TEDSummit
Ellen Jorgensen: What you need to know about CRISPR
艾倫‧卓根森: 關於 CRISPR，你該知道什麼？
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我們該復活猛瑪象嗎？或是修改人類胚胎？把認為對人類有害的物種全部消滅？基因模組修改科技 CRISPR 讓這一切都可能實現，但它是怎麼辦到的呢？科學家艾倫卓根森要為我們這些科學門外漢抽絲剝繭，解釋關於CRISPR的迷思和現況。
Ellen Jorgensen - Biologist, community science advocate
Ellen Jorgensen is at the leading edge of the do-it-yourself biotechnology movement, bringing scientific exploration and understanding to the public. Full bio
Ellen Jorgensen is at the leading edge of the do-it-yourself biotechnology movement, bringing scientific exploration and understanding to the public. Full bio
Double-click the English transcript below to play the video.
大家都有聽過「CRISPR」 嗎？
00:12
So, has everybody heard of CRISPR?
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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 --
it's for genome editing --
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這是一種基因修改技術，
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.
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
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
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.
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
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.
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,
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."
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
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.
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.
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
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,
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
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.
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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就像是導向飛彈的兩部分。
01:53
So the Cas9 --
I love to anthropomorphize --
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
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，
將 Cas9 帶到特定RNA片段，
02:05
until it finds the exact spot
where it matches.
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.
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.
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,
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;
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.
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
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,
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,
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.
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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這引起第一階段反應。
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.
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
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,
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.
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。
我們想的那麼簡單。
03:32
The second repair pathway
is a lot more interesting.
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,
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,
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.
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
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,
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
scientific advances
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因為它促成了好幾項
科學的新進展。
04:24
that it's going to catalyze.
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04:26
The thing that's special about it
is this modular targeting system.
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?
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,
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.
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
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,
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?"
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."
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
materials for an experiment
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ㄧ般實驗耗材的錢是一定的，
05:19
from thousands of dollars
to hundreds of dollars,
to hundreds of dollars,
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從幾千塊到幾百塊都有，
05:21
and it cuts the time a lot, too.
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當然也很花時間。
05:23
It can cut it from weeks to days.
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多則幾星期，少則幾天。
05:26
That's great.
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就很了不起了。
05:27
You still need a professional lab
to do the work in;
to do the work in;
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而且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.
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.
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.
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,
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.
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。
加州柏克萊大學爭得不可開交。
05:54
It's really fascinating
to watch it happen,
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
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."
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
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.
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。
做些簡單研究還算便宜。
06:21
How about easy?
Let's look at that claim.
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.
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
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
want to do one repair pathway
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為什麼有些細胞用第一種修復，
06:43
and some cells would rather do the other.
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有些卻喜歡用第二種。
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
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,
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 --
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.
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
of some little girl
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有很多小女生，
白血病痊癒的案例，
07:05
who they saved from leukemia
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07:07
by taking the blood out, editing it,
and putting it back
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.
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,
into the whole body,
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但想要直接進入人體，
可能要透過病毒。
07:18
you're probably going
to have to use a virus.
to have to use a virus.
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拿一個病毒，把 CRISPR 放進去，
07:20
So you take the virus,
you put the CRISPR into it,
you put the CRISPR into it,
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讓病毒感染細胞。
07:22
you let the virus infect the cell.
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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.
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.
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?
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,
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.
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.
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,
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
to make a particular thing happen
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如果改變基因組的某部分，
身體的改變會怎麼被觸發？
08:05
by changing particular spots
in the genome.
in the genome.
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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.
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
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,
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
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 and fermentation vats,
production and 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.
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,
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
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,
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.
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
a certain percentage of people
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我們的社會允許這一小撮人，
投入全部的時間心力做研究。
09:10
to spend all their time doing research.
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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.
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,
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,
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 --
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)
ABOUT THE SPEAKER
Ellen Jorgensen - Biologist, community science advocateEllen Jorgensen is at the leading edge of the do-it-yourself biotechnology movement, bringing scientific exploration and understanding to the public.
Why you should listen
In 2009, after many years of working as a molecular biologist in the biotech industry, together with TED Fellow Oliver Medvedik, Jorgensen founded Genspace, a nonprofit community laboratory dedicated to promoting citizen science and access to biotechnology. Despite criticism that bioresearch should be left to the experts, the Brooklyn-based lab continues to thrive, providing educational outreach, cultural events and a platform for science innovation at the grassroots level. At the lab, amateur and professional scientists conduct award-winning research on projects as diverse as identifying microbes that live in Earth's atmosphere and (Jorgensen's own pet project) DNA-barcoding plants, to distinguish between species that look alike but may not be closely related evolutionarily. Fast Company magazine named Genspace one of the world's "Top 10 innovative companies in education."
Ellen Jorgensen | Speaker | TED.com