BACTERIOLOGICAL REVIEWS, Sept. 1974, p. 251-271Copyright 0 1974 American Society for Microbiology

Vol. 38, No. 3Printed in U.S.A.

Beginnings of Bacteriology in CaliforniaL. S. McCLUNG AND K. F. MEYER,

Department of Microbiology, Indiana University, Bloomington, Indiana 47401, and George Williams HooperFoundation for Medical Research, University of California, San Francisco, California 94122

INTRODUCTION ............................................................. 251RECOGNITION OF THE GERM THEORY OF DISEASE AND OTHEREARLY CONSIDERATIONS OF BACTERIOLOGY ....... .................. 253

INSTRUCTION AND RESEARCH IN BACTERIOLOGY AT STANFORDUNIVERSITY ................................................................ 254

INSTRUCTION AND RESEARCH IN BACTERIOLOGY AT THE UNIVER-SITY OF CALIFORNIA ................... .................................. 256

INSTRUCTION AND RESEARCH IN BACTERIOLOGY IN SOUTHERNCALIFORNIA ................................................................ 261

DEVELOPMENT OF THE STATE HYGIENIC LABORATORY ...... ......... 263STUDIES ON SPECIFIC BACTERIAL DISEASES, TOGETHER WITHSOME NOTES RELATIVE TO THE HISTORY OF PUBLIC HEALTHACTIVITIES ................................................................. 264

EARLY INDUSTRIAL BACTERIOLOGY .......... ............................ 269LITERATURE CITED.271

INTRODUCTIONAn endeavor has been made to trace the rise

of bacteriology in California from its earlybeginnings to approximately 1915. By this datethe early formative period had concluded, andthe main trends of development were estab-lished. As far as possible, the data included inthis review have been verified, although in someinstances it has been necessary to use advancecatalogue announcements of universities as thereference source. This may have resulted inoccasional inaccuracies, for the appointmentslisted may not have been fulfilled, although theannouncements were printed in good faith atthe time. This account necessarily is only areconstruction of the period from the informa-tion available to us. Important omissions mayexist, and for these we offer our apologies. Thetime available for this compilation did notpermit the gathering of certain material, e.g.,early laboratories of bacteriology in the munici-pal health departments, the various medicalcolleges in southern California, some of whichprobably offered some instruction in bacteriol-ogy before 1915, and more extensive material onindustrial microbiology. In order to orient read-ers it may be well to include a brief summary ofthe early history of the relationships of theacademic institutions to be considered in thisreview. The University of California (1868) grewout of the College of California (1855), whichhad an earlier beginning (1853) as the ContraCosta Academy or Oakland College School (5,25). As a state university, a large endowment

' Deceased, 27 April 1974.

was available through the Morrell Act, provid-ing land grants. The Leland Stanford JuniorUniversity at Palo Alto, founded in 1885, butnot opened until 1891, was established as aresult of a private endowment by Senator andMrs. Leland Stanford in memory of their sonwho had died at the age of 16. The firstpresident was David Starr Jordan, a well-knownbiologist who came to Stanford from IndianaUniversity and who selected a faculty particu-larly strong in the sciences.The University of California at Los Angeles

(1927) had its beginning in 1919 when theRegents of the University of California took overthe Normal School at Los Angeles and, inaddition to the training of teachers, establishedcertain lower division courses. Instruction inbacteriology at this institution, therefore, wasnot initiated until after the close of the period tobe discussed. Likewise, instruction and researchin biology did not begin until 1928 at theCalifornia Institute of Technology, as it hasbeen called since 1920, after development froma local school of arts and crafts founded inPasadena in 1891.

It is striking that the medical schools of bothStanford University and the University of Cali-fornia had origins apart from the universitywith which they became affiliated (5, 9, 10, 12,15, 16). The first medical school was establishedby Elias Samuel Cooper in 1858 with the firstcourses of lectures beginning on 12 May 1859.Cooper, a surgeon, was 36 years old at the time,having graduated in medicine, after 2 years ofstudy, from St. Louis University at the age of18. Although the quality of the first faculty has

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been questioned, the right to issue diplomas wasobtained by Cooper from the University of thePacific (Santa Clara). In 1872, with the death ofthe founder, the Pacific Medical Faculty joinedwith Hugh H. Toland's group. The first facultyincluded Cooper as Professor of Anatomy andSurgery, R. Beverly Cole (later President of theAmerican Medical Association), Professor ofObstetrics and Diseases of Women and Childrenand Physiology (also Dean), and J. Morrison,Professor of Principles and Practice of Medicineand Pathology. In 1859 Levi Cooper Lane joinedthe faculty as Professor of Physiology, and in1862 A. J. Bowie joined as Professor of Theoryand Practice in Medicine. After the death ofCooper in 1862, Bowie became Professor ofSurgery and, in 1863, Henry Gibbons was ap-pointed to the chair of Materia Medica andBotany and J. F. Morse to the chair of Medi-cine. In the 5-year period 1858-1864, the schoolgraduated 28 students.On 5 November 1864, the Toland Medical

School began instruction in San Francisco inToland Hall, a commodious building of brickand stone on Stockton Street near Chestnut. Bythen the Cooper school was languishing, and allstudents moved to the Toland School; on theirpetition, Lane and Gibbons were appointed tothe faculty of the Toland School, but Cole wasnot invited. Toland, a native of North Carolina,graduated, presumably in medicine, in 1828 (atthe age of 22) from Transylvania University(Lexington, Kentucky), and after 2 years ofpractice in his native state and 2.5 years ofmedical study in France, he returned to NorthCarolina to practice. He moved to California in1852 to seek his fortune in the gold fields, but in1853 he sold his mine in Calaveras County andmoved to San Francisco where he set up alucrative medical practice. It has been esti-mated that his yearly income was more than$40,000 (16). The morning hours were devotedto private patients, and the afternoons accom-modated clinic patients to whom he did notmake a charge. In the same building, Dr.Toland's drug store filled most of Toland'sprescriptions and, in addition, he operated alarge mail order business. Patients from Califor-nia and neighboring states sent an account oftheir symptoms, and medicine was sent byWells, Fargo and Company express!

Differences in policy concerning election ofnew faculty led Lane and Gibbons to resign in1870 from the Toland school and to reorganizethe old Cooper school. All students but onefollowed, and in 1873 the Toland school affili-ated with the University of California. When

the University of California began classes, anattempt was made to induce the Toland Collegeto affiliate with the University as the MedicalDepartment. Largely owing to the fact that thiswould entail the loss of the name "TolandMedical College" it was not until 1873 thatunion was possible. Among the early graduateswere Joseph P. Widney, who later organized theCollege of Medicine of the University of South-ern California, and George Henry Falkiner Nut-tall, later a well-known biologist.The Medical Department continued in the

old quarters until a new location was providedin 1895 by Adolph Sutro, then Mayor of SanFrancisco. Although objections were raised be-cause the site (the present Parnassus Street hillcampus overlooking the Golden Gate Park) wassome 5 miles distant from the business center,the gift was accepted. Originally medicine, law,dentistry, pharmacy, and veterinary medicinewere to be housed in separate buildings. Theseplans did not materialize completely, andupon the later disestablishment of the Veteri-nary Department this building was used for theGeorge Williams Hooper Foundation for Medi-cal Research.Although the early Cooper group, as noted

above, was for a time associated with theToland School, they later withdrew and estab-lished a new school, on 5 July 1870, under thedirection of Levi Cooper Lane, a nephew ofElias Cooper (18). The school was located in abuilding on Stockton Street between Geary andPowell Streets on the site of the present depart-ment store, Liberty House and Rhodes, and thenew school served as a Medical Department tothe adjoining University (City) College, a Pres-byterian institution. Other changes were madeand under the name Cooper Medical Collegeand later the Medical College of the Pacific, theschool continued from 1882 to 1912. The schoolwas housed in 1886 in new quarters provided byLane on Webster and Sacramento Streets.Lane, who had not consulted the faculty regard-ing the new building, stipulated that thereshould be an annual lecture series of publicmedical lectures (16). He also founded a courseof medical lectures which brought prominentmedical men of Europe and eastern Americato the college. He later built a second buildingand in 1894 the Lane Hospital. Before his deathin 1902 these properties were deeded to thecollege. In 1909, the school was absorbed byStanford University after earlier negotiationsbetween Lane and President Jordan.That rivalry existed between the schools of

Lane and Toland is evident in the following

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quotation from Harris (9): "These two groupsthereafter maintained a competitive aloofness.Nor has hell, high water or the expandingdesires of the University of California, as pic-turesquely expressed in 1873, sufficed to mergethem into one school."

RECOGNITION OF THE GERM THEORYOF DISEASE AND OTHER EARLY

CONSIDERATIONS OF BACTERIOLOGYAlthough not concerned entirely with bacte-

ria and bacteriologists, the first attempt toorganize the microscopists of San Francisco wason 4 January 1870 by members of the CaliforniaAcademy of Sciences. This was a short-livedaffair and reorganization occurred on 12 April1872, at which time a $10 fee was assessedtogether with $2.50 monthly dues. That thesemonies were saved for the purchase of a firstclass microscope and accessories was no doubtdue to the stimulus provided by the visit of awell-known London optician who proudly dis-played a fancy aluminum binocular instrument.The records of the Transactions of the group(the San Francisco Microscopical Society) pub-lished in 1890 indicate that the early awakeningof interest in bacteria in California coincidedwith the advent of G. M. Sternberg of the U.S.Army who, in the early 1880s, began a series oflectures and demonstrations. This, we believe,may have been true, for courses of instructionconcerning bacteria were not included in theuniversities until a later date, and it is likelythat the historian of the Society was in fullpossession of the facts.As early as 1874 the San Francisco Micro-

scopical Society heard lectures on fungi, but notuntil 1885 was a topic directly concerned withbacteria. Eight such discussions were includedon the program by 1893. They were, with thedates and speakers, as follows: "PathogenicBacilli," J. H. Stollard, 24 June 1885; "Bac-teria," J. M. Selfridge, 8 July 1885; "The GermTheory of Disease," Joseph Le Conte, 12 March1890; "Gonococci from a Case of Ophthalmia,"Kaspar Pischl, 7 October 1891; "Some PracticalBearings of Bacteria," C. E. Cooper, 16 March1892; "The Spirillum of Asiatic Cholera," H. E.Saunders, and "History of the Cholera Epidem-ic," R. H. Freund, a "double bill" for the date of7 September 1892; and "Culture Methods in theStudy of Micro-Organisms," C. P. Bates, Feb-ruary 1893.

George M. Sternberg addressed (17 October1882) the San Francisco County Medical Soci-ety on the topic "Micrococci and MICRO-COCCI" (21). He reported personal experi-

ments on the inoculation of experimental ani-mals with human saliva, particularly withrelation to malaria and yellow fever. A moregeneral lecture, "Bacteria, and the GermTheory of Disease," appeared in the same yearin the Transactions of the California MedicalSociety published in the Pacific Medical andSurgical Journal (20).

Sternberg, a true pioneer, deserves inclusionin this account for another reason, although itdoes not relate directly to California. Earlier(1878), while at the remote post of Walla Walla,Washington, he began his work on "the thermaldeath point of pathogenic organisms and thegermicidal value of certain chemical and physi-cal agents." This must be considered to be thefirst bacteriological research to be conducted inthe West and, when considered along with thework of Burrill and Welch in the East, it ranksamong the earliest in the United States. Theseinvestigations were continued later in Washing-tin, D.C., and Baltimore and were published in1886 under the title "Disinfection and Individ-ual Prophylaxis Against Infectious Disease." In1885 the report of this work was awarded one ofthe four Lomb prizes by the American PublicHealth Association (22).

