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StephenFriend_2014-_猎寻“未知的遗传英雄”_
Approximately 30 years ago, when I was in oncology at the Children's Hospital in Philadelphia , a father and a son walked into my office and they both had their right eye missing, and as I took the history, it became apparent that the father and the son had a rare form of inherited eye tumor , retinoblastoma , and the father knew that he had passed that fate on to his son. 大约在30年以前, 当我还在 费城儿童医院的肿瘤科 一对父子走进我的办公室 他们两人都没有了右眼, 当我询问了病史,很明显 父亲和儿子都患有一种罕见形式的 遗传性的眼睛肿瘤,视网膜母细胞瘤, 父亲知道他把那种噩运 传给了儿子。
Approximately:adv.大约,近似地;近于; oncology:n.[肿瘤]肿瘤学; Philadelphia:n.费城(美国宾夕法尼亚州东南部港市); apparent:adj.显然的;表面上的; inherited:v.继承(金钱、财产等);接替(责任等);继任;(inherit的过去式和过去分词) tumor:n.肿瘤;肿块;赘生物; retinoblastoma:n.[肿瘤]成视网膜细胞瘤;眼癌(有遗传性);
That moment changed my life. 那个时刻改变了我的生活。
It propelled me to go on and to co-lead a team that discovered the first cancer susceptibility gene, and in the intervening decades since then, there has been literally a seismic shift in our understanding of what goes on, what genetic variations are sitting behind various diseases . 它促使我去 带领一个研究小组,并发现了 第一个肿瘤易感基因, 从那时介入起算的十年来, 我们在对肿瘤发生的研究上 已经有了天翻地覆的进展 暨存在在各种各样的疾病背后 的基因变异。
propelled:adj.推进的;v.推动;驱使(propel的过去分词); cancer:n.癌症;恶性肿瘤; susceptibility:n.敏感性;感情;磁化系数; intervening:adj.介于中间的;v.介入(intervene的ing形式); literally:adv.按字面:字面上:确实地: seismic:adj.地震的;因地震而引起的; shift:n.移动;变化;手段;轮班;v.移动;转变;转换; genetic:adj.基因的;遗传学的; variations:n.变奏曲,变更;[生物]变种(variation的复数形式); diseases:n.[医]病(disease的复数);[医]疾病;[植保]病害;疾病种类;
In fact, for thousands of human traits , a molecular basis that's known for that, and for thousands of people, every day, there's information that they gain about the risk of going on to get this disease or that disease. 事实上,数以万计的人类特征中, 就是那些已知的分子基础所决定, 对很多人来说,每天 他们都获得很多信息 关于得上这个 或那个疾病的危险。
traits:n.特性,特质,性格(trait的复数); molecular:adj.[化学]分子的;由分子组成的;
At the same time , if you ask, 同时,如果你问,
At the same time:同时;另一方面;与此同时;
Has that impacted the efficiency , how we've been able to develop drugs? “那对效率有影响吗？” 我们如何能研发药物？“
impacted:adj.压紧的;结实的;嵌入的;(人口)稠密的;v.装紧;挤满(impact的过去分词); efficiency:n.效率;效能;功效;
the answer is not really. 回答是不确定的。
If you look at the cost of developing drugs, how that's done, it basically hasn't budged that. 如果你看看研发药物的花费
at the cost of:以…为代价; basically:adv.主要地,基本上; budged:vi.挪动; vt.使让步; n.羔羊皮;
And so it's as if we have the power to diagnose yet not the power to fully treat . 那么,就像我们的确有能力来做出诊断 但还美有能力来治愈。
diagnose:vt.诊断;断定;vi.诊断;判断; treat:v.治疗;处理;招待;款待;n.款待;乐事;乐趣;
And there are two commonly given reasons for why that happens. 至于缘何会出现这样的现象 有两个常见的理由
One of them is it's early days . 其中之一是早期。
early days:初期;为时尚早;前期;
We're just learning the words, the fragments , the letters in the genetic code . 我们刚刚学会, 基因编码字母的只言片语
fragments:n.碎片(fragment的复数);片断;[计]分段;v.破碎(fragment的三单形式);打碎; genetic code:n.遗传密码;
We don't know how to read the sentences. 我们不知道怎样阅读整段基因。
We don't know how to follow the narrative . 我们不知道怎样理解它的叙述。
narrative:n.叙述;故事;讲述;adj.叙事的,叙述的;叙事体的;
