Ladies and gentlemen, I present to you the human genome.
女士们先生们, 我向您展示人类基因组
(Applause)
(鼓掌)
Chromosome one -- top left, bottom right -- are the sex chromosomes. Women have two copies of that big X chromosome; men have the X and, of course, that small copy of the Y. Sorry boys, but it's just a tiny little thing that makes you different. So if you zoom in on this genome, then what you see, of course, is this double-helix structure -- the code of life spelled out with these four biochemical letters, or we call them bases: A, C, G and T. How many are there in the human genome? Three billion. Is that a big number? Well, everybody can throw around big numbers. But in fact, if I were to place one base on each pixel of this 1280x800-resolution screen, we would need 3,000 screens to take a look at the genome. So it's really quite big.
左上是一号染色体 右下是性染色体 女性有两条那个大大的X染色体 男性有个X 当然,还有个小小的Y 男士们,不好意思,就是那个小东西让你不同 如果放大这条基因组 你看到的当然就是这个双螺旋结构 生命的密码就是由这些生化的字母组成 或者说碱基,对吧: A, C, G 和 T 人类基因组有多少这样的结构?30亿 这个数字大吧? 谁都能随便谈论大数字 但是,如果我把一个碱基放在 这个1280×800屏幕的一个像素上 得要三千个屏幕一睹人类基因组 所以这是非常大的
And perhaps because of its size, a group of people -- all, by the way, with Y chromosomes -- decided they would want to sequence it.
也许因为这个规模的缘故 一群人-都是带Y染色体的 他们决定进行测序
(Laughter)
(笑声)
And so 15 years, actually, and about four billion dollars later, the genome was sequenced and published. In 2003, the final version was published, and they keep working on it. That was all done on a machine like this. It costs about a dollar for each base -- a very slow way of doing it.
15年,实际上花了大约40亿 基因组获得测序并公开了 2003年最终“完成图”面世,他们继续完善它 这些都是由这样个机器完成的 每个碱基大概要花费1美元 这样工作非常缓慢
Well, folks, I'm here to tell you that the world has completely changed, and none of you know about it. So now what we do is take a genome, we make maybe 50 copies of it, we cut all those copies up into little 50-base reads, and then we sequence them, massively parallel. Then we bring that into software and reassemble it, and tell you what the story is. So to give you a picture of what this looks like, the Human Genome Project: 3 gigabases, right? One run on one of these modern machines: 200 gigabases in a week. And that 200 is going to change to 600 this summer, and there's no sign of this pace slowing. The price of a base, to sequence a base, has fallen 100 million times. That's the equivalent of you filling up your car with gas in 1998, waiting until 2011, and now you can drive to Jupiter and back twice.
不过各位,我今天来要告诉你们 这个世界大变模样了 你们还不知道呢 我现在做的是获取一个基因组 将其复制50份 然后分割成50个碱基读数 然后进行大规模同时测序 然后用软件 重新合成并给你解读 为了让你更直观地了解 人类基因组测序工程:3GB, 在这样的机器上测序: 一周可完成200GB 这个夏天将有望提升至600 并且这种增长没有放缓的趋势 所以每个碱基测序的价钱 下降了一千万倍 这就像你1998年给车加满油 等到2011年 能到木星两个来回
(Laughter)
(笑声)
World population, PC placements, the archive of all of medical literature, Moore's law, the old way of sequencing, and here's all the new stuff. Guys, this is a long scale; you don't typically see lines that go up like that. So the worldwide capacity to sequence human genomes is something like 50,000 to 100,000 human genomes this year. We know this based on the machines that are being placed. This is expected to double, triple or maybe quadruple year over year for the foreseeable future. In fact, there's one lab in particular that represents 20 percent of all that capacity: It's called the Beijing Genomics Institute. The Chinese are absolutely winning this race to the new Moon, by the way. What does this mean for medicine?
世界人口 PC配置 医学文献档案 摩尔定律 旧的测序方式,然后是这些新玩意 各位,这是个对数尺度 你不会常看到趋势像那样上升 所以世界范围内可进行人类基因组测序的能力 今年大概是五万到十万人类基因组 这是依据被配置的机器估算的 而这在未来可能会 每年翻两番,三番,甚至四番 实际上,有一个实验室 具备所有测序能力中的百分之二十 就是华大基因 中国人毫无疑问正在领跑这场新的登月竞赛 这对药学来说什么意义呢?
