利用免疫系统预防、治疗与治愈癌症 | Alex Marson博士

一些有创业精神的年轻人或女性，或者两者兼有，会投身其中。

Well, some entrepreneurial young guy or gal or both launch into it.

我想了解免疫系统与癌症之间的关系。

I wanna understand the relationship between the immune system and cancer.

是的。

Yeah.

但也许我们首先应该谈谈癌症。

But perhaps first we should talk about cancer.

它是什么，又不是什么。

What it is and what it isn't.

我认为外界对癌症存在很多误解，认为癌症在我们不太遥远的过去并不存在。

I think there's a lot of misunderstanding out there that cancer did not exist in our not so distant past.

我的意思是，人们常说，哦，癌症是一种新现象，因为出现了这些带有电磁场和辐射的设备。

I mean, hear this, like people say, oh, you know, cancer is a new thing because of the advent of, you know, all these devices with EMFs and radiation.

但我肯定不这么认为。

That's certainly not what I believe.

癌症已经存在了非常非常长的时间吗？

Has cancer been around a very, very long time?

我们有这方面的证据吗？

Do we have evidence for that?

是的。

Yeah.

对。

Yeah.

如果有人真的感兴趣，我强烈推荐这本书《万病之王》，它是一部关于癌症作为疾病的传记，讲述了从有记录以来各种肿瘤及其伴随的痛苦的悠久历史。

I mean, if anyone's really interested, I would highly recommend this book, The Emperor of All Maladies, is really a biography of cancer as a disease, and talk about, I mean, the long history of going back as far as there's records of tumors of various kinds and the misery associated with that.

我们现在对癌症的理解非常不同，对吧？

We have a very different understanding of cancer right now, right?

我认为癌症是我们对疾病拥有最深入遗传学理解的领域之一。

And I think cancer is one of the most sophisticated where we have one of the most sophisticated genetic understandings of disease.

这并不意味着我们总能采取有效措施，但现在我们可以理解细胞中积累的突变。

It doesn't mean we can always do things about it, but now we can understand mutations that accumulate in cells.

突然间，健康细胞内的DNA就是它的程序。

And all of a sudden so the DNA inside of a healthy cell is their programming.

所以如果你有一个皮肤细胞，你的DNA就会编程这个皮肤细胞成为皮肤细胞。

So if you have a skin cell, your DNA is programming your skin cell to be a skin cell.

在癌症中，突然间，细胞内出现了一系列突变，导致它失去了正常的调控。

In cancer, all of a sudden, some combination of mutations emerge in that cell that lose its normal regulation.

皮肤细胞不再从DNA接收到正确的信号来保持在正确的位置，而是进入了一种不受控制地分裂的模式。

The skin cell is no longer getting the proper signals from its DNA to stay in the right place, and it goes and switches into a mode where it's dividing out of control.

结果是，这些细胞会转变为癌细胞，开始分裂，并失去正常的结构。

And the result is that those cells will then transform into cancer cells, they'll start dividing, they'll lose the normal architecture.

风险在于，它们可能会破坏所在组织的正常功能，或者进一步积累突变，从而实际上开始扩散到身体的远端部位，这就是转移——当癌症从一个局部部位扩散到身体其他部位时。

The risk is that they can disrupt things in the tissue where they are, or that further mutations can accumulate and they can actually start spreading into distant sites in the body, and that's metastasis, when a cancer goes from one local site to another part of the body.

随着这一过程的发生，这些癌细胞实际上是一个进化过程，它们获得了专注于自身生存的新基因。

And as that happens, those cancerous cells it's really an evolutionary process where those cancerous cells have acquired new genetics that are focused on their well-being.

这些细胞在分裂、失控地生长，并且抢占资源，以牺牲人体正常协调为代价进行增殖。

Those cells are dividing, they're growing out of control, and they're taking the resources, they're growing at the expense of the normal coordination of the human body.

这正是癌症最核心的本质。

And and that's that's really at at its core what what cancer is.

这是一种遗传性疾病，细胞失去正常调控，在各种组织中失控分裂。

It's genetic disease where cells lose the normal pro pro regulation and are dividing out of control in various tissues.

我能想象出那个画面：一个原本健康的细胞发生了突变。

I can see the picture in my mind where otherwise healthy cell gets a mutation.

我们可以讨论突变是如何产生的，然后它开始产生子细胞。

We can talk about how mutations arise, And but then starts spitting off daughter cells

是的。

Yep.

正如人们所称的那样。

As it's referred to.

是的。

Yep.

为什么子细胞必然继承突变，从而产生更多细胞？

Why would the daughter cells inherit the mutation necessarily to then create more cells?

因为这就是肿瘤的增殖。

Because that's the proliferation of the tumor.

是的。

Yeah.

细胞确实会将DNA传递给子细胞。

Certainly cells propagate their DNA into their daughter cells.

但我可以想象一种情况：每天我们的一些细胞都会发生突变，分裂出几个子细胞，而这些子细胞是终末分化的，对吧？

But I could imagine a situation where every day some of our cells get a mutation, spit off a couple daughter cells, and then those daughter cells are terminal, as we say, right?

它们不会再产生更多细胞。

And they don't create more cells.

这种现象每天在全身各处都在发生吗？

Is that happening all over the body every day?

那么，究竟是什么机制让能够继续增殖的DNA从一个细胞传递到下一个细胞呢？

So does this so how is it that the DNA that creates the further propagation gets passed from one cell to the next?

我认为这种情况一直在持续发生。

I do think this is happening constantly.

这是一个过程，每当细胞存在时，尤其是在它分裂时，我们细胞内的DNA复制都会出现一些不完美之处。如果细胞要复制，DNA就必须自我复制。

It's a process that every time a cell is around, especially as it's dividing, there is some imperfection in how the DNA the DNA has inside each of our cells, if that cell is going to replicate, the DNA has to replicate itself.

因此，你会得到两份应该完全相同的DNA副本，分别传递给该分裂细胞的两个子细胞。

So you end up with two copies of DNA that should be the same, each one being passed on to the two daughter cells of that dividing cell.

DNA复制的这个过程是不完美的。

That process of DNA replication is imperfect.

如果在复制过程中出现任何损伤，这两份副本中的一份可能会与另一份不同，从而导致一个子细胞出现突变，而另一个则没有。

And if there's any kind of damage during that process, one of those two copies might end up different than the other one, in which case you end up with a mutation now in one daughter cell and not the other.

如果这种突变是有害的或破坏性的——大多数突变确实如此——这些细胞可能会开始死亡。

If that is deleterious or if it's damaging, which probably most mutations are, those cells might start to die off.

明白了。

Okay.

DNA出错了。

The DNA got messed up.

携带这些DNA的细胞会死亡。

Those cells that are carrying that DNA die.

是的，它们无法吸收葡萄糖。

Yeah, they can't take up glucose.

它们根本无法进行细胞活动。

They just can't do cell stuff.

细胞内有许多调控机制，一旦发现问题，就会向该细胞发送程序性细胞死亡信号，当细胞出现异常时，会通过各种过程自行崩解。

And there's a lot of control mechanisms in the cell that say, something's wrong, let's send a programmed cell death signal to that cell, and cells will kind of implode with various processes when something is wrong.

这种情况大多数时候都会发生。

And that happens most of the time.

问题是，如果这种变化突然不再具有破坏性，反而成为一种信号——现在细胞开始生长得更多了。

The problem is if that change all of a sudden starts to not be damaging, but to actually be a signal, okay, now the cell is growing more.

由于这种突变，细胞获得了一些优势。

It has some benefit that it's accumulated as a result of that mutation.

现在，这个细胞会开始更频繁地分裂，携带最初突变的细胞可能会开始更频繁地分裂。

Now that cell will start to divide more and that cell that's carrying that first mutation might start dividing more.

