TED2006
Joe DeRisi: Solving medical mysteries
乔德里西解决医学难题
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生物化学家乔德里西讲述了通过DNA诊断病毒（和治疗疾病）的新方法。他的研究可以帮助我们了解疟疾，非典，禽流感 - 以及日常生活中百分之六十的无法确诊的病毒感染。
Joe DeRisi - Biochemist
Joe DeRisi hunts for the genes that make us sick. At his lab, he works to understand the genome of Plasmodium falciparum, the deadliest form of malaria. Full bio
Joe DeRisi hunts for the genes that make us sick. At his lab, he works to understand the genome of Plasmodium falciparum, the deadliest form of malaria. Full bio
Double-click the English transcript below to play the video.
00:12
How can we investigate
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怎么说呢？我们应该如何来研究
00:15
this flora of viruses that surround us, and aid medicine?
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那些围绕在我们身边，又同时帮助医学发展的病毒？
00:20
How can we turn our cumulative knowledge of virology
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我们怎样才能把我们积累的有关病毒的知识
00:24
into a simple, hand-held, single diagnostic assay?
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变成简单、可行的方法运用到诊断中去？
00:28
I want to turn everything we know right now about detecting viruses
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我想将所有我们现在已知的有关检测病毒
00:31
and the spectrum of viruses that are out there
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和病毒图谱的方法
00:33
into, let's say, a small chip.
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变成，比如说，一块小小的芯片。
00:36
When we started thinking about this project --
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当我们开始思考这个计划时 -
00:38
how we would make a single diagnostic assay
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我就在想我们如何通过一个简单的诊断
00:41
to screen for all pathogens simultaneously --
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将所有的病原体同时检测出来 -
00:44
well, there's some problems with this idea.
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其实这个想法实施起来有一些困难。
00:46
First of all, viruses are pretty complex,
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首先，病毒是相当复杂的，
00:50
but they're also evolving very fast.
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同时它们的进化速度相当快。
00:54
This is a picornavirus.
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这是一种小核糖核酸病毒
00:55
Picornaviruses -- these are things that include
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小核糖核酸病毒包括了
00:57
the common cold and polio, things like this.
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普通感冒和小儿麻痹症之类的病症。
01:00
You're looking at the outside shell of the virus,
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你们仔细看病毒的外壳
01:02
and the yellow color here are those parts of the virus
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这些黄色的部分
01:05
that are evolving very, very fast,
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进化得很快，非常快，
01:07
and the blue parts are not evolving very fast.
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而那些蓝色的部分则进化得相对缓慢。
01:09
When people think about making pan-viral detection reagents,
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当人们想到制造泛用型病毒检测剂时
01:12
usually it's the fast-evolving problem that's an issue,
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病毒的快速演变是个问题，
01:16
because how can we detect things if they're always changing?
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因为我们如何能够对一直变化着的病毒进行检测呢？
01:18
But evolution is a balance:
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但是进化是一种平衡：
01:20
where you have fast change, you also have ultra-conservation --
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哪里有快速变化，哪里也会有超级保守 -
01:24
things that almost never change.
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有些东西几乎是不变的。
01:26
And so we looked into this a little more carefully,
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所以我们要再看仔细些，
01:29
and I'm going to show you data now.
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现在我要向你们展示一些数据。
01:30
This is just some stuff you can do on the computer from the desktop.
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这些东西你在桌子的电脑上就可以完成。
01:33
I took a bunch of these small picornaviruses,
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我将一些小核糖核酸病毒
01:35
like the common cold, like polio and so on,
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如普通感冒和小儿麻痹症等
01:37
and I just broke them down into small segments.
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分割成小的片段，
01:41
And so took this first example, which is called coxsackievirus,
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第一个例子是柯萨奇病毒，
01:44
and just break it into small windows.
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我将它们放到小玻璃片上，
01:46
And I'm coloring these small windows blue
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然后我将这些小玻璃染成蓝色
01:48
if another virus shares an identical sequence in its genome
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如果有另一个病毒有着和那个病毒相同的
01:53
to that virus.
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基因序列.
01:54
These sequences right up here --
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这里的序列——
01:56
which don't even code for protein, by the way --
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顺便说一句，这些序列甚至没有同蛋白质编码-
01:58
are almost absolutely identical across all of these,
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几乎完全与所有这些相同，
02:01
so I could use this sequence as a marker
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所以我将这个序列做为一个标记物
02:05
to detect a wide spectrum of viruses,
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来检测更多的病毒，
02:07
without having to make something individual.
