§58. Milieu Interieur
Ancient medicine emphasized nature’s power to heal. Doctors had little choice, there being practically nothing they could do for internal disease except make a prognosis and watch.
Hippocratic authors anticipated progress in their art. Galen remained guardedly optimistic, but Locke gave up the expectation of progress. It is not until the early nineteenth century, more than two millennia after Hippocrates and a century after Locke, that medical knowledge took a first step beyond its ancient authorities, with a burst of progress in experimental physiology. The word “physiology” comes from a work of 1554 by Jean Fernel, Physiologia, who defined his subject as “the nature of the healthy man, all his forces and all his functions.” Physiology is distinct from the classical medical sciences of prognosis, hygiene, and therapeutics, and different again from postmortem anatomy. Albrecht von Haller called it “anatomy in motion.” In its modern form, physiology is the science of functions and functional constants of living organisms.78It took a couple of centuries after Hippocrates, and the relocation of medical research in Alexandria, for physicians to decide that the internal organs were worth studying. For a long time thereafter, anatomy seemed the obvious way to study organs. Galen advanced medicine more than anyone had with his anatomical research, which Vesalius continued in the Renaissance, illustrating the anatomist’s inner world in unprecedented detail. The renewed science of anatomy did more for the emergence of a new empiricism than it did for medicine. Anatomy imposes consciousness of limitations, resisting universal generalizations. The real, deep diversity of nature is constantly if inadvertently discovered in surprises that discipline experience and make it hesitant and consciously fallible. Comparative anatomy revealed whole new dimensions of diversity—among species, among individuals, among their parts.
Yet however estimable it may be as a science, anatomy has little value for medicine. It discovers the shapes and structures of organs but cannot elucidate the difference between health and disease. To know the parts is not yet to know the functions, and without knowledge of function anatomy is useless to a physician, as medical empiricists long contended.79As a fledgling science, physiology copied the best current model of science. Unfortunately that was Descartes’s mechanism. That a living body is a machine is easily said, but genuinely mechanical concepts are seldom helpful in physiology, which kept the new science primitive pending a better paradigm. By the nineteenth century the new model science is chemistry. Instead of comparing the stomach to a mill, which does not advance research much, study the chemical changes of the stomach. How does digestion change the body's chemistry? These are much better research questions, and chemistry was beginning to master the instruments that could advance them. Daniel Fahrenheit introduced his thermometer in 1715. In 1780, Antoine Lavoisier demonstrated the calorimeter, an instrument to measure the heat of chemical reactions. Microscopes had been in use since the seventeenth century. Harvey's experimental work on circulation was a model of research. Boyle, Locke, and Joseph Priestley conducted experimental research on respiration, which Lavoisier's experiments identified as combustion. Experiments by Spallanzani in the eighteenth century showed that oxygen is absorbed and carbon dioxide released by all tissues and organs.
Nineteenth- century breakthroughs in physiology are associated with three generations of French experimentalists: Fran^ois-Joseph-Victor Broussais, Francois Magendie, and Claude Bernard. Magendie, who was Bernard's teacher, was a man of the laboratory, not the hospital or military surgery, and experimental physiology was for him the physics of vital phenomena. In a notable series of animal experiments he successfully isolated the contribution of several classes of chemicals (e.g., alkaloids).
Doctors then and always felt free to disdain the latest theories. Broussais made a plea for the medical relevance of physiology. “The characteristic traits of diseases must be sought in physiology.... Enlighten me with a scientific analysis of the often confused cries of the suffering organs.... Teach me about their reciprocal influences.” Surveying the strides of the fledgling physiology, a prominent medical observer of the time (Littre) said, “While theory in medicine once was suspect and served only as a target, so to speak, for the facts that demolished it, today, owing to its subordination to physiological laws, it has become an effective instrument of research and a faithful rule of conduct.”80Physiology became a science when it became experimental. Bernard, the most accomplished of this group, agrees with the medical-empiricist critique of anatomy but uses it to the advantage of a physiology undreamed of by Galen or Locke. “Dead anatomy teaches nothing; it merely leans on that which experimental physiology teaches.” “How could the form of a liver cell show us that sugar is made in it?” “Experimental physiology is in itself the one active science of life, because by defining the necessary conditions of vital phenomena it will succeed in mastering them.” With new instruments, refined laboratory skill, and experimental imagination, Bernard clarified the distinction between organ and gland, identified and measured many internal secretions, and was the effective founder of endocrinology.81
In his Introduction to the Study of Experimental Medicine (1865), Bernard says that the subject matter of physiology makes no difference to experimental method. “Life brings absolutely no difference into the scientific experimental method.” Experiments, which he defines as “nothing but reasoning by whose help we methodically submit our ideas to experience,” test ideas that are not themselves products of experience. We submit to the test of experience something we have never experienced but only imagine, a hypothesis that goes beyond all experience.
