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Translator: Joseph Geni
Reviewer: Joanna Pietrulewicz
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譯者: Yuqiu Liu
審譯者: Marssi Draw
這是一間結核病的病房,
00:13
This is a tuberculosis ward,
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這張照片拍攝於 19 世紀晚期,
00:16
and at the time this picture was taken
in the late 1800s,
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00:19
one in seven of all people
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那個時候,每七個人之中就有一個人
00:22
died from tuberculosis.
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死於結核病。
00:24
We had no idea
what was causing this disease.
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當時沒人知道
這種疾病的病因是什麼。
只能猜想
00:28
The hypothesis was actually
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00:30
it was your constitution
that made you susceptible.
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是因為體質因素讓人染病。
00:33
And it was a highly romanticized disease.
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結核病當時還是
一種被高度浪漫化的疾病,
00:36
It was also called consumption,
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它又被稱為憔悴症,
被視為是詩人、藝術家
00:39
and it was the disorder of poets
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和知識分子才有的失調病症。
00:42
and artists and intellectuals.
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有些人甚至認為它會讓人極為敏感
00:45
And some people actually thought
it gave you heightened sensitivity
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00:48
and conferred creative genius.
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並賦予創造才華。
00:52
By the 1950s,
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到了 1950 年代,
00:54
we instead knew
that tuberculosis was caused
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我們知道了結核病
00:57
by a highly contagious
bacterial infection,
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是由一種高傳染性的
細菌感染所引起,
01:00
which is slightly less romantic,
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這就不那麼浪漫了。
但這個發現也帶來了好消息,
01:03
but that had the upside
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01:05
of us being able to maybe
develop drugs to treat it.
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那就是我們可能
可以研發藥物治療結核病。
01:08
So doctors had discovered
a new drug, iproniazid,
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所以醫生發明了一種新藥
──異菸鹼異丙醯肼,
01:11
that they were optimistic
might cure tuberculosis,
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希望可以治癒結核病。
他們把這種藥給病人用,
01:15
and they gave it to patients,
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01:16
and patients were elated.
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病人都欣喜若狂,
01:18
They were more social, more energetic.
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變得更樂於社交,更充滿活力,
01:22
One medical report actually says
they were "dancing in the halls."
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一份醫療報告甚至稱病人們都
「在走廊上跳舞」。
01:27
And unfortunately,
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不幸的是,
這並不一定是因為
他們的病情有所好轉。
01:29
this was not necessarily
because they were getting better.
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01:32
A lot of them were still dying.
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許多病人仍瀕臨死亡。
01:35
Another medical report describes them
as being "inappropriately happy."
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另一份醫療報告說這些病人
「開心得不正常」。
01:43
And that is how the first
antidepressant was discovered.
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這就是第一種抗抑鬱劑的研發歷史。
01:47
So accidental discovery
is not uncommon in science,
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意外發現在科學中很常見,
但是僅僅有幸運的意外是不夠的。
01:52
but it requires more
than just a happy accident.
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01:55
You have to be able to recognize it
for discovery to occur.
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你還需要有辨識出它的能力。
01:59
As a neuroscientist,
I'm going to talk to you a little bit
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作為一個神經學家,
我要和大家分享我自己的親身經歷。
02:02
about my firsthand experience
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我的經歷也充滿了意外,
02:03
with whatever you want to call
the opposite of dumb luck --
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02:06
let's call it smart luck.
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就讓我們稱它為有心的意外吧。
02:08
But first, a bit more background.
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首先,我要多講一些背景。
02:12
Thankfully, since the 1950s,
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非常幸運地,自從1950 年代以來,
我們研發了其他
可以治癒結核病的藥物。
02:15
we've developed some other drugs
and we can actually now cure tuberculosis.
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儘管其他國家還可能存在結核病,
至少在美國
02:19
And at least in the United States,
though not necessarily in other countries,
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02:22
we have closed our sanitoriums
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我們關閉了結核病療養院,
02:24
and probably most of you
are not too worried about TB.
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大多數人也不太擔憂患結核病。
02:28
But a lot of what was true
in the early 1900s
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但是 20 世紀早期,
02:31
about infectious disease,
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關於傳染病的種種狀況
02:33
we can say now
about psychiatric disorders.
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現在正在精神疾病領域上演。
02:36
We are in the middle
of an epidemic of mood disorders
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我們正處於精神疾病氾濫的年代,
02:39
like depression and post-traumatic
stress disorder, or PTSD.
