Scientific disciplines embody commitments to particular questions and approaches, scopes and audiences; they exclude as well as include. Developmental biology is no exception, and it is useful to reflect on what it has kept in and left out since the field was founded after World War II. To that end, this article sketches a history of how developmental biology has been different from the comparative, human and even experimental embryologies that preceded it, as well as the embryology that was institutionalized in reproductive biology and medicine around the same time. Early developmental biology largely excluded evolution and the environment, but promised to embrace the entire living world and the whole life course. Developmental biologists have been overcoming those exclusions for some years, but might do more to deliver on the promises while cultivating closer relations, not least, to reproductive studies.
Last year's 70th anniversary of the British Society for Developmental Biology (BSDB) was an opportunity to stand back, to consider how the subject came about and what has made it distinctive, and to reflect on present arrangements. This historical commentary takes stock through the theme of inclusion and exclusion.
Science is organized into disciplines that shape training, identity and funding; they define the important problems and how these should be addressed. Disciplines are made, not found. Making one is a political project of carving out questions, approaches and scope, and recruiting patrons and audiences, in relation to what went before and to other sciences (e.g. Nyhart, 1995; Lenoir, 1997). Claiming an identity involves deciding what to include or exclude, what will be in and what will be out. Practitioners negotiate the boundaries of their own field and the terms of their relations with neighbours. Developmental biologists have done this explicitly in electing not to merge with cell biology societies in the 1980s and early 1990s, and in the BSDB's 2013 decision not to add ‘stem cell’ to its name. [For a possible merger of the BSDB with the British Society for Cell Biology, see Martin Johnson's Chairman's report 1985-86, BSDB Newsletter, no. 13 (Spring 1986), pp. 10-11 (1986-1(#13) at bsdb.org/2018/04/29/bsdb-archive/). For the 1992 vote against merging the (American) Society for Developmental Biology and the American Society for Cell Biology, see SDB and ASCB records (library.umbc.edu/speccoll/findingaids/coll022.php and library.umbc.edu/speccoll/findingaids/coll008.php). For the stem cell vote, see Martinez Arias (2013).]
In this view, when ‘developmental biology’ was founded after World War II, it was not just another word for embryology (Horder, 2010). Nor has it been simply an expanded version, although ‘experimental embryology across the living world’ used to come close, and the field has broadened in recent decades. It is also a stretch to present developmental biology as ‘the stem cell of biological disciplines’ (Gilbert, 2017). That is because – to begin closer to the beginning – 18th-century ‘generation’ was the common ancestor of embryology as well as research on heredity and reproduction, while anatomy gave rise to many other sciences (Jacob, 1982; Hopwood, 2018a; Cunningham, 2010). Nineteenth- and early 20th-century embryology did then contribute to several fields, including immunology and genetics, yet developmental biology was not there from the start, but was itself ‘budded off’. It is more accurate, and more respectful of the differences, to think in terms of a family of disciplines or research programmes that have shared interests in embryos and in development, but had their own identities and asked somewhat different questions (Hopwood, 2009).
I shall argue for the distinctiveness of developmental biology by first introducing the three programmes that dominated research between the 1880s and the 1930s: comparative, experimental and human embryology. I shall then review how the questions and approaches, scope and audiences of developmental biology made it different from any of those. Meetings, funding, journals, societies, courses and textbooks defined the new speciality. In the 1950s, for the first time, when a colleague asked, ‘What do you do?’, you could answer, ‘I'm a developmental biologist’. By the 1970s, you could expect them to understand the response.
Exceptions to my generalizations may come to mind; I aim to sketch a big picture within which to place developmental biology, not to paint the detailed portrait that would need more historical research. Though I shall conclude by exploring the significance of inclusion and exclusion today, I have not published in Development for over a quarter of a century (Hopwood et al., 1992). Having become a historian of science and medicine, I know more about research on embryos in 1819 and 1919 than in 2019. So I shall not presume to take a strong line on the present, let alone the future, but shall risk a few remarks about how thinking in terms of what is in and what is out might put strategies for renewal into perspective.
