What you need to know about CRISPR | Ellen Jorgensen

881,095 views ・ 2016-10-24

TED


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譯者: Aaron Shoo 審譯者: 易帆 余
00:12
So, has everybody heard of CRISPR?
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大家都有聽過「CRISPR」 嗎?
00:15
I would be shocked if you hadn't.
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沒聽過就太落伍了。
00:18
This is a technology -- it's for genome editing --
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這是一種基因組編輯技術,
00:21
and it's so versatile and so controversial
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非常萬用卻又極具爭議,
00:24
that it's sparking all sorts of really interesting conversations.
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因而引起了各種有趣的討論。
00:28
Should we bring back the woolly mammoth?
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我們該讓猛瑪象復活嗎?
00:31
Should we edit a human embryo?
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我們要去修改人類胚胎嗎?
00:34
And my personal favorite:
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還有我最喜歡的這個:
00:36
How can we justify wiping out an entire species
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我們能夠接受,
用這項技術,
00:40
that we consider harmful to humans
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將我們人類認為有害的物種,
00:43
off the face of the Earth,
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從地球上完全消失嗎?
00:44
using this technology?
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00:47
This type of science is moving much faster
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這類的科學進展地太快了,
00:50
than the regulatory mechanisms that govern it.
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遠超過制訂規範的腳步。
00:53
And so, for the past six years,
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所以在過去六年,
00:55
I've made it my personal mission
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我給自己一個任務,
00:57
to make sure that as many people as possible understand
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盡可能讓更多人去了解,
01:00
these types of technologies and their implications.
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這類的科技和它們的意義。
01:04
Now, CRISPR has been the subject of a huge media hype,
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媒體現在很愛講「CRISPR」,
01:09
and the words that are used most often are "easy" and "cheap."
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又愛用「輕易」和「廉價」來形容。
01:14
So what I want to do is drill down a little bit deeper
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所以我想要聊得深一點,
01:17
and look into some of the myths and the realities around CRISPR.
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檢視關於「CRISPR」的迷思和現實。
01:22
If you're trying to CRISPR a genome,
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如果要對基因組進行「CRISPR」,
01:25
the first thing that you have to do is damage the DNA.
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首先要破壞它的 DNA。
01:29
The damage comes in the form of a double-strand break
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也就是破壞染色體的雙股螺旋。
01:32
through the double helix.
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01:33
And then the cellular repair processes kick in,
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接著細胞的修復機制會開始介入,
01:37
and then we convince those repair processes
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我們會讓修復過程
01:39
to make the edit that we want,
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照我們期望的方向進行,
01:42
and not a natural edit.
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而不是自然發展。
01:43
That's how it works.
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大概是這樣。
01:45
It's a two-part system.
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這個系統包含兩個部分。
01:47
You've got a Cas9 protein and something called a guide RNA.
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「Cas9 蛋白質」和「嚮導 RNA」。
01:51
I like to think of it as a guided missile.
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就像是導向飛彈。
01:53
So the Cas9 -- I love to anthropomorphize --
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所以「Cas9」
──我喜歡用擬人法來說──
01:56
so the Cas9 is kind of this Pac-Man thing
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「Cas9」就像是小精靈,
01:59
that wants to chew DNA,
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想要把 DNA 吃掉。
02:01
and the guide RNA is the leash that's keeping it out of the genome
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而「嚮導 RNA」則是負責 將 Cas9 帶到特定 RNA 片段,
02:05
until it finds the exact spot where it matches.
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直到它找到執行任務的位置。
02:08
And the combination of those two is called CRISPR.
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兩者結合就是所謂的「CRISPR」。
02:11
It's a system that we stole
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這是我們取法於一種
02:13
from an ancient, ancient bacterial immune system.
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非常古老的細菌免疫系統。
02:17
The part that's amazing about it is that the guide RNA,
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驚人的地方在於,「嚮導 RNA」
只需要 20 個字母的核酸序列,
02:22
only 20 letters of it,
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02:23
are what target the system.
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就能定位目標。
02:26
This is really easy to design,
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這很省事,
02:28
and it's really cheap to buy.
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也非常省錢。
02:30
So that's the part that is modular in the system;
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只要依照需求微調細節,
02:35
everything else stays the same.
