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JoeDeRisi_2006-_解决医学难题_
How is it, how can we investigate this flora of viruses that surround us, and aid medicine? 怎么说呢？我们应该如何来研究 那些围绕在我们身边,又同时帮助医学发展的病毒？
investigate:v.调查;研究;审查; flora:n.植物区系;植物群;
How can we turn our cumulative knowledge of virology into a simple, hand-held , single diagnostic assay ? 我们怎样才能把我们积累的有关病毒的知识 变成简单、可行的方法运用到诊断中去？
cumulative:adj.累积的; virology:n.[病毒]病毒学,滤过性微生物学; hand-held:adj.手提式的,便携式的; diagnostic:adj.诊断的;特征的;n.诊断法;诊断结论; assay:n.化验;试验;vt.分析;化验;尝试;vi.鉴定;经检验证明内含成分;
I want to turn everything we know right now about detecting viruses and the spectrum of viruses that are out there into, let's say, a small chip . 我想将所有我们现在已知的有关检测病毒 和病毒图谱的方法 变成,比如说,一块小小的芯片。
detecting:n.检测;检定;v.发现;探知(detect的现在分词);adj.探测的; spectrum:n.光谱;频谱;范围;余象; chip:v.削,凿;削成碎片;剥落;碎裂;n.[电子]芯片;筹码;碎片;(食物的)小片;薄片;
When we started thinking about this project -- how we would make a single diagnostic assay to screen for all pathogens simultaneously -- well, there's some problems with this idea. 当我们开始思考这个计划时 - 我就在想我们如何通过一个简单的诊断 将所有的病原体同时检测出来 - 其实这个想法实施起来有一些困难。
pathogens:n.[基医]病原体;病原菌;[基医]致病菌; simultaneously:adv.同时地;
First of all , viruses are pretty complex , but they're also evolving very fast. 首先,病毒是相当复杂的, 同时它们的进化速度相当快。
First of all:adv.首先; complex:adj.复杂的;合成的;n.复合体;综合设施; evolving:v.(使)逐渐形成,逐渐演变;进化形成;(evolve的现在分词)
This is a picornavirus. 这是一种小核糖核酸病毒
Picornaviruses -- these are things that include the common cold and polio , things like this. 小核糖核酸病毒包括了 普通感冒和小儿麻痹症之类的病症。
common cold:na.感冒; polio:n.小儿麻痹症(等于poliomyelitis);脊髓灰质炎;
You're looking at the outside shell of the virus, and the yellow color here are those parts of the virus that are evolving very, very fast, and the blue parts are not evolving very fast. 你们仔细看病毒的外壳 这些黄色的部分 进化得很快,非常快, 而那些蓝色的部分则进化得相对缓慢。
shell:n.壳;炮弹;壳层;骨架;v.脱壳;剥壳;采集贝壳;用壳体包被;short.shewill;
When people think about making pan-viral detection reagents , usually it's the fast-evolving problem that's an issue , because how can we detect things if they're always changing? 当人们想到制造泛用型病毒检测剂时 病毒的快速演变是个问题, 因为我们如何能够对一直变化着的病毒进行检测呢？
detection:n.侦查,探测;发觉,发现;察觉; reagents:n.[试剂]试剂(reagent的复数); issue:n.重要议题;争论的问题;v.宣布;公布;发出;发行;
But evolution is a balance: where you have fast change, you also have ultra-conservation -- things that almost never change. 但是进化是一种平衡: 哪里有快速变化,哪里也会有超级保守 - 有些东西几乎是不变的。
evolution:n.演变;进化;发展;渐进;
And so we looked into this a little more carefully, and I'm going to show you data now. 所以我们要再看仔细些, 现在我要向你们展示一些数据。
This is just some stuff you can do on the computer from the desktop . 这些东西你在桌子的电脑上就可以完成。
stuff:n.东西:物品:基本特征:v.填满:装满:标本: desktop:n.桌面;桌面(显示使用程序图标的计算机屏幕);
I took a bunch of these small picornaviruses, like the common cold, like polio and so on, and I just broke them down into small segments , and so took this first example, which is called Coxsackievirus , and just break it into small windows. 我将一些小核糖核酸病毒 如普通感冒和小儿麻痹症等 分割成小的片段, 第一个例子是柯萨奇病毒, 我将它们放到小玻璃片上,
a bunch of:一群;一束;一堆; segments:n.片段; v.把…分割成段; Coxsackievirus:n.柯萨基病毒;
And I'm coloring these small windows blue if another virus shares an identical sequence in its genome to that virus. 然后我将这些小玻璃染成蓝色 如果有另一个病毒有着和那个病毒相同的 基因序列.
