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Richard Resnick 談歡迎加入基因革命

Richard Resnick: Welcome to the genomic revolution

 

Photo of three lions hunting on the Serengeti.

講者:Richard Resnick

2011年7月演講,2011年9月在TEDxBoston上線

 

翻譯:洪曉慧

編輯:朱學恆

簡繁轉換:洪曉慧

後製:洪曉慧

字幕影片後制:謝旻均

 

影片請按此下載

MAC及手持裝置版本請按此下載

閱讀中文字幕純文字版本

 

關於這場演講

在這場淺顯易懂的TEDxBoston演講中,Richard Resnick說明基因組定序的廉價及快速性質將如何顛覆目前的健康照護(及保險、政治)體制。

 

關於Richard Resnick

Richard Resnick是基因組企業界的先鋒,他是基因組軟體製造商GenomeQuest的執行長。

 

為什麼要聽他演講

Richard Resnick是GenomeQuest的執行長,這是一間為基因組療法建立支援軟體的公司-利用基因組處理程序的廉價和易得優勢,研究及發展個人化的治療方法。他是Mosaic生物資訊公司的前執行長;在成為生物企業家之前,他在麻省理工學院Eric Lander的領導下擔任人類基因組計畫成員。

 

Richard Resnick的英語網上資料

Home: genomequest.com

 

[TED科技‧娛樂‧設計]

已有中譯字幕的TED影片目錄(繁體)(簡體)。請注意繁簡目錄是不一樣的。

 

Richard Resnick 談歡迎加入基因革命

女士先生們,我現在給你們看的是人類基因組。(掌聲)左上角是一號染色體,右下角是性染色體。女性有兩條大X染色體,男性有一條大X染色體,當然,還有一條小Y染色體。男性們,抱歉,但就是這小小的東西讓你有所不同。因此,如果你將這個基因組放大,你們所看到的,當然就是這個雙螺旋結構,由四個生化字母拼成的生命密碼,或稱之為鹼基,對嗎?A,C,G和T。人類基因組中有多少這樣的組合?30億。這是個大數目嗎?好吧,每個人都可以隨意使用大數字,但如果我將每個鹼基當成一個像素,放在這個解析度為1280×800的螢幕上,需要3000個螢幕才能遍覽所有基因組,所以這個數字確實相當大。

 

或許因為它的大小,有一群人-順帶一提,全都是擁有Y染色體的人,決定將它定序。(笑聲)15年來,花費約40億美元後,人們完成基因組定序,並將結果發表。2003年發表了最終版本,目前他們繼續進行這項工作,全都用像這樣的機器進行,每個鹼基大約花費一美元-是一種非常緩慢的方式。

 

好,各位,我在這裡告訴你們,世界已經完全改變,但你們並不知道。所以,現在我們所做的是,取一個基因組,大約將它複製50份,我們將所有複製樣本切割成個50鹼基大小,同時進行大規模定序,然後我們用軟體將它進行重組,並解讀其結果。這是為了讓你們對人類基因組計劃有個概念:30億個鹼基,對嗎?逐一在這些現代機器上定序,每星期可定序2000億個鹼基。到了今年夏天,這個數字將由2000億變成6000億,而且步伐並沒有減緩的跡象。因此,每個鹼基的價格,定序一個鹼基的價格已減少一億倍,相當於你在1998年將車子加滿油,等到2011年,就能開車來回木星兩次。

 

(笑聲)

 

世界人口、個人電腦裝置、所有醫學文獻檔案、摩爾定律、傳統定序法,這裡代表所有新科技。各位,這是一張對數標度圖,通常不會看到像這樣的上升曲線,因此,今年全球定序人類基因組的總量大約是5萬至10萬個人類基因組。我們知道這與機器設置的數量有關,預計每年會以兩倍、三倍或四倍的速度成長,這是未來的展望。事實上,有個實驗室定序的基因組數量佔全球的20%,就是北京華大基因研究中心。順帶一提,中國人絕對能贏得這項新的登月競賽。這對醫療來說意味著什麼?

