TEDxNewYork
Rebecca Brachman: Could a drug prevent depression and PTSD?
Rebecca Brachman: Kan et medikament forebygge depression og PTSD?
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Vejen til bedre medicin er brolagt med tilfældige, men revolutionerende opdagelser. I denne flotte fortælling om, hvordan forskning nogle gange kommer bag på videnskaben, deler neurovidenskabskvinden Rebecca Brachman den nyeste forskning, som er opstået på baggrund af et heldigt gennembrud, der måske kan forebygge psykiske sygdomme som depression og PTSD fra nogensinde at opstå. Og lyt efter en uventet -- og kontroversiel -- drejning.
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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Dette er en tuberkuloseafdeling.
00:16
and at the time this picture was taken
in the late 1800s,
in the late 1800s,
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Da dette billede blev taget
i slutningen af 1800-tallet
i slutningen af 1800-tallet
00:19
one in seven of all people
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døde ét ud af syv mennesker i verden
00:22
died from tuberculosis.
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af tuberkulose.
00:24
We had no idea
what was causing this disease.
what was causing this disease.
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Vi anede ikke,
hvad der forårsagede sygdommen.
hvad der forårsagede sygdommen.
00:28
The hypothesis was actually
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Hypotesen var faktisk,
00:30
it was your constitution
that made you susceptible.
that made you susceptible.
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at det var din menneskelige tilstand,
der gjorde dig modtagelig.
der gjorde dig modtagelig.
00:33
And it was a highly romanticized disease.
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Det var en meget romantiseret sygdom.
00:36
It was also called consumption,
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Sygdommen blev også kaldt konsumption,
00:39
and it was the disorder of poets
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og var anset for at være
en sygdom for poeter,
en sygdom for poeter,
00:42
and artists and intellectuals.
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kunstnere og intellektuelle.
00:45
And some people actually thought
it gave you heightened sensitivity
it gave you heightened sensitivity
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Nogle mennesker troede faktisk,
at sygdommen gjorde dig ekstra følsom,
at sygdommen gjorde dig ekstra følsom,
00:48
and conferred creative genius.
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og gav dig ekstraordinære kreative evner.
00:52
By the 1950s,
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Omkring 1950'erne
00:54
we instead knew
that tuberculosis was caused
that tuberculosis was caused
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vidste vi dog at tuberkulose
var forårsaget af en
var forårsaget af en
00:57
by a highly contagious
bacterial infection,
bacterial infection,
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yderst smitsom, bakteriel infektion,
01:00
which is slightly less romantic,
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som er noget mindre romantisk.
01:03
but that had the upside
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Dog havde det den positive egenskab,
01:05
of us being able to maybe
develop drugs to treat it.
develop drugs to treat it.
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at vi nu kunne udvikle medicin,
som måske kunne behandle sygdommen.
som måske kunne behandle sygdommen.
01:08
So doctors had discovered
a new drug, iproniazid,
a new drug, iproniazid,
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Læger havde opdaget
et nyt medikament, iproniazid,
et nyt medikament, iproniazid,
01:11
that they were optimistic
might cure tuberculosis,
might cure tuberculosis,
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som de optimistisk troede
kunne kurere tuberkulose.
kunne kurere tuberkulose.
01:15
and they gave it to patients,
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De gav det til patienter
01:16
and patients were elated.
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og patienterne blev opstemte.
01:18
They were more social, more energetic.
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De blev mere sociale, mere energiske.
01:22
One medical report actually says
they were "dancing in the halls."
they were "dancing in the halls."
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En medicinsk rapport fortæller faktisk,
at de "dansede på gangene".
at de "dansede på gangene".
01:27
And unfortunately,
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Men desværre,
01:29
this was not necessarily
because they were getting better.
because they were getting better.
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var det ikke nødvendigvis fordi,
de fik det bedre.
de fik det bedre.
01:32
A lot of them were still dying.
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Mange af patienterne døde stadig.
01:35
Another medical report describes them
as being "inappropriately happy."
as being "inappropriately happy."
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En anden medicinsk rapport
beskrev dem som "upassende glade".
beskrev dem som "upassende glade".
01:43
And that is how the first
antidepressant was discovered.
antidepressant was discovered.
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Og således blev det
første antidepressivum opdaget.
første antidepressivum opdaget.
01:47
So accidental discovery
is not uncommon in science,
is not uncommon in science,
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Opfindelser ved en fejl er således ikke
sjælden indenfor videnskaben,
sjælden indenfor videnskaben,
01:52
but it requires more
than just a happy accident.
than just a happy accident.
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men det kræver noget mere
end blot held i uheld.
end blot held i uheld.
01:55
You have to be able to recognize it
for discovery to occur.
for discovery to occur.
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Man bliver nødt til at kunne genkende det
for at kunne opdage det.
for at kunne opdage det.
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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Som forsker i neurovidenskab,
vil jeg fortælle en smule om
vil jeg fortælle en smule om
02:02
about my firsthand experience
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min egen oplevelse med
02:03
with whatever you want to call
the opposite of dumb luck --
the opposite of dumb luck --
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hvad end du ønsker at kalde
det modsatte af ren og skær held --
det modsatte af ren og skær held --
02:06
let's call it smart luck.
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lad os kalde det intelligent held.
02:08
But first, a bit more background.
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Men først lidt mere baggrundsviden.
02:12
Thankfully, since the 1950s,
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Gudskelov, har vi siden 1950'erne
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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udviklet andre typer medicin,
og kan nu kurere tuberkulose.
og kan nu kurere tuberkulose.
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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I USA i hvert fald,
ikke nødvendigvis i andre lande,
ikke nødvendigvis i andre lande,
02:22
we have closed our sanitoriums
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har vi lukket vores sanatorier,
02:24
and probably most of you
are not too worried about TB.
are not too worried about TB.