它的两个子细胞现在都会传递这种让它们分裂更频繁的突变。

Both of its daughters now will pass on this mutation that's made it divide more.

如果在后续的轮次中又发生第二次突变，这种组合可能会使细胞从仅仅略微增加分裂，转变为迅速失控并发展为完全的癌症。

And if in subsequent rounds it gets a second hit, the combination may go from just cells that are dividing a little bit more to cells that take off and become full blown cancer.

现在有一些过程会加速这一进程。

Now there's certain processes that will accelerate that.

其中之一是接触会导致DNA损伤的物质，对吧？

One was exposure to things that cause DNA damage, right?

最主要的是吸烟。

The major one is smoking.

当吸烟使化学物质进入肺部时，肺细胞会暴露在这些化学物质中，从而导致更多的DNA损伤和突变。

When smoking causes chemicals to go into your lungs, the lung cells get exposed to these chemicals that then cause higher amounts of DNA damage, more mutations.

随着突变频率的增加，你更有可能积累一系列突变，这些突变会逐步导致癌症的发生。

And just as you have more mutations at a higher frequency, you're more likely to accumulate a set of mutations that will gradually go on to cause the generation of cancer.

加速这一过程的另一种方式是，有些人天生具有患癌的遗传易感性。

Another way that this process can be accelerated is that some people carry an underlying genetic predisposition to cancer.

所以人们可能听说过BRCA基因，这些基因会增加患乳腺癌和其他类型癌症的风险。

So people will likely have heard of the BRCA or the BRCA genes which predispose to breast cancer and other types of cancer.

这些人从一开始就携带一个已经使他们更容易积累突变的基因拷贝，整个过程发生的频率更高。

There people start with one copy that's already setting them on a road to higher risk of mutations accumulating and the whole process happens with a higher frequency.

因此，具有这种遗传倾向的人更容易走向癌细胞的发展。

And so this march towards cancer cells is more likely to occur in people with that type of predisposition.

BRCA突变有多常见？

How common is the BRCA mutation?

它在男性和女性中的分布是否均等？

Is it equally distributed in men and women?

是的，你能告诉我们些什么？

Yeah, what can you tell us?

每个人都应该进行BRCA检测吗？

And should everyone get tested for BRCA?

这里有很多问题。

And there's a lot of questions here.

我会一个一个地再问一遍。

I'll ask them again one by one.

当然，我们还会讨论一些可能具有保护作用的因素，但绝对最重要的是避免吸烟。

And then of course we'll talk about things that could be protective, just, but certainly avoiding smoking would be paramount.

那么，呼吸有多常见呢？

So how common is breath?

就诱变剂而言，主要的有吸烟和紫外线照射导致黑色素瘤。

In terms of mutagens, like the big ones are smoking, sun exposure for melanoma.

你知道，阳光照射还有其他平衡作用。

You know, they're another balancing features of sun exposure.

是的。

Yeah.

我们可以谈谈。

We can talk

关于这个。

about that.

但显然，紫外线是导致皮肤DNA损伤的风险因素。

But clearly UV is a risk factor for DNA damage in the skin.

是的，我的意思是，我完全愿意公开表态。

Yeah, I mean, I'm perfectly happy going on record.

我关于阳光所说的那些话，已经被曲解了无数种方式。

The things I've said around sunlight have been contorted in so many different ways.

现在简直像被拧成了麻花。

It's like a pretzel twist now.

不，更像是派对上的那种气球动物，但乱七八糟的。

No, it's more like one of those balloon animals at a party, but it's a mess.

过多的紫外线对皮肤细胞有害。

Too much UV is bad for skin cells.

就是不好。

It's just bad.

你需要一些，但太多就不好了。

You need some, but too much is bad.

长波长的光很有益，而这也正是挑战所在。

Long wavelength light is great for and therein lies the challenge.

是的。

Yeah.

但没错，我喜欢阳光，但你不希望暴露在过量的紫外线下。

But, yeah, love sunlight, but you don't want excessive UV.

大家别晒伤了。

Don't get avoid getting sunburn, folks.

是的，谢谢。

Yeah, thank you.

所以，BRCA基因突变，我和这个有个人关联，因为我两位导师——我的研究生导师和博士后导师——都死于BRCA突变相关的癌症，一位50岁，另一位刚过60岁，情况非常残酷，尤其是我知道其中一位的子女。

So yeah, the BRCA mutation, I have a personal relationship to this because I lost both my graduate advisor and my postdoctoral advisor to BRCA mutation related cancers, 50 and just a little bit older than 60 and the other, and you know, brutal, especially when you, you know, one of them I know their kids.

而且，年轻人得癌症真的很让人痛心，我知道他们童年时的癌症，但BRCA似乎挺常见的。

And, you know, it's just for young people getting cancer, and I know their childhood cancers, but BRCA seems pretty common.

我不太记得具体数字。

I don't know the numbers off the top of my head.

我的意思是，它们并不是癌症的主要数量成因。

I mean, they're not the major, like, numerical causes of cancer.

在所有癌症中，它只占少数。

In the scheme of cancers that develop, it's a minority.

它只是全部癌症中相对较少的一部分。

It's a relatively small set number of the full set of cancers.

问题是，如果你个体继承了BRCA突变，你患癌的风险会非常高。

The problem is if you inherit a BRCA mutation as an individual you have a very high risk of developing cancer.

因此，作为个体，你的风险会大幅上升，尤其是某些特定类型的癌症。

So as an individual your risk goes way way up and of certain types of cancer in particular.

我们现在可以以相当低廉的价格进行检测，是的。

We can all get tested for it now pretty cheaply, Yes.

是的。

Yeah.

如果家族中有癌症史，尤其是BRCA突变和其他几种突变，进行检测是强烈推荐的。

That's certainly recommended if there's a family history of cancer for BRCA mutations and a couple of other ones.

但你说得对，这些检测是可以获得的。

But you're right, the tests are available.

你刚才提到了男性和女性。

And you asked about men and women.

实际上，男性在BRCA基因的发现过程中起到了一些作用。

Actually was men were some of the ways that those BRCA genes were identified.

因为男性患乳腺癌非常罕见，那些确实患上乳腺癌的男性引发了人们的思考：也许他们存在某种潜在的遗传易感性，这帮助科学家发现了这些基因。

Because it's so rare for men to develop breast cancer, the ones who did develop it, there was a thought, well, maybe there's an underlying genetic predisposition, and that helped identify those genes.

很有趣。

Interesting.

每个人都应该接受BRCA检测吗？你知道，有些生活方式因素可以降低你的癌症风险。

Everyone get tested for BRCA, you know, because there are lifestyle factors that can reduce your cancer risk.

我想聊聊致突变物。

I'd like to talk about mutagens.

是的。

Yeah.

吸烟有害。

Smoking bad.

我要明确表示，电子烟有害，也许没吸烟那么严重，但仍然远远比不使用电子烟糟糕得多。

I'll go on record saying vaping bad, perhaps not as bad as smoking, but still way, way worse than not vaping.

保护电子烟的争论超出了我的理解范围，但好吧，各人有各人的选择。

The battle to sort of protect vaping is like beyond me, but okay, to each their own.

环境中的工作场所危害，比如已知的诱变剂。

Environmental sort of in workplace hazards, you know, like known mutagens.

你在实验室工作，接触诱变剂。

You work in a laboratory, you're working with mutagens.

是的。

Yeah.

对吧？

Right?

你接触的东西会直接破坏DNA。

You're working with things that literally pull DNA apart.

对。

Yes.

我一直担心在实验室工作。

It's always worried me working in a laboratory.

实验室里有很多致癌化学物质。

There are a lot of carcinogenic chemicals in a laboratory.

这是有原因的。

For a good reason.

对。

Right.

