David Agus: A new strategy in the war against cancer

翻译人员: xiaomei he 校对人员: xiang fei

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

我是个癌症医生，三、四年前的一天我走出办公室

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

经过医院的药房，

and this was the cover of Fortune magazine

一本封面为“为何我们被癌症战败的”的《财富》杂志

sitting in the window of the pharmacy.

摆放在药房的橱窗里

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

作为一个癌症医生，你看到这个，

and you get a little bit downhearted.

会有些沮丧。

But when you start to read the article by Cliff,

里面有一篇克里夫的文章，

who himself is a cancer survivor,

他本人也是癌症幸存者，

who was saved by a clinical trial

临床试验性治疗挽救了他的生命。

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

当时他的父母开车从纽约市到纽约州北部

to get an experimental therapy for --

接受试验性治疗，

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

他患有霍金斯病（淋巴瘤），试验性治疗救了他的命。

he makes remarkable points here.

他在这篇文章里提出了一个很重要的问题。

And the point of the article was that we have gotten

这篇文章的核心是

reductionist in our view of biology,

用简化论者的眼光

in our view of cancer.

来看待生物学、看待癌症。

For the last 50 years, we have focused on treating

这50年里，我们一直关注于

the individual gene

个体基因治疗

in understanding cancer, not in controlling cancer.

和对癌症的认识，而不是控制癌症。

So, this is an astounding table.

这是一张让人吃惊的图表,

And this is something that sobers us in our field everyday

它使我们每天在我们这个领域保持清醒。

in that, obviously, we've made remarkable impacts

很明显，我们在心血管病方面

on cardiovascular disease,

取得了显著的进步。

but look at cancer. The death rate in cancer

但看看癌症呢？50年里癌症死亡率

in over 50 years hasn't changed.

没有改变。

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

我们在某些疾病的治疗上取得了一点点成绩，象慢性粒细胞性白血病，

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

我们有一种药片可以使100%的病人缓解。

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

但是，总的来说，我们并没有在抗击癌症的战斗中取得进展。

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

所以今天我要讲的是

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

为什么我会这样想，

and then go out of my comfort zone

然后走出我自己舒适区，

and tell you where I think it's going,

告诉你我认为它会走向哪里，

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

新的方法在哪里——

in terms of treating cancer.

我们希望推进癌症的治疗。

Because this is wrong.

因为这样是错的。

So, what is cancer, first of all?

所以，首先癌症是什么？

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

如果一个人血液检测不正常，就会去看医生。

they stick a needle in.

医生会给病人扎一针，

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

我们今天诊断癌症的方法是通过型态辨识。

Does it look normal? Does it look abnormal?

它看起来正常吗？还是看起来异常？

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

病理学家就象这样盯着这个塑料瓶看。

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

这是正常细胞，这是癌细胞。

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

这就是今天最先进的癌症诊断。

There's no molecular test,

没有分子检测，

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

没有以前提到的基因测序，

there's no fancy looking at the chromosomes.

也别对染色体有任何幻想。

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

这就是我们用的最先进的技术。

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

我很清楚作为一名癌症医生，我无法治疗晚期癌症。

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

顺便提一句，我坚信要早期诊断癌症，

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

这是你可以有效抗击癌症的唯一途径，通过早期发现它。

We can prevent most cancers.

我们能够预防很多癌症。

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

前面我们提及预防心脏疾病，

We could do the same in cancer.

对于癌症我们也同样可以这样做。

I co-founded a company called Navigenics,

我和别人共同创立了一个公司叫基因导航公司，

where, if you spit into a tube --

如果你把痰吐到一个试管里，

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

我们可以看到35或40种疾病遗传标记物，

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

在许多癌症中都可以检测得到。

you start to identify what you could get,

如果早期检测到这些标记分子，

and then we can start to work to prevent them.

