O S L E R L I B R A R Y N E W S L E T T E RMcGill University, Montreal, Canada No. 76-June 1994

Osler and Drugs

In the course of his lifetime WilliamOsler was periodically labelled a “thera-peutic nihilist”. The charge is dealt withby Harvey Cushing, whose life of Oslermay well be read not only as outstandingmedical biography, but also as fine litera-ture.(1) On the subject of Oslerian materiamedica, Cushing presents two aspects.On the one hand, he writes, " Like manyother pathologists, he was.. . imbuedwith the futility of most of the drugs i ncommon use” (p. 166), and adds that “hisonly weak spot was in therapeutics, if ahealthy scepticism concerning drugs maybe regarded as a weakness” (p. 340). On theother hand, he “was a good therapeutist... and used drugs not empirically,but sci-entifically” (p. 268).

The basis for the “nihilist” charge wasclearly in Osler’s requirement that usefuldrugs have known and specific actions,and that they be offered in prescriptionsthat ordered single drugs. In a lecture in1907 at the Philadelphia College of Phar-macy and Sciences Osler is reputed tohave recognized only 13 drugs that hadsignificant value in medicine. (2) The ac-companying article by David Machtthrows considerable light on Osler’s pre-ferred therapeutic agents, although thelist of commonly prescribed drugs for pa-tients he saw at home extended upwardsto fifty.

Osler began his practice contempora-neously with the development of modernpharmacology, in a period when inert ortoxic chaff was being separated fromtherapeutically useful grain. One mustconclude that Osler, although not directlyinvolved in scientific revaluation of thera-peutics as practised in a growing numberof medical school laboratories, hadsensed the basic principles of the new dis-cipline, thereby deserving Macht’sdescription of him as a “pioneer in ra-tional pharmacology ”. (3)

-Theodore L. Sourkes

1. H. Cushing. The Life of Sir William Osler.London: Oxford U. Press. 1940.

2. L.G. Rowntree. Osler at the College ofPharmacy and Sciences of Philadelphia. Bull.Johns Hopkins Hosp. 101: 306-310 (1957).

3. D.I. Macht. Osler’s prescriptions and ma-teria medica. Trans. Am. Therap. Soc. 35: 69-85(1936).

OSLER’S PRESCRIPTIONSAND MATERIA MEDICA

he present study is aresult of a happy con-catenation of three cir-cumstances. Firstly, I hadthe good fortune to be amember of the last class(the class of 1906) at the

Johns Hopkins Medical School which stud-ied under the late William Osler. Secondly,until the retirement of Prof. John J. Abel in1932, I was for many years a lecturer inpharmacology at the Johns Hopkins Medi-cal School; and in that capacity I not onlylectured on pharmacodynamics but gave aseparate course of lectures on pharma-cotherapy and prescription writing.Thirdly, I have been connected with thefirm of Hynson, Westcott & Dunning foralmost ten years as director of pharma-cological and medical research; and in thatcapacity I have had an opportunity tostudy the prescription files of the retail de-partment there. The retail department ofthis corporation is well known as one of themost ethical and scientific pharmacies inthe country, and in its files can be foundprescriptions written by the most eminentAmerican physicians.

In as much as I have always been inter-ested in the development of prescriptionwriting, I have made a careful study of lit-erally tens of thousands of prescriptions inthe old files of this pharmacy and analyzedthem in respect to their form; that is, gram-mar, spelling, use of Latin, etc.; in respectto their pharmaceutical accuracy as to ma-teria medica, dosage, incompatibilities, etc.;and also in respect to their rationale. Thisinvestigation, which I hope to publish later,led to a discovery of special interest. As Isystematically perused the files of prescrip-t ions I came occasional ly upon aprescription written by Doctor Osler. It iswell known that Osler did most of hismedical work at the Johns Hopkins Hospi-tal, and that outside its walls he saw butfew patients except in consultation. Conse-quently, very few prescriptions in Osler’sown handwriting are in existence. It hap-pened, however, that Osler lived for yearson the southwest corner of Charles andFranklin Streets, in Baltimore, directly op-posite the pharmacy of Hynson, Westcott& Dunning, then located on the southeastcorner of the same intersection. Osler was afrequent visitor at the pharmacy and on

Original pharmacy of Hynson, Westcott & Co.Southeast corner of Charles and Franklin Streets.

friendly terms with the owners and clerks.As a result, whenever he did write what wemay call an “extramural” prescription forsome patient who visited him at his homeoffice, it was almost invariably filled at thepharmacy of Hynson, Westcott & Dunning.I decided, therefore, to search through theprescription files covering the period ofOsler’s residence in Baltimore, a period ofabout eight years, and collect all of his pre-scriptions for critical study. The result ofthis research, presented in this paper, is ofconsiderable interest from the standpointof medical and pharmaceutical history be-cause of the light it throws on Osler’sattitude towards drugs and on the subjectof so-called therapeutic nihilism.

