The internal environment (or ''milieu intérieur'' in
French; ) was a concept developed by
Claude Bernard,
a French physiologist in the 19th century, to describe the
interstitial fluid and its
physiological capacity to ensure protective stability for the
tissues and
organs of
multicellular organism
A multicellular organism is an organism that consists of more than one cell (biology), cell, unlike unicellular organisms. All species of animals, Embryophyte, land plants and most fungi are multicellular, as are many algae, whereas a few organism ...
s.
Etymology
Claude Bernard 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, who had employed the phrase "milieu de l’intérieur" as a synonym for the ancient
hippocratic idea of
humors. 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.
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. Von Rokitansky suggested that illness originated in damage to this vital microcirculation or internal system of communication.
Hans Eppinger (1879–1946), a professor of
internal medicine
Internal medicine, also known as general medicine in Commonwealth nations, is a medical specialty for medical doctors focused on the prevention, diagnosis, and treatment of diseases in adults. Its namesake stems from "treatment of diseases of ...
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 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 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.
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 computer scientist, mathematician, and philosopher. He became a professor of mathematics at the Massachusetts Institute of Technology ( MIT). A child prodigy, Wiener late ...
to the notion of
cybernetics
Cybernetics is the transdisciplinary study of circular causal processes such as feedback and recursion, where the effects of a system's actions (its outputs) return as inputs to that system, influencing subsequent action. It is concerned with ...
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 ...
creating self-regulation in the
nervous system
In biology, the nervous system is the complex system, highly complex part of an animal that coordinates its behavior, actions and sense, sensory information by transmitting action potential, signals to and from different parts of its body. 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 science, scientific study of function (biology), functions and mechanism (biology), mechanisms in a life, living system. As a branches of science, subdiscipline of biology, physiology focuses on how organisms, organ syst ...
(he indeed received the first
French 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,
Lawrence J. Henderson, and particularly
Walter Cannon and his idea of
homeostasis
In biology, homeostasis (British English, British also homoeostasis; ) is the state of steady internal physics, physical and chemistry, chemical conditions maintained by organism, living systems. This is the condition of optimal functioning fo ...
, 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 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 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 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 and in DNA.
The structured water can form channels of energy flow for protons (unlike electrons that flow through the
protein structure to create
bio-electricity). 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 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 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 cells of the
connective tissue
Connective tissue is one of the four primary types of animal tissue, a group of cells that are similar in structure, along with epithelial tissue, muscle tissue, and nervous tissue. It develops mostly from the mesenchyme, derived from the mesod ...
s" consisting of highly
polymerized 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).
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 end of life; the irreversible cessation of all biological functions that sustain a living organism. Death eventually and inevitably occurs in all organisms. The remains of a former organism normally begin to decompose sh ...
.
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 of an object or system due to the body's position relative to other objects, or the configuration of its particles. The energy is equal to the work done against any restoring forces, such as gravity ...
. 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 ''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 cellular processes; the ...
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 of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...
, 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, a group of cells that are similar in structure, along with epithelial tissue, muscle tissue, and nervous tissue. It develops mostly from the mesenchyme, derived from the mesod ...
s (
fascia,
tendon
A tendon or sinew is a tough band of fibrous connective tissue, dense fibrous connective tissue that connects skeletal muscle, muscle to bone. It sends the mechanical forces of muscle contraction to the skeletal system, while withstanding tensi ...
s,
bone
A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...
s, etc.). transforms mechanical energy (pressure, torsion, stretch) into
electromagnetic energy, 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. 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
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell.
Neurotra ...
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)
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
glycosaminoglycans (provided by sulfate and
carboxylate 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, 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, ...
processes, including
membrane transport,
antigen–antibody interactions,
protein synthesis,
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 wat ...
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, ...
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 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.
Notes
{{DEFAULTSORT:Milieu interieur
Control theory
Organizational cybernetics
Homeostasis
Medical terminology
Physiology
Scientific terminology
Systems theory
French medical phrases