Wilhelm Roux, ”The Struggle of the Parts in the Organism”, and Cell Selection

I thought I was done with the topic of cancer, but nope! From What history tells us XXVIII. What is really new in the current evolutionary theory of cancer?, (2012), I found some interesting history about the idea that cancer is an atavism:

The link between mutations and cancer had been proposed very early, at the beginning of the 20th century, by Theodor Boveri. He conceived the origin of cancer as the abnormal distribution of chromosomes during cell division, provoking a regression of the cell to an uncontrolled, egoistic behaviour (Boveri 1914).

The idea that cancer cells were unregulated cells that had escaped any control by the body was clearly at odds with the model that tumour cells evolve as organisms do. Once again, cancer was seen as the return to an ancestral, uncontrolled state, not the result of an open evolution.

This opposition probably explains why Wilhelm Roux did not propose an evolutionary model of cancer in his 1881 book on the fight of the parts within organisms (Roux 1881, 2012). This book was immediately well received, but rapidly forgotten. Roux proposed that a struggle between the different parts of the organism – molecules, cells, tissues and organs – took place during development. Somehow, he extended Darwinian competition to what happened within organisms during development. This competition of the different parts of the organism for resources was essential for the optimization of physiological adaptation.

Basically, Wilhelm Roux thought that in the development of a single body, the parts of a body are fighting over resources, just as bodies fight over resources in an ecosystem. The result of this (well-organized) fight is a fine and optimized body.

Since tumours also compete for food with the rest of the organism, it might have seemed appropriate to include them in the picture. Roux did not, because he considered that these cells had embryonic characteristics... and were utterly unregulated. Their behaviour could not be compared to the well-regulated competition that took place during the development of organisms (Roux 1881, 2012, p 69).

... competition between parts of an organism? Who is this guy? We'll follow Selection within organisms in the nineteenth century: Wilhelm Roux’s complex legacy (2012).

Wilhelm Roux

Wilhelm Roux was a 19-century experimental embryologist who was best known for pioneering Entwickelungsmechanik [developmental mechanics]... In 1881 he used Charles Darwin’s theory of natural selection to describe the relationships between cells and the development of organs in embryos, and published these ideas in Der Kampf der Theile im Organismus. Ernst Haeckel praised the work, but Roux’s mentor, Gustav Schwalbe, had a distaste for the book’s philosophical nature: “Do not ever write philosophical book of this kind again, otherwise you will never become a professor of anatomy.”

But Charles Darwin liked it:

“As far as I can imperfectly judge, it is the more important book on evolution, which as appeared for some time”... What is so noteworthy in this book to arouse Darwin’s attention? To put it simply, nothing less than the extension of darwinian processes inside organisms. 

Roux assumed that “there is a struggle going on within every organism, between the organic molecules, the cells, the tissues, and the organs. [The book’s] basis is that every cell that best performs its function is, in consequence, at the same time best nourished, and best propagates its kind” ... he envisions the body as a space full of contradictory forces, with structures of different scales and different shapes, and wants to explain its development.

An analogy that reminds one of social darwinism:

"Just as the struggle of assemblies has led to the survival of the strongest, it can have acted, and can still act in the same way at the level of the parts, when such an interaction of the parts internally exists. Is it impossible for the State to exist when citizens compete with each other and that only the fittest can influence the general course of events?” (SPO, p. 65)

Roux refers several times to this ‘State’ metaphor for illustrative purpose, but it is also as a reminiscent of his professor Rudolf Virchow, founder of the cellular theory, who depicted bodies as “cellular democracy” or “republics of cells” (Virchow, 1858).

Struggle between molecules 

Roux meant by "molecules" everything that is below the celluar level. So a mitochondria counts.

The struggle of molecules is the starting point of Roux’s journey into the inner body: he assumes their intrinsic differences, that consequently make them compete for space and metabolites, with subsequent differential assimilation capacities... molecules may be successful by lasting longer, or by better saving energy, but mainly, by having a better capacity for growth, when assimilation prevails over degradation.

In this way, the struggle between molecules allows the molecules in a cell to be selected, and thus optimize the cell to take on whatever traits the location of the cell demands.

