Model angst

As I contemplate presenting my research plans in job talks, I’m worried about clearly conveying what we get out of quantitative models. The vast majority of biologists don’t build or use quantitative models, which I recognize is a reasonable consequence of the history of the field, but I find it shocking nonetheless. What this means is that many of these researchers don’t share my fundamental outlook, and, as good skeptical scientists, they won’t take it for granted that models are useful. In fact they’ve probably seen plenty of examples of bad models.

So here is how I justify my mathematical modeling work: Continue reading “Model angst”

Science musings

What biologists need to do more of:

A major goal in all sciences is to be able to explain large-scale phenomena as consequences of the interactions of small-scale components. This is what drives me to study what I’m studying – in my case, the large scale-phenomena are patterns of gene expression, and the small-scale components are transcription factors and DNA binding sites.

Biologists do a lot of measuring of large-scale phenomena, via genomics or classical genetic phenotying. Biologists also spend a lot of time discovering what the small-scale components and interactions are. But they don’t really spend enough effort trying to understand how it is that large-scale phenomena are consequences of the interactions of small-scale components.

Just to be clear: your typical blob-and-arrow pathway diagram featured in Figure 7 of nearly every Cell paper (Fred Cross calls these ‘Figure 7 models’) is not the answer to this question, because it is essentially impossible, in nearly all cases, to predict the large-scale behavior just by looking over one of those diagrams.

Theory vs Experiment in biology, 150 years ago

150 years later, biology still suffers from the tension between creating a rigorous theory and creating a descriptive narrative of experimental results:

From Toulmin and Goodfield’s The Architecture of Matter, p. 331:

[Claude] Bernard not only succeeded in stating acceptable terms for reconciling physiology with physics and chemistry, but also demonstrated in his own experimental enquiries how this compromise was worked out in practice.

Today Bernard is thought of as a scientist – as one of the founders of modern physiology – and so he was. But he spoke of his own work as ‘experimental medicine’, and the name is significant. For, throughout the two hundred years which separated him from Harvey and Descartes, the central problem had been to combine the natural philosopher’s theoretical vision with the medical anatomist’s fidelity to experience. (This was the problem Hippokrates dismissed as insoluble.) The secret of Bernard’s success ay in his capacity to bring these two elements in physiology into fruitful intellectual harmony. Both in his original researches and in his analysis of physiological method, Bernard treated the animal frame as a functioning whole. Though his experimental work was rigorously quantitative and chemical, he always saw the particular process he was studying in their relation to the rest of the body; and this made him the natural successor to Harvey and Galen, as much as to Liebig and Descartes. As we shall see, it also made him less dependent that his predecessors on the hypothesis of a ‘vital principle’. For he showed that the special characteristics of organisms could be explained as resulting from the complexity and interconnectedness of their bodily processes, without the need to introduce any uniquely ‘vital’ cause into one’s account.

Today we still have trouble straddling the line between what Eric Davidson calls “bits of causality swimming in a sea of phenomenology” and rigorous, quantitative theories that explain how complex interactions between ordinary physical molecules give rise to living processes.

Gene Logic: Finding your (micro)Identity

The secret to success in life is to find your identity, particularly if you are a cell. Achieving and holding an identity is the prime concern of life at its most fundamental, cellular level; it is the key to engaging in behavior which best meets the challenges and demands of the molecular thicket that is the environment of the cell. Life can downright bewildering on the micron level. An identity makes this world navigable. Identity determines how a cell looks, what it eats, and the company it keeps. It specifies what environmental signals can be received, and what responses those signals elicit. An E. coli bacterium metabolizing a favorite monosaccharide in your gut, a yeast cell looking to hook up with one of the opposite gender, a nerve cell in your brain primed for an electric response, that light-detecting rod cell in your retina, the myocyte harboring a molecular power train in your bicep, and a cancer cell gone rogue: each of these has at its core an identity that dictates its behavior.
Continue reading “Gene Logic: Finding your (micro)Identity”

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