Biochemists' Study of Embryonic Development in the 1930s

Between Biochemists and Embryologists – The Biochemical Study
of Embryonic Induction in the 1930s
RONY ARMON
Jacques Loeb Centre for the History and Philosophy of the Life Sciences,
Department of Philosophy
Ben-Gurion University of the Negev
P.O. Box 653, 84105 Beer-Sheva
Israel
E-mail: armonr@bgu.ac.il
Abstract. The discovery by Hans Spemann of the ‘‘organizer’’ tissue and its ability to
induce the formation of the amphibian embryo’s neural tube inspired leading
embryologists to attempt to elucidate embryonic inductions’ underlying mechanism.
Joseph Needham, who during the 1930s conducted research in biochemical embryology,
proposed that embryonic induction is mediated by a specific chemical entity embedded
in the inducing tissue, surmising that chemical to be a hormone of sterol-like structure.
Along with embryologist Conrad H. Waddington, they conducted research aimed at the
isolation and functional characterization of the underlying agent. As historians clearly
pointed out, embryologists came to question Needham’s biochemical approach; he
failed to locate the hormone he sought and eventually abandoned his quest. Yet, this
study finds that the difficulties he ran into resulted primarily from the limited conditions
for conducting his experiments at his institute. In addition, Needham’s research
reflected the interests of leading biochemists in hormone and cancer research, because it
offered novel theoretical models and experimental methods for engaging with the
function of the hormones and carcinogens they isolated. Needham and Waddington
were deterred neither by the mounting challenges nor by the limited experimental
infrastructure. Like their colleagues in hormone and cancer research, they anticipated
difficulties in attempting to establish causal links between complex biological
phenomena and simple chemical triggering.
Keywords: Joseph Needham, Conrad Waddington, the Spemann organizer,
embryology, biochemistry, Cambridge, scientific disciplines, model organisms
Journal of the History of Biology Ó Springer 2010
DOI 10.1007/s10739-010-9266-0

Introduction
The problem of how the amphibian organizer tissue induces the for-
mation of the main body axis in embryonic development has captured
the interest of embryologists and the general biological research com-
munity since its discovery in 1924 (Hamburger, 1988; Maienschein,
1997; Gilbert, 2001; Sander and Faessler, 2001). Leading biologists,
primarily zoologist Charles M. Child, claimed that metabolic gradients
commencing from the organizer was the cause of its inductive effects.
And yet, even suggestions that the organizer induces by transmitting
ultra-weak ultraviolet radiation or bio-electric currents were not over-
ruled (Needham et al., 1934, pp. 393–395; Brachet, 1986; Beloussov,
1997; Alexandre, 2006). Whereas Paul Weiss and other theoretically-
inclined biologists posited induction as merely contributing to a
‘‘morphogenetic field’’ of interactions governing differentiation, leading
embryologists still considered the organizer to be a central agent and the
problem of induction as deeply confounding (Waddington and Schmidt,
1933; Harrison, 1933; Weiss, 1935; Haraway, 1976; Hamburger, 1988,
pp. 134–135; Horder, 2001; Thieffry, 2001; Gilbert, 2003). Yet further
studies, conducted in the early 1930s, only exacerbated the confusion
concerning the mechanism sought. Experiments conducted by Johannes
Holtfreter in Otto Mangold’s laboratory in Berlin and in parallel by
Spemann and his colleagues demonstrated inductions by minced, cru-
shed, dried, heated, or alcohol-extracted organizer tissue and also that
such treatments conferred induction capabilities on livers, kidneys and
other adult tissues (Hamburger, 1988, pp. 93–115). Neither of the the-
ories existing could explain why organizer tissues losing much of their
properties still induce and why the other tissues examined harbor
inducing capabilities.
However, for one investigator, the Cambridge biochemist Joseph
Needham (1900–1995), Holtfreter’s recent findings signaled a way out of
the maze. Needham’s primary quest was to establish the biochemical
study of embryonic development. During the 1920s and 1930s, he
studied embryonic metabolism and the chemical properties of the
developing egg, and in 1931, published an encyclopedic monograph
(Chemical Embryology) summarizing the known facts on the biochem-
istry of the developing embryo (Needham, 1931a; Gurdon and Rod-
bard, 2000; Armon, 2010). Needham saw the findings of inductions by
extracted tissues as indicating a breakthrough in ‘‘the borderline field of
biochemistry and experimental biology,’’ because they suggested that
embedded biochemical factors, rather than the tissues’ structures as a
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whole, govern their inducing capacity (Holorenshaw, 1973, p. 7).
Believing that biochemists would be drawn into teaming up with
experimental biologists in studying the phenomena, Needham pro-
claimed the organizer tissue’s ‘‘further elucidation along physico-
chemical lines’’ as ‘‘perhaps the outstanding problem of embryology’’
(Needham, 1935a, p. 456). Hypothesizing that the factor responsible for
the organizer’s effect was a hormone-like entity, similar in structure to
recently-discovered sterols, he commenced research towards its identi-
fication and functional characterization.
Conrad H. Waddington, who was the prime experimental embryol-
ogist in Britain, joined Needham and together they led the biochemical
analysis of the organizer phenomena over the next 6 years. Their team,
which included Needham’s wife, the muscle biochemist Dorothy Moyle
Needham and other researchers recruited for this project, tested
induction by sterol-holding fractions from amphibian and liver tissues
as well as available hormones and carcinogens. They succeeded in
demonstrating inductions thereby supporting Needham’s hypothesis,
yet embryologists who performed similar tests demonstrated that
diverse chemical substances are capable of inducing. While Needham
took their results seriously, he remained certain that his biochemical
approach was crucial for understanding the organizer’s effect. However,
after years of intensive experimentation (1933–1939), he conceded fail-
ure to obtain his goal and abandoned the quest; his program petered out
without any followers. While Needham had productive ideas about how
the organizer works and while the research approach he proposed was
novel and pioneer, he managed to advance only to a limited extent.
Historians surveying the biochemical search for the identity of the
organizer, and in particular Needham and Waddington’s program,
highlight the quest as courageous but also place emphasis on its final
failure. Scott Gilbert claims that the biochemical approach was ham-
pered by its assumption of a single ‘‘master molecule,’’ which embry-
ologists found too simplistic for explaining induction (Gilbert and
Saxe´ n, 1993). According to Jan Witkowski, the organizer program was
a pioneering attempt to analyze embryonic development biochemically,
yet the contemporaneous level of biochemical knowledge and technique
limited the quest (Witkowski, 1985, 1987). Viktor Hamburger and Tim
Horder claim that failure to locate a specific factor and recognition of
the complex process of neural-tube formation led embryologists to focus
on the reacting tissue rather than the inducing stimuli (Hamburger,
1988; Horder, 2001). Donna Haraway and Pnina Abir-Am counted
Needham and Waddington among researchers who aimed at explaining
BETWEEN BIOCHEMISTS AND EMBRYOLOGISTS

embryonic development mechanistically but in a non-reductive manner,
yet as following an organicist approach which was soon abandoned
(Haraway, 1976; Abir-Am, 1987, 1991). Needham is cited as a leading
figure among those who participated in the so-called ‘‘gold-rush’’ for
finding the secret mechanism of induction, attempting to obtain – but
finally relinquishing – a chemical explanation to the phenomena.
While current historiography is rich in describing Needham’s theo-
retical motivations and his efforts at deciphering the key embryological
riddle of his time, little is written about the relevance of his research to
biochemists. In a similar manner, historical studies of Waddington’s
contributions to embryology focus primarily on his studies of the avian
organizer center and on contributions he made from the 1940s onwards
to developmental genetics and evolutionary theory. They relate his pro-
ject with Needham only in passing (Robertson, 1977; Yoxen, 1986; Hall,
1992; Stern, 2000). However, as historiographical reconstructions of
other research programs – such as T.H. Morgan’s program in Drosophila
genetics and the endocrinological research conducted by the Organon
Company – highlight, theoretical aims can be achieved only as long as the
skills, tools and research materials needed for experimental tests are at
hand (Clarke, 1987; Fujimura and Clarke, 1992; Kohler, 1994; Oud-
shoorn, 1994). While Needham targeted an embryological problem, he
worked at a biochemical institute with a biochemical approach. Yet, little
can be gauged from current scholarship concerning his ability to anchor
his research in his home discipline. Historiographies of biochemistry at
Cambridge place Needham as expanding biochemistry towards problems
in embryology, but say little about how his program reflected concerns of
the biochemists with which he collaborated and of those who worked at
his side (Kohler, 1982, Chap. 4; Weatherall and Kamminga, 1996).
This study, which employs Needham’s archival and published
records for a detailed reconstruction of his program, reveals that its
relevance for biochemists was crucial in promoting and in holding up
his study.1
The organizer program at Cambridge experienced difficulties
primarily because researchers at Needham’s institute were only mini-
mally interested in his initiative, and the institute itself possessed neither
the infrastructure for the hormone’s isolation nor access to the many
embryos needed for testing its effects. However, biochemists elsewhere,
who were studying sterol hormones and analog substances, found
Needham’s research useful for examining the biological functions of the
substances they isolated. Like Needham and Waddington, they
1
I examined both Needham and Waddington’s archives, but only Needham’s
archive documents their studies on the amphibian organizer.
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encountered difficulties in attempting to explain on a molecular level the
biological functions they investigated. While leading embryologists
questioned the biochemical approach to the organizer problem, the
biochemists with whom he collaborated regarded his views to be plau-
sible and deemed his experiments fruitful. With their support he
bypassed institutional limitations, though only to a limited degree.
Sterols and Inductors
Needham began exploring the physico-chemical basis of embryonic
induction at a time when scientific and industrial interests in sterol
hormones and vitamins expanded significantly. Following advances in
lipid chemistry and discoveries in endocrinology and nutrition science
during the 1920s, biochemists isolated and characterized active biolog-
ical sterols and studied their chemical structures and physiological
functions. By the early 1930s, the respective roles of Vitamin D in bone
development and of estrogens in inducing estrous were well established,
and significant efforts were invested in the chemical and physiological
characterization of these and other sterols. Biochemists and physiolo-
gists saw the newly-discovered biological factors as bearing the promise
of new preventive and ameliorative cures, and their research efforts
enjoyed the collaboration and support of leading clinicians and drug
manufacturers (Gaudillie` re, 2004; Oudshoorn, 1994; Rasmussen, 2002;
Kamminga, 1998; Weatherall, 1990, pp. 83–102, 117–140).
British chemists and biochemists played a central role in the study of
sterol molecules and in elucidating their chemical structures and physi-
ological effects. As with diverse therapeutically-related research pro-
grams, the Medical Research Council (MRC) promoted hormone and
vitamins studies, assisting companies and their collaborating scientists
with initiating clinical trials and in the standardization of their products.
Working primarily through the MRC, pharmaceutical companies col-
laborated with a host of clinical and basic research institutes, including
the MRC’s own National Institute of Medical Research (NIMR), the
Lister Institute, hospitals’ clinical laboratories, research labs in medical
schools, and academic departments of physiology and biochemistry
(Quirke, 2007, Part 1; Williams, 2005). Guy F. Marrian, of UCL’s
Department of Physiology and Biochemistry, and Ernest C. Dodds,
director of the Courtauld Institute of Biochemistry at The Middlesex
Hospital in London, conducted pioneer isolation, synthesis and testing of
female sex hormones and their analogs. Otto Rosenheim, who worked at

