Stephen Friend: The hunt for "unexpected genetic heroes"

62,599 views ・ 2014-05-29

TED


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譯者: Jenna Tsai 審譯者: Jonathan Zhang
00:12
Approximately 30 years ago,
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大約是在三十年前
00:14
when I was in oncology at the Children's Hospital
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當我還在費城一間兒童醫院的腫瘤科
00:17
in Philadelphia,
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工作的時候
00:19
a father and a son walked into my office
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一位爸爸帶著兒子走進我的辦公室
00:22
and they both had their right eye missing,
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他們都失去了右眼
00:25
and as I took the history, it became apparent
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在我翻查病歷之中,明顯發現
00:28
that the father and the son had a rare form
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父子倆都患有罕見形式的
00:30
of inherited eye tumor, retinoblastoma,
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遺傳性眼瘤,視網膜母細胞瘤,
00:34
and the father knew that he had passed that fate
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爸爸知道是他將這個厄運
00:37
on to his son.
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傳給他兒子的。
00:39
That moment changed my life.
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那一刻改變了我的人生。
00:41
It propelled me to go on
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它鼓勵我繼續工作
00:43
and to co-lead a team that discovered
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並且去領導一個首先發現
00:47
the first cancer susceptibility gene,
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癌症易感基因的團隊。
00:50
and in the intervening decades since then,
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從那時以來的幾十年之間,
00:53
there has been literally a seismic shift
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簡直是發生了一場巨變,
00:56
in our understanding of what goes on,
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對於我們所認知的一切,
00:58
what genetic variations are sitting behind
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以及各種疾病背後所隱藏的
01:01
various diseases.
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遺傳變異。
01:03
In fact, for thousands of human traits,
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事實上,數千個人類遺傳特徵
01:06
a molecular basis that's known for that,
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是已知的分子基礎。
01:08
and for thousands of people, every day,
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而對於數千個人,每一天,
01:11
there's information that they gain
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他們都會得到
01:14
about the risk of going on to get this disease
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關於患有此疾病或其他疾病
01:16
or that disease.
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風險的訊息
01:18
At the same time, if you ask,
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同時,如果你問道:
01:21
"Has that impacted the efficiency,
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「若它已經影響了功效,
01:23
how we've been able to develop drugs?"
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我們要怎麼做才能開發出新藥?」
01:25
the answer is not really.
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答案並不確定。
01:27
If you look at the cost of developing drugs,
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如果你去查看開發藥物的成本,
01:29
how that's done, it basically hasn't budged that.
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以及它是如何完成的, 基本上它並無太大改變。
01:33
And so it's as if we have the power to diagnose
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所以這就像是我們有能力去診斷,
01:37
yet not the power to fully treat.
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卻沒有能力去全力救治病人。
01:40
And there are two commonly given reasons
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這裡有兩個常見的原因
01:43
for why that happens.
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說明為什麼會有這種狀況發生 :
01:44
One of them is it's early days.
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其一是,還在初期階段,
01:48
We're just learning the words, the fragments,
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我們才剛了解到遺傳密碼中的詞彙
01:51
the letters in the genetic code.
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片段還有字母。
01:53
We don't know how to read the sentences.
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我們並不知道如何讀出整段句子,
01:55
We don't know how to follow the narrative.
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我們也不知道怎麼接續整個故事。
01:58
The other reason given is that
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另一個原因是
02:00
most of those changes are a loss of function,
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大部分變化的發生是因為功能的喪失,
02:02
and it's actually really hard to develop drugs
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事實上,真的很難去開發
02:05
that restore function.
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具有恢復功能的藥物。
02:07
But today, I want us to step back
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但今天,我要大家退一步,
02:09
and ask a more fundamental question,
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問一個更基本的問題,
02:11
and ask, "What happens if we're thinking
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「如果我們假想
02:14
about this maybe in the wrong context?"
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這是在個前後關係錯誤的情況又會怎麼樣?」
02:16
We do a lot of studying of those who are sick
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我們對於那些生病的人做了很多研究,
02:19
and building up long lists
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也建立了一長串
02:22
of altered components.
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構成因素的列表。
02:25
But maybe, if what we're trying to do
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但也許,若我們試著去做的
02:28
is to develop therapies for prevention,
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是開發一種預防疾病的療法;
02:31
maybe what we should be doing
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也許我們應該做的
02:32
is studying those who don't get sick.
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是去研究那些沒有生病的人;
02:35
Maybe we should be studying those
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也許我們真的該去研究那些
02:37
that are well.
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健康的人。
02:39
A vast majority of those people
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這些人絕大多數
02:41
are not necessarily carrying a particular
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未必攜帶著特定的
02:43
genetic load or risk factor.
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遺傳基因或危險因素。
02:45
They're not going to help us.
