Jewish Invention Myths: The Xenopus Laevis Pregnancy Test

As an addendum to my article debunking the claim that jews invented the pregnancy test (1) I thought I’d delve into a related controversy over who developed what became known as the toad pregnancy test (aka the Hogben test) where the urine of a pregnant woman is injected into a South African toad called Xenopus Laevis and how it reacts indicates whether a woman is pregnant or not.

The controversy here is about who deserves to be awarded priority for the discovery of the Hogben test: is it the British left-wing scientist Lancelot Hogben or the two jewish scientists Hillel Shapiro and Harry Zwarenstein.

It hinges on whether Hogben or Shapiro and Zwarenstein discovered that you could create a successful pregnancy test using Xenopus Laevis as a base.

The most detailed look into the controversy on priority was provided by John Gurdon and Nick Hopwood in their article in International Journal of Developmental Biology in 2000 where they write how:

‘Most of Hogben’s experimental work was in the new field of comparative endocrinology. While in Edinburgh, he had begun studying the physiology of the pituitary gland, using primarily hypophysectomy and the provision of pituitary extracts to investigate the hormonal control of skin colour change in frogs. Once in Cape Town, Hogben took advantage of the local fauna. Following the example of South African physiologists, notably W.A. Jolly, he continued the work, conducted until then on European amphibia, with Xenopus laevis. Such ‘a godsend’ (Hogben and Hogben 1998, p. 101) did he find it that he named his house after the animal. The Communist printer and editor Eddie Roux recalled that, with the ‘brilliant and outrageous’ Hogben as host, ‘Parties at Xenopus were rarely formal’ (quoted in Hogben and Hogben, 1998, p. 215).

With David Slome and Enid Charles, Hogben initiated a programme to investigate various physiological changes following removal of the pituitary. On 17 March 1930, he reported to the Royal Society of South Africa that hypophysectomised female Xenopus suffered ovarian involution, whilst both implantation of glands and injection of ox anterior pituitary extracts induced ovulation (Hogben, 1930). Removal of the anterior lobe also prevented the animals’ characteristic secretion of slime in response to handling. Hogben presented this work as demonstrating more definitively than had been possible in mammals the effect of the pituitary on the ovaries, and generalising it to all land vertebrates (Hogben et al., 1931; on the mammalian studies, see Oudshoorn, 1994). He inspired H. Zwarenstein of the Department of Physiology in Cape Town to come and learn his method of hypophysectomising Xenopus, and Zwarenstein and his student H.A. Shapiro began a series of studies following up issues raised by the research of Hogben and his group (Shapiro and Zwarenstein, 1933).

Hogben’s communication (1930) would later be taken to have shown in principle that Xenopus might be used as an indicator of the presence of gonadotrophins in the urine of pregnant women, but neither this nor the full report (Hogben et al., 1931) mentioned pregnancy testing. He appears initially to have had other priorities, and it was at the outset far from clear that it would prove possible to make Xenopus the test animal of choice. But with pregnancy diagnosis a prominent early product of the reproductive sciences (Clarke, 1998), these endocrinologists can hardly have been unaware of the possibility of clinical application.’ (2)

So, in summary Hogben was experimenting with the physiological changes in Xenopus Laevis – specifically its skin colour – in line with changes in its pituitary gland which then signalled certain endocrine conditions such as pregnancy in late 1920s and wrote about them in a brief report in 1930 and then again in 1931.

However, while he mentioned that pregnancy was one of these conditions; he didn’t specifically mention pregnancy testing which is the basis of Shapiro and Zwarenstein assertion of priority because they specifically mention it in their 1933 report on the subject.

As Gurdon and Hopwood go on to explain:

