The Amphibian Pregnancy Test

How does a frog know you’re knocked up?

I’ve got to find a better gig …

A fungus that grows on the backs of frogs may be responsible for the extinction of dozens of species, say the authors of a study published in Thursday’s issue of Nature. Amphibian chytrid fungus seems to have spread around the world astride the South African clawed frog, Xenopus laevis, which was exported for use as a pregnancy test. Wait a second—how do you use a frog to test for a baby?

You inject some urine into its dorsal lymph sac in the morning and check back at the end of the day. A dose of a pregnant woman’s pee will cause a female South African clawed frog to lay eggs within eight to 12 hours. The test also works on male frogs, which produce sperm in response to the injection.

The frog test works because a pregnant woman’s urine contains a hormone called human chorionic gonadotropin, or hCG. Most modern pregnancy tests rely on the detection of hCG using other means: The standard home test kit, for example, flags hCG with prepared antibodies. But until the 1960s, the best way to detect the hormone was to inject urine into an animal and wait to see what happened.

In the late 1920s, a German chemist, Selmar Aschheim, teamed up with a gynecologist, Bernhard Zondek, to develop the first of these procedures, called the “A-Z test.” The doctors would repeatedly inject five female mice with a woman’s urine over several days. Then they’d kill the mice, dissect them, and examine their ovaries—enlarged or congested specimens would signal a pregnancy. Within a few years a slightly better test was developed; it used rabbits.

Meanwhile, embryologists had been studying amphibians for many years. Frogs and newts tend to have large eggs that can be easily examined and manipulated. The development of a fertilized egg also takes place over a fairly long period of time and in plain view. (Mammalian embryos start out very small and begin their development inside the mother.) Amphibian eggs weren’t perfect, though—researchers had to wait for spawning season to get samples for their work.

In 1930, a scientist based in Cape Town, South Africa, named Lancelot Hogben reported that he could use ox hormones to control ovulation in a local frog species—Xenopus laevis. His discovery was important for two reasons: First, it provided embryologists with a frog that could produce eggs year-round. Second, it provided doctors with a new animal for pregnancy testing. By 1933, doctors were using the “Hogben test” to detect hCG in urine.

The Hogben test was both rapid and reliable, and it spread quickly throughout Europe and the United States over the next two decades. Scientists were able to rear the clawed frogs in captivity, but it was easier to import them from Africa in large numbers. Either way, the reliance on live animals posed problems for the big testing centers. Even a facility with several thousand frogs could be shut down by a virulent disease outbreak. The development of new testing methods in the 1960s made the Hogben test obsolete.

Bonus Explainer: What did people do before the A-Z test? Urine tests of one kind or another have been in use for thousands of years. According to a source from around 1350 B.C, ancient Egyptians sprinkled a woman’s urine on wheat and barley seeds; she was pregnant if they sprouted. Centuries later, doctors used “uroscopy,” or the visual inspection of urine, to make their judgments. A Persian physician described the telltale signs of pregnancy: “The color may approach that of chick-pea water, or be yellow with a bluish or iridescent tint in it. … ” (The sight of the uroscopist holding up a vial of piss would later become the iconic image of the chemist in Western culture.)

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Explainer thanks Glenn Braunstein of the Cedars-Sinai Medical Center.