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這樣的人不會幫到我們什麼。
02:47
There are going to be those individuals
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但他們未來將會是
02:49
who are carrying a potential future risk,
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潛在的高危險群
02:52
they're going to go on to get some symptom.
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他們很有機會得到一些症狀,
02:53
That's not what we're looking for.
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但這也不是我們要找的。
02:55
What we're asking and looking for is,
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我們正在尋找的是
02:57
are there a very few set of individuals
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有沒有少數的個體
03:00
who are actually walking around
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在我們身邊活得好好的,
03:03
with the risk that normally would cause a disease,
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事實上卻處在隨時 會患上各種疾病的風險中,
03:07
but something in them, something hidden in them
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但某個東西在他們身體裡,隱藏在深處
03:10
is actually protective
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實際上是具保護性的,
03:11
and keeping them from exhibiting those symptoms?
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並克制他們顯現出症狀?
03:15
If you're going to do a study like that, you can imagine
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如果你打算進行此類研究,你可以想像
03:17
you'd like to look at lots and lots of people.
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你會想要研究好多好多人。
03:20
We'd have to go and have a pretty wide study,
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我們必須去實施一個特別廣泛的研究,
03:23
and we realized that actually
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並且我們發現事實上
03:25
one way to think of this is,
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有一種思考方式可以告訴我們這是什麼
03:26
let us look at adults who are over 40 years of age,
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讓我們先看看年過40的成人,
03:30
and let's make sure that we look at those
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然後確保那些人
03:33
who were healthy as kids.
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在孩提時代也是健康的。
03:35
They might have had individuals in their families
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在他們的家庭中也許有人
03:37
who had had a childhood disease,
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曾經在幼年發病
03:39
but not necessarily.
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但卻不是十分嚴重。
03:41
And let's go and then screen those
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讓我們去篩選那些
03:43
to find those who are carrying genes
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有攜帶兒童期疾病
03:45
for childhood diseases.
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基因的人。
03:47
Now, some of you, I can see you
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現在,我可以看到你們有些人
03:49
putting your hands up going, "Uh, a little odd.
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手想要舉起來說:「蛤?這有點怪。
03:52
What's your evidence
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你有什麼證據
03:53
that this could be feasible?"
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可以證明這是可行的?」
03:55
I want to give you two examples.
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我想給你們舉兩個例子。
03:57
The first comes from San Francisco.
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第一個是發生在舊金山,
04:00
It comes from the 1980s and the 1990s,
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1980 到 1990 年代這個時期,
04:03
and you may know the story where
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你也許知道這個情況:
04:05
there were individuals who had very high levels
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曾經有些人被高水平的
04:08
of the virus HIV.
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人類免疫缺陷病毒(HIV)所感染,
04:09
They went on to get AIDS.
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他們接著患上了愛滋病。
04:11
But there was a very small set of individuals
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但有少部分人
04:14
who also had very high levels of HIV.
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同樣也有高水平的 HIV 病毒,
04:17
They didn't get AIDS.
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他們卻沒有得愛滋病。
04:18
And astute clinicians tracked that down,
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機敏的臨床醫生追蹤下來,
04:21
and what they found was they were carrying mutations.
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發現他們身上帶有基因變異。
04:24
Notice, they were carrying mutations from birth
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注意!他們是自從出生就有此
04:28
that were protective, that were protecting them
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保護作用的變異,
讓他們不至於得到愛滋。
04:30
from going on to get AIDS.
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04:31
You may also know that actually a line of therapy
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你也許知道事實上有一連串治療
04:34
has been coming along based on that fact.
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是根據這事實而研發出來的。
04:37
Second example, more recent, is elegant work
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第二個較近來的例子,是個漂亮的工作
04:41
done by Helen Hobbs,
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由海倫·霍布斯完成。
04:42
who said, "I'm going to look at individuals
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她說 : 「我要去研究那些
04:45
who have very high lipid levels,
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高脂肪水平的人。
04:47
and I'm going to try to find those people
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然後再從這些
04:49
with high lipid levels
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高血脂水平的人裡面
04:51
who don't go on to get heart disease."
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找出沒有得到心臟疾病的人。」
04:53
And again, what she found was
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再一次,她也發現
04:56
some of those individuals had mutations
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在這之中的一些人也有變異,
04:58
that were protective from birth that kept them,
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也是從他們出生時就開始保護著他們,
05:01
even though they had high lipid levels,
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儘管他們的脂肪水平很高。
05:03
and you can see this is an interesting way
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各位可以看到這是個有趣的方式
05:06
of thinking about how you could develop
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去思考我們該如何發展出
05:08
preventive therapies.