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不需要再进行个别实验。
02:10
Now, over here there's great diversity:
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在那些进化迅速的地方
02:12
that's where things are evolving fast.
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你会看到很大的差异，
02:14
Down here you can see slower evolution: less diversity.
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在这里你可以看到缓慢的变化和较小的差异。
02:18
Now, by the time we get out here to, let's say,
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现在我们再看看别的，比如说
02:20
acute bee paralysis virus --
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蜜蜂急性肠道病毒
02:22
probably a bad one to have if you're a bee ---
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这应该是蜜蜂界中最严重病毒-
02:24
this virus shares almost no similarity to coxsackievirus,
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这种病毒和柯萨奇病毒几乎没有任何相似之处，
02:29
but I can guarantee you that the sequences that are most conserved
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但是我可以向你保证在右侧屏幕中的病毒中的
02:33
among these viruses on the right-hand of the screen
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最保守的基因序列
02:35
are in identical regions right up here.
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都在相同的区域里。
02:38
And so we can encapsulate these regions of ultra-conservation
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因此我们可以简述这些进化中的超保守区域 -
02:41
through evolution -- how these viruses evolved --
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这些病毒如何进化的——
02:44
by just choosing DNA elements or RNA elements
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仅通过选择这些区域的DNA或RNA片段
02:47
in these regions to represent on our chip as detection reagents.
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作为检测试剂在我们的芯片上表现出来。
02:51
OK, so that's what we did, but how are we going to do that?
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那是我们所做的，但我们如何去做呢？
02:54
Well, for a long time, since I was in graduate school,
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很长时间以来，自从我读研究生
02:56
I've been messing around making DNA chips --
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我一直在试验DNA芯片 -
02:59
that is, printing DNA on glass.
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即在玻璃上打印DNA。
03:01
And that's what you see here:
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你们看，就是这个：
03:02
These little salt spots are just DNA tacked onto glass,
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这些小的盐点是DNA留在玻璃上的印记，
03:05
and so I can put thousands of these on our glass chip
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同样我可以在玻璃芯片上放上千个盐点
03:08
and use them as a detection reagent.
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然后把它们作为检测试剂。
03:10
We took our chip over to Hewlett-Packard
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我们把芯片带到惠普公司，
03:12
and used their atomic force microscope on one of these spots,
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用他们的原子显微镜来观察其中的一个点，
03:14
and this is what you see:
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你们看到的就是这个：
03:16
you can actually see the strands of DNA lying flat on the glass here.
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你们能很清楚地看到在玻璃上的DNA链，
03:19
So, what we're doing is just printing DNA on glass --
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所以我们现在所做的就是将DNA打印在玻璃上，
03:22
little flat things -- and these are going to be markers for pathogens.
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那些又小又平的东西是要作为病原体的标记物。
03:26
OK, I make little robots in lab to make these chips,
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我在实验室里用小机器人来制造这些芯片，
03:29
and I'm really big on disseminating technology.
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我真的非常热衷于传播科技。
03:32
If you've got enough money to buy just a Camry,
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如果你刚好有钱去买一辆凯美瑞汽车，
03:35
you can build one of these too,
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那你也可以制造一个这个，
03:37
and so we put a deep how-to guide on the Web, totally free,
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我们在网站上有个免费的如何做的指南，
03:41
with basically order-off-the-shelf parts.
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附带基本的组件订购部分 -
03:43
You can build a DNA array machine in your garage.
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你可以在你的车库里生产一个DNA芯片机器。
03:46
Here's the section on the all-important emergency stop switch.
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这部分是所有重要的紧急开关。
03:49
(Laughter)
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（笑声）
03:51
Every important machine's got to have a big red button.
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每个重要的机器都有一个大的红色按钮。
03:54
But really, it's pretty robust.
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但真的，非常坚固。
03:56
You can actually be making DNA chips in your garage
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你可以在你的车库里制作DNA芯片，
03:59
and decoding some genetic programs pretty rapidly. It's a lot of fun.
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快速解码一些遗传程序。非常有趣。
04:03
(Laughter)
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（笑声）
04:04
And so what we did -- and this is a really cool project --
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所以我们做的——是一个非常酷的项目——
04:08
we just started by making a respiratory virus chip.
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我们是从制作呼吸道病毒芯片开始的。
04:10
I talked about that --
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我讲的是
04:12
you know, that situation where you go into the clinic
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你知道，那种情况，你进了诊所，
04:14
and you don't get diagnosed?