这就是所谓的yes。

This is the yeah.

我们试图研究癌症，但确实接触了大量可能致癌的物质。

We're trying to study cancer, but we're certainly working around a lot of things that could cause cancer.

是的。

Yeah.

化学物质、辐射。

Chemicals, radiation.

是的。

Yeah.

我不知道你那边怎么样。

I don't know if you about you.

我做了很多实验，用放射性标记细胞。

I did a lot of lot of experiments, radio labeling cells.

是的。

Yeah.

我的意思是，幸运的是，我们使用的是放射性标记的氨基酸，辐射水平据说——我也相信——没有其他一些那么危险。

I mean, we well, fortunately, we worked with, you know, radio tagged amino acids with radiation that was, we were told, and I do believe was not as dangerous as some of the others.

但没错，化学物质暴露确实是个大问题。

But, yeah, I mean, so chemical exposures are a big one.

没错。

Yep.

还有那些油漆、稀释剂和车库里东西上的标签，都是真的。

And so those labels on paints and thinners and stuff in the garage, that's real.

这是个真实的问题。

That's a real thing.

它们会引发细胞突变。

They mutate cells.

这些物质的强度存在一个从强到弱的谱系。

And there's some spectrum of stronger and less strong ones.

我认为我们常常是在缺乏充分数据的情况下运作，但有很多物质被怀疑是潜在的致突变物。

And I think oftentimes we're operating in an absence of great data, but I think there's a lot of things are implicated as potential mutagens.

杀虫剂。

Pesticides.

记住这一点。

Remember that.

我们观察农村地区癌症发病率，那些地方的作物经常喷洒杀虫剂。

We look at cancer rates in rural areas near where crops are dusted with pesticides.

我们曾请斯旺来过这里，她说：听好了，癌症风险和内分泌干扰物风险，可以把大城市想象成又脏又危险的地方。

We've had Swan came on here and she's like, Listen, the cancer risks, the endocrine disruptor risks, think of it as like big cities as dirty and dangerous.

而且它们出于某些特定原因。

And they are for certain reasons.

但她表示，如果你真的看到这些癌症与环境因素相关的激增，那么比起公交车尾气，更可能是农药造成的。

But she said, if you really see the spikes in these cancers related to environmental factors, it's less so bus exhaust than it is pesticides.

我的意思是，这种暴露并不是均匀或公平分布的。

I mean, is not evenly or fairly distributed.

有些人接触到这些物质的程度要高得多。

Some people get exposed way more to these things.

而我们对它们的研究还不够。

And we haven't studied them enough.

我们需要更多的研究，才能真正回答这个问题，好吧。

We need way more study to really be able to answer, okay.

而且人们不应该被抛在一边，我的意思是，这让我感到惊讶的是，我们竟然要靠自己去弄清楚每种产品的风险有多大。

And and people shouldn't be left I mean, this is my this is me just speaking as in it's kind of amazing to me how much we're left on our own to be figuring out what the risk of individual products is.

我认为，我们应该在明确真正风险所在的地方投入更多资源。

And I I think it's a place where we should be investing a lot more to get clarity on where the real risks are.

正如你们许多人知道的，我几乎已经服用了AG1十五年了。

As many of you know, I've been taking AG1 for nearly fifteen years now.

我早在2012年就发现了它，那时我还没有开始做播客，从那以后我每天都服用。

I discovered it way back in 2012, long before I ever had a podcast, and I've been taking it every day since.

我开始服用AG1的原因，也是我至今仍在服用的原因，是因为据我所知，AG1是市场上质量最高、成分最全面的基础营养补充剂。

The reason I started taking it and the reason I still take it is because AG1 is to my knowledge, the highest quality and most comprehensive of the foundational nutritional supplements on the market.

它将维生素、矿物质、益生元、益生菌和适应原融合在单一勺子中，易于饮用，味道也很好。

It combines vitamins, minerals, prebiotics, probiotics, and adaptogens into a single scoop that's easy to drink and it tastes great.

它的设计旨在支持肠道健康、免疫健康和整体能量水平。

It's designed to support things like gut health, immune health, and overall energy.

它通过帮助填补你日常饮食中可能存在的营养缺口来实现这一点。

And it does so by helping to fill any gaps you might have in your daily nutrition.

当然，每个人都应该努力摄入营养丰富的全食物。

Now, of course, everyone should strive to eat nutritious whole foods.

我每天确实都这么做，但人们经常问我，如果你只能选择一种补充剂，你会选哪一种？

I certainly do that every day, but I'm often asked if you could take just one supplement, what would that supplement be?

我的答案始终是AG1，因为它对支持我的身体健康、心理健康和表现至关重要。

And my answer is always AG1 because it has just been oh, so critical to supporting all aspects of my physical health, mental health, and performance.

这是我通过自身使用AG1的经验得出的结论，我也不断听到其他每天使用AG1的人有同样的反馈。

I know this from my own experience with AG1, and I continually hear this from other people who use AG1 daily.

如果你想尝试AG1，可以访问drinkag1.com/huberman获取特别优惠。

If you would like to try AG1, you can go to drinkag1.com/huberman to get a special offer.

限时优惠：订阅AG1即可免费获得六份旅行装AG1和一瓶维生素D3K2。

For a limited time, AG1 is giving away six free travel packs of AG1 and a bottle of vitamin D3K2 with your subscription.

再次提醒，前往drinkag1.com/huberman，即可免费获得六份旅行装AG1和一瓶维生素D3K2。

Again, that's drinkag1 with the numeral 1.com/huberman to get six free travel packs and a bottle of vitamin d three k two with your subscription.

我偶尔会在牙医那里拍X光片，是的。

I get X rays at the dentist now and again Yeah.

但我更不愿意拍X光片。

But I prefer not to get them.

X光会导致基因突变。

X rays cause mutations.

是的。

Yeah.

同样，剂量上存在权衡。

Again, there's a trade off in the dose.

当然。

Sure.

你知道，当你需要拍X光片时，那就得拍，但我不会为了好玩而去拍。

I You know, when you need an x-ray, you need an x-ray, but I wouldn't do them for fun.

对。

Right.

我的一些同事更喜欢在机场接受人工缓慢搜身，而不是通过扫描仪。

I mean, I have colleagues who prefer to do the slower manual pat down at the airport to going through the scanner.

他们告诉我，这是一种低剂量的辐射。

It's a low level of radiation is what they tell me.

但如果你经常旅行，就会多次接受这种低剂量辐射。

But if you're traveling a lot, you're getting multiple low level exposures.

我们知道飞行员也是如此，这出于其他原因——虽然你们可以告诉我们，但从大气层面来看，他们接触到的辐射更多。

And we know pilots, and this is for other reasons, because they're, you know, you can tell us, but atmospherically, they're exposed to more radiation.

飞行员的癌症发病率更高。

Cancer rates are higher in pilots.

现在他们也坐得很多，前列腺问题啊。

Now they're sitting a lot too, prostate kids.

好吧。

Okay.

那里有很多因素。

There's a bunch of things there.

但你自己会避免在机场通过扫描仪吗？

But do you yourself avoid the scanner at the airport?

说实话，我会，但我不能说这有数据支持。

Honestly, I I do, but I can't say that there's data for that.

我和你的感受一样。

I I feel the same way as you.

比如，如果能避免，我就尽量少用。

Like, if I can avoid it, I I try to minimize.

嗯。

Mhmm.

但这种做法并不是基于我有什么内部知识，我只是和你有同样的

But I that's not based on some inside knowledge I have, but I have the same

嗯。

Mhmm.

偏见，当然。

Bias of Sure.

是的。

Yeah.

越少越好。

Less seems better.

是的。

Yeah.

我的意思是我并不想针对扫描仪行业。

I mean, well, I'm not out to get the scanner industry.