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預防疾病的療法。
05:10
The project that we're working on
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而現在我們正在做的計畫
05:12
is called "The Resilience Project:
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叫做「恢復力計畫:
05:15
A Search for Unexpected Heroes,"
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搜索潛藏的基因英雄。」
05:16
because what we are interested in doing is saying,
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因為我們感興趣的就是
05:18
can we find those rare individuals
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我們是否能夠找到那些
可能擁有保護作用遺傳基因的少數人?
05:21
who might have these hidden protective factors?
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05:25
And in some ways, think of it as a decoder ring,
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在某些方面,想像它是個解碼環,
05:28
a sort of resilience decoder ring
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一種我們正試著建立的
05:30
that we're going to try to build.
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一個恢復力的解碼環。
05:32
We've realized that we should do this in a systematic way,
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我們已了解到必須有條理的方式去建立,
05:36
so we've said, let's take every single
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所以就之前提過的,我們先來看每一個
05:38
childhood inherited disease.
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兒童期發病的遺傳性疾病。
05:40
Let's take them all, and let's pull them back a little bit
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我們先全部研究一遍,
退後一步,
05:42
by those that are known to have severe symptoms,
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透過那些嚴重症狀病患
05:45
where the parents, the child,
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身邊知道他們曾生病過的
05:47
those around them would know
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05:48
that they'd gotten sick,
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父母、子女和其他人,
05:50
and let's go ahead and then frame them again
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接著我們透過已知的
05:53
by those parts of the genes where we know
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某些特定的世道交替原則,
05:56
that there is a particular alteration
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而得出有些變異位於
05:58
that is known to be highly penetrant
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有著很高遺傳機率的基因上
06:01
to cause that disease.
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再去發展並表達出這些基因片段。
06:04
Where are we going to look?
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我們會關注哪些地方?
06:05
Well, we could look locally. That makes sense.
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我們可以從當地開始,這合乎情理。
06:08
But we began to think, maybe we should look
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但我們又想,也許我們應該關注
06:10
all over the world.
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這整個世界。
06:11
Maybe we should look not just here
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我們該關注的不只是在一個地方,
06:13
but in remote places where their might be
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還有偏遠地區,
06:15
a distinct genetic context,
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那裡可能會有與其他不同的遺傳基因背景,
06:18
there might be environmental factors
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更有可能會有某些
06:20
that protect people.
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保護人們的環境因素。
06:21
And let's look at a million individuals.
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讓我們來檢視一百萬個人。
06:25
Now the reason why we think it's a good time
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現在,我們覺得這時候
06:28
to do that now
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是這麼做的好時機,
06:30
is, in the last couple of years,
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因為在過去的幾年,
06:31
there's been a remarkable plummeting in the cost
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從事此類型分析的花費、
06:34
to do this type of analysis,
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這數據生成類型的費用
06:36
this type of data generation,
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明顯地暴跌。
06:38
to where it actually costs less to do
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事實上數據生成以及分析
06:40
the data generation and analysis
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比樣本處理及收集
06:43
than it does to do the sample processing and the collection.
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花的錢還要少。
06:46
The other reason is that in the last five years,
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另一個原因是在最近五年裡
06:50
there have been awesome tools,
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有很不錯的工具以及
06:52
things about network biology, systems biology,
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有關網路生物學、系統生物學的東西,
06:55
that have come up that allow us to think
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被發明出現來讓我們思考
06:57
that maybe we could decipher
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我們能夠解碼
06:59
those positive outliers.
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這絕對異常值的可能性。
07:01
And as we went around talking to researchers
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就當我們到處和研究人員
07:03
and institutions
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及機構談話,
07:05
and telling them about our story,
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告訴他們我們的故事,
07:07
something happened.
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有件事發生了。
07:08
They started saying, "This is interesting.
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他們進而開始說:「這真是有趣。
07:11
I would be glad to join your effort.
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我願意加入幫忙,
07:14
I would be willing to participate."
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我很樂意參與。」
07:16
And they didn't say, "Where's the MTA?"
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他們並沒有問:「有醫療技術助理嗎? 」
07:19
They didn't say, "Where is my authorship?"
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他們也沒有問:「我有沒有著作權? 」
07:22
They didn't say, "Is this data going to be mine? Am I going to own it?"
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他們更沒有問:「這資料會不會是我的?我能夠擁有它嗎?
07:26
They basically said, "Let's work on this
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他們基本上只說了:「我們就一起
07:29
in an open, crowd-sourced, team way
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用開放的、大眾資源、團隊的方式
07:32
to do this decoding."
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來解碼吧!」
07:35
Six months ago, we locked down
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六個月前,我們鎖定了
07:37
the screening key for this decoder.