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og de fleste af jer er formentlig ikke
særligt bekymrede for TB.
særligt bekymrede for TB.
02:28
But a lot of what was true
in the early 1900s
in the early 1900s
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Men meget af det,
vi vidste i det tidlige 1900-tal
vi vidste i det tidlige 1900-tal
02:31
about infectious disease,
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om smitsomme sygdomme,
02:33
we can say now
about psychiatric disorders.
about psychiatric disorders.
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kan vi nu sige om psykiatriske sygdomme.
02:36
We are in the middle
of an epidemic of mood disorders
of an epidemic of mood disorders
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Vi står midt i en epidemi
af psykiske sygdomme,
af psykiske sygdomme,
02:39
like depression and post-traumatic
stress disorder, or PTSD.
stress disorder, or PTSD.
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som depression og posttraumatisk
stress syndrom, eller PTSD.
stress syndrom, eller PTSD.
02:44
One in four of all adults
in the United States
in the United States
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Én ud af fire af alle voksne i USA
02:48
suffers from mental illness,
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lider af en psykisk sygdom,
02:50
which means that if you haven't
experienced it personally
experienced it personally
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som betyder, at hvis du ikke
har oplevet det personligt
har oplevet det personligt
02:53
or someone in your family hasn't,
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og ingen i din familie har,
02:55
it's still very likely
that someone you know has,
that someone you know has,
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er det stadig meget sandsynligt
at nogen du kender har,
at nogen du kender har,
02:58
though they may not talk about it.
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selv om de ikke snakker om det.
03:02
Depression has actually now surpassed
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Depression har faktisk nu overhalet
03:05
HIV/AIDS, malaria, diabetes and war
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HIV/AIDS, malaria, diabetes og krig,
03:10
as the leading cause
of disability worldwide.
of disability worldwide.
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som den førende årsag
til uarbejdsdygtighed i verden.
til uarbejdsdygtighed i verden.
03:13
And also, like tuberculosis in the 1950s,
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Og som tuberkulose i 1950'erne,
03:17
we don't know what causes it.
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ved vi ikke hvad der forårsager det.
03:19
Once it's developed, it's chronic,
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Når det er udviklet, er det kronisk,
03:21
lasts a lifetime,
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varer livet ud,
03:22
and there are no known cures.
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og der er ingen kendte kure for det.
03:26
The second antidepressant we discovered,
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Det andet antidepressivum, vi opdagede,
03:28
also by accident, in the 1950s,
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også ved et uheld i 1950'erne,
03:31
from an antihistamine
that was making people manic,
that was making people manic,
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fra en antihistamin
der gjorde folk maniske,
der gjorde folk maniske,
03:35
imipramine.
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var imipramin.
03:38
And in both the case of the tuberculosis
ward and the antihistamine,
ward and the antihistamine,
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I begge tilfælde, både ved
tuberkuloseafdelingen og antihistaminet,
tuberkuloseafdelingen og antihistaminet,
03:41
someone had to be able to recognize
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skulle nogen kunne genkende,
03:43
that a drug that was designed
to do one thing --
to do one thing --
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at medicin som var
designet til at gøre én ting --
designet til at gøre én ting --
03:46
treat tuberculosis
or suppress allergies --
or suppress allergies --
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at behandle tuberkulose
eller holde allergi i skak --
eller holde allergi i skak --
03:48
could be used to do
something very different --
something very different --
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kunne anvendes til
at gøre noget helt andet --
at gøre noget helt andet --
03:51
treat depression.
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at behandle depression.
03:53
And this sort of repurposing
is actually quite challenging.
is actually quite challenging.
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Denne form for nyorientering
er meget udfordrende.
er meget udfordrende.
03:56
When doctors first saw
this mood-enhancing effect of iproniazid,
this mood-enhancing effect of iproniazid,
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Da læger først så denne
stemningsændrende effekt af iproniazid,
stemningsændrende effekt af iproniazid,
04:00
they didn't really recognize
what they saw.
what they saw.
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vedkendte de sig faktisk ikke,
hvad de så.
hvad de så.
04:02
They were so used to thinking about it
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De var så vante til,
at tænke på det
at tænke på det
04:04
from the framework
of being a tuberculosis drug
of being a tuberculosis drug
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ud fra den ramme,
at det var tuberkulosemedicin,
at det var tuberkulosemedicin,
04:07
that they actually just listed it
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at de blot oplistede
den opløftende effekt,
den opløftende effekt,
04:09
as a side effect, an adverse side effect.
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som en bivirkning, en ugunstig bivirkning.
04:12
As you can see here,
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Som I kan se her,
04:13
a lot of these patients in 1954
are experiencing severe euphoria.
are experiencing severe euphoria.
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oplevede mange patienter i 1954
gennemgribende eufori.
gennemgribende eufori.
04:18
And they were worried
that this might somehow interfere
that this might somehow interfere
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Lægestanden var bekymrede for,
at dette ville gribe ind
at dette ville gribe ind
04:22
with their recovering from tuberculosis.
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i patienternes helbredelse
af tuberkulose.
af tuberkulose.
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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Så de anbefalede kun iproniazid
i ekstreme TB-tilfælde,
i ekstreme TB-tilfælde,
04:31
and in patients that were
highly emotionally stable,
highly emotionally stable,
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og kun til patienter der var
enormt emotionelt stabile,
enormt emotionelt stabile,
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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som er den helt modsatte effekt af,
hvordan vi bruger det som antidepressivum.
hvordan vi bruger det som antidepressivum.
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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De var så vant til at anskue dette,
fra denne ene sygdoms perspektiv,
fra denne ene sygdoms perspektiv,
04:44
they could not see the larger implications
for another disease.
for another disease.
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at de ikke kunne gennemskue,
at det kunne anvendes til en anden sygdom.
at det kunne anvendes til en anden sygdom.
