In 2000, a company called ViroPharma
ran clinical trials of pleconaril,
a new pill designed to treat
the common cold.
In many patients, the pill helped.
But in 7 of them,
just a few days into the treatment,
researchers found mutated virus variants
that were almost completely resistant
to pleconaril.
Viruses are always mutating, but this one
mutated so quickly that it managed
to outmaneuver years of research
and development in just a few days.
If you didn't have an immune
system and caught a cold,
the infection would quickly spread
deep into your lungs.
Rampant viral replication would destroy
tissue there,
until your lungs couldn’t supply your body
with enough oxygen
and you’d asphyxiate.
Unfortunately, for millions of people
around the world who live
with a less-than-fully-functional
immune system
or who are on immunosuppressant drugs,
this is a real risk:
“minor” infections can turn serious
or even deadly.
But if you're fortunate enough to have
a fully functional immune system,
a cold will probably give you
a few relatively mild symptoms.
On average, adults catch more than
150 colds throughout their lives.
And despite the fact
that the symptoms are similar,
the cause could be different each time.
Common colds are caused by at least
8 different families of virus,
each of which can have
its own species and subtypes.
How can so many different viruses
cause the same illness?
Well, viruses can only invade
our bodies in a few ways:
one is to come in on a breath.
We have to breathe, so our immune system
sets up a bunch of frontline defenses
and these are actually what produce
many of the symptoms of a cold.
Your mucus-y, dripping nose is your immune
system trapping and flushing out virus.
Your fever is your immune system
raising your body temperature
to slow down viral replication.
And your inflamed, well, everything,
that’s your immune system
widening your blood vessels
and recruiting its white blood cell army
to help kill the virus.
So, if the common cold is caused
by many different viruses,
is a cure even possible?
Here’s one fact in our favor:
a single family of viruses causes
30 to 50% of all colds:
rhinovirus.
If we could eliminate all
rhinovirus infections,
we’d be a long way towards curing
the common cold.
There are two main ways to fight a virus:
vaccines and antiviral drugs.
The first attempt to create a rhinovirus
vaccine was a success—
but a short-lived one.
In 1957, William Price vaccinated 50 kids
with inactivated rhinovirus
and gave 50 others a placebo.
Soon afterwards, a rhinovirus outbreak
spread throughout the kids.
In the vaccinated group, only 3 got sick.
In the placebo group, 23 did—
almost 8 times as many.
And despite the small numbers,
this was promising:
the immune systems of vaccinated kids
were successfully
recognizing and responding to rhinovirus.
But later trials of the vaccine showed
no protection at all— none.
This wasn’t Price’s fault—
no one at the time knew that rhinovirus
had multiple subtypes.
Price’s vaccine,
for reasons we don’t fully understand,
didn't provide broad protection,
meaning it was only effective against one
or maybe a few subtypes of rhinovirus—
out of 169 subtypes and counting.
Sometimes, when we make a vaccine,
we get lucky.
The mRNA COVID vaccines, for example,
effectively protect us against severe
disease and death
across the original virus
and variants too.
But we have yet to create a broadly
protective vaccine against rhinovirus,
or any other virus that causes
the common cold.
Okay, what about antiviral drugs?
Viruses hijack human cellular machinery
to replicate and spread,
so it’s hard to make a molecule
that’s toxic to the virus
without also being toxic to the human.
And even if you manage to do that,
the virus could mutate
out of reach of the drug.
Viruses are slippery beasts.
We have, though, had some
incredible successes:
we eradicated smallpox thanks
to an effective vaccine,
the fact that it can’t hide
out in other species,
and its relatively low mutation rate.
HIV, on the other hand, mutates so quickly
that in an untreated individual,
every possible single-letter mutation
in the virus’s genetic code
could, in theory,
be produced in a single day.
Despite trying for decades,
we still don’t have a vaccine.
But we do have an effective
cocktail of HIV drugs
that the virus can’t easily mutate
away from.
Unfortunately,
we are stuck with colds for now.
But the last few decades have featured
some entirely game-changing
medical breakthroughs,
like mRNA vaccines and CRISPR.
CRISPR could be particularly promising
as an antiviral agent,
because it originally evolved in bacteria
as an immune defense against viruses.
In fact, early in the COVID-19 pandemic,
a research team showed that
a CRISPR system could degrade
coronavirus and influenza genomes
in our lung cells.
They called their system prophylactic
antiviral CRISPR in human cells.
Or, for short, PAC-MAN.