So a woman, age 37, presents with stage 2 estrogen receptor-positive breast cancer. She is treated with surgery, chemotherapy and radiation. She goes home. Two years later, she comes back with stage 3C ovarian cancer, unfortunately; treated again with surgery and chemotherapy. She comes back three years later at age 42 with more ovarian cancer, more chemotherapy. Six months later, she comes back with acute myeloid leukemia. She goes into respiratory failure and dies eight days later.
如果一个37岁的女性 她患有II期ER阳性乳腺癌 她正在接受手术治疗,化疗和放射治疗 她回家了 2年后,她发现患上III期C卵巢癌 不幸的是,再次接受手术和化疗 3年后她42岁 又患上卵巢癌,接受更多的化疗 6个月后 她患上急性髓性白血病 最后呼吸衰竭八天后死亡
So first: the way in which this woman was treated, in as little as 10 years, will look like bloodletting. And it's because of people like my colleague, Rick Wilson, at the Genome Institute at Washington University, who decided to take a look at this woman postmortem. And he took skin cells, healthy skin and cancerous bone marrow, and sequenced the whole genomes of both of them in a couple of weeks, no big deal. Then he compared those two genomes in software, and what he found, among other things, was a deletion -- a 2,000-base deletion across three billion bases in a particular gene called TP53. If you have this deleterious mutation in this gene, you're 90 percent likely to get cancer in your life.
首先她接受的10年治疗 基本就是放血 正因为有人,比如我的同事,里克・威尔森 他工作与华盛顿大学的基因组研究所 决定对她尸检 他进行测序,他取了皮肤细胞,健康的皮肤 和癌化的骨髓 他测定两者的所有基因组 区区几周后 他用软件对比两组基因组 他发现了 30亿碱基里 有两千个碱基的丢失 这是在一个叫TP53的基因上 如果这个基因发生有害突变 就有百分之九十的可能患癌
So unfortunately, this doesn't help this woman, but it does have severe -- profound, if you will -- implications to her family. I mean, if they have the same mutation, and they get this genetic test and they understand it, then they can get regular screens and can catch cancer early, and potentially live a significantly longer life.
很不幸这没能帮到这位女性 但这对她的家人来说 是很重要深刻的启示 如果他们有同样的突变 他们接受基因测试然后了解到该情况 他们就可以接受常规检查并早点发现病症 从而可以大大延长生命
Let me introduce you to the Beery twins, diagnosed with cerebral palsy at the age of two. Their mom is a very brave woman who didn't believe it; the symptoms weren't matching up. And through some heroic efforts and a lot of Internet searching, she was able to convince the medical community that, in fact, they had something else. They had dopa-responsive dystonia. And so they were given L-Dopa, and their symptoms did improve, but they weren't totally asymptomatic. Significant problems remained.
让我来介绍毕瑞兄妹 他们在2岁时被诊断为脑瘫 他们的母亲是个非常勇敢的女性 她不相信诊断符合症状 通过她不懈努力和网上搜索 她说服了医疗人员 他们患是另一种病 多巴反应性肌张力失常 所以采用L-多巴治疗 他们的病情确实有所改善 但是并没有完全消除 仍然存在严重的问题
Turns out the gentleman in this picture is a guy named Joe Beery, who was lucky enough to be the CIO of a company called Life Technologies. They're one of two companies that makes these massive whole-genome sequencing tools. And so he got his kids sequenced. What they found was a series of mutations in a gene called SPR, which is responsible for producing serotonin, among other things. So on top of L-Dopa, they gave these kids a serotonin precursor drug, and they're effectively normal now. Guys, this would never have happened without whole-genome sequencing. At the time -- this was a few years ago -- it cost $100,000. Today it's $10,000, next year, $1,000, the year after, $100, give or take a year. That's how fast this is moving.
