Eureka! Before and After

In ancient Greece — and I’m talking 250 BC here — they didn’t have indoor plumbing. So, when men wanted to get clean and unwind after a long hard day… they went to the baths.

There were large pools where multiple men could soak together, and smaller tubs for individuals.

This story takes place in the Greek city of Syracuse (which technically is on Sicily, which today is part of Italy, but back then that island was part of Greece). Anyway, In Syracuse, there lived a man named Archimedes. He was a mathematician, and an inventor, and a lot of other things. Generally, he was regarded as the smartest guy in town – and that was a blessing but it was also a curse – because yes it meant he could solve really complicated problems, but it also meant people were always coming to him asking him to solve really complicated problems.

Archimedes – or Archie as his friends called him (actually never mind, I just made that up.) — would often go to the baths to relax and try and solve those problems.

Now on one particular day, he had a real puzzler: The King — a guy named Hiero II — had ordered him to solve a mystery.

You see the King had a new crown – a beautiful gold crown – but he was a little paranoid and thought maybe the goldsmith who made it was ripping him off. He suspected that the crown was actually made of silver, and just covered in a thin layer of gold.

So, he told Archimedes to find out if the crown was solid gold.

That is the puzzle Archimedes was mulling over as he took off his toga and dipped his toes in a lukewarm bath.

There are a few simple ways to answer the king’s question that he’d already dismissed: He couldn’t melt the crown down and examine the metal, the king would never forgive  that. Nor could he scrape the surface to see what was beneath it – again, damaging the crown that was just out of the question.

Whatever he did, it had to be non-destructive.

Now, Archimedes already knew that gold was almost twice as dense as silver. And since density is the relationship between mass and volume, he thought maybe he could get at an answer to the king’s question by calculating both those values for the crown.

He could put the crown on a scale and figure out the mass… that was easy… but how could he calculate the volume of such an odd shaped object?

Let me be clear here… This was no academic assignment you do for class – when the King tells you to solve a mystery … you’d better solve it – the penalty for failure was swift and severe.

And so, with his head swirling in circles, Archimedes climbs into the tub for a soak.

And then a funny thing happens.

The attendants had filled his tub right to the brim… so as he lowered himself in… the tub overflowed. Water spilled over the lip and onto the ground. And not just a little bit of water… quite a bit of water.

“How much water did I just waste?” Archimedes thought.

And then it hit him… the amount of water displaced is exactly equal to his body’s volume. It didn’t matter what his mass was… all the water cared about was his volume.

He could use a tub of water to measure the volume of the crown!!!

He could lower it into a totally full container of water, and then measure how much water overflowed, to figure out the exact volume of the crown.

Once he knew both the mass and the volume, he could calculate the density and figure out if it was made of pure gold or not!

He had done it! He had found a way to solve the King’s dilemma!

Archimedes was so excited that he jumped out of the tub… sprinted from the baths… down the street …all the way to his house.

But in his haste, he forgot to grab his toga back off the hook on the wall.

So, the citizens of Syracuse were treated to the sight of a middle aged mathematician, buck naked, dripping with water, running down the middle of the road yelling “I found it! I found it!” And since he was yelling that in Greek … what he actually said was…. “Eureka!”

I’m Dan Riskin and this is “Inside the Breakthrough – How Science comes to Life,” where we look at discoveries from the past, to better understand our future.

“We live today in an age of science”

That’s from 1954.

“The elaborate paraphernalia of the scientist is nothing more than a tool for thinking.”

That was true then, and it’s true today. “Thinking like a scientist” is way more important than having a fancy laboratory.

“What is this ‘Scientific Method?’”

That question was asked in the 1950’s. Its roots go back thousands of years and we’re still asking it today. When it comes to science, it’s the method that matters, so we’re going to do our part to try to understand that.

I care about all this because I’m a scientist. Mostly I work on bats — but a bunch of other stuff, too: Pterosaurs, mice, shrews.

But on top of that I’m a science journalist — I spent years with Discovery Channel interviewing scientists, researchers, innovators and explorers… trying to understand how they work, and how they think.

All that… has led me here:

This podcast is produced by SciMar – a research group working toward their own  breakthrough in the way we prevent, detect, manage, and treat type 2 diabetes. Instead of focusing on the pancreas, the researchers at SciMar are focused on the liver. In simple terms, they are solving an old problem, using a new perspective… just like Archimedes.

The story of SciMar and its founder Dr Wayne Lautt is a contemporary one (it’s still being written actually.) But it’s also an ancient one. It is a story as old as the very idea of ‘science.’

