Is There a Link Between Cancer and Heart Disease? | Nicholas Leeper | TED

翻译人员: Yin Wu 校对人员: Yanyan Hong

In two decades of practicing medicine,

我在医疗领域工作的二十年间， 接触过很多医疗诊断。

I've encountered a wide number of medical diagnoses.

You see, it turns out that there are more than 60,000 different medical diagnoses

其实，可以被写在患者的病历卡上的 医疗诊断多于六万种。

that you can list on a patient's chart.

You can actually be diagnosed with a burn injury

如果你的滑水橇着火了， 你其实可以被诊断为烧伤。

when your water skis catch on fire.

There are also codes if you need surgery after being bitten by a pig,

连被猪咬伤到需要做手术 这种事也有诊断代码，

（笑声）

(Laughter)

hit by a spacecraft,

或是被飞行器撞伤，

(Laughter)

（笑声）

stabbed while crocheting,

织毛线时被戳伤，

or my favorite,

还有我最喜欢的一个， 与姻亲发生剧烈冲突。

due to extreme problems with your in-laws.

(Laughter)

（笑声）

But the best of all has got to be the code

但是最妙的诊断代码是： 被卷进飞机引擎。

for getting sucked into a jet engine.

And the reason that I like this one is because this is not the code

我喜欢这个是因为，

这代码不是给 第一次被卷进去的人用的，

for the first time this happens, but for the subsequent encounter.

而是给第二次的人用的。

(Laughter)

（笑声）

So there must be people on this Earth

所以地球上一定有人 两次被卷进飞机引擎。

that have been sucked into a jet engine twice.

(Laughter)

（笑声）

But I think, you know, kidding aside,

好了，不开玩笑了，

we have to recognize

我们也需要认识到，

that every last one of us in this room

在这房间里坐着的每一位 最有可能死于这两个诊断中的一个。

is most likely to die of only one of two diagnoses.

And these, of course, are either cancer

这两个诊断也当然就是 癌症或者心血管疾病。

or cardiovascular disease.

This speaks to the incredible public health importance

这说明了这两种疾病 对于公众健康的巨大影响，

of these two diseases

and the urgent, unmet medical need to develop new therapies

以及我们对于开发这两种疾病的新疗法

有着紧迫而尚未满足的医疗需求。

directed against them.

A lot of people are not surprised

对于这两种疾病的致命性， 很多人并不感到惊奇。

that these two diseases claimed so many lives.

After all, they are very different biologically,

毕竟，从生物医学角度来看， 它们有很大的差异，

they have different risk factors,

有着不同的风险因素，

and they affect very different patient populations.

也影响着不同的患者群体。

But for the next 15 minutes or so,

但在接下来的十五分钟里，

I would like to propose a different hypothesis.

我将提出一个不同的假设。

That perhaps they actually have quite a lot in common.

那就是，或许它们有很多相似之处。

And even more importantly,

并且更重要的是，

I would like to suggest that if we think about them this way,

我认为，如果我们以这种方式来思考它们，

we might be able to develop new therapies

我们可能可以研发出新的疗法 同时作用于这两种疾病。

that could treat both diseases at the same time.

So before I tell you why I believe this hypothesis,

在我解释我为什么相信这个假设之前，

let me lay out the counter arguments against it.

让我先把反方观点列出来。

I think many people would say

我想很多人会认为，

that the old man who smokes cigarettes his whole life

一个抽了一辈子烟的老人突发心脏病，

and has a heart attack

shares very little in common with a young person

与一个突然得大肠癌的年轻人，

who develops colon cancer out of the blue.

没什么相似之处。

But we now know that the risk factors for these diseases

但是我们现在知道， 这两种疾病的风险因素有显著的重合。

have significant overlap.

And the things that cause one disease can also put you at risk for the other.

导致一种疾病的因素可能会让你 成为另一种疾病的高危人群。

Well, that may be true,

好吧，就算这是真的，

but we know that genetically these diseases couldn't be more different.