To celebrate the meeting of the XIIthInternational Congress of Pharmacol-ogy in Montreal from July 24 to July 30of this year, the Osler Library Newsletterdevotes this issue to reprinting a classicarticle on Osler’s attitude to drugs.David I. Macht’s essay on “Osler’s pre-scriptions and materia medica”, firstpublished in the Transactions of theAmerican Therapeutic Society for 1936, isintroduced here by Dr. TheodoreSourkes, an eminent research pharma-cologist and long-time member of theLibrary’s Board of Curators. Congressparticipants as well as regular readersof the Newsletter are sure to enjoy thislively refutation of the charge of“therapeutic nihilism” long levelledagainst Osler.

The initial letter on this page is reproduced from Alexander Nesbitt (ed.) Decorative alphabets and initials, plate 50, Dover Publications, 1959.

Table 1Materia Medica

Acacia, 1 Elixir, ferri quininae, et Potassii iodidum, 6Acetphenetidinum, 1 strychninae phosphatum, 2 Santoninum (trochisci), 1Acidum boricum, 1 Ergota (Fraser’s tablets of Sodii bicarbonas, 2Amylis nitris, 1 ergotin in ãã gr. l), 23 Sodii phosphas, 3Antipyrina, 1 Extractum belladonnae, 1 Spiritus aetheris compositus, 3Aqua Glandulae suprarenales, 1 Spiritus ammonii aromaticus, 3Aqua rosae, 2 Glycerinum 2 Spiritus camphorae, 1Argenti nitras, 1 Glycerylis nitras, 12 Strychninae sulphas (pills: l/60Atropinae sulphas, 2 Hydrargyrum cum creta, 1 gr., 5; l/32 gr., 1; l/30 gr., 1;Bismuthi subcarbonas, 1 Hydrargyri chloridum mite, 1 l/100 gr., 1)Calumba (cordial), 1 Liquor calcis, 1 SulphonethylmethanumCamphora, 1 Liquor potassii arsenitis 2 (trional), 1Carbo ligni, 1 Opii pulvis, 1 Sulphur praecipitatum, 1Cinchona calisaya (elixir of Phenol liquefactum, 1 Syrupus ferri iodidi, 3

F. and C.), 1 Phenylis salicylas, 2 Thyroideum (tablets, 1;Cocaina (sulphate), 1 Pilulae ferri carbonatis powdered gland, 1)Colchicinae (tablets: l/100 gr.), 1 (Blaud’s pills), 5 Tinctura aconiti, 2Creosotum, 1 Pituitarium (dried gland Tinctura iodi, 1Digitalis (digitalin, Merck), 1 powder), 1 Tinctura nucis vomicae, 4

Potassii bromidum, 3 Tinctura opii, 1

Table 2Compound Prescriptions

I. Pulvis opii et ex. belladonnae (suppositories)II. Potassii iodidum, calumba cordial, and water

III. Salol and phenacetinIV. Sulphur precip., camphor, acacia, liquor calcis,

and aqua rosaeV. Phenol, tr. iodi, glycerin, and water

(internal use)VI. Tablets of bismuth and charcoal

VII. Powders of antipyrin and salolVIII. Creosote, glycerin, and water

IX. Acid boric and aqua rosaeX. Spiritus camphorae and tr. aconiti

(internal use)

Description of Osler’s Prescriptions

Among the 200,000 prescriptions filed inthis pharmacy from 1898 to 1906, I found130 written by Osler. These, carefully sepa-rated and analyzed, were found to includeone or more prescriptions of fifty differenttypes. It was interesting to note that thegreat majority of the entire number weresimple prescriptions; that is, called for but asingle ingredient. There were found onlyten compound prescriptions; i.e., those call-ing for a combination of two or moreingredients. Fifty different drugs or chemi-cals were mentioned in this collection ofOsler’s prescriptions. The subjoined Table1 gives a list of all the drugs prescribed.The numerals following the names of thesedrugs indicate how often each of the fiftywas recommended in the whole series of130 prescriptions. Most of the prescriptionswere written in ink; only occasionally wasone jotted down in pencil. The majoritywere written on sheets torn from smallscratch pads of plain white or buff paper.Rarely did I find one written on a regularprescription blank bearing Osler’s nameand address at the top. Most of the pre-scriptions were signed only with theinitials, “W. O.” Osler seldom wrote hisname in full. For the most part, his pen-manship was quite legible. In nearly everycase the whole prescription, except the sig-nature, was written in Latin. The directionsfor use of the prescribed agent were invari-ably specified in English. There were fewgrammatical errors. From the standpoint ofLatin materia medica the drugs mentionedwere correctly designated. One curious ex-ception to this was a prescription callingfor Blaud’s pills, described by Osler as Pilu-lae Ferri Sulphatis instead of Carbonatis.For reasons of economy it is impossible toreproduce all the Osler prescriptions I have