So, what we’re going to do here is tell that new story, using a whole bunch of old stories. Along the way, we’ll hang out with characters like Archimedes and Galileo, Newton and Einstein, Curie and Fleming, and the duo of Banting and Best.

This is episode 1 – “Eureka!”

Dr Lautt’s ‘Eureka Moment’ came in 1989 – but let’s not jump the gun. Let’s start with a discovery that happened 60 years before that.

“Medical science today owes much to one of the great scientific achievements of recent times.”

Listen carefully, because the most important moment of this story … doesn’t come at the beginning, or at the end… it’s buried somewhere in the middle.

“The discovery of a wonder drug now saving thousands of lives.”

You’ll know it when we get there. I promise. Because it’s the moment where someone yells “Eureka,” or at least something really close to Eureka. You’ll see.

We’ll start with the first world war.

That lasted for four and a half years.

20 million people died.

Half of those were civilians, and half were soldiers.

Some of those soldiers died on the battlefield. But an alarming number of them died in hospitals… survival rates at military hospitals were horrific… Mostly because of infections.

Taking a bullet to the shoulder, or getting a deep cut on your leg from climbing over a string of barbed wire… those shouldn’t be fatal injuries. But in the early part of the 20th century – that’s exactly what they were. Any open wound was an entry point for bacteria which would cause infection, which all too often, proved lethal.

One young man that had a front row seat to this tragedy was Scottish doctor Alexander Fleming. As a member of the Royal Army Medical Corp, he served in battlefield hospitals on the western front.

Dr. Fleming is the ‘Eureka’ guy in this story – but not yet.

Young Alexander was the child of a humble farming family – when he was just 7, his father died. That made their daily life difficult. But thanks to his hard work and keen mind he received scholarships to attend college and eventually medical school.

He was incredibly smart, but not particularly tidy or hygienic. That sloppiness actually led to what he later described as “the greatest discovery of my career.”

If you’ll pardon my terrible scottish accent.

He was doing research at St Mary’s hospital in London, England… studying bacteria.

On one particular day Alexander showed up for work with a runny nose. He wasn’t the kinda guy that would take a day off work just because he had a little cold.

I do want to say here… if you are sick, please please please don’t go into the office. No one there wants to listen to you sniff and snort and cough. No one there wants to spend tomorrow feeling as crappy as you do today. Stay home. Don’t be a Fleming.

Anyway, on this particular day, let’s make an exception.

So… a bit of snot dripped from Fleming’s nostril into a petri dish.

He knew right away that sample was contaminated so he pushed it to the side of his desk and continued working on the rest of his samples.

That’s where it sat for the rest of the day… the rest of the week… and half of the next week…

In all that time… numerous colonies of bacteria grew out of the sample in the dish… but there were two spots in the dish … exactly where his nose mucus had fallen … that were still completely clear.

Fleming had discovered a new enzyme. It was found in nasal mucus… but also in tears, saliva, skin, hair and fingernails. It was part of the body’s natural bacteria killing system. He named it lysozyme.

It was an amazing discovery – but it is not the eureka moment he is remembered for.

You see, Lysozyme had its limits. It was kinda weak… it worked really slowly, and was most effective against the least harmful types of bacteria.

But still, it grabbed the attention of the medical community and boosted his profile.

Now “boosted his profile” I’m really overstating it – I mean he was a researcher studying bacteria in a lab. He’s not exactly on the front page of the newspaper every day.

Still – he had a good life. He got married and had two children.

In the Summer of 1928 – a decade after the end of World War I – he awoke on a particularly hot and muggy August day in the city of London. So Alexander Fleming decided to take his family out of the city for a couple weeks. They headed north to his native Scotland and enjoyed a relaxing holiday by the sea-side.

When he returned to work – the first week of September — the samples he had been working on before he left were still sitting out on his work bench.

He had been studying Staphylococcus aureus. This is a bacteria that’s really common… in most cases it causes minor skin irritations like zits… or respiratory stuff like a sinus infection… in extreme cases it can cause staph infections that can be fatal. Even today 50-thousand people die every year in the United States from staph infections.

Despite that potential for danger … Dr Fleming had just left it sitting on his desk for two weeks while he played at the beach with his family.

What Fleming found when he returned, was that in one of the dishes… some mould had grown.

There must have been some kind of contaminant in there… maybe a bread crumb or something… because this is exactly the same green fuzzy mould you find on old bread.

So, around the edges, where the mould had touched the bacteria culture, there was a clear liquid.

He looked at it under a microscope and was blown away.

“I say gentlemen. Here is something interesting. Take a look at this dish.”

The mould appeared to be breaking down the walls of the cells in the bacteria. It wasn’t just inhibiting its growth… it was actively attacking the Staphylococcus bacteria.