identical:adj.同一的;完全相同的;n.完全相同的事物; sequence:n.顺序; v.按顺序排列; genome:n.基因组;染色体组;
These sequences right up here -- which don't even code for protein , by the way -- are almost absolutely identical across all of these, so I could use this sequence as a marker to detect a wide spectrum of viruses, without having to make something individual . 这里的序列—— 顺便说一句,这些序列甚至没有同蛋白质编码- 几乎完全与所有这些相同, 所以我将这个序列做为一个标记物 来检测更多的病毒, 不需要再进行个别实验。
sequences:n.[数][计]序列,顺序;继起的事(sequence的复数形式); protein:n.蛋白质; by the way:顺便说一下; absolutely:adv.绝对地;完全地; marker:n.记分员;书签;标识物;作记号的人; individual:n.个人;有个性的人;adj.单独的;个别的;
Now, over here there's great diversity : that's where things are evolving fast. 在那些进化迅速的地方 你会看到很大的差异,
diversity:n.差异(性):多样性:多样化:
Down here you can see slower evolution: less diversity. 在这里你可以看到缓慢的变化和较小的差异。
Now, by the time we get out here to, let's say, acute bee paralysis virus -- probably a bad one to have if you're a bee --- this virus shares almost no similarity to Coxsackievirus, 现在我们再看看别的,比如说 蜜蜂急性肠道病毒 这应该是蜜蜂界中最严重病毒- 这种病毒和柯萨奇病毒几乎没有任何相似之处,
acute:adj.严重的,[医]急性的;敏锐的;激烈的;尖声的; paralysis:n.麻痹;无力;停顿; similarity:n.类似;相似点;
but I can guarantee you that the sequences that are most conserved among these viruses on the right-hand of the screen are in identical regions right up here. 但是我可以向你保证在右侧屏幕中的病毒中的 最保守的基因序列 都在相同的区域里。
guarantee:n.保证;担保;保证人;保证书;抵押品;v.保证;担保; conserved:adj.保守的;v.保存;保全(conserve的过去式); right-hand:adj.得力的;右手的,用右手的; regions:n.地区;地域;行政区;左近;(region的复数)
And so we can encapsulate these regions of ultra-conservation through evolution -- how these viruses evolved -- by just choosing DNA elements or RNA elements in these regions to represent on our chip as detection reagents. 因此我们可以简述这些进化中的超保守区域 - 这些病毒如何进化的—— 仅通过选择这些区域的DNA或RNA片段 作为检测试剂在我们的芯片上表现出来。
encapsulate:vt.压缩;将…装入胶囊;将…封进内部;概述;vi.形成胶囊; evolved:v.(使)逐渐形成;进化;进化形成;(evolve的过去分词和过去式) elements:n.要素;基本部分;少量;一群;(element的复数) represent:v.代表;表现;描绘;回忆;再赠送;
OK, so that's what we did, but how are we going to do that? 那是我们所做的,但我们如何去做呢？
Well, for a long time, since I was in graduate school , 很长时间以来,自从我读研究生
graduate school:研究所,研究院;
I've been messing around making DNA chips -- that is, printing DNA on glass. 我一直在试验DNA芯片 - 即在玻璃上打印DNA。
messing:v.使不整洁;弄脏;弄乱;随地便溺;(mess的现在分词) chips:炸土豆条(chip的复数)
And that's what you see here: 你们看,就是这个:
These little salt spots are just DNA tacked onto glass, and so I can put thousands of these on our glass chip and use them as a detection reagent. 这些小的盐点是DNA留在玻璃上的印记, 同样我可以在玻璃芯片上放上千个盐点 然后把它们作为检测试剂。
tacked:[水运]抢风行驶;[五金]平头钉;
We took our chip over to Hewlett-Packard and used their atomic force microscope on one of these spots, and this is what you see: you can actually see the strands of DNA lying flat on the glass here. 我们把芯片带到惠普公司, 用他们的原子显微镜来观察其中的一个点, 你们看到的就是这个: 你们能很清楚地看到在玻璃上的DNA链,
atomic:adj.原子的,原子能的;微粒子的; microscope:n.显微镜; strands:n.线; v.搁浅;
So, what we're doing is just printing DNA on glass -- little flat things -- and these are going to be markers for pathogens. 所以我们现在所做的就是将DNA打印在玻璃上, 那些又小又平的东西是要作为病原体的标记物。
markers:n.(表示方位的)标记,记号;标识;表示;记号笔;(marker的复数)
OK, I make little robots in lab to make these chips, and I'm really big on disseminating technology . 我在实验室里用小机器人来制造这些芯片, 我真的非常热衷于传播科技。
disseminating:v.散布,传播(信息、知识等);(disseminate的现在分词) technology:n.技术;工艺;术语;
If you've got enough money to buy just a Camry , you can build one of these, too, and so we put a deep how-to guide on the Web, totally free, with basically order-off-the-shelf parts -- you can build a DNA array machine in your garage . 如果你刚好有钱去买一辆凯美瑞汽车, 那你也可以制造一个这个, 我们在网站上有个免费的如何做的指南, 附带基本的组件订购部分 - 你可以在你的车库里生产一个DNA芯片机器。
Camry:n.凯美瑞(汽车款式); how-to:adj.指引的;解释作法的; basically:adv.主要地,基本上; array:n.数组,阵列;排列,列阵;大批,一系列;衣服;v.排列,部署;打扮; garage:n.车库;汽车修理厂;飞机库;v.把…送入车库;把(汽车)开进车库;
Here's the section on the all-important emergency stop switch. 这部分是所有重要的紧急开关。
all-important:adj.非常重要的;首要的; emergency:n.紧急情况;突发事件;非常时刻;adj.紧急的;备用的;
(Laughter) （笑声）
Every important machine's got to have a big red button. 每个重要的机器都有一个大的红色按钮。
But really, it's pretty robust . 但真的,非常坚固。
robust:adj.强健的;健康的;粗野的;粗鲁的;
You can actually be making DNA chips in your garage, and decoding some genetic programs pretty rapidly. It's a lot of fun. 你可以在你的车库里制作DNA芯片, 快速解码一些遗传程序。非常有趣。
