Milieu Interieur
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The internal environment (or ''milieu intérieur'' in
French French (french: français(e), link=no) may refer to: * Something of, from, or related to France ** French language, which originated in France, and its various dialects and accents ** French people, a nation and ethnic group identified with Franc ...
) was a concept developed by
Claude Bernard Claude Bernard (; 12 July 1813 – 10 February 1878) was a French physiologist. Historian I. Bernard Cohen of Harvard University called Bernard "one of the greatest of all men of science". He originated the term ''milieu intérieur'', and the a ...
, a French physiologist in the 19th century, to describe the
interstitial fluid In cell biology, extracellular fluid (ECF) denotes all body fluid outside the cells of any multicellular organism. Total body water in healthy adults is about 60% (range 45 to 75%) of total body weight; women and the obese typically have a lower ...
and its
physiological Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical ...
capacity to ensure protective stability for the tissues and
organs In biology, an organ is a collection of tissues joined in a structural unit to serve a common function. In the hierarchy of life, an organ lies between tissue and an organ system. Tissues are formed from same type cells to act together in a fu ...
of
multicellular organism A multicellular organism is an organism that consists of more than one cell, in contrast to unicellular organism. All species of animals, land plants and most fungi are multicellular, as are many algae, whereas a few organisms are partially uni- ...
s.


Etymology

Claude Bernard Claude Bernard (; 12 July 1813 – 10 February 1878) was a French physiologist. Historian I. Bernard Cohen of Harvard University called Bernard "one of the greatest of all men of science". He originated the term ''milieu intérieur'', and the a ...
used the French phrase ''milieu intérieur'' (internal environment in English) in several works from 1854 until his death in 1878. He most likely adopted it from the histologist
Charles Robin Charles Robin (October 30, 1743 – June 10, 1824) was an entrepreneur from the Isle of Jersey who traded between the maritime region of Canada and the British Isles. Fishery trader He was born in Saint Brélade, Jersey in 1743. By 1763, he was t ...
, who had employed the phrase "milieu de l’intérieur" as a synonym for the ancient
hippocratic Hippocrates of Kos (; grc-gre, Ἱπποκράτης ὁ Κῷος, Hippokrátēs ho Kôios; ), also known as Hippocrates II, was a Greek physician of the classical period who is considered one of the most outstanding figures in the history of ...
idea of
humors Humorism, the humoral theory, or humoralism, was a system of medicine detailing a supposed makeup and workings of the human body, adopted by Ancient Greek medicine, Ancient Greek and Medicine in ancient Rome, Roman physicians and Greek philosoph ...
. Bernard was initially only concerned with the role of the blood but he later included that of the whole body in ensuring this internal stability.Gross, C. G. (1998
"Claude Bernard and the constancy of the internal environment"
Neuroscientist 4: 380–38

.
He summed up his idea as follows: Bernard's work regarding the internal environment of regulation was supported by work in Germany at the same time. While Rudolf Virchow placed the focus on the cell, others, such as Carl von Rokitansky (1804–1878) continued to study humoral pathology particularly the matter of
microcirculation The microcirculation is the circulation of the blood in the smallest blood vessels, the microvessels of the microvasculature present within organ tissues. The microvessels include terminal arterioles, metarterioles, capillaries, and venules. ...
. Von Rokitansky suggested that illness originated in damage to this vital microcirculation or internal system of communication. Hans Eppinger Jr. (1879–1946), a professor of internal medicine in Vienna, further developed von Rokitansky's point of view and showed that every cell requires a suitable environment which he called the
ground substance Ground substance is an amorphous gel-like substance in the extracellular space that contains all components of the extracellular matrix (ECM) except for fibrous materials such as collagen and elastin. Ground substance is active in the development, m ...
for successful microcirculation. This work of German scientists was continued in the 20th century by Alfred Pischinger (1899–1982) who defined the connections between the ground substance or
extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...
and both the hormonal and autonomic nervous systems and saw therein a complex system of regulation for the body as a whole and for cellular functioning, which he termed the ground regulatory (''das System der Grundregulation'').


