0:00:08.060,0:00:11.076
This is a tuberculosis ward,

0:00:11.100,0:00:14.916
and at the time this picture was taken[br]in the late 1800s,

0:00:14.940,0:00:17.556
one in seven of all people

0:00:17.580,0:00:19.340
died from tuberculosis.

0:00:19.780,0:00:22.540
We had no idea[br]what was causing this disease.

0:00:23.140,0:00:25.196
The hypothesis was actually

0:00:25.220,0:00:28.476
it was your constitution[br]that made you susceptible.

0:00:28.500,0:00:31.236
And it was a highly romanticized disease.

0:00:31.260,0:00:34.076
It was also called consumption,

0:00:34.100,0:00:37.236
and it was the disorder of poets

0:00:37.260,0:00:39.996
and artists and intellectuals.

0:00:40.020,0:00:43.756
And some people actually thought[br]it gave you heightened sensitivity

0:00:43.780,0:00:45.980
and conferred creative genius.

0:00:47.700,0:00:49.836
By the 1950s,

0:00:49.860,0:00:52.436
we instead knew[br]that tuberculosis was caused

0:00:52.460,0:00:55.836
by a highly contagious[br]bacterial infection,

0:00:55.860,0:00:58.036
which is slightly less romantic,

0:00:58.060,0:01:00.316
but that had the upside

0:01:00.340,0:01:03.676
of us being able to maybe[br]develop drugs to treat it.

0:01:03.700,0:01:06.716
So doctors had discovered[br]a new drug, iproniazid,

0:01:06.740,0:01:10.116
that they were optimistic[br]might cure tuberculosis,

0:01:10.140,0:01:11.916
and they gave it to patients,

0:01:11.940,0:01:13.716
and patients were elated.

0:01:13.740,0:01:17.236
They were more social, more energetic.

0:01:17.260,0:01:21.860
One medical report actually says[br]they were "dancing in the halls."

0:01:22.500,0:01:24.116
And unfortunately,

0:01:24.140,0:01:26.860
this was not necessarily[br]because they were getting better.

0:01:27.420,0:01:29.620
A lot of them were still dying.

0:01:30.660,0:01:37.260
Another medical report describes them[br]as being "inappropriately happy."

0:01:38.220,0:01:41.820
And that is how the first[br]antidepressant was discovered.

0:01:42.980,0:01:47.036
So accidental discovery[br]is not uncommon in science,

0:01:47.060,0:01:50.196
but it requires more[br]than just a happy accident.

0:01:50.220,0:01:53.660
You have to be able to recognize it[br]for discovery to occur.

0:01:54.500,0:01:57.236
As a neuroscientist,[br]I'm going to talk to you a little bit

0:01:57.260,0:01:58.676
about my firsthand experience

0:01:58.700,0:02:01.916
with whatever you want to call[br]the opposite of dumb luck --

0:02:01.940,0:02:03.556
let's call it smart luck.

0:02:03.580,0:02:06.300
But first, a bit more background.

0:02:07.460,0:02:10.116
Thankfully, since the 1950s,

0:02:10.139,0:02:14.116
we've developed some other drugs[br]and we can actually now cure tuberculosis.

0:02:14.140,0:02:17.796
And at least in the United States,[br]though not necessarily in other countries,

0:02:17.820,0:02:19.316
we have closed our sanitoriums

0:02:19.340,0:02:23.020
and probably most of you[br]are not too worried about TB.

0:02:23.900,0:02:26.556
But a lot of what was true[br]in the early 1900s

0:02:26.580,0:02:28.436
about infectious disease,

0:02:28.460,0:02:31.100
we can say now[br]about psychiatric disorders.

0:02:31.820,0:02:34.836
We are in the middle[br]of an epidemic of mood disorders

0:02:34.860,0:02:38.620
like depression and post-traumatic[br]stress disorder, or PTSD.

0:02:39.300,0:02:43.156
One in four of all adults[br]in the United States

0:02:43.180,0:02:44.660
suffers from mental illness,

0:02:45.180,0:02:48.316
which means that if you haven't[br]experienced it personally

0:02:48.340,0:02:50.636
or someone in your family hasn't,

0:02:50.660,0:02:53.916
it's still very likely[br]that someone you know has,

0:02:53.940,0:02:55.580
though they may not talk about it.