04:49
And to be fair,
it's not entirely their fault.
it's not entirely their fault.
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Det er ikke kun deres fejl alene.
04:52
Functional fixedness
is a bias that affects all of us.
is a bias that affects all of us.
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Fastlåst fokus er en partiskhed,
der påvirker os alle.
der påvirker os alle.
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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Det er tendensen til kun,
at kunne tænke på et objekt
at kunne tænke på et objekt
04:58
in terms of its traditional
use or function.
use or function.
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ud fra dets traditionelle
formål eller funktion.
formål eller funktion.
05:01
And mental set is another thing. Right?
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Og egen tankegang har også betydning.
05:03
That's sort of this preconceived framework
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Det er sådan set den forudindtagede ramme,
05:05
with which we approach problems.
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hvormed vi tilgår problemer.
05:07
And that actually makes repurposing
pretty hard for all of us,
pretty hard for all of us,
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Og det gør faktisk nyorientering
ret svært for os alle,
ret svært for os alle,
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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hvilket formentligt er årsagen til,
at de gav et helt TV-show til fyren,
at de gav et helt TV-show til fyren,
05:14
like, really great at repurposing.
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som var god til nyorientering.
05:16
(Laughter)
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(Latter)
05:19
So the effects in both the case
of iproniazid and imipramine,
of iproniazid and imipramine,
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Effekten af iproniazid
og imipramin i begge tilfælde
og imipramin i begge tilfælde
05:23
they were so strong --
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var så stærke,
05:24
there was mania,
or people dancing in the halls.
or people dancing in the halls.
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at der opstod mani
eller dans på gangene.
eller dans på gangene.
05:27
It's actually not that surprising
they were caught.
they were caught.
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Det er faktisk ikke overraskende
at disse blev opdaget.
at disse blev opdaget.
05:30
But it does make you wonder
what else we've missed.
what else we've missed.
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Men det rejser spørgsmålet om,
hvad vi ellers har overset.
hvad vi ellers har overset.
05:35
So iproniazid and imipramine,
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Så, iproniazid og imipramin
05:37
they're more than just
a case study in repurposing.
a case study in repurposing.
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er mere end blot eksempler på
nyorientering.
nyorientering.
05:39
They have two other things in common
that are really important.
that are really important.
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De har to andre ting til fælles,
som er virkelig vigtige.
som er virkelig vigtige.
05:42
One, they have terrible side effects.
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Et er at de har forfærdelige bivirkninger.
05:45
That includes liver toxicity,
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Det inkluderer leverforgiftning,
05:47
weight gain of over 50 pounds,
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vægtforøgelser på over 25 kg,
05:50
suicidality.
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selvmordstanker.
05:52
And two, they both
increase levels of serotonin,
increase levels of serotonin,
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Og to, de øger begge serotonin-niveauet,
05:56
which is a chemical signal in the brain,
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som er et kemisk signalstof i hjernen,
05:59
or a neurotransmitter.
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eller neurotransmitter.
06:01
And those two things together,
right, one or the two,
right, one or the two,
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De to ting tilsammen, eller en eller to,
06:03
may not have been that important,
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var måske ikke så vigtig,
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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men de to tilsammen betød,
at vi måtte udvikle sikrere medikamenter,
at vi måtte udvikle sikrere medikamenter,
06:09
and that serotonin seemed
like a pretty good place to start.
like a pretty good place to start.
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og serotonin virkede
som et godt udgangspunkt.
som et godt udgangspunkt.
06:13
So we developed drugs
to more specifically focus on serotonin,
to more specifically focus on serotonin,
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Så vi udviklede medicin
som fokuserede mere på serotonin,
som fokuserede mere på serotonin,
06:17
the selective serotonin
reuptake inhibitors, so the SSRIs,
reuptake inhibitors, so the SSRIs,
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de selektive serotonin-
genoptagelseshæmmere, altså SSRI'erne,
genoptagelseshæmmere, altså SSRI'erne,
06:21
the most famous of which is Prozac.
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hvoraf den mest berømte nok er Prozac.
06:24
And that was 30 years ago,
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Det er 30 år siden,
06:26
and since then we have mostly
just worked on optimizing those drugs.
just worked on optimizing those drugs.
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og sidenhen har vi mest arbejdet med
at optimere disse medikamenter.
at optimere disse medikamenter.
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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SSRI'erne er bedre end
den medicin, der kom før dem,
den medicin, der kom før dem,
06:32
but they still have a lot of side effects,
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men de har stadig mange bivirkninger,
06:35
including weight gain, insomnia,
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inklusiv vægtforøgelse, søvnløshed,
06:38
suicidality --
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selvmordstanker --
06:40
and they take a really long time to work,
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og det tager utroligt
lang tid før de virker,
lang tid før de virker,
06:42
something like four to six weeks
in a lot of patients.
in a lot of patients.
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omkring fire til seks uger
for mange patienter.
for mange patienter.
06:45
And that's in the patients
where they do work.
where they do work.
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Og det er for patienterne,
hvor det virker.
hvor det virker.
06:47
There are a lot of patients
where these drugs don't work.
where these drugs don't work.
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Der er mange patienter,
hvor medikamenterne ikke virker.
hvor medikamenterne ikke virker.
06:50
And that means now, in 2016,
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Og det betyder, at vi i 2016
06:53
we still have no cures
for any mood disorders,
for any mood disorders,
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stadig ingen kur
har mod psykiske lidelser,
har mod psykiske lidelser,
06:57
just drugs that suppress symptoms,
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blot medicin der hæmmer symptomerne.
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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Hvilket faktisk er forskellen mellem,
at tage en smertestillende imod infektion
at tage en smertestillende imod infektion
07:03
versus an antibiotic.
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versus et antibiotikum.