那么就可以做些工作来预防癌症。

Because the problem is, when you have advanced cancer,

因为当前对于晚期癌症

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

我们还做不了很多，并不象某些统计数字所说的那样。

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

癌症是一种老年人的疾病。

Why is it a disease of the aged?

为什么是老年人的疾病？

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

因为在我们有了孩子之后，进化不再对我们感兴趣。

See, evolution protected us during our childbearing years

我们在生育年龄之内时进化保护我们，

and then, after age 35 or 40 or 45,

但在我们35或40或45岁后，

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

进化和我们不再有什么关系了，因为我们已经有后代了。

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

所以如果你注意观察癌症的话，可以看到

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

小孩患癌症非常非常罕见，大约一年几千例。

As one gets older? Very, very common.

但当年龄大了以后，就非常非常普遍了。

Why is it hard to treat?

为什么癌症很难治疗？

Because it's heterogeneous,

是因为它的多样化，

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

这种多样化对于癌症进化来说，是一个很理想的环境。

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

它挑选出那些坏的有攻击性的细胞，

what we call clonal selection.

我们叫做克隆选择。

But, if we start to understand

但是如果我们开始认识到

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

癌症并不只是一个分子的缺陷，其实更复杂，

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

那么我们就会寻找新的治疗方法，就象我将向你们展示的那样。

So, one of the fundamental problems we have in cancer

癌症的根本问题之一是

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

我们用一些形容词、它的一些症状来进行描述。

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

我感觉疲倦，我有浮肿，我有疼痛等等。

You then have some anatomic descriptions,

还有一些解剖学描述，

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

你做了CT扫描，肝脏有一个3厘米的异物。

You then have some body part descriptions:

然后是身体部位的描述，

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

它在肝脏、在乳房、在前列腺。

And that's about it.

就是这样。

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

我们用来描述癌症的词语非常非常少，

It's basically symptoms.

基本上是症状，

It's manifestations of a disease.

是疾病的临床表现。

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

让人兴奋的是在过去2到3年中，

the government has spent 400 million dollars,

政府投入4亿美元，

and they've allocated another billion dollars,

他们还投入了另10亿美元

to what we call the Cancer Genome Atlas Project.

给我们叫做癌症基因组图谱的项目。

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

目的是对癌症的所有基因进行测序，

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

它给了我们一个新的词汇，用一个新的词汇对癌症进行描述。

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

18世纪50年代中期法国

they started to describe cancer by body part.

开始用身体部位描述癌症，

That hasn't changed in over 150 years.

150年来一直这样。

It is absolutely archaic that we call cancer

我们把癌症叫做前列腺癌、乳腺癌，

by prostate, by breast, by muscle.

这显然太老套了。

It makes no sense, if you think about it.

仔细想想，它没有任何意义。

So, obviously, the technology is here today,

所以，很明显，我们现在拥有的技术，

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

几年以后又会改变。

You will no longer go to a breast cancer clinic.

你不用再去乳腺癌诊所，

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

你会去HER2扩增诊所，或EGFR激活诊所，

and they will go to some of the pathogenic lesions

他们会检测一些病理学损害

that were involved in causing this individual cancer.

就是引发癌症的独特病因。

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

所以我们希望我们能从艺术医学

more to the science of medicine,

走向科学医学，

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

能象对传染性疾病那样，

which is look at that organism, that bacteria,

检查微生物，细菌，

and then say, "This antibiotic makes sense,

然后说这个抗生素有意义，

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

因为细菌对它有反应。

When one is exposed to H1N1, you take Tamiflu,

如果一个人接触了H1N1,服用达菲，

and you can remarkably decrease the severity of symptoms

他的症状就会明显减轻，

and prevent many of the manifestations of the disease.

并且会预防许多其它临床症状。

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

因为我们知道你有什么病，我们知道如何进行治疗。

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

虽然我们现在不能生产疫苗，但那是另一回事。

The Cancer Genome Atlas is coming out now.

癌症基因图谱就要问世了。

The first cancer was done, which was brain cancer.