0:02:57.220,0:03:00.516
Depression has actually now surpassed

0:03:00.540,0:03:05.396
HIV/AIDS, malaria, diabetes and war

0:03:05.420,0:03:08.676
as the leading cause[br]of disability worldwide.

0:03:08.700,0:03:12.316
And also, like tuberculosis in the 1950s,

0:03:12.340,0:03:14.396
we don't know what causes it.

0:03:14.420,0:03:16.356
Once it's developed, it's chronic,

0:03:16.380,0:03:17.876
lasts a lifetime,

0:03:17.900,0:03:20.220
and there are no known cures.

0:03:21.660,0:03:23.876
The second antidepressant we discovered,

0:03:23.900,0:03:26.356
also by accident, in the 1950s,

0:03:26.380,0:03:29.580
from an antihistamine[br]that was making people manic,

0:03:30.860,0:03:32.060
imipramine.

0:03:33.220,0:03:36.876
And in both the case of the tuberculosis[br]ward and the antihistamine,

0:03:36.900,0:03:38.596
someone had to be able to recognize

0:03:38.620,0:03:41.036
that a drug that was designed[br]to do one thing --

0:03:41.060,0:03:43.636
treat tuberculosis[br]or suppress allergies --

0:03:43.660,0:03:46.396
could be used to do[br]something very different --

0:03:46.420,0:03:47.620
treat depression.

0:03:48.380,0:03:51.396
And this sort of repurposing[br]is actually quite challenging.

0:03:51.420,0:03:55.356
When doctors first saw[br]this mood-enhancing effect of iproniazid,

0:03:55.380,0:03:57.836
they didn't really recognize[br]what they saw.

0:03:57.860,0:03:59.716
They were so used to thinking about it

0:03:59.740,0:04:02.516
from the framework[br]of being a tuberculosis drug

0:04:02.540,0:04:04.596
that they actually just listed it

0:04:04.620,0:04:07.396
as a side effect, an adverse side effect.

0:04:07.420,0:04:08.571
As you can see here,

0:04:08.596,0:04:12.620
a lot of these patients in 1954[br]are experiencing severe euphoria.

0:04:13.900,0:04:17.516
And they were worried[br]that this might somehow interfere

0:04:17.540,0:04:20.396
with their recovering from tuberculosis.

0:04:20.420,0:04:26.676
So they recommended that iproniazid[br]only be used in cases of extreme TB

0:04:26.700,0:04:30.380
and in patients that were[br]highly emotionally stable,

0:04:31.220,0:04:35.116
which is of course the exact opposite[br]of how we use it as an antidepressant.

0:04:35.140,0:04:39.596
They were so used to looking at it[br]from the perspective of this one disease,

0:04:39.620,0:04:43.540
they could not see the larger implications[br]for another disease.

0:04:44.380,0:04:47.076
And to be fair,[br]it's not entirely their fault.

0:04:47.100,0:04:49.876
Functional fixedness[br]is a bias that affects all of us.

0:04:49.900,0:04:53.356
It's a tendency to only[br]be able to think of an object

0:04:53.380,0:04:55.980
in terms of its traditional[br]use or function.

0:04:56.740,0:04:58.636
And mental set is another thing. Right?

0:04:58.660,0:05:00.676
That's sort of this preconceived framework

0:05:00.700,0:05:02.476
with which we approach problems.

0:05:02.500,0:05:05.756
And that actually makes repurposing[br]pretty hard for all of us,

0:05:05.780,0:05:09.316
which is, I guess, why they gave[br]a TV show to the guy who was,

0:05:09.340,0:05:11.140
like, really great at repurposing.

0:05:11.660,0:05:13.540
(Laughter)

0:05:14.180,0:05:18.516
So the effects in both the case[br]of iproniazid and imipramine,

0:05:18.540,0:05:19.916
they were so strong --

0:05:19.940,0:05:22.156
there was mania,[br]or people dancing in the halls.

0:05:22.180,0:05:25.316
It's actually not that surprising[br]they were caught.

0:05:25.340,0:05:28.820
But it does make you wonder[br]what else we've missed.

0:05:30.020,0:05:32.196
So iproniazid and imipramine,

0:05:32.220,0:05:34.636
they're more than just[br]a case study in repurposing.