07:04
A painkiller will make you feel better,
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Smertestillende gør dig bedre tilpas,
07:06
but is not going to do anything
to treat that underlying disease.
to treat that underlying disease.
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men behandler ikke
den underliggende sygdom.
den underliggende sygdom.
07:10
And it was this flexibility
in our thinking
in our thinking
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Det var fleksibiliteten
i vores måde at tænke på,
i vores måde at tænke på,
07:13
that let us recognize
that iproniazid and imipramine
that iproniazid and imipramine
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der lod os anerkende,
at iproniazid og imipramin
at iproniazid og imipramin
07:16
could be repurposed in this way,
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kunne anvendes på en anden måde,
07:18
which led us to the serotonin hypothesis,
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som ledte os til serotonin-hypotesen,
07:20
which we then, ironically, fixated on.
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som vi så, ironisk nok, fastlåste os på.
07:23
This is brain signaling, serotonin,
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Dette er hjernesignaler, serotonin,
07:26
from an SSRI commercial.
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fra en SSRI-reklame.
07:27
In case you're not clear,
this is a dramatization.
this is a dramatization.
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Dette en illustration.
07:30
And in science, we try
and remove our bias, right,
and remove our bias, right,
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Og i videnskaben forsøger vi
at fjerne vores partiskhed
at fjerne vores partiskhed
07:34
by running double-blinded experiments
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ved at foretage
dobbeltblindede eksperimenter.
dobbeltblindede eksperimenter.
07:37
or being statistically agnostic
as to what our results will be.
as to what our results will be.
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eller være statistisk agnostiske
overfor hvad vores resultater måtte blive.
overfor hvad vores resultater måtte blive.
07:40
But bias creeps in more insidiously
in what we choose to study
in what we choose to study
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Men partiskhed sniger sig ind i hvad,
vi vælger at studere,
vi vælger at studere,
07:45
and how we choose to study it.
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og hvordan vi vælger,
at studere det.
at studere det.
07:48
So we've focused on serotonin now
for the past 30 years,
for the past 30 years,
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Så vi har fokuseret
på serotonin de sidste 30 år
på serotonin de sidste 30 år
07:51
often to the exclusion of other things.
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ofte på bekostning af andre løsninger.
07:54
We still have no cures,
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Vi har stadig ingen kur,
07:57
and what if serotonin
isn't all there is to depression?
isn't all there is to depression?
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og hvad nu hvis serotonin ikke er
det altomfattende svar på depression?
det altomfattende svar på depression?
08:00
What if it's not even the key part of it?
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Hvad hvis det ikke
er en central del af det?
er en central del af det?
08:02
That means no matter how much time
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Det betyder,
at uanset hvor meget tid
at uanset hvor meget tid
08:04
or money or effort we put into it,
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eller penge eller arbejde vi hælder i det,
08:07
it will never lead to a cure.
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vil det aldrig lede til en kur.
08:10
In the past few years,
doctors have discovered
doctors have discovered
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I de senere år har lægestanden opdaget
08:13
probably what is the first truly new
antidepressant since the SSRIs,
antidepressant since the SSRIs,
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det formentlig eneste rigtigt
nye antidepressivum siden SSRI'erne,
nye antidepressivum siden SSRI'erne,
08:18
Calypsol,
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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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og det virker rigtigt hurtigt,
inden for få timer eller en dag,
inden for få timer eller en dag,
08:23
and it doesn't work on serotonin.
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og det virker ikke på serotonin.
08:25
It works on glutamate,
which is another neurotransmitter.
which is another neurotransmitter.
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Den virker på glutamat,
som er en anden neurotransmitter.
som er en anden neurotransmitter.
08:28
And it's also repurposed.
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Det er også en nyorientering.
08:29
It was traditionally used
as anesthesia in surgery.
as anesthesia in surgery.
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Det blev oprindeligt brugt
som anæstesi under operationer.
som anæstesi under operationer.
08:33
But unlike those other drugs,
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Men modsat de andre medikamenter,
08:35
which were recognized pretty quickly,
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som blev opdaget relativt hurtigt,
08:37
it took us 20 years
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tog det os 20 år
08:38
to realize that Calypsol
was an antidepressant,
was an antidepressant,
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for at indse at Calypsol
var et antidepressivum,
var et antidepressivum,
08:41
despite the fact that it's actually
a better antidepressant,
a better antidepressant,
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til trods for at det formentlig
er et bedre antidepressivum
er et bedre antidepressivum
08:44
probably, than those other drugs.
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end de andre typer medicin.
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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Det er angiveligt på grund af det faktum,
at det er et bedre antidepressivum,
at det er et bedre antidepressivum,
08:50
that it was harder for us to recognize.
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at det var sværere for os at opdage.
08:52
There was no mania to signal its effects.
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Der var ingen mani
som tegn på dets effekt.
som tegn på dets effekt.
08:54
So in 2013, up at Columbia University,
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I 2013, på Columbia University,
08:57
I was working with my colleague,
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samarbejdede jeg med min kollega,
08:59
Dr. Christine Ann Denny,
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Dr. Christine Ann Denny,
09:01
and we were studying Calypsol
as an antidepressant in mice.
as an antidepressant in mice.
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3800
hvor vi studerede Calypsol
som et antidepressivum på mus.
som et antidepressivum på mus.
09:05
And Calypsol has, like,
a really short half-life,
a really short half-life,
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Calypsol har rigtigt kort halveringstid,
09:08
which means it's out of your body
within a few hours.
within a few hours.
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hvilket betyder det er ude
af din krop indenfor få timer.
af din krop indenfor få timer.
09:11
And we were just piloting.
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Dette var blot testforsøg.
09:13
So we would give an injection to mice,
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Vi gav mus en indsprøjtning
09:15
and then we'd wait a week,
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og ventede så en uge,
09:16
and then we'd run
another experiment to save money.
another experiment to save money.
