David Agus: A new strategy in the war against cancer

譯者: Ching-Yi Wu 審譯者: Sunshine Wang

I'm a cancer doctor, and I walked out of my office

我是個腫瘤科醫師。三、四年前，有一天

and walked by the pharmacy in the hospital three or four years ago,

我走出辦公室，經過醫院裡的藥劑部

and this was the cover of Fortune magazine

看到那時在櫥窗裡頭的

sitting in the window of the pharmacy.

《財星》的雜誌封面

And so, as a cancer doctor, you look at this,

當然，對一個腫瘤科醫師而言，看到這樣的封面

and you get a little bit downhearted.

心情會有一點不好過

But when you start to read the article by Cliff,

當你讀起這篇由克里夫

who himself is a cancer survivor,

一位何杰金氏症的患者所寫的文章

who was saved by a clinical trial

他是位癌症的倖存者

where his parents drove him from New York City to upstate New York

當時他為了接受實驗性的治療

to get an experimental therapy for --

每天由父母開車，從紐約市前往北紐約州

at the time -- Hodgkin's disease, which saved his life,

最後這項臨床試驗救了他的生命

he makes remarkable points here.

他提到一個非常重要的觀點：

And the point of the article was that we have gotten

從生物學角度

reductionist in our view of biology,

還有從癌症研究角度來說

in our view of cancer.

我們有許多化約論者

For the last 50 years, we have focused on treating

在過去五十年，將研究焦點集中在

the individual gene

治療個別的基因

in understanding cancer, not in controlling cancer.

這是為了瞭解癌症，而非控制癌症

So, this is an astounding table.

這是個讓人驚奇的圖表

And this is something that sobers us in our field everyday

卻也令我們這個領域的人心情沉重

in that, obviously, we've made remarkable impacts

顯然地，就心血管疾病而言

on cardiovascular disease,

醫藥已有重大的影響

but look at cancer. The death rate in cancer

但看看癌症吧！其死亡率

in over 50 years hasn't changed.

於過去五十年間並沒有改變

We've made small wins in diseases like chronic myelogenous leukemia,

在對抗如慢性骨髓性白血病等疾病得了小勝

where we have a pill that can put 100 percent of people in remission,

藥物治療的痊癒率達百分之百

but in general, we haven't made an impact at all in the war on cancer.

然而，普遍來說，我們的研究尚未在對癌症的戰爭上起多大作用

So, what I'm going to tell you today,

所以，我今天將告訴各位的是

is a little bit of why I think that's the case,

我認為我們還打不贏這場仗的原因

and then go out of my comfort zone

並走出我的舒適區

and tell you where I think it's going,

告訴你們癌症研究的方向

where a new approach -- that we hope to push forward

以及我們希望要如何

in terms of treating cancer.

將癌症療法往前推進一步的新方法

Because this is wrong.

因為，我們現在的做法是錯誤的

So, what is cancer, first of all?

首先，什麼是癌症？

Well, if one has a mass or an abnormal blood value, you go to a doctor,

如果有個人身上出現腫塊，或是血壓不正常，他會去看醫生

they stick a needle in.

現代的醫生會把針刺進腫塊吸取細胞

They way we make the diagnosis today is by pattern recognition:

藉著查看細胞型態來進行診斷

Does it look normal? Does it look abnormal?

細胞看起來正常嗎？或是不正常？

So, that pathologist is just like looking at this plastic bottle.

病理學家就是靠著觀察像是這樣的寶特瓶

This is a normal cell. This is a cancer cell.

這是正常細胞，這是癌症細胞

That is the state-of-the-art today in diagnosing cancer.

那就是現今最先進的癌症診斷技術

There's no molecular test,

沒有分子檢查

there's no sequencing of genes that was referred to yesterday,

沒有已成過去的定基因序列

there's no fancy looking at the chromosomes.

也沒有很炫的染色體觀察

This is the state-of-the-art and how we do it.

這就癌症診斷最先進的方法

You know, I know very well, as a cancer doctor, I can't treat advanced cancer.

身為一個腫瘤科醫師，我心知肚明末期癌症是無法治療的

So, as an aside, I firmly believe in the field of trying to identify cancer early.

所以，容我岔題一下，我堅信早期診斷癌症的重要性

It is the only way you can start to fight cancer, is by catching it early.

對抗癌症的唯一方法是早期發現它

We can prevent most cancers.

我們可以藉此預防大部分的癌症

You know, the previous talk alluded to preventing heart disease.

我在稍早曾提過心臟病的預防

We could do the same in cancer.

