[ Clock ticking ]
-If you were born in 1900,
you could expect to live on average just 32 years.
Today, global life expectancy is more than twice that.
It's one of the greatest achievements in human history.
♪
-This is the story of the ideas that have in the space of
just a century or two changed what it is to be us
by transforming the kind of lives we might live --
no longer short and under the shadow of disease,
but healthy and long.
I'm David Olusoga, a historian.
I have to say, it does look like the sort of laboratory
you see in the "Frankenstein" movies.
-And I'm science writer Steven Johnson.
-The average Black American lives
three and a half years less than the average American.
-That to me is just really shocking.
-We're investigating the forgotten heroes
of global health --
people whose life saving discoveries have tamed
some of the world's most deadly diseases.
-We were at a very exciting era of biochemistry
and it was only a question of time
before we would hit the gold.
-One of their biggest innovations was medical drugs.
Today, as the world grapples with another deadly pandemic,
we reveal how drugs became one of the most powerful tools
we have in the fight for extra life.
♪
-I'm in the U.S., and David is in the U.K.
In the current climate,
this is the only way we could meet.
David. -Steven, how are you doing?
-Good. -Good to see you.
-Good to see you, too.
-This is the new normal -- life in 2021.
-Couple of pals hanging out, just having a little chat.
[ Laughter ]
You want to kick it off, David?
-I take a drug because of a thyroid disease
every day of my life.
If I don't take that drug, I'll die.
If I go and look at the census records for people
with the same condition 100 years ago,
their life expectancy, their outcomes are appalling.
It killed people.
-The repertoire of magic bullets,
of life-saving medicines
that have been developed over the past few decades
is really one of the most consequential developments
of modern life.
I mean, in the United States,
compared to 1900, people live about 30 years longer.
We expect that our children will live into adulthood,
that will get to meet our grandchildren.
-We do take it for granted. I take it for granted.
I like to think of my work as an historian that I'm somebody
who is really cognizant of the centrality of the story
of disease and medicine.
But in making this program,
I've realized that I've still not grasped
the scale of how medicine has been
just one of the greatest revolutions in human history.
-I've always been fascinated with this --
this story of rising life expectancy.
One of the things that was most surprising to me
is the invention of actual functional medical drugs
arrives on the historical stage surprisingly late.
We invented, you know, automobiles and planes
and radio and television.
But medicine was actually lagging behind
those more conventional
kind of markers of technological progress.
-I think that revolution had given us a sense of impunity,
that there would always be a medicine.
And despite all the tragedies we've been through
and the terrible cost of this pandemic,
maybe there is a positive in this
that we realize we desperately need
to recognize the incredible revolution
and the heroes behind it that have given us all of this,
given this this extra life.
♪
-At the beginning of the last century, a medical revolution
began that would lead to safe and effective drugs for all,
causing life expectancy here in the U.S. to rocket upwards.
We take it for granted today that when we go to the pharmacy
to treat a bee sting or an eye infection
or a headache, the remedy will work.
But even in the early 20th century,
taking medicines was gambling with your life.
-What's important to remember here is that throughout history
and until relatively recently, many medical treatments were,
to put it kindly,
a bit questionable.
-Duffield's Concentrated Medicinal Fluid Extracts,
which contains belladonna from the deadly plant nightshade,
arsenic...
and mercury --
all of which are deadly toxins.
-It was all rather unscientific and until recently there was
no system to determine if medications were safe
or if they had any positive effects.
-1900, an era of quack cures and bogus remedies
and life expectancy in the United States
was just...
49 years.
But then 34 years after this catalog was published,
there would come a discovery
that would change drugs and medicine forever.
Penicillin.
The discovery of penicillin
was a catalyst for dramatic increases
in life expectancy across the whole world.
♪
The numbers are staggering.
In the United States before antibiotics,
30% of all deaths were related to infections.
You could get a simple scrape, just a minor cut,
and an infection would develop and you could be dead in a week.
The magnitude of mortality
caused by those kinds of infections was just terrifying.
-We've forgotten the scale of the horror because antibiotics,
which is such an incredible magic bullet
that made all of that suddenly brush that whole world away
that our ancestors just took for granted.
And I just mean our grandparents' generation.
I don't mean back hundreds of years.
