Life's Ratchet: How Molecular Machines Extract Order from Chaos

by Hoffmann, Peter M.

  Let the adventure begin.

  1

  The Life Force

  The human body is a machine that winds itself, a living picture of perpetual motion.

  —JULIEN OFFRAY DE LA METTRIE

  Come, said my soul, Such verses for my Body let us write, (for we are one).

  —WALT WHITMAN, LEAVES OF GRASS

  LIFE IS THE DANCE OF A BEE AND THE ROAR OF A LION. IT IS the tangle of a rain forest and the mortal battle between bacteria and host. Life is amoeba and elephant, evolution and extinction, and the power to transform a planet. The complexity and variety of life is staggering, but for physicists, life begins at a more basic level. All life started as a circle dance of molecules billions of years ago. The lion and the bee, the humble yeast and the mighty blue whale all share the same jittering molecules in their cells; we are all cousins.

  But while life is based on molecules and energy, it seems to defy a purely physical explanation. When we look at a living being, we immediately recognize it as alive, as fundamentally different from a rock or a cloud. Yet, when we try to define life, we run into difficulties. There seems to be something indefinable, some special ingredient that separates inanimate matter from living flesh. When a loved one dies, we despair at not being able to recreate life. It is as though a special ingredient, a “life force,” has left the body. Life seems forever beyond our powers and understanding.

  And yet, we know that modern science has the power to manipulate life. From genetic engineering to brain imaging, science has penetrated living matter to its very core. The dichotomy between our everyday experience of the purposefulness and magic of life, and the fact that when we go looking for the magic ingredient, we only find matter and mechanism, has occupied human minds for thousands of years. It has led to a drawn-out battle between those who see purpose and those who see mechanism. In this battle, sometimes one side gained the upper hand, sometimes the other. Has the battle finally been decided? And if yes, who won?

  The Secret

  If I had to vote for the most abused scientific terms, energy, power, and force would be on the short list. According to the motivational speaker Bob Proctor, human beings are an incredible source of power and could use the “power in their body” to illuminate “a whole city for nearly a week.”*

  Since Proctor is so precise (“nearly a week”—why not a whole week?), it may be worth double-checking his calculations. It turns out that it is quite easy to calculate the power rating of a human being. Power, in physics, measures how fast energy is transformed from one form to another, and not the amount of available energy. Proctor is confusing power with energy. But I don’t want to quibble about that. Let’s pretend he means that the power rating of one human is equivalent to the hundreds of thousands of light bulbs that illuminate a city.

  Humans transform energy from food into motion, heat, and thought. Energy is conserved. The energy we expend during a day comes from the food we eat. A typical energy intake from food is 2,500 food calories per day. One food calorie is equal to 4,184 joules of energy. A human consuming 2,500 food calories takes in approximately 10.5 million joules (2,500 calories × 4,148 joules) in energy from food a day. This sounds like a lot. However, a day has 86,400 seconds, and therefore the rate at which our bodies transform this energy is 10.5 million joules divided by 86,400 seconds, or about 120 watts (where 1 watt = 1 joule per second). Far from illuminating a whole city, a human being has about the same power rating as one light bulb.

  Humans talk, write, walk, and love using the same amount of energy per second as a light bulb, a device that does nothing but shine light and get hot. This amazing fact, far from denigrating humans, is a testament to how efficient a human body is. But even more importantly, it is a testament to the wondrous complexity of our bodies, which can do so much with so little.

  Humans and other living beings are not sources of energy. We are consumers of energy, taking high-grade energy in the form of food and releasing it in the form of low-grade heat into the environment. When we stop eating, we starve and die. This simple truth is nothing new, yet books like Rhonda Byrne’s The Secret (which claims that “human beings manage their own magnetizing energy”) sell millions of copies, making us believe that there are untapped sources of energy within us.* Why is this idea so persuasive? Where did this notion of life force or energy come from?