collected, but I have selected for copying asufficient number to give an idea of Osler’sstyle, the type of prescriptions he wroteand the drugs he employed.

Perhaps the most striking feature aboutthis collection is the fact that, in contradis-t i n c t i o n t o so-called compoundprescriptions, the great majority were sim-ple prescriptions and recommended onlysingle ingredients. In every case the singleingredient prescribed was a drug the phar-macological properties of which werepretty well known even thirty or fortyyears ago. Thus, for instance, Osler pre-scribed nux vomica; the composition of thisdrug was generally known and the phar-macological action of its alkaloids was wellunderstood by all cultured physicians. Thesame is true of colchicum, which Osler fre-quently prescribed for gouty conditions.The same is also true of Blaud’s pills, ofatropine, phenacetin, aconite, ergot, nitro-glycerin and all the other drugs heprescribed. In the whole collection therewere found only ten compound prescrip-tions and the ingredients of these ten areset forth in Table 2. Here I class such simplecombinations as those of salol and phen-acetin, bismuth and charcoal, boric acidand rose water, none of which would beregarded as a strictly compound prescrip-tion at the present time.

Figure 1 shows a prescription for nuxvomica, often ordered by Doctor Osler.Figures 2 and 3 are two of Osler’s simpleprescriptions calling, respectively, for com-pound spirits of ether and a preparation ofcolchicum. Note that in Figure 3 the pre-scription is written on a regular blankbearing Osler’s name and address. Also ob-serve his signature, the characteristicinitials instead of his full name.

2

Another interesting feature may benoted regarding the drugs of Osler’schoice. In 1916, Prof. Victor Robinson, Edi-tor of the Medica l Rev i ew o f Rev i ews ,published a valuable symposium. Basinghis query on the well-known statement ofDr. Oliver Wendell Holmes, in the “Auto-crat of the Breakfast Table,” that we couldwell dispense with most drugs if we wouldonly retain the five big ones in the wholelist, he asked leading American physiciansand pharmacologists to select what theyconsidered the five most important drugsin the United States Pharmacopeia. Themajority of answers received by ProfessorRobinson listed the five most useful andimportant of all drugs as follows: (1)opium, (2) digitalis, (3) quinine, (4) mer-cury and (5) ether. A glance at his materiamedica in our collection (table 1) revealsthat Osler employed each of the Big Five.Of course, any one who has had the goodfortune to study under or come in contactwith him at the Johns Hopkins Hospitalknows very well how enthusiastically andextensively Osler prescribed all five ofthese drugs.

Figure 4 [Ed. note: figure not repro-duced] is an order for a preparation ofdigitalis. This is one of the rare prescrip-tions written in pencil. Figure 5 is a simpleprescription for tincture of opium, the mostuseful of all drugs, and Figure 6, an orderfor a mixture of chalk and mercury.

It is interesting to note, in studyingOsler’s simple prescriptions, that he em-ployed three kinds of endocrine products,namely the thyroid, suprarenal and pitui-tary glands. These were to be administeredorally in the form of powder or tablets. Ofcourse, it is well known that Osler was oneof the first to become enthusiastic about the

treatment of cretinism with thyroid prepa-rations; and we are all familiar with thepicture, frequently reproduced in text-books, of the infant whom Osler treated inthis way. Figure 7 is an order for thyroidextract written on a regular prescriptionblank with Osler’s name and address at thetop, and signed with his initials.

Discussion

This analysis of our collection of Osler’sprescriptions logically leads to a discussionof his materia medica in general and ofthe unfortunate sobriquet of “therapeuticnihilist,” often applied to William Oslerboth by his contemporaries and posterity.Osler’s knowledge of drugs and his use ofthem certainly lent no support to this term.Even in the comparatively small number ofhis prescriptions that I have collected fiftydifferent ingredients are mentioned. If we

turn the pages of his “Practice of Medicine“(the edition of 1906, which was my text-book when a student), we find that Oslermentions 170 different drugs although hedoes not recommend all of them. The listincludes: (1 ) drugs act ing on thecardiorenal system, (2) purgatives, (3) diu-retics, (4) anthelmintics, (5) opiates andother narcotics, (6) antipyretics, (7) tonics,(8) hypnotics, general anesthetics and alco-hol, (9) antiseptics, (10) acids and alkalis,(11) powerful alkaloids and other activeprinciples and (12) a large number of mis-cellaneous drugs, including metallic salts,antitoxins, vaccines, etc.

