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MinaBissell_2012G-_引导癌症新理解的实验_
Now, I don't usually like cartoons, [00:12]
I don't think many of them are funny, [00:15]
I find them weird . But I love this cartoon from the New Yorker. [00:18]
weird:adj.奇怪的;奇异的;离奇的;n.命运;宿命;命运女神;
(Text: Never, ever think outside the box .) (Laughter) [00:23]
think outside the box:跳出固有思维模式;跳脱框架思考;解放思想;
So, the guy is telling the cat, don't you dare think outside the box. [00:25]
Well, I'm afraid I used to be the cat. [00:33]
I always wanted to be outside the box. [00:37]
And it's partly because I came to this field from a different background, chemist and a bacterial geneticist . [00:40]
chemist:n.化学家;药剂师;药房;化学师; bacterial:adj.[微]细菌的; geneticist:n.遗传学者;
So, what people were saying to me about the cause of cancer , sources of cancer , or, for that matter, why you are who you are, didn't make sense . [00:48]
cancer:n.癌症;恶性肿瘤; sources:n.来源;出处;起源;根源;原因;v.(从…)获得(source的第三人称单数和复数) make sense:有意义;讲得通;言之有理;
So, let me quickly try and tell you why I thought that and how I went about it. [00:59]
So, to begin with, however, [01:05]
I have to give you a very, very quick lesson in developmental biology , with apologies to those of you who know some biology. [01:07]
developmental:adj.发展的;启发的; biology:n.(一个地区全部的)生物;生物学;
So, when your mom and dad met, there is a fertilized egg, that round thing with that little blip . [01:17]
fertilized:v.使受精;使受粉;使受胎;使受孕;施肥于;(fertilize的过去分词和过去式) blip:n.(在雷达屏幕显示出的)物体光点;
It grows and then it grows, and then it makes this handsome man. [01:25]
(Applause) [01:32]
So, this guy, with all the cells in his body, all have the same genetic information. [01:34]
So how did his nose become his nose, his elbow his elbow, and why doesn't he get up one morning and have his nose turn into his foot? [01:44]
elbow:n.肘;弯头;肘状物;v.用肘推;挤进;讨价还价;
It could. It has the genetic information. [01:53]
You all remember, dolly , it came from a single mammary cell. [01:56]
dolly:n.洋娃娃;手推车;移动式摄影车;洗衣搅棒;v.用移动车移动;移动摄影车; mammary:adj.乳腺的;[解剖]乳房的;
So, why doesn't it do it? [02:00]
So, have a guess of how many cells he has in his body. [02:02]
Somewhere between 10 trillion to 70 trillion cells in his body. [02:07]
trillion:n.[数]万亿;adj.万亿的;num.[数]万亿;
Trillion! [02:15]
Now, how did these cells, all with the same genetic material, make all those tissues ? [02:17]
tissues:n.纸巾,手巾纸;(人、动植物细胞的)组织;(tissue的复数)
And so, the question I raised before becomes even more interesting if you thought about the enormity of this in every one of your bodies. [02:23]
enormity:n.巨大;暴行;极恶;
Now, the dominant cancer theory would say that there is a single oncogene in a single cancer cell, and it would make you a cancer victim . [02:35]
dominant:adj.显性的;占优势的;支配的,统治的;n.显性; oncogene:n.[遗][肿瘤]致癌基因; victim:n.受害人;牺牲品;牺牲者;
Well, this did not make sense to me. [02:46]
Do you even know how a trillion looks? [02:50]
Now, let's look at it. [02:53]
There it comes, these zeroes after zeroes after zeroes. [02:55]
Now, if .0001 of these cells got mutated , and .00001 got cancer, you will be a lump of cancer. [03:00]
mutated:突变;变成;经受突变; lump:n.肿块;(通常为无定形的)块;隆起;笨重的人;v.把…归并一起(或合起来考虑);
You will have cancer all over you. And you're not. [03:12]
Why not? [03:14]
So, I decided over the years, because of a series of experiments that this is because of context and architecture . [03:17]
series:n.系列,连续;[电]串联;级数;丛书; context:n.环境;上下文;来龙去脉; architecture:n.建筑学;建筑风格;建筑式样;架构;
And let me quickly tell you some crucial experiment that was able to actually show this. [03:27]
