I'm a cancer doctor, and I walked out of my office and walked by the pharmacy in the hospital three or four years ago, and this was the cover of Fortune magazine sitting in the window of the pharmacy.
我是個腫瘤科醫師。三、四年前,有一天 我走出辦公室,經過醫院裡的藥劑部 看到那時在櫥窗裡頭的 《財星》的雜誌封面
And so, as a cancer doctor, you look at this, and you get a little bit downhearted. But when you start to read the article by Cliff, who himself is a cancer survivor, who was saved by a clinical trial where his parents drove him from New York City to upstate New York to get an experimental therapy for -- at the time -- Hodgkin's disease, which saved his life, he makes remarkable points here. And the point of the article was that we have gotten reductionist in our view of biology, in our view of cancer. For the last 50 years, we have focused on treating the individual gene in understanding cancer, not in controlling cancer.
當然,對一個腫瘤科醫師而言,看到這樣的封面 心情會有一點不好過 當你讀起這篇由克里夫 一位何杰金氏症的患者所寫的文章 他是位癌症的倖存者 當時他為了接受實驗性的治療 每天由父母開車,從紐約市前往北紐約州 最後這項臨床試驗救了他的生命 他提到一個非常重要的觀點: 從生物學角度 還有從癌症研究角度來說 我們有許多化約論者 在過去五十年,將研究焦點集中在 治療個別的基因 這是為了瞭解癌症,而非控制癌症
So, this is an astounding table. And this is something that sobers us in our field everyday in that, obviously, we've made remarkable impacts on cardiovascular disease, but look at cancer. The death rate in cancer in over 50 years hasn't changed. We've made small wins in diseases like chronic myelogenous leukemia, where we have a pill that can put 100 percent of people in remission, but in general, we haven't made an impact at all in the war on cancer.
這是個讓人驚奇的圖表 卻也令我們這個領域的人心情沉重 顯然地,就心血管疾病而言 醫藥已有重大的影響 但看看癌症吧!其死亡率 於過去五十年間並沒有改變 在對抗如慢性骨髓性白血病等疾病得了小勝 藥物治療的痊癒率達百分之百 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, is a little bit of why I think that's the case, and then go out of my comfort zone and tell you where I think it's going, where a new approach -- that we hope to push forward in terms of treating cancer. Because this is wrong.
所以,我今天將告訴各位的是 我認為我們還打不贏這場仗的原因 並走出我的舒適區 告訴你們癌症研究的方向 以及我們希望要如何 將癌症療法往前推進一步的新方法 因為,我們現在的做法是錯誤的
So, what is cancer, first of all? Well, if one has a mass or an abnormal blood value, you go to a doctor, they stick a needle in. They way we make the diagnosis today is by pattern recognition: Does it look normal? Does it look abnormal?
首先,什麼是癌症? 如果有個人身上出現腫塊,或是血壓不正常,他會去看醫生 現代的醫生會把針刺進腫塊吸取細胞 藉著查看細胞型態來進行診斷 細胞看起來正常嗎?或是不正常?
So, that pathologist is just like looking at this plastic bottle. This is a normal cell. This is a cancer cell. That is the state-of-the-art today in diagnosing cancer. There's no molecular test, there's no sequencing of genes that was referred to yesterday, there's no fancy looking at the chromosomes. This is the state-of-the-art and how we do it.
病理學家就是靠著觀察像是這樣的寶特瓶 這是正常細胞,這是癌症細胞 那就是現今最先進的癌症診斷技術 沒有分子檢查 沒有已成過去的定基因序列 也沒有很炫的染色體觀察 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. So, as an aside, I firmly believe in the field of trying to identify cancer early. It is the only way you can start to fight cancer, is by catching it early. We can prevent most cancers. You know, the previous talk alluded to preventing heart disease. We could do the same in cancer. I co-founded a company called Navigenics, where, if you spit into a tube -- and we can look look at 35 or 40 genetic markers for disease, all of which are delayable in many of the cancers -- you start to identify what you could get, and then we can start to work to prevent them. Because the problem is, when you have advanced cancer, we can't do that much today about it, as the statistics allude to.