decoding:v.解码;破译(尤指密码);译解,理解(外文);(decode的现在分词) genetic:adj.基因的;遗传学的;
(Laughter) （笑声）
And so what we did -- and this is a really cool project -- we just started by making a respiratory virus chip. 所以我们做的——是一个非常酷的项目—— 我们是从制作呼吸道病毒芯片开始的。
respiratory:adj.呼吸的;
I talked about that -- you know, that situation where you go into the clinic and you don't get diagnosed ? 我讲的是 你知道,那种情况,你进了诊所, 但没有得到诊断。
clinic:n.诊所;临床实习;(医院的)门诊部;门诊时间; diagnosed:v.诊断(疾病);判断(问题的原因);(diagnose的过去分词和过去式)
Well, we just put basically all the human respiratory viruses on one chip, and we threw in herpes virus for good measure -- 好,我们刚好把所有人类呼吸道病毒 放在一张芯片上,然后又加入疱疹病毒以更好的测定。
herpes:n.[皮肤]疱疹; for good measure:作为额外增添;另外;
I mean, why not? 为什么不呢？
The first thing you do as a scientist is, you've got to make sure the stuff works. 作为一个科学家第一件要做的事就是 确定你要做的工作。
And so we did is just take tissue culture cells and infected them with various viruses, and we take the stuff and fluorescently label the nucleic acid , 我们所做的就是提取组织培养细胞, 用不同的病毒感染它们, 用荧光标记核酸,
tissue:n.纸巾,手巾纸;(人、动植物细胞的)组织; infected:adj.带菌的; v.传染; (infect的过去分词和过去式) label:n.标签;标记;谓;唱片公司;v.贴标签于;用标签标明; nucleic acid:n.核酸;
the genetic material that comes out of these tissue culture cells -- mostly viral stuff -- and stick it on the array to see where it sticks. 来自这些组织培养细胞的遗传物质—— 大部分是病毒类的东西——把它粘在芯片上。
viral:adj.滤过性毒菌引起的;滤过性毒菌的;
Now, if the DNA sequences match, they'll stick together , and so we can look at spots. 如果DNA序列是匹配的,它们就会粘在一起, 我们来看这些点。
stick together:在一起;团结一致;互相支持;
And if spots light up, we know there's a certain virus in there. 如果它们发亮了,我们就知道那有某种病毒。
That's what one of these chips really looks like, and these red spots are in fact signal coming from the virus. 那是其中一张芯片的样子, 这些红点实际上是来自病毒的信号。
And each spot represents a different family of virus or species of virus. 每一个点代表不同的病毒家系 或者病毒物种。
represents:v.代表;维护…的利益;相当于;(represent的第三人称单数) species:n.[生物]物种;种类;
And so, that's a hard way to look at things, so I'm just going to encode things as a little barcode , grouped by family, so you can see the results in a very intuitive way. 要看清它们是很困难的, 所以我把它们编成小的条码, 按家系分组,这样你可以直接看到结果。
encode:vt.(将文字材料)译成密码;编码,编制成计算机语言; barcode:n.条形码;条码技术; intuitive:adj.直觉的;凭直觉获知的;
What we did is, we took tissue culture cells and infected them with adenovirus , and you can see this little yellow barcode next to adenovirus. 我们所做的就是提取组织培养细胞, 用腺病毒感染, 你可以在腺病毒旁边看到这个小的黄色条码。
adenovirus:n.腺病毒;
And, likewise , we infected with parainfluenza-3 -- that's a paramyxovirus -- and you see a little barcode here. 同样我们用副流感病毒-3感染——— 它是副粘病毒——你在这看到小的条码。
likewise:adv.同样地;也;
And then we did respiratory syncytial virus. 然后我们又用呼吸道合胞病毒。
syncytial:adj.合胞体的;多核的;
That's the scourge of daycare centers everywhere -- it's like boogeremia, basically. 这是所有日托中心的灾难—— 大体上说就象是鼻粘膜病。
scourge:vt.鞭打;蹂躏;严斥;痛斥;n.鞭;灾祸;鞭子;苦难的根源; daycare:n.日托;日间照管儿童;
(Laughter) （笑声）
You can see -- you can see that this barcode is the same family, but it's distinct from parainfluenza-3, which gives you a very bad cold. 你能看到这个条码是同一家系的, 但它与副流感病毒-3不同, 它会使你患非常严重的感冒。
distinct:adj.明显的;独特的;清楚的;有区别的;
And so we're getting unique signatures , a fingerprint for each virus. 所以我们要有独特的标记,每一种病毒都有一种指纹。
unique:adj.独特的,稀罕的;[数]唯一的;n.独一无二的人或物; signatures:n.签名;鲜明特征(signature的复数); fingerprint:n.指纹;手印;vt.采指纹;
Polio and rhino : they're in the same family, very close to each other. 小儿麻痹症病毒和鼻病毒:它们是同一家系的,相互非常接近。
rhino:n.犀牛(等于rhinoceros);钱;现金;
Rhino's the common cold, and you all know what polio is, and you can see that these signatures are distinct. 鼻病毒是普通感冒,你们都知道小儿麻痹是什么, 你们可以看到这些标记是不同的。
And Kaposi's sarcoma-associated herpes virus gives a nice signature down here. 和卡波济氏肉瘤相关的疱疹病毒 底端有很好的标记。
And so it is not any one stripe or something that tells I have a virus of a particular type here; it's the barcode that in bulk represents the whole thing. 所以不是一条带或是什么东西 来告诉我说这里有一个特殊的病毒; 是大量的条码代表整体。
stripe:n.条纹;线条;杠;种类;v.使…成条纹状; bulk:n.大部分;主体;(大)体积;大(量);v.扩展;增大;堆积起来;形成大块;
All right, I can see a rhinovirus -- and here's the blow-up of the rhinovirus's little barcode -- but what about different rhinoviruses? 我能看到鼻病毒, 这是放大的鼻病毒的小条码, 那么不同的鼻病毒呢？