The other reason given is that most of those changes are a loss of function, and it's actually really hard to develop drugs that restore function. 另一个现存的理由是 大部分的基因变化是功能的缺失, 实际上很难通过发展药物 来重建功能。
restore:v.恢复;修复;恢复(某种情况或感受);使复原;
But today, I want us to step back and ask a more fundamental question, and ask, What happens if we're thinking about this maybe in the wrong context ? 但今天,我希望大家后退一步 问问更基本的问题, 再问,“如果我们关于这些的看法 是在错误的背景下,那么会发生什么呢？“
fundamental:n.基础; adj.十分重大的; context:n.环境;上下文;来龙去脉;
We do a lot of studying of those who are sick and building up long lists of altered components . 我们对那些生病的人做了很多研究 并且积攒了一个 不同组成的长长的目录。
altered:adj.改变了的:v.(使)改变,更改,改动:(alter的过去分词和过去式) components:n.部件;组件;成份(component复数);
But maybe, if what we're trying to do is to develop therapies for prevention , maybe what we should be doing is studying those who don't get sick. 但也许,如果我们尝试去做的是 为了预防来发展治疗, 也许我们应该做的 是研究那些没有生病的人。
therapies:n.治疗方法(therapy复数形式); prevention:n.预防;阻止;妨碍;
Maybe we should be studying those that are well. 也许我们应该研究那些 健康的人。
A vast majority of those people are not necessarily carrying a particular genetic load or risk factor . 绝大部分的那些人 也许没有承载一个特别的 遗传累赘或者危险因子。
majority:n.大部分:大多数:多数票:成年人: necessarily:adv.必要地;必定地,必然地; factor:n.因素;要素;[物]因数;代理人;v.做代理商;v.把…作为因素计入;
They're not going to help us. 他们对我们没有帮助。
They're going to be those individuals who are carrying a potential future risk, they're going to go on to get some symptom . 他们将是那些 带有潜在的会发病的危险因子 他们会有某些症状。
individuals:n.[经]个人;[生物]个体(individual的复数); potential:n.潜能;可能性;[电]电势;adj.潜在的;可能的;势的; symptom:n.症状;征候;征兆;
That's not what we're looking for. 那不是我们要找的。
What we're asking and looking for is, are there a very few set of individuals who are actually walking around with the risk that normally would cause a disease, but something in them, something hidden in them is actually protective and keeping them from exhibiting those symptoms ? 我们要找的是, 只有很少的一组个体 那些没有发病的, 但事实上有着能引起疾病的危险因子 在他们体内有某些东西,有某些东西藏在里面 事实上起着保护作用 使他们免于出现那些症状？
normally:adv.正常地;通常地,一般地; protective:adj.防护的;关切保护的;保护贸易的; exhibiting:v.展览;展出;表现,显示,显出;(exhibit的现在分词) symptoms:n.症状;征候;征兆;(symptom的复数)
If you're going to do a study like that, you can imagine you'd like to look at lots and lots of people. 如果你要做那样一个研究,你能想像 你不得不去看看很多这样的人。
We'd have to go and have a pretty wide study, and we realized that actually one way to think of this is, let us look at adults who are over 40 years of age, and let's make sure that we look at those who were healthy as kids. 我们已经有了很大范围的研究, 我们意识到事实上 有一个思考的办法是, 让我们看看四十岁以上的成年人, 让我们确定我们看着那些 像孩子一样健康的人。
They might have had individuals in their families who had had a childhood disease, but not necessarily. 在他们的家庭中,可能有某个人 在孩提时有了病, 但也不一定。
childhood:n.童年;幼年;孩童时期
And let's go and then screen those to find those who are carrying genes for childhood diseases. 让我们到那些 人群里筛选,看谁携带着 在儿童时就发病的基因。
genes:n.基因;(gene的复数)
Now, some of you, I can see you putting your hands up going, Uh, a little odd . 现在,你们中的某些人,我能看见你们 高举着手,“呵,有点古怪。
odd:adj.古怪的;奇数的;n.奇数;
What's your evidence that this could be feasible ? 你的证据呢 你能证明这是可行的吗？“
evidence:n.证据,证明;迹象;明显;v.证明; feasible:adj.可行的;可能的;可实行的;
I want to give you two examples. 我想给你们两个例子。
The first comes from San Francisco. 第一个来自旧金山。
