Jules - Antoine Regnauld

Jules-Antoine Regnauld (1822-1895), French physician and pharmacist, who carried researches about mydriatic alkaloids (such as atropine), electrochemical phenomena, electromotive force, amalgams, properties of mixing in saline solutions, physiology, electrophysiology, fluorescence in live tissues, medical chemistry, anesthesia, and vision phenomena. Life and career Very little information is available about the early life and education of Jules-Antoine Regnauld (Figure 1). Fig 1: Jules-Antoine Regnauld (1822-1895). Jaime Wisniak Department of Chemical Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel 84105 [email protected] Revista CENIC Ciencias Biológicas, Vol. 46, No. 2, pp. 168-181, mayo-agosto, 2015. 169 He was born in Paris on November 26, 1822, the son of a pharmacist, who died in 1839 leaving a very modest fortune to his wife and children. According to Charles-Jules-Ernest Cadet de Gassicourt (1826-1900) this two harsh events turned Jules into the introvert person he was known for his whole life. Under these circumstances, Jules decided to follow the profession of his father and take an apprenticeship in a Parisian pharmacy and hospital pharmacies. In 1844, he became hospital pharmacist and took a position at the Hôpital des Cliniques (1844-1855), while simultaneously following medical studies at the Faculté de Médecine de Paris, from where he graduated in 1847, after successfully defending a thesis about the generation of electricity in organized entities. In 1844, he was elected member of the Société de Pharmacie. He continued his education at the Faculté des Sciences de Paris and received his degree of docteur-ès-sciences (1851) with a thesis about electromotive forces and a new method for their measurement. In 1856, he began working at the Hôpital de la Charité in Saint-Etienne (18561859) and in 1857 he won an aggregation contest, which allowed him to follow an academic teaching and research career. Thus in 1857 he was appointed professor of physics at the École Supérieure de Pharmacie, replacing Eugène Souberain (1797-1859), his father-in-law; followed by an appointment to the chair of pharmacology at the Faculté de Médecine (1859-1891). In 1859, he was appointed director of the Pharmacie Central des Hôpitaux Civils, a position he kept until 1876 [Marie-Victor Ernest Beaudrimont (1821-1885) replaced him]. In 1861, he was elected member of the Académie Nationale de Médicine (section of physics and medical chemistry), of which he became its vice president in 1891 and president in 1892. Jules-Antoine Regnauld passed away in Paris, on February 9, 1895, after being ill for some time. His wife and only son, Eugène, survived him. By his express wish no official delegation was present at his funeral and no eulogies were pronounced. Paul Regnard (1850-1927) replaced him at the Académie de Médicine. SCIENTIFIC WORK Regnauld published about 60 papers, booklets, and books describing the results of his research on amalgams, anesthesia, batteries, electrophysiology, ether, medicine, physiology, vision phenomena, and phenomena of mixing of solutions. As customary for all candidates to the Académie Nationale de Médecine, he published a booklet describing his researches and achievements. Vision phenomena In 1838, Charles Wheatstone (1802-1875), in a groundbreaking paper, reported some new phenomena of binocular vision. According to him, "when an object is viewed at so great distance that the optic axes of both eyes are sensibly parallel when directed towards it, the perspective projections of it, seen to each eye separately is similar, and the appearance to the two eyes is precisely the same when the object is seen by one eye only...This similarity no longer exists when the object is placed so near the eyes that to view it the optic axes must converge; under these conditions a different perspective projection of it is seen by each eye, and these perspectives are more dissimilar as the convergence of the optic axes becomes greater." In particular, Wheatstone remarked "that if a blue disk was presented to the right eye and a yellow disk to the corresponding part of the left eye, instead of a green disk which would appear it these two colors head mingled before their arrival at a single eye, the mind will perceive the two colors indistinctly one or the other alternatively predominating either partially or wholly over the disc." Wheatstone explained this phenomenon by assuming that the retina contained two compartments and the papilla present in each unit was excited simultaneously. These results could be easily observed using the stereoscope apparatus of Wheatstone's invention. According to Jean Bernard Foucault (1819-1868) and Regnauld, the majority of researchers who had investigated the phenomena of visualization of rays of different refrangibility, had Revista CENIC Ciencias Biológicas, Vol. 46, No. 2, pp. 168-181, mayo-agosto, 2015. 