但我们也知道，从遗传角度上分析， 这两种疾病是非常不同的。

I'm sure many of you have heard about these cancer genes

你们很可能听说过，

that can be mutated in families

一些与癌症相关的基因突变出现在家族中，

that could put both mother and daughter at risk for breast cancer.

可能使得母女都成为乳腺癌的高危人群。

We know that those genes have nothing to do with heart attack,

我们知道这些基因和心脏病没关系，

and that's true also.

这也是真的。

But I would point out that those genes were discovered decades ago,

但我想指出这些基因是几十年前被发现的，

before the Human Genome Project

那时候我们还没有人类基因组计划，

and before we could scan all three billion base pairs at the same time.

也并不能一次性扫描人类的 30 亿对碱基。

And when we do this for patients having heart attack,

我们在扫描心脏病患者的基因组时，

we find that the top hotspot for having a heart attack

发现引发心脏病的高危基因位点 在第九染色体上，

is located on chromosome nine,

shown here with these blue dots.

在图上被标示为蓝色的点。

And what shocked the world when this paper was first published

这个研究震惊了世界的一点是，

was that this genetic locus has nothing to do with smoking

这个基因位点与抽烟、 胆固醇、或是糖尿病毫无关系，

or cholesterol or diabetes.

But actually seems to control a well-known cancer gene

相反，它似乎控制着一个著名的癌症基因，

that's mutated in patients with melanoma, brain cancer,

这个基因在罹患皮肤癌，脑癌，肺癌等的

患者中常常是突变了的。

lung cancer, etc.

And so for decades,

几十年来，我们一直专注于 传统意义上的心血管疾病的风险因素，

we've been focusing on the traditional cardiac risk factors.

But the genetics now tell us

但是基因告诉我们，

that the most important factor may actually have to do

最最重要的因素实际上 可能与一个著名的癌症基因有关。

with a well-known cancer gene instead.

Well, that's an interesting observation,

这是个非常有意思的观察，

but we know that if you look under the microscope

但是我们也知道， 当我们从显微镜下看这两种疾病，

at these two diseases,

they couldn't be more different.

它们是完全不同的。

When I was in medical school,

我在读医学院的时候，

I was taught that cancer is really just about cells dividing too quickly.

教授们教我， 癌症就是细胞分裂得太快了。

And you can imagine this lung tumor

正如你想象的那样， 肺部肿瘤慢慢变大，占据了整个肺部，

growing over time and taking over the lung,

and that this has nothing to do with what happens in heart disease,

而这与心血管疾病毫无关系。

which is a problem that, I was taught,

因为据我所学， 心脏病是由胆固醇累积造成的，

was due to the buildup of cholesterol

that can ultimately lead to the blockage of an artery

这最终会导致动脉栓塞， 引起心肌梗塞或中风。

and a heart attack or a stroke.

And to be sure, both of these biological processes are critically important.

我们很清楚地知道， 这两个生物过程极其重要。

But I would point out that the modern-day textbook of these diseases

但我也想指出，在如今的教科书上， 我们越来越难区分这两种疾病。

is getting harder and harder to tell apart.

We now know that both of these conditions are dominated

我们现在了解到， 这两种疾病都有大量涌入的

by the influx of inflammatory cells

炎症细胞、免疫细胞、异常血管， 甚至干细胞。

and immune cells and abnormal blood vessels

and even stem cells.

And so maybe the textbooks that I used are out of date.

所以大概是我用的课本太老了。

Well, at this point, you might say these are interesting observations,

此时此刻，你可能在想， 这些观察的确很有趣，

but is there any clinical data which would suggest

不过有没有临床数据可以证明

that patients with one disease are actually at higher risk of the other?

患有其中一种疾病的人 有更大的风险得另一种疾病？

Turns out that investigators, both in Asia and Europe,

事实上，亚洲和欧洲的研究者们 都在验证这一假设。

have now started to test this hypothesis.

