homeostasis: a historical perspective
“true stability results when the supposed order and the supposed disorder are in balance. a truly stable system expects the unexpected, is prepared to be interrupted, expects to be transformed.”
tom robbins (American novelist, b. 1936)1
The concept that body regulation is necessary for health dates back to the ancient Greeks. The Greek physician/philosopher Alcmaeon of Croton (fl. 500 BC) proposed what may be called a “balance of opposites” to explain health and disease. he used a political analogy to define health and disease stating that: “health is the equal rights of functions, wet-dry, hot-cold, bittersweet and so on; but the single rule of either is detrimental.” (free man, 1948). thus, inequality of power leads to tyranny in a political system and disease in the body. This concept was extended by Hippocrates of Kos (ca. 460-ca. 377 BC) who proposed that health was the product of the balance and mixture of four body fluids or humors: blood, phlegm, yellow bile and black bile. he wrote that:
“health is chiefly that state in which these constituent substances are in correct proportion to each other, both in strength and quantity, and are well mixed. pain occurs when one of these substances is deficient or in excess, or is separated in the body and does not mix with the others”. (Chadwick and Mann, 1950)
thus, medicine became a process “of subtraction and addition: subtraction of what is left over, addition of what is missing”. (Jones, 1923). Hippocrates further recognized the role of nature’s helping hand in the healing process (vis medicatrix naturae), the body’s ability to heal itself (Hall, 1975). it was the doctor’s job to clear the way for nature to take its course. this concept became the basis of medicine in the following centuries until the dawn of the modern era.
Implicit in this concept of the “healing power of nature” is the assumption that the subunits of the body act cooperatively to restore health when the normal state of the organism is disturbed. Physiology, as a discipline dedicated to understanding how the parts of the body work together to maintain health, has its origins in the sixteenth century. the term physiology was first introduced by jean francois fernel (ca. 1497-1558, figure 1) in 1542 [from naturali parte medicinee (on the natural part of medicine)] as the study of the function of the healthy body as opposed to of pathology, the study of disease (hall, 1975). William Harvey (1578-1657) was the first individual to use carefully designed experiments on humans and animals to establish the function of a major body organ system with his description of the circulation of the blood. this application of physiology is illustrated in the following short quote from his seminal publication “exercitatio anatomica de motu cordis et de circulacione sanguinis in animalibus” 1628 (anatomical exercises on the movement of the heart and the circulation of blood in living beings, first English translation 1653):
“It has been shown by reason and experiment that the blood by the beating of the ventricles flows through the lungs and is pumped throughout the body… the blood in the body of the animal moves in a circle continuously , and… the action or function of the heart is to achieve this pumping. this is the only reason for movement and heartbeat.” (Harvey, 1628/1653)
Over the ensuing centuries, the concept of physiology has evolved and a central tenet has emerged that unites the various subdisciplines of physiology: the quest to understand how the various components of the body work together to maintain a healthy state. Only by understanding normal bodily function can disturbances that lead to disease be determined and ultimately corrected to restore a healthy state.
As we have seen, a rudimentary understanding of the regulation and control of bodily functions dates back to the sixth century BC in Greece. Despite sporadic progress over the centuries (Adolph, 1961), it was not until the nineteenth century that systematic physiological research produced major advances in this concept. Our modern understanding of physiological regulation rests firmly on the shoulders of two giants in the field: Claude Bernard (figure 2) and Walter Cannon (figure 3) who described regulations in terms of the constancy of the internal environment and homeostasis, respectively.
French physiologist Claude Bernard (1813-1878), often referred to as the founder of modern experimental physiology, was perhaps the first to fully appreciate that living systems possess an internal stability that buffers and protects the system. organism against a constantly changing external environment (Cooper, 2008). He recognized that the body has mechanisms that operate in a coordinated manner to maintain a relatively constant temperature and blood glucose concentration, and this internal stability was vital to the health of the organism. he concluded that: “la fixité du milieu intérieur est la condition de la vie libre, independante” (bernard, 1865) [the fixity (i.e. constancy or stability) of the internal environment is the condition for free and independent life] . What is often overlooked and must be emphasized is that in this statement Bernard proposed a new and radical hypothesis: the stability of the “milieu intérieur” was the antecedent (i.e., necessary for) and not the consequence (result) of a free and independent life (turner, 2017).