Sternberg was stationed at Fort Mason (SanFrancisco) from 1881 to 1884. Here, at his ownexpense, he equipped a laboratory and in 1881,after Koch's discovery, demonstrated the tuber-cle bacillus and obtained photomicrographs.Some regard this as the first demonstration ofthe organism in America. Without question,much of the early work performed by Sternbergat Fort Mason eventually found its way into his"Manual of Bacteriology" which, however, wasnot published until 1892. In 1893 Sternberg wasappointed Surgeon General, and he continuedin that office until retirement in 1902.Another individual who greatly influenced

the medical opinion of the day in regard tobacteriological matters was Joseph HenryWythe (also spelled, during the early years,Wythes). In the third (1877) and fourth (1880)editions of his book, "The Microscopist", whichwere dedicated to the San Francisco Microscop-ical Society, there were short accounts concern-ing bacteria, although there was no mention ofthese organisms in the previous editions eventhough Leeuwenhoek was referred to briefly inthe earlier editions. To quote from the thirdedition (26):

"Bacilli are minute transparent, rod like bodies,sometimes jointed, and often exhibiting a vascil-lating motion. It is probable that the germs offungi develop themselves into these bodies when

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in a water containing animal matter, and intoyeast in a saccharine solution. The universaldiffusion of sporules of fungi in the atmospherereadily accounts for their appearance in suchfluids, and Pasteur's experiments are quite con-clusive."

Although born (1822) in England, Wythe hadbeen educated in Philadelphia where, in 1842,he was ordained as a Methodist minister. Hegraduated (1850) from the Philadelphia Medi-cal School and 12 years later became a surgeonin the Union Army. In this capacity he wasassigned to Camp Union in Sacramento in 1863,but soon resigned. By 1874 Wythe settled inOakland, where he became Professor of Micros-copy and Histology at the Pacific MedicalCollege in San Francisco (later Cooper College).The inclusion of the word "bacteriology" in theannouncement in 1885 of his lectures at theCooper College was probably the first appear-ance of that subject in a western curriculum. By1892, "Cocci, bacilli and spirobacteria" wereincluded in his syllabus for students, "Outlinesof Normal and Pathological Histology." He, too,gave lectures at meetings of the medical socie-ties. At the Anniversary Meeting of the SanFrancisco Medical Society, in November 1879,he addressed the assembly on the topic "Dis-ease-Germs." This was published (1879) in thePacific Medical and Surgical Journal as was alater (1882) report, "Organic Germs in Relationto Disease."

Another early consideration of bacteria wasincluded in the report of M. M. Chipman (2)entitled "Micro-organisms and Their Relationsto Human and Animal Life." This 21-pageaccount was the report (with Chipman as Chair-man) of the Committee on Public Hygiene andState Medicine made to the Medical Society ofthe State of California and was published in theTransactions of the Society for 1889.At the 28th annual meeting (19 to 22 April

1898) of the Medical Society of the State ofCalifornia in Fresno, the program included thefollowing papers on bacteriological topics:George L. Cole, "Sero-therapy," R. A. Fergu-son, "Malaria, and the Autogenous FebrileConditions in Kern Valley, and W. N. Sherman,"Practical Microscopy and Bacteriology for thePhysician." At the 30th meeting (17 to 19 April1900) in San Francisco, the program included:Henry A. L. Ryfkogel, "Present Pandemic ofBubonic Plague"; Maurice W. Brown, "TheDemonstration of Tubercle Bacilli in theUrine"; Daniel E. Osborne, "Typhus Fever";and William Ellery Briggs, "The Pathologyand Treatment of Infectious Diseases of theCornea."

INSTRUCTION AND RESEARCH INBACTERIOLOGY AT STANFORD

UNIVERSITYThe first president of Stanford University,

David Starr Jordan, an M.D. although he neverpracticed medicine, favored a strong sciencefaculty. One of the many wise selections hemade was the appointment in 1910 of HansZinsser to organize the work in bacteriology.Some instruction on nonpathogenic bacteriahad been included in the Department of Botanyas early as 1897-1898 by George James Peirce,who had received instruction in Alfred Fischer'scourse in Leipzig, had later worked for theMassachusetts State Board of Health, and,also, had investigated typhoid in Indiana whileserving as Assistant Professor at the University.Peirce's interest in bacteria is reflected in thisearly instructional work as well as in publica-tions on the root tubercules of the bur cloverand on bacteria of salt brines.Of some interest is the list of students during

the early period, and some of these who laterattained prominence included in 1897-1898:Wilfred H. Kellogg, Associate Professor of Pre-ventive Medicine and Hygiene, University ofCalifornia, and Director of Bacteriological Lab-oratories of the California State Department ofHealth; Clara Stoltenberg, Professor of Anat-omy, Stanford University; and Ray LymanWilbur, President of Stanford University. In1898-1899 the classes included LeRoy R.Abrams, Professor of Biology and Director ofNatural History Museum, Stanford University,and in 1899-1900, P. K. Gilman, ClinicalProfessor of Surgery, Stanford Medical School.Susan L. Dyer, well known as a civic-mindedcitizen, J. F: Illingsworth, Research Associate inthe Bishop Museum in Honolulu, and LouisKroeck, Professor of Biological Sciences of theCollege of the Pacific are listed in 1900-1901. J.I. W. McMurphy, Professor of Botany, StanfordUniversity, was included in 1907-1908. Theabove names were selected from a list of thirty-five persons who were taught in the years1897-1900.Although Joseph H. Wyeth was listed as

Professor of Microscopy and Histology in the1884 catalogue of the Cooper Medical College,bacteriology as an optional and obligatory sub-ject of study was not mentioned until 1893. Inthe Annual Announcement for that year, op-tional subjects for the 1st year included Bacteri-ology (Ball), and in the 2nd year one of the eightcourses listed was Theory and Practice of Medi-cine, Bacteriology and Physical Diagnosis.None of the available announcements gives theinitials of Professor Ball, but it is probable that

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this was Et. Benjamin Ball, who was in 1874 anAgrege at the Faculty of Medicine in Paris. Ithas not been possible to trace how and when hecame to San Francisco. In 1898 Albert Abrams,Professor of Pathology, had the "latest appara-tus for study of pathology and its cognatebranch-bacteriology." Beginning as early as1899, William Ophils, who obtained his doc-tor's degree at Gdttingen in 1895, was associatedwith Abrams, usually as Professor of Pathology,although one year (1903-1904) he was titledProfessor of Pathology and Bacteriology. In1897-1898 he had been a member of the staff ofthe University of Missouri. By 1907-1908Ophills and assistants (presumably H. R.Oliver, Assistant Professor of Clinical Pathol-ogy, and George B. Worthington, Assistant inPathology) were announced for a course in Bac-teriology in the first semester in the curriculumof the 2nd-year medical students. The texts tobe used were Muir and Ritchie, and McFarland,with Sternberg as an additional reference book.In 1908-1909 Robert Eckles Swain, AssociateProfessor of Chemistry, announced a practicallaboratory course in bacteriology.With the uniting of the Cooper Medical

College with Stanford University in 1909, thefaculty included the combination of Ophuls inPathology and the newly appointed Hans Zins-ser in Bacteriology. Ophuls was, by that time,assisted by Ernest C. Dickson. Four courseswere listed for Zinsser and assistants in theannouncement for 1911-1912. These were Gen-eral Bacteriology, Immunity, Bacteriology inRelation to Public Health, and Conferences onRecent Problems in Immunity. Dickson wasscheduled to teach Applied Bacteriology, whichincluded the examination of blood, stools, pus,urine, and the serum reactions.At the time of Zinsser's arrival on the Stan-

ford Campus in Palo Alto, the question of spacefor the future bacteriological laboratory arose.After rejecting an unsuitable space in the mainquadrangle, assignment was made of a sectionof the old museum building which had beenpartially destroyed by the earthquake. Duringthe first summer this space was equipped,partitions were erected, various plumbing andelectrical fixtures were installed, and an animalhouse was built. Although the work was notcompleted when the semester started in the fall,by Christmas there was available a fairly well-equipped laboratory sufficient for the staff andthe teaching of a small class. Because thislaboratory was late in completion, the firstcourse actually was given in an improvisedclassroom and laboratory in the corridor be-tween two of the museum buildings. The first

class consisted of eight men and one woman,and one-half of these persons later enteredbacteriology or pathology as a profession.Advanced students of this period included

Edward Carey, who assisted Zinsser in researchactivities and who later became head of theBender Laboratory in Albany, New York, H. J.Sears, later Professor of Bacteriology in theMedical School of the University of Oregon, andElouise Jameison, who was particularly welltrained in physics. Some of the students metweekly in Zinsser's home with Stewart Young,Professor of Physical Chemistry, to discussproblems relating physical chemistry to immu-nity. Zinsser at this time was engaged in thepreparation of the manuscript for the firstedition of his immunology text "Infection andResistance," which, however, was not publisheduntil after he went to Columbia University in1913. Zinsser has remarked upon the cordialrelations with F. P. Gay, at the University ofCalifornia, and his benefit from association withGeorge McCoy of the U.S. Public Health Serv-ice and others concerned with public healthproblems.

Arthur Meinhart, who had been with Zinsserat St. Luke's Hospital in New York City, servedas technical assistant in the department. An-other included in the early teaching staff wasMarcus C. Terry, later with the United StatesVeteran's Hospital in Knoxville, Iowa. Gros-beck Walsh, previously a medical officer for aRailroad Company at Manaos in the Amazonand later Chief Medical Officer for a large coaland iron company in Birmingham, Alabama,also was a student during this period. Anotherwas Frank Maltaner, later well known for hiswork at the State Health Laboratories in Al-bany, New York. Georgiana Spooner, later Mrs.Victor Burke, also assisted with the teachingand other activities. H. J. Sears, previouslymentioned, continued with teaching dutiesuntil he received the Ph.D. degree in 1916, atwhich time he accepted the position of citybacteriologist in Berkeley. In this position hefollowed Carl L. A. Schmidt, later Professor ofBiochemistry at the University of California.

During this period the bacteriological labora-tories of Stanford University took part in thestudy and control of local health problems.These included investigations concerning poli-omyelitis, tuberculosis, and typhoid outbreaksthat were traced to milk, problems of localwater supplies, and scattered outbreaks ofsmallpox. One of the latter began in an itinerantcircus, and examinations included the tatooedman, the bearded lady, and other freaks of theside show, together with a band of Sioux Indians

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and Mexican vaqueros!In 1913 Zinsser resigned from Stanford to

accept a position with Columbia University. In1923 he became the head of the Department ofBacteriology and Immunology in Harvard Uni-versity Medical School, and his success andrenown in this position are widely known. AfterZinsser's resignation, Wilfred Hamilton Man-waring, who had obtained his M.D. from JohnsHopkins in 1904, was appointed Professor inBacteriology and Experimental Pathology. Hewas well trained in pathology and bacteriology,having been associated with this work in theUniversity of Chicago and Indiana University.In 1907-1908, as Traveling Fellow of the Rocke-feller Foundation he had studied, among otherplaces, in the laboratories of von Wassermann,Ehrlich, and Emil Fischer.

In later years, beyond the scope of thisaccount, the Department of Bacteriology on thePalo Alto campus was developed by Manwar-ing, whereas the work in the Medical Schoolcontinued under the direction of Ernest C.Dickson. Although it was not published until1918, the initial work, which formed the back-ground for the extensive monograph on botu-lism, was included among the early researchinvestigations of the latter individual. In1913-1914, with Manwaring as Professor, thefaculty at Palo Alto included H. J. Sears asInstructor, Marcus Claude Terry as Assistant(Protozoology), and Russell Van Arsdale Leeand Arthur Richard Meinhart as Undergradu-ate Assistants. The curriculum was expanded toinclude the following courses: General Bacteri-ology, Medical Bacteriology, Industrial Bacteri-ology, Introduction to Immunity, Hygienic Lab-oratory Methods, Aseptic Technic, Seminaryand Journal Club, and Advanced Work (Thesisand Research). Professor Manwaring retired in1937 and died in 1960.

