Constellation

The Human Cell Atlas (HCA) combines, in its name and institutional structure, a hyper-modern form of distributed expertise, and a singular mythological figure of towering strength. ‘Atlas’ ties the project to a deep history of totalizing collections of images, with its origins in cartography and a significance that ranges into meteorology, pathology, colour theory, art history and the organization of knowledge itself. But the HCA is also an exemplar of ‘consortium science’ – a distinctive modern form of collaborative endeavour with specific links to post-war international organizations, communications technologies, and ways of ordering and funding laboratory research. The identification of the cell as a fundamental biological unit is also as much a philosophical as it is a pragmatic gesture, binding the HCA to a history that is more recent and provocative than that of the Atlas, older and less singular than that of ‘Big Biology’. The dialogue between the HCA and Constellations is formed, to my mind, through a pattern of keywords – or perhaps better, key-images or -objects – and a rich sense of technological fecundity. Leaving aside the most complex of them all (the Human) and introducing the most complex objects of our daily lives (clouds), ‘In Media Res’ offers three ways to begin thinking historically about the HCA.

1. Atlas

The Atlas is a paradoxical object. Since the word was first carried over from ancient mythology – by the engraver, cosmographer and mapmaker Gerard Mercator in his grand cartographic project published between 1585 and 1595 – it has come to connote a particular kind of order: the cosmic harmony of the God’s eye view. More subtly to us, but self-evidently to Mercator’s contemporaries, the Atlas speaks of the immaculate power of knowledge to permit colonial expansion through navigation, regularise time through astronomy and encompass the globe on a flat printed surface. Mercator knew best of all that the synchronic presentation of a God’s-eye view necessitated a causative story of creation and development. ‘I recognized,’ writes Mercator, ‘that that to cosmography and geography also belong the origin and the history of the heavens and of the earth and of their parts.’

Already by the mid-seventeenth century, however, the term ‘atlas’ had come to refer to vast – almost miscellaneous – collections of images, icons or facts. Against the ideal or universal type of the Atlas, then, we can set its mundane and altogether stranger existence on earth. Art historian Georges Didi-Huberman points out that this paradox is rooted in a more fundamental opposition, between the form of an idea and the reality of an image. In the Atlas the epistemic and the aesthetic are fused, and the result can be explosive.

But there are other, less high-minded ways to deconstruct the Atlas. We can ask, for example, what – or even who – is this ‘Atlas’? Is it the Greek god, not now ‘bearing’ the heavens but, in Mercator’s astonishing image, crafting them: the deification of the cartographer? Or does the Atlas stand for the systematic ordering of the world, triangulated into just this arrangement of geometric forms? Perhaps it is simply a very large format of paper: ‘Atlas Paper’, larger even than ‘Elephant’ and ‘Imperial’ and on sale at all good stationers since at least the early-eighteenth century. Is it then possible to discard the atlas altogether and imagine a world in which it was not Mercator’s term that stuck, but rather his contemporary and rival Abraham Ortelius’ ‘theatrum’/‘theatre’, or perhaps the even stranger ‘mirror’. These metaphors are no less visual, and are more obviously spatial, but they do not build up the cartographer – and by extension the map owner – into such a towering mythological significance. The new science of the cosmos must have, after all, its own ancient figure of modernity.

Fig. 1: Mercator’s Atlas — [Fig. 1: Mercator’s *Atlas*]

In a perceptive analysis, historian Ayesha Ramachandran explores the figure of Atlas as embodiment, arguing that Mercator’s imagery takes us deep into the duality at the heart of the global mapping project: the world map must appear to be a natural imitation, and it must also be understood as a contrivance – a natural-creative act. But why is the Atlas ‘explosive’, to use Didi-Huberman’s surprising word? Because the Atlas also demands a kind of creative expansion, or fecundity. The Atlas does not merely represent – it generates. This has more to do with the second borrowing of the term ‘Atlas’, now moving from cartography into every other visual discipline. It cannot be a coincidence that the first time ‘atlas’ was used for a collection of non-cartographic images was Wilhelm Gumppenberg’s Atlas Marianus of 1657, which collects together icons of the Virgin Mary from the four corners of the earth. Just as the cosmographer Atlas heroically straddles the earth and holds the heavens in his hands, so too the Virgin Mary bridges the sacred and profane.

Fig. 2: Atlas Marianus — [Fig. 2: *Atlas Marianus*]

Browsing the super-abundance of the Atlas is, according to Didi-Huberman, a form of imaginative play, and is no different from the scientific practice of ‘reading the world’ – a task that cannot be done with words or images alone. So the Atlas is a special kind of tool: it doesn’t just record the world, but opens up to create new and surprising connections in – what? Here the metaphors of inside/outside break down, but this is just what Mercator intended when he made Atlas take down the heavens from his shoulders and inscribe them, examine them, represent them anew.

