TED日本語 - リチャード・レズニック: ゲノム革命の時代へようこそ

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TED日本語 - リチャード・レズニック: ゲノム革命の時代へようこそ

TED Talks

ゲノム革命の時代へようこそ
Welcome to the genomic revolution
リチャード・レズニック
Richard Resnick

内容

TEDxBostonで行われたこのわかりやすいスピーチの中で、リチャード・レズニックが、どれほど安価に、そして速く、ゲノムの配列解析が健康管理(そして保険や政治)を激変させようとしているのかを語ります。

Script

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)

皆さん 人間のゲノムをお見せしましょう (拍手) 第1染色体が左上にあって 右下は性染色体です 女性は大きい性染色体Xを2本持ち 男性はXと小さい性染色体Yを 持っています 男性の皆さん 残念ですが女性との差はたったこれだけです この染色体を拡大すると 二重らせん構造が現れ 生命の情報が 4種類の遺伝記号 A, C, G, T という塩基で 記されています 人間は30億個の塩基を持っています ものすごい数でしょう? 数が大きいと訳がわからなくなりますが 1280x800の解像度の画面に 1ピクセルあたり1つの塩基を置くと ゲノムを見渡すのに3,000の画面が必要です 本当にものすごい数です

巨大だったからかもしれませんが Y染色体を持つ人たちのグループが 配列の解析をしようと思いつきました (笑) 15年と40億ドルのお金をかけて ゲノムの配列が解析・公表されました 2003年には最終版が公表され 今も研究が続いています 解析はこんな機械で行われました 塩基一つあたり約1ドルかかり 時間がかかるやり方です

でも皆さん 私はこの状態が 一変していることに 誰も気づいてないと言いたいのです 現在は一つのゲノムに対し 50個ほどのコピーを作り 50個に分けた塩基の配列をそれぞれ 並行して解読するやり方です それをソフトウェアに入力して 再構成して結果を出します これがどんな感じかと言うと ヒトゲノム計画では 30億の塩基を調べました この機械を使えば 1週間で2千億個の塩基が分析できます この夏には6千億になり まだまだスピードは上がりそうです ですから塩基1つの配列解析のコストは 100万分の1になりました これは1998年に満タンにした車のガソリンで 2011年になったら 木星まで2往復できたのと同じです

(笑)

世界の人口や パソコンの台数 全ての医学論文のアーカイブ ムーアの法則 従来の解析方法 そしてこれが全く新しい方法です このグラフは対数尺度です 線がこんな感じに跳ね上がることは普通ありません 世界でヒトゲノムを解析するスピードは 今のところ年に5万から10万人分です 使われている機器に基づく推定です 当分は 年ごとに2倍 3倍もしくは4倍に 増えていくことでしょう 実際の話 ある研究所は 世界の2割の解析能力を持っています 北京ゲノム研究所です 中国は現代版「月レース」で着実に勝利を収めつつあります 医療における影響は何でしょう?

ある37歳の女性がいました ステージ2のエストロゲン性乳がんにかかり 手術 化学療法 放射線療法を受け 退院しました 2年後 ステージ3の卵巣がんになり再入院しました 残念なことに 治療はまた手術と化学療法でした 3年後 42歳で卵巣がんが再発し また化学療法を受けました そして半年後 急性の骨髄性白血病になり 呼吸不全を起こして8日後に亡くなりました

まず この女性が受けた治療は10年もしないうちに 瀉血のように根拠がないものだと見なされるでしょう ワシントン大学のゲノム研究所にいる 私の同僚のリック・ウィルソンたちが 遺体を検視したおかげです 健康な皮膚の細胞と がんにかかった骨髄を採取し 2週間で 両方のゲノムを解析しました 大したことではありません そしてこの2つのゲノムを比較し 発見したことの1つが 30億の塩基のうち2千個が TP53という特定の遺伝子の中で 欠損していることでした この遺伝子に有害突然変異が起きると 90%の確率でがんにかかります

あの女性を助けることにはなりませんが 彼女の家族に対しては 厳しく深刻な意味を持っています もし彼らに同じ変異があって それが遺伝子検査でわかれば 定期的に検査することで がんを早期発見でき 寿命を大幅に伸ばせるかもしれません

ビアリー家の双子の話をします 2歳の時 脳性麻痺と診断されました 母親は決然とした人で 症状のつじつまが合わない筈はないと 多大な努力とネット検索の末に 子どもは脳性麻痺ではないことを 医学界に 納得させました 実際にはドーパ反応性ジストニアだったのです L-Dopaという薬を処方され 症状は改善しましたが 完全にはなくならず まだ障害を抱えていました

でも写真の男ジョー・ビアリーは 運よくライフ・テクノロジーという 会社のCIOでした 2社ある大型全ゲノム解析機の 製造企業の1つだったのです 彼は自分の子どもたちのゲノムを解析し SPRという遺伝子に一連の変異があるのを見つけました この遺伝子はセロトニンを作ります そこでL-Dopaに併せてセロトニン前駆薬を与えると 子どもたちは全く正常になりました ゲノム解析がなければ起こり得なかったことです 数年前には10万ドルかかりましたが 今は1万ドル 来年には1,000ドル 再来年ごろには100ドルになります これほど速く進歩しているのです