-What I love about the story is that it is truly
a story of international collaboration,
a broad network of people with different talents
coming together to solve this truly life-transforming problem.
-But that incredible story of all of these people
coming together with these specialist skills,
that's not what I learned at school.
All I was taught about the breakthrough
that was penicillin was one moment and one guy.
♪
Everybody has heard the name Alexander Fleming.
He's somebody we all study at school.
What he was fascinated by was the hidden micro world
that lies beyond our vision.
He became obsessed with microbes, bacteria,
and he studied them relentlessly.
During the First World War, Fleming had served
in the Royal Army Medical Corps,
and in France, in the hospitals behind the Western Front,
he had seen at first hand the consequences
of bacterial infection --
septicemia...
gangrene.
Of the millions of soldiers who died in World War One,
it's estimated that around a third were not killed
by shellfire or machine guns, but by disease.
Fleming understood as well as anybody possibly could
the desperate, urgent need for new treatments
to combat bacterial infection.
London 1928 -- Fleming is working in his lab.
♪
The story of Alexander Fleming
gives hope to anyone with an untidy desk
because his untidiness
was actually critical to what happened.
In the summer of 1928,
Fleming left a petri dish contaminated
with the bacteria staphylococcus on his desk uncovered.
He then went off on a vacation,
but he left...
one of the windows of his laboratory wide open.
♪
A microscopic fungal spore is blown in through a window,
perhaps escaped from a downstairs laboratory.
Pivoting and floating on a sea of turbulent air,
it sinks down onto
one of Fleming's uncovered petri dishes.
♪
On the 3rd of September 1928, Alexander Fleming
returns to his laboratory and to his untidy desk.
This is the groundbreaking moment...
...because Fleming starts to look through
all the petri dishes he left on his desk,
and something catches his eye.
♪
On one of the dishes, he sees that a mold has grown.
And around the mold, there was no staphylococcus bacteria.
♪
What Fleming concludes
is that the bacteria has been killed by something produced
by the mold,
and so this naturally occurring mold,
something that's literally in the air,
could be a bacteria killer.
This was a discovery of enormous significance,
one that was eventually to win Alexander Fleming
the Nobel Prize.
-And I think a lot of people assume when they hear
the Fleming story
that after Fleming makes this accidental discovery,
within a couple of years penicillin is available
as a medicine changing the world.
But in fact, the development of the drug itself
effectively gets paused for a decade
after Fleming's accidental discovery.
-We so much want to believe
and that sort of Hollywood story of accidental discovery,
kind of addicted to that sort of narrative.
You know, Fleming's amazing guy,
and we shouldn't take it away from him.
He understood he discovered something significant,
but he didn't have all the skills needed.
He wasn't a chemist.
He couldn't have taken things much further.
And I think more importantly, he didn't have the network
needed to transform an accident in a petri dish
to the drug that changed the world.
-You need to have networks of people with different skills,
different fields of expertise
coming together to solve a problem.
And in fact, that's exactly what happens
in the history of penicillin.
♪
-So, let's pick up the story here in Oxford in 1938.
Just two decades after a conflict
in which millions had died of bacterial infection,
Europe is teetering on the edge of another war.
♪
Howard Florey, a very driven
and very talented Australian scientist,
is running an institute of pathology.
He and his team are studying the pathogens
that cause disease in humans.
They are searching for substances
that might kill bacteria.
In an age before computers, this means poring over reams
of scientific journals in dusty libraries.
One day in 1938,
a member of Florey's team uncovers a decade-old paper.
When Florey reads Alexander Fleming's now-obscure paper,
and we think that happens in this office
that was then his office,
he doesn't necessarily recognize
the enormous potential of penicillin mold.
He wasn't thinking that he'd stumbled upon the drug
that was to change history.
Rather, he just found what he was reading interesting.
Now, Florey had hired two brilliant biochemists,
Ernst Chain and Norman Heatley.
They were a perfect team -- three people in the right place
at the right time with complementary skills.
And under the firm direction of Florey,
they began their investigations.
But the first task was to hunt down the exact same mold
that Fleming had stumbled across all those years earlier --
the difficulty being that there are tens of thousands
of known species of mold.
♪
In an amazing stroke of luck,
the team find some suitable mold growing
in a laboratory in the building.
Now, this is really fortuitous
because otherwise it might have taken them months
to source this specific type of mold.