0:05:34.660,0:05:37.636
They have two other things in common[br]that are really important.

0:05:37.660,0:05:40.156
One, they have terrible side effects.

0:05:40.180,0:05:42.796
That includes liver toxicity,

0:05:42.820,0:05:45.796
weight gain of over 50 pounds,

0:05:45.820,0:05:47.596
suicidality.

0:05:47.620,0:05:51.796
And two, they both[br]increase levels of serotonin,

0:05:51.820,0:05:54.156
which is a chemical signal in the brain,

0:05:54.180,0:05:55.380
or a neurotransmitter.

0:05:56.380,0:05:58.876
And those two things together,[br]right, one or the two,

0:05:58.900,0:06:00.516
may not have been that important,

0:06:00.540,0:06:04.276
but the two together meant[br]that we had to develop safer drugs,

0:06:04.300,0:06:07.820
and that serotonin seemed[br]like a pretty good place to start.

0:06:08.660,0:06:12.556
So we developed drugs[br]to more specifically focus on serotonin,

0:06:12.580,0:06:16.236
the selective serotonin[br]reuptake inhibitors, so the SSRIs,

0:06:16.260,0:06:18.996
the most famous of which is Prozac.

0:06:19.020,0:06:20.996
And that was 30 years ago,

0:06:21.020,0:06:24.220
and since then we have mostly[br]just worked on optimizing those drugs.

0:06:24.740,0:06:27.956
And the SSRIs, they are better[br]than the drugs that came before them,

0:06:27.980,0:06:30.076
but they still have a lot of side effects,

0:06:30.100,0:06:32.996
including weight gain, insomnia,

0:06:33.020,0:06:34.220
suicidality --

0:06:35.100,0:06:37.436
and they take a really long time to work,

0:06:37.460,0:06:39.996
something like four to six weeks[br]in a lot of patients.

0:06:40.020,0:06:42.196
And that's in the patients[br]where they do work.

0:06:42.220,0:06:45.076
There are a lot of patients[br]where these drugs don't work.

0:06:45.100,0:06:48.476
And that means now, in 2016,

0:06:48.500,0:06:52.316
we still have no cures[br]for any mood disorders,

0:06:52.340,0:06:54.396
just drugs that suppress symptoms,

0:06:54.420,0:06:58.476
which is kind of the difference between[br]taking a painkiller for an infection

0:06:58.500,0:06:59.916
versus an antibiotic.

0:06:59.940,0:07:01.796
A painkiller will make you feel better,

0:07:01.820,0:07:04.900
but is not going to do anything[br]to treat that underlying disease.

0:07:05.700,0:07:08.036
And it was this flexibility[br]in our thinking

0:07:08.060,0:07:10.996
that let us recognize[br]that iproniazid and imipramine

0:07:11.020,0:07:13.116
could be repurposed in this way,

0:07:13.140,0:07:15.116
which led us to the serotonin hypothesis,

0:07:15.140,0:07:18.140
which we then, ironically, fixated on.

0:07:18.980,0:07:21.516
This is brain signaling, serotonin,

0:07:21.540,0:07:22.796
from an SSRI commercial.

0:07:22.820,0:07:25.180
In case you're not clear,[br]this is a dramatization.

0:07:25.660,0:07:29.716
And in science, we try[br]and remove our bias, right,

0:07:29.740,0:07:32.116
by running double-blinded experiments

0:07:32.140,0:07:35.836
or being statistically agnostic[br]as to what our results will be.

0:07:35.860,0:07:40.156
But bias creeps in more insidiously[br]in what we choose to study

0:07:40.180,0:07:41.900
and how we choose to study it.

0:07:43.260,0:07:46.836
So we've focused on serotonin now[br]for the past 30 years,

0:07:46.860,0:07:49.100
often to the exclusion of other things.

0:07:49.860,0:07:51.220
We still have no cures,

0:07:52.180,0:07:55.596
and what if serotonin[br]isn't all there is to depression?

0:07:55.620,0:07:57.676
What if it's not even the key part of it?

0:07:57.700,0:07:59.876
That means no matter how much time

0:07:59.900,0:08:02.636
or money or effort we put into it,

0:08:02.660,0:08:04.580
it will never lead to a cure.