crucial:adj.重要的;决定性的;定局的;决断的;
To begin with, I came to work with this virus that causes that ugly tumor in the chicken. [03:33]
ugly:adj.丑陋的;邪恶的;令人厌恶的; tumor:n.肿瘤;肿块;赘生物;
Rous discovered this in 1911. [03:41]
It was the first cancer virus discovered, and when I call it "oncogene," meaning "cancer gene." [03:44]
So, he made a filtrate , he took this filter which was the liquid after he passed the tumor through a filter, and he injected it to another chicken, and he got another tumor. [03:52]
filtrate:vi.过滤;vt.过滤;筛选;n.[化学]滤液; filter:n.滤波器;过滤器;滤光器;滤声器;v.过滤;渗入;(用程序)筛选;缓行; injected:v.(给…)注射(药物等); (inject的过去分词和过去式)
So, scientists were very excited, and they said, a single oncogene can do it. [04:04]
All you need is a single oncogene. [04:08]
So, they put the cells in cultures, chicken cells, dumped the virus on it, and it would pile up, and they would say, this is malignant and this is normal. [04:11]
dumped:v.丢弃,扔掉;丢下;抛弃;倾销,抛售;(dump的过去分词和过去式) pile:n.桩;堆;摞;桩柱;v.堆放;摞起;叠放;放置; malignant:adj.[医]恶性的;有害的;有恶意的;n.保王党员;怀恶意的人;
And again this didn't make sense to me. [04:20]
So for various reasons, we took this oncogene, attached it to a blue marker , and we injected it into the embryos . [04:22]
attached:adj.依恋;v.重视;把…固定;(attach的过去分词和过去式) marker:n.记分员;书签;标识物;作记号的人; embryos:n.胚;胚胎;人类胚胎;(embryo的复数)
Now look at that. There is that beautiful feather in the embryo. [04:31]
Every one of those blue cells are a cancer gene inside a cancer cell, and they're part of the feather. [04:35]
So, when we dissociated the feather and put it in a dish, we got a mass of blue cells. [04:44]
dissociated:adj.离解的;分裂的;v.分离(dissociate的过去分词); mass:n.块,团; adj.群众的,民众的; v.聚集起来,聚集;
So, in the chicken you get a tumor, in the embryo you don't, you dissociate, you put it in a dish, you get another tumor. [04:51]
What does that mean? [04:58]
That means that microenvironment and the context which surrounds those cells actually are telling the cancer gene and the cancer cell what to do. [04:59]
microenvironment:n.[生](动植物生长的)微(小)环境;
Now, let's take a normal example. [05:13]
The normal example, let's take the human mammary gland . [05:17]
gland:n.腺;密封压盖;
I work on breast cancer. [05:20]
So, here is a lovely human breast. [05:21]
And many of you know how it looks, except that inside that breast, there are all these pretty, developing, tree-like structures . [05:24]
tree-like:[林]树枝状的; structures:n.结构; v.建造(structure的第三人称单数形式);
So, we decided that what we like to do is take just a bit of that mammary gland, which is called an "acinus," [05:32]
where there are all these little things inside the breast where the milk goes, and the end of the nipple comes through that little tube when the baby sucks . [05:40]
nipple:n.乳头,奶头;奶嘴; sucks:v.吮吸;吸;咂;啜;抽吸;抽取;(suck的第三人称单数)
And we said, wonderful! Look at this pretty structure. [05:51]
We want to make this a structure, and ask the question, how do the cells do that? [05:54]
So, we took the red cells -- you see the red cells are surrounded by blue, other cells that squeeze them, and behind it is material that people thought was mainly inert , [06:00]
squeeze:v.挤;紧握;勒索;压榨;n.压榨;紧握;拥挤;佣金; mainly:adv.大多;大部分;主要地;首要地; inert:adj.[化学]惰性的;呆滞的;迟缓的;无效的;
and it was just having a structure to keep the shape, and so we first photographed it with the electron microscope years and years ago, and you see this cell is actually quite pretty. [06:12]
electron microscope:n.电子显微镜;
It has a bottom, it has a top, it is secreting gobs and gobs of milk, because it just came from an early pregnant mouse. [06:24]