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抑鬱症和創傷後壓力疾患
就是精神疾病的兩個例子。
02:44
One in four of all adults
in the United States
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在美國,
每四個成年人中
就有一個患有精神病,
02:48
suffers from mental illness,
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02:50
which means that if you haven't
experienced it personally
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這就意味著
即使你或你的家人沒有精神類疾病,
02:53
or someone in your family hasn't,
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02:55
it's still very likely
that someone you know has,
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你認識的人當中
很可能有精神病患者,
02:58
though they may not talk about it.
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即使他們不談論自己的疾病。
03:02
Depression has actually now surpassed
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抑鬱症已經超過
03:05
HIV/AIDS, malaria, diabetes and war
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愛滋病、瘧疾、糖尿病、戰爭,
03:10
as the leading cause
of disability worldwide.
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成為世界上導致殘疾的首要因素。
03:13
And also, like tuberculosis in the 1950s,
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就像 1950 年代的結核病一樣,
03:17
we don't know what causes it.
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抑鬱症目前病因不明。
03:19
Once it's developed, it's chronic,
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一旦發病,
03:21
lasts a lifetime,
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這種慢性病會持續一生,
03:22
and there are no known cures.
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而且目前無法治癒。
03:26
The second antidepressant we discovered,
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在 1950 年代,
我們從一種抗組織胺藥中
03:28
also by accident, in the 1950s,
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意外地發現了第二種抗抑鬱的藥物。
03:31
from an antihistamine
that was making people manic,
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這種會使人感到興奮的藥物
03:35
imipramine.
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是伊米帕明。
03:38
And in both the case of the tuberculosis
ward and the antihistamine,
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在這兩個關於
結核病和抗組織胺藥例子中,
03:41
someone had to be able to recognize
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必須要有人意識到
03:43
that a drug that was designed
to do one thing --
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原本發明用來
治療結核病或過敏的藥物,
03:46
treat tuberculosis
or suppress allergies --
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03:48
could be used to do
something very different --
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可能用在非常不同的方面──
03:51
treat depression.
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治療抑鬱症。
03:53
And this sort of repurposing
is actually quite challenging.
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這種改變用途的作法其實困難重重。
03:56
When doctors first saw
this mood-enhancing effect of iproniazid,
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當醫生第一次見到異菸鹼異丙醯肼
對情緒的影響時,
04:00
they didn't really recognize
what they saw.
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他們並沒有意識到這個成效,
04:02
They were so used to thinking about it
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他們一貫的想法就是
04:04
from the framework
of being a tuberculosis drug
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異菸鹼異丙醯肼
是治療結核病的藥物,
04:07
that they actually just listed it
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以至於他們認為他們所見到的
是藥物的副作用,
04:09
as a side effect, an adverse side effect.
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而且是不良的副作用。
04:12
As you can see here,
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像這張圖片中顯示的,
04:13
a lot of these patients in 1954
are experiencing severe euphoria.
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1954 年很多病人患有嚴重的欣快症。
04:18
And they were worried
that this might somehow interfere
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醫生甚至擔心
這會影響病人的結核病情。
04:22
with their recovering from tuberculosis.
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04:25
So they recommended that iproniazid
only be used in cases of extreme TB
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所以他們建議,只有病症十分嚴重,
04:31
and in patients that were
highly emotionally stable,
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而且病人情緒十分穩定時,
才使用異菸鹼異丙醯肼,
04:36
which is of course the exact opposite
of how we use it as an antidepressant.
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這與我們今天用這種藥物來
抗抑鬱的情形正好相反。
他們太習慣從結核病的角度
來考量這種藥物,
04:40
They were so used to looking at it
from the perspective of this one disease,
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04:44
they could not see the larger implications
for another disease.
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以至於他們不能意識到
它對其他疾病更大的作用。
04:49
And to be fair,
it's not entirely their fault.
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說句公道話,這也不是他們的錯,
我們所有人都受功能固著影響。
04:52
Functional fixedness
is a bias that affects all of us.
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04:54
It's a tendency to only
be able to think of an object
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功能固著使我們看到一種事物時,
04:58
in terms of its traditional
use or function.
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傾向只想到其傳統固有的
作用和功能。
05:01
And mental set is another thing. Right?
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思維定式是另一回事,對吧?
05:03
That's sort of this preconceived framework
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那是我們處理問題的時候
05:05
with which we approach problems.