rhinovirus:n.[病毒]鼻病毒; blow-up:n.单相交;发脾气;放大;
How do I know which rhinovirus I have? 我怎么知道我有哪种鼻病毒？
There's 102 known variants of the common cold, and there's only 102 because people got bored collecting them: there are just new ones every year. 已知普通感冒有102种变异, 仅仅只有102种是因为人们已经厌倦去收集它们了, 每年都有新的。
variants:n.[计]变体;变异型(variant的复数); bored:adj.无聊的;厌倦的;烦闷的;v.使厌烦;钻,凿,挖;(bore的过去分词和过去式)
And so, here are four different rhinoviruses, and and you can see, even with your eye, without any fancy computer pattern-matching recognition software algorithms, that you can distinguish each one of these barcodes from each other. 这里有4种不同的鼻病毒, 你可以看到,即使用你的眼睛就可以, 而不用任何计算机模式匹配 识别软件, 你就可以区分这些条码。
fancy:n.幻想; adj.想象的; v.想象; pattern-matching:模式匹配; recognition:n.识别;认识;承认;认可; distinguish:vt.区分;辨别;使杰出,使表现突出;vi.区别,区分;辨别; barcodes:n.条形码;条码技术;
Now, this is kind of a cheap shot, because I know what the genetic sequence of all these rhinoviruses is, and I in fact designed the chip expressly to be able to tell them apart , but what about rhinoviruses that have never seen a genetic sequencer ? 这是某种划算的作法, 因为我知道所有这些鼻病毒的遗传序列, 并且实际上我设计了芯片 能够明确地区分它们, 但对于还不知道遗传序列的鼻病毒怎么办呢？
expressly:adv.清楚地,明显地;特别地,专门地; tell them apart:把他们区分开; sequencer:n.程序装置,[计]定序器;
We don't know what the sequence is; just pull them out of the field. 我们不知道它的序列,那就不要做它们。
So, here are four rhinoviruses for which we never knew anything about -- no one's ever sequenced them -- and you can also see that you get unique and distinguishable patterns. 这是4个鼻病毒 我们对此一无所知, 没有人对它们做过测序,你也能看到 你得到了独特的且可识别的格局。
sequenced:[数][计]序列; distinguishable:adj.可区别的;辨认得出的;可辨识的;
You can imagine building up some library, whether real or virtual , of fingerprints of essentially every virus. 你可以想象建立一个资料室,无论是真实的或是虚拟的, 收藏基本病毒的指纹。
virtual:adj.[计]虚拟的;实质上的,事实上的(但未在名义上或正式获承认); fingerprints:n.[法][特医]指纹(fingerprint的复数); v.取…的指印(fingerprint的三单形式); essentially:adv.本质上;本来;
But that's, again, shooting fish in a barrel , you know, right? 但这又是瓮中捉鳖,对吧？
barrel:n.桶;枪管;一桶(的量);v.飞驰;
You have tissue culture cells: there's a ton of virus. 你有组织培养细胞:有大量的病毒。
What about real people? 那么人呢？
You can't control real people, as you probably know. 你控制不了人,就象你所知道的。
You have no idea what someone's going to cough into a cup, and it's probably really complex, right? 你不知道某个人会往杯子里咳出什么东西, 它可能非常复杂,对不对？
It could have lots of bacteria , it could have more than one virus, and it certainly has host genetic material, so how do we deal with this? 可能有许多细菌,可能有一种以上的病毒, 它肯定有宿主遗传物质, 对此我们怎么办？
bacteria:n.[微]细菌;
And how do we do the positive control here? 我们如何做阳性对照？
positive:adj.积极的;[数]正的,[医][化学]阳性的;确定的;n.正数;[摄]正片;
Well, it's pretty simple. 非常简单。
That's me, getting a nasal lavage . 要是我就做鼻灌洗。
nasal:adj.鼻的;鼻音的;n.鼻骨;鼻音;鼻音字; lavage:vt.[临床]灌洗;清洗;n.[临床]灌洗;洗胃;
And the idea is, let's experimentally inoculate people with virus so we -- this is all IRB-approved, by the way; they got paid. 这个想法就是我们实验性地用病毒给人们接种, 这是经人体实验委员会批准的,他们是拿薪水的。
experimentally:adv.实验上;用实验方法;实验式地; inoculate:vt.[医]接种;嫁接;灌输;
And basically we experimentally inoculate people with the common cold virus. 简单讲我们用普通感冒病毒 给人接种。
Or, even better, let's just take people right out of the emergency room -- undefined , community-acquired respiratory tract infections . 或者更好的是我们把人们 从急诊室解救出来, ——未明确的群体获得性呼吸道感染。
emergency room:n.急诊室; undefined:adj.不明确的;未下定义的; tract:n.束;地带;小册子;大片土地; infections:n.传染病;口腔病害(infection复数形式);
You have no idea what walks in through the door. 你不知道什么会从那个门进来,
So, let's start off with the positive control first, where we know the person was healthy. 所以让我们以阳性对照开始, 我们知道某人是健康的。
They got a shot of virus up the nose, let's see what happens. 他们的鼻子受到病毒的袭击, 让我们看发生了什么。
Day zero: nothing happening. 当天:什么都没发生。
They're healthy; they're clean -- it's amazing. 他们仍然是健康的,清洁的——很奇怪。
Actually, we thought the nasal tract might be full of viruses even when you're walking around healthy. 实际上我们认为他们的鼻道会充满病毒, 即使你是在健康人周围走动。
It's pretty clean. If you're healthy, you're pretty healthy. 它相当清洁,如果你是健康的,你是相当健康。
Day two: we get a very robust rhinovirus pattern, and it's very similar to what we get in the lab doing our tissue culture experiment. 第二天:我们得到了很强的鼻病毒模式, 与我们在实验室做组织培养实验 得到的非常相似。