the NIMR, as well as leading organic chemist, Isidor M. Heilbron,
studied the chemical structure and physiological effect of vitamin D.
These and other scientists collaborated with local companies, which by
the early 1930s placed both vitamin D and sex hormones as commercial
preparations, and in turn gained from these companies ample materials
for their chemical analyses (Rosenheim and Webster, 1928, p. 1426;
Marrian, 1929, p. 1098; Anonymous, 1933; Morton, 1972; Dickens, 1975;
Jones, 1992; Wolf, 2004). And while scientists tested novel products, they
presented fundamental discoveries as well: In 1932, Rosenheim and his
colleague, Harold King, revised the structural formula of sterols. Their
finding was confirmed by the structural studies of J.D. Bernal and became
accepted worldwide by leading researchers in the field (Rosenheim and
King, 1934; King, 1956, pp. 260–263).
Needham was inspired by leading investigators in the rapidly-
developing study of sterol substances, some of whom were his close
colleagues. Rosenheim advised him from an early stage of his career
(Rosenheim, 1923). Bernal shared Needham’s biological and political
interests (Werskey, 1978; Abir-Am, 1987). Solly Zuckerman and
Bertold P. Wiesner, who studied hormonal influences on sexual differ-
entiation and behavior, became his acquaintances (Zuckerman, 1932;
Weisner, 1933; Needham, 1938a).2
Developmental geneticist Leslie
Dunn, who deemed Needham’s work in chemical embryology pio-
neering, had published a series of studies demonstrating the crucial role
of vitamin D as an agent in bone development (Needham, 1931a,
pp. 1360–1363; Marie, 2004). Needham hoped that identifying the
hormone underlying the organizer effect would ensue with similar vigor
and success as that which characterized the discovery of other func-
tional sterols. ‘‘Twenty years ago,’’ he wrote, ‘‘it would have been dif-
ficult, if not impossible, to conceive of a crystalline vitamin in a bottle’’
(Needham, 1931a, pp. 1626). But following the success with vitamin D,
‘‘it is probably not fantastic to picture, no doubt in the remote future,
the amphibian organizer in a crystalline state.’’
In fact, the recent excitement vis-a`-vis sterol hormones bolstered in
Needham an earlier interest in the role of hormones in morphogenesis.
Back when he was writing Chemical Embryology, he proposed that
induction may be a hormonal effect. For that matter he relied on
findings, published in 1912 by J.F. Gudernatsch and a decade later by
2
Lectures on sex hormones and their physiological and behavioral effects abounded
in the scientific conferences that Needham attended (Programs of annual conferences of
the Society of Experimental Biology and the Biochemical Society, 1934–1936. Need-
ham’s Papers, Cambridge University Library, files J.234 and J.14).
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Needham’s colleagues, Julian Huxley and Lancelot T. Hogben, that
thymus and pituitary extracts induce metamorphosis in amphibian
embryos (Churchill, 1993). Metamorphosis is a radical morphogenetic
process. Within a short time, the tadpole completely alters its form and
the functions of its transformed parts. That such a transformation could
be induced by a hormone suggested to Needham that embryonic
induction could be caused in a similar manner (Gudernatsch, 1932;
Needham, 1931a, pp. 468, 565, 1335–1358, 1348–1349, 1626–1627). He
called embryonic hormones ‘‘biochemical policemen,’’ assuming that
they direct development along specific pathways (Needham, 1931a,
pp. 1358). Confident that embryonic induction could be triggered by
sterol-like hormone embedded in the organizer tissue, Needham began
to aim at its isolation and characterization.
Concurrently, in other laboratories at Cambridge, Waddington was
making significant advances in the study of embryonic induction. He
had to juggle the Cambridge zoological department and the private
Strangeways Research Laboratory (SRL), in order to conduct his
experiments. Nevertheless, despite precarious institutional settings,
Waddington made significant advances in the study of induction,
identifying an inducing organizer-like tissue in avian embryos (Stern,
2000). In parallel, he visited Spemann’s and Mangold’s laboratories to
learn the techniques for experimenting with amphibians, familiarizing
himself with both the theoretical and empirical aspects of their field of
research (Waddington et al., 1936, p. 174; Yoxen, 1986). Needham and
Waddington shared an interest in embryology and more broadly, an
interest in explaining the organization in biological systems, and in
1932, they teamed up with theoretical biologist Joseph H. Woodger,
Bernal and mathematician Dorothy Wrinch to establish a forum
(known as the ‘‘Theoretical Biology Club’’) for discussing these prob-
lems (Abir-Am, 1987, 1988). It was around that time that Needham
proposed the biochemical quest, and Waddington, ready with the nee-
ded biological knowledge and technique, joined and became co-leader
of the organizer research (Waddington, 1932).
Needham and Waddington’s program initiated with a visit during
the spring of 1933 to leading centers of experimental embryology in
Germany. Needham visited Spemann’s Laboratory in Freiburg, while
Waddington, who conducted most of the experiments, worked on them
alongside Holtfreter in Mangold’s laboratory. By extracting the orga-
nizer tissue and testing the ability of extracts and sterols-holding frac-
tions to induce neural tube formation, Waddington hoped to gain
insight into the characters of the inducing component. However, while

he was assisted by Mangold’s staff and facilities, he managed to obtain
only preliminary results. Waddington was hampered by difficulties with
the extraction methods and the preparation of implants from the sub-
stances extracted, and by toxicity to the embryos of certain reagents. He
managed to obtain only a few positive results, demonstrating only
partial formation of neural tubes. Nevertheless, the experiments per-
formed sufficed to demonstrate inductions by cell-free extracts and by
ether soluble fractions (Waddington, 1933; Needham et al., 1934). The
ability to demonstrate inductions despite many possible artifacts per-
suaded Needham and Waddington that they had pursued a correct
path.3
While still hesitant in publications, Needham was not so in sci-
entific addresses. In the summer of 1933, just after his return from
Germany, he addressed the Third International Congress for Experi-
mental Cytology (Cambridge) and expressed conviction in the chemical
identity of the inductor molecule.4
A colleague wrote to him that
‘‘several people came back from Cambridge with the story that at the
cytology congress you had been breaking fresh ground and almost
know what the organizer was made of’’ (Wells, 1933).
Needham and Waddington planned further extractions from bio-
logical sources while they simultaneously prepared for the testing of
sterols and similar substances for induction capabilities. The second
strategy supplemented the first because it promised a direct demon-
stration of the ability of sterols to induce; in addition, it overcame
potential objections that inductions by biological extracts resulted from
impurities retained in tissue samples (Waddington et al., 1934). Grad-
ually, the testing of chemical analogs became crucial because amphibian
embryos, which formed the natural choice as a biological source, could
not be employed for that cause. In Germany and during their initial
experiments at Cambridge, Needham and Waddington made some
attempts to extract the hormone directly from amphibians, yet they
found that thousands of embryos were needed for securing a single
3
In their first report, sent as correspondence to Nature, Needham and Waddington
cited two additional factors as potential hindrances to positive results, even when
implantations went well. The first cause for concern was possible modifications to the
inducing substances brought about by the cumbersome extraction procedure. A second
concern touched on the limited ability of the factor to diffuse from the implant to the
target tissue (Waddington et al. 1933).
4
Needham was a member of the organizing committee of the congress. While in
Germany, and just after he received the preliminary results, he made sure that his paper
would be squeezed into the program (Needham, Draft letter to Vice Chancellor, un-
dated; H.B. Fell to Needham, 29 May 1933; Annotated congress handbook, Joseph
Needham’s Papers, Cambridge University Library, files A.88 and H.11).
RONY ARMON

