In Search of Cell History: The Evolution of Life's Building Blocks

  • Franklin M. Harold
University of Chicago Press: 2014. 9780226174143 | ISBN: 978-0-2261-7414-3

Franklin Harold's In Search of Cell History is a wonderful book. Harold has for 60 years been an intelligent and clear-minded researcher and observer in the fields of cell and molecular biology. His book is a loving distillation of connections within the incredible diversity of life in the biosphere, framing one of biology's most important remaining questions: how did life begin?

This is also a personal account. Here is Harold musing after washing the dishes: “I look upon my work and see that it is good, and I have no doubt that the same need to find order in the universe motivates much of science.” Using this deceptively casual approach, he cleans up the vast untidy mess of biology and stacks the fundamental concepts in an orderly and creative way for readers to enjoy.

Deep-sea hydrothermal vents may have provided the conditions for the origins of life. Credit: Richard Bizley/SPL

The content of each chapter can be found in any good undergraduate biology text, but Harold fits the information into a larger context, often in unexpected ways. For instance, he discusses geochemist Michael Russell's idea that physical processes in hydrothermal vents could produce proton gradients, in which one side of a barrier membrane is acidic, the other alkaline. The movement of protons across these gradients supplies energy to all life now, and perhaps did so even in the first primitive life. Harold also reveals how much biologists can learn from geologists about the history of life on Earth. For instance, liquid water appeared on Earth more than 4 billion years ago; half a billion years later, the first known microbes (now fossilized in Australian rock) appeared.

I do have a quibble. Harold argues that, notwithstanding the vast literature, progress has gone little beyond the findings of Soviet biochemist Alexander Oparin and British polymath J. B. S. Haldane more than 80 years ago, when they independently argued that Louis Pasteur's dictum 'All life from life' was wrong. Oparin and Haldane theorized that life may have emerged on a sterile prebiotic Earth through a series of chemical and physical processes.

I confess to being more optimistic than Harold. There has been extraordinary progress in understanding the principles by which life works at the molecular level, and that can be applied to the question of how life begins. Over the past eight decades, it has become clear that the basic molecules of life can be synthesized through well-understood chemical reactions. The Strecker synthesis, for instance, produced amino acids from methane, ammonia, hydrogen and water vapour in Stanley Miller's famous 1950s experiment testing the Oparin–Haldane hypothesis. Furthermore, amino acids, nucleobases and lipid-like molecules — the building blocks of life — are present in carbon-containing meteorites. That makes it entirely plausible that similar organic compounds were available on the prebiotic Earth, waiting to be caught up in whatever process led to life's beginning.

A depiction of an animal cell. Credit: Russell Kightley/SPL

There is more. In the 1960s, biophysicist Alec Bangham discovered that phospholipids assemble into cell-sized compartments (liposomes), and chemist Leslie Orgel found that chemically activated nucleotides — the organic molecular subunits of nucleic acids — spontaneously combine, or polymerize, into short strands of RNA. We now understand how light energy is captured by green plants, that the molecule adenosine triphosphate (ATP) is the energy currency of all life and that enzymes such as polymerases use that energy to catalyse the polymerization of amino acids into proteins, and of nucleotides into nucleic acids. The molecular foundation of evolution became clear when DNA's structure and function were established by Francis Crick and James Watson in the 1950s and 1960s. Finally, we know how to encapsulate all those reactions in lipid compartments that mimic cell membranes, and several pioneering laboratories are taking the first steps towards fabricating microscopic systems of molecules that display the fundamental properties of life.

Harold writes about these topics, so it seems that we have made considerable progress after all. If we use a jigsaw puzzle as a metaphor, more than 80 years ago we opened the box and found hundreds of loose pieces; today, some of them have been correctly placed around the edges of the puzzle. We still cannot see the picture in the centre, but I am satisfied that we have the framework.

Thousands of young biologists work mostly on the narrowly defined problems that are the crux of successful grantsmanship. Harold's book is like a balloon that will let them rise above the trees for a while and look down to better understand the scope and shape of the forest — and perhaps then descend to pluck some low-hanging fruit. Senior scientists like myself will take pleasure in comparing perspectives with Harold's. This is, after all, a story to conjure with — that of how life began and evolved into eukaryotic cells, a hundred trillion of which compose the human body. No one can yet tell this story in its entirety, but Harold's book is a good place to start.