So that's great, but again, cheap shot, right? 很好,这又是划算的作法,对吧？
We put a ton of virus up this guy's nose. So -- 我们在这个人的鼻子里放大量的病毒,
(Laughter) （笑声）
- I mean, we wanted it to work. I mean, he really had a cold. 我指,我们希望能这样。他真的感冒了。
So, how about the people who walk in off the street? 走过这条街的人会怎么样？
So here are two individuals represented by their anonymous ID codes. 这里的两个人各自用他们的身份识别码代表,
individuals:n.[经]个人;[生物]个体(individual的复数); represented:v.代表; (represent的过去式和过去分词) anonymous:adj.匿名的,无名的;无个性特征的;
They both have rhinoviruses; we've never seen this pattern in lab. 他们都有鼻病毒,我们在实验室从未见过这种类型。
We sequenced part of their viruses; they're new rhinoviruses no one's actually even seen. 我们做了部分测序, 它们是新的鼻病毒,没人见过。
Remember, our evolutionary-conserved sequences we're using on this array allow us to detect even novel or uncharacterized viruses, because we pick what is conserved throughout evolution. 记住,我们在这个芯片上所用的 进化—保守序列使我们能够检测出 新的或无特征的病毒, 因为我们是从整个进化中挑出的保守序列。
novel:adj.新奇的;异常的;n.小说; throughout:adv.自始至终,到处;全部;prep.贯穿,遍及;
Here's another guy. You can play the diagnosis game yourself here. 这是另一个人。你可以自己在这玩诊断游戏。
diagnosis:n.诊断;
These different blocks represent the different viruses in this paramyxovirus family, so you can kind of go down the blocks and see where the signal is, you know. 这些不同的块代表 副粘病毒系中不同的病毒, 你可以在这些块下面 看到信号在哪里。
Well, doesn't have canine distemper; that's probably good. 没有犬瘟热,那样可能不错。
canine:adj.犬的;犬齿的;犬科的;似犬的;n.犬;[解剖]犬齿;
(Laughter) （笑声）
But by the time you get to block nine, you see that respiratory syncytial virus. 但当你看到第9块时, 你可以看到呼吸合胞病毒。
Maybe they have kids. And then you can see, also, the family member that's related: RSVB is showing up here. 也许它们有后代了。你也可以看到 与其相关的家系成员:RSVB在这里出现了。
So, that's great. 太好了。
Here's another individual, sampled on two separate days -- repeat visits to the clinic. 这是另外一个人,分2天抽取了血样, 他反复到诊所来。
This individual has parainfluenza-1, and you can see that there's a little stripe over here for Sendai virus: that's mouse parainfluenza. 这人有副流感病毒-1, 你能看到这有一条带, 这是仙台病毒:是小鼠副流感病毒。
The genetic relationships are very close there. That's a lot of fun. 有很强的遗传关联,非常有趣。
So, we built out the chip. 因此,我们制作了芯片,
We made a chip that has every known virus ever discovered on it. 芯片上有每一个发现的已知病毒。
Why not? Every plant virus, every insect virus, every marine virus. 每一种植物病毒,每一种昆虫病毒,每一种海产病毒。
marine:adj.海的;海产的;海生的;海船的;n.(尤指美国或英国皇家)海军陆战队士兵;
Everything that we could get out of GenBank -- that is, the national repository of sequences. 我们可以从基因库得到每样东西, 也就是国家基因序列库。
repository:n.贮藏室,仓库;知识库;智囊团;
Now we're using this chip. And what are we using it for? 现在我们来用这个芯片。我们用它做什么？
Well, first of all, when you have a big chip like this, you need a little bit more informatics , so we designed the system to do automatic diagnosis. 首先,你有一个大的象这样的芯片, 你需要一些信息, 我们设计的这个系统是自动诊断。
informatics:n.[图情][计]信息学;情报学(复数用作单数); automatic:adj.自动的;无意识的;必然的;n.自动步枪;自动换挡汽车;
And the idea is, we simply have virtual patterns -- because we're never going to get samples of every virus; it would be virtually impossible. But we can get virtual patterns, and compare them to our observed result, 这个想法是我们仅有虚拟模式, 因为我们不可能得到每一个病毒的样本, 它是完全不可能的。但是我们能得到虚拟模式, 将它与我们观察到的结果进行比较,
virtually:adv.事实上,几乎;实质上; compare:v.比较;对比;n.比较; observed:adj.观察的;观测的;v.观察;遵守;注意到(observe的过去分词形式);
which is a very complex mixture , and come up with some sort of score of how likely it is this is a rhinovirus or something. 这是一个非常复杂的混合物,于是我们提出了某种记分法, 即它是鼻病毒或什么东西的可能性有多大。
mixture:n.混合;结合体;混合物;集合体; come up with:提出;想出;赶上;
And this is what this looks like. 这就是它看起来的样子。
If, for example, you used a cell culture that's chronically infected with papilloma , you get a little computer readout here, and our algorithm says it's probably papilloma type 18. 例如,如果你的细胞培养 用乳突病毒慢慢感染, 你得到一个计算机读出, 我们的算式表示它可能是乳突病毒18型。
chronically:adv.长期地;慢性地;习惯性地; papilloma:n.刺瘤,乳突淋瘤; readout:n.读出;读出器;
And that is, in fact, what these particular cell cultures are chronically infected with. 实际上培养细胞的病毒就是 慢性感染。
So let's do something a little bit harder. 让我们来做困难点的事吧。
We put the beeper in the clinic. 我们把蜂鸣器放在诊所里。
beeper:n.能发出哔哔声音的仪器;导弹遥控员;
