I wanna tell you a story about a lizard.

This lizard lives in the desert, so sadly, it has no idea what an angler fish is.

And the angler fish, it's probably never even heard of land, much less lizards.

And neither of these weird animals has any idea that a few chemicals swimming around in their bodies help some humans wearing funny coats invent one of the most important medicines of the 21st century.

But like most stories, this one isn't just about a fish or a lizard.

It's about something else too, about why we do science in the first place, about why people and governments come together to give money to scientists, and about what kind of questions scientists should ask about what kind of knowledge is most useful and how science can do the most good for the world.

(pensive music) Hey, smart people.

Joe here.

More than 40% of American adults today have obesity.

If current trends continue by 2050, that means more than two in three American adults will be obese.

And these trends are similar around the world.

This is a huge health crisis since obesity increases chances of diabetes, heart disease, cancer, and lots more.

There are a huge number of reasons behind this that I'm not really gonna dig into here.

Some physical, some psychological, some are even influenced by society.

But all that aside, the important thing to acknowledge is how incredibly difficult it can be for people with obesity to lose that weight and how few safe options doctors have had to help them, which is why it was such a big deal when these hit the market.

Drugs like these have completely revolutionized how doctors treat diabetes and weight loss, and frankly, it seems like there's another new use for them announced every few weeks.

This video is about how we discovered these world changing drugs.

That story is weird and fascinating, but I'm just gonna come clean that I think the real lesson we should take from this story is that really interesting and important things happen when we let scientists go wherever their curiosity guides them, even if the questions they end up asking seem ridiculous or even like a waste of time right now because decades down the road, that might lead to an answer we don't even have the question for yet.

In the late 1970s, a couple scientists in Boston were trying to find the gene that carries the instructions for making a hormone called glucagon.

Scientists have been interested in glucagon since the 1920s because it's one of the two main hormones our bodies use to regulate blood sugar.

Basically, when the pancreas releases glucagon into the bloodstream, blood sugar goes up, and when the pancreas releases insulin, which is sort of the opposite of glucagon, blood sugar goes down.

In healthy bodies, these two hormones sort of work in concert to keep blood sugar at a healthy level.

But if you have type two diabetes, basically the body stops producing insulin or becomes less sensitive to insulin.

So a person has chronically high blood sugar and this whole balance is thrown off.

So in the seventies, these scientists decided they'd find the gene for glucagon by studying angler fish.

Why angler fish?

Well, it turns out these creepy deep sea monsters have an entire organ for making glucagon, and it was just much easier to dissect that organ out than it was to painstakingly pluck the tiny number of glucagon making cells out of like a mouse's pancreas.

I mean, work smarter, not harder, right?

And they did find the gene for glucagon, and they were surprised to discover that the same gene that makes glucagon also makes two other small peptides.

They named them glucagon-like peptide 1 and glucagon-like peptide 2, because scientists are very creative.

So now we have this new hormone, GLP-1, and nobody knows what it does.

So a bunch of different scientists started testing it in Petri dishes and in animals, and it turns out GLP-1 increases insulin release and lowers blood sugar and slows the rate the stomach empties out and makes people feel more full and eat less, exactly the things that could help treat type two diabetes.

So if we could inject people with GLP-1, this could be an incredible treatment for diabetes.

There's just one problem.

Like most hormones, GLP-1 doesn't stick around for long.

It's broken down almost as fast as it's secreted, basically in just minutes, which meant it didn't have much chance of working as a drug.

And that's where the lizard comes in.

(curious music) Gila monsters are very, very weird.

These lizards live in the desert and they don't move real fast, so they may only catch and eat a meal like five to 10 times a year, and when they do eat, they may eat half their body weight at once.

So between these long periods of not eating and eating a ton, they must have some way to keep their metabolism running smoothly and their blood sugar balanced.

Now, Gila monsters are also one of the only venomous lizards on earth.

Their venom is basically their spit.

Now, in the 1970s and early eighties, some scientists had noticed that if animals got stung or bit by certain venomous creatures, the victim's pancreas would start secreting all kinds of hormones.

So one team of scientists decided to basically test every venom they could find on pancreas cells to see if any of them did anything.

And one venom in particular made pancreas's start secreting like you wouldn't believe, Gila monster venom.

They wrote a paper about all this like scientists do, and then nobody really did anything with it for the next 10 years.

But fast forward to the early nineties, and this other scientist in the Bronx read that paper about the amazing effects of Gila monster venom spit on Guinea pig pancreases and decided to try and figure out what was in that stuff.

And hidden in this cocktail of toxins, he isolated a tiny peptide, a chain of just 39 amino acids.

He called it Exendin-4.

It turns out that this little chain of amino acids from heli monster venom turns on the same switches in a mammal's pancreas as GLP-1 does.