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但没有得到诊断。
04:16
Well, we just put basically all the human respiratory viruses
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好，我们刚好把所有人类呼吸道病毒
04:18
on one chip, and we threw in herpes virus for good measure --
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放在一张芯片上，然后又加入疱疹病毒以更好的测定。
04:21
I mean, why not?
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为什么不呢？
04:22
The first thing you do as a scientist is,
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作为一个科学家第一件要做的事就是
04:24
you make sure stuff works.
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确定你要做的工作。
04:25
And so what we did is, we take tissue culture cells
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我们所做的就是提取组织培养细胞，
04:28
and infect them with various viruses,
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用不同的病毒感染它们，
04:30
and we take the stuff and fluorescently label the nucleic acid,
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用荧光标记核酸，
04:34
the genetic material that comes out of these tissue culture cells --
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来自这些组织培养细胞的遗传物质——
04:37
mostly viral stuff -- and stick it on the array to see where it sticks.
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大部分是病毒类的东西——把它粘在芯片上。
04:41
Now, if the DNA sequences match, they'll stick together,
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如果DNA序列是匹配的，它们就会粘在一起，
04:43
and so we can look at spots.
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我们来看这些点。
04:45
And if spots light up, we know there's a certain virus in there.
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如果它们发亮了，我们就知道那有某种病毒。
04:47
That's what one of these chips really looks like,
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那是其中一张芯片的样子，
04:49
and these red spots are, in fact, signals coming from the virus.
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这些红点实际上是来自病毒的信号。
04:52
And each spot represents a different family of virus
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每一个点代表不同的病毒家系
04:55
or species of virus.
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或者病毒物种。
04:56
And so, that's a hard way to look at things,
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要看清它们是很困难的，
04:58
so I'm just going to encode things as a little barcode,
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所以我把它们编成小的条码，
05:00
grouped by family, so you can see the results in a very intuitive way.
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按家系分组，这样你可以直接看到结果。
05:04
What we did is, we took tissue culture cells
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我们所做的就是提取组织培养细胞，
05:06
and infected them with adenovirus,
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用腺病毒感染，
05:08
and you can see this little yellow barcode next to adenovirus.
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你可以在腺病毒旁边看到这个小的黄色条码。
05:12
And, likewise, we infected them with parainfluenza-3 --
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同样我们用副流感病毒-3感染———
05:15
that's a paramyxovirus -- and you see a little barcode here.
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它是副粘病毒——你在这看到小的条码。
05:17
And then we did respiratory syncytial virus.
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然后我们又用呼吸道合胞病毒。
05:20
That's the scourge of daycare centers everywhere --
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这是所有日托中心的灾难——
05:22
it's like boogeremia, basically.
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大体上说就象是鼻粘膜病。
05:24
(Laughter)
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（笑声）
05:25
You can see that this barcode is the same family,
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你能看到这个条码是同一家系的，
05:29
but it's distinct from parainfluenza-3,
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但它与副流感病毒-3不同，
05:31
which gives you a very bad cold.
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它会使你患非常严重的感冒。
05:33
And so we're getting unique signatures, a fingerprint for each virus.
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所以我们要有独特的标记，每一种病毒都有一种指纹。
05:36
Polio and rhino: they're in the same family, very close to each other.
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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。
05:39
Rhino's the common cold, and you all know what polio is,
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鼻病毒是普通感冒，你们都知道小儿麻痹是什么，
05:41
and you can see that these signatures are distinct.
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你们可以看到这些标记是不同的。
05:44
And Kaposi's sarcoma-associated herpes virus
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和卡波济氏肉瘤相关的疱疹病毒
05:47
gives a nice signature down here.
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底端有很好的标记。
05:49
And so it is not any one stripe or something
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所以不是一条带或是什么东西
05:51
that tells me I have a virus of a particular type here;
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来告诉我说这里有一个特殊的病毒；
05:53
it's the barcode that in bulk represents the whole thing.
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是大量的条码代表整体。
05:57
All right, I can see a rhinovirus --
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我能看到鼻病毒，
05:59
and here's the blow-up of the rhinovirus's little barcode --
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这是放大的鼻病毒的小条码，
06:01
but what about different rhinoviruses?
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那么不同的鼻病毒呢？
06:03
How do I know which rhinovirus I have?
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我怎么知道我有哪种鼻病毒？
06:05
There're 102 known variants of the common cold,
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已知普通感冒有102种变异，
06:08
and there're only 102 because people got bored collecting them:
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仅仅只有102种是因为人们已经厌倦去收集它们了，
06:11
there are just new ones every year.
