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William Prout: Early 19th Century Physician-Chemist Louis Rosenfeld In the early 19th century, the discoveries of new sub- stances in the healthy and diseased body spawned a search for chemical explanations for physiologic phe- nomena to guide medical diagnosis and control therapy. William Prout’s work on the nature and treatment of diseases of the urinary organs established his reputation as one of Britain’s most distinguished physiological chemists. Prout was very skeptical of chemical remedies because of possible side effects, but he suggested iodine treatment for goiter. He emphasized that a satisfactory diet should include carbohydrates, fats, protein, and water. In 1824, he showed that the acid of the gastric juice was hydrochloric acid. Prout applied chemical methods and reasoning to physiology and was criticized for his view that the body’s vital functions could be explained by chemistry. His remedy for lack of progress in animal chemistry was for physiologists to become chemists. Prout stimulated much discussion on atomic theory by his hypothesis that the atomic weights of all chemical elements are whole-number multiples of the atomic weight of hydrogen and that the chemical ele- ments were condensed from hydrogen atoms. © 2003 American Association for Clinical Chemistry In an age when the description of disease was often a mere catalog of symptoms, there were few medical men in the early 19th century who appreciated the usefulness of chemistry in the explanation and treatment of disease. Although investigations in the chemistry of disease were being carried out in the 1820s, 1830s, and 1840s, its application in routine diagnosis was not widespread. The work of several British physician-chemists—Rees (1), Bence Jones (2), and Marcet (3)— has been described in previous issues of this journal, and elsewhere by N.G. Coley (4–6) and F.W. Putnam (7). The subject of this article is William Prout (1785–1850) (Fig. 1). Like many other 19th century physicians of humble origins, Prout’s earlier education was almost negligible and was over by the age of 13. By the age of 17, aware of his own educational deficiencies, he pursued a pattern of systematic learning, first in a private academy and then in a classical seminary. He was encouraged to study medi- cine at the University of Edinburgh. (Oxford and Cam- bridge were outside his social status.) Thus, in 1808, at age 23, he enrolled at Edinburgh. He was graduated MD in June 1811. He next “walked the wards” of the United Hospitals of St. Thomas’s and Guy’s to obtain practical experience and passed the examination for licentiate of the Royal College of Physicians in December 1812. Prout was admitted as a Fellow of the Royal College of Physi- cians in 1829; he also served two terms as vice-president of the Medical Society of London (8, 9 ). Prout was an early riser who did some of his scientific work before he breakfasted at 7 in the morning. The remainder of the day was devoted to his patients. Besides his extensive town practice in urinary disorders, packages arrived daily from the country for analysis. Prout was not primarily a clinician and had a reputation for being lax in charging his patients. Most of his analyses and scientific experiments were made with ingenious apparatus of his own design, for which he spared no expense in construc- tion. This seeming unconcern about money kept him from the financial success of many of his colleagues at a time when great fortunes could be made in the practice of medicine (9, 10 ). During the first half of the 19th century, clinical chem- istry emerged from applications of chemistry to medical diagnosis. The discoveries of new substances in the healthy and diseased body that accompanied the begin- ning of scientific medical research, and the development of organic and physiological chemistry, spawned a wave of interest in clinical chemistry as a recognizable identity in the late 1830s and 1840s. There followed a systematic search for pathologic changes in the chemical composition of body fluids to guide medical diagnosis, follow the course of the disease, and control therapy. A search for chemical explanations for physiologic phenomena be- came a major preoccupation of leading scientists during the 19th century. Address for correspondence: 1417 East 52nd Street, Brooklyn, NY 11234. Received November 14, 2002; accepted January 15, 2003. Clinical Chemistry 49:4 699 –705 (2003) History 699

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William Prout: Early 19th CenturyPhysician-Chemist

