From mouse ovaries to African frogs: the birth of the modern pregnancy test

Ever since the first woman missed her period, humanity has wanted a reliable pregnancy test. Despite the modern pregnancy test’s ubiquity, it was only in the last few months, when I received a positive test result myself, that I thought to look into the history of how the modern home pregnancy test came to be.

While researching this article, it struck me that my mother, when pregnant with me, would have used an at home pregnancy test, but it would have looked nothing like the ones we have today. Her mother, on the other hand, when pregnant with her, would have needed to see a doctor to discover she was pregnant. The modern home pregnancy test is a surprisingly recent invention. As succinctly put by Erin Maglaque in an article for the London Review of Books, “Nasa launched a chimpanzee into space before women had access to reliable… home pregnancy testing”¹.

Ancient civilisations developed their own testing methods. In particular, a papyrus found in Egypt and dating from 1,500 to 1,300 BCE described one such test. A pregnant woman would urinate on cereal seeds (e.g. wheat, barley or buckwheat), if the seeds sprouted then the woman was pregnant. Surprisingly, this test has been verified using modern scientific methods, with 70% of urine samples from pregnant women stimulating germination². It is thought that this effect is due to an increased concentration of oestrogen in the urine of pregnant women initiating germination and stimulating plant development.

1927 was when the first scientific leap forward was made in terms of detecting pregnancy. In particular, two German scientists, Selmar Aschheim and Bernhard Zondek, discovered that the urine of a pregnant woman contained a hormone, which is now known as human chorionic gonadotropin (hCG). They further found that, due to the presence of hCG, injecting this urine into an immature female mouse caused physiological changes that could be determined visually by euthanising the mouse and then dissecting it and examining its ovaries. In particular, if the mouse had been injected with urine from a pregnant women, the ovaries of the mouse would become enlarged and red dots would be visible thereon, due to maturation of the ovaries and haemorrhage into the ovarian follicles. Additionally, luteinization would take place, this is the process by which a temporary gland, called a corpus luteum, would form in the ovary after ovulation to prepare the uterus for a potential pregnancy. Corpus luteum would be identified as small yellow dots on the ovaries^3,4. This testing method became known as the Aschheim–Zondek test (A–Z test).

In 1930 a British scientist, called Lancelot Hogben, found that if an African clawed frog (Xenopus laevis) was injected with the urine of a pregnant woman it caused the frog to spontaneously lay eggs⁵. The test was found to be highly reliable, with one study finding that for 1,000 cases tested there were no false positives and only 11 false negatives⁶. The Hogben test also provided a result more quickly than the A-Z test, within 2 to 8 hours for the Hogben test as opposed to about 100 hours for the A-Z test². Additionally, the test did not require the frogs to be killed, and they could be reused in further tests. Accordingly, the Hogben test soon became the world standard.

It took 30 years before the next advancement in pregnancy testing was discovered. In 1960, two Swedish scientists, Leif Wide and Carl Axel Gemzell, developed an immunological pregnancy test. The test comprised providing a solution in a transparent tube, the solution comprised (i) red blood cells from sheep coated in hCG, (ii) an antibody specific to hCG, and (iii) urine provided by a woman who may or may not be pregnant. If the woman was not pregnant then the antibody would bind to the hCG on the red blood cells, causing agglutination. This would appear as a uniform, opaque, diffuse sediment at the bottom of the tube. Conversely, if the woman was pregnant then the antibody would bind to the hCG which was present in the urine sample, and would inhibit agglutination. The red blood cells would then diffuse to the bottom of the tube, where they would appear as a reddish-brown ring. The Wide-Gemzell test was found to be 98% accurate⁶. While the Wide-Gemzell test was widely adopted, it was still conducted by scientists in labs. Accordingly, the entire process of a woman providing a doctor with a urine sample, the sample being shipped to the lab, and the result being relayed back to the doctor took a considerable amount of time.

In 1967, Margaret Crane, an American product designer, was working at Organon Pharmaceuticals. She saw the Wide-Gemzell test being conducted in Organon’s labs, and had the realisation that this test could be conducted by women at home. She developed her own prototype and took it to the company. At first, Crane’s idea was not warmly received. As reported in the New York Times:

“The company’s market was doctors, and doctors would hate this product that made their services seem less necessary. On top of that, her managers seemed terrified by scenarios in which hysterical women killed themselves. “What if a senator’s daughter, unmarried, found she was pregnant and jumped off a bridge?” one asked. “The company would have to go under for that.””⁷

However, Organon’s parent company in the Netherlands thought Crane’s idea was worth exploring. Other designs for a home pregnancy test were considered, but it was Crane’s that was ultimately selected. This diagnostic test was protected with a US patent (US 3,579,306).

Crane’s at-home pregnancy test was a hit. However, it required a user to wait two hours before they got a result. It was also very sensitive, and could produce a false negative result if it was moved or even placed near an operating washing machine. Accordingly, there was still room for improvement.

It took two further innovations to develop the modern pregnancy test. The first innovation was developed in 1980 by Paul Davis and Philip Porter, British scientists working for Unilever. Davis and Porter developed an assay that used monoclonal antibodies (mAbs) to bind a target hormone to a solid support and to further bind a detection marker to the solid support. The detection marker could then be used to infer the presence of the hormone of interest (e.g. hCG). This innovation was protected by European Patent No. EP0042755.

The second innovation was developed in 1987 by Keith May, Michael Prior and Ian Richards, three further British scientists also working for Unilever. May, Prior and Richards designed an assay architecture which caused the test steps required in Davis and Porter’s method to happen automatically and in the correct order. This further innovation was protected by European Patent No. EP0291194, the first patent for a lateral flow test.⁸

The Clearblue lateral-flow pregnancy test was released in 1988 and rapidly became the market leader. It is worth noting that this innovation is clearly not restricted to the field of detecting pregnancy, as anyone who can remember the covid pandemic will attest.

While various modifications have been made to the pregnancy test in the intervening 30+ years, e.g. providing digital tests, these tests still use the same underlying technology developed in the 1980s. From 1927 to 1988, the modern pregnancy test was just over 60 years in the making. From mouse ovaries to African frogs, the story shows that innovations can come from unlikely places. Furthermore, it can take multiple innovations developed over time to reach a perfected product.

[1] https://www.lrb.co.uk/the-paper/v47/n07/erin-maglaque/frog-free

[2] https://pmc.ncbi.nlm.nih.gov/articles/PMC10525168/#:~:text=In%20Egyptian%20papyri%20dating%20from,that%20the%20woman%20was%20pregnant.

[3] https://pmc.ncbi.nlm.nih.gov/articles/PMC5906949/#:~:text=The%20discovery%20of%20human%20chorionic,be%20commercially%20available%20even%20today.

[4] https://embryo.asu.edu/pages/aschheim-zondek-test-pregnancy

[5] https://www.theatlantic.com/science/archive/2017/05/how-a-frog-became-the-first-mainstream-pregnancy-test/525285/

[6] https://journals.co.za/doi/pdf/10.10520/AJA20785135_43336

[7] https://www.nytimes.com/2016/07/31/opinion/sunday/could-women-be-trusted-with-their-own-pregnancy-tests.html

[8] https://www.cytivalifesciences.com/en/us/knowledge-center/lateral-flow-test-history?srsltid=AfmBOorgjNKo7pNnlh_YkNVQRuMHIJa8KKsEhsWRcbww4lltiuLQQ77X