Soon We'll Cure Diseases With a Cell, Not a Pill | Siddhartha Mukherjee | TED Talks

譯者: Wink Wong 審譯者: Karen SONG

I want to talk to you about the future of medicine.

我想跟大家探討醫學的未來。

But before I do that, I want to talk a little bit about the past.

未開始前，我要先講過去的醫學。

Now, throughout much of the recent history of medicine,

由從前一直到近代的醫學歷史，

we've thought about illness and treatment

我們愛用非常簡單的模式

in terms of a profoundly simple model.

來思考疾病和治療。

In fact, the model is so simple

其實這些模式非常簡單，

that you could summarize it in six words:

可以用6個字總結：

have disease, take pill, kill something.

染病、吃藥和除病。

Now, the reason for the dominance of this model

這個模式佔了優勢

is of course the antibiotic revolution.

當然是抗生素革命。

Many of you might not know this, but we happen to be celebrating

或許你不知道，我們剛剛

the hundredth year of the introduction of antibiotics into the United States.

慶祝美國引進抗生素100週年。

But what you do know

但你必定知道

is that that introduction was nothing short of transformative.

引入抗生素後，發展迅速。

Here you had a chemical, either from the natural world

這些化學物不是從自然界得來，

or artificially synthesized in the laboratory,

便是在實驗室人工合成。

and it would course through your body,

它會進入人體，

it would find its target,

找尋自己的目標，

lock into its target --

然後鎖定目標——

a microbe or some part of a microbe --

一種微生物或者它的一部分，

and then turn off a lock and a key

然後非常敏捷地、專門地

with exquisite deftness, exquisite specificity.

阻止細菌等像鎖鑰般結合。

And you would end up taking a previously fatal, lethal disease --

最後把你從以前患的致命疾病——

a pneumonia, syphilis, tuberculosis --

肺炎、梅毒，結核病，

and transforming that into a curable, or treatable illness.

變成可以治癒的疾病。

You have a pneumonia,

患了肺炎，

you take penicillin,

可以用盤尼西林

you kill the microbe

殺死微生物，

and you cure the disease.

然後痊癒。

So seductive was this idea,

這個概念很吸引人，

so potent the metaphor of lock and key

用鎖鑰結合的比喻，然後除病

and killing something,

非常有效。

that it really swept through biology.

而且這個概念已橫掃生物學界。

It was a transformation like no other.

那種改變真是不同凡響。

And we've really spent the last 100 years

科學家在以往的100年間，

trying to replicate that model over and over again

竭盡所能不停複製這類模式，

in noninfectious diseases,

應用在非傳染疾病，例如慢性疾病——

in chronic diseases like diabetes and hypertension and heart disease.

糖尿病、高血壓和心臟病。

And it's worked, but it's only worked partly.

結果是可行的，但只是部分有效。

Let me show you.

讓我告訴你為什麼會這樣。

You know, if you take the entire universe

如果以人體所有的

of all chemical reactions in the human body,

化學反應，

every chemical reaction that your body is capable of,

身體都能夠進行的每個化學反應，

most people think that that number is on the order of a million.

大部分人都會認為大約有1百萬次

Let's call it a million.

那就把它算作1百萬。

And now you ask the question,

現在你會問，

what number or fraction of reactions

其實所有藥物或醫學化學

can actually be targeted

可以鎖定的反應

by the entire pharmacopoeia, all of medicinal chemistry?

有幾多次或幾多部分呢？

That number is 250.

答案是250。

The rest is chemical darkness.

其他仍是未知數。

In other words, 0.025 percent of all chemical reactions in your body

換言之，人體內的所有的化學反應

are actually targetable by this lock and key mechanism.

就只有0.025%是由 這個鎖鑰機制視為目標。

You know, if you think about human physiology

試想像人類的生理

as a vast global telephone network

就如全球的電話網絡，

with interacting nodes and interacting pieces,

佈滿互通的伺服器和其他組件，

then all of our medicinal chemistry

然後所有的醫學化學

is operating on one tiny corner

就在網絡的最外邊，

at the edge, the outer edge, of that network.

在那裡最小的角落運作。

It's like all of our pharmaceutical chemistry

好像所有的藥物化學

is a pole operator in Wichita, Kansas

就在堪薩斯州威奇塔市 當電話接線生

who is tinkering with about 10 or 15 telephone lines.