Louis Rosenfeld

In the early 19th century, the discoveries of new sub-stances in the healthy and diseased body spawned asearch for chemical explanations for physiologic phe-nomena to guide medical diagnosis and control therapy.William Prout’s work on the nature and treatment ofdiseases of the urinary organs established his reputationas one of Britain’s most distinguished physiologicalchemists. Prout was very skeptical of chemical remediesbecause of possible side effects, but he suggested iodinetreatment for goiter. He emphasized that a satisfactorydiet should include carbohydrates, fats, protein, andwater. In 1824, he showed that the acid of the gastricjuice was hydrochloric acid. Prout applied chemicalmethods and reasoning to physiology and was criticizedfor his view that the body’s vital functions could beexplained by chemistry. His remedy for lack of progressin animal chemistry was for physiologists to becomechemists. Prout stimulated much discussion on atomictheory by his hypothesis that the atomic weights of allchemical elements are whole-number multiples of theatomic weight of hydrogen and that the chemical ele-ments were condensed from hydrogen atoms.© 2003 American Association for Clinical Chemistry

In an age when the description of disease was often amere catalog of symptoms, there were few medical men inthe early 19th century who appreciated the usefulness ofchemistry in the explanation and treatment of disease.Although investigations in the chemistry of disease werebeing carried out in the 1820s, 1830s, and 1840s, itsapplication in routine diagnosis was not widespread. Thework of several British physician-chemists—Rees (1 ),Bence Jones (2 ), and Marcet (3 )—has been described inprevious issues of this journal, and elsewhere by N.G.Coley (4–6) and F.W. Putnam (7 ). The subject of thisarticle is William Prout (1785–1850) (Fig. 1).

Like many other 19th century physicians of humbleorigins, Prout’s earlier education was almost negligible

and was over by the age of 13. By the age of 17, aware ofhis own educational deficiencies, he pursued a pattern ofsystematic learning, first in a private academy and then ina classical seminary. He was encouraged to study medi-cine at the University of Edinburgh. (Oxford and Cam-bridge were outside his social status.) Thus, in 1808, at age23, he enrolled at Edinburgh. He was graduated MD inJune 1811. He next “walked the wards” of the UnitedHospitals of St. Thomas’s and Guy’s to obtain practicalexperience and passed the examination for licentiate ofthe Royal College of Physicians in December 1812. Proutwas admitted as a Fellow of the Royal College of Physi-cians in 1829; he also served two terms as vice-presidentof the Medical Society of London (8, 9 ).

Prout was an early riser who did some of his scientificwork before he breakfasted at 7 in the morning. Theremainder of the day was devoted to his patients. Besideshis extensive town practice in urinary disorders, packagesarrived daily from the country for analysis. Prout was notprimarily a clinician and had a reputation for being lax incharging his patients. Most of his analyses and scientificexperiments were made with ingenious apparatus of hisown design, for which he spared no expense in construc-tion. This seeming unconcern about money kept him fromthe financial success of many of his colleagues at a timewhen great fortunes could be made in the practice ofmedicine (9, 10 ).

During the first half of the 19th century, clinical chem-istry emerged from applications of chemistry to medicaldiagnosis. The discoveries of new substances in thehealthy and diseased body that accompanied the begin-ning of scientific medical research, and the developmentof organic and physiological chemistry, spawned a waveof interest in clinical chemistry as a recognizable identityin the late 1830s and 1840s. There followed a systematicsearch for pathologic changes in the chemical compositionof body fluids to guide medical diagnosis, follow thecourse of the disease, and control therapy. A search forchemical explanations for physiologic phenomena be-came a major preoccupation of leading scientists duringthe 19th century.

Address for correspondence: 1417 East 52nd Street, Brooklyn, NY 11234.Received November 14, 2002; accepted January 15, 2003.