secreting:vt.藏匿;私下侵吞;分泌; gobs:n.凝块;水兵;vi.吐唾沫; pregnant:adj.怀孕的;富有意义的;
You take these cells, you put them in a dish, and within three days, they look like that. [06:33]
They completely forget. [06:38]
So you take them out, you put them in a dish, they don't make milk. They completely forget. [06:42]
For example, here is a lovely yellow droplet of milk on the left, there is nothing on the right. [06:47]
droplet:n.小滴,微滴;
Look at the nuclei . The nuclei in the cell on the left is in the animal, the one on the right is in a dish. [06:54]
nuclei:n.核心,核子;原子核(nucleus的复数形式);
They are completely different from each other. [07:01]
So, what does this tell you? [07:04]
This tells you that here also, context overrides . [07:06]
overrides:n.重写; v.重写;
In different contexts , cells do different things. [07:11]
contexts:n.环境,[计]上下文(context复数);
But how does context signal? [07:14]
So, Einstein said that "For an idea that does not first seem insane , there is no hope." [07:17]
insane:adj.疯狂的;精神病的;极愚蠢的;
So, you can imagine the amount of skepticism [07:26]
skepticism:n.怀疑论;怀疑的态度;
I received -- couldn't get money, couldn't do a whole lot of other things, but I'm so glad it all worked out. [07:32]
So, we made a section of the mammary gland of the mouse, and all those lovely acini are there, every one of those with the red around them are an acinus, [07:38]
and we said okay, we are going to try and make this, and I said, maybe that red stuff around the acinus that people think there's just a structural scaffold , maybe it has information, maybe it tells the cells what to do, maybe it tells the nucleus what to do. [07:50]
stuff:n.东西:物品:基本特征:v.填满:装满:标本: structural:adj.结构的;建筑的; scaffold:n.脚手架;鹰架;绞刑台;vt.给…搭脚手架;用支架支撑; nucleus:n.核,核心;原子核;
So I said, extracellular matrix , which is this stuff called ECM, signals and actually tells the cells what to do. [08:08]
extracellular:adj.(位于或发生于)[生物]细胞外的(副词extracellularly); matrix:n.[数]矩阵;模型;[生物][地质]基质;母体;子宫;[地质]脉石;
So, we decided to make things that would look like that. [08:17]
We found some gooey material that had the right extracellular matrix in it, we put the cells in it, and lo and behold , in about four days, they got reorganized and on the right, is what we can make in culture. [08:21]
gooey:adj.胶粘的;感伤的;n.胶粘物;蜜糖; behold:v.看;注视;把...视为;int.瞧;看呀; reorganized:v.重组(reorganize的过去分词);整顿;重新制定;adj.重组的;重新制定的;
On the left is what's inside the animal, we call it in vivo , and the one in culture was full of milk, the lovely red there is full of milk. [08:35]
vivo:v.活泼地; adj.生动的;
So, we Got Milk, for the American audience. [08:45]
All right. And here is this beautiful human cell, and you can imagine that here also, context goes. [08:48]
So, what do we do now? [08:59]
I made a radical hypothesis . [09:01]
radical:n.自由基;激进分子;游离基;adj.根本的;彻底的;完全的;全新的; hypothesis:n.假设;
I said, if it's true that architecture is dominant, architecture restored to a cancer cell should make the cancer cell think it's normal. [09:04]
restored:adj.精力充沛的;精力恢复的;v.修复;恢复健康;(restore的过去分词和过去式)
Could this be done? [09:18]
So, we tried it. [09:19]
In order to do that, however, we needed to have a method of distinguishing normal from malignant, and on the left is the single normal cell, human breast, put in three-dimensional gooey gel that has extracellular matrix, it makes all these beautiful structures. [09:22]
distinguishing:v.区分;辨别;分清;看清;认出;听出;(distinguish的现在分词) three-dimensional:adj.三维的;立体的;真实的; gel:vi.胶化;n.[物化]凝胶,胶体;
On the right, you see it looks very ugly, the cells continue to grow, the normal ones stop. [09:41]
