Life's Ratchet: How Molecular Machines Extract Order from Chaos
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—MARY SHELLEY, FRANKENSTEIN
Irritability, one of Kielmeyer’s five vital forces, spurred the imagination of scientists, philosophers, and writers. One of them was La Mettrie, who was most impressed by the motions of muscles separated from their animal hosts. La Mettrie made irritability the center of his argument that life is pure mechanism, a complicated clockwork. But irritability also supported vitalist ideas: If muscles could move on their own, did this not prove the presence of a vital force? And could such a vital force, if distilled to its essence, not be used to bring life to dead tissue? At the height of the Romantic period, in the early 1800s, such speculation inspired a young woman with literary aspirations, vacationing with her lover in a villa on Lake Geneva, to write a novel.
Mary Wollstonecraft Shelley (1797–1851) conceived the idea for her novel Frankenstein; or, The Modern Prometheus, when she and her husband Percy Bysshe Shelley were holed up in the Villa Diodati with several friends, including the poet Lord Byron. It was 1816, the dreary “year without a summer,” when a giant eruption of the Indonesian volcano Tambora darkened the European skies. During late-night chats, she and her friends talked about the increasingly gruesome experiments of scientists who were applying high voltages to dead animals and humans to demonstrate irritability. When her friends challenged each other to write a story or poem to entertain themselves, Shelley conceived of a gothic horror story about a scientist creating life from dead flesh.
The study of irritability, which La Mettrie had used as evidence for the mechanical nature of life, reached fever pitch when scientists of the day discovered that the newly founded science of electricity could be used to study living organisms. The iconic experiment of this era was conducted by Luigi Galvani (1737–1798), who attached a charged Leyden jar (a capacitor to store large amounts of electrical charge) to severed frog legs and observed that they kicked and twitched when electricity passed through them. Such experiments suggested that electricity could be the mysterious vital force philosophers had sought for centuries. In 1803, Galvani’s nephew, Giovanni Aldini, went as far as to experiment with human corpses, making their faces twitch, their eyes open, and their extremities lift up. Such horrible experiments were supposed to show that “animal electricity” was a vital force responsible for the motion of muscles as it traveled along the nervous system. Unfortunately, what these experiments really inspired (much helped by Shelley’s novel) was the idea of the overreaching, mad scientist—a figure that has since dominated much of the public’s imagination.
I had not read Shelley’s book until I started writing this book (although I was familiar with several movie versions, including the classic with Boris Karloff as the monster) and was surprised to find that Shelley never mentioned exactly how Dr. Frankenstein vitalized his creation. Shelley’s hero deliberately keeps the reader in the dark, supposedly to prevent a repeat of the tragedy about to unfold: “I see by your eagerness and the wonder and hope which your eyes express, my friend, that you expect to be informed of the secret with which I am acquainted,” explains Frankenstein in the novel, “that cannot be; listen patiently until the end of my story, and you will easily perceive why I am reserved on that subject.” The giant switches and the lightning storm seen in various movie versions are all inventions of Hollywood, but it is clear that the studies of irritability, which were in the news in the early 1800s, provided the inspiration for Shelley’s iconic novel.
Ever since its discovery by the Greeks (electron means “amber” in Greek, and amber generates static electricity when rubbed), electricity was considered a mysterious force and a subtle fluid. Such a mysterious force had to have some connection to the great mystery of life. Even Newton had suggested that electricity was responsible for animal motion. In the second edition of Philosophiae Naturalis Principia Mathematica, he speculated that the “subtle spirit” of electricity, transmitted through the nerves, “stimulated sensations” and “moved limbs.”
Who was the inspiration for Shelley’s Dr. Frankenstein? With animal electricity as the scientific object du jour, there were many candidates for this rather ignoble honor. Aldini, who passed large currents through the limbs of recently hanged criminals in front of large London crowds—to horrific effect—was certainly one of them. Another was Johann Wilhelm Ritter (1776–1810), a German scientist who preferred to apply the large currents to himself instead. Applied to his eyes, they made him see red and blue flashes, depending on which electric pole he had connected to his eyeball. Ritter died at a young age of unknown causes—but repeatedly electrocuting oneself cannot be too healthy.