所做的第一个癌症是脑癌。

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

下个月，12月底，就会看到卵巢癌，

and then lung cancer will come several months after.

几个月后是肺癌。

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

另外还有蛋白质组学方面，我要讲几分钟，

which I think is going to be the next level

我认为从对疾病的认识和分类来讲

in terms of understanding and classifying disease.

它将提升一个水平。

But remember, I'm not pushing genomics,

但记住，我不是要推动基因组学、

proteomics, to be a reductionist.

蛋白组学，做一个简化论者。

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

我这样做，我们才能够确定我们面临什么问题。

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

我们要达到什么目标现在还有很大的分歧。

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

今天的医疗保健，我们在疾病治疗上

in terms of treating disease --

花了很多钱——

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

大部分钱花在一个人一生中最后两年。

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

而在明确我们所面临的问题上我们只花了很少的钱，或者没花。

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

如果我们能够开始向这个方向走，确定我们面临什么问题，

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

我们就会做得好得多。

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

如果我们做得能够再进一步并预防疾病，

we can take it enormously the other direction,

我们就可以完全朝着另一个方向去做。

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

很明显，那就是我们需要的方向，向前走。

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

这是国家癌症研究院的网站。

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

在这里我要告诉你们它是错的。

So, the website of the National Cancer Institute

国家癌症研究院网站

says that cancer is a genetic disease.

说癌症是遗传性疾病。

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

这个网站说，癌症就是有个体突变，

and maybe a second, and maybe a third,

或有第2个，第3个，

and that is cancer."

那就是癌症。

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

但是，作为一个癌症医生，就我所了解的

This isn't a genetic disease.

它不是一种遗传性疾病。

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

你看那，那是个肝脏，有结肠癌，

and you see into the microscope a lymph node

你从显微镜看，有一个淋巴结，

where cancer has invaded.

癌症就是从那侵入的。

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

你看CT扫描能知道肿瘤在肝脏的哪个位置。

Cancer is an interaction of a cell

癌症是细胞与环境相互作用的结果，

that no longer is under growth control with the environment.

使细胞的生长不再受控制。

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

它不是抽象的，它与环境相互作用。

It's what we call a system.

这就是我们所说的系统。

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

作为一名癌症医生，我的目标不是去认识癌症。

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

我认为这50年来的根本问题

is that we have strived to understand cancer.

是我们一直致力于去认识癌症，

The goal is to control cancer.

我们的目标是去控制癌症。

And that is a very different optimization scheme,

这是非常不同的优化方案，

a very different strategy for all of us.

对于我们所有人来说是非常不同的策略。

I got up at the American Association of Cancer Research,

我参加了美国癌症研究协会的

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

一个最大的癌症研究会议，20，000人参加。

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

当时我说，我们犯了个错误，

We've all made a mistake, myself included,

我们都犯了个错误，包括我自己，

by focusing down, by being a reductionist.

我们的重点错了，我们成为简化论者。

We need to take a step back."

我们需要倒退一步。

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

无论你相信与否，观众中有嘘声。

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

人们感到不安了，但这是我们向前走的唯一一条路。

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

几年前我非常幸运遇到了Danny Hillis。

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

我们被推到了一起，但最初我们谁也没打算见面。

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

我说：“我真的想见一个从迪斯尼来的家伙吗？一个设计电脑的家伙？”

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

而他说，他真想会见另一个医生。

But people prevailed on us, and we got together,

但人们说服了我们，我们凑到了一起，

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

我做了非常具有革新性的，绝对革新的项目。

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

我们一起设计、一起建立模型——

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

许多主意都是来自Danny，来自他的团队——

the modeling of cancer in the body as complex system.

体内癌症模型是非常复杂的系统。

And I'll show you some data there

我会给你们显示一些数据，

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

我真的认为它可以用一种不同的新方法达到目标。

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

关键是当你看成这些变量、这些数据时，

you have to understand the data inputs.