It comes from the 1980s and the 1990s, and you may know the story where there were individuals who had very high levels of the virus HIV . 在1980年和1990年之间, 你们也许知道 那些个体有着很高水平的 艾滋病毒
HIV:n.艾滋病病毒;
They went on to get AIDS. 他们后来得上了艾滋。
But there was a very small set of individuals who also had very high levels of HIV. 但有很少一组个体 虽然有着很高的艾滋病毒水平
They didn't get AIDS. 他们没有得病。
And astute clinicians tracked that down, and what they found was they were carrying mutations . 精明的临床医生追踪下去, 他们发现的是那些人携带着基因变异。
astute:adj.机敏的;狡猾的,诡计多端的; clinicians:临床医生(clinician的名词复数); tracked:v.跟踪;追踪;(track的过去分词和过去式) mutations:n.[遗]突变;变化;转变(mutation的复数形式);
Notice, they were carrying mutations from birth that were protective, that were protecting them from going on to get AIDS. 注意,他们的变异是天生的。 那具有保护性,保护他们 不会得上艾滋病。
You may also know that actually a line of therapy has been coming along based on that fact. 你也许还知道有一个治疗流程 根据这个事实而启动了。
therapy:n.治疗,疗法;
Second example, more recent, is elegant work done by Helen Hobbs, who said, I'm going to look at individuals who have very high lipid levels, and I'm going to try to find those people with high lipid levels who don't go on to get heart disease. 第二个例子,最近的,是由 海伦.霍伯斯做的漂亮的工作, 她说,“我会研究那些有 着很高血脂水平的个体, 我会努力来发现这些 有着高血脂水平 但没有患心脏病的人。“
elegant:adj.高雅的,优雅的;讲究的;简炼的;简洁的; lipid:n.[生化]脂质;油脂;
And again, what she found was some of those individuals had mutations that were protective from birth that kept them, even though they had high lipid levels, and you can see this is an interesting way of thinking about how you could develop preventive therapies. 再一次的,她发现的是 一些个体基因上有突变, 而那些天生的突变保护他们免于疾病, 尽管他们有着很高水平的血脂。 你能明白这是个有趣途径 它让你想到你怎样才能拓展出 预防性治疗。
preventive:n.预防药;预防法;adj.预防的,防止的;
The project that we're working on is called The Resilience Project: 我们在进行的项目是 叫做“弹性课题:
Resilience:n.恢复力;弹力;顺应力;
A Search for Unexpected Heroes, because what we are interested in doing is saying, can we find those rare individuals who might have these hidden protective factors ? 对未预料的英雄的研究,“ 因为我们感兴趣做的是 我们能找到少见的 有着这种隐性的保护因子个体吗？
Unexpected:adj.意外的,想不到的; factors:n.因素(factor的复数); v.做代理商;
And in some ways, think of it as a decoder ring, a sort of resilience decoder ring that we're going to try to build. 在某种意义上,把它当做解码器环, 是一种 我们尝试建造的具有弹性的解码器环。
decoder:n.解码器,译码器;译码员;
We've realized that we should do this in a systematic way, so we've said, let's take every single childhood inherited disease. 我们已经意识到我们应该系统性地尝试, 我们已经说过,让我们拿每一个 儿童遗传病来研究。
systematic:adj.系统的;体系的;有系统的;[图情]分类的;一贯的,惯常的;
Let's take them all, and let's pull them back a little bit by those that are known to have severe symptoms, where the parents, the child, those around them would know that they'd gotten sick, and let's go ahead and then frame them again by those parts of the genes where we know that there is a particular alteration that is known to be highly penetrant to cause that disease. 让我们看着所有的人,让我们把它们范围缩小一点点 用那些 父母,孩子有着已知的严重的症状的病来说, 那些周围的人都知道 他们会生病, 让我们继续并且给他们再次定位 用我们已经知道的某些部分的基因 那些有着特别改变而 总所周知是引起 那种疾病的高度相关的基因。
severe:adj.极为恶劣的;十分严重的;严厉的;苛刻的; frame:n.框架; v.设计; adj.有木架的; alteration:n.修改,改变;变更; highly:adv.高度地;非常;非常赞许地;
