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

譯者: Lilian Chiu 審譯者: Helen Chang

In two decades of practicing medicine,

在行醫的二十年間，

I've encountered a wide number of medical diagnoses.

我碰過相當多種的醫療診斷。

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

結果發現，在病人的病歷上

可以列出的醫療診斷就有超過六萬種。

that you can list on a patient's chart.

You can actually be diagnosed with a burn injury

你有可能被診斷為滑水板著火

when your water skis catch on fire.

燃燒造成的燒傷。

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

如果你被豬咬了之後需要 動手術，也有對應的診斷碼，

(Laughter)

（笑聲）

hit by a spacecraft,

被太空船撞到也有，

(Laughter)

（笑聲）

stabbed while crocheting,

打毛線時被刺傷也有，

or my favorite,

還有我最愛的，

due to extreme problems with your in-laws.

和姻親的極端問題造成傷害。

(Laughter)

（笑聲）

But the best of all has got to be the code

但所有診斷碼中最讚的 應該是被噴射引擎吸入。

for getting sucked into a jet engine.

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

我這麼喜歡這個診斷碼是因為 它不是初次被吸入的代碼，

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

而是後續再次被吸入。

(Laughter)

（笑聲）

So there must be people on this Earth

所以世界上一定有人 曾被吸入噴射引擎兩次過。

that have been sucked into a jet engine twice.

(Laughter)

（笑聲）

But I think, you know, kidding aside,

但，不開玩笑了，

we have to recognize

我們必須要知道，在這裡的每一個人

that every last one of us in this room

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

將來最有可能的死亡診斷 大概都是這兩個其中之一：

And these, of course, are either cancer

當然，一個是癌症，

or cardiovascular disease.

另一個是心血管疾病。

This speaks to the incredible public health importance

這就說明了這兩種疾病的 公衛重要性有多高，

of these two diseases

and the urgent, unmet medical need to develop new therapies

且迫切需要針對它們開發新的 治療方式，而這需要尚未被滿足。

directed against them.

A lot of people are not surprised

大部分人並不意外 這兩種疾病帶走這麼多人命。

that these two diseases claimed so many lives.

After all, they are very different biologically,

畢竟，這兩種疾病 在生物學上非常不同，

they have different risk factors,

風險因子也不同，

and they affect very different patient populations.

會影響的病人族群也非常不同。

But for the next 15 minutes or so,

但在接下來的約十五分鐘， 我想要提一個不同的假設：

I would like to propose a different hypothesis.

That perhaps they actually have quite a lot in common.

它們可能其實有很多共通點。

And even more importantly,

更重要的是，我想提出，如果 我們能用這種方式看待它們，

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

we might be able to develop new therapies

我們可能可以開發新的治療方式，

that could treat both diseases at the same time.

來同時治療這兩種疾病。

So before I tell you why I believe this hypothesis,

在我告訴各位我為什麼 相信這個假設之前，

let me lay out the counter arguments against it.

讓我先列出反對它的論點。

I think many people would say

我想，許多人會認為，

that the old man who smokes cigarettes his whole life

一生都在抽菸且有心臟病發作的老人

and has a heart attack

shares very little in common with a young person

和出乎意料得到大腸癌的 年輕人沒有什麼共通點。

who develops colon cancer out of the blue.

But we now know that the risk factors for these diseases

但現在我們知道 這兩種疾病的風險因子

have significant overlap.

有很大一部分重疊。

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

造成其中一種疾病的因子可能會 讓你有得到另一種疾病的風險。

Well, that may be true,

也許如此，但我們知道這兩種 疾病在遺傳學上非常不同。

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

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

我相信很多人曾聽過 癌症基因有可能會突變，

that can be mutated in families

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

在家族中會讓母女都有乳癌的風險。

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

我們知道那些基因 和心臟病發作無關，

and that's true also.

那也是真的。

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

但我要強調，那些基因 是數十年前發現的，

before the Human Genome Project

是在人類基因組計畫之前，

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

是在我們能同時掃瞄 三十億鹼基對之前。

And when we do this for patients having heart attack,

當我們針對心臟病 發作的病人做掃瞄時，

we find that the top hotspot for having a heart attack

我們發現心臟病發作的最熱點

is located on chromosome nine,

位在第九號染色體，

shown here with these blue dots.

