Source: Revue d’histoire des sciences 24(4), 1971, pp. 289–298
Contents
[289] The emergence of bioenergetics was preceded by a protobiochemical phase in which the pseudophysical concept of life forces [forces-de-vie] prevailed. Belief in a specific and unique form of the matter constituting organisms is bound up with the idea that this nature is produced by the action of the vital force, regarded as the source of the distinctive characteristics of living matter by all thinkers who do not adopt the mechanistic theory of life first proposed by the atomists and subsequently adopted by philosophers such as Gassendi or Descartes, and by biologists such as Schwann.
Haller recognised aspects of this distinctive character in the principles of irritability and sensibility, manifestations of the vital force abolished at death.[T1]
During the second half of the eighteenth century, a tendency developed in France to bring life under the rule of natural laws, as Newton had done in physics. Within this outlook the mechanistic schools, adherents of Descartes’s animal-machine, were to develop. The vitalists, meanwhile, divided into two groups. One, predominant at Montpellier, where its most illustrious representatives were Bordeu and Barthez, recognised a “vital principle” at the origin of the phenomena of life. This was not a spiritualist view of the kind represented, for example, by Stahl’s anima.[T2] In Barthez’s thought, so often misunderstood, the “vital principle” is a general principle comparable to gravitation, a factor common to the forms of life. Barthez regards the “vital principle” as manifesting itself through a series of forces: impulsive force, attractive force, forces of affinity, motor forces and sensory forces. Barthez draws a very clear distinction between the soul and the “vital principle”. After death, the matter of the body is restored to inorganic nature, while the “vital principle” is restored to the principle of the Universe. The soul, for its part, returns to God, who gave it to [290] humanity and who ensures its immortality. For Barthez, chemistry can come into contact with the matter of life only when life has left it.[290.1] Having distinguished the tissues of the organism, Bichat specifies that their vital properties must be regarded as variants of Haller’s principles: irritability and sensibility. For him, as for Barthez, these principles are not spiritualist in nature, but neither are they chemical. On the contrary, they oppose physical and chemical phenomena. They maintain the constituents of living matter in a form of combination from which they are separated after death to form new associations, those that are the object of the chemist’s study.[290.2] For Bichat, as for Barthez, the living state is a specific form of organisation; this is why both are sometimes described as organo-vitalists.
The organo-vitalist conception holds that, in becoming organised, and without losing its fundamental properties, matter, by virtue of the distinctive and original composition and texture it assumes, becomes, within its organised aggregate, the scene of specifically biological acts and manifestations of dynamic modalities distinct from those of the inorganic order.
We may note that the concept of actions opposing the chemical equilibrium established after death is perfectly valid for modern biochemistry.
In 1795, a disciple of Kant, Reil,[290.3] subjected the concept of vital force to critical examination, defining it as the expression of the organisation of the components of the organism: matter and forces. Reil lists a series of these forces: physical force, vital force, vegetative force, animal force, and so on.
In 1793, organic forces themselves formed the subject of a study by Kielmeyer, who considered their distribution in the living world.
Life forces ruled non-mechanistic biology until the publication of Schwann’s Microscopic Investigations,[290.4] which in 1839, as Temkin puts it,[290.5] fired the first shot [291] opening the campaign against vital force and its pseudophysical varieties. Theodor Schwann, a deeply religious thinker, was nevertheless a rationalist and a mechanist. After proposing the cellular theory of the origin of organisms, Schwann formulated views according to which organic phenomena are cellular in nature. For him, the cell is not only a unit of form but also a unit of metabolism and a source of organic phenomena such as nutrition and growth, the organism itself existing through the interplay of the cells’ reciprocal actions. As he explicitly states, the molecules of each cell form part of an assemblage from whose nature its metabolic powers arise. This view of Schwann’s had a considerable impact, particularly in Germany. In place of the life forces then in favour, it substitutes the physical properties of the molecules constituting cells, and declares that no other force need be invoked to interpret the living machine.
The concept of energy and that of its conservation took shape around the middle of the nineteenth century, when agreement emerged that the disappearance of one “force” was always accompanied by the appearance of another “force”. Rosen[291.1] has stressed the relationship between this observation, technological expansion and the development of accounting practices. It was particularly in Cornwall that the practice of energy accounting developed, notably as applied by Watt, who, using his steam engine to pump water from mines, charged his customers one-third of the difference between the cost of feeding the horse that would have driven the pump and the cost of the coal consumed by the engine. It was within the circle of French engineers that Sadi Carnot first formulated the concept of the conservation of energy; but, Carnot having died of cholera in 1832, his notes were not published until 1878.