笨拙地處理10條或15條電話線。

So what do we do about this idea?

我們根據這個概念要怎麼做？

What if we reorganized this approach?

要是改革這些方法又如何？

In fact, it turns out that the natural world

其實結果是大自然給我們的啟示，

gives us a sense of how one might think about illness

跟我們以前對疾病的了解，

in a radically different way,

簡直是天淵之別，

rather than disease, medicine, target.

不是由疾病，繼而藥物， 最後目標。

In fact, the natural world is organized hierarchically upwards,

事實上，大自然的規則是下而上，

not downwards, but upwards,

不是由上而下，而是由下而上，

and we begin with a self-regulating, semi-autonomous unit called a cell.

首先由細胞開始，那是可以自我 調節和半自主的單位。

These self-regulating, semi-autonomous units

這些細胞造成器官，

give rise to self-regulating, semi-autonomous units called organs,

也是自我調整和半自主的單位。

and these organs coalesce to form things called humans,

器官合併一起，造成人類，

and these organisms ultimately live in environments,

這些生物是部分自我調整 和部分半自主，

which are partly self-regulating and partly semi-autonomous.

最後在週圍環境生活。

What's nice about this scheme, this hierarchical scheme

這種階級流程真不錯，

building upwards rather than downwards,

向上發展，而不是向下建立，

is that it allows us to think about illness as well

可讓我們思考疾病

in a somewhat different way.

有點不同。

Take a disease like cancer.

就以癌症這種疾病為例。

Since the 1950s,

自從1950年代以來，

we've tried rather desperately to apply this lock and key model to cancer.

我們竭力地把鎖鑰模式 來治療癌症。

We've tried to kill cells

探用多種的化療和標鈀治療，

using a variety of chemotherapies or targeted therapies,

嘗試消滅癌細胞，

and as most of us know, that's worked.

而且多數人都知道，那是成功的。

It's worked for diseases like leukemia.

它治療白血病這類疾病很有效。

It's worked for some forms of breast cancer,

對幾種類型的乳癌也有效。

but eventually you run to the ceiling of that approach.

但是利用這個方法 最終也到了極限。

And it's only in the last 10 years or so

只是到了最近10年來，

that we've begun to think about using the immune system,

我們漸漸想到利用免疫系統治病，

remembering that in fact the cancer cell doesn't grow in a vacuum.

還記起癌細胞其實 不是在真空生長。

It actually grows in a human organism.

而是在人體內生長。

And could you use the organismal capacity,

因為人類有免疫系統，

the fact that human beings have an immune system, to attack cancer?

可否用生物能力去攻擊癌症呢？

In fact, it's led to the some of the most spectacular new medicines in cancer.

其實已經有好些驚人的 新癌症藥物因此硏製了。

And finally there's the level of the environment, isn't there?

最後到了環境這一階段，是不是？

You know, we don't think of cancer as altering the environment.

我們不認為癌症改變環境。

But let me give you an example of a profoundly carcinogenic environment.

但讓我告訴你一個例子， 那是極度致癌的環境。

It's called a prison.

它叫做「囚禁」。

You take loneliness, you take depression, you take confinement,

你如果孤獨、抑鬱、自我封閉，

and you add to that,

再加上

rolled up in a little white sheet of paper,

捲起一張小小的白紙

one of the most potent neurostimulants that we know, called nicotine,

把最強的神經興奮劑 叫做「尼古丁」放進去，

and you add to that one of the most potent addictive substances that you know,

也加入了最易上癮的物質，

and you have a pro-carcinogenic environment.

最後形成了致癌的環境。

But you can have anti-carcinogenic environments too.

但你也可以製造防癌的環境。

There are attempts to create milieus,

我們嘗試去創造周圍環境，

change the hormonal milieu for breast cancer, for instance.

例如改變引致乳癌的激素環境。

We're trying to change the metabolic milieu for other forms of cancer.

還有不斷努力改變其他癌症的 新陳代謝環境。

Or take another disease, like depression.

或者以另一類疾病如抑鬱來說，

Again, working upwards,

又是從向上的方向治療。

since the 1960s and 1970s, we've tried, again, desperately

自從1960到1970年代， 我們拼命地不斷嘗試

to turn off molecules that operate between nerve cells --

阻止分子在神經細胞之間運行,

serotonin, dopamine --

如血清素，安多芬，

and tried to cure depression that way,

希望用這些方法治療抑鬱症，

and that's worked, but then that reached the limit.