We can understand why Osler was fre-quently misnamed “therapeutic nihilist”only when we consider his attitude to-wards therapeutics and his method ofprescribing. Osler invariably preferred toprescribe only such single and specific

drugs with the pharmacological action ofwhich he was familiar; in other words, hewas a rational pharmacotherapist, inmarked contradistinction to the misguidedpolypharmacists or prescribers of shotgunprescriptions of his own day as well as thatof his predecessors and perhaps - of hissuccessors. Figures 8, 9 and 10 illustrate thetypes of compound prescription Oslerwrote. Here we have, first, an order, writ-ten in English, for a simple combination ofantipyrin and salol; then, a dermatologicalprescription calling for a lotion containingsulphur, camphor, lime water, rose waterand gum arabic; and, finally, an order for amixture or solution of creasote in glycerinand water. To appreciate this better, weneed only compare some of Osler’s pre-scriptions, reproduced herewith, with thefollowing prescriptions, written not bycheap and obscure practitioners but bysome of the leaders of the medical profes-sion in Baltimore - men who were

Figure 1

Figure 5

Figure 2 Figure 3

Figure 7

Figure 6

colleagues of William Osler. A glance at afew of these shotgun prescriptions revealsat once the difference between Osler’s atti-tude towards pharmacotherapy and thatof the majority of physicians of his time.Figure 11 is a prescription written by one ofOsler’s distinguished colleagues, whichcalls for a mixture of quinine hypo-phosphite, hydrast ine , euonymin,strychnine, hydrocyanic acid, bichloride ofmercury and arsenious acid. Figure 12, acompound prescription written by anotherof Osler’s contemporaries, is notable not somuch for the number as for the extraordi-nary character of its ingredients. It is anorder for cocaine hydrochloride, extract ofcannabis indica, quinine salicylate andacetanilid in capsules for internal admini-stration. Figure 13, a prescription writtenby a third leading Baltimore practitioner, isan order for a combination even more pre-posterous from the standpoint of modernpharmacodynamics. This prescription callsfor a mixture of opium syrup, fluid extractof belladonna and the juice of hemlock. Icould easily reproduce a dozen more suchshotgun prescriptions with the number ofingredients ranging from three to fifteenbut these will suffice to bring out the differ-ence between the pharmacotherapy of

Osler and that which was more prevalentin his time.

It was this reserve and aversion to theprescribing of chemicals or drugs with theaction of which he was not thoroughly ac-quainted that earned Osler the title of“therapeutic nihilist” and this repugnanceon his part to irrational concoction contain-ing a multitude of obscure ingredientsreally marked the beginning of a new era inmedicine, the era of modern rational phar-macotherapy. In Osler’s day the status ofscientific experimental pharmacodynamicswas not yet well developed and little ornothing was known concerning the phar-macological action of drug combinations.For this reason, Osler could not honestlyand logically write compound prescrip-tions or recommend combination of drugsand the simple prescription is thereforepredominant in our collection. The samewas true of many of his students, particu-larly of his most eminent pupil andadmirer, William Thayer.... Dr. Thayer’sprescriptions, well known as models ofneatness, simplicity and therapeutic ration-alism, were written in the metric system ofwhich he was an ardent advocate.

Thus a study of Osler’s materia medicaand prescription writing reveals the factthat he was not a therapeutic nihilist at all.On the contrary, he prescribed a greatmany drugs and made mention of manymore. He was a pioneer in rational phar-macotherapy. However, because in histime pharmacology was only in its infancyOsler realized the inadequacy of theknowledge then prevailing concerning theaction of drugs and therefore prescribedonly chemical agents the physiological ac-tion of which had been sufficientlydemonstrated. He detested the irrationalvagaries and mystic combinations ofpolypharmaceutical nature recommendedby his contemporaries and it was this traitthat set him apart from them as a sort ofradical and gave him the unsavory epithetof “therapeutic nihilist.” As a matter offact, such an attitude was a vital link be-tween the scholasticism of the past and thescientific medicine of the present.