But this is where their luck runs out.
♪
So, they'd found some mold in the laboratory.
What's the next step?
-First of all, they had to grow the mold up in great volumes
and great amounts, and that was no easy feat.
-And the penicillin is not the mold itself.
It is something produced by the mold.
-Yeah, that's absolutely right.
You can grow the fungus up,
but then you have to get the mold to produce the drug
and then you have to purify the drug.
-Producing and refining the new drug was a complicated process
of trial and error -- a multi-staged operation,
each stage having to be tinkered with and refined
until it was as efficient as possible.
After months of intense research,
the team managed to produce a tiny amount
with which to begin experimentation.
-And the critical experiment was to see
whether it could cure infection in vivo.
In other words, an infected mouse.
Early in 1940,
they gave eight animals a lethal injection,
the bacterium called streptococcus,
and four those animals received penicillin treatment.
♪
-So, all eight mice have been injected
with a lethal dose of bacteria.
Four have been given penicillin
and four haven't, so they're the control animal.
-Absolutely. Yes.
-So what was the result of that experiment?
-Within a few hours,
the control animals who didn't receive penicillin
started showing signs of systemic infection.
And within about 15 hours, all of them had died.
But all the animals treated with penicillin were perfectly happy.
Alongside Fleming and the famous story of the petri dish,
this is the other eureka moment in the story of penicillin,
because if you imagine being part of the Oxford team
when seeing those results -- half of the poor mice have died,
but half of them have survived --
and what that strongly suggests
is that this does fight bacterial infection.
But where are they really?
All they've done is they've proved principle.
They're nowhere near having a workable drug.
-What's completely up for grabs at this point
is the crucial question
of whether they can make enough of this stuff
to make a difference in humans.
Florey remarks at some point
that he would need 3,000 times as much penicillin
as they currently have to test it on just a single person.
And so what you get into at this point
is a very different kind of challenge, right?
This is about scaling it up and mass producing it.
-Let's remember the date. This is May 1940.
This is one of the darkest moments in the Second World War.
There are soldiers dying on operating theaters
from infections right at that moment.
So the potential and the journey they have still to go
are just both enormous.
Severely lacking in resources, Florey, Chain, and Heatley
tried to scale up production
with whatever they had to hand.
Is that a milk churn? -It's a milk churn
because they didn't have any other large volume receptacles
and it's being poured into a cast iron bathtub there.
-Bathtub.
-This is remarkably... low tech.
-It is. Very simple.
-All this equipment and material
is suspended on bits of wood
which have been hammered and screw together.
-I have to say, it does look like the sort of laboratory
you see in a "Frankenstein" movie.
-[ Chuckles ]
-So, this is what it's all about.
-This is what it's all about.
-And this is still not anywhere near the scale you're going to
need to have. Clearly, if you're going to
produce a drug which would be given worldwide,
then you need to do this on a huge scale.
-After seven months, the Oxford team now
have a few precious grams of penicillin,
enough to test on a human being.
Rural Oxfordshire --
a 43-year-old police constable,
Albert Alexander, is tending to his roses.
Bacteria surround us in the world.
We just can't see them.
Beautiful roses
and their thorns are covered
with millions of potentially deadly bacteria.
A rose thorn slices across his face.
Bacteria make their way into the wound.
And over the next few days,
he begins to get sick.
-Sometimes the first symptom is a high-temperature fever,
because a high temperature
generally inhibits the growth of bacteria.
-So it's a defense mechanism when we have a high temperature.
-Absolutely. This high temperature
is used by our body to kill the pathogen.
-What else can the body do at that moment?
-Then white blood cells are recruited
in the area of the infection,
which is basically to the production of pus.
It's a thick fluid that is composed
by that white blood cells and bacteria.
-So, the person who's sick, do they
stay conscious through this
or do they start losing consciousness?
-Generally, they will lose consciousness.
Oxygen in the blood will decrease.
Some organs might start to fail.
And this will highly likely
lead to death.
-For four months,
bacteria rampage through Albert Alexander's body.
He's lost one of his eyes to the infection
and, too weak to move,
he is near death.
February 1941 -- the new test compound,
penicillin, is administered to Alexander.
Nearly two years of the Oxford team's work rests
on this moment.