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for så at lave et nyt forsøg
for at spare penge.
for at spare penge.
09:20
And one of the experiments I was running,
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I et af de forsøg jeg foretog
09:22
we would stress the mice,
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stressede vi musene
09:23
and we used that as a model of depression.
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og brugte det som
en simulation af depression.
en simulation af depression.
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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I første omgang
så det slet ikke ud til at virke.
så det slet ikke ud til at virke.
09:29
So we could have stopped there.
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Så vi kunne have stoppet der.
09:31
But I have run this model
of depression for years,
of depression for years,
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559540
2896
Men jeg har brugt denne
simulation af depression i mange år,
simulation af depression i mange år,
09:34
and the data just looked kind of weird.
192
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1896
og dataene så mærkelige ud.
09:36
It didn't really look right to me.
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Det så forkert ud for mig.
09:38
So I went back,
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Så jeg startede forfra,
09:39
and we reanalyzed it
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og reanalyserede dataene
09:41
based on whether or not they had gotten
that one injection of Calypsol
that one injection of Calypsol
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3816
baseret på, hvorvidt musene havde
fået den ene indsprøjtning af Calypsol
fået den ene indsprøjtning af Calypsol
09:44
a week beforehand.
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572860
1200
ugen forinden.
09:46
And it looked kind of like this.
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574940
2016
Og det så nogenlunde sådan ud.
09:48
So if you look at the far left,
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Hvis I ser længst mod venstre,
09:51
if you put a mouse in a new space,
200
579140
2496
og hvis vi putter
en mus ind i det nye rum,
en mus ind i det nye rum,
09:53
this is the box, it's very exciting,
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dette er boksen,
det er meget spændende,
det er meget spændende,
09:55
a mouse will walk around and explore,
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så vil en mus krybe rundt og udforske,
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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og den lyserøde streg forestiller sporet,
hvor musene har gået.
hvor musene har gået.
10:02
And we also give it
another mouse in a pencil cup
another mouse in a pencil cup
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3176
Og vi gav dem en
anden mus i en blyantholder,
anden mus i en blyantholder,
10:05
that it can decide to interact with.
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som den kan beslutte at interagere med.
10:07
This is also a dramatization,
in case that's not clear.
in case that's not clear.
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3216
Dette er også en dramatisering,
hvis der skulle herske tvivl om det.
hvis der skulle herske tvivl om det.
10:10
And a normal mouse will explore.
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3696
En normal mus vil
udforske sine omgivelser,
udforske sine omgivelser,
10:14
It will be social.
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være social.
10:16
Check out what's going on.
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Prøv at se hvad der sker.
10:18
If you stress a mouse
in this depression model,
in this depression model,
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2896
Hvis man stresser en mus
i denne depressionssimulation,
i denne depressionssimulation,
10:20
which is the middle box,
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som er den midterste boks,
10:23
they aren't social, they don't explore.
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er de ikke sociale,
de udforsker ikke.
de udforsker ikke.
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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613020
3280
De gemmer sig for det meste
i det bageste hjørne, bag en kop.
i det bageste hjørne, bag en kop.
10:29
Yet the mice that had gotten
that one injection of Calypsol,
that one injection of Calypsol,
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3096
Men musene som havde fået
den ene indsprøjtning af Calypsol,
den ene indsprøjtning af Calypsol,
10:32
here on your right,
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1200
her til højre,
10:34
they were exploring, they were social.
216
622060
1960
udforskede, og de var sociale.
10:36
They looked like they
had never been stressed at all,
had never been stressed at all,
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De så ud til aldrig
at have været udsat for stress,
at have været udsat for stress,
10:40
which is impossible.
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1200
hvilket er en umulighed.
10:42
So we could have just stopped there,
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1720
Vi kunne have valgt at stoppe dér,
10:44
but Christine had also used
Calypsol before as anesthesia,
Calypsol before as anesthesia,
220
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4296
men Christine havde også
brugt Calypsol som anæstesi før,
brugt Calypsol som anæstesi før,
10:49
and a few years ago she had seen
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1576
og for nogle år siden, så hun,
10:50
that it seemed to have
some weird effects on cells
some weird effects on cells
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2376
at det lod til at have
en mærkelig effekt på celler
en mærkelig effekt på celler
10:53
and some other behavior
223
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1216
og anden adfærd,
10:54
that also seemed to last
long after the drug,
long after the drug,
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3016
som lod til at virke lang tid
efter medicinens indtag,
efter medicinens indtag,
10:57
maybe a few weeks.
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til et par uger efter.
10:58
So we were like, OK,
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1256
Så vi tænkte: Okay,
10:59
maybe this is not completely impossible,
227
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2176
måske er det ikke en total umulighed,
11:02
but we were really skeptical.
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1496
men vi var virkelig skeptiske.
11:03
So we did what you do in science
when you're not sure,
when you're not sure,
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Så vi gjorde hvad man gør,
når man ikke er sikker:
når man ikke er sikker:
11:06
and we ran it again.
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1200
Vi gentog forsøgene.
11:08
And I remember being in the animal room,
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Jeg kan huske
at jeg var i dyre-afsnittet,
at jeg var i dyre-afsnittet,
11:11
moving mice from box to box
to test them,
to test them,
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659500
3656
ved at flytte mus fra
boks til boks for at teste dem,
boks til boks for at teste dem,
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
233
663180
3616
og Christine sad faktisk på gulvet
med sin computer i skødet,
med sin computer i skødet,
11:18
so the mice couldn't see her,
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1416
så musene ikke
kunne se hende,
kunne se hende,
11:20
and she was analyzing
the data in real time.
the data in real time.
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og hun analyserede dataene i realtid.