active sample – and those were just not available.5
While Needham
began using liver tissues, which Holtfreter had shown to induce and
which were available in significant quantities, he pursued the testing
chemical analogs as well.
Already at an early stage of Needham’s research, he convinced his
colleagues to send him sterol samples from their stocks to test for
induction capabilities. Responding to a missive Needham sent while in
Germany, Rosenheim wrote that the facts noted in the letter as already
discovered warrant the hope that the substance responsible for the effect
may be isolated in the near future (Rosenheim, 1933). Harold J.
Channon, the Chair of the Biochemical Department at Liverpool
University, who focused his research on sterol metabolism in the liver
(Channon et al., 1934; Pitt, 2003), sent Needham samples from a liver
fractionation he conducted.6
Marrian sent him samples of sex hormones
while Rosenheim and Francis H. Carr, the BDH’s director, sent samples
of vitamin D analogs. The BDH was their major producer in Britain
(Kamminga, 1998, p. 95) and Carr promised Needham the collabora-
tion of his staff in case the samples sent were found to be active (Carr,
1934; Needham et al., 1934, p. 419; Waddington et al., 1935, p. 308).
Leading biochemists studying sterol hormones and vitamins responded
favorably to the idea that induction is mediated by a molecule similar to
the ones that they investigated.
Biochemists studying carcinogens, primarily James W. Cook from
the Royal Cancer Hospital in London, were also interested in Need-
ham’s research and contributed to his cause. Cook worked on Ernest
Kennaway’s team, which focused on the cause of coetaneous cancer
caught by workers using pitch, tar, or tarry compounds (Kennaway,
1924; Austoker, 1988, pp. 120–123; Luch, 2005). In the early 1930s, the
program developed into a systematic attack on the chemical basis of
carcinogenesis, and over the course of that research it was found that
carcinogens isolated from coal tar, classified as polycyclic aromatic
hydrocarbons (PAHs), had structures that were similar to the sterol
backbone. As the structures assumed for PAHs and for sterols were
similar and because both embryogenesis and carcinogenesis involve
5
See Needham et al. 1934, pp. 402–404; Waddington et al. 1935, p. 303 and below.
6
In 1934 Needham heard Channon presenting his recent results in the annual
meeting of the Biochemical Society. Needham’s annotations include this telling sen-
tence: ‘‘Please, Please, give us some of all fractions…’’ (Agenda of meeting of the
Biochemical Society, 13 Oct 1934. Joseph Needham’s Papers, Cambridge University
Library, file E.148).

morphological changes, Needham’s hypothesis implied that both bio-
logical phenomena may be induced by similar substances. Cook fol-
lowed Needham’s research with interest, supplying him with samples
from his stock for testing their effects on embryonic induction (Cook
et al., 1932; Cook, 1934; Robertson, 1976).
Yet, while Needham convinced leading biochemists of the plausi-
bility of his hypothesis, he knew better than to attempt to persuade
embryologists that induction by the organizer resulted merely from
hormonal triggering. Embryologists, including Waddington, conceptu-
alized neural tube formation as depending on the state of the induced
and neighboring tissues, rather than merely on the organizer’s effect.
Waddington defined the concept of the ‘‘individuation field’’ as denot-
ing a whole set of interactions by which the induced tissue reaches its
differentiated state, and dedicated much of his parallel studies towards
elucidating these very interactions (Waddington, 1934a, p. 216; 1934b,
pp. 221–222). Accordingly, Needham and Waddington claimed that the
hormone they sought was crucial only as a trigger – as ‘‘an evocator’’ of
a complex multi-factor process (Needham et al., 1934, pp. 408–410).
Distinguishing ‘‘evocation’’ from ‘‘individuation,’’ they could focus on
the triggering agent while avoiding potential criticism of reducing a
complex biological phenomenon to the activity of a single agent. At
the same time, making that distinction did not reduce the biochemical
relevance of their study, because their partners were also studying
‘‘evocators’’ of biological phenomena. Like Needham, they showed
hormones and carcinogens to be stimulants of complex events, and
could say little about the casual mechanism linking triggers with their
effects.7
Daring yet cautious, Needham and Waddington felt armed with
an adequate working hypothesis to embark on the riddle of embryonic
induction. It minimized potential objections by expert embryologists
without compromising the biochemical importance of their experiments.
Team and Procedure
While overcoming theoretical hurdles with little effort, Needham
encountered significant practical difficulties in attempting to establish
his research program. His first problem was in recruiting biochemists for
handling tissue extractions and preparing them for implantation,
because apart from Dorothy Needham, other researchers from his
Institute could not be lured to join. Needham’s chemical embryology
7
See Martini and Pecile, 1964 and below.
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stood alongside the studies of Marjory Stephenson in bacterial metab-
olism, Malcolm Dixon in enzymology, and Ernest Baldwin in com-
parative biochemistry, in exploring novel fields of biochemical research.
And yet his colleagues were mainly concerned with the study of inter-
mediary metabolism and with the development of novel methods for the
task and had little motivation for getting involved in his challenging
program. Even Dorothy’s collaboration was limited, because she – like
her colleagues – was primarily committed to a highly demanding line of
metabolic research. However, Joseph’s scientific reputation and aca-
demic status greatly assisted him in recruiting biochemists from other
places. He was the recognized founder of chemical embryology, which
many accepted to be an important field of biochemical research. As a
result, in 1932, he was awarded the official fellowship of his college and
honored with the Doctor of Science degree. Most important, just prior
to his travel to Germany, in the spring of 1933, Needham was appointed
Reader in Biochemistry, positioning him as second-in-command to
Frederick G. Hopkins, the institute’s renowned director (Cambridge
University Registry, 1932; Needham, 1932, 1933a). Needham’s
esteemed stature and scientific prestige allowed him to recruit
researchers and research students from abroad, thereby compensating
for the limited interest shown by his colleagues.
Rudolf Lemberg and Wiktor W. Nowinski, biochemists who were
eager to conduct research at Cambridge, formed the backbone of
Needham’s team. Lemberg arrived in 1934 from Heidelberg University
with experience in organic chemistry and as a specialist in bile pigments.
Because he was Jewish, the recently-established racial laws in Nazi
Germany forced him to resign; he was invited by Hopkins to Cambridge
where he joined Needham’s team while continuing to pursue his
bile-acids research (Needham, 1931b; Lemberg, 1934, 1965).8
Nowinski was formally enrolled at Warsaw University but at the time
worked at the Physiological Institute in Berne under the distinguished
endocrinologist Leon Asher. Nowinski asked to be invited to Cam-
bridge, and because he studied the endocrinology of sex differentiation,
Needham was very responsive and welcomed him on board. Nowinski
was happy to come, although he received no research grant and had to
support himself. He departed after a few weeks, yet some months later
Needham managed to secure him a visiting Rockefeller Fellowship and
Nowinski happily returned (Nowinski, 1934). In addition to Lemberg
8
On the status of immigrant scientists in Britain and the efforts of Hopkins and other
British scientists to assist them, see Medawar, Pyke and Mendellson, 2001; Morrell,
1997, pp. 369–372; Werskey, 1978, Chap. 7.

and Nowinski, research students who came to Cambridge for other
purposes joined Needham for occasional tasks. Arthur Cohen came
from McGill University (Montreal) to the SRL for conducting tissue
transplantation experiments with Waddington. William E. Van Heyn-
ingen, a skilled organic chemist, came from the University of Stel-
lenbonsch in South Africa to advance his Ph.D., and joined Dorothy’s
project (Needham and Van Heyningen, 1935; Van Heyningen, 1936;
1987, pp. 51–68; Waddington and Cohen, 1936; Waddington et al.,
1936, p. 206). However, both participated in tasks pertaining to the
evocator search as well.
Team members had scientific – as well as professional and personal –
motivations for joining Needham. Lemberg was a traumatized refugee
in need of housing and a place of employment. Nowinski could remain
in Poland but because he too was Jewish, anti-Semitic sentiments
stonewalled his academic progress. Work at the prestigious institute
with Needham as a leading figure promised each one significant
opportunity for career advancement. Dorothy was an expert in muscle
biochemistry, yet she lacked a stable academic position or research
fellowship. Joseph was her provider, her intimate as well as her scientific
partner.9
Waddington embarked on a career in experimental embryol-
ogy, yet at Cambridge, as at other British universities, embryology was
an under-developed research discipline.10
He was in a precarious aca-
demic status since he did not finish his Ph.D. His financial state was
unstable and thus he had to devote much of his time to teaching rather
than research. Needham’s solid institutional position and strong
ambition for promoting embryological research promised a more sus-
tainable path (Yoxen, 1986).11
9
The Needhams worked in different research fields but had collaborated on occasion
since the early days of their respective careers. During the 1920s, they studied cellular
oxidation–reduction processes and in the early 1930s, conducted research in compara-
tive biochemistry (Needham and Needham, 1925; Needham et al., 1932; Teich, 2003;
Armon, Interview with Mikula´ sˇ Teich, 17 May, 2006).
10
The embryological research existing was conducted primarily in the Oxford Zoo-
logical Department and to a large extent followed on the morphological tradition and
its occupation with the relationship between evolution and development (Ridley, 1985;
Horder, 2008).
11
Needham tried to promote Waddington to an official university position but with
little success (Memorandum on the Zoological Department by a Committee appointed
by the General Board in Easter Term 1935; Needham, comments on that report (Note),
The Cambridge Biochemical Institute archive, Cambridge University Library, file 4.2).
On Needham’s attempts to institutionalize embryological research at Cambridge, see
below.
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Needham had the biochemical side of the project in place: Lemberg
and Nowinski formed the core of the chemical preparation team; Cohen
and Van Heyningen were on hand for certain fractionations; and
Dorothy was in charge of the final preparation of the implants. The
biological side – that is, performing the many implantations needed in
order to get a few positive results – was Waddington’s responsibility
(Needham, 1934a, b, 1935b, c; Waddington et al., 1935, pp. 292, 298).
Yet, a skilled histologist was needed as well to section implanted
embryos and examine whether neural induction took place. Since the
embryos did not survive to a stage of well-defined neural tube, the
changes could only be monitored in sections made during their early
development. Needham secured an emergency grant from the Royal
Society and later annual grants from the Rockefeller Foundation and
employed one of Mangold’s skilled histological assistants (Needham,
1933b; Tisdale, 1935; Waddington et al., 1935, p. 308; 1936, p. 195).
Despite the relative isolation of his program at Cambridge, Needham
established a highly skilled work force for extracting the hypothesized
sterol and testing the inducing capabilities of its chemical analogs.
In addition to recruiting scientists, Needham encountered difficulty
with access to amphibian species, as they were only available during the
laying season in spring and even then – only to a limited extent. Among
other reasons, Needham’s visit to Germany was motivated by the
availability of tritons (the salamander genus now known as Notoph-
thalmus) in local ponds. Needham preferred salamander embryos sim-
ilar to the ones Spemann and Holtfreter used, so that his and their
results would be comparable (Needham, 1933b).12
However, the pre-
valent salamander species at Cambridge was far less abundant than in
Germany and, in addition, Needham encountered cold springs during
which their fecundity and egg quality greatly decreased (Waddington
et al., 1936, p. 199). Since obtaining few positive results demanded many
tests, the limited supply of organisms greatly hindered Needham’s
progress. He had to diversify his sources and ask colleagues for
amphibians from other species. His queries bore fruit: Mangold sent
tritons from the species he used; a colleague in Algiers sent frogs of a
local species. A small grant that Waddington managed to secure
allowed for the purchase of axolotls (Waddington, 1935a). Yet, the
consequence of using diverse species was diversity in the results obtained
and hardship in achieving a coherent experimental demonstration.
12
On the growing importance of salamanders as model organisms in experimental
embryology, see Beetschen, 1996.