身為一個腫瘤科醫師,我心知肚明末期癌症是無法治療的 所以,容我岔題一下,我堅信早期診斷癌症的重要性 對抗癌症的唯一方法是早期發現它 我們可以藉此預防大部分的癌症 我在稍早曾提過心臟病的預防 我們也能如此預防癌症 我是一間叫做「基因領航」的公司的共同創辦人 我們能從你吐到試管的口水裡 檢查35到40種疾病的分子標記 這些是在癌症篩選時,晚期才診斷出的分子標記 我們從找出你可能得的病開始 然後才得以開始來預防疾病 因為,問題就在於,當你得到末期癌症 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. Why is it a disease of the aged? Because evolution doesn't care about us after we've had our children. See, evolution protected us during our childbearing years and then, after age 35 or 40 or 45, it said "It doesn't matter anymore, because they've had their progeny." So if you look at cancers, it is very rare -- extremely rare -- to have cancer in a child, on the order of thousands of cases a year. As one gets older? Very, very common.
這是因為,癌症其實是一種跟老化相關的疾病 為什麼呢? 因為有了孩子後,演化就不在乎我們了 個體健康在生育年齡時受到保護, 但是,過了35, 40或是45歲, 因為已經有了子嗣,演化認為這個人就不再重要了。 請看看癌症的發生率,很少、非常非常少小孩 得到癌症,大概是一年幾千個案例 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? Because it's heterogeneous, and that's the perfect substrate for evolution within the cancer. It starts to select out for those bad, aggressive cells, what we call clonal selection. But, if we start to understand that cancer isn't just a molecular defect, it's something more, then we'll get to new ways of treating it, as I'll show you.
癌症為什麼難治呢? 這是因為它具有異質性 這對癌症的演變是非常完美的生存條件 癌症始於選擇出惡性、具侵略性的細胞 這就是所謂的細胞株選擇 如果我們開始明白 癌症不只是一種分子缺陷,它是更嚴重的疾病 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 is that, right now, we describe it by a number of adjectives, symptoms: "I'm tired, I'm bloated, I have pain, etc." You then have some anatomic descriptions, you get that CT scan: "There's a three centimeter mass in the liver." You then have some body part descriptions: "It's in the liver, in the breast, in the prostate." And that's about it. So, our dictionary for describing cancer is very, very poor. It's basically symptoms. It's manifestations of a disease.
癌症之於我們,有個最基本的問題: 現在都是用一些形容詞或是症狀來描述它, 像是「累」、「脹氣」、「痛」等。 或是解剖學上的敘述 你去做電腦斷層掃描,在肝臟找到一個「三公分的腫瘤」 也可以描述腫瘤出現的部位 如在肝臟、乳房,或是攝護腺 大概就是這樣了 我們用來描述癌症的詞彙非常、非常少 基本上就是症狀 或是疾病的表徵
What's exciting is that over the last two or three years, the government has spent 400 million dollars, and they've allocated another billion dollars, to what we call the Cancer Genome Atlas Project. So, it is the idea of sequencing all of the genes in the cancer, and giving us a new lexicon, a new dictionary to describe it. You know, in the mid-1850's in France, they started to describe cancer by body part. That hasn't changed in over 150 years. It is absolutely archaic that we call cancer by prostate, by breast, by muscle. It makes no sense, if you think about it.
令人振奮的是,過去兩三年來 政府花了四億美金 並挪出十幾億美金 進行所謂的「癌症基因圖譜」計畫 希望能定序癌症細胞中所有的基因 讓我們得以為癌症建立一本新詞海來描述這個疾病 以癌症發生的部位來描述疾病 始於1850年代中期的法國 這樣的情況經過150年並沒有太大改變 我們描述癌症的方式的確是非常古老 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 仔細想想,這沒有道理
So, obviously, the technology is here today, and, over the next several years, that will change. You will no longer go to a breast cancer clinic. You will go to a HER2 amplified clinic, or an EGFR activated clinic, and they will go to some of the pathogenic lesions that were involved in causing this individual cancer. So, hopefully, we will go from being the art of medicine more to the science of medicine, and be able to do what they do in infectious disease, which is look at that organism, that bacteria, and then say, "This antibiotic makes sense, because you have a particular bacteria that will respond to it." When one is exposed to H1N1, you take Tamiflu, and you can remarkably decrease the severity of symptoms and prevent many of the manifestations of the disease. Why? Because we know what you have, and we know how to treat it -- although we can't make vaccine in this country, but that's a different story.
