waking up in the middle of the night
because I’d heard screaming coming from
the hallway when I opened my bedroom
door what I saw was my dad pressing a
knife up against my mom’s throat
threatening to end her life if she my
sister and I didn’t leave the house that
night now eventually we got him to stop
and put the knife down and go to bed and
I don’t remember exactly what words were
exchanged that night but what I do
remember very clearly was that I could
tell my dad had been drinking that night
now I think this is a much more common
phenomenon than what most of you
realized I mean think about the last
time you’re at a party and you probably
saw someone there who had a little bit
too much to drink they might have gotten
a little loud a little aggressive or
maybe even violent well it turns out
that this behavior alcohol induced
aggression is a much more widespread
phenomenon than what most people realize
and in the US alone 40% of violent
offenders admit to being intoxicated
during the time of the crime which is so
substantial and this includes violent
offenses such as assault rape and even
murder and to have to deal with this 40%
of individuals that do get incarcerated
it cost the United States roughly
eighteen point six billion dollars a
year that’s billion with a B and just to
put that number into perspective that’s
roughly 2.6 billion dollars shy of
nasa’s yearly budget or it’s enough to
buy half of everybody in texas and
iphone x so if this is such a
devastating problem is anyone doing
anything to stop this I mean can we do
anything to stop this well as a
neuroscientist the way that I would
answer this question is by saying it’s
by asking what are the building blocks
of this behavior more specifically what
are the genes and neurons that are
contributing to making a person become
more violent after they consume alcohol
so it’s not really well known what
exactly causes alcohol induced
aggression
and we’re in a pretty tight spot here
because it’s a pretty tricky behavior to
study especially in humans I mean think
about the kind of experiment that you
have to do at its most basic level right
so say you got a hundred volunteers to
agree to be in this experiment what you
would do is give them a shot of whiskey
bottle of beer and then say okay so in
about five seconds there’s going to be
someone else who’s also had a drink he’s
gonna come through that door and he may
or may not want to try to kick your butt
so I don’t know about you guys but I
wouldn’t really want to volunteer for
that especially because I don’t really
have any upper-body strength but this is
also highlighting a fact that there’s
very complicated sort of ethical
implications that are involved with
doing human research where humans are
acting aggressively towards each other
and not only that even if we could get
the study funded what would the results
look like well humans are extremely
diverse they’re diverse in their
drinking habits they’re diverse in their
lifestyles and they’re also diverse in
their genetic makeup and this is also
underscored by the fact that not
everybody in the population becomes
violent after consuming alcohol some
people in fact use alcohol as an excuse
to become violent and there’s also those
that don’t really need alcohol to be
aggressive and so if this is such a
tricky behavior to understand in humans
and such a devastating behavior that
affects all of us is there anything that
we can use to study this well what I’m
going to propose is we use the common
fruit fly or Drosophila melanogaster and
some of you guys might be thinking oh
god this girl’s going to talk about
flies well in the next few slides I will
have hopefully convinced you of why I
think this is a good model organism for
studying this behavior so some of you
might be also thinking wait a second do
fruit flies even get drunk so I’m about
to show you a video and what you’re
looking at right here is a fly just kind
of putzing around in his vial and at the
top you see is straw that’s delivering
alcohol vapor into the vial and after
seven minutes in that alcohol vapor what
you can see is that the flies moving
around a lot
more sluggishly he’s losing postural
control it’s kind of stumbling about
still cleaning himself and after five
more minutes inside of that alcohol
vapor what you also see is he zooming
around even slower until he falls back
down and he can’t get back up so this
looks pretty familiar right I mean kind
of sounds like us and so basic answer is
yes
flies can get drunk well not only that
but flies also share 75% of
disease-causing genes with humans which
is very substantial and it tells us if
we study something in flies we can
likely translate this result into humans
and flies also have a lot of readily
available transgenic lines that we can
use flies also have a very short
lifespan which means we can do a lot
more experiments in a shorter period of
time
and finally flies also share a natural
relationship with alcohol where you’ve
probably seen that a bunch of flies just
kind of aggregated on like a patch of
rotting fruit well that piece of rotting
fruit has ethanol on it or alcohol and
what that means is that flies have
evolved a lot of shared alcohol
behaviors for instance they can acquire
tolerance to alcohol they can also show
signs and symptoms of withdrawal and
they can also seek alcohol despite
negative consequence so going back to
the original question can we use flies
as a model to look at alcohol induced
aggression well it turns out that people
have been studying fly aggression for a
very long time and especially in the
past decade it’s been studied quite
extensively and the way that’s been
classically modeled is by looking at
this fly aggression chamber and so what
you see here are two male flies just
kind of duking it out with each other
and on the centre you see a golden ish
kind of blob well that’s fly food and on
top of the fly food you see a
decapitated female and she’s decapitated
because we don’t want her to move from
the food patch and she’s there because
she brings all the boys to the yard okay