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這解碼環的篩選鍵。
07:41
My co-lead, a brilliant scientist, Eric Schadt
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我的共同領導,艾里克沙特,一個出色的科學家,
07:45
at the Icahn Mount Sinai School of Medicine in New York,
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在紐約的伊坎西奈山醫學院,
07:48
and his team,
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以及他的團隊,
07:50
locked in that decoder key ring,
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鎖定了一個解碼環的鑰匙圈,
07:53
and we began looking for samples,
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所以我們開始尋找樣本,
07:55
because what we realized is,
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因為我們了解到的是
07:57
maybe we could just go and look
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也許我們可以直接去看
07:58
at some existing samples to get some sense of feasibility.
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那些存在的樣本,去發現一些可行性。
08:01
Maybe we could take two, three percent of the project on,
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也許這個計畫我們可以先做個兩三成
08:04
and see if it was there.
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然後再看看可不可行。
08:05
And so we started asking people
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所以我們就開始詢問人們
08:07
such as Hakon at the Children's Hospital in Philadelphia.
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比如在費城兒童醫院的哈康主任、
08:11
We asked Leif up in Finland.
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在芬蘭的雷夫、
08:13
We talked to Anne Wojcicki at 23andMe,
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基因技術公司 23andMe 的創辦人安妮.沃西基、
08:17
and Wang Jun at BGI,
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華大基因的王俊。
08:19
and again, something remarkable happened.
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又一次,一些顯著的事情發生了。
08:21
They said, "Huh,
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他們說:「哈,
08:23
not only do we have samples,
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我們不只有樣本,
08:24
but often we've analyzed them,
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我們還要去分析他們,
08:27
and we would be glad to go into
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我們很樂意去檢視
08:28
our anonymized samples
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匿名的樣本,
08:29
and see if we could find those
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去看看我們能不能找到
08:32
that you're looking for."
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你們正在找的東西。」
08:33
And instead of being 20,000 or 30,000,
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我們分析的樣本不只是兩、三萬而已,
08:35
last month we passed one half million samples
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上個月我們已分析超過 50 萬。
08:39
that we've already analyzed.
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08:40
So you must be going,
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所以你一定會說
08:42
"Huh, did you find any unexpected heroes?"
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「嘿!你找到潛藏的基因英雄了嗎?」
08:48
And the answer is, we didn't find one or two.
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答案是,我們不只找到一、兩個。
08:50
We found dozens of these strong candidate
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我們找到了許多個強大的
08:53
unexpected heroes.
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基因英雄候選人。
08:55
So we think that the time is now
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所以我們認為現在是時候
08:58
to launch the beta phase of this project
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展開這個計劃的測試階段,
09:00
and actually start getting prospective individuals.
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實際上也開始有了預期中的對象。
09:03
Basically all we need is information.
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基本上我們所需要的是資訊。
09:06
We need a swab of DNA
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我們需要棉棒來取樣基因,
09:08
and a willingness to say, "What's inside me?
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以及自願說出「我身體裡面有什麼?」
09:11
I'm willing to be re-contacted."
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我願意再次得到聯繫。」
09:15
Most of us spend our lives,
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當涉及到健康與疾病,
09:18
when it comes to health and disease,
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我們大部分都為此傾注了心血
09:20
acting as if we're voyeurs.
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表現地就像是偷窺狂一樣。
09:23
We delegate the responsibility
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我們將責任委託給
09:26
for the understanding of our disease,
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能了解疾病、
09:28
for the treatment of our disease,
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能治療疾病的
09:30
to anointed experts.
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權威專家們。
09:33
In order for us to get this project to work,
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為了幫助我們讓計畫有所成效,
09:37
we need individuals to step up
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我們需要有人站出來
09:39
in a different role and to be engaged,
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以一個不同的角色來參與,
09:43
to realize this dream,
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去實現這個夢想,
09:45
this open crowd-sourced project,
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也需要這對外開放的大眾資源計畫
09:49
to find those unexpected heroes,
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來找到那些潛藏的英雄們,
09:52
to evolve from the current concepts
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從目前我們對資源與限制的概念
09:55
of resources and constraints,
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逐漸發展到
09:57
to design those preventive therapies,
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發明出預防疾病的治療、
10:01
and to extend it beyond childhood diseases,
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擴展範圍到兒童期疾病之外,
10:03
to go all the way up to ways
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在整個過程中,我們可以發展到
10:05
that we could look at Alzheimer's or Parkinson's,
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研究阿茲海默症及帕金森氏症,
10:09
we're going to need us
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我們需要
10:11
to be looking inside ourselves and asking,
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捫心自問:
10:14
"What are our roles?
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「我們的角色是什麼?
10:16
What are our genes?"
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我們的基因是什麼?」
10:18
and looking within ourselves for information
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看看我們自己,想想以前
10:21
we used to say we should go to the outside,
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我們常說應該到走到外面
10:23
to experts,
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去找專家們,
10:25
and to be willing to share that with others.
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然後樂意與人分享。
10:29
Thank you very much.
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非常感謝各位。
10:32
(Applause)
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(掌聲)
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