我认为让人们听到这一点很有用，即即使没有正式的数据，只要对机制有理解，也能让人采取谨慎态度。

I think it's useful for people to hear that, that you could that one can have no formal data, but an understanding of mechanism that leads them to hedge.

是的。

Yeah.

知道这些很好。

It's good to know.

有没有致突变物？还有，致癌物和致突变物是一回事吗？

Are there any mutagens and well, is a carcinogen and a mutagen the same thing?

所以它们密切相关。

So they're closely related.

致突变物，我认为是指你改变了细胞中的DNA。

Mutagen, I think, means that you're mutating, that you're changing the DNA in the cell.

这就是它的意思。

That's that's the idea.

这些突变可能与癌症有关，也可能无关，但由于你增加了突变的发生，几乎不可避免地也提高了患癌的风险，而致癌物就是那些会增加癌症发生率的物质。

Those mutations may or may not be linked to cancer, but by virtue of the fact that you're causing more mutations, almost inevitably you're also increasing the risk of cancer, and carcinogens are things that increase the rate of cancer.

我喜欢烤肉。

I love barbecued meat.

我不喜欢烧烤酱，因为它太甜了，但我喜欢带焦香的肉。

I don't like barbecue sauce because it's sweet, but I like meat with a char.

是的。

Yeah.

对。

Yeah.

焦痕有害吗？

Is the char bad?

我觉得有。

I think so.

我的意思是，我也喜欢，但确实如此。

I mean, I like it too, but yeah.

再次强调，这些都是生活中的权衡决策。

Again, these are balancing decisions in life.

当然。

Sure.

但没错，总体而言，肉类已被认为是潜在的致癌物，尤其是在结直肠癌方面。

But yes, there's some I mean, meat in general has been implicated as a potential carcinogen, especially in colorectal cancer.

关于这一点有一些数据支持。

There's some data around that.

是的。

Yeah.

我对这些数据的理解——不是关于焦炭的数据，而是关于肉类的数据——是复杂的。

My read of those data, not the char data, but the meat data is it's tricky.

这只是我的观点，我需要明确说明，这是我对文献的解读：许多研究比较了富含红肉的饮食和植物性饮食，但问题是，富含红肉的饮食通常还包含其他许多因素。

This is just my standpoint, I want to make sure I put brackets around this, that this is my read of the literature, is that many of the studies that looked at meat rich red meat rich diets versus plant based diets, the problem is a lot of times the red meat enriched diets had a bunch of other things in them.

比如，食材来源并没有被考虑进去。

Like sourcing wasn't considered.

还有很多淀粉类食物。

There was also a lot of starches.

因为现在很多人似乎感觉更好了，至于长寿方面还不确定，但吃红肉、水果和蔬菜时他们感觉更舒服。

Because nowadays you find people who seem to at least feel better, who knows about the longevity aspect, but feel better eating red meat, fruits, and vegetables.

淀粉类食物要少量摄入。

Limited amounts of starches.

所以我觉得营养学研究一团糟。

So I feel like the nutrition studies are a mess.

简直是一场灾难。

They're kind of a disaster.

我对这一点确实没有清晰的认识。

I certainly don't have clarity on that.

是的。

Yeah.

这似乎改变了方向。

It seems like it changes the direction.

我认为关于纤维，我们有一些相当不错的常识性直觉。

I think some things we have pretty good common sense intuition about Fiber.

超加工食品可能不太好。

Ultra processed foods are probably bad.

但我认为我们究竟该吃哪些全食物的平衡，可能还需要进一步厘清。

But I think the balance of exactly what whole foods we're eating probably still needs to be worked out.

你怎么看待关于食用色素的数据？这现在非常及时。

How do you think about the data on like, for instance, food dyes this is very timely.

是的。

Yeah.

对。

Yeah.

某种食用色素

Where a certain food die

是的。

Yeah.

在实验室中以极高浓度

At a very, very, very high concentration in laboratory

动物身上，是的。

animals Yeah.

会显著增加这些动物患肿瘤和癌症的概率。

Creates a significantly higher incidence of tumors and cancers in those animals.

是的。

Yeah.

但人类食物中食用色素的含量仅为那极小的一部分。

But then the amount of food dye that's in the human food is a tiny fraction of that.

是的。

Yeah.

我并不是想在这里谈政治。

I'm not trying to get political here.

我只是认为，作为人们思考问题的框架，这个环境中肯定存在许多致癌物。

I just think as a framework for people to think about, there are many carcinogens, I'm sure right in this environment.

我不怀疑这张桌子上的油漆，事实上，如果他们真的用了这种材料，一旦误食可能会导致癌症。

I don't doubt that the lacquer on this table, in fact, if that's even what they used, if ingested could cause cancer.

我不怀疑这一点，对吧？

I don't doubt that, right?

但我并不认为在这种形式下，每天长时间靠近它就会导致癌症，我对此表示怀疑。

But I don't know that in its form here being near it for many hours a day does that, doubt it.

我们并没有在吸入这张桌子。

We're not inhaling the table.

这正是我所说的这种混乱程度。

This is what I mean by this level of confusion.

我认为我们都生活在这种背景性的困惑之中。

I think we all live with this background confusion of things.

你提到的那些研究显示高浓度暴露，但这对我们日常生活没有任何意义。

Some study has been published in my you said, high concentrations exposure doesn't mean anything in our lives.

相对风险是多少？

What's the relative risk?

所以我从吸烟、日晒说起，然后提到还有一个尾部。

So that's why I start with smoking, sunlight, and then say there's a tail.

我认为我们还不完全了解这种分布究竟是怎样的。

And I don't think we know fully what that distribution is yet.

我确信有一些因素的组合正在增加我们患癌症的风险。

I'm sure there are some combination of things that are increasing our risk of cancer.

我们真的不知道如何权衡暴露的持续时间和暴露量。

We don't really know how to weigh duration and amount of exposure.

这就是为什么我觉得这对人们来说真的很可怕。

And this is why I think it's really scary to people.

人们认识一些吸烟但没得肺癌的人。

People don't know, you know, know smokers who don't get lung cancer.

是的。

Yeah.

也有不吸烟却得病的人。

And non smokers who do.

还有不吸烟的人也会得。

And non smokers who do.

所以我认为，人们会想，到底是什么造成了伤害，不幸的是，这严重损害了人们对医学的信任，因为信息太混乱了。

And so I think people go, well, like what It actually has caused, I believe, a lot of damage in the faith in medicine, unfortunately, because the messaging is all is mixed up.

是的。

Yeah.

我认为如今人们正在尽力保护自己。

I think that nowadays people are trying to do what they can to protect themselves.

是的。

Yeah.

但人们还是会得癌症。

But people still get cancer.

即使你做得一切都对，还是可能得癌症。

You can do everything right and still get cancer.

即使你没有BRCA基因突变也是如此吗？

Is that even if you don't have a BRCA mutation?

当然。

Absolutely.

我的意思是，绝对如此。

I mean, absolutely.

你知道，我总觉得，最后一件事你也不想做就是把某人的行为归因于癌症。

You know, I think the last thing you ever want to do is like attribute someone's actions to cancer.

我的意思是，癌症是一种概率性疾病，某些基因突变会导致一种极其严重的疾病。

I mean, it is a probabilistic disease where some set of mutations occur that cause a really devastating disease.

所以，是的，我的意思是，我们并不知道答案，我们必须对此保持谦逊。

And so, yeah, I mean, we don't know the answers, and I think we have to be humble about that.

现在，我认为我们也可以讨论一下，当癌症发生时，我们该如何应对和治疗？

Now, what I think we can also talk about is, well, how do we handle, how do we treat cancer when it comes up?