And just last year,

去年，一篇非常重要的文献在德国发表了。

a very important article was published out of Germany,

where they looked at more than 100,000 individuals

他们研究了超过十万名 充血性心力衰竭的患者，

with congestive heart failure

and they found that these people were at much higher risk

发现这些人得癌的机率比普通人高出很多。

of developing cancer.

This is really interesting

这很有趣，

and suggests to me that indeed having one disease

也预示患有其中一种疾病 确实会升高患另一种的风险。

may put you at risk of the other.

But this also raises a very important scientific principle

但我们需要记住一个重要的科学原理， 相关性并不代表因果关系。

that association is not the same as causation.

And if you wanted to test that hypothesis,

所以如果真的想要证实这个假设，

you would have to do an experiment where you took a healthy individual

你需要故意让一个健康的人心肌梗死，

and then intentionally gave them a heart attack.

You'd have to let some time go by

你得等一段时间，然后看看 他身体里发生了什么变化，

to see what changes occur throughout the body.

And then you could determine if their rate of cancer was higher

据此判断他得癌的几率是不是变高了。

or vice versa, if their rate of heart disease was higher.

或是把顺序反过来，判断他 得心脏病的几率是不是变高了。

Now, obviously, we can't do this type of an experiment in human beings.

很显然，我们不能在人身上做这种实验。

This would be unethical.

那是不道德的。

But this type of an experiment is done in research laboratories

但是在全球各地的实验室里，

every day around the world

这种实验每天都在用来 模拟人类疾病的小鼠身上进行着。

in mouse models of human disease.

Just last year, two very important studies were published

就在去年， 两个非常重要的研究成果被发表了。

where investigators took healthy mice

研究者们在健康的小鼠皮下植入了小肿瘤，

and then implanted small tumors underneath their skin.

They looked at the rate at which these cancers would grow over time.

然后观察肿瘤生长的速率。

And what they found in both studies was that the mice who had heart disease

在这两个研究里，他们都发现，

有心脏疾病的小鼠得癌的几率更高。

had much higher rates of cancer.

And what was fascinating to me

尤其吸引到我注意力的是，

was that they were able to confirm these findings

研究者们证实了， 这个实验结果对于许多种不同的肿瘤都适用，

across a wide range of tumors,

suggesting to me that really the presence of heart disease

这似乎意味着心血管疾病 足以加速癌症的发展。

is sufficient to accelerate cancer growth.

So having heard all this,

听了这些，我们自然而然地会问， 我们现在能做些什么。

the natural question is whether we can do anything about this.

So outside of my work at Stanford, one of my volunteer roles

除了我的斯坦福的工作， 我还在美国心脏协会从事一项志愿者工作。

is with the American Heart Association.

And one of our public health initiatives is called Life’s Simple Seven.

我们的一个公共卫生倡议叫 Life’s Simple Seven（生活中的简单七件事）。

We try to get patients with a history of heart disease

我们试着让有心脏病史的患者

to control these very simple and straightforward risk factors

控制一些简单明了的风险因素， 比如锻炼、胆固醇和饮食。

like exercise, cholesterol and diet.

The idea here is that if you can control these,

我们的想法是，如果你能控制住这些，

you should be able to lower your risk

你应该可以降低 心血管疾病再次发作的风险。

of having additional cardiovascular events.

This is now pretty widely accepted.

这是一个被广泛接受的概念。

But what's fascinating to me

但有趣的是，

is that a group of investigators have now looked at the association

一群研究者分析了 这些风险因素与癌症的关联。

with these risk factors and cancer.

And in a study with more than 10,000 individuals

在一个超过一万人参与， 持续近二十年的研究中，

who were followed for almost two decades,

they found the people who had optimal control

他们发现控制住了这些 （心脏病的）风险因素的人

of all their risk factors

had a pretty low rate of developing cancer.