‘To continue research in reproductive physiology, he imported Xenopus and set up a colony in the basement of his laboratory, a building he described as ‘like a delapidated early-nineteenth-century Baptist chapel’ (Hogben and Hogben, 1998, p. 121). Hogben recruited Charles Bellerby, who had experience with pituitary extracts, to attempt to establish ovulation of Xenopus as a reliable bioassay. This did not simply follow from Hogben’s preliminary work; they had to confirm lack of spontaneous ovulation and determine conditions for a reproducible response. The major threat to the test, however, was Zwarenstein and Shapiro’s report (1933) of ovarian atrophy in unoperated animals kept in captivity. Bellerby (1933) showed that if instead of keeping the frogs in a cold underground room, he housed them in warm and well lit surroundings he could eliminate the ‘captivity effect’ and achieve reliability of testing close to 100% (see further Alexander and Bellerby, 1935). (Rana, incidentally, was found to be wholly unsuitable.) In a preliminary report to the Royal Society of South Africa in October 1933, Shapiro and Zwarenstein announced that in the previous month they had successfully used Xenopus in 35 pregnancy tests. The following spring Nature carried an excerpt from this report (Shapiro and Zwarenstein, 1933) and short papers from both Bellerby (1934) and Shapiro and Zwarenstein (1934) describing this new rapid diagnosis of early pregnancy. Priority for the Xenopus test became publicly contested between Hogben and Zwarenstein when in response to Crew’s (1939) attachment of Hogben’s name to the test, the South African group insisted that they had independently performed it first (Gunn, 1939a,b). Hogben (1939, 1946a,b) claimed that their work derived from his own in South Africa, where he had left members of his laboratory (inconclusively) pursuing a test, and from Bellerby’s, about which he said Zwarenstein had learned on a visit to London. He further accused Zwarenstein of delaying things by the ‘exploit in defective animal husbandry’ (Hogben, 1939, p. 39) which produced the so-called ‘captivity effect’, suggesting that the test required freshly caught animals and so would be useless outside South Africa. The dispute was never resolved (Shapiro and Zwarenstein, 1946; Zwarenstein, 1985).

Shortly after arriving back in Britain, Hogben had sent Crew some Xenopus and encouraged him to investigate their suitability for pregnancy testing (Hogben, 1939). Initially, the Edinburgh Station had difficulty maintaining the frogs, and was perhaps put off by the ‘captivity effect’, but by 1937 Crew was keen enough to import 1500 animals from the Cape. He kept Xenopus by thirties in galvanised metal tanks, transferring frogs overnight into individual glass jars with perforated platforms for the test itself (Fig. 4B). He and others compared Xenopus, mouse and rabbit results, and concluded that ‘the Hogben test’ was quickest and for most purposes the best (Crew, 1939; Landgrebe, 1939). Just one injection of urine containing gonadotrophic hormone into the dorsal lymph sac induced egg-laying 8-12 h later. The Edinburgh laboratory carried out tens of thousands of tests over the next two decades. Other British laboratories offered a similar service, and after the War the frogs were also available for consultation in the basement of the Family Planning Association clinic in Sloane Street, London (Oakley, 1984, p. 97).’ (3)

Now it is clear from the above that what happened as something like this:

1930: Hogben initially reports that Xenopus Laevis’ endocrine system could be used as an indicator for different conditions; one of which is pregnancy.

1931: Hogben fully documents that Xenopus Laevis’ endocrine system could be used as an indicator for different conditions; one of which is pregnancy.

1933: Shapiro and Zwarenstein report they have conducted 35 pregnancy tests using Xenopus Laevis’ endocrine system.

Put another way: Shapiro and Zwarenstein’s claim is based upon their physically performing the first pregnancy test using Xenopus Laevis’ endocrine system in 1933 and Hogben not using the words ‘pregnancy test’ in his two papers of 1930 and 19331 but skipping over the fact that Hogben did mention their potential use as an indicator of pregnancy.

What we can see here is that Shapiro and Zwarenstein have essentially gazumped Hogben’s discovery and presented it as their own – for example we know from Gurdon and Hopwood’s research that Zwarenstein at the very least was closely following Hogben’s work on Xenopus Laevis and came to South Africa primarily to follow in Hogben’s footsteps – and would have almost have certainly read Hogben’s 1930 and 1931 papers on Xenopus Laevis seen his suggestion they could be used to indicate pregnancy and gone away and performed a physical test which proved Hogben right but which then Shapiro and Zwarenstein then claimed as their own much to the chagrin and upset of Hogben which then resulted in a bitter and never-resolved controversy over who should be awarded priority over the discovery.

The truth is while Shapiro and Zwarenstein are often credited as its discoverers; the test they performed is called the ‘Hogben test’ not the ‘Shapiro Zwarenstein test’, (4) which tells us that the scientific community were – and are still - well aware that Shapiro and Zwarenstein unfairly gazumped Hogben and while they did perform the first tests. The tests that they performed in 1933 was based upon Hogben’s discoveries and research from 1930/1931 and they merely proved Hogben right rather than discovering it on their own.

Thus, we can see that jews didn’t invent the Xenopus Laevis pregnancy test either!

References

(1) See my article: https://karlradl14.substack.com/p/jewish-invention-myths-the-pregnancy

(2) John Gurdon, Nick Hopwood, 2000, ‘The introduction of Xenopus laevis into developmental biology: of empire, pregnancy testing and ribosomal genes’, International Journal of Developmental Biology, Vol. 44, p. 45

(3) Ibid., p. 46

(4) Jesse Olszynko-Gryn, ‘When pregnancy tests were toads: The Xenopus test in the early NHS’, Wellcome History, Winter 2013, p. 2