“I’d say something in that mould is destroying the staph in that dish.”

This was his eureka moment.

It looks good. Very good.

It was a beautiful combination of years of study, with a singular moment of serendipity. Fleming was so ecstatic about the discovery… he… well, he… took another couple weeks’ vacation.

Seriously.

He was just stopping into the lab because he had been given a promotion and I guess there was some paperwork to do… but once that was done… he took off for another couple weeks.

Historians like to point to these singular moments, these supposed turning points in history, that in hindsight are earth shattering… but often in the moment… they’re just another day in the lab.

In this case – as with so many other discoveries — there had been a decade of work leading up to that Eureka moment… and before it would make any impact… there was another decade of work yet to come.

Mould is notoriously slow to grow… I know you’re thinking it appears pretty quick on your bagels… but really … to get a usable quantity of it, and then separate out the active chemicals… that takes a lot of time.

After a year of growing mould and testing it on various bacteria, Fleming named the active chemical Penicillin and published a paper about the world’s first bacteria killer…. It was called an “anti-biotic.”

The discovery was greeted with a yawn.

I mean, in theory people thought it was interesting … but in practice… you needed so much mould to harvest the active compounds to be able to do anything real with it.

A few dates to put it in context:

• Fleming’s eureka moment came in 1928.
• His paper naming in Penicillin, 1929.
• But for the next ten years this is just a laboratory curiosity. It was used by some chemists to separate different kinds of bacteria… but using it as medicine… people aren’t even thinking about that.

In fact, once, when a doctor asked him if penicillin could ever be used on patients… Fleming answered: “I don’t know. It’s too unstable. It will have to be purified, and I can’t do that.”

I just assume he sounded exactly like Sccotty but I don’t really know that either.

Other people eventually got involved. And in 1941… 13 years “post-Eureka” … they put penicillin to the test.

A police officer by the name of Albert Alexander was in the hospital.

He had scratched his face on a rose bush. The scratch crossed his cheek from the corner of his mouth to just under his left eye.

The scratch got infected.

The infection spread… his face was covered in sores and one of his eyes had to be removed.

It appeared to all involved, that Constable Alexander was going to die.

Researchers had been testing small doses of penicillin on mice and the results were promising – but this was a human, and the dose he was going to need was much larger. They considered Albert’s dire condition … and decided this was the opportunity for a bold experiment.

They gave him an intravenous infusion of 160 mg of penicillin. And they waited.

Within 24 hours, his temperature had dropped, and the infection had begun to heal. He was even able to eat a meal.

So they gave him another dose of penicillin, but they didn’t have much more on hand. They started collecting the patient’s own urine and extracted any unprocessed penicillin they could from the pee, and giving that to him again.

But even doing that, on the fifth day they had none left.

The patient, who had shown such a promising recovery, started to deteriorate. The infection returned… a few weeks later…. He died.

They had shown that penicillin could slow an infection, but the manufacture and storage of penicillin was the insurmountable challenge.

So, you remember how this story started during the first World War? Well… guess what… it’s the 1940’s and now the world is at war again.

“On Dec 7th, 1941 Japan like its infamous axis partners struck first and declared war afterwards.”

In March of 1942 American doctors – for the first time ever — used penicillin to successfully treat a patient with septicemia – that’s blood poisoning. That single test used up half of all the penicillin in the whole country!

The military realized they needed to find a way to produce it at industrial levels.

And that is exactly what they did.

Within two years… in preparation for the D-Day landings in June 1944…. They had generated 2.3 Million doses.

That supply of antibiotics saved thousands of lives… but it didn’t happen until 15 years after Dr Alexander Fleming came home from his holidays, and said “It looks good. It looks very very good.”

I mean, I wish he had said “eureka” but you can’t change history.

So, what’s the takeaway from all this?

What part of my long rambling story are you supposed to remember a week from now?

Well, most people latch onto the moment of discovery – the benign accident – the fact that he left something on his desk for two weeks unattended. People love telling that story

You’ve probably heard that the microwave oven was invented when a technician stood too close to a vacuum tube and a chocolate bar melted in his pocket… or that Viagra was tested on men as a treatment for a heart condition and then a bunch of patients wouldn’t give the drugs back when they had leftover pills, and researchers discovered that perhaps it was also influencing the blood flow to other parts of the body.

We love those explanations for a couple reasons.

One — they are easy to remember. 

But Two – they make us feel like “hey, I could have done that!”

But when we think that way, we’re kind of kidding ourselves. The truth is, Eureka moments are actually the middle of a long stretch of hard work. Fleming spent years studying bacteria and viruses. That gave him the perspective to see what was really happening in that petri dish. Most of us would have simply been grossed out by the mould and tossed it in the sink to be washed out.