我們也能如此預防癌症

I co-founded a company called Navigenics,

我是一間叫做「基因領航」的公司的共同創辦人

where, if you spit into a tube --

我們能從你吐到試管的口水裡

and we can look look at 35 or 40 genetic markers for disease,

檢查35到40種疾病的分子標記

all of which are delayable in many of the cancers --

這些是在癌症篩選時，晚期才診斷出的分子標記

you start to identify what you could get,

我們從找出你可能得的病開始

and then we can start to work to prevent them.

然後才得以開始來預防疾病

Because the problem is, when you have advanced cancer,

因為，問題就在於，當你得到末期癌症

we can't do that much today about it, as the statistics allude to.

誠如統計資料告訴我們的，直到今日，我們還是束手無策

So, the thing about cancer is that it's a disease of the aged.

這是因為，癌症其實是一種跟老化相關的疾病

Why is it a disease of the aged?

為什麼呢？

Because evolution doesn't care about us after we've had our children.

因為有了孩子後，演化就不在乎我們了

See, evolution protected us during our childbearing years

個體健康在生育年齡時受到保護，

and then, after age 35 or 40 or 45,

但是，過了35, 40或是45歲，

it said "It doesn't matter anymore, because they've had their progeny."

因為已經有了子嗣，演化認為這個人就不再重要了。

So if you look at cancers, it is very rare -- extremely rare --

請看看癌症的發生率，很少、非常非常少小孩

to have cancer in a child, on the order of thousands of cases a year.

得到癌症，大概是一年幾千個案例

As one gets older? Very, very common.

但是隨著人們年齡漸長，癌症就變得非常常見

Why is it hard to treat?

癌症為什麼難治呢？

Because it's heterogeneous,

這是因為它具有異質性

and that's the perfect substrate for evolution within the cancer.

這對癌症的演變是非常完美的生存條件

It starts to select out for those bad, aggressive cells,

癌症始於選擇出惡性、具侵略性的細胞

what we call clonal selection.

這就是所謂的細胞株選擇

But, if we start to understand

如果我們開始明白

that cancer isn't just a molecular defect, it's something more,

癌症不只是一種分子缺陷，它是更嚴重的疾病

then we'll get to new ways of treating it, as I'll show you.

就能找到治療的新方法，我將介紹給各位

So, one of the fundamental problems we have in cancer

癌症之於我們，有個最基本的問題：

is that, right now, we describe it by a number of adjectives, symptoms:

現在都是用一些形容詞或是症狀來描述它，

"I'm tired, I'm bloated, I have pain, etc."

像是「累」、「脹氣」、「痛」等。

You then have some anatomic descriptions,

或是解剖學上的敘述

you get that CT scan: "There's a three centimeter mass in the liver."

你去做電腦斷層掃描，在肝臟找到一個「三公分的腫瘤」

You then have some body part descriptions:

也可以描述腫瘤出現的部位

"It's in the liver, in the breast, in the prostate."

如在肝臟、乳房，或是攝護腺

And that's about it.

大概就是這樣了

So, our dictionary for describing cancer is very, very poor.

我們用來描述癌症的詞彙非常、非常少

It's basically symptoms.

基本上就是症狀

It's manifestations of a disease.

或是疾病的表徵

What's exciting is that over the last two or three years,

令人振奮的是，過去兩三年來

the government has spent 400 million dollars,

政府花了四億美金

and they've allocated another billion dollars,

並挪出十幾億美金

to what we call the Cancer Genome Atlas Project.

進行所謂的「癌症基因圖譜」計畫

So, it is the idea of sequencing all of the genes in the cancer,

希望能定序癌症細胞中所有的基因

and giving us a new lexicon, a new dictionary to describe it.

讓我們得以為癌症建立一本新詞海來描述這個疾病

You know, in the mid-1850's in France,

以癌症發生的部位來描述疾病

they started to describe cancer by body part.

始於1850年代中期的法國

That hasn't changed in over 150 years.

這樣的情況經過150年並沒有太大改變

It is absolutely archaic that we call cancer

我們描述癌症的方式的確是非常古老

by prostate, by breast, by muscle.

攝護腺的上就叫攝護腺癌、乳房的上叫乳癌、或是肌肉上的叫肌瘤

It makes no sense, if you think about it.

仔細想想，這沒有道理

So, obviously, the technology is here today,

顯然的，以今日的技術，

and, over the next several years, that will change.

在未來數年內，這樣的情況將會改變

You will no longer go to a breast cancer clinic.

妳將不再上乳癌門診

You will go to a HER2 amplified clinic, or an EGFR activated clinic,

而是去HER2基因增幅門診，或是表皮生長因子受體活化門診

and they will go to some of the pathogenic lesions

醫生們將直接對一些引起

that were involved in causing this individual cancer.