When somebody shows up, and the hospital doesn't know what to do because they can't diagnose it, they call us. 病人来了,而医院不知道做什么, 因为医院无法诊断,他们就叫我们。
That's the idea, and we're setting this up in the Bay Area. 就是因为这个,我们在海湾地区装了这个东西。
And so, this case report happened three weeks ago. 这是三周前的一个病例。
We have a 28-year-old healthy woman, no travel history, 一个28岁健康女性,无旅行史,
[unclear], doesn't smoke, doesn't drink. 不抽烟喝酒,
10-day history of fevers, night sweats, bloody sputum -- she's coughing up blood -- muscle pain. 发烧10天,盗汗,血痰, 咳嗽带血,肌肉疼痛。
bloody:adj.血腥的;血淋淋的;v.血染; sputum:n.[生理]痰;唾液; muscle:n.肌肉;力量;v.加强;使劲搬动;使劲挤出;
She went to the clinic, and they gave her antibiotics , right, and then sent her home. 她来到诊所,医生给她抗生素, 然后送她回家。
antibiotics:n.抗菌素;抗生素(如青霉素);(antibiotic的复数)
She came back after ten days of fever, right -- still has the fever -- and she's hypoxic -- she doesn't have much oxygen in her lungs. 10天以后她又来了,仍然发烧, 她还缺氧——肺部缺氧。
hypoxic:含氧量低的;
They did a CT scan . 医生给她做了CT扫描。
CT scan:n."CATscan"的单数;
A normal lung is all sort of dark and black here. 正常的肺这都是暗的和黑的,
All this white stuff -- it's not good. 这些白的东西都不好。
This sort of tree and bud formation indicates there's inflammation; there's likely to be infection. 这种分支和芽胞的形成显示病人有炎症, 她有可能是感染了。
bud:n.芽,萌芽;蓓蕾;vi.发芽,萌芽;vt.使发芽; formation:n.形成;编队;组成;队形; indicates:v.表明指示,显示;(indicate的第三人称单数)
OK. So, the patient was treated then with a third-generation cephalosporin antibiotic, and doxycycline , and on day three, didn't help: she progressed to acute failure. 因此给病人用 第三代抗生素头孢菌素和强力霉素进行治疗。 第三天,没有任何作用:她发展为急性衰竭。
patient:adj.有耐心的,能容忍的;n.病人;患者; treated:v.以…态度对待;把…看作;(treat的过去分词和过去式) cephalosporin:n.[药]头孢菌素; doxycycline:n.[药物]强力霉素,脱氧土霉素,多四环素;
They had to intubate her, so they put a tube down her throat and they began to mechanically ventilate her. 医生不得不给她插管,把管子插到她的喉咙里, 开始为她机械换气。
intubate:v.把管子插进; mechanically:adv.机械地;呆板地;物理上地; ventilate:vt.使通风;给…装通风设备;宣布;
She could no longer breathe for herself. 她不能自主呼吸了。
What to do next? Don't know. 下一步做什么？不知道。
Switch antibiotics, so they switched to another antibiotic, and Tamiflu, which -- it's not clear why they thought she had the flu -- but they switched to Tamiflu. 换抗生素,然后医生就换了另一种抗生素, 然后达菲, 不清楚为什么医生认为她患了感冒, 但他们改用达菲。
And on day six, they basically threw in the towel. 第六天,他们基本放弃了。
You do an open lung biopsy when you've got no other options . 如果没有别的选择,就是打开肺部做活组织检查。
biopsy:n.活组织检查;切片检查法;v.活组织检查;切片检查法; options:n.选择; v.得到或获准进行选择; (option的三单形式)
There's an eight percent mortality rate with just doing this procedure , and so basically -- and what do they learn from it? 做这个的死亡率是8%。 但从这一步能得到什么？
mortality:n.死亡数,死亡率;必死性,必死的命运; procedure:n.步骤;手术;(商业、法律或政治上的)程序;
You're looking at her open lung biopsy. 你看她的肺部组织,
And I'm no pathologist , but you can't tell much from this. 我不是病理学家,但你从这一步也讲不出什么。
pathologist:n.病理学家;
All you can tell is, there's a lot of swelling : bronchiolitis . 你能说的也就是有许多肿胀:细支气管炎。
swelling:n.膨胀;肿胀;肿胀处;v.膨胀;肿胀;(使)鼓出;(使)增加;(swell的现在分词) bronchiolitis:n.[内科]细支气管炎;[内科]毛细支气管炎;
It was unrevealing: that's the pathologist's report. 它没有结果:这是病理学家的报告。
And so, what did they test her for? 所以,为什么进行这些检测？
They have their own tests, of course, and so they tested her for over 70 different assays , for every sort of bacteria and fungus and viral assay you can buy off the shelf: 当然,他们做了许多检测, 他们为她做了70多项检测, 对每一种细菌、真菌和病毒都进行了测定。 你从这看到的:
assays:试验; fungus:n.真菌,霉菌;菌类;
SARS, metapneumovirus, HIV , RSV -- all these. SARS、间质性肺炎病毒、HIV、RSV——所有这些。
HIV:n.艾滋病病毒;
Everything came back negative . Over 100,000 dollars worth of tests. 结果每项都是阴性。这些检测价值10万美元。
negative:adj.[数]负的;消极的;否定的;阴性的;n.否定;负数;[摄]底片;v.否定;拒绝;
I mean, they went to the max for this woman. 我是指他们为这个妇女尽了最大的努力。
And basically on hospital day eight, that's when they called us. 在医院第8天,他们叫我们去了。
They gave us endotracheal aspirate -- you know, a little fluid from the throat, from this tube that they got down there -- and they gave us this. 他们给了我们气管内吸取物, 你知道,从喉咙取的一点液体, 从这个管子里,他们下到这个部位。
endotracheal:adj.[解剖]气管内的; aspirate:vt.送气发音;吸入;adj.送气音的;n.送气音;抽出物; fluid:adj.流动的;流畅的;不固定的;n.流体;液体;
We put it on the chip; what do we see? Well, we saw parainfluenza-4. 我们把它放在芯片上,我们看到了什么？副流感病毒-4.