你必须了解数据的输入。

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

如果我给你量体温超过30天，

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

然后我问平均体温是多少，

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

当它回落到98.7，我会说太好了。

But if during one of those days

但是如果其中一天

your temperature spiked to 102 for six hours,

有6个小时你的体温峰值达到102，

and you took Tylenol and got better, etc.,

然后你服用泰诺感觉好多了...

I would totally miss it.

而我却丢失了这个数据。

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

所以医学上一个根本的问题

is that you and I, and all of us,

是你和我，以及我们所有的人，

we go to our doctor once a year.

我们一年看一次医生。

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

我们的数据元素互不关联，我们对此没有时间函数。

Earlier it was referred to this direct life device.

不久前，我们使用了这个叫做第一手生命的设备。

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

我已用了2个半月。

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

它真是个令人难以置信的装置，不是因为它告诉我

how many kilocalories I do every day,

每天我有多少卡路里，

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

而是因为它24小时监测我一天中做了什么。

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

我没有意识到我在桌子前已经坐了3小时，

and I'm not moving at all.

没有一点活动。

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

这个类似输入系统中有许多功能

are really different than we understand them,

与我们所了解的完全不同，

because we're not measuring them dynamically.

因为我们不是动态地进行测定。

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

你可以把癌症想象为一个系统，

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

它有输入、输出和中间状态。

So, the states, are equivalent classes of history,

状态相当于病史、

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

癌症病人；输入就是环境、

the diet, the treatment, the genetic mutations.

饮食、治疗、遗传变异；

The output are our symptoms:

输出就是症状：

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

有疼痛吗？肿瘤在发展吗？有浮肿吗等等。

Most of that state is hidden.

许多情况是隐藏的。

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

所以我们能做的是我们要改变输入，

we give aggressive chemotherapy,

我们给与积极的化疗。

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

然后我们说输出好些吗？疼痛有所改善吗？等等。

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

所以，问题不仅仅是一个系统，

it's multiple systems on multiple scales.

它是多维度上的多个系统，

It's a system of systems.

是多系统中的一个系统。

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

在你观察新出现的系统时，

you can look at a neuron under a microscope.

你在显微镜下看到神经细胞。

A neuron under the microscope is very elegant

镜下的神经细胞非常漂亮，

with little things sticking out and little things over here,

有些小的突起，

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

当你把它们放到一起，放到一个复杂的系统中时，

and you start to see that it becomes a brain,

你看到它变成了大脑，

and that brain can create intelligence,

大脑可以产生智慧。

what we're talking about in the body,

我们谈论的是机体内的事，

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

癌症就是这样模仿它的，象个复杂的系统。

Well, the bad news is that these robust --

坏消息是这些旺盛——

and robust is a key word --

旺盛是一个关键词——

emergent systems are very hard to understand in detail.

系统要详细了解它们是很困难的。

The good news is you can manipulate them.

好消息是你可以操纵它们，

You can try to control them

也可以努力控制它们

without that fundamental understanding of every component.

即使你并不是完全了解其每个元素。

One of the most fundamental clinical trials in cancer

二月份的新英格兰医学杂志

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

刊登了一篇关于癌症的最基本的临床试验，

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

对象是停经前患乳腺癌的妇女。

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

这里有最糟糕的乳腺癌病例。

They had gotten their chemotherapy,

他们都接受化疗，

and then they randomized them,

然后把他们随机分成2组，

where half got placebo,

1组用安慰剂，

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

另1组用唑来磷酸，一种影响骨代谢的药物，

It's used to treat osteoporosis,

它过去一直用于治疗骨质疏松，

and they got that twice a year.

一年用2次。

They looked and, in these 1,800 women,

他们观察到

given twice a year a drug that builds bone,

每年给这1800名妇女用2次药，

you reduce the recurrence of cancer by 35 percent.

癌症的复发率减少了35%。

Reduce occurrence of cancer by a drug

降低癌症复发率所用的药物

that doesn't even touch the cancer.