不同個體癌症的不正常病理變化下手

So, hopefully, we will go from being the art of medicine

我們希望狀況能夠從目前的醫療技術

more to the science of medicine,

進步到醫療科學

and be able to do what they do in infectious disease,

如我們治療傳染病一般

which is look at that organism, that bacteria,

找出病原，如細菌

and then say, "This antibiotic makes sense,

再選出合適的抗生素

because you have a particular bacteria that will respond to it."

也就是那些只對特定細菌起作用的藥物

When one is exposed to H1N1, you take Tamiflu,

這就像一個人感染了新流感病毒，服用克流感後

and you can remarkably decrease the severity of symptoms

症狀的嚴重程度能顯著減少

and prevent many of the manifestations of the disease.

同時還能預防疾病的許多表徵

Why? Because we know what you have, and we know how to treat it --

為什麼？因為我們知道你得了什麼病，也知道如何治療

although we can't make vaccine in this country, but that's a different story.

即使在這個國家我們無法製造疫苗──那又是另一回事了

The Cancer Genome Atlas is coming out now.

「癌症基因圖譜」即將現世

The first cancer was done, which was brain cancer.

第一個定序完成的癌症是腦癌

In the next month, the end of December, you'll see ovarian cancer,

在下個月，2009年12月底，卵巢癌的圖譜也將完成

and then lung cancer will come several months after.

幾個月後的肺癌基因圖譜也會完成

There's also a field of proteomics that I'll talk about in a few minutes,

等一下，我會提到另一個領域：

which I think is going to be the next level

癌症的蛋白質體學，這是在了解和分類疾病上

in terms of understanding and classifying disease.

下一個層級的研究

But remember, I'm not pushing genomics,

但是，請記住，我並沒有讓基因體學家

proteomics, to be a reductionist.

或蛋白質體學家成為化約論者的意思

I'm doing it so we can identify what we're up against.

我的做法是讓我們找出所對抗的目標

And there's a very important distinction there that we'll get to.

這跟化約論者有非常重要的不同

In health care today, we spend most of the dollars --

現代的醫療，把大部份的錢

in terms of treating disease --

用在治療疾病

most of the dollars in the last two years of a person's life.

尤其是用來拯救病患最後兩年的生命

We spend very little, if any, dollars in terms of identifying what we're up against.

卻花極少的錢在找出我們得對抗的標的

If you could start to move that, to identify what you're up against,

如果能夠開始脫離舊思維，來找出我們得對抗的

you're going to do things a hell of a lot better.

現況將得到相當大的改善

If we could even take it one step further and prevent disease,

更進一步，如果能預防疾病

we can take it enormously the other direction,

疾病將被導向另一個完全不同的方向

and obviously, that's where we need to go, going forward.

顯然的，癌症醫學要往前邁進，這是必然的發展方向

So, this is the website of the National Cancer Institute.

這是美國國家癌症研究所的網頁

And I'm here to tell you, it's wrong.

我人在這裡是為了告訴大家，他們錯了

So, the website of the National Cancer Institute

美國國家癌症研究所的網頁上說

says that cancer is a genetic disease.

癌症是一種基因疾病

The website says, "If you look, there's an individual mutation,

即基因有一處

and maybe a second, and maybe a third,

兩處、或是三處的變異

and that is cancer."

就是癌症

But, as a cancer doc, this is what I see.

但是，身為腫瘤科醫師，我是這樣看的：

This isn't a genetic disease.

癌症不是基因疾病

So, there you see, it's a liver with colon cancer in it,

像這樣，這是一個大腸癌轉移的肝臟

and you see into the microscope a lymph node

在顯微鏡下觀察，這個淋巴結

where cancer has invaded.

有癌症侵入

You see a CT scan where cancer is in the liver.

在電腦斷層掃描下，可見肝臟裡有腫瘤

Cancer is an interaction of a cell

癌症起因是生長不再受控制的細胞

that no longer is under growth control with the environment.

和環境間的交互作用

It's not in the abstract; it's the interaction with the environment.

這不是獨立分離的狀態，而是細胞跟環境間的互動

It's what we call a system.

也就是所謂的「系統」。

The goal of me as a cancer doctor is not to understand cancer.

以一個腫瘤科醫師來說，我的職志並不是了解癌症

And I think that's been the fundamental problem over the last five decades,

我認為，我們花大量精神在了解癌症上

is that we have strived to understand cancer.

這是過去五十年來問題的所在

The goal is to control cancer.

我想做的，是控制癌症

And that is a very different optimization scheme,

對我們來說，這是非常與眾不同的樂觀看法

a very different strategy for all of us.

