演讲MP3+双语文稿:第一种能够治愈癌症的疗法
听力课堂TED音频栏目主要包括TED演讲的音频MP3及中英双语文稿，供各位英语爱好者学习使用。本文主要内容为演讲MP3+双语文稿:第一种能够治愈癌症的疗法，希望你会喜欢！
【演讲人及介绍】Carl June
卡尔·琼，抗击癌症的著名先驱
【演讲主题】第一种能够治愈癌症的疗法
【演讲文稿-中英文】
Translated by Li Ying (Amelia) Hu Reviewedby Wanna Shi
00:12
So this is the first time I've told thisstory in public, the personal aspects of it. Yogi Berra was a world-famousbaseball player who said, "If you come to a fork in the road, takeit." Researchers had been, for more than a century, studying the immune systemas a way to fight cancer, and cancer vaccines have, unfortunately, beendisappointing. They've only worked in cancers caused by viruses, like cervicalcancer or liver cancer.
这是我第一次在公众场合从个人层面来讲这件事。约吉·贝拉（Yogi Berra）是一名世界著名的棒球运动员，他曾说：“当你遇到时机，请把握住它吧。”一个多世纪以来，研究人员一直在研究用免疫系统来抗癌，但不幸的是，癌症疫苗的开发一直不尽如人意。这些疫苗只对由病毒引起的癌症起作用，如宫颈癌或肝癌，
00:45
So cancer researchers basically gave up onthe idea of using the immune system to fight cancer. And the immune system, inany case, did not evolve to fight cancer; it evolved to fight pathogensinvading from the outside. So its job is to kill bacteria and viruses. And thereason the immune system has trouble with most cancers is that it doesn'tinvade from the outside; it evolves from its own cells. And so either theimmune system does not recognize the cancer as a problem, or it attacks acancer and also our normal cells, leading to autoimmune diseases like colitisor multiple sclerosis.
所以癌症研究人员基本上放弃了用免疫系统来抗癌的思路。无论如何，免疫系统都没能进化到足以抗癌的地步，只能对抗外来入侵的病原体。它的职责就是杀灭细菌和病毒。免疫系统之所以难以对抗大多数的癌症，是因为引起癌症的并不是外来入侵的病原，而是人体自身细胞出现了癌变。所以免疫系统要么没有识别癌症，要么既攻击癌细胞，又攻击正常细胞，结果引发了自身免疫性疾病，如结肠炎或多发性硬化症。
01:26
So how do you get around that? Our answerturned out to be synthetic immune systems that are designed to recognize andkill cancer cells. That's right -- I said a synthetic immune system. You dothat with genetic engineering and synthetic biology. We did it with thenaturally occurring parts of the immune system, called B cells and T cells.These were our building blocks. T cells have evolved to kill cells infectedwith viruses, and B cells are the cells that make antibodies that are secretedand then bind to kill bacteria. Well, what if you combined these two functionsin a way that was designed to repurpose them to fight cancer? We realized itwould be possible to insert the genes for antibodies from B cells into T cells.
那该怎么办呢？我们的解决办法是设计合成免疫系统，用它来识别并杀死癌细胞。对，我说的是合成免疫系统，可以通过基因工程和合成生物学来实现，使用免疫系统中自然产生的部分，即 B 细胞和 T 细胞。这些是构建免疫系统的基本单位。T 细胞可以杀死染上病毒的细胞，而 B 细胞则可以分泌出抗体，通过与细菌相结合来消灭细菌。如果把这两种功能结合起来，改变其功能用来抗癌，那会怎样？我们发现，可以将 B 细胞的抗体基因注入 T 细胞。
02:21
So how do you do that? Well, we used an HIVvirus as a Trojan horse to get past the T cells' immune system. The result is achimera, a fantastic fire-breathing creature from Greek mythology, with alion's head, a goat's body and a serpent's tail. So we decided that theparadoxical thing that we had created with our B-cell antibodies, our T cellscarrier and the HIV Trojan horse should be called "Chimeric AntigenReceptor T cells," or CAR T cells. The virus also inserts genetic informationto activate the T cells and program them into their killing mode.