顯然的,以今日的技術, 在未來數年內,這樣的情況將會改變 妳將不再上乳癌門診 而是去HER2基因增幅門診,或是表皮生長因子受體活化門診 醫生們將直接對一些引起 不同個體癌症的不正常病理變化下手 我們希望狀況能夠從目前的醫療技術 進步到醫療科學 如我們治療傳染病一般 找出病原,如細菌 再選出合適的抗生素 也就是那些只對特定細菌起作用的藥物 這就像一個人感染了新流感病毒,服用克流感後 症狀的嚴重程度能顯著減少 同時還能預防疾病的許多表徵 為什麼?因為我們知道你得了什麼病,也知道如何治療 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. The first cancer was done, which was brain cancer. In the next month, the end of December, you'll see ovarian cancer, and then lung cancer will come several months after. There's also a field of proteomics that I'll talk about in a few minutes, which I think is going to be the next level in terms of understanding and classifying disease. But remember, I'm not pushing genomics, proteomics, to be a reductionist. I'm doing it so we can identify what we're up against. And there's a very important distinction there that we'll get to.
「癌症基因圖譜」即將現世 第一個定序完成的癌症是腦癌 在下個月,2009年12月底,卵巢癌的圖譜也將完成 幾個月後的肺癌基因圖譜也會完成 等一下,我會提到另一個領域: 癌症的蛋白質體學,這是在了解和分類疾病上 下一個層級的研究 但是,請記住,我並沒有讓基因體學家 或蛋白質體學家成為化約論者的意思 我的做法是讓我們找出所對抗的目標 這跟化約論者有非常重要的不同
In health care today, we spend most of the dollars -- in terms of treating disease -- most of the dollars in the last two years of a person's life. We spend very little, if any, dollars in terms of identifying what we're up against. If you could start to move that, to identify what you're up against, you're going to do things a hell of a lot better. If we could even take it one step further and prevent disease, we can take it enormously the other direction, and obviously, that's where we need to go, going forward.
現代的醫療,把大部份的錢 用在治療疾病 尤其是用來拯救病患最後兩年的生命 卻花極少的錢在找出我們得對抗的標的 如果能夠開始脫離舊思維,來找出我們得對抗的 現況將得到相當大的改善 更進一步,如果能預防疾病 疾病將被導向另一個完全不同的方向 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. And I'm here to tell you, it's wrong. So, the website of the National Cancer Institute says that cancer is a genetic disease. The website says, "If you look, there's an individual mutation, and maybe a second, and maybe a third, and that is cancer." But, as a cancer doc, this is what I see. This isn't a genetic disease. So, there you see, it's a liver with colon cancer in it, and you see into the microscope a lymph node where cancer has invaded. You see a CT scan where cancer is in the liver. Cancer is an interaction of a cell that no longer is under growth control with the environment. It's not in the abstract; it's the interaction with the environment. It's what we call a system.
這是美國國家癌症研究所的網頁 我人在這裡是為了告訴大家,他們錯了 美國國家癌症研究所的網頁上說 癌症是一種基因疾病 即基因有一處 兩處、或是三處的變異 就是癌症 但是,身為腫瘤科醫師,我是這樣看的: 癌症不是基因疾病 像這樣,這是一個大腸癌轉移的肝臟 在顯微鏡下觀察,這個淋巴結 有癌症侵入 在電腦斷層掃描下,可見肝臟裡有腫瘤 癌症起因是生長不再受控制的細胞 和環境間的交互作用 這不是獨立分離的狀態,而是細胞跟環境間的互動 也就是所謂的「系統」。
The goal of me as a cancer doctor is not to understand cancer. And I think that's been the fundamental problem over the last five decades, is that we have strived to understand cancer. The goal is to control cancer. And that is a very different optimization scheme, a very different strategy for all of us.