History

Bernard created his concept to replace the ancient idea of life forces with that of a mechanistic process in which the body's physiology was regulated through multiple mechanical equilibrium adjustment feedbacks. Walter Cannon's later notion of homeostasis (while also mechanistic) lacked this concern, and was even advocated in the context of such ancient notions as
vis medicatrix naturae ''Vis medicatrix naturae'' (literally "the healing power of nature", and also known as ''natura medica'') is the Latin rendering of the Greek ''Νόσων φύσεις ἰητροί'' ("Nature is the physician(s) of diseases"), a phrase attributed ...
. Cannon, in contrast to Bernard, saw the self-regulation of the body as a requirement for the evolutionary emergence and exercise of intelligence, and further placed the idea in a political context: "What corresponds in a nation to the internal environment of the body? The closest analogue appears to be the whole intricate system of production and distribution of merchandise". He suggested, as an analogy to the body's own ability to ensure internal stability, that society should preserve itself with a technocratic bureaucracy, "biocracy". The idea of milieu intérieur, it has been noted, led
Norbert Wiener Norbert Wiener (November 26, 1894 – March 18, 1964) was an American mathematician and philosopher. He was a professor of mathematics at the Massachusetts Institute of Technology (MIT). A child prodigy, Wiener later became an early researcher i ...
to the notion of
cybernetics Cybernetics is a wide-ranging field concerned with circular causality, such as feedback, in regulatory and purposive systems. Cybernetics is named after an example of circular causal feedback, that of steering a ship, where the helmsperson m ...
and
negative feedback Negative feedback (or balancing feedback) occurs when some function (Mathematics), function of the output of a system, process, or mechanism is feedback, fed back in a manner that tends to reduce the fluctuations in the output, whether caused by ...
creating self-regulation in the
nervous system In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes th ...
and in nonliving machines, and that "today, cybernetics, a formalization of Bernard's constancy hypothesis, is viewed as one of the critical antecedents of contemporary cognitive science".


Early reception

Bernard's idea was initially ignored in the 19th century. This happened in spite of Bernard being highly honored as the founder of modern
physiology Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical ...
(he indeed received the first
French French (french: français(e), link=no) may refer to: * Something of, from, or related to France ** French language, which originated in France, and its various dialects and accents ** French people, a nation and ethnic group identified with Franc ...
state funeral for a scientist). Even the 1911 edition of Encyclopædia Britannica does not mention it. His ideas about milieu intérieur only became central to the understanding of physiology in the early part of the 20th century. It was only with
Joseph Barcroft Sir Joseph Barcroft (26 July 1872 – 21 March 1947) was a British physiologist best known for his studies of the oxygenation of blood. Life Born in Newry, County Down into a Quaker family, he was the son of Henry Barcroft DL and Anna Richar ...
, Lawrence J. Henderson, and particularly
Walter Cannon Walter Bradford Cannon (October 19, 1871 – October 1, 1945) was an American physiologist, professor and chairman of the Department of Physiology at Harvard Medical School. He coined the term "fight or flight response", and developed the theory ...
and his idea of
homeostasis In biology, homeostasis (British English, British also homoeostasis) Help:IPA/English, (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physics, physical, and chemistry, chemical conditions maintained by organism, living systems. Thi ...
, that it received its present recognition and status. The current 15th edition notes it as being Bernard's most important idea.


Idea of internal communication

In addition to providing the basis for understanding the internal physiology in terms of the interdependence of the cellular and extracellular matrix or ground system, Bernard's fruitful concept of the milieu intérieur has also led to significant research regarding the system of communication that allows for the complex dynamics of homeostasis.