11:22
And I remember us yelling,
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Jeg kan huske, at vi råbte,
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,
237
671940
3296
som man faktisk ikke må
i et dyre-afsnit, hvor dyrene testes,
i et dyre-afsnit, hvor dyrene testes,
11:27
because it had worked.
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1576
fordi det havde virket.
11:28
It seemed like these mice
were protected against stress,
were protected against stress,
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676860
4376
Det virkede som om,
at musene var immune overfor stress,
at musene var immune overfor stress,
11:33
or they were inappropriately happy,
however you want to call it.
however you want to call it.
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681260
3056
eller var upassende glade,
eller hvordan man nu vil beskrive det.
eller hvordan man nu vil beskrive det.
11:36
And we were really excited.
241
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2440
Vi var virkelig forventningsfulde.
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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3480
Og så blev vi virkelig skeptiske
fordi det var for godt til at være sandt.
fordi det var for godt til at være sandt.
11:43
So we ran it again.
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1200
Så vi gjorde det igen.
11:45
And then we ran it again in a PTSD model,
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Så eksperimenterede vi igen
imod en PTSD-simulation,
imod en PTSD-simulation,
11:48
and we ran it again
in a physiological model,
in a physiological model,
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696500
2416
og gentog det igen
i en fysiologisk simulation,
i en fysiologisk simulation,
11:50
where all we did was give stress hormones.
246
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2216
hvor vi kun uddelte stresshormoner.
11:53
And we had our undergrads run it.
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1616
Og vores studerende lavede det.
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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4120
Og så havde vi vores samarbejdspartnere
i Frankrig til at gøre forsøgene.
i Frankrig til at gøre forsøgene.
11:59
And every time someone ran it,
they confirmed the same thing.
they confirmed the same thing.
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3216
Hver eneste gang nogen kørte forsøgene,
bekræftede de det samme.
bekræftede de det samme.
12:03
It seemed like
this one injection of Calypsol
this one injection of Calypsol
250
711020
2816
Det virkede til,
at en enkelt indsprøjtning af Calypsol,
at en enkelt indsprøjtning af Calypsol,
12:05
was somehow protecting
against stress for weeks.
against stress for weeks.
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på en eller anden måde
beskyttede mod stress i ugevis.
beskyttede mod stress i ugevis.
12:09
And we only published this a year ago,
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1856
Vi publicerede dette for et år siden,
12:11
but since then other labs
have independently confirmed this effect.
have independently confirmed this effect.
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4080
men siden da, har andre laboratorier,
uafhængigt, bekræftet denne virkning.
uafhængigt, bekræftet denne virkning.
12:15
So we don't know what causes depression,
254
723940
1920
Vi ved ikke
hvad der skyldes depression,
hvad der skyldes depression,
12:18
but we do know that stress
is the initial trigger
is the initial trigger
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3696
men vi ved,
at stress er den første udløser
at stress er den første udløser
12:22
in 80 percent of cases,
256
730180
2336
i 80 procent af tilfældene,
12:24
and depression and PTSD
are different diseases,
are different diseases,
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2216
og at depression og PTSD
er forskellige sygdomme,
er forskellige sygdomme,
12:26
but this is something
they share in common.
they share in common.
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734780
2016
men dette har de til fælles.
12:28
Right? It is traumatic stress
259
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1816
Det er traumatisk stress,
12:30
like active combat or natural disasters
260
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2896
såsom i kampzoner, ved naturkatastrofer,
12:33
or community violence or sexual assault
261
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vold i samfundet eller seksuelle overfald,
12:36
that causes post-traumatic
stress disorder,
stress disorder,
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som udløser posttraumatisk stress syndrom,
12:38
and not everyone that is exposed to stress
develops a mood disorder.
develops a mood disorder.
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5616
ikke alle der udsættes for stress
udvikler en psykisk lidelse.
udvikler en psykisk lidelse.
12:44
And this ability to experience
stress and be resilient
stress and be resilient
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2896
Denne evne til at opleve stress,
og være resilient i forhold til den,
og være resilient i forhold til den,
12:47
and bounce back and not develop
depression or PTSD
depression or PTSD
265
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4160
at komme igennem den,
og ikke udvikle depression eller PTSD,
og ikke udvikle depression eller PTSD,
12:52
is known as stress resilience,
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kendes som stress-resiliens,
12:54
and it varies between people.
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1856
og varierer fra person til person.
12:56
And we have always thought of it
as just sort of this passive property.
as just sort of this passive property.
268
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3336
Vi har altid tænkt på det
som en passiv egenskab.
som en passiv egenskab.
13:00
It's the absence of susceptibility factors
269
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2536
Det er fraværet af modtagelighed
13:02
and risk factors for these disorders.
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og risikofaktorer for disse sygdomme.
13:05
But what if it were active?
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Men hvad hvis det var aktiv?
13:08
Maybe we could enhance it,
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1496
Måske kunne vi forbedre det
13:09
sort of akin to putting on armor.
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2160
lidt ligesom at tage en rustning på.
13:13
We had accidentally discovered
the first resilience-enhancing drug.
the first resilience-enhancing drug.
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4600
Vi havde ved et tilfælde opdaget
det første resiliens-forbedrende stof.
det første resiliens-forbedrende stof.
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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2776
Vi indsprøjtede kun
en meget lille dosis af stoffet,
en meget lille dosis af stoffet,
13:21
and it lasted for weeks,
276
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1576
og det varede i ugevis,
13:23
and that's not like anything
you see with antidepressants.
you see with antidepressants.
277
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3216
meget ulig hvad
vi ellers ser med antidepressiva.
vi ellers ser med antidepressiva.
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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4320
Men det er sammenligneligt med,
hvad vi ser i immunitetsvacciner.
hvad vi ser i immunitetsvacciner.