Eureka moments aren’t an artifact of history — don’t ever believe someone who says there is nothing left to discover – obviously there is – In fact, Eureka moments still happen every day.

That’s my segway from the past to the present. Pretty clever eh?

You see, that’s what this show is all about: using those historical stories to understand what SciMar is doing right now. And we’re going to check in with them every episode.

When I first heard about SciMar – like any critical thinker, I did my best to come in with an open mind, but I was skeptical. I mean, Diabetes has been around for thousands of years — there is an Egyptian papyrus’ from the third dynasty that describes an illness with exactly same symptoms – so they’re probably talking about it then. The Ancient Greeks were the ones that gave Diabetes its name … and a hundred years ago humans basically figured it out. Fredrick Banting and Charles Best proved you can treat it with Insulin, which is a hormone that comes from the pancreas. Case closed, right?

So now this research group from Manitoba, Canada says the key to diagnosing, and reversing, the disease lies with a hormone called HISS that comes from the liver… And they say that same hormone can help treat heart disease! …  Well, it fills my head with many, many questions. But don’t worry. We’ve got plenty of time to flush those out.

Today I want to start with their founder Dr Wayne Lautt and his Eureka moment:

I’ve actually had a number of them in my career. And each time before the eureka moment, there was always a serendipity moment.

Today, Dr Lautt is the principal investigator behind SciMar, but in the 1980’s he was at the University of Manitoba, as the head of the department of pharmacology and therapeutics.

My serendipity moment was in 1989, the Soviet Union dissolved and the Canadian government came up with the idea to offer Ukrainian scientists the opportunity to come to Canada for a three month period.

So… A communist country on the other side of the world implodes… then the government introduces an intellectual exchange program… and suddenly Dr Lautt finds himself collaborating with a researcher from Ukraine.

I asked him what he was interested in and he said, well, he wants to study the effect of insulin on the brain.

So they did an experiment to test that, and found… well… nothing.

We found that insulin in the blood wasn’t really having any direct impact on the brain. So, that was a real puzzler. We were totally flummoxed, not really able to explain it.

Now, Dr Lautt is not a brain guy…. his expertise revolves around the nerves connected to the liver… so he started tinkering with those, but still working in the context of the “insulin in the brain” experiment.

So, we cut the nerves and repeated it. What we found was that cutting the nerves to the liver wasn’t affecting the liver at all, it was affecting the hind limbs. That was a eureka moment, because that meant that there was a hormone that was being released from the liver that was being controlled by these parasympathetic nerves that was affecting the peripheral tissues, primarily muscle. At that moment then, I told the whole lab, “Guys, we’re shifting gears. We’re going to take a look at this.”

Lautt figured out that an unidentified hormone must be involved in controlling glucose levels in the body. He decided to focus the lab’s efforts on finding that hormone.

The tearing down of the Berlin Wall was not supposed to lead to a breakthrough in diabetes research… but it did, because research is a road without a map.

So you can’t get to a eureka moment by plodding resolutely ahead. Something had to be ready at the right time, in the right place for whatever reason, that led you to think about something that you had never considered before. Certainly after a eureka moment, then heavy plodding comes.

Just like Archimedes and Fleming, Lautt’s Eureka moment was really just a simple observation.

• Water flowing out of a tub
• Mould in a petri dish
• Reduced glucose uptake by the hindlimbs of a lab animal.

OK… maybe not quite as obvious.

But because those observations were sandwiched between decades of study and many years of hard work… those moments of ‘Eureka,’ changed the way we understand the world.

The two primary conditions that have to be present for a Eureka moment to have impact? The existing knowledge of the scientist, and a ton of work after the fact to put it in motion.

But there is another factor that turns an ‘observation’ into a ‘discovery’ … and that is timing. Too soon, or too late and a Eureka moment is just … well, it’s a petri dish you have to wash.

We’ll look at the importance of timing in the next episode of “Inside the Breakthrough” – is called “Bad Timing. We’ll share a couple stories from history — and also take the next step on the journey with Dr Lautt.

By the end of season one, we’ll find out if the SciMar team has made a discovery that will change the course of human health.

I’m Dan Riskin. Be sure to subscribe wherever you listen.

New episodes come out every two weeks.

One last thing before we go… that gold crown that the King asked Archimedes to check out? … it was less dense than pure gold… so some other metal had been mixed in… And when the king found out he’d been cheated… well… no one ever heard from that goldsmith again.

You could say he got Archimedes screwed. (laugh)

That is a nerdy joke, that’s all that is.