この写真のニック君は バットマンと水鉄砲がお気に入りです 飢餓の被害者のように膨らんだお腹で 小児科にきていました 物を食べていないのではなく 何かを食べると腸が開いて 消化物が胃に戻るのです 数え切れない手術のあと 彼は母親に言いました  「ママ 僕のためにお祈りして すごく痛いの」 主治医がたまたま臨床遺伝学を学んでいたので 問題が何か分からぬまま とにかくゲノムの解析をしました すると単一点突然変異が プログラム細胞死を司る遺伝子に起こっていました 彼の体は食べ物に対して 何らかの免疫反応を起こしていたようでした これはプログラム細胞死を引き起こす自然な反応ですが 下方制御する遺伝子が壊れていました ここから 骨髄移植が必要だとわかり 手術が行われました 9か月間の厳しいリハビリを終え 今では 普通にステーキを食べています

(笑)

万能の診断方法として ゲノムを使える可能性が 開けています それはもう 実現しています どういうことかと言うと ゲノム診断により 会場の皆さんの寿命が 5~20年ほど長くなるということです 何と素晴らしい話でしょう 人類の地球に対する負担や食糧増産の余地などを 考えなければ の話ですが 全く同じ技術は 新しい種類のトウモロコシや 大豆 その他の穀物を 育てることにも使われ 干ばつや洪水 害虫や殺虫剤に強い 品種が生まれています 人口が増えていく限り 遺伝子組み換え食品を育て 口にしなければならない それが今日 私が取る立場です 食べなくてもいいという方が いれば話は別ですが 誰もいませんね

これはタイプライターです 何十年もの間 どの机にも置かれていました しかしこれによって実質的に消滅させられました そしてより一般的なワープロが現れました 要は途絶を重ねていったのだということです ボブ・メトカルフェがイーサネットを発明し あらゆるコンピュータを結びつけ 全てを変えました 気づいたときにはネットスケープとヤフーがいて あのドットコム・バブルが起きました (笑) でも心配は不要です iPodやフェイスブック そして アングリーバードが救ってくれました (笑)

私たちは今 ここにいます ここが現時点のゲノム革命です 考えてみて下さい これらの点が あなたの個々の塩基を表しているのではなく 世界中のゲノムの繋がりだとしたら 私は最近生命保険に入りました こんな質問に答えさせられました A: 遺伝子検査を受けたことがない B: 受けたことがある C: 受けたがそれについては答えない ありがたいことに私は「A」だったので 正直にそのまま答えました でももし「C」だったらどうなっていたか?

一般向けのゲノム活用が広まるでしょう 遺伝子的に恋人と相性が良いかどうか 知りたいですよね? iPhoneで遺伝子解析?アプリにおまかせです

(笑) ゲノムでカスタマイズされたマッサージはいかが? 既に ある研究所では 俗に言う浮気遺伝子のAVPR1の 対立遺伝子を検査しています 今日カップルで来ている方は 相手の口腔に入れた綿棒を ラボに送れば確信できます (笑) 心筋症を示唆するゲノムを持つ 大統領を選びたいと思いますか? 2016年の大統領選で 候補者が 4年分の納税申告書だけでなく 自分のゲノムも公表したとします これが非常に望ましいゲノムで 他の候補者にも公表を迫ったとしたら? そんなことは起こらないと思いますか? マケインの時にこれがあったら? (笑)

皆さんの中で 私と同じレズニックという 名字の方がいたら 手を挙げて下さい 誰もいませんか? 普通1~2人はいるのですが 私の祖父は10人兄弟で お互い嫌い合っていて 世界中別の地域に移住したので 私は他のレズニックさんたちと 血縁がある可能性が高いのではと思います 私のゲノムが匿名でソフトに入力され ある従兄弟のゲノムもそこにあれば その二つを比べて関連づけることが できるかもしれません 難しくありません 現にそのソフトは私の会社にあります 更にもう一つ想像してみて下さい ソフトが「遠縁の従兄弟と会ってみませんか?」と 互いの同意を得ることができたら? 両者が「はい」と言えば 染色体版リンクトインの出来上がりです

(笑)

これは多分良いことですよね? 一族とのつながりが広まります でもこれは悪いことでもあります 父親の方は手を挙げて下さい 専門家によれば あなた方の1~3%は 子どもの真の父親ではありません

(笑) 見て下さい - (笑)

これらのゲノム 23対の染色体は 少なくとも今のところ人間関係の質や社会の本質を 表すものではありません どのような新技術でも 人類のため役立てるかどうかは 全て私たち次第なのです だから皆さんには 今起きているゲノム革命のことを知り 良い方向へ影響づけてほしいのです

ありがとう

(拍手)

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