Embryology was made a science in the decades around 1800 when the old anatomy and the broad framework of ‘generation’ began to break down. Teratology was established rather separately in the same period. Much research compared the development of vertebrate embryos, and analysed them in terms of germ layers and cells. By the 1850s, professors in the German universities were teaching medical students in dedicated courses. Although their lectures and demonstrations nominally tackled ‘human embryology’, the chick and domestic mammals provided much of the content, especially for early stages. For a long time, embryology had no societies and seldom its own departments, but evolutionism soon drew attention to the science (Hopwood, 2009).
From the 1860s, Darwinists prized embryos as evidence of common descent, and ontogeny as an aid to constructing phylogenies (Gould, 1977; Hopwood, 2015). Comparative embryology built much of the edifice of Darwinian biology as it inspired imperial safaris to bring home ‘living fossils’ and ‘missing links’ (Bowler, 1996; Hall, 2001). The most extreme was the ‘winter journey’ of Robert Falcon Scott's Antarctic expedition in 1911. The biologist Edward Wilson attached ‘the greatest possible importance’ to the embryology of the emperor penguin, that ‘nearest approach to a primitive form…of a bird’ (Wilson, 1907, p. 31). He froze to death with Scott, but a team-mate brought back three eggs – to a sadly rather lukewarm reception (Raff, 1996, pp. 1-4).
Evolutionists rarely claimed medical relevance; embryology was not in that sense a matter of life and death. It was much more important than that: at stake was where humanity came from, why we are here and where we are going. This gave embryology public prominence for the first time. But embryologists, comparative anatomists and palaeontologists increasingly disagreed on the relations of ontogeny and phylogeny, and particularly the doctrine of recapitulation. Their rancorous disputes threw the field into crisis and by 1900 were driving young researchers away (Gould, 1977, pp. 167-206; Hopwood, 2015, pp. 171-187). Comparative embryologists still innovated. For example, in 1911 they founded the first society for the science, the International Institute of Embryology. Members of this elitist club collected embryos of endangered mammals in European colonies and produced normal plates (Nieuwkoop, 1961; Hopwood, 2007). Yet after World War I, other research programmes made the running, led by experimental embryology or ‘developmental mechanics’: the most direct ancestor of developmental biology.
From the 1880s, Wilhelm Roux and other experimentalists had asked not how organisms evolved, but how in physiological terms one stage becomes the next, especially how an egg turns into a larva or adult (Maienschein, 1991; Nyhart, 1995). That is a prime illustration of how questions about embryos have varied and changed. Developmental mechanics paid much attention to regulation and regeneration, and had links to medicine, for example, through the experimental generation of malformations and claims to human rejuvenation (Maienschein, 2011; Sengoopta, 2003). Plants were included in principle (Roux et al., 1912), but plant embryology was more integrated into the rest of botany; most articles in Roux's journal dealt with amphibia and marine invertebrates. In the early 20th century the approach was conspicuous in the first centres for biology as distinct from anatomy, zoology or botany. But the earliest specifically embryological research institute focused on humans.
That institute was the Department of Embryology at the Johns Hopkins University in Baltimore, which the Carnegie Institution of Washington, one of those private philanthropies that had begun to fund new fields, founded in 1914. The Carnegie Department institutionalized the methods, invented in German-speaking Europe, of collaborating with clinicians to collect early human embryos, then analysing these by serial sectioning and plastic reconstruction (Hopwood, 2000, 2002). The mission was anatomical and pathological – to set up norms of development and explain deviations from them – and potential medical benefits helped justify support. Evolution was largely off the agenda and few experiments were possible. The Carnegie scientists instead concentrated on detailed descriptions of human developmental anatomy, eventually including the first two weeks. These fed into medical teaching and are still used today (e.g. de Bakker et al., 2016). Between the world wars, the department also pioneered tissue culture, studies of monkey embryology and reproduction, and cine films. In the 1940s, researchers there analysed the results of early attempts to fertilize human eggs in vitro (Maienschein et al., 2004; Buklijas and Hopwood, 2008; Morgan, 2009; Marsh and Ronner, 2008, pp. 104-110).