Tritons responded well to implementations, but the axolotls barely
survived to a stage of significant tissue formation and the frogs did not
show the expected ectodermal reactions (Waddington et al., 1935,
pp. 292–295, 302, 306).
Developing an efficient method for converting liquid extracts into
solid implants formed a major obstacle as well. Needham’s team tried
diverse protocols but none yielded satisfactory results. First they tried
solidification with gelatin – alone, with glycogen, and with starch, but
the implants were too stiff and therefore failed to be incorporated into
the embryos. The team then tried to coagulate the extract with egg
protein on a hot plate. Now the resulting implants were better incor-
porated by embryos, but controls with protein alone showed some level
of induction and the substances tested seemed to diffuse only partially
from the implants to the embryos. Yet, the coagulating technique had to
be retained because neither time nor organisms were available for
testing additional protocols (Needham, 1934b; Needham et al., 1934,
p. 402; Waddington et al., 1935, pp. 291–292). With an abundance of
organisms and unlimited time, additional methods could have been
tested for better efficiency. Had a suitable method been at hand, it could
have been adapted to a variety of organisms. For Needham, neither
option was available. He had to employ the scarce and diverse embryos
both for developing the implantation method and for demonstrating the
verity of his hypothesis.
Needham and Waddington overcame their material and methodo-
logical limitations by accommodating the diversity of results obtained
into permissive and graded categories. Their method was based on
visual inspection of implanted embryos and their classification to levels
of induction. But instead of looking only for perfect results, they
examined any formation of neural cells as a possible signal of an
inducing effect (Figure 1). Class A denoted ‘‘fully-formed neural tubes;’’
class C denoted ‘‘solid rods of neural cells;’’ and an intermediate class B
denoted ‘‘histologically differentiated neural cells, columnar in shape,
tightly packed together to form one- or two-layered ‘‘palisades’’-like
epithelium’’ (Waddington et al., 1935, pp. 292–294). When the palisade
form was found in some of the controls, Needham had to expand the
categories. Now class B signified the control palisade while B+ signified
‘‘palisades better than the controls.’’ Needham instructed the reader to
take grade B++ (‘‘palisades much better than the controls’’) as a likely
positive signal, while the finer palisade classified as B+++, ‘‘must be
taken as certainly positive.’’ With the graded system Needham set the
RONY ARMON

measure for evocation and simultaneously incorporated the entire range
of results obtained.13
Despite the difficulties with materials and methods, Needham man-
aged – albeit only barely – to demonstrate that the sterol hypothesis was
plausible. In the initial experiments, his team was implanting sterol-rich
fractions from tritons, calf livers extracts they performed, and fractions
which Channon sent. Fractions rich in sterols, Needham reported,
induced ‘‘formation of palisades considerably better than the control
palisades.’’ Among these, he emphasized, one sample even produced ‘‘a
thin walled induced neural tube’’ (Waddington et al., 1935, p. 302).
When a fraction that was treated with digitonin (an agent used for
sterols purification) yielded positive results, Needham saw even stronger
proof for his claim. Scarcity of embryos prevented him from testing
Rosenheim and Carr’s vitamin D samples and Needham failed to
crystallize the active substance from digitonin extracts. Yet experi-
menting with carcinogens sent by Cook further confirmed Needham’s
Figure 1. Needham and Waddington’s scale of induction and their use of it in classi-
fying their results. The classes A to B++ denoted positive results, class B+ a case
in doubt, while classes D to S marked morphologies pointing at negative results
(Waddington et al., 1936. Courtesy of The Royal Society)
13
Needham admitted that his grading system may seem too permissive, but claimed
that his results were similar to the ones relied on by other embryologists (Needham
et al., 1934, p. 412; Waddington et al., 1935, p. 294).

claim. He tested seven carcinogens; while five of them yielded an
undifferentiated cellular proliferation, the other two demonstrated
typical inductions (Waddington and Needham, 1935). As the carcino-
gens were highly purified, their evocation effects could not be related to
contaminants. Neither tests with biological extracts nor tests with
chemical analogs alone sufficed for proving Needham to be right.
However, together they strengthened his claim that the ‘‘active principle
of the amphibian organization center’’ is of sterol – or similar –
chemical structure.
Embryologists were slow in responding to Needham’s claims, though
a few commenced parallel studies of the chemical basis of induction.
Yet, his results immediately spoke to the interests of certain leaders in
the study of sterol molecules. In 1932, Cook and Dodds demonstrated
that certain carcinogens and vitamin D analogs can trigger estrous in a
manner similar to estrogens (Cook et al., 1933; Robertson, 1976,
pp. 78–79; Dickens, 1975, pp. 242–245). Their experiments were moti-
vated by efforts to identify synthetic analogs of the female sex hormones
which could be of clinical value. However, the results raised an
important theoretical issue as well, because they negated the view that
only specific hormones could induce the physiological effects tradi-
tionally related to them (Dodds, 1934a; Dickens, 1975). Like Cook and
Dodds, Needham pondered the mechanism linking chemical structure
and physiological effects in sterols and sterol-like substances. Viewed
from this perspective, his demonstration of embryonic induction by
Cook’s carcinogens extended the class of biological functions found for
these molecules. After Dodds heard about Needham’s findings, he
invited him to address the Biochemical Section of the British Empire
Cancer Campaign’s Biennial Conference (1934). Needham agreed and,
upon his request, Waddington was invited to speak as well (Dodds,
1934b; Couch, 1934). Their evocation tests now stood alongside their
colleagues’ studies of the diverse functions of carcinogens and estrogens.
Objections and Maneuvers
With Hopkins’ support, Needham and Waddington disseminated the
results of the study in ways that reached a wide range of scientific
audiences and also captured the interest of the general public. Needham
wrote the main experimental reports, which Hopkins – who served as
the president of the Royal Society – communicated to the society’s
Biological Proceedings. In a widely-publicized presidential address that
Hopkins gave at the annual conference of the British Association for the
RONY ARMON

Advancement of Science (BAAS), he praised the organizer program as
demonstrating biochemistry’s ability to address complex biological
problems.14
With the support of James M. Luck, editor of the newly-
established (1932) Annual Review of Biochemistry, Needham won the
opportunity to introduce his topic to biochemists worldwide.
Responding to an invitation by Luck, who was Needham’s longtime
acquaintance, he became the journal’s reviewer of progress in chemical
embryology and in 1935 introduced Spemann and Holtfreter’s findings
concerning the organizer, presenting research at Cambridge as a logical
follow-up.15
Waddington addressed specialist zoologists in a series of
publications in the Journal of Experimental Biology.16
Needham gained another opportunity to present his recent findings
and further broaden their theoretical implications when he received, in
late 1934, an invitation to give the Terry Lectures at Yale University.
The lectures were given annually by prominent scientists, who were
asked to discuss the implications of their recent discoveries on the
relationship between science and religion and their contribution to
human welfare.17
Needham, who was a prolific author on matters of
science, religion, and society, was convinced that his studies of the
organizer bore important philosophical consequences. In the lectures
and in the resulting book, Order and Life (1936a), he proposed that
studies in biochemical embryology, primarily those concerned with
embryonic induction, highlight the ability of physico-chemical concepts
and tools to engage complex biological processes. Deciphering
biochemically the organizer’s effect, he claimed, would significantly
14
Hopkins’ communication to the Royal Society is acknowledged at the opening of
each of Needham’s publications on the organizer. Hopkins’ address was reported in
Nature (Hopkins, 1933), and in The Times (Newspaper clip, Needham’s Papers,
Cambridge University Library, file E.145).
15
Murray completed his doctorate at the Cambridge Biochemical Institute in the
1920s; he and Needham were associates, and maintained a personal and scientific cor-
respondence. Needham reviewed novel findings in chemical embryology in the issues of
1932, 1933, and 1935 (Needham, 1935a, pp. 454–456; Luck, 1999, pp. 20–27; Luck to
Needham, Correspondence, 1931–1932. Needham’s Papers, Cambridge University
Library, file F.122).
16
Waddington discussed the evocation theory while publishing induction experiments
with avian embryos which he conducted in parallel to the amphibian tests (Waddington,
1934a, b, c).
17
InformationregardingtheTerryLectureshipandpastlecturersisavailableonthewebsite
of The Dwight H. Terry Lectureship, http://www.yale.edu/terrylecture/index.html (Accessed
15 November 2008).