Although the Atlas itself is a tool of anachronism, the general – if tentative – theory of the Atlas needs to be located in a historical sequence that begins with the transformation of the sciences in the sixteenth century. The form of collected maps to which Mercator gave the name ‘Atlas’ originates in the decades following the ‘voyages of discovery’ of Columbus and his European contemporaries. The discipline of cosmography, of which Mercator was perhaps the most famous practitioner, is a hybrid science of astronomy, political geography, ethnography and empire. But if we set the specific term aside for a moment we can see that the Atlas-form – the systematic/analytic collection of images – can also be found at the birth of modern anatomy, in Andreas Vesalius famous 1543 De Humani Corporis Fabrica.

As Ramachandran points out, the early-modern understanding of the microcosm/macrocosm – in which the world is understood on analogy with the body, and vice versa – is mediated very precisely through the Atlas as a new technology of seeing and understanding. The spatial arrangement within the bound covers of the anatomical/cartographic Atlas goes beyond any propositional account of the order of knowledge or the relation of parts to wholes: instead, the gesture is fundamentally aesthetic and generative. New objects of analysis are brought into being, and into contact with one another, through the paper technology of the engraved plate. Mercator’s metaphor was as powerful as its namesake, and within a century the Atlas was in common use. In fact it was quickly used to describe other iconographic collections, and had, as mentioned, come to refer to a particularly large paper size – and by extension anything printed on that size of paper. These two meanings – the generic and the bibliographic – travelled together at least through the eighteenth century. Scale and form remained at least as important as the idea of a systematic sequence of images. This is a crucial feature of the Atlas, and brings us back to the idea of fecundity, of explosive generation and creative energy. Each Atlas performs its own interactive materiality.

Fig. 4c: Image(s) from Albinus’ anatom — [Fig. 4: Image(s) from Albinus’ anatomy]

The ordering and presentation of images is not simply an act of storage or record-keeping – it is an act of community and discipline formation. This can be seen in the medical atlases that proliferated throughout the nineteenth century: these are the instruments of the new clinical science so brilliantly analysed by Michel Foucault in The Birth of the Clinic. Here creation relies on the ordering principle at a grand scale: the invention of the ‘medical gaze’ – in which the patient is seen as if for the first time as a site of actual and potential pathological sequence – replaces disease classification with the reordering of the pathological body, famously broken down by Foucault into the modern ‘spaces’ of, first, the disease itself, then the human body, and finally the social-institutional-political space of modern medical knowledge itself. While the ‘clinic’ is seen as the ideal form of the social space of modern medicine, the medical atlas must be its ideal representation.

The Human Cell Atlas is, in many ways, the completion of this particular historical trajectory. Foucault understood that ‘the body’ was a specific historical construct, brought into being simultaneously with a new set of disciplines and a new conception of disease. Could the body, wondered Foucault, disappear again, to be replaced with something altogether stranger – a new geometry of disease and its relation to living tissue? If we follow Foucault in thinking that revolutions in the sciences are at once theoretical, technical and spatial, then the HCA offers just this possibility, of answering Foucault’s strange-sounding questions:

When will we be able to define the structures that determine, in the secret volume of the body, the course of allergic reactions? Has anyone ever drawn up the specific geometry of a virus diffusion in the thin layer of a segment of tissue?

The ‘spaces’ of the HCA, are then the specific locations of individual cells – now not necessarily linked together in one individual body, and certainly not contained in one tissue sample or dissected corpse. The cells of the HCA are at once highly specific – they are analysed one-by-one using the relatively new technique of single-cell RNA sequencing (scRNA-seq) – and perfectly generic: they can serve as reference cells in an Atlas of the human body that is multi-dimensional in relation to age, gender, personal history, pathology, etc. This possibility – ‘the specific geometry of a virus’ – was precisely at issue in the HCA’s response to the Covid-19 pandemic, as presented in a paper aptly called ‘The Network Effect’, which pairs the ‘network’ of scientists working in tandem on a single problem with the spatial location of the gene that codes for the Sars-Cov-2 receptor ACE2.