Well, what the hell's parainfluenza-4? 副流感病毒-4到底是什么东西？
No one tests for parainfluenza-4. No one cares about it. 没人检测过副流感病毒-4,没人关注它。
In fact, it's not even really sequenced that much. 实际上都没有对它进行过大段测序,
There's just a little bit of it sequenced. 只测了一小段。
There's almost no epidemiology or studies on it. 对它几乎也没有流行病学的研究。
epidemiology:n.流行病学;传染病学;
No one would even consider it, because no one had a clue that it could cause respiratory failure. 没人考虑过它, 因为没人知道它会造成呼吸衰竭。
clue:n.提示;迹象;(纵横填字谜、游戏或问题的)提示词语;v.提示;为…提供线索;
And why is that? Just lore . There's no data -- no data to support whether it causes severe or mild disease . 为什么会这样？只是传说,没有数据—— 没有数据支持它是造成严重的疾患还是轻微疾病。
lore:n.知识;学问;全部传说;(动物的)眼光知识; severe:adj.极为恶劣的;十分严重的;严厉的;苛刻的; mild:adj.温和的; n.(英国的一种)淡味麦芽啤酒; disease:n.病,[医]疾病;弊病;vt.传染;使…有病;
Clearly, we have a case of a healthy person that's going down. 但清楚的是我们有这样一个病例,一个健康人倒下了。
OK, that's one case report. 这是一例报道。
I'm going to tell you one last thing in the last two minutes that's unpublished -- it's going to come out tomorrow -- and it's an interesting case of how you might use this chip to find something new and open a new door. 在最后两分钟,我要告诉你们最后一件事情, 还没有公开——明天就会出来—— 是一个很有趣的例子,你如何用这个芯片 发现新的东西,打开一扇新门。
unpublished:adj.未公开出版的;未发表过的;
Prostate cancer . I don't need to give you many statistics about prostate cancer . Most of you already know it: third leading cause of cancer deaths in the US. 前列腺癌。我不需要给你许多关于 前列腺癌的统计数据,你们大多对它已经有所了解, 美国癌症第三大死因。
Prostate:adj.前列腺的;n.[解剖]前列腺; cancer:n.癌症;恶性肿瘤; statistics:n.统计数字;统计资料;统计学;(statistic的复数)
Lots of risk factors , but there is a genetic predisposition to prostate cancer. 它有许多危险因素, 其中一个是它的遗传倾向。
factors:n.因素(factor的复数); v.做代理商; predisposition:n.倾向;素质;易染病体质;
For maybe about 10 percent of prostate cancer, there are folks that are predisposed to it. 大约10%的前列腺癌患者 亲属中有这种倾向。
predisposed:adj.先有倾向的,先有意向的; v.预先有倾向的;
And the first gene that was mapped in association studies for this, early-onset prostate cancer, was this gene called RNASEL. 对早期发作的前列腺癌进行的关联性研究绘制了第一个基因图, 这个基因叫做RNASEL。
association:n.协会;关联;联想;交往; early-onset:早发型;早期的;
What is that? It's an antiviral defense enzyme . 它是什么？它是一种抗病毒防御酶。
antiviral:adj.抗病毒的;抗滤过性病原体的;n.抗病毒物质(等于antidote); enzyme:n.[生化]酶;
So, we're sitting around thinking, 我们坐在一起思考
Why would men who have the mutation , a defect in an antiviral defense system, get prostate cancer? 为什么有突变的、 抗病毒防御系统有缺陷的男人患前列腺癌？
mutation:n.[遗]突变;变化;元音变化; defect:n.缺陷;缺点;毛病;v.叛变;背叛;投敌;
It doesn't make sense -- unless, maybe, there's a virus. 这没什么意义——除非,也许是有一种病毒。
make sense:有意义;讲得通;言之有理;
So, we put tumors --- and now we have over 100 tumors -- on our array. 我们把肿瘤——现在我们有100多种肿瘤——放到芯片上,
tumors:n.肿瘤(tumor的复数);
And we know who's got defects in RNASEL and who doesn't. 我们知道谁RNASEL有缺陷,谁没有。
defects:n.缺点;瑕疵;不合格品(defect的复数);v.叛变(defect的三单形式);
And I'm showing you the signal from the chip here, and I'm showing you for the block of retroviral oligos . 我给你们看来自芯片的信号, 给你们看反转录病毒块。
retroviral:逆转录病毒的; oligos:少;
And what I'm telling you here from the signal is, that men who have a mutation in this antiviral defense enzyme, and who have a tumor, often have -- 40 percent of the time -- a signature which reveals a new retrovirus . 从这个信号中我可以告诉你们 抗病毒防御酶有突变的男人 有肿瘤的机会是40%, 这个标志显示了一种新的逆转录病毒。