那该怎么做呢？我们用一个艾滋病病毒（HIV）作为特洛伊木马，避开 T 细胞的免疫系统，结果造出了个喀迈拉（嵌合体），那是古希腊故事中狮头、羊身、蛇尾的吐火怪物。我们用 B 细胞的抗体、以 T 细胞为载体，以 HIV 为特洛伊木马造出了一个自相矛盾的东西，我们决定把它叫做“嵌合抗原受体 T 细胞”或 CAR-T 细胞。该病毒还插入了基因信息，以激活 T 细胞，并将其编程，使其进入杀灭模式。
03:05
So when CAR T cells are injected intosomebody with cancer, what happens when those CAR T cells see and bind to theirtumor target? They act like supercharged killer T cells on steroids. They startthis crash-defense buildup system in the body and literally divide and multiplyby the millions, where they then attack and kill the tumor. All of this meansthat CAR T cells are the first living drug in medicine. CAR T cells break themold. Unlike normal drugs that you take -- they do their job and getmetabolized, and then you have to take them again -- CAR T cells stay alive andon the job for years. We have had CAR T cells stay in the bodies of our cancerpatients now for more than eight years. And these designer cancer T cells, CART cells, have a calculated half-life of more than 17 years. So one infusion cando the job; they stay on patrol for the rest of your life.
我们将 CAR-T 细胞注入癌症患者体内，当这些细胞看到并粘附于其肿瘤靶点，会发生什么？它们就像类固醇上强悍的 T 细胞杀手，开始在体内建立防撞系统，分裂并繁殖出数百万个细胞，然后攻击并杀死肿瘤细胞。这些都意味着 CAR-T 细胞是医学史上首款活体药物。CAR-T 细胞击破霉菌，它们不像患者服用的普通药物——普通药物在发挥药效后会被代谢掉，然后患者得再服药，而 CAR-T 细胞则可存活多年，且药效很持久。我们的癌症患者其体内的 CAR-T 细胞至今已存活了 8 年多。这些定制的癌症 T 细胞，即 CAR-T 细胞，其半衰期预计超过 17 年，所以输一次药液就可以守护病人的余生。
04:06
This is the beginning of a new paradigm inmedicine. Now, there was one major challenge to these T-cell infusions. Theonly source of T cells that will work in a patient are your own T cells, unlessyou happen to have an identical twin. So for most of us, we're out of luck. Sowhat we did was to make CAR T cells. We had to learn to grow the patient's ownT cells. And we developed a robust platform for this in the 1990s. Then in1997, we first tested CAR T cells in patients with advanced HIV-AIDS. And wefound that those CAR T cells survived in the patients for more than a decade.And it improved their immune system and decreased their viruses, but it didn'tcure them.
这是医学新模式的开始。但这种 T 细胞疗法面临着一个巨大的挑战。能在患者体内起作用的 T 细胞，其唯一来源是自体的 T 细胞，除非患者碰巧有个同卵双胞胎。所以对于大多数人来说，我们都没这么幸运。所以为了创造 CAR-T 细胞，我们得学会培育患者自体的 T 细胞。20 世纪 90年代，我们开发了一个强大的平台，1997 年，我们首次在晚期艾滋病患者身上测试了 CAR-T 细胞。我们发现，这些 CAR-T 细胞在病人体内存活了十多年。它增强了患者的免疫系统，并减少了病毒，但它并没能治愈患者。
04:55
So we went back to the laboratory, and overthe next decade made improvements to the CAR T cell design. And by 2010, webegan treating leukemia patients. And our team treated three patients withadvanced chronic lymphocytic leukemia in 2012. It's a form of incurableleukemia that afflicts approximately 20,000 adults every year in the UnitedStates. The first patient that we treated was a retired Marine sergeant and aprison corrections officer. He had only weeks to live and had, in fact, alreadypaid for his funeral. The cells were infused, and within days, he had highfevers. He developed multiple organ failures, was transferred to the ICU andwas comatose. We thought he would die, and, in fact, he was given last rites.But then, another fork in the road happened. So, around 28 days after the CAR Tcell infusion, he woke up, and the physicians finally examined him, and thecancer was gone. The big masses that had been there had melted. Bone marrowbiopsies found no evidence of leukemia, and that year, in our first threepatients we treated, two of three have had durable remissions now for eightyears, and one had a partial remission.