得癌的几率都比较小。

But for each risk factor which fell out of control,

但是每当有一个因素没有被控制好，

the risk of malignancy went up.

得癌的机率就上升了。

And you can see that the group who had poor control of all seven risk factors

7个风险因素都没有控制好的人 得癌的几率最高，

had by far the highest rates of cancer,

with nearly a doubling of the risk.

几乎翻了倍。

So this suggests to me that,

这对我来说意味着，

in fact, if we want to control cancer,

如果我们想要控制癌症， 我们可以从控制心血管风险开始。

we might start by controlling our cardiac risk profile.

So this is fine and we continue to encourage our patients to do this.

所以我们继续鼓励我们的患者 去控制这些风险因素。

But the reality is that even if I had a magic wand

但是就算我有一根魔法棒，

and could somehow optimally control everybody's risk factors,

可以完美地控制每个人的这 7 个风险因素，

we know that we would still be dealing with both the number one

我们依然要与这两种世上 第一和第二致命的疾病做斗争。

and number two causes of death worldwide.

This tells us that we need to find new therapies

这说明我们需要新的疗法 用于治疗，甚至是预防两种疾病。

that could treat or even prevent these conditions in the first place.

Now our laboratory chooses to do this

我的实验室打算用一种 无偏见的遗传学方法研究这个问题。

with an unbiased genetics approach.

We take biopsies from patients

我们对实验参与者进行活检。

with or without a wide variety of tumors,

参与者们包括： 不同癌症的患者或不患癌症的人，

or with and without cardiovascular disease.

有心血管疾病的患者 和没有心血管疾病的人。

And instead of looking at one gene at a time,

我们不只是专注于个别基因，

we scan the whole genome and look at the expression of all 20,000 genes.

而是扫描整个基因组， 检测全部两万个基因的表达水平。

You can plot these on a plot like this

你可以做出这样的一幅图， 图中每个灰色的点代表一个基因。

where each gray dot represents its own gene.

And when you acquire enough samples,

当你有了足够多的样本， 你就可以渐渐发现一些规律，

you can begin to identify patterns of those genes

which are bad for cancer

有的基因会增加癌症风险， 而有的基因会降低这一风险。

versus those that protect against it.

And do the same type of an experiment

通过类似的实验，

to find those things that will accelerate or prevent against cardiovascular disease.

我们也可以发现增加 或降低心血管疾病风险的基因。

Now, I think the clever part of this approach

我认为这一研究方法的聪明之处在于，

is to integrate these

我们可以合并这两个实验， 同时分析它们的结果。

and to run these analyses simultaneously.

When you do this, we can begin to look at factors in the red quadrant.

这样，我们就可以关注到 红色象限里的基因。

These are genes that we suspect should be bad

我们预测这些基因会同时 增加心血管疾病和癌症的风险，

for both heart disease disease and cancer

and must be avoided at all costs.

所以我们必须预防它们。

Or even better,

更妙的是，

perhaps we can find factors in the blue quadrant

我们可以关注到蓝色象限里的基因，

that should be able to protect against both diseases.

从而预防这两种疾病。

We hypothesize that those factors in the blue quadrant could be prioritized

我们优先研究蓝色象限里的基因，

to help us find new medicines to cure these two leading killers.

因为这可能会帮助我们找到 治愈这两大杀手疾病的新疗法。

Now our group has run these analyses on several thousand individuals.

我的实验室现在正在数千人身上 进行这一分析。

This work is still underway,

这项工作仍在进行中，

but so far we've identified a list of about three dozen pathways

但截至现在我们已经发现了 三十多个需要重点关注的通路。

that we do think should be prioritized.

Now, time will tell if these work.

接下来，时间会告诉我们 它们是不是行得通——

If all of them work, if some, if any of them work.

是不是它们都行得通， 还是只有一些或个别几个可以。

We just don't know.

这些还是未知的。

But I do want to show you a couple of examples

但我想给你们举几个例子， 来表明我们是在正确的方向上。

that would suggest that we're on the right path.