在圖上用藍點呈現。

And what shocked the world when this paper was first published

這篇論文首次刊出時 震撼了世界，因為它發現

was that this genetic locus has nothing to do with smoking

這個基因所在位置完全無關乎

or cholesterol or diabetes.

抽菸、膽固醇，或糖尿病。

But actually seems to control a well-known cancer gene

反而似乎是在控制 一個很知名的癌症基因，

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

這個基因在有黑色素瘤、腦癌、

肺癌等疾病的病人體內會突變。

lung cancer, etc.

And so for decades,

所以，數十年來，我們的焦點都 放在傳統的心臟病風險因子上，

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

But the genetics now tell us

但現在遺傳學告訴我們， 最重要的因子

that the most important factor may actually have to do

反而可能是和一個 知名的癌症基因有關。

with a well-known cancer gene instead.

Well, that's an interesting observation,

觀察到這種現象十分有趣， 但我們知道如果用顯微鏡看

but we know that if you look under the microscope

這兩種疾病，它們大大不同。

at these two diseases,

they couldn't be more different.

When I was in medical school,

我在醫學院學到的是

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

癌症只是細胞分裂太快速。

And you can imagine this lung tumor

各位可以想像，這個肺部腫瘤

growing over time and taking over the lung,

隨時間長大，佔據整個肺部，

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

且這和心臟病的狀況完全無關。

據我所學，心臟病這個問題 源自於膽固醇升高，

which is a problem that, I was taught,

was due to the buildup of cholesterol

that can ultimately lead to the blockage of an artery

最終導致動脈阻塞、 心臟病發作，或中風。

and a heart attack or a stroke.

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

不可否認，這兩種 生物學過程都極重要。

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

但我要強調，關於 這些疾病的現代教科書

is getting harder and harder to tell apart.

越來越難分別出來。

We now know that both of these conditions are dominated

我們現在知道，支配這些疾病的包括

by the influx of inflammatory cells

大量湧進炎症細胞，

and immune cells and abnormal blood vessels

以及免疫細胞，以及異常血管，

and even stem cells.

甚至幹細胞。

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

也許，我用的教科書已經過時了。

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

此時，各位可能會說， 這是很有趣的觀察，但，

有沒有任何臨床資料指出

but is there any clinical data which would suggest

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

患有其中一種疾病的病人， 得到另一種疾病的風險也較高？

Turns out that investigators, both in Asia and Europe,

結果是，亞洲和歐洲的研究者

have now started to test this hypothesis.

現在都開始測試這項假設。

And just last year,

就在去年，德國刊出了 一篇非常重要的文章，

a very important article was published out of Germany,

where they looked at more than 100,000 individuals

他們研究了超過十萬名 有充血性心力衰竭的人，

with congestive heart failure

and they found that these people were at much higher risk

發現這些人得到 癌症的風險更高許多。

of developing cancer.

This is really interesting

這很有趣，對我的意義是，

and suggests to me that indeed having one disease

的確，患有一種疾病的確會讓你 有更高的風險得到另一種疾病。

may put you at risk of the other.

But this also raises a very important scientific principle

但，這也帶出了一條 非常重要的科學原則，

that association is not the same as causation.

有關聯不表示有因果關係。

And if you wanted to test that hypothesis,

若你想要檢定那個假設，

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

你就得做個實驗， 找來健康的受試者，

and then intentionally gave them a heart attack.

並刻意讓他們心臟病發作。

You'd have to let some time go by

你得等一段時間，看看 他們的身體有什麼改變發生。

to see what changes occur throughout the body.

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

接著你就能判定他們 得癌症的機率是否更高，

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

或反過來，他們得到 心臟病的機率是否更高。

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

很明顯，我們不能 用人類來做這種實驗。

This would be unethical.

這有違倫理。

But this type of an experiment is done in research laboratories

但，全世界每天都有這種實驗 在研究實驗室中進行，

every day around the world

in mouse models of human disease.

