8
Xenopus
series of papers to convincingly demonstrate the totipotency
of somatic nuclei (Fischberg et al., 1958; Gurdon, 1960;
Gurdon, 1962; Gurdon et al., 1958; Laskey and Gurdon,
1970). These experiments laid the foundation of our modern
understanding of nuclear reprogramming (Gurdon, 2017),
and, together with Shinya Yamanaka, Gurdon was honored
with the Nobel Prize in 2012.
Accordingly, much has now been written about Gurdon
and his work, so I won’t add the story here (Yamada et al.,
2015; Yamanaka and Blau, 2010). I will, however, direct the
reader to some delightful retrospectives by Sir John himself
(Gurdon, 2013a, 2013b). When reading these “memoirs” from
2013, one should bear in mind that in the same year, Gurdon
continued his work on nuclear reprogramming (Miyamoto
et al., 2013) and produced an authoritative review of the current state of the feld (Halley-Stott et al., 2013).
1.4. SOME UNSUNG HEROES OF
EARLY DEVELOPMENTAL BIOLOGY
RESEARCH WITH XENOPUS
Gurdon’s work had an outsized impact on developmental
biology, and I’d argue it also had a big impact on the history of Xenopus. In terms of biology, those high-prof le f ndings obviously helped to spur the frog to widespread use as
a model organism. From the standpoint of history, however,
the glare of those bright discoveries may also have obscured
other work using Xenopus in the mid-20th century, as little
is now written of several other notable discoveries.
For example, nuclear pores were discovered in Xenopus
(Beck and Hurt, 2017). Harold “Mick” Callan, who had built
radar equipment during WWII, worked under Waddington
in Edinburgh in the beginning of his career in biology (Gall,
2003). He would become far more well known for his work
on lampbrush chromosomes, but in 1949 and 1950, with the
help of S.G. Tomlin at King’s College London, he became
the frst to examine the nuclear membrane with “the” electron microscope (Callan et al., 1949; Callan and Tomlin,
1950). Using both Xenopus and Triturus oocyte nuclei, they
described the double layers of nuclear membranes as well
as the nuclear pores for the frst time. They did, however,
mistakenly conclude that the pores traversed only the outer
nuclear membrane. It would take decades for the idea of
nuclear pores to become commonly accepted, but Callan’s
method of exploiting large oocyte nuclei would be crucial to
that effort (Beck and Hurt, 2017; Gall, 2003).
Xenopus also played a key role in our understanding of primordial germ cells, still a murky area in the 1950s. Working
at times with Fischberg, Antoine Blackler developed methods for the transplantation of germ cells in Xenopus, again
using the anucleolate mutant as a marker, and thereby provided the f rst direct experimental demonstration that germ
plasm-containing cells in the very early embryo colonized
the gonad and were responsible for producing the gametes
(Blackler and Fischberg, 1961; Blackler, 1958, 1960). A modifed version of this germ cell transplantation approach was
recently developed for isolating CRISPR-based mutations
in essential genes (Blitz et al., 2016). There are, of course,
numerous other discoveries from this period, but from the
large cast of characters using Xenopus in the middle 20th
century, I’ll discuss two in more detail that I feel deserve
more attention from modern practitioners.
The frst is Elizabeth Deuchar. A PhD student with
C.H. Waddington in Edinburgh, she would publish dozens
of papers from her independent lab and write a handful of
books. Her work included not only of-their-time microsurgical experiments on embryonic induction and somite segmentation (Deuchar and Burgess, 1967; Waddington and
Deuchar, 1953) but also more forward-looking biochemical
studies in embryos (Deuchar, 1956, 1961), as well as early
studies of regeneration in Xenopus ( Deuchar, 1975a ). Later,
she would make the move to mammalian embryos, describing
a decades-ahead-of-its-time method for time-lapse imaging of
gastrula stage rat embryos (Deuchar and Parker, 1972).
