Importance and ValueOF -

Experimental Research

DOCTORATE ADDRESS

DELIVERED AT THE GRADUATING EXERCISES OE THE COELLEGE OEPHYSICIANS AND SURGEONS, CHICAGO, ILL.,

feb. 2i, 1887.

- BY -

N. SENN, M. D., Milwaukee, Wis.Professor of Principles and Practice of Surgery and Clinical

Surgery.

Reprinted from the Western Medical Reporter, March , tSRj.

Press of 0. F ANSELL CO., 196 Clark St., Chicago

Importance and Value-OF-

Experimental Research

DOCTORATE ADDRESSDELIVERED AT THE GRADUATING EXERCISES OE THE COLLLEGE OE

PHYSICIANS AND SURGEONS, CHICAGO, ILL.,

EEB. 21, 1887.

BY

N. SENN, M. D., Milwaukee, Wis.Professor of Principles arid. Practice of Surgery and. Clinical

Surgery.

Reprinted from the Western Medical Reporter , March, 1887.

Press of C. F. ANSEUU CO., 196 Clark St., Chicago.

Importance and Value of Experimental Research.N. SEJNN, M.X).

Professor of Principles and Practice of Surgery.

ADoctorate Address delivered at the Fifth Annual Commencement Exercises of the College of Physi-cians and Surgeons, Chicago, Feb. 21, 1887.

Genteemen of the Graduating

Ceass:—To-day marks a new era in yourlives. The time you have been so anx-iously awaiting has arrived. The dreamsof your youth are realized. You have leftthe college building where you spent somany days in acquiring a knowledge ofthe healing art, and in recognition ofwork well done you have just been re-ceived into the ranks ofa great and nobleprofession. The pleasant relations whichhave existed between us as teachers andstudents have come to a close. As teach-ers we congratulate you, as colleagueswewelcome you and extend to you the righthand of fellowship. With parental soli-citude we shall follow you into the arenaof active professional life, fully confidentthat every one of you will meet with wellmerited success.

An honorable struggle for a remuner-ative practice is justifiable and desirable,but a successful career is not always to bemeasured by weight in gold. One of thegreat objects in life must be to becomecontributors to science. Even at thevery threshold ofyour professional careeryou have incurred a heavy debt, in thepayment of which some of the very bestefforts of your lives will be required.During yonr pupilage you have enjoyedadvantages that were not in reach of stu-dents even a few years ago. The progress

made in medicine and surgery and theallied sciences during the last two decadesis unparalleled in the history of medicine.One discovery has followed another untilwe have witnessed a complete revolutionin the treatment of injuries and disease.Text-books of a few years ago that werethen considered as standard authoritiesare now consigned to the shelves of theantiquarian, as the very principles uponwhich their teachings were based haveundergone a radical change. You havebeen instructed in the most recent ad-vances pertaining to your profession.You have been made familiar with bothancient and modern literature, and havethus derived the benefit resulting fromthe accumulation of knowledge which ithas required centuries to develop. Youowe to science a debt which can only bepaid by faithful and persevering studyand research, in enlarging its boundariesand in increasing its store of wealth.While you are no longer students underthe supervision of teachers you shoulddedicate your future lives to the stmTyand improvement ofyour chosen profes-sion. We have inherited a trust whichcan only be invested profitably by hard,unselfish work. The study of medicineis inexhaustible and affords ample scopeto occupy all your leisure moments. Asteachers we have simply laid the founda-

4tion for your medical education and mustleave it to your own efforts and inclina-tions to complete the structure. Com-mence your life-work with a firm deter-mination to continue your studies in asystematic manner. It is not only neces-sary for you to keep familiar with thecurrent medical literature, but you shouldalso strive to render material aid in thefuture growth and development of ourscience. A reward greater in value thangold, and more enduring than fame, is aconsciousness of having contributed tothe increase of knowledge.

With a view of pointing out to you theright direction in which such work canbe accomplished, I have selected as thesubject of my address, “The Importanceand Value of Experimental Research.”Experimental research implies the neces-sity of resorting to vivisection. It is notmy intention to argue in justification ofthis method of investigation, as vivisec-tions in original researches are performedonly when questions in hand cannot besolved bjr any other method ofstudy, andalways with a definite object in view, andwith this restriction no intelligent com-munity has the moral right to interfere.

