Biology needs more egg whites.

By | November 22, 2004

Biology needs more egg whites. While much of cooking is art, any aspiring chef knows that the soufflé is pure science, requiring just the right mix of the perfect ingredients.

Many of the ingredients in the life sciences are irresistible, at whatever scale you care to look. Exquisite protein structures are revealed as minute molecular machinery. Multiplex cascades of signaling reactions connect to transfer information from surface to interior. At higher levels, the tangled web of interactions that control even the simplest immune response is being unwound, and we're beginning to make headway in the bounteous complexities of neuronal signaling. Metabolism and physiology, interactions between organisms and within whole ecosystems – a rich crop of fruits is being harvested by the relentless perfectionism of scientists.

But there's a difficulty. In soufflés as in life science, a binding agent must be present. In the case of science the binding agent ties knowledge together, allowing the application of information gained at one scale to a problem in another. That this is lacking isn't due simply to lack of communication between researchers in different disciplines; it's a tough problem.

Here's one illustration, taken from the previous issue of The Scientist: "Despite all of the interest in how evolution really works, and despite all we know about the genetic pathways that build tissues, we have surprisingly few real examples where traits in natural populations are understood at the molecular level."1 That's the inability to apply knowledge across scale, in a nutshell.

Lack of coherence can occur across smaller-scale differences, too. Take signal transduction: The polypeptide components of signaling complexes are well described. But on the cell-surface membrane, what are the energetic constraints? How many complexes form, why do they form, and for how long? How is a signal that's generated at the surface transduced through the chunky soup of the cytoplasm to the nucleus? It's all a bit of a black box when it comes to dynamics.

Theoretical and modeling approaches offer one solution to biology's binding-agent problem. In the second example above, prediction of the bulk physical properties of the membrane could help explain biological specificity and complexity. For example, the rigidity of membrane lipids helps constrain the orientation of interacting proteins, potentially holding huge, otherwise randomly interacting molecules in a configuration that optimizes the binding opportunity. This may explain why low-affinity interactions are permitted to control such powerful biological outputs.

A multitude of other theoretical biology approaches can be found; for another example, see the recent story on computational neuroscience.2Common elements include origins in the physical sciences and mathematics, and a focus on the bulk properties of systems rather than fixating on biological specificity. Such properties are invariant across biological scale and provide a means to transfer and test concepts at different levels of study.

Theoretical biology is not new; it has a long and illustrious history. What could be revolutionary, however, is the full integration of theoreticians into the development of modern biology. We already have two philosophies working together: Experimental hypothesis testing, arguably still the main source of knowledge in the life sciences, is integrating beautifully with "discovery science," the mining of huge databases using bioinformatics to identify novel patterns and connections that couldn't be found by lab research.

Theoretical biology could be just the egg white we need to keep it all together.

Richard Gallagher, Editor (rgallagher@the-scientist.com)

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