contribute to redeeming the science of biology of its vitalist and holistic
skeptics, legitimating mechanistic approaches to all its problems
(Needham, 1936a).
Taken as a whole, Needham’s scientific and philosophical publica-
tions reflected the wide relevance of his research and probably generated
extensive interest in his work. As he anticipated, biochemists studying
active sterols showed increasing interest in his program and greatly
expanded his supply network. Towards the 1935 laying season,
Rosenheim sent new vitamin D derivatives and samples from a recent
study he conducted with cholesterol and bile acids, while Channon,
despite having limited amounts, arranged for Needham extracts from
his recent fractionations (Rosenheim and Webster, 1935; Channon,
1935; Needham, 1935d). In addition, Needham gained interesting
materials from leading American and Continental scientists. Harry
Sobotka from Mount Sinai Hospital in New York sent bile acid
derivatives. Charles E. Bills, Director of the Research Laboratory of the
Mead Johnson and Company, sent him samples of novel vitamin D
derivatives and of by-products from their production. He promised to
send Needham additional and more pure substances if the samples sent
were found to be inducing (Sobotka, 1934; Needham, 1935e). Needham
also piqued the interest of Nobel laureates for their work on sterols,
Leopold Ruzicka and Adolf Windaus. Ruzicka, who performed re-
search for the CIBA Company at the Swiss Institute of Technology, sent
recently-made androgen analogs, while Windaus, head of the chemical
institute at the University of Go¨ ttingen, sent plant sterols which he was
investigating.18
Of special importance for Needham was an opportunity
to visit, soon after he left Yale, Rudolf Scho¨ nheimer’s laboratory at the
College of Physicians and Surgeons at Columbia University.19
The visit
was important because Scho¨ inheimer’s laboratory formed the world
center for the study of sterol metabolism and because his wife, Salome
Gluecksohn-Scho¨ nheimer, had been a student in Spemann’s lab prior to
emigrating to the U.S. (Waddington, 1935c).20
Needham earned the
opportunity to discuss his findings with the Scho¨ nheimers and obtained
18
Windaus and Ruzicka won the Nobel Prize in Chemistry, Windaus in 1928 for his
role in identifying the chemical formula of the sterol structure and Ruzicka in 1939 for
his studies on male sex hormones and analog substances (Ruzicka to Needham, 8 May
1935; Windaus to Needham, 29 April 1935. Needham’s Papers, Cambridge University
Library, file E.55. Website of the Nobel Prize, http://nobelprize.org (Accessed 10
October 2007)).
19
On Scho¨ nheimer’s research, see Kohler, 1977.
20
Salome, who became a renowned contributor to developmental genetics, is known
better as Glu¨ cksohn-Waelsch, her married name after Rudolf’s death in 1941.
RONY ARMON

many samples produced by Rudolf and his researchers (Needham,
1935e).21
Yet, whereas the results of the Cambridge group garnered interest in
the biochemical research community, Needham had to face significant
challenges by embryologists. Else Wehmeier, who conducted research at
Spemann’s lab, and F.G. Fischer, from the chemical institute of the
same university, found glycogen to be an inducing substance, and in
subsequent experiments demonstrated induction by muscle adenylic
acid, thymonucleic acid (now known as DNA), and a variety of fatty
acids as well. The findings of inductions by diverse substances chal-
lenged Needham’s view of induction as specific to sterols. Rejecting his
claims, Wehmeier and Fischer suggested that an acidic stimulus, rather
than the presence of particular chemical entity, suffices for triggering the
neurolation response. Around the same time, Lester G. Barth from
Columbia University’s Zoological Department, demonstrated that cer-
tain brain lipids were inductive to a similar degree (Barth, 1934;
Needham et al., 1934, pp. 413–415; Fischer et al., 1935; Waddington
et al., 1935, pp. 289–291, 305). And while some embryologists chal-
lenged Needham’s theory, evidence, even from his lab, accumulated in
favor of the theory of metabolic gradients. In 1933, M.W. Woerdeman
demonstrated a high metabolic consumption of glycogen in areas
undergoing neurolation, while Jean Brachet demonstrated a metabolic
gradient across the amphibian gastrula. Wishing to examine the gradi-
ents theory himself, Needham tested induction by respiratory catalysts.
In 1935, Brachet visited Cambridge and together they demonstrated
that methylene blue – a catalyst which was structurally different from
the sterols – nevertheless induced neural tube formation in amphibian
embryos (Needham, 1933d; Needham et al., 1934, p. 417; Waddington
et al., 1936, pp. 173–177, 192). Evidence seemed to be mounting against
the chemical specificity of the inducing stimulus and in favor of the
metabolic approach for explaining the organizer’s effect. As a result,
leading embryologists began to cast serious doubt on Needham’s claims
and regarding the utility of his biochemical approach.
However, instead of deflating Needham’s hopes of isolating the evo-
cator, the doubts stimulated him into developing novel research venues.
Integrating all findings concerning substances and metabolic processes
capable of inducing, he suggested a hypothesis that incorporated both
21
Needham made efforts to keep in touch with Scho¨ nheimer’s lab after his return by
sending Van Heyningen there as a visiting researcher (A.V. Hill to Needham, Feb 5
1936; Van Heyningen to Needham 27 Oct and 5 Nov, 1936. Needham’s Papers,
Cambridge University Library, files E.130 and M.92).

metabolic and hormonal mechanisms. Induced tissues, he suggested,
already contain evocators, yet they were bound in complex with glycogen
and protein. Therefore, the evocator is naturally ‘‘masked’’ and inactive.
Glycogen and brain lipids induced, he claimed, because they were impure
and contained sterols.22
Metabolic activity and acidic agents induced
indirectly by releasing embedded evocators from their masked state:
energy metabolism consumes glycogen while acidic substances denature
bound proteins (Figure 2). The theory also explained the early ﬁndings in
Spemann and Mangold’s labs of inductions by crushed, narcotized, and
heated organizer tissues. These, Needham suggested, merely resulted
from the release of embedded evocators (Waddington, Needham and
Brachet, 1936, pp. 184–188).Modifying his theory of induction, Needham
accommodated recent objections while retaining the hypothesized
evocator as a central component.
Figure 2. Needham’s masked evocator model. The upper left area represents the host
neural tube; the lower right represents the induced neural tube where the normal pro-
cess takes place. According to Needham’s model, the evocator in a masked form
((E)) is released to a free and active form (E), which in turn induces a neutralization
response. Experimentally observed inductions can be the result of the implementation
of an agent (X) that unmasks an embedded evocator and allows it to induce the for-
mation of a secondary neural tube (from Shen, 1939, p. 144. Reproduced with per-
mission of the Company of Biologists)
22
The claim was plausible because glycogen was isolated from liver which was known
to have a high level of cholesterol and its products. Needham’s correspondences
(Needham, 1933e; Fox, 1934) reveal that methods for glycogen and brain lipids
extraction were very crude and could not be claimed to result in pure substances.
RONY ARMON

Wishing to demonstrate the verity of his conceptions, Needham
placed the testing of the newly-arriving sterols on hold, dedicating the
rest of the laying season (in 1935) towards demonstrating that inductions
by glycogen, brain lipids, and acids resulted from sterols retained despite
their extraction. Purifying non-specific inductors tackled theoretical
objections while simultaneously enhancing Needham’s practical aims,
because if extracts of the substances tested would be found inducing they
could later serve for further extracting the evocator. Exploiting his pri-
vate contacts and scientific reputation, Needham obtained glycogen
from scientists who isolated it from a variety of sources and by a variety
of methods. In addition, he instructed Cohen to isolate glycogen from
livers of animal material available in the lab and extract them for sterols
(Needham, 1933e, 1934b; Fox, 1934; Waddington et al., 1935,
pp. 300–308). Responding to Barth’s results, Needham entrusted
Nowinski to extract brain lipids for sterols and in an attempt to face
Wehmeier and Fischer’s critique, he tested induction by extracting
sterols from a thymonucleic acid sample. The quality of results varied;
while glycogen extracts induced, only a few embryos survived implan-
tations of fractions from brain origin. However, because certain induc-
tions were obtained, Needham suggested that sterol impurities could
have caused inductions – both in his and in Barth’s tests. The thymo-
nucleic extract failed to induce, but alluding to previous demonstrations
by his team of inductions with alkaline liver extracts, Needham rejected
the claim that acidic stimulus is the inducing trigger (Needham, 1934c;
Waddington et al., 1935, pp. 290, 299–301, 305; Waddington, Needham
Nowinski et al. 1936, pp. 199–206). As in experiments aimed at dem-
onstrating his claims, the ones he designed to refute his critics were also
conducted under a highly-constrained time schedule and with limited
resources available. Nevertheless, Needham believed that the results
obtained now and beforehand supplied evidence that sufficed to face all
mounting challenges and support his new working hypothesis.
In parallel to expanding supply and interest on the part of biochemists
studying sterols, Needham and Waddington began to explore the impli-
cations of their studies for understanding the mechanism of cancer.
Waddington proposed that since both tumorigenesis and morphogenesis
involve changes to growth patterns, both processes could be governed by
morphogenetic fields; while in development they guide accurate patterns
of growth, cancerous growth results from an escape from their control. So
convinced was Waddington in the parallelism of morphogenesis and
cancerous growth that he proposed that embryologists’ success in
explaining the former makes it ‘‘profitable to consider the way in which