也是非常不同的策略

I got up at the American Association of Cancer Research,

在一場大型研討會，

one of the big cancer research meetings, with 20,000 people there,

某個美國癌症研究協會的大會中，在約兩萬個人面前

and I said, "We've made a mistake.

我站起來說：「我們錯了

We've all made a mistake, myself included,

我們，包括我自己，都錯了

by focusing down, by being a reductionist.

錯在我們太過專注於目前的研究，錯在我們都是化約論者

We need to take a step back."

我們得往後退一步。」

And, believe it or not, there were hisses in the audience.

無論你相信與否，觀眾們發出噓聲

People got upset, but this is the only way we're going to go forward.

人們為此感到沮喪，但這是我們唯一能走的路

You know, I was very fortunate to meet Danny Hillis a few years ago.

我很榮幸能在數年前認識Danny Hillis

We were pushed together, and neither one of us really wanted to meet the other.

我們是被逼著碰面，一點都不想認識彼此

I said, "Do I really want to meet a guy from Disney, who designed computers?"

我說：「我一定得跟這個在迪士尼設計電腦的人見面嗎？」

And he was saying: Does he really want to meet another doctor?

他也問，有必要再跟另一個醫生見面嗎？

But people prevailed on us, and we got together,

但旁人說服了我們，我們碰面了

and it's been transformative in what I do, absolutely transformative.

這會面是我生涯的轉捩點，我的生涯整個不同了

We have designed, and we have worked on the modeling --

我們一起設計一套

and much of these ideas came from Danny and from his team --

體內癌症複雜系統的模型

the modeling of cancer in the body as complex system.

大部分的主意是Danny和他的團隊提供的

And I'll show you some data there

我將在這裡展示部分

where I really think it can make a difference and a new way to approach it.

我認為可以改變並找出癌症新療法的數據

The key is, when you look at these variables and you look at this data,

關鍵是，當你看著這些變數，跟這些數據

you have to understand the data inputs.

你得先明白輸入值是什麼

You know, if I measured your temperature over 30 days,

舉例來說，我幫你量體溫量了30天

and I asked, "What was the average temperature?"

想知道，你的平均體溫是多少

and it came back at 98.7, I would say, "Great."

平均37度，這樣很好

But if during one of those days

不過，如果這30天裡有一天

your temperature spiked to 102 for six hours,

你的體溫有6個小時高達近39度

and you took Tylenol and got better, etc.,

你吃了退燒藥，燒退了......

I would totally miss it.

我則完全不會注意到這些變化

So, one of the problems, the fundamental problems in medicine

所以，醫學有個根本問題

is that you and I, and all of us,

即是你、我、我們所有人

we go to our doctor once a year.

每年看一次醫生

We have discrete data elements; we don't have a time function on them.

我們只有零碎的數據，沒有這些數據跟時間的關係

Earlier it was referred to this direct life device.

稍早，有提到生活即時監測系統

You know, I've been using it for two and a half months.

我已經使用這樣的儀器兩個半月了

It's a staggering device, not because it tells me

這是一個令人驚奇的機器

how many kilocalories I do every day,

不是因為它告訴我我每天消耗多少卡路里

but because it looks, over 24 hours, what I've done in a day.

而是它能監測我一天24小時的所有活動

And I didn't realize that for three hours I'm sitting at my desk,

我以前從來不知道當我坐在書桌前3小時

and I'm not moving at all.

我是一動也不動的

And a lot of the functions in the data that we have as input systems here

因為我們不曾進行動態測量

are really different than we understand them,

數據中，有許多輸入的功能變數

because we're not measuring them dynamically.

跟我們的理解是相當不同的

And so, if you think of cancer as a system,

同理，如果你認為癌症自成系統

there's an input and an output and a state in the middle.

就會有輸入值、輸出值、跟介於兩者之間的狀態

So, the states, are equivalent classes of history,

因此，中間狀態就是生活史

and the cancer patient, the input, is the environment,

對一個癌症病人來說，輸入值就是環境

the diet, the treatment, the genetic mutations.

飲食、接受過的治療跟基因突變

The output are our symptoms:

輸出值就是我們的症狀：

Do we have pain? Is the cancer growing? Do we feel bloated, etc.?

疼痛與否？腫瘤生長與否？脹氣與否？

Most of that state is hidden.

大部分的情況下，中間狀態並不可見

So what we do in our field is we change and input,

所以我們腫瘤科醫師只能改變輸入值

we give aggressive chemotherapy,

給予病人積極化療

and we say, "Did that output get better? Did that pain improve, etc.?"