Although Bernard was highly honored and the most famous French scientist during his lifetime, his hypothesis that the stability of the internal environment was independent of external conditions, first articulated in 1854, was largely ignored for the next few years. 50 years. Gross (2009) has proposed three reasons for the delay between the publication of Bernard’s ideas and their acceptance: (1) Pasteur’s exciting discoveries in bacteriology that had immediate application in the prevention and treatment of disease came to dominate biological investigations; (2) the gap between evolutionary thinking and general physiology: it took time to realize that natural selection provided the means by which regulatory control could evolve; and (3) the technology needed to measure the internal environment was not yet available.
However, in the late 19th and early 20th centuries, various researchers adopted Bernard’s ideas, both as a central explanatory concept and as a blueprint for research in physiology. Among those influenced by Bernard were physiological luminaries such as William M. Bayliss, Ernest H. starling, joseph barcroft, j. yes haldano, and c. yes sherrington in england, and l. J. henderson and walter b. cannon in america (adolph, 1961; cooper, 2008; gross, 2009). Starling, in fact, coined the phrase “the wisdom of the body” to describe maintaining a constant internal environment (Cooper, 2008). Walter Cannon later popularized this phrase when he used it as the title of his book in which he introduced the concept of homeostasis. In 1900, Charles R. Richet (1850-1935), a student of Bernard, who later won the Nobel Prize for Physiology and Medicine, emphasized the dynamic stability of the internal environment. The following quote, as we shall see, foreshadowed the definition provided by Walter Cannon.
“The living system is stable… it must be so in order not to be destroyed, dissolved or disintegrated by colossal forces, often adverse, that surround it. by an apparent contradiction, it maintains its stability only if it is excitable and capable of modifying itself according to external stimuli and adjusting its response to the stimulus. in a certain sense, it is stable because it is modifiable: the slight instability is the necessary condition for the true stability of the organism”. (richett, 1900)
This concept of a constant internal environment (milieu intérieur) was extended by the American physiologist Walter Cannon (1871-1945) (Cooper, 2008). coined the term homeostasis from the Greek words Ǒμoιoς (hómoios) “similar” and στάσις (stásis) “to be still” (together meaning to remain similar and not remain the same) to describe the self-regulating processes by which a biological system maintains stability while adapting to changing environmental conditions. homeostasis is often misconstrued as unchanging or stagnant. However, Cannon deliberately selected the Greek word for similar, “hómoios”, instead of the word for equal, “homo”, to express the idea that internal conditions can vary; that is, they are similar but not identical (stability but within a range of values that allows the organism the freedom to adapt). homeostasis, then, is the tendency of a system to maintain internal stability as a result of the coordinated response of its parts to any situation or stimulus that disturbs normal conditions or function. therefore, the term homeostasis attempts to convey two ideas: (1) an internal stability within a range of values and (2) the coordinated dynamic response that maintains this internal stability (self-regulatory goal-seeking behavior). As he explains in the following quote from his influential monograph, “The Wisdom of the Body,” published in 1932:
“the coordinated physiological processes that maintain most of the stationary states in organisms are very complex and peculiar to living beings: they involve, as they can, the brain and nerves, the heart, the lungs, the kidneys and the spleen, all working in cooperation – I have suggested a special designation for these states, homeostasis. the word does not imply, something fixed and immobile, a stagnation. it means a condition, a condition that may vary, but is relatively constant. (cannon, 1963)
as cannon emphasizes, homeostasis is not static; rather, it is a dynamic, self-adjusting system that maintains viability in the face of changing environmental demands. Echoing Bernard, homeostasis is a unique property of living organisms and may be responsible for life itself. More recently, Turner (2017) described homeostasis as a dynamic imbalance: Dynamic, like a stable internal environment, requires continual monitoring and adjustments (again, a self-regulating process) to maintain a balance between opposing forces (what he calls imbalance). ) so that a free and independent life is possible. he went further and stated that “properly understood, homeostasis is the fundamental property of life, what distinguishes it from non-life. in short, homeostasis is life.” (turner, 2017).
The final piece of the homeostasis puzzle was provided by the application of systems engineering control theory to explain self-regulation in biological systems. the “constancy” of internal physicochemical conditions is largely maintained by the often complex interplay of multiple negative (and positive) feedback systems. The interaction of these regulatory mechanisms not only increases the stability of the system, but also provides redundancy (backup) so that the failure of a component does not necessarily lead to a catastrophe. therefore, from its inception, physiological investigations have been directed at understanding the organism (be it a microbe, a plant, an animal, or a human being) as a single functional entity.