所以我们又回到实验室，在接下来的十年里，我们改进了 CAR-T 细胞的设计。到了 2010 年，我们开始治疗白血病患者。2012 年，我们的团队治疗了三位晚期慢性 淋巴细胞白血病患者。这是一种无法治愈的白血病，在美国，每年折磨着约两万名成人。我们治疗的第一位病人是位退役海军中士、前狱警，他只有几周可活了，实际上，他已经为自己筹备好了葬礼。在给他注入了 CAR-T 细胞后，几天内，他发起了高烧，多个器官开始衰竭，被转到重症监护室，他昏迷不醒。我们以为他要死了，他接受了临终祷告。但后来出现了转机，在注射了 CAR-T 细胞大约 28 天后，他醒了，医生给他做了最终检查，他的癌症消失了，原来在那里的大肿块已经消肿了，骨髓活检未发现白血病迹象。那一年，在我们首批治疗的三位患者中，其中两位的病情持续缓解，至今已八年了，一位病情得到了部分缓解。
06:13
The CAR T cells had attacked the leukemiain these patients and had dissolved between 2.9 and 7.7 pounds of tumor in eachpatient. Their bodies had become veritable bioreactors for these CAR T cells,producing millions and millions of CAR T cells in the bone marrow, blood andtumor masses. And we discovered that these CAR T cells can punch far abovetheir weight class, to use a boxing analogy. Just one CAR T cell can kill 1,000tumor cells. That's right -- it's a ratio of one to a thousand. The CAR T celland its daughter progeny cells can divide and divide and divide in the bodyuntil the last tumor cell is gone.
这种 CAR-T 细胞攻击了这些患者的白血病细胞，并且使每位患者的肿瘤消减了 2.9-7.7 磅。他们的身体已经成为这些 CAR-T 细胞名副其实的生物反应器，在骨髓、血液和肿瘤组织中繁殖出数百万个 CAR-T 细胞。用拳击来打个比方，我们发现，这些 CAR-T 细胞可以与远远超过他们重量等级的对手对打。一个 CAR-T 细胞就能杀死 1000 个肿瘤细胞，没错，这是一对一千的比率。CAR-T 细胞及其子代细胞可以在体内不断分裂，直到最后一个肿瘤细胞消失。
06:58
There's no precedent for this in cancermedicine. The first two patients who had full remission remain todayleukemia-free, and we think they are cured. These are people who had run out ofoptions, and by all traditional methods they had, they were like modern-dayLazarus cases. All I can say is: thank goodness for those forks in the road.
这在癌症医学史上前所未有。最先的两位病人的病情完全好转，至今一直没再出现白血病细胞，我们相信，他们已经痊愈了。他们用尽了所有的传统方法，均告无效，他们一筹莫展，而现在他们就像是现代的拉撒路病例。【注：泛指医学上“起死回生”的现象】我只能说：谢天谢地，时来运转。
07:23
Our next step was to get permission totreat children with acute leukemia, the most common form of cancer in kids. Thefirst patient we enrolled on the trial was Emily Whitehead, and at that time,she was six years old. She had gone through a series of chemotherapy andradiation treatments over several years, and her leukemia had always come back.In fact, it had come back three times. When we first saw her, Emily was veryill. Her official diagnosis was advanced, incurable leukemia. Cancer hadinvaded her bone marrow, her liver, her spleen. And when we infused her withthe CAR T cells in the spring of April 2012, over the next few days, she didnot get better. She got worse, and in fact, much worse. As our prisoncorrections officer had in 2010, she, in 2012, was admitted to the ICU, andthis was the scariest fork in the whole road of this story.
我们的下一步是要得到批准，治疗儿童急性白血病，这是最常见的儿童肿瘤性疾病。我们收治第一位参加试验的病人是艾米莉 · 怀特黑德（Emily Whitehead），当时，她年仅六岁。在过去几年里，她接受了 一系列的化疗和放疗，但她的白血病总是复发。实际上，复发了三次。我们第一次看到艾米丽时，她病得很重。她的正式诊断是白血病晚期，没得治了，癌症细胞已侵入她的骨髓、肝脏和脾脏。我们在 2012 年 4 月春为她进行了 CAR-T 细胞治疗，在接下来的日子里，她的病情不见好转，反而每况愈下，事实上，她的病情出现了恶化。就像 2010 年那位狱警所经历的那样，2012 年，她进了重症监护室，这是整个故事中最可怕的一个关口。
08:21
By day three, she was comatose and on lifesupport for kidney failure, lung failure and coma. Her fever was as high as 106degrees Fahrenheit for three days. And we didn't know what was causing thosefevers. We did all the standard blood tests for infections, and we could notfind an infectious cause for her fever. But we did find something very unusualin her blood that had never been seen before in medicine. She had elevatedlevels of a protein called interleukin-6, or IL-6, in her blood. It was, infact, more than a thousandfold above the normal levels. And here's where yetanother fork in the road came in.
