1.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？
2.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？
3.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。
4.When we started thinking about this project — how we would make a single diagnostic assay to screen for all pathogens simultaneously —
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 –
5.well, there’s some problems with this idea.
其实这个想法实施起来有一些困难。
6.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。
7.This is a picornavirus.
这是一种小核糖核酸病毒
8.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。
9.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,
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，
10.and the blue parts are not evolving very fast.
而那些蓝色的部分则进化得相对缓慢。
11.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？
12.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。
13.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。
14.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。
15.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,
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，
16.and so took this first example, which is called Coxsackievirus, and just break it into small windows.
第一个例子是柯萨奇病毒， 我将它们放到小玻璃片上，
17.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.
18.These sequences right up here — which don’t even code for protein, by the way — are almost absolutely identical across all of these,
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，
19.so I could use this sequence as a marker to detect a wide spectrum of viruses, without having to make something individual.
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。
20.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，
21.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。
22.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，
23.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。
24.And so we can encapsulate these regions of ultra-conservation through evolution — how these viruses evolved — by just choosing DNA elements or RNA elements
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
25.in these regions to represent on our chip as detection reagents.
作为检测试剂在我们的芯片上表现出来。
26.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？
27.Well, for a long time, since I was in graduate school, I’ve been messing around making DNA chips — that is, printing DNA on glass.
很长时间以来，自从我读研究生 我一直在试验DNA芯片 – 即在玻璃上打印DNA。
28.And that’s what you see here: These little salt spots are just DNA tacked onto glass, and so I can put thousands of these on our glass chip
你们看，就是这个： 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
29.and use them as a detection reagent.
然后把它们作为检测试剂。
30.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，
31.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。
32.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。
33.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,
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，
34.with basically order-off-the-shelf parts — you can build a DNA array machine in your garage.
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。
35.Here’s the section on the all-important emergency stop switch.
这部分是所有重要的紧急开关。
36.(Laughter) Every important machine’s got to have a big red button.
（笑声） 每个重要的机器都有一个大的红色按钮。
37.But really, it’s pretty robust.
但真的，非常坚固。
38.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。
39.(Laughter) And so what we did — and this is a really cool project — we just started by making a respiratory virus chip.
（笑声） 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。
40.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。
41.Well, we just put basically all the human respiratory viruses on one chip, and we threw in herpes virus for good measure — I mean, why not?
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。 为什么不呢？
42.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。
43.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，
44.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。
45.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。
46.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。
47.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。
48.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。
49.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。
50.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。
51.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。
52.And then we did respiratory syncytial virus.
然后我们又用呼吸道合胞病毒。
53.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。
54.(Laughter) 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.
（笑声） 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。
55.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。
56.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。
57.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。
58.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。
59.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。
60.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？
61.How do I know which rhinovirus I have?
我怎么知道我有哪种鼻病毒？
62.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。
63.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,
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，
64.that you can distinguish each one of these barcodes from each other.
你就可以区分这些条码。
65.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
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
66.expressly to be able to tell them apart, but what about rhinoviruses that have never seen a genetic sequencer?
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？
67.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。
68.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。
69.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。
70.But that’s, again, shooting fish in a barrel, you know, right?
但这又是瓮中捉鳖，对吧？
71.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。
72.What about real people?
那么人呢？
73.You can’t control real people, as you probably know.
你控制不了人，就象你所知道的。
74.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？
75.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？
76.And how do we do the positive control here?
我们如何做阳性对照？
77.Well, it’s pretty simple.
非常简单。
78.That’s me, getting a nasal lavage.
要是我就做鼻灌洗。
79.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。
80.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。
81.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。
82.You have no idea what walks in through the door.
你不知道什么会从那个门进来，
83.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。
84.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。
85.Day zero: nothing happening.
当天：什么都没发生。
86.They’re healthy; they’re clean — it’s amazing.
他们仍然是健康的，清洁的——很奇怪。
87.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。
88.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。
89.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。
90.So that’s great, but again, cheap shot, right?
很好，这又是划算的作法，对吧？
91.We put a ton of virus up this guy’s nose. So — (Laughter) — I mean, we wanted it to work. I mean, he really had a cold.
我们在这个人的鼻子里放大量的病毒， （笑声） 我指，我们希望能这样。他真的感冒了。
92.So, how about the people who walk in off the street?
走过这条街的人会怎么样？
93.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，
94.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。
95.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。
96.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。
97.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。
98.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。
99.Well, doesn’t have canine distemper; that’s probably good.
没有犬瘟热，那样可能不错。
100.(Laughter) But by the time you get to block nine, you see that respiratory syncytial virus.
（笑声） 但当你看到第9块时， 你可以看到呼吸合胞病毒。
101.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。
102.So, that’s great.
太好了。
103.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。
104.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。
105.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。
106.So, we built out the chip.
因此，我们制作了芯片，
107.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。
108.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。
109.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。
110.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？
111.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。
112.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,
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，
113.and compare them to our observed result, 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.
将它与我们观察到的结果进行比较， 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。
114.And this is what this looks like.
这就是它看起来的样子。
115.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。
116.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。
117.So let’s do something a little bit harder.
让我们来做困难点的事吧。
118.We put the beeper in the clinic.
我们把蜂鸣器放在诊所里。
119.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。
120.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。
暂无讨论，说说你的看法吧