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其他部分則維持不變。
02:37
This makes it a remarkably easy and powerful system to use.
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所以是非常輕易卻有力的系統。
02:42
The guide RNA and the Cas9 protein complex together
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「Cas9 蛋白質」 和「嚮導RNA」複合體
02:46
go bouncing along the genome,
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沿著基因組探索,
02:48
and when they find a spot where the guide RNA matches,
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找到符合「嚮導 RNA」的位置時,
02:51
then it inserts between the two strands of the double helix,
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它們會插進雙股螺旋結構,
02:54
it rips them apart,
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把雙股螺旋拆開,
02:56
that triggers the Cas9 protein to cut,
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「Cas9 蛋白質」負責分解片段。
02:59
and all of a sudden,
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這個時候,
03:01
you've got a cell that's in total panic
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你的細胞會很恐慌
03:03
because now it's got a piece of DNA that's broken.
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因為某部分的 DNA 斷裂了。
03:07
What does it do?
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那怎麼辦呢?
03:08
It calls its first responders.
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這引起初期應變。
03:10
There are two major repair pathways.
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有兩種主要修復途徑:
03:13
The first just takes the DNA and shoves the two pieces back together.
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第一種是找到 斷裂的 DNA 把它塞回去。
03:18
This isn't a very efficient system,
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這通常沒什麼效率,
03:20
because what happens is sometimes a base drops out
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因為結果要不是少一個鹼基
03:23
or a base is added.
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就是多一個鹼基。
03:25
It's an OK way to maybe, like, knock out a gene,
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若只想把某個基因去除還可以,
03:28
but it's not the way that we really want to do genome editing.
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但要剪輯基因組卻不是 我們想的那麼簡單。
03:32
The second repair pathway is a lot more interesting.
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第二種修復途徑就有趣多了。
03:35
In this repair pathway,
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這種修復方法,
03:36
it takes a homologous piece of DNA.
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需要一段同源 DNA。
03:39
And now mind you, in a diploid organism like people,
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大家知道,人的染色體是成對的,
03:42
we've got one copy of our genome from our mom and one from our dad,
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一半來自媽媽,一半來自爸爸,
03:46
so if one gets damaged,
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所以,若有一邊受損了,
03:47
it can use the other chromosome to repair it.
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可以用另一半染色體去修補。
03:50
So that's where this comes from.
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這就是修補的原理。
03:52
The repair is made,
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受損修好了,
03:54
and now the genome is safe again.
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基因組又恢復正常了。
03:56
The way that we can hijack this
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我們要做手腳的部分,
03:58
is we can feed it a false piece of DNA,
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是補上一段不一樣的 DNA,
04:02
a piece that has homology on both ends
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兩端接點是同源基因,
04:04
but is different in the middle.
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但中間的排序不一樣。
04:06
So now, you can put whatever you want in the center
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所以中間是什麼沒差,
04:08
and the cell gets fooled.
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細胞都會信以為真。
04:10
So you can change a letter,
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你可以更動其中一個序列,
04:12
you can take letters out,
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把其中一個密碼取出來,
04:13
but most importantly, you can stuff new DNA in,
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更甚者,塞一段新的 DNA 進去,
04:16
kind of like a Trojan horse.
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就像特洛伊木馬。
04:19
CRISPR is going to be amazing,
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「CRISPR」很神奇,
04:21
in terms of the number of different scientific advances
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因為它促成了好幾項
04:24
that it's going to catalyze.
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科學的新進展。
04:26
The thing that's special about it is this modular targeting system.
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它特別的是精準執行系統。
04:29
I mean, we've been shoving DNA into organisms for years, right?
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將 DNA 植入有機體不是新技術。
04:33
But because of the modular targeting system,
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但有了制式化的定位系統,
04:35
we can actually put it exactly where we want it.
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就可以將它放在確切的位置。
04:39
The thing is that there's a lot of talk about it being cheap
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目前很多人說它有多便宜,
04:45
and it being easy.
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然後多好做。
04:46
And I run a community lab.
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我帶領一個社區型實驗室。
04:50
I'm starting to get emails from people that say stuff like,
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我開始收到電郵問說,
04:53
"Hey, can I come to your open night
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「嘿,我可以去你們那邊,
04:56
and, like, maybe use CRISPR and engineer my genome?"