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Preparation and Analysis of UreaIn seeking the cause of urinary calculi, Antoine FrancoisFourcroy (1755–1809) and Nicholas Vauquelin(1763–1829) investigated the composition of urine anddeveloped procedures for the isolation and study of urea.There had been earlier descriptions. Johannes van Hel-mont (1577–1644) (11 ) had isolated two salts from urine:one was sea salt, which he said was taken with food; theother, salt of urine, was of different crystalline form and,unlike the sea salt, was volatile when heated (probablyurea). Sometime before 1727, Hermann Boerhaave (1668–1738), the renowned Dutch physician-chemist, describeda crystalline residue obtained from urine that he hadconcentrated by heating, filtering, washing, and evaporat-ing, which he called “the native salt of urine” and whichhe distinguished from sea salt (sodium chloride), alsopresent in urine. Hilaire Marin Rouelle (1718–1779) in1773 prepared an impure urea from the alcoholic extractof an evaporated urine residue. Rouelle called it matieresavonneuse (soapy matter). In England in 1797, WilliamCruickshank (1745–1800) added concentrated nitric acidto evaporated urine and obtained crystalline urea nitrate.

In 1799 Fourcroy and Vauquelin prepared a nearlypure urea, which they named uree (12 ). They prepared amuch purer urea in 1808 when the sparingly soluble ureanitrate was neutralized by aqueous potassium carbonate.After evaporation to dryness, the residue was extractedwith alcohol to separate the urea from the potassiumnitrate. Evaporation of the alcoholic solution yieldedcrystals of urea. Because an aqueous solution of ureadecomposes on boiling to carbonic acid, acetic acid, and

ammonia, they speculated that ammonia-containing cal-culi might be formed by the partial fermentation of ureain the bladder.

Finally in 1817, a pure urea product was isolated, itsproperties, appearance, and chemical reactions were de-scribed, and its analysis was accurately determined byWilliam Prout (first exhibited, he said, at some lectures hehad given 3 years earlier). Prout introduced a purificationstep with animal charcoal before extraction with boilingalcohol. This became the textbook method of choice forthe preparation of urea. Prout’s analysis (by combustion)of the percentage composition of the component elementsof urea was virtually identical with the values calculatedfrom what we now know to be its formula (13, 14 ).

Prout used Gay-Lussac’s method (1816) of completelyoxidizing the urea with black oxide of copper, which at asuitable temperature readily gives up its oxygen to hy-drogen and carbon but not to nitrogen. The nitrogen,uncombined, was collected in a calibrated gasometer.Prout calibrated his weights with platinum standards,and all materials to be analyzed were dried over sulfuricacid in a vacuum apparatus of his own design, at �200 °F(13 ). Prout was meticulous in his analytical techniquesand strove for purity of reagents and organic substances.

Years later, Prout acknowledged that “from its compo-sition I was satisfied that it might be formed artificially. Imade numerous attempts to form it, but did not succeed;and the honour of forming the first organic product artificiallyis due to Wohler”. Prout also claimed to have found urea(or a substance having most of its properties) in blood in1816. Believing it was accidental, he did not pursue theinquiry, but made a note of it (15 ).

Chemical science had a slow and difficult beginning.Nearly a century elapsed between the first isolation ofurea by Boerhaave and the preparation and analysis of thefirst pure specimen by Prout. Only a few years later, in1828, the laboratory synthesis of urea by Friedrich Wohler(1800–1882) played an important role in stimulating fur-ther synthesis in organic chemistry.

Prout’s HypothesisProut’s name is associated with the two hypotheses ofintegral atomic weights and the unity of matter, i.e., theatomic weights of all chemical elements are whole-num-ber multiples of the atomic weight of hydrogen. Hesuggested that hydrogen might be the primary matterfrom which all other “elements” were formed. This wasexpressed in two papers in the Annals of Philosophy (1815,1816). They were titled “The Relationship between Spe-cific Gravities of Bodies in Their Gaseous State, and theWeights of Their Atoms”. The papers dealt with thecalculation of the specific gravities (relative densities) ofthe elements from the published data of other chemists.He derived an excellent value for hydrogen, which owingto its light weight had been very difficult to determineaccurately by experiment.

“Prout’s Hypothesis” was perhaps his most widely

Fig. 1. William Prout.From a miniature by Henry Wyndham Phillips (Courtesy of the Royal College ofPhysicians of London).

