TEDxBoston 2011
Jay Bradner: Open-source cancer research
杰•博拉德哪尔：开发源码式癌症研究
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癌症如何知道它是癌症？杰•博拉德哪尔的实验室发现了一种可以解答这个问题的分子JQ1.杰的实验室不但没有专利注册JQ1,反而把他们的发现发表出来，并为40所其他实验室寄出样本以便试验使用。这是一个激励未来开发源码式癌症研究的最新展望。
Jay Bradner - Research scientist
In his lab, Jay Bradner, a researcher at Harvard and Dana Farber in Boston, works on a breakthrough approach for subverting cancer .. and he’s giving the secret away. Full bio
In his lab, Jay Bradner, a researcher at Harvard and Dana Farber in Boston, works on a breakthrough approach for subverting cancer .. and he’s giving the secret away. Full bio
Double-click the English transcript below to play the video.
00:15
I moved to Boston 10 years ago, from Chicago,
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我在十年前从芝加哥搬到波士顿
00:19
with an interest in cancer and in chemistry.
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有心研究癌症和化学
00:22
You might know that chemistry is the science of making molecules --
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你们可能知道化学是门研究分子形成的科学
00:25
or to my taste, new drugs for cancer.
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但对我是门研究癌症药物的学问
00:29
And you might also know that, for science and medicine,
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你们也可能知道对科学和医药来说
00:32
Boston is a bit of a candy store.
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波士顿有点像糖果店
00:35
You can't roll a stop sign in Cambridge
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在波士顿剑桥区的每一个十字路口
00:38
without hitting a graduate student.
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你都会碰到至少一名研究生
00:40
The bar is called the Miracle of Science.
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在那里有叫科学奇迹的酒吧
00:42
The billboards say "Lab Space Available."
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有叫“出租实验室”的广告牌
00:46
And it's fair to say that in these 10 years,
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可以说这是近十年较常见的
00:48
we've witnessed absolutely the start
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其实这仅仅是我们所看到的
00:51
of a scientific revolution -- that of genome medicine.
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一个科学进化的结果，遗传基因科学的开始
00:54
We know more about the patients that enter our clinic now
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我们现在对来我们实验室的患者
00:56
than ever before.
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要比以前知道得多
00:58
And we're able, finally, to answer the question
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我们终于可以回答
01:00
that's been so pressing for so many years:
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这个困扰我们多年的问题
01:03
why do I have cancer?
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那就是，我为什么得癌症？
01:06
This information is also pretty staggering.
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这个问题的答案比较复杂
01:08
You might know that,
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你们也许已经知道
01:10
so far in just the dawn of this revolution,
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至此在这科学革命之黎明
01:12
we know that there are perhaps 40,000 unique mutations
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我们知道大约有四万种基因变异
01:15
affecting more than 10,000 genes,
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影响大约一万个基因
01:18
and that there are 500 of these genes
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这一万个基因中大约有五百个基因
01:20
that are bona-fide drivers,
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是可恶变的
01:22
causes of cancer.
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致癌的
01:24
Yet comparatively,
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相比之下
01:26
we have about a dozen targeted medications.
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我们只有大约十几个有针对性的治疗方法
01:29
And this inadequacy of cancer medicine
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我对这种癌症治疗不足性的认识
01:32
really hit home when my father was diagnosed
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深有体会是在我父亲被诊断为
01:34
with pancreatic cancer.
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胰腺癌
01:37
We didn't fly him to Boston.
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当时我们没有让他飞到波士顿
01:39
We didn't sequence his genome.
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我们没有测试他的基因顺序
01:41
It's been known for decades
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因为多年来人类已知
01:43
what causes this malignancy.
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基因变异原因
01:45
It's three proteins --
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是三种蛋白质
01:47
Ras, Myc and P53.
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Ras, MIC 和 P53
01:50
This is old information we've known since about the 80s,
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这是我们从八十年代就已经知道的老信息了，
01:53
yet there's no medicine I can prescribe
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但至今我仍然没有药方
01:55
to a patient with this
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可以开给患者
01:57
or any of the numerous solid tumors
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不论是什么大肿瘤
01:59
caused by these three horsemen
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由以上三种蛋白质引起的
02:01
of the apocalypse that is cancer.
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癌症
02:04
There's no Ras, no Myc, no P53 drug.