Returning to the figure of the Atlas, it would be misleading to suggest that this form of organizing knowledge tends towards medicine in particular, or has a unique relation to the fixing of the medical gaze in the nineteenth century. In fact the Atlas serves its didactic and encyclopaedic function in a range of disciplines, with perhaps the common feature that the significance of the Atlas to a discipline is in direct proportion to the obscurity of that discipline’s central objects of inquiry. This is why the Atlas plays such an outsized role in Lorraine Daston’s and Peter Galison’s extraordinary account of the history of objectivity. Scientific atlases, for Daston and Galison, are the tools that orient specific research communities around unruly objects of study: the cloud, the snowflake, colour, nebulae, the brain, nanospheres, microorganisms, sub-atomic particles, the surface of the sun. In each case, Daston and Galison insist, Atlases are ‘the dictionaries of the sciences of the eye’:

The atlases drill the eye of the beginner and refresh the eye of the old hand.

This is why the Human Cell Atlas’ name is so provocative: what does it mean to train the eye of the biological researcher, when the object – the cell – is one that we can ‘see’ so well, after more than two hundred years of looking?

Fig. 5e: Various atlas images — [Fig. 5: Various atlas images]

2. Cell

The cell has taken a wandering path through the history of biology. The word was borrowed, by Robert Hooke in 1665, from monastic architecture. Using a state-of-the-art compound microscope made to his own design, Hooke observed cavities in organic substances – most famously cork – and imagined that these were like the little chambers in which monks live.

In the early nineteenth century the meaning is inverted and the ‘cell’ becomes a container, not an absence. Cell theory, as it was developed in the German Lands by Matthias Jakob Schleiden and Theodor Schwann, converts structure into function and repositions the cell as the fundamental unit of the living organism. But the cell was not only a functional and foundational component of plant and animal tissues – it was also a container for the hopes of a synthetic biology. Romantic principles of unity and vital force – codified in the programmatic Naturphilosophie of the early-nineteenth century – informed both the experimental programme that resulted in cell theory and its reception across Europe. Here was a common organic object that could be to biology what the elements were to chemistry. Where previous researchers had used ever more powerful microscopes to find the smallest possible constituent parts of living tissues – finding mysterious fluids, fibres and globules that defied illustration or replicability – Schleiden and Schwann offered a much larger (and indeed highly variable) unit of analysis. Crucially, the cell seemed to have a life of its own, obeying the principle of development – ‘omnis cellula e cellula’ / ‘every cell from a pre-existing cell’ – that could serve for diverse tissue structures within one organism, and for the plant and animal kingdoms. The language of the cell – though it is as much a visual as a verbal language – is change or transformation.

If the cell was, in this sense, created by scientists working with a Romantic or ‘naturphilosophic’ approach to nature, then it also in turn had its own creative energy. In fact the debate about the level of autonomy accorded to the cell was itself generative: as historian Staffan Müller-Wille points out, evolutionary thought itself also concerns law-like cycles and generations, and particulate matter as simultaneously ‘formed-by’ and ‘forming’. So too, out of a drive towards unity comes a mass of differentiation. Schwann in particular was not content to allow the cell-as-biological-unity to stand as a conclusion: rather the ubiquity of the cell in fundamentally different tissues and organisms provides an entirely new basis of empirical research, barely now informed by speculation about the unity of life.

So the consolidation of the cell as an object of research was a conciliatory moment in the history of biology, but it set in place a research programme that could only lead to fragmentation, differentiation, even division.

Of course between nineteenth-century cell theory and our own ‘post genomic’ age lies the chasm of DNA and the precise understanding of the nature of heritable material. Yet many of the same questions remain: how should we understand the relationship between parts and wholes? What is the correct ‘unit’ of analysis in biology? These questions resonate at once with Charles Darwin’s own reflections on the relationship between the cell semi-autonomous and evolution as somehow determined by heritable particles, and with present-day questions about genetic determinism vs epigenetics. What is entirely new is the relationship, in the HCA, between the technical innovation that permits single-cell resolution in the analysis of gene-expression, the totalizing ambition to map all human cells, and the scale of the scientific network involved, which reaches around the world and is utterly dependent on modern communications technologies.

3. Cloud

Because they are defined by transformation, clouds have served as both a fertile metaphor – most recently and provocatively in distributed computation – and as a test-case of the limits of the scientific imagination.

Strange as it might seem, the cell and the cloud have much in common. Both were constructed as exemplary scientific objects under the influence of German Romanticism, and both speak to the constructive ability of the observational sciences at times of great technical change. For the followers of Schleiden and Schwann, the cell could stand as a unitary principle bringing together all living beings into a single system. This was the age of a revolution in both the practices of microbiology and in evolutionary thought. We can even see shades of political sentiment in the question that vexed nineteenth century biologists: does each cell develop autonomously and create its own structures, or are the forms of all cells determined by the structures of which they must be a part? For his part, Schwann thought that the latter allowed for an unacceptable ‘autocracy of the organism’. The cell, in this view, is the classical liberal subject: utterly free within the constraints of circumstance.