The Conservation of Force—Or How Vitalism Was Vanquished by a Frog Leg
Although the late eighteenth to the mid-nineteenth century had become the age of teleomechanists and vitalists, by the mid-nineteenth century, mechanism had again gained the upper hand. This return to mechanistic explanations was mainly the work of two men: the English naturalist Charles Darwin (1809–1882), who destroyed teleology, and the German physiologist and physicist Hermann von Helmholtz (1821–1894), who vanquished the vital force.
Helmholtz was one of the last truly universal scientists. He made significant contributions to medicine, biology, and physics, in areas as diverse as heat in animals, irritability, the vital force, thermodynamics, electro dynamics, the conservation of energy, turbulence in liquids, and the physiology of the senses. His insights were groundbreaking, and most have withstood the test of time. He also invented several new experimental apparatuses, including the ophthalmoscope, the special microscope eye doctors point at your eyes to check the retina. His broad knowledge allowed him to make novel connections between different sciences. He could look at a system as complex as living tissue and determine the one parameter that linked it to the inanimate, mechanical world. He decided that this parameter was energy.
Physicists of the more arrogant sort often think that the interactions between physics and biology are purely one-way: Physics may explain biology, but biology has no bearing on physics. To cure such a misguided view of science, one should consider how Helmholtz came to argue for the law of energy conservation (or the conservation of force, as he called it). Helmholtz, trained as a physician, started his scientific career working on physiological experiments. It was these biological experiments that convinced him of the law of energy conservation.
Energy conservation had been in the air for a while. Descartes, Newton, and Leibniz had all argued for some quantity to be conserved in interactions between material corpuscles, although they could not agree on the type of conserved quantity (Newton argued for momentum or quantity of motion, while Leibniz argued for kinetic energy or vis viva [“the living force”]). Others had shown that work and kinetic energy could be converted into one another, for example, during free fall. Heat had been shown to be a type of motion, and it was already known that kinetic energy could be converted to heat through friction. In 1845, James Joule (1818–1889) showed that a fixed amount of work would result in a fixed amount of heat (what he called the mechanical equivalent of heat): “When equal quantities of mechanical effect are produced by any means whatever from purely thermal sources, or lost in purely thermal effects, then equal quantities of heat are put out of existence or are generated.”
Drawing on his own biological observations and diligent studies of mathematical physics, Helmholtz extended energy conservation to all types of energy, thus declaring energy conservation a fundamental law of the universe. He showed how the conservation of energy can be mathematically derived from simple assumptions. While the mathematical treatment was Helmholtz’s achievement alone, the idea of a universal law of energy conservation had been formulated some years earlier by another German scientist, Julius Robert von Mayer (1814–1878). Just like Helmholtz, Mayer was a physician venturing into physics and was also inspired by biology to proclaim the universal law of energy conservation. Helmholtz was unaware of Mayer’s 1841 paper when he published his own ideas six years later. In his paper, Mayer repudiated vital f
orces, as Helmholtz would do a short time later, and stated that “the cause of the chemical tension produced in the plant . . . is physical force.” This physical force, or energy, as we would say today, was the same as the energy that would be obtained if we were burning the plant. Furthermore, this energy had to come from somewhere. If we postulated a mysterious vital force— a force that would require no source—we would be “carried . . . into unbridled fantasy,” and all further investigation would “be cut off.” No, said Mayer, the real explanation had to be that energy and matter were only converted from one form to another, and “that creation of either one or the other never takes place.” In other words, even in something as complicated as a plant or an animal, energy was only transformed, but never created or destroyed. This is the universal statement of energy conservation.