到了第三天，她出现了肾衰竭、肺衰竭，她昏迷不醒，得靠仪器来维持生命，她一连三天发高烧，高达 41 摄氏度，而我们却不知道她发烧的原因。我们做了所有的标准血液检查，排查感染，却未发现引起发烧的感染病因。但我们的确在她的血液中发现了异常，这在医学史上前所未见。她血液里一种叫白细胞介素-6（IL-6）的蛋白质含量过高。事实上，比正常水平高出一千多倍，这又是一个关口。
09:08
By sheer coincidence, one of my daughtershas a form of pediatric arthritis. And as a result, I had been following as acancer doc, experimental therapies for arthritis for my daughter, in case shewould need them. And it so happened that just months before Emily was admittedto the hospital, a new therapy had been approved by the FDA to treat elevatedlevels of interleukin-6. And it was approved for the arthritis that my daughterhad. It's called tocilizumab. And, in fact, it had just been added to thepharmacy at Emily's hospital, for arthritis.
非常巧合的是，我有一个女儿得了小儿关节炎，因此，作为一名癌症医生，为了我的女儿，我一直在关注关节炎实验性疗法，以备她会用到。就在艾米丽入院前几个月，美国食品药品监督管理局（FDA）批准了一种治疗 白细胞介素-6含量过高的新疗法。这种疗法获得批准，用于治疗 我女儿所得的这类关节炎，名为 IL-6 受体单克隆抗体注射剂（tocilizumab），该药刚被添加到艾米丽所住医院的药房，用来治疗关节炎。
09:47
So when we found Emily had these very highlevels of IL-6, I called her doctors in the ICU and said, "Why don't youtreat her with this arthritis drug?" They said I was a cowboy forsuggesting that. And since her fever and low blood pressure had not respondedto any other therapy, her doctor quickly asked permission to the institutionalreview board, her parents, and everybody, of course, said yes. And they triedit, and the results were nothing short of striking.
所以当我们发现艾米丽的 IL-6 含量这么高，我打电话给她的重症监护室医生，我说：“你不妨用这种关节炎药给她治疗一下吧？”他们说，我提这么个建议，简直就是个莽夫。由于其他治疗对她的高烧和低血压都没效，她的医生很快向机构审查委员会申请了许可，并征求了她父母的同意，自然，大家都同意了。于是他们尝试了这种药，结果疗效非常惊人。
10:16
Within hours after treatment withtocilizumab, Emily began to improve very rapidly. Twenty-three days after hertreatment, she was declared cancer-free. And today, she's 12 years old andstill in remission.
接受 IL-6 受体单克隆抗体治疗几个小时后，艾米丽开始迅速好转。治疗 23 天后，她体内已经没有癌细胞了。现在，她 12 岁了，仍然在康复中。
10:34
(Applause)
（掌声）
10:44
So we now call this violent reaction of thehigh fevers and coma, following CAR T cells, cytokine release syndrome, or CRS.We've found that it occurs in nearly all patients who respond to the therapy.But it does not happen in those patients who fail to respond. So paradoxically,our patients now hope for these high fevers after therapy, which feels like"the worst flu in their life," when they get CAR T-cell therapies.They hope for this reaction because they know it's part of the twisting andturning path back to health. Unfortunately, not every patient recovers.Patients who do not get CRS are often those who are not cured. So there's astrong link now between CRS and the ability of the immune system to eradicateleukemia.
我们现在把这种在注入 CAR-T 细胞后出现高烧和昏迷的强列反应 称为细胞因子释放综合征（CRS）。我们发现，几乎所有对该治疗 有反应的病人都出现了这种症状，但那些（对治疗）没有反应的病人则没有这些症状。所以这很矛盾，现在，我们的病人在接受 CAR-T 细胞治疗时，都希望能发高烧，这种感觉就像是“得了有生以来最严重的流感”。他们希望有这种反应，因为他们知道这是迈向恢复健康之路上 必经的坎坷与曲折。不幸的是，并不是每位病人都能康复。没有出现 CRS 症状的病人通常无法治愈。所以 CRS 与免疫系统清除白血病细胞的能力紧密相关。
11:33
That's why last summer, when the FDAapproved CAR T cells for leukemia, they also co-approved the use of tocilizumabto block the IL-6 effects and the accompanying CRS in these patients. That wasa very unusual event in medical history. Emily's doctors have now completedfurther trials and reported that 27 out of 30 patients, the first 30 wetreated, or 90 percent, had a complete remission after CAR T cells, within amonth. A 90 percent complete remission rate in patients with advanced cancer isunheard of in more than 50 years of cancer research. In fact, companies oftendeclare success in a cancer trial if 15 percent of the patients had a completeresponse rate.