The concept of the conservation of energy first appears in the scientific literature in 1842, formulated by Robert Mayer,[291.2] who derived it from a consideration of life forces. A physician aboard a Dutch ship, Mayer, in accordance with the custom of the time, practised treatment by [292] bloodletting. This method, so disparaged subsequently, nevertheless lay at the origin of R. Mayer’s discovery. He observed that the venous blood of the sailors he bled was redder in Java than it was in Holland. At that time, the prevailing theory taught that heat supplied plants with the force necessary to manufacture organic substances by becoming a force of affinity. These organic substances, or at least sugars and fats, underwent combustion in the presence of oxygen in the blood of the capillary networks, producing the body’s heat. In the lesser deoxygenation of venous blood in the tropics, Mayer saw evidence of a reduced need for thermogenesis and confirmation of the relationship between internal combustion and thermogenesis, a relationship proposed by Lavoisier but disputed notably by Barthez.
Everyone knew at the time that work produced heat, but Mayer’s originality lay in recognising that a certain quantity of work corresponds to a certain quantity of heat.
It was the discovery of this equivalence that led Mayer to interpret through general energetic principles the phenomena that had previously led to the conception of the various life forces. Mayer formulated the principle that, in the organism, the oxidation of carbon and hydrogen leads to the production of heat and work. The mechanical equivalence of heat showed that oxidation processes are the physical condition of the organism’s capacity to perform work, while at the same time making it possible to establish a numerical relationship between consumption and work.
Lavoisier’s theory that respiration, regarded as combustion, was the sole source of animal heat had soon been shaken by the discovery within organisms of heat-producing mechanisms such as muscular contraction. In 1824, the Paris Academy of Sciences had offered a prize for a study of animal heat. Two submissions reached it, one from Dulong and the other from Despretz, who won the prize.
Considering the heat produced and the food ingested, neither experimenter, despite what one sometimes reads, recognised agreement between the two values. Like Lavoisier’s, their calculations started from the oxidation [293] of carbon and hydrogen, and were therefore inaccurate. Only after the principle of the conservation of energy had been recognised, and Hess’s principle formulated in 1840, was bioenergetics able to make its first start. Hess’s principle states that the quantity of heat released by a chemical process is independent of the intermediate stages separating the initial and final states.
This principle, which Liebig in any case denied with regard to organisms, was initially misapplied because of the then prevailing idea that heat represented the only form of energy leaving the organism. In terms of the net balance, this is the case only when the organism performs no work.
The concept so familiar to us, of food as the source of the organism’s energy—which some authors long continued to regard as resulting from mechanical phenomena such as friction—could become established only after the abandonment of Liebig’s views. According to these, sugars and fats represented the only heat-producing, that is, energy-providing foods, while proteins played no part in these phenomena and constituted tissue-building foods [aliments plastiques], compensating for losses resulting from the wear of tissues.[T3]
A quantitative study required measurement of the quantity of protein metabolised in a given time. This measurement can be made by determining the nitrogen excreted, but establishing this criterion was not to be easy.
The first experimental study devoted to this question dates from 1852 and is due to Bidder and Schmidt.[293.1] They observed that, in dogs and cats, nitrogen ingested in the form of meat is recovered as nitrogen excreted in urine and faeces. But this conclusion gave rise to lively controversies that ended only with Voit’s demonstration,[293.2] in 1857, of what is called “nitrogen balance”. Over 58 days, Voit gave a dog 29 kg of meat, that is, 986 g of nitrogen. During the same period he found 943.7 g of nitrogen in the dog’s urine and 39.1 g in its faeces: a total of 982.8 g of nitrogen, whereas the dog had received 986 g.
[294] But this agreement might have been a chance result if, for example, there were also a balance between the incorporation of atmospheric nitrogen into the organism’s proteins and a gaseous excretion of nitrogen or ammonia. Such possibilities obviously had to be ruled out.
As regards the utilisation of atmospheric nitrogen, later demonstrated in certain microorganisms, Lavoisier had ruled out this possibility in humans. Experiments by Regnault and Reiset on animals placed in the air contained under an inverted bell jar established that atmospheric nitrogen was not utilised.