以一個腫瘤科醫師來說,我的職志並不是了解癌症 我認為,我們花大量精神在了解癌症上 這是過去五十年來問題的所在 我想做的,是控制癌症 對我們來說,這是非常與眾不同的樂觀看法 也是非常不同的策略
I got up at the American Association of Cancer Research, one of the big cancer research meetings, with 20,000 people there, and I said, "We've made a mistake. We've all made a mistake, myself included, by focusing down, by being a reductionist. We need to take a step back." And, believe it or not, there were hisses in the audience. People got upset, but this is the only way we're going to go forward.
在一場大型研討會, 某個美國癌症研究協會的大會中,在約兩萬個人面前 我站起來說:「我們錯了 我們,包括我自己,都錯了 錯在我們太過專注於目前的研究,錯在我們都是化約論者 我們得往後退一步。」 無論你相信與否,觀眾們發出噓聲 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. We were pushed together, and neither one of us really wanted to meet the other. I said, "Do I really want to meet a guy from Disney, who designed computers?" And he was saying: Does he really want to meet another doctor? But people prevailed on us, and we got together, and it's been transformative in what I do, absolutely transformative. We have designed, and we have worked on the modeling -- and much of these ideas came from Danny and from his team -- the modeling of cancer in the body as complex system. And I'll show you some data there where I really think it can make a difference and a new way to approach it.
我很榮幸能在數年前認識Danny Hillis 我們是被逼著碰面,一點都不想認識彼此 我說:「我一定得跟這個在迪士尼設計電腦的人見面嗎?」 他也問,有必要再跟另一個醫生見面嗎? 但旁人說服了我們,我們碰面了 這會面是我生涯的轉捩點,我的生涯整個不同了 我們一起設計一套 體內癌症複雜系統的模型 大部分的主意是Danny和他的團隊提供的 我將在這裡展示部分 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, you have to understand the data inputs. You know, if I measured your temperature over 30 days, and I asked, "What was the average temperature?" and it came back at 98.7, I would say, "Great." But if during one of those days your temperature spiked to 102 for six hours, and you took Tylenol and got better, etc., I would totally miss it. So, one of the problems, the fundamental problems in medicine is that you and I, and all of us, we go to our doctor once a year. We have discrete data elements; we don't have a time function on them.
關鍵是,當你看著這些變數,跟這些數據 你得先明白輸入值是什麼 舉例來說,我幫你量體溫量了30天 想知道,你的平均體溫是多少 平均37度,這樣很好 不過,如果這30天裡有一天 你的體溫有6個小時高達近39度 你吃了退燒藥,燒退了...... 我則完全不會注意到這些變化 所以,醫學有個根本問題 即是你、我、我們所有人 每年看一次醫生 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. You know, I've been using it for two and a half months. It's a staggering device, not because it tells me how many kilocalories I do every day, but because it looks, over 24 hours, what I've done in a day. And I didn't realize that for three hours I'm sitting at my desk, and I'm not moving at all. And a lot of the functions in the data that we have as input systems here are really different than we understand them, because we're not measuring them dynamically.
稍早,有提到生活即時監測系統 我已經使用這樣的儀器兩個半月了 這是一個令人驚奇的機器 不是因為它告訴我我每天消耗多少卡路里 而是它能監測我一天24小時的所有活動 我以前從來不知道當我坐在書桌前3小時 我是一動也不動的 因為我們不曾進行動態測量 數據中,有許多輸入的功能變數 跟我們的理解是相當不同的
And so, if you think of cancer as a system, there's an input and an output and a state in the middle. So, the states, are equivalent classes of history, and the cancer patient, the input, is the environment, the diet, the treatment, the genetic mutations. The output are our symptoms: Do we have pain? Is the cancer growing? Do we feel bloated, etc.? Most of that state is hidden. So what we do in our field is we change and input, we give aggressive chemotherapy, and we say, "Did that output get better? Did that pain improve, etc.?"