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每年都有新的。
06:13
And so, here are four different rhinoviruses,
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这里有4种不同的鼻病毒，
06:15
and you can see, even with your eye,
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你可以看到，即使用你的眼睛就可以，
06:17
without any fancy computer pattern-matching
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而不用任何计算机模式匹配
06:19
recognition software algorithms,
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识别软件，
06:21
that you can distinguish each one of these barcodes from each other.
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你就可以区分这些条码。
06:24
Now, this is kind of a cheap shot,
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这是某种划算的作法，
06:26
because I know what the genetic sequence of all these rhinoviruses is,
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因为我知道所有这些鼻病毒的遗传序列，
06:29
and I in fact designed the chip
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并且实际上我设计了芯片
06:30
expressly to be able to tell them apart,
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能够明确地区分它们，
06:32
but what about rhinoviruses that have never seen a genetic sequencer?
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但对于还不知道遗传序列的鼻病毒怎么办呢？
06:36
We don't know what the sequence is; just pull them out of the field.
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我们不知道它的序列，那就不要做它们。
06:38
So, here are four rhinoviruses
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这是4个鼻病毒
06:40
we never knew anything about --
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我们对此一无所知，
06:42
no one's ever sequenced them -- and you can also see
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没有人对它们做过测序，你也能看到
06:45
that you get unique and distinguishable patterns.
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你得到了独特的且可识别的格局。
06:47
You can imagine building up some library, whether real or virtual,
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你可以想象建立一个资料室，无论是真实的或是虚拟的，
06:50
of fingerprints of essentially every virus.
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收藏基本病毒的指纹。
06:52
But that's, again, shooting fish in a barrel, you know, right?
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但这又是瓮中捉鳖，对吧？
06:55
You have tissue culture cells. There are a ton of viruses.
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你有组织培养细胞：有大量的病毒。
06:57
What about real people?
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那么人呢？
06:59
You can't control real people, as you probably know.
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你控制不了人，就象你所知道的。
07:01
You have no idea what someone's going to cough into a cup,
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你不知道某个人会往杯子里咳出什么东西，
07:05
and it's probably really complex, right?
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它可能非常复杂，对不对？
07:08
It could have lots of bacteria, it could have more than one virus,
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可能有许多细菌，可能有一种以上的病毒，
07:11
and it certainly has host genetic material.
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它肯定有宿主遗传物质，
07:13
So how do we deal with this?
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对此我们怎么办？
07:14
And how do we do the positive control here?
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我们如何做阳性对照？
07:16
Well, it's pretty simple.
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非常简单。
07:18
That's me, getting a nasal lavage.
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要是我就做鼻灌洗。
07:20
And the idea is, let's experimentally inoculate people with virus.
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这个想法就是我们实验性地用病毒给人们接种，
07:25
This is all IRB-approved, by the way; they got paid.
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这是经人体实验委员会批准的，他们是拿薪水的。
07:30
And basically we experimentally inoculate people
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简单讲我们用普通感冒病毒
07:33
with the common cold virus.
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给人接种。
07:34
Or, even better, let's just take people
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或者更好的是我们把人们
07:36
right out of the emergency room --
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从急诊室解救出来，
07:37
undefined, community-acquired respiratory tract infections.
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——未明确的群体获得性呼吸道感染。
07:41
You have no idea what walks in through the door.
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你不知道什么会从那个门进来，
07:43
So, let's start off with the positive control first,
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所以让我们以阳性对照开始，
07:46
where we know the person was healthy.
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我们知道某人是健康的。
07:48
They got a shot of virus up the nose,
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他们的鼻子受到病毒的袭击，
07:50
let's see what happens.
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让我们看发生了什么。
07:51
Day zero: nothing happening.
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当天：什么都没发生。
07:53
They're healthy; they're clean -- it's amazing.
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他们仍然是健康的，清洁的——很奇怪。
07:55
Actually, we thought the nasal tract might be full of viruses
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实际上我们认为他们的鼻道会充满病毒，
07:57
even when you're walking around healthy.
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即使你是在健康人周围走动。
07:58
It's pretty clean. If you're healthy, you're pretty healthy.
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它相当清洁，如果你是健康的，你是相当健康。
08:00
Day two: we get a very robust rhinovirus pattern,
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第二天：我们得到了很强的鼻病毒模式，
08:04
and it's very similar to what we get in the lab
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与我们在实验室做组织培养实验
08:06
doing our tissue culture experiment.
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得到的非常相似。
08:07
So that's great, but again, cheap shot, right?