Work by Szent-Györgyi

Initial work was conducted by
Albert Szent-Györgyi Albert Imre Szent-Györgyi de Nagyrápolt ( hu, nagyrápolti Szent-Györgyi Albert Imre; September 16, 1893 – October 22, 1986) was a Hungarian biochemist who won the Nobel Prize in Physiology or Medicine in 1937. He is credited with fi ...
who concluded that organic communication could not be explained solely by the random collisions of molecules and studied energy fields as well as the connective tissue. He was aware of earlier work by Moglich and Schon (1938) and Jordan (1938) on non-electrolytic mechanisms of charge transfer in living systems. This was further explored and advanced by Szent-Györgyi in 1941 in a Koranyi Memorical Lecture in Budapest, published in both ''Science'' and ''Nature'', wherein he proposed that proteins are
semi-conductors A semiconductor is a material which has an electrical conductivity value falling between that of a conductor, such as copper, and an insulator, such as glass. Its resistivity falls as its temperature rises; metals behave in the opposite way. ...
and capable of rapid transfer of free electrons within an organism. This idea was received with skepticism, but it is now generally accepted that most if not all parts of the extracellular matrix have semiconductor properties. The Koranyi Lecture triggered a growing molecular-electronics industry, using biomolecular semiconductors in
nanoelectronic Nanoelectronics refers to the use of nanotechnology in electronic components. The term covers a diverse set of devices and materials, with the common characteristic that they are so small that inter-atomic interactions and quantum mechanical pr ...
circuits. In 1988 Szent-Györgyi stated that "Molecules do not have to touch each other to interact. Energy can flow through... the electromagnetic field" which "along with water, forms the matrix of life." This water is related also to the surfaces of proteins, DNA and all living molecules in the matrix. This is a structured water that provides stability for metabolic functioning, and related to collagen as well, the major protein in the
extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...
and in DNA. The structured water can form channels of energy flow for protons (unlike electrons that flow through the
protein structure Protein structure is the three-dimensional arrangement of atoms in an amino acid-chain molecule. Proteins are polymers specifically polypeptides formed from sequences of amino acids, the monomers of the polymer. A single amino acid monomer ma ...
to create
bio-electricity Bioelectromagnetics, also known as bioelectromagnetism, is the study of the interaction between electromagnetic fields and biological entities. Areas of study include electromagnetic fields produced by living cells, tissues or organisms, the e ...
). Mitchell (1976) refers to these flow as 'proticity'.