 

有位37歲的女性,罹患第2期雌激素受體陽性乳癌,她進行了手術、化療及放射線治療,之後她回家休養。兩年後,她罹患了第3期卵巢癌,不幸的是,她再次進行手術和化療。三年後,42歲的她再度罹患更嚴重的卵巢癌,並接受更多的化療。半年後,她罹患急性骨髓性白血病,八天後因呼吸衰竭而死亡。

 

因此,首先,這位婦女進行的治療方式,在短短10年後,看起來就像放血那麼落後,這是因為某些人,像我任職於華盛頓大學基因組研究所的同事Rick Wilson,決定在這位女性過世後替她做些檢測。他為她做基因定序,取了健康的皮膚細胞和發生癌病變的骨髓,他在幾星期內將這兩樣組織整個基因組定序,小事一樁,對嗎?然後他用軟體比對了這兩個基因組,他發現其中有個缺失。在30億個鹼基中,在一個叫做TP的特定基因上,有2000個鹼基的缺失。如果這個基因發生有害突變,一生中就有90%的機會可能罹患癌症。

 

不幸的是,這未能幫上這位女性的忙,但確實對她的家人產生深刻的影響。我的意思是,如果他們擁有相同的突變基因,只要進行這個基因測試,就能瞭解這個情況,那麼他們可進行定期篩檢,早期發現癌症,或許能因此活得更長久。

 

讓我來介紹一下Beery雙胞胎,他們在兩歲時被診斷出罹患腦性麻痺。他們的母親是個非常勇敢的女性,她不相信這個與症狀不符的診斷,經過一番艱苦的努力和許多的網路搜尋,她終於說服醫學界,事實上,他們罹患的是某種其他疾病。他們罹患的是多巴反應性肌張力障礙,因此服用左旋-多巴進行治療。他們的症狀確實有所改善,但沒有完全消除,依然存在嚴重的問題。

 

看一下這張照片,這是一位名叫Joe Beery的男士,他相當幸運地在一間叫做生命科技的公司擔任資訊長,這是製造整套基因組定序工具的兩大公司之一。因此他將孩子們的基因進行定序,他們發現在一個叫SPR的基因上有一系列的突變,這個基因負責製造血清素等相關功能。因此除了左旋-多巴之外,他們讓這些孩子服用一種血清素前驅藥物,現在他們已恢復正常。各位,這在基因組定序完成之前是不可能做到的。在當時-這是幾年前的事-這個成本是十萬美元,現在成本是一萬美元,明年會是一千美元,後年將會是一百美元,每年都會有所變化,這就是這個技術發展的速度。

 

這是小Nick-他喜歡蝙蝠俠和水槍。當Nick出現在兒童醫院時,挺著像饑荒兒童那樣腫脹的肚子。這不是因為他沒有進食,而是因為當他進食時,他的腸道基本上呈打開狀態,使糞便流入他的腹腔中。歷經上百次手術後,他看著媽媽說,「媽媽,請為我祈禱,我實在太痛苦了。」他的兒科醫生碰巧有臨床遺傳學背景,他不知道疾病發生的原因,但他說,「我們不妨為這個孩子做基因組定序。」他們發現的是,在一個負責控制程序性細胞死亡的基因上有一個單點突變,因此,其中原因在於,基本上他發生某些跟食物有關的免疫反應。這是個自然反應,導致一些細胞程序性死亡,但調控這項功能的基因有所缺陷。因此,對這個情形來說,這表示,當然,必須進行骨髓移植治療。他接受了這項手術,經過9個月艱苦的復原期後,他現在可以吃淋上A1醬的牛排。

 

(笑聲)

 

今天,使用基因組作為普遍診斷方法正逐漸成為醫療的前景,就是現在,此時此刻。這對全人類來說,意味著這房間裡每一個人都可以多活個5年、10年或20年,只因為這項技術。這是個神奇的故事,除非你思考人類在這個星球上的足跡,及我們持續生產糧食的能力。所以結果是,同樣的科技也被用來種植能高度耐旱、耐洪水、蟲害和農藥的新品種玉米、小麥、大豆和其他作物。注意,只要人口持續增加,我們將不得不繼續種植和食用基因改造食品,這是目前唯一可行的方法,除非在場聽眾有人打算自願停止進食。不,沒人會這麼做。

 