Accounts of the time report that she was quiet and shy
(Bellairs, 1980; Fellows of St Hugh’s College, 1980), though
it’s clear that she wasn’t easily intimidated. Her hilariously
scathing letter to Nature taking issue with a paper by
Francis Crick on diffusion in embryos should be required
reading (Crick, 1970; Deuchar, 1970). In the end, time has
proven Crick largely right, but the issue continues to be
studied a half-century later (e.g. Müller et al., 2013), and we
should all admire her lively debating style! Sadly, Elizabeth
Deuchar passed away from cancer in 1979, at the young age
of 52.
Luckily for us, she completed a book in 1975 that provides a remarkably comprehensive accounting of Xenopus
research during the mid-20th century. In the book’s rather
touching preface, she paid tribute to Xenopus and to the
embryos she obtained from tests at the Pregnancy Diagnosis
Center in Edinburgh. She laments, however, that many of
her embryos “alas!—perished in the cold and vibration as I
bicycled with them . . . over the cobbled streets” back to her
lab (Deuchar, 1975b).
Another now-underappreciated pioneer of Xenopus
research is Osamu Nakamura. Nakamura trained under Yo
Kaname Okada, who together with Katsuma Dan established Japan as a powerhouse of experimental embryology
in the frst half of the 20th century (Okada, 1994). In the
1920s and 1930s, Okada and others like Tsuneo Yamada
brought cutting-edge techniques in amphibian embryology
back from France and Germany, and Nakamura’s early successes included improving the methods for vital dye fate
mapping and correcting earlier errors in urodele fate maps,
taking advantage of the fact that “Kyoto is a newt paradise”
(Asashima, 2002). In the 1960s, Nakamura published an
important series of lectures advocating the use of the new
methods of molecular biology for studying the embryo,
though of course this idea was ahead of its time and would
not become a reality for two decades more.
By the 1970s, Nakamura had adopted Xenopus as his
primary research material. In 1971, he used vital dye staining to produce the very frst fate map of the blastula-stage
Xenopus embryo (Nakamura and Kishiyama, 1971). Later
Xenopus
series of papers to convincingly demonstrate the totipotency
of somatic nuclei (Fischberg et al., 1958; Gurdon, 1960;
Gurdon, 1962; Gurdon et al., 1958; Laskey and Gurdon,
1970). These experiments laid the foundation of our modern
understanding of nuclear reprogramming (Gurdon, 2017),
and, together with Shinya Yamanaka, Gurdon was honored
with the Nobel Prize in 2012.
Accordingly, much has now been written about Gurdon
and his work, so I won’t add the story here (Yamada et al.,
2015; Yamanaka and Blau, 2010). I will, however, direct the
reader to some delightful retrospectives by Sir John himself
(Gurdon, 2013a, 2013b). When reading these “memoirs” from
2013, one should bear in mind that in the same year, Gurdon
continued his work on nuclear reprogramming (Miyamoto
et al., 2013) and produced an authoritative review of the current state of the feld (Halley-Stott et al., 2013).
1.4. SOME UNSUNG HEROES OF
EARLY DEVELOPMENTAL BIOLOGY
RESEARCH WITH XENOPUS
Gurdon’s work had an outsized impact on developmental
biology, and I’d argue it also had a big impact on the history of Xenopus. In terms of biology, those high-prof le f ndings obviously helped to spur the frog to widespread use as
a model organism. From the standpoint of history, however,
the glare of those bright discoveries may also have obscured
other work using Xenopus in the mid-20th century, as little
is now written of several other notable discoveries.
For example, nuclear pores were discovered in Xenopus
(Beck and Hurt, 2017). Harold “Mick” Callan, who had built
radar equipment during WWII, worked under Waddington
in Edinburgh in the beginning of his career in biology (Gall,
2003). He would become far more well known for his work
on lampbrush chromosomes, but in 1949 and 1950, with the
help of S.G. Tomlin at King’s College London, he became
the frst to examine the nuclear membrane with “the” electron microscope (Callan et al., 1949; Callan and Tomlin,
1950). Using both Xenopus and Triturus oocyte nuclei, they
described the double layers of nuclear membranes as well
as the nuclear pores for the frst time. They did, however,
mistakenly conclude that the pores traversed only the outer
nuclear membrane. It would take decades for the idea of
nuclear pores to become commonly accepted, but Callan’s
method of exploiting large oocyte nuclei would be crucial to
that effort (Beck and Hurt, 2017; Gall, 2003).