In the red quadrant, one of the factors we found relates to inflammation.

在红色象限里， 我们发现的因素之一与炎症有关。

And we often think of inflammation as being bad,

我们常常认为，炎症是不好的；

but in reality, this is a process

但事实上，炎症只是 一个我们的身体进化出来的过程，

that our body evolved to help us recover from injury

它能够帮助我们从受伤中恢复，

or to mount a fever to fight off an infection.

或是通过发烧来抵抗感染。

But of course, there are always times

但当然了，总有一些时候 我们的身体有太多炎症了。

where our body has too much of something.

In this case,

比如说，一种罕见的遗传综合征的 患儿有着过度活跃的炎症反应，

there's a rare genetic syndrome

where children can be born with overactive inflammation,

and they can have recurrent episodes of high fevers and rashes

他们会有反复发作的高烧和皮疹，

and other neurocognitive and developmental delays.

以及其他神经认知和发育上的迟缓。

Now in a triumph of science,

而现在，因为科学的巨大成功，

investigators have pinpointed the exact molecule responsible for this,

研究者们已经明确了 导致这些症状的分子，

and they developed a drug that can block it.

并且开发出了可以阻断它的药物。

These children who have these rashes that I mentioned before

这些曾经有着不断发作的皮疹的孩子

can have a relatively remarkable improvement on these drugs

服药后症状有了明显的改善，

and almost get back to a normal quality of life.

并且几乎可以恢复正常的生活质量。

But relevant to today's talk,

而与今天的演讲相关的是，

it turns out that there are a group of cardiologists

有一群心血管科医生数十年来一直预测，

who, for decades, have hypothesized

that these same inflammatory factors may also be driving heart disease.

这些炎症因子也可能导致心血管疾病。

They were able to convince the company that makes this drug

他们努力说服开发这一药物的制药公司

to do a trial to look at the effect of this medicine

在有心脏病或中风病史的患者中 进行一项研究，

in patients who had had a heart attack or a stroke in the past.

去看看它有没有效果。

And really, it was no surprise to many of us

说实话，当研究结果被发表时， 我们并没有感到很惊讶。

when the results of this trial were published.

And they showed that, in fact, compared to a placebo,

结果表明，和安慰剂相比，

that this medicine could prevent recurrent cardiovascular events.

这一药物可以预防心血管疾病的再次发作。

But our algorithms predict that this drug

但我们实验室的算法也预测到，

should not only help prevent heart disease

这一药物不仅能预防心血管疾病， 应该也能预防癌症。

but also should be able to prevent cancer.

And so this particular article gained a lot of attention

这篇科研文章更加引人注意的一点是，

because when they unblinded their results,

当研究者们公开他们的结果时，

the investigators were shocked to find

他们惊讶地发现，

that not only were the patients having fewer heart attacks

这些患者不仅有更少的心血管疾病，

but they were having a much lower rate of developing lung cancer

他们罹患肺癌和死于癌症的几率 也大大降低了。

and a much lower rate of even dying from cancer.

In fact, these results were so surprising and powerful

这些结果真的很令人吃惊和有说服力，

that I understand the company that makes this drug

所以据我所知，这家制药公司现在 将这一药物优先宣传为抗癌药物，

is now pivoting and prioritizing this as a cancer drug,

because the effects were so significant.

因为药效着实显著。

How about another example from the blue quadrant this time?

关于蓝色象限，我们有什么例子吗？

Well, here we come to one of my favorite cells in the body,

让我们来看看身体里我最喜欢的一种细胞，

which is an immune cell called the macrophage.

一种被称为巨噬细胞的免疫细胞。

Now, macrophage is from the Greek, meaning "big eater."

巨噬细胞这个词来自希腊语， 意思是“大胃王”。

And the role of this cell is to patrol the body,

它们在身体里巡逻，就像哨兵一样，

like a sentinel,

and it looks for invading bacteria.

