Imagine you woke up tomorrow to discover
that forty years had passed,
Rip Van Winkle style.
After the brief moment of excitement to see the future,
you realize half your life is gone and
you have to make peace with that.
For many of those with an unusual disease called
encephalitis lethargica, or EL,
that was basically what happened.
In the late 1960s and early 70s,
after years of almost a complete stupor,
they suddenly woke up.
While some had trouble understanding
that time had passed,
others revealed they were
mostly aware of every passing day,
they just hadn’t been able to move.
Pretty soon, though,
the same medication that had
allowed them to wake up
caused such debilitating side effects
that almost every patient had
to return to the way they were before.
The story of E.L.is a tragic one,
but it also says a lot about
the brain chemistry that translates will into action,
what happens when disease interferes,
and how even the most promising
drugs can unexpectedly backfire.
It all began around 1917,
when people began to suffer severe sleepiness,
delirium, problems moving their eyes and paralysis.
Over the next several years
there were about a million cases worldwide,
I’ll talk of a view that the disease
which people started calling”Sleeping Sickness”,
caused inflamation in your part of the brain
we now know it’s involved
in keeping you conscious.
But doctors couldn’t find an effective treatment
and the disease, which we now think it was a virus,
killed about a third of the people it infected.
When the flu epidemic started killing
tens of millions of people in 1918,
people cannot stop talking about EL as much.
But unfortunately, even among those who survived EL,
the story didn’t stop there.
After their initial recovery, sometimes years or even decades later,
many developed symptoms
similar to Parkinson’s disease.
In Parkinson’s some nerve tissues start to break down,
causing things like tremors,
stiffness, and slow movement.
But it generally develops in older people
and the patients who had EL weren’t necessarily old.
In some ways, these patients’
symptoms were also more extreme.
For example, they’d sometimes slow down
and completely stop moving,
holding whatever awkward positions they found themselves in,
even if someone else moved their body.
Eventually, a lot of them became catatonic or immobile.
Later on, some would describe the experience as a resistance
that would stop them from moving the way they wanted to.
Even weirder, they’d occasionally move
in response to some stimulus
like by catching a ball if you threw it to them.
Researchers knew that Parkinson came from the deterioration in the”substantia nigra”,
a part of the brainstem involved
in motivation and movement.
So doctors figured that
EL patients’ symptoms were connected to that part of the brain too.
But without any useful treatments,
patients in this state were mostly just left
to live in hospitals and mental institutions for decades.
At least until the late 1960s,
in the Bronx’s hospital where the now famous neurologist Oliver Sacks
who was just starting his career,
decided to try a newly invented drug called”L-DOPA”.
That’s when some of the patients suddenly woke up.
See those deteriorating neurons
in the brain were responsible for transmitting Dopamine,
a neurotransmitter involved in reward and motivation.
In other areas of the brain,
dopamine is associated with feelings of reward and pleasure,
but in the substantia nigra it seems to be associated
with the motivation to move at all.
You can’t just fix the problem
by taking straight up dopamine
because it can’t cross the blood-brain barrier.
But L-DOPA was a form of dopamine that could get into
the brain and stimulate the dopamine receptors there.
In 1967 this drug was found
to help people with Parkinson’s disease,
so Sacks thought it might help EL patients too.
And it worked!
Almost every patient experienced
some kind of miraculous awakening
and returned to health
at least at first.
One patient, identified only as Rose R.,
began telling stories of celebrities
like George Gershwin, all in perfect detail,
even though they’d happened more than 40 years earlier.
She also knew the dates of big events
that happened while she was catatonic
like Pearl Harbor or The Kennedy Assassination
but said”None of it felt real”.
Others like a patient named Leonard L.,
were eager just to leave the hospital,
which he called a”human zoo”,
to experience the outside world.
or in some cases just days,
almost everyone began to suffer
severe problems with the drug.
Some had hallucinations,
explosive and aggressive behavior
or sexual side effects.
On top of that,
the drug seemed to lose its effectiveness over time.
Sacks tried to find doses that would work
without such extreme side effects,
but for almost every patient,
there was just no middle ground.
Very few were able to continue treatment
beyond a couple of months,
and afterward, they went right back to they way they were
or got even worse.
And although some of the patients who could talk said
they were grateful to have
another taste of “full experience” again,
others said they felt newly robbed
of the life they almost got back.
The fact that the drug worked at all supported
what doctors thought was happening in those patients’ brains.
L-DOPA stimulated the “substantia nigra”,
compensating for the degraded neurons.
For the patients, it suddenly felt like the”resistance” was gone
when they wanted to do something they actually could.
But doctors didn’t expect the drug to backfire so badly
They hadn’t seen that response
with people with Parkinson’s desease,
although it did start to happen later on,
it just took longer.
There are probably several reasons
for the severe side effects in EL patients.
For one thing, these people had been suffering for decades,
so their neurons had degraded
more than in Parkinson’s patients,
who are usually diagnosed late in life.
Another problem was that L-DOPA couldn’t be targeted
to just the “substantia nigra”.
Eventually it overstimulated their reward system too,
leading to side effects like aggression,
impulse control and hyper-sexuality.
It’s also possible that byproducts
of dopamine are neurotoxic in high doses
and can cause hallucinations,
which would explain why these side effects
also happened in late-stage Parkinson’s patients.
There is a lot we still don’t know about all of this.
The cause of the original EL outbreak is a mystery:
it infected tons of people
and then almost completely disappeared.
And even though there have been only a handful of cases
since there’s no reason to think
the epidemic couldn’t happen again.
Still, if nothing else,
what happened with L-DOPA taught us a lot
about how our brains translate desires into actions.
When the process works,
we don’t even have to think about it,
but when it starts to break down,
fixing it takes a lot more
than just replacing what’s missing.
L-DOPA might have seemed like a miracle drug at first
but its effects on the brain were a double-edged sword,
and in the end it hurt more than it helped.
Thanks for watching this episode of SciShow Psych,
and thanks especially to our patrons
on Patreon who make this show possible.
If you’re interested in learning about
more of the history and science
that helps us understand our brains,
you can go to youtube.com/scishowpsych and subscribe.