Xenopus also played a key role in our understanding of primordial germ cells, still a murky area in the 1950s. Working
at times with Fischberg, Antoine Blackler developed methods for the transplantation of germ cells in Xenopus, again
using the anucleolate mutant as a marker, and thereby provided the f rst direct experimental demonstration that germ
plasm-containing cells in the very early embryo colonized
the gonad and were responsible for producing the gametes
(Blackler and Fischberg, 1961; Blackler, 1958, 1960). A modifed version of this germ cell transplantation approach was
recently developed for isolating CRISPR-based mutations
in essential genes (Blitz et al., 2016). There are, of course,
numerous other discoveries from this period, but from the
large cast of characters using Xenopus in the middle 20th
century, I’ll discuss two in more detail that I feel deserve
more attention from modern practitioners.
The frst is Elizabeth Deuchar. A PhD student with
C.H. Waddington in Edinburgh, she would publish dozens
of papers from her independent lab and write a handful of
books. Her work included not only of-their-time microsurgical experiments on embryonic induction and somite segmentation (Deuchar and Burgess, 1967; Waddington and
Deuchar, 1953) but also more forward-looking biochemical
studies in embryos (Deuchar, 1956, 1961), as well as early
studies of regeneration in Xenopus ( Deuchar, 1975a ). Later,
she would make the move to mammalian embryos, describing
a decades-ahead-of-its-time method for time-lapse imaging of
gastrula stage rat embryos (Deuchar and Parker, 1972).
Accounts of the time report that she was quiet and shy
(Bellairs, 1980; Fellows of St Hugh’s College, 1980), though
it’s clear that she wasn’t easily intimidated. Her hilariously
scathing letter to Nature taking issue with a paper by
Francis Crick on diffusion in embryos should be required
reading (Crick, 1970; Deuchar, 1970). In the end, time has
proven Crick largely right, but the issue continues to be
studied a half-century later (e.g. Müller et al., 2013), and we
should all admire her lively debating style! Sadly, Elizabeth
Deuchar passed away from cancer in 1979, at the young age
of 52.
Luckily for us, she completed a book in 1975 that provides a remarkably comprehensive accounting of Xenopus
research during the mid-20th century. In the book’s rather
touching preface, she paid tribute to Xenopus and to the
embryos she obtained from tests at the Pregnancy Diagnosis
Center in Edinburgh. She laments, however, that many of
her embryos “alas!—perished in the cold and vibration as I
bicycled with them . . . over the cobbled streets” back to her
lab (Deuchar, 1975b).
Another now-underappreciated pioneer of Xenopus
research is Osamu Nakamura. Nakamura trained under Yo
Kaname Okada, who together with Katsuma Dan established Japan as a powerhouse of experimental embryology
in the frst half of the 20th century (Okada, 1994). In the
1920s and 1930s, Okada and others like Tsuneo Yamada
brought cutting-edge techniques in amphibian embryology
back from France and Germany, and Nakamura’s early successes included improving the methods for vital dye fate
mapping and correcting earlier errors in urodele fate maps,
taking advantage of the fact that “Kyoto is a newt paradise”
(Asashima, 2002). In the 1960s, Nakamura published an
important series of lectures advocating the use of the new
methods of molecular biology for studying the embryo,
though of course this idea was ahead of its time and would
not become a reality for two decades more.
By the 1970s, Nakamura had adopted Xenopus as his
primary research material. In 1971, he used vital dye staining to produce the very frst fate map of the blastula-stage
Xenopus embryo (Nakamura and Kishiyama, 1971). Later