The attention Lavoisir gave to human physiology was the outcome of a long butlogical progression.His numerous reflections in the domain of hygiene and public health led him gradually to consider the factors determining the state of health or illness and to adopt an approach similar to that of a physiologist.However, when hewrote down in his laboratory notebook on February 20, 1773 his celebrated research program on "the air that fixes itself to or is released from bodies," he was not thinking about these matters.At the time, his plan was strictly chemical: he wanted to develop a general theory explaining the five circumstances in which, according to him, air fixed itself or was released from chemical bodies: vegetation, respiration, combustion, calcination and chemical combinations.

Seventeen years later, he was envisaging medical applications for his research activities.They could, he said, "diminish the mass of evils that afflict the human species, (...),increase itsenjoyment and well being.And even if the new routes opened up could prolong the average life of mankind by only a few years, or even a few days,then thescientist, too, could aspire to the glorious title of 'benefactor of humanity'." (Lavoisier, Oeuvres, vol. II, p. 703.)


The Physiology of Respiration

This was a phenomenon that for twenty years Lavoisier kept encountering at each stage of his research.Already in May 1777, he had published his "Experiments on Animal Respiration and the ChangesOccuringWhen Air Passes Through the Lungs," complemented by a paper on the combustion of candles in atmosphericand "eminently breathable" air.These ideas were developed in the "Mémoire sur la chaleur" written with Laplace and published on June 18, 1783.In February 1785 he had read to the RoyalSociety of Medicine a paper describing"the changes that occur in air in the various circumstances where people come together in groups." In the first paper he wrote on animal respiration, presented at the Academy on November 17, 1790, he presented the synthesis of his findings.

- The purpose of respiration, he said, is not to cool the blood, as was believed in ancient times.It is rather "a slow combustion of carbon and hydrogen, similar in every way to that which takes place in a lamp or lighted candle and, in that respect, breathing animals are active combustible bodies that are burning and wasting away."(Lavoisier, Oeuvres, vol. II, p. 691.)

- It is atmospheric air which furnishes the oxygen necessary for this combustion.The blood provides the fuel and its oxidation in the lungs explains the change in color.This combustion produces carbonic gas and water.
- This combustion isalso the source of body heat."Since air vitalcannot be converted into carbonic acid except by an addition of carbon, and cannot be converted into water except by an addition of hydrogen, and the double combination cannot occur unless theair vitalloses a part of its specific caloric, the result is that the effect of respiration is to extract from the blood a portion of carbon and hydrogen and to replace it with a portion of its specific caloric.During circulation, the caloric is distributed with the blood through the animal system, and maintains that almost constant temperature observed in all breathing animals.(Lavoisier, Oeuvres, vol. II, p. 692.)
- This combustion has an energetic cost: "Since it is the very substance of the animal, it is the blood which transports the fuel.If the animal did not habitually replace, through nourishing themselves,what they losethrough respiration, "the lamp would very soon run out of oil and the animal would perish, just as the lamp goes out when it lacks fuel."(Lavoisier, Oeuvres, vol. II, p. 691.)

In this elegant metaphor, F.L.H. Holmes points out , Lavoisier formulated for the first time an enlarged conception of the equilibrium necessary between nourishment and the consumption of nutriments.According to Holmes, "it was no longer a matter just of the combustion of carbon and hydrogen supplied from the blood; the substance of the animal itself was consumed in respiration.Nourishment and respiration were part of one large process encompassing much of the 'animal economy'."(L. Holmes, Lavoisier and theChemistry of Life, Madison-London, University of Wisconsin Press, 1985, p. 450.)