the new embryological theories would formulate the well-known prob-
lems of cancer research’’ (Waddington, 1935b, pp. 606–607). Needham
was initially more cautious because he distinguished growth processes –
such as in cancer – from differentiation, which was a unique feature of
embryonic development (Needham, 1933c; 1936b, p. 1596). Yet, building
on Waddington’s conceptions and the demonstration of the evocating
power of carcinogens, he gradually changed his mind, suggesting that the
evocator is a member of a group of growth-promoting substances – tightly
controlled in embryogenesis but growing uncontrolled when cancer
ensues (Needham, 1936b, c). Like Waddington, Needham presented a
theory of cancerous growth that was based on his morphogenetic con-
ceptions and extended the relevance of their primarily embryological
study to cancer research.
Embryologists at the time were far from ready to leap into cancer
research and to adopt Needham and Waddington’s approach. In fact,
Woerdeman criticized their interpretation of induction by carcinogens
as reflecting resemblance to natural evocators (Woerdeman, 1936).
However, in medical circles in Britain, Needham’s speculative expla-
nation of the cancerous action of carcinogens earned significant atten-
tion. In 1936, he was invited to give the annual Oliver-Sharpey Lectures
of the Royal College of Physicians and to address the Pathological
Section of Royal Society of Medicine (RSM). At both events he dis-
cussed in detail ‘‘the chemical aspects of normal and cancerous growth,’’
describing his embryological research and extending its prospective
clinical relevance.23
When the British Medical Association (BMA) was
preparing its Annual Meeting (1936), Needham was nominated a vice-
president of the Section on Physiology and Biochemistry, which was
aimed at discussing fundamental findings in these disciplines and their
bearing on medical practice. That year, he led and introduced a session
on ‘‘Substances Promoting Normal and Abnormal Growth,’’ in which
Dodds, Cook and his co-researchers, Harold Burrows and Alexander
Haddow, presented their latest findings on hormones and carcinogens
(Needham, 1935f).24
Needham also managed to have his lectures pub-
23
Needham was given ample space to present his views. At Needham’s request, the
RSM organized a special session where he was the only speaker (Needham, Corre-
spondence with RSM officers, Dec 1935–April 1936. Needham’s Papers, Cambridge
University Library, file G.44–G.45).
24
In addition to joining Needham’s session, Burrows, Cook and other members of
their lab read and commented on Needham’s paper to the BMA before he presented
that paper (Burrows to Needham, 16 June 1936, Needham’s Papers, Cambridge Uni-
versity Library, file H.23).
RONY ARMON

lished in the best medical venues, both in the RSM’s Proceedings and in
The British Medical Journal (BMJ).25
As was the case in the field of hor-
mone research, he was able to exploit biomedical interests in the substances
he examined for embryological functionality, and also to seek novel ways
for extending his research program and its relevance.
The Last Tests
However, just when Needham was exploring novel research paths, his
team of biochemists departed and he could not fund or recruit replacers.
Whereas the Rockefeller Foundation’s grants sufficed to cover the
funding for Nowinski and the histological technician, other funding
sources were indirect and contingent. Thus, Needham exploited regular
grants which he obtained from the Government Grant Committee of
the Royal Society, but he could do so only to a limited degree because
they were primarily dedicated to his parallel studies in embryonic
metabolism (Needham et al., 1934, p. 419; Waddington, Needhem and
Brachet, 1936, p. 195).26
Lemberg, Cohen and Van Heyningen relied on
short-term fellowships: Cohen and Van Heyningen came with visiting
fellowships they earned from their universities, while Lemberg was
supported by the Academic Assistance Council, which was established
in Britain to assist German refugee scientists. When their respective
fellowships terminated, they left Cambridge and in so doing dismantled
the biochemical team (Waddington and Cohen, 1936, p. 219; Van
Heyningen, 1987, pp. 58–59).27
In addition, Needham and Waddington
hoped to hire a technician to take care of the many implantations
Waddington did, thus freeing him from that daunting task and allowing
him to focus on his parallel lines of research. Yet, no funding
was available for that, and doctoral students in zoology could not be
25
Initially Needham turned to the editor of The Lancet for the publication of his
Oliver-Sharpey Lectures but the editor found them to be too technical. Yet, Needham
managed to get them published in a revised form in the RSM’s Proceedings. In pub-
lishing his BMA talk, he asked the BMJ editor that the paper be published as soon as
possible and purchased a large quantity of reprints for distribution in personal corre-
spondence (Needham, 1936b, c, d).
26
Inferred from Needham’s reports on grants expanses to the Royal Society,
1925–1940 (Needham’s Papers, Cambridge University Library, files B.1–B.18).
27
Lemberg wanted to stay in Cambridge, but no funding was available to support
him (Rimington and Gray, 1976, p. 257). Van Heyningen went to Schoenheimer’s
laboratory at Columbia (See n. 21). Cohen’s publications record testifies that he
returned to McGill, probably soon after leaving Cambridge.

recruited to take Waddington’s place. Needham wrote to the Rocke-
feller Foundation that research students require interesting ideas that
could lead to publications and ‘‘dare not face a long run of negative
results’’ encountered in the organizer program (Needham, 1936e).
Aware of his limited support base, Needham made an effort to position
his program as part of a safe institutional base by trying to persuade the
Rockefeller Foundation to support the establishment of an independent
research center for chemical embryology. Yet, with little interest exhibited
on the part of university authorities and without the unanimous support
of the scientific advisors with whom the Rockefeller Foundation con-
sulted, the program was finally rejected (Abir-Am, 1987, 1988). On some
level, Needham’s appeal to the relatively well-invested field of cancer
research was another attempt – albeit less explicit – to gain support for his
program. He even tried to initiate at the Cambridge Biochemical Institute
a research forum of colleagues whose studies were, or could be, related to
cancer (Needham, 1936f). Yet, the idea that carcinogens act as evocators
in stimulating the production of tumors soon became controversial.
Needham’s publication in the BMJ led to a debate that ensued across the
pages of the journal over the next few months, and while not all corre-
spondents objected his ideas, leading researchers and physicians called
for a clear distinction between embryonic and tumorigenic induction
(Cramer,1936; Manson,1936; Harkness, 1936;Kelly, 1937). As Needham
failed to garner the financial or institutional means for re-establishing the
evocator search, he put it on hold, pursuing instead his interest in
embryonic metabolism.28
However, he did not relinquish the evocator
quest, hoping to return to it when the people and resources he needed for
the task could be recruited (Needham, 1935g).
Indeed, despite the disintegration of the biochemical team and the
drying up of funding, Waddington managed to resume experiments
and present results of high quality. Towards the 1937 laying season,
Needham obtained from Rosenheim, Dodds, Marrian, Cook and his
co-researcher, Eric Boyland, a plethora of carcinogens and hormones
(Waddington, 1938; Rosenheim, 1937; Parke, 1986; See Figure 3).
While the biochemical team disbanded, much of the labor it previously
performed was not necessary because the chemicals were purified
by their suppliers. In addition to gaining pure substances, Holtfreter,
who also made significant efforts to identify the inductor’s properties
28
In the years 1936–1939, Needham and researchers he recruited measured changes of
glycogen levels in the process of induction, carbohydrate combustion in the early em-
bryo, and metabolic gradients during gastrulation (Heatley et al., 1937; Needham and
Nowinski, 1937; Boell et al., 1939).
RONY ARMON

(1934–1938), supplied Needham with tritons in high quality and num-
bers (Hamburger, 1988, Chap. 9; Gerhart, 1996; Waddington, 1938a,
p. 371). For the first time since their experiments commenced,
Waddington had available molecules as well as organisms of high
quality. His results improved accordingly. Whereas in previous years he
was happy to have palisade forms, he now obtained a large proportion
of well-formed neural tubes (Figure 4). Additionally, Waddington
succeeded in improving the induction assay, and in replacing the
qualitative grading scheme with quantitative criteria for distinguishing
levels of induction.29
He demonstrated clearly that sterols and carcin-
ogens were efficient inductors while only a small level of induction was
obtained by controls containing protein coagula alone or biologically
inactive substances (Needham, 1937a; Waddington, 1938a).
However, Needham and Waddington also presented evidence which
seemed to necessitate a rethinking of the sterol hypothesis and a
reconsideration of their methodology of research. Certain estrogenic
Figure 3. The wide range of materials obtained by Needham and Waddington for
evocation test towards the 1937 laying season, and names of their suppliers (the fig-
ure is based on Table I from Waddington 1938a, p. 367. Courtesy of the Royal Soci-
ety. Suppliers names are added based on acknowledgments in p. 371)
29
The quantitative measures were the percentage and size of the neural tubes formed.