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known contribution to chemistry. It stimulated discussionand improvement of analysis and forced interest in thedetermination of accurate atomic weights, and thereby inthe atomic theory, and in a search for a system ofclassification of the elements (16, 17 ). Published anony-mously at first, Prout quickly identified himself as theauthor when he found that his ideas had been accepted bythe eminent chemist Thomas Thomson, founder of theAnnals of Philosophy. Prout was content to leave thepromotion of his speculation to the status of a law toThomson while he himself returned to perfecting tech-niques of organic analysis.

Analysis of UrineEntering the 19th century and the era of atomic weightsand atomic theory, chemistry began to disengage from itsqualitative and descriptive character in the previous cen-tury when applications of chemistry to medicine weredirected to the understanding of disease rather than to itsrelief. “Chemistry being a science of observation”, Proutlooked forward to the time “when chemistry shall bebrought more under the control of the laws of quantity. . .” (18 ). To those scientists known as vitalists, it wasinconceivable that bodily functions could be explained bychemistry. They believed that the composition and work-ings of the body required a study of the vital functions,and they denied chemistry a role in physiology. Prout wasan early and consistent advocate of the benefits to bederived from the application of chemistry to physiologyin the treatment of disease (8 ). He also favored the studyof physics and chemistry by medical students. One ofProut’s admirers was Henry Bence Jones (1813–1873),who in 1850 credited him with being first to make theconnection between chemistry and medical practice (19 ).

In 1814 Prout advertised a course of evening lectureson animal chemistry in his home. The topics were respi-ration and urine chemistry. Urine was subjected to sys-tematic and scientific examination by Prout. His majorwork, An Inquiry Into the Nature and Treatment of Gravel,Calculus, and Other Diseases Connected with a DerangedOperation of the Urinary Organs (1821), was very popularand helped establish his reputation in Great Britain andEurope as one of Britain’s distinguished physiologicalchemists. Prout’s goal was to establish a coherent connec-tion between the chemical processes of metabolism andexcretion, as manifest in the urine, and the observedchanges in the patient’s clinical status.

By 1825, when the second edition of his book waspublished, now renamed An Inquiry Into the Nature andTreatment of Diabetes, Calculus, and Other Affections of TheUrinary Organs, most of our present-day knowledge of thecomposition of urinary stones had been discovered. Thisbook is one of the earliest to contain a list of “Tests,Apparatus, &c. required in making Experiments on theUrine”, and this included litmus paper (blue and red),turmeric paper (plant extract exhibits color change fromyellow to reddish-brown, and violet on drying, and is a

test for alkalinity), a specific gravity bottle or a smallportable hydrometer that Prout designed, blowpipe, for-ceps, two small discs of plate glass for discriminating pusfrom mucus, and a watch glass for detecting an excess ofurea on addition of nitric acid. “These, with one or twosmall test tubes, and small stoppered phials, containingsolutions of pure ammonia, potash, and nitric acid, can bereadily packed into a small portable case, or pocket book,and will be sufficient, by the aid of a common taper orcandle, to perform all the experiments on the urine, andurinary productions, that are commonly necessary in apractical point of view” (20 ). Alexander Marcet haddescribed a portable chemical kit in 1817 and showed aline drawing of its components (3 ). Barely a year afterProut’s list of tests and apparatus, Richard Bright’s (1789–1858) studies of renal disease would add a spoon to thisportable laboratory, for revealing the presence of albuminin heated urine.