170 reached the opposite conclusion, that is, the visual appearance would be a mixture of the two colors. For these reason they decided to repeat and extend Wheatstone's experiments, using the stereoscope of his invention because "it offered a simple mean of eliminating all possible complications which would affect the correctness of the physiological results". The experiments were conducted as follows: Two plane mirrors forming a variable dihedral angle were attached to the stereoscope and their vertical edge was placed symmetrically in relation to that of the two glasses of the stereoscope. Two large circular apertures perforated the vertical supports, which housed the grooves for introducing the image. The two grooves carried glasses, each pasted with identical circular screens of white paper, and of a diameter less that of the apertures. Two large complementary rays, obtained by chromatic polarization, were directed horizontally on the plane mirrors, which reflected them on the circular screens. This produced two colored discs, which become the images conveyed by the stereoscope to the corresponding elements of the retinae. Proper appropriate disposition of the polarizing apparatus allowed successively passing numerous complementary tints, while varying at the same time the intensity of the two colored images and the intensity of one or other of the images separately. Foucault and Regnauld reached the following conclusions: (1) When the corresponding elements of the retinae were excited simultaneously, the alternations of activity or inertness of one of the eyes was generally perceived at the initiation of the experiment; occasionally one of the tints was perceived, and at other times its complementary one; but after an interval, which varied very much in different individuals, only a single white circle was seen; (2) When the eyes were in some degree accustomed to this unusual mode of impression, the tendency to recomposition of the light became so strong in some persons that the screens might present successively all the complementary tints which the apparatus furnished without there being any sensation corresponding to the colors; the white light alone was seen; (3) On diminishing the intensity of one of the colors, the other remaining constant, recomposition still took place; but the white disc appeared to become covered more or less strongly with the predominant color; (4) When the intensity of the two complementary rays was varied in the same manner for the two ray beams, the recomposition took place more easily at the beginning of the observation, as their intensity was more moderated; (5) Of the complementary rays examined, the sensible blue and the yellow tints were best adapted for the experiment and immediately furnished the sensation of white. To Foucault and Regnauld this result was due to easy of accommodation of the eyes to the portions of the spectrum occupied by these rays; and (6) Except for few exceptions, the sensation of white light could be produced by any two complementary chromatic impressions in each of the eyes; that the sensation solely of white arising from two complementary rays was independent of any mutual action of these rays externally to the visual apparatus and that the luminous impressions produced on the retinae retained their properties even to the innermost recesses of the brain. Fluorescence of the transparent media of the eye According to Regnauld, it was well known that the luminous radiations emanating from the sun, from a fire, or from an electric battery, contained three sorts of rays in different proportions, viz., luminous, thermal, and chemical rays. The chemical rays were particularly abundant in the violet, ultraviolet, and higher portions of the spectrum. It was also known that bodies such as quinine sulfate, uranium glass, and many others, had the property of fixing these rays, that is, absorbing them instead of reflecting or permitting them to pass by and thus becoming luminous of themselves. This property of fixing these chemical rays was named of fluorescence, and the bodies possessing were called fluorescent. Regnauld found that many constituent parts of the eye became fluorescent under the influence of ultraviolet radiation, which he separated by means of a very pure and large Nicol prism. By successive inclination of the prism it was possible to receive over a screen, parallel or divergent rays of refrangibility increasing from blue to ultraviolet and non-visible. In this zone, a very Revista CENIC Ciencias Biológicas, Vol. 46, No. 2, pp. 168-181, mayo-agosto, 2015. 171 fluorescent substance such as a plate of uranium glass, revealed the existence of a dark field, where the tested material (e.g. transparent cornea, crystalline, hyaloid body, and retina) should be located. Since it was not possible to report the intensity of the phenomenon in relation to an invariable unit, Regnauld chose to compare it to the fluorescence of ordinary glass tubes illuminated by the long sparks transmitted through a rarefied gas. His results indicated that (a) in man and mammals the cornea fluoresced in a very slight degree; (b) in man and mammals (e.g the sheep, dog, cat, and rabbit) the crystalline lens possessed the highest degree fluorescent properties. In these animals, and also in many birds, the central part of the lens [the endophaine of Pierre Henry de Valenciennes (1750-1819) and Edmond Frémy (18141894)] retained this property even after being desiccated at a low temperature; (c) the central portion of the crystalline of many aquatic vertebrata and mollusks (the phaconine of Valenciennes and Fremy) was almost entirely without fluorescence; (d) the hyaloid body was weakly fluorescent. The phenomenon seemed to be due to the hyaline membrane because the vitreous humour was not fluorescent; (e) the retina of a human