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然後用 CRISPR 整一下基因嗎?」
04:59
(Laugher)
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(笑聲)
05:01
Like, seriously.
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這是真的。
05:03
I'm, "No, you can't."
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我只好回「抱歉,不行」。
05:05
(Laughter)
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(笑聲)
05:06
"But I've heard it's cheap. I've heard it's easy."
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「但聽說不貴而且不難嘛。」
05:08
We're going to explore that a little bit.
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讓我來解釋一下。
05:10
So, how cheap is it?
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到底是有多「廉價」?
05:12
Yeah, it is cheap in comparison.
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相較之下是蠻便宜的。
05:15
It's going to take the cost of the average materials for an experiment
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一般實驗耗材的錢可以省不少,
05:19
from thousands of dollars to hundreds of dollars,
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從幾千塊到幾百塊,
05:21
and it cuts the time a lot, too.
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當然也可以省時間。
05:23
It can cut it from weeks to days.
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從原本的幾星期到幾天就可以。
05:26
That's great.
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這些很了不起。
05:27
You still need a professional lab to do the work in;
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但是這仍要專業的實驗室才能做;
05:30
you're not going to do anything meaningful outside of a professional lab.
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在實驗室外做不出什麼東西。
05:34
I mean, don't listen to anyone who says
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不要聽人家亂說,
05:36
you can do this sort of stuff on your kitchen table.
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以為這在廚房流理台就做得好。
05:39
It's really not easy to do this kind of work.
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這也沒有想像中這麼容易。
05:43
Not to mention, there's a patent battle going on,
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更別提他們還在打專利的官司。
05:46
so even if you do invent something,
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先不管你用這個做出什麼,
05:48
the Broad Institute and UC Berkeley are in this incredible patent battle.
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麻省理工的博德研究所和 加州柏克萊大學爭得不可開交。
05:54
It's really fascinating to watch it happen,
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看他們這樣也是挺精彩的,
05:57
because they're accusing each other of fraudulent claims
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因為雙方都在指控對方說謊,
06:00
and then they've got people saying,
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然後兩邊都有人說:
06:02
"Oh, well, I signed my notebook here or there."
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「你看是我先申請專利的。」
06:05
This isn't going to be settled for years.
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總之還要拖好多年。
06:07
And when it is,
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等到塵埃落定,
06:08
you can bet you're going to pay someone a really hefty licensing fee
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想必要把大筆專利金付給贏家
06:11
in order to use this stuff.
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才能用這項技術。
06:13
So, is it really cheap?
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所以真的便宜嗎?
06:15
Well, it's cheap if you're doing basic research and you've got a lab.
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其實,如果只是在實驗室 做些簡單研究還算便宜。
06:21
How about easy? Let's look at that claim.
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那它簡單嗎?我們來看看。
06:24
The devil is always in the details.
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魔鬼藏在細節裡。
06:27
We don't really know that much about cells.
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我們其實不了解細胞。
06:31
They're still kind of black boxes.
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他們就像黑盒子。
06:32
For example, we don't know why some guide RNAs work really well
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比如說我們不懂為什麼
有些嚮導 RNA 有用、有些沒用。
06:37
and some guide RNAs don't.
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06:39
We don't know why some cells want to do one repair pathway
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為什麼有些細胞用某種修復法,
06:43
and some cells would rather do the other.
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有些卻喜歡用另外的方法。
06:46
And besides that,
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除此之外,
06:47
there's the whole problem of getting the system into the cell
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把 CRISPR 丟進人體就是大問題。
06:50
in the first place.
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06:51
In a petri dish, that's not that hard,
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在培養皿一點都不難,
06:53
but if you're trying to do it on a whole organism,
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但要放進一個有機體,
06:56
it gets really tricky.
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就沒那麼容易了。
06:58
It's OK if you use something like blood or bone marrow --
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如果用血液或骨髓還可能,
07:01
those are the targets of a lot of research now.
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現在實驗多以這兩個為目標。
07:03
There was a great story of some little girl
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有很多小女生,
07:05
who they saved from leukemia
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白血病痊癒的案例,
07:07
by taking the blood out, editing it, and putting it back
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先取出血液,處理完再放回去,
07:10
with a precursor of CRISPR.
