“The Vital Question” by Nick Lane

Artist’s model, 2016

Occasionally a book comes along that completely transforms how you look at a subject, and this is one of them. Nick Lane is an English biochemist with a gift for writing about complex science for a lay readership. Readers vary in their background knowledge of a subject, and the science writer faces a tradeoff between reaching a broad audience on a superficial level and a smaller audience with some technical background. I think Lane has achieved the right balance, but to present his subject in enough detail to depict the tight logic supporting his findings and speculations, the balance was necessarily skewed toward the technical.

And what an amazing, intricately woven theory he presents! His argument is based on solid findings from a variety of scientific disciplines, extended by careful logic into testable hypotheses to form what is almost a biological theory of everything.

In an environment where genetics dominates both research and its popularization, Lane injects basic issues of physics and chemistry that in my experience as an avid science reader are seldom raised in writings about biology. Physics and chemistry seriously constrain the options available to support life, and from these constraints Lane derives a convincing story about the origin of life in general and complex life in particular.

In discussing how cells use nutrients to create the energy needed to sustain life processes, he brings to life the staggering complexity of the microscopic machines that do the job. In this essay, I will explain some terms and quote Lane’s vivid description.

Organic (carbon-containing) molecules in organisms can be classified as proteins, fatty acids, carbohydrates and nucleotides (such as DNA and RNA). One nucleotide, ATP (short for adenosine triphosphate) is a small molecule often referred to as the “molecular unit of currency” that provides the energy to drive cellular processes such as the synthesis of proteins and membranes, movement, cellular division, and transport of materials within a cell.

ATP stores its energy as mechanical stress in a chemical bond, and releases this energy when one of its three phosphate groups breaks free, relaxing the bond. Each cell “spends” on average a staggering ten million ATP molecules a second, and our 40 trillion cells spend our body weight of ATP every day. We only have about 6 grams of ATP molecules, so they must be recharged with energy every minute of so.

The cellular machinery that recharges ATP molecules is as universal as the genetic code, implying that it arose at the origin of life. The system is surprisingly complicated and counter-intuitive, which highly constrains the environmental conditions necessary for such a system to evolve. Discarding one proposal after another, Lane makes a convincing case that life began within the minute pores of alkaline hydrothermal vents, larger and cooler cousins of the more famous “black smokers” found by the submersible Alvin on the seafloor at spreading centers. Detail by detail, he traces the likely sequence of events that resulted in this universal power plant of life.

The centerpiece of the book is Lane’s proposal for resolving what he calls the “black hole” at the center of life’s evolution. The single-celled bacteria and their archaea cousins – prokaryotes – are the original life forms that evolved early in the history of the planet. While by any standard bacteria and archaea are soberingly complex, eukaryotes – protists, animals, plants, algae, fungi and yeasts – exceed them in size and complexity by many orders of magnitude.

The great puzzle is that in the fossil record, eukaryotes appear fully formed, around 1.5 billion years ago. Instead of the expected radiation of different kinds of eukaryotes, and of intermediate forms between prokaryotes and eukaryotes, there is one branch, one LECA (last eukaryotic common ancestor), seemingly fully formed like Athena from the head of Zeus, with all the complex machinery found in its descendants. Why did this happen?

Lynn Margulis established that mitochondria, the organelles in eukaryotes that contain the machinery for producing ATP, are descended from a bacteria that was somehow incorporated into an archaea as an “endosymbiont,” “endo” meaning inside (much later, a photosynthesizing cyanobacteria was incorporated into plants and algae as an endosymbiont, the chloroplast). Mitochondria have their own tiny genome that is passed down through mothers; perhaps you have heard of “mitochondrial Eve”, the mother of us all.

Lane proposes that the newly incorporated mitochondria rapidly transferred their DNA to their new host, causing havoc that was only averted successfully on one occasion. Endosymbiosis is extremely rare, and because of the conflict between the genomes of the host and the endosymbiont, most such natural experiments quickly lead to extinction. But plainly it worked for LECA or we wouldn’t be here. At the end of the book he describes a recently discovered bacterium with an endosymbiont, that appears to be developing complexity. Its extreme rarity demonstrates the difficulty for such collaborations to survive and evolve.

Mitochondria are the heroines of the book, and I will close with Lane’s description of an imaginary trip through a mitochondrion by an ATP-sized person:

Take a dizzying ride down into one of your cells, let’s say a heart muscle cell. Its rhythmic contractions are powered by ATP, which is flooding out from the many large mitochondria, the powerhouses of the cell. Shrink yourself down to the size of an ATP molecule, and zoom in through a large protein pore in the external membrane of a mitochondrion. We find ourselves in a confined space, like the engine room of a boat, packed with overheating protein machinery, stretching as far as the eye can see. The ground is bubbling with what look like little balls, which shoot out from the machines, appearing and disappearing in milliseconds. Protons! The whole space is dancing with the fleeting apparitions of protons, the positively charged nuclei of hydrogen atoms. No wonder you can barely see them! Sneak through one of those monstrous protein machines into the inner bastion, the matrix, and an extraordinary sight greets you. You are in a cavernous space, a dizzying vortex where fluid walls sweep past you in all directions, all jammed with gigantic clanking and spinning machines. Watch your head! These vast protein complexes are sunk deeply into the walls, and move around sluggishly as if submerged in the sea. But their parts move at amazing speed. Some sweep back and forth, too fast for the eye to see, like the pistons of a stream engine. Others spin on their axis, threatening to detach and fly off at any moment, driven by pirouetting crankshafts. Tens of thousands of these crazy perpetual motion machines stretch off in all directions, whirring away, all sound and fury, signifying…what?

You are at the epicentre of the cell, the site of cellular respiration, deep within the mitochondria….

I hope you are inspired to explore this remarkable book.

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