♪
[ Heart beating ]
♪
Within hours, his temperature falls, his appetite returns --
the wonder drug is beating the rioting bacteria.
But the penicillin is running out.
Even after being reconnected from Alexander's urine,
Florey, Chain, and Heatley simply cannot produce enough
and he dies in March 1941.
-I've always been haunted by that story of Albert Alexander.
I mean, it just is such a representative example
of what life was like before the invention of penicillin.
-It's one of those stories that shows the difference between
sort of movies and reality, because if this was a movie,
the first person treated with antibiotics
would be the first person saved.
But it doesn't work like that.
But they have shown that it was effective,
and now they face this almost impossible task of trying
to produce enough to treat more people.
And they're in the middle of a war.
These are scientists cycling
back and forth from their laboratory
to the hospital where poor Albert Alexander is dying.
If this was today, they would have huge companies
and governments pouring millions of dollars into their efforts.
They'd be doing huge clinical trials.
-And that's the question for us today, right?
Particularly in the middle of a pandemic
is given all the resources and expertise
that we have now that Florey and his team didn't have,
can we accelerate that timetable?
-Today, scientists are finding new ways to fast track drugs
to patients.
At Oxford University,
one of the leading government advisers on COVID-19,
Professor Horby, helped to establish the Recovery Trial.
It's one of the fastest drug trials ever set up,
and initially it looked at whether already available drugs
could be repurposed for the pandemic.
I think people imagine when you say the phrase
"clinical trial" is that you're trying a new drug.
Now, that's not what the Recovery Trial was doing.
-We started with existing drugs that were in
the cupboard licensed for other indications.
If these drugs are shown to work in COVID,
then you can just get them out the pharmacy and out
of the pharmacy cupboard straight away.
-So, if your trial hits upon a preexisting drug
that has some efficacy with COVID,
then it's already on people's shelves.
It's literally already in the factories
and we know how to make it. -Yeah, that's right.
And you can -- the doctors just can reach for that new drug
and they can do that pretty much
in any hospital around the world.
So, we would have it benefit not just for high-income countries,
but countries everywhere.
-How did you select these preexisting drugs?
-Initially it was a part of a government committee
that I sit on where we got some experts together
and we went through the list
and one of them is a steroid, dexamethasone.
-This anti-inflammatory steroid used for allergies and asthma
turned out to have a surprising effect on COVID-19 patients.
-Dexamethasone reduces mortality quite significantly,
particularly in patients on a ventilator,
so severely on patients in intensive care,
which for us was just jaw-dropping
but also fantastic news because it's an incredibly cheap drug
that is available in every country in the world.
And literally people could get it off the shelf
the same day that we announced the results.
-So, there are people who have survived COVID
who wouldn't have done had this trial
not identified that particular steroid
as something that could help them?
-Their estimate is that from the date
we announced the result until the end of 2020,
we would have saved around 12,000 lives in the U.K.
And if you extrapolate that globally,
it could have saved half a million lives.
-Here she comes.
A big round of applause, everybody.
[ Cheers and applause ]
-By testing off-the-shelf drugs
available via existing supply chains,
Horby and his team found treatments for COVID-19
within just months.
Back in 1941, with the war intensifying,
Florey and his team
were still nowhere near a workable mass market drug.
It had already taken over a decade
to progress the promising find into enough of the drug
to trial on a single patient.
Penicillin-producing mold was such medical gold dust
that staff took some of the spores
and they smeared them down the insides of their coats
so that in the event of a German invasion,
they could escape and they could grow fresh cultures abroad.
♪
But despite throwing everything they had at the problem,
in this volatile time,
the team simply could not make enough penicillin.
Florey grew increasingly frustrated.
He knew that he was on to something,
but the British government didn't have the resources
to offer help, and the pharmaceutical companies,
they were working flat out for the war effort.
To them, working on penicillin just didn't seem
important enough to commit scarce resources.
And so to Florey,
the United States began to look like a safe haven
where he and his team could continue with their research.
July in 1941, in a scene straight out of "Casablanca,"
Florey and Heatley
pack much of the world's supply of penicillin
into a briefcase and take a Pan Am Clipper to New York.
They tell U.S. Immigration
they're on important medical business
for the war effort.
It's at this point in the story that a feature
of Howard Florey's personality becomes central
because he brings people together.