所以，去年夏天，FDA 在批准用 CAR-T 细胞治疗白血病时，还批准了使用 IL-6 受体单克隆抗体注射剂来阻断这些患者出现的 IL-6 影响和伴随而来的 CRS 症状。这在医学史上极不寻常。艾米丽的医生们已经完成了进一步的试验，并在报告中指出，在首批治疗的 30 位病人中，有 27 位，或者说 90% 的病人，在用 CAR-T 细胞治疗后的一个月内，病情得到了完全缓解。晚期癌症患者病情完全缓解率达 90%，这在 50 多年的癌症研究中闻所未闻。事实上，如果癌症试验的结果有 15% 的患者获得完全缓解，制药公司一般就会宣布该癌症试验成功。
12:28
A remarkable study appeared in the"New England Journal of Medicine" in 2013. An international study hassince confirmed those results. And that led to the approval by the FDA forpediatric and young adult leukemia in August of 2017.
2013 年，《新英格兰医学杂志》 发表了一项令人瞩目的研究。此后，一项国际性研究 证实了这些研究结果。FDA 因而于 2017 年 8 月批准了将该疗法用于治疗儿童和年轻人的白血病。
12:45
So as a first-ever approval of a cell andgene therapy, CAR T-cell therapy has also been tested now in adults withrefractory lymphoma. This disease afflicts about 20,000 a year in the UnitedStates. The results were equally impressive and have been durable to date. Andsix months ago, the FDA approved the therapy of this advanced lymphoma with CART cells. So now there are many labs and physicians and scientists around theworld who have tested CAR T cells across many different diseases, andunderstandably, we're all thrilled with the rapid pace of advancement. We're sograteful to see patients who were formerly terminal return to healthy lives, asEmily has. We're thrilled to see long remissions that may, in fact, be a cure.
作为首个获得批准的细胞与基因疗法，CAR-T 细胞疗法现在也已用于试验性 治疗患有难治性淋巴瘤的成年人。这种疾病每年折磨着 近 2 万名美国患者，治疗结果也同样令人瞩目，且效果持久至今。六个月前，FDA 批准了用 CAR-T 细胞治疗晚期淋巴瘤。现在世界上有很多实验室、医生和科学家都在试用 CAR-T 细胞治疗许多不同的疾病，毫无疑问，我们大家都为迅猛的进展感到振奋。我们很高兴看到，那些以前得了绝症的病人，像艾米丽一样康复，健康地生活。我们很兴奋地看到，病情长期得到缓解，实际上可能是治愈了。
13:34
At the same time, we're also concernedabout the financial cost. It can cost up to 150,000 dollars to make the CAR Tcells for each patient. And when you add in the cost of treating CRS and othercomplications, the cost can reach one million dollars per patient. We mustremember that the cost of failure, though, is even worse. The currentnoncurative therapies for cancer are also expensive and, in addition, thepatient dies. So, of course, we'd like to see research done now to make thismore efficient and increase affordability to all patients. Fortunately, this isa new and evolving field, and as with many other new therapies and services,prices will come down as industry learns to do things more efficiently.
同时，我们也在关注着医疗费。为一位病人合成 CAR-T 细胞的费用高达 15 万美元，加上治疗 CRS 和其他并发症的费用，每个病人的治疗费高达一百万美元。但是，我们还要记住，如果治疗失败，费用会更高。目前，对癌症无疗效的治疗费用也十分高昂，而且病人依然会面临死亡。我们当然希望看到我们现在所做的研究能更有效，并让所有病人都能付得起治疗费。所幸，这是个新领域，仍在不断地发展，随着许多其他新疗法和服务的出现，行业效率会提高，治疗价格会下降。
14:21
When I think about all the forks in theroad that have led to CAR T-cell therapy, there is one thing that strikes me asvery important. We're reminded that discoveries of this magnitude don't happenovernight. CAR T-cell therapies came to us after a 30-year journey, along aroad full of setbacks and surprises. In all this world of instant gratificationand 24/7, on-demand results, scientists require persistence, vision andpatience to rise above all that. They can see that the fork in the road is notalways a dilemma or a detour; sometimes, even though we may not know it at thetime, the fork is the way home.
我想着这一路走来，在研制 CAR-T 细胞治疗中所遇到的各种重大关头，有一件事我觉得非常重要。我们意识到，这些重大发现并非一蹴而就。我们花了 30 年，CAR-T 细胞疗法才得以问世，这一路走来，虽道路曲折，但不乏惊喜。当今世界，人们追求即时满足，全天候按需出结果，在这样的世界里，科学家需要坚持不懈、有远见、有耐心，才能战胜这一切，才能看清，岔道口并不总是进退两难的困境，或者要绕道而行；有时，在当时可能还不知道，这个路口就是通往成功之路。
15:03
Thank you very much.
感谢大家。
15:04
(Applause)
（掌声）
- 频道推荐
- |
- 全站推荐
- 推荐下载
- 网站推荐