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没有针对Ras, MIC或P53的药物
02:07
And you might fairly ask: why is that?
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那么你可能要问：为什么会这样？
02:09
And the very unsatisfying, yet scientific, answer
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一个不令人满意的但科学的回答是
02:12
is it's too hard.
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它太难了
02:14
That for whatever reason,
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也就是说，不管什么原因
02:16
these three proteins have entered a space in the language of our field
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这三种蛋白质被这个领域称为
02:19
that's called the undruggable genome --
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无药可治的基因－－
02:21
which is like calling a computer unsurfable
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就像一台不能上网的电脑
02:23
or the Moon unwalkable.
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或者是无法行走的月球
02:25
It's a horrible term of trade.
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这是行业里很可怕的词汇
02:27
But what it means
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但它意味着
02:29
is that we fail to identify a greasy pocket in these proteins,
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我们是否无法辨别有害蛋白质
02:31
into which we, like molecular locksmiths,
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就像在锁定分子
02:34
can fashion an active, small, organic molecule
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可以演变成小段活动有机分子一样
02:37
or drug substance.
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或者是药物替代品
02:39
Now as I was training in clinical medicine
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现在我受训于临床医学，
02:41
and hematology and oncology
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血液学，肿瘤学
02:43
and stem cell transplantation,
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及干细胞移植
02:45
what we had instead,
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我们有的是
02:47
cascading through the regulatory network at the FDA,
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从美国食品和药物管理局批下来的
02:50
were these substances --
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这些药物，包括
02:52
arsenic, thalidomide
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砷， 莎利宝迈
02:54
and this chemical derivative
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及化学引发物来自
02:56
of nitrogen mustard gas.
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氮糜爛性的芥氣
02:58
And this is the 21st century.
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我们已经是处在21世纪了
03:01
And so, I guess you'd say, dissatisfied
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我想你们应该不满于
03:03
with the performance and quality of these medicines,
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今天的医学表现和质量
03:05
I went back to school in chemistry
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我因此回到了化学学院
03:08
with the idea
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想到
03:10
that perhaps by learning the trade of discovery chemistry
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也许通过化学发现
03:13
and approaching it in the context of this brave new world
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进入这个新的领域
03:16
of the open-source,
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以开发源码式，
03:18
the crowd-source,
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群体合作式，
03:20
the collaborative network that we have access to within academia,
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通过一个学术研发合作网络
03:23
that we might more quickly
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我们也许可以更快地
03:25
bring powerful and targeted therapies
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把有效的和有目标的治疗方法
03:27
to our patients.
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带给我们的患者
03:29
And so please consider this a work in progress,
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请对这个正在运行的工作给予考虑
03:32
but I'd like to tell you today a story
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我今天给你们讲一个故事
03:34
about a very rare cancer
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这是有关一种非常罕见的癌症
03:36
called midline carcinoma,
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它叫中线癌
03:38
about the protein target,
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相关蛋白质目标，
03:40
the undruggable protein target that causes this cancer,
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是一种不可治愈的蛋白质目标引起这种癌症
03:42
called BRD4,
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它叫BRD4
03:44
and about a molecule
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及相关分子
03:46
developed at my lab at Dana Farber Cancer Institute
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是由我在妲妠珐波尔癌症学院的实验室开放出来的
03:48
called JQ1, which we affectionately named for Jun Qi,
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叫JQ1，我们昵称它军齐(Jun Qi)，
03:51
the chemist that made this molecule.
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与做出这个分子的化学家同名
03:54
Now BRD4 is an interesting protein.
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BRD4是一种有趣的蛋白质
03:57
You might ask yourself, with all the things cancer's trying to do to kill our patient,
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你可能要问自己， 癌症在用各种方法试图杀害我们的患者，
04:00
how does it remember it's cancer?
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它怎么会记得它是癌症呢？
04:02
When it winds up its genome,
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当它把它的遗传物质卷起来，
04:04
divides into two cells and unwinds again,
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分成两个细胞，再展开
04:06
why does it not turn into an eye, into a liver,
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为什么它不变成一只眼睛，一个肝脏
04:08
as it has all the genes necessary to do this?
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充分使用它所有的基因呢？
04:11
It remembers that it's cancer.