這是一台打字機,數十年來每張辦公桌上的主角。事實上,打字機基本上已被這個東西所取代,然後是更一般性文字處理器的出現。但最後,發生一個影響力勝於一切的事件,就是Bob Metcalfe發明了乙太網路,以及基本上改變了一切的所有計算機網路連結。突然間,我們有了Netscape、Yahoo,事實上,我們擁有整個網際網路泡沫。(笑聲)不過別擔心,這很快地被iPod、Facebook所拯救。事實上,是憤怒鳥。(笑聲)

 

瞧,這就是我們目前的發展,這就是當今的基因革命,這就是我們所處的時代。所以我希望你們思考的是:這意味著什麼?當這些點代表的不是你基因組的個別鹼基,而是與全球基因組的連結?我最近剛買了人壽保險,我得回答下列問題:A.我從未接受過基因測試。B.我接受過測試,願意提供資料。C.我接受過測試,但不願提供資料。謝天謝地,我能回答A,這是很誠實的回答,以免我的人壽保險代理人正在聽這場演講。但如果我的回答是C,會發生什麼情形?

 

基因組學的消費應用將蓬勃發展,你想看看自己在基因上是否與女朋友相容嗎?沒問題。想用你的iPhone進行DNA定序嗎?有相關的應用程式。(笑聲)想進行個人化的基因組按摩嗎?目前已有一個實驗室針對AVPR基因上的等位基因334,即所謂的欺騙基因進行測試。因此,今天與你們重要的另一半一起來的在場聽眾,只要轉身面向他,刮一下他的口腔內側,將結果送到實驗室就能確定了。(笑聲)你真的想選一位基因組顯示可能罹患心肌疾病的總統嗎?思考一下,如果現在是2016年,主要候選人公布的不只是她過去四年的稅後所得,還有她的個人基因組。這看起來相當不錯,然後她挑戰所有競爭對手都這麼做。你認為這不會發生嗎?你認為這對John McCain有幫助嗎?

 

(笑聲)

 

聽眾中有多少人跟我一樣姓Resnick?請舉手。有人嗎?沒有。一般來說會有一、兩位。我祖父是10個Resnick兄弟當中的一個,他們彼此憎恨,他們全都搬到全球不同的地方。因此,很可能我跟曾遇過的每位Resnick都有點親戚關係,但我並不知道。因此,想像一下,如果我的基因組已可識別並存在軟體中,另一位親戚的基因組也存在那裡,並有可比對這兩個基因組、找出其中關連性的軟體。這並非難以想像的事,我公司目前就有可以做到這一點的軟體。因此,再想像一個情形:這個軟體可以要求雙方簽署相互同意書,「你願意與另一位親戚見面嗎?」如果我們兩人都說好,瞧!歡迎來到染色體LinkedIn網站。

 

(笑聲)

 

這或許是件好事,對嗎?你能舉辦更大的家族聚會等等,但或許這也是一件壞事。這房間裡有多少位已經當爸爸的人?請舉手。好,專家認為,這些人當中有1~3%,事實上並不是你孩子的父親。(笑聲)瞧!

 

(笑聲)

 

這些基因組,這23條染色體,它們無法代表我們人際關係的品質或社會的本質-至少目前還不能。正如任何新科技一樣,是否將它用於增進人類福祉,都掌握在我們手中。因此,我敦促大家都應有所醒覺,參與並影響發生在你周遭的基因革命。

 

謝謝。

 

(掌聲)

 

以下為系統擷取之英文原文

About this Talk

In this accessible talk from TEDxBoston, Richard Resnick shows how cheap and fast genome sequencing is about to turn health care (and insurance, and politics) upside down.

About the Speaker

Richard Resnick is on the front lines of the business of genomes, as CEO of GenomeQuest, a maker of genomic software. Full bio and more links Richard Resnick is on the front lines of the business of genomes, as CEO of GenomeQuest, a maker of genomic software. Full bio and more links

Transcript

Ladies and gentlemen, I present to you the human genome. (Applause) Chromosome one, top left. Bottom right are the sex chromosomes. Women have two copies of that big X chromosome; men have the X and, of course, that small copy of the Y. Sorry boys, but it's just a tiny little thing that makes you different. So if you zoom in on this genome, then what you see, of course, is this double helix structure -- the code of life spelled out with these four biochemical letters, or we call them bases, right: A, C, G and T. How many are there in the human genome? Three billion. Is that a big number? Well, everybody can throw around big numbers. But in fact, if I were to place one base on each pixel of this 1280 by 800 resolution screen, we would need 3,000 screens to take a look at the genome. So it's really quite big.

