[ 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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