而这正是我们之前进行的两个对话真正交汇的地方——当我们谈到免疫系统时，我们深入探讨了许多关于免疫系统不同细胞组成的详细机制。

And this is where these two conversations that we've been having really come together of when talking about the immune system, we went through a lot of I think, actually, went through a lot of sort of detailed mechanism thinking about the different cell constituents of our immune system.

我告诉你，我上医学院的时候——那也没多久以前，我2010年毕业——当时的主流观点是：别浪费时间去研究癌症免疫学。

I will tell you that when I went to medical school, which wasn't that long ago, graduated in 2010, The dogma was don't waste time thinking about cancer immunology.

癌症免疫学是一个毫无进展的领域。

Cancer immunology is a field that's going nowhere.

我的意思是，我当时在波士顿，可能那里存在一些地域偏见，但这种想法在当时是主流观点，即我们该如何治疗癌症。

I mean, think I was in Boston and I think that was maybe there was some local bias in that direction, but this was mainstream of thinking about how we would treat cancer.

那时，癌症的治疗方法主要是化疗，这种疗法已经存在了几十年，本质上是给人体注射毒素，这些毒素对癌细胞的毒性大于对健康细胞的毒性，让患者忍受所有副作用，因为他们必须如此才能清除癌细胞。

At that point, the way that cancer was being treated was chemotherapy, which is something that's been around for decades, it's basically give toxins to the body that will be more toxic to the cancer cells than to the healthy cells and ask people to endure all the side effects because they have to to get rid of the cancer cells.

而至今，这仍然是癌症治疗的主要手段。

And that's still the mainstay of cancer treatment.

我们都希望做得比这更好。

We all want to do better than that.

这非常难受。

It's very unpleasant.

极其，极其难受。

Very, very unpleasant.

不仅难受，而且更糟。

Unpleasant and worse.

我的意思是，人们忍受着巨大的痛苦，我们让患者经历如此可怕的事情，因为这已经是我们的最佳选择。

I mean, people endure hard you know, it's we put people through horrific things because it's the best we can do.

然后，出现了一种新的思路：好吧，让我们尝试开发针对我们之前讨论过的突变的靶向药物。

And then there was a wave of thinking, okay, well, let's try to make drugs that are targeted to the mutations that we talked about.

那曾是当时的热门方向。

And that was the hot thing.

在我上医学院的时候，这被视为充满希望的途径：我们已经能够测量出癌细胞内积累的这些突变。

That was the promising avenue when I was in medical school of like, okay, now we've really measured these are mutations that accumulate inside of cancer cells.

这些突变正是导致癌症的原因。

This is what's causing cancer.

让我们开发专门针对这些突变的药物。

Let's make drugs that go after those things.

事实证明，尽管这一方向带来了许多积极成果，患者的生存期得以延长，但癌症总有办法绕过这些治疗。

And it turned out that that was although a lot of good has come from that, people have extended lives, cancer has a way of working around that.

所以这些是细胞周期抑制剂吗？

So these are cell cycle inhibitors?

信号通路，

Signaling,

各种突变会影响细胞的生长特性，目前已经设计出一些靶向药物，用于抑制那些导致细胞失控分裂的通路。

various mutations affect these growth properties of cells, and there's targeted drugs that have been designed to go after some of those pathways that are making the cells divide out of control.

我认为确实取得了成效，但癌症会通过突变绕过这些治疗，就像我们之前谈到的细菌对抗生素产生耐药性一样。

I think that benefit has come, but cancer has ways of mutating around that and could be developing resistance, the same way we talked about resistance in bacteria to antibiotics.

一旦暴露在这些药物下，癌细胞能够迅速进化并对其产生耐药性。

If they're exposed, cancer cells can evolve quickly and can become resistant to these targeted modifications.

一种全新的抗癌思路已经出现，那就是利用我们一开始提到的免疫系统的力量，将其引导至攻击癌症靶点。

What has emerged as a whole new way of thinking about going after cancer is using the power of the immune system that we talked about at the beginning and redirecting that against cancer targets.

这彻底改变了我们对癌症治疗的思考方式。

This has changed how we think about cancer treatment.

我们的希望是，每个人体内都拥有这样一个免疫系统，它会遍布身体的每一个器官。

The hope is that all of us have this immune system that goes through every organ in our body.

它在体内循环流动。

It circulates.

我们体内有白细胞不断循环，寻找那些不该出现的东西。

We have white blood cells that are constantly going around and looking for things that shouldn't be there.

我们能否激活免疫系统来对抗癌症？

Can we unleash that immune system against cancer?

我们的希望是，利用我们之前提到的免疫系统细胞，它们经过精密进化，能够准确判断：这是健康细胞，这不是健康细胞，这个细胞应该在这里，那个不该在这里。

And the hope would be that the cells that our immune system we talked about, how they're really exquisitely evolved to make a determination of this is a healthy cell, this is not a healthy cell, cell should be here, this should not.

如果我们能实现这种精准度，让免疫系统产生持久反应，清除癌细胞的同时保留健康细胞，这正是我们所追求的目标。

If we could get that level of precision where we could have a durable immune response that gets rid of the cancer cells but leaves the healthy cells intact, that is what we want.

这不再是科幻，而是已经获批并用于治疗多种癌症的现实疗法。

Now that is not science fiction and is now approved and used to treat a number of different cancers.

这种疗法首次应用是在一类名为检查点抑制剂或免疫疗法的药物中。

The first place where this happened was in a class of medicines called Checkpoint Inhibitors or immunotherapy drugs.

很多人可能都听说过这些药物。

A people lot will have heard of these things.

PD-1、CTLA-4是一些靶点，已有药物通过输注方式作用于这些位于T细胞表面的分子。

PD-one, CTLA-four are some targets where there are drugs that get infused that hit these things that are on the surface of T cells.

它们实际上是T细胞的天然刹车。

And they actually are natural breaks to the T cells.

T细胞可能存在于我们体内，但处于关闭状态或激活不足，无法有效对抗癌症。

T cells might be in our body there but turned off or not turned on enough to be strong enough against cancer.

对于某些类型的癌症来说，如果开发出一种能作用于T细胞刹车的药物，T细胞就会变得更强大，只需解除刹车，就能释放它们来对抗癌症，这简直是奇迹。

And for certain types of cancer it's been absolutely miraculous that if you make a drug that hits the brake on T cells, the T cells go stronger and they can be unleashed against cancer just by taking the brakes off of them.

它在哪些类型的癌症中取得了成功？

What sorts of cancers has it The been successful

这方面的典范是黑色素瘤。

poster child for this has been melanoma.

一个重大的成功案例是吉米·卡特，他患有黑色素瘤——一种侵袭性的皮肤癌，已经扩散到大脑，原本被认为是绝症。

One of the big success cases was Jimmy Carter who had a melanoma, which is a skin cell, aggressive skin cancer that had already gone to his brain, which was thought of as a death sentence.

他接受了检查点抑制剂治疗，结果基本上被治愈了。

And he got treated with Checkpoint Inhibitors and basically it was cured.

太惊人了。

Amazing.

太神奇了。

Amazing.

于是你看到这些肿瘤真的在缩小，不仅仅是他一个人，现在有很大一部分黑色素瘤患者对这种疗法都有反应。

And so you saw these tumors just shrink away and not just him, but in large fraction of melanoma patients now respond to these.

这彻底改变了黑色素瘤的治疗方式。

And so that has changed how melanoma is treated.

其他癌症也有不同程度的响应，因为某些类型的癌症确实会对这种疗法产生反应。

And other cancers to varying degrees because some types of cancers can respond to this.

这是一种通过药物释放我们体内已有的T细胞的疗法。

That's taking a drug that unleashes the T cells that are already in our body.