He meets people and creates this sort of complicated network
of specialisms and skills and convinces people,
including the government, that this is a project
that they absolutely have to support.
-And that ultimate project is really an incredibly powerful
story of scientific discovery and global collaboration.
And yet the top secret military project during World War Two
that we always hear about is the Manhattan Project,
the development of the atomic bomb.
But to me, the penicillin story, it deserves far more attention
because it's actually the story about inventing
a life-saving drug
and not a weapon of mass destruction.
-Even with all of those resources
and all of those experts and industrialists
that Florey brings together, it still takes them years
to get from Florey's discovery
to a mass-produced penicillin drug.
-The American company Pfizer, up until then known
for making the citric acid in sodas,
decides to take on the challenge.
♪
The problem was to grow the Penicillium mold
required nutrients and oxygen from the air,
but that could only happen here at this thin film
at the surface, a relatively tiny area.
So the big idea was to blow air through a nutrient-rich broth.
♪
So instead of just growing the antibiotic-producing mold
at the surface,
they hope to grow it through the entire broth,
a so-called submerged culture.
That, at least, was the plan.
Executing it on an industrial scale was another matter.
They convert an old Brooklyn ice factory,
scrounging an industrial boiler from Indiana
and an old elevator from Long Island.
Engineers installed 14 giant fermentation tanks,
each with a 7,500-gallon capacity.
The vats were filled with a sugar-rich corn steep liquor
and a little bit of penicillin mold.
The air was turned on.
Nobody knew the right amount of oxygen to put into the system.
Nobody knew what was going to happen.
♪
But the results were spectacular.
The yield was five times the highest estimate.
A few months later, when allied troops landed at D-Day,
they had penicillin in their packs --
penicillin made in this room.
It was the dawn of the antibiotic age.
What had been incurable was now curable.
What could have been fatal was now just a minor illness.
-One of the immediate effects of the arrival of penicillin
was that it takes diseases
that had destroyed millions of lives
and it transforms them overnight to being treatable conditions.
And that's -- that's miraculous.
-Diseases like tuberculosis and syphilis that basically
antibiotics kind of took off the table as a threat.
And all of that had a massive impact
on life expectancy in the antibiotic era.
Global life expectancy was extended by two decades.
-And there's another effect that it's easy to overlook,
which is that it doesn't just gift us with these extra years.
It opens up the possibilities of elective surgery,
and people who wouldn't have dreamed
of going under the surgeon's knife in an age
when infection was, you know,
sometimes killing a quarter of people on the operating table
could suddenly contemplate these life-improving operations.
-And it opened the door
for the next generation of medical drugs.
♪
The discovery that penicillin could kill bacteria ranks
up there with splitting the atom,
with the moon landing -- a giant leap forward
in human progress and life expectancy.
But there were other wonder drugs to be discovered
that could attack other great pathogens
that had plagued humanity for millennia.
We've all been living through a new threat to our lives,
this time caused by a virus.
During the coronavirus pandemic,
life expectancy in the U.S. fell by one year.
Viruses are much smaller than bacteria --
100 million can fit on a pinhead --
and antibiotics can't attack them.
Slipping inside a host cell,
they reproduce by hijacking the cells own machinery,
and most viruses eventually destroy their host cell.
♪
Influenza, Ebola, and COVID-19 are all caused by viruses,
notoriously hard to study and even harder to treat.
But by the 1970s, a pioneer called Gertrude Elion
began using new scientific methods
to custom build effective antiviral drugs.
Gertrude Elion was born in New York City in 1918
to immigrant parents.
She lost her grandfather to cancer
and her fiancé
to a bacterial infection of the heart.
-I had determined when I was 15 years old
that I was going to be a scientist.
I entered college at that age and I was going to be a chemist.
And what's more, I was going to find a cure for cancer.
In 1944, Elion joined
the pharmaceutical company Burroughs Wellcome.
-We were at a very exciting era of biochemistry.
We were finding out things so rapidly
and things were progressing with such excitement.
And it was only a question of time
before we would really hit the gold.
-She started working with Dr. George Hitchings.
Together, they were amazingly prolific.
In terms of drug development,
they were a dream team.
So how did they do it?
Thank you so much.
Alright, this is my molecule building kit.
So, we're gonna need five nitrogen.