In his famous essay of 1847, “Über die Erhaltung der Kraft” (“About the conservation of force”), Helmholtz, then only twenty-six, followed much the same line of argument that Mayer had set forth. Helmholtz felt that postulating mysterious vital forces added nothing to the investigation of how life works. Moreover, the presence of vital forces that could generate mechanical force from nothing would make it possible to construct a perpetuum mobile, a machine that generates energy from nothing. It was widely accepted that this was impossible. Energy conservation had to be correct, and special vital forces could not exist. Helmholtz showed that the law of energy conservation could be mathematically proven. He only needed to make the assumption that matter was made of pointlike particles, interacting through forces depending only on the distance between the particles. This mathematical proof and the expansive view of the new law met with some resistance from his older colleagues. Soon, however, new experiments proved Helmholtz and his fellow energy conservers correct.
Helmholtz was a dedicated mechanist from the beginning. Although he had studied with the influential researcher and teacher Johannes Peter Müller (1801–1858), who was part of the teleomechanist faction, he despised the very idea of invoking a vital force to explain anything. He designed several experiments to prove that vital forces were unnecessary to explain irritability. Most of these experiments, ironically, were to be performed on frog legs, the favorite experimental object of Galvani. Galvani, of course, had presented his frog leg experiments as support for vitalism.
In the first set of experiments, Helmholtz set out to prove that motion in muscles is caused by chemical processes, that is, that animal motion is a physicochemical process and is not related to any mysterious vital force. To prove this, he irritated frog legs several hundred times by passing electrical currents through them, just as Galvani had done. He then made several chemical extracts of the irritated frog legs and compared the extracts with extracts from non-irritated frog legs. He found that if the muscles had been irritated, a water-based extract lost mass and an ethanol-based extract gained an equivalent amount of mass. Clearly, some chemical compound in the muscles had been changed from a water-soluble to an alcohol-soluble form through the action of the muscles. This proved that the motion of the muscles caused a chemical change in the muscles, and Helmholtz concluded that muscles were machines that converted chemical to mechanical energy.
To establish that this energy was purely chemical, he next compared the heat that can be released upon chemical breakdown of food, called the latent heat, with the latent heat of excreted substances in animals. This was Lavoisier’s experiment. However, since the time of Lavoisier, more-refined experiments had improved on Lavoisier’s guinea pig. Helmholtz reviewed these experiments and concluded that the difference in energy between food and excrement accounted well for the observed animal heat. He was able to correct an error introduced by Lavoisier and the famous German chemist Justus von Liebig (1803–1873): Liebig (like Lavoisier before him) believed that the energy expended by an animal was exactly the same as oxidizing (burning) the animal’s food in the oxygen the animal breathes. But the French physicist Pierre Louis Dulong (1785–1838) and the Belgian physicist César-Mansuète Despretz (1798–1863) had shown in their careful repeats of Lavoisier’s experiments that an animal generated about 10 percent more energy than could be accounted for by the oxidation from respiration alone. This left an opening to the vitalists, who could point to the missing 10 percent as the contribution of the vital force. Instead, Helmholtz showed, the missing 10 percent came from the oxygen already contained in food, especially in carbohydrates and sugars. If this additional oxygen was included, food energy perfectly matched animal heat plus energy of the excrements, and no vital force was needed.
One more experiment was needed to completely eliminate the need for the vital force: Helmholtz had to show unequivocally that the energy to move muscles was contained in the chemical energy of the muscles (which they had received from food) and did not come from someplace else. At the time, it was known that a loss of the nervous system led to a cooldown of the body. Therefore, some biologists believed that the nervous system provided a source of vital force or animal heat. Helmholtz devised an ingenious setup to eliminate this last refuge of the vital force. By irritating three selections of tissue—a frog leg with its attached spinal nerve, a frog leg without the nerve, and the nerve without the leg—he ventured to show that any temperature increase due to the motion of the leg originated in the leg and was not due to any vital energies transferred to the leg from the nerves. To measure the minute temperature increase of a moving frog leg, he constructed a very sensitive device, comprising a thermocouple (a kind of electrical thermometer, which converts temperature into voltages), a magnetic coil to magnify the resulting voltage, and a dial that displayed the temperature after calibration of the device. His setup was accurate enough to record temperature changes as small as one-thousandth of a degree. Moreover, this setup was a physical representation of the law of energy conservation: Chemical energy in the frog leg (unleashed by electrical irritation) was converted into mechanical energy (motion of the leg), then into heat, electrical energy (thermocouple), magnetic energy (coil), and, finally, mechanical motion of the dial.