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很好，这又是划算的作法，对吧？
08:10
We put a ton of virus up this guy's nose. So --
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我们在这个人的鼻子里放大量的病毒，
08:12
(Laughter)
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（笑声）
08:13
-- I mean, we wanted it to work. He really had a cold.
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我指，我们希望能这样。他真的感冒了。
08:17
So, how about the people who walk in off the street?
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走过这条街的人会怎么样？
08:21
Here are two individuals represented by their anonymous ID codes.
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这里的两个人各自用他们的身份识别码代表，
08:23
They both have rhinoviruses; we've never seen this pattern in lab.
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他们都有鼻病毒，我们在实验室从未见过这种类型。
08:27
We sequenced part of their viruses;
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我们做了部分测序，
08:29
they're new rhinoviruses no one's actually even seen.
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它们是新的鼻病毒，没人见过。
08:32
Remember, our evolutionary-conserved sequences
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记住，我们在这个芯片上所用的
08:34
we're using on this array allow us to detect
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进化—保守序列使我们能够检测出
08:36
even novel or uncharacterized viruses,
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新的或无特征的病毒，
08:38
because we pick what is conserved throughout evolution.
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因为我们是从整个进化中挑出的保守序列。
08:42
Here's another guy. You can play the diagnosis game yourself here.
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这是另一个人。你可以自己在这玩诊断游戏。
08:45
These different blocks represent
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这些不同的块代表
08:47
the different viruses in this paramyxovirus family,
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副粘病毒系中不同的病毒，
08:49
so you can kind of go down the blocks
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你可以在这些块下面
08:50
and see where the signal is.
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看到信号在哪里。
08:52
Well, doesn't have canine distemper; that's probably good.
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没有犬瘟热，那样可能不错。
08:55
(Laughter)
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（笑声）
08:57
But by the time you get to block nine,
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但当你看到第9块时，
08:59
you see that respiratory syncytial virus.
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你可以看到呼吸合胞病毒。
09:01
Maybe they have kids. And then you can see, also,
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也许它们有后代了。你也可以看到
09:04
the family member that's related: RSVB is showing up here.
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与其相关的家系成员：RSVB在这里出现了。
09:06
So, that's great.
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太好了。
09:07
Here's another individual, sampled on two separate days --
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这是另外一个人，分2天抽取了血样，
09:10
repeat visits to the clinic.
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他反复到诊所来。
09:12
This individual has parainfluenza-1,
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这人有副流感病毒-1，
09:15
and you can see that there's a little stripe over here
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你能看到这有一条带，
09:17
for Sendai virus: that's mouse parainfluenza.
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这是仙台病毒：是小鼠副流感病毒。
09:20
The genetic relationships are very close there. That's a lot of fun.
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有很强的遗传关联，非常有趣。
09:24
So, we built out the chip.
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因此，我们制作了芯片，
09:25
We made a chip that has every known virus ever discovered on it.
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芯片上有每一个发现的已知病毒。
09:29
Why not? Every plant virus, every insect virus, every marine virus.
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每一种植物病毒，每一种昆虫病毒，每一种海产病毒。
09:32
Everything that we could get out of GenBank --
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我们可以从基因库得到每样东西，
09:34
that is, the national repository of sequences.
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也就是国家基因序列库。
09:36
Now we're using this chip. And what are we using it for?
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现在我们来用这个芯片。我们用它做什么？
09:39
Well, first of all, when you have a big chip like this,
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首先，你有一个大的象这样的芯片，
09:41
you need a little bit more informatics,
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你需要一些信息，
09:43
so we designed the system to do automatic diagnosis.
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我们设计的这个系统是自动诊断。
09:45
And the idea is that we simply have virtual patterns,
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这个想法是我们仅有虚拟模式，
09:48
because we're never going to get samples of every virus --
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因为我们不可能得到每一个病毒的样本，
09:50
it would be virtually impossible. But we can get virtual patterns,
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它是完全不可能的。但是我们能得到虚拟模式，
09:53
and compare them to our observed result --
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将它与我们观察到的结果进行比较，
09:55
which is a very complex mixture -- and come up with some sort of score
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这是一个非常复杂的混合物，于是我们提出了某种记分法，
09:59
of how likely it is this is a rhinovirus or something.
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即它是鼻病毒或什么东西的可能性有多大。
10:02
And this is what this looks like.
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这就是它看起来的样子。
10:04
If, for example, you used a cell culture
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例如，如果你的细胞培养
10:06
that's chronically infected with papilloma,
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用乳突病毒慢慢感染，
10:08
you get a little computer readout here,
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你得到一个计算机读出，
10:10
and our algorithm says it's probably papilloma type 18.