Modern medicine and surgery arefounded upon a study of the organs ofthe body and their functions, that is,upon a knowledge —the more thoroughthe better—of the mechanism with whichthey have to deal. Empirical medicineand surgery have a foundation since theyrest upon the observation of isolatedfacts, but the mere collection of informa-tion without reasoning upon it is useless,and mauy disconnected facts cannot con-struct a system capable of further devel-opment. A thorough knowledge of thestructure of the body with which the phy-sician and surgeon has to deal, the rela-tions of its functions in health will enablehim to act promptly and intelligently in

case of injury or disease. Rational treat-ment is based upon sound physiology.Experimentation is part of a system, —

the physiological system, and part of a

method,—the experimental method, Ascientific investigator is never a randomexperimenter. A comprehensive and ac-curate knowledge of the ancient andmodern literature, and an intimate ac-quaintance with everything that is knownrelating to the subject is essential forsuccessful work. As modern medicineand surgery are so intimately related toand associated with physiology, it isproper to ask: “What has experimentalresearch done toward the development ofthe latter science?”

Erasistratus thought that the arteriescontained air. Galen was a diligent ex-perimenter, and his observations soontaught him that this was not the fact.He found that when an artery was cutblood escaped. He believed, however,that the arteries contained, besides blood,air or vital spirits, and that their functionconsisted in distributing this vivifyingsubstance to the whole body. He wasthe first great experimental physiologist,and the knowledge derived from vivisec-tion had elevated him to a position ofprominence and influence which survivedhim for centuries. The physiology ofthe circulation after his time remainedmuch in the same condition until thebeginning of the 17th century. The greatmotor power of the heart was unknownto medical men of that time and thedirection of the blood current throughthe vessels had not been ascertained.Practical observation at the bedside, andupon battlefields, had failed to familiar-ize thephysician with the true mechanismof the circulation. The observationsmade upon living animals were directedmore toward the study of anatomy thanphysiology. In the beginning of the

517th century Harvey followed the foot-

steps of Galen and laid the foundation formodern physiology by his discovery ofthe circulation. Malpighi and Leouwen-hook, the founders of microscopical an-atomy, were the first to observe the pas-sage of the blood from the right to theleft side of the heart through the pulmo-nary capillaries of a living frog by vivi-section, thus adding the last link toHarvey’s chain of evidence. Only a fewyears ago the researches of Waller andCohnheim made on the circulation of theblood in lower animals have demonstrat-ed the migration of white corpusclesthrough the capillary walls—a discoverywhich furnishes an adequate explanationof many pathological conditions, which,without it, would haveremained shroudedin darkness.

Intracardiac pressure was first studiedby Stephen Hales, who published hisobservations in 1732. The same subject,which of course could only be studiedupon living animals, was investigated byPoiseuille, and more recently by AlfredW. Volkmann, who published the resultof his researches in a large volume in1850, entitled “Die Haemodynamik nachVersuchen.” As a result of these inves-tigations a number of ingenious instru-ments, as the kymograph, sphygmo-graph, and cardiograph have been devisedwhich have rendered material diagnostitialaid to the physician and surgeon, ascer-taining the most delicate changes in thecirculation, and are most valuable meansin studying the fluctuations of disease.Haller, the great physiologist, demon-strated by his careful observations onliving animals the independent muscularcontractions in the arteries, a discoveryfully confirmed by the experiments ofHunter and Thomson. Claude Bernard,Brown-Sequardand others established byexperimentation the regulation of the

blood supply to the various organs throughthe medium of the action of the nervoussystem upon the organs ofcirculation.

Gaspardus Asellius, a distinguishedItalian anatomist, in 1662, while experi-menting upon a dog which had just hada full meal, accidentally discovered thelacteal vessels which appeared as “anumber of fine white cords,” which he atfirst supposed to be nerves, but which,when punctured, proved to contain milkyfluid. As at this time it was the generalbelief that the liver was the exclusivehaemato-genetic organ, he failed to searchfor the proximal termination of the lac-teal vessels and entertained the beliefthat they terminated in the liver, anopinion which prevailed until Jean Pec-quet, while experimenting for anotherpurpose, discovered the thoracic duct, andby further research succeeded in tracingthe general course and distribution of thelymphatic system.