但是，症狀有變好嗎？疼痛有改善嗎？

And so, the problem is that it's not just one system,

這問題就在於，癌症並非只限一個系統

it's multiple systems on multiple scales.

它有著多個系統跟多重範圍

It's a system of systems.

是有多個系統的系統

And so, when you start to look at emergent systems,

你若想開始看看系統群是如何發生的

you can look at a neuron under a microscope.

你可以看看顯微鏡下的神經細胞

A neuron under the microscope is very elegant

一個神經細胞在顯微鏡下是非常優雅的

with little things sticking out and little things over here,

很少突起，也很少別的東西

but when you start to put them together in a complex system,

但是，如果把神經細胞放進一個複雜系統

and you start to see that it becomes a brain,

你會注意到它們變成一個大腦

and that brain can create intelligence,

可以產生智能

what we're talking about in the body,

我們正討論的，即是在身體中

and cancer is starting to model it like a complex system.

癌症正開始型塑一個複雜系統

Well, the bad news is that these robust --

然而，有個壞消息：

and robust is a key word --

我們很難了解

emergent systems are very hard to understand in detail.

這些強壯的系統的細節─「強壯」是關鍵字

The good news is you can manipulate them.

好消息則是，我們可以操縱這些系統

You can try to control them

你可以在對這系統的組成毫無了解的狀態下

without that fundamental understanding of every component.

試著操縱它們

One of the most fundamental clinical trials in cancer

2009年2月，《新英格蘭雜誌》

came out in February in the New England Journal of Medicine,

刊出一個關於癌症的基礎臨床研究

where they took women who were pre-menopausal with breast cancer.

以更年期來臨前的乳癌患者為樣本

So, about the worst kind of breast cancer you can get.

這些都是有著最嚴重程度的乳癌病人

They had gotten their chemotherapy,

她們在接受化療後

and then they randomized them,

被隨機分成兩組

where half got placebo,

一組服用安慰劑

and half got a drug called Zoledronic acid that builds bone.

一組則服用能幫助成骨

It's used to treat osteoporosis,

用來治療骨質疏鬆症的唑來磷酸

and they got that twice a year.

她們每年服藥兩次

They looked and, in these 1,800 women,

服用的唑來磷酸的

given twice a year a drug that builds bone,

1800名婦女中

you reduce the recurrence of cancer by 35 percent.

乳癌復發率降低35%

Reduce occurrence of cancer by a drug

癌症的復發率

that doesn't even touch the cancer.

因為一個跟癌細胞無關的藥物降低了

So the notion, you change the soil, the seed doesn't grow as well.

這告訴我們，你改變土壤，種子也就跟著不長了

You change that system,

你改變這個系統

and you could have a marked effect on the cancer.

就能對癌症產生顯著影響

Nobody has ever shown -- and this will be shocking --

從來沒有人能證明─這真是令人訝異

nobody has ever shown that most chemotherapy

沒有人證明過，大部分的化療藥物

actually touches a cancer cell.

真的能影響癌症細胞

It's never been shown.

這一點從來沒被證明過

There's all these elegant work in the tissue culture dishes,

投藥，讓藥物對癌細胞產生影響

that if you give this cancer drug, you can do this effect to the cell,

這一切都是在培養皿裡優雅地進行

but the doses in those dishes are nowhere near

但是在培養皿裡施予的藥物劑量

the doses that happen in the body.

跟人體治療的劑量差距太大了

If I give a woman with breast cancer a drug called Taxol

標準療程是每三個星期開

every three weeks, which is the standard,

紫杉醇給乳癌婦女服用

about 40 percent of women with metastatic cancer

這藥能對約40%

have a great response to that drug.

的乳癌轉移病人有療效

And a response is 50 percent shrinkage.

其中有50%腫瘤會縮小

Well, remember that's not even an order of magnitude,

請記住，我還沒有談到作用程度

but that's a different story.

那是另外一課題

They then recur, I give them that same drug every week.

當乳癌復發，我改成每個禮拜開立紫杉醇

Another 30 percent will respond.

有30%的病人對治療有反應

They then recur, I give them that same drug

她們又再復發，我仍給予同樣的藥物

over 96 hours by continuous infusion,

但改為96小時持續注射

another 20 or 30 percent will respond.

這時只有20-30%的人對治療有反應

So, you can't tell me it's working by the same mechanism in all three size.

我們無法分辨，紫杉醇在這三種不療程的治療機轉是否相同

It's not. We have no idea the mechanism.

是的，我們不知道治療機轉為何

So the idea that chemotherapy may just be disrupting

所以也不知道化療是不是

that complex system,

破壞了癌症的複雜系統

just like building bone disrupted that system and reduced recurrence,

就如成骨藥物破壞癌症系統並降低復發率

chemotherapy may work by that same exact way.