做的是人類疾病的老鼠模式。

Just last year, two very important studies were published

在去年，有兩篇 非常重要的論文被刊出，

where investigators took healthy mice

研究者採用健康的老鼠，

and then implanted small tumors underneath their skin.

將小腫瘤植入到牠們的皮膚下。

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

他們探究這些癌症 隨時間的成長速度。

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

兩篇論文都有同樣的發現： 有心臟病的老鼠

had much higher rates of cancer.

癌症成長的速度也比較快。

And what was fascinating to me

很吸引我的是，

was that they were able to confirm these findings

他們確認多種腫瘤具有同樣的現象，

across a wide range of tumors,

suggesting to me that really the presence of heart disease

對我的意義是，確實， 只要有心臟病的存在，

is sufficient to accelerate cancer growth.

就足以加速癌症的成長。

So having heard all this,

所以，聽到這一切之後，

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

很自然會問，對此， 我們有沒有什麼對策？

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

除了我在史丹佛的工作之外， 我也在美國心臟協會當志工。

is with the American Heart Association.

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

我們有一套公衛指引叫做 「生活簡單七件事」。

We try to get patients with a history of heart disease

我們希望有心臟病病史的病人能夠

to control these very simple and straightforward risk factors

控制好這些非常簡單 又直接的風險因子，

like exercise, cholesterol and diet.

比如運動、膽固醇，和飲食。

The idea here is that if you can control these,

背後的概念是如果你能把這些 控制做好，應該就比較不會

you should be able to lower your risk

of having additional cardiovascular events.

發生額外的心血管事件。

This is now pretty widely accepted.

現在這觀念已被廣為接受。

But what's fascinating to me

但，吸引我的是， 現在有一群研究者在研究

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

這些風險因子和癌症之間的關聯。

with these risk factors and cancer.

And in a study with more than 10,000 individuals

有一項研究，對象超過一萬個人，

who were followed for almost two decades,

追蹤時間近二十年，

they found the people who had optimal control

他們發現，能把風險因子 控制到最理想的人，

of all their risk factors

had a pretty low rate of developing cancer.

得到癌症的比例就相當低。

But for each risk factor which fell out of control,

但，每有一個風險因子失控，

the risk of malignancy went up.

惡性腫瘤的風險就會上升。

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

各位可以看到，七個風險因子 通通沒控制好的族群，

had by far the highest rates of cancer,

是目前癌症比率最高的族群，

with nearly a doubling of the risk.

風險變成接近兩倍。

So this suggests to me that,

這告訴我，如果我們想要控制癌症，

in fact, if we want to control cancer,

we might start by controlling our cardiac risk profile.

我們可能可以從控制好 心血管風險做起。

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

這很好，我們也持續 鼓勵我們的病人這麼做。

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

但，現實是，就算我有魔杖，

and could somehow optimally control everybody's risk factors,

且能以某種方式把大家的 風險因子都控制到最理想，

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

我們知道，我們仍然要面對全世界

and number two causes of death worldwide.

第一名和第二名的死因。

This tells us that we need to find new therapies

這表示，我們需要 找到新的治療方式，

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

能夠治療這些疾病或甚至 一開始就預防它們發生。

Now our laboratory chooses to do this

我們的實驗室選擇採用 一種無偏差的遺傳學方法。

with an unbiased genetics approach.

We take biopsies from patients

我們從病人取得活組織切片，

with or without a wide variety of tumors,

包括有和沒有多種腫瘤的病人，

or with and without cardiovascular disease.

或有和沒有心血管疾病的病人。

And instead of looking at one gene at a time,

我們不是一次看一個基因， 而是掃瞄整個基因組，

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

觀察所有兩萬個基因的表現。

You can plot these on a plot like this

結果可以畫在這樣的圖上，

where each gray dot represents its own gene.

每個灰點都代表其自己的基因。

And when you acquire enough samples,

當你取得足夠樣本， 就可以開始找模式，

you can begin to identify patterns of those genes

which are bad for cancer

比較對癌症不好的基因 vs. 保護對抗癌症的基因。

versus those that protect against it.

And do the same type of an experiment

再做同樣的實驗，

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

去找出什麼會加速 或預防心血管疾病。

Now, I think the clever part of this approach

我認為這個方法的聰明之處

is to integrate these

and to run these analyses simultaneously.