Prout’s routine for testing urine began with the 24-hvolume, the color, and the transparency. Some of theimmaginative notions of the uroscopists of the past werestill in evidence here. The belief persisted that the urine’svolume, color, and appearance were indicative of certainpersonality traits and were characteristic of particulardiseases. Specific gravity was measured and, if �1.030,was considered diagnostic of diabetes. The reaction ofurine, known to normally be acid, was taken with litmuspaper. Albuminous urine (protein) was detected by heatcoagulation, and bile by the yellow staining of linen.Sugar in the urine was still recognized by taste—therewas no other test—and was “not found in the blood evenof individuals labouring under diabetes, in whose urine itexists in the greatest abundance; . . . ”. An excess of urea—regarded as abnormal but of vague significance—wasinferred from the length of time for crystallization tooccur when nitric acid was added to the urine on a watchglass. Prout claimed that in diabetes and some otherdiseases of the urine, very little urea is sometimes present.The color and appearance of any sediment settling out onstanding were noted, but no microscopic examination wasmade (21 ). Some of the tests may have been crude, butthey were chemical tests.

Prout’s book appeared in five editions and underwentseveral name changes, appearing finally in 1848 as On theNature and Treatment of Stomach and Renal Diseases; Beingan Inquiry Into the Connexion of Diabetes, Calculus, and OtherAffections of the Kidney and Bladder, with Indigestion. Asedition followed edition, even contemporary reviewerscriticized Prout for not examining and explaining some ofthe theoretical issues involved in physiology. Seeking toavoid controversy, he would settle these points with astrong conviction that almost appears as dogmatism. Hisinertia and conservatism were sharply criticized by TheLancet (22 ).

The book’s lack of chemical formulae, which hadbecome almost universally adopted in the 1830s butwhich Prout dismissed as unphilosophical expedients

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because they did not represent true compositions, and hisomission of discoveries and advances made on the Con-tinent showed an inability to keep up with the newerdevelopments in chemistry and physiology and led torapid replacement by other texts, notably that of GoldingBird (1814–1854) (23, 24 ). Prout’s progressively worsen-ing deafness since youth was a contributing factor. Itreduced his personal contacts with other scientists, whichmade it difficult to keep up with the newer discoveriesand advances in chemistry and physiology on the Conti-nent. When, after 1830, his hearing loss became completehe withdrew from scientific society. Much of Prout’sresearch had foreshadowed that of Justus Liebig (1803–1873) and his school, but was soon eclipsed by theirachievements in the 1830s and 1840s (8, 25 ). Prout neverreferred to the action of oxygen on tissues, whereas Liebigand Wohler based all their studies on the concept of tissueoxidation. He also ignored the discovery of pepsin andG.J. Mulder’s (1802–1880) proteine.

Chemical RemediesUnlike many physicians, Prout had no wonderful remedyto offer for urinary calculi; the only real solution was theknife, for “When a calculus is once formed, its furtherenlargement is probably a common chemical process, andwill proceed whether the urine be healthy or not, for allurine naturally contains the ingredients most commonlymet with in calculi” (26 ).

Prout was very skeptical of so-called chemical reme-dies because of the possibility of dangerous side effectsand their potential for ultimately aggravating the disease.Because “the object of the chemical practitioner is atbest . . . to prevent the effects of disease rather than toremove it”, he considered “chemical remedies as pallia-tives only”, and attributed “their acknowledged goodeffects” to “their general than their chemical operation;. . . ” (26 ).

Prout, however, did have a chemical remedy. Afteriodine salts were found in certain marine life forms, itoccurred to him that burnt sponge (a well-known remedyfor goiter) might owe its properties to the presence ofiodine. In 1816, after trying hydriodate of potash (potas-sium iodate) on himself in small doses and experiencingno ill effects, Prout suggested iodine treatment for goiter.This therapy was successfully adopted by Dr. John Elli-otson (1791–1868) at St. Thomas’s Hospital early in 1819(27 ).

A Satisfactory DietIn 1827, “On the Ultimate Composition of Simple Alimen-tary Substances, with Some Preliminary Remarks on theAnalysis of Organized Bodies in General” (28 ) earnedProut the Copley Medal, the highest distinction of theRoyal Society. In this publication, considered duringProut’s life his most important paper, Prout reported onhis researches on food. He was the first to classifyalimentary principles (foodstuffs) into saccharinous (car-

bohydrates), oleaginous (fats), and albuminous (proteins).The main purpose of this paper was to describe anaccurate procedure for the analysis of organic materials,for which he used very expensive equipment of his owndesign, and especially to determine the exact compositionof these major divisions and the subsequent changesinduced in them. Prout added water to his trio of food-stuffs and laid great stress on its role in assimilation. Heurged that a satisfactory diet should include all fourfoodstuffs and be modelled on the great alimentary pro-totype—milk.