The ancients entertained the mostvague ideas in relation to the respiratoryfunctions, believing that the air passedthrough the lung into the cavity of thechest, from there into the heart, where itcame into direct contact with the blood.This opinion represented the wholeknowledge upon this subject until the be-ginning of the 17thcentury, and was en-dorsed by such famous authorities as Har-vey, Hall, and Boerhave. A series ofexperiments made by Haller demonstrat-ed to the satisfaction of physiologists themechanism of the respiratory function.Mayow, by experiment and logical induc-tion, came to the conclusion that theatmospheric airwas a compound,contain-ing as one of its elements a body towhich he assigned the properties pos-sessed by oxygen, which from its supposedanalogy to nitric acid he called nitro-ae-rial spirit. To this element of the airhe attributed an active and essential part

6in the process of combustion and respira-tion. Black, in 1759, showed by experi-ments the presence ofcarbonic acid in theexpired air; and in 1770, Priestly provedby the same means the analogy of respi-ration to combustion, and asserted thatatmospheric air in itspassage through thepulmonary circulation lost some of itsoxygen. Lavoisier’s skillful and labori-ous experiments resulted in an accurateknowledge of the chemical changeswhich take place in the inspired air dur-ing the respiratory process. More recentexperiments have determined almostwith arithmetical precision the amountof oxygen consumed and carbonic acidexhaled by an individual during a speci-fied time. Lowr er found when examiningthe open thorax of a living animal thatthe difference between the color of ar-terial and venous blood took place in thecapillaries of the lungs and referred thisphenomenon to a chemical change inthe blood itself. The true explanation ofthis change was furnished by Priestly,whose experiments convinced the scien-tific world that the alteration was due tothe purifying of the blood by means ofthe oxygen of the air. Our ancestorsentertained a very peculiar idea concern-ing the complicated process which wenow consider essential for healthy diges-tion and assimilation. The transforma-tion of food into chyle was supposed tobe effected entirely by the moisture andheat of the stomach producing a changewhich they termed “concoction.” Thenappeared the mechanical theory whichadvanced the idea that the mechanicaldivision of food in the stomach by tritu-ration constituted the most importantpart of digestion. Still later it was be-lieved that the food introduced into thestomach underwent a process of putre-faction before it could be absorbed andutilized in the body.

Experimental research again had tocome to the rescue of science to demon-strate the fallacy of all of these absurddoctrines. Spallanzani and Stephensshowed that the mucous membrane ofthe stomach secreted a digestive fluid—

the gastric juice—and made careful ex-periments to determine the effects of thissubstance upon different kinds of food.Our knowledge of digestion as elucidat-ed further by Hunter, Cruikshank, Ma-gendie, Voit and many others is based al-most exclusively upon the results derivedfrom patient and persevering experimen-tation on animals which have succeededin solving the problems of digestion, ab-sorption and nutrition, until this part ofphysiology has reached an enviable de-gree of perfection. The physiology ofthe nervous system furnishes one of thestrongest and most convincing claims infavor of the indispensable value ofexperi-mental research.

Galen gave public demonstrations illus-trating the effects of injuries to the cere-bro-spinal centres in animals. He divid-ed the spinal cord in the cervical regionand showed how this procedure affectedthe respiratory and other movements.He also studied carefully the phenomenafollowing section of the cord in otherplaces, and, by comparing the differentresults, obtained a fair knowledge relat-ing to the more important functions ofthis nervous centre.

P'rom this time little or no progresswas made until Sir Charles Bell, Mageu-die and Mueller again resorted to im-proved methods of experimentation tothrowmore light upon this important sub-ject. The motor function of the anteriorroots of the spinal nerves was clearlypointed out by Bell in a few carefully con-ducted experiments and his views weresubsequently confirmed and elaboratedby Magendie. The numerous and accu-

7rate experiments made by Mueller uponthe anterior and posterior roots of thespinal nerves in frogs lead to accurate con-clusions as to the more important func-tions of the spinal cord.

Marshall Hall discovered the reflexfunction of the nervous system and per-sistently and enthusiastically demonstrat-ed the correctness of his views by experi-mentson animals.

