Biological Relativity

The last two decades have signaled a shift away from the reductionist paradigm in the sciences, notably with the rise in systems-approaches. Ecology and environmental science has been doing this for some time; but for a long time, many biologists and chemists preferred to stick with reductionist projects – simpler, cleaner, and very successful throughout the twentieth century in advancing our understanding of nature. The limitations of the reductionist paradigm have become more apparent, and I expect it to slowly die from a thousand cuts. 

 

The latest book-length stab at reductionism is Denis Noble’s Dance to the Tune of Life, published in 2017. Noble is a biologist at Oxford (since the 1960s), noted for his advances to our understanding to the physiology of the heart, and is often credited as a pioneer in systems biology. He’s been arguing against the reductionist paradigm of biology’s Central Dogma and Modern Synthesis for decades, while pushing for an alternative view he calls Biological Relativity. But he started out as a reductionist, and in a brief account of his personal scientific journey, he tells the tale of how mathematics and computing, coupled with experimentally studying protein channels in the Hodgkin Cycle, led to his ‘conversion’ into a systems biologist.

 

What is Biological Relativity? In a nutshell, there is no “privileged level of causation” in biology. The book’s postscript sums his argument in a series of pithy statements:

·      Organisms, including their genetic material, are necessarily open systems.

·      Open systems are necessarily influenced by processes at larger scales.

·      Meaning and function are natural features of larger-scale phenomena in biology, not of individual molecules.

·      The reason is that physico-chemical processes at smaller scales are necessarily constrained by higher scales. Even a molecular determinist has to admit this.

·      What is ordered and functional at higher scales can appear stochastic (random) and non-functional at lower scales.

·      Lack of purpose at the molecular scale does not therefore entail lack of purpose at other scales.

 

Noble marshals a series of arguments through his book, beginning with principles of relativity in physics. He quickly gets into biology by introducing the difference between scales and levels: “Scale refers to the dimensions and boundaries of a chosen subset of nature. Level refers to (often roughly) distinct forms of organisation… Scale is a more neutral description than level since it does not depend on organisation, even though different forms of organisation occur at the different scales. By contrast, the conept of level depends precisely on what we identify as forms of organisation. The level of cells depends on the form of organisation we call a cell, which is viewed as being above the level of molecules and, in multicellular organisms, below that of the whole organism.”

 

Hence, ‘level’ is a metaphysical concept. Noble elaborates this with examples from biology and philosophy. But his take-home message is that “a cell is vastly more than its DNA, and an organism is vastly more than a collection of cells. All of that ‘vastly more’ is passed on to subsequent generations…” with profound consequences when you look at things from a systems point of view. Noble does not shy away from language about ‘natural purposiveness’, sometimes referred to as teleology or teleonomy (depending on how you split the differences). Noble credits the gifted writing skills of Richard Dawkins in The Selfish Gene, but argues that Dawkins’ reductionist view has led biologists and the general public astray in the range of ‘nature’ versus ‘nurture’ debates that are widespread today.

 

Here’s what Noble has to say: “… it is combinations of genes, or rather combinatorial total interactions between large numbers of their products, RNAs and proteins, that are important functionally… the functional pattern may not be visible at a molecular level... one of the reasons why Neo-Darwinists use a gene-centric view to claim that all variation is random with respect to function. The non-randomness may only be evident if one takes a high[er] level perspective… most single genes contribute very little to complex functions, which is why the correlations between genes and complex diseases have been found to be a matter of large numbers of very small effects… The atomistic view was never going to be of much use in physiology and pathology.”

 

In my field of computational chemistry, the dictum is to use the “right level of theory (methodology) for the right problem”. At the quantum level, we cannot solve the Schrodinger equation exactly for anything beyond a one-electron system, so we make approximations. The larger our system, the more approximations we make. Error-cancellation is our friend. What seem like simplistic models can in some cases give you very good predictions (when compared to ‘clean’ experimental results, often unavailable for interesting systems). So I’m in sympathy with Noble when he argues that “we should ascribe functions and purposes to the level at which they make sense, which is the level at which they constrain the interactions of the system at lower levels. This constraint is also what canalises those interactions to serve the natural purposiveness of organisms.”

 

The nub of the problem, according to Noble is a clash of conceptual categories between the mechanical view and the “functionally purposive” view. Noble categorizes the former as “the unjustified assumption is that organisms are closed, determinate systems” and that “demonstrating pure ‘blind’ mechanism at one level does not guarantee the absence of function at a higher level.” The problem with the reductionist view, and one that as a chemist I’m used to taking, is that it privileges the atomistic or molecular level. I call as witness the huge shift in grant funding opportunities towards the molecular sciences in the last half century, quite prominent in molecular biology. Organismal level biologists are getting shut out. Without denigrating the amazing advances in molecular biology, Noble would argue that it’s a huge mistake to privilege a particular level when arguing about causation. Noble also reminds his readers that DNA isn’t the all-important director of cell affairs. It’s more like a very useful data-storage-bank that the organism utilizes as it goes through the motions of life.

 

As I moved into studying self-assembly and complex systems, and puzzled over origin-of-life chemistry, I’ve gone through a similar journey. My initial focus was on prebiotic chemistry pathways to make particular molecules that extant life now uses. How and where those molecules were used in an ‘open’ living system were less of a concern. Why? Because it’s easier to reduce a problem into something bite-sized and more manageable, especially if you exclusively work with undergraduates in your research program. I was relatively successful at this, but I now think it’s somewhat of a dead-end approach. I’m moving on to messier systems, thinking about non-equilibrium thermodynamics, and puzzling over how to appropriately choose boundary conditions in multi-level modeling.

 

I’m using the phrase ‘multi-level’ for the first time; previously I used ‘multi-scale’, but Noble’s distinction has made me more aware that I need to think more about functional relationships and less about molecular structure. The chemist’s dictum that “(molecular) structure dictates function” is one I’m moving away from. When taking on larger-scale multi-level systems, a Chemical Relativity seems in order! I’m feeling just a tad more ready to study of Life Itself.