- The variations in oxygen concentration in the air do not change the consumption by the organism."It is known that the purer the air in which combustion occurs, the faster the combustion.Thus, for example, within a given time, much more charcoal, or any other fuel, is consumed in vital air than in atmospheric air.It had always been thought that the same was true for respiration, that it ought to accelerate in vital air, and then release - either in the lungs or circulatory system - a greater quantity of caloric.But the experiment has destroyed all these assumptions whichwere based only on analogy." (Lavoisier, Oeuvres, vol. II, p. 694.)
- Nitrogen is not a respiratory gas.It enters the lungs and comes out unchanged.
- A relationship exists between the mechanical work carried out by a living being and the measurable biochemical phenomena which are its driving force.Wanting to measure these gaseous exchanges and the effects that digestion and muscular activity had on them, Lavoisier and Laplace invented the calorimeter which allowed him to measure the heat relased by an animal, to compare it to that released by the combustion of charcoal and thus to determine the animal's expenditure of energy.Then he measured the oxygen consumption corresponding to this expenditure and was able to establish several general notions concerning respiration: movements and digestion increase its rhythm and the consumption of air.
Eager to confirm these hypotheses for man, his assistant Seguin dressed himself in a special suit made of taffeta coated with elastic gum, through which no air or humidity could penetrate.It was closed above the head by a strong ligature.A tube stuck around his lips with putty allowed him to breath.His consumption of oxygen was measured in different situations.Inactive and on an empty stomach, at an ambient temperature of 32.5° C., he consumed 400 millilitersper minute.

Thus was born the notion of an inescapable basic expenditure of energy, linked to minimal physiological activity, independent of all exterior stimulation: it was the future basal metabolism. The consumption increased during digestion as well as with lowered temperatures and muscular exercise."We have succeeded in observing two laws of the utmost importance: the first is that the increase in the number of heartbeats is in quite direct proportion to the sum of the weights lifted to a determined height; the second is that the quantity of vital air consumed is in directproportion to the product of the inspirations throughheartbeats."(Lavoisier, Oeuvres, vol. II, p. 696.)

Then Lavoisier gives the description of Seguin's efforts during a quarter of an hour to raise a weight of fifteen poundsto a height of six hundred fifty feet. "It should be noted," writes Pierre Dejours, "that in the same paper, theauthors proposed two biometric laws, perhaps the first to be enunciated: on the one hand, the correlation between therate at which the heartbeatsandthe energy consumed duringthe exercise; and on the other, the correlation between oxygen consumption and the respiratory and heartbeatrates.The data of modern physiology have shown these laws to be exact."(P. Dejours, "Lavoisier physiologiste," inIl y a 200 ans Lavoisier,C. Demeulenaere-Douyère, ed., Paris, Technique et Documentation Lavoisier, 1995, p. 14.)

At this time, Lavoisier also expressed one of the first laws of the physiology ofexertion and invented the modern methods of objective measurements of specific jobs which are used in occupationalmedicine: measurement of heartbeatrate, a procedurestill used universally today, and of the oxygen consumed, now discarded since the former suffices.It should be noted that Sequin claimed his contribution to this discovery.

- The locus of this combustion, maintained by respiration, remained unknown to Lavoisier.Sometimes, he asked himself if the carbonic gas wasformed "in the lungs or during circulation, by the combination of oxygen from the air with the carbon from the blood."At other times, he approached the correct hypothesis: "It is possible," he wrote, "that a part of this carbonic acid is formed by digestion, that it is introduced into the circulation with the chyle and when it reaches the lungs isreleased from the blood as the oxygen combines with it through a superior affinity." (Lavoisier, Oeuvres, vol. II, p. 702.)

By the end of his investigation, Lavoisier had identified the biological regulators the equilibrium of which assures a state of health: respiration, which brings the combustion agent, oxygen; nutrition, which furnishes the fuels, hydrogen and carbon; and thermogenesis, or the production of heat resulting from this combustion.It remained for him to define its counterweight, thermolysis, or loss of heat, produced by perspiration.

The Physiology of Perspiration

Lavoisier assumed that perspiration continuously drew water from the organism and combined it with the caloric to transform it into vapor; the loss of the caloric led to a cooling which maintained the constant temperature of the body."It is not only by the pores of the skin that this aqueous emanation takes place," Lavoisier specified."A considerable quantity of humidity is also exhaled by the lungs at each expiration."(Lavoisier, Oeuvres, vol. II, p. 706.)