INSTRUCTION AND RESEARCH INBACTERIOLOGY AT THE UNIVERSITY

OF CALIFORNIAIt will be necessary to consider the beginning

of formal instruction in bacteriology at theUniversity of California in some detail becauseof the confusion of names which appear and,also, because there may well have been twoindependent beginnings. The instructors ofmedical, veterinary, and dental bacteriologywere appointed frequently for 1 year only, andoften one man served in two or more depart-ments. In this manner the early history of theseparate branches is somewhat interlocked as isalso the history of the other main beginning,

namely, that in the College of Agriculture,which later gave rise to the Department ofBacteriology. We will first develop the instruc-tion in the medical and related departmentsand later consider the significant role of theagricultural group.

It is possible, although no record has beenfound, that Joseph Le Conte, whose brotherJohn was the third President of the University,mentioned bacteria in his courses on naturalhistory, for his wide knowledge on various topicsis well known and also because of his interest inanimal diseases as is reflected by a note pub-lished in Science in 1886 on the cause of rabies(11). In addition, on 12 March 1890, he lecturedbefore the San Francisco Microscopical Societyon the topic, "The Germ Theory of Disease." Inthe schedule of studies of "Mr. D." published inthe report of the President of the University for1894-1896 there is mention of 24 units of zool-ogy, 4 of which were for bacteriology. It can bepresumed that this was credit for special studyfor no course in bacteriology (except in theMedical Department) was listed.Some interest, even some attempt at instruc-

tion, is noted in the courses listed in theannouncements of the Toland College of Medi-cine. As early as 1889-1890, Douglass W. Mont-gomery was listed as Professor of Pathology andMicroscopy, and in 1890-1891, Arnold A. D'An-cona, Professor of Physiology, gave instructionin physiology and microscopy and here the "useof the microscope is fully taught." It is unlikely,however, that either of these were concernedwith bacteria. According to the announcementof 1892-1893, George H. F. Nuttall, Associate inHygiene at Johns Hopkins, was engaged as"Special Lecturer on Bacteriology." That thisappointment was made with considerable prideis reflected by the following quotation from theabove source:

"The eminent position of Professor Nuttall as awriter and original investigator in this impor-tant branch of Medical Science bespeaks theincalculable advantage to be derived from hisinstruction. These lectures will be illustratedby original cultures and slides prepared byProfessor Nuttall personally. If possible, thelectures will be delivered under the UniversityExtension Series, in which case the professionat large, and such of the general public as maybe interested in medical progress will have anopportunity to attend."

Unfortunately, however, for numerous reasons,the appointment to join the Toland College ofMedicine was never consummated. No furthermention of the appointment has been found in

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the announcements of the College, and it is notmentioned in obituaries of Nuttall (7, 13).

In 1893-1894 Thomas Bowhill, listed as "Lec-turer on Bacteriology," gave lectures on theexamination, classification, and culture of bac-teria in Course no. 16, included in the curricu-lum of the 1st year of the medical course. JohnCampbell Spencer, raised in title from theprevious year of Assistant to Chair of Pathologyand Histology to Professor of Bacteriology, islisted for instruction in the postgraduate studies(San Francisco Polyclinics). It was furtherstated that:

"A bacteriological laboratory has been recentlysupplied with complete apparatus for the studyof the natural history of pathology and bacte-rial life and courses for each study will be givenas the demand arises."

In the next year, 1894-1895, Spencer, as

Professor of Pathology and Histology (Medi-cine) and Professor of Bacteriology (Post-Grad-uate), again was included in the faculty, as was

Bowhill. For the first time the Veterinary De-partment (California Veterinary College) ap-

peared, and Bowhill apparently gave such in-struction in bacteriology as was required by thisdepartment. In the following year, 1895-1896,Thomas Bowhill (Dean of the Faculty) was

Professor of the Principles and Practice ofVeterinary Surgery, Pathology, and Bacteriol-ogy. In this department, bacteriology was one ofthe topics listed for study in the 3rd-yearcurriculum.

In 1896-1897, with Spencer still in charge ofthe postgraduate medical department, two clin-ical assistants were added in the bacteriologicallaboratory. These were Charlotte B. Springer(Demonstrator in Bacteriology) and Mary A.Sperry. These appointments were continuedthrough 1898-1899. This year, however, Bowhillwas replaced in the Veterinary Department byHenry B. A. Kugeler as Lecturer on Pathologyand Bacteriology.

In 1897-1898 the Veterinary Department(with seven students) again made a change bythe appointment of Guido E. Caglieri, Lectureron Pathology and Bacteriology, to instruct the3rd-year students. Woodhead's "Bacteriology"is cited as the text. This arrangement lasted for1 year only, for in 1898-1899 Philip T. Brown,who also taught pathology, replaced Caglieri.The announcement further states:

"The importance and practical value of thissubject are becoming more and more evident,and therefore, its essentials will be fully consid-ered. The preparation of culture media and

methods of cultivating, staining and examiningbacteria will be described."

Although bacteriology was included in thecurriculum of the 4th year of the MedicalDepartment, no specific course was mentioned.Henry A. L. Ryfkogel was Director of theClinical Laboratories, and in 1899-1900 he wasgiven the title Instructor in Bacteriology, Di-rector of the Clinical Laboratory, and AssistantCurator. This year J. (sic) M. Mouser wasProfessor of Bacteriology. The same arrange-ment continued in 1900-1901, and the Veteri-nary Department failed to attract a singlestudent that year.

In 1901-1902 an important change was madein that bacteriology was included as one of thethree divisions of pathology for which AlonzoEnglebert Taylor, Professor of Pathology, was ingeneral charge. The actual instruction appar-ently was given by Ryfkogel, who was assisted inthe clinics by Harriet Symonds, as was instruc-tion in the Dental Department. Silas (sic) M.Mouser continued as Professor of Bacteriology.During the next few years various additions

and changes were listed. John S. Engs(1902-1903, 1903-1904) became Instructor inBacteriology in the Dental Department andlater (1904-1905) Acting Professor of Bacteriol-ogy and Pathology. Ryfkogel continued, butwith various changes in title including Instruc-tor in Pathology, Professor of Pathology andGeneral Microscopy, and Associate Professor ofSurgery. Philip K. Brown reappeared(1904-1905) as Instructor in Clinical Pathology.

In the College of Agriculture (Berkeley Cam-pus) the background for the beginning of bacte-riological instruction is related to the well-known work of Hilgard. In 1874 Eugene Wolde-mar Hilgard was appointed Professor of Agricul-ture, and although a laboratory in agriculturalchemistry was equipped for him in 1875, it wasnot until 1880 that the state Legislature passedan appropriation to provide special instructionin the arts and sciences pertaining to viticultureand enology, the theory and practice of fermen-tation. It is possible that these undertakingsgive the University of California priority in theactual establishment of an Agricultural Experi-ment Station in connection with a UnitedStates land grant college.By 1890-1891 Professor Hilgard, assisted by

L. Paparelli and G. E. Colby and later(1893-1894) by Hayne, gave a short specialcourse in the chemistry and analysis of mustsand wines and in practical vinification and laterin olive culture. Also, an enlarged (basementand three cellar rooms in the Experiment Sta-

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tion Building) and newly equipped viticulturallaboratory was described as "the only one of itskind in America." The experimental work ofProfessor Hilgard in the above topics, andothers, became outstanding and a source ofpride to the now firmly established College ofAgriculture, which throughout the years haspioneered in agricultural research. In additionto this increasingly important memorial, theCollege of Agriculture perpetuates his name inthe agricultural journal Hilgardia and also hasdesignated one of the buildings Hilgard Hall.

Although 'there appears no reason to believethat Professor Hilgard was trained in bacteriol-ogy (except for his understanding of yeasts aswas current at the time), he was of vitalimportance by virtue of his foresight in theappointments made to the staff of the College ofAgriculture. His wisdom in relation to inves-tigators for the diseases of plants will be referredto later, but of special interest was the appoint-ment on 12 January 1897 of Frederic TheodoreBioletti as Instructor in Wine Making andBacteriology. Bioletti was, at this time, a gradu-ate student in systematic botany. He had be-come interested in bacteriology and had ob-tained some knowledge of the fundamentals ofthe subject from C. W. Woodworth. AlthoughWoodworth was employed as an entomologist,he had received training in bacteriology inrelation to diseases of plants in the laboratory ofProfessor Burrill at the University of Illinoiswhere he had investigated broom corn disease.

In the beginning, Bioletti's official dutieswere concerned mainly with the wine cellar andpractical experiments on the production ofquality wines under California conditions. He isknown widely for this work developed duringthe long years of his association with the Uni-versity of California. In addition to the numer-ous publications from the College of Agriculturewhich bear his name, many practical articles onall phases of the wine industry are to be found inthe newspapers of the period. In addition someactual experiments on bacteria were reported.

In the announcement for 1896-1897, Agricul-ture 9B: Elementary Bacteriology was listed,and it is probable that this lecture course wasthe beginning of instruction in bacteriology onthe Berkeley campus. By the next year a labora-tory course was initiated, and the title of thelecture course was expanded to include "Lec-tures on Bacteriology and the Relation ofMicro-organisms to Agriculture, Industry andDisease." That year, in addition to the above,Bioletti was listed for: Agriculture 9C: Zymo-logy (lectures on the micro-organism of fermen-

zation), Agriculture 10A: Bacteriological Analy-sis (laboratory study of the methods of bacterio-logical investigation of water, milk, etc., andmethods of testing antiseptics and disinfect-ants), and Agriculture 25: Special Research inBacteriology (primarily for graduates). Also,Woodworth and Bioletti presented Agriculture9: Parasitic Plant Diseases.This arrangement, with minor changes, ap-

parently continued through 1901, and by thistime Bioletti's title had become Instructor inCharge of Viticulture, Olive Culture and Bacte-riology. Others who assisted during this period,particularly in the studies relating to the wineindustry, were G. E. Colby, Antonio Minotti dalPiaz, and A. P. Hayne. In January 1902,Bioletti obtained a 2-year leave to -go to Africafor work in the wine industry in that region.During this period he was instructor at Elsen-berg College, Cape Colony, South Africa. Uponhis return to the University, he continued vari-ous researches relative to wine, but did notpursue again his interest in bacteriology. Heremained actively interested in the problems ofthe wine industry until he became emeritus in1935. During the period that he was away thewine work was taken over by E. H. Twight(graduate of Ecole Nationale d'Agriculture deMontpellier), whereas the courses in bacteriol-ogy were assigned to Archibald Robinson Ward,who was titled Veterinarian in the ExperimentStation. Later, William Vere Cruess joined thestaff, and his interest in practical fermentationproblems is reflected in many publications.

Because the lecture notes of Bioletti, knownto have been used by 1900, are available, it ispossible to indicate the nature and extent of theinstruction. Somewhat ambitiously, the coursebegan:

"Though the study of bacteria may be consid-ered as one of the youngest of the sciences, notdating back in a strictly scientific sense muchmore than 35 years, it has become of immenseimportance and has widened out to such anextent that a short course like the presentcannot pretend to treat it fully in all details.Bacteria are being studied in three principalways. The botanist studies them from thebiological point of view investigating theirforms, life history and affinities, the chemistand manufacturer are particularly interested intheir action on the media in which they liveand the industrial uses to which they can beput, while the physician gives most of hisattention to their relations to disease and thevarious functions of the animal organism. Theobject of this course of lectures is to cover allthis ground in a general, and necessarily some-

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what superificial way and thus by a quickpreliminary survey of the whole field to gainsome knowledge of what has been accom-plished in bacteriology, of the present state ofopinion as to the nature of bacteria and of theindustrial and hygienic relations between bac-teria and ourselves. This is intended as a kindof popular exposition of the subject, which,taken in connection with the laboratory work inmethods of investigation and the study ofparticular forms, should serve as good prepara-tion for further work in any special branch ofthe study."