In 1831 Prout referred to the saccharinous group offoodstuffs as “hydrates of carbon” (29 ). However, CarlSchmidt (1822–1894) is generally credited with originatingthe term “carbohydrate” (kohlenhydrate) in 1844 for thosesugars containing hydrogen and oxygen in the same ratioas in water (30 ).

Chemistry vs Physiology: The Case Against VitalismIn his three Gulstonian lectures on “The Application ofChemistry to Physiology, Pathology, and Practice”, at theRoyal College of Physicians in 1831 (29 ), Prout com-plained that the physiologists paid too much attention tomechanical or even metaphysical explanations in biology,whereas for him biology called for the application ofchemistry. Citing the lack of progress in animal chemistry,he attributed this to the inherent difficulty of the subjectbut also to the lack of understanding by the pure, i.e.,inorganic, chemist of the unfamiliar field of biology.Prout’s remedy for this lack of progress was for physiol-ogists to become chemists (31 ). This was reminiscent of anearlier appeal in 1816 when he stated: “Chemistry, how-ever, in the hands of the physiologist, who knows how toavail himself of its means, will, doubtless, prove one ofthe most powerful instruments he can possess; . . . ”. Fur-thermore, cautioned Prout, “Organic substances shouldbe compared with one another, and not with inorganicones, with which they have little or no analogy”. Headvised the physiological chemist to pay attention only towhat is actually observed and to avoid superfluous ex-periment and visionary hypothesis (32 ).

Prout’s Gulstonian lectures got him embroiled in arunning acrimonious debate with Wilson Philip in thepages of the London Medical Gazette (33 ). Philip, a physi-ologist and vitalist, could see no value in applying chem-ical methods and reasoning to the problems of physiol-ogy. Philip resented Prout’s claim that almost no progresshad been made in physiology in 20 years. Philip charged:“Chemistry, and the science of the vital functions, are ofso different a nature, that if they be pursued with ardour,and without this nothing can be done in such subjects, theone will tend constantly to abstract the mind from, andperhaps in some degree to unfit it for, the other; . . . ” (34 ).By the 1840s, the vitalist Philip did a complete turnaroundto Prout’s viewpoint, even claiming that the nervoussystem was essentially chemical. Prout, on the other hand,despite his call for the application of chemistry to biology

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became more committed to vitalism, but avoided a newconfrontation.

It always remained a shortcoming of Prout’s scientificmethod to use lack of knowledge as an argument forvitalism. Prout believed that there exists “in all livingorganised bodies some power or agency, whose operationis altogether different from the operation of the commonagencies of matter, and on which the peculiarities oforganised bodies depend, . . . ”. Of the various hypothesesexplaining these differences, Prout favored that of “inde-pendent existing vital principles or ‘agents,’ superior to,and capable of controlling and directing, the forces oper-ating in inorganic matters; on the presence and influenceof which the phenomena of organisation and of lifedepend” (35 ). Despite these expressions of vitalism,Prout’s application of chemistry to biology brought himcriticism from vitalists.

A strong prejudice existed in those days among theleading physicians against chemical doctrines, and thequarrels that ensued among them were frequently viru-lent and vituperative. Personal antagonisms were aired inthe medical journals, most notably The Lancet, whosefounder and editor, Thomas Wakley (1795–1862), wasadept at provoking dissension. The letters to the editorwere often lengthy and frequently signed by a pseud-onym. Accusations of bias or incompetence against indi-viduals or institutions usually generated a response andcounter-response, which went on from issue to issue andhelped stimulate circulation of the journal.

