'1' U. s VNl J~ LrB. PRIMERO

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Renaissance anatomical illustrations often followed artistic conventions (situar-ing the skeleton in a lifelike pose in a landscape) and played wittily on th .tensions between life and death. The contemplation of the skull prefigllr'~Hamlet's later meditation. Line drawing, Vnlv rd d 1Iarnus o, Histeria di' IfI

composicion dei cuerco bunmno (Rorn ': A. Snlnlllnn'l1 & A. Lnfr 'ri, 1556).

THEGREATEST BENEFIT

TO MANKIND

A Medical History ofHumanity fram

Antiquity ta the Present

ROY PORTER

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334 SCIENTIFIC MEDICINE IN THE NINETEENTH CENTURY

constituent was later shown to be strychnine. ln 1817, with Pierre JosephPelletier (1788-1842), Magendie performed experiments on emeticsand the nature of vomiting, and showed that the emetic properties ofipecacuanha were due to a substance he named emetine.

Together with Joseph Caventou (1795-1877), Pelletier enjoyed aseries of spectacular successes in refining the active therapeutic agentsin natural drugs: between 1818 and 1821 they obtained strychnine,brucine, veratrine, cinchonine, quinine and caffeine. Nicotine followedin 1828, atropine in 1833. Above all, opium was subjected to analysis.ln 1803-4 the French pharmacists C. L. Derosne (1780-1846) andArmand Seguin (1767-1835) isolated from raw opium a crystalline sub-stance whose chemical nature they could not elucidate. The Germanpharmacist Friedrich Wilhelm Sertürner (1783-1841) showed it wasalkaline, and called it Morphium (morphine).

Through such experiments in alkaloid chemistry, the active prin-ciple was being extracted from many vegetable substances long used inpharmacy; and once this was concentrated in chemical form, purity,strength and dosage could at last be regulated. Many new alkaloids werebrought to light. PierreJean Robiquet (1780-184°) introduced codeinein 1832, Philip Lorenz Geiger (1785-1836) explored aconitine, atro-pine, colchicine, daturine and hyoscyamine, and in 1860 AlbertNiemann (1834-61) isolated cocaine.

These alkaloids set the stage for a pharmacological transformation.The pharmacist and the physician now had potent medicaments whichincluded morphine, codeine, quinine, cocaine, colchicine, ephedrine,atropine, reserpine and digitoxin. The therapeutic potential of the alka-loids was stressed in works such as Magendie's Formulaire pour la pré-paration et l' emploi de plusieurs nouveaux médicamens (1821) [Formularyfor the Preparation and Use of Several New Drugs]; this pocket book.for practising physicians dealt almost entirely with the clinical use 01

the new alkaloid remedies.The first chair of pharmacology was established in 1847 at thc

University of Dorpat (now Tartu, Estonia) and held by RudolfBuchheim (1820-79), a Leipzig graduate who translated the c1ru[J;,manual written by the London chemist, Jonathan Pereira (1804-5J 'Training students in his new pharmacological institute, Buchh 'jlll

helped launch the science as a laboratory discipline. One of his pupil: ,Oswald Schmiedeberg (1838- 192I), succeecled him at Dorpat and lntrtmoved to Strasbourg in 1872, which was then being turn d intu 11

SCIENTIFIC MEDICINE IN THE NINETEENTH CENTURY 335

German showcase after its seizure in the Franco-Prussian War. Schmie-deberg set up a major centre for experimental pharmacology, studyingchloroform and other anaesthetics and narcotics, digitalis, and drugssuch as nicotine and muscarine with actions related to the autonomicnervous system. Pharmacology had been put on the academic map, andthe pharmacologists he trained went elsewhere in Germany and furtherafield, creating new pharmacology departments.

EXPERIMENTAL SCIENCE IN

BRITAIN AND AMERICA

These laboratory-based research traditions in physiology, histology,cytology, pharmacology and cognate fields found their perfect habitaton the German campus. Anglo-American pastures were arid by contrastoAround 1830 British savants launcheda 'Science in Decline' scare cam-paign, blaming backwardness on lack of public funding, but politiciansraised the counter-scare of jobbery, aware that there were no votes infunding science and medicine, and relying on the ritual incantation ofNewton, Harvey and other heroes.

The situation for medical researchers was not helped by the rise ofanti-vivisection agitation, encouraged by Queen Victoria. This came toa head at the 1874 meeting of the British Medical Association after anexperiment by the French psychiatrist Valentin Magnan (1835-1916)on two unanaesthetized dogs led to a cruelty prosecution. Though thisfailed, a Royal Commission followed. The resulting 1876 Cruelty toAnimals Act, a classic British compromise, permitted licensed doctorsto undertake vivisection, but only under strict conditions; continuingprotests help to explain why the public was not minded to give formedical research.