因此，我研究的重点是：我之前说过，我们正处在一个生物学的非凡时代，能够以极高的精确度干预我们体内的细胞，而我们通常只受限于自己的想象力。

The focus of my research then is, well, the first thing I said was we're living in this amazing moment of biology where we can do things to cells in our body that with incredible precision and we're often just limited by our imagination.

我们现在可以看到，我们不必仅仅局限于体内天然存在的、具有随机分布传感器的T细胞。

And what we can see now is that we don't actually have to just be limited to the cells, T cells that are naturally in our body that already have this random distribution of sensors.

我们实际上可以为T细胞基因工程地制造一个这样的传感器，并将其植入T细胞中。

We can actually genetically make one of these sensors for T cells and put it into T cells.

我们可以插入一个基因，使T细胞表面表达某种物质，从而让它们被编程去搜索并摧毁癌细胞。

We can put a gene that encodes something on the surface of T cells that will make them programmed to search and destroy for cancer cells.

这通常被称为嵌合抗原受体T细胞。

Now this is largely known as chimeric antigen receptor T cells.

这是一个长期的术语。

That's a long term.

它们通常简称为CAR T细胞，即嵌合抗原受体。

They're known for short as CAR T cells, chimeric antigen receptor.

所谓‘嵌合’，意思是这些成分是拼接在一起的。

And what that means, chimeric, is that these are stitched together.

这是一种在实验室中设计出来的受体，自然界中并不存在，但可以被插入DNA片段，并递送至T细胞中。

This is a receptor that was designed in a lab, does not exist in nature, but can be put into a piece of DNA, delivered into a T cell.

当这段DNA进入T细胞的基因组后，T细胞便会开始制造出现在其表面的蛋白质，充当这些人工传感器。

And when that DNA goes into the genetic code of the T cell, all of a sudden the T cell will start making proteins that go on its surface and act as these artificial sensors.

当这些经过改造的T细胞像输血一样被重新输入患者体内时，这些CAR就会靶向癌细胞。

And those CARs then when those T cells get reinfused into a patient the way that you get like a blood transfusion, those CARs are directed to go against cancers.

这已经应用于某些类型的白血病和淋巴瘤。

This has been done for certain types of leukemia and lymphoma.

并且已经取得了令人惊叹的成功案例。

And there's been these amazing success stories.

让我和全世界震惊的是，2012年有一位小女孩，她是首位接受CAR T细胞治疗癌症的儿童患者。

The thing that woke up me and the world was in 2012 there was a young girl who was the first pediatric patient to be treated with a CAR T cell for cancer.

她因此成为了一位英雄人物，名叫艾米莉·怀特海德。

So she's become a heroic figure, Emily Whitehead.

当时她大约八岁。

She was, I think, eight at the time.

她患有一种白血病，不知为何，所有治疗都失败了，没有任何办法有效。

And she had a form of leukemia that hadn't it just was for some reason, whatever reason, it failed all the treatments and it just nothing worked.

她原本被安排回家接受临终关怀。

She was going to be sent home on hospice.

她在八岁时就已经用尽了所有可能的治疗手段。

She had exhausted all the possibilities at the age of eight.

她参与了一项当时高度实验性的治疗，接受了CAR T细胞治疗。

And she got enrolled in a, at that time, highly experimental treatment to get these CAR T cells.

因此，她的血液细胞被通过一次大规模的献血方式取出。

So her blood cells were taken out in a big blood donation.

她的自身T细胞被进行了基因改造。

Her own T cells were genetically modified.

我们可以谈谈这个过程是如何实现的。

And we can talk about how that was done.

实际上，当时使用了一种相当原始的技术，利用了病毒——慢病毒。

It was actually done with a pretty crude technique that's been around, actually used viruses, lentiviruses.

这些是经过改造的HIV病毒，用于传递一段编码CAR的额外DNA。

These are sort of modified HIV viruses to deliver this extra piece of DNA that encoded the CAR.

这项操作是在她的细胞上进行的。

This was done on her cells.

在将这段额外的基因插入T细胞后，这些T细胞被重新输回她的体内。

And then after that extra gene was put into the T cells, the T cells were reinfused into her body.

但这并不是一条坦途。

And it was not a straightforward course.

她最终住进了重症监护室。

She ended up in the ICU.

免疫系统在实时运作中，人们必须想办法控制免疫反应和副作用。

The immune system had in real time people had to figure out how to control the immune systems and the side effects.

但当这些得到控制后，她的癌细胞突然消失了。

But as that was controlled, all of a sudden her cancer cells disappeared.

太神奇了。

Amazing.

而慢病毒本身并没有引发超过其治疗益处的免疫反应。

And the lentivirus itself didn't spark an immune reaction that was No.

超过了它所携带的治疗效果吗？

That outweighed the benefits of cargo?

没有。

No.

令人惊讶的是，它真的没有。

Amazingly, it really hasn't.

我的意思是，人们确实讨论过使用这些慢病毒的风险，我们稍后会谈到我们现在如何能做得更好。

I mean, there's been some discussion about the risks of using these lentiviruses, and we'll talk in a second about how we could do better now.

是的。

Yeah.

人们听到把病毒放进细胞、再放进人体，肯定会有很多人吓坏。

People are gonna hear putting viruses into cells and putting them into humans, and a bunch of people will freak out.

但我向你保证，像腺病毒这种类似感冒病毒的东西，或者慢病毒这种与HIV相似的病毒——当然，他们并没有给她注入HIV，而是改造了病毒，所以它们并不是在传递HIV。

But I promise you that things like adeno, which is like a cold virus, or lenti, which is similar to HIV, and of course they didn't give her HIV, they changed the virus, so they're not delivering HIV.

这些病毒非常了不起，因为它们能长期表达你特意插入其中的基因。

These viruses are incredible because they can create long lasting expression of genes that you deliberately put into them.

它们就像一个运输工具。

They're a shuttle.

这真是生物学理解的惊人应用，对吧？我们原本研究病毒是因为它们的危险性，但后来我们发现，病毒进化得非常擅长作为运输工具，将遗传物质递送到细胞中。

It's an amazing application of biological understanding, right, that all of a sudden we've been studying viruses because of the risk that they have, but we've learned that they can deliver, that viruses have evolved to be very good shuttles, and to deliver their genetic material into cells.

我认为，病毒已经进化到能够利用我们的生物学和基因。

The way I think of it that is the viruses have evolved to take advantage of our biology and our genes.

是的。

Yeah.

所以在这些情况下，我们完成了终极的反击。

And so we did the ultimate touche in these instances.

你们太擅长劫持我们细胞的DNA并进行增殖了。

Like, you're so good at at hijacking our cells' DNA and proliferating.

好吧。

Alright.

我们将利用你们来帮助我们，而不是伤害我们。

We'll leverage you to help us as opposed to hurt us.

对吧？

Right?

完全正确。

That's exactly right.

这件事发生在2012年。

And so that was done in 2012.

艾米莉·怀特黑德当时八岁。

Emily Whitehead was eight.

这是在宾夕法尼亚大学进行的一种实验性治疗。

It was done as an experimental treatment at the University of Pennsylvania.

如今，多年过去，艾米莉·怀特黑德不仅治愈了白血病，还正在宾夕法尼亚大学攻读医学预科。

And the story now is that now, all these years later, Emily Whitehead is not only cured of her leukemia, she's pre med at the University of Pennsylvania.

太棒了。

So awesome.

所以没人能忽视他们。

So no one could ignore them.

这突然颠覆了我几年前在医学院学到的教条——我们应该忽略癌症免疫疗法。

This was just all of a sudden this dogma that I had just been taught a couple of years early in medical school that we should ignore the cancer immunotherapy.

我们当时错了。

We were just wrong.

突然间，整个领域醒悟了，意识到免疫系统不仅仅局限于保护我们免受病毒和细菌的侵害。

And all of a sudden the field woke up and said, Okay, the immune system is not just limited to protecting us from viruses and bacteria.