0:08:05.500,0:08:08.076
In the past few years,[br]doctors have discovered

0:08:08.100,0:08:13.020
probably what is the first truly new[br]antidepressant since the SSRIs,

0:08:13.540,0:08:14.836
Calypsol,

0:08:14.860,0:08:18.316
and this drug works very quickly,[br]within a few hours or a day,

0:08:18.340,0:08:20.236
and it doesn't work on serotonin.

0:08:20.260,0:08:22.940
It works on glutamate,[br]which is another neurotransmitter.

0:08:23.380,0:08:24.876
And it's also repurposed.

0:08:24.900,0:08:27.980
It was traditionally used[br]as anesthesia in surgery.

0:08:28.540,0:08:30.196
But unlike those other drugs,

0:08:30.220,0:08:32.035
which were recognized pretty quickly,

0:08:32.059,0:08:33.756
it took us 20 years

0:08:33.780,0:08:36.436
to realize that Calypsol[br]was an antidepressant,

0:08:36.460,0:08:39.316
despite the fact that it's actually[br]a better antidepressant,

0:08:39.340,0:08:40.956
probably, than those other drugs.

0:08:40.980,0:08:45.076
It's actually probably because of the fact[br]that it's a better antidepressant

0:08:45.100,0:08:46.995
that it was harder for us to recognize.

0:08:47.019,0:08:49.100
There was no mania to signal its effects.

0:08:49.580,0:08:52.676
So in 2013, up at Columbia University,

0:08:52.700,0:08:54.276
I was working with my colleague,

0:08:54.300,0:08:56.276
Dr. Christine Ann Denny,

0:08:56.300,0:09:00.100
and we were studying Calypsol[br]as an antidepressant in mice.

0:09:00.660,0:09:03.476
And Calypsol has, like,[br]a really short half-life,

0:09:03.500,0:09:06.556
which means it's out of your body[br]within a few hours.

0:09:06.580,0:09:07.996
And we were just piloting.

0:09:08.020,0:09:10.276
So we would give an injection to mice,

0:09:10.300,0:09:11.596
and then we'd wait a week,

0:09:11.620,0:09:14.300
and then we'd run[br]another experiment to save money.

0:09:15.020,0:09:17.156
And one of the experiments I was running,

0:09:17.180,0:09:18.836
we would stress the mice,

0:09:18.860,0:09:21.076
and we used that as a model of depression.

0:09:21.100,0:09:24.436
And at first it kind of just looked[br]like it didn't really work at all.

0:09:24.460,0:09:25.980
So we could have stopped there.

0:09:26.540,0:09:29.436
But I have run this model[br]of depression for years,

0:09:29.460,0:09:31.356
and the data just looked kind of weird.

0:09:31.380,0:09:33.236
It didn't really look right to me.

0:09:33.260,0:09:34.476
So I went back,

0:09:34.500,0:09:35.996
and we reanalyzed it

0:09:36.020,0:09:39.836
based on whether or not they had gotten[br]that one injection of Calypsol

0:09:39.860,0:09:41.060
a week beforehand.

0:09:41.940,0:09:43.956
And it looked kind of like this.

0:09:43.980,0:09:46.116
So if you look at the far left,

0:09:46.140,0:09:48.636
if you put a mouse in a new space,

0:09:48.660,0:09:50.916
this is the box, it's very exciting,

0:09:50.940,0:09:53.076
a mouse will walk around and explore,

0:09:53.100,0:09:57.396
and you can see that pink line[br]is actually the measure of them walking.

0:09:57.420,0:10:00.596
And we also give it[br]another mouse in a pencil cup

0:10:00.620,0:10:02.676
that it can decide to interact with.

0:10:02.700,0:10:05.916
This is also a dramatization,[br]in case that's not clear.

0:10:05.940,0:10:09.636
And a normal mouse will explore.

0:10:09.660,0:10:10.900
It will be social.

0:10:11.620,0:10:12.996
Check out what's going on.

0:10:13.020,0:10:15.916
If you stress a mouse[br]in this depression model,

0:10:15.940,0:10:17.220
which is the middle box,

0:10:18.100,0:10:19.996
they aren't social, they don't explore.

