence of the disease increases with age.

对于某些疾病，其患病率随着年龄的增长而增加的原因非常明显。

Andrew Huberman:

安德鲁·休伯曼：

Yeah, like age-related macular degeneration.

是的，就像年龄相关性黄斑变性一样。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Sure.

当然。

Or cardiovascular disease is by far the most obvious because it's an area under the curve exposure problem.

或者心血管疾病是迄今为止最明显的，因为它是暴露问题曲线下的一个区域。

The more exposure to lipoproteins and the more the endothelium gets damaged, the more likely you are to accumulate plaque, and again, it totally makes sense why 10-year-olds don't have heart attacks and 80-year-olds do.

接触脂蛋白越多，内皮受损越多，斑块积聚的可能性就越大，这也是为什么 10 岁的人不会患心脏病而 80 岁的人却会患心脏病的原因。

But when you sort of acknowledge that, well, hey, anybody's accumulating genetic mutations.

但当你承认这一点时，好吧，嘿，任何人都在积累基因突变。

We're always surrounded and being bombarded by things that are altering the genome of our cells.

我们总是被改变我们细胞基因组的事物所包围和轰炸。

Is it simply a stochastic process where the longer you live, the more of these mutations are going to occur until at some point one of them just wins?

这是否只是一个随机过程，你活得越久，这些突变就会发生越多，直到某个时候其中一个突变获胜？

I think that's got to be a big part of it.

我认为这一定是其中的重要组成部分。

But I think another part of it, and I clearly am not alone in thinking this, is that our immune system's getting weaker and weaker as we age.

但我认为另一部分原因是，随着年龄的增长，我们的免疫系统变得越来越弱，显然我并不是唯一一个这么想的人。

Right?

正确的？

People become more susceptible to infections as they get older, and I think that's equally playing a role in our susceptibility to cancer.

随着年龄的增长，人们变得更容易受到感染，我认为这在我们对癌症的易感性中也发挥着同样的作用。

So yeah, I think the question is how do you modulate immunity as you age?

所以，是的，我认为问题是随着年龄的增长，如何调节免疫力？

And to me, that's one of the most interesting things about rapamycin, potentially, is that when taken the right way, it seems to enhance cellular immunity, which again, that's potentially a really big deal.

对我来说，雷帕霉素最有趣的事情之一可能是，如果采取正确的方法，它似乎可以增强细胞免疫力，这又可能是一件大事。

Again, at least in short-term human experiments in response to vaccination, it's enhancing vaccine response.

同样，至少在针对疫苗接种的短期人体实验中，它增强了疫苗反应。

So the question is, would that translate into cancer?

那么问题来了，这会转化为癌症吗？

Nobody knows.

没有人知道。

Could that be one of the reasons why animals treated with rapamycin live longer and get less cancer?

这可能是接受雷帕霉素治疗的动物寿命更长、患癌症更少的原因之一吗？

Don't know.

不知道。

It could also be that it's at a fundamental level that's targeting nutrient sensing.

也可能是它在基础层面上以营养传感为目标。

Where I was going with that story was that, maybe I'll back up for a moment.

我讲这个故事的目的是，也许我会暂时支持一下。

Why melanoma?

为什么是黑色素瘤？

So we didn't really know this 30, 40 years ago in the early days of immunotherapy, but what we know now is that most cancers probably have about 40 mutations in them.

因此，30、40 年前免疫疗法的早期阶段我们并不真正了解这一点，但我们现在知道的是，大多数癌症可能有大约 40 个突变。

That's ballpark.

这就是大概。

Forty, fifty mutations is standard fare for a cancer.

四十、五十个突变是癌症的标准发生。

But melanoma happens to be one of the cancers that has many, many more mutations, and the more mutations a cancer has, the more likelihood that it will produce an antigen that's recognized as non-self.

但黑色素瘤恰好是具有很多很多突变的癌症之一，并且癌症的突变越多，它产生被识别为非自身抗原的可能性就越大。

And that's why in the early days of immunotherapy, the only things that worked were IL-2 against metastatic melanoma and kidney cancer, because kidney cancer turned out to also be one of those cancers that, for reasons that are not clear, produced hundreds of mutations.

这就是为什么在免疫疗法的早期，唯一有效的是针对转移性黑色素瘤和肾癌的 IL-2，因为事实证明肾癌也是那些由于尚不清楚的原因而产生数百种突变的癌症之一。

And so it's no surprise that the early studies of checkpoint inhibitors were also done in metastatic melanoma, where you basically have more shots on goal.

因此，检查点抑制剂的早期研究也在转移性黑色素瘤中进行也就不足为奇了，在这种情况下，基本上有更多的射门机会。

Again, if I'm going to take the brakes off my immune system, I might as well do it in an environment where there are more chances for my T cells to find something to go nuts against.

再说一次，如果我要解除免疫系统的刹车，我最好在一个 T 细胞有更多机会找到疯狂对抗的东西的环境中进行。

So it's 2013, 2014, and this friend of mine who has something called Lynch syndrome, which is one of those few hereditary or germline mutations that results in a huge increase in the risk of cancer.

现在是 2013 年、2014 年，我的一位朋友患有林奇综合症，这是少数几种导致癌症风险大幅增加的遗传性或种系突变之一。

He had already had colon cancer at about the age of 40, and had survived that.

他在40岁左右就已经患上了结肠癌，并且幸存了下来。

It was a stage three cancer, but he had survived it.

这是第三期癌症，但他活了下来。

Well, now, five years later, had developed pancreatic cancer.

五年后的现在，他患上了胰腺癌。

And when he went to see the surgeon, they said, "Yeah, there's nothing we can do." It's too advanced.

当他去看外科医生时，他们说：“是的，我们无能为力。”太先进了。

To put that in perspective, that is a death sentence, and that's a six-month survival.

换个角度来看，这就是死刑，而那是六个月的生存期。

And at around that time, there was a study that had come out in "The New England Journal of Medicine" that had talked about how patients with Lynch syndrome had lots of mutations.

大约在那个时候，《新英格兰医学杂志》上发表了一项研究，谈到林奇综合症患者如何有大量突变。

And so we talked with his doctors about the possibility of enrolling him in one of the Keytruda trials.

因此，我们与他的医生讨论了让他参加一项 Keytruda 试验的可能性。

There was one going on, I think, at Stanford.

我认为斯坦福大学正在发生这样的事情。

And the thinking being, well, you would want to target a checkpoint inhibitor against somebody who has a lot of mutations.

我们的想法是，你会希望针对具有大量突变的人使用检查点抑制剂。

And even though typically we don't see that in pancreatic cancer, his is a unique variant of it because it's based on this.

尽管我们通常在胰腺癌中看不到这一点，但他的癌症是其独特的变体，因为它是基于此的。

And so sure enough, he was tested for these mismatch repair genes.

果然，他接受了这些错配修复基因的测试。

He had them, enrolled in the trial, and amazingly, had not only a complete regression of his cancer, and he's still alive and cancer-free today, 10 years later, but the treatment worked so well at activating his immune system that his immune system completely destroyed his pancreas.

他接受了这些治疗，参加了试验，令人惊讶的是，他的癌症不仅完全消退，而且 10 年后的今天他仍然活着，没有癌症，而且治疗在激活他的免疫系统方面效果非常好，以至于他的免疫系统完全摧毁了他的胰腺。

So now he has effectively had a pancreatectomy based on his immune system.

所以现在他已经根据他的免疫系统有效地进行了胰腺切除术。