中英對照
Cancer.Many of us have lost family,friends or loved onesto this horrible disease.I know there are some of you in the audiencewho are cancer survivors,or who are fighting cancer at this moment.My heart goes out to you.While this word often conjures up emotions of sadness and anger and fear,I bring you good news from the front lines of cancer research.The fact is, we are starting to win the war on cancer.In fact, we lie at the intersectionof the three of the most exciting developments within cancer research.
癌症，這可怕的疾病，讓許多人失去親友摯愛。我知道在座的你們，有人是癌症的倖存者，有人則正在對抗癌症，我的心與你們同在。癌症常讓人聯想到悲傷、憤怒與恐懼。讓我由癌症研究前線的角度 向各位報告一個好消息。我們在抗癌的戰爭中正開始顯現出勝勢。我們正處於數個研究的交叉點之中，也就是在癌症研究中三項最令人興奮的發展。
The first is cancer genomics.The genome is a compositionof all the genetic information encoded by DNAin an organism.In cancers, changes in the DNA called mutationsare what drive these cancers to go out of control.Around 10 years ago, I was part of the team at Johns Hopkinsthat first mapped the mutations of cancers.We did this first for colorectal,breast, pancreatic and brain cancers.And since then, there have been over 90 projects in 70 countriesall over the world,working to understand the genetic basis of these diseases.Today, tens of thousands of cancers are understooddown to exquisite molecular detail.
首先是癌症基因組。基因組是包含在生物 DNA 內，所有的基因訊息。癌細胞裡面的DNA 變化稱作突變，是造成癌細胞失控的主因。十年前我是約翰霍普金斯醫學院的團隊之一。此團隊率先探測到癌細胞突變。我們最開始是在直腸癌、乳癌、胰腺癌和腦癌細胞中進行。自此之後全球有 70 個國家，超過 90 個研究計畫，著手了解癌症的遺傳基礎。如今上萬種癌症能透過精微的分子細節加以了解。
The second revolution is precision medicine,also known as "personalized medicine."Instead of one-size-fits-all methods to be able to treat cancers,there is a whole new class of drugs that are able to target cancersbased on their unique genetic profile.Today, there are a host of these tailor-made drugs,called targeted therapies,available to physicians even todayto be able to personalize their therapy for their patients,and many others are in development.
第二項變革是精準醫療，也稱「個人化醫療」。相較於一藥治萬病的癌症治療方式，現在有一種全新等級的藥物能依照癌症的基因檔案，以標靶方式進行治療。現在對這樣量身訂做的藥物有一個專有名詞，即「標靶治療」。這種藥讓當今的醫生能為病人量身訂做適合的治療，還有許多藥物正在研發中。
The third exciting revolution is immunotherapy,and this is really exciting.Scientists have been able to leverage the immune systemin the fight against cancer.For example, there have been ways where we find the off switches of cancer,and new drugs have been able to turn the immune system back on,to be able to fight cancer.In addition, there are ways where you can take away immune cellsfrom the body,train them, engineer them and put them back into the bodyto fight cancer.Almost sounds like science fiction, doesn’t it?
第三項的革新是免疫療法，這著實振奮人心。科學家能夠讓免疫系統發揮作用，對抗癌症。例如我們已找出許多遏止癌細胞的方法，及能重啟免疫系統的新藥物，以對抗癌症。此外現在也有方法能自人體取出免疫細胞，然後訓練它們，改變其基因結構後，再重新植入體內，以對抗癌症。聽起來很像科幻小說，對嗎？
While I was a researcher at the National Cancer Institute,I had the privilege of working with some of the pioneers of this fieldand watched the development firsthand.It’s been pretty amazing.Today, over 600 clinical trials are open,actively recruiting patients to explore all aspects in immunotherapy.
當我還是美國國立癌症研究所的研究員時，我有幸能與這個領域的先驅共事，第一手目睹發展過程，感覺頗為神奇。現在有六百多種臨床試驗，積極地公開招募病患以探索免疫療法的各個方面。
While these three exciting revolutions are ongoing,unfortunately, this is only the beginning,and there are still many, many challenges.Let me illustrate with a patient.Here is a patient with a skin cancer called melanoma.It’s horrible; the cancer has gone everywhere.However, scientists were able to map the mutations of this cancerand give a specific treatment that targets one of the mutations.And the result is almost miraculous.Tumors almost seem to melt away.Unfortunately, this is not the end of the story.A few months later, this picture is taken.The tumor has come back.The question is: Why?The answer is tumor heterogeneity.Let me explain.