化療有可能利用一樣的機制

The wild thing about that trial also,

這個臨床試驗的另外一件奇事是

was that it reduced new primaries, so new cancers, by 30 percent also.

原發癌，即新生成腫瘤的發生率因為唑來磷酸也降低30%

So, the problem is, yours and mine, all of our systems are changing.

所以，我們的問題是，所有的系統不斷變動

They're dynamic.

他們是動態系統

I mean, this is a scary slide, not to take an aside,

請看看這張關於世界性肥胖問題的可怕投影片

but it looks at obesity in the world.

不要因為它可怕就忽視不看

And I'm sorry if you can't read the numbers, they're kind of small.

很抱歉，字很小，可能看不到這些數字

But, if you start to look at it, that red, that dark color there,

請看這些紅色或深色區域

more than 75 percent of the population

在這些國家中

of those countries are obese.

肥胖人口占總人口75%以上

Look a decade ago, look two decades ago: markedly different.

這跟十年前，二十年前很不一樣

So, our systems today are dramatically different

也就是說，今天我們身處的環境系統

than our systems a decade or two ago.

跟十年、二十年前很不一樣

So the diseases we have today,

我們今日會得的疾病

which reflect patterns in the system over the last several decades,

反映出過去數十年外在環境系統模式的轉變

are going to change dramatically over the next decade or so

同樣的概念

based on things like this.

人類的疾病在未來數十年也將有劇烈的變動

So, this picture, although it is beautiful, is a 40-gigabyte picture

這張漂亮的40 GB大的圖

of the whole proteome.

是完整蛋白質體

So this is a drop of blood that has gone through a superconducting magnet,

在一滴血液經過一個超導磁鐵時

and we're able to get resolution

磁力能將血液中的成分分離開來

where we can start to see all of the proteins in the body.

現在看到的是身體中所有的蛋白質成份

We can start to see that system.

可以看到身體這個系統

Each of the red dots are where a protein has actually been identified.

每一個紅點就是一個被分離出的蛋白質

The power of these magnets, the power of what we can do here,

我們有能力利用這些磁鐵的磁力

is that we can see an individual neutron with this technology.

觀察每一個中子

So, again, this is stuff we're doing with Danny Hillis

這就是我們正跟Danny Hillis和工作團隊

and a group called Applied Proteomics,

合作進行的應用蛋白質體計畫

where we can start to see individual neutron differences,

這讓我們得以觀察每一個中子的差異

and we can start to look at that system like we never have before.

以前所未有的角度觀察一個系統

So, instead of a reductionist view, we're taking a step back.

也因此，向後退一步，不以化約論者的眼光看事情

So this is a woman, 46 years old,

這是一名46歲的女性

who had recurrent lung cancer.

她的肺癌復發

It was in her brain, in her lungs, in her liver.

除肺臟外，還轉移到腦部、及肝臟

She had gotten Carboplatin Taxol, Carboplatin Taxotere,

她接受雞尾酒治療如Carboplatin合併Taxol, Taxotere

Gemcitabine, Navelbine:

Gemicitabene或是Navelbine

Every drug we have she had gotten, and that disease continued to grow.

她接受所有我們給予的藥物，但腫瘤仍繼續長大

She had three kids under the age of 12,

她有三名未滿12歲的子女

and this is her CT scan.

這是她的電腦斷層掃描

And so what this is, is we're taking a cross-section of her body here,

也就是我們做她身體這處橫切面的造影

and you can see in the middle there is her heart,

如你所見，中間這裡是她的心臟

and to the side of her heart on the left there is this large tumor

心臟的左邊有一個大腫瘤

that will invade and will kill her, untreated, in a matter of weeks.

若是沒有接受治療，這腫瘤具侵入性並能在數周內殺死她

She goes on a pill a day that targets a pathway,

她每天服用一顆針對某個致病機轉的藥物

and again, I'm not sure if this pathway was in the system, in the cancer,

但同樣的，我不清楚這個機轉是否存在於這個癌症系統

but it targeted a pathway, and a month later, pow, that cancer's gone.

但是，使用這個針對某機轉的藥物一個月後，腫瘤消失了！

Six months later it's still gone.

六個月後，腫瘤仍不見蹤影

That cancer recurred, and she passed away three years later from lung cancer,

後來，癌症復發，她在三年後死於肺癌

but she got three years from a drug

但是，這藥為她爭取了三年的壽命

whose symptoms predominately were acne.

這三年唯一顯著的症狀是痤瘡

That's about it.