eye retained, even eighteen hours after death, certain fluorescence not at all comparable in intensity to that of the crystalline lens of mammals, as Hermann von Helmholtz (1821-1894) had reported previously; and (f) Regnauld believed that if we must attribute the accidents caused by weakly luminous radiations of the electric light to the phenomena of fluorescence, it is above all in the energetic action on the crystalline that it is natural to look for an explanation. The impression, which the cornea experimented, must nevertheless not be neglected. Regnauld finished this paper with some remarks regarding the safety of the vision process: The fluorescent properties of the cornea and the crystalline provided an almost impassable obstacle to the chemical rays inappropriate for the vision process and those dangerous to the retina. This effect was particularly important when the eye was subjected to an abundant flux of ultraviolet rays, as in the case of light produced by electricity. For this reason the present efforts to introduce electrical lamps for the illumination of cities and towns was fraught with dangers; the use of this type of light could have a slow and deadly effect on the eyes of the inhabitants. Mixtures of saline solutions Refractive index Regnauld published several papers reporting certain changes that took place during the mixing of saline solutions of different composition and nature. The first one studied the possible changes of the average refractive index that occurred when mixing two aqueous solution of known refractive index, which did not go through a double decomposition, in a given proportion. The solutions were sufficiently diluted to remain as such after their mixing. Regnauld did not make use of the direct value of the refractive indexes but of a simple procedure, which indicated the nature and direction of the change. For this purpose he used the apparatus designed by Gustav Robert Kirchhoff (1824-1887) and Robert Wilhelm Bunsen (1811-1899), where the flint prism of the photometer was replaced by a hollow glass receptacle, built of parallel blades in a way to create a prismatic cavity of fixed angle. Regnauld used this apparatus to examine the changes in refractive index when mixing solutions of sodium acetate with solutions of zinc (or copper) sulfate, nitrate, and copper, and of sodium formate with the same salts of zinc or copper. The compositions of both the solutions being compared were adjusted by dilution so as to produce the same refractive index relative to the D line. This procedure assured that the mass ratio of the two salts was constant during the standardization process. Regnauld found that mixing a solution containing a strong acid and a weak base with another having a weak acid and a strong base produced a resulting solution having a lower index of refraction. According to Regnauld, since the mass ratio of the solutes was constant implicated that the groups of the salts had rearranged themselves in a different manner. To confirm the correctness of his hypothesis he carried the inverse experiment, that is, mixing a solution of Revista CENIC Ciencias Biológicas, Vol. 46, No. 2, pp. 168-181, mayo-agosto, 2015. 172 copper or zinc acetate, with a another of sodium nitrate or sulfate, etc. In this situation, the mixture of the solutions could lead to the formation of salts resulting from the union of a weak acid with a weak base, and the opposite effect would be observed: an increase of the refractive index. The result of these experiments confirmed his theory. In the second part of this work Regnauld repeated the experiments using a variety of pairs of additional salts of potassium, calcium, ammonia, copper, zinc, nickel, manganese, cadmium, and iron, selected in such a way that their mixing occurred without chemical reactions. Once again, he observed a decrease in the refraction index when the original solutions contained a strong acid combined with a weak base or a strong base combined with a weak acid, or an increase in the refractive index when the mixture of the solutions could lead to the formation of salts resulting from the union of a weak acid with a weak base. Regnauld also measured the density of the solutions, before and after mixing them, and noted that pairs that produced a decrease in the refraction index were accompanied by an increase of volume, while those who produced an increase in the value of the index exhibited a decrease in the volume. Heat of dilution It was thought that the heat effect during the dissolution of a salt should be less than the heat necessary to melt it because the chemical interaction between the salt and the water provided the part of the heat necessary for melting the salt. In 1850, Charles Cléophras Person proved that this conception was wrong. For example, he mentioned that 49 calories were necessary for melting one gram of potassium nitrate, 69 calories for dissolving it in 5 g of water, and 80 calories for dissolving it in 20 g of water. This was the common result for salts that showed little affinity for water: the heat effect increased with the amount of water employed, although not proportionally. Salts showing a large affinity for water showed the opposite effect. Thus, under the same conditions as above, calcium chloride required 41 calories to melt and only 20 for dissolution. All kinds of phenomena occurred in between