免疫系统可以被利用，甚至可能被重新设计，以帮助我们对抗癌症以及其他疾病。

The immune system can be exploited and potentially reengineered to protect us from cancer and maybe other diseases.

那是2012年。

So that was 2012.

2012年也是埃马纽埃尔·夏彭蒂耶和詹妮弗·杜德纳在《科学》杂志上发表论文的一年，他们介绍了名为CRISPR的新技术。

2012 also was the year that a paper got published in Science by Emmanuelle Charpentier and Jennifer Doudna that introduced this new technology called CRISPR.

我们稍后会谈到，但CRISPR本质上是一种重写DNA序列的工具。

And we can we'll talk about this, but CRISPR fundamentally is a tool to rewrite DNA sequences.

这项技术也是在2012年问世的。

That came out in 2012.

就我个人而言，2012年也是我搬到旧金山、建立一个研究T细胞以及遗传如何影响T细胞的实验室的年份。

And on a personal level, 2012 was also the year that I moved to San Francisco to start a lab studying T cells and how genetics influences T cells.

我当时四处观察，试图弄清楚我的实验室该做什么。

I was looking around and trying to figure out what my lab would do.

就在那一刻，我带着一个空实验室抵达，而与此同时，全世界得知了T细胞能够治愈癌症，我们拥有一种可能重写DNA序列的工具，并且我们不再受限于那些笨拙的慢病毒——那是当时我们最好的工具，但在插入遗传物质时既笨拙又不精确。

And all of a sudden, I was arriving with an empty lab space at exactly the same moment that the world was shown that T cells could cure cancer, and that we had a tool that could potentially rewrite DNA sequences, and that we wouldn't be limited to these lentiviruses, which are kind of clunky, the best tools we had at the time, but pretty clunky and non precise in how they insert genetic material.

突然间，我们可以想象，可以利用T细胞并借助CRISPR技术，在基因组中精准定位，进行靶向修改，从而精确编程细胞的行为。

All All of sudden, we could imagine that we could take T cells and use CRISPR to actually pick individual places in the genome and make targeted changes to program exactly how cells behave.

这构成了我持续研究的基础。

And that is the basis for my ongoing work.

多年来，我们投入了大量工作，使CRISPR技术能够在T细胞中发挥作用，探索哪些遗传改变最能有效将T细胞转化为治愈不同疾病患者的免疫疗法。

We've put a lot of work over the years into being able to now take CRISPR technology, get it to work in T cells, to learn the rules about what are the genetic changes that will be most effective at making T cells into immunotherapies that cure patients with different diseases.

然后进一步推进，真正利用CRISPR制造出可输入患者体内的T细胞，实现前所未有的精准度和效力。

And then to go all the way and then actually use CRISPR to make T cells that can be input into patients with new levels of precision and power.

目前这些成果已进入临床试验阶段。

And that's in clinical trials now.

我们现在正将这些经过CRISPR工程改造的CAR-T细胞投入临床试验。

We're now in clinical trials with these CRISPR engineered CAR T cells.

我们不仅针对历史上CAR-T细胞已取得成效的白血病，还在思考如何让这些疗法适用于导致癌症死亡的最常见原因——实体瘤。

And we're not just going after leukemias, where these CAR T cells have historically worked, but we're also thinking about can we make these work for the really common causes of cancer deaths, solid tumors.

这一直是个挑战，我们可以谈谈这个问题。

And that's been a challenge, and we can talk about that.

但要让T细胞在肿瘤中找到正确的靶点，并在本质上具有免疫抑制性的肿瘤微环境中发挥作用，需要利用CRISPR技术设计出额外的基因编辑，以对抗癌症的策略。

But getting T cells to find the right targets in tumors and then work inside of tumor environments, which are inherently immunosuppressive, requires figuring out additional gene edits that are now possible with CRISPR to try to beat the cancer at its own game.

如果癌症正在进化以躲避免疫系统的识别，那么借助CRISPR，我们现在可以尝试领先一步，制造出能够抵抗癌症所有攻击手段的T细胞，从而更有效地发挥作用。我认为，我们正站在一个关键的临界点上，即将拥有精确的CRISPR工程化细胞，这些细胞有望在不产生化疗副作用的情况下，开始逐步消除癌症。

If cancer is evolving to make itself cloaked from the immune system, now with CRISPR we can think about getting one step ahead and making T cells that are able to resist all the tricks that cancers throw at it to be more and I think we're on the brink of having precise CRISPR engineered cells that will, I I hope, start to melt away cancers without the side effects of chemotherapy.

太惊人了。

Amazing.

真的太惊人了。

Just amazing.

这位年轻女性的故事非常精彩。

And the story of this young woman is spectacular.

在我们讨论CRISPR技术之前，我有两个问题。

I have two questions before we talk about CRISPR technology.

是的。

Yeah.

第一个问题是，这是真的吗？

The first one is, is it true?

我相信是真的。

I believe it is.

但随着年龄增长，患癌风险真的会增加吗？

But is it true that cancer risk goes up as we get older?

如果是这样，为什么？

And if so, why?

所以这是第一个问题。

So that's the first question.

另一个问题与你所描述的免疫疗法有关，即它如何能够精准靶向癌细胞而不对身体其他部位造成影响，而这正是化疗和放疗的主要问题。

And then the other question has to do with how the immunotherapy that you described was able to target the cancer and and not cause problems elsewhere, which is kind of the major issue of chemo and and radiation therapy.

但再重复一遍第一个问题：为什么随着年龄增长，突变会更多？

But the first question again was, you know, why more mutations as we get older?

我认为有一些癌症在儿童时期达到高峰，在身体发育过程中会存在某些儿童癌症的风险。

So I think there's there's a few cancers that that peak in childhood, and there's risk as the body's developing of certain cancer, childhood cancers.

比如儿童白血病，当我们谈到艾米莉·怀特海德时就是这种情况。

There's childhood leukemias, for example, and that like when we talk about Emily Whitehead.

但大多数癌症，正如你所说，确实呈现出这种上升趋势，它们主要是生命后期的疾病。

But most cancers, as you said, exactly as you said, that there's this sort of increase, and they're largely disease of later stages of life.

我认为原因在于，回想一下我们之前讨论过的癌症成因：这是细胞逐渐积累突变的演化过程。

I think that the reason for that is remember when we talked about what causes cancer, it's this evolution where cells start to accumulate mutations.

其中许多带有突变的细胞会自然死亡，这只是一个随时间展开的过程。

Numerically, a lot of those cells that have the mutations will die off, and it's just a game that unfolds over time.

你拥有的细胞分裂和在体内停留的时间越长，积累的损伤就越多，最终这些损伤更有可能将细胞转化为癌细胞。

And the more time you have cells dividing and sticking around in the body, they're accumulating more damage, and eventually you're more likely that that damage would actually transform the cells into a cancer cell.

所以时间在这里是一个关键因素。

So time is a big factor here.

时间和累积的损伤。

Time and just accumulated damage.

另一个问题是，你知道，这种携带慢病毒载体的T细胞是如何知道该攻击癌细胞而不是其他东西的？

The other question was, you know, how is it that the lentivirus knows to that lentiviral cargo carrying T cells know to attack the cancer and not something else?

所以这是这个领域的一个关键问题，对吧？

So this is a key question for the field, right?

我认为其中一个非常成功的关键，是一群来自不同地方的科学家共同做出的明智选择，他们锁定的靶点正是首个CAR T细胞疗法所使用的靶点。

And I think one of the things that worked incredibly well was a brilliant choice by a group of scientists in a few different places that converged on the target that was used in the first CAR T cell.

这个靶点是一种被称为CD19的蛋白质。

And what the target is known as a protein called CD19.

