The LEGO guide to reductionism


Fashions come and go, but one toy seems to outlast all trends – Lego. And enthralling as these coloured bricks are in their own terms, they also offer an instructive means of explaining* one of the most important principles in science – reductionism.

Reductionism has been the prevailing practical philosophy in molecular bioscience virtually from its inception. The approach is simple, and familiar to any child who’s been confronted by a radio or some other piece of consumer engineering – if you want to understand how it works, take it apart.

Take it apart brick by brick, in Lego terms. Find out how many bricks are in the finished piece, find out which bricks are in contact with which other ones, find out where each brick lies in the overall model, and find out what shape each brick is. With all that to hand, you can go on to determine in what order the components are assembled into the model, and – hopefully – what the model itself does. In essence, it’s like trying to work out what the instruction manual is by starting with the finished piece (or rather, an unlimited supply of finished pieces to take apart).

The analogy goes further. Bricks that look similar may well do similar things, so gaining in-depth knowledge of one type of piece may let you infer what its twins/relatives do in other models. Similarly, by gradually getting experience/gaining insight into smaller, simpler models you can eventually tackle larger and more complex ones.

That is, in a nutshell, what molecular bioscience has been up to. Purifying individual complexes (whether ribosomes, nuclear pores, nucleosomes, flagella, and many, many more), figuring out what proteins and/or nucleic acids they contain, what each of those components does in isolation, what their high-resolution structures are, and how they fit together.

Each of those achievements can sometimes require a small army of people, often working independently and in different labs across the globe, and each requires an ensemble of practical approaches. Tom Pollard of Yale University summarised it neatly when he observed that genetics gives us the number of components, biochemistry gives us the reactions and rates, and cell biology gives the localisations, amounts, and interactions. Putting those elements together in a mathematical model, and seeing how close that model matches the physical reality, lets us see how close we are to comprehending the overall process. And as each successive Lego model is solved, that lets it be integrated into a larger and more detailed whole – nothing less than the sum of our understanding of cells and organisms in their totality.

* To adults who may find the whole tone of this piece somewhat infantile, it’s worth pointing out that the same analogy can be made with IKEA products…or is IKEA simply Lego for grown-ups?

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