Gradually English-speaking medical students deserted the hospitaIsof Paris for the laboratories of Germany. ln the 1830S a few would-bech mists were seeking out Liebig in Giessen and some microscopistsw re enrolling with Müller in Berlin. Within fifty years, however, droveswcr pursuing biology and medicine in Heidelberg, Vienna, Leipzig,M unich and half a dozen other centres. There were about 15,000 Ameri-1'1118 alone by 1914, mostly going for clinical instruction, though some111\ I a bee-line for the laboratories, like the pathologist William Henry, ,I h (I 850- 1934), who studied physiology under Ludwig.

336 SCIENTIFIC MEDICINE IN THE NINETEENTH CENTURY

Welch's later career was associated with the university that plantedthe German ideal in the USA: Johns Hopkins in Baltimore. On hisreturn in 1878, after establishing a pathology laboratory at Be11evueHospital Medical School, New York, he accepted the pathology chairat johns Hopkins, which he occupied for thirty-four years, building upa research tradition and making a major discovery: the anaerobic baci11usof gas gangrene, Bacillus aerogenes capsulatus. Though the number ofAmerican medical schools investing in science remained sma11,by 1900there was a ferment of scientific activity at Harvard, Pennsylvania,Ann Arbor (Michigan) as we11as at Johns Hopkins, where the medicalstaff were fu11-time and so were spared the distractions of privatepractice. In 1896 Welch helped to start the Journal of ExperimentalMedicine.

English medical students flocked to Germany too, but in Britainmedicine remained heavily clinical, dictated by the demands of bread-and-butter private practice; pure research independent of healing wassomewhat suspect and attracted scant state support. Laissez-faire andutilitarian politics combined with Oxbridge's genteel traditions werenot conducive to careers in medical research. William Prout had con-ducted his animal chemical researches privately; and the talented neuro-physiologist Marsha11 Ha11 (179°- 1857) never obtained an academicpost, doing a11his experiments at home and funding them with patients'guineas. From the 183os, however, the founding of University Co11egeand King's Co11egeLondon began to change things. Wi11iam Sharpey(1802-80), an Edinburgh graduate who had studied in Paris, wasappointed in 1836 to the University Co11ege chair in anatomy anelphysiology, a post he held for thirty-eight years. The father of Britishacademic physiology, he trained fine students, including Joseph Lister(1827-1912) and Michael Foster (1836-19°7).

By the 1870SEnglish physiology was beginning to thrive - indeed,as Ludwig's generation died off in the 189os, leadership passed toBritain, thanks largely to Foster, who set physiology on its feet as :111

autonomous discipline. Moving in 1870 to Trinity Co11ege,Cambridgc,he bred a research school that included Sherrington, Dale and Adriun,and these in turn promoted the discipline in the universities and medi '111

schools. Foster's studies of the heartbeat (was it muscular or neurologi '1\1

in nature?) were expanded by these protégés into wider explorariourof the physiology of the autonomic nervous system and the h III it'1IItransmission of nerve impulses. He also helped to set up thc Briti li

SCIENTIFIC MEDICINE IN THE NINETEENTH CENTURY 337

Physiological Society (1876), founded the Journal of Physiolog;y (1878)and organized the physiologists' first international congress (1889).Meanwhile at University Co11ege London, John Burdon Sanderson(1828-19°5) taught physiology, and when he moved to Oxford as thefirst Waynflete professor of physiology, his place was taken by EdwardSchãfer (later Sharpey-Schãfer) (185°- 1935), who played a pioneeringrole in the investigation of hormones.

FRANCE: CLAUDE BERNARD

And what of France? French medicine was so closely identified withthe hospital that it was slow to assimilate the new German initiatives;the newly nationalized universities remained engines for instruction,examining and accreditation rather than research. In the German-speaking world, th,e jigsaw of diverse sma11principalities (political unifi-cation did not occur until 1871) nurtured Iocal pride, the upshot beinga score of prestigious university departments and institutes, pursuingdistinctive research programmes, stimulating competition andcreatinga lively job market. In France, by contrast, Paris stood alone; extremecentralization, the product of the Revolution, produced uniformity, andthe ensconced hospital tradition discouraged new initiatives.

N evertheless, Laennec, Louis and Broussais had worthy successors.Pierre-François Rayer (1793-1867), who became dean of the ParisMedical School and physician successively to King Louis Philippe andNapoleon Ill, researched the gouty kidney; andJean Cruveilhier (1791-1874) presented the first description of multiple sclerosis in his Anatomie

pathologique du corps humain (1829-42) [Pathological Anatomy of theHuman Body]. Pick of the bunch was Gabriel Andral (1797- 1876), whosucceeded Broussais at the Charité. An eclectic ('by necessity', he wrilycommented), he aimed to reconcile the pathology of Laennec, the stat-istics of Louis and Broussais' physiology, while rejecting the idée fixe ofinflammation as the root of a11disease. The attempts he made in hisTraité d'anatomie pathologique (1829) [Treatise of Pathological Anatomy]to integrate physiology and pathology proved fruitful (see below).

