That Old Martyr of Science – the Frog!
Updated: Jul 13
There once was a frog lurking in the murky waters of southern Africa. It was an odd-looking beastie and anatomists were fascinated by it. It sported bulging, immovable eyes on the top of its head and black claws on three of its toes. Its slippery skin was marked with little stitch-like sensory organs along its sides. Its hands and feet were so different from that of other frogs that they earned the frog its generic name – Xenopus, from the Greek for “strange foot”. Yet, the African clawed frog, Xenopus laevis, would have remained an oddity in colonial aquaria were it not for the combination of a quirky scientist and a pregnancy test.
The Rise of Xenopus and the Pregnancy Test
The scientist in question was Lancelot Hogben, an eccentric British endocrinologist, who conducted research at the University of Cape Town in South Africa for a few years during the 1920s. Hogben specifically used frogs to answer questions about certain hormones. Once in Africa, he turned to the indigenous amphibians to find a suitable replacement. Xenopus laevis was the obvious choice since it was already widely used in teaching and research in South Africa at the time. It could be found in every farm dam in the area and is also a no-nonsense animal to keep in the lab. Hogben soon realized that Xenopus laevis had even more tricks up its sleeve that made it ideal to work with. Its long breeding season could be prolonged with the help of readily available mammalian hormones. Xenopus are extremely hardy and can reach breeding age six months after hatching. It is said that he liked his new study animal so much that he even named his house “the Xenopus”, where he used to entertain guests.
Although he experimented widely with Xenopus laevis’ reaction to different hormones, it was actually two of his colleagues down the hall, Hillel Shapiro and Harry Zwarenstein, who managed to put two and two together. If gonadotropins, a class of hormones also present in the urine of pregnant women, can induce a female Xenopus laevis to lay eggs, well… wouldn’t the urine of a pregnant woman do exactly that? Shapiro and Zwarenstein reported on this eureka-moment in 1933. In their report, they detailed how the injection of the urine of a pregnant woman under the skin of a female Xenopus laevis would induce her to start laying eggs within the next 18 hours (her being the frog, not the pregnant lady in question). And surprisingly enough, this test was quite accurate. After ten years of tests, Shapiro and Zwarenstein noted that injection of Xenopus with the urine correctly determined pregnancy in more than 98% of cases. One doctor wrote to them to commend their method: “Thank you for your report on the pregnancy test on Mrs. X. You may be interested to know that out of one GP of many years’ standing, one specialist gynecologist and one frog, only the frog was correct.”
This discovery might not seem like much to women in the 21st century, but at the time a rapid pregnancy test was a game-changer for women who had to rely on the examination of their physical symptoms, peeing on sacks of grain in ancient Egypt, so-called piss prophets in medieval Europe and even the dissection of up to five rabbits in the early 1900s to determine whether they were pregnant. The use of the test spread like wildfire across the world and along with it travelled Xenopus laevis. This ‘godsend’, as Hogben once put it to a colleague, was suddenly available, not only to women, but also to researchers all over the world. Within a few decades, publications on Xenopus laevis far outnumbered those on all the other model amphibians combined. By the time the Xenopus test was replaced by home pregnancy tests, the frog was already firmly established in biological research.
Pregnancy testing made Xenopus laevis a readily available, well-studied laboratory animal, but it was the rise of the growing field of developmental biology in the 1940s that allowed Xenopus laevis to become one of the most widely used model animals of all time, even as far away as outer space. Embryologists used Xenopus laevis to elucidate the first steps of embryonic development, including Nieuwkoop & Faber’s Normal Table of the morphology and timing of all 66 developmental stages from fertilization to froglet. Biochemists employed it to study gene activity during early development, ultimately leading to it being the first animal to be cloned. However, it was also genetics that brought an end to Xenopus laevis’ usefulness in the lab. It has four sets of genes (tetraploid) instead of the usual two (diploid), making it trickier than it should be to conduct genetic manipulations. Combined with the fact that modern immunological pregnancy tests had by now fully replaced Xenopus laevis, breeding facilities all over the world started closing their doors in the 1970s.
However, Xenopus was not ready to disappear from the scene. These hardy frogs managed to successfully establish and subsequently become invasive on four continents outside Africa after release into the wild, making it one of the most widely distributed amphibians in the world. Global biological invasions, especially ones at the scale of Xenopus laevis, are ecologically unfortunate events, but they do provide researchers with replicates of populations on different continents, in different climatic regions, with different invasion histories. This can be seen as a kind of “natural experiment” with several independent replicates, if you will. Among others, two South African PhD students have taken up the challenge to add to the long list of Xenopus laevis publications, this time in the light of its status as model invader.
