The ‘Cell State’ Revived?

Jonathan Birch

What is an organism? Ask any two biologists from any two different sub-disciplines, and you’d probably get two different answers. A physiologist would give you a physiological answer, an immunologist would give you an immunological answer, a developmental biologist would give you a developmental answer, an evolutionary theorist would give an evolutionary answer… and so on. There would, of course, be some important recurring themes (organisms are ‘integrated wholes’, they are ‘organized’, they are in some sense ‘autonomous’) but as soon as we get down to details it’s plurality, not unity, that prevails.

Perhaps the more interesting question is: why does it matter? This is not a merely rhetorical question. The absence of any standard definition of ‘organism’ has clearlytroubled many eminent biologists throughout the history of the field, and continues to do so. Yet, in most areas of biology, progress seems to be unimpeded by the absence of such a definition. So why does anyone care at all?

My suspicion is that ‘defining the organism’ is often a means by which biologists hope to extend the explanatory reach of their subfield. In other words, it’s a subtle attempt to assert that’s one’s subfield occupies a special, privileged, fundamental position in relation to the rest of biology. If the organism is defined in terms of evolutionary theory, then other biologists cannot afford to be ignorant of evolutionary theory (cf. Richard Dawkins, The Extended Phenotype, 1982). Likewise, if the organism is defined in terms of physiology, then other biologists cannot afford to ignore physiology (cf. Scott Turner, The Extended Organism, 2000) … and so on.

In recent years, some of the most interesting work on the nature of the organism has come from social evolution theorists. In particular, David Queller and Joan Strassmann have influentially argued that ‘the organism is simply a unit with high cooperation and low conflict among its parts’ (‘Beyond Society: The Evolution of Organismality’, Phil Trans R Soc B, 2009). The thought here, in essence, is that the ‘functional integration’ characteristic of an organism may legitimately be regarded as a social phenomenon: the product of complex cooperative interactions among the organism’s lower-level constituents.

The idea that a socially complex insect colony may be regarded as a ‘super-organism’ is reasonably well known, though highly controversial. Queller and Strassmann’s proposal can be seen as a clever inversion of this idea: if we can say that a socially complex colony constitutes a higher-level organism, then why can’t we also say that a multicellular organism is a socially complex colony of cells—and even that a unicellular organism is a socially complex colony of organelles?

Though this idea may sound strange to modern ears, it actually has a surprisingly long history. We can trace its origins at least as far back as the 1850s, when the pioneering pathologist Rudolf Virchow described the organism as a ‘cell state’ (or ‘zellenstaat’). Virchow’s analogy was adopted and adapted by the zoologist Ernst Haeckel, who referred to cells as ‘elementary organisms’. The notion was widespread and influential at the time, but it all but disappeared from biology in the early twentieth century. Its decline probably reflected the rise of physiology and biochemistry, disciplines that downplayed the autonomy of the cell and emphasized its role as a chemical factory—a subordinate part of a larger whole (see Andrew Reynolds, ‘The Theory of the Cell State and the Question of Cell Autonomy in Nineteenth and Early Twentieth-Century Biology’, Science in Context, 2007).

What, then, explains its modern revival by Queller and Strassmann? It seems clear enough that, as with so many organism-definers before them, Queller and Strassmann’s ultimate aim is to maximize the explanatory scope and stature of their subfield. Social evolution theory is growing fast, and it has big ambitions. It increasingly aspires to explain not merely why ants build nests, why meerkats make alarm calls, and why vampire bats share blood, but also how new levels of organism come into existence during so-called ‘evolutionary transitions in individuality’ (cf. Andrew Bourke, Principles of Social Evolution, 2011). Queller and Strassmann’s definition can be read as a manifesto for this expanded paradigm: if organisms are simply units with high cooperation and low conflict among their parts, then social evolution theory will be indispensable to the project of explaining the origin and nature of the organism.

Like the ‘super-organism’ analogy, however, the ‘cell state’ analogy is controversial. I’m a fan of both analogies, but I also understand why they attract considerable scepticism. In the case of the cell state, I think we find two main sources of discontent. The first is the concern that the cells in a multicellular organism should not be regarded as social agents in their own right, because they lack the necessary functional autonomy. They cannot survive for long outside the organism (except in very specific conditions), and their ‘behaviour’ is extremely plastic, largely determined not by their internal constitution but rather by the signals they receive from other cells. Yet the more you try to spell out the precise sense in which cells lack ‘functional autonomy’, the more you realize that the same could be said of virtually any agent in a highly integrated society, humans included. Humans too cannot survive outside a society, except in very specific conditions. Humans too exhibit extremely plastic behaviour, largely determined not by their internal constitution but by the signals they receive from others. Much the same could be said of workers in insect societies. This form of tight-knit interdependence doesn’t preclude social agency—it’s an inescapable consequence of social complexity.

The second concern is that the cells in an organism can hardly be seen as ‘cooperating’ in the standard technical sense of the term, because in social evolution theory an agent is said to ‘cooperate’ when it confers a fitness payoff on another individual, often (though not always) at a cost to itself. Can the cells in an organism really be regarded as bearers of Darwinian fitness, trading payoffs like prisoners in a prisoner’s dilemma, or like donors and free-riders in a public goods game? For example, can apoptosis really be regarded as a process in which a cell altruistically sacrifices its own fitness to confer a benefit on others (cf. Samir Okasha, Evolution and the Levels of Selection, 2006)? I suspect that, in the end, this worry implicates the same kinds of considerations about ‘functional autonomy’ that were implicated in the first worry. There is an intuition that, to be a bearer of fitness, an entity should be ‘in control’ of its own behaviour and functioning. But have the cells in an organism really lost control to any greater extent than the workers in a social insect colony?

There are big open questions here; and it is difficult to tell, at this stage, how useful the Queller-Strassmann definition of the organism will prove. More generally, it is difficult to tell how much social evolution theory will ultimately be able to explain about the origin and nature of the organism. But I think there can be no doubt that the account may prove useful, and is at least worthy of further investigation. The ‘cell state’ analogy is back.

Johnathan Birch
University of Cambridge