0:10:20.020,0:10:23.300
They mostly just kind of hide[br]in that back corner, behind a cup.

0:10:24.020,0:10:27.116
Yet the mice that had gotten[br]that one injection of Calypsol,

0:10:27.140,0:10:28.340
here on your right,

0:10:29.060,0:10:31.020
they were exploring, they were social.

0:10:31.740,0:10:34.220
They looked like they[br]had never been stressed at all,

0:10:35.020,0:10:36.220
which is impossible.

0:10:37.260,0:10:38.980
So we could have just stopped there,

0:10:39.780,0:10:44.076
but Christine had also used[br]Calypsol before as anesthesia,

0:10:44.100,0:10:45.676
and a few years ago she had seen

0:10:45.700,0:10:48.076
that it seemed to have[br]some weird effects on cells

0:10:48.100,0:10:49.316
and some other behavior

0:10:49.340,0:10:52.356
that also seemed to last[br]long after the drug,

0:10:52.380,0:10:53.636
maybe a few weeks.

0:10:53.660,0:10:54.916
So we were like, OK,

0:10:54.940,0:10:57.116
maybe this is not completely impossible,

0:10:57.140,0:10:58.636
but we were really skeptical.

0:10:58.660,0:11:01.196
So we did what you do in science[br]when you're not sure,

0:11:01.220,0:11:02.420
and we ran it again.

0:11:03.460,0:11:06.476
And I remember being in the animal room,

0:11:06.500,0:11:10.156
moving mice from box to box[br]to test them,

0:11:10.180,0:11:13.796
and Christine was actually sitting[br]on the floor with the computer in her lap

0:11:13.820,0:11:15.236
so the mice couldn't see her,

0:11:15.260,0:11:17.516
and she was analyzing[br]the data in real time.

0:11:17.540,0:11:18.916
And I remember us yelling,

0:11:18.940,0:11:22.236
which you're not supposed to do[br]in an animal room where you're testing,

0:11:22.260,0:11:23.836
because it had worked.

0:11:23.860,0:11:28.236
It seemed like these mice[br]were protected against stress,

0:11:28.260,0:11:31.316
or they were inappropriately happy,[br]however you want to call it.

0:11:31.340,0:11:33.780
And we were really excited.

0:11:34.820,0:11:38.300
And then we were really skeptical,[br]because it was too good to be true.

0:11:38.860,0:11:40.060
So we ran it again.

0:11:40.740,0:11:43.476
And then we ran it again in a PTSD model,

0:11:43.500,0:11:45.916
and we ran it again[br]in a physiological model,

0:11:45.940,0:11:48.156
where all we did was give stress hormones.

0:11:48.180,0:11:49.796
And we had our undergrads run it.

0:11:49.820,0:11:53.940
And then we had our collaborators[br]halfway across the world in France run it.

0:11:54.780,0:11:57.996
And every time someone ran it,[br]they confirmed the same thing.

0:11:58.020,0:12:00.836
It seemed like[br]this one injection of Calypsol

0:12:00.860,0:12:03.620
was somehow protecting[br]against stress for weeks.

0:12:04.180,0:12:06.036
And we only published this a year ago,

0:12:06.060,0:12:10.140
but since then other labs[br]have independently confirmed this effect.

0:12:10.940,0:12:12.860
So we don't know what causes depression,

0:12:13.460,0:12:17.156
but we do know that stress[br]is the initial trigger

0:12:17.180,0:12:19.516
in 80 percent of cases,

0:12:19.540,0:12:21.756
and depression and PTSD[br]are different diseases,

0:12:21.780,0:12:23.796
but this is something[br]they share in common.

0:12:23.820,0:12:25.636
Right? It is traumatic stress

0:12:25.660,0:12:28.556
like active combat or natural disasters

0:12:28.580,0:12:31.036
or community violence or sexual assault

0:12:31.060,0:12:33.340
that causes post-traumatic[br]stress disorder,

0:12:33.980,0:12:39.596
and not everyone that is exposed to stress[br]develops a mood disorder.

0:12:39.620,0:12:42.516
And this ability to experience[br]stress and be resilient

0:12:42.540,0:12:46.700
and bounce back and not develop[br]depression or PTSD

0:12:47.500,0:12:49.756
is known as stress resilience,

0:12:49.780,0:12:51.636
and it varies between people.