根本就没有接触到癌症。

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

它的概念是土地改变了，种子也就不生长了。

You change that system,

你改变了癌症系统，

and you could have a marked effect on the cancer.

对癌症有明显成效。

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

从没有人展示过——这是很令人震惊的——

nobody has ever shown that most chemotherapy

从没有人展示过大多数化疗

actually touches a cancer cell.

实际上触及了癌细胞。

It's never been shown.

从未展示过。

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

在组织培养皿中做了所有这些工作，

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

如果给肿瘤药物，那么对细胞也可以这样做，

but the doses in those dishes are nowhere near

但是培养皿所用剂量

the doses that happen in the body.

与机体所用剂量是不同的。

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

如果我给乳腺癌妇女使用紫杉醇这种药物，

every three weeks, which is the standard,

每三周使用一次，这是标准剂量，

about 40 percent of women with metastatic cancer

大约40%转移癌患者

have a great response to that drug.

对这个药都有很大的反应。

And a response is 50 percent shrinkage.

一种反应是50%人的肿瘤缩小了。

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

记住，这不是一个数量级，

but that's a different story.

它是另一回事。

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

有人复发了，我每周给他们相同的药物，

Another 30 percent will respond.

又有30%的人有反应。

They then recur, I give them that same drug

又复发了，我还是给他们同样的药物

over 96 hours by continuous infusion,

96小时以上连续输注，

another 20 or 30 percent will respond.

又20或30%的人有反应。

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

这样，你不能说对这三批病人我采用了同样的治疗机制。

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

它不是。我们对此机制也没有什么概念。

So the idea that chemotherapy may just be disrupting

可能是化疗破坏了

that complex system,

那个复杂的系统，

just like building bone disrupted that system and reduced recurrence,

就象骨代谢药破坏了那个系统而减少了复发一样，

chemotherapy may work by that same exact way.

化疗可能也是完全同样的作用。

The wild thing about that trial also,

关于这项试验还有一件离奇的事情，

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

它减少了新的原发癌，新的癌症，也是30%。

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

所以问题是，包括你的和我的问题，我们所有的系统都在变化，

They're dynamic.

它们是动态的。

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

这是一张可怕的幻灯片，没把它拿掉，

but it looks at obesity in the world.

它展示的是世界上的肥胖人口。

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

我很遗憾，如果你读不到这些数字，有些小。

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

但如果你仔细看，红色和黑色的，

more than 75 percent of the population

那些国家

of those countries are obese.

75%以上的人口肥胖。

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

看看10年前，20年前，非常不同。

So, our systems today are dramatically different

所以今天我们的系统与10年、20年前相比

than our systems a decade or two ago.

有很大的不同。

So the diseases we have today,

我们今天的疾病

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

所反应的是过去几十年里的系统模式，

are going to change dramatically over the next decade or so

而在以后10年里或在这个基础上

based on things like this.

将会发生巨大的变化。

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

这张照片，看起来挺漂亮，是整个蛋白质组400亿字节的

of the whole proteome.

一张照片。

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

它只用一滴血经过超导磁，

and we're able to get resolution

我们就能够得出结论：

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

我们从哪可以开始看到机体所有蛋白质。

We can start to see that system.

我们可以看整个系统了。

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

每个红点就是蛋白质被鉴定的地方。

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

这些磁力，我们在这里所能做的

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

是用这个技术我们能看到个体的中子。

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

这就是我们与Danny Hillis

and a group called Applied Proteomics,

和一个叫做应用蛋白组学的团队所做的事情，

where we can start to see individual neutron differences,

我们可以看到个体中子的差异，

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

过去我们从来没有见过。

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

我们用后退一步取代了从简化论者的角度看待这个问题。

So this is a woman, 46 years old,

这个妇女，46岁，

who had recurrent lung cancer.