As for the elimination of ammonia in expired air, this amounts to mere traces in the rabbit, as Bachl[294.1] demonstrated in 1869. Urea is eliminated in perspiration only in very small quantities. To determine the quantity of nitrogen lost through hair, nails and epidermal shedding, Moleschott[294.2] collected the hair and nail clippings of a group of men each month and obtained only negligible quantities.
But might expired air also contain nitrogen originating in food? This was ruled out by Krogh’s very precise experiments.[294.3]
The method proposed by Voit, consisting in determining the quantity of protein metabolised from the quantity of urea nitrogen excreted in urine, was therefore considered valid.
To determine which substances undergo metabolism in the organism, Pettenkofer and Voit[294.4] built an apparatus in Munich, with financial support from King Maximilian II of Bavaria, that allowed measurement of total carbon excretion, both in the air and in urine and faeces, of nitrogen excretion and of oxygen consumption. From these experiments they were able to conclude that the quantity of oxygen used in respiration depends on the nature of the substances metabolised. They were able to establish many new facts: that during starvation the organism consumes fats and proteins, that exercise increases fat consumption, and so on.
[295] In these memorable experiments, Rubner and Voit calculated the potential energy value of food from the quantities of CO₂ and water formed in metabolism.
Direct measurement of the heat of combustion of food appeared necessary. At that time it was thought that tissues directly “burnt” proteins, fats and sugars, and methods were therefore introduced to determine the heat of combustion of these substances using calorimeters.
It would nevertheless be a mistake to suppose that the theory of the combustion of food during respiration, regarded as the generator of animal heat, held undisputed sway. In his Lectures on Animal Heat, published in 1876, Claude Bernard expresses doubts about it. Why, he asks, is the heat produced by muscular contraction regarded as resulting from the direct combustion of carbon and hydrogen?
It was to answer these objections and confirm Lavoisier’s views that Rubner[295.1] published, in 1894, an impressive series of results that left no further doubt about the metabolic origin of the energy transformed in organisms. First he had determined a series of calorific values for food: 4.1 kcal/g of protein, 9.3 kcal/g of fat and 4.1 kcal/g of carbohydrate. Having become a professor at Marburg, Rubner built a calorimeter there with which he could determine exactly the heat released by a dog. The apparatus also allowed him to measure the oxygen consumed and CO₂ excreted and to calculate the heat resulting from metabolism. The perfect agreement between the heat produced and the calculated heat left no doubt about the doctrine that metabolism is the sole source of energy in the organism: a doctrine that henceforth acquired the status of a paradigm. It is sometimes assumed that these experiments by Rubner demonstrated the validity of the law of the conservation of energy for organisms. In fact, they confirm the legitimacy of applying Hess’s principle. It was in 1899 that Atwater and Rosa,[295.2] through experiments performed with a bicycle ergometer combined [296] with an apparatus for measuring metabolism by the respiratory method, demonstrated the validity of the law of the conservation of energy in the human organism.
In everything we have related, the objective was to demonstrate the production of animal heat from metabolism and to establish the equality between the heat produced and the chemical energy of the molecules metabolised. The conditions of these experiments were defined so as to prevent the production of work; at that time heat was considered the source of work. We read, for example, in Claude Bernard’s Lectures on Animal Heat:[296.1] “If we call the heat that warms the animal to a constant temperature its maintenance ration, and that which is transformed into work its activity ration, we must recognise that there is no antagonism between the two, no necessary reciprocity.” Other celebrated physiologists, such as Engelmann or Pflüger, accepted that all forms of work performed in an organism were derived from heat. The second law of thermodynamics obviously posed serious difficulties for adopting such a theory. Engelmann[296.2] circumvented it by supposing the existence of a Carnot cycle at the level of the dark and light bands of muscle fibres, which, in his view, functioned as heat engines. Pflüger,[296.3] for his part, considered that the carbon dioxide resulting from metabolism was formed within large molecules and caused explosions within them, producing vibrations that could bring about a local temperature increase of up to 10,000 °C and constituted the source of mechanical work. Such fanciful imaginings were, however, vigorously opposed by physiologists such as Fick and biochemists such as A. Gautier. The theory that became generally accepted until the end of the nineteenth century held that the chemical energy of organic molecules was transformed during metabolism directly into mechanical energy, electrical energy, chemical energy or heat. This formulation was accompanied by a declaration of agnosticism concerning the phenomena involved.