0:12:51.660,0:12:54.996
And we have always thought of it[br]as just sort of this passive property.

0:12:55.020,0:12:57.556
It's the absence of susceptibility factors

0:12:57.580,0:12:59.660
and risk factors for these disorders.

0:13:00.620,0:13:02.500
But what if it were active?

0:13:03.420,0:13:04.916
Maybe we could enhance it,

0:13:04.940,0:13:07.100
sort of akin to putting on armor.

0:13:08.220,0:13:12.820
We had accidentally discovered[br]the first resilience-enhancing drug.

0:13:13.740,0:13:16.516
And like I said, we only gave[br]a tiny amount of the drug,

0:13:16.540,0:13:18.116
and it lasted for weeks,

0:13:18.140,0:13:21.356
and that's not like anything[br]you see with antidepressants.

0:13:21.380,0:13:25.700
But it is actually kind of similar[br]to what you see in immune vaccines.

0:13:26.180,0:13:29.116
So in immune vaccines,[br]you'll get your shots,

0:13:29.140,0:13:32.516
and then weeks, months, years later,

0:13:32.540,0:13:34.876
when you're actually exposed to bacteria,

0:13:34.900,0:13:37.356
it's not the vaccine in your body[br]that protects you.

0:13:37.380,0:13:38.756
It's your own immune system

0:13:38.780,0:13:42.916
that's developed resistance and resilience[br]to this bacteria that fights it off,

0:13:42.940,0:13:45.076
and you actually never get the infection,

0:13:45.100,0:13:48.156
which is very different[br]from, say, our treatments. Right?

0:13:48.180,0:13:51.996
In that case, you get the infection,[br]you're exposed to the bacteria,

0:13:52.020,0:13:55.876
you're sick, and then you take,[br]say, an antibiotic which cures it,

0:13:55.900,0:13:59.140
and those drugs are actually working[br]to kill the bacteria.

0:13:59.780,0:14:02.276
Or similar to as I said before,[br]with this palliative,

0:14:02.300,0:14:05.156
you'll take something[br]that will suppress the symptoms,

0:14:05.180,0:14:07.876
but it won't treat[br]the underlying infection,

0:14:07.900,0:14:11.236
and you'll only feel better[br]during the time in which you're taking it,

0:14:11.260,0:14:13.196
which is why you have to keep taking it.

0:14:13.220,0:14:15.916
And in depression and PTSD --

0:14:15.940,0:14:17.916
here we have your stress exposure --

0:14:17.940,0:14:20.556
we only have palliative care.

0:14:20.580,0:14:23.076
Antidepressants only suppress symptoms,

0:14:23.100,0:14:25.956
and that is why you basically[br]have to keep taking them

0:14:25.980,0:14:27.676
for the life of the disease,

0:14:27.700,0:14:29.900
which is often[br]the length of your own life.

0:14:30.940,0:14:35.156
So we're calling our resilience-enhancing[br]drugs "paravaccines,"

0:14:35.180,0:14:36.716
which means vaccine-like,

0:14:36.740,0:14:39.236
because it seems[br]like they might have the potential

0:14:39.260,0:14:41.076
to protect against stress

0:14:41.100,0:14:44.516
and prevent mice from developing

0:14:44.540,0:14:47.300
depression and post-traumatic[br]stress disorder.

0:14:47.780,0:14:51.220
Also, not all antidepressants[br]are also paravaccines.

0:14:52.300,0:14:53.916
We tried Prozac as well,

0:14:53.940,0:14:55.300
and that had no effect.

0:14:56.060,0:14:59.076
So if this were to translate into humans,

0:14:59.100,0:15:01.676
we might be able to protect people

0:15:01.700,0:15:03.956
who are predictably at risk

0:15:03.980,0:15:07.836
against stress-induced disorders[br]like depression and PTSD.

0:15:07.860,0:15:10.996
So that's first responders[br]and firefighters,

0:15:11.020,0:15:15.156
refugees, prisoners and prison guards,

0:15:15.180,0:15:17.260
soldiers, you name it.