Of the three research programmes – comparative, experimental and human – experimentation was dominant by the 1930s, when various new initiatives sprang up around it, notably developmental genetics and chemical embryology (Keller, 1986; Abir-Am, 1994; Fantini, 2000). Hans Spemann and Hilde Mangold's discovery of the amphibian organizer was thrilling, but failure to find out its mode of action dampened the excitement considerably (Hamburger, 1988; Fäßler, 1997). Embryology faced more general challenges by the 1940s. Especially in the USA, it was separated from and threatened by genetics, which profited from its uses in breeding plants, animals and humans (Gilbert, 1998). In an age of striving for the unity of science, research on embryos was fragmented and marginal. On the eve of the massive postwar expansion in government funding, embryology was poorly placed to benefit. Developmental biology might have been designed to solve these problems, and to an extent it was.
Defining developmental biology
The expression ‘developmental biology’ first gained wide currency in the postwar USA, by then the major world power and pouring money into science. Taking the lead, Paul Weiss, the emigré Austrian, Chicago professor and Chairman of the Division of Biology and Agriculture at the National Research Council, pushed the National Science Foundation (NSF) to adopt the term. In 1952, the NSF replaced old divisions with a few categories that applied across the living world and so could integrate biology while allowing support for medical research (Appel, 2000, pp. 63-66; Brauckmann, 2013; Crowe et al., 2015) (Fig. 1). In 1956, a series of international meetings promoted the field (Weiss, 1957, 1958). Three years later, when the journal Developmental Biology was launched, with significant European input, the subject was already a going concern. Practitioners traced this back to an important incubator for the convergence between embryology and genetics: the Society for the Study of Development and Growth, renamed the Society for Developmental Biology in 1965 (Oppenheimer, 1966) (Table 1).
Weiss introduced the first issue of Developmental Biology by calling on authors to unite the phenomena of ‘development and growth’, which had been dealt with in many disciplines, from plant physiology to oncology, and included the ‘seriation of stages of chick embryos’, ‘nutrient control of bacterial growth’ and ‘repair of a broken bone’. The processes of interest ranged from growth, differentiation and morphogenesis through maturation and ageing, regulation and regeneration. Tackling these would require engagement with ‘broad problems’, but Weiss otherwise committed to ‘diversity’ and to accepting work ‘[w]hether analytical or descriptive, technical or theoretical, whether using a molecular or an organismic approach, whether dealing with microorganisms, plants, animals, or man’ (Weiss, 1959; further: Keller, 1995). Weiss claimed activities that had a place in Roux's grandest plans for developmental mechanics, but put more emphasis than Roux's followers ever had in practice on embracing the whole living world, including microbes.
In that heyday of science funding by block grants, developmental biologists found it fairly easy to claim applicability. Weiss himself had worked during the war on nerve regeneration and even contributed to surgical innovations. A ‘growth and development’ perspective potentially illuminated numerous medical problems, but fed into and drew most generally on cancer research, which had been prominent in the foundation of the Growth Society itself (Crowe, 2014). It was widely accepted that ‘organized development’ ‘may throw light upon’ ‘malignant growth’ and vice versa (Berrill, 1971, p. 516).