照片中的男士叫乔・毕瑞 很幸运地他是 一家叫做生命科技的公司的首席信息官 这家公司是 提供基因组测序设备的两大供应商之一 所以他测定他的孩子(的基因) 他们发现了SPR基因上的一个系列突变 这个片段与产生血清素的功能相关 所以除了L-多巴,他们也用血清素前体药物辅以治疗 孩子们恢复正常了 各位,没有基因组测序这些都无法实现 当时,几年前的时候,花费高达10万美元 如今是一万美元,明年会是一千 后年是一百 就是这么快
So here's little Nick -- likes Batman and squirt guns. And it turns out Nick shows up at the children's hospital with this distended belly, like a famine victim. And it's not that he's not eating; it's that when he eats, his intestine basically opens up and feces spill out into his gut. So a hundred surgeries later, he looks at his mom and says, "Mom, please pray for me. I'm in so much pain." His pediatrician happens to have a background in clinical genetics and he has no idea what's going on, but he says, "Let's get this kid's genome sequenced." And what they find is a single-point mutation in a gene responsible for controlling programmed cell death. So the theory is that he's having some immunological reaction to what's going on -- to the food, essentially. And that's a natural reaction, which causes some programmed cell death, but the gene that regulates that down is broken. And so this informs, among other things, of course, a treatment for bone marrow transplant, which he undertakes. And after nine months of grueling recovery, he's now eating steak with A1 sauce.
这是小尼克 他喜欢蝙蝠侠和水枪 尼克去儿童医院接受治疗 他的肚子涨得像饥荒儿童一样 这不是因为他不吃 而是他吃的时候,他的肠子就打开 废物进入腹腔 在经历了无数手术后 他看着妈妈说“妈妈, 为我祈祷吧,我十分痛苦“ 他的儿科医生恰好有临床遗传学方面的背景 他不知道问题出在哪儿 他说”让我们给他做基因组测序吧“ 然后他们在控制程序性细胞死亡的基因上 发现一个单点突变 所以根源就是他对 食物有种免疫反应 这是种自然反应,它会导致程序性细胞死亡 但这个基因的此种功能出现问题 所以对于这个问题 他接受了骨髓移植的治疗 9个月艰难的康复期后 他能吃A1沙司了
(Laughter)
(笑声)
The prospect of using the genome as a universal diagnostic is upon us today. Today. It's here. And what it means for all of us is that everybody in this room could live an extra 5, 10, 20 years, just because of this one thing. Which is a fantastic story, unless you think about humanity's footprint on the planet, and our ability to keep up food production. So it turns out that the very same technology is also being used to grow new lines of corn, wheat, soybean and other crops that are highly tolerant of drought, of flood, of pests and pesticides. Now, look -- as long as we continue to increase the population, we'll have to continue to grow and eat genetically modified foods. And that's the only position I'll take today. Unless there's anybody in the audience who'd like to volunteer to stop eating? None, not one.
利用基因组 作为万能诊断方法的前景 正在到来 就是今天,就在这里 这对这屋子里的每一个人来说 意味着我们可以多活十到二十年 就是因为这项技术 这是个神奇的故事 当然还有人类遍布全球的足迹 和我们追赶粮食产量的能力 不过 这项技术 同样可以被利用于 种植新型玉米,麦子,大豆和其他粮食 能够抵抗干旱和洪水 害虫和杀虫剂 随着人口不断增长 我们会不得不使用转基因产品 这是我的唯一立场 除非观众中有人 决定绝食 不,没人会 这是个打字机
This is a typewriter, a staple of every desktop for decades. And, in fact, the typewriter was essentially deleted by this thing. And then more general versions of word processors came about. But ultimately, it was a disruption on top of a disruption. It was Bob Metcalfe inventing the Ethernet, and the connection of all these computers that fundamentally changed everything. Suddenly we had Netscape, we had Yahoo. And we had, indeed, the entire dot-com bubble.
数十年前每个书桌上都有一个 实际上,打字机完全被这个取代了 然后是更多代文字处理器面世 不过,最令人措手不及的 还是鲍勃・梅得卡夫发明了以太网 电脑的联网 革命性地改变了一切 突然我们就有了Netscape,雅虎 然后是整个互联网的泡沫经济
(Laughter)
(笑声)
Not to worry though, that was quickly rescued by the iPod, Facebook and, indeed, Angry Birds.
不过别担心 iPod, Facebook又拯救了我们 当然还有愤怒地小鸟
(Laughter)
(笑声)
Look, this is where we are today. This is the genomic revolution today. This is where we are. What I'd like you to consider is: What does it mean when these dots don't represent the individual bases of your genome, but they connect to genomes all across the planet? I just recently had to buy life insurance, and I was required to answer: A. I have never had a genetic test; B. I've had one, here you go; or C. I've had one and I'm not telling. Thankfully, I was able to answer A, and I say that honestly, in case my life insurance agent is listening. But what would have happened if I had said C?