這三項振奮人心的革新仍持續進行中，不幸的是這僅是開端，眼前仍面臨重重挑戰。讓我用病患照片做說明。這名病人罹患名為「黑素瘤」的皮膚癌。很可怕，癌細胞四處擴散。但是科學家探測出癌細胞的突變，並針對其中一種突變給予特殊治療。結果幾乎可說是奇蹟。腫瘤幾乎消失不見。不幸的是，故事還沒結束。幾個月後又照了這張照片，腫瘤又復發了。這不禁讓人思考為什麼 ？答案是「腫瘤異質性」。容我解釋。
Even a cancer as small as one centimeter in diameterharbors over a hundred million different cells.While genetically similar,there are small differences in these different cancersthat make them differently prone to different drugs.So even if you have a drug that’s highly effective,that kills almost all the cells,there is a chance that there’s a small populationthat’s resistant to the drug.This ultimately is the populationthat comes back,and takes over the patient.
就算癌細胞小到只有一公分的直徑，也包含了上億種不同的細胞。儘管有相似的基因，不同的癌細胞有著微小的差異，讓不同的藥適用不同癌細胞。所以就算有一種超級有效的藥，幾乎能夠殺掉所有細胞，卻仍可能有一小叢細胞，對這種藥物是有抵抗力的。這類細胞到最後，終究還是會復發，在病人身體蔓延。
So then the question is: What do we do with this information?Well, the key, then,is to apply all these exciting advancements in cancer therapy earlier,as soon as we can,before these resistance clones emerge.The key to cancer and curing cancer is early detection.And we intuitively know this.Finding cancer early results in better outcomes,and the numbers show this as well.For example, in ovarian cancer, if you detect cancer in stage four,only 17 percent of the women survive at five years.However, if you are able to detect this cancer as early as stage one,over 92 percent of women will survive.But the sad fact is, only 15 percent of women are detected at stage one,whereas the vast majority, 70 percent,are detected in stages three and four.
所以問題是，對於這樣的資訊 我們能做些甚麼？關鍵在於加緊腳步將上述的醫療進展及早應用於癌症治療。且愈快愈好，免得這些抗藥細胞植株出現。治療癌症的關鍵是及早發現。我們其實也知道，及早發現癌症會有較好的治療結果，這也受到研究數據證實。以卵巢癌來說若到第四期才偵測到癌細胞，能存活五年的婦女只有 17%。但是若能在第一期就偵測到癌症，有超過 92% 的婦女能存活下來。令人難過的是只有 15% 的婦女 能在第一期偵測到癌症，絕大多數約七成的婦女是在第三、四期才知道罹癌。
We desperately need better detection mechanisms for cancers.The current best ways to screen cancer fall into one of three categories.First is medical procedures,which is like colonoscopy for colon cancer.Second is protein biomarkers, like PSA for prostate cancer.Or third, imaging techniques,such as mammography for breast cancer.Medical procedures are the gold standard;however, they are highly invasiveand require a large infrastructure to implement.Protein markers, while effective in some populations,are not very specific in some circumstances,resulting in high numbers of false positives,which then results in unnecessary work-ups and unnecessary procedures.Imaging methods, while useful in some populations,expose patients to harmful radiation.In addition, it is not applicable to all patients.For example, mammography has problems in women with dense breasts.
我們急需更好的癌症偵測機制。目前最佳的癌症偵測方式有三種。第一是醫療行為，像是以結腸鏡檢測結腸癌。第二是蛋白質生物標記，像檢測前列腺癌的前列腺特異抗原 。第三是醫學影像技術，如偵測乳癌的乳房造影檢查。醫療行為是黃金準則，不過具高侵入性，需要推行大型的醫療設備。蛋白質生物標記對某些族群有效，在有些情況下效果並不理想，誤判的比例很高，往往白費力氣和工夫。造影檢查對某些族群有效，讓病人暴露在有害的放射線下，也不適合所有病人。例如乳房造影檢查對有緻密乳房的婦女有一定難度，
So what we need is a method that is noninvasive,that is light in infrastructure,that is highly specific,that also does not have false positives,does not use any radiationand is applicable to large populations.Even more importantly,we need a method to be able to detect cancersbefore they’re 100 million cells in size.Does such a technology exist?Well, I wouldn’t be up here giving a talk if it didn’t.