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它记得它是癌症
04:13
And the reason is that cancer, like every cell in the body,
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原因是它是癌症，就像人体内的每个细胞上
04:16
places little molecular bookmarks,
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放有细小的分子标记，
04:18
little Post-it notes,
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就像便利贴
04:20
that remind the cell "I'm cancer; I should keep growing."
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提醒细胞“我是癌症，我应当不停的长大"
04:23
And those Post-it notes
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而那些便利贴
04:25
involve this and other proteins of its class --
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引进这个蛋白质和它同级的别种蛋白质
04:27
so-called bromodomains.
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这些别种蛋白质叫做Bromodomains.
04:29
So we developed an idea, a rationale,
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以此我们推理
04:32
that perhaps, if we made a molecule
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或许，如果我们造出一个分子
04:34
that prevented the Post-it note from sticking
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避免让便利贴粘到它
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by entering into the little pocket
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让便利贴进入小口袋
04:38
at the base of this spinning protein,
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口袋位置在这旋转的蛋白质基底上
04:40
then maybe we could convince cancer cells,
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那么，也许我们能够让癌细胞相信
04:42
certainly those addicted to this BRD4 protein,
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尽管染上BRD4蛋白质
04:45
that they're not cancer.
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但它们不是癌细胞
04:47
And so we started to work on this problem.
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于是我们开始着手解决这个问题
04:49
We developed libraries of compounds
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我们开发了合成物储藏馆
04:51
and eventually arrived at this and similar substances
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我们逐渐得到今天的结果及类似的物质
04:54
called JQ1.
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它叫JQ1.
04:56
Now not being a drug company,
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因为我们不是制药公司，
04:58
we could do certain things, we had certain flexibilities,
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我们能够做一些事情，有一些灵活度
05:01
that I respect that a pharmaceutical industry doesn't have.
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这些是制药业所没有的
05:04
We just started mailing it to our friends.
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我们刚刚开始把它寄给我们的朋友
05:06
I have a small lab.
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我有个小实验室
05:08
We thought we'd just send it to people and see how the molecule behaves.
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我们想我们就把它寄给别人，看这分子如何表现
05:10
And we sent it to Oxford, England
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于是我们把它寄给了英国牛津
05:12
where a group of talented crystallographers provided this picture,
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那里的结晶师给了我们这个照片
05:15
which helped us understand
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它帮助我们了解到
05:17
exactly how this molecule is so potent for this protein target.
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这个分子是如何对这种蛋白质目标准确地施力
05:20
It's what we call a perfect fit
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它就是我们所说的完美对象
05:22
of shape complimentarity, or hand in glove.
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拥有相配的外体，就像戴着手套的手
05:24
Now this is a very rare cancer,
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这是一种罕见的癌症
05:26
this BRD4-addicted cancer.
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一种BRD4附体的癌症。
05:28
And so we worked with samples of material
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我们使用的样本材料
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that were collected by young pathologists at Brigham Women's Hospital.
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来自布利格姆妇女医院的年轻病理学家
05:34
And as we treated these cells with this molecule,
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我们用我们的这种分子了治疗这些样本细胞
05:37
we observed something really striking.
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我们观察到非常惊人的结果
05:39
The cancer cells,
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这些癌细胞
05:41
small, round and rapidly dividing,
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又小又圆，快速分裂
05:43
grew these arms and extensions.
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长出胳膊和延长部分
05:45
They were changing shape.
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它们还变形
05:47
In effect, the cancer cell
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实际上，癌细胞
05:49
was forgetting it was cancer
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正在忘记它是癌细胞
05:51
and becoming a normal cell.
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而且在转变成正常细胞
05:54
This got us very excited.
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这个观察让我们很兴奋
05:57
The next step would be to put this molecule into mice.
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下一步是把这分子注入的老鼠身上
06:00
The only problem was there's no mouse model of this rare cancer.
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我们唯一的问题是没有患有这种罕见癌症的老鼠
06:03
And so at the time that we were doing this research,
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就在这个研究过程中
06:06
I was caring for a 29 year-old firefighter from Connecticut
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我在康州治疗一位29岁的消防员
06:09
who was very much at the end of life
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他已接近他的生命终点了
06:12
with this incurable cancer.
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就是因为这种不可治愈的癌症
06:14
This BRD4-addicted cancer
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这种BRD4附体的癌症
06:16
was growing throughout his left lung,
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正在他的左肺里扩散
06:18
and he had a chest tube in that was draining little bits of debris.