同理,如果你認為癌症自成系統 就會有輸入值、輸出值、跟介於兩者之間的狀態 因此,中間狀態就是生活史 對一個癌症病人來說,輸入值就是環境 飲食、接受過的治療跟基因突變 輸出值就是我們的症狀: 疼痛與否?腫瘤生長與否?脹氣與否? 大部分的情況下,中間狀態並不可見 所以我們腫瘤科醫師只能改變輸入值 給予病人積極化療 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, it's multiple systems on multiple scales. It's a system of systems. And so, when you start to look at emergent systems, you can look at a neuron under a microscope. A neuron under the microscope is very elegant with little things sticking out and little things over here, but when you start to put them together in a complex system, and you start to see that it becomes a brain, and that brain can create intelligence, what we're talking about in the body, and cancer is starting to model it like a complex system. Well, the bad news is that these robust -- and robust is a key word -- emergent systems are very hard to understand in detail. The good news is you can manipulate them. You can try to control them without that fundamental understanding of every component.
這問題就在於,癌症並非只限一個系統 它有著多個系統跟多重範圍 是有多個系統的系統 你若想開始看看系統群是如何發生的 你可以看看顯微鏡下的神經細胞 一個神經細胞在顯微鏡下是非常優雅的 很少突起,也很少別的東西 但是,如果把神經細胞放進一個複雜系統 你會注意到它們變成一個大腦 可以產生智能 我們正討論的,即是在身體中 癌症正開始型塑一個複雜系統 然而,有個壞消息: 我們很難了解 這些強壯的系統的細節─「強壯」是關鍵字 好消息則是,我們可以操縱這些系統 你可以在對這系統的組成毫無了解的狀態下 試著操縱它們
One of the most fundamental clinical trials in cancer came out in February in the New England Journal of Medicine, where they took women who were pre-menopausal with breast cancer. So, about the worst kind of breast cancer you can get. They had gotten their chemotherapy, and then they randomized them, where half got placebo, and half got a drug called Zoledronic acid that builds bone. It's used to treat osteoporosis, and they got that twice a year. They looked and, in these 1,800 women, given twice a year a drug that builds bone, you reduce the recurrence of cancer by 35 percent. Reduce occurrence of cancer by a drug that doesn't even touch the cancer. So the notion, you change the soil, the seed doesn't grow as well. You change that system, and you could have a marked effect on the cancer.
2009年2月,《新英格蘭雜誌》 刊出一個關於癌症的基礎臨床研究 以更年期來臨前的乳癌患者為樣本 這些都是有著最嚴重程度的乳癌病人 她們在接受化療後 被隨機分成兩組 一組服用安慰劑 一組則服用能幫助成骨 用來治療骨質疏鬆症的唑來磷酸 她們每年服藥兩次 服用的唑來磷酸的 1800名婦女中 乳癌復發率降低35% 癌症的復發率 因為一個跟癌細胞無關的藥物降低了 這告訴我們,你改變土壤,種子也就跟著不長了 你改變這個系統 就能對癌症產生顯著影響
Nobody has ever shown -- and this will be shocking -- nobody has ever shown that most chemotherapy actually touches a cancer cell. It's never been shown. There's all these elegant work in the tissue culture dishes, that if you give this cancer drug, you can do this effect to the cell, but the doses in those dishes are nowhere near the doses that happen in the body.
從來沒有人能證明─這真是令人訝異 沒有人證明過,大部分的化療藥物 真的能影響癌症細胞 這一點從來沒被證明過 投藥,讓藥物對癌細胞產生影響 這一切都是在培養皿裡優雅地進行 但是在培養皿裡施予的藥物劑量 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 every three weeks, which is the standard, about 40 percent of women with metastatic cancer have a great response to that drug. And a response is 50 percent shrinkage. Well, remember that's not even an order of magnitude, but that's a different story. They then recur, I give them that same drug every week. Another 30 percent will respond. They then recur, I give them that same drug over 96 hours by continuous infusion, another 20 or 30 percent will respond. So, you can't tell me it's working by the same mechanism in all three size. It's not. We have no idea the mechanism. So the idea that chemotherapy may just be disrupting that complex system, just like building bone disrupted that system and reduced recurrence, chemotherapy may work by that same exact way. The wild thing about that trial also, was that it reduced new primaries, so new cancers, by 30 percent also.