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我们的算式表示它可能是乳突病毒18型。
10:14
And that is, in fact, what these particular cell cultures
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实际上培养细胞的病毒就是
10:16
are chronically infected with.
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慢性感染。
10:18
So let's do something a little bit harder.
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让我们来做困难点的事吧。
10:20
We put the beeper in the clinic.
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我们把蜂鸣器放在诊所里。
10:21
When somebody shows up, and the hospital doesn't know what to do
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病人来了，而医院不知道做什么，
10:24
because they can't diagnose it, they call us.
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因为医院无法诊断，他们就叫我们。
10:26
That's the idea, and we're setting this up in the Bay Area.
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就是因为这个，我们在海湾地区装了这个东西。
10:28
And so, this case report happened three weeks ago.
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这是三周前的一个病例。
10:30
We have a 28-year-old healthy woman, no travel history,
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一个28岁健康女性，无旅行史，
10:33
[unclear], doesn't smoke, doesn't drink.
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不抽烟喝酒，
10:36
10-day history of fevers, night sweats, bloody sputum --
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发烧10天，盗汗，血痰，
10:40
she's coughing up blood -- muscle pain.
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咳嗽带血，肌肉疼痛。
10:42
She went to the clinic, and they gave her antibiotics
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她来到诊所，医生给她抗生素，
10:46
and then sent her home.
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然后送她回家。
10:47
She came back after ten days of fever, right? Still has the fever,
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10天以后她又来了，仍然发烧，
10:51
and she's hypoxic -- she doesn't have much oxygen in her lungs.
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她还缺氧——肺部缺氧。
10:54
They did a CT scan.
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医生给她做了CT扫描。
10:55
A normal lung is all sort of dark and black here.
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正常的肺这都是暗的和黑的，
10:59
All this white stuff -- it's not good.
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这些白的东西都不好。
11:01
This sort of tree and bud formation indicates there's inflammation;
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这种分支和芽胞的形成显示病人有炎症，
11:04
there's likely to be infection.
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她有可能是感染了。
11:06
OK. So, the patient was treated then
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因此给病人用
11:09
with a third-generation cephalosporin antibiotic and doxycycline,
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第三代抗生素头孢菌素和强力霉素进行治疗。
11:13
and on day three, it didn't help: she had progressed to acute failure.
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第三天，没有任何作用：她发展为急性衰竭。
11:17
They had to intubate her, so they put a tube down her throat
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医生不得不给她插管，把管子插到她的喉咙里，
11:20
and they began to mechanically ventilate her.
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开始为她机械换气。
11:21
She could no longer breathe for herself.
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她不能自主呼吸了。
11:23
What to do next? Don't know.
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下一步做什么？不知道。
11:25
Switch antibiotics: so they switched to another antibiotic,
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换抗生素，然后医生就换了另一种抗生素，
11:28
Tamiflu.
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然后达菲，
11:30
It's not clear why they thought she had the flu,
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不清楚为什么医生认为她患了感冒，
11:32
but they switched to Tamiflu.
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但他们改用达菲。
11:34
And on day six, they basically threw in the towel.
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第六天，他们基本放弃了。
11:36
You do an open lung biopsy when you've got no other options.
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如果没有别的选择，就是打开肺部做活组织检查。
11:40
There's an eight percent mortality rate with just doing this procedure,
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做这个的死亡率是8%。
11:42
and so basically -- and what do they learn from it?
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但从这一步能得到什么？
11:45
You're looking at her open lung biopsy.
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你看她的肺部组织，
11:47
And I'm no pathologist, but you can't tell much from this.
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我不是病理学家，但你从这一步也讲不出什么。
11:49
All you can tell is, there's a lot of swelling: bronchiolitis.
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你能说的也就是有许多肿胀：细支气管炎。
11:52
It was "unrevealing": that's the pathologist's report.
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它没有结果：这是病理学家的报告。
11:55
And so, what did they test her for?
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所以，为什么进行这些检测？
11:58
They have their own tests, of course,
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当然，他们做了许多检测，
11:59
and so they tested her for over 70 different assays,
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他们为她做了70多项检测，
12:02
for every sort of bacteria and fungus and viral assay
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对每一种细菌、真菌和病毒都进行了测定。
12:05
you can buy off the shelf:
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你从这看到的：
12:07
SARS, metapneumovirus, HIV, RSV -- all these.
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SARS、间质性肺炎病毒、HIV、RSV——所有这些。
12:10
Everything came back negative, over 100,000 dollars worth of tests.