and so this video might be a little bit
too fast for the untrained eye so I’m
just going to show you one quick move
that’s a pretty robust to move that fly
is often engage in called the lunge and
so you can see in here the lunge is in
slow motion the fly is rearing up on its
hind legs and just slamming down
on the unsuspecting opponent and it can
be pretty devastating if you’re on the
receiving end of the lunge if you’re a
fly alright so what our lab did was we
took this very classical model of
looking at fly aggression and we asked
ourselves do flies become more
aggressive after consuming alcohol and
the results were pretty surprising so on
the left hand side what you’re looking
at is the video of two super flies
fighting in that same kind of aggression
chamber and so you can see that the
fight is very short-lived and there’s a
very clear winner and loser and the
winner is the guy that stays on the feed
patch so when we take a look at the
intoxicated flies what we see is
something entirely different and you can
see that both of these flies are
fighting on that same food patch except
basically not any of them are letting up
there is no clear winner or loser at
this point and they’re just really going
at it with each other and so I think we
can all agree that there’s obviously a
difference between how these sober flies
fight and how these intoxicated flies
fight so we we took a look at the data
by hand analyzing all of these videos
and it was probably on the order of like
200 hours of videos that we all had to
analyze and what we found was something
quite striking we found that the
intoxicated fly spent a greater
significantly greater amount of time
fighting than the sober flies did need
right
so okay why should we care that a couple
of drunk flies are getting more
aggressive with each other right what
does this mean for us humans right come
on what can we get out of this well
going back to the original problem that
it’s very difficult for us to be able to
study this behavior in humans because of
the methodological ethical and diverse
complications well why can’t we use
fruit flies as a model organism and it’s
especially relevant because humans have
so many genes humans have 20,000 protein
coding genes that’s a lot of genes well
not all of them are going to be involved
in regulating alcohol induced aggression
in fact only a very small subset of them
so how can we understand what is
relevant what does contribute to this
behavior well I’m going to take you
through very common strategy called a
forward genetic screen and the forward
genetic screen will allow us to identify
these gene targets extend these results
from flies to rodent models such as mice
and rats and then eventually extend
these results into humans as well so
first what you would have to do in a
forward genetic screen and flies is you
take a collection of mutants and each of
these mutants has a single unique
mutation in a gene such as a dopamine
receptor an actin binding protein or a
transcription factor and that’s okay if
you guys don’t know what that is and so
what you do is you test all of these
mutants for that behavior to look to see
whether or not they can acquire alcohol
induced aggression and more specifically
what you’re looking at is the animals
that didn’t acquire alcohol and
discretion because what that means is
the gene that they have mutation and
probably affects this behavior and so we
would take these flies and look at what
mutations they have and eventually pick
out the same kinds of mutations and in
rats and mice as well and then we would
perform the same set of experiments in
rats and mice and eventually be able to
pinpoint in the human genome which genes
are of interest to us okay so you’re
probably thinking this girl’s talking a
lot about genes right well genes are
super important because they could some
of them code for proteins and what we
can do is develop drugs against these
proteins to either enhance or inhibit
their activity effectively changing the
behavior that they’re involved with as
well
and so what if we could find these genes
and develop a drug against them well
what we would be able to do is make this
drug give it to someone and whereas they
would normally become a violent drunk
because they took these pills they would
just be a happy drunk right and so some
of you might be thinking well can’t we
just get these guys to stop drinking
well it turns out that this is a much
more difficult problem to solve and I
think the statistic perfectly highlights
how difficult it is to solve where 90%
of alcoholics relapse within the first
four years of treatment I mean that’s
pretty bad right and this includes
treatments such as drug therapies like
naltrexone or non direct therapies like
Alcoholics Anonymous or counseling so
it’s a very difficult problem to solve
and at the root of this disease is
alcoholism but one of the major symptoms
of this disease is alcohol induced
violence so it probably would just be
good enough to find a way to treat a
symptom of this disease to understand
how we can stop it and save all those
future victims of alcohol induced
violence and save the United States
there’s billions and billions of dollars
and prevent those people from even being
incarcerated in the first place and
ideally what would happen is this drug
would be available to everybody your mom
your sister your fraternity brother and
so you could take this drug preemptively
even if you don’t necessarily have a
history of alcoholism either and so this
can only really be possible within our
lifetimes if we move forward with this
form of genetic screen by performing
these experiments in flies and so what I
want to end my talk with is by saying
that it’s not always the most obvious
strategy that gets you the correct
answers sometimes in fact the most
obvious strategies fail and then that’s
when you have to take the unconventional
route the creative one to try to
understand the route of this behavior
and so what I argue is that if we can
unplanned fly violence we can somehow
understand how to end human alcohol induced violence as well thank you