0:15:18.220,0:15:22.020
And to give you a sense[br]of the scale of these diseases,

0:15:22.620,0:15:25.676
in 2010, the global burden of disease

0:15:25.700,0:15:29.540
was estimated at 2.5 trillion dollars,

0:15:30.060,0:15:31.596
and since they are chronic,

0:15:31.620,0:15:34.836
that cost is compounding[br]and is therefore expected to rise

0:15:34.860,0:15:38.100
up to six trillion dollars[br]in just the next 15 years.

0:15:39.460,0:15:41.039
As I mentioned before,

0:15:41.064,0:15:45.140
repurposing can be challenging[br]because of our prior biases.

0:15:45.860,0:15:47.380
Calypsol has another name,

0:15:48.100,0:15:49.300
ketamine,

0:15:50.380,0:15:51.940
which also goes by another name,

0:15:52.460,0:15:53.876
Special K,

0:15:53.900,0:15:56.300
which is a club drug and drug of abuse.

0:15:57.540,0:16:00.636
It's still used across the world[br]as an anesthetic.

0:16:00.660,0:16:03.516
It's used in children.[br]We use it on the battlefield.

0:16:03.540,0:16:06.516
It's actually the drug of choice[br]in a lot of developing nations,

0:16:06.540,0:16:08.396
because it doesn't affect breathing.

0:16:08.420,0:16:13.100
It is on the World Health Organization[br]list of most essential medicines.

0:16:13.580,0:16:17.140
If we had discovered ketamine[br]as a paravaccine first,

0:16:17.820,0:16:20.676
it'd be pretty easy for us to develop it,

0:16:20.700,0:16:24.556
but as is, we have to compete[br]with our functional fixedness

0:16:24.580,0:16:27.380
and mental set that kind of interfere.

0:16:28.700,0:16:32.556
Fortunately, it's not[br]the only compound we have discovered

0:16:32.580,0:16:36.020
that has these prophylactic,[br]paravaccine qualities,

0:16:36.700,0:16:38.900
but all of the other drugs[br]we've discovered,

0:16:39.780,0:16:41.956
or compounds if you will,[br]they're totally new,

0:16:41.980,0:16:45.596
they have to go through[br]the entire FDA approval process --

0:16:45.620,0:16:49.196
if they make it before[br]they can ever be used in humans.

0:16:49.220,0:16:50.876
And that will be years.

0:16:50.900,0:16:53.156
So if we wanted something sooner,

0:16:53.180,0:16:55.556
ketamine is already FDA-approved.

0:16:55.580,0:16:58.276
It's generic, it's available.

0:16:58.300,0:17:02.460
We could develop it for a fraction[br]of the price and a fraction of the time.

0:17:03.380,0:17:07.756
But actually, beyond[br]functional fixedness and mental set,

0:17:07.780,0:17:11.356
there's a real other challenge[br]to repurposing drugs,

0:17:11.380,0:17:12.579
which is policy.

0:17:13.179,0:17:15.395
There are no incentives in place

0:17:15.419,0:17:19.155
once a drug is generic and off patent[br]and no longer exclusive

0:17:19.179,0:17:21.516
to encourage pharma companies[br]to develop them,

0:17:21.540,0:17:22.969
because they don't make money.

0:17:23.380,0:17:26.500
And that's not true for just ketamine.[br]That is true for all drugs.

0:17:27.579,0:17:33.236
Regardless, the idea itself[br]is completely novel in psychiatry,

0:17:33.260,0:17:37.156
to use drugs to prevent mental illness

0:17:37.180,0:17:38.540
as opposed to just treat it.

0:17:39.740,0:17:44.796
It is possible that 20, 50,[br]100 years from now,

0:17:44.820,0:17:48.916
we will look back now[br]at depression and PTSD

0:17:48.940,0:17:52.156
the way we look back[br]at tuberculosis sanitoriums

0:17:52.180,0:17:53.380
as a thing of the past.

0:17:54.180,0:17:59.420
This could be the beginning of the end[br]of the mental health epidemic.

0:18:00.380,0:18:03.580
But as a great scientist once said,

0:18:04.900,0:18:07.156
"Only a fool is sure of anything.

0:18:07.180,0:18:09.220
A wise man keeps on guessing."

0:18:11.044,0:18:12.284
Thank you, guys.

0:18:12.780,0:18:16.846
(Applause)