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他靠左胸上插的一细管来排除废物
06:20
And every nursing shift
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每个护士轮班期间
06:22
we would throw this material out.
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都要把细管内废物清掉
06:24
And so we approached this patient
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因此我们找到这位患者
06:26
and asked if he would collaborate with us.
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问他是否愿意与我们合作
06:28
Could we take this precious and rare cancerous material
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我们是否可以把他稀有的，拥有癌症的排泄物
06:32
from this chest tube
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从细管里拿出来
06:34
and drive it across town and put it into mice
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送到城的另一边，注入到老鼠身上
06:36
and try to do a clinical trial
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通过临床试验
06:38
and stage it with a prototype drug?
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做成药物初本？
06:40
Well that would be impossible and, rightly, illegal to do in humans.
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但是，这不可能，人体试验不道德，不合法
06:43
And he obliged us.
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而且他已为我们尽了义务
06:46
At the Lurie Family Center for Animal Imaging,
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在卢瑞家庭动物图像中心
06:48
my colleague, Andrew Kung, grew this cancer successfully in mice
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我的同事安德鲁•康成功地把这癌症转到了老鼠身上
06:51
without ever touching plastic.
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他在这过程中连塑料都没有碰
06:53
And you can see this PET scan of a mouse -- what we call a pet PET.
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你可以看看这老鼠的PET扫描，我们叫它老鼠PET
06:56
The cancer is growing
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这癌症在扩散
06:58
as this red, huge mass in the hind limb of this animal.
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也就是这老鼠后肢上的大块红色组织
07:01
And as we treat it with our compound,
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我们用我们的合成物对老鼠进行治疗
07:03
this addiction to sugar,
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加上糖分
07:05
this rapid growth, faded.
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癌细胞不扩散了
07:07
And on the animal on the right,
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在这动物的右侧
07:09
you see that the cancer was responding.
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你可以看到癌症在反应
07:12
We've completed now clinical trials
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我们现在已完成动物实验
07:14
in four mouse models of this disease.
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用了4个动物模本
07:16
And every time, we see the same thing.
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每一次我们都看到同样的结果
07:18
The mice with this cancer that get the drug live,
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患有癌症的老鼠用药后活了下来
07:20
and the ones that don't rapidly perish.
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而那些没有用药的就很快死掉了
07:25
So we started to wonder,
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于是我们开始思考
07:27
what would a drug company do at this point?
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此时制药公司会做什么？
07:29
Well they probably would keep this a secret
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也许他们会把秘密保留下来
07:31
until they turn a prototype drug
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直到他们把药物雏形
07:33
into an active pharmaceutical substance.
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变成一种活跃的药物实体
07:35
And so we did just the opposite.
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而我们恰恰会做相反的事
07:37
We published a paper
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我们发表了一篇文章
07:39
that described this finding
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描述了我们的发现
07:41
at the earliest prototype stage.
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尽管是早期雏形
07:43
We gave the world the chemical identity of this molecule,
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我们向世界提供了这种分子的化学身份
07:46
typically a secret in our discipline.
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这是违反我们业内常规
07:48
We told people exactly how to make it.
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我们准确告诉了所有人如何制作这种分子
07:50
We gave them our email address,
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我们提供了我们的电子信箱地址
07:52
suggesting that, if they write us,
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向人们提议如果他们写信给我们
07:54
we'll send them a free molecule.
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我们会为他们提供免费分子
07:56
We basically tried to create
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我们基本上是试图创造
07:58
the most competitive environment for our lab as possible.
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我们自己的实验室所能面对的最具竞争力的环境
08:00
And this was, unfortunately, successful.
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不幸的是， 很成功
08:02
(Laughter)
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（笑声）
08:04
Because now when we've shared this molecule,
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因为我们现在与众分享我们的分子
08:06
just since December of last year,
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就从去年12月
08:08
with 40 laboratories in the United States
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和美国的40家实验室，
08:10
and 30 more in Europe --
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欧洲30多家实验室，
08:12
many of them pharmaceutical companies
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其中很多是来自制药公司
08:14
seeking now to enter this space,
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开始进入这个领域
08:16
to target this rare cancer
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目标是这个罕见的癌症
08:18
that, thankfully right now,
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有幸的是，现在这是
08:20
is quite desirable to study in that industry.
