7
A Quick History of Xenopus
A major research thrust for Hogben at the time, which had
begun with Julien Huxley (Huxley and Hogben, 1922), was
hormonal control of color changes in amphibia. He adopted
Xenopus immediately upon his arrival in Cape Town, calling the animal a “godsend” (Hogben, 1998) (p.  101). Not
only were the frogs plentiful, but they were “endowed with
a very striking capacity for colour change” (Hogben et al.,
1931). Moreover, the animals could routinely survive precise removal of the pituitary, allowing him to ask important
questions. In a brief report to the Transactions of the Royal
Society of South Africa in 1930, and in a more thorough
study the following year in the Journal of Experimental
Zoology, he reported that not only did removal of the pituitary disrupt color change but also elicited a profound “retrogression” of the ovaries (Hogben, 1930, 1998). This result
was important because while the pituitary was implicated in
the control of ovarian function, this direct experiment had
not been possible in mammals. Perhaps even more striking,
however, was the fnding that extracts of the pituitary, when
injected into Xenopus, were suffcient to induce ovulation
(Hogben et al., 1931).
It’s worth noting here that the J. Exp. Zool. paper was coauthored together with David Slome and also Hogben’s wife,
Enid Charles, who was pursuing her PhD in Cape Town. Enid
was every bit as compelling a character as her husband, and
she, too, was both an ardent activist and an exceptional scientist. She worked frst on endocrinology and reproductive biology but later emerged as a pioneering demographer and worked
for the World Health Organization (Wargon, 2005); she also
once risked her life in South Africa to smuggle two Bantu men
in the trunk of her car past vigilante checkpoints looking to
lynch the men (Hogben, 1998, pp. 114–115). With the rise of
Apartheid, Lancelot and Enid left South Africa abruptly in the
1930s, with Hogben becoming the chair of social biology at
the London School of Economics, bringing Xenopus with him
(Hogben, 1998, p. 121). Curiously, though their experiments in
South Africa clearly demonstrated that, in principle, Xenopus
could be used as a pregnancy test, this obvious application was
never mentioned in those frst two papers.
Exactly what happened next in this story has been
much debated, but Hillel Shapiro and Harry Zwarenstein
in Cape Town pursued the use of Xenopus as a pregnancy
test, reporting their f ndings frst in the Proceedings of the
Royal Society of South Africa in 1933 (see (Gurdon and
Hopwood, 2000) and then in Nature in 1934 (Shapiro and
Zwarenstein, 1934). In London, Charles Bellerby was simultaneously pursuing the same goal (Bellerby, 1934). Though
Shapiro and Zwarenstein reported their results frst, the test
came to be known as the “Hogben Pregnancy Test” after an
article by the infuential head of the Pregnancy Diagnosis
Laboratory in Edinburgh, Frank Crew (1939). This led to a
lively argument in the pages of the British Medical Journal,
which sadly was never resolved (see Gurdon and Hopwood,
2000). I’ll not re-litigate the issue and instead will simply
concur with J.W.C. Gunn, who—serendipitously presaging a
famous quote by Viktor Hamburger—suggested that “a little
credit be given to the humble batrachian, which seems to
give an invariably correct diagnosis” (Gunn, 1939). Over the
next 20 years or so, the Xenopus pregnancy test became the
worldwide state of the art. Thus, by the mid-20th century,
substantial colonies of Xenopus could be found in several
universities (Van Sittert and Measey, 2016).
Among the most signifcant for this story was the colony at the Utrecht Laboratories in the Netherlands, where
a young Pieter Nieuwkoop pursued his PhD studies under
Nazi occupation during World War II (Gerhart, 1987).
Nieuwkoop described Xenopus as an “important acquisition” for embryologists, noting its robust and rapid development as well as its amenability to microsurgery (Nieuwkoop
and Van De Kamer, 1946). Shortly after, Nieuwkoop and
Faber began the tedious but essential task of creating an intimately detailed normal table for Xenopus ( 1956 ), a sourcebook whose wealth of information is still critical to the
day-to-day work of Xenopus researchers and is available in
a more recent reprinting (Nieuwkoop and Faber, 1994).
Of course, amphibians had already played a central role
in experimental embryology for half a century, but researchers had been restricted to the breeding seasons of their local
species (Beetschen, 2004). Now, Xenopus and the pregnancy test provided not just an amphibian that could be
induced to lay eggs year-round but also one that was already
kept in laboratories across the world. Xenopus then quickly
evolved into a “model organism,” a concept just coming into
focus in the mid-20th century (Leonelli and Ankeny, 2013).
Nieuwkoop, of course, went on to use Xenopus to make a
wide range of seminal contributions to our understanding of
early vertebrate development (Gerhart, 1997, 1999).
The Pregnancy Diagnosis Center in Edinburgh also remained
an important source of Xenopus for developmental biologists,
especially C.H. Waddington and his legions of trainees
(Slack, 2002). Among these was Michaïl Fischberg, who
joined Waddington’s group in 1948. When Fischberg left to
establish his own group at Oxford, he took Xenopus with him
(Gurdon and Hopwood, 2000). Fischberg then had the foresight to isolate mutants of Xenopus that lack nucleoli (Elsdale
et al., 1958), a resource that would have a profound impact on
both developmental and molecular biology. Fischberg, too,
would introduce Xenopus to its most important advocate, a
young PhD student named John Gurdon.
A middling student of biology in school, Gurdon was
admitted to the biology program at Oxford essentially
by accident (Gurdon, 2008). However, during his PhD,
Fischberg put him onto the knotty problem of nuclear totipotency, and the rest is history. The concept of nuclear
transplantation originated with Rauber’s unsuccessful
experiments with frogs and had been attempted several times
over the decades (Beetschen and Fischer, 2004; Rauber,
1886). Fischberg and Gurdon knew that work done in
Rana by Briggs and King suggested that some transplanted
nuclei from somatic cells could sustain development, but
this capacity seemed to be lost at later stages (Briggs and
King, 1952, 1953; King and Briggs, 1954). In what must be
among the most remarkable PhD theses in modern biology,
Gurdon used genetically marked anucleolate mutants in a