標準療程是每三個星期開 紫杉醇給乳癌婦女服用 這藥能對約40% 的乳癌轉移病人有療效 其中有50%腫瘤會縮小 請記住,我還沒有談到作用程度 那是另外一課題 當乳癌復發,我改成每個禮拜開立紫杉醇 有30%的病人對治療有反應 她們又再復發,我仍給予同樣的藥物 但改為96小時持續注射 這時只有20-30%的人對治療有反應 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 是的,我們不知道治療機轉為何 所以也不知道化療是不是 破壞了癌症的複雜系統 就如成骨藥物破壞癌症系統並降低復發率 化療有可能利用一樣的機制 這個臨床試驗的另外一件奇事是 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. They're dynamic. I mean, this is a scary slide, not to take an aside, but it looks at obesity in the world. And I'm sorry if you can't read the numbers, they're kind of small. But, if you start to look at it, that red, that dark color there, more than 75 percent of the population of those countries are obese. Look a decade ago, look two decades ago: markedly different. So, our systems today are dramatically different than our systems a decade or two ago. So the diseases we have today, which reflect patterns in the system over the last several decades, are going to change dramatically over the next decade or so based on things like this.
所以,我們的問題是,所有的系統不斷變動 他們是動態系統 請看看這張關於世界性肥胖問題的可怕投影片 不要因為它可怕就忽視不看 很抱歉,字很小,可能看不到這些數字 請看這些紅色或深色區域 在這些國家中 肥胖人口占總人口75%以上 這跟十年前,二十年前很不一樣 也就是說,今天我們身處的環境系統 跟十年、二十年前很不一樣 我們今日會得的疾病 反映出過去數十年外在環境系統模式的轉變 同樣的概念 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 of the whole proteome. So this is a drop of blood that has gone through a superconducting magnet, and we're able to get resolution where we can start to see all of the proteins in the body. We can start to see that system. Each of the red dots are where a protein has actually been identified. The power of these magnets, the power of what we can do here, is that we can see an individual neutron with this technology. So, again, this is stuff we're doing with Danny Hillis and a group called Applied Proteomics, where we can start to see individual neutron differences, and we can start to look at that system like we never have before. So, instead of a reductionist view, we're taking a step back.
這張漂亮的40 GB大的圖 是完整蛋白質體 在一滴血液經過一個超導磁鐵時 磁力能將血液中的成分分離開來 現在看到的是身體中所有的蛋白質成份 可以看到身體這個系統 每一個紅點就是一個被分離出的蛋白質 我們有能力利用這些磁鐵的磁力 觀察每一個中子 這就是我們正跟Danny Hillis和工作團隊 合作進行的應用蛋白質體計畫 這讓我們得以觀察每一個中子的差異 以前所未有的角度觀察一個系統 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, who had recurrent lung cancer. It was in her brain, in her lungs, in her liver. She had gotten Carboplatin Taxol, Carboplatin Taxotere, Gemcitabine, Navelbine: Every drug we have she had gotten, and that disease continued to grow. She had three kids under the age of 12, and this is her CT scan. And so what this is, is we're taking a cross-section of her body here, and you can see in the middle there is her heart, and to the side of her heart on the left there is this large tumor that will invade and will kill her, untreated, in a matter of weeks. She goes on a pill a day that targets a pathway, and again, I'm not sure if this pathway was in the system, in the cancer, but it targeted a pathway, and a month later, pow, that cancer's gone. Six months later it's still gone. That cancer recurred, and she passed away three years later from lung cancer, but she got three years from a drug whose symptoms predominately were acne. That's about it.
這是一名46歲的女性 她的肺癌復發 除肺臟外,還轉移到腦部、及肝臟 她接受雞尾酒治療如Carboplatin合併Taxol, Taxotere Gemicitabene或是Navelbine 她接受所有我們給予的藥物,但腫瘤仍繼續長大 她有三名未滿12歲的子女 這是她的電腦斷層掃描 也就是我們做她身體這處橫切面的造影 如你所見,中間這裡是她的心臟 心臟的左邊有一個大腫瘤 若是沒有接受治療,這腫瘤具侵入性並能在數周內殺死她 她每天服用一顆針對某個致病機轉的藥物 但同樣的,我不清楚這個機轉是否存在於這個癌症系統 但是,使用這個針對某機轉的藥物一個月後,腫瘤消失了! 六個月後,腫瘤仍不見蹤影 後來,癌症復發,她在三年後死於肺癌 但是,這藥為她爭取了三年的壽命 這三年唯一顯著的症狀是痤瘡 就只是這樣
So, the problem is that the clinical trial was done, and we were a part of it, and in the fundamental clinical trial -- the pivotal clinical trial we call the Phase Three, we refused to use a placebo. Would you want your mother, your brother, your sister to get a placebo if they had advanced lung cancer and had weeks to live? And the answer, obviously, is not. So, it was done on this group of patients. Ten percent of people in the trial had this dramatic response that was shown here, and the drug went to the FDA, and the FDA said, "Without a placebo, how do I know patients actually benefited from the drug?" So the morning the FDA was going to meet, this was the editorial in the Wall Street Journal. (Laughter) And so, what do you know, that drug was approved.