这就是我们今天所处(的环境) 这是基因革命地时代,我们所处地时代 我希望你们考虑的是: 如果这些点不是代表你的基因的碱基 而是整个星球上基因相连 这意味着什么? 我不久前才买了人身保险 我被这样问道: A.我从来没有进行过基因测试,B.我有过,没戏了 C.我有过但我不说出来 很幸运,我还能选A 要是我的保险代理人在听着的话我可确实没说谎 如果我选的是C呢? 基因组学的消费需求将大大增加
Consumer applications for genomics will flourish. Do you want to see if you're genetically compatible with your girlfriend? DNA sequencing on your iPhone? There's an app for that.
你想不想知道 你跟女友的基因是否兼容?当然 要不要在你的iPhone上基因测序?有这么一个应用 (笑声)
(Laughter)
Personalized genomic massage, anyone? There's already a lab today that tests for allele 334 of the AVPR1 gene, the so-called cheating gene.
有人想要个人定制的基因学按摩吗? 如今已经有个实验室 为AVPR1基因上的等位基因334测序 所谓的欺骗基因
(Laughter)
谁今天是和你重要的另一半一起来的
So anybody who's here today with your significant other, just turn over to them, swab their mouth, send it to the lab and you'll know for sure.
只要转过去,刮下他/她的口腔 寄到那个实验室你就知道了 (笑声)
(Laughter)
你想不想选一个
Do you really want to elect a president whose genome suggests cardiomyopathy? Think of it -- it's 2016, and the leading candidate releases not only her four years of back-tax returns, but also her personal genome. And it looks really good. Then she challenges all her competitors to do the same. Do you think that's not going to happen? Do you think it would have helped John McCain?
可能患心肌病的总统? 假设,现在是2016年 竞选人不仅公开 她四年的税后申报 还有她的个人基因组 看上去很不错 然后她要求其他的竞争者也这么做 你觉得这不可能发生? 你觉得这会帮到约翰・麦凯恩? (笑声)
(Laughter)
观众里有多少人
How many people in the audience have the last name Resnick, like me? Raise your hand. Anybody? Nobody. Typically, there's one or two. So my father's father was one of 10 Resnick brothers. They all hated each other, and all moved to different parts of the planet. So it's likely I'm related to every Resnick that I ever meet, but I don't know. So imagine if my genome were De-identified, sitting in software, And a third cousin's genome was also sitting there, and there was software that could compare the two and make these associations. Not hard to imagine. My company has software that does this right now. Imagine one more thing, that that software is able to ask both parties for mutual consent: "Would you be willing to meet your third cousin?" And if we both say yes -- voilà! Welcome to Chromosomally LinkedIn.
跟我同一个姓,雷斯尼克?请举手 有人是吗? 没有 明显,有一两个 我父亲是雷斯尼克10兄弟种的一个 他们相互不喜欢 他们移居到这世界上不同的角落 所以好比 我与我遇到过的雷斯尼克都有关系,但我不确定 试想如果我的基因组被确定,保存在软件里 一个三表兄弟的基因组也是 有软件可以对比两个(样本) 并且联系上 不难想像,我的公司就有这样的软件 那么再像一下 如果软件可向双方征询同意书 “你想不想与你的三表兄见面?” 如果两人都说是 耶!欢迎来到染色体LinkedIn网站
(Laughter)
(笑声)
Now this is probably a good thing, right? Bigger clan gatherings and so on. But maybe it's a bad thing as well. How many fathers in the room? Raise your hands. OK, so experts think that one to three percent of you are not actually the father of your child.
这也许是个好事 你可以有个大家族 也可能是坏事 这屋子里有多少父亲?请举手 好的,专家认为你们中间百分之一到三的人 并不是你孩子的父亲
(Laughter)
(笑声)
Look --
这个-
(Laughter)
(笑声)
These genomes, these 23 chromosomes, they don't in any way represent the quality of our relationships or the nature of our society -- at least not yet. And like any new technology, it's really in humanity's hands to wield it for the betterment of mankind or not. And so I urge you all to wake up and to tune in and to influence the genomic revolution that's happening all around you.
这些基因组,这23个染色体 它们并不代表我们人际关系的质量 或者我们这个社会的性质-至少目前还没有 如同任何新科技 都取决与人类自己 是否用于对人类有益的一面 所以我强烈期望你们所有人醒悟 并参与到这场发生在你们周围的基因革命 谢谢
Thank you.
(Applause)
(鼓掌)