In our own day, a group of distin-guished and faithful investigators, amongthem Westphal, Ferrier, Hitzig and thelamented Gudden, have been patientlystudying the difficult subject of cerebrallocalization, and the result of their laborshas paved the way for successful surgicaltreatment of a number of lesions of thebrain and its envelopes which heretoforeinvariably resulted in a fatal termination.Muscular contraction was attributed byGalen and his followers to the brain andthe spinal cord. This idea was basedupon the results of his experimentsas he invariably produced muscularparalysis below the point of section ofthe spinal cord. Haller by his ingeniousexperiments showed the fallacy of thisdoctrine which had been handed downfrom generation to generation as an un-disputed fact by demonstrating the exist-ence of an inherent irritablity of themuscular fibre, entirely separate and dis-tinct, of the nervous system.

I might proceed and enumerate count-less instances where the results of experi-mental research have directly or indirect-ly contributed to the growth anddevelopment of the science of physiolo-gy, but you must have been convinced bythis time that modern physiology consistsof a systematic arrangement of facts de-rived almost exclusively from experimen-tation. Future advances in physiologycan only be realized through the laborsof patient and careful experimenters.

The value of experimental researchfrom a practical standpoint becomesmore apparent when we contemplate theachievements of modern surgery. Theeffects of the different anaesthetics had tobe carefully determined on animals be-fore it was deemed prudent and safe toapply them in practice. Subcutaneousinjections of anodynes were used in thelaboratories for years with a view of pre-venting pain before this prompt and re-liable method of relieving pain found itsway into general practice.

Artificial respiration was practiced uponanimals by Vesalius, Hooke, Lower andothers, as a means ofprolongin glife, longbefore it was applied to the resuscitationof human beings. Transfusion, as a life-saving operation, is based entirely uponthe results derived from experimentation,and can beresorted to as a reliable meas-ure in cases of sudden dangerous loss ofblood, a procedure which so far hassaved more than half the cases in whichit has been attempted. Browu-Sequardhas shown that in cases of poisoning withcarbonic oxide gas this substance makesa more stable compound with the coloringmaterial of the blood, which incapacitatesthe red corpuscles from mixing with oxy-gen, so that in grave cases of this kindthis surgical resource constitutes the onlypossible chance of saving life. Quite re-cently numerous experiments have beenmade on animals to test the influence ofintravenous infundations of saline solu-tions in the treatment of acute anaemiaas first advocated by Schwarz, and theencouraging results which have been at-tained have placed this simple and effec-tive procedure upon the list of well-estab-lished legitimate surgical resources.

The subject of callus production, re-generation and growth of bone has beenmade almost exclusively on the loweranimals, and this part ofsurgical pathol-

8

ogy is intimately associated with thenames of Duhamel, Sir Astley Cooper,Ollier, Maas, Busch, Wolff, and our ownBrainard. The results of these experi -

ments have opened a wide field for con-servative surgery which has resulted inthe saving of thousands of useful limbsby the substitution of sub-periosteal re-section for the too frequent resort tomutilating operations. Only a few yearsago acute suppurative osteomyelitis con-stituted a subject about which but littlewas known. To-day, thanks to thepatient labors of Kocher, Rosenbach andOgston, it furnishes the most strikingtopic of the great value of experimentalresearch. For years surgeons have dread-ed to expose themedullary tissue in bone-operations for fear of producing osteomye-litis and the disastrous consequencesfollowing it,—thrombo-phlebitis, pyae-mia and septicaemia.

Experiments have shown that the mye-loid tissue in bone can be torn, contused,crushed, burned, cauterized and the sub-sequent inflammation will invariably as-sume a plastic type, provided infection isprevented. On the other hand, it hasbeen found that in animals previouslyinfected with pus-microbes, injury to themedullary tissue is almost invariably fol-lowed by suppurative osteomyelitis at theseat of traumatism. We are thereforeforced to assume that the floating germs,which might have remained inert for anindefinite period of time, find at the seatof traumatism favorable conditions forlocalization and reproduction, and arethe essential and direct cause of the sup-purative inflamation.

That common and heretofore obscuredisease, rachitis, has been made an ob-ject of patient experimentation by Kas-sowitz, who has shown that the diseasecan be artificially produced in animals bythe administration of large doses ofphos -

phorus, which causes increased vascu-larity of bone and osteo-porosis ; on theother hand the same author has demon-strated that the prolonged administrationof minute doses produce an opposite, acurative effect. Numerous practitionershave applied the results of these observa-tions in practice and the majority of themagree with Kassowitz that minute dosesofphosphorus constitute almost a specificin the treatment of rachitis. Hagenbachreports twenty consecutive cases treatedsuccessfully by this method.