Examination of the subsequent lectures, how-ever, reveals that the course was largely botani-cal in aspect, with corresponding neglect of themedical phases, as might be expected fromBioletti's training. After the introductory lec-ture on historical notes, two lectures were de-voted to physical characteristics of bacteria(form, size, nuclear structure, motility, etc.)and two to reproductive processes (binary fis-sion and spores). Then followed a short quiz:

"What are the general forms of bacteria?How large are bacteria?What is the structure of the bacterial cell?What do you know of the color of bacteria?(Are bacteria animals or plants? Why?)Why do we consider bacteria to belong

to the vegetable kingdom?What are their nearest allies?"

Then followed classification (systems of Du-Jardin, Cohn, Zopf, Billroth, Mace, andMigula), distribution (including Lister's airspray and Tyndall's experiment), species de-scriptions and methods of study (gelatine [sic]plate, potato surface, guinea pig for tuberclebacilli, and use of hydrogen in culturing tetanusspores), soil bacteriology (nitrogen cycle), waterbacteriology, effects of physical and chemicalagents on bacteria and the bacteriology offermentation (alcoholic, acetic, lactic, and bu-tyric fermentations). In the laboratory course,the students were taught the essentials of tech-nique, and this was followed by exercises con-cerning the purification of yeast or variousfundamental procedures concerning fermenta-tion.

Apparently A. R. Ward was the first personassociated with the University of California forany considerable length of time who had re-ceived specialized training in bacteriology.Thus, with the change in individuals, the mainemphasis on bacteriological problems shifted todairy bacteriology and problems relating toveterinary sanitary science. Although the work

of Bioletti had been in the basement rooms ofthe old Agricultural Building, the laboratorieswere now housed in a renovated horse shedlocated where the Stephens Union now stands.From 1902-1906 teaching and research in bacte-riology were conducted in the Division of Veteri-nary Science of the College of Agriculture withA. R. Ward in charge. Beginning in 1904, Wardwas assisted by Clarence Melvin Haring, whotook charge of the laboratory work.

According to Arbura (1), Ward, who hadgraduated from Cornell in 1901 with the degreesof B.S.A. and D.V.M., was the first veterinarianappointed to the University of California fac-ulty. At Cornell, Ward had been a student ofVeranus A. Moore, who spent the summer of1903 in California, during which time Wardinitiated work on poultry diseases, and estab-lished a Poultry Pathology Station in Petaluma.In addition to his work on fowl cholera andavian tuberculosis, he published on anthrax,hog cholera, and blackleg, and was instrumen-tal in the establishment of a certified dairy inAlameda County. In this connection he servedas veterinarian and bacteriologist to theAlameda County Medical Milk Commission. Inaddition to the initiation of a course in dairymicrobiology at the University, he also taughtbacteriology at the San Francisco VeterinaryCollege. He remained in California until 1910,at which time he accepted a position as Terri-torial Veterinarian for the Philippine Islands. In1919 he was placed in charge of the Division ofPathology of the U.S. Bureau of Animal Indus-try. Later he left that position to engage incommercial and private dairy bacteriology workin Detroit.

In 1906, an appropriation by the State Legis-lature became available to establish at Berkeleya diagnostic laboratory for the State Board ofHealth. Ward's title was changed to AssistantProfessor of Bacteriology and Director of theState Hygienic Laboratory as will be explainedlater. In the announcement of courses, bacteri-ology was listed under the Department of Hy-giene. The laboratory work of instruction, re-search, and the routine diagnosis for the StateBoard of Health continued to function in theVeterinary Science Laboratory until 1907.As a result of the earthquake and fire on April

1906, the instruction in bacteriology in theMedical School was transferred to Ward inBerkeley. This did not have an immediate effectin expanding the teaching activities at Berkeleybecause during 1906-1907 there were only threestudents in the sophomore class in medicine.By the fall of 1907, a frame building for

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pathology and bacteriology had been erected onthe southeastern part of the Berkeley Campus.The first floor was occupied by the Departmentof Pathology under the direction of AlonzoTaylor. The second floor was devoted to theactivities of the State Hygienic Laboratory,instruction in bacteriology, and the AgriculturalExperiment Station work in Veterinary Science.These activities were so intermingled that whenWard resigned and Wilbur Augustus Sawyerbecame Director of the State Hygienic Labora-tory in 1910, it was difficult to decide whichequipment belonged to the State and which tothe Departments of Hygiene and Agriculture.Because of crowded conditions, provision wasfinally made to house the Division of VeterinaryScience in another building, and the HygieneBuilding, as it was then called, was enlargedand the name was changed to Pathology andBacteriology Building.About this time, bacteriology at the Univer-

sity of California advanced a considerable stepforward by the appointment in 1910 of Frede-rick Parker Gay as Professor of Pathology tosucceed Alonzo E. Taylor, who had returned toPhiladelphia. At the same time, and at Gay'srequest, Glanville Y. Rusk was appointed As-sistant Professor. In addition to other duties,Professor Gay was requested to give some un-dergraduate instruction in bacteriology and toorganize the course in medical bacteriologywhich was badly in need of attention. Thiscourse numbered about 17 students.

In addition to the above, the following wereavailable for instructional and research work:Margaret Henderson (soon to retire as Mrs.Wilbur A. Sawyer) as Instructor, and John N.Force as Assistant Professor of Hygiene. Ayoung medical student, Oswald H. Robertson(later Professor of Medicine at the University ofChicago), conducted some work on the problemof rabies. By 1911, another addition to the staffwas made possible, and this was the appoint-ment of John G. Fitzgerald as Associate Profes-sor of Bacteriology. During these same years,Ivan Clifford Hall served as an assistant in thedepartment in the capacity of technician in thepreparation of media and staining solutions. Atthe same time he was employed at the CutterBiological Laboratory, and in 1913 he resignedfrom the University to assume a full-time posi-tion with the Cutter Laboratory.

In 1913 Fitzgerald resigned to become Di-rector of the newly established Connaught Lab-oratories in Toronto, and he was succeeded byKarl Friedrich Meyer who, however, resigned in1915 to join the staff of the George WilliamsHooper Foundation for Medical Research,

which had been opened on 7 March 1914 andwas located on the medical campus in SanFrancisco. At this time Ivan C. Hall wasbrought back to the University as AssistantProfessor of Bacteriology. In 1913 the AcademicSenate of the University ruled that the lowerdivision course, General Bacteriology andMicrobiology in the Department of Pathologyand Bacteriology, be offered as a cultural coursefor students in agriculture, hygiene, and sani-tary engineering, social sciences and naturalscience. Meyer was requested to give the coursewhich entailed 5 h of lecture each week andlaboratory sections from 7 to 10 p.m. In 1914,the enrollment included 286 students.One needs only to scan the bibliography of

the papers published during this period to seethat research was pursued actively. Gay, to-gether with his associates and students, pro-duced some 40 papers between 1910 and 1914.The various problems ranged from Rusk's com-parison of chemical and microchemicalmethods for glycogen determination to V. Ade-lung's study of the antigenic properties of thepoison oak glucoside to Fitzgerald's review ofthe history of immunity in America. Severalwell-defined lines of investigation emerged. Sixarticles referred to the origin of antibodies,whereas four others were concerned with themechanism of the fixation reaction. A series offour other papers, representing collaborationbetween F. P. Gay and T. Brailsford Robertson,Associate Professor of Physiological Chemistryin the Department of Physiology, dealt with theprotein fraction responsible for specificity.These reports detailed experiments on caseinand its split products, and on the combinationwith globulin to form a new product, globulincaseinate. The importance of this pioneer workis reflected in the later development of thetopic, notably by Landsteiner. Other articlesreported experiments on methods of typhoidvaccination and the experimental typhoid car-rier condition in rabbits.

It has been indicated that the early courses ofbacteriology introduced and taught in the Col-lege of Agriculture by F. T. Bioletti were takenover by A. R. Ward and were the background,through the Department of Hygiene and laterthe combined Department of Pathology andBacteriology, for the Department of Bacteriol-ogy in the University of California. Continuingthis story has led us astray from the College ofAgriculture, but we desire to return to it now inorder to discuss others interested in the agricul-tural applications of the new science in additionto the viticultural experiments of Hilgard andBioletti.

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By far the most important of these are theextensive studies relating to plant pathology.Fortunate indeed was the selection-by Hilgardof Ralph E. Smith, in 1903, as Plant Pathologistto the Experiment Station of the University.The first course in plant pathology was offeredin 1904 and continued later by R. E. Smith, C.0. Smith, and E. B. Babcock. In May 1905, A.M. West was added to the staff as AssistantPlant Pathologist, and in July of the same yearE. H. Smith received a similar appointment.Because a large portion of the investigativework required field experiments and study, anumber of individuals were appointed duringthe early years. These included B. J. Jones, E.B. Babcock, R. J. McKeown, C. 0. Smith, H. J.Ramsey, T. F. Hunt, N. D. Ingram, and forshorter periods, W. H. Volck, R. Sale, 0. Butler,and A. B. Mitzmain.By 1906 it was possible for the Plant Patholo-

gist to report on the "main lines of work" whichwere in progress:

(i) Walnut blight: this disease, most serious inthe southern part of the state where the com-mercial crop was principally grown, was appar-ently peculiar to the west coast. The disease wasshown to be a blight of a bacterial nature andthe etiologic agent, Pseudomonas juglandis, wasisolated from diseased tissue described and usedin the artificial reproduction of the disease.

(ii) Pear blight: the investigation concerningpear blight disease was financed by an appro-priation direct from the State Legislature, andthe Experiment Station staff was aided by M.B. Wiate of the U.S. Department of Agriculturewho, at the time, was the leading authority onpear blight.

(iii) Lemon rot: this disease, commonlytermed "brown rot," was a peculiarly virulent,rapidly spreading decay of lemons in the pack-ing house and marketing box. Contributionsfrom the industry made research on this diseasepossible, and it was discovered quickly that thecause was a fungus theretofore undescribed.The organism was studied in detail and de-scribed as Pythiacystis citrophthora, and ofpractical value was the finding that the sporeswere not developed on the fruit but rather in thesoil of the orchard. The chief source of infectionwas the water of the washing tank.

(iv) Beet blight: another disease, upon whichresearch was possible due to grants from theindustries affected, was a peculiar stunting ornondevelopment of the sugar beet.

(v) Peach blight and "shot hole fungus": the"shot hole fungus" of the apricot was importantalso as an agent in a similar disease in peachesand also almonds. Spraying with Bordeaux

mixture proved effective in control.Other diseases investigated included "blos-

som-end rot" of tomatoes, asparagus rust, androse disease. Another important contribution ofthis group resulted from the studies of Clayton0. Smith regarding further proof of infectiousnature of crown gall, with particular referenceto the host plant. The importance of the investi-gations of the above group concerning the vari-ous diseases of plants was sufficient to attract aconvention of the American PhytopathologicalSociety at Berkeley in August 1915. R. E. Smithhad reviewed the progress of this research in thepresidential address of the Western AmericanPhytopathological Society during the meetingof this group at Corvalis, Oregon, in December1914.

In addition, one other topic investigated by amember of the staff of the Agricultural Experi-ment Station involved the field of soil bacteriol-ogy. For this work, Charles B. Lipman, laterDean of the Graduate School of the University,was appointed in 1909. The majority of the earlypublications of Lipman were concerned with theantagonistic effect of ions in relation to bacte-rial growth or metabolic processes. In additionto research activities, he initiated a course ofinstruction in soil bacteriology.