Clouds, meanwhile, might seem to float free of politics – and also to transcend the vagaries of history – but in fact the classificatory system that gave scientific shape to their unstable forms emerged in a specific political and historical context and can be dated quite precisely.

In late 1802 a young Quaker chemist called Luke Howard gave a short lecture to the ‘Askesian Society’, a relatively short-lived non-conformist group interested in natural knowledge as a form of self-discipline and self-improvement. In his talk, Howard introduced the four basic terms that underpin our classification of the clouds to this day: cirrus, cumulus, stratus and nimbus, with combinations of these accounting, as Howard saw it, for all possible forms of cloud that could exist. Howard’s classification was, like his religion, studiously non-hierarchical: his classification was horizontal in the sense that there were no families or species, only genera that moved into and out of one another through a process of what he called ‘modification’. Unlike his Quakerism, however, Howard’s system was motivated by a deeply iconographic sensibility. Howard taught himself to depict clouds in watercolour and produced, mainly for his own private research, a series of drawings now preserved at the Science Museum, London.

In the end Howard despaired of the possibility of communicating his system visually, but the meteorological community of which he was only loosely a part saw things differently, and already by the mid-nineteenth century a wide range of often highly divergent illustrations of the new classification were in circulation. The process by which Howard’s system was made into a workable scientific resources was threefold: first, his horizontal classification was broken apart and rebuilt in the image of strict hierarchy, with clouds arranged, like living organisms, into genera, species and varieties; second, where Howard eventually demurred from the possibility of using illustrations to depict type specimens of clouds, the international community of meteorologists turned to a mix of photography and diagrams to construct, in 1896, the first ‘cloud atlas’; third, the later nineteenth-century meteorologists understood clouds as signifiers of a new general science of the atmosphere, now decomposed into different regions by latitude and altitude. In fact Howard began his paper on cloud classification by denying this possibility:

If clouds were the mere result of the condensation of vapour in the masses of atmosphere which they occupy, if their variations were produced by tile movements of the atmosphere alone, then indeed might the study of them be deemed an useless pursuit of shadows, an attempt to describe forms which, being the sport of winds, must be ever varying, and therefore not to be defined.

In this way clouds passed from the Romantic paradigm of ‘truth to nature’ – in which the confident observer sought to record nature using the skills of the artist – to the ‘mechanical objectivity’ of the camera, and on to the ‘trained judgment’ of the discerning climate scientist. In this way clouds, as exemplary scientific objects, have followed the sequence of what Daston and Galison call ‘epistemic virtues’: the norms by which scientists have crafted not only their subjects of study but also their personal conduct. The Romantic genius gave way to the disinterested observer, who in turn gave way to the expert mediator.

By the second half of the twentieth century another scientific figure of authority appeared on the scene, not this time characterised by any individual attributes, but by a corporate identity. In the years following World War II so-called ‘Big Science’ brought together massive government funding, the interconnection of disparate research labs and the development of large-scale research projects like the ‘International Geophysical Year’ and the ‘International Biological Programme’. Unlike the Big Science of the physicists, which required ever larger particle accelerators and introduced problems of engineering and scale, the international consortium projects in the geophysical and life sciences were, fundamentally, about data-collection.

Transformations in the scale and ambition of the life sciences also involve transformations in the way scientific information is mediated. This much is evident from the history of Atlas, sketched above. Here we return, finally, to metaphor, and to a new image of scientific communication – the cloud. One of the most persistent metaphors that has attended the development of distributed communications technologies is ‘the cloud’, now turning the uncertainty of the meteorological phenomenon into a powerful generative metaphor for collective technological empowerment. (The relationship is deeper than the metaphor though: computing power has always been tested against the complexity of climate modelling, and the idea of massively parallel processing was suggested as early as 1922 by another Quaker meteorologist, Lewis Fry Richardson.)

This suggestive shift of language – in its own way as profound as the adoption of ‘Atlas’ from mythology – reminds us that scientific objects like the cloud, the cell, the human body are created and maintained in chains of what Bruno Latour calls ‘circulating reference’. The ways in which reference circulates will then give shape to the kinds of scientific objects available to us: the semi-divine body of the world in the classical Atlas, the pathologised body of the clinical atlas, the distributed and aggregated body of the Human Cell Atlas.

1. Atlas

2. Cell

3. Cloud

Further reading