所以我們需要一種 不具侵入性的方法、不需用到大型醫療設備、具高特異性、不會有誤判、不會用到放射線，而且能適用於廣大族群。更重要的是，我們需要的是 能夠偵測到癌細胞的方法，尤其是在癌細胞數目達到上億之前發現。這樣的技術存在嗎？如果沒有，我就不會站在這裡演講。
I’m excited to tell you about this latest technology we』ve developed.Central to our technology is a simple blood test.The blood circulatory system, while seemingly mundane,is essential for you to survive,providing oxygen and nutrients to your cells,and removing waste and carbon dioxide.Here’s a key biological insight:Cancer cells grow and die faster than normal cells,and when they die,DNA is shed into the blood system.Since we know the signatures of these cancer cellsfrom all the different cancer genome sequencing projects,we can look for those signals in the bloodto be able to detect these cancers early.So instead of waiting for cancers to be large enough to cause symptoms,or for them to be dense enough to show up on imaging,or for them to be prominent enoughfor you to be able to visualize on medical procedures,we can start looking for cancers while they are relatively pretty small,by looking for these small amounts of DNA in the blood.
我很高興將我們最新發展的技術與各位分享。此項技術的核心是簡易的血液檢驗。血液循環系統看似沒甚麼，對人類的生存卻至關重要，能為人體細胞提供氧氣和養分，移除廢物和二氧化碳。從生物觀點來說的關鍵是：癌細胞的生長和死亡速度比正常細胞來得快，當癌細胞死亡時，DNA 會進入血液循環系統。我們從所有不同癌症的 基因組定序計畫中，知曉了各種癌細胞的基因特點，我們便可從血液中尋找罹癌訊號，好能及早偵測到癌症。與其等到癌細胞增殖並造成明顯症狀，或癌細胞密集到足以顯影，或讓癌細胞生長到足以透過醫療行為目測到，我們能在癌細胞還未成氣候時開始進行偵測，尋找血液中微量的 DNA。
So let me tell you how we do this.First, like I said, we start off with a simple blood test --no radiation, no complicated equipment --a simple blood test.Then the blood is shipped to us,and what we do is extract the DNA out of it.While your body is mostly healthy cells,most of the DNA that’s detected will be from healthy cells.However, there will be a small amount, less than one percent,that comes from the cancer cells.Then we use molecular biology methods to be able to enrich this DNAfor areas of the genome which are known to be associated with cancer,based on the information from the cancer genomics projects.We’re able to then put this DNA into DNA-sequencing machinesand are able to digitize the DNA into A’s, C’s, T’s and G’sand have this final readout.Ultimately, we have information of billions of lettersthat output from this run.We then apply statistical and computational methodsto be able to findthe small signal that’s present,indicative of the small amount of cancer DNA in the blood.
跟大家解釋這如何進行。先從簡易的血液檢驗開始，不需放射線和複雜的設備，就是簡單的血液檢驗。然後血液取樣運送到本團隊，我們從血液中取出 DNA。此時人體的細胞大多是健康的，因此取得的DNA多是來自健康細胞。但有不到 1% 的微量 DNA，是來自癌細胞。我們接著運用分子生物法，根據從癌症基因組計劃獲得的信息，富集此與癌細胞有關的 DNA。我們將採得的 DNA 置入 DNA 定序儀器，儀器將 DNA 數位化成A、C、T 和 G 四種鹼基 ，並進行資料分析。我們最後從儀器分析結果，得出數十億 DNA 符號的資訊。研究團隊接著用統計數據和電腦判讀，藉以找出資料中，顯示血液中微量DNA 癌細胞的微小訊息。
So does this actually work in patients?Well, because there’s no way of really predicting right nowwhich patients will get cancer,we use the next best population:cancers in remission;specifically, lung cancer.The sad fact is, even with the best drugs that we have today,most lung cancers come back.The key, then, is to seewhether we’re able to detect these recurrences of cancersearlier than with standard methods.
