The First Reliable Hormone-Based Pregnancy Test: Bernhard Zondek

The first reliable hormone-based pregnancy test looked nothing like the plastic sticks sold in pharmacies today. A single analysis required several young mice, days of observation, and an examination of their ovaries. One of the scientists who developed it was Bernhard Zondek, born on July 29, 1891.

A modern pregnancy can be confirmed at home within minutes. A century ago, even a physician could not always diagnose it confidently at an early stage. A missed period, nausea, and physical changes had other possible explanations, while unmistakable clinical signs often appeared much later.

The solution emerged from the new science of hormones: chemical signals that allow organs to regulate one another. Zondek and his colleague Selmar Aschheim realized that the urine of a pregnant woman contained a substance capable of producing visible changes in the ovaries of a laboratory animal.

Five mice instead of one test strip

Zondek worked at Berlin’s Charité hospital, where he studied the relationship between the pituitary gland and the reproductive organs. In 1927, he and Aschheim described a biological method for detecting hormones associated with the anterior pituitary. In 1928, they applied the same principle to pregnancy diagnosis.

A woman’s urine was injected into several immature female mice over three days. Roughly one hundred hours after the first injection, the animals were killed and their ovaries examined. If the sample contained sufficient hormonal activity, the ovaries developed mature follicles, hemorrhagic areas, and corpora lutea—changes that would not normally occur in animals so young.

The procedure became known as the Aschheim–Zondek reaction. Contemporary reports placed its accuracy near 98% when the original protocol was followed carefully. The result, however, took several days, required colonies of specially maintained animals, and depended partly on the laboratory’s experience in recognizing the ovarian changes.

The test did not detect an embryo or prove that a viable fetus was present. It detected hormonal activity from tissue associated with pregnancy. A positive result could therefore also occur in hydatidiform mole, choriocarcinoma, and certain testicular tumors. This apparent limitation later made hormone testing useful in oncology as well as obstetrics.

The right test with an incomplete explanation

Aschheim and Zondek initially believed that the substance they detected was produced by the anterior pituitary gland. The interpretation was understandable because its biological effects resembled those of known pituitary hormones.

It later became clear that the main source was trophoblast—the tissue that contributes to the developing placenta. The molecule is now known as human chorionic gonadotropin, or hCG.

After an embryo implants in the uterine lining, hCG supports the corpus luteum in the ovary. The corpus luteum continues producing progesterone, which maintains the uterine lining and supports the early pregnancy.

Modern test strips look for the same biological signal that Zondek’s mice revealed. What has changed is the detector. Instead of waiting for an entire animal to respond, today’s tests use antibodies that bind selectively to hCG and produce a visible line.

The instrument changed dramatically, but the central diagnostic idea remained the same: pregnancy can be recognized through a molecular signal released by its developing tissues.

From Berlin to Jerusalem

Bernhard Zondek was born in Wronke in the German Empire, now the Polish town of Wronki. He studied medicine in Berlin, received his doctorate in 1919, and trained in obstetrics, gynecology, and endocrinology at the Charité. By the late 1920s, he was a professor and headed a gynecology department at a Berlin hospital.

After the Nazis came to power, Zondek lost his positions because he was Jewish. He left Germany in 1933, worked for a time in Stockholm, and moved to Mandatory Palestine in 1934.

In Jerusalem, he continued his hormone research at the Hebrew University and Hadassah Hospital. His work covered ovarian regulation, pituitary hormones, pregnancy disorders, and hormonally active tumors. He received the Israel Prize in Medicine in 1958 and was elected to the Israel Academy of Sciences and Humanities in 1959.

Zondek died in New York on November 8, 1966. By then, animal bioassays were beginning to give way to faster immunological methods. The principle behind the modern home test nevertheless remained intact: an invisible hormonal signal could be converted into a clear diagnostic answer.