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结果每项都是阴性。这些检测价值10万美元。
12:14
I mean, they went to the max for this woman.
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我是指他们为这个妇女尽了最大的努力。
12:17
And basically on hospital day eight, that's when they called us.
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在医院第8天，他们叫我们去了。
12:20
They gave us endotracheal aspirate --
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他们给了我们气管内吸取物，
12:22
you know, a little fluid from the throat,
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你知道，从喉咙取的一点液体，
12:24
from this tube that they got down there -- and they gave us this.
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从这个管子里，他们下到这个部位。
12:26
We put it on the chip; what do we see? Well, we saw parainfluenza-4.
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我们把它放在芯片上，我们看到了什么？副流感病毒-4.
12:31
Well, what the hell's parainfluenza-4?
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副流感病毒-4到底是什么东西？
12:33
No one tests for parainfluenza-4. No one cares about it.
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没人检测过副流感病毒-4，没人关注它。
12:36
In fact, it's not even really sequenced that much.
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实际上都没有对它进行过大段测序，
12:39
There's just a little bit of it sequenced.
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只测了一小段。
12:41
There's almost no epidemiology or studies on it.
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对它几乎也没有流行病学的研究。
12:43
No one would even consider it,
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没人考虑过它，
12:45
because no one had a clue that it could cause respiratory failure.
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因为没人知道它会造成呼吸衰竭。
12:48
And why is that? Just lore. There's no data --
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为什么会这样？只是传说，没有数据——
12:51
no data to support whether it causes severe or mild disease.
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没有数据支持它是造成严重的疾患还是轻微疾病。
12:55
Clearly, we have a case of a healthy person that's going down.
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但清楚的是我们有这样一个病例，一个健康人倒下了。
12:58
OK, that's one case report.
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这是一例报道。
13:01
I'm going to tell you one last thing in the last two minutes
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在最后两分钟，我要告诉你们最后一件事情，
13:03
that's unpublished -- it's going to come out tomorrow --
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还没有公开——明天就会出来——
13:06
and it's an interesting case of how you might use this chip
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是一个很有趣的例子，你如何用这个芯片
13:09
to find something new and open a new door.
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发现新的东西，打开一扇新门。
13:11
Prostate cancer. I don't need to give you many statistics
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前列腺癌。我不需要给你许多关于
13:15
about prostate cancer. Most of you already know it:
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前列腺癌的统计数据，你们大多对它已经有所了解，
13:18
third leading cause of cancer deaths in the U.S.
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美国癌症第三大死因。
13:20
Lots of risk factors,
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它有许多危险因素，
13:22
but there is a genetic predisposition to prostate cancer.
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其中一个是它的遗传倾向。
13:26
For maybe about 10 percent of prostate cancer,
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大约10%的前列腺癌患者
13:28
there are folks that are predisposed to it.
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亲属中有这种倾向。
13:30
And the first gene that was mapped in association studies
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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，
13:34
for this, early-onset prostate cancer, was this gene called RNASEL.
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这个基因叫做RNASEL。
13:38
What is that? It's an antiviral defense enzyme.
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它是什么？它是一种抗病毒防御酶。
13:41
So, we're sitting around and thinking,
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我们坐在一起思考
13:43
"Why would men who have the mutation --
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为什么有突变的、
13:45
a defect in an antiviral defense system -- get prostate cancer?
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抗病毒防御系统有缺陷的男人患前列腺癌？
13:50
It doesn't make sense -- unless, maybe, there's a virus?"
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这没什么意义——除非，也许是有一种病毒。
13:53
So, we put tumors --- and now we have over 100 tumors -- on our array.
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我们把肿瘤——现在我们有100多种肿瘤——放到芯片上，
13:59
And we know who's got defects in RNASEL and who doesn't.
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我们知道谁RNASEL有缺陷，谁没有。
14:02
And I'm showing you the signal from the chip here,
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我给你们看来自芯片的信号，
14:05
and I'm showing you for the block of retroviral oligos.
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给你们看反转录病毒块。
14:09
And what I'm telling you here from the signal, is
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从这个信号中我可以告诉你们
14:11
that men who have a mutation in this antiviral defense enzyme,
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抗病毒防御酶有突变的男人
14:15
and have a tumor, often have -- 40 percent of the time --
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有肿瘤的机会是40%，
14:19
a signature which reveals a new retrovirus.
327
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这个标志显示了一种新的逆转录病毒。
14:23
OK, that's pretty wild. What is it?
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有点太疯狂了。它是什么？
14:26
So, we clone the whole virus.