Beyond the hospital system, France created few niches for re-s archers, as is revealed by the chequered career of François Magendiewho, though a brilliant experimentalist, long languished in clinical posts.But the fact that lavish facilities are not everything is shown by the

338 SCIENTIFIC MEDICINE IN THE NINETEENTH CENTURY

career ofhis great protégé, Claude Bernard (1813-78). Though he neverenjoyed the establishment of a Liebig or a Virchow and, .lacking .s~chan institutional base, did not create a research school in the Ludwigianmanner, Bernard proved second to none as an experimentalist andthinker.

The youthful Burgundian's ambition was to shine as a dramatist,and one of his plays, Rose du Rbõne, was performed in Lyon when hewas just twenty. But a shrewd critic persuaded him that his métier layelsewhere, and so he turned to medicine, moving to Paris to becomein 1841 Magendie's assistant at the College de France. There was nolooking back: in a dazzling career he gained chairs at the Sorbonneand the Museum of Natural History, the presidency of the FrenchAcademy and a seat in the Senate. Bernard's brilliance lay in his superbexperimental techniques, based, as with Magendie, on bold anim~lexperimentation. (His wife turned anti-vivisectionist; they separated m1870, but not before he had spent her dowry to finance his research.)

Bernard's experiments covered many aspects of physiology: the oxy-genation of blood; blood temperature and its changes; the opium alka-loids and the sympathetic nerves; the vasodilator nerves and their rolein regulating blood-flow; and the action of poisons like carbon monoxidc(which he found killed by displacing oxygen from haemoglobin) andcurare, the South American alkaloid which killed by muscular paralysis.

Curare studies led Bernard to conclude that certain drugs acted ;lI

strictly localized and well-defined sites, discounting old convictions thatdrugs had some general bodily influence. Curare worked only wher . li

nerve met the muscle on which it acted, causing paralysis by preventinthe nerve impulse from making the muscle contract. Similar spc 'i(i('action points became recognized for other drugs; such drug 'recepto I'. '

later assumed huge importance in pharmacological research.His key investigations overturned an old tenet: that whereas plunt

could synthesize complex substances, in animaIs fats, sugars and protc I1

could be broken down (as Liebig's animal chemistry attempted to shm )but not built up. Experiments Bernard conducted in 1855 show ,(\ 11t1\1if an animal were fed on a sugar diet, glucose could be recover .d 1'1'(1111

the portal vein leading from the gut to the liver, and frorn thc h 'Plll I

veins carrying blood from the liver to the circulation. Sugar hlld \ I

dently passed through the liver. Feeding it on a sugarle s di .t, h ' 10111111,

as expected, no sugar in the portal vein; but the blood in th h 'Plll k Isurprisingly contained high lucose cone ntrati ns, an I sugol' \'ollld II

SCIENTIFIC MEDICINE IN THE NINETEENTH CENTURY 339

~xtracted from liver tissue itself Evidently the liver was praducing sugarmdependently. In other words, the body could make its own chemicalsin nor~al.functioning - for the sugar here produced was not pathologi-cal, asm diabetes, The process was called by Bernard 'internal secretion',the first use of a term later fundamental to endocrinology.

Further experiments confirmed that the sugar was not formed inthe blood, but was a result of some sugar-forming substance in the liver:in 1857 he discovered this and called it glycogen (a kind of 'animalstarch'), showing it was stored for later use by the organism as glucoseand broken down when needed. Extending these carbohydrate meta-bolism researches, he found sugar in amniotic and cerebro-spinal fluid,and explored the breakdown of sugar by the tissues. ln similar studieshe examined the function of pancreatic juice. juice from a living animalhad first been collected in the seventeenth century by Regnier de Graafwho, finding it acid, had held that its function was to separate out thenutritious par~s of the food. Bernard's teacher Magendie had alsoobtained pancreatic juice from a living animal but, while suspecting thatthe pancreas was a salivary gland, was baffled as to its physiologicalfunction.

Once again, Bernard performed a series of ingenious experiments.He found there was no secretion in a fasting dog but that, once it hadeaten, the descent of the acid chyle into the duodenum stimulated theflow of pancreatic juice which transformed starch into sugar (maltose).ln other words, digestion in the stomach was only a preliminary to thefurther digestive action of the juices released from the pancreas.