and carcinogenic substances expected to induce did not have that effect,
while certain non-sterol hydrocarbons such as squalene were shown to
induce. Needham was probably not surprised by the result with squa-
lene, as Channon had recently found it to be a factor in the metabolism
of sterols (Channon and Tristram, 1937). To a certain extent, Needham
was even pleased about it, because squalene was a product of fish liver
oil that was intensively studied for its nutritional value. Thus, the
findings of squalene’s inducing capacity opened a novel venue for
searching evocators in the familiar and available oils from which it was
originally extracted (Rosenheim, 1935). But while extending the range
of probable inductors was somewhat encouraging in practical terms,
Waddington concluded his experimental report with the admission that
‘‘it would certainly not be profitable at the present stage to attempt to
form any hypothesis as to the chemical basis of inducing power’’
(Waddington, 1938, p. 370). Substantiating such a hypothesis, he cau-
tioned, necessitates the testing of a much larger range of substances.
Yet, Waddington began questioning the very strategy of using arti-
ficial inducers, because it necessitated clear-cut criteria for distinguish-
ing substances inducing due to their structural analogy to the natural
evocator from those inducing by catalyzing its release. The only crite-
rion available for distinguishing specific from non-specific inductions
Figure 4. Comparison of the evocation results from Needham’s early (1935a, b) and
late (1937c) experiments. I used Needham’s notation: I.n.t denotes ‘‘induced neural
tube’’ and H.n.t denotes ‘‘host neural tube.’’ While early tests had shown only some
level of cellular elongation (see area circled in b), inductions obtained in 1937 were
comparable to the form of the natural neural tube (a and b are taken from a plate
added to Waddington et al. 1936; c is taken from a plate added to Waddington,
1938a. Courtesy of the Royal Society)
RONY ARMON

was that, like other hormones, specific inductors were expected to work
in low doses. However, Needham and Waddington admitted that the
dose criterion was indirect and decisive only to a limited degree, and
concluded that while the function of synthetic inducers remains an
important problem, ‘‘a return must be made to the investigation of the
chemical properties of evocating and non-evocating tissues from the
embryo’’ (Waddington, 1938a, p. 370). They split their efforts accord-
ingly, so that Waddington invested in further improving the assay’s
quantitative basis while Needham sought funding that would enable
them to reestablish the biochemical team and return to extracting nat-
ural sources.
Waddington managed to establish a method for preparing implants
which, to a certain extent, could be said to contain different concen-
trations of the inducing substance. He could not experiment with it
because he was about to embark on a research trip to the U.S. during
which he planned to visit leading embryological and genetics research
centers (Fell, 1937; Yoxen, 1986; Stern, 2000). But the joining of
another refugee scientist allowed the induction tests to proceed. In late
1937, Shih-Chang Shen came from the Physiological Department at the
Union Medical College at Peiping. The atrocities of the Sino-Japanese
war left Peiping an almost deserted city and Shen, who had to leave in a
great hurry, won a visiting Rockefeller Fellowship and landed at the
SRL.30
Waddington joined Shen to the evocator search and taught him
the necessary techniques for preparing the implants and for conducting
the implantations. Employing a carcinogen that was shown to induce in
previous essays and which Waddington obtained again from Kenn-
away’s group, Shen prepared coagulates with different concentrations
and demonstrated that induction can be considered, at least roughly, to
be a dose–response reaction (Figure 5). The results confirmed that
induction by sterol-like compounds fell ‘‘within the range of activity of
hormones, vitamins, and other stimulating substances,’’ reinforcing the
claim that sterols probably act as an ‘‘imitation of the normal orga-
nizer,’’ rather than indirectly, ‘‘by liberating the organizer substance
masked in the ventral ectoderm’’ (Shen, 1939, p. 148).
Shen’s findings were highly crucial in responding to novel challenges
which Holtferter and Barth presented. Holtferter also searched for the
30
Along with Shen arrived another Chinese scientist, Lu Gwei-Djen, who inspired
Needham’s interests in China, became his lover, and later became his scholarly partner
as well (Winchester, 2008). Regarding Shen however, Needham was suspicious of his
research qualifications and so he refused a request by the Rockefeller Foundation to
host him. Yet, when Fell was similarly requested, she immediately agreed to find Shen a
place at the SRL (Needham, 1937b; Fell, 1937).

chemical basis of induction, yet in parallel studies he saw that embry-
onic gastrulae are able to differentiate in detachment of signals from the
organizer region and that the species-specific pattern of differentiation
observed relies in the main on the reacting – rather than the inducing –
tissues (Gerhart, 1996). Barth, who expended his studies on the orga-
nizer, obtained neurulation responses upon stimulation with digitonin,
acids, and alkalis (Barth and Graff, 1938). Relying on their findings,
both Holtfreter and Barth suggested that the organizer mainly releases
induction capabilities inherent in the responding tissues. During
Waddington’s travel to the U.S., he heard and debated with Barth, who
addressed the prestigious annual Symposium on Quantitative Biology in
Cold Spring Harbor (1938). Waddington felt that he responded well on
the spot, yet he later noted that Barth’s views had a significant impact,
leading to an assumption that inductions obtained in Cambridge merely
resulted from ‘‘unspecific stimulus.’’31
Shen’s results demonstrated
inductions in concentrations far lower than those obtained by Whemier
and Fischer or by Barth, and were crucial for sustaining the claim that
the results in Cambridge were specific to the molecule Shen tested (Shen,
1939, pp. 147–148).
Figure 5. The dose–response curve of Shen’s induction tests (from Shen, 1939, p. 146.
Reproduced with permission of the Company of Biologists)
31
Waddington requested Needham to send him slides showing high-quality results, in
order to persuade his skeptical colleagues. Many of the skeptics he heard were from
Barth’s department which Waddington visit for working with L.C. Dunn (Waddington
and Conrad, 1938b).
RONY ARMON

But while Waddington and Shen came up with novel results and a
better testing method, Needham failed to obtain the funds needed for
studying natural evocators, and in addition, saw the slashing of existing
resources. The Government Grant Committee of the Royal Society
reduced his annual grant, thereby limiting his ability to purchase
research organisms and materials. The Rockefeller Foundation did not
renew the funding for the histological technician because their grants
were only meant to allow Needham to work until the university found a
stable funding source. University authorities did not do so and even
prevented Needham from using his departmental budget to pay his
much-needed histological technician. Anxious to avoid the cessation of
his project, he began to pay a technician out of pocket (Needham,
1938b, c; 1939; Tisdale, 1938; Waddington, 1938b). In an application
Needham submitted to diverse foundations, he complained that his
research was under funded despite its contributions to embryology,
biochemistry and medicine; still, the foundations’ representatives all
failed to be impressed.32
It was due to Hopkins, to whom Needham
pleaded for support in the emergency situation, that he succeeded in
obtaining an emergency grant from the Royal Society. However, that
grant sufficed for only one year, leaving prospects for further funding
sources practically nil (Needham, 1938c, d, 1939).
Nevertheless, Waddington, who returned from the U.S. eager to
resume experiments, continued the tests with artificial inductors, pre-
senting novel findings in order to counter Barth’s claims. ‘‘I feel that
while I have been away,’’ he wrote Needham while still in the U.S., ‘‘you
have been holding the fort in the most difficult time we have had
yet’’ (Waddington, 1938c). Waddington began to reorient his research
towards developmental genetics, which from the early 1940s constituted
his key area of research, but he continued to supervise Shen in fur-
thering the induction tests. In spring 1939, Shen tested and demon-
strated the carcinogen’s inducing activity on isolated pieces of
embryonic epidermis. No effects were observed in the controls, and so it
was safe to claim that the substance’s stimulus is specific (Shen, 1942).
Barth mounted further challenges by publishing demonstrations of
induction in isolated amphibian ectoderms brought about solely by their
cultivation in a salt solution (Barth, 1941). In response, Waddington
claimed that Barth’s measurements were applicable only to large and
relatively organized tissues and emphasized Shen’s failure to obtain
32
Needham communicated with The Department of Scientific and Industrial
Research, The Sir Halley Stewart Trust, The Josiah Macy, Jr. Foundation and The
Levehumle Foundation (Needham, 1938c).

inductions in controls.33
Thus, during the laying seasons of the years
1937–1939, despite limited resources, Needham and Waddington suc-
ceeded in presenting novel results and in improving the method’s
quantitative basis.
Improving the induction assay had another related purpose, which
was to enhance the testing capabilities of their program in case resources
for its re-establishment would become available. Needham saw Cook’s
carcinogen testing program as a model for the way in which studies on
embryonic induction should proceed. Earlier, in a letter to the
Rockefeller Foundation, he wrote that ‘‘when one reflects on the
advances which have been made in our knowledge of cancer by
the laborious painting of compounds on skin of animals by the staff of
the Fullham Road Hospital, one can see easily that problems such as
ours, no less interesting, can only be solved by similar mass-production
methods’’ (Needham, 1936e). Following recent successes in garnering
results of high-quality, Needham sought means for establishing just
such a routine unit which would be based on new research students in
biochemistry he sought to recruit, and technicians paid to handle bio-
logical assays and the subsequent histological sections (Needham, 1939).
The improved methods, whose quantitative basis was gradually
enhanced by Waddington and Shen’s experiments, could be integrated
into this unit and enhance its capabilities for testing the inducing power
of candidate substances.
Yet Britain’s preparations for war, which translated into the slashing
of governmental support for fundamental research programs, ruled out
any opportunity for the re-establishment of the evocator search. Many
scientific projects came to a standstill and some science laboratories and
technical colleges closed down.34
While certain colleagues at Cambridge
– primarily enzymologist Malcolm Dixon and bacterial physiologist
Marjory Stephenson – succeeded in applying their research to pro-
spective biomedical concerns, thereby recruiting suitable state funds,
Needham failed to do so (Armon, 2010). In addition, the cost of
materials rose significantly while the income of universities declined in
response to the reduced number of students. As a result, authorities in
Cambridge slashed departmental research grants, demanded the great-
est economy in research expenditures, and encouraged researchers to
33
Waddington added his comment while Shen’s, 1942 paper was in the proof stage
(p. 10).
34
Needham learned on the situation and got involved as member of the Cambridge
branch of the Association of Scientific Workers (Needham’s Papers, Cambridge
University Library, file B.237).
RONY ARMON

