How Life Works — why there’s more to it all than DNA

I can’t read Philip Ball’s ambitious and eye-opening book without remembering the stupidest thing I ever heard a scientist say. It was in grad school, years ago, at a seminar on big questions in biology.

Living things have different kinds of symmetry, we were reminded. Humans are bilateral: you can bisect us and get two mirror images. The real mystery, the prof intoned, was how you get a human, which is bilateral, out of DNA, which is not.

I was the only non-molecular biologist there. “We don’t start life as strands of DNA,” I spluttered. “We start as eggs and sperm. Did your dad never have that chat with you?” I hoped the slight levity would soften my outburst. It didn’t. He ignored me. Everyone else glared. I snuck out.

Such near-deification of DNA as the controller of everything in biology also irks Ball in How Life Works, the prolific science writer’s latest outing. In 1953, Watson and Crick, famed publishers of its double helix structure, called it the secret of life — as though “life itself somehow inheres in the DNA molecule”, Ball complains, like a latter-day soul. He goes on to explain why it’s much more interesting than that.

When the Human Genome Project sequenced a human’s DNA, scientists were shocked to find only some 20,000 genes for proteins, the same as a much less complex worm

Some DNA-centrism was understandable, after the momentous discoveries of how it carries recipes for our proteins between generations. DNA works via the tellingly named Central Dogma: it is transcribed into RNA, which is translated into proteins, which do all the tasks of living, from digesting food to having freckles. It seemed this was all we needed. The information flows only one way. DNA rules. It is, we are repeatedly told, “the blueprint of life”.

Except the research that Ball describes shows it doesn’t, and it isn’t. One clue was that when the Human Genome Project sequenced a human’s DNA in 2003, scientists were shocked to find only some 20,000 genes for proteins, the same as a much less complex worm. How could this be? What else produces our complexity?

Well, for starters, besides the Central Dogma’s protein-coding DNA, we carry a lot of DNA — far more than a worm does — that codes for smallish RNAs which control the transcription of other genes. These are made depending on where the cell is, and what else is happening or has happened in and outside it, in a fiendishly complex network of feedbacks.

In a further complication, our genes for proteins don’t always make just one, but sometimes dozens of variants, each doing wildly different things, depending on different splicing and processing of the RNA after it is transcribed. Our DNA may carry a similar number of proven protein recipes as a worm’s, but evolution — especially the mega-leap from single to multi-celled organisms — led to increased complexity via more levels of control. Our genes do more.

Importantly, there is no DNA blueprint for how this unfolds. We all (as I spluttered long ago) start as cells, the lowest level of biological organisation that is actually alive. Eggs divide, leading to asymmetric signals in the cells that trigger different genes, and those differences trigger still more. We emerge from these epigenetic interactions, “above” DNA which, Ball writes, itself has no “agency”. It is merely a resource that the organism draws on during this process.

To understand this, we need to focus less on isolated molecules, more on intact cells and tissues, the real locus of control — including their electrical properties, which I was delighted to read are getting more attention as cellular control mechanisms.

And it’s not just genes that aren’t as simple as we thought. Remember those diagrams in biology texts of biomolecules interacting like locks and keys? Not the case. At a molecular scale, proteins are wobbly, vibrating, often intrinsically unstructured strings of atoms that interact briefly at best, with varying specificity. This isn’t clockwork: the complex system moves towards the “right” stable state by many possible paths, governed by interactions at many levels.

Ball argues that this looseness is needed for multicellular complexity to emerge despite the occasional mistakes that would crash more rigid chains of interactions — and also so the whole system can evolve. Biology’s crusade to “find the gene” for traits from aggression to cancer has so often failed possibly because it was the wrong question: the real controls can be way above genes in the hierarchy from cell to organism.

So, says Ball, we need to change our thinking. Evidently, given the research cited here, some biologists have. More will, I would suggest, if more biologists are taught the science of complexity. But paradigms in science are infamously stubborn: many have undoubtedly clung too long to a DNA-centric model, causing wasted efforts in science and medicine — and perhaps more bizarre things too.

US police want to use facial recognition technology on faces generated by crime scene DNA. Yet DNA has been found to predict only a few general features of faces. Many identifying details are probably epigenetic, making this a recipe for unjust accusations. As long as popular wisdom regards DNA as a blueprint, such nonsenses will happen. Let’s hope this book gets more young biologists spluttering in seminars.

How Life Works: A User’s Guide to the New Biology by Philip Ball, Picador £22, 560 pages

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