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所使用的先入為主框架。
05:07
And that actually makes repurposing
pretty hard for all of us,
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這使得我們都很難
為事物想出新用途,
05:10
which is, I guess, why they gave
a TV show to the guy who was,
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所以那些總能舊物新用的人
05:14
like, really great at repurposing.
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才有機會上電視吧!
05:16
(Laughter)
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(笑聲)
05:19
So the effects in both the case
of iproniazid and imipramine,
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異菸鹼異丙醯肼和伊米帕明
藥效都很強,
05:23
they were so strong --
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服用的人會變得狂躁,
05:24
there was mania,
or people dancing in the halls.
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有些人會興奮得在走廊上跳舞。
05:27
It's actually not that surprising
they were caught.
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所以發現他們的抑鬱作用
不讓人意外。
05:30
But it does make you wonder
what else we've missed.
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但這讓我們不免懷疑,
是不是漏了什麼。
異菸鹼異丙醯肼和伊米帕明
05:35
So iproniazid and imipramine,
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05:37
they're more than just
a case study in repurposing.
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不僅僅是舊藥新用的例子,
05:39
They have two other things in common
that are really important.
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他們還有另外兩個重要的共同點。
05:42
One, they have terrible side effects.
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第一,他們都有巨大的副作用,
05:45
That includes liver toxicity,
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包括肝中毒、
05:47
weight gain of over 50 pounds,
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體重增加超過 20 公斤、
05:50
suicidality.
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自殺傾向等。
05:52
And two, they both
increase levels of serotonin,
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第二,他們都會增加
血清素的分泌量。
05:56
which is a chemical signal in the brain,
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血清素是大腦中的一種化學信號,
05:59
or a neurotransmitter.
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或稱為神經傳遞質。
06:01
And those two things together,
right, one or the two,
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單一種副作用可能不那麼重要,
06:03
may not have been that important,
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但是這兩種副作用同時出現,
06:05
but the two together meant
that we had to develop safer drugs,
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使得研發更安全的藥物十分必要。
06:09
and that serotonin seemed
like a pretty good place to start.
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血清素就是我們研發新藥的起點。
06:13
So we developed drugs
to more specifically focus on serotonin,
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所以我們研發了
專門針對血清素的藥物,
06:17
the selective serotonin
reuptake inhibitors, so the SSRIs,
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選擇性血清素再吸收抑制劑,
又稱 SSRIs。
06:21
the most famous of which is Prozac.
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百憂解是 SSRIs 中最著名的了。
這是 30 年前的事情了,
06:24
And that was 30 years ago,
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自那之後,我們主要
就在優化這些藥物。
06:26
and since then we have mostly
just worked on optimizing those drugs.
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06:29
And the SSRIs, they are better
than the drugs that came before them,
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SSRIs 比之前的藥物要好,
06:32
but they still have a lot of side effects,
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但是他們仍然有很多副作用,
包括體重增加、失眠、
06:35
including weight gain, insomnia,
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自殺傾向。
06:38
suicidality --
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SSRIs 發揮藥效也非常緩慢,
06:40
and they take a really long time to work,
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06:42
something like four to six weeks
in a lot of patients.
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很多病人要服用四到六週才能見效。
這還是對病人有效的情況。
06:45
And that's in the patients
where they do work.
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06:47
There are a lot of patients
where these drugs don't work.
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對於另一些病人,
這類藥是無效的。
這就意味著直到現在,2016 年,
06:50
And that means now, in 2016,
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06:53
we still have no cures
for any mood disorders,
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我們仍然沒有
治療任何精神病的藥物,
06:57
just drugs that suppress symptoms,
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只有可以緩解症狀的藥物。
06:59
which is kind of the difference between
taking a painkiller for an infection
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這其中的區別就像是治療感染時,
是服用止痛藥,
07:03
versus an antibiotic.
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還是服用抗生素。
07:04
A painkiller will make you feel better,
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止痛藥可以減緩症狀,
07:06
but is not going to do anything
to treat that underlying disease.
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但是並不能治療
引起這些症狀的疾病。
07:10
And it was this flexibility
in our thinking
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我們思維的可變通性
讓我們意識到
異菸鹼異丙醯肼和伊米帕明
07:13
that let us recognize
that iproniazid and imipramine
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可以被用作治療抑鬱症,
07:16
could be repurposed in this way,
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也使我們注意到血清素,
07:18
which led us to the serotonin hypothesis,
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諷刺的是,我們就此
失去了可變通性。
07:20
which we then, ironically, fixated on.
