Life versus the molecular storm

lifes-ratchetRichard Feynman put it best: “Things on a very small scale behave like nothing that you have any direct experience about. They do not behave like waves, they do not behave like particles, they do not behave like clouds, or billiard balls, or weights on springs, or like anything that you have ever seen… Because atomic behavior is so unlike ordinary experience, it is very difficult to get used to, and it appears peculiar and mysterious to everyone.”

The same could be said about things on a very large scale, such as planets and galaxies. It could also be said about extremes of time and temperature – we have no direct experience with microseconds and millions of years, or with what happens at thousands of degrees or near absolute zero. Scientific concepts that deal with such extremes defy our meso-scale common sense.

We respond to these assaults on our intuition sometimes with gee-whiz fascination, and at other times, when cherished beliefs are on the line, with resistance. Can our mundane actions really change the climate of something so large as the earth? How could we possibly have descended from small, furry dinosaur prey? And if a tornado whipping through a junkyard can’t spontaneously create a Boeing 747, can it really be true that complex, living, self-directing beings are formed out of molecules that merely follow the laws of physics and chemistry, without the guiding influence of vital spirits?

Nanoscale Weird Tales

That last question is the subject of Peter Hoffmann’s fine book, Life’s Ratchet: How molecular machines extract order from chaos, an introduction to biology in the nanoscale realm. This weird world operates in a constant “molecular storm” (i.e., the battering of random thermal motion), where careful accounts are kept in the currency of free energy. The science that explains how this world operates is statistical thermodynamics – a field that may not sound as sexy as the Higgs Boson, genomics, or quantum computing. But in fact, it’s one of the hottest scientific topics out there right now, because it’s the science of how the macroscopic emerges from the microscopic. It is crucial for understanding the nanoscale machines and systems that build life from molecules.

Hoffmann has written a fun, accessible introduction to under-popularized concepts like Brownian ratchets, entropy, free energy, cooperativity, and the Second Law of Thermodynamics, drawing on examples from mayonnaise to snowflakes. He has a knack for metaphors: molecular motors are like a nanoscale Sisyphus who exploits Brownian motion to move his boulder. Lipid molecules “are a kind of conjoined twin, with each part having different affinities. In a mixture of oil and water, lipids can satisfy each part of their split personality.” What’s the difference between myosin and kinesin? “While myosin-V strides, kinesin-I waddles.” Building our intuition with his metaphors, Hoffman explains how the sophisticated operations of the cell occur spontaneously in an environment of molecular chaos and blind physical forces.

This book is pitched at a broad audience, so if you’re a biophysicist, you’ll find it covers very familiar ground. However, this is the book you want to buy for your relatives so that they understand what you do. Few well-written popular science books deal with biophysics, and so the odds are that even voracious consumers of popular science will find some new ideas. A friendly warning: I was almost turned off at the beginning of the book, when Hoffmann covers science history with the ‘how close were Aristotle and Lavoisier to the real answer’ approach, which has long been rejected by people who seriously consider the history of science. However, Hoffmann’s tour of thinking about atoms from Democritus through Helmholtz to Boltzmann and Einstein is entertaining and establishes some valuable context for the rest of the book. If you find the beginning a little frustrating, keep going and you’ll be rewarded.

Genetic Gripes

While I’m listing complaints, let’s turn to some particularly bone-headed comments in the book about genetics. Having moved from a biophysics department to a genetics department, I’m acutely aware of how biophysicists tend to disregard genetics, viewing DNA as just one particularly lazy macromolecule among many. (Geneticists, in turn, often consider proteins a side show.) In discussing the history of genetics, Hoffmann suggests that Francis Galton’s ideas about eugenics would never work because ‘offspring tend to regress towards the mean’, making selective breeding for, say, intelligence impossible. This will seem odd to those agricultural geneticists who run quite successful eugenics programs for plants and animals in spite of normally distributed phenotypes. We certainly could selectively breed humans for all sorts of traits, if it weren’t horribly, profoundly unethical to do so.

Hoffmann also attacks what he characterizes as the DNA-centered view of life. He suggests that an excessive focus on DNA gives ammunition to creationists: “The whole idea of DNA containing information is, in my opinion, one of the main culprits in maintaining the myth of creationism and intelligent design.” Why? Because the “DNA-centered view emphasizes chance over necessity,” and because DNA, in the absence of protein machinery to read it, is meaningless: “I think the utter insufficiency of the information in DNA to specify an organism is one of the most powerful arguments for evolution.”

What Hoffmann is missing here is the role of heritable information. Nobody doubts that the physical properties of individual proteins and their ionic environment are what cause molecular complexes to self-assemble and assume their functional shapes. And yes, sometimes biologists insufficiently appreciate that physical laws give us, in Stuart Kauffman’s term, “order for free”, order which does not need to be explicitly specified by DNA. But the most fundamental difference between self-assembling snowflakes and self-assembling living beings is that living beings inherit genetic information and snowflakes don’t. Building on his discussions of Brownian ratchets that harvest order from chaos, Hoffman suggests that evolution also operates like a ratchet – but this is only true because we have the stabilizing pawl of an inherited genotype. In the absence of the influence of genetic information, cells could not self-propagate, and life would peter out in the face of molecular chaos.

Gripes aside, Life’s Ratchet is a valuable introduction to the non-intuitive, nanoscale world at the foundation of our biology. To quote Peter Hoffmann quoting the great biologist Ernst Mayr, one of the big questions we face is “how living, as a process, can be the product of molecules who themselves are not living.” Much of the answer is coming into view, thanks to the ingenuity of biophysicists.

Author: Mike White

Genomes, Books, and Science Fiction

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