在於整合並同時分析。

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

這麼做，就能開始研究

紅色象限中的因子。

These are genes that we suspect should be bad

我們懷疑這些基因對於 心臟病及癌症兩者都不好，

for both heart disease disease and cancer

and must be avoided at all costs.

應該要不計代價避免。

Or even better,

更好的是，

perhaps we can find factors in the blue quadrant

也許我們能找到藍色象限中的因子，

that should be able to protect against both diseases.

它們應該能保護我們， 對抗這兩種疾病。

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

我們假設在藍色象限中的 這些因子能夠被擺在優先順位，

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

來協助我們找到新藥，

來治癒這兩種頭號殺手。

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

我們的團隊已經分析了數千個人。

This work is still underway,

研究仍然在進行中，

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

但目前我們已經找出了 近四十條途徑，

that we do think should be prioritized.

認為它們都該被擺在優先順位。

Now, time will tell if these work.

時間會證明這是否行得通，

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

它們全部、當中幾種、 當中任何一種是否行得通。

We just don't know.

我們還不知道。

But I do want to show you a couple of examples

但我想舉幾個例子， 顯示我們的方向是對的。

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

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

在紅色象限中，我們找到的 其中一個因子和發炎有關。

And we often think of inflammation as being bad,

我們通常都認為發炎是不好的，

but in reality, this is a process

但事實上，它是個過程，

that our body evolved to help us recover from injury

我們的身體演化出這個過程 來協助我們從受傷中復元，

or to mount a fever to fight off an infection.

或者用發燒的方式來擊退感染。

But of course, there are always times

但，當然，總是有些時候 我們的身體會有太多某種東西。

where our body has too much of something.

In this case,

在這個例子中，

there's a rare genetic syndrome

有一種罕見的遺傳症候群，

where children can be born with overactive inflammation,

孩子出生時可能就有 過度活躍的發炎，

and they can have recurrent episodes of high fevers and rashes

他們有可能會一再發高燒和起疹子，

and other neurocognitive and developmental delays.

還有其他神經認知和發展上的延遲。

Now in a triumph of science,

科學上有成功的進展，

investigators have pinpointed the exact molecule responsible for this,

研究者已經針對這種疾病 精確找出了確實的分子反應，

and they developed a drug that can block it.

並開發出了一種藥物來阻止它。

These children who have these rashes that I mentioned before

我剛才提到這些會起疹子的孩子，

can have a relatively remarkable improvement on these drugs

用了這些藥物之後， 有相對十分驚人的改善，

and almost get back to a normal quality of life.

且幾乎可以找回正常的生活品質。

But relevant to today's talk,

但和今天的演說 相關的是，結果發現，

it turns out that there are a group of cardiologists

數十年來，有一群 心臟病學家就已經假設

who, for decades, have hypothesized

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

同樣這些發炎因子 也有可能會促成心臟病。

They were able to convince the company that makes this drug

他們成功說服該公司 製造這種藥物來做試驗，

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

以研究藥物的效果，

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

對象是以前有過心臟病 發作或中風的病人。

And really, it was no surprise to many of us

實際上，當這個試驗的結果被刊出時，

when the results of this trial were published.

我們多半不感到吃驚。

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

結果指出，事實上，和安慰劑相比，

that this medicine could prevent recurrent cardiovascular events.

這種藥物能夠預防 一再發生心血管事件。

But our algorithms predict that this drug

但我們的演算法預測，這種 藥物不僅能協助預防心臟病，

should not only help prevent heart disease

but also should be able to prevent cancer.

也應該能預防癌症。

And so this particular article gained a lot of attention

所以這篇文章得到了 很多關注，因為，

because when they unblinded their results,

當他們將結果解盲時，

the investigators were shocked to find

研究者很訝異，他們發現 不僅病人的心臟病發作減少，

that not only were the patients having fewer heart attacks

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

他們得到肺癌的機率也低很多，

and a much lower rate of even dying from cancer.