INSTRUCTION AND RESEARCH INBACTERIOLOGY IN SOUTHERN

CALIFORNIAAs will be discussed below, the present School

of Medicine of the University of Southern Cali-fornia, which opened in 1928, had its roots in theCollege of Physicians and Surgeons, whereasthe School of Medicine of the University ofCalifornia, Los Angeles, grew out of the LosAngeles Medical Department of the Universityof California.

According to Kress (10), the State of Califor-nia chartered the University of Southern Cali-fornia in 1880, and the College of Liberal Artsbegan the following year. Five years later(1885), the Medical Department was inaugu-rated with J. P. Widney (A.M., University ofPacific, and M. D., Toland Medical School,1866) as Dean. The original faculty does not lista Professor of Bacteriology, but it is noteworthythat C. A. H. de Szigethy, Professor of Pathol-ogy, was listed also as professor of genitourinaryorgans. The first session of the College was heldin a brick building at 447 Aliso Street, but in1895 the College moved to a more extensive siteextending from Buena Vista to Castelar, be-tween Ord and Alpine Streets. In addition to aFounder's Building (a three-story structure fac-ing Buena Vista) which was erected that year,

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the Hendryx Pathological Laboratory wasopened in 1899. At the dedication of the latterbuilding, it was stated by H. G. Brainerd, thenDean of the Medical College, that "the bacterio-logical laboratories [of the United States] prac-tically date since the day of Koch's greatdiscovery of the tubercle bacillus." Although by1901 the College had 87 students and 31 mem-bers of the faculty, the maintenance became tooexpensive and the school was discontinued by1909. In that year the College of Medicine of theUniversity of Southern California became theLos Angeles Medical Department of the StateUniversity of California under the Regents ofthe University at Berkeley. Beginning that year,all new students admitted to the medical curric-ulum were required to complete the first 2 yearsof the program on the Berkeley campus wherethey received instruction in Pathology underAlonzo Engelbert Taylor, and Philip Rahtjen,M.D., served as instructor in bacteriology andStanley P. Black, A.B., M.D., served as Profes-sor of Pathology and Bacteriology in Los Ange-les. From 1911-1913 the chair of bacteriology inthe southern branch of the University of Califor-nia Medical School was occupied jointly byWalter B. Brem and Herman Zeiler. The LosAngeles Medical Department of the Universityof California continued to offer undergraduatecourses until 1914, when it became the SelwynEmmett Graves Memorial Post GraduateSchool. When the Medical Department becamea unit of the University of California, the thenrapidly growing University of Southern Califor-nia was left without a medical curriculum.

In 1903 a second College of Medicine waschartered by the state in Los Angeles. This wasknown as The College of Physicians and Sur-geons, and on 13 August 1904 the cornerstonewas laid for a "new and elegant" building at 516East Washington Street. The second floor wasdevoted to pathological, bacteriological, andphysiological laboratories, and each studentwas furnished with a Bausch and Lomb micro-scope with oil immersion lens. The originalfaculty roster lists Ernest Bryant Hoag, B.S.,A.M., M.D., as Professor of Pathology, Bacteri-ology and Clinical Microscopy, and Rose A.Bebb, M.D., as Instructor in Bacteriology andClinical Microscopy. Between 1905 and 1910this college graduated approximately 40 stu-dents. In 1909, the College of Physicians andSurgeons became the Medical Department ofthe University of Southern California. The fa-culty under the new union lists Andrew Fre-mont Wagner, A.M., M.D., as Associate Profes-sor of Bacteriology and Pathology.

As mentioned above, it would seem that thefirst bacteriologist worthy of note in the south-ern section of the state was Stanley P. Black, apupil and protege of Christian Fenger, whocame to Los Angeles in 1897. Black was the firstto teach the subject in that area and did muchto introduce bacteriology in the practice ofmedicine and to stimulate public health controlwithin the region. He served as Professor ofBacteriology in the Medical Department of theUniversity of Southern California from theopening of the Hendryx Laboratory in January1899, until 1911. The reference source materialat times lists Black as Professor of Bacteriology,Histology and Clinical Microscopy and also asProfessor of Pathology and Bacteriology. EthelLeonard, Associate in Bacteriology beginning in1903, was promoted to Professor in 1908 and waselected to succeed Professor Black.To quote from the 14th Annual Announce-

ment (1898-1900) of the University of SouthernCalifornia concerning the course of instruction:

"Professor Black teaches Bacteriology by practi-cal laboratory work. Each student prepares hisown culture media. The first half of the course isdevoted to the cultivation of the principal non-pathogenic bacteria, so that the technique maybe thoroughly mastered. Then the principal path-ogenic bacteria are studied. Particular stress islaid on the diagnosis of diphtheria, typhoid(Widal's test) and tuberculosis. Thorough drill isgiven in the more practical methods. Four con-secutive hours on three days of the week duringtwo months are devoted to this course."

At this time the course was included in thecurriculum of the 3rd year, but later it wasmoved to the 2nd year. With Leonard, instruc-tion was expanded to include animal inocula-tion, the study of anaerobes, and special ad-vanced instruction.

Ethel Leonard was, in the early years(1903-1907), the bacteriologist of the city of LosAngeles and in that capacity established thefirst laboratory for the city. She was succeeded,in the spring of 1907, by Jessie Horton. Thislaboratory was first located in the tower in asmall attic room of the old City Hall on Broad-way between 2nd and 3rd Streets. In 1904 thelaboratory was moved into the small annex atthe side and rear of the City Hall. With themore commodious quarters (still only 20 by 30feet) the work increased materially. During thisperiod, the routine included regular trips up theriver for sanitary inspection, with bacteriologi-cal counts on gelatin being made on the water,milk counts, diphtheria cultures, Widal tests on

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dried blood, sputum examinations for the tu-bercle bacilli, and smears for gonococci.

In San Diego, H. A. Thompson was the firstcity bacteriologist. He was appointed in 1909;previously, the work had been done by F. H.Mead, health officer. Thompson continued inthat capacity except for a brief period duringthe war (1917-1919) when the work was done bya Miss Laneroux.

DEVELOPMENT OF THE STATEHYGIENIC LABORATORY

It has been noted earlier that the history ofthe State Hygienic Laboratory was connectedintimately in many ways with the developmentof the history of bacteriology at the Universityof California. Thomas M. Logan, trained atCharleston College and with an M.D. from theMedical College of South Carolina and who haddescribed the 1850 and 1852 cholera epidemicsin Sacramento, was the motivating force inpublic health in California. He organized theCalifornia State Board of Health in 1870 andserved as its first Secretary until his death in1876. He recognized the necessity not only offull support of the medical profession, but alsoof inserting public health into the curriculum ofthe medical schools and of the entire Universityas well. In 1872, the Regents of the University ofCalifornia established a Professorship in Sani-tary Science and appointed Logan "so thatevery graduating class can go out properlyinformed in the great art of preserving theindividual and the public health." The patternsof close relationship between the State Boardand its departments with the University appro-priately culminated in establishment of theState Hygienic Laboratory. At the time, themoving spirit in the establishment of the StateHygienic Laboratory of the State Board ofHealth was George Frederick Reinhardt, Uni-versity Physician and Professor of Hygiene inthe University of California. Largely through hisinfluence the University contributed housingand the services of professional staff, and theState Legislature legalized the existence of thelaboratory. On 1 July 1905 it came officially intobeing on the university campus in the smallone-story frame Veterinary Science Building(built over a horse-shed) on the bank of Straw-berry Creek, as has been mentioned. In its earlyyears, the laboratory served the State Board ofHealth by making bacteriological tests for phy-sicians and health officers, and also made cer-tain chemical tests of foods. This last functionwas under the supervision of Professor M. E.Jaffa, and on 1 January 1908, this was made into

a separate State Food and Drug Laboratory withJaffa as Director.The University assigned the duties of Director

of the new State Hygienic Laboratory to Ar-chibald R. Ward, Assistant Professor of Bacteri-ology. This was in addition to his teachingresponsibilities. A full-time Assistant, MargaretHenderson, was appointed. Students were em-ployed as helpers in the laboratory as needed.When Ward resigned from the University ofCalifornia, relinquishing his position as Di-rector, the Regents of the University of Califor-nia appointed Wilbur A. Sawyer to this positionon 1 July 1910, but the position was then on apart-time basis. On 1 July 1911 the Directorshipwas made full-time, and the salary was there-after paid by the State Board of Health insteadof the University. Sawyer continued to serve asDirector until he resigned in August 1915 toaccept the position of Secretary and ExecutiveOfficer of the State Board of Health and laterwas well known as Director of the InternationalHealth Division of the Rockefeller Foundation.The position of Assistant (full-time bacteri-

ologist) was given up by Margaret Henderson on1 July 1908, when she became Instructor in theDepartment of Hygiene of the University ofCalifornia with duties concerning the teachingof bacteriology to the medical, engineering,agricultural, and other students. She was suc-ceeded by Elsie Cole, who occupied the positionfor 1 year, and she was followed by DorotheaVan Orden. The new title of Chief Bacteriolo-gist was held successively by C. W. Bonynge (1March to 30 June 1910), C. B. McGlumphy (1July 1910 to 1 September 1911), and Eleanor C.Seymour (27 September 1911 to 30 April 1912).Esther Skolfield was Acting Chief Bacteriologistfrom March 1 until Jacob Casson Geiger be-came Chief Bacteriologist on July 1, 1912.Thereafter Skolfield served as Assistant Bacte-riologist until 15 March 1914, when she re-signed and was succeeded by Violet M. Bath-gate. On 20 January 1914, Grace A. Macmillanwas appointed Laboratory Assistant, and soonafterward undertook the performance of theWasserman tests, with which she had had pre-vious experience.Both routine work and research were carried

on from the beginning. Mailing cases for send-ing specimens and printed directions were sentto the smaller cities and the country districts,for the larger cities had made provisions alreadyfor some public health laboratory service. In thebeginning, examinations of diphtheria culturesmade up a large proportion of the work. At thetime there was great interest in exploring the

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possibilities of controlling diphtheria outbreaksby discovering all carriers through repeatedthroat and nose cultures and isolating all per-sons harboring diphtheria bacilli as determinedby morphological and staining characteristics.With the cooperation of health officers andeducational authorities, large numbers of schoolchildren and the contacts of reported cases wereexamined repeatedly and, as an example of oneof the earliest of field studies of the laboratory,the systematic control of a diphtheria outbreakat the Southern California State Hospital (forthe insane) was attempted in June and July of1908. This involved the taking of repeatedcultures from the 1,115 people in the institutionand the prolonged segregation of many personson the basis of the laboratory results. Theessential limitations of the method, even thoughthoroughly applied under exceptionally favora-ble conditions, became apparent.At this time examinations were made for the

diagnosis of the following diseases: diphtheria,malaria, typhoid fever (Widal test and fecalexaminations), and tuberculosis. Water andmilk were examined bacteriologically for evi-dence of contamination. Later the laboratorymade routine examinations also for syphilis(Wasserman test), gonococcal infection, rabies,plague, anthrax, hookworm disease, and in factany conditions of public health interest. Specialinvestigations involved field and laboratoryinvestigation of many diseases including diph-theria, bubonic plague, human glanders,human rabies, poliomyelitis, typhoid outbreaksand carriers, scarlet fever, and dysentery.Although it well deserves mention, space does

not permit further elaboration on the specificproblems which occupied the time and atten-tion of the energetic staff of the State HygienicLaboratory. One needs only to refer to thepublished papers of the period to observe thatthe topics which were discussed above werefully investigated and, also, other more transi-tory problems were studied as they arose. Theactivity of the laboratory in the investigation ofcertain diseases which were attacked by thecombined efforts of this group and others will bementioned later.