  The idea that life is infused with special energies or forces is as ancient as humanity itself. When people today are attracted to books like The Secret, it may be because the idea of a life force is deeply engrained in our psyche. For at least a hundred thousand years, humans have tried to bridge the gulf between life and death by placing flowers, food, or tools in burials with their departed. For our ancestors, death was an unnatural state, as all of nature seemed to be ever changing, moving, and alive.

  Nature’s powers of motion and change were associated with anima, the soul. Animism, the belief that all of nature was alive and governed by spiritual forces, survived the centuries and was part of respectable European philosophizing well into the twentieth century.* The use of “magic” crystals and magnets for healing is still part of some people’s beliefs today, as they believe that these items have special energies that affect life and health. In animism, not only animals, but also rocks, the wind, the river, were alive. In such a belief system, the concept of dying did not make much sense. The ancients believed that when a person died, he or she was not really dead, but instead the person’s spirit had moved somewhere else. It was important to supply the dead person with tools and gifts for this new existence. Our now familiar distinction between living beings and lifeless matter evolved much later. Once this happened, most things—rocks, water, air—were recognized as lifeless, and living became a mystery in need of explanation. Living matter was now seen as being substantially different from all other matter and had to be endowed with extraordinary forces or a soul. We call such a belief vitalism.

  Vitalism began with the Greeks, most notably with the philosopher and scientist Aristotle (384–322 BCE). For Aristotle, life was different from inanimate matter because it had “soul”; it was “animated.” It is not a coincidence that we identify the word animated with being in motion. Purposeful motion, which includes locomotion, growth, and internal motion of the organism, was for Aristotle (and still is today) the most conspicuous attribute of life.

  Aristotle spent a lot of time thinking about the soul, as recorded in his book De Anima. He identified several problems with defining soul: Is the soul a whole, or is it made of parts? Are there different types of souls for horses, dogs, and people? What is the soul’s relationship to the body? Aristotle realized there was a problem distinguishing the soul from the body: “Are all affectations of the complex of body and soul, or is there any among them peculiar to the soul itself ? . . . there seems to be no case in which the soul can act or be acted upon without involving the body.” But despite raising this issue, Aristotle never addressed the question about the necessity of the soul. In fact, he would have found such a question absurd—for him and his fellow Greeks, the existence of a soul was self-evident: “Knowledge of the soul . . . contributes greatly to the advance of truth in general, and, above all, to our understanding of Nature, for the soul is . . . the principle of . . . life.”

  FIGURE 1.1. Democritus—typically shown as the bearded, laughing philosopher. In the history of science, he certainly had the last laugh. After all, he was (mostly) right about atoms.

  Atomism

  When I learned about Greek philosophy in high school, I first noticed all the things the Greeks got wrong. To my teenage self, it seemed naive to think of earth or fire as elements. In truth, the Greeks made enormous progress, from their belief in Olympian gods Zeus and Hera to their model of nature using four elements. The Greeks were also the first people to base ideas on scientific observations. The philosopher Anaximenes of Miletus (585–529 BCE) determined that air was the fundamental element, because it could be rarefied or condensed. H
e based this idea on his observations of evaporation, condensation, drying, and wetting. Other observations that guided Greek philosophy included the growth of seeds (Anaximander), breathing (Anaximenes), fossils in rock (Xenophanes), the necessity of water for life and buoyancy (Thales), and the random motion of suspended dust (Democritus; Figure 1.1).

  Aristotle was, without a doubt, the most prolific (and most scientific) of all Greek philosophers. In De Anima, he provided a comprehensive overview of what his predecessors thought of the mystery of the soul. Based on meager experimental evidence, ancient philosophers ventured surprisingly close to modern ideas: According to Aristotle, the philosopher Democritus imagined the soul as a fire consisting of myriads of jostling particles, which Democritus called “atoms.” Democritus got the idea for the incessant motion of atoms from observing the random movements of dust grains in beams of sunlight. As we will see, the ceaseless motion of atoms and molecules plays a central role in our modern understanding of life—a motion we can rightly call a molecular storm.