The recent advances in pharmacologycannot be attributed exclusively to the iso-lation of active principles and a detailedstudy of the physiological effects of old andnew chemicals. Among the greatest discov-

Figure 8

Figure 9

Figure 11 Figure 12

4

Figure 10

Figure 13

eries of modern medicine must be reck-oned the findings made concerning theinteraction of various pharmacodynamicagents when administered either in combi-nation with each other, or in immediatesuccession, one after the other, and particu-larly the phenomena of pharmacologicalsynergism and antagonism. I discussed thesein detail elsewhere (American Druggist,1934, 90, 46). A study of what has some-times been termed “the problem of two ormore” in connection with drugs has led tosome of the most valuable contributions ofmodern rational pharmacotherapy and isalso of fascinating interest when examinedfrom the historical point of view. Such anexercise enables the student of medicineand pharmacy to understand more clearlythe evolution of prescription writing fromancient polypharmacy and kakopharmacy,through the periods of pharmaceutical andtherapeutic superstition and mysticism, tothe reactionary age of therapeutic nihilismbeginning with Osler and followed by therise of modern experimental pharmacologyand leading to the gradual development ofrational pharmacotherapy in our day.Osler’s persistence in prescribing only sin-gle ingredients of well-known potent drugsmarked the logical transition from thetherapeutic obscurantism and mysticism ofthe past to the modern rational prescrip-tion writing of the present; and I amconfident that my modest estimate of hismateria medica and prescription writingwould meet with the same approval fromDoctor Osler, were he living today, that heaccorded one of my earlier publication....

Eight hundred years ago there lived inCairo a great physician, Moses Mai-monides, who was also regarded by hiscontemporaries as a sort of therapeutic ni-hilist. Maimonides believed in VisMedicatrix Naturae, or the healing power ofMother Nature, in properly balanced restand exercise, in dietetics, in the beneficialeffect of sunshine and the judicious use ofspecific drugs, the action of which he un-derstood. In one of his treatises, he wroteas follows: Now, most physicians are greatlyin error in that they think that medicationstrengthens the health: it weakens and pervertsit: and for this reason hath Aristotle said thatmost of the patients who die do so through themedicines of physicians. When interference ofthe physicians is indicated, his task should be tosustain the strength of the patient and to pro-mote Nature in her efforts a repair. Mostphysicians, however, err in their treatment; in-stead of endeavoring to assist Nature, theyweaken the body with their prescriptions.“ Inletter and in spirit his quotation exactly ex-presses the views on therapeutics held byOsler eight centuries later. He also assertedthe importance of Vis Medicatrix Naturae, ofhygienic measures, of dietetic therapy,properly balanced rest and exercise, of sun-shine and of the judicious employment ofscientifically studied medicaments. His so-called therapeutic nihilism was merelyanother spelling for therapeutic rationalismand marked the dawn of modern scientificpharmacotherapy. Although Maimonidesbecame the greatest physician of his timeand the court physician of Saladin, themost famous of sultans, and his services

were sought after by Richard the Lion-hearted, his advanced ideas on materiamedica and the practical employment ofdrugs were obscured by the succeedingdark ages. It is only now that he is regardedas the leading physician of mediaeval Ara-bic and Hebrew medicine, and his views ontherapeutics are recognized as marking adistinct epoch in the history of medicine.Let us hope that the modern era of rationaltherapeutics, ushered in by William Osler,may not be similarly hampered.

There are sinister powers of darkness,prejudice, racial hatred, mass hysteria andexaggerated egotism stalking abroad and,amazing as it may seem, aspersions are ac-tually being cast on the value of themedical contributions of such men as Jen-ner, Koch, Virchow, Ehrlich, Neisser andvon Behring. I cannot refrain from conclud-ing with a fervent prayer for more powerto such organizations as The AmericanTherapeutic Society, which carries on theteachings and ideals of humanists and sci-entists of Osler’s type.

-David I. Macht

FRIENDS OF THE OSLER LIBRARY

The appeal to the Friends for the 1993-94 academic year concluded at the end ofMay. The Library gratefully acknowledgesthe support it has received from Friends,both old and new, who have responded tothe appeal for funds this year. Over theyear, 291 Friends have given a total of ap-proximately $20 ,042 . Most of thecontributions have come from Friends inCanada and the United States of America.However, very welcome contributionshave come also from Australia, Chile, Ger-many, Japan, Switzer land, Uni tedKingdom and the West Indies.

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Editorial Committee for the Newslet-ter: Faith Wallis, Osler Librarian andEditor; Edward H. Bensley, HonoraryOsler Librarian and Consulting Editor;Wayne LeBel, Assistant History ofMedicine Librarian and Assistant Edi-tor; Lily Szczygiel, Editorial Assistant.

Legal Deposit 2/1994 ISSN 0085-4557