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07:23
This is brain signaling, serotonin,
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這是來自一個 SSRI 廣告的
07:26
from an SSRI commercial.
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血清素大腦訊號。
07:27
In case you're not clear,
this is a dramatization.
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這是誇大的表現形式。
07:30
And in science, we try
and remove our bias, right,
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在科學領域,我們盡力去除偏見,
像是進行雙盲實驗,
07:34
by running double-blinded experiments
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或不預設實驗結果
以免干擾統計過程。
07:37
or being statistically agnostic
as to what our results will be.
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07:40
But bias creeps in more insidiously
in what we choose to study
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但是我們的研究方向和研究方法
07:45
and how we choose to study it.
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也是偏見的一種潛在表現形式。
07:48
So we've focused on serotonin now
for the past 30 years,
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我們專注於血清素的研究
已經達 30 年之久,
07:51
often to the exclusion of other things.
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放棄了很多研究其他藥物的機會。
07:54
We still have no cures,
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我們仍然沒有找到治療方法,
07:57
and what if serotonin
isn't all there is to depression?
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萬一血清素不足以治癒抑鬱症呢?
08:00
What if it's not even the key part of it?
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萬一血清素不是
治癒抑鬱症的關鍵呢?
08:02
That means no matter how much time
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那將會意味著
08:04
or money or effort we put into it,
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不管我們投入多少時間、
金錢或心血,
08:07
it will never lead to a cure.
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我們仍然不能治癒抑鬱症。
08:10
In the past few years,
doctors have discovered
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過去的幾年間,
醫生研發了自 SSRIs 以來
第一種真正的新抗抑鬱劑,
08:13
probably what is the first truly new
antidepressant since the SSRIs,
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08:18
Calypsol,
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可利普索 (Calypsol)。
08:19
and this drug works very quickly,
within a few hours or a day,
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這種藥見效很快,
幾個小時到一天就見效,
08:23
and it doesn't work on serotonin.
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而且不是透過血清素發揮作用,
08:25
It works on glutamate,
which is another neurotransmitter.
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而是透過另一種神經傳遞質
──麩胺酸──發揮作用的。
08:28
And it's also repurposed.
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這也是舊藥新用的例子。
08:29
It was traditionally used
as anesthesia in surgery.
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那本來是手術中的麻醉藥。
08:33
But unlike those other drugs,
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不像之前的幾種藥物
08:35
which were recognized pretty quickly,
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都在短時間內被發現抗抑鬱的功效,
我們花費了 20 年
08:37
it took us 20 years
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08:38
to realize that Calypsol
was an antidepressant,
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才發現可利普索的抗抑鬱功效,
08:41
despite the fact that it's actually
a better antidepressant,
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即使它抗抑鬱的功效
可能比其他幾種藥物
08:44
probably, than those other drugs.
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都要好。
08:45
It's actually probably because of the fact
that it's a better antidepressant
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可能正是因為它的抗抑鬱效果好,
我們更不容易發現它的藥效。
08:50
that it was harder for us to recognize.
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沒有引起狂躁,
所以沒人發現藥效。
08:52
There was no mania to signal its effects.
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08:54
So in 2013, up at Columbia University,
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2013 年,在哥倫比亞大學,
08:57
I was working with my colleague,
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我和我的同事,
08:59
Dr. Christine Ann Denny,
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克里斯汀.安.丹尼博士,
09:01
and we were studying Calypsol
as an antidepressant in mice.
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一起研究可利普索
作為老鼠的抗抑鬱劑。
09:05
And Calypsol has, like,
a really short half-life,
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可利普索的半衰期很短,
09:08
which means it's out of your body
within a few hours.
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所以幾小時內就被代謝出體外。
09:11
And we were just piloting.
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我們做了些嘗識性的實驗。
我們給老鼠注射這種藥,
09:13
So we would give an injection to mice,
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09:15
and then we'd wait a week,
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等待一週,
09:16
and then we'd run
another experiment to save money.
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然後重複實驗,來到達省錢的目的。
在一次試驗中,
09:20
And one of the experiments I was running,
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09:22
we would stress the mice,
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我們對老鼠施壓,
09:23
and we used that as a model of depression.
189
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以模仿人類的抑鬱狀態。
起初這種方法看起來
並沒有任何效果。
09:26
And at first it kind of just looked
like it didn't really work at all.