Hitchings and Elion realized
that through careful study of how our cells interact
with compounds and pathogens like viruses,
they could build highly efficient,
targeted drugs to do specific tasks.
So, first we connect these three nitrogens...
This was a revelation --
building synthetic drugs atom
by atom from the ground up.
In the 1970s, Elion and her team built a new drug
that would revolutionize our approach to tackling viruses.
Picture this -- Atlanta 1978.
Trudy Elion is at a conference
filled with expectant scientists.
It's the creme de la creme of drug makers and creators
from around the world.
She presents a paper on a miraculous new compound.
It's the first highly selective antiviral drug
targeting the herpes virus.
It's called acyclovir.
It's unlike anything the world has ever seen before.
Thank you. Thank you so much.
Was there a sudden burst of applause?
Did the audience realize
the magnitude of what they were seeing?
I like to think so because this speech marked a milestone
in the history of human health.
And like the discovery of penicillin 50 years before,
it ushered in a new age of medicine,
this time targeting viruses.
[ Applause ]
Together, the work of Elion and Hitchings paved the way
for designer drugs,
helping to treat a huge range of illnesses from leukemia
to malaria to arthritis.
The techniques Trudy Elion developed over her career
provided a foundation for many other researchers.
-Unfortunately, I never got to meet her,
but I think her work certainly is inspirational.
Fleming gets the credit for,
you know, discovering penicillin by serendipity.
But these folks did it by rational design.
-Professor David Ho would use antiviral drugs
made using rational design
to solve one of the great medical mysteries
and save millions of lives.
-1980, when I was just finishing up my medical training,
when I had a patient who presented to the hospital
with a multitude of infections.
He was treated, went home for a while
and then shortly after died of other infections.
He was a young gay man, and we did not know
how to explain his case.
And a few weeks later,
a similar young man came to the hospital again,
and so we were staring
at a potentially infectious lethal disease,
and that is quite scary.
-Ho was witnessing the start of the AIDS epidemic
sweeping America.
The new virus was fatal
to almost every person it infected.
-San Francisco, Los Angeles and New York
report the highest number of AIDS cases.
But all across the country, the disease is on the rise
-At the Center for Disease Control in Atlanta,
where 400 cases have been reported,
a special task force has now been set up --
a disease experts are now calling a national epidemic.
-It's so interesting to look back at that period
from the perspective of the current pandemic,
because HIV was a death sentence.
I mean, the infection
mortality rate was very close to 100%.
-You and I must have been both kids
in the '80s when HIV emerged.
Even at that age, I imagine that science and doctors
had an answer to every disease
and it seemed the end of diseases --
not the emergence of a new one.
So it was absolutely terrifying.
-And it took years for them
to ultimately identify that HIV virus.
And you compare that to COVID-19,
and within weeks of this, the virus is identified
and its genome is sequenced.
And so the pace of discovery
and understanding is so much faster today
than it was back in the early '80s.
-I think it's important to remember that, you know,
medical science got there in a way
because now there's all sorts of antiviral treatments for HIV.
But it's sometimes disturbing the way people talk about it,
as if it's in the rearview mirror,
as if it's something of the past.
HIV is still very, very much with us.
And in the time since it's emerged,
it's claimed over 40 million lives.
-First recognized in 1981,
the HIV virus swiftly spread around the world.
The race was on for new,
more effective antivirals to tackle it.
-In the early '90s, we were studying a new class of drugs
that attack HIV called protease inhibitors.
-Protease inhibitors are carefully designed drugs
that stop the virus replicating in our cells.
-When you intervene with a drug like the protease inhibitor,
we essentially shut off production.
-But the real revelation came when Ho applied math
to what they were witnessing.
-We were able to come to a major conclusion
about the dynamics of HIV replication.
-The virus was making billions of copies of itself every day.
Crucially, in doing so,
it was also making millions of mutations.
-We discerned that the virus was making so many mutations
and it was a given
that the virus will quickly escape our drugs
if we administer them one at a time.
But then we could do the math further to show
that if you were to administer three at a time
or four at a time,
it became exceedingly difficult for HIV to escape.
The first phase of the AIDS pandemic really ended
with the combination antiretroviral therapy.
-Now Professor Ho and his team
are using their extensive expertise,
tackling new viruses on SARS-CoV-2.