Where are we going to look? 我们要看的是什么呢？
Well, we could look locally . That makes sense. 首先,我们可以局部地看,那很有道理。
locally:adv.在本地;局部地;在地方上;
But we began to think, maybe we should look all over the world. 然后我们想想,也许我们应该看看 全世界。
Maybe we should look not just here but in remote places where their might be a distinct genetic context, there might be environmental factors that protect people. 也许我们应该看的不只是这儿 而是在遥远的地方 可能有着独特的基因背景 也许是环境的因素 保护者人们。
remote:adj.偏远的;偏僻的;遥远的;久远的; distinct:adj.明显的;独特的;清楚的;有区别的;
And let's look at a million individuals. 让我们看一百万个体。
Now the reason why we think it's a good time to do that now is, in the last couple of years, there's been a remarkable plummeting in the cost to do this type of analysis , this type of data generation, to where it actually costs less to do the data generation and analysis than it does to do the sample processing and the collection. 我们认为现在是个很好的时候, 理由是,现在 以及在过去的几年中, 做这种类型的分析, 这种类型的数据推导, 在花费上有着显着的垂直的下降 事实上 在数据推导和分析上的花费 少于标本的处理和收集。
remarkable:adj.卓越的;非凡的;值得注意的; plummeting:n.垂直落下; adj.直线下降的; v.垂直落下; analysis:n.分析;分解;验定; processing:v.加工;处理;审核;数据处理;v.列队行进;缓缓前进;(process的现在分词)
The other reason is that in the last five years, there have been awesome tools, things about network biology , systems biology , that have come up that allow us to think that maybe we could decipher those positive outliers . 在过去的五年中,另一个原因是, 有了特别棒的工具, 像联网生物学,系统生物学 发展起来后,可以让我们想到 也许我们可能解译 那些正性的结果。
awesome:adj.令人敬畏的;使人畏惧的;可怕的;极好的; biology:n.(一个地区全部的)生物;生物学; decipher:n.密电译文;v.解释; positive:adj.积极的;[数]正的,[医][化学]阳性的;确定的;n.正数;[摄]正片; outliers:n.[分化]异常值;离群值;离开本体的东西;局外人(outlier的复数);
And as we went around talking to researchers and institutions and telling them about our story, something happened. 当我们跟研究人员 和研究所讨论 并且告诉他们我们的故事, 和那些发生的事情。
institutions:n.机构;慈善机构;风俗习惯,制度;(institution的复数)
They started saying, This is interesting. 他们开始说,“这有些意思,
I would be glad to join your effort. 我很高兴来跟你一起的努力,
I would be willing to participate . 我愿意参加。”
participate:v.参加;参与;
And they didn't say, Where's the MTA? 他们并没有说,“MTA在哪里？”
They didn't say, Where is my authorship ? “他们没有说,”我的作者署名在哪里？“
authorship:n.(书等的)原创作者,来源;作者的身份;著述业;
They didn't say, Is this data going to be mine? Am I going to own it? 他们没有说,“这个结果是我的吗？我是这个结果的主人吗？“
They basically said, Let's work on this in an open, crowd-sourced, team way to do this decoding . 他们只是说,”让我们 在一个开放的,有人群资源的,以合作的方法 来一起工作,解开这个难题。“
decoding:v.解码;破译(尤指密码);译解,理解(外文);(decode的现在分词)
Six months ago, we locked down the screening key for this decoder. 六个月之前,我们锁定了 这个难题的筛选关键。
My co-lead, a brilliant scientist, Eric Schadt at the Icahn Mount Sinai School of Medicine in New York, and his team, locked in that decoder key ring , and we began looking for samples, because what we realized is, maybe we could just go and look at some existing samples to get some sense of feasibility . 我的同僚,一个非常聪明的科学家,诶瑞克.夏特 在纽约的爱肯蒙特塞纳医学院, 他的小组 锁定了那个解码环的关键, 我们开始寻找标本, 因为我们意识到的是, 也许我们可以继续看 一些现存的标本来得到某些。。
Mount:n.山;坐骑;山峰;衬纸板;v.登上;爬上;攀登;准备; key ring:n.钥匙圈;钥匙环; feasibility:n.可行性;可能性;
Maybe we could take two, three percent of the project on, and see if it was there. 也许我们能让项目有百分之二或三的进展, 看看它是否是我们想要的,