190
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09:29
So we could have stopped there.
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我們本可就此停止實驗。
09:31
But I have run this model
of depression for years,
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但是這麼多年
同抑鬱模型打交道的經驗告訴我,
09:34
and the data just looked kind of weird.
193
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這些數據有些不尋常。
09:36
It didn't really look right to me.
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我察覺到了一些異樣。
09:38
So I went back,
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所以我仔細檢查
09:39
and we reanalyzed it
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並重新分析了實驗結果,
著重分析這些老鼠是不是在一週之前
09:41
based on whether or not they had gotten
that one injection of Calypsol
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已經被注射過一次可利普索。
09:44
a week beforehand.
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1200
09:46
And it looked kind of like this.
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結果看起來就像這張圖片。
09:48
So if you look at the far left,
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看最左邊的這張圖,
一隻老鼠被放到了一個新的空間,
09:51
if you put a mouse in a new space,
201
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09:53
this is the box, it's very exciting,
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在這個新盒子裡,牠很興奮。
09:55
a mouse will walk around and explore,
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牠在盒子裡爬來爬去的探索,
這些粉紅色線就是牠爬行的軌跡。
09:58
and you can see that pink line
is actually the measure of them walking.
204
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10:02
And we also give it
another mouse in a pencil cup
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我們還把另一隻老鼠放到筆筒裡,
10:05
that it can decide to interact with.
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這樣牠就可以和這隻老鼠互動。
10:07
This is also a dramatization,
in case that's not clear.
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這也是誇張的表現形式,
大家不要誤會。
10:10
And a normal mouse will explore.
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一隻正常的老鼠會探索新空間,
10:14
It will be social.
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和其他老鼠社交,
10:16
Check out what's going on.
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觀察周圍發生的事情。
如果你施壓
讓老鼠進入抑鬱狀態,
10:18
If you stress a mouse
in this depression model,
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10:20
which is the middle box,
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像中間的圖所示,
牠就不會社交,不探索新空間,
10:23
they aren't social, they don't explore.
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大多時間就是躲在角落的杯子後面。
10:25
They mostly just kind of hide
in that back corner, behind a cup.
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然而那些被注射過可利普索的老鼠,
10:29
Yet the mice that had gotten
that one injection of Calypsol,
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如右圖所示,
10:32
here on your right,
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1200
牠們仍然探索新空間,仍然社交,
10:34
they were exploring, they were social.
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10:36
They looked like they
had never been stressed at all,
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就像我們不曾施加壓力一樣。
這是不可能的。
10:40
which is impossible.
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1200
10:42
So we could have just stopped there,
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我們本來可就此止步。
10:44
but Christine had also used
Calypsol before as anesthesia,
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但是克里斯汀曾把可利普索
當做麻醉劑使用,
在幾年之前她就觀察到
10:49
and a few years ago she had seen
222
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10:50
that it seemed to have
some weird effects on cells
223
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這種藥物對細胞和其他一些行為
有奇怪的影響,
10:53
and some other behavior
224
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10:54
that also seemed to last
long after the drug,
225
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這些影響會持續一段時間,
10:57
maybe a few weeks.
226
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大概幾週左右。
10:58
So we were like, OK,
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我們就想,好吧,
10:59
maybe this is not completely impossible,
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這大概也不是完全不可能發生的,
但是很值得懷疑。
11:02
but we were really skeptical.
229
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1496
11:03
So we did what you do in science
when you're not sure,
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就像在科學領域
遇到其他你不確定的事情一樣,
11:06
and we ran it again.
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1200
我們重複了實驗。
11:08
And I remember being in the animal room,
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我還記得當時我在動物室,
11:11
moving mice from box to box
to test them,
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3656
把老鼠從一個盒子
移到另一個以檢測牠們的狀態,
11:15
and Christine was actually sitting
on the floor with the computer in her lap
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3616
克里斯汀坐在地板上,
大腿上放著電腦,
11:18
so the mice couldn't see her,
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這樣老鼠就看不到她了,
11:20
and she was analyzing
the data in real time.
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她就同步分析著數據。
11:22
And I remember us yelling,
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我記得我們大叫了,
11:23
which you're not supposed to do
in an animal room where you're testing,
238
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3296
儘管在實驗進行中的動物室大叫
是不恰當的,
11:27
because it had worked.
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因為這種藥見效了。
11:28
It seemed like these mice
were protected against stress,
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這些老鼠似乎對壓力狀態產生抗體,
11:33
or they were inappropriately happy,
however you want to call it.