Inclusivity had its limits. It is well known that developmental biology, also as established through textbooks and graduate programmes in the early 1970s, excluded evolution and tended to ignore the environment beyond the laboratory (but see e.g. Mintz, 1958). That was in part because the field followed experimental embryology and in part because of the lure of biomedical dollars. It is less often noted that not only did ‘embryology’ mean something altogether more traditional to generations of medical students, and to some of their teachers, but developmental biologists also organized separately from reproductive biology. This was institutionalized around the same time, but in laboratories linked to farms, clinics and population control (Clarke, 1998) (Table 1). Mammalian developmental biologists moved between these worlds, however (and in Markert and Papaconstantinou, 1975, the SDB embraced reproduction). In the 1970s, embryo transfer was made an agricultural industry and in the 1980s in vitro fertilization became a medical one (Betteridge, 2003; Henig, 2004; Hopwood, 2018b).
A few developmental biologists joined more medically oriented embryologists, paediatricians and others in the teratology societies that were set up from 1960, initially in the USA and Japan. These responded to worries about congenital malformations – their visibility greater after World War II, as mortality and morbidity from other causes declined – and attracted funding from a new Human Embryology and Development Study Section of the National Institutes of Health. The thalidomide tragedy then amplified their concerns (Kalter, 2003; Dron, 2016; further: Donnai and Read, 2003).
The UK, like other countries which I cannot cover here, made a less researched and apparently more gradual transition to developmental biology, with much interaction across the Atlantic (Table 1). [For other countries, see the special issues of the International Journal of Developmental Biology, www.ijdb.ehu.es/web/issues/special-countries/.] Young initiatives, including chemical embryology and developmental genetics, had been well represented in the UK since the 1930s. But the London Embryologists' Club, the forerunner of the BSDB, did not portray itself as a disciplinary innovation when founded 71 years ago in 1948. The minutes of the first meeting identified three useful, but hardly revolutionary, aims: ‘[i]nformal discussion of problems of embryology’, ‘meet[ing] embryologists from other countries’ and ‘compil[ing] a record of research material in this country’ (Slack, 2000) (Fig. 2). Yet given the divisions between comparative, experimental and human approaches, it was novel just to bring them together (Hopwood, 2009).
The London club encompassed all kinds of projects, and a wide range of species, including humans, though not much explicitly comparative work (Slack, 2000). Research expanded and diversified, not least through the rise of molecular biology. The club went national as the Society for Developmental Biology in 1964, an obvious step, although it is unclear why it was taken then. The remit was ‘those aspects of animal and plant biology that are connected with developmental processes’ (SDB-1964 at bsdb.org/2018/04/29/bsdb-archive/). To avoid confusion with the American society, which was renamed the next year, the British one added the first ‘B’ in 1969. The programme of the inaugural meeting of the national society, hosted by John Gurdon in Oxford, shows varied interests: biochemistry (proteins and DNA) and transplantation; plants and animals, including humans and hydra; and adult tissues as well as embryos (Fig. 3). But neither evolution nor environmental matters were represented; any clinical relevance was implicit.
The Company of Biologists had founded the Journal of Embryology and Experimental Morphology (JEEM) in 1953, following an initiative of the International Institute in Utrecht, as ‘a new periodical…primarily devoted to morphogenesis’. The cumbersome name signalled a pooling of resources for ‘embryologists’, like the London club, more than any reorganization of ‘the science of development’. JEEM sought ‘contributions’ about ‘how living, non-pathological structures are built up, increased, maintained, repaired [and] transformed, either at the supracellular, or cellular, or macromolecular level’. With a focus on ‘the animal realm’ and only ‘occasional papers or reviews’ expected to ‘throw out a bridge towards morphogenesis in unicellular and plant organisms’ (Dalcq, 1953), the taxonomical scope was narrower than Developmental Biology or Current Topics in Developmental Biology. By contrast, JEEM was less exclusively experimental, biophysical and biochemical – and thus more open to, for example, descriptive human embryology – though it became more similar with its relaunch as Development in 1987 (Wylie, 2012).