這技術對病患真的有用嗎？由於目前還無法真正預測哪個病人會罹癌，適於此研究的最好族群是：癌症緩解期的病患，更明確來說：肺癌。令人難過的是就算使用最好的藥物，絕大多數的肺癌仍會復發。接下來的關鍵是，我們是否能比一般方法更早偵測到癌細胞的復發。
We just finished a major trialwith Professor Charles Swanton at University College London,examining this.Let me walk you through an example of one patient.Here’s an example of one patient who undergoes surgeryat time point zero,and then undergoes chemotherapy.Then the patient is under remission.He is monitored using clinical exams and imaging methods.Around day 450, unfortunately, the cancer comes back.The question is: Are we able to catch this earlier?During this whole time, we』ve been collecting blood seriallyto be able to measure the amount of ctDNA in the blood.So at the initial time point, as expected,there’s a high level of cancer DNA in the blood.However, this goes away to zero in subsequent time pointsand remains negligible after subsequent points.However, around day 340, we see the rise of cancer DNA in the blood,and eventually, it goes up higher for days 400 and 450.
我們的團隊與倫敦學院大學 查爾斯·史汪頓教授 剛完成一項主要試驗，檢驗這項技術。讓我用一名病患來舉例說明。這名病患在研究的時間起始點，接受手術，然後接受化療，接著病人進入癌症緩解期。團隊用臨床檢查和造影技術監測。癌細胞不幸在第 450 天復發。問題來了：我們能夠及早知道嗎？在這段期間我們定期抽血，以測量血液循環腫瘤 DNA。剛開始時不出所料，血液中有大量的癌細胞 DNA。但是接下來癌細胞 DNA 消失 ，又過一段時間後僅剩微乎其微的癌細胞。但是血液中癌細胞 DNA 的量到第 340 天開始增加，它在第 400 到 450 天數量更多了。
Here’s the key, if you』ve missed it:At day 340, we see the rise in the cancer DNA in the blood.That means we are catching this cancer over a hundred days earlierthan traditional methods.This is a hundred days earlier where we can give therapies,a hundred days earlier where we can do surgical interventions,or even a hundred days less for the cancer to growor a hundred days less for resistance to occur.For some patients, this hundred days means the matter of life and death.We’re really excited about this information.
這裡就是關鍵，如果你沒有了解到。在第 340 天我們看到血液中癌細胞 DNA 的增加，這代表我們比傳統方式早了一百多天，偵測到癌細胞。也就是我們能提早100 多天治療病人。能提早 100 多天進行手術，讓癌症少 100 多天的時間生長，讓癌細胞少 100 多天的時間復發。對有些病人而言這100天乃是生死交關的關鍵。這消息令人振奮。
Because of this assignment, we』ve done additional studies nowin other cancers,including breast cancer, lung cancerand ovarian cancer,and I can’t wait to see how much earlier we can find these cancers.
也因此我們目前對其他癌症，進行更多的研究，包括乳癌、肺癌，和卵巢癌。我迫不及待想知道我們能多早發現這些癌症。
Ultimately, I have a dream,a dream of two vials of blood,and that, in the future, as part of all of our standard physical exams,we』ll have two vials of blood drawn.And from these two vials of blood we will be able to comparethe DNA from all known signatures of cancer,and hopefully then detect cancers months to even years earlier.Even with the therapies we have currently,this could mean that millions of lives could be saved.And if you add on to that recent advancements in immunotherapyand targeted therapies,the end of cancer is in sight.
我有個終極夢想。兩小瓶的血液取樣，在未來將成為健康檢查程序的一部分，採取兩小瓶血液取樣。從這兩瓶取樣我們可以比較來自所有具癌症跡象的 DNA，希望能早幾個月甚至幾年偵測到癌症。就算以我們現有的治療方式，提早發現癌症代表能拯救上百萬的生命。若加上近期的免疫療法的進步，以及標靶式治療的進步，終結癌症就近在咫尺。
The next time you hear the word "cancer,"I want you to add to the emotions: hope.Hold on.Cancer researchers all around the world are working feverishlyto beat this disease,and tremendous progress is being made.
下次當你聽到「癌症」一詞，我期許各位也能想到「希望」，永不放棄。全球的癌症研究人員正積極努力，期能戰勝癌症，也已有重大的進展。
This is the beginning of the end.We will win the war on cancer.And to me, this is amazing news.
這是癌症之終結的開端，我們終會打贏對抗癌症的戰爭。對我來說，這是很棒的好消息。
Thank you.
謝謝各位。
(Applause)
（掌聲）