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Jump to Key Points The Ancient Egyptians Used Grain
The oldest documented pregnancy test in human history dates back to ancient Egypt. In 1400 BC, pregnant women were instructed to urinate on a mixture of barley and wheat grains. If the barley sprouted, a boy would be born. If the wheat sprouted, a girl would be born. If neither grain sprouted, the woman was not pregnant.
In 1927, the German gynecologists Selmar Aschheim (1878-1965) and Bernhard Zondek (1891-1966) developed another pregnancy test that involved the urine of women suspected of being pregnant. This time, the urine was not sprayed onto grains but injected into juvenile mice or unmated hares. If the woman was pregnant, the injection caused the animals’ ovaries to swell.
These pregnancy tests, later known as the Aschheim-Zondek test, had several drawbacks. The less expensive murine test took a full 4 days, whereas the more expensive rabbit-based test, in which a rabbit was injected and then dissected to examine the ovaries, still took 2 days. In both cases, the animals died.
The First Ranine Pregnancy Test
In the 1930s, British scientist, zoologist, and statistician Lancelot Hogben (1895-1975) developed a more animal-friendly pregnancy test. During a research stay in South Africa, he encountered African clawed frogs (Xenopus laevis), which measured up to 13 cm long, had five toes, and lacked both a tongue and eyelids. Hogben was initially drawn to the frogs for their unusual morphology, but he became especially interested in their ability to change skin color to match their surroundings: They darkened in dim light and turned white in well-lit aquariums.
- Ancient pregnancy tests used urine + grains; sprouting suggested pregnancy.
- Aschheim-Zondek test used urine injection into mice/rabbits; animals died.
- Xenopus laevis test detected urinary hCG; spawning occurred within 5 hours.
- Frog assay accuracy reached 99.8%; cheaper and nonlethal vs prior bioassays.
- Modern tests still rely on hCG detection, now via antibody-based assays.
To test his theory that the frogs’ color changes were driven by hormones from the pituitary gland, Hogben removed the gland from his specimens. The procedure eliminated their ability to adapt their skin color to their surroundings, but it also unexpectedly caused the female frogs’ ovaries to atrophy. To reverse that effect, Hogben then injected pituitary extracts from oxen into the frogs. The injections triggered immediate spawning, even without a male present, and the response was so pronounced that a single drop of the ox hormone extract could prompt the laying of hundreds of eggs.
Hogben’s background in human medicine now proved beneficial. Human chorionic gonadotropin (hCG) levels surge during human pregnancy between the 6th and 12th weeks of gestation before dropping sharply. During this peak, hCG is detectable in the urine of pregnant women.
In a burst of scientific enthusiasm, Hogben reasoned that because humans and oxen were both mammals and because ox hormones had caused the frogs to spawn, urine containing hCG might also cause frogs to spawn.
The Frog Test Achieves 99.8% Accuracy
In fact, Hogben discovered shortly thereafter that the ranine pregnancy test worked. The test was more cost-effective than previous tests because frogs are relatively undemanding animals that eat almost anything, from chopped liver to dead flies. It was faster because frogs spawned within 5 hours of being injected with human hCG. Finally, the frogs did not have to be sacrificed.
Hogben was so fascinated by his discovery that he named his South African home “Xenopus.”
The lower production costs allowed for lower retail prices, which boosted demand. In the 1940s, demand for Hogben’s frog test skyrocketed. The largest laboratories in England exported tens of thousands of tests annually to countries all over the world. The test’s accuracy was 99.8%.
Despite the commercial success of his test, Hogben did not retire. Instead, the physiologist — whose research efforts had previously been limited for years by a lack of funding and family resources — expanded his scientific activities. When the German Nazis began promoting eugenics, Hogben traveled to Norway specifically to speak out publicly against them. Unfortunately, the Nazis invaded the country shortly thereafter. Hogben was forced to flee to the US with his family.
Conclusion
The history of the pregnancy test is also a history of gender equality and women’s self-determination. Viewed in this light, Hogben rarely receives the recognition he deserves in the history of medicine. Although modern pregnancy tests use antibodies instead of clawed frogs to specifically detect the beta subunit of hCG, the principle of using hCG as a marker of pregnancy has remained relevant ever since Hogben’s serendipitous discovery of the ranine pregnancy test.
This story was translated from Univadis Germany, part of the Medscape Professional Network.
