What is Living?

In 1944, the physicist Erwin Schrodinger published the landmark What is Life. Since then it is requisite for origin-of-life books to address this question early on. In Nick Lane’s The Vital Question (one of my summer reading goals), the first chapter is unsurprisingly titled “What is Life?” Lane goes through the usual discussion, with very engaging prose – accessible to the non-scientist, and strewn with nuggets that the experts will appreciate. Here’s a paragraph on genomes.

“Genomes are the gateway to an enchanted land. The reams of code, 3 billion letters in our own case, read like an experimental novel, an occasionally coherent story in short chapters broken up by blocks of repetitive text, verses, blank pages, streams of consciousness: and peculiar punctuation. A tiny proportion of our own genome, less than 2%, codes for proteins; a larger portion is regulatory; and the function of the rest is liable to cause intemperate rows among otherwise polite scientists.”

But having briefly set the stage, Lane goes on to what he thinks is the much more important question “What is Living?” – the title of the second chapter. This, I think, is much more appropriate and useful and I think he is on the right track in his focus on energy transduction. Two main questions are posed by Lane in this chapter. “Why does all life conserve energy in the form of proton gradients across membranes? And how (and when) did this peculiar but fundamental process evolve?”

It does seem very curious that living systems essentially make use of redox chemistry, the transfer of electrons for all its bioenergetic needs. While different organisms use different redox carriers and “food” sources, they all make use of proton gradients. Lane also emphasizes the interplay between thermodynamics and kinetics. Thermodynamics may drive the redox reaction, but it is the existence of kinetic barriers under our particular environmental conditions that allows life to flourish. If not for these barriers, organic matter would explode in a ball of fire releasing (and wasting) heat all in one go. But life has evolved to exploit the margins in between, and the cascade of intricate molecular machines that have evolved to extract this “vital” energy are a thing of beauty.

The second law of thermodynamics plays a key role in allowing the formation of complex mixtures of molecules, linked together in cyclic dances, and increasing the overall entropy spreading it out across both space and time. Emphasized throughout the first two chapters is the importance in considering the environment that bathes such molecular systems. This is another part of Lane’s approach that I think is right on the money. He has a great illustration that even references the Harry Potter books.

“The second law of thermodynamics states that entropy – disorder – must increase, so it seems odd at first glance that a spore or a virus should be so stable… Take a spore and smash it to smithereens… Surely entropy must have increased! What was once a beautifully ordered system, capable of resuming growth as soon as it found suitable conditions, is now a random non-functional assortment of bits – high entropy by definition. But no!... Grind up a spore and the overall entropy hardly changes, because although the crushed spore itself is more disordered, the component parts now have a higher energy than they did before – oils are mixed with water, immiscible proteins are rammed hard together. This physically ‘uncomfortable’ state costs energy. If a physically comfortable state releases energy into the surroundings as heat, a physically uncomfortable state does the opposite. Energy has to be absorbed from the surroundings, lowering their entropy, cooling them down. Writers of horror stories grasp the central point in their chilling narratives – almost literally. Spectres, poltergeists and Dementors chill, or even freeze, their immediate surroundings, sucking out energy to pay for their unnatural existence.”

While Lane’s ideas on bioenergetics are not new, it is his masterful weaving together of physics, chemistry and biology that will allow him to support an intriguing hypothesis for the source of life’s origins. I will get to those details in a subsequent post as I make my way slowly through subsequent chapters. In the meantime, Lane points out many interesting observations in the world of molecular biology. Eukaryotic radiation is oddly monophyletic compared to the diversity of bacteria and archaea. (He will suggest a single endosymbiotic event compared to the Margulis serial endosymbiosis theory.) He also effectively argues that the archezoa (eukaryotes lacking mitochondria) came later. And he marvels at the surprising complexity of the eukaryote – something I had not quite appreciated until reading his examples and illustrations.

Several years ago, when I decided to move some of my research projects towards understanding the origin of life, I was looking to leverage my expertise as a computational chemist to ask some interesting questions. I settled on the importance of mapping the free energy of molecular systems as they “complexified” and how the thermodynamics and kinetics would change under different environmental conditions. (Hence, I think Lane asks the right questions.) I’m nowhere close to answering the questions (although I am working on it), but it is the asking of good questions that is key. I hope that is something my students learn in my chemistry classes. How do you ask good questions? (They seem much more interested in quickly finding the “correct” answer.) One thing I appreciate about Lane’s first two chapters is that he poses one interesting question after another!