The input/output method and the use of scales were as always much in evidence.To determine the weight of water lost through perspiration, it sufficed to determine the total weight loss of an individual within a given time and then to subtract from it the amount of water lost by respiration. In the"Premier mémoire sur la transpiration des animaux"("First Paper on Animal Perspiration"),heanalyzed the respective roles of cutaneous and pulmonary perspirationsand respiration: to break down the water loss connected with each of these three phenomena, the methods used "although simple in theory, presented extreme difficulties in practice."(Lavoisier, Oeuvres, vol. II, p. 709.)We are forced to admit today that they were notsurmounted.The authors lost control of both the experimental protocol and that of the physiological theory.The complexity of the hydro-electrolytic exchanges in the lungs far surpassed what they could imagine.

In 1791, Lavoisier had been successively elected National Treasury Commissioner, member of the Committee on Weights and Measures, Treasurer of the Academy of Sciences and member of the Advisory Board for Arts and Trades.Thisextraordinarily talented man who had been able to hold ten jobs at once began to be overwhelmed, to the detriment of his personal research.

In presenting his second paper on perspiration at the Academy on February 22, 1792, he announced that "the experiments described belonged entirely to Seguin," his student and assistant.(Quoted by M. Daumas, Lavoisier théoricienet expérimentateur, Paris, P.U.F., 1955, p. 65.)Lacking experimental results, and always more at ease in the domain of political ideas, Seguinhad concentrated on describing social disparities: "This evenness of temperature which the wealthy man obtains with so much effort by combining the production of two hemispheres - Indian silk and Spanish wool- by using a multitude of men to weave precious fabrics, is reached by the poor man in a much less complicated way, one that makes him dependent on no one: nature simply accelerates his respiration in proportion to his needs."(Lavoisier, Oeuvres, vol. V, p. 388.)

One can imagine that Lavoisier took a certain distance regarding his young assistant whose daring theories rather alarmed him.In eighteen years of study and reflection, he did however, cover the essential questions: the role of pulmonary ventilation; its relationship to the circulation of blood and combustion; the mechanisms of body heat and homeothermia; and the regulation of the respiratory function and its relationship to perspiration and nutrition.


The Animal Machine

Certainly, many questions remainedunanswered.More than a century would pass before it wasestablished that respiration is intended to produce the energy necessary for the maintenance and development of living structures, and that this energy comes from oxidation - which takes place in the microscopic bodies, mitochondrions, at the center of cells and tissues - of three classes of organic substances: carbohydrates, lipids and proteins.But Lavoisier had made the essential link between respiration and perspiration, body heat and nutrition, foreshadowing the modern concept of biological energetics. "The animal machine is governed principally by three main regulators: respiration which consumes hydrogen and carbon and providesthe caloric;perspiration, which increases or decreases, depending on whether more or less caloric isneeded; and finally, disgestion, which restores to the blood what it has lost through respiration and perspiration."(Lavoisier, Oeuvres, vol. II, p. 700.)

Lavoisier had understood that carbon is necessary for combustion and that it is transported by the blood.A half century later, Claude Bernard (1813-1878) demonstrated that the real fuels are the carbohydrates absorbed by the intestines and carried to the liver by the portal vein.But Lavoisier had in any case understood that an organism's functions aresubjected to a regulating system permitting the individual to adapt to all circumstances."Is he inactive or resting? Then circulation as well as respiration is slowed down.He uses less air.His lungs exhale less carbon and hydrogen and consequently he needs less food.Does he have to make an effort?Respiration accelerates, he consumes more air and loses more hydrogen and carbon.Consequently, he needs to restore his strength more often, especially by nutrition."(Lavoisier, Oeuvres, vol. II, pp. 699-700.)