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3056
或者你也可以說牠們開心得不正常。
11:36
And we were really excited.
242
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2440
我們非常興奮。
11:39
And then we were really skeptical,
because it was too good to be true.
243
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然後我們不敢相信,
因為這個結果好得有點不真實。
11:43
So we ran it again.
244
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1200
所以我們重複了實驗。
11:45
And then we ran it again in a PTSD model,
245
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在創傷後壓力疾患的模型下
重複了實驗。
11:48
and we ran it again
in a physiological model,
246
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2416
又在生理模型中做了一次,
11:50
where all we did was give stress hormones.
247
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2216
這部分只給老鼠注射焦慮荷爾蒙。
11:53
And we had our undergrads run it.
248
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然後讓大學生重複實驗。
11:54
And then we had our collaborators
halfway across the world in France run it.
249
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我們讓在世界另一端
法國的共同研究者重複實驗。
11:59
And every time someone ran it,
they confirmed the same thing.
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3216
所有重複實驗的人
都確認了同樣的結果。
看起來注射一次可利普索,
12:03
It seemed like
this one injection of Calypsol
251
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2816
12:05
was somehow protecting
against stress for weeks.
252
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2760
可以使人幾週內都對焦慮免疫。
12:09
And we only published this a year ago,
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我們在一年前發表了這個實驗結果,
那之後其他實驗室
也獨立驗證了這個結果。
12:11
but since then other labs
have independently confirmed this effect.
254
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4080
12:15
So we don't know what causes depression,
255
735940
1920
我們不知道抑鬱症的病因是什麼,
12:18
but we do know that stress
is the initial trigger
256
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但是我們知道百分之八十的抑鬱症
12:22
in 80 percent of cases,
257
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2336
都是壓力引起的。
12:24
and depression and PTSD
are different diseases,
258
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2216
抑鬱症和創傷後壓力疾患
是不同的病,
12:26
but this is something
they share in common.
259
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2016
但是它們有一個共同點,
12:28
Right? It is traumatic stress
260
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1816
那就是它們都由
巨大的精神壓力引起,
12:30
like active combat or natural disasters
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2896
像戰鬥、自然災害、
12:33
or community violence or sexual assault
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社區暴力、性侵,
這些會引起創傷後壓力疾患,
12:36
that causes post-traumatic
stress disorder,
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2280
12:38
and not everyone that is exposed to stress
develops a mood disorder.
264
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5616
並不是每一個經歷精神壓力的人
都會出現精神疾病。
12:44
And this ability to experience
stress and be resilient
265
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這種在經歷壓力後能發揮韌性、
12:47
and bounce back and not develop
depression or PTSD
266
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4160
迅速復原,而不患抑鬱症
或創傷後壓力疾患的能力,
12:52
is known as stress resilience,
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772500
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被稱作抗壓性。
12:54
and it varies between people.
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1856
抗壓性因人而異。
12:56
And we have always thought of it
as just sort of this passive property.
269
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3336
我們之前一直把抗壓性
當做一種被動屬性,
一種對疾病的不易感染性
13:00
It's the absence of susceptibility factors
270
780020
2536
13:02
and risk factors for these disorders.
271
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和不受影響性。
13:05
But what if it were active?
272
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1880
但這會不會其實是一種積極屬性呢?
13:08
Maybe we could enhance it,
273
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1496
也許我們能增強這種屬性,
13:09
sort of akin to putting on armor.
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像多加一件盔甲一樣。
13:13
We had accidentally discovered
the first resilience-enhancing drug.
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4600
我們意外發現了
第一種提升抗壓性的藥物。
13:18
And like I said, we only gave
a tiny amount of the drug,
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2776
我剛剛提到了,
我們只給老鼠一點點這種藥,
13:21
and it lasted for weeks,
277
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1576
藥效卻持續了數週。
這是任何抗抑鬱劑都做不到的。
13:23
and that's not like anything
you see with antidepressants.
278
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3216
13:26
But it is actually kind of similar
to what you see in immune vaccines.
279
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4320
這其實有點像免疫疫苗。
13:31
So in immune vaccines,
you'll get your shots,
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2936
如果你接種了疫苗,
數週、數月、數年後,
13:34
and then weeks, months, years later,
281
814140
3376
13:37
when you're actually exposed to bacteria,
282
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2336
你接觸到細菌的時候,
13:39
it's not the vaccine in your body
that protects you.