13:31
So in immune vaccines,
you'll get your shots,
you'll get your shots,
279
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2936
Ved immunitetsvacciner
får du en indsprøjtning,
får du en indsprøjtning,
13:34
and then weeks, months, years later,
280
802140
3376
og uger, måneder eller år senere,
13:37
when you're actually exposed to bacteria,
281
805540
2336
når du faktisk udsættes for bakterier,
13:39
it's not the vaccine in your body
that protects you.
that protects you.
282
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2456
er det ikke vaccinen i din krop,
der beskytter dig.
der beskytter dig.
13:42
It's your own immune system
283
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1376
Det er dit eget immunsystem,
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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4136
som har udviklet resistens og resiliens
overfor disse bakterier, og nedkæmper dem,
overfor disse bakterier, og nedkæmper dem,
13:47
and you actually never get the infection,
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så du faktisk aldrig får den infektion.
13:50
which is very different
from, say, our treatments. Right?
from, say, our treatments. Right?
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Hvilket er ganske forskelligt fra
f.eks. behandlinger.
f.eks. behandlinger.
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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I tilfælde af at du får infektionen,
er du eksponeret for bakterien,
er du eksponeret for bakterien,
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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du bliver syg, og så indtager du
et antibiotikum, som så kurerer det,
et antibiotikum, som så kurerer det,
14:00
and those drugs are actually working
to kill the bacteria.
to kill the bacteria.
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og de stoffer arbejder faktisk
på at slå bakterien ihjel.
på at slå bakterien ihjel.
14:04
Or similar to as I said before,
with this palliative,
with this palliative,
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Som jeg sagde tidligere,
med dette palliativ
med dette palliativ
14:07
you'll take something
that will suppress the symptoms,
that will suppress the symptoms,
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tager du noget som vil
undertrykke symptomerne,
undertrykke symptomerne,
14:10
but it won't treat
the underlying infection,
the underlying infection,
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men som ikke behandler
den underliggende infektion,
den underliggende infektion,
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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og du får det kun bedre
mens du tager stoffet,
mens du tager stoffet,
14:16
which is why you have to keep taking it.
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og derfor skal man fortsætte indtaget.
14:18
And in depression and PTSD --
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Ved depression og PTSD --
14:20
here we have your stress exposure --
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her er din eksponering for stress --
14:22
we only have palliative care.
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så har vi kun palliativ hjælp.
14:25
Antidepressants only suppress symptoms,
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Antidepressiva undertrykker
blot symptomer,
blot symptomer,
og derfor er du nødt til,
at blive ved med at tage dem
at blive ved med at tage dem
14:28
and that is why you basically
have to keep taking them
have to keep taking them
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14:30
for the life of the disease,
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hele sygdommens liv,
14:32
which is often
the length of your own life.
the length of your own life.
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som tit korrelerer med længden af dit liv.
14:35
So we're calling our resilience-enhancing
drugs "paravaccines,"
drugs "paravaccines,"
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Så vi kalder vore resiliens-forbedrende
stoffer for "paravacciner",
stoffer for "paravacciner",
14:40
which means vaccine-like,
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som betyder
"vaccine-lignende",
"vaccine-lignende",
14:41
because it seems
like they might have the potential
like they might have the potential
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fordi det virker til
at de måske har potentialet til
at de måske har potentialet til
14:44
to protect against stress
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at beskytte mod stress,
14:46
and prevent mice from developing
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og forhindre mus i at udvikle
14:49
depression and post-traumatic
stress disorder.
stress disorder.
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depression og posttraumatisk
stress syndrom.
stress syndrom.
14:52
Also, not all antidepressants
are also paravaccines.
are also paravaccines.
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Det er ikke alle antidepressiva,
der også fungerer som paravacciner.
der også fungerer som paravacciner.
14:57
We tried Prozac as well,
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Vi prøvede også med Prozac,
14:58
and that had no effect.
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og det havde ingen effekt.
15:01
So if this were to translate into humans,
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Så hvis vi skal
overføre dette til mennesker,
overføre dette til mennesker,
15:04
we might be able to protect people
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så er vi muligvis
i stand til at beskytte folk,
i stand til at beskytte folk,
15:06
who are predictably at risk
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som antageligt er i fare for
15:08
against stress-induced disorders
like depression and PTSD.
like depression and PTSD.
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at udvikle stress-inducerede lidelser
som depression og PTSD.
som depression og PTSD.
15:12
So that's first responders
and firefighters,
and firefighters,
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Det er f.eks. ambulancepersonnel
og brandmænd,
og brandmænd,
15:16
refugees, prisoners and prison guards,
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flygtninge, indsatte i fængsler
og fængselsbetjente,
og fængselsbetjente,
15:20
soldiers, you name it.
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soldater og så videre.
15:23
And to give you a sense
of the scale of these diseases,
of the scale of these diseases,
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For at formidle en fornemmelse
af omfanget af disse sygdomme,
af omfanget af disse sygdomme,
15:27
in 2010, the global burden of disease
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var den samlede globale byrde
af sygdom i 2010
af sygdom i 2010
15:30
was estimated at 2.5 trillion dollars,
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estimeret til 2,5 billioner dollars,
15:35
and since they are chronic,
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og eftersom de er kroniske,
15:36
that cost is compounding
and is therefore expected to rise
and is therefore expected to rise
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tiltager omkostningerne betragteligt,
og forventes at stige
og forventes at stige
15:39
up to six trillion dollars
in just the next 15 years.
in just the next 15 years.
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til op mod seks billioner dollars
alene indenfor de næste 15 år.
alene indenfor de næste 15 år.
15:44
As I mentioned before,
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Som jeg nævnte før,
15:46
repurposing can be challenging
because of our prior biases.
because of our prior biases.
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kan nyorientering være en udfordring
grundet vores forudindtagethed.
grundet vores forudindtagethed.