The technical term is it's a GLP-1 receptor agonist, and just like GLP-1, it increases insulin release, it lowers blood sugar, the stomach empties slower, but it was different from GLP-1 in one really important way.

Here's the thing you gotta understand about venom.

Whatever chemicals are in an animal's venom, whatever they do, the animal makes them and then they just have to sit inside the animal's body until they're used.

This means they have to be stable, they have to last longer without breaking down.

And this peptide in Gila monster spit instead of disappearing in minutes like GLP-1, it can last for hours.

That meant maybe it could work as a drug.

For years, John Ang tried to tell people what he'd found, how huge this could be for diabetes, but he couldn't get anyone to pay attention.

It was just too weird.

And let's be honest, it is very weird, but it also works.

(curious music) One drug company finally decided to give it a shot, literally.

(crickets chirping) And in 2005, a synthetic version of this peptide from Gila Monster spit was approved by the FDA as a diabetes drug.

As other drug companies started to see the potential of these peptides, they started tweaking them like chemists playing with Legos.

They added little bits of other molecules to make them last longer in the body so people could take fewer doses.

They found other small peptides that control insulin and appetite by acting on two or even three metabolic switches instead of just one.

And more of these will hit the market in the next few years.

What surprised researchers the most is that not only do these work to control type two diabetes, they also help people with obesity lose weight like nothing else really ever has.

We're talking like five to 15% of a person's body weight in a year, and we think these GLP-1 like drugs work in part by traveling to the brain and triggering these molecular switches in parts of the brain that control appetite and hunger, they make people's brains feel full and they eat less.

You can find thousands of videos on social media from people explaining how this has changed their lives, and with that has come a lot of money.

To put that into scale, Novo Nordisk, the Danish company behind Ozempic and Wegovy is now worth more than the entire economy of Denmark.

There's also a lot of important discussion out there of when people should take these and why, and we still have a ton to learn about how and why they work in the first place.

But the fact is they do work like nothing else doctors have ever seen.

Nobody could have predicted that a couple scientists looking for hormones in angler fish or a guy squirting lizard venom on a rodent pancreas would lead to this.

And that's really what this story is about.

(curious music continues) For much of the last century, there's been a quiet fight in science about the superior.. of applied versus pure research.

In other words, science for the sake of creating knowledge and science done for the sake of making useful things.

Consider someone like Albert Einstein.

For all the revolutionary physics that he discovered, you'd struggle to identify a single invention that he brought into the world.

On the other extreme, someone like Thomas Edison was a prolific inventor, but did very little discovering of his own.

In past centuries, this distinction between so-called applied and pure research didn't really exist.

Science was understood to be about knowledge seeking, something closer to philosophy.

And besides, in the time of scientists like Newton or Faraday, research was just as likely to be funded by personal wealth or private benefactors as it was by a government.

In modern times, the nature of this debate usually centers on how money is spent.

And since most modern research funding comes from governments, there's a desire to see as much direct economic benefit as possible, as quickly as possible, and we periodically face calls to eliminate research about seemingly useless knowledge.

- $700,000 was spent to study how male parrots attract their mate, really?

- But as we've just seen, and has history has proven many times, it's not always easy to identify whether knowledge that seems useless now will one day prove very useful.

By some estimates, a quarter of the world's GDP in some way relies on quantum mechanics.

A field that a century ago was driven only by theory and curiosity.

After World War II, when Bell Labs began work on transistors, it started as an effort to better understand the physics of semiconductors.

But now most of our daily lives and the world economy depend on inventions that those researchers couldn't have predicted.

The worldwide web began as a way for physicists and other scientists to share data, and when John von Neumann built a strange mechanical device to solve logical problems in the 1940s, who could have predicted that he was creating the programming and memory architecture that's used in almost every computer on earth today?

In between the two extremes of science done purely for creating knowledge and science done for the sake of making useful things, there seems to be another way, a balance between discovery and invention.

One that political scientists Donald Stokes called Pasteur's Quadrant.

Now this balance of curiosity and use driven science is named for Louis Pasteur, the French microbiologist with discoveries like the germ theory of disease, Pasteur operated in the quadrant of pure knowledge, but with lifesaving inventions like pasteurization to safely preserve food.

He also operated in the quadrant of applied knowledge.

An individual scientist or even a piece of knowledge may move from quadrant to quadrant in ways that are difficult or impossible to predict.

As new knowledge and applications come along like angler fish organs, and lizard spit.

Pasteur himself viewed the dichotomy of pure versus applied research as a false one.

He once wrote, "There is no such thing as a special category of science called applied science.

There is science and its applications, which are related to one another as the fruit is related to the tree that has borne it."

It's very hard to predict the usefulness of knowledge that seems useless today.

Perhaps it's better that we start to view knowledge its itself as useful, and let the future show us precisely what that means.

Stay curious.

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Wow, that was smooth.

Pre-read!

I was always like- Checking myself in the monitor here real quick.

Okay.