The Physiology of Nutrition

Trying to reach a better understanding of the physiology of nutrition, on July 28, 1792, Lavoisier proposed that the Academy award a prize for research on the subject: 5000 livres would be given to the best study on animalization, that is, the organic synthesis of animal tissues after the absorption of food.He had guessed that the liver plays an essential role in this process."It is known that the liver occupies considerable space in animals' bodies;that a part of the abdominal vascular system is destined to this viscera; that the blood is disposed there in a particular way for the secretion of bile; thatall other functions depend on the constant and regular flow of this substance; that the liver exists in all animal orders, including insects and worms; that it is often accompanied by a gall bladder, depending on the nature ofthese beings; that there is an essentialrelationship between the spleen, the pancreas and the liver.Here then , forthe first time in years,is data that anatomy has offered for the speculation of physiologists. (...)It is easy to foresee that other than the secretion of bile, or rather through the secretion of bile, an organ as important in size, connections and vascular structures as the liver fills a whole system of functions, the extent of which science has not yet grasped."(Lavoisier, Oeuvres, vol. VI, p. 35.)

Lavoisier recalled that the initialphases of the physiology of digestion were already well known: the successive actions of saliva in the mouth, gastric juices in the stomach,and of bile andpancreatic juices which convertnourishment into chyle, of which "one part is absorbed in the blood to compensate for the losses that are constantly taking place through respiration and perspiration," and"all the material that Nature cannot used is rejected in the form of excrement."(Lavoisier, Oeuvres, vol. VI, p. 34.)

But many unknowns remained: the anatomiesof the liver and gall bladder; the chemical composition of bileand the hepatic parenchyma in various animal species; the difference between the composition of the blood in the portal vein and that in other regions of the body; the definitions of the functions of the liver and bile and their relationship to other organs; the main illnesses of the liver and the biliary tract in both human beings and animals.In his commentary, Lavoisier underlined the importancehe attributed to the hepatic function in anabolism.In a most original way, he expressed his confidence in the capacity of chemistry to explore the mechanisms of life."By proposing this subject and emphasizing all its difficulties, the Academy realizes that it will require chemical research basedin particular on the recently acquired analytical means of chemistry.It feels and hopes that this work will oblige those who undertake it to determine the nature of the blood in the portal vein, and to compare it with the arterial and venous blood in other regions.(...)It is time to take up the complicated questions presented by the phenomena ofthe animal system , and it is from the joint efforts of physics, anatomy and chemistry that we can hope to find answers."(Lavoisier, Oeuvres, vol. VI, pp. 35-36.)

Along with the chemical revolution, Lavoisier hadalso beguna revolution in biology.Claude Bernard, in turn, would show that the phenomena which occur in the living body, conform to laws as precise and stable as those in inanimatesubstances.But he would bear witness to the importance ofthe contributions of Lavoisier whom he considered to be, after WilliamHarvey (1578-1657), the most important figure in modern biology.

"Lavoisier," he wrote, "had already clearly shown that the physico-chemical phenomena of living beings are sustained by the same causes as those of mineral bodies.He showed thatbreathing animalsand calcinedmetalsabsorb from the air the sameactive and vital principle, oxygen,and that the absence of this respirable air stops calcination as well as respiration.In another experiment, Lavoisier and Laplace demonstrated that oxygen, in penetrating living beings, engenders the organic heat that sustains them, by a real combustion similar to the combustion of fire boxes.The ancient myth of life compared to a flame that blazes and isthen extinguished was no longer a simple metaphor but a scientific reality.The same chemical conditions feed the fire in inorganic nature and life in organic nature. If, starting from the fact pointed out by Lavoisier, we have now come down to the experimental analysis of vital functions, we shall see that in all tissues and organs, it is oxygen that is always both the stimulator of physico-chemical phenomena and the condition of the functional activity of organized matter.Oxygen penetrates animals bythe respiratory surface, and circulation spreadslife in all the organs and organic elements by distributing the oxygen dissolved in the arterial blood."(Claude Bernard, "Le problème de la physiologie générale," in La science expérimentale, Paris, Baillière, 1878, pp. 122-23.)