I've heard a senior colleague say that there is nothing fundamental left to be discovered in biology. It's a nagging worry some people have, including myself. What's left, according to some (including one of molecular biology's founders Sydney Brenner), is to work out the details of particular systems, implied by already established paradigms - kind like chemistry.

Chemistry's done, in terms of fundamental principles. There obviously is a lot we still don't know in this field, but what we don't know isn't likely to be earth shattering. Is this true in biology as well? As far as I can tell, just about everything discovered in biology now is readily understandable in terms of biochemistry, molecular biology, evolution, and genetics. Genome Wide Association Studies have opened up the mystery of "the missing heritability" - the classic case being human height, a trait for which we know a number of contributing genetic variants, all of which explain only a small fraction of height heritability.

But basically we know the answer to the missing heritability is going to be one of several options: a few rare variants of large effect, many, many common variants of small effect, something in between, or even epigenetics - heritable changes of DNA/chromatin methylation. The heritability of quantitative traits is a mystery, but not one that promises to overthrow any of our well established, big ideas about genes.

Another example is what I consider to be the most novel discovery in molecular biology during the course of my short career - the regulation of gene expression by micro RNAs. Here again is nothing earth shattering - it's an amazing phenomenon, but just one more case of how genes are regulated, something that fits easily into our basic understanding of molecular biology.

Contrast this with physics - we'll start with Newton:

Newton's unique contribution lay in the imaginative integration of many ideas into a single picture. This quality of imaginative integration is shared by many of the greatest scientific theories. Starting with a comparatively simple step, but systematically carrying carrying the analysis through an unexpectedly wide field, such theories have the power to present old problems in an entirely new light. Whole new fields of study are opened up to patient and industrious enquiry. As a result, what had seemed to be old, insoluble difficulties appear to us in retrospect, perhaps unfairly, as mere confusions of mind.

- Toulmin and Goodfield, The Fabric of the Heavens, p. 240

This kind of unification has happened over and over again in physics - electricity and magnetism, atomic theory with thermodynamics, quantum mechanics to explain atomic phenomena, general relativity, etc...

It's happened in biology to - key aspects of evolution - descent with modification, natural selection as an evolutionary mechanism, the unification of genetics and evolution through population genetics, heredity as the passing on of discrete genes, and most recently, molecular biology with the basic processes of transcription and translation.

But what are the fundamental question in biology today? Today, "whole new fields of study" are opened up by technology (think metagenomics), not by new deep theories about biology.

Here's another way of putting it: where is the biological analog of particle physics? The primary reason for particle physics is to test the soundness of the deepest laws of physics. Lee Smolin, in The Trouble With Physics, outlines five fundamental questions, such as how do we unify general relativity with quantum mechanics. The answers to any one of these fundamental questions could have extremely broad implications for our understanding of the basic laws of physics.

No such questions exist in biology, as far as I can tell, with the exception of the question of the origins of the first living cells.

So where should young biologists, interested in fundamental questions, put their energy? Or are we wasting our time agonizing over what is fundamental? There are plenty of important questions to work on - understanding disease and disease risk, working out the details of cellular differentiation and development, figuring out how to efficiently engineer biological systems so that we can harness biology to make fuels, synthesize drugs, and clean up environmental contaminants.

The molecular biologists of the 1950's and 60's made discoveries that changed how all biologists think about their work (at least those who work at the level of cells and molecules). I don't see any questions being researched today that have the same potential.

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