雖然有效，但是很快到了極限。

And we now know that what you really probably need to do

我們知道現在可能最需要

is to change the physiology of the organ, the brain,

改變器官和腦部的生理機能，

rewire it, remodel it,

替它們重新接線，重新改造。

and that, of course, we know study upon study has shown

當然多次的研究證明

that talk therapy does exactly that,

說話治療完全辦得到，

and study upon study has shown that talk therapy

但經過不斷的研究證明說話治療

combined with medicines, pills,

再加上藥物，

really is much more effective than either one alone.

比接受單一的治療更加有效。

Can we imagine a more immersive environment that will change depression?

可否想像一個較為浸淫式 虛擬實境，將會改善抑鬱症嗎？

Can you lock out the signals that elicit depression?

可否封鎖引致抑鬱症的 神經信號呢？

Again, moving upwards along this hierarchical chain of organization.

又再次沿著這條組織階級向上移。

What's really at stake perhaps here

最危險可能

is not the medicine itself but a metaphor.

不是藥物，而是比喻意義。

Rather than killing something,

不要只是去消滅病菌，

in the case of the great chronic degenerative diseases --

以最慢性退化性疾病為例---

kidney failure, diabetes, hypertension, osteoarthritis --

腎衰竭、糖尿病、 高血壓和骨關節炎，

maybe what we really need to do is change the metaphor to growing something.

或許我們真的要把 這個比喻改為培養。

And that's the key, perhaps,

可能這就是答案，

to reframing our thinking about medicine.

改變我們對醫學的想法。

Now, this idea of changing,

這種改革思想，

of creating a perceptual shift, as it were,

產生認知的轉移，

came home to me to roost in a very personal manner about 10 years ago.

是源於大約10年前， 我自作自受的後果。

About 10 years ago -- I've been a runner most of my life --

大約10年前，我常常跑步。

I went for a run, a Saturday morning run,

有一個星期六，我去跑步，

I came back and woke up and I basically couldn't move.

回家，跟著一覺醒來 ，我簡直動彈不得。

My right knee was swollen up,

右腳膝蓋腫起來，

and you could hear that ominous crunch of bone against bone.

可以聽到骨頭間嘎吱作響， 非常恐怖。

And one of the perks of being a physician is that you get to order your own MRIs.

做醫生有一樣好處， 便是自己預約磁力共振。

And I had an MRI the next week, and it looked like that.

我在隨後的星期照了磁力共振，

Essentially, the meniscus of cartilage that is between bone

基本上，在骨中間的軟骨半月板

had been completely torn and the bone itself had been shattered.

已經全部撕破，而且骨碎裂。

Now, if you're looking at me and feeling sorry,

如果你很同情我，

let me tell you a few facts.

那麼讓我告訴你一些真相。

If I was to take an MRI of every person in this audience,

如果我替在座每位觀眾 照磁力共振，

60 percent of you would show signs

將會有六成人的結果顯示

of bone degeneration and cartilage degeneration like this.

像這般的骨頭和 軟骨退化的跡象。

85 percent of all women by the age of 70

而女性到了70歲，便有85％的人

would show moderate to severe cartilage degeneration.

有中度到嚴重的軟骨退化。

50 to 60 percent of the men in this audience

而在座的男士有50至60％

would also have such signs.

也會有這些跡象。

So this is a very common disease.

所以這是很常見的疾病。

Well, the second perk of being a physician

做醫生有第二個好處。

is that you can get to experiment on your own ailments.

就是可以替自己的小病做實驗。

So about 10 years ago we began,

所以大約10年前，我們開始著手，

we brought this process into the laboratory,

把這些方法帶到實驗室。

and we began to do simple experiments,

從做簡單的實驗開始，

mechanically trying to fix this degeneration.

呆板地想解決退化的問題。

We tried to inject chemicals into the knee spaces of animals

我們給動物的膝蓋注射化學物，

to try to reverse cartilage degeneration,

想挽救軟骨退化。

and to put a short summary on a very long and painful process,

經過冗長又痛苦的過程， 只可以用幾句總結。

essentially it came to naught.