The Acid of Gastric JuiceIn 1824, William Prout showed that the acid of the gastricjuice was hydrochloric acid. Gastric digestion had longbeen the subject of speculation and experimentation. VanHelmont discovered the significance of acid in gastricdigestion, which up to that time and for long after wasattributed to heat and trituration, but he reasoned thatgastric digestion is not attributable to acidity as such,because neither vinegar nor lemon juice will digest food.He attributed digestion to a specific “vital acidity”. VanHelmont gave his chemical concept of digestion a vitalis-tic identity by stating that the acid in the stomach is notthe vital agent itself, but made its action possible (11 ).

The iatrochemical school that succeeded Van Helmontexplained all body functions as being determined bychemical reactions without direction by any mystical orspiritual force. Gastric digestion was regarded as a chem-ical fermentation, with saliva playing an important initialrole. With progressing mechanization of theoretical med-icine in the early 18th century, the human organism wasregarded as a machine and digestion as a mechanicalprocess subject to physical laws. Van Helmont’s vitalisticdoctrine of acid digestion was replaced by a theory ofliquefaction resulting from agitation. The reasoning wasthat a chemical substance in the stomach capable ofconverting solid food, notably meat, into a fluid wouldalso dissolve the fleshy wall of the stomach (36 ).

The iatromechanical theory of gastric digestion byagitation of the food with resulting liquefaction domi-nated until the latter half of the 18th century. A new lineof investigation was opened by the French physicist, Renede Reaumur (1683–1757), who persuaded a kite (a speciesof buzzard that easily disgorges what it does not digest) toswallow open-ended tubes containing food. His experi-ment in 1752 demonstrated the dissolving action of gastricfluid on the regurgitated foods.

These findings were extended by the Italian physiolo-gist Lazzaro Spallanzani (1729–1799), who administeredfood samples in perforated metallic tubes to a largevariety of animals. The containers were removed byregurgitation or by sacrificing the animal, and the con-tents were examined for weight loss and other changes.Spallanzani experimented on himself with food swal-lowed in linen bags, which he recovered for analysis. Healso obtained samples of his own gastric fluid by regur-gitating on an empty stomach. In 1782 he studied thesolvent action of gastric fluid on foodstuffs outside thebody at different temperatures and concluded that thebasic factor in digestion is the solvent property of the“gastric juice”, a term he introduced. He demonstratedthat trituration was not involved other than to make foodparticles more accessible to this juice. By showing that thesolvent action of the gastric fluid can act outside the body,Spallanzani disposed of previously held mechanisms ofdigestion attributed to mixing aided by heat, putrefaction,trituration, and fermentation, in favor of a chemicaltheory of solution. However, he failed to recognize thatthe solvent action of the gastric juice is attributable to itsacidity (37 ).

A new advance came from John Richardson Young(1782–1804) in his MD thesis for the University of Penn-sylvania. “An Experimental Inquiry Into the Principles ofNutrition and the Digestive Process” (1803) showed thatthe solvent principle of gastric juice is an acid and is partof the normal gastric secretion. Experimenting with starv-ing frogs and using litmus paper, Young demonstratedthe acidity of gastric fluid, but wrongly concluded that itwas phosphoric acid (38–40).

Prout had also favored phosphoric acid as responsiblefor the acidity of gastric juice, before discovering the truenature of the acid in the stomachs of animals. His report,read before the Royal Society of London on December 11,1823, was published early in the following year (41 ).Prout identified free muriatic acid (hydrochloric acid) inthe gastric juice of various animals and humans after ameal and suggested that it was derived from the commonsalt of the blood by the force of galvanism (electricity).

Barely 1 month after Prout’s publication, hydrochloricacid was independently identified in gastric juice by adifferent method by Friedrich Tiedemann (1781–1861)and Leopold Gmelin (1788–1853). They gave Prout creditfor the discovery of hydrochloric acid, but they alsoclaimed to have found butyric and acetic acid in thegastric juice. Their investigation was published in Die

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Verdauung nach Versuchen (2 volumes, 1826–27) (Experi-ments in Digestion).

