The Aschheim–Zondek pregnancy test

A hormone detected through an animal response

Selmar Aschheim and Bernhard Zondek developed their reaction in Berlin in the late 1920s.^[1] The test involved injecting urine into immature female mice and examining ovarian changes produced by gonadotropin activity.^[1] A 2014 history of the test describes it as the first modern test for what is now called human chorionic gonadotrophin, or hCG, and as the first such test used at large scale.^[1]

The reaction translated hormone activity in urine into a visible response in an animal. That made an otherwise invisible signal accessible to a laboratory using biological observation. It did not show the fetus directly, which is why the interpretation depended on understanding the origin of the hormone.

A postal service for differential diagnosis

Aschheim and Zondek’s work was introduced in 1927–28, and a Lancet editorial mentioned the reaction in October 1928.^[1] Edinburgh’s service soon advertised a result about a week after receiving urine, generally from two weeks after a missed period.^[1] The system could be standardized and sent through the post, yet its authors stressed that a positive result signified placental activity. That limitation made clinical interpretation as important as the animal reaction itself.

The 2014 historical study argues that adoption reflected doctors’ increasing reliance on laboratory differential diagnosis, not simply replacement of a woman’s knowledge that she was pregnant.^[1] The placental signal had uses in evaluating abnormal tissue and suspected hormonal problems, helping make the service valuable beyond a yes-or-no pregnancy answer.

Placental activity and clinical interpretation

The mechanism is important. hCG is produced by placental tissue; a positive reaction therefore did not directly demonstrate a live fetus.^[1] The same hormone signal could help investigate conditions involving abnormal placental tissue, including some tumours.^[1] In Britain, laboratories received urine by post and performed thousands of tests for doctors in the 1930s.^[1] The result usually took days and required living animals and specialized staff.

Doctors could send a specimen to a specialized center instead of maintaining animals and expertise in every practice. That arrangement separated sample collection, laboratory work and interpretation. It also meant that turnaround included transport and the biological reaction, rather than the immediate result familiar from later home tests.

Changing animals and replacing the bioassay

Later bioassays changed the animal and the turnaround time. The Friedman rabbit test reduced the wait, while frog tests could show ovulation without opening the animal’s abdomen.^[2] A recent historical review notes that frogs could be reused, unlike the routinely sacrificed mice and rabbits.^[2] Immunoassays and then home tests replaced animal bioassays. The phrase “the rabbit died” is therefore a cultural remnant, not a description of how modern tests work.

In mouse and rabbit methods, examination of the ovaries was part of obtaining a result, regardless of whether it indicated pregnancy.^[2] Later frog methods could detect the reaction without the same sacrifice. The change reduced a practical and ethical burden while leaving the central distinction intact: a hormone signal still required interpretation.