283
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2456
保護你的不是你接種的疫苗,
13:42
It's your own immune system
284
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1376
而是你的免疫系統,
13:43
that's developed resistance and resilience
to this bacteria that fights it off,
285
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4136
它產生了對這種細菌的抵抗力,
從而能夠殺菌。
13:47
and you actually never get the infection,
286
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2136
你就永遠不會感染這種細菌了。
這和治療不同,對吧?
13:50
which is very different
from, say, our treatments. Right?
287
830100
3056
13:53
In that case, you get the infection,
you're exposed to the bacteria,
288
833180
3816
說到治療,
你會先暴露在細菌中,感染疾病,
生病後你會服用治療性藥物,
比如說抗生素,
13:57
you're sick, and then you take,
say, an antibiotic which cures it,
289
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3856
14:00
and those drugs are actually working
to kill the bacteria.
290
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3240
這些藥物會殺死細菌。
14:04
Or similar to as I said before,
with this palliative,
291
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2496
或者像我之前描述的,
你會服用緩解劑,
14:07
you'll take something
that will suppress the symptoms,
292
847300
2856
來緩解症狀,
14:10
but it won't treat
the underlying infection,
293
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2696
但是並不從根本上治療疾病,
14:12
and you'll only feel better
during the time in which you're taking it,
294
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3336
只是服用緩解劑的時候
你會覺得好一點,
14:16
which is why you have to keep taking it.
295
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1936
所以你需要一直服用緩解劑。
14:18
And in depression and PTSD --
296
858220
2696
針對抑鬱症和創傷後壓力疾患──
14:20
here we have your stress exposure --
297
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1976
圖中顯示了人承受的精神壓力──
14:22
we only have palliative care.
298
862940
2616
我們只有舒緩醫學。
14:25
Antidepressants only suppress symptoms,
299
865580
2496
抗抑鬱劑只能舒緩症狀,
這就是為什麼基本上
你需要一直服用藥物,
14:28
and that is why you basically
have to keep taking them
300
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2856
14:30
for the life of the disease,
301
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直到這種疾病結束,
14:32
which is often
the length of your own life.
302
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2200
這一般也是病人生命結束的時候。
14:35
So we're calling our resilience-enhancing
drugs "paravaccines,"
303
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4216
所以我們稱這種
提升抗壓性的藥物「類疫苗」,
14:40
which means vaccine-like,
304
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1536
就是說它像疫苗一樣,
14:41
because it seems
like they might have the potential
305
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2496
因為它們似乎有
14:44
to protect against stress
306
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1816
預防壓力的潛力,
可以預防老鼠患
14:46
and prevent mice from developing
307
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3416
14:49
depression and post-traumatic
stress disorder.
308
889540
2760
抑鬱症和創傷後壓力疾患。
14:52
Also, not all antidepressants
are also paravaccines.
309
892780
3440
而且,並不是所有的抗抑鬱劑
都是類疫苗。
14:57
We tried Prozac as well,
310
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我們也測試了百憂解,
14:58
and that had no effect.
311
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1360
沒有任何效果。
如果我們把類疫苗應用到人類身上,
15:01
So if this were to translate into humans,
312
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我們可能就可以保護那些
15:04
we might be able to protect people
313
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2576
15:06
who are predictably at risk
314
906700
2256
非常容易受到像抑鬱症
和創傷後壓力疾患
15:08
against stress-induced disorders
like depression and PTSD.
315
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3856
這種壓力引起的疾病影響的人了。
15:12
So that's first responders
and firefighters,
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這些人包括急救者、消防隊員、
難民、囚犯、監獄守衛、
15:16
refugees, prisoners and prison guards,
317
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4136
15:20
soldiers, you name it.
318
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士兵等等。
15:23
And to give you a sense
of the scale of these diseases,
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這些疾病有多大的規模呢,
15:27
in 2010, the global burden of disease
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2010 年,這類疾病
給全球造成經濟損失
15:30
was estimated at 2.5 trillion dollars,
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約 2.5 兆美元,
而且因為這些都是慢性病,
15:35
and since they are chronic,
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15:36
that cost is compounding
and is therefore expected to rise
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經濟損失也會逐年增加,
15:39
up to six trillion dollars
in just the next 15 years.
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預計在未來的 15 年內
會增加到六兆美元。
15:44
As I mentioned before,
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像我剛剛講的,
舊藥新用是很困難的,
因為我們有先入為主的偏見。
15:46
repurposing can be challenging
because of our prior biases.