choose the cheapest line of investigation possible (Needham, 1940). The
organizer program, which demanded resources not available at Cam-
bridge and bore no immediate relationship to war-related biochemical
projects, stood little chance of progressing. Thus, just when Needham
and Waddington obtained their best results and offered what they felt
was a significantly improved research method, their collaborative study
of the organizer tissue had to be terminated. Each parted to a different
research path: Waddington invested primarily in developmental genetics
while Needham commenced an intensive study of the role of protein
fibers in morphogenetic processes. And yet, they remained interested in
the problem of induction, attempting to link their new studies with
the program they left behind (Waddington, 1940, Needham, 1942,
pp. 165–187; Dainty et al., 1944).
However, while Waddington and Needham’s departure reflected
neither despair nor loss of faith in the importance of their quest, it
ended without followers – and biologists who examined Needham’s
findings declared his claims misguided. Haddow emphasized (1943)
that Needham demonstrated inductions in low concentrations only by
a carcinogen, which though structurally related to a sterol was a dif-
ferent substance. Therefore, the claim that the natural evocator is a
steroid substance could only be partially justified by his experiments
(Haddow, 1943). Zoologists Janet and Robert Briggs studied the
influence of the same carcinogen as Shen employed on amphibian
embryogenesis, demonstrating (1942) that it caused retardation rather
than enhancement of the morphogenetic processes involved. They
acknowledged that differences between theirs and Needham’s results
could have been the result of differences in the species of amphibian
used or in the method of administering the carcinogen. Yet, they
claimed that further studies would be needed before this substance
could be taken to be an inductor (Briggs and Briggs, 1943). However,
further studies by Holtfreter of neural differentiations in isolated
ectodermal tissues suggested that the chemicals found ‘‘inducing’’ did
so by cytolizing cells in the responding tissue, thereby releasing factors
necessary for induction to proceed (Ebert, 1985; Gerhart, 1996). Later
findings concerning the effects of carcinogens on embryonic induction
were explained as reflecting cytolytic effects rather than specific stim-
ulations (Horowitz, 1943; Brachet, 1950, pp. 422–424; Hayashi, 1959;
Saxe´ n and Toivonen, 1962, pp. 111–112). Ultimately, Needham’s
program terminated and his theories were gradually refuted by the
researchers who followed.

The Quest and Its Purposes
As Needham’s declared aim was to decipher an embryological mystery
and as he failed to produce the molecule he sought, it is hardly sur-
prising that the prevalent historiographical picture focuses on his
embryological aims and limited ability to achieve them. Yet, while
embryologists came to reject his claim, on the biochemical terrain he
explored his limitations were seen as plausible and as inviting further
research rather than departure. While Cook and Dodds searched their
molecules for chemical characters that grant them estrogenic and
carcinogenic capabilities, they found these effects to be elicited by
diverse chemical groups. In fact, in their framework, which Needham
happily embraced, the finding of only limited correlation between
chemical structures and the physiological functions they triggered,
encouraged further research rather than presented evidence of a mis-
taken path. The finding that embryonic induction is mediated by a
wider class of substances than Needham initially anticipated led
embryologists to question his approach, but did not hinder interest by
his collaborators in the results he obtained. Indeed, while Needham
and Waddington were struggling to sustain their program, Cook –
despite his highly-invested research field – did not attain results that
were any more conclusive.
While Cook found carcinogenic substances to share certain chemical
characteristics, he also found that diverse compounds elicit malignant
tumors. ‘‘It is impossible at the present stage to explain this property,’’
he admitted (1938), ‘‘and it seems useless to attempt to define any
common feature of molecular structure’’ (p. 13). Yet in no way did he
see that limitation as cause for retreat. Rather, he emphasized that ‘‘the
availability of a wide range of carcinogenic compounds and closely
related inactive substances has provided much material for the investi-
gation of the mode of their biological action,’’ and expressed the belief
‘‘that the mechanism of carcinogenesis by these chemical substances will
in due time be laid bare by further experimental work.’’ Two years later,
he concluded that ‘‘in carcinogenesis we have a biological phenomenon
which may be attributed to a variety of different substances and agen-
cies,’’ and yet ‘‘this is by no means unique, for the same is true for other
biological phenomena’’ (Cook, 1940, p. 338). Despite the testing of
hundreds of substances, his experiments led only to general chemical
categorizations of the biological functions he studied. Like Needham,
Cook learned to appreciate the complexity of the phenomena he studied
and the difficulties in explaining it biochemically.
RONY ARMON

That is not to say that Cook and colleagues in his research field
accepted Needham’s claims. Whereas Needham suggested that carcin-
ogens may be the prime cause of malignant growth, Cook adopted the
view held by other cancer researchers that carcinogenic stimulation was
only a secondary factor (Murray et al., 1933; Austoker, 1988,
pp. 91–138). To a certain degree, findings in Cook’s lab even contrasted
Needham’s idea that carcinogens are growth stimulants, as Haddow
demonstrated that some cancer-causing agents could also inhibit tumor
growth (Haddow and Robinson, 1937). And yet, taken as a whole, the
findings of growth, anti-growth, differentiation and endocrine effects for
carcinogens and steroids begged for a new research approach to deci-
pher their mechanism – or mechanisms – of action (Dodds, 1934a;
Bergel, 1977). Needham’s theory and assay did just that. At least to a
certain degree, the program he pieced together for studying morpho-
genetic processes biochemically served as a platform for exploring the
mechanisms by which diverse hormones and carcinogens elicited their
normal and pathological effects.
Accordingly, the graded induction results were questioned by
embryologists, but far less so, if at all, by Needham’s collaborators.
Embryologists suspected that results obtained at Cambridge may not
represent true inductions, because while implantations of living orga-
nizer tissues induced well-developed neural structures, tests with tissue
extracts and pure chemicals gave only rudimentary organs (Barth, 1939;
Horowitz, 1943). However, his collaborators in hormone and carcino-
gen research were used to handling assays which produced less than
clear-cut results. For example, the results of estrogenic assays for sex
hormones were strongly influenced by the rate of injections and medium
in which substances were dissolved, the frequency with which the effects
were examined, and the type of reaction regarded by a particular re-
searcher as a positive response (Doisy and MacCorquodale, 1936;
Parkes, 1938).35
The variable factors influencing assays were so many,
wrote Marrian (1933), ‘‘that it is quite impossible to compare the figures
for the potency of either crystalline substance as published from dif-
ferent laboratories’’ (p. 193). Excitement vis-a`-vis the potential findings
of novel hormones, he later recollected (1966), led frequently to pre-
mature publications (p. viii). The results of Needham’s morphogenetic
assay failed to impress leading embryologists; however, for his collab-
orators, whose field of research necessitated a certain level of interpre-
tive flexibility, his results were acceptable. Because Needham pioneered
35
For similar concerns regarding the study of carcinogens, see: Cook et al. 1932,
pp. 456–457; Cook, 1940.

the biochemical study of induction, he was in a position to establish the
assay for its testing, criteria for which results are acceptable, and
explanation for the non-specific results he obtained.
In addition, Needham’s program was probably instrumental for his
collaborators in that the very experiments he conducted for testing the
morphogenetic effects of sterols explored novel functions for the
hormones and carcinogens which they already discovered. If his theory
was correct, his experiments stood a chance of finding a novel function
for the samples they sent. Inducing fractions were potential candidates
for future extraction of underlying molecular agents, while molecules
already purified could emerge as carriers of additional – and highly
central – biological functions. As Nicholas Rasmussen pointed
out, hormone researchers during the 1930s expressed great interest in
finding ‘‘master molecules’’ governing vital processes and phenomena
(Rasmussen, 2002). Indirectly, Needham suggested that a molecule that
may be a prime guide of embryonic development may already be laying
on his collaborators’ laboratory shelves. As clinicians and industrialists
were sharing scientific interest in the functions of the substances
Needham tested, his program – through its collaborative links –
addressed a broader context than that guiding embryologists who were
skeptical of his approach.
Needham began with a search for a certain hypothesized factor, and
his research subsequently expanded into a study of existing hormones
and carcinogens. Consequently, he gathered the interest of the bio-
chemists who produced them in the results of his work and garnered
their support for the program that he was piecing together. While
embryologists doubted Needham’s approach from a preliminary stage
of his study, his program produced results which he – as well as his
collaborators – could trust. To a significant degree, as this paper clearly
shows, Needham and Waddington shared the skepticism of their critics
and were constantly modifying their claims in accordance with accu-
mulated evidence. Indeed, they did not find the hormone they sought,
yet it was the search for it that garnered the program value in the eyes of
their collaborators. While they did not accept Needham’s theoretical
claims and broad speculations, his conceptions formed the basis for
experiments which engaged the function of the molecules they synthe-
sized and isolated. As Needham worked under increasingly harsh con-
ditions and examined a problem that was much less clearly defined than
the problems they were investigating, his efforts may have even been
perceived to be somewhat heroic. It was his biochemical quest rather
than embryological aim that crystallized the partnerships which enabled
RONY ARMON

his experiments to proceed despite the highly limited conditions under
which he performed his research.
Acknowledgements
This paper is a revision of a chapter from my dissertation, written
under the supervision of Oren Harman at the Graduate Program for
Science, Technology and Society at Bar-Ilan University (Approved,
April 2010). Additional research and writing took place during a
research fellowship at The Jacques Loeb Centre for the History
and Philosophy of the Life Sciences at Ben-Gurion University of the
Negev. I want to express heartfelt thanks to Oren for his unwavering
support and assistance. In addition, I would like to thank Tim
Horder, Pnina Abir-Am Scott Gilbert and the anonymous referees for
their careful reading and comments, and Ute Deichmann, Tony Tra-
vis, Menachem Fisch, Noah Efron, and Raz Chen for their kind
interest and advice during various stages of my research. While ad-
vised by esteemed scholars, any faults or ﬂaws in this paper are my
own. This work was supported in part by a research fellowship from
The Jacques Loeb Centre for which I am most grateful. Finally,
I would to thank the staff at the Cambridge University Library
and The University of Edinburgh for their assistance in my archival
research.
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