The Introduction à l'étude de la médecine expérimentale (1865) [Intro-duction to the Study of Experimental Medicine] spelt out Bernard'sI hilosophy in a grand vindication of the experimental method for bio-medicine. Hospital medicine, he insisted, had two limitations. Being anobservational science it was essentially passive, akin to natural history;\I1,d~e sickbed involved too many imponderables to permit precise

'I ntl~c ~der~tanding. Scientific progress demanded active experi-111 nta~on m .StrlCtlycontrolled environments. Moreover, the pathologi-I' ti I sion which the clinicians had fetishized was not the ideal entrée toti "a e, since it was its end-point. ln short, pathology was blind without,,11 . iol gy; pathological processes could best be studied in experimental111 1II1IIs in regulated laboratory surroundings.

Tn I n together, physiology, pathology and pharmacology formeddi triumvirate of experimental medicine, allowing exploration of the

rclations b .tw "11 normul nud I nlholo 'I '111Iun 'Llo!l., in plllli mln nt thebiochemicallev 1.Rathcr as with .harity an n r th hristian vil' 1 s,of'the three sciences physiology was the foremost, because disease , B '1"-

nard taught, were not ontological but the result of excessive or defectiv 'physiological functions; conversely, as his curare experiments hadshown, drugs 01' poisons acted only by altering such normal or abnormalfunctions.

Science should proceed by testing hypotheses through experimenta-tion. Although (he conceded) the life sciences were not strict1yreducibl .to physics and chemistry in the manner suggested by the Germanmaterialists, science would stand or fall by one golden rule: determinisrn.If physiological events were in some ways less certain than physicalones, that was a consequence of the multiplicity of variables encounteredin complex living organisms.

Bernard was no reductionist 01' materialist; animaIs and hurnanswere not puppets 01' Cartesian automata, and this was because higherorganisms created their own internal environment (milieu intérieur),their living cell communities. Complex physiological mechanismsadjusted the sugar, oxygen and salt concentrations of the blood aneltissue fluids. Body temperature was equilibriated in response to externa Ifluctuations through temperature regulation (e.g., sweating), alterationsin blood pressure and oxygen supply (e.g., panting), and changes in th .water and chemicals (electrolytes) in the bloodstream. It was thanks tothese sustaining mechanisms - later termed 'homeostasis' by the Har-vard physiologist Walter Cannon (1871-1945) - that higher organisrnsachieved a measure of autonomy within the determinism imposed bynatural law. 'The stability of the internal environment', Bernarddeclared, 'is the prime requirement for free, independent existencc.'Physiology's key role for future medical investigation was thus estab-lished, and hospital medicine somewhat sidelined. 'An author h:lsdefined sickness as "a function that leads to death", as opposed to nnormal function that sustains life', he observed.

I do not need to say that this definition of sickness seems to mepure fantasy. AlI functions have as their object the sustaining oflife and tend constantly to restore the physiologicalcondition whenit is disturbed. The tendency persists in all morbid conditions, andit is this that already constituted for Hippocrates the healing powerof nature.

Llke Vil' -/ OW, B 'l'nl1l'(/ thu s e/ vut -(/ LI! - phy. iolo 1'1111110<1'1of dis aseabov t1 ana 011 o-patholo i ial, 'M di .inc is t11C s icnce f sickness;physioJogy is the science of Iife, thus physiology must be the scientificbasis of medicine.'

C L I N I C A L P R A C T I C E A N D C L.I N I C A L S C I E N C E

The pathological gaze penetrating the diseased body and the eye ofmicroscopy formed part of wider attempts to apply the methods ofscience to the whole medical enterprise, including the regular businessof clinical medicine. Alongside failures in the body's structure 01' archi-tecture, defects in its functioning would also be studied.

For a long time practical medicine got by almost without techno-logy. 'We had few instruments of precision,' recalled Robert Morris(1857-1945), looking back on the beginning of his medical career inNew York in the 1880s:

There was the stethoscope which, then as now, gave inside infor-mation in accordance with the sort of ear that was behind it. Theclinical thermometer required three minutes for registering tem-perature, and people in general were more or less unfamiliar withits meaning. An old lrish lady in one of our Bellevue Hospitalwards would not allow a thermometer to be put in her mouth onthe ground that the doctor had put it in that of a patient in thenext bed who had died less than an hour afterward....

Before the year 1870,in this country there were no laboratoriesexcepting those of anatomy, because the expense of laboratoriesseemed too great for the teachers who divided fees that werereceived from students.

But the desire was expressed for more precise recording of physiologicalprocesses and pathological events, and this was to materialize in newvisualizing and measuring devices like Ludwig's kymograph. The piece-meal observations typical of earlier investigations were transformed intosystematic bodies of knowledge; take for instance what became thespecialty of haematology.

In the seventeenth century the microscope had first affordedglimpses into the composition of blood. Swammerdam and Malpighinoted 'small globules' which were red blood cells, and Leeuwenhoekfound that most mammals had circular red globules, while those of