基本上一無所收穫。

Nothing happened.

什麼事也沒有發生過。

And then about seven years ago, we had a research student from Australia.

跟著大約7年前， 來了一位澳洲研究生。

The nice thing about Australians

澳洲人的優點

is that they're habitually used to looking at the world upside down.

就是他們習慣把世界倒轉來看。

(Laughter)

（笑聲）

And so Dan suggested to me, "You know, maybe it isn't a mechanical problem.

於是Dan向我提議說： 可能不是機械問題，

Maybe it isn't a chemical problem. Maybe it's a stem cell problem."

也不一定是化學問題， 可能是幹細胞問題。

In other words, he had two hypotheses.

換言之，他有兩個假說。

Number one, there is such a thing as a skeletal stem cell --

第一，真是有這樣的骨幹細胞--

a skeletal stem cell that builds up the entire vertebrate skeleton,

這些細胞建立整個脊髓骨架，

bone, cartilage and the fibrous elements of skeleton,

骨頭，軟骨和骨纖維。

just like there's a stem cell in blood,

就像血液裡有幹細胞，

just like there's a stem cell in the nervous system.

神經系統有幹細胞一樣。

And two, that maybe that, the degeneration or dysfunction of this stem cell

第二，這些幹細胞可能 退化或者失去功能，

is what's causing osteochondral arthritis, a very common ailment.

引起骨關節炎這些常見的小病。

So really the question was, were we looking for a pill

最有問題是我們本應 找尋幹細胞，

when we should have really been looking for a cell.

卻去找新藥物。

So we switched our models,

於是我們改變模式，

and now we began to look for skeletal stem cells.

開始尋找骨幹細胞。

And to cut again a long story short,

長話短說，

about five years ago, we found these cells.

大約5年前，我們發現了這些細胞。

They live inside the skeleton.

它們就在骨頭裡。

Here's a schematic and then a real photograph of one of them.

這幅是圖解，還有其中一張實照。

The white stuff is bone,

白色的東西是骨質，

and these red columns that you see and the yellow cells

見到紅色部分和黃色的細胞。

are cells that have arisen from one single skeletal stem cell --

那是由一粒骨質幹細胞 變成的多個細胞--

columns of cartilage, columns of bone coming out of a single cell.

由一粒細胞洐生了軟骨和骨。

These cells are fascinating. They have four properties.

這些幹細胞非常有趣， 它有4種特質。

Number one is that they live where they're expected to live.

第一，它們就在適當的地方存在。

They live just underneath the surface of the bone,

剛好在骨頭表面的底下，

underneath cartilage.

在軟骨下面。

You know, in biology, it's location, location, location.

生物學非常重視位置、位置…

And they move into the appropriate areas and form bone and cartilage.

它們走到適當的地方 做成骨和軟骨。

That's one.

那就是幹細胞 。

Here's an interesting property.

它有種有趣的特質。

You can take them out of the vertebrate skeleton,

你把它從脊髓抽出來，

you can culture them in petri dishes in the laboratory,

放在實驗室的有蓋培養皿𥚃 做細菌培養，

and they are dying to form cartilage.

它們渴望製造軟骨。

Remember how we couldn't form cartilage for love or money?

還記得我們怎麼不能因為 愛或金錢去製造軟骨嗎？

These cells are dying to form cartilage.

這些細胞卻極想製造軟骨。

They form their own furls of cartilage around themselves.

製造自己的軟骨卷起來包圍自己。

They're also, number three,

還有，第三

the most efficient repairers of fractures that we've ever encountered.

它是我們所見過最佳 修復骨節的能手。

This is a little bone, a mouse bone that we fractured

這是一塊小骨頭。 那是我們折斷的老鼠骨頭，

and then let it heal by itself.

跟著任由它自己癒合。

These stem cells have come in and repaired, in yellow, the bone,

這些幹細胞進入黃色的骨質丶

in white, the cartilage, almost completely.

白色的軟骨裡，差不多修復一切。

So much so that if you label them with a fluorescent dye

它非常能幹甚至你用螢光染料 把它顯示出來，

you can see them like some kind of peculiar cellular glue

可以見到它像一些特別的細胞膠水，

coming into the area of a fracture,

流入骨折的地方，

fixing it locally and then stopping their work.