California was such a large area to serve thatthe need for branch laboratories soon becameevident. Their principal purpose at first was togive more prompt reports on diphtheria culturesand other diagnostic specimens, but later theyalso administered the Pasteur treatment forrabies by using material manufactured at themain laboratory. The following branches wereestablished with part-time bacteriologists incharge. Southern Branch in Los Angeles was

established 1 November 1909, Stanley P. Blackin charge until 16 January 1914, when Walter V.Brem took over. San Joaquin Valley Branch inFresno was established 1 August 1910, C. W.Bonynge in charge until September 10, 1910;Ernest Pring from then until 31 October 1910and R. A. Forrest to 4 February 1911. Aftertemporary closure, the laboratory was reopenedunder W. W. Cross on 15 August 1911. NorthernCalifornia Branch in Sacramento was estab-lished 1 March 1912 with F. F. Gundrum incharge.

STUDIES ON SPECIFIC BACTERIALDISEASES, TOGETHER WITH SOMENOTES RELATIVE TO THE HISTORYOF PUBLIC HEALTH ACTIVITIES

It is not out of place to consider briefly someof the available information concerning theearly medical thought of the region as a back-ground for more specific accounts of the variousdiseases. A list of the early medical journalspublished on the Pacific Coast which weredevoted to these accounts may be found inHarris (9) and in Gardiner (8). These included,with the date of the initial number: Northwest-ern Medical and Surgical Journal, 1853; SanFrancisco Medical Journal, 1856; CaliforniaState Journal of Medicine, 1856; MarysvilleMedical and Surgical Reporter, 1858; PacificMedical and Surgical Journal, 1858; Transac-tions of the Medical Society of California, 1858;California Medical Gazette, 1868; San Fran-cisco Medical Press, 1860; Western Lancet,1872; Pacific Journal of Health, 1870; SouthernCalifornia Practitioner, 1886; Pacific Record ofMedicine and Pharmacy, 1886; and SacramentoMedical Times (Occidental Medical Times),1887.As early as 1855, Henry Gibbons, lecturing

before the Pioneer Society of Sacramento, re-ferred to the three worlds: "The sensible, thetelescopic and the microscopic." Although car-bolic acid was mentioned by 1871, it was notuntil 1879 that the Listerian technique was usedin laboratories on the west coast. The accept-ance of the germ theory of disease was not with-out considerable confusion and hesitancy, yet by1871 Gibbons referred to the "poison germs ofPettenkofer" in discussing cholera and, in 1874,Logan used the term "germs" in referring to ayellow fever epidemic outside California. Also,to quote from Harris (9), "Cluness in 1875regarded sewage and topography not as causalbut as predisposing conditions to scarlet fever,and in 1877 Van Wyck said the same fordiphtheria."That others mixed the germ theory with the

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older belief concerning fungi as the cause ofinfections is illustrated by the reference by JohnKunkler, assistant army surgeon at Camp Stan-ford and graduate of Cooper Medical College, tothe fact that an outbreak of measles in 1862 wasdue to fungi, but his father, E. A. Kunkler,stated "zymotic disease was due to little frag-ments of organic substance arising from deadmatter in polluted air." Even the outstandingmicroscopist of the day, J. H. Wythe, mixed theidea of disease germs and fungoid growth.Others, too, mixed the theories or were slow toaccept the new, but finally the doctrine ofListerism was established. By the 1880s and1890s the bacterial origin of many diseases wasaccepted as revealed by the Reports of the StateBoard of Health.A legislative act creating a California State

Board of Health was approved by Governor H.H. Haight on 8 March 1870. In the creation ofthis Board, California was preceded by Massa-chussetts, but only by a year. The Californiabody was organized immediately and soon be-came active, and the early problems consideredby this worthy group are recorded in the pub-lished Reports. Reorganization of the CaliforniaState Medical Society was accomplished by theBoard in October of 1870. The newly electedpresident, Thomas Logan, reviewed the medicalprogress of the State from 1856. In 1871 theAmerican Medical Association convened, with156 in attendance, in San Francisco. The Asso-ciation also honored the city with the 45thAnnual Meeting in 1894. Likewise, the SeventhPan-American Medical Congress convenedthere in 1915.

It is beyond the scope of this review toconsider in detail the many interesting factsconcerning the epidemiology of the variousdiseases in California and the neighboringstates although, because of their local impor-tance, we must include discussions of certaindiseases. We refer again to Harris (9) and othersources for a general background.As early as 1785, literature on the prevention

of smallpox was received in California fromSpain, but it remained until 1797 for officialquarantine laws to be invoked (Santa Barbara).According to Cook (3), smallpox was not presentprior to 1806, but cowpox was noted in or priorto that year. Although only the bare details ofthe arrival of vaccine in 1817 are available, it isrecorded that in 1821 some 40 children werevaccinated with lymph brought from Lima. By1828-1829 the disease was in epidemic form onthe California coast, and vaccination was prac-ticed on several thousand persons. Anotherepidemic occurred during the period 1837-1839,

and others occurred in 1844 and 1868. It isinteresting to note that the first public hospitalin California was one result of the 1844 seige.Likewise, the first Board of Health, formed byfive citizens in Monterey, was another. Addi-tional epidemics occurred in 1868-1869,1876-1877, and in 1888. Two attempts, bothunsuccessful, were made in the 1880s to manu-facture smallpox vaccine from California calves.Measles appeared in epidemic form as early

as 1806 with a recurrence in 1826-1827, and anepidemic of unknown sort, possibly influenza,was responsible for the deaths of thousands ofIndians in 1829-1833.Important contributions to the study of coc-

coidiomycosis were made by Emmet Rixford,who first found the organism in California, andby William Ophuls, who proved the organismwas a fungus and not a protozoa (14).

Cholera was a serious problem in 1850 andagain in 1852. Accounts vary, but in the 1850epidemic it has been stated that 15% of thepopulation of Sacramento, 10% at San Jose, and5% at San Francisco died of the disease. Toquote from an early account (19) concerning thelatter epidemic:

"Cholera again visited the city in the fall of thisyear; though its ravages were slight. Howevermuch may be said for the general healthiness ofthe place, little praise can be given for the verydirty state in which the greater part was allowedto remain-and nearly the same may justly besaid of its condition in 1854. The streets werethickly covered with black rotten mud. Thesewere the proper dunghills of the town, and weremade a general depot for all kinds of rubbish andhousehold sweepings, offals and filth. Sometimesthe rains came and scattered the abominablestuffs, carrying part of them into the bay; at othertimes the heats gradually dried them up. Rats-huge, fat lazy things, prowled about at pleas-ure, and fed on the dainty garbage. The pedes-trian at night, stumbling along the uneven pave-ments, and through streets that were only a seriesof quagmires, would occasionally tread on theloathsome, bloated, squeaking creatures, andstart back in disgust and horror, muttering acurse or two at such a villainously unclean town.These animals abounded in such great numbersthat entire sacks and barrels of flour and breadhave been destroyed by them in a single night in astorehouse. They were of several varieties, eachdiffering in color."

By 1893 a typhoid epidemic was studiedbacteriologically and traced to milk contami-nated with human dejecta. In the previous year,amoebic dysentery was considered and Wythe,in 1891, had reported Loeffler's work on thecultivation of the diphtheria organism. This was

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followed, by 1895, by the use of throat culturesand antitoxin (secured from New York City) inSan Francisco and Los Angeles (10). To combatthis disease, California was possibly the firststate to supply free antitoxin to the needy.Tubercle bacilli were found in milk in 1887 andactinomycosis in cattle by 1888. Other diseases,including tetanus, anthrax, glanders, and lep-rosy, were observed, but no outstanding bacte-riological contributions were made.The report, in 1892, from Covelo near Marys-

ville, of a fatal case of rabies is recorded in theannals of California medical history. In 1899 thedisease was reported to have been present inSouthern California, reappearing in 1906. InNovember of 1909 there was an extensive out-break in dogs in Pasadena, and at that time theinvestigations of rabies was begun by the StateHygienic Laboratory. In 1910 and subsequentyears, rabies spread steadily northward throughterritory in which the disease had never beforebeen known. Brains from dogs and other ani-mals (186 brains were examined, with 122positive by 11 November 1910) were examinedfor rabies in the State Hygienic Laboratory, inthe pathological laboratory of Stanley P. Blackin Los Angeles, and in the laboratory of the Cityof Los Angeles. Of these examinations, 37 weremade at the State Hygienic Laboratory, withpositive results in 23 cases. These examinationsincreased in number, with positive diagnosisbeing made either by the Negri bodies or byanimal inoculation, and in 1910-1912, 243 ani-mal brains were examined with 188 positive,and in 1912-1914, 770 were examined with 606positive.The treatment of the persons bitten presented

a difficult problem for there was no "PasteurInstitute" for the treatment of rabies on thePacific coast. The State Hygienic Laboratorysecured virus for treatment of persons at firstfrom the Hygienic Laboratory of the U.S. PublicHealth and Marine Hospital in Washington,D.C., and administered the material to localcases in Southern California through the labora-tories there. In 1910 the Director of the StateHygienic Laboratory, W. A. Sawyer, urged thatthe State Board of Health authorize the estab-lishment of a "Pasteur Institute" as a depart-ment of the laboratory. In this he was supportedby Frederick P. Gay, then Professor of Bacteri-ology at the University of California. Not onlywas valuable time being lost under the existingmethod, but it was understood that the Hy-gienic Laboratory in Washington had no inten-tion of continuing to supply the needed virusindefinitely. In fact the supply ceased to be

available at about the time other provisions weremade in California. The nearest Pasteur Insti-tutes for making and administering the viruswere in St. Louis, Austin (Texas), Minneapolis,and Chicago.On 18 May 1912, the State Board of Health

authorized the manufacture of the Pasteur virusat the Hygienic Laboratory and its administra-tion to those who needed it and were unable topay the high cost of obtaining it otherwise. Aspecial room was prepared for removing andhandling rabbit cords with due precautions forasepsis. The laboratory was inspected by arepresentative of the U.S. Public Health Serviceon 3 June 1912, and after that day all virus usedby the laboratory was of its own manufacture.Before the end of the biennium ending 30 June1912, Pasteur treatments with the laboratory'svirus had been given at the main laboratory inBerkeley, its branches in Sacramento, Fresno,and Los Angeles, and by deputized bacteriolo-gists in the laboratories of the SacramentoBoard of Health, the Los Angeles Board ofHealth, the San Francisco Board of Health, andthe Letterman General Hospital of the U.S.Army in San Francisco. In these laboratories,119 persons were treated from 1 September 1911to 30 June 1912. One hundred of these personshad been bitten by animals, the brains of whichshowed Negri bodies.A still larger number was treated in the next

biennial period (1912-1914), and two new sta-tions for the administration of the virus werearranged for at the laboratory of the San DiegoBoard of Health and the U.S. Naval Hospital atMare Island. The number of persons treated inthe several laboratories was 466. In 330 casesNegri bodies had been found in the brains of thebiting animal or the diagnosis had been con-firmed by the inoculation of laboratory animals.In the last half of the year 1914, only 87 personswere treated in the laboratories mentioned, forthere was a decided drop in the monthly num-ber of persons requiring treatment in October1914, and a lower demand thereafter.The exact history of typhoid in the state is not

available and need not be included, for to do sowould lead into the question of the early sani-tary problems of the state and the attempts atsolution. In the later history, it is of interest thatin addition to the usual Widal tests on driedblood specimens sent through the mails, theState Hygienic Laboratory, for a number ofyears beginning September 1908, was ready tosend out a small tube of bile with the Widaloutfit for use in making blood cultures as adiagnostic measure in suspected cases of ty-