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我们行业里比较合乎需求的
08:24
But the science that's coming back from all of these laboratories
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来自这些实验室的
08:27
about the use of this molecule
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对这分子的研究
08:29
has provided us insights
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已经为我们提供
08:31
that we might not have had on our own.
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我们自己不可能得到的洞悉
08:33
Leukemia cells treated with this compound
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用这种合成物治疗过的白血病细胞
08:35
turn into normal white blood cells.
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会转变成正常白血球
08:38
Mice with multiple myeloma,
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患有骨髓瘤的老鼠
08:40
an incurable malignancy of the bone marrow,
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在骨髓里带有不可治愈的癌症，
08:43
respond dramatically
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会明显的接受
08:45
to the treatment with this drug.
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这种药物治疗
08:47
You might know that fat has memory.
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你可能知道脂肪带有记忆
08:49
Nice to be able to demonstrate that for you.
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能够向你们演示这个真的很好
08:53
And in fact, this molecule
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事实上，这种分子
08:55
prevents this adipocyte, this fat stem cell,
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避免这种含脂肪细胞，这种肥胖干细胞
08:58
from remembering how to make fat
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记忆发胖
09:01
such that mice on a high fat diet,
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比如说高脂肪饮食的老鼠
09:03
like the folks in my hometown of Chicago,
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就像我芝加哥故乡人
09:06
fail to develop fatty liver,
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不会得脂肪肝，
09:08
which is a major medical problem.
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一个重大医学问题
09:11
What this research taught us --
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这个研究教给我们 -
09:13
not just my lab, but our institute,
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不止我的实验室，而且我们学院
09:15
and Harvard Medical School more generally --
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及哈佛医学院，更广泛的讲 -
09:17
is that we have unique resources in academia
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我们拥有学术界独有的资源
09:19
for drug discovery --
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有助于药物发现 -
09:21
that our center
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也就是说，我们中心
09:23
that has tested perhaps more cancer molecules in a scientific way
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尽管我们以科学方式测试过很多癌症分子，
09:25
than any other,
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远多于其他中心，
09:27
never made one of its own.
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但我们从来没有制作过任何癌症分子
09:29
For all the reasons you see listed here,
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从那些你们能够看到的理由
09:31
we think there's a great opportunity for academic centers
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我们认为学术研究中心有很好的机会
09:34
to participate in this earliest, conceptually-tricky
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参与早期，概念化，
09:37
and creative discipline
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和有创意的领域
09:40
of prototype drug discovery.
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去发现药物雏形
09:44
So what next?
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那么，下一步是什么？
09:46
We have this molecule, but it's not a pill yet.
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我们有了这个分子，但它还不是药片
09:48
It's not orally available.
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它还不可口服。
09:51
We need to fix it, so that we can deliver it to our patients.
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我们需要改变它，以便可以送给我们的患者。
09:54
And everyone in the lab,
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每一位在实验室工作的人，
09:56
especially following the interaction with these patients,
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特别是那些与患者直接打交道的人，
09:58
feels quite compelled
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深刻体会
10:00
to deliver a drug substance based on this molecule.
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把这分子变成药物的紧迫性。
10:02
It's here where I have to say
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我在这里要说的是
10:04
that we could use your help and your insights,
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我们可以使用你们的帮助，你们的洞悉，
10:06
your collaborative participation.
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你们的合作参与。
10:08
Unlike a drug company,
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不像制药公司，
10:10
we don't have a pipeline that we can deposit these molecules into.
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我们不需要有储放这些分子的管道。
10:13
We don't have a team of salespeople and marketeers
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我们不一定要有一批销售人员和市场开发人员，
10:16
that can tell us how to position this drug against the other.
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不需要有这些人告诉我们如何给这药定位。
10:19
What we do have is the flexibility of an academic center
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我们拥有的是学术中心的灵活度
10:21
to work with competent, motivated,
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以便集中合作与有能力，有动力，
10:24
enthusiastic, hopefully well-funded people
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有激情，又最好有资助的人
10:27
to carry these molecules forward into the clinic
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来把这些分子推入临床
10:29
while preserving our ability
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同时保留我们有
10:31
to share the prototype drug worldwide.
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与世界分享药物雏形的能力。
10:34
This molecule will soon leave our benches
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这种分子将很快离开我们
10:36
and go into a small startup company
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走向一家小的创业公司
10:38
called Tensha Therapeutics.