然而,問題是,當臨床實驗進行的時候 我們有參與其中 在這個基礎的 先驅的臨床試驗裡─我們稱為第三期 我們拒絕使用安慰劑 你會希望妳的母親、兄弟姊妹,在他們有末期癌症 只剩幾個星期能活時,服用安慰劑嗎? 答案很明顯,是「不」 所以,這群病人參與了臨床實驗 你可以看到,10%的病人對治療有顯著的反應 然而,當藥物被送到食品藥物管理局審查 他們認為,沒有使用安慰劑 我們怎麼知道病人是因為藥物受惠的? 這是在食品藥物管理局開會的那個早上 華爾街日報的社論 (笑) 你知道,這個藥物後來被核准
The amazing thing is another company did the right scientific trial, where they gave half placebo and half the drug. And we learned something important there. What's interesting is they did it in South America and Canada, where it's "more ethical to give placebos." They had to give it also in the U.S. to get approval, so I think there were three U.S. patients in upstate New York who were part of the trial. But they did that, and what they found is that 70 percent of the non-responders lived much longer and did better than people who got placebo. So it challenged everything we knew in cancer, is that you don't need to get a response. You don't need to shrink the disease. If we slow the disease, we may have more of a benefit on patient survival, patient outcome, how they feel, than if we shrink the disease.
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 也就是受試者的一半服用藥物,一半服用安慰劑 讓我們得以從中學到些重要的事 有趣的是,這實驗是在南美跟加拿大進行的 在那裡,使用安慰劑比較道德 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 這實驗裡有三個美國病人 住在北紐約州 研究人員進行試驗,發現 對藥物無反應的受試者中,有70% 比服用安慰劑的受試者活得更久且更好 這結果有益於我們對癌症的了解: 病人不需要對藥物有反應 我們也不需要縮小病灶 只要我們能減慢疾病進程,我們將 比縮小病灶能學到更多有關 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 and you've got a two centimeter mass in your liver, and you come back to me in three months and it's three centimeters, did that drug help you or not? How do I know? Would it have been 10 centimeters, or am I giving you a drug with no benefit and significant cost? So, it's a fundamental problem. And, again, that's where these new technologies can come in.
問題在於,如果我是這名醫師,今天我看到這樣的斷層攝影 判定你的肝臟裡有個2公分的腫瘤 三個月後你回診,腫瘤變成3公分 藥物能否幫助你呢? 我該怎麼知道呢? 如果這腫瘤有10公分大,我是不是給你一個 沒有效但是花費驚人的藥物? 是的,這就是問題所在 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 -- well, the ultimate goal is that you prevent disease, right? The ultimate goal is that you prevent any of these things from happening. That is the most effective, cost-effective, best way we can do things today. But if one is unfortunate to get a disease, you'll go into your doctor's office, he or she will take a drop of blood, and we will start to know how to treat your disease. The way we've approached it is the field of proteomics, again, this looking at the system. It's taking a big picture.
顯然地,我們的目標是,你去醫生的辦公室─ 沒錯,終極目標當然是預防疾病 是預防任何疾病的發生 這是最有效、節省成本 我們現在所能做的最好的事 但,如果有人很不幸的生病了 還是得去醫生的辦公室,取一滴血 我們就開始知道如何治療疾病 而蛋白質體學可以被用來找出治療方法 從這個角度來看癌症這個系統 我們能得到一個疾病的全景
The problem with technologies like this is that if one looks at proteins in the body, there are 11 orders of magnitude difference between the high-abundant and the low-abundant proteins. So, there's no technology in the world that can span 11 orders of magnitude. And so, a lot of what has been done with people like Danny Hillis and others is to try to bring in engineering principles, try to bring the software. We can start to look at different components along this spectrum.