这只是这种存在于多种B细胞上的物质的名称。

That's just the name of this thing that's found on a lot of different types of B cells.

这让我们回到了刚才的讨论。

So this brings us back to this discussion.

白血病本身是免疫细胞的癌症，也就是B细胞的癌症。

The leukemias themselves are a cancer of the immune cells, so they're cancer of B cells.

CD19存在于许多不同类型的B细胞白血病和淋巴瘤的表面。

And CD19 is found on the surface of many a large number of different types of B cell leukemias and lymphomas.

我明白了。

I see.

我认为这里有一个偶然的发现是，B细胞本身，即天然健康的B细胞，其表面也带有CD19。

I think one of the things that turns out to be serendipitous here is that B cells themselves, natural healthy B cells actually also have CD19 on their surface.

巧合的是，人体能够耐受这些细胞的消失。

What just turns out to be serendipitous is that the body can tolerate those cells going away.

因此，这种治疗之所以对癌症特别有效、安全且相对耐受性良好，是因为其附带损伤实际上并不严重。

And so what has made this a particularly effective and safe and relatively well tolerated treatment for cancer is that the collateral damage is actually not that damaging.

在这种情况下，T细胞并没有严格区分癌细胞和健康细胞。

That T cells in this case are not strictly distinguishing between cancer and health.

它们不仅清除白血病细胞，还清除了一并出现的B细胞。

They're not just getting the leukemia cells, they are getting collateral B cells.

但总体而言，从初步来看，人们是可以没有这些细胞而生存的。

But by and large, to a first approximation, people can live without those cells.

因此，这一副作用是可以接受的。

And so that side effect has just been tolerable.

对于更多类型的癌症，找到这种平衡会变得越来越困难，对吧？

Finding that balance gets harder and harder for more cancers, right?

如果你开始考虑胰腺癌或脑癌，找到那些即使作用于健康胰腺或健康大脑也不会产生毒性的靶点，会变得越来越困难。

If you start to think about pancreatic cancer or brain cancer, finding targets that if you hit the healthy pancreas or the healthy brain are not toxic, it's harder and harder.

因此，人们正在思考越来越多的精细方法，来寻找仅存在于癌细胞而不存在于健康细胞上的靶点，或者思考如何让细胞依赖于识别多个特征，从而实现有时被称为‘双因素认证’的机制。

So people are thinking about more and more sophisticated ways to look for these targets that are selectively found on the cancer cell and not on the healthy cell, or to think about ways that you might actually make the cell depend on recognizing multiple features so that you can have what's sometimes talked about as like a two factor authentication.

比如，T细胞只有在同时发现这两个特征时才会杀死癌细胞，而即使其中一个特征可能存在于健康细胞上，但这两个特征的组合却不会出现在健康细胞上。

Like the T cell will only kill cancer if it finds this and this, and that combination of things are not found on healthy cells even if one or the other might be.

因此，人们正在思考如何让T细胞的这种识别系统变得更加精细。

So people are thinking about how do we get more sophisticated about building these discrimination systems into T cells.

构建这些系统的基础元件已经存在，但每种癌症的具体方案都需要创新。

The building blocks are there, but the specifics for each cancer have to be invented.

但我们已经具备了实现这些目标的工具。

But we have the tools to do that.

太棒了。

Awesome.

在我们讨论CRISPR之前，还有一个问题，我知道很多人会想知道。

Before we talk about CRISPR, there was one other question that I know many people will be thinking about.

几年前，也许是五到十年前，人们曾广泛讨论甚至对生酮饮食治疗或预防癌症抱有相当大的热情。

A few years back, maybe five, ten years back, there was a lot of discussion, maybe even some enthusiasm about ketogenic diets to treat or prevent cancer.

根据我对相关文献的了解，对于某些癌症，它或许——我要特别强调‘或许’——可能有所帮助。

And my understanding from looking at that literature was that for some cancers, it perhaps, I want to bold underline and capitalize perhaps, might help.

但对于其他癌症，反而可能使情况更糟。

But for other cancers, could make things worse.

而最近，我开始更多地听到关于低谷氨酰胺饮食的说法。

And then I also more recently started hearing about low glutamine diets.

当然，这就是互联网的运作方式。

So and of course, this is the way the internet works.

但我确实看到一些发表在不错期刊上的论文，至少是在探索这一方向。

But I did see some papers in some decent journals, you know, that at least were exploring this.

所以，所谓的低碳饮食，不如直接称其为低糖饮食。

So our low they're just low carb let's call it what they are.

生酮饮食是否已被证明对癌症的治疗或预防有效？

Ketogenic diets, have they been shown to be useful for treatment or avoidance of cancer?

我得听你的。

I have to defer to you.

其实我真的不知道答案。

I actually I don't I don't know the answer to that.

是的。

Yeah.

好的。

Okay.

我猜人们仍在研究这个问题。

My my guess is that people are still looking at this.

对。

Yeah.

但你知道，当时也有观点认为它们对某些类型的痴呆症可能有帮助。

But you know, there was also the idea that they could be useful for certain forms of dementia.

曾经有人试图把痴呆症称为三型糖尿病。

There was an effort to call dementia, you know, type three diabetes.

但根据我与该领域专家的交流，我的理解是，它可能通过间接机制产生帮助，但无法彻底解决问题。

But my understanding from talking to the experts in this is that it might help through indirect mechanisms, but that it's not going to solve the problem.

好的。

Okay.

谢谢你能听我讲完这个小小的死胡同。

Well, thanks for entertaining that little cul de sac that I created.

CRISPR。

CRISPR.

给我们讲讲CRISPR的故事。

Tell us the story of CRISPR.

因为我觉得CRISPR是生物学和医学中那种几乎人人都听说过的有趣技术。

Because I think CRISPR is one of those funny things in biology and medicine that almost everybody has heard about in the general population.

大多数人知道它和基因改造有关，但它有点像人工智能。

Most people know it has something to do with changing genes, but it's sort of like AI.

是的。

Yeah.

它已经出现了。

It's here.

它很强大。

It's powerful.

它让某些人感到害怕。

It scares certain people.

它让其他人感到兴奋。

It excites other people.

但大多数人并不知道它是如何运作的，因为根本没有动力去了解。

But most people don't know how it works because there's really no incentive to.

但我认为，CRISPR的故事实际上也是关于科学如何运作的故事。

But I think the story of CRISPR is actually also a story about how science works.

是的。

Yeah.

这也很重要。

And that's important too.

我认为这完全正确。

I think it's exactly true.

我认为这是一个完美的例证，说明了某个无人计划的发现如何改变了生物学。

I think it is a perfect illustration of something where a discovery happened with a no one was planning but changed biology.

让我用两个独立的脉络来讲述这个故事。

Let me tell you this story in two separate arcs.

其中一个脉络是关于对DNA的理解。

One arc is the arc of understanding DNA.

你知道，如果回溯到沃森和克里克的时代，那就是理解双螺旋结构，从而理解DNA序列的结构。

You know, if you go back to Watson and Crick, it's understanding the double helix to understand the structure of what a DNA sequence is.

这一理解逐渐成熟。

That matures.

我们学会了测序，以便能够测量由T、C、G以各种组合构成的序列，这些序列将成为编程细胞内蛋白质合成的基本单元。

We've learned how to sequence to understand the to be able to measure a row of a t's and c's and g's that in whatever combination they are will start to be the building blocks for programming which proteins get made inside a cell.

大约在2000年，我们迎来了人类基因组的首份草图，这是全球耗资数十亿美元的项目，旨在绘制出一个人类基因组的初步序列，成为生物学和医学史上的一个里程碑。

And then around 2000, we get to the first draft of the human genome, which is this multibillion dollar project across the world to come up with a draft of one human genome sequence, milestone for biology and medicine.