In the early 1930s, biologists working in  southern Africa realized that you could use female Xenopus as an assay for human pregnancy.

Hold up.

A frog that’s a pregnancy test!?

Xenopus, also known as the African  Clawed Frog, was minding its own business in South African ponds for millions of  years.

But then, something changed.

In the mid-20th century, scientists found a  surprising use for these frogs.

And before we knew it, Xenopus labs were popping up everywhere.

The reason: pregnancy tests!

But how can a frog tell you if you’re pregnant?

And why are  these frogs so important to science today?

I’m Shane Campbell-Staton, and this is Human Footprint.

Xenopus means strange foot.

Jim Hanken is the Curator of Herpetology at the Harvard Museum of Comparative  Zoology.

He was one of my mentors in grad school, and amphibians are his thing.

Three of the hind toes have a black keratinized claw.

I'm assuming that's where “African clawed frog” comes from.

African clawed frog.

You got it.

In grad school, we talked about  Xenopus like THE model system.

Model systems are the species we  study because there’s something about their biology that gives us  deeper insight into how life works.

Model systems are literally the “lab  rats” of the scientific world.

It always struck me as the weirdest choice.

Yeah, it’s a historical accident.

In Ancient Egypt people were peeing on wheat,  barley and other kinds of grain.

If it sprouts, she's pregnant.

If it doesn’t sprout, she’s not pregnant.

It was actually found  to be accurate 75 to 80% of the time.

So this is a pregnancy test that worked,  developed 3000 years ago, or more.

Kelsey Tyssowski is a biologist at Harvard who’s  written about the history of pregnancy tests.

So it was called the Hogben test,  after Lancelot Hogben, who... Lancelot Hogben.

Yes.

Got to be British, if you're named Lancelot.

Now everyone’s got their thing, and apparently Hogben’s thing was injecting animals with  urine.

What he discovered is that if you inject a pregnant woman’s urine into a female  Xenopus, the frog will ovulate and lay eggs.

What is it exactly, in the urine – There's a hormone in the urine of pregnant women called human chorionic gonadotropin,  hCG, and it goes up really really high.

Kelsey explained that when an embryo  first implants in a woman’s uterus, her hCG levels spike.

And that hormone turns out to be very similar to another hormone called  luteinizing hormone, which causes ovulation.

Okay.

hCG in human urine can cause other mammals to ovulate too…and in the  early 20th century, doctors could actually order a mouse or rabbit-based pregnancy test.

They inject into animals.

The problem was, they had to kill and  dissect the animal to find out the result.

So the Hogben Test was a revolution.

Demand exploded as Xenopus became the go-to pregnancy test around the globe.

The fact that Xenopus were really useful for pregnancy testing, inspired people  to figure out, "How do we keep a lot of Xenopus like living in a lab space?"

Xenopus labs started popping up everywhere And scientists began to realize that they could  use these frogs and their eggs to answer all kinds of questions.

Are you pregnant?

Researchers eventually came up with easier ways  to measure hCG in urine – no frogs required.

But by then, Xenopus was firmly established as a  model system in biology.

They were first used for embryological research after scientists discovered  they could breed the frogs in aquariums, Providing a steady supply of robust eggs that  didn’t need to be collected in the wild.

More recently, researchers have been studying this frog's ability to regenerate its brain and  spinal cord during larval stages.

With these benefits to the scientific community, it was  clear these frogs weren’t going anywhere.

How many frogs do you think you have here?

We have over ten thousand frogs.

The epicenter of modern Xenopus research is tucked  away in a basement in a quiet town on the coast of Massachusetts: The National Xenopus Resource.

We focus on transgenic, inbred and mutant frogs.

Marko Horb is the director here.

And despite all this talk about mutants…he’s  more of a Willy Wonka than a Dr. Moreau.

Somebody wants a mutant, they tell me what  gene, I have technicians that work on that, they’ll make the mutant, it's like a  shop.

You want something, you order it from me We make it.

And we give it to you.

Different research questions require frogs that carry different combinations of genes.

When  a scientist needs a particular collection of genes that hasn’t been assembled before, Marko’s  the dude that’ll put it together for them.

And yeah, THIS is actually what he  likes to do in his spare time.

What are Xenopus being used for?

Developmental biology…how organs develop and how different cells are formed.

People use  the eggs and the oocytes from the frog… Marko’s talking about research that’s already  led to new discoveries, technologies, medicines… And will undoubtedly lead to many more.

But in our quest for one kind of knowledge, I can’t help but wonder if we’re  leaving another behind.

In the early 1990s, frogs around the world  started…disappearing.

In just a few decades, dozens of wild species had been  reduced to memories And a few pickled specimens in museums.

We got Rheobatrachus That's Atelopus…This is a poison frog.

[More frog species] Everything that we're looking  at here has gone extinct.

All of these are believed to be extinct.

The killer is a fungus called chytrid.

These are fungi that proliferate in the  skin of amphibians.

The frog stresses out physiologically and dies.

Biologists  literally walking along a mountain stream would see large numbers of dead or dying frogs  on the rocks next to the stream, or floating in the water.

It was just unheard of.

Chytrid has probably existed and infected certain amphibians for thousands of years.

What’s new is the massive global trade in amphibians for pets, food, and yeah…science.

Chytrid has spread all over the world exposing frogs and salamanders to a disease  many of them have never faced before.

It’s the largest pandemic the world has ever seen.

And in just a few decades, it’s driven dozens of amphibian species to extinction.

And yet, this thing is doing perfectly fine, more than fine.

Some species can resist it very readily,  other species cannot.

Xenopus tolerates  chytrid infection.

It's a tough frog.

We don't know for sure what role Xenopus  are playing in the chytrid pandemic But they certainly aren’t helping.

They can carry  chytrid without getting sick.

And thanks to us, they’re world travelers.

Escaped and  released frogs have made Xenopus an invasive species on four continents.

Research on these frogs has improved our lives, but as we transformed one frog  species into a global phenomenon, we left others on the brink of collapse.

You've dedicated your entire life to understanding these branches of the tree of life.

Do you  still remain hopeful about their future?

We know there's tremendous uninventoried,  biological diversity out there, unnamed species, undiscovered species, and it's a race against time  right now to find them.

So maybe it sounds silly or it's very unsatisfactory, but I find it's a bit of a  consolation to get out there and try to while they're still there, try to find them.

And in so doing  reveal the further wonders of our planet.

Let's do what we can to  save as much as we can.

Agreed.

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