And you see here in higher magnification the normal acinus and the ugly tumor. [09:47]
magnification:n.放大;放大率;放大的复制品;
So we said, what is on the surface of these ugly tumors ? [09:54]
tumors:n.肿瘤(tumor的复数);
Could we calm them down -- they were signaling like crazy and they have pathways all messed up -- and make them to the level of the normal? [09:58]
signaling:n.发信号;打信号; like crazy:拼命地;发疯似的; pathways:n.小路;小径(pathway的复数); messed:v.使不整洁;弄脏;弄乱;随地便溺(mess的过去分词和过去式)
Well, it was wonderful. Boggles my mind. [10:08]
Boggles:v.犹豫,退缩;惊恐;n.犹豫,退缩;惊奇;
This is what we got. [10:13]
We can revert the malignant phenotype . [10:15]
revert:vi.回复;重提;返祖遗传;归还;vt.使回复原状;n.恢复原状者; phenotype:n.表型,表现型;显型;
(Applause) [10:19]
And in order to show you that the malignant phenotype [10:21]
I didn't just choose one, here are little movies, sort of fuzzy , but you see that on the left are the malignant cells, all of them are malignant, we add one single inhibitor in the beginning, and look what happens, they all look like that. [10:25]
fuzzy:adj.模糊的;失真的;有绒毛的; inhibitor:n.[助剂]抑制剂,抗化剂;抑制者;
We inject them into the mouse, the ones on the right, and none of them would make tumors. [10:42]
We inject the other ones in the mouse, 100 percent tumors. [10:48]
So, it's a new way of thinking about cancer, it's a hopeful way of thinking about cancer. [10:51]
We should be able to be dealing with these things at this level, and these conclusions say that growth and malignant behavior is regulated at the level of tissue organization and that the tissue organization is dependent on the extracellular matrix and the microenvironment. [10:57]
conclusions:n.结论,总结;决定;(conclusion的复数) regulated:v.约束,控制,管理;(regulate的过去式和过去分词) organization:n.组织;机构;体制;团体; dependent on:依赖于;依靠;
All right, thus form and function interact dynamically and reciprocally . [11:18]
interact:v.互相影响;互相作用;n.幕间剧;幕间休息; dynamically:adv.动态地;充满活力地;不断变化地; reciprocally:adv.相互地;相反地;互惠地;
And here is another five seconds of repose , is my mantra . Form and function. [11:26]
repose:n.休息;睡眠;静止;vt.使休息;寄托于;vi.休息;座落;长眠;依靠;静卧;建立于; mantra:n.咒语(尤指四吠陀经典内作为咒文或祷告唱念的);颂歌;
And of course, we now ask, where do we go now? [11:34]
We'd like to take this kind of thinking into the clinic . [11:38]
clinic:n.诊所;临床实习;(医院的)门诊部;门诊时间;
But before we do that, I'd like you to think that at any given time when you're sitting there, in your 70 trillion cells, the extracellular matrix signaling to your nucleus, [11:41]
the nucleus is signaling to your extracellular matrix and this is how your balance is kept and restored. [11:55]
We have made a lot of discoveries, we have shown that extracellular matrix talks to chromatin . [12:04]
chromatin:n.核染色质;核染质;
We have shown that there's little pieces of DNA on the specific genes of the mammary gland that actually respond to extracellular matrix. [12:09]
specific:adj.特殊的,特定的;明确的;详细的;[药]具有特效的;n.特性;细节;特效药; genes:n.基因;(gene的复数) respond:vi.回答;作出反应;承担责任;n.应答;唱和;
It has taken many years, but it has been very rewarding . [12:19]
rewarding:adj.有益的;值得做的;报酬高的;v.奖励;奖赏;给以报酬;(reward的现在分词)
And before I get to the next slide, I have to tell you that there are so many additional discoveries to be made. [12:23]
additional:adj.附加的,额外的;
There is so much mystery we don't know. [12:33]
And I always say to the students and post-docs I lecture to, don't be arrogant , because arrogance kills curiosity . [12:35]
lecture:n.演讲;讲座;讲课;谴责;v.开讲座;讲授;讲课;指责;告诫 arrogant:adj.自大的,傲慢的; arrogance:n.自大;傲慢态度; curiosity:n.好奇,好奇心;珍品,古董,古玩;
Curiosity and passion . [12:45]