Bernard’s emphasis on the value of an imaginative hypothesis distinguishes him from the fustier empiricism of his teachers and colleagues. Experimental method by itself produces nothing. Rules cannot generate content. An idea is indispensable. “I consider it, therefore, an absolute principle that experiments must always be devised in view of a preconceived idea, no matter if the idea be not very clear nor very well defined.” He says, “We must give free rein to our imagination; the idea is the essence of all reasoning and all invention. All progress depends on that. It cannot be smothered or driven away on the pretense that it may do harm; it must only be regulated and given a criterion, which is quite another matter.”82One of his own best hypotheses is the simple idea that there is one physiology for all living things. We tend to forget that this had to be invented or how recently it was. Physiological dualism, with a distinct physiology for plants and animals, was defended in Bernard’s time by the eminent physiologist Jean- Baptiste Dumas. The implications ofBernard’s “hypothesis” are vast, imparting an unsuspected continuity to plant and animal life. The traditional view was that only plants have the capacity to generate nutriment from inorganic matter; animals have to take what they require from plants. Bernard refuted that, demonstrating that all animals produce needed nutriments by the internal operation of organs and glands. Only experiments could have discovered that the function of the liver is to synthesize glucose. The discovery was a surprise even to Bernard and a paradox for contemporaries, not unlike Galileo seeing moons orbiting Jupiter.83
Come-by-chance observation is the old way in medicine, the new way is experimental. The usual sites of medical observation—the bedside, hospital, or autopsy—are inadequate for the research Bernard envisions. Clinicians and anatomists are passive; they merely watch, and neither control nor seek to control the phenomena they examine.
“I consider hospitals only as the entrance to scientific medicine; they are the first field of observation that a physician enters; but the true sanctuary of medical science is a laboratory; only there can he seek explanations of life in the normal and pathological states by means of experimental analysis.” The search is not solely for explanations, because the proof of understanding is control of the phenomena. “The observer accepts phenomena just as nature sets them before him; the experimenter makes them appear under conditions of which he is the master.” That is the goal of Bernard's experimental medicine, “to conquer living nature, act upon vital phenomena, and regulate and modify them”84Experimentation is an ethical no less than epistemological method, not just a way of knowing but knowing as a way of life. Bernard has four principles for an experimental life:
• Do not fear doubt. “Only doubt promotes experiment; it is doubt, finally, which determines the form of experimental reasoning.”
• Uphold determinism. Everything has a cause and experiments search it out, with hypotheses that combine imagination and method.
• Never stop trying to destroy your conclusions. Do not let an opportunity pass to falsify your favorite idea.
• Live without certainty, experimentally, with never more than an experimental commitment to experimental outcomes.
It is a stumbling block for experimenters to think they know something (anything at all), and take for absolute such insights as can never not be relative. Caution is crucial. “Experiment makes him, moment by moment, conscious of both his relative and his absolute ignorance.” Bernard refers to “an intellectual attitude which seems paradoxical but which, in my opinion, expresses the true spirit of an investigator,” namely, that “we must firmly believe in principles, but must question formulae.”85
Bernard's most admired concept is that of the internal milieu (milieu interieur), an internal liquid environment that combines all the physiological and chemical conditions of cellular life.
“This it is which the physiologists and physicians should study and know, for by its means they can act on the histological units which are the only effective agents in vital phenomena.” In his exploration of this physiological environment Bernard showed how internal secretions regulate consistency (homeostasis), compensating for perturbations and providing a new degree of independence from variations in the external environment. He was also able to establish that disease occurs as a deviation in some vital parameter, too much or too little internal secretion.86Formerly diseases were regarded as entities. They came and went with winds, seasons, maybe even turpitude. Physicians could not do much once disease struck except estimate how long it would stay and what devastation it would wrack. Bernard discovered that “every disease has a corresponding normal function of which it is only the disturbed, exaggerated, diminished, or obliterated expression,” an organ being just that much too active or deficient in the secretions that are its physiological function. To give an example, he first listed the major medical symptoms of diabetes, then observed, “Strictly speaking, none of these symptoms represents a new phenomenon, unknown to the normal state, save for their intensity which varies in the normal state and in the diseased state.”87
When people believed diseases were entities with their own nature, their only thought was to be wary of them. But once diseases are regarded as abnormal departures from normal states, physicians might think of eliminating them. Bernard sees experimental medicine as the model of what medicine should be in a modern, industrial society. Let there be no more expectant medicine, no more obsessive classification, and no more hope invested in postmortem anatomy. “To dominate living nature scientifically, to conquer it for the benefit of man: that is the fundamental idea of the experimental physician.” Medicine’s ancient philanthropy is renewed, as is the expectation of progress in medical knowledge and power. Ancient medicine was observational, passive, and descriptive; however, “with the aid of the active, experimental sciences, man becomes an inventor of phenomena, a foreman in the factory of creation, and there is no limit to the power that he may obtain over nature.”88