在那裡固定折骨，然後停止工作。

Now, the fourth one is the most ominous,

現在到了第四最不利的特點，

and that is that their numbers decline precipitously,

就是隨著年紀漸老，

precipitously, tenfold, fiftyfold, as you age.

幹細胞的數目以10倍， 50倍急劇減少。

And so what had happened, really,

真正發生了的事情，

is that we found ourselves in a perceptual shift.

就是我們發現自己轉變了態度。

We had gone hunting for pills

我們過去不停找尋藥物，

but we ended up finding theories.

但是最後得出理論。

And in some ways

在某些方面

we had hooked ourselves back onto this idea:

我們又再次抓緊這個概念：

cells, organisms, environments,

細胞、生物丶環境，

because we were now thinking about bone stem cells,

因為我們想到硏究骨幹細胞，

we were thinking about arthritis in terms of a cellular disease.

把關節炎視為細胞疾病。

And then the next question was, are there organs?

跟著另一個問題是， 在器官有沒有幹細胞？

Can you build this as an organ outside the body?

可否在人體以㚈，用它建成器官？

Can you implant cartilage into areas of trauma?

可否植入軟骨到受創傷的地方？

And perhaps most interestingly,

或者最有趣的

can you ascend right up and create environments?

可否一直上階級頂部，製造環境。

You know, we know that exercise remodels bone,

大家都知道運動可以重塑骨質，

but come on, none of us is going to exercise.

但是沒有人願意去運動。

So could you imagine ways of passively loading and unloading bone

試想像有那些被動的方法， 可以把骨裝上和卸下來，

so that you can recreate or regenerate degenerating cartilage?

讓退化的軟骨重生呢？

And perhaps more interesting, and more importantly,

最有趣又重要的是

the question is, can you apply this model more globally outside medicine?

可否在醫學以㚈， 把這個模式應用到全世界呢？

What's at stake, as I said before, is not killing something,

我曾經說問題不是消滅什麼，

but growing something.

而是培養什麼。

And it raises a series of, I think, some of the most interesting questions

這樣喚起我們怎樣 思考未來醫學等

about how we think about medicine in the future.

一連串的問題。

Could your medicine be a cell and not a pill?

藥可否是細胞，而不是藥丸？

How would we grow these cells?

我們要怎樣培養這些細胞？

What we would we do to stop the malignant growth of these cells?

怎麼做才可以阻止 惡性幹細胞生長？

We heard about the problems of unleashing growth.

我們聽說過細胞 不受控制生長的問題。

Could we implant suicide genes into these cells

可否把自殺式基因植入這些細胞，

to stop them from growing?

阻止它繼續增生？

Could your medicine be an organ that's created outside the body

可否把體㚈製造的器官當成藥，

and then implanted into the body?

然後植入體內？

Could that stop some of the degeneration?

可否阻止身體一些地方退化？

What if the organ needed to have memory?

如果器官需要有記憶呢？

In cases of diseases of the nervous system some of those organs had memory.

就以神經系統疾病為例， 有些器官載有記憶。

How could we implant those memories back in?

怎樣才能把記憶植入 到那些器官呢？

Could we store these organs?

我們可否儲藏這些器官？

Would each organ have to be developed for an individual human being

個人的每副器官是否要先生長，

and put back?

才放回人體內。

And perhaps most puzzlingly,

最令人苦惱的

could your medicine be an environment?

是可否把環境當作藥物？

Could you patent an environment?

可否替環境買專利權？

You know, in every culture,

每種文化，

shamans have been using environments as medicines.

薩滿巫帥一直用自然力量當作藥。

Could we imagine that for our future?

可否猜想得到未來的醫學呢？

I've talked a lot about models. I began this talk with models.

我已經談論很多有關模式的問題。 我開始時講模式。

So let me end with some thoughts about model building.

所以讓我總結也講創造模式。

That's what we do as scientists.

這是科學家的分內事。

You know, when an architect builds a model,

一位建築師建造一個模型，

he or she is trying to show you a world in miniature.

這位建築師正把世界 變成縮樣給你看；

But when a scientist is building a model,

但是科學家建立一個模式，

he or she is trying to show you the world in metaphor.

是把世界變成比喻，

He or she is trying to create a new way of seeing.