問題在於,這樣的一個技術 當我們只看一個體內的蛋白質 就有含量從低到高 十一個不同程度的等級 這個世界還沒有技術能處理十一個程度的等級 所以,Danny Hillis跟其他人正著手解決這個問題 試著利用一些工程原理來寫出個軟體 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. And I think one of the exciting things that is starting to happen now is that people from those fields are coming in. Yesterday, the National Cancer Institute announced a new program called the Physical Sciences and Oncology, where physicists, mathematicians, are brought in to think about cancer, people who never approached it before. Danny and I got 16 million dollars, they announced yesterday, to try to attach this problem. A whole new approach, instead of giving high doses of chemotherapy by different mechanisms, to try to bring technology to get a picture of what's actually happening in the body.
稍早,我們曾經提過跨領域合作 我認為有個令人振奮的事情正開始進行中 那就是不同領域的人正開始參與癌症研究 昨天,美國國家癌症研究所宣布開始一個新計畫: 物理科學及腫瘤學 這讓物理學家跟數學家都得以貢獻他們對癌症的想法 這都是以前從未參與這類研究的人 他們昨天也宣布,Danny跟我得到一筆1億6千萬的研究經費 將用來解決這個問題: 我們想找到,在不使用高劑量的化療藥物的情況下 利用一個不同機轉的新方法 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 -- because I think it's important to understand it. What happens is every protein in your body is charged, so the proteins are sprayed in, the magnet spins them around, and then there's a detector at the end. When it hit that detector is dependent on the mass and the charge. And so we can accurately -- if the magnet is big enough, and your resolution is high enough -- you can actually detect all of the proteins in the body and start to get an understanding of the individual system.
因為我認為了解這技術很重要 請給我兩秒鐘,告訴你這是怎麼辦到的 身體中每一個蛋白質都帶電 所以,當我們把蛋白質噴進一個磁場,它們會旋轉 而機器的末端有個偵測器 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 更精確一點來說,如果這個磁鐵夠大 解析度夠高 就能偵測體內所有的蛋白質 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, instead of having paper in my chart, in your chart, and it being this thick, this is what data flow is starting to look like in our offices, where that drop of blood is creating gigabytes of data. Electronic data elements are describing every aspect of the disease. And certainly the goal is we can start to learn from every encounter and actually move forward, instead of just having encounter and encounter, without fundamental learning.
就一個腫瘤科醫師來說 我們,還有你們都不再需要厚厚的紙本病歷 相對的,你們會開始在醫生的辦公室看到 從一滴血得來的好幾GB的數據流 電子數據將能夠形容一個疾病的所有樣貌 當然,目標是我們能從每一次看診學到一些東西 讓我們對癌症的了解能確實向前推進 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. We need to start to think differently and radically. And so, I implore everyone here: Think differently. Come up with new ideas. Tell them to me or anyone else in our field, because over the last 59 years, nothing has changed. We need a radically different approach.
總而言之,我們必須不再用化約論者的方式思考 我們需要從各式各樣不同的角度思考 我想告訴這裡的每一位,用不同的思考模式,來點新主意 把這些想法告訴我或其他從事癌症研究的人 因為,過去59年來,事情從來就沒有改變 我們需要完全不同的做法
You know, Andy Grove stepped down as chairman of the board at Intel -- and Andy was one of my mentors, tough individual. When Andy stepped down, he said, "No technology will win. Technology itself will win." And I'm a firm believer, in the field of medicine and especially cancer, that it's going to be a broad platform of technologies that will help us move forward and hopefully help patients in the near-term.
當英特爾的創辦人葛洛夫 這位強悍的人是我的導師之一 從董事長的位子退下來時,他這麼說: 「沒有一種科技是贏家,科技本身就是贏家。」 我堅信,醫學,尤其是癌症醫學 將會是個技術交流的大平台 這能幫助我們往前邁進 也希望在不久的將來能幫助病人
Thank you very much.
非常謝謝大家