  Unfortunately, Aristotle found the ideas of Democritus and Pythagoras absurd. For him, movement is the result of thought and will, not the random motion of atoms: “Democritus says that . . . atoms . . . owing to their ceaseless movements draw the . . . body after them and so produce its movements. . . . we may object that it is not in this way that the soul appears to originate motion in animals—it is through intention or process of thinking.”

  Thus, from the Greek philosophers to the early-nineteenth-century biologists, there were three possible solutions to the problem of explaining life: Assume an overarching, universal principle that determines the purpose of the entire universe (animism); assume a special life force that distinguishes life from matter, thus reserving purpose for life alone (vitalism); or deny purpose altogether (mechanism, atomism). All of these approaches had their problems. Animism erased the clear distinction of the inanimate and the alive, vitalism gratuitously introduced an unseen force and raised the additional question of how this force interacted with the body, and atomism seemed impotent to account for those of life’s activities that seemed to show clear purposefulness, such as growth and reproduction.

  Atomism made a brief resurgence with the philosopher Epicurus (341–270 BCE) and was later revived by the Roman philosopher Lucretius (99–55 BCE) in his famous poem De rerum natura. Explaining the universe as the result of atomic motion, Epicurus invented the “swerve”—the sudden, random swerving of atoms that otherwise would move on straight, predictable paths. The swerve explained how atoms clumped together or bounced off each other. It explained creation, spontaneity, chance, and free will. While the idea of the swerve seems gratuitous, Epicurus understood that an atomistic explanation of the universe needed a mixture of necessity and chance.

  However, the difficulty of reconciling the random motion of atoms with the obvious purposefulness of life doomed atomism for many centuries and has cast a long shadow on our understanding of life until today. The battle of soul versus the atom continued to be central to understanding life, even though the terms changed and biological knowledge became more refined.

  For the most part, the ancients vacillated between vitalism and animism. Aristotle clearly understood that life was special and did not postulate souls for rocks and mountains. He did, however, think of motion as due to a purpose. A rock “wanted” to fall down, because it was made of the element earth and wanted to go back to the earth. On the other hand, the Stoics (a school of philosophy founded by Zeno of Citium circa 300 BCE) believed in a more animistic world, where a mysterious ordering force, the pneuma (“breath”) gave rise to all existence. The pneuma was like an ancient version of “the force” in Star Wars, the fictional energy field created by all living things.

  With the rise of Christianity, both the atomism of Epicurus and the animism of the Stoics became discredited. For the early Christians, Plato’s philosophy, which was based on the transcendent world of ideas and not our material reality, was much more palatable. Plato’s universe was the result of reason, not chance. Steeped in Platonic philosophy, the evangelist John wrote: “In the beginning was the Word, and the Word was with God, and the Word was God.” Following John, the early Church, and especially St. Augustine, equated this “Word” or reason with God, and the world of ideas with heaven. The material world was relegated to a corrupted reflection of the spiritual world, which contained the real truth, the truth of God.

  Many writings of Aristotle, lost in the West for nearly a thousand years, were saved by the Muslims. In the twelfth century, his works reentered Western philosophy. The early schools of theology in Paris, Oxford, Toledo, and Cologne, which later became universities, were stunned when they encountered the comprehensive knowledge contained in Aristotle’s numerous writings, from logic to physics, statecraft to biology. Unlike Plato, Aristotle saw the material world as primary, and ideas as mere generalizations of observed objects and phenomena. In this, he was quite close to what scientists believe today.