The BSDB and these journals were not the whole story because society members wore various other hats. As in the USA, the establishment of the reproductive sciences shaped these hybrid identities (Table 1). With the growing ability to culture mammalian embryos, the large UK community of mammalian embryologists played an increasing role in the BSDB and also attended meetings of the Society for the Study of Fertility (Graham, 2000; Clarke, 2007). Some have gone to conferences of the International Embryo Transfer Society, which is oriented towards animal breeding, or the European Society of Human Reproduction and Embryology, which has concentrated on IVF (Betteridge, 2003; Brown, 2005). There was and is mutual exclusion, too: the organization that claims, with over 800 members, to be ‘the UK's only professional body representing embryologists’ is not the BSDB, but the Association of Clinical Embryologists (www.embryologists.org.uk, last accessed 9 November 2018).
Developmental biology may, then, consider itself the main successor of experimental embryology. The somewhat separate institutionalization of embryos in reproductive biology and medicine cautions against assuming that developmental biology monopolized research after 1960. Like its principal predecessor, it has rather been one kind of embryology among several and with a scope for the most part more restricted even than Weiss's vision implied.
Detailed historical investigation will be needed to establish the extent to which developmental biologists realized that vision. Expansion surely made space for new areas of research, from nuclear transplantation, through embryonal carcinoma and embryonic stem cells, to plant systems. But after 30 years ‘the goal of easy discourse between animal and plant developmental biologists still seem[ed]’, to one American sea-urchin specialist, ‘only on the horizon’ (Wilt, 1990). In 1994, a celebration and stock-taking included ‘all multicellular organisms’, but concentrated on the core topics of embryogenesis, morphogenesis and regeneration (Hines et al., 1994), which had long been the focus of developmental biology textbooks too.
The initial advance of developmental biology was no simple ‘molecularization’ (Crowe et al., 2015), but cells, genes and molecules did move centre stage as the control of gene expression became the overriding interest. The pull of genetics gave developmental biology a different species profile from the old experimental embryology; mice, flies and worms were later joined by thale cress and zebrafish. In the 1980s, the combination of traditional but large-scale genetic and embryological methods with gene and antibody cloning produced an explosion of knowledge, which I do not claim to represent fully with two journal covers (Fig. 4). Problems set in the earlier 20th century were solved, or their solution made to appear imminent.
The field expanded, on one measure from 690 researchers internationally in 1949 to some 3400 in 1980 (Faber and Salomé, 1981). Membership of the BSDB rose from 186 in 1965 and 400 in 1980 to 1246 in 2000 (BSDB Newsletter, no. 2, 1980, p. 2, 1980-1(#2) at http://bsdb.org/2018/04/29/bsdb-archive/; Slack, 2000). Yet the investment then necessary to carry out this sort of work reinforced the concentration on a few not entirely representative species (Bolker, 1995; but see also Davies, 2007). Narrowing was a precondition of deepening, and the advantages of exclusion, of concentrating on egg to embryo in a handful of model organisms and a few experimental systems, were well rehearsed. In similar ways, a tight focus had allowed the Carnegie Department to describe human developmental anatomy in exquisite detail and Spemann's school to elucidate the behaviour of the organizer, though with diminishing returns.
In developmental biology, a period of soul-searching followed the excitement of the 1980s and 1990s. When the field was founded, money had flowed and scientists enjoyed more freedom in research than ever before or since. Calls for applications grew louder in the 1970s, and eventually reached developmental biology. As funders required pay-offs to justify higher levels of support, all biologists felt more pressure to make the case (e.g. Gilbert, 2017; Maartens et al., 2018). [Knowing the amount of money available per developmental biologist would define pressures that might have favoured inclusion or exclusion, but the era of model organisms shows that expansion and a certain narrowing could go hand in hand.] It should be reassuring to remember that practical demands have often driven fundamental discoveries, such as in bacteriology and immunology, endocrinology and the control of reproduction (e.g. Oudshoorn, 1994; Brock, 1999).