15:50
Calypsol has another name,
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Calypsol har et andet navn,
15:53
ketamine,
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941100
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ketamin,
15:55
which also goes by another name,
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som igen kaldes noget andet,
15:57
Special K,
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Special K,
15:58
which is a club drug and drug of abuse.
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som er et feststof
og et misbrugsstof.
og et misbrugsstof.
16:02
It's still used across the world
as an anesthetic.
as an anesthetic.
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Det anvendes stadig globalt
som et anæstesi-præparat.
som et anæstesi-præparat.
16:05
It's used in children.
We use it on the battlefield.
We use it on the battlefield.
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Det anvendes til børn.
Vi bruger det på slagmarker.
Vi bruger det på slagmarker.
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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956540
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Det er faktisk det foretrukne præparat
i mange udviklingslande,
i mange udviklingslande,
16:11
because it doesn't affect breathing.
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fordi det ikke påvirker vejrtrækning.
16:13
It is on the World Health Organization
list of most essential medicines.
list of most essential medicines.
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Den er på WHO's liste over
de mest uundværlige mediciner i verden.
de mest uundværlige mediciner i verden.
16:18
If we had discovered ketamine
as a paravaccine first,
as a paravaccine first,
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Havde vi opdaget ketamin
som en paravaccine først,
som en paravaccine først,
16:22
it'd be pretty easy for us to develop it,
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970820
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havde det været let for os
at udvikle stoffet yderligere,
at udvikle stoffet yderligere,
16:25
but as is, we have to compete
with our functional fixedness
with our functional fixedness
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men vi skal bekæmpe vores fastlåste fokus
16:29
and mental set that kind of interfere.
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og vores respektive udgangspunkt.
16:33
Fortunately, it's not
the only compound we have discovered
the only compound we have discovered
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Heldigvis er det ikke
det eneste medikament, vi har opdaget,
det eneste medikament, vi har opdaget,
16:37
that has these prophylactic,
paravaccine qualities,
paravaccine qualities,
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som har disse profylaktiske
og paravaccinale egenskaber,
og paravaccinale egenskaber,
16:41
but all of the other drugs
we've discovered,
we've discovered,
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men alle de andre medikamenter,
vi har opdaget,
vi har opdaget,
16:44
or compounds if you will,
they're totally new,
they're totally new,
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eller blandinger
af medikamenter, er helt nye.
af medikamenter, er helt nye.
16:46
they have to go through
the entire FDA approval process --
the entire FDA approval process --
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De skal igennem hele
den medicinske godkendelsesproces --
den medicinske godkendelsesproces --
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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hvis de da overhovedet bliver mulige
at godkende til brug for mennesker.
at godkende til brug for mennesker.
16:54
And that will be years.
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Og det tager årevis.
16:55
So if we wanted something sooner,
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Så, hvis vi vil have noget
til at ske tidligere,
til at ske tidligere,
16:58
ketamine is already FDA-approved.
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så er ketamin allerede
godkendt til medicinbrug.
godkendt til medicinbrug.
17:00
It's generic, it's available.
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Det er godkendt og tilgængeligt
til menneskeligt forbrug.
til menneskeligt forbrug.
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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Vi kan udvikle det for
en brøkdel af prisen og tiden.
en brøkdel af prisen og tiden.
17:08
But actually, beyond
functional fixedness and mental set,
functional fixedness and mental set,
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Men ud over fastlåst fokus,
og mentalt udgangspunkt,
og mentalt udgangspunkt,
17:12
there's a real other challenge
to repurposing drugs,
to repurposing drugs,
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så er der en anden udfordring
med at anvende medikamenter på ny,
med at anvende medikamenter på ny,
17:16
which is policy.
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1199
som er politik.
17:18
There are no incentives in place
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Der er ikke noget incitament,
17:20
once a drug is generic and off patent
and no longer exclusive
and no longer exclusive
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når et medikament ikke er patenteret
og dermed ikke længere ekslusivt
og dermed ikke længere ekslusivt
17:24
to encourage pharma companies
to develop them,
to develop them,
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for medicinalindustrien
til at udvikle dem,
til at udvikle dem,
17:26
because they don't make money.
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fordi de ikke tjener penge.
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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Det gælder ikke kun ketamin.
Det gælder alle stoffer.
Det gælder alle stoffer.
17:32
Regardless, the idea itself
is completely novel in psychiatry,
is completely novel in psychiatry,
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Uanset hvad er idéen i sig selv
en nyskabelse i psykiatrien,
en nyskabelse i psykiatrien,
17:38
to use drugs to prevent mental illness
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at bruge medicin til
at forebygge psykiske sygdomme
at forebygge psykiske sygdomme
17:42
as opposed to just treat it.
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modsat blot at behandle dem.
17:44
It is possible that 20, 50,
100 years from now,
100 years from now,
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5056
Det er muligt,
at vi om 20, 50, 100 år,
at vi om 20, 50, 100 år,
17:49
we will look back now
at depression and PTSD
at depression and PTSD
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vil se tilbage på depression og PTSD
17:53
the way we look back
at tuberculosis sanitoriums
at tuberculosis sanitoriums
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på samme måde, som vi ser
tilbage på tuberkulosesanatorier
tilbage på tuberkulosesanatorier
17:57
as a thing of the past.
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som et fortidslevn.
17:59
This could be the beginning of the end
of the mental health epidemic.
of the mental health epidemic.
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Dette kunne være begyndelsen på enden
af den psykiske lidelses epidemi.
af den psykiske lidelses epidemi.
18:05
But as a great scientist once said,
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Men som en stor videnskabsmand
engang sagde:
engang sagde:
18:09
"Only a fool is sure of anything.
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"Kun en tåbe er skråsikker
på noget som helst.
på noget som helst.
18:12
A wise man keeps on guessing."
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En vis mand bliver ved med at gætte."
18:16
Thank you, guys.
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Tak skal I have.
18:17
(Applause)
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(Bifald)
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