Work in Germany

Work in Germany over the last half-century has also focused on the internal communication system, in particular as it relates to the ground system. This work has led to their characterization of the ground system or
extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...
interaction with the cellular system as a 'ground regulatory system', seeing therein the key to homeostasis, a body-wide communication and support system, vital to all functions. In 1953 a German doctor and scientist, Reinhold Voll, discovered that points used in
acupuncture Acupuncture is a form of alternative medicine and a component of traditional Chinese medicine (TCM) in which thin needles are inserted into the body. Acupuncture is a pseudoscience; the theories and practices of TCM are not based on scientifi ...
had different electrical properties from the surrounding skin, namely a lower resistance. Voll further discovered that the measurement of the resistances at the points gave valuable indications as to the state of the internal organs. Further research was done by Dr. Alfred Pischinger, the originator of the concept of the 'system of ground regulation', as well as Drs. Helmut Schimmel, and Hartmut Heine, using Voll's method of electro-dermal screening. This further research revealed that the gene is not so much the controller but the repository of blueprints on how cells and higher systems should operate, and that the actual regulation of biological activities (see Epigenetic cellular biology) lies in a 'system of ground regulation'. This system is built on the ground substance, a complex connective tissue between all the cells, often also called the extra-cellular matrix. This ground substance is made up of 'amorphous' and 'structural' ground substance. The former is "a transparent, half-fluid gel produced and sustained by the
fibroblast A fibroblast is a type of cell (biology), biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and plays a critical role in wound ...
cells of the
connective tissue Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...
s" consisting of highly
polymerized In polymer chemistry, polymerization (American English), or polymerisation (British English), is a process of reacting monomer molecules together in a chemical reaction to form polymer chains or three-dimensional networks. There are many for ...
sugar-protein complexes. The ground substance, according to German research, determines what enters and exits the cell and maintains homeostasis, which requires a rapid communication system to respond to complex signals (see also
Bruce Lipton Bruce Harold Lipton (born October 21, 1944) is an American developmental biologist noted for his views on epigenetics. In his book ''The Biology of Belief'', he claims that beliefs control human biology rather than DNA and inheritance. Lipton' ...
). This is made possible by the diversity of molecular structures of the sugar polymers of the ground substance, the ability to swiftly generate new such substances, and their high interconnectedness. This creates a redundance that makes possible the controlled oscillation of values above and below the dynamic homeostasis present in all living creatures. This is a kind of fast-responding, "short term memory" of the ground substance. Without this labile capacity, the system would quickly move to an energetic equilibrium, which would bring inactivity and
death Death is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...
. For its biochemical survival, every organism requires the ability to rapidly construct, destroy and reconstruct the constituents of the ground substance. Between the molecules that make up the ground substance there are minimal surfaces of
potential energy In physics, potential energy is the energy held by an object because of its position relative to other objects, stresses within itself, its electric charge, or other factors. Common types of potential energy include the gravitational potentia ...
. The charging and discharging of the materials of the ground substance cause 'biofield oscillations' (photon fields). The interference of these fields creates short lived (from 10–9 to up to 10–5 seconds) tunnels through the ground substance. Through these tunnels, shaped like the hole through a donut, large chemicals may traverse from capillaries through the ground substance and into the functional cells of organs and back again. All
metabolic Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
processes depend upon this transport mechanism. Major ordering energy structures in the body are created by the ground substance, such as
collagen Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...
, which not only conducts energy but generates it, due to its piezoelectric properties. Like quartz crystal, collagen in the ground substance and the more stable
connective tissue Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...
s (
fascia A fascia (; plural fasciae or fascias; adjective fascial; from Latin: "band") is a band or sheet of connective tissue, primarily collagen, beneath the skin that attaches to, stabilizes, encloses, and separates muscles and other internal organs. ...
,
tendon A tendon or sinew is a tough, high-tensile-strength band of dense fibrous connective tissue that connects muscle to bone. It is able to transmit the mechanical forces of muscle contraction to the skeletal system without sacrificing its ability ...
s,
bone A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...
s, etc.). transforms mechanical energy (pressure, torsion, stretch) into
electromagnetic energy In physics, electromagnetism is an interaction that occurs between particles with electric charge. It is the second-strongest of the four fundamental interactions, after the strong force, and it is the dominant force in the interactions of a ...
, which then resonates through the ground substance (Athenstaedt, 1974). However, if the ground substance is chemically imbalanced, the energy resonating through the body loses coherence. This is what occurs in the adaptation response described by
Hans Selye János Hugo Bruno "Hans" Selye (; hu, Selye János; January 26, 1907 – October 16, 1982) was a pioneering Hungarian-Canadian endocrinologist who conducted important scientific work on the hypothetical non-specific response of an organism to s ...
. When the ground regulation is out of balance, the probability of chronic illness increases. Research by Heine indicates that unresolved emotional traumas release a neurotransmitter substance P which causes the collagen to take on a hexagonal structure that is more ordered than their usual structure, putting the ground substance out of balance, what he calls an "emotional scar "providing" an important scientific verification that diseases can have psychological causes." (see also
Bruce Lipton Bruce Harold Lipton (born October 21, 1944) is an American developmental biologist noted for his views on epigenetics. In his book ''The Biology of Belief'', he claims that beliefs control human biology rather than DNA and inheritance. Lipton' ...
)


Work in the U.S.

