Let's Mix Things up
by Thomas Heams

Illustration: David Benqué

Can we compare a cell with a computer? Two recent articles seem to support this very common metaphor. One describes the first computer model of an entire cell)00776-3, which opens the way for very interesting simulations such as testing the effect of mutations or the action of drugs. The other boasts that an entire book has been ‘encoded’ in a negligible quantity of DNA, making the molecule that carries our genes a potential storage system for tomorrow’s nano hard-drives. A cell lives in a computer and DNA could be a computer component; is this a seductive symmetry or a tautology?

After all, when we speak about genetic information or program it is because DNA is capable of storage and transmission, two characteristics which justify the analogy. If one figure bridges these two worlds it is Alan Turing, who would have turned one hundred this year. His theoretical “machines” contributed as much to the birth of computing as to the formation of the concept of a genetic code.

This metaphor has triggered a remarkable research program since the 1950s through molecular biology and thousands of genes that were first studied one by one, then in vast sequencing programs which culminated in the human genome project at the turn of the Millennium. This deep-rooted logic continues in the current wave of synthetic biology — a stimulating, while still fuzzy, engineering approach which presents life like a Lego kit within our reach. Some projects include genetic hyper-modification of bacteria for medical or industrial uses while others aim at nothing less than recreating life in the laboratory.

The projects are diverse, yet they all stand on a common foundation: a decisive trust in DNA’s (re)programmable capacity and the conviction that it is the data processor, the program of cellular life. The two fairly recent articles mentioned earlier continue the long lineage of this dominant mindset.

It is, however, perfectly legitimate to question these foundations. After decades of a reductionist approach, genetics is weighted down by mountains of data which it is trying to escape by rushing forward in an expensive race, much to the delight of technology merchants. A convincing systems biology, one which could at last create a coherent whole out of millions of individual results, is only emerging laboriously. We rely on the power and sophistication of computers (them again!) to try to find patterns, as if we had already given up on the human brain in the face of this task. A few pioneering works aside, multi-scale synthesis (from molecule to organism) is still nowhere to be seen; growing complexity is a convenient explanation for this stalling, as if the very techniques deployed to reach our goal were keeping us from getting there!

This is precisely where we may have been blinded, or misled, by the cell-computer metaphor. According to a number of recent papers, the inner workings of a cell could have less to do with a high precision machine and more with an intrinsic chaos, allowing for great adaptability. While counter-intuitive, this idea brings a new richness and flexibility to our conceptual framing. It includes the Darwinian paradigm of evolution through natural selection and broadens it; the idea of a genetic program (etymologically: “written in advance”) is replaced by that of a toolbox, which each cell uses with different aims and varying degrees of freedom. This idea has been cautiously suggested for a long time. Now that it is backed up by numerous experimental observations, it is gaining traction amongst biologists. Questions around the importance of these chaotic processes as well as their opposition, or not, with high-precision evolutionary mechanisms outline a fascinating and still vastly unexplored field.

Why even mention this debate which seems to belong in a discussion amongst researchers? The first reason is that they open up an alternative to the insane race we are currently witnessing. Making room for cellular chaos in our explanations of biology would prevent us from looking for programs that don’t exist. It is also about questioning the current stockpiling of data: would we try to understand the climate by plotting every cloud and drop of rain on earth? One day, computer science may well produce a precise model of a hypothetical average cell, but what good will it be if such a cell doesn’t exist?

Another reason to raise these questions is the absolute necessity of demystifying scientific objects. When it comes to DNA this is a daunting task: wouldn’t the public understand GMO’s or cloning better if it hadn’t been bombarded by expressions — some very flattering for scientists — such as “the great book of life” and its variants, or if it was clearly explained that a genome depends on cellular machinery as much as the other way around, or if we highlighted how many rational modifications to genetic programs actually fail? In this regard, synthetic biology is a textbook case. As an enticing and diverse field, it has attracted scores of social scientists and philosophers so that, as it emerges as a scientific discipline, it also becomes a real-time narrative of itself, blurring the line between promises and achievements. This auto-reflexive discourse is synthetic biology’s secret-weapon. Even as results start to appear, storytelling always creeps in: the text mentioned above, encoded by George Church into DNA, is … his latest book, to be published shortly, about synthetic biology! This amazing PR stunt reveals the tight links between genes and the words passed on to our collective imaginary. Life’s grammar is used to store a story about life. What a mise en abyme! But synthetic biology deserves better than being just another 2.0 avatar of the computer-cell. It shows great potential: behind the slogans, its champions are often amongst those watching cellular chaos and its cascading implications with the most attention.

Let’s hope that these approaches continue to cross-pollinate: if this dialogue were to catch on, an unprecedented opportunity for high-level qualitative research would be within reach, one that could challenge the current quantitative binge. Accepting creative chaos to understand the living would be a breakthrough and, for once, a great program.

Thomas Heams is a molecular biologist and reader in animal genomics at AgroParisTech.

This article originally appeared in Le Monde Sciences et Technologies 20/09/2012 under the title: Mettons du désordre dans nos idées. Translated from the French by David Benqué.