甚至連因為癌症 過世的機率也低很多。

In fact, these results were so surprising and powerful

事實上，這些結果相當驚人且強大，

that I understand the company that makes this drug

據我所知，該公司 現在正在轉變方向，

is now pivoting and prioritizing this as a cancer drug,

將它優先作為癌症藥物，

because the effects were so significant.

因為效果是如此顯著。

How about another example from the blue quadrant this time?

再來舉個藍色象限的例子如何？

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

這裡就要提到我最愛的 人體細胞之一，

which is an immune cell called the macrophage.

那就是巨噬细胞，一種免疫細胞，

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

巨噬 macrophage 這個字是來自希臘文。

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

這種細胞的角色是 像哨兵一樣在身體中巡邏，

like a sentinel,

and it looks for invading bacteria.

尋找入侵的細菌。

When it sees them, it actually will eat them

發現它們時，巨噬細胞會吃掉它們，

and remove them from our body before they can expand

在它們能增長並造成身體感染 之前就把它們從體內除掉。

and cause an infection.

But just like in the last example, there are oncologists

但，就如同上一個例子，

有些腫瘤學家假設

who have hypothesized that these macrophages

這些巨噬細胞不僅必須要吃掉細菌，

don't just have to eat bacteria,

but they also have to look for and eat cancer cells

也得尋找並吃掉癌細胞，

and hopefully get rid of them before they can grow

希望能在癌細胞成長 和轉移之前就把它們解決。

and metastasize.

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

所以，有一個重大計畫 就是希望能開發藥物，

that can increase the appetite of these cells

來增加這些細胞的食慾， 幫助它們去追殺腫瘤。

to help them go after those tumors.

Now, this story is still in its early days,

這個故事目前才在前幾章，剛開始，

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

還不清楚這種方法行不行得通。

But some of the early studies would suggest

但一些早期的研究指出，

that patients who have metastatic lymphoma,

有轉移性淋巴瘤的病人，

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

他們的電腦斷層掃瞄結果 顯示全身性的擴散，

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

而這些病人對這類藥物 可能會有很不凡的反應。

And you can imagine here that the tumors are melting away

各位可以想像，腫瘤因為 被吃掉了而在消失中，

as they're being eaten by these cells

這些細胞的食慾增加， 所以開始吃它們。

due to their increased appetite.

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

但同樣的，我們發現 我們的演算法預測

that, yes, this drug should work for cancer,

是的，這種藥物對癌症應該有效，

but we think it might also work for heart disease.

但我們認為它對心臟病應該也有效。

And so we've now gone back and retrospectively analyzed

所以現在我們回頭去， 用回溯性的方式

分析同樣這些癌症病人的 同樣這些掃瞄結果。

the same CAT scans from the same cancer patients.

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

但這次不是要研究 來自他們身上腫瘤的信號，

we can look at the signal in their blood vessels.

我們改成研究他們血管中的信號。

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

這裡我用箭頭標記的地方是頸動脈。

This is the artery

頸動脈負責將血液帶到腦部，

that brings the blood to the brain,

this is where cardiovascular disease will build up

心血管疾病通常會逐漸在此處形成，

in patients before they have a stroke.

接著病人就可能會中風。

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

我們發現，不僅 他們的癌症在消失中，

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

同時他們的心血管疾病也在消失中。

And so, once again,

所以，同樣的，

these algorithms are predicting

這些演算法預測我們可能 可以找出一些治療方法，

that we may be able to identify therapies

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

具有雙重用途，

同時對付兩種疾病。

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

我們還不知道

這些其他的途徑 是否會有同樣的成功，

will have the same type of success.

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

但我們能肯定知道的，

是伽利略在近四百年前 教我們的道理，

almost four centuries ago,

and that there is no such thing as settled science.

那就是：沒有所謂已解決的科學。

We must challenge dogma,

我們必須要挑戰信條， 我們必須要打破傳統的窠臼。

we must break down traditional silos.

Because if we do,

因為如果我們能做到，

we may no longer be powerless against these leading killers,

面對這些頭號殺手， 我們可能就不會無能為力，

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

事實上，還有可能可以找到方法來治療

世界上的這兩個頭號殺手。

Thank you.

謝謝。

(Applause)

（掌聲）