And perhaps because of its size, a group of people -- all, by the way, with Y chromosomes -- decided they would want to sequence it. (Laughter) And so 15 years, actually, and about four billion dollars later, the genome was sequenced and published. In 2003, the final version was published, and they keep working on it. That was all done on a machine that looks like this. It costs about a dollar for each base -- a very slow way of doing it.

Well folks, I'm here to tell you that the world has completely changed and none of you know about it. So now what we do is we take a genome, we make maybe 50 copies of it, we cut all those copies up into little 50-base reads, and then we sequence them, massively parallel. And then we bring that into software, and we reassemble it and we tell you what the story is. And so just to give you a picture of what this looks like, the Human Genome Project: 3 gigabases, right. One run on one of these machines: 200 gigabases in a week. And that 200 is going to change to 600 this summer, and there's no sign of this pace slowing. So the price of a base, to sequence a base, has fallen 100 million times. That's the equivalent of you filling up your car with gas in 1998, waiting until 2011, and now you can drive to Jupiter and back twice.

(Laughter)

World population, PC placements, the archive of all the medical literature, Moore's law, the old way of sequencing, and here's all the new stuff. Guys, this is a log scale; you don't typically see lines that go up like that. So the worldwide capacity to sequence human genomes is something like 50,000 to 100,000 human genomes this year. And we know this based on the machines that are being placed. This is expected to double, triple or maybe quadruple year over year for the foreseeable future. In fact, there's one lab in particular that represents 20 percent of all that capacity. It's called the Beijing Genomics Institute. The Chinese are absolutely winning this race to the new Moon, by the way. What does this mean for medicine?

So a woman is age 37. She presents with stage 2 estrogen receptor-positive breast cancer. She is treated with surgery, chemotherapy and radiation. She goes home. Two years later, she comes back with stage three C ovarian cancer. Unfortunately, treated again with surgery and chemotherapy. She comes back three years later at age 42 with more ovarian cancer, more chemotherapy. Six months later, she comes back with acute myeloid leukemia. She goes into respiratory failure and dies eight days later.

So first, the way in which this woman was treated, in as little as 10 years, will look like bloodletting. And it's because of people like my colleague, Rick Wilson, at the Genome Institute at Washington University, who decided to take a look at this woman postmortem. And he sequenced, he took skin cells, healthy skin, and cancerous bone marrow, and he sequenced the whole genomes of both of them in a couple of weeks, no big deal. And then he compared those two genomes in software, and what he found, among other things, was a deletion, a 2,000-base deletion across three billion bases in a particular gene called TP53. If you have this deleterious mutation in this gene, you're 90 percent likely to get cancer in your life.

So unfortunately, this doesn't help this woman, but it does have severe, profound if you will, implications to her family. I mean, if they have the same mutation, and they get this genetic test, and they understand it, then they can go and get regular screens, and they can catch cancer early and potentially live a significantly longer life.

Let me introduce you now to the Beery twins, diagnosed with cerebral palsy at the age of two. Their mom is a very brave woman who didn't believe that the symptoms weren't matching up, and through some heroic efforts and a lot of Internet searching, she was able to convince the medical community that, in fact, they had something else. What they had was dopa-responsive dystonia. And so they were given L-Dopa, and their symptoms did improve, but they weren't totally asymptomatic. Significant problems remained.

Turns out the gentleman in this picture is a guy named Joe Beery, who was lucky enough to be the CIO of a company called Life Technologies. They're one of the two companies that makes these massive whole genome sequencing tools. And so what he did was he got his kids sequenced. And what they found was a series of mutations in a gene called SPR, which is responsible for producing serotonin, among other things. So on top of L-Dopa, they gave these kids a serotonin precursor drug, and they're effectively normal now. Guys, this would never have happened without whole genome sequencing. And at the time -- this was a few years ago -- it cost $100,000. Today it's $10,000. Next year it's $1,000. The year after it's $100, give or take a year. That's how fast this is moving.

