How Pregnancy Tests Led to the Decimation of Frog Populations

Published by on November 28, 2023

With readily available pregnancy tests stocked across drugstore shelves, it is hard to imagine a time when determining pregnancy was not so simple a task. Instead of the easy-to-use plastic cartridge we commonly imagine, the earliest reliable pregnancy tests utilised Xenopus laevis, also known as the African clawed frog (Nuwer, 2013). 

This method for identifying pregnancy using frogs was first developed in the 1930s by Lancelot Hogben and his students, Hillel Shapiro and Harry Zwarenstein (Shapiro and Zwarenstein, 1934). While studying the African clawed frog’s camouflage abilities in South Africa, they ran into an interesting response when they injected the frogs with pituitary extract from an ox. To the surprise of the group, the frog started ovulating after the injection (Kean, 2017). Hogben immediately recognized that the ox extract and human chorionic gonadotropin (hCG) were chemically similar, and the idea to use this for pregnancy tests was put into action (Figure 1).

Figure 1. Chicago Sun-Times press photograph from 1952 depicting medical technicians performing frog pregnancy tests. (Olszynko-Gryn, 2018).

The hormone hCG is created by the trophoblast tissue in an early embryo, and is ideal for pregnancy testing as it is only created in women during the first trimester of pregnancy (Betz and Fane, 2023). Named the Hogben Test, frogs were used to detect the presence of hCG in urine, as they would ovulate when exposed to it (Figure 1). Urine samples would be injected into frogs, and after 2 to 8 hours, pregnancy could be confirmed if the frog had produced eggs (Figure 2) (Nuwer, 2013). The Hogben Test was revolutionary as earlier methods would test hCG concentrations by injecting urine into female mice or rabbits, then sacrificing the animal and examining any changes in the ovaries. The Hogben Test was much faster, less harmful to the animals, and less expensive as frogs could be reused (Polack, 1949). While pregnancy testing was reserved for emergencies previously, the more convenient Hogben Test allowed all women to benefit from earlier knowledge of pregnancy. 

Figure 2. Images from an article in the British Medical Journal that helped popularise the Hogben Test among doctors. The image on the left shows a top down view of an ovulating frog. The middle top image shows swelling of the cloaca, an indicator of ovulation. The bottom middle image shows the cloaca of a frog that is not ovulating. The image to the right shows the setup of the test, with a frog in a small tank above a mesh separator. This allowed eggs to drop to the bottom of the tank and be easily identified (Elkan, 1938).

Between the 1930s and 1950s, thousands of frogs were shipped to hospitals all over the world and had established themselves as a staple in medical supply closets (Nuwer, 2013). In the 1960s, chemical pregnancy tests were developed and the Hogben Test became obsolete. Correspondingly, many hospitals simply released their remaining frog stock into the wild (Jones, 2013). Though they did not know at the time, African clawed frogs are carriers of the deadly amphibian chytrid fungus. Released frogs went on to wreak havoc on local ecosystems by spreading the disease, leading to the extinction of more than 200 amphibian species (Jones, 2013).

Their time in hospital labs also established African clawed frogs as important laboratory animals, as they were also used for scientific experimentation. In fact, more than 71 500 frogs were exported for lab use between 1998 and 2004 (Jones, 2013). A lack of regulation on ensuring exported frogs are disease-free has led to challenges in mitigating the environmental impact (Vredenburg, et al., 2013).

The use of the African clawed frog allowed the development of a revolutionary pregnancy testing method, but their release also had devastating ecological repercussions. While research into treatments and conservation is underway, there must be greater pressure to regulate exports and protect frogs. After all, we owe it to our amphibian friends. 

References

Betz, D. and Fane, K., 2023. Human chorionic gonadotropin. In: StatPearls. Treasure Island (FL): StatPearls Publishing. Available at: <http://www.ncbi.nlm.nih.gov/books/NBK532950/> [Accessed 28 November 2023].

Elkan, E.R., 1938. The Xenopus pregnancy test. Br Med J, 2(4067), pp.1253–1274. https://doi.org/10.1136/bmj.2.4067.1253.

Jones, N., 2013. Pregnancy test helped to bring frog-killing fungus to the US. Nature. [online] https://doi.org/10.1038/nature.2013.13013.

Kean, S., 2017. The birds, the bees, and the froggies. Science History Institute. Available at: <https://scihist.com/stories/magazine/the-birds-the-bees-and-the-froggies/> [Accessed 28 November 2023].

Nuwer, R., 2013. Doctors used to use live African frogs as pregnancy tests. [online] Smithsonian Magazine. Available at: <https://www.smithsonianmag.com/smart-news/doctors-used-to-use-live-african-frogs-as-pregnancy-tests-64279275/> [Accessed 28 November 2023].

Olszynko-Gryn, J., 2018. Pregnancy testing with frogs. In: L. Kassell, N. Hopwood and R. Flemming, eds. Reproduction: Antiquity to the Present Day. Cambridge: Cambridge University Press. pp.672–672. https://doi.org/10.1017/9781107705647.084.

Polack, S.S., 1949. The Xenopus pregnancy test. Canadian Medical Association Journal, 60(2), p.159.

Shapiro, H.A. and Zwarenstein, H., 1934. A rapid test for pregnancy on Xenopus lævis. Nature, 133(3368), pp.762–762. https://doi.org/10.1038/133762a0.

Vredenburg, V.T., Felt, S.A., Morgan, E.C., McNally, S.V.G., Wilson, S. and Green, S.L., 2013. Prevalence of Batrachochytrium dendrobatidis in Xenopus collected in Africa (1871–2000) and in California (2001–2010). PLOS ONE, 8(5), p.e63791. https://doi.org/10.1371/journal.pone.0063791.