passion:n.激情;热情;酷爱;盛怒;
You need to always think, what else needs to be discovered? [12:47]
And maybe my discovery needs to be added to or maybe it needs to be changed. [12:51]
So, we have now made an amazing discovery, a post-doc in the lab who is a physicist asked me, what do the cells do when you put them in? [12:56]
physicist:n.物理学家;物理学研究者;
What do they do in the beginning when they do? [13:05]
I said, I don't know, we couldn't look at them. [13:08]
We didn't have high images in the old days. [13:10]
images:n.印象;声誉;形象;画像;雕像;(image的第三人称单数和复数)
So she, being an imager and a physicist, did this incredible thing. [13:12]
imager:n.成像器,图象机; incredible:adj.难以置信的,惊人的;
This is a single human breast cell in three dimensions . [13:17]
dimensions:n.规模,大小;
Look at it. It's constantly doing this. [13:21]
constantly:adv.不断地;时常地;
Has a coherent movement. [13:23]
coherent:adj.连贯的,一致的;明了的;清晰的;凝聚性的;互相耦合的;粘在一起的;
You put the cancer cells there, and they do go all over, they do this. They don't do this. [13:26]
And when we revert the cancer cell, it again does this. [13:32]
Absolutely boggles my mind. [13:36]
Absolutely:adv.绝对地;完全地;
So the cell acts like an embryo. What an exciting thing. [13:38]
So I'd like to finish with a poem. [13:43]
Well I used to love English literature , and I debated in college, which one should I do? [13:46]
literature:n.文学;文献;文艺;著作; debated:v.讨论,辩论;思考;盘算;(debate的过去分词和过去式)
And unfortunately or fortunately, chemistry won. [13:52]
unfortunately:adv.不幸地;
But here is a poem from Yeats. I'll just read you the last two lines. [13:56]
It's called "Among the School Children." [14:02]
'"O body swayed to music / O brightening glance / [14:05]
swayed:v.(使)摇摆,摇动;说服;使相信;使动摇;(sway的过去分词和过去式) brightening:v.(使)更明亮;(使)快活起来;(使)有希望;(brighten的现在分词) glance:v.浏览;扫视;瞥一眼;匆匆一看;n.一瞥;扫视;匆匆一看;
How [can we know] the dancer from the dance?" [14:09]
And here is Merce Cunningham, [14:13]
I was fortunate to dance with him when I was younger, and here he is a dancer, and while he is dancing, he is both the dancer and the dance. [14:14]
The minute he stops, we have neither. [14:23]
So it's like form and function. [14:27]
Now, I'd like to show you a current picture of my group. [14:30]
I have been fortunate to have had these magnificant students and post-docs who have taught me so much, and I have had many of these groups come and go. [14:36]
They are the future and I try to make them not be afraid of being the cat and being told, don't think outside the box. [14:46]
And I'd like to leave you with this thought. [14:56]
On the left is water coming through the shore, taken from a NASA satellite. [14:58]
On the right, there is a coral . [15:05]
coral:n.珊瑚;珊瑚虫;adj.珊瑚的;珊瑚色的;
Now if you take the mammary gland and spread it and take the fat away, on a dish it looks like that. [15:08]
Do they look the same? Do they have the same patterns? [15:15]
Why is it that nature keeps doing that over and over again ? [15:19]
over and over again:adv.一再地;反复不断地;
And I'd like to submit to you that we have sequenced the human genome , we know everything about the sequence of the gene, the language of the gene, the alphabet of the gene, [15:23]
submit:vt.使服从;主张;呈递;vi.提交;服从; sequenced:[数][计]序列; genome:n.基因组;染色体组;
But we know nothing, but nothing, about the language and alphabet of form. [15:33]
So, it's a wonderful new horizon , it's a wonderful thing to discover for the young and the passionate old, and that's me. [15:40]
horizon:n.地平线;(欲望、知识或兴趣的)范围; passionate:adj.热情的;热烈的,激昂的;易怒的;
So go to it! [15:50]
(Applause) [15:52]