Can you tell me about the sense of urgency
in this lab right now?
-When China shut down Wuhan,
we knew this was going to be a big matter,
and very soon the first case was identified in New York,
here at our hospital,
and our team mobilized.
They've been, you know, working 14-, 15-hour days
and working through the weekend.
That's the level of dedication.
-Is there something about SARS-CoV-2
in the way that it mutates?
-SARS-CoV-2 does mutate, but its mutation rate
as compared to HIV seems to be slower.
So overall, the mutational challenge posed by SARS-CoV-2
is probably not as great as that of HIV.
-So less of a need for a cocktail.
-Less of a need, but there may still be a need.
You may not need three drugs, but you might need two.
-Do you think we're ever heading towards a future
where there's just one pill that can combat any emerging virus?
-That would be really nice to have one pill
that takes care of viruses.
I think maybe -- maybe a long time from now we could do that.
But in the short term, what we could do
is perhaps one pill or one antibody
that could take care of a pretty large family of coronaviruses.
But it's going to be a continual struggle.
As we make progress,
the pathogens have an enormous capability to evolve and adapt
and escape from our vaccines, our antibodies, our drugs.
-Mutant strains of SARS-CoV-2 to continue to appear.
Both viruses and bacteria are ever-moving targets.
Were caught in a game of cat and mouse,
and already we're seeing our current deck of antibiotics
begin to fail.
-In the story of antibiotics,
we've also become victims of our own success
because the great specter hanging over all of this
and hanging over all of us is antibiotic resistance.
-We think that something like 700,000 people a year are dying
because of antimicrobial resistance,
because of these new superbugs.
And that number is projected to reach as high
as 10 million a year by 2050 if we don't do something about it.
-The idea of returning to the world before antibiotics,
a world where if you cut yourself
on a rose in the garden,
you could be dead in weeks,
or a world where surgeries become impossible
because of infections in the operating theater,
the idea of returning to that world,
the world of our ancestors,
it's just -- it's too horrific to imagine.
-I think there's a tendency to assume that the progress
we've made over the last 100 years or so
will just continue on
because enlightenment science is doing its thing.
But these are battles that have to be kind of continually fought
and new threats inevitably emerge.
COVID-19 is only the latest reminder of that.
And so in a way, what we need now is --
is not just the innovation of a new pill, a new medicine,
as important as that would be,
but we may need a different kind of innovation,
which is a new kind of institution
capable of developing, testing and distributing
at scale, at a global scale, a new class of antibiotics
that can fight off these superbugs.
In early 2019,
a cross-disciplinary team of scientists at MIT
came together to tackle antibiotic resistance.
-What drives me to go to work every day?
The prospect of saving people's lives, full stop.
To contribute long-lasting and meaningful solutions
to the antibiotic resistance crisis.
We discovered antibiotics so quickly and got so good at it
that we stopped thinking about it as a problem,
and that caught up with us in a big way.
You know, the evolution of resistance
in bacterial pathogens didn't stop, even though we did.
-The last time we successfully introduced
a new class of antibiotic drugs was over 30 years ago.
-We really need to ramp up efforts
both within the academic world and the commercial world
to replenish our antibiotic arsenal.
-But finding new antibiotics
is not always cost-effective for drug companies.
-Discovering drugs is hard. -It's time-intensive.
It's laborious.
-So if you're a drug company, I can make, you know,
an anticoagulant that someone's going to take every day
for the rest of their life, perhaps,
or I can develop an antibiotic that might be used for a week.
How do you get your money back?
We can't rely on the free market economy
to encourage antibiotic development.
So it has to be treated, in my opinion,
more like a public health problem, much like COVID-19.
-Jim designs drugs,
and as a biochemist, John test new antibiotics in the lab.
But to help them find new antibiotics faster
and cheaper than ever before,
they're working with a specialist
in artificial intelligence.
-I believe that we are just in the very beginning
of seeing the advantages of A.I. in drug discovery.
-Artificial intelligence has permeated
every aspect of our life.
It tells us what we might want to watch
and what we might want to buy,
and it helps self-driving cars not crash into each other,
so it's just a natural progression
that A.I. was going to
increasingly influence drug discovery
and health care in general.
-Regina's expertise in A.I.
enabled the team to open the door
to a whole new way of discovering drugs.