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用的是 CRISPR 的前體。
07:12
And this is a line of research that people are going to do.
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這是目前的一個研究方向。
07:15
But right now, if you want to get into the whole body,
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但想要直接進入人體,
07:18
you're probably going to have to use a virus.
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可能要透過病毒。
拿一個病毒,把 CRISPR 放進去,
07:20
So you take the virus, you put the CRISPR into it,
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07:22
you let the virus infect the cell.
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讓病毒感染細胞。
07:24
But now you've got this virus in there,
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可是病毒會留在體內,
07:26
and we don't know what the long-term effects of that are.
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搞不好長期會有什麼影響。
07:29
Plus, CRISPR has some off-target effects,
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CRISPR 也未必百發百中,
07:31
a very small percentage, but they're still there.
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失誤機率很小但也不是沒有。
07:34
What's going to happen over time with that?
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長遠來看會不會有問題?
07:38
These are not trivial questions,
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這些不是小問題,
07:40
and there are scientists that are trying to solve them,
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科學家正在想辦法解決,
07:42
and they will eventually, hopefully, be solved.
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也希望最後都能被解決。
07:45
But it ain't plug-and-play, not by a long shot.
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但絕非一蹴可幾,而且機會渺茫。
07:48
So: Is it really easy?
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所以有那麼容易嗎?
07:51
Well, if you spend a few years working it out in your particular system,
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如果你花個幾年摸透自己的身體,
07:55
yes, it is.
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那應該就不難。
07:57
Now the other thing is,
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但有另一個問題是,
07:59
we don't really know that much about how to make a particular thing happen
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如果改變基因組的某部分,
08:05
by changing particular spots in the genome.
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身體的改變會怎麼被觸發?
08:09
We're a long way away from figuring out
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比如說,我們還要很久才會知道
08:11
how to give a pig wings, for example.
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怎麼給豬一對翅膀。
08:14
Or even an extra leg -- I'd settle for an extra leg.
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或多一隻腿,這就很了不起了。
08:17
That would be kind of cool, right?
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這聽起來很酷吧?
08:18
But what is happening
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但現在的情況是,
08:20
is that CRISPR is being used by thousands and thousands of scientists
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無數的科學家正用 CRISPR,
08:24
to do really, really important work,
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做很重要的研究,
08:27
like making better models of diseases in animals, for example,
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比如說用動物建立疾病的模型;
08:32
or for taking pathways that produce valuable chemicals
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或是去製造珍貴的化學物質,
08:37
and getting them into industrial production in fermentation vats,
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將他們投入工業級生產發酵;
08:42
or even doing really basic research on what genes do.
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或是研究最基本的基因行為。
08:46
This is the story of CRISPR we should be telling,
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這才是 CRISPR 該被討論的,
08:48
and I don't like it that the flashier aspects of it
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而不是那些虛華的表象,
08:52
are drowning all of this out.
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掩蓋檯面下的這些努力。
08:54
Lots of scientists did a lot of work to make CRISPR happen,
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許多科學家努力讓 CRISPR 成真,
08:58
and what's interesting to me
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而我覺得欣慰的,
09:00
is that these scientists are being supported by our society.
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是我們的社會給予他們支持。
09:05
Think about it.
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想想看。
09:06
We've got an infrastructure that allows a certain percentage of people
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我們的社會允許這一小撮人,
09:10
to spend all their time doing research.
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投入全部的時間心力做研究。
09:14
That makes us all the inventors of CRISPR,
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所以我們都是 CRISPR 的發明人,
09:18
and I would say that makes us all the shepherds of CRISPR.
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我們也都變成 CRISPR 的監督人。
09:23
We all have a responsibility.
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我們都有責任。
09:25
So I would urge you to really learn about these types of technologies,
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所以我鼓勵大家多認識這些科技,
09:30
because, really, only in that way
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因為真的只有這樣,
09:32
are we going to be able to guide the development of these technologies,
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我們才能引導這些科技的發展、
09:36
the use of these technologies
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這些科技的應用,
09:38
and make sure that, in the end, it's a positive outcome --
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而且確保最後的正面產出,
09:43
for both the planet and for us.
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無論是對地球或是對我們。
09:46
Thanks.
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謝謝。
09:47
(Applause)
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(掌聲)
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