TEDxNewYork
Rebecca Brachman: Could a drug prevent depression and PTSD?
蘿貝卡．布拉赫曼: 藥物能夠預防抑鬱症和創傷後壓力疾患嗎？
Filmed:
Readability: 4.6
1,563,420 views
人類研製新藥的過程充滿了意外，也充滿了革命性的發現。在這場關於科學的演講中，神經學家蘿貝卡．布拉赫曼分享了一個偶然發現的突破性療法，這個療法可能可以預防抑鬱症和創傷後壓力疾患等精神障礙。敬請聆聽這個一波三折，出人意料而且充滿爭議的故事。
Rebecca Brachman - Neuroscientist, writer, entrepreneur
Rebecca Brachman is a pioneer in the field of preventative psychopharmacology, developing drugs to enhance stress resilience and prevent mental illness. Full bio
Rebecca Brachman is a pioneer in the field of preventative psychopharmacology, developing drugs to enhance stress resilience and prevent mental illness. Full bio
Double-click the English transcript below to play the video.
00:13
This is a tuberculosis ward,
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這是一間結核病的病房，
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,
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.
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。
這種疾病的病因是什麼。
00:28
The hypothesis was actually
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只能猜想
00:30
it was your constitution
that made you susceptible.
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，
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，
00:39
and it was the disorder of poets
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被視為是詩人、藝術家
和知識分子才有的失調病症。
00:42
and artists and intellectuals.
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00:45
And some people actually thought
it gave you heightened sensitivity
it gave you heightened sensitivity
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有些人甚至認為它會讓人極為敏感
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
that tuberculosis was caused
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我們知道了結核病
00:57
by a highly contagious
bacterial infection,
bacterial infection,
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是由一種高傳染性的
細菌感染所引起，
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。
01:03
but that had the upside
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但這個發現也帶來了好消息，
01:05
of us being able to maybe
develop drugs to treat it.
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。
可以研發藥物治療結核病。
01:08
So doctors had discovered
a new drug, iproniazid,
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，
──異菸鹼異丙醯肼，
01:11
that they were optimistic
might cure tuberculosis,
might cure tuberculosis,
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希望可以治癒結核病。
01:15
and they gave it to patients,
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他們把這種藥給病人用，
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."
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」。
「在走廊上跳舞」。
01:27
And unfortunately,
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不幸的是，
01:29
this was not necessarily
because they were getting better.
because they were getting better.
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這並不一定是因為
他們的病情有所好轉。
他們的病情有所好轉。
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."
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」。
「開心得不正常」。
01:43
And that is how the first
antidepressant was discovered.
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,
is not uncommon in science,
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意外發現在科學中很常見，
01:52
but it requires more
than just a happy accident.
than just a happy accident.
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但是僅僅有幸運的意外是不夠的。
01:55
You have to be able to recognize it
for discovery to occur.
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
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 --
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，
02:15
we've developed some other drugs
and we can actually now cure tuberculosis.
and we can actually now cure tuberculosis.
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我們研發了其他
可以治癒結核病的藥物。
可以治癒結核病的藥物。
02:19
And at least in the United States,
though not necessarily in other countries,
though not necessarily in other countries,
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儘管其他國家還可能存在結核病，
至少在美國
至少在美國
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.
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
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.
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
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.
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。
就是精神疾病的兩個例子。
02:44
One in four of all adults
in the United States
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，
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
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,
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，
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.
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
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,
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,
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，
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 --
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，
治療結核病或過敏的藥物，
03:46
treat tuberculosis
or suppress allergies --
or suppress allergies --
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03:48
could be used to do
something very different --
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.
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,
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，
對情緒的影響時，
04:00
they didn't really recognize
what they saw.
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
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，
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，
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.
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
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
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,
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，
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.
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。
抗抑鬱的情形正好相反。
04:40
They were so used to looking at it
from the perspective of this one disease,
from the perspective of this one disease,
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他們太習慣從結核病的角度
來考量這種藥物，
來考量這種藥物，
04:44
they could not see the larger implications
for another disease.
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。
它對其他疾病更大的作用。
04:49
And to be fair,
it's not entirely their fault.
it's not entirely their fault.
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說句公道話，這也不是他們的錯，
04:52
Functional fixedness
is a bias that affects all of us.
is a bias that affects all of us.
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我們所有人都受功能固著影響。
04:54
It's a tendency to only
be able to think of an object
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.
use or function.
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傾向只想到其傳統固有的
作用和功能。
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,
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，
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,
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,
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，
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.
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.
they were caught.