Roux imagines several examples: the cells that “contract strongly and quickly” are selected in the muscle regions, the ones that “best use a stimulus to attract and transform the matter to be released” give glands, an the ones that “do not use the stimulus for themselves but let it pass through them” give rise to the nerves. 

It actually isn't completely wrong! 

When regulatory molecules are widely outnumbered by their available target sites, an intrinsic topological competition occurs among these sites for regulators (Nan et al., 1997)... And at the evolutionary timescale, one may also recall famous cases of competitive relationships between such ‘parts’: intragenomic conflicts for example, arise when genes that do not follow the same transmission rules, are described in terms of “selfish DNA” dynamics (Orgel and Crick, 1980). Maternally transmitted mitochondrial DNA versus genomic DNA, or Y-chromosome DNA (paternally transmitted) can exhibit evolutionary features of such “struggles”.

Struggle between cells, and stochastic gene expression

It turns out that genes are not expressed deterministically. There's some randomness in the heart of celluar DNA expression.

... cells are not strictly equivalent to computers, and that even if evolutionary forces select precise genetic programs to answer to variations in the (local) environment, the intrinsic stochastic nature of molecular event prevents these adapted answers to be delivered with absolute certainty.

This provides the variation upon which a darwinian struggle can happen between cells within a multicelluar organism.

the cellular level is the one where even today, a struggle of parts could be considered the more relevant. 

Suddenly, Nietzsche makes an appearance!

Roux mostly depicts a direct form of struggle, with molecules and cells destroying others ones. He refers several times to military metaphores: “When parts struggle against each other to acquire an ever greater efficiency, the overall performance should also increase, in the same way that the efficiency of an army increases when officers compete and when the best among them are selected to train the novice soldiers.” (SPO, p. 107). This is indeed a restrictive reading of darwinian ideas, but it paradoxically contributed to SPO’s legacy, thanks to the works of Friedrich Nietzsche. Indeed, the German philosopher, who had fluctuating feelings about darwinism (Moore, 2002, Richardson, 2004), is known to have considered Roux’s book as his gate toward physiology, a discipline he would develop a special interest for, and to have endorsed Roux’s premises, that he once brilliantly summarized in one fragment by the formula “uniformity is pure delirium”. SPO had a seminal influence on of one his major concepts, the will to power (Wille zur Macht), in which in describes organisms as being built by forces from within, consistent with intra-organismic conflicts of all parts (Müller-Lauter, 1978).

For more on that, you can read on Wikipedia.

Struggle between tissues and organs 

the struggle of tissues and organs mainly acts in maintaining what has been achieved by the lower-level struggle: “[the struggle of tissues] will therefore result in a balance between the different tissues” (SPO, p. 97). Struggles of tissues and organs also lead to a mechanistic consequence, “the principle of self-formation of adaptative size ratios”.

Neural selection

Another major selectionist theory is the ‘selective stabilization of synapses’ (Changeux et al., 1973, Changeux and Danchin, 1976), later confirmed and even explicitly named ‘neural darwinism’ (Edelman, 1987, Edelman and Mountcastle, 1978). It states that at some critical points of brain development, more synaptic contacts than needed are formed, out of which some are later stabilized on the basis of network activity, while the others do not last. Here again, the development of the brain, a structure with one of the most complex architecture ever known, seems to be better explained by an exploratory cell behavior and subsequent selection than by any fine-tuned program.

This strongly reminds me of the feral neuron theory.

Modern view on celluar competition

From Darwin's multicellularity: from neurotrophic theories and cell competition to fitness fingerprints (2014):

Metazoans have evolved ways to engage only the most appropriate cells for long-term tissue development and homeostasis. In many cases, competitive interactions have been shown to guide such cell selection events. In Drosophila, a process termed cell competition eliminates slow proliferating cells from growing epithelia. Recent studies show that cell competition is conserved in mammals with crucial functions like the elimination of suboptimal stem cells from the early embryo and the replacement of old T-cell progenitors in the thymus to prevent tumor formation. Moreover, new data in Drosophila has revealed that fitness indicator proteins, required for cell competition, are also involved in the culling of retinal neurons suggesting that ‘fitness fingerprints’ may play a general role in cell selection.