就只是這樣

So, the problem is that the clinical trial was done,

然而，問題是，當臨床實驗進行的時候

and we were a part of it,

我們有參與其中

and in the fundamental clinical trial --

在這個基礎的

the pivotal clinical trial we call the Phase Three,

先驅的臨床試驗裡─我們稱為第三期

we refused to use a placebo.

我們拒絕使用安慰劑

Would you want your mother, your brother, your sister

你會希望妳的母親、兄弟姊妹，在他們有末期癌症

to get a placebo if they had advanced lung cancer and had weeks to live?

只剩幾個星期能活時，服用安慰劑嗎？

And the answer, obviously, is not.

答案很明顯，是「不」

So, it was done on this group of patients.

所以，這群病人參與了臨床實驗

Ten percent of people in the trial had this dramatic response that was shown here,

你可以看到，10%的病人對治療有顯著的反應

and the drug went to the FDA,

然而，當藥物被送到食品藥物管理局審查

and the FDA said, "Without a placebo,

他們認為，沒有使用安慰劑

how do I know patients actually benefited from the drug?"

我們怎麼知道病人是因為藥物受惠的？

So the morning the FDA was going to meet,

這是在食品藥物管理局開會的那個早上

this was the editorial in the Wall Street Journal.

華爾街日報的社論

(Laughter)

（笑）

And so, what do you know, that drug was approved.

你知道，這個藥物後來被核准

The amazing thing is another company did the right scientific trial,

令人驚訝的是，另一個公司做了科學上設計正確的臨床實驗

where they gave half placebo and half the drug.

也就是受試者的一半服用藥物，一半服用安慰劑

And we learned something important there.

讓我們得以從中學到些重要的事

What's interesting is they did it in South America and Canada,

有趣的是，這實驗是在南美跟加拿大進行的

where it's "more ethical to give placebos."

在那裡，使用安慰劑比較道德

They had to give it also in the U.S. to get approval,

他們也得在美國進行實驗，這樣食品藥物管理局才會允許藥物上市

so I think there were three U.S. patients

這實驗裡有三個美國病人

in upstate New York who were part of the trial.

住在北紐約州

But they did that, and what they found

研究人員進行試驗，發現

is that 70 percent of the non-responders

對藥物無反應的受試者中，有70%

lived much longer and did better than people who got placebo.

比服用安慰劑的受試者活得更久且更好

So it challenged everything we knew in cancer,

這結果有益於我們對癌症的了解：

is that you don't need to get a response.

病人不需要對藥物有反應

You don't need to shrink the disease.

我們也不需要縮小病灶

If we slow the disease, we may have more of a benefit

只要我們能減慢疾病進程，我們將

on patient survival, patient outcome, how they feel,

比縮小病灶能學到更多有關

than if we shrink the disease.

病人的存活率、癒後跟他們的感覺

The problem is that, if I'm this doc, and I get your CT scan today

問題在於，如果我是這名醫師，今天我看到這樣的斷層攝影

and you've got a two centimeter mass in your liver,

判定你的肝臟裡有個2公分的腫瘤

and you come back to me in three months and it's three centimeters,

三個月後你回診，腫瘤變成3公分

did that drug help you or not?

藥物能否幫助你呢？

How do I know?

我該怎麼知道呢？

Would it have been 10 centimeters, or am I giving you a drug

如果這腫瘤有10公分大，我是不是給你一個

with no benefit and significant cost?

沒有效但是花費驚人的藥物？

So, it's a fundamental problem.

是的，這就是問題所在

And, again, that's where these new technologies can come in.

這也是這些新技術可以介入的地方

And so, the goal obviously is that you go into your doctor's office --

顯然地，我們的目標是，你去醫生的辦公室─

well, the ultimate goal is that you prevent disease, right?

沒錯，終極目標當然是預防疾病

The ultimate goal is that you prevent any of these things from happening.

是預防任何疾病的發生

That is the most effective, cost-effective,

這是最有效、節省成本

best way we can do things today.

我們現在所能做的最好的事

But if one is unfortunate to get a disease,

但，如果有人很不幸的生病了

you'll go into your doctor's office, he or she will take a drop of blood,

還是得去醫生的辦公室，取一滴血

and we will start to know how to treat your disease.

我們就開始知道如何治療疾病

The way we've approached it is the field of proteomics,

而蛋白質體學可以被用來找出治療方法

again, this looking at the system.

從這個角度來看癌症這個系統

It's taking a big picture.

我們能得到一個疾病的全景

The problem with technologies like this is

問題在於，這樣的一個技術

that if one looks at proteins in the body,

當我們只看一個體內的蛋白質

there are 11 orders of magnitude difference

就有含量從低到高

between the high-abundant and the low-abundant proteins.