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所以發現他們的抑鬱作用
不讓人意外。
不讓人意外。
05:30
But it does make you wonder
what else we've missed.
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。
是不是漏了什麼。
05:35
So iproniazid and imipramine,
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異菸鹼異丙醯肼和伊米帕明
05:37
they're more than just
a case study in repurposing.
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.
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,
increase levels of serotonin,
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第二，他們都會增加
血清素的分泌量。
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,
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,
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.
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,
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，
專門針對血清素的藥物，
06:17
the selective serotonin
reuptake inhibitors, so the SSRIs,
reuptake inhibitors, so the SSRIs,
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選擇性血清素再吸收抑制劑，
又稱 SSRIs。
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。
06:24
And that was 30 years ago,
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這是 30 年前的事情了，
06:26
and since then we have mostly
just worked on optimizing those drugs.
just worked on optimizing those drugs.
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自那之後，我們主要
就在優化這些藥物。
就在優化這些藥物。
06:29
And the SSRIs, they are better
than the drugs that came before them,
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，
06:35
including weight gain, insomnia,
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包括體重增加、失眠、
06:38
suicidality --
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自殺傾向。
06:40
and they take a really long time to work,
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SSRIs 發揮藥效也非常緩慢，
06:42
something like four to six weeks
in a lot of patients.
in a lot of patients.
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很多病人要服用四到六週才能見效。
06:45
And that's in the patients
where they do work.
where they do work.
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這還是對病人有效的情況。
06:47
There are a lot of patients
where these drugs don't work.
where these drugs don't work.
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對於另一些病人，
這類藥是無效的。
這類藥是無效的。
06:50
And that means now, in 2016,
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這就意味著直到現在，2016 年，
06:53
we still have no cures
for any mood disorders,
for any mood disorders,
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我們仍然沒有
治療任何精神病的藥物，
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
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，
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.
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。
引起這些症狀的疾病。
07:10
And it was this flexibility
in our thinking
in our thinking
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我們思維的可變通性
07:13
that let us recognize
that iproniazid and imipramine
that iproniazid and imipramine
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讓我們意識到
異菸鹼異丙醯肼和伊米帕明
異菸鹼異丙醯肼和伊米帕明
07:16
could be repurposed in this way,
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可以被用作治療抑鬱症，
07:18
which led us to the serotonin hypothesis,
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也使我們注意到血清素，
07:20
which we then, ironically, fixated on.
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諷刺的是，我們就此
失去了可變通性。
失去了可變通性。
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.
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,
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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07:37
or being statistically agnostic
as to what our results will be.
as to what our results will be.
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或不預設實驗結果
以免干擾統計過程。
以免干擾統計過程。
07:40
But bias creeps in more insidiously
in what we choose to study
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,
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，
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?
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？
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
不管我們投入多少時間、
金錢或心血，
金錢或心血，
08:04
or money or effort we put into it,
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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
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，
第一種真正的新抗抑鬱劑，
08:13
probably what is the first truly new
antidepressant since the SSRIs,
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,
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，
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.
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。
──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.
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，
08:37
it took us 20 years
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我們花費了 20 年
08:38
to realize that Calypsol
was an antidepressant,
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,
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
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
that it's a better antidepressant
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可能正是因為它的抗抑鬱效果好，
08:50
that it was harder for us to recognize.
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我們更不容易發現它的藥效。
08:52
There was no mania to signal its effects.
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沒有引起狂躁，
所以沒人發現藥效。
所以沒人發現藥效。
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.
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。
作為老鼠的抗抑鬱劑。
09:05
And Calypsol has, like,
a really short half-life,
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.
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。
09:13
So we would give an injection to mice,
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我們給老鼠注射這種藥，
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.
another experiment to save money.
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然後重複實驗，來到達省錢的目的。
09:20
And one of the experiments I was running,
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在一次試驗中，
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.
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以模仿人類的抑鬱狀態。
09:26
And at first it kind of just looked
like it didn't really work at all.
like it didn't really work at all.
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起初這種方法看起來
並沒有任何效果。
並沒有任何效果。
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,
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，
同抑鬱模型打交道的經驗告訴我，
09:34
and the data just looked kind of weird.
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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，
09:41
based on whether or not they had gotten
that one injection of Calypsol
that one injection of Calypsol
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著重分析這些老鼠是不是在一週之前
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，
09:51
if you put a mouse in a new space,
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一隻老鼠被放到了一個新的空間，
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，
09:58
and you can see that pink line
is actually the measure of them walking.
is actually the measure of them walking.