So here's little Nick -- likes Batman and squirt guns. And it turns out Nick shows up at the children's hospital with this distended belly like a famine victim. And it's not that he's not eating, it's that when he eats, his intestine basically opens up and feces spill out into his gut. So a hundred surgeries later, he looks at his mom and says, "Mom, please pray for me. I'm in so much pain." His pediatrician happens to have a background in clinical genetics and he has no idea what's going on, but he says, "Let's get this kid's genome sequenced." And what they find is a single-point mutation in a gene responsible for controlling programmed cell death. So the theory is that he's having some immunological reaction to what's going on to the food essentially, and that's a natural reaction, which causes some programmed cell death. But the gene that regulates that down is broken. And so this informs, among other things, of course, a treatment for bone marrow transplant, which he undertakes. And after nine months of grueling recovery, he's now eating steak with A1 sauce.

(Laughter)

The prospect of using the genome as a universal diagnostic is upon us today. Today, it's here. And what it means for all of us is that everybody in this room could live an extra five, 10, 20 years just because of this one thing. Which is a fantastic story, unless you think about humanity's footprint on the planet and our ability to keep up food production. So it turns out that the very same technology is also being used to grow new lines of corn, wheat, soybean and other crops that are highly tolerant of drought, of flood, of pests and pesticides. Now look, as long as we continue to increase the population, we're going to have to continue to grow and eat genetically modified foods, and that's the only position that I'll take today. Unless there's anybody in the audience that would like to volunteer to stop eating? None, not one.

This is a typewriter, a staple of every desktop for decades. And in fact, the typewriter was essentially deleted by this thing. And then more general versions of word processors came about. But ultimately, it was a disruption on top of a disruption. It was Bob Metcalfe inventing the Ethernet and the connection of all these computers that fundamentally changed everything. And suddenly we had Netscape, and we had Yahoo and we had, indeed, the entire dotcom bubble. (Laughter) Not to worry though, that was quickly rescued by the iPod, Facebook and, indeed, angry birds. (Laughter)

Look, this is where we are today. This is the genomic revolution today. This is where we are. So what I'd like you to consider is: What does it mean when these dots don't represent the individual bases of your genome, but they connect to genomes all across the planet? So I just recently had to buy life insurance. And I was required to answer: A. I have never had a genetic test, B. I've had one, here you go, and C. I've had one and I'm not telling. Thankfully, I was able to answer A, and I say that honestly in case my life insurance agent is listening. But what would have happened if I had said C?

Consumer applications for genomics, they will flourish. Do you want to see whether you're genetically compatible with your girlfriend? Sure. DNA sequencing on your iPhone? There's an app for that. (Laughter) Personalized genomic massage anyone? There's already a lab today that tests for allele 334 of the AVPR1 gene, the so-called cheating gene. So anybody who's here today with your significant other, just turn over to them and swab their mouth, send it to the lab and you'll know for sure. (Laughter) Do you really want to elect a president whose genome suggests cardiomyopathy? Now think of it, it's 2016 and the leading candidate releases not only her four years of back tax returns, but also her personal genome. And it looks really good. And then she challenges all of her competitors to do the same. Do you think that's not going to happen? Do you think it would have helped John McCain?

(Laughter)

How many people in the audience have the last name Resnick like me? Raise your hand. Anybody? Nobody. Typically, there's one or two. So my father's father was one of 10 Resnick brothers. They all hated each other. And they all moved to different parts of the planet. So it's likely that I'm related to every Resnick that I ever meet, but I don't know. But imagine if my genome were deidentified, sitting in software, and a third cousin's genome was also sitting there, and there was software that could compare these two and make these associations. Not hard to imagine. My company has software that does this right now. And so imagine one more thing: that that software is able to ask both parties for mutual consents, "Would you be willing to meet your third cousin?" And if we both say yes, voila! Welcome to chromosomally LinkedIn.

(Laughter)

Now this is probably a good thing, right? You have bigger clan gatherings and so on. But maybe it's a bad thing as well. How many fathers in the room? Raise your hands. Okay, so experts think that one to three percent of you are not actually the father of your child. (Laughter) Look --

(Laughter)

These genomes, these 23 chromosomes, they don't in any way represent the quality of our relationships or the nature of our society -- at least not yet. And like any new technology, it's really in humanity's hands to wield it for the betterment of mankind, or not. And so I urge you all to wake up and to tune in and to influence the genomic revolution that's happening all around you.

Thank you.

(Applause)
 


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转基因食物不太能接受

Anonymous, 2011-11-22 17:55:43

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