[297] Meanwhile, the science of thermodynamics was developing, and in 1923 the publication of Lewis and Randall’s Thermodynamics and the Free Energy of Chemical Substances[297.1] brought biochemists, for whom it became a constant companion, knowledge of the views introduced by Willard Gibbs. These included, in particular, the two concepts of energy, whose variations determine the possibility of total heat exchange, and entropy, whose variation determines the possibility of performing work. As Boltzmann had already seen in 1886 with regard to the biosynthetic phenomena carried out by plants, the organism depends neither on matter nor on energy, but on entropy, or more precisely on the negentropy made available during the transfer of energy from the hot sun to the cold earth. As Schrödinger put it,[297.2] life “feeds on negative entropy”, drawing towards itself, as it were, a current of negentropy that compensates for the increase in entropy occurring within it, and is thus able to maintain itself at a stationary and relatively low level of entropy.[T4]
Nevertheless, despite numerous studies of the biochemical mechanisms of respiratory oxidations and much work in the field of oxidation–reduction, modern views of bioenergetics begin with Warburg’s discovery in 1937 of the formation of adenosine triphosphate through coupling with an oxidation–reduction reaction: the enzymatic oxidation of phosphoglyceraldehyde during glycolysis.
It should be noted that adenosine triphosphate had been known for several years as an energy-rich compound. But Lohmann, who had discovered it, placed its role within the context of muscular contraction and its mechanical aspects. It should also be noted that, as early as 1924, Kluyver had stressed that endergonic reactions were conceivable only if coupled with exergonic reactions.[T5]
Coupling with ATP formation in the second oxidation–reduction of glycolysis, the enzymatic oxidation of phosphopyruvate, was demonstrated by Meyerhof; subsequently, the coupling of oxidative phosphorylation with respiration was established by Kalckar and Belitzer.[T6]
[298] In our current theory, the principal source of energy within organisms lies in the oxidation–reduction reactions arising from the transfer of electrons from substrates of cellular metabolism produced from food.
Within this perspective, what place remains for the heat that dominated all earlier conceptions? Animal heat is now merely a waste product of the successive stages of the metabolic scheme. The free energy of the oxidation–reduction reactions arising from the transfer of electrons from metabolic substrates is used to form the energy-rich bond constituted by ATP’s pyrophosphate linkage.[T7] During this storage, part of the energy is dissipated as heat. The pyrophosphate linkage is the source of all the organism’s capacities for work: mechanical work, osmotic work and chemical work. During this transformation into work, some of the energy is again dissipated as heat. For Aristotle, heat explains all the phenomena of life, and for Lavoisier it remains the driving force behind all its manifestations. For us it is now merely a waste product of functioning—even if some animals have developed mechanisms for using it to regulate body temperature, as we ourselves do in our cars in winter. The tragic contrast between the warmth of life and the cold of death had naturally led humanity to invest it with a singularly exaggerated significance.
Marcel Florkin
About this edition
Version 0.2. Source: Marcel Florkin, “Des forces-de-vie à la bioénergétique”, Revue d’histoire des sciences 24, no. 4 (1971), pp. 289–298. Original publication. Numbers in the text mark original pages. Original references retain their page-local numbering in the labels below. Translator’s notes explain contextual vocabulary and distinguish historical biochemical formulations. Quotations follow the French source. Bibliographic details are transmitted as printed unless explicitly noted.
T1. “Irritability” here means a tissue’s capacity to respond to stimulation; “sensibility” concerns sensitivity or sensation. These are the physiological principles discussed in the following account of Haller and Bichat.↩︎
T2. Latin anima means “soul”. Florkin distinguishes Stahl’s explanation through the soul from Barthez’s general vital principle.↩︎
T3. Plastique here concerns forming and maintaining tissues. Florkin is describing the historical division between tissue-building and energy-providing foods.↩︎
T4. “Negentropy” means negative entropy. The passage concerns the conditions for maintaining organisation through exchanges with the environment; its assertion of independence from matter and energy belongs to Florkin’s formulation of this argument.↩︎
T5. An endergonic reaction requires an input of free energy; an exergonic reaction releases free energy. Coupling links the reactions so that an energetically favourable overall process can drive the requiring step.↩︎
T6. The source calls the phosphopyruvate step an “oxidation–reduction” and an “oxidation”. This wording is retained. In the usual description of glycolysis, phosphoenolpyruvate transfers phosphate to ADP to form ATP; that step is not itself an oxidation–reduction reaction.↩︎
T7. “Energy-rich bond” translates Florkin’s historical terminology. The useful free-energy change concerns the overall reaction, including its products and conditions; breaking an isolated bond requires energy.↩︎