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這些粉紅色線就是牠爬行的軌跡。
10:02
And we also give it
another mouse in a pencil cup
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.
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。
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。
10:18
If you stress a mouse
in this depression model,
in this depression model,
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如果你施壓
讓老鼠進入抑鬱狀態，
讓老鼠進入抑鬱狀態，
10:20
which is the middle box,
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像中間的圖所示，
10:23
they aren't social, they don't explore.
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牠就不會社交，不探索新空間，
10:25
They mostly just kind of hide
in that back corner, behind a cup.
in that back corner, behind a cup.
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大多時間就是躲在角落的杯子後面。
10:29
Yet the mice that had gotten
that one injection of Calypsol,
that one injection of Calypsol,
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然而那些被注射過可利普索的老鼠，
10:32
here on your right,
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如右圖所示，
10:34
they were exploring, they were social.
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牠們仍然探索新空間，仍然社交，
10:36
They looked like they
had never been stressed at all,
had never been stressed at all,
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就像我們不曾施加壓力一樣。
10:40
which is impossible.
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這是不可能的。
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,
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，
當做麻醉劑使用，
10:49
and a few years ago she had seen
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在幾年之前她就觀察到
10:50
that it seemed to have
some weird effects on cells
some weird effects on cells
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這種藥物對細胞和其他一些行為
10:53
and some other behavior
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有奇怪的影響，
10:54
that also seemed to last
long after the drug,
long after the drug,
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這些影響會持續一段時間，
10:57
maybe a few weeks.
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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，
11:02
but we were really skeptical.
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但是很值得懷疑。
11:03
So we did what you do in science
when you're not sure,
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，
遇到其他你不確定的事情一樣，
11:06
and we ran it again.
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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,
to test them,
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把老鼠從一個盒子
移到另一個以檢測牠們的狀態，
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
on the floor with the computer in her lap
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克里斯汀坐在地板上，
大腿上放著電腦，
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.
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,
in an animal room where you're testing,
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儘管在實驗進行中的動物室大叫
是不恰當的，
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,
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.
however you want to call it.
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或者你也可以說牠們開心得不正常。
11:36
And we were really excited.
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我們非常興奮。
11:39
And then we were really skeptical,
because it was too good to be true.
because it was too good to be true.
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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。
因為這個結果好得有點不真實。
11:43
So we ran it again.
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所以我們重複了實驗。
11:45
And then we ran it again in a PTSD model,
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在創傷後壓力疾患的模型下
重複了實驗。
重複了實驗。
11:48
and we ran it again
in a physiological model,
in a physiological model,
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又在生理模型中做了一次，
11:50
where all we did was give stress hormones.
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這部分只給老鼠注射焦慮荷爾蒙。
11:53
And we had our undergrads run it.
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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.
halfway across the world in France run it.
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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。
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.
they confirmed the same thing.
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所有重複實驗的人
都確認了同樣的結果。
都確認了同樣的結果。
12:03
It seemed like
this one injection of Calypsol
this one injection of Calypsol
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看起來注射一次可利普索，
12:05
was somehow protecting
against stress for weeks.
against stress for weeks.
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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，
12:11
but since then other labs
have independently confirmed this effect.
have independently confirmed this effect.
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那之後其他實驗室
也獨立驗證了這個結果。
也獨立驗證了這個結果。
12:15
So we don't know what causes depression,
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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
is the initial trigger
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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,
256
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都是壓力引起的。
12:24
and depression and PTSD
are different diseases,
are different diseases,
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抑鬱症和創傷後壓力疾患
是不同的病，
是不同的病，
12:26
but this is something
they share in common.
they share in common.
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但是它們有一個共同點，
12:28
Right? It is traumatic stress
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那就是它們都由
巨大的精神壓力引起，
巨大的精神壓力引起，
12:30
like active combat or natural disasters
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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，
12:36
that causes post-traumatic
stress disorder,
stress disorder,
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這些會引起創傷後壓力疾患，
12:38
and not everyone that is exposed to stress
develops a mood disorder.
develops a mood disorder.
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並不是每一個經歷精神壓力的人
都會出現精神疾病。
都會出現精神疾病。
12:44
And this ability to experience
stress and be resilient
stress and be resilient
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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
depression or PTSD
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迅速復原，而不患抑鬱症
或創傷後壓力疾患的能力，
或創傷後壓力疾患的能力，
12:52
is known as stress resilience,
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被稱作抗壓性。
12:54
and it varies between people.
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抗壓性因人而異。
12:56
And we have always thought of it
as just sort of this passive property.
as just sort of this passive property.