Koch’s great discovery of the cause oftuberculosis has revolutionized the treat-ment of numerous affections which wTereformerlv described under the vague termof scrofula but which are now known tobe tubercular in their origin and in theirtendencies. The familiar manifestationsof so-called scrofula in children, chroniclymphadenitis, tumor albus, and fungousdisease of bone, and lupus in the adult,are now well recognized tubercularlesions. In all of these affections theessential primary cause, the bacillus oftuberculosis has been found so constantlythat the direct relationship between causeand effect admits of no further argument.But not only the germ has been found inalmost every instance but it has been iso-lated and cultivated upon an artificialsoil, and animals infected with the newgrowth have furnished the crucial test ofthe tubercular nature of the lesion—re-production of the samecondition histolog-ically, pathologically and clinically. Rec-ognizing the danger arising from localdissemination and generalization throughthe vascular system, modern surgeons areunanimous in adopting early and thor-ough local measures, with a firm beliefthat by a complete removal of the localproduct, the patient is protected againstembolic tuberculosis from the local de-posit.

9Subcutaneous surgery has only been

carried on in a scientific manner and withsuccessful results since the repair of ten-dons after subcutaneous division wasstudied on animals by Hunter, Stromeyer,Von Ammon, Bouvier, Guerinand others.

The healing of wounds was made anobject of careful experimentation byHunter, Thiersch and Gussenbauer, andthe scientific and practical informationthus gained has been of great value inthe advancement of surgery. Suturingof divided nerves has become an estab-lished practice since the publication ofthe results of their experimental work byGluck and Wolberg. An experimentalstudy of cicatrization in blood vesselsafter ligature, by Jones, Travers, Porta,Hunter, Zwicky, Weber and more recentauthors, has gradually led to accurate andcorrect ideas concerning the immediateaction of the ligature and the processeswhich are initiated, destined to effectdefinitive obliteration of the lumen ofthe vessel.

Lister’s experiments upon the use ofthe catgut ligature have led to practicalresults which alone would constitute amonument w’hich will render the nameof the greatest of living surgeons immor-talwherever surgery is practiced. Brown-Sequard studied, experimentally, howlong the tissues can be left completelydeprived of blood without risk of gan-grene, observations which led to the useof Esmarch’s great invention, substitu-tion of the elastic constrictor for the ordi-nary imperfect tourniquet in the preven-tion and arrest of hemorrhage.

Wound fever was studied experimen-tally, by Lee, Bennet, Pasteur, Colin,Toussaint, Weber, Breuer, Chroback,Bergmann and Koch. The researches ofthese men prepared the way to antisepticsurgery as first taught and practiced byLister. The value and importance of the

antiseptic treatment of wounds is nowalmost universally accepted, as the fun-damental principles upon which it restsare no longer theories but facts abund-antly substantiated by experimental re-search.

The aetiology, pathology and morbid an-atomy of thrombosis and embolism couldonly be solved by patient and perseveringexperimentation by such able investiga-tors as Virchow and Panum. Pyaemiaand septicaemia, the surgeon’s greatestenemies in the pre-antiseptic times, havebeen carefully studied by experimenters,and we have every reason to hope thatwork in the same direction in the nearfuture will reveal the true pathology andrelationships of these, themost importantof all wound infective diseases.

Experiments on dogs made by Wini-warter with a view to determine the feas-ibility of operative measures upon thestomach, has resulted in the establish-ment of pylorectomy by Billroth, whichhas established the practical applicationof the knowledge thus gained; and a longseries of cases, which, if they have notresulted in adding much to the durationof life, demonstrate the justifiability ofa resort to the knife in well selected cases.

The history of intestinal surgery is inti-mately associated with experimental re-search, and the names of Jobert, Grossand Parks will always be remembered inconnection with this department of sur-gery. Before Simon ventured to resort tonephrectomy in man he studied the effectof this operation upon animals. As aresult of these observations extirpationof the kidney is now a well establishedoperation and has already gained a legiti-mate sphere in cases heretofore aban-doned to certain death. The results ofextirpation of the spleen in animals hassatisfied surgeons that this organ can beremoved with safety and a fair prospect

of success in cases of injury or localdisease.