十一個不同程度的等級

So, there's no technology in the world that can span 11 orders of magnitude.

這個世界還沒有技術能處理十一個程度的等級

And so, a lot of what has been done with people like Danny Hillis and others

所以，Danny Hillis跟其他人正著手解決這個問題

is to try to bring in engineering principles, try to bring the software.

試著利用一些工程原理來寫出個軟體

We can start to look at different components along this spectrum.

讓我們得以在這樣的尺度下觀察不同的蛋白質組成

And so, earlier was talked about cross-discipline, about collaboration.

稍早，我們曾經提過跨領域合作

And I think one of the exciting things that is starting to happen now

我認為有個令人振奮的事情正開始進行中

is that people from those fields are coming in.

那就是不同領域的人正開始參與癌症研究

Yesterday, the National Cancer Institute announced a new program

昨天，美國國家癌症研究所宣布開始一個新計畫：

called the Physical Sciences and Oncology,

物理科學及腫瘤學

where physicists, mathematicians, are brought in to think about cancer,

這讓物理學家跟數學家都得以貢獻他們對癌症的想法

people who never approached it before.

這都是以前從未參與這類研究的人

Danny and I got 16 million dollars, they announced yesterday,

他們昨天也宣布，Danny跟我得到一筆1億6千萬的研究經費

to try to attach this problem.

將用來解決這個問題：

A whole new approach, instead of giving high doses of chemotherapy

我們想找到，在不使用高劑量的化療藥物的情況下

by different mechanisms,

利用一個不同機轉的新方法

to try to bring technology to get a picture of what's actually happening in the body.

來試著得到一個癌症在身體中是如何發生的即時藍圖

So, just for two seconds, how these technologies work --

因為我認為了解這技術很重要

because I think it's important to understand it.

請給我兩秒鐘，告訴你這是怎麼辦到的

What happens is every protein in your body is charged,

身體中每一個蛋白質都帶電

so the proteins are sprayed in, the magnet spins them around,

所以，當我們把蛋白質噴進一個磁場，它們會旋轉

and then there's a detector at the end.

而機器的末端有個偵測器

When it hit that detector is dependent on the mass and the charge.

根據這些蛋白質的質量跟帶電量，它們打到偵測器上的時間也不同

And so we can accurately -- if the magnet is big enough,

更精確一點來說，如果這個磁鐵夠大

and your resolution is high enough --

解析度夠高

you can actually detect all of the proteins in the body

就能偵測體內所有的蛋白質

and start to get an understanding of the individual system.

進一步讓我們得以了解每一個人的身體系統

And so, as a cancer doctor,

就一個腫瘤科醫師來說

instead of having paper in my chart, in your chart, and it being this thick,

我們，還有你們都不再需要厚厚的紙本病歷

this is what data flow is starting to look like in our offices,

相對的，你們會開始在醫生的辦公室看到

where that drop of blood is creating gigabytes of data.

從一滴血得來的好幾GB的數據流

Electronic data elements are describing every aspect of the disease.

電子數據將能夠形容一個疾病的所有樣貌

And certainly the goal is we can start to learn from every encounter

當然，目標是我們能從每一次看診學到一些東西

and actually move forward, instead of just having encounter and encounter,

讓我們對癌症的了解能確實向前推進

without fundamental learning.

而非就只是一次又一次的看診，卻學不到東西

So, to conclude, we need to get away from reductionist thinking.

總而言之，我們必須不再用化約論者的方式思考

We need to start to think differently and radically.

我們需要從各式各樣不同的角度思考

And so, I implore everyone here: Think differently. Come up with new ideas.

我想告訴這裡的每一位，用不同的思考模式，來點新主意

Tell them to me or anyone else in our field,

把這些想法告訴我或其他從事癌症研究的人

because over the last 59 years, nothing has changed.

因為，過去59年來，事情從來就沒有改變

We need a radically different approach.

我們需要完全不同的做法

You know, Andy Grove stepped down as chairman of the board at Intel --

當英特爾的創辦人葛洛夫

and Andy was one of my mentors, tough individual.

這位強悍的人是我的導師之一

When Andy stepped down, he said,

從董事長的位子退下來時，他這麼說：

"No technology will win. Technology itself will win."

「沒有一種科技是贏家，科技本身就是贏家。」

And I'm a firm believer, in the field of medicine and especially cancer,

我堅信，醫學，尤其是癌症醫學

that it's going to be a broad platform of technologies

將會是個技術交流的大平台

that will help us move forward

這能幫助我們往前邁進

and hopefully help patients in the near-term.

也希望在不久的將來能幫助病人

Thank you very much.

非常謝謝大家