Other challenges have been organizational, technical and intellectual: the welter of necessary but not always electrifying detail; the stresses of fragmentation into competing subfields; and the politics of species choice (Hopwood, 2011). The difficulty of negotiating relations with the rapidly multiplying stem cell field has loomed large amidst the hope, horror and hype about regenerative medicine (Maehle, 2011; Maienschein, 2011). Many developmental biologists have talked of ‘decline’ from a ‘golden age’ (e.g. St Johnston, 2015), though others, and some of the same people, see a gilded present and a bright future (St Johnston, 2015; Gilbert, 2017; Maartens and Tabin, 2018; see also Pourquié, 2012, 2018; and Zon, 2019). With renewal in progress, I hope that looking back will place recent trends and aid reflection on the next paths to take.
Strategies for renewal
Developmental biologists have long drawn strength from embracing approaches and methods of neighbouring fields. The default strategy is to include the latest techniques, such as systems analysis based on ‘-omics’ and model-building, gene editing and organoids, advanced imaging and soft-matter physics, but to apply them to deepening core studies of embryogenesis (St Johnston, 2015). One of the most striking changes since I left the field is a general move to quantification, with the mainstreaming of mathematical modelling and routine interaction between ‘wet’ and ‘dry’ biology. It is a source of optimism that new methods enlarge the range of options – inclusion and exclusion is not from a fixed menu – but this is not enough. On the one hand, the postwar founders of developmental biology enacted major exclusions that have been relaxed as the costs have become clear. On the other, those early developmental biologists made promises about inclusion that are relevant still.
The founding promise was to study development across the living world. That sounds inclusive, but researchers' expectation that the principles would be the same in all multicellular organisms increasingly justified their focus on just a few. Interest in diversity for its own sake goes back to the renaissance of ‘evolution and development’ around 1980 and gained momentum with the discovery of the conserved colinearity of Hox genes and the rise of ‘evo-devo’ in the 1990s (Laubichler and Maienschein, 2007). Since then, it has been popular to go beyond model organisms, to introduce new ones and to work on several, with less of a trade-off in depth than there used to be, thanks to techniques such as RNAi and CRISPR/Cas (Hopwood, 2011). Humans, previously marginal to developmental biology, have attracted renewed attention as stem cell cultures have opened differentiation and morphogenesis to experimentation (Pourquié et al., 2015).
A second promise is less generally appreciated: developmental biology proposed to study the life course and not just egg to embryo, or even sexual maturity. Today, more effort is going into understanding later processes, from organogenesis through histogenesis to physiological function. Developmental biology has played a role in ageing research, not least in relation to programmed cell death (Jiang, 2013). Looking to life cycles could reduce the continuing separation from reproductive studies and might help go further still. The current ecological crisis makes a compelling argument for seeking a wider synthesis, and research increasingly includes the environmental regulation of reproduction and development, evolution and health (Gluckman et al., 2010; Gilbert and Epel, 2015).
Developmental biology has not been just (experimental) embryology by another name. Rather, developmental biology was made after World War II with a particular set of inclusions and exclusions, and has been reworked ever since. By including evolution and humans, the field has now expanded to encompass versions of all three earlier embryologies that I picked out. As you continue to remake it today, you are including or excluding questions and approaches, species and audiences, all the time.
I have leant towards an inclusive strategy, and pointed to opportunities, for example, in reproduction and in ecology, in the conviction that developmental biology will end up stronger and more effective if it can succeed in tackling more. But I accept that, at almost every historical juncture, a commentator could have emphasized either inclusion or exclusion as the productive move. My brief is less for one vision or another, and more for the value of standing back, seeing the bigger picture and considering how it matters what is kept in and what is left out.
The article is based on a talk at the 2018 BSDB Spring Meeting in Warwick. I thank Andreas Prokop for the invitation to speak; Aidan Maartens for commissioning this piece; Scott Gilbert, Alex Gould, Jeremy Green, Tim Horder, Martin Johnson, Aidan Maartens, Alfonso Martinez Arias and two anonymous reviewers for comments on drafts; and Mike Taylor and Ian Bolton for scans.