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15:50
Calypsol has another name,
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可利普索有另一個名字,
氯胺酮,
15:53
ketamine,
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15:55
which also goes by another name,
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也被稱為
15:57
Special K,
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K 他命,
15:58
which is a club drug and drug of abuse.
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是夜店裡的娛樂性藥物,
也是被濫用的藥物。
16:02
It's still used across the world
as an anesthetic.
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在世界各地仍被用來當麻醉劑使用。
16:05
It's used in children.
We use it on the battlefield.
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用在兒童身上,
我們在戰場上也使用它。
16:08
It's actually the drug of choice
in a lot of developing nations,
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它其實還是很多發展中國家
優先選擇的藥物,
16:11
because it doesn't affect breathing.
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因為它不會影響呼吸。
16:13
It is on the World Health Organization
list of most essential medicines.
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它也被世界衛生組織
列入最基本的藥物。
16:18
If we had discovered ketamine
as a paravaccine first,
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如果我們最初是把氯胺酮
當做類疫苗研發出來,
16:22
it'd be pretty easy for us to develop it,
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那麼繼續發展它的這個功效
就會很容易。
16:25
but as is, we have to compete
with our functional fixedness
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但事實是,
我們要對抗自己的功能固著
16:29
and mental set that kind of interfere.
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和思維定式等干預。
16:33
Fortunately, it's not
the only compound we have discovered
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幸運的是,
這並不是我們所發現的唯一一種
16:37
that has these prophylactic,
paravaccine qualities,
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具有預防疾病的類疫苗化合物,
16:41
but all of the other drugs
we've discovered,
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但我們所發現的其他的類似藥物,
16:44
or compounds if you will,
they're totally new,
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或者說是化合物,
都是從未被使用過的,
16:46
they have to go through
the entire FDA approval process --
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必須要經過食品藥物管理局批准,
16:50
if they make it before
they can ever be used in humans.
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批准不過的話,
可能永遠沒人有機會服用。
16:54
And that will be years.
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即使批准過了,也會花費數年。
16:55
So if we wanted something sooner,
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如果我們想要很快能用的藥物,
16:58
ketamine is already FDA-approved.
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氯胺酮已經被管理局批准了。
17:00
It's generic, it's available.
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它很普遍,也容易買到。
17:03
We could develop it for a fraction
of the price and a fraction of the time.
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優化它會花費比較少的金錢
和比較短的時間。
17:08
But actually, beyond
functional fixedness and mental set,
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但其實,除了功能固著和思維定式,
17:12
there's a real other challenge
to repurposing drugs,
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還有一個阻礙舊藥新用的因素,
17:16
which is policy.
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那就是政策。
一旦一種藥物變得普及,
17:18
There are no incentives in place
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17:20
once a drug is generic and off patent
and no longer exclusive
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並且不再受專利保護,
製藥公司就沒有研發它的動力了,
17:24
to encourage pharma companies
to develop them,
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17:26
because they don't make money.
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因為他們研發這種藥賺不到錢。
17:28
And that's not true for just ketamine.
That is true for all drugs.
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這種情況不僅適用於氯胺酮,
也適用於所有的藥。
17:32
Regardless, the idea itself
is completely novel in psychiatry,
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儘管如此,在精神病學領域,
這種透過藥物預防心理疾病,
17:38
to use drugs to prevent mental illness
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而不是發病後治療的想法,
17:42
as opposed to just treat it.
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是非常新穎的。
17:44
It is possible that 20, 50,
100 years from now,
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也許 20 年,50 年,100 年過後,
17:49
we will look back now
at depression and PTSD
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我們會回顧抑鬱症
和創傷後壓力疾患,
17:53
the way we look back
at tuberculosis sanitoriums
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像我們今天回顧結核病療養院一樣,
17:57
as a thing of the past.
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它們也會成為歷史。
17:59
This could be the beginning of the end
of the mental health epidemic.
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我們的發現可能會開啟
心理疾病氾濫年代的終結。
18:05
But as a great scientist once said,
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但是像一位偉大的科學家曾經說的,
18:09
"Only a fool is sure of anything.
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「只有蠢人才對一切都有把握。
18:12
A wise man keeps on guessing."
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智者總會不斷猜想。」
謝謝大家。
18:16
Thank you, guys.
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18:17
(Applause)
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(掌聲)
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