And so we started asking people such as Hakon at the Children's Hospital in Philadelphia. 于是我们开始请求一些人 比如费城儿童医院的哈空,
We asked Leif up in Finland. 和远在芬兰的列夫。
We talked to Anne Wojcicki at 23andMe, and Wang Jun at BGI, and again, something remarkable happened. 我们跟诊所”23和我“的安.沃基次可 以及在BGI的王军也有了对话, 又一次,有了很显着的进展。
They said, Huh, not only do we have samples, but often we've analyzed them, and we would be glad to go into our anonymized samples and see if we could find those that you're looking for. 他们说,”呵, 我们不仅有标本, 而且我们还分析过, 我们很愿意来找出 我们那些匿名的标本, 看看我们是否能找到那些 你们在找的。“
analyzed:v.分析(analyze的过去式和过去分词);检讨; anonymized:隐去姓名资料;使匿名;
And instead of being 20,000 or 30,000, last month we passed one half million samples that we've already analyzed. 上个月,我们 有了过50十万的标本而不是2万或三万 我们已经分析过了这些标本。
So you must be going, 那么,你肯定会说,
Huh, did you find any unexpected heroes? “哈,你发现了那个未知的英雄了吗？”
And the answer is, we didn't find one or two. 回答是肯定的。我们不是发现了一个或两个。
We found dozens of these strong candidate unexpected heroes. 我们发现了一打这样的 作为未知的英雄的候选
So we think that the time is now to launch the beta phase of this project and actually start getting prospective individuals. 现在我们认为是时候 来进入这个项目的第二阶段 实际上是要得到那些有前景的个体。
launch:v.发射(导弹,火箭等); n.发射; beta:n.贝它(希腊字母表的第二个字母); phase:n.阶段;时期;月相;(月亮的)盈亏;v.分阶段进行;逐步做; prospective:adj.未来的;预期的;n.预期;展望;
Basically all we need is information. 我们基本上需要的就是信息。
We need a swab of DNA and a willingness to say, What's inside me? 我们需要一些DNA 和参与者自愿地说,“我里面有什么？”
swab:n.药签,[外科]拭子; vt.打扫,擦拭; willingness:n.乐意;心甘情愿;自动自发;
I'm willing to be re-contacted. 我愿意你们再跟我接触。“
Most of us spend our lives, when it comes to health and disease, acting as if we're voyeurs . 我们把自己的大部分生活 花在健康和疾病上, 好像做了偷窥者一样。
voyeurs:n.偷看下流场面的人;窥淫狂者;vi.窥淫;
We delegate the responsibility for the understanding of our disease, for the treatment of our disease, to anointed experts. 我们有责任 来弄懂我们的疾病, 以便来治疗我们的疾病, 成为在行的专家。
delegate:n.代表; v.授(权); treatment:n.治疗;疗法;对待;处理;讨论; anointed:v.傅,涂(圣油、圣水);(anoint的过去分词和过去式)
In order for us to get this project to work, we need individuals to step up in a different role and to be engaged , to realize this dream, this open crowd-sourced project, to find those unexpected heroes, to evolve from the current concepts of resources and constraints , to design those preventive therapies, and to extend it beyond childhood diseases, to go all the way up to ways that we could look at Alzheimer's or Parkinson's, we're going to need us to be looking inside ourselves and asking, 为了让这个项目可以运作, 我们需要个体站出来 在各种角色上参与, 意识到这个梦想, 这个开放的人群资源项目, 是为了发现那些未知的英雄们。 来更新现有概念 的来源和限制 来设计那些预防性的治疗, 并且能够延续和超越儿童时期发生的疾病, 一直上升到 我们能够认识海尔滋莫或者巴金森氏疾病的高度, 我们会需要我们 深入自己并且问
engaged:adj.已订婚的; v.吸引住; (engage的过去分词和过去式) evolve:v.(使)逐渐形成;进化;进化形成; resources:n.[计][环境]资源; v.向…提供资金(resource的第三人称单数); constraints:n.[数]约束;限制;约束条件(constraint的复数形式); extend:vt.延伸; vi.延伸;
What are our roles? “我们的角色是什么？
What are our genes? 我们的基因是什么？”
and looking within ourselves for information we used to say we should go to the outside, to experts, and to be willing to share that with others. 从我们自身来寻找信息 我们常说我们应该走出去, 去成为专家, 愿意去跟人分享
Thank you very much. 非常感谢
(Applause) （鼓掌）。