Prout’s results were confirmed by the classic researchof US Army surgeon William Beaumont (1785–1853) onAlexis St. Martin, a 19-year-old French-Canadian furtrapper who developed a gastric fistula that remainedafter the wound from an accidental gunshot in 1822 hadhealed. Beaumont studied the appearance and function ofthe exposed living stomach over several years and pro-vided new information about the nature of the gastricjuice and the process of digestion in the stomach. Hepublished his findings in Experiments and Observations onthe Gastric Juice and the Physiology of Digestion (1833).Beaumont recognized the acid character of the gastricjuice in response to food and alcohol. Its identity asmuriatic acid was verified at the University of Virginiaand at Yale (42 ). Old ideas, however, die hard. Writers ongastric physiology continued to deny the presence ofhydrochloric acid in gastric juice or mentioned it merelyas one of the acids present.

Francois Magendie (1783–1855), a French experimentalphysiologist, attributed gastric acidity to lactic acid. Be-cause of his reputation, the acid’s identity remained anopen question for many years, despite Prout’s discovery.As late as 1856, Claude Bernard (1813–1878), the promi-nent French physiologist and former student of Ma-gendie, still accepted his teacher’s view.

Investigators considered that the hydrochloric acidwas produced secondarily. They believed that the pri-mary acid secreted was lactic acid, which then acted onthe sodium chloride present to produce the hydrochloricacid that Prout and others had found. Still others attrib-uted gastric acidity primarily to the presence of acidphosphates in the juice. Only Beaumont had actuallyhandled pure gastric juice, and the material examined wasusually mixed with other juices and food residues. Some-times the juice stood for a time before it was analyzed,long enough for some lactic acid to be produced byfermentation of carbohydrates, especially in gastric con-tents of low acidity. It was so contrary to physiologicprobability that it was difficult for some physiologists toaccept the idea that acid as strong as hydrochloric acid,with a pH of 0.9 or less, could be secreted by the living(parietal) cells of the stomach in the mammalian body(9, 43 ). In 1850, Henry Bence Jones wrote: “This gastricjuice, then, is a highly acid fluid secreted by the stom-ach. . . . What acid it is has not yet been determined.Hydrochloric, phosphoric, acetic, lactic, and butyric acids,have each been said to exist in the gastric juice” (44 ).

All doubt was finally dispelled in 1852 by publicationof Gastric Juice and Metabolism. A Physiological-ChemicalInvestigation by Friedrich Bidder (1810–1894) and CarlSchmidt (1822–1894) of the University of Dorpat. Fromtheir quantitative analyses of the gastric juice collected bymeans of a fistula created in different species of liveanimals, they demonstrated that the acid of gastric juice isexclusively hydrochloric acid (43 ).

Final DaysProut was of middle height and slim figure. The expres-sion of his face combined benevolence with great intelli-gence, and his bland manner inspired confidence and setthe most nervous patient at ease. He always dressed withscrupulous neatness, usually in black, with gaiters or silkstockings. Although Prout had been ailing for some time,his death was relatively unexpected. Sensing his ap-proaching death, he asked that no postmortem examina-tion should be made. Death came from an obscure pul-monary illness, almost certainly an abscess bursting intothe lungs (8–10). Prout’s discovery of hydrochloric acid inthe gastric juice, and that none other was present undernormal circumstances—a discovery of fundamental im-portance in the explanation of the chemistry of diges-tion—was mentioned either in passing or not at all in hisobituaries (9, 10 ).

Prout was one of those physician-chemists whoseinvestigative work in physiological chemistry contributedto the foundations of modern clinical chemistry. Hisbiography shows how varied were his interests at a timewhen the boundaries between chemistry and physiologywere not clearly separated, defined, or understood. Wemust study the history of the past—there is nowhere elseto look—to understand how we arrived at the present andto prepare for the future. If we ignore history or take it forgranted, we would become orphans in time—castawayson a desert island called “the present”—with no idea ofwhere we came from or where we are going.

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