肺癌复发。

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

她的脑部、肺脏、肝脏都有癌细胞。

She had gotten Carboplatin Taxol, Carboplatin Taxotere,

她接受了紫杉醇卡铂、卡铂泰索帝、

Gemcitabine, Navelbine:

Gemcitabene和诺维本。

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

我们有的每一种药她都用了，但是癌症继续发展。

She had three kids under the age of 12,

她的三个孩子都在12岁以下，

and this is her CT scan.

这是她的CAT扫描。

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

这是什么？是我们为她做的横截面图。

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

中间是她的心脏，

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

心脏左边有一个很大的肿瘤，

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

如果不治疗，几周内肿瘤就会侵犯她并杀死她。

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

她每天服用一片药，药物目标是影响代谢过程的途径，

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

我也不确定在这个系统中，在这个癌症里，这个途径是否存在

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

但药物起效了，一个月后，肿瘤消失了。

Six months later it's still gone.

六个月后，仍然没有复发。

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

3年后，癌症又复发了，她死于肺癌，

but she got three years from a drug

但是她通过服药又活了3年，

whose symptoms predominately were acne.

主要症状是痤疮。

That's about it.

就是这样。

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

临床试验已经做了，

and we were a part of it,

我们参与了其中一部分，

and in the fundamental clinical trial --

在基本的临床试验中，

the pivotal clinical trial we call the Phase Three,

关键的一个试验我们叫它第三阶段，

we refused to use a placebo.

我们拒绝使用安慰剂。

Would you want your mother, your brother, your sister

如果你的母亲、兄弟、姐妹是晚期肺癌，

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

生命只有几个星期的时间了，你愿意让他们使用安慰剂吗？

And the answer, obviously, is not.

很明显，答案是不。

So, it was done on this group of patients.

所以这一组病人是这样做的。

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

试验中10%的病人有明显的反应，正如这里显示的，

and the drug went to the FDA,

然后我们把药物送到FDA，

and the FDA said, "Without a placebo,

FDA说没有安慰剂，

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

我怎么知道病人是真正从这个药物获益的？

So the morning the FDA was going to meet,

所以这天早上FDA开会，

this was the editorial in the Wall Street Journal.

这是华尔街杂志的编辑部。

(Laughter)

（笑声）

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

你知道，那个药物被批准了。

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

令人惊讶的一件事是另一个公司也恰好做了这项科学试验，

where they gave half placebo and half the drug.

他们用一半安慰剂，一半药物。

And we learned something important there.

我们从那也听说了一些重要的事情。

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

有意思的事情是他们在南美和加拿大做的，

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

在那些地方“给予安慰剂更道德一些”。

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

这个药物在美国也要得到批准，

so I think there were three U.S. patients

我想在纽约州北部有3个美国病人

in upstate New York who were part of the trial.

参与了试验。

But they did that, and what they found

试验发现

is that 70 percent of the non-responders

70%的无反应病人

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

比使用安慰剂的病人生存时间更长、生活质量更高。

So it challenged everything we knew in cancer,

它对我们所了解的癌症提出了挑战，

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

那就是你不需要有什么反应，

You don't need to shrink the disease.

你不需要在疾病面前退缩。

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

如果我们能够延缓疾病的发展，

on patient survival, patient outcome, how they feel,

比我们在疾病面前退缩，

than if we shrink the disease.

对于病人的存活、病人的后果及病人的感受会有更多好处。

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

问题是，如果我就是这个医生，今天我拿到你的CAT扫描，

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

你的肝脏有个2厘米的东西，

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

3个月后你回来找我，那个东西3厘米了，

did that drug help you or not?

那么那个药物对你是否有帮助？

How do I know?

我怎么知道呢？

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

它可能原本会长到10厘米，或我给你的药

with no benefit and significant cost?

没有任何作用而且非常昂贵？

So, it's a fundamental problem.