these two cases, potassium phosphate, for example, required the same amount of heat for melting and for dissolving in water. Person wrote that these and other experiences showed that it was necessary to accept the existence of a heat of dilution. Regnauld went on to prove that the variation of heat observed by Person during the dilution of a salt was not related with the accompanying change in density of the solution. For this purpose he prepared a saturated solution of nine different salts at 15 C, then mixed each suddenly with an equal volume of water, observed the direction of the temperature change, then let the liquid achieve thermal equilibrium and measured its density at 15 C. The results indicated that the dilution process of solutions of sodium nitrate, potassium nitrate, sodium hyposulfite, and sodium sulfate was endothermic, while for those of sodium acetate, zinc acetate, and zinc sulfate, was exothermic. The solution of sodium phosphate showed no change in temperature. A comparison of the calculated density (weighted average of that of the components) was always less than the experimental one. In other words, the actual effect was one of contraction, independently of the thermal effect. Volume changes In a following publication Regnauld reported additional data about the changes of volume that occurred during the isothermal (15 C) neutralization of alkaline solutions with acids. In this opportunity his experimental technique consisted in neutralizing equal volumes of solutions containing one equivalent of base (KOH, NaOH, baryta, and ammonia) or one equivalent of acid (sulfuric, nitric, phosphoric, chlorhydric, acetic, and tartaric), and measuring the density of each solution and that of the resulting one. He determined the change in volume (positive or negative) by comparing the latter result with the theoretical density [calculated as (d1 + d2)/2] 27 Revista CENIC Ciencias Biológicas, Vol. 46, No. 2, pp. 168-181, mayo-agosto, 2015. 173 The experimental results indicated that independently of the dilution and the nature of the acid that combined with NaOH, KOH, and baryta, the neutralization process was always accompanied by an increase in volume (expansion). The opposite result, contraction, was obtained with ammonia. Interesting enough, both phenomena were accompanied by a strong exothermic effect. Regnauld believed that the difference in behavior originated from the role played by the water in both types of basic solutions. In spite of its solubility in water, ammonia did not produce a stable combination with the elements of water; the gas dissolved according to the laws of gas solubility and escaped under vacuum, heat, or by simple diffusion into the atmosphere. Without preassuming the existence of a hydrate of ammonium oxide, it could be said that this liquid behaved in the same manner as if the elements of NH3 were condensed physically by water, as they were by carbon (adsorption), with the corresponding exothermic effect. KOH and NaOH represented a completely different picture; the new structure was built at the expense of materials solidly united. These hydrates had long been likened to salts and their production was always accompanied by contraction and heat release. Electrochemistry Regnauld wrote that famous scientists such as Georg Ohm (1789-1854), Gustav Fechner (18011887). Johann Christian Poggendorff (1796-1877), and James Prescott Joule (1818-1889), had developed methods and apparatus for measuring the electromotive force, which unfortunately were all indirect. The value of the force was calculated from the intensity of the current, or was implicitly included. In addition, all the methods required knowledge of the resistance of the circuit. In a series of papers he described a new method (which he named the opposition method) for measuring the electromotive force, based on the cancellation of the resistances. The values were determined directly, without going through the intermediate steps of measuring the resistances or the intensities. The bases of the new method were as follows: Assume two voltaic cells composed of the same elements but of different size, that is, the metallic plates do not have the same dimensions, the liquid layers have different depth or section, etc. Under these circumstances each cell will produce a current of different intensity. If, for example, the positive element of one cell were connected to the positive element of the other cell, and the same was done with the negative elements, then no current would be produced. If the same arrangement were built with cells of different nature, a current would be generated having intensity equal to the difference of the intensity produced by each cell [Regnauld remarked that Michael Faraday (1791-1867) had mentioned these ideas but never formulated them explicitly]. Assume now that the intensity of the two cells is expressed by e1/r1 and e2/r2, respectively, where ei represents the electromotive force and ri the resistance. If the cells are connected as described above, the net electromotive force will be given by the difference (e1 e2) but the resistance of the circuit will be (r1 + r2); hence the intensity i of current will now be given by (1) Equation 1 shows that if e1 = e2, no current will flow, independently of the value of (r1 + r2). The same reasoning may be applied to series of cells in opposition, that is