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我們之前一直把抗壓性
當做一種被動屬性，
當做一種被動屬性，
13:00
It's the absence of susceptibility factors
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一種對疾病的不易感染性
13:02
and risk factors for these disorders.
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和不受影響性。
13:05
But what if it were active?
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但這會不會其實是一種積極屬性呢？
13:08
Maybe we could enhance it,
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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.
the first resilience-enhancing drug.
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我們意外發現了
第一種提升抗壓性的藥物。
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,
a tiny amount of the drug,
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我剛剛提到了，
我們只給老鼠一點點這種藥，
我們只給老鼠一點點這種藥，
13:21
and it lasted for weeks,
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藥效卻持續了數週。
13:23
and that's not like anything
you see with antidepressants.
you see with antidepressants.
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這是任何抗抑鬱劑都做不到的。
13:26
But it is actually kind of similar
to what you see in immune vaccines.
to what you see in immune vaccines.
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這其實有點像免疫疫苗。
13:31
So in immune vaccines,
you'll get your shots,
you'll get your shots,
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如果你接種了疫苗，
13:34
and then weeks, months, years later,
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數週、數月、數年後，
13:37
when you're actually exposed to bacteria,
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你接觸到細菌的時候，
13:39
it's not the vaccine in your body
that protects you.
that protects you.
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保護你的不是你接種的疫苗，
13:42
It's your own immune system
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而是你的免疫系統，
它產生了對這種細菌的抵抗力，
從而能夠殺菌。
從而能夠殺菌。
13:43
that's developed resistance and resilience
to this bacteria that fights it off,
to this bacteria that fights it off,
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13:47
and you actually never get the infection,
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你就永遠不會感染這種細菌了。
13:50
which is very different
from, say, our treatments. Right?
from, say, our treatments. Right?
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這和治療不同，對吧？
13:53
In that case, you get the infection,
you're exposed to the bacteria,
you're exposed to the bacteria,
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說到治療，
你會先暴露在細菌中，感染疾病，
13:57
you're sick, and then you take,
say, an antibiotic which cures it,
say, an antibiotic which cures it,
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生病後你會服用治療性藥物，
比如說抗生素，
比如說抗生素，
14:00
and those drugs are actually working
to kill the bacteria.
to kill the bacteria.
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這些藥物會殺死細菌。
14:04
Or similar to as I said before,
with this palliative,
with this palliative,
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或者像我之前描述的，
你會服用緩解劑，
你會服用緩解劑，
14:07
you'll take something
that will suppress the symptoms,
that will suppress the symptoms,
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來緩解症狀，
14:10
but it won't treat
the underlying infection,
the underlying infection,
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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,
during the time in which you're taking it,
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只是服用緩解劑的時候
你會覺得好一點，
你會覺得好一點，
14:16
which is why you have to keep taking it.
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所以你需要一直服用緩解劑。
14:18
And in depression and PTSD --
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針對抑鬱症和創傷後壓力疾患──
14:20
here we have your stress exposure --
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圖中顯示了人承受的精神壓力──
14:22
we only have palliative care.
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我們只有舒緩醫學。
14:25
Antidepressants only suppress symptoms,
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抗抑鬱劑只能舒緩症狀，
14:28
and that is why you basically
have to keep taking them
have to keep taking them
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這就是為什麼基本上
你需要一直服用藥物，
你需要一直服用藥物，
14:30
for the life of the disease,
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直到這種疾病結束，
14:32
which is often
the length of your own life.
the length of your own life.
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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,"
drugs "paravaccines,"
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所以我們稱這種
提升抗壓性的藥物「類疫苗」，
提升抗壓性的藥物「類疫苗」，
14:40
which means vaccine-like,
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就是說它像疫苗一樣，
14:41
because it seems
like they might have the potential
like they might have the potential
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因為它們似乎有
14:44
to protect against stress
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預防壓力的潛力，
14:46
and prevent mice from developing
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可以預防老鼠患
14:49
depression and post-traumatic
stress disorder.
stress disorder.
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抑鬱症和創傷後壓力疾患。
14:52
Also, not all antidepressants
are also paravaccines.
are also paravaccines.
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而且，並不是所有的抗抑鬱劑
都是類疫苗。
都是類疫苗。
14:57
We tried Prozac as well,
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我們也測試了百憂解，
14:58
and that had no effect.