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phoid fever. Although there was little demandfor the culture outfits on the part of physicians,the outfits were used to advantage in fieldinvestigations by the laboratory staff. Thismethod, originally suggested by Peabody, wasfound to be practical and convenient for it re-quired only about 15 drops of blood from the earof the patient and frequently demonstrated thepresence of typhoid bacilli in the blood duringthe 1st week of the disease.One of the principal motives of the investiga-

tions of water for the presence of colon bacilli asevidence of population was protection againstwaterborne typhoid fever. Outbreaks of thisdisease were traced to various causes, but thepollution of drinking water was of major impor-tance with respect to the number of personsinvolved. An outstanding outbreak definitelyproved to be due to a contaminated watersupply was the one at Healdsburg from 15 Julyto 22 September 1914. In the town, with apopulation of 2,100, there were 90 cases oftyphoid fever with 7 deaths. The piped publicwater supply was incriminated, and an interest-ing feature of this study was that the pollutedwater passed through 42 yards of gravel to reachthe nearest of the wells.A type of investigation of special interest at

the time was the unraveling of mysteriousoutbreaks of typhoid fever caused by carriers.Two of the investigations carried out by theState Hygienic Laboratory before 1915 hadfeatures of special interest and deserve mention.In the first of these studies, 27 cases of typhoidfever among sailors were traced to one carrier, awinch driver whose work had nothing to do withthe food of the crew. Another carrier whobecame widely known was a woman innocentlyresponsible for infecting 93 persons in Hanfordin March of 1914. The cases were all traced tofood served at a church dinner and supper, andthe carrier was discovered through the work ofthe laboratory staff of the Hygienic Laboratory.Unique features of the outbreak were the free-dom of the town from cases due to other sources,incubation periods as short as 3 or 4 days inextreme cases, and the spread of the diseaseprimarily through a dish of cooked spaghetti.The experimental work showed that suchdishes, if large, are very difficult to sterilize byordinary cooking. The Hygienic Laboratory un-dertook the manufacture of typhoid vaccine andits free distribution to physicians on 1 March1914. This vaccine was the Gay-Claypole sensi-tized antityphoid vaccine.The announcement in 1912 by M. J. Rosenau

of the transmission of poliomyelitis by the

stable fly, Stomoxys calcitrans, was of especialimportance to California for the disease wasprevalent. Immediate cooperative studies wereperformed by the State Hygienic Laboratoryand W. B. Herms of the College of Agricultureof the University of California. It was notpossible to transmit the disease from experi-mentally infected rhesus monkeys to well onesunder the conditions of the experiments throughthe agency of the stable fly. Later, Sawyerreported the transmission of poliomyelitis to arhesus monkey from the rectal washings of aboy.We come now to a sad but true story (4). It

has been told often and the accounts are varied,but no one can relate the tale with pride. Weshall condense these remarks to a brief surveyfor the details of the exact condition are availa-ble in many publications including the officialreports of the Surgeon General of the UnitedStates. On 16 March 1900 in San Francisco, theAssistant City Physician suspected plague to bethe cause of death of a Chinese man seen in aChinese mortuary. In anticipation of just suchan actuality, Surgeon General Wyman, Chief ofthe U.S. Marine Hospital Service, had detailedcertain of his personnel to acquaint themselveswith the available knowledge regarding plaguesince the disease had spread recently fromBombay to Hong Kong, the Philippines, andJapan. It is indeed fortunate that among thesethere was one, Joseph J. Kinyoun, who, invarious laboratories in America and Europe,had received extensive training on the subjectincluding instruction from the Kitasato. It isfortunate, too, that at the instigation of anothergreat pioneer, William H. Welch, the JohnsHopkins University had sent Simon Flexnerand L. F. Barker to the Philippines and India tostudy the disease.The records show that Wilson, the Assistant

City Physician, called in the City Bacteriolo-gist, W. H. Kellogg, who began a study of theautopsy tissues and cultures. Because facilitiesfor animal inoculation were not available in thecity laboratory, the study was continued byKinyoun at the Angel Island quarantine station.In proper time, the suspected diagnosis wasconfirmed and, although elaborate thanks wereoffered by the city supervisors, the surprisingend to this event was an immediate attempt tosurpress the information, and Kellogg was re-lieved of his position. Although great forces,including the Governor, various business organi-zations, and even the State Board of Health (!)were united to prevent news of the findings fromspreading, the situation grew so critical that the

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United States Government intervened when, in1901, a neutral Federal commission composed ofSimon Flexner, F. G. Novy, and L. F. Barkerwas appointed to investigate the condition.The presence of the disease was confirmed

speedily, and the statistics reveal that by 1903more than 100 cases had occurred. The cleanupcampaign was not completely effective for thedisease reappeared, in an outbreak of nearly 200cases, after the earthquake and great fire of1906. These outbreaks are insignificant whencompared with the thousands of deaths re-ported in other epidemics of plague, but weshould remain thankful that all of the publichealth authorities were not in accord with thefollowing bit of doggerel which appeared duringthe period (9):

"Have you heard of the deadly bacillus,Scourge of a populous land.Bacillus that threatened to kill usWhen found in a Chinaman's gland?"

Although not a complete account of the abovestory, the small volume "Eradicating Plaguefrom San Francisco: Report of the Citizens'Health Committee and an Account of Its Work"prepared by Frank Morton Todd (historian forthe committee) should be consulted for theinteresting material relating to the organizationand work of the committee in uniting thecommunity in various antiplague measures(24). The Federal health authorities were firstunder the direction of A. H. Glennan, then*Joseph H. White, and later Rupert Blue whoafterwards became Surgeon General. In thesecond epidemic the personnel included W.Colby Rucker, C. W. Vogel, R. H. Creel, CarrollFox, G. W. McCoy, J. R. Hurley, Bruce Foulkes,P. M. Thomas, L. S. Schmitt, J. L. Howard, G.A. Weyer, C. H. Woolsey, G. M. Converse, H.H. Hopkins, A. D. Prentice, Herbert Gunn, H.A. Stansfield, John N. Force, Gavin J. Telfer,Morton R. Gibbons, and Herman J. Schlagater.During the 1st year of the State Hygienic

Laboratory, a culture received from a municipallaboratory proved to be the plague bacillus.During the plague epidemic of 1907-1908 in thebay region, the organism was isolated by theLaboratory in 5 of 13 suspected human cases inOakland and Berkeley. In 1908, fleas from 1,844rats were examined, but the plague bacillus wasfound in none of them. In the following bien-nium, little work on plague was done in theLaboratory, although both laboratory and fieldstudies were conducted by the U.S. PublicHealth Service and the Marine Hospital Servicewith the cooperation of the State Board ofHealth. In the next years attention was directed

toward the campaign, conducted by the U.S.Public Health Service since May 1907, onground squirrel eradication. The diagnosis ofoccasional cases of human plague during theseyears was aided by isolation of the causalorganism by the State Hygienic Laboratory.

In 1908, following the recognition of two fatalrural cases of human plague, a special trappingcrew and J. D. Long collected 423 groundsquirrels on a ranch outside of Concord. W. B.Wherry recognized three and, subsequently,four squirrels, found dead in a field near thehouse where one of the victims had lived, to beinfected with the plague organism. Under theguidance of George W. McCoy, 150,000 squirrelswere trapped or shot south of the SacramentoRiver and west of the San Joaquin. Of these, 402or 0.26% were infected with plague.Although some are inclined to look no further

than the immediate question when doing rou-tine work, this was not true of George W.McCoy, who was in charge of the autopsies ofthe thousands of wild rodents examined in theabove survey. McCoy had reported for duty atthe U.S. Marine Hospital in San Francisco inthe summer of 1900, and although at first hismain assignment was to treat sailors for "what-ever befell them," he often accompanied Kin-youn or Donald Currie, also of the Service, tosee suspected human cases of plague and assistin the laboratory examinations. It should berecorded that John Nivison Force, later Profes-sor of Hygiene, and L. L. Schmitt, later Profes-sor of Preventive Medicine, at the University ofCalifornia were interns at the Marine Hospitalat this time. C. F. Craig was pathologist at theArmy's Letterman Hospital.But to return to McCoy, in the second plague

outbreak he was assigned to the task of exami-nation of the rodents for gross lesions followingthe methods outlined in the report of the"Indian Commission," the importance of whichhad been verified by William B. Wherry, previ-ously an associate of Theobald Smith. Blue hadnoted several years earlier an association be-tween squirrel hunting and consequent develop-ment of plague in hunters and had predictedthat infection would be found in ground squir-rels (Citellus beecheyi). This was confirmed,and the extent of infection in squirrels then wasshown to be confined to the area south of theSacramento River and west of the San Joaquin.During the course of these examinations, etc.,

other pathological conditions in rodents wererevealed, including nephritis, malignant andbenign tumors, lung abscesses, rat leprosy, andtuberculosis (bovine type) in squirrels. Oneadditional discovery deserves a more extendednotice.

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A question emerging from these studies con-cerned the advisability of putting time andmoney into the "plague-like disease of rodents."It is to the credit of Dr. Blue, who thought thatthe condition should be examined thoroughly,remarking, in effect, "who knows, some day itmay be found a disease of man." This predic-tion proved to be true and thus a new disease,tularemia, was identified.

In the Federal Plague Laboratory, there was aself-imposed rule that no case of human orrodent plague was to be reported officially untila culture had been obtained. Failure to isolate aculture from ground squirrels with gross lesionsnot distinguishable from those of plague led tothe reference "plague-like disease of rodents."The successful cultivation of the causative orga-nisms was, to some extent, a matter of chanceaccording to McCoy. In addition to Wherry,others associated in this work were Arthur A.O'Neill, clinician, and Charles W. Chapin,bacteriologist. They tried almost all of themedia that anyone had ever used for difficultlycultivable organisms, but without even a suspi-cion of success. One day, rather than discardsome Dorset's egg medium which had been usedin tuberculosis work, egg medium was inocu-lated with material from a ground squirrel, andas a result the causal organism was isolated.McCoy has indicated that the success of thismedium was probably due to its content ofcystine. Further study led to the proposal of thename Bacterium tularense for the organism.

It is also interesting to record that Wherry,who was familiar with this work on this"plague-like disease," later, while associatedwith the University of Cincinnati, first correctlydiagnosed tularemia in humans (6). Four of thestaff of the San Francisco Laboratory hadsuffered from the disease, although the illnesseswere not diagnosed as such. Indeed the attend-ing clinician remarked that it must be due tosomething "picked up" in the laboratory! AsStimson (23) has observed:

"Tularemia offers a striking example of thediscovery of the causative organism before thehuman disease was known. In other words, thebacteriological investigation had been done whenthe disease was first recognized. It is also avaluable illustration of the causes for the failureto get customary returns from routine experi-ments."

EARLY INDUSTRIAL BACTERIOLOGYThe first clinical laboratory in central Califor-

nia was that established in 1897 in connectionwith Cutter's Prescription Pharmacy in Fresno.The early work of this laboratory included

various analytical chemical procedures andother tests such as urinalyses and blood counts.About 1900, this organization first began tohandle biological products, and the first of thesewas a blackleg vaccine. The staff at this timeincluded Edward Ahern Cutter, responsible forthe pharmaceuticals, and Fred Twining, incharge of the bacteriological products. About1900, the work was sharply split into the chemi-cal and bacteriological phases.By 1901, three other products were added

-anthrax vaccine, tuberculin, and mallein.This same year saw a change in that the firmwas incorporated as Cutter Analytic Labora-tory. In the summer of 1903, the biologicalproducts portion of the company was trans-ferred to Berkeley to a site near the bay onParker Street. Although the production unitswere located in Berkeley, a shipping office wasmaintained, until the 1906 earthquake, acrossthe bay in San Francisco. Members of the firmduring this period recall that about one suitcasefull of supplies from Berkeley vwas needed eachweek to take care of the orders deliveredthrough the San Francisco office.