Helmholtz found that the presence of the nerves made no difference and that a nerve alone did not heat up at all. As long as the muscles moved the same amount, they heated up by the same amount, regardless of the presence of a nerve. In Helmholtz’s view, the idea of a vital force was now untenable.
It would be too easy to conclude that the physicists carried the day. Yes, Helmholtz and others had shown that anything happening in a body—all the hallmarks of being alive, from animal heat to irritability— had to occur within the energy budget prescribed by the physicochemical world. If there was such a thing as a vital force, it had to be a force without energy and thus without potency. After Helmholtz, vital forces quickly fell from favor and have not been resurrected since, at least not in serious science. Nevertheless, for all of his single-minded eradication of the vital force, Helmholtz and his fellow physicists could not explain how unformed matter could organize into a complex organism. He had shown that it must happen within the law of energy conservation, but this did not explain how living beings formed. His research merely removed vital forces from the list of possible explanations.
Thanks to Helmholtz and others, biology returned to mechanism by the end of the nineteenth century, but not to the primitive, naive mechanism of the seventeenth-century mechanical philosophers. It was now clear that all biological processes occurred within the framework of chemistry and physics. The two disciplines were key to explaining physiological processes, such as irritability or animal heat. But it was equally clear that biology was fundamentally different from physics and biology: Complexity and development remained to be explained. Purpose was not yet exorcised.
Darwin and Mendel: From Chance to Purpose
The essential debates surrounding the mysteries of life never really changed. New findings brought the controversy over purpose versus mechanism into sharper relief, but the dilemma of biology in the late nineteenth century was fundamentally the sa
me as the ancient debates between Aristotle and Democritus. By the 1850s, nobody could deny that to explain life’s processes, physical, chemical, and mechanical forces had to be invoked. Yet mechanics seemed woefully insufficient to explain the extraordinary complexity and purposefulness of life. Mechanical explanations had become more powerful, and with the work of Helmholtz and his contemporaries, it was now clear that all forces or energies active in life were also present in inanimate matter. But this could not explain purpose. The dilemma of the physicists was the same dilemma Democritus had faced. How can complexity emerge from chaos?
The person who rescued mechanism from the bugbear of purpose was Charles Robert Darwin. Together with Alfred Russell Wallace (1823–1913), Darwin developed the theory of evolution based on natural selection. The idea of evolution was not entirely new. Ever since they noticed how different life forms were related to each other and to extinct forms, scientists had wondered if species could change over time. But without a satisfactory mechanism, the idea of evolution went nowhere.
Meticulously argued and written in a surprisingly accessible style, Darwin’s revolutionary Origin of Species presented a strong case for natural selection as the driving force of evolution. Despite its general acceptance in modern science, Darwin’s theory was absolutely earth-shattering and counter intuitive when it was published in 1859. When his contemporaries looked at marvelously designed plants and animals, Darwin’s claim that these forms could have emerged by a blind, step-by-step process seemed outrageous.
Yet the theory was persuasive: Darwin’s faithful supporter, the biologist Thomas Henry Huxley (1825–1895), exclaimed upon reading the book: “How extremely stupid not to have thought of that!” Indeed, like many brilliant ideas, Darwin’s is exceedingly simple: All species exist as a population of individuals, each one a little bit different from every other. How these variations arose was unknown to Darwin (today we have a pretty good idea), but that they did exist was obvious. Over time, the variations that led to more reproductive success would surely increase in the population. In other words, individuals with a variation that allowed them to mate more successfully would have more offspring, and soon there would be more individuals with this particular variation. As conditions change or as populations are cut off from other populations, different variations will be favored and new species can emerge. Because the process is extremely slow, there are few opportunities to observe the emergence of a new species in a human lifetime.