-So the question is, can we design molecule
which would be hard for pathogen to adapt to?
And when we started it, we really didn't
even have a budget.
It was like, just try
and see how far you can push the boundaries.
-What we were able to do was train a computer model
to learn features of molecular structures
that were associated with antibacterial activity.
-The computer was given 2,500 molecules,
and it began to learn which chemical structures
were linked to antibacterial properties.
And then when the computer was given a molecule
it hadn't seen before,
it could check the chemical structure and accurately predict
if it was likely to kill bacteria.
-We were able to scan hundreds of millions of molecules
in silico to identify the one
who was promising properties.
-Our algorithm ran predictions
on 107 million molecules
on three to four days.
To put that in perspective,
if I were to test those 107 million molecules
in the laboratory, I calculated it out.
That would have taken me something like 14 years
if I did it all day, every day.
-The computer model found about 120 molecules,
potential drugs, that showed promising antibiotic properties.
John Stokes then tested the short list, and within days,
the team had identified one particular molecule
that could become
first new class of antibiotics in decades.
-I first observed that this molecule was inhibiting
the growth of E. coli in a dish.
It had a structure that wasn't similar
to known antibiotics, really.
Cool.
That wasn't exciting.
Not yet.
-The molecule SU3327 was renamed halicin.
-We named halicin after HAL, the A.I.-based computer
in the movie "2001: A Space Odyssey."
-The next question was, well, does it work against
other pathogenic species that are problematic?
-John Stokes tested halicin
on a number of antibiotic-resistant superbugs.
-John had reported to us the results,
and he was very excited about the results.
-halicin is one of the more potent antibiotics
discovered to date, and it has remarkable activity
against a wide range of pathogens,
including multi-drug-resistant, extensively drug-resistant,
and pan-resistant pathogens.
And so it opens up tremendous possibilities
and expands our capabilities dramatically.
-I feel like the discovery of halicin
was perhaps a defining moment in showing that machine
learning has real promise in drug discovery, period.
-In the hunt for new drugs,
A.I. has potential far beyond just antibiotics.
-This technology can change life sciences.
-Human intelligence and machine intelligence, right?
-We are very hopeful that this platform
can be extended to other infectious diseases,
including SARS-CoV-2 and other viral infections,
as well as to complex disease like cancer,
metabolic disorders, neurological conditions.
Over the coming decades,
the progress we're going to make against
these diseases is going to be tremendous.
-This question, I think, that people need to ask,
which is, you know, if you open up your cabinet
in the bathroom and there's some drug
that you take that makes you healthier,
that maybe even is keeping you alive,
how many people actually stop and say,
"Where did this come from?"
Right? What is the story of this magic bullet?
-The heroes in this story,
the key characters in this revolution,
most of us don't know their names
because they're not celebrated.
Walk around your city or your town
and the statues will be to politicians and to generals.
They won't be to medical pioneers.
-But the history of how we ended up living longer lives
is so vitally important.
Took effectively 16 years for penicillin
to go from the initial discovery
to a drug that was actually functioning.
It took about less than 10 years for the antivirals
to be developed for HIV.
Where will we be with antivirals for COVID-19?
We don't know yet, but I suspect it will be faster.
But Big Pharma is much more interested
in pursuing new cancer treatments
that are just far more profitable.
I mean, it's a kind of market failure, right?
We have this urgent health problem,
but the private sector on its own
is not going to solve the problem.
-One of the many differences between modern drug development
and what happened with Fleming and penicillin
is there's no place for accident anymore.
We're not reliant on the serendipity
or finding a petri dish
with this remarkable mold in it.
It's much more these days
a story of rational drug development
and also of the sharing of information globally,
instantly among medical teams.
-And it also opens the door for this idea
that medicine is now something
that human beings are capable of creating at scale.
-This is arguably the biggest story in human history --
how we doubled our life expectancy.
-As the world grapples with another deadly pandemic,
we reveal how data became one of the most powerful tools
we have in the fight for extra life.
-Cholera was finally driven from the city of London,
not by a new medicine, but by data.
-This person's been ill for nine and a half days
without knowing it, spreading the virus,
when he could have been caught with a smart watch.
-This is arguably the biggest story in human history --
how we doubled our life expectancy.
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