The most remote abdominal organ, thepancreas, has been submitted to experi-mental investigation, and the results thusobtained have shown the feasibility andjustifiability of surgical interference ina number of well defined lesions. Ex-periments upon the liver of animals haveshown the necessity of resorting to localmeasures in arresting hemorrhage wherethis organ is injured, and o securing acondition for the visceral wound whichwill favor the healing process, and, at thesame time, prevent the disastrous conse-quences resulting from escape ofbile andwound secretions into the peritonealcavity.

Desault, Albers, Koeberle and Hueteradvocated the propriety of extirpation ofthe larynx, but the advisability of thisoperation had to be tested by Czernyupon dogs before surgeons could be in-duced to adopt it as a legitimate surgicalprocedure. Within a few years 96 extir-pations of the larynx have been made,with 32 cures and 64 deaths, a satisfactoryshowing when we consider that withoutit all of these patients were doomed to diea horrible death from asphyxia.

Successful extirpations of portions ofthe lung in animals by Gluck and Schmidhave encouraged surgeons to attack thisimportant organ (in well selected cases),when the seat of localized lesions, andin corroboration of the value of theseexperiments I will only refer to the suc-cessful case of Kroenlein, who extirpateda piece of sarcomatous lung with a por-tion of the chest-wall, and the patient notonly recovered from the operation butwas reported in good health and withoutany indications of a return of the diseaseafter two years.

I have only enumerated a number ofthe most convincing illustrations of the

value of experimental research to thepractice of surgery, but enough has beensaid to substantiate the assertion that it isthe foundation of modern surgery. Itwould be difficult to point outpathologicalconditions or operative measures whichdo not show the impress and great valueof this method of investigation. Therecent rapid advances in surgery are en-tirely owing to original experimentalwork. German surgery leads the world,because the leading surgeons of thatcountry are original investigators.

If the brilliant achievements of modernsurgery are the direct outcome of experi-mental research, it requires no argumentto show that future improvements willdepend upon the same method of investi-gation. The American profession has asyet not realized the importance of originalwork. Instead of borrowers we must be-come producers.

I can give you no better advice on thisoccasion than to devote your leisuremoments, from the very beginning ofyourprofessional career, to original workof this kind. The means for such anundertaking may be limited, but perse-verance will overcome difficulties. Yourefforts will be appreciated and your almamater will look with pride upon the re-sults of your labors. Your colleagueswill esteem your motives to promote sci-ence and your work will command therespect of the entire profession . Anothergreat advantage only to be acquired byoperations upon animals is dexterity inthe use of instruments and delicacy ofmanipulation in the performance of diffi-cult operations. Visceral surgery canonly be learned in this manner. Opera-tions upon the gastro intestinal canalshould invariably be practiced upon ani-mals before attempting it on man. Acourse in operative surgeryon the cadaveris utterly inadequate to prepare a student

sufficiently to perform gastrotoniy, intes-tinal resection, or even apply intestinalsutures with requisite speed and accuracy.Proficiency in abdominal surgery canonly be acquired by operating upon livingtissues. Ligation of arteries in their con-tinuities, again, is another operation inthe technique of which you can only per-fect yourselves by practicing upon ani-mals. It must have become apparent toyou that in order to succeed as scientificmen you are not to lead a life of leisure.

If in the beginning of your practicetime hangs heavy and patients comeslowly, do not become discouraged.Utilize every moment of your time toprepare yourselves the better for yourwork. Identify yourselves with the localmedical societies and take an active partin the scientific work. Keep abreastwith the advances in medical science by

reading and studying the best literature.Take an active part in preventive medi-cine, and act as guardians of publichealth. Become at once original investi-gators. If you do all these things youwill have no just cause of complaint of asurplus of time, or to seek places of idleamusement. The laboratory, the books,the journals, the microscope, the medicalsocieties will become your most devotedand truest friends. When the curtainshall drop behind the scene of a busy,well spent life, a coming grateful genera-tion will inscribe your names upon thewalls of the temple of science which youhave helped to erect. In bidding you anaffectionate farewell I will give you thewatchword that will secure your entranceinto the ranks of successful men;—work ,

uninterrupted, hard, faithful , honestwork.