While the initial work on identifying the importance of the ground regulatory system was done in Germany, more recent work examining the implications of inter and intra-cellular communication via the extra-cellular matrix has taken place in the U.S. and elsewhere. Structural continuity between
extracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
, cyst skeletal and nuclear components was discussed by Hay, Berezny et al. and Oschman. Historically, these elements have been referred to as ground substances, and because of their continuity, they act to form a complex, interlaced system that reaches into and contacts every part of the body. Even as early as 1851 it was recognized that the nerve and blood systems do not directly connect to the cell, but are mediated by and through an extracellular matrix. Recent research regarding the electrical charges of the various glycol-protein components of the extracellular matrix shows that because of the high density of negative charges on
glycosaminoglycan Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units (i.e. two-sugar units). The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case ...
s (provided by sulfate and
carboxylate In organic chemistry, a carboxylate is the conjugate base of a carboxylic acid, (or ). It is an ion with negative charge. Carboxylate salts are salts that have the general formula , where M is a metal and ''n'' is 1, 2,...; ''carboxylat ...
groups of the uronic acid residues) the matrix is an extensive redox system capable of absorbing and donating electrons at any point. This electron transfer function reaches into the interiors of cells as the cytoplasmic matrix is also strongly negatively charged. The entire extracellular and cellular matrix functions as a biophysical storage system or accumulator for electrical charge. From
thermodynamic Thermodynamics is a branch of physics that deals with heat, work, and temperature, and their relation to energy, entropy, and the physical properties of matter and radiation. The behavior of these quantities is governed by the four laws of ther ...
, energetic and geometrical considerations, molecules of the ground substance are considered to form minimal physical and electrical surfaces, such that, based on the mathematics of minimal surfaces, minuscule changes can lead to significant changes in distant areas of the ground substance. This discovery is seen as having implications for many physiological and
biochemical Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology an ...
processes, including
membrane transport In cellular biology, membrane transport refers to the collection of mechanisms that regulate the passage of solutes such as ions and small molecules through biological membranes, which are lipid bilayers that contain proteins embedded in them. Th ...
, antigen–antibody interactions,
protein synthesis Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the product ...
, oxidation reactions, actin–myosin interactions, sol to gel transformations in
polysaccharide Polysaccharides (), or polycarbohydrates, are the most abundant carbohydrates found in food. They are long chain polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages. This carbohydrate can react with wa ...
s. One description of the charge transfer process in the matrix is, "highly vectoral electron transport along
biopolymer Biopolymers are natural polymers produced by the cells of living organisms. Like other polymers, biopolymers consist of monomeric units that are covalently bonded in chains to form larger molecules. There are three main classes of biopolymers, cl ...
pathways". Other mechanisms involve clouds of negative charge created around the proteoglycans in the matrix. There are also soluble and mobile charge transfer complexes in cells and tissues (e.g. Slifkin, 1971; Gutman, 1978; Mattay, 1994). Rudolph A. Marcus of the California Institute of Technology found that when the driving force increases beyond a certain level, electron transfer will begin to slow down instead of speed up (Marcus, 1999) and he received a
Nobel Prize in chemistry ) , image = Nobel Prize.png , alt = A golden medallion with an embossed image of a bearded man facing left in profile. To the left of the man is the text "ALFR•" then "NOBEL", and on the right, the text (smaller) "NAT•" then "M ...
in 1992 for this contribution to the theory of electron transfer reactions in chemical systems. The implication of the work is that a vectoral electron transport process may be greater the smaller the potential, as in
living systems Living systems are open self-organizing life forms that interact with their environment. These systems are maintained by flows of information, energy and matter. In the last few decades, some scientists have proposed that a general living systems ...
.


Notes

{{DEFAULTSORT:Milieu interieur Control theory Cybernetics Homeostasis Medical terminology Physiology Scientific terminology Systems theory French medical phrases