reveals:v.揭示;显示;透露;展示;(reveal的第三人称单数) retrovirus:n.[病毒]逆转录酶病毒(一种致肿瘤病毒);
OK, that's pretty wild. What is it? 有点太疯狂了。它是什么？
So, we clone the whole virus. 所以我们克隆了整个病毒。
clone:v.克隆; n.克隆动物(或植物);
First of all, I'll tell you that a little automated prediction told us it was very similar to a mouse virus. 首先,自动诊断告诉我们 它与小鼠病毒非常相似。
automated:adj.自动化的;v.(使)自动化;(automate的过去式和过去分词) prediction:n.预报;预言;
But that doesn't tell us too much, so we actually clone the whole thing. 但它没有告诉我们很多, 所以实际上我们还是克隆了全部。
And the viral genome I'm showing you right here? 我在这里给你们显示这个病毒基因组？
It's a classic gamma retrovirus, but it's totally new; no one's ever seen it before. 这是一个典型的伽玛逆转录病毒,是个新的病毒, 以前没人见过它。
classic:n.名著;优秀的典范;adj.最优秀的;第一流的;有代表性的;典型的; gamma:n.微克;希腊语的第三个字母;
Its closest relative is, in fact, from mice, and so we would call this a xenotropic retrovirus, because it's infecting a species other than mice. 它最近的亲系,实际上是来自小鼠, 我们把它叫做嗜异性逆转录病毒, 它除了感染小鼠,也感染其它物种。
relative:adj.相对的;有关系的;成比例的;n.亲戚;相关物;[语]关系词;亲缘植物; infecting:v.传染;使携带病菌;使感染;(infect的现在分词)
And this is a little phylogenetic tree to see how it's related to other viruses. 这是个树形系统分类 可以看到它与其它病毒的关系。
phylogenetic:adj.[生物]系统发生的;动植物种类史的;
And then we've done it for many patients now, and we can say that they're all independent infections. 我们对许多病人都是这样做的, 我们认为他们都是独立感染的。
patients:n.接受治疗者,病人;(patient的复数) independent:adj.独立的; n.无党派议员(或候选人等);
They all have the same virus, but they're different enough that there's reason to believe that they've been independently acquired . 他们都有同一种病毒, 但又有很大的不同,而且有理由相信 都是独立获得的。
independently:adv.独立地;自立地; acquired:adj.习得的; v.获得; (acquire的过去分词和过去式)
Is it really in the tissue? And I'll end up with this. Yes. 它真的在组织里吗？我将以这个结束我的演讲。是的。
We take slices of these biopsies of tumor tissue and use material to actually locate the virus, and we find cells here with viral particles in them. 我们利用肿瘤组织切片, 放置这个病毒, 我们发现细胞里有病毒颗粒,
slices:n.切片,切割(slice的复数形式);v.切成薄片(slice的三单形式); biopsies:活组织检查; locate:v.确定…的准确地点;把…安置在(或建造于);创办于(某地); particles:n.微粒,粒子;粒子系统;碎木料(particle的复数形式);
These guys really do have this virus. 这些人的确都有这个病毒。
Does this virus cause prostate cancer? 这种病毒导致前列腺癌吗？
Nothing I'm saying here implies causality . I don't know. 我在这所说的一切都没有这个因果关系,我不知道。
implies:v.意味着(imply的第三人称单数);蕴含;暗指; causality:n.因果关系;
Is it a link to oncogenesis? I don't know. 它与肿瘤的发生有关吗？我不知道。
Is it the case that these guys are just more susceptible to viruses? 是因为这些人对病毒敏感吗？
susceptible:adj.易受影响的;易感动的;容许…的;n.易得病的人;
Could be. And it might have nothing to do with cancer. 可能是吧。对于癌症它可能什么也做不了,
have nothing to do with:与…无关;
But now it's a door. 但它是一扇门。
We have a strong association between the presence of this virus and a genetic mutation that's been linked to cancer. 这个病毒与肿瘤遗传变异之间 有很强的关联。
presence:n.存在;出席;参加;风度;仪态;
That's where we're at. 这就是现在我们所知道的。
So, it opens up more questions than it answers, I'm afraid, but that's what, you know, science is really good at. 所以我想它提出了更多的没有答案的问题, 但这就是科学所在。
This is all done by folks in the lab; 这都是我们实验室做的,
I cannot take credit for most of this. 大多数的成果我都不能居功。
This is a collaboration between myself and Don. 这是我和Don的合作。
collaboration:n.合作;勾结;通敌;
This is the guy who started the project in my lab, and this is the guy who's been doing prostate stuff. 这个人在我的实验室开始这个项目, 这个人是做前列腺研究的。
Thank you very much. 非常感谢。