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沒有任何效果。
15:01
So if this were to translate into humans,
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如果我們把類疫苗應用到人類身上，
15:04
we might be able to protect people
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我們可能就可以保護那些
15:06
who are predictably at risk
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非常容易受到像抑鬱症
和創傷後壓力疾患
和創傷後壓力疾患
15:08
against stress-induced disorders
like depression and PTSD.
like depression and PTSD.
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這種壓力引起的疾病影響的人了。
15:12
So that's first responders
and firefighters,
and firefighters,
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這些人包括急救者、消防隊員、
15:16
refugees, prisoners and prison guards,
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難民、囚犯、監獄守衛、
15:20
soldiers, you name it.
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士兵等等。
15:23
And to give you a sense
of the scale of these diseases,
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
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，
15:35
and since they are chronic,
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而且因為這些都是慢性病，
15:36
that cost is compounding
and is therefore expected to rise
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.
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。
會增加到六兆美元。
15:44
As I mentioned before,
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像我剛剛講的，
15:46
repurposing can be challenging
because of our prior biases.
because of our prior biases.
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舊藥新用是很困難的，
因為我們有先入為主的偏見。
因為我們有先入為主的偏見。
15:50
Calypsol has another name,
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可利普索有另一個名字，
15:53
ketamine,
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氯胺酮，
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。
也是被濫用的藥物。
16:02
It's still used across the world
as an anesthetic.
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.
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。
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,
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，
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.
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。
列入最基本的藥物。
16:18
If we had discovered ketamine
as a paravaccine first,
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，
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。
就會很容易。
16:25
but as is, we have to compete
with our functional fixedness
with our functional fixedness
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但事實是，
我們要對抗自己的功能固著
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
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
這並不是我們所發現的唯一一種
16:37
that has these prophylactic,
paravaccine qualities,
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,
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,
they're totally new,
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或者說是化合物，
都是從未被使用過的，
都是從未被使用過的，
16:46
they have to go through
the entire FDA approval process --
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.
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。
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.
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。
和比較短的時間。
17:08
But actually, beyond
functional fixedness and mental set,
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,
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。
17:18
There are no incentives in place
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一旦一種藥物變得普及，
17:20
once a drug is generic and off patent
and no longer exclusive
and no longer exclusive
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並且不再受專利保護，
17:24
to encourage pharma companies
to develop them,
to develop them,
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製藥公司就沒有研發它的動力了，
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.
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。
也適用於所有的藥。
17:32
Regardless, the idea itself
is completely novel in psychiatry,
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，
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,
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
at depression and PTSD
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我們會回顧抑鬱症
和創傷後壓力疾患，
和創傷後壓力疾患，
17:53
the way we look back
at tuberculosis sanitoriums
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.
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。
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。」
18:16
Thank you, guys.
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謝謝大家。
18:17
(Applause)
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（掌聲）
ABOUT THE SPEAKER
Rebecca Brachman - Neuroscientist, writer, entrepreneurRebecca Brachman is a pioneer in the field of preventative psychopharmacology, developing drugs to enhance stress resilience and prevent mental illness.
Why you should listen
Current treatments for mood disorders only suppress symptoms without addressing the underlying disease, and there are no known cures. The drugs Rebecca Brachman is developing would be the first to prevent psychiatric disorders such as post-traumatic stress disorder (PTSD) and depression.
Brachman completed her PhD at Columbia University, prior to which she was a fellow at the National Institutes of Health, where she discovered that immune cells carry a memory of psychological stress and that white blood cells can act as antidepressants and resilience-enhancers. Brachman's research has been featured in The Atlantic, WIRED and Business Insider, and her work was recently described by Dr. George Slavich on NPR as a "moonshot project that is very much needed in the mental health arena."
In addition to conducting ongoing research at Columbia, Brachman is an NYCEDC Entrepreneurship Lab Fellow and cofounder of Paravax -- a biotech startup developing vaccine-like prophylactic drugs ("paravaccines") -- along with her scientific collaborator, Christine Ann Denny. She is also working on a non-profit venture to repurpose existing generic drugs for use as prophylactics, and previously served as the Interim Program Director for Outreach at the Zuckerman Institute at Columbia University.
Brachman is also a playwright and screenwriter. She holds Bachelor's degrees in both neuroscience and creative wWriting, and she is currently working on a tech-focused writing project with her long-time writing partner, Sean Calder ("Grimm," "Damages," "ER"). She served as the director of NeuWrite, a national network of science-writing groups that fosters ongoing collaboration between scientists, writers and artists, and she has been featured as a storyteller at The Story Collider.
(Photo: Kenneth Willardt)
Rebecca Brachman | Speaker | TED.com