  While Aristotle’s ideas threatened the established neoplatonic theology of the time, he could not be ignored. His philosophy was too comprehensive and too well reasoned to be dismissed. A new philosophy, scholasticism, was born to reconcile Aristotle’s philosophy and science with Christian theology. Not everything in Aristotle’s books was counter to Christian beliefs. For example, he clearly dismissed atomism and the accompanying idea of chance as an important player in the universe. For Aristotle, the most important force was purpose. Motion also required an explanation and could not be attributed to the unexplained random motion of atoms. Instead, Aristotle postulated a first mover—which St. Thomas Aquinas, the most famous of the twelfth-century scholastic philosophers, equated with God. In living beings, the soul was the prime mover. According to Aristotle, “[the soul] acts and [the body] is acted upon, and the [body] is moved and the [soul] moves.”

  Aristotle’s concept of the soul has survived until today, and is evident in the catechism of the Catholic Church: “‘Soul’ also refers to the innermost aspect of man, that which is of greatest value in him, that by which he is most especially in God’s image: ‘soul’ signifies the spiritual principle in man. . . . The unity of soul and body is so profound that one has to consider the soul to be the ‘form’ of the body: i.e., it is because of its spiritual soul that the body made of matter becomes a living, human body; spirit and matter, in man, are not two natures united, but rather their union forms a single nature.” This idea of the soul as the form of the body, which renders it alive, comes from Aristotle. The Catholic catechism contains two meanings to the word soul: Aristotle’s life-giving “form” and a “spiritual principle.” Even though these two meanings are often conflated, they are radically different concepts.

  Modern physics, chemistry, and evolution can explain what makes a cell or an organism alive and what gives it “form.” Bodies are complex assemblies of interacting cells, operating according to an evolved program written in the cell’s DNA. A soul is not needed as the source of form, locomotion, nutrition, or reproduction (in contrast to what Aristotle thought). The concept of soul may make sense in the second meaning—as a noncorporeal, unique essence of a human being; as a shorthand to aspects of a living being that encompasses personality, dignity, intelligence, mind, and the connection to others.

  The Christian adoption of Aristotelian ideas, while at first quite radical, put a straightjacket on science for many centuries. The Greek philosophers welcomed debate, and it is reasonable to assume that Aristotle would have been horrified to learn that his musings were now taken as gospel.

  Medicine and Magic

  The vitalistic ideas of the Greek philosophers, as well as their early penchant for scientific observation, profoundly influenced the practical science of life: medicine. Originally based on magic and faith-healing, medicine was put on a more rational footing by Hippocrates and other Hippocratic thinkers around the time of Aristotle. Medicine became a rational science, based on an understanding of the un
iverse. Greek (and, later, Roman) medicine culminated in the ideas of Galen (129–217 AD), whose books dominated Western medicine for fourteen hundred years. As late as 1559, a member of the London College of Physicians had to publicly rescind his comments when he dared to criticize Galen in front of his colleagues.

  Galen’s medicine, based on Aristotle’s philosophy and Stoic ideas, was heavily vitalistic: It was loosely based on the four Greek elements, which he called the body’s vital fluids (or “humors”). Galen believed that the pneuma, the “life spirit” that circulated in the air, entered the body through the lungs. In the heart, the pneuma mixed with blood (one of the four humors) and produced the “vital spirits,” which were responsible for movement. As part of the soul, these vital spirits were associated with heat, which, according to Galen, was generated in the heart when blood mixed with air. The connections between air, heat, and soul were a recurring theme from ancient Greece to the dawn of the scientific age. And as we will see, thinking of heat as the “living power” is not so far from reality as you might think.

  Ancient medicine combined observations (in Galen’s case, mostly by dissecting animals) with a philosophical understanding of the universe. For the ancient physicians, life was associated with heat, and heat was generated by fire (one of the four traditional elements), which must be nourished by air (another of the elements). This kind of reasoning sometimes came close to the right answers, but ultimately, the ancients were victims of their own philosophical predilections. Without the methods of modern science—controlled experiments, the testing of hypotheses and quantitative arguments—medicine remained in a rut for more than fourteen hundred years.