Natasha Kruger specifically uses the tadpoles to figure out how immature stages of animals (as opposed to adults) contribute to invasion success. The description of the Xenopus laevis tadpole stages by Nieuwkoop & Faber have formed the basis of the development of tests, such as the Larval Amphibian Growth and Development Assay (LAGDA) and the Test Guideline for the Amphibian Metamorphosis Assay (AMA), to assess the effects of various living and non-living factors on tadpole shape, size and growth rate.
These detailed descriptions opened the door to delve deeper into the role of tadpoles during invasions, answering questions around predator avoidance strategies, and the effects of environmental changes. For instance, Natasha assessed the effects of translocation on the morphology and development of native Xenopus laevis tadpoles in South Africa. She moved tadpoles from the summer rainfall region to the winter rainfall region in South Africa and vice versa. On a weekly basis, she measured their body size, timing to metamorphosis and survival to determine the effects of living in a foreign environment. She found that both groups ‘matched’ the local tadpoles in morphology and development but not in terms of survival. This shows us that when Xenopus laevis is translocated to a completely opposite climatic region, it adjusts to perform just as well as the local tadpoles but with a lesser chance of survival. Additionally, Natasha found that Xenopus laevis tadpoles can identify and respond to predators (known and unknown) in the invasive range. It is not known whether their response is effective against these predators, but the presence of a response shows their ability to rapidly adapt to their new surroundings. These aspects can contribute to the species’ invasion success. Overall, her study and the many previous studies on Xenopus laevis tadpoles highlight the importance of including tadpoles when studying amphibians, both native and invasive. Indeed, big things often have small beginnings.
Anneke Lincoln Schoeman is more interested in the tiny animals that could travel along with Xenopus laevis. These are the parasites, of course! In its native range, Xenopus laevis harbors a diverse community of many parasite species. So many, in fact, that some refer to it as a parasite taxi. But is this taxi successful in carrying its parasites overseas? That would not seem to be the case. Xenopus laevis has fewer parasites in its newly invaded ranges, which might hint at higher fitness in comparison to parasite-laden native counterparts. This supports a long-standing hypothesis in invasion ecology across many global replicates. In South Africa, Xenopus laevis and its many parasites also serve as an intriguing model to investigate the interactions of these animals both in time and space in the emerging field of co-evolutionary biology. From Anneke’s investigations, it would seem as if parasites change along with their hosts not only over time (thus evolution), but also over geographical distance.
From our work and that of other investigators, it is clear that Xenopus laevis will model for science for a little bit longer, despite having a plus-sized genome. In the eyes of biologists, Xenopus laevis has evolved from oddity to celebrated laboratory animal, to an infamous model for global invasions. In a way, this is also the trajectory of modern science as we enter the Anthropocene.
Natasha Kruger, PhD is a graduate from Stellenbosch University, South Africa, and the University of Claude Bernard Lyon 1, France. Her research interests include Herpetology, Invasion Biology and Evolution. She can be found on Twitter (@NatashaKrugerSA), ResearchGate (Natasha Kruger) and her personal website (AfriXen). Natasha is also active in community outreach and would love to connect with you and your classroom if you’d like to learn more about frogs and their use as model organisms in science.
Anneke Lincoln Schoeman is currently undertaking her PhD study at the North-West University in South Africa. After majoring in entomology, she invaded the field of parasitology. She is especially interested in how the relationships between animals and their parasites change in time and space, which marries her two favourite fields: evolutionary biology and invasion ecology. She can be found on Twitter (@anneke_lincoln) and ResearchGate (Anneke Lincoln Schoeman). You’re welcome to find out more about her research and involvement in community outreach on her very own blog (Outward Eye).
Read more about our work
Kruger, N., Measey, J., Herrel, A. & Secondi, J. 2019. Anti–predator strategies of the invasive African clawed frog, Xenopus laevis, to native and invasive predators in western France. Aquatic Invasions, 14:1–11.
Schoeman, A.L., Kruger, N., Secondi, J. & du Preez, L.H. 2019. Repeated reduction in parasite diversity in invasive populations of Xenopus laevis: a global experiment in enemy release. Biological Invasions, 21:1323–1338.