讓大家用新的眼光看世界。

The former is a scale shift. The latter is a perceptual shift.

前者是轉變比例， 後者是改變看法。

Now, antibiotics created such a perceptual shift

現在發明抗生素， 成功地改變我們近百年來

in our way of thinking about medicine that it really colored, distorted,

對藥物的看法。

very successfully, the way we've thought about medicine for the last hundred years.

以前的看法是過度誇張 和歪曲事實。

But we need new models to think about medicine in the future.

但我們還是需要新模式 去硏究未來的醫學。

That's what's at stake.

這是問題的癥結。

You know, there's a popular trope out there

這𥚃有個流行的比喻詞

that the reason we haven't had the transformative impact

就是我們治療疾病

on the treatment of illness

沒有轉移性影響

is because we don't have powerful-enough drugs,

因爲缺乏威力的藥物，

and that's partly true.

有部分原因是對的。

But perhaps the real reason is

或許真正的原因

that we don't have powerful-enough ways of thinking about medicines.

就是沒有權威性的醫學思想。

It's certainly true that

如果發現新藥物，

it would be lovely to have new medicines.

真是最好不過了。

But perhaps what's really at stake are three more intangible M's:

或者最麻煩是多了 3種無形的結局：

mechanisms, models, metaphors.

方法、模式、比喻。

Thank you.

多謝。

(Applause)

（鼓掌聲）

Chris Anderson: I really like this metaphor.

Chris Anderson：我很喜歡這種比喻方法。

How does it link in?

它是怎樣聯繫上來？

There's a lot of talk in technologyland

在technology land 有很多人討論

about the personalization of medicine,

用藥個人化，

that we have all this data and that medical treatments of the future

我們有全部資料描述未來的醫療

will be for you specifically, your genome, your current context.

會替病人的基因組和 週圍的環境度身訂造。

Does that apply to this model you've got here?

這種療法是否適用於你的模式呢？

Siddhartha Mukherjee: It's a very interesting question.

Siddhartha Mukherjee: 這個問題很有趣。

We've thought about personalization of medicine

我們曾經認真思考過以基因組

very much in terms of genomics.

來進行個人化醫學。

That's because the gene is such a dominant metaphor,

因為基因是如此重要的比喻，

again, to use that same word, in medicine today,

我又再次用這個詞語 來談論今天的醫學，

that we think the genome will drive the personalization of medicine.

基因組會推動個人化醫療。

But of course the genome is just the bottom

當然基因組一如既往，

of a long chain of being, as it were.

只是存在鎖鏈階梯最低一級

That chain of being, really the first organized unit of that, is the cell.

而細胞就是這裡 首個有組織的單位。

So, if we are really going to deliver in medicine in this way,

如果我們真是要這樣 表達醫學的概念。

we have to think of personalizing cellular therapies,

那麼就從個人化細胞治療開始，

and then personalizing organ or organismal therapies,

然後是個人化器官治療，

and ultimately personalizing immersion therapies for the environment.

最後是個人化虛擬環境治療。

So I think at every stage, you know --

所以我想在每個階段

there's that metaphor, there's turtles all the way.

有這麼一個比喻，世界是龜駄著龜一路到無窮無盡。

Well, in this, there's personalization all the way.

而個人化治療也會一直發展下去。

CA: So when you say medicine could be a cell

CA: 所以如果你說的藥 可能是細胞，

and not a pill,

不是藥片，

you're talking about potentially your own cells.

可能是病人自己的細胞。

SM: Absolutely. CA: So converted to stem cells,

SM：當然。 CA：於是轉向研究幹細胞，

perhaps tested against all kinds of drugs or something, and prepared.

或者檢測所有藥物， 然後製造出來。

SM: And there's no perhaps. This is what we're doing.

SM：沒有「或者」這回事。 我們正在做這些事情。

This is what's happening, and in fact, we're slowly moving,

其實已經慢慢地發展，

not away from genomics, but incorporating genomics

不是放棄基因組，而是把它合併而成

into what we call multi-order, semi-autonomous, self-regulating systems,

所謂多重等級，半自動， 自我控制的系統，

like cells, like organs, like environments.

例如細胞丶器官和環境。

CA: Thank you so much.

CA：多謝你接受訪問。

SM: Pleasure. Thanks.

SM：不用客氣。多謝大家。