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所以我们克隆了整个病毒。
14:27
First of all, I'll tell you that a little automated prediction told us
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首先，自动诊断告诉我们
14:31
it was very similar to a mouse virus.
331
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它与小鼠病毒非常相似。
14:33
But that doesn't tell us too much,
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但它没有告诉我们很多，
14:34
so we actually clone the whole thing.
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所以实际上我们还是克隆了全部。
14:36
And the viral genome I'm showing you right here?
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我在这里给你们显示这个病毒基因组？
14:38
It's a classic gamma retrovirus, but it's totally new;
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这是一个典型的伽玛逆转录病毒，是个新的病毒，
14:41
no one's ever seen it before.
336
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以前没人见过它。
14:42
Its closest relative is, in fact, from mice,
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它最近的亲系，实际上是来自小鼠，
14:45
and so we would call this a xenotropic retrovirus,
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我们把它叫做嗜异性逆转录病毒，
14:49
because it's infecting a species other than mice.
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它除了感染小鼠，也感染其它物种。
14:52
And this is a little phylogenetic tree
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这是个树形系统分类
14:54
to see how it's related to other viruses.
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可以看到它与其它病毒的关系。
14:56
We've done it for many patients now,
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我们对许多病人都是这样做的，
14:59
and we can say that they're all independent infections.
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我们认为他们都是独立感染的。
15:02
They all have the same virus,
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他们都有同一种病毒，
15:03
but they're different enough that there's reason to believe
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但又有很大的不同，而且有理由相信
15:06
that they've been independently acquired.
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都是独立获得的。
15:08
Is it really in the tissue? And I'll end up with this: yes.
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它真的在组织里吗？我将以这个结束我的演讲。是的。
15:10
We take slices of these biopsies of tumor tissue
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我们利用肿瘤组织切片，
15:13
and use material to actually locate the virus,
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放置这个病毒，
15:15
and we find cells here with viral particles in them.
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我们发现细胞里有病毒颗粒，
15:19
These guys really do have this virus.
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这些人的确都有这个病毒。
15:21
Does this virus cause prostate cancer?
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这种病毒导致前列腺癌吗？
15:23
Nothing I'm saying here implies causality. I don't know.
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我在这所说的一切都没有这个因果关系，我不知道。
15:27
Is it a link to oncogenesis? I don't know.
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它与肿瘤的发生有关吗？我不知道。
15:29
Is it the case that these guys are just more susceptible to viruses?
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是因为这些人对病毒敏感吗？
15:33
Could be. And it might have nothing to do with cancer.
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可能是吧。对于癌症它可能什么也做不了，
15:36
But now it's a door.
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但它是一扇门。
15:37
We have a strong association between the presence of this virus
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这个病毒与肿瘤遗传变异之间
15:40
and a genetic mutation that's been linked to cancer.
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有很强的关联。
15:43
That's where we're at.
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这就是现在我们所知道的。
15:44
So, it opens up more questions than it answers, I'm afraid,
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所以我想它提出了更多的没有答案的问题，
15:48
but that's what, you know, science is really good at.
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但这就是科学所在。
15:50
This was all done by folks in the lab --
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这都是我们实验室做的，
15:52
I cannot take credit for most of this.
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大多数的成果我都不能居功。
15:53
This is a collaboration between myself and Don.
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这是我和Don的合作。
15:54
This is the guy who started the project in my lab,
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这个人在我的实验室开始这个项目，
15:57
and this is the guy who's been doing prostate stuff.
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这个人是做前列腺研究的。
15:59
Thank you very much. (Applause)
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非常感谢。
ABOUT THE SPEAKER
Joe DeRisi - BiochemistJoe DeRisi hunts for the genes that make us sick. At his lab, he works to understand the genome of Plasmodium falciparum, the deadliest form of malaria.
Why you should listen
Joseph DeRisi is a molecular biologist and biochemist, on the hunt for the genomic basis of illness. His lab at UCSF is focused on the cause of malaria, and he's also poked into SARS, avian flu and other new diseases as they crop up. His approach combines scientific rigor with a nerd's boundary-breaking enthusiasm for new techniques -- one of the qualities that helped him win a MacArthur "genius" grant in 2004. A self-confessed computer geek, DeRisi designed and programmed a groundbreaking tool for finding (and fighting) viruses -- the ViroChip, a DNA microarray that test for the presence of all known viruses in one step.
In 2008, DeRisi won the Heinz Award for Technology, the Economy and Employment.
Joe DeRisi | Speaker | TED.com