The Small Sample Size of Humanity

Comparisons to machines and information processors hide what's most fascinating about the human body: its underlying randomness.
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(PHOTO: SERGEY NIVENS/SHUTTERSTOCK)

(PHOTO: SERGEY NIVENS/SHUTTERSTOCK)

Ever since the Greeks invented science (and probably earlier), people have asked, “Is life caused by the same physical processes that underlie the non-living world?” Humans have often tried to answer this question by turning to the workings of our own inventions, comparing living things to pumps, steam engines, clocks, and computers. But when we compare life to machines, we miss one of life's most unique features: The orderly functions of living things emerge from a shockingly random foundation. By exploring this randomness, researchers are gaining new insights into what makes life tick.

Descartes famously declared that animals were machines (PDF). In the 17th century, comparisons between living things and machines were common among scientists and philosophers, who argued that bodies were comprised of pumps, levers, springs, and wires that act according to the same physical laws that govern the workings of machines built by humans. It was a useful comparison; The action of the heart loses its mystery when you see it as a pump that operates much like the one at the local city well.

These days we make similar comparisons, although we've updated them to fit our cultural shift from a focus on mechanical labor to information processing. Living cells are often compared to a computer, receiving inputs and generating outputs according to a genetic program. While humans build hardware and software, nature makes wetware.

Physicists and biologists have now recognized that to understand the physical basis of life, we need to embrace the randomness, and try to understand how you build a reliable system out of unreliable parts.

WHILE THESE COMPARISONS ARE often a useful way to think about the inner workings of living things, the analogy with devices engineered by humans misses one of the most mystifying and unique features at life's core: its pervasive randomness. The Austrian physicist Erwin Schrödinger was one of the first to explicitly lay out the challenge that the randomness inside living cells presented to the conventional laws of physics. He was hunkered down in Dublin during the winter of 1943, waiting out the war in Europe, when he gave an influential series of lectures (PDF) on the physical basis of life.

Most physical laws, Schrödinger noted, are statistical—they only work well when they're applied to systems made up of a very large number of molecules. The laws of physics describe the world with stunning accuracy, but that accuracy comes from the fact that most of the phenomena we observe in the world involve trillions of molecules. In the aggregate, the behavior of these molecules is highly ordered, but considered only a few at a time, molecules are unpredictable.

The random behavior of a collection of molecules is like a series of coin flips. We can predict with very high confidence that, after one million flips of a fair coin, the number of heads and tails will be almost exactly matched. But if you flip that coin only 10 times, you shouldn't be too surprised if you see heads come up twice as often as tails. With small numbers, large fluctuations away from the expected result are common.

This is where life presents a paradox: Living things are among the most complex, highly ordered assemblages of molecules that we know of, and yet, at the fundamental level of the cell, life is not made up of enough molecules to expect any kind of ordered behavior. Small numbers of molecules, wrote Schrödinger, "much too small to display exact statistical laws," manage to somehow "play a dominating role in the very orderly and lawful events within a living organism." So what gives? Is life an exception to the laws of physics?

Fortunately for physicists, the answer is no. This is partly because, as Schrödinger presciently figured out, living beings pack a lot of information into stable, giant molecular structures like chromosomes, which aren't subject to many of the random fluctuations that beset small molecules. But in general, as researchers have discovered, life on the micron scale really is shockingly random. Physicists and biologists have now recognized that to understand the physical basis of life, we need to embrace the randomness, and try to understand how you build a reliable system out of unreliable parts. Unlike a machine or a computer, living things have to pull signals out of molecular noise.

THE RANDOM NOISE INSIDE our cells has recently become a hot and controversial topic in biology. Is noise a bug or a feature? Is it something that the cell merely tolerates, or is noise an integral part of our functioning? There is some evidence that a cell's molecular static can be used to its advantage. Researchers have found that noise explains why some bacteria in a population resist antibiotics when most of their genetically identical siblings are wiped out, and noise may play a role in stabilizing the intricate body patterns that are established in a developing embryo.

A particularly intense focus of study is the noisy process of switching genes on and off, a process that is central to nearly everything that happens inside your cells. Switching on a gene is not like flipping a light switch. Rather, it's like the faulty light switch in my basement, which has a success rate substantially less than 100 percent. Researchers are reverse engineering this noisy process, and learning just how it is that our generally reliable bodies can be composed of unreliable parts. Anders Hansen and Erin O'Shea at Harvard University recently showed that gene switches make a trade-off; A switch can filter out a noisy input signal, but at the cost of creating a noisier output. Within the cell, noise can be managed, but not eliminated.

By thinking of living things in terms of the devices that we build, we can easily miss how life creates unrivaled order from molecular chaos. This process is unlike anything else found in nature. It's a process that is our unique heritage from the time when Earth's very first self-replicating proto-cells tamed the molecular randomness of an inanimate world.

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