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它叫Tensha Therapeutics。
10:40
And really this is the fourth of these molecules
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这真的是第四种分子
10:43
to kind of graduate from our little pipeline of drug discovery,
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从我们小小的药物发现管道里毕业
10:46
two of which -- a topical drug
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其它两种 - 一种是常用药
10:49
for lymphoma of the skin,
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用于治疗皮肤癌，
10:52
an oral substance for the treatment of multiple myeloma --
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另一种是治疗几种骨髓癌的口服药 -
10:55
will actually come to the bedside
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将很快来到床边
10:57
for first clinical trial in July of this year.
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今年7月进入初期临床试验。
10:59
For us, a major and exciting milestone.
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对我们来说，这是一个重大及令人兴奋的里程碑
11:03
I want to leave you with just two ideas.
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我想要给你们留下两个主意。
11:05
The first is
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第一个是
11:07
if anything is unique about this research,
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如果我们这个研究有什么特别的话，
11:10
it's less the science than the strategy --
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那是较少的科学更多的战略
11:12
that this for us was a social experiment,
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给了我们一个社会试验
11:14
an experiment in what would happen
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它向我们显示了什么是可能发生的，
11:17
if we were as open and honest
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如果我们开放和诚实
11:20
at the earliest phase of discovery chemistry research
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在发现化学研究最早期
11:22
as we could be.
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尽我们所及之力。
11:24
This string of letters and numbers
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这一串字母和数字
11:26
and symbols and parentheses
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标码和括弧
11:28
that can be texted, I suppose,
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我想是可以通过短信发出
11:30
or Twittered worldwide,
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或者是微博到全世界
11:32
is the chemical identity of our pro compound.
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是我们这个合成物的化学身份。
11:35
It's the information that we most need
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我们最需要的信息
11:37
from pharmaceutical companies,
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来自制药公司，
11:39
the information
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这信息
11:41
on how these early prototype drugs might work.
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是有关早期药物雏形如何工作。
11:44
Yet this information is largely a secret.
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至今，这样的信息大多数是行业秘密。
11:47
And so we seek really
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所以我们正在寻求的
11:49
to download from the amazing successes
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是下载惊人的成功，
11:51
of the computer science industry two principles:
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两个原则，来自计算机学行业：
11:54
that of opensource and that of crowdsourcing
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那就是开放源码和群体源码
11:57
to quickly, responsibly
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尽快地，负责地，
12:01
accelerate the delivery of targeted therapeutics
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把目标治疗法送给
12:04
to patients with cancer.
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癌症患者
12:06
Now the business model involves all of you.
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这个商业模式需要我们都参与
12:09
This research is funded by the public.
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这个研究借助于公共资源
12:11
It's funded by foundations.
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它是由基金会资助的
12:13
And one thing I've learned in Boston
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另外，我在波士顿学到一样东西
12:15
is that you people will do anything for cancer -- and I love that.
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那就是，你们所有人将都会为癌症治疗做事 - 我很喜欢。
12:17
You bike across the state. You walk up and down the river.
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有人骑单车跨州，有人走路过河
12:20
(Laughter)
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（笑声）
12:22
I've never seen really anywhere
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我在哪里都没有见过
12:24
this unique support
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如此独特地
12:26
for cancer research.
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支持癌症研究。
12:28
And so I want to thank you
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我还要感谢你们
12:30
for your participation, your collaboration
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感谢你们的参与，你们的合作
12:33
and most of all for your confidence in our ideas.
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更多的是你们对我们的信心。
12:36
(Applause)
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（鼓掌）
ABOUT THE SPEAKER
Jay Bradner - Research scientistIn his lab, Jay Bradner, a researcher at Harvard and Dana Farber in Boston, works on a breakthrough approach for subverting cancer .. and he’s giving the secret away.
Why you should listen
A doctor and a chemist, Jay Bradner hunts for new approaches to solving cancer. As a research scientist and instructor in medicine at Harvard and Dana Farber Cancer Institute, he and his lab are working to subvert cancer's aggressive behavior by reprogramming the cell's fundamental identity. A molecule they're working on, JQ1, might do just that. (And he’s giving it away in order to spur faster open-source drug discovery.) If you're a researcher who'd like a sample of the JQ1 molecule, contact the Bradner Lab.
Jay Bradner | Speaker | TED.com