四处寻找入侵的细菌。

When it sees them, it actually will eat them

巨噬细胞会吃掉它找到的细菌，

and remove them from our body before they can expand

在细菌扩散到全身并引发感染之前清除它们。

and cause an infection.

But just like in the last example, there are oncologists

就像我刚刚提到的那个例子一样，

肿瘤科医生预测 这些巨噬细胞不仅能吃掉细菌，

who have hypothesized that these macrophages

don't just have to eat bacteria,

but they also have to look for and eat cancer cells

它们还能寻找并吃掉癌症细胞，

and hopefully get rid of them before they can grow

希望能在这些肿瘤生长和转移之前 将其清除干净。

and metastasize.

And so there's been a major initiative to develop medicines

他们提出一项重要的倡议，

that can increase the appetite of these cells

想要开发出能增强这些细胞的食欲， 并帮助它们清除肿瘤的药物。

to help them go after those tumors.

Now, this story is still in its early days,

现在这个故事才刚刚开始，

and it's unclear if this type of an approach will work.

我们还并不确定这类方法会不会奏效。

But some of the early studies would suggest

但一些早期研究表明，

that patients who have metastatic lymphoma,

一些淋巴瘤的患者，通过CAT （计算机 X 射线轴向分层造影）扫描，

which you can see spread throughout this person's body on their CAT scan,

你可以看见这个人的肿瘤 已经扩散到身体各处，

that they may have a remarkable response to these types of drugs.

而这些患者可能 对这类药物有很好的响应。

And you can imagine here that the tumors are melting away

你可以想象到，当巨噬细胞食欲大增时，

as they're being eaten by these cells

它们会吃掉肿瘤细胞， 所以肿瘤就渐渐消失了。

due to their increased appetite.

But once again, what we found is that our algorithms predict

但再一次地，我们的算法预测到，

that, yes, this drug should work for cancer,

的确，这个药物可以抗癌，

but we think it might also work for heart disease.

但它可能同时也对心血管疾病有效。

And so we've now gone back and retrospectively analyzed

所以我们现在对那些肿瘤患者的 CAT 扫描结果进行了回顾性分析，

the same CAT scans from the same cancer patients.

But this time, instead of looking at the signal from their tumors,

但这次，我们的注意力 并不在肿瘤的信号，

we can look at the signal in their blood vessels.

而是在血管的信号。

And here I'm pointing with the arrow to the carotid artery.

这里箭头所指的地方是颈动脉，

This is the artery

血液经由这条动脉流进大脑，

that brings the blood to the brain,

this is where cardiovascular disease will build up

在患者中风发作前， 心血管病变就在这里发展积累。

in patients before they have a stroke.

And what we found is that while their cancer was melting away,

而我们发现，在肿瘤渐渐消失的同时，

it looks like their cardiovascular disease was melting away, too.

心血管病变也在渐渐消失。

And so, once again,

所以，又一次地，

these algorithms are predicting

这些算法预计了，

that we may be able to identify therapies

我们或许能够开发出同时作用于 癌症和心血管疾病的疗法。

that could be dual purposed to attack both conditions at the same time.

We don't yet know if any of these other pathways

我们尚且不清楚 是否其他的通路也会如此成功，

will have the same type of success.

But what we do know for sure is the lesson that Galileo taught us

但我们清楚地知道的是，

伽利略几乎四个世纪前 教给我们的话是正确的：

almost four centuries ago,

and that there is no such thing as settled science.

没有什么科学原理是一成不变的。

We must challenge dogma,

我们必须挑战权威，

we must break down traditional silos.

我们必须打破传统。

Because if we do,

因为如果我们这样做，

we may no longer be powerless against these leading killers,

面对这两个最致命的疾病时， 我们可能不再无能为力，

but may, in fact find ways to treat the world's two leading killers.

而是可能会找到治疗它们的方法。

Thank you.

谢谢。

(Applause)

（掌声）