所以这是根本问题。

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

也就是这些新技术产生的原因。

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

所以很明显你进医生办公室的目标是——

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

预防疾病的发生，对。

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

最终目标是防止疾病发生。

That is the most effective, cost-effective,

这是我们今天能做的

best way we can do things today.

最有效、最经济的做法。

But if one is unfortunate to get a disease,

但如果你不幸患病了，

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

你就会去看医生，医生就会为你抽点血，

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

然后就知道如何治疗你的疾病。

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

我们的方法还是蛋白组学方面的，

again, this looking at the system.

就是这个系统，

It's taking a big picture.

一张大图。

The problem with technologies like this is

这种技术的问题是

that if one looks at proteins in the body,

如果观察机体的蛋白质，

there are 11 orders of magnitude difference

在高丰度蛋白和低丰度蛋白之间

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

有11个数量级的差异。

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

世界上没有一种技术能够跨越11个数量级。

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

所以我们与Danny Hillis和其他人所做的很多事情

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

是想引进工程原理，引进软件。

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

我们就可以看到频谱间的不同组分。

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

前面谈论过跨学科，谈论了合作。

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

我认为一个令人激动的事情是

is that people from those fields are coming in.

其它领域的人们已开始介入。

Yesterday, the National Cancer Institute announced a new program

昨天，国家癌症研究所公布了一个新的项目，

called the Physical Sciences and Oncology,

叫做物理科学和肿瘤学，

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

物理学家、数学家都介入研究癌症，

people who never approached it before.

而这些人以前从未接触过。

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

Danny和我拿到了1600万美元，他们昨天公布了，

to try to attach this problem.

尝试解决这个问题。

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

一个全新的方法，不是给予高剂量的化疗药物，

by different mechanisms,

而是通过不同的机制

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

能够有一种技术可以得到一张照片告诉我们机体内究竟发生了什么。

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

所以，用2秒钟，这些技术是如何工作的——

because I think it's important to understand it.

因为我认为了解它是重要的。

What happens is every protein in your body is charged,

它是怎么回事呢？你身体里的每个蛋白都是带电的，

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

磁性物质围绕蛋白质旋转，

and then there's a detector at the end.

最后有一个检测器，

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

它何时能碰到那个检测器要根据它的质量和电荷。

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

所以很精确地，如果它磁性很强，

and your resolution is high enough --

你的分辨率也很高，

you can actually detect all of the proteins in the body

你就可以检测机体内所有的蛋白质，

and start to get an understanding of the individual system.

就可以了解这个个体系统。

And so, as a cancer doctor,

作为一名癌症医生，

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

你、我都不需要这么厚的纸质文件，

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

可以用办公室的数据流代替，就象这样，

where that drop of blood is creating gigabytes of data.

一滴血产生千兆字节的数据。

Electronic data elements are describing every aspect of the disease.

电子数据可以描述疾病的每一个方面。

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

当然目标是我们可以从每一个问题中了解问题，

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

就能够前进一步，而不仅仅是反复遇到问题

without fundamental learning.

而没有根本的了解。

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

结论是我们需要远离简化论的思想。

We need to start to think differently and radically.

我们需要完全不同的想法。

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

所以我请求在座的每一位，用不同的方法去思考，提出新的思路。

Tell them to me or anyone else in our field,

去告诉我们这个领域里的每一个人，

because over the last 59 years, nothing has changed.

因为在过去59年里，什么也没改变。

We need a radically different approach.

我们需要一个完全不同的方法。

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

当Andy Grove辞去英特尔董事会主席时——

and Andy was one of my mentors, tough individual.

他是我的顾问之一，很强硬的一个人

When Andy stepped down, he said,

当他辞职时，他说

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

“没有任何技术能够赢，技术本身才会赢”。

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

我坚信在医学领域，特别是癌症领域，

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

有一个广阔的技术平台

that will help us move forward

可以帮助我们前进，

and hopefully help patients in the near-term.

也有希望在近期内帮助病人。

Thank you very much.

非常感谢。