In 1904 diphtheria antitoxin and smallpoxvaccine were added to the biologics issued bythis company. Others, including rabies vaccineand antistreptococcus serum, were added about1906. In 1912 the manufacture of tetanus anti-toxin was started. Ivan C. Hall was a memberof the staff during this period and this problemwas assigned to him. A quarter of a block of landat Sixth Street and Grayson was obtained andfenced, and a small laboratory was built espe-cially for this work. Here, in 1912, the firsttetanus antitoxin produced west of the Missis-sippi was prepared by Ivan C. Hall, his brother,Rex C. Hall, Emma Staples, and Otis Coving-ton. At this time so great was the fear of tetanussurrounding this work that no one other thanthe above-named staff was allowed to enterthese grounds. Likewise, these workers werenot permitted in the main laboratories. In 1913the tetanus laboratory was placed in the chargeof Loren Taber, later dentist in San Francisco,and Ivan C. Hall was transferred to the main lab-oratory to devote time to the diagnostic labora-tory and the manufacture of vaccines. This con-tinued until he returned to the University in1915.The research direction of the laboratory of

this company in 1902 was under George Hendryfor a period of about 6 months until his death.From 1903-1905, L. C. Layson, formerly associ-ated with a drug store in Louisville, Kentucky,with some experience with Parke Davis prod-ucts, was in charge. From 1905 to 1910 MilesTrowbridge served. In 1910 Harry E. Foster,

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who had graduated at the University of Califor-nia and had done postgraduate work at Cornelland Harvard, was appointed to the position.

In this era in San Francisco, the PasteurVaccine Company was represented by CadoganMcClure with an office at 110 Jessie Street.Thomas G. Finley served in the same capacityfor the H. K. Mulford Company with an officeat 41 Stevenson Street.We have mentioned previously the important

work of the College of Agriculture of the Univer-sity of California in the development of theviticultural industry. Another phase of thisstory concerns the laboratory organized by theindustry. It should be remembered that in theearly days a bacteriologist was at the same timea chemist, an agriculturalist, a distiller, etc.The vine had been introduced to California bythe Franciscan Fathers late in the 18th century.In the early 1860s Haraszthy was sent by theGovernor of California to study the wines andvines of Europe, and upon his return he broughtmany varieties of V. vinifera, including the"Zinfandel." About the same time there was aninflux of German, French, and Italian settlerswho brought additional varieties. Naturallymany of these were unsuited to Californiaconditions, and rule of thumb methods wereemployed to settle the difficulties. One of thebest studies on the improvement of quality wasin 1887-1893 by the Viticultural Commission, ofwhich Charles Wetmore was the president, andE. W. Hilgard directed the work. About thistime, a representative of the Italian Govern-ment, Signor Guido Risotti, visited Californiaand made a report to his government on the viti-cultural industry of the state. The importance ofhis visit is reflected in the impression he madeon the wine merchants, especially Henry Lach-man, the General Superintendent of the Cali-fornia Wine Association, which exported ap-proximately one-half of the wine produced inCalifornia.

Risotti's influence was such that the Califor-nia Wine Association established a small labo-ratory with Charles Ash, later chief chemist ofthe California Packing Corporation, in charge.Naturally the early duties involved chemistry aswell as bacteriology, but fundamental observa-tions of great practical value to the industryresulted.

In relation to industrial bacteriology, somepoints concerned with early dairy bacteriologyin California may be of interest. The StateHygienic Laboratory, under Ward, cooperatedin the supervision of the certified dairies. Onesuch was the Walnut Grove Dairy of Oakland,owned by the Burroughs Brothers who, about

1905, started a certified dairy in Piedmont. Atthis time Ward was bacteriologist and veter-inarian for the Alameda County Medical MilkCommission, and the above-mentioned dairyand others started about this time were in-cluded in the supervision. By 1912 certified milkconstituted 3% of all milk delivered in the citiesin Alameda County, and from 1911 C. L.Roadhouse was in charge of the work relating tothese dairies.Beginning in 1909, Roadhouse had been in

charge of the supervision of the dairies outsidethe city limits which delivered milk in SanFrancisco. Due to lack of proper cleaning andsterilizing of equipment, high bacterial countswere obtained frequently. Most of the milk soldto the retail trade was left at the door in apitcher or some container set outside the doorby the household. Very few bottles were used fordistributing milk and those that were in usewere not sterilized in the proper manner. In1909 only one dairy in San Franciso was pas-teurizing milk and delivering it in bottles. Theflash method of pasteurization was used. In1911 the Health Department of Berkeley passedan ordinance which provided for the supervisionof the city's milk supply and the licensing of themilk producers and milk distributors.Burton G. Philbrick, who received the B.S.

degree in 1902 from Massachusetts Institute ofTechnology, was in charge of the bacteriologicallaboratories of the Peoples Water CompanyLaboratories at 1014 Broadway in Oakland from1907 to 1911. Then he and Frederick M. Eatonorganized the Eaton-Philbrick laboratory at 444Market Street in San Francisco. This was acommercial chemical-bacteriological laboratory(1911-1914), and the bacteriological work wasdone by Philbrick.

ACKNOWLEDGMENTSWe wish to acknowledge our grateful thanks to the

many individuals who contributed material, either inwritten form or in interviews, for the compilation ofthis review of the history of bacteriology and alliedsciences in California. In particular, we are indebtedto the following: Charles Ash, C. W. Boynge, W. V.Cruess, F. P. Gay, I. C. Hall, C. M. Haring, HenryHarris, G. W. McCoy, George P. Peirce, Burton G.Philbrick, W. A. Sawyer, R. E. Smith, A. R. Ward,and Hans Zinsser. We have incorporated their remi-niscences in this account, often quoting freely fromthe original without reference, and we regret that limi-tations of space have necessitated condensation of thematerial submitted to us. For recent aid in recheckingoriginal materials we are indebted also to Franz K.Bauer of the School of Medicine, University of South-ern California, Claire Still, Lane Medical Library,Stanford University School of Medicine, and Eliza-

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BEGINNINGS OF BACTERIOLOGY IN CALIFORNIA

beth Crahan, Library of the Los Angeles CountyMedical Association.The initial draft of this paper was completed in

1940 (after library research and interviews in1937-1939), and a copy, with a bibliography of thepublications of the period, was deposited in theArchives of the then Society of American Bacteriolo-gists. This bibliography has been deleted from thepresent publication, but may be obtained from thesenior author. We have now placed in the Archives ofthe American Society for Microbiology the writtenaccounts indicated above, a small number of relatedreprints, a photograph of the horse shed which wasconverted to the first bacteriological laboratory at theUniversity of California, and an undated (but circa1913) snapshot of the Stanford University group(Frank Maltener, Arthur Meinhardt, M. C. Terry,Grosbeck Walsh, Hans Zinsser, "Jim," a monkey, anunidentified caretaker, and another individual-pos-sibly H. J. Sears). We have also deposited photographsof Charles Ash, Edward Cutter, Sr., Ernest C. Dick-son, F. P. Gay, William OphUls, Emmet Rixford, A.R. Ward, and Hans Zinsser (dated 1915). Photographsof Elias Samuel Cooper, H. H. Toland and LeviCooper Lane are included in a Rixford reference (16).

LITERATURE CITED1. Arburua, J. M. 1966. Narrative of the veterinary

profession in California. California VeterinaryMedical Association, Oakland.

2. Chipman, M. M. 1889. Micro-organisms and theirrelations to human and animal life. MedicalSociety of California, Transactions.

3. Cook, S. F. 1939. Smallpox in Spanish andMexican California, 1770-1845. Bull. Hist.Med. 7:153-191.

4. Evans, G. H. 1938. Plague epidemics in SanFrancisco: historical notes. Calif. West. Med.49:383-384.

5. Ferrier, W. W. 1930. Origin and development ofthe University of California. Sather Gate BookShop, Berkeley.

6. Fischer, M. 1938. William B. Wherry: bacteriolo-gist. Charles C Thomas, publisher, Springfield,Ill.

7. G-S, G. S., and D. K. 1938. George HenryFalkiner Nuttall, 1862-1937. Parasitology30:403-418.

8. Gardiner, F. T. 1939. Early California medicaljournals. Ann. Med. Hist. (3rd ser.) 1:325-342.

9. Harris, H. 1932. California's medical story. J. W.Stacey Inc., San Francisco.

10. Kress, G. H. 1910. A history of the medicalprofession of Southern California, 2nd ed.Times-Mirror Printing and Binding House, LosAngeles.

11. Le Conte, J. 1886. Germ of hydrophobia. Science8:102.

12. Lyman, G. D. 1925. The scalpel under three flagsin California. Calif. Hist. Soc. Quart.4:142-206.

13. Mathesan, R. 1938. In memoriam. George H. F.Nuttall, 1862-1937. J. Parasitol. 24:180-183.

14. Ophuls, W., and H. C. Moffitt. 1900. A newpathogenic mould. (Formerly described as aprotozoon: Coccidioides immites pyogenes.)Preliminary report. Philadelphia Med. J.5:1471-1472.

15. Rixford, E. 1913. Early medical schools on thePacific coast. Pac. Med. J. 56:154-156.

16. Rixford, E. 1928. Early history of medical educa-tion in California. Ann. Surg. 81:321-332.

17. Rixford, E. 1931. Early history of coccidioidalgranuloma in California. Calif. State Dep.Public Health Spec. Bull. no. 57, Sacramento.

18. Rixford, E. 1933. Levi Cooper Lane. Surg. Gyne-col. Obstet. 56:246-250.

19. Soule, F., J. H. Gihon, and J. Nisbet. 1855.Annals of San Francisco. D. Appleton and Co.,New York.

20. Sternberg, G. M. 1882. Bacteria and the germtheory of disease. Pac. Med. Surg. J. 15:68-72.

21. Sternberg, G. M. 1882. Micrococci and MICRO-COCCI. Pac. Med. Surg. J. 15:249-252.

22. Sternberg, M. L. 1920. George Miller Sternberg: abiography. Amer. Med. Ass., Chicago.

23. Stimson, A. M. 1938. A brief history of bacterio-logical investigations of the United States Pub-lic Health Service. U.S. Public Health Rep.,Suppl. no. 141, Washington, D.C.

24. Todd, F. M. 1909. (March 31) Eradicating plaguefrom San Francisco: report of the Citizen'sHealth Committee and an account of its work.Press of C. A. Murdock and Co., San Francisco.

25. Willey, S. H. 1887. History of the College ofCalifornia. Calif. Hist. Soc. Papers 1:1-247.

26. Wythe, J. H. 1877. The microscopist: a manual ofmicroscopy and compendium of the micro-scopic sciences, micro-minerology, microchem-istry, biology, histology, and pathological his-tology, 3rd ed. Lindsay and Blakiston, Phila-delphia.

In addition to the above, the items listed below andothers were searched for material relating to appoint-ments, courses, and other items.Cooper Medical College. Catalogs. 1884, 1885,

1887-1909.Medical College of the Pacific. Catalogs. 1872,

1874-1882.Medical Society of the State of California. AnnualMeeting Programs. 1898 and 1900.

San Francisco Microscopical Society. Transactions.1893.

Stanford University. Catalogs. 1908-1915.State Board of Health of California. Biennial Re-

ports. 1st (1870-71), 3rd (1874-75), 9th(1884-86)-23rd (1912-14). Monthly Bulletins.vol. 1 (1905)-5 (1910), 8 (1912)-12 (1917).

Toland College of Medicine. Catalogs. 1878-1888.University of California. Catalogs of Officers and

Students. 1892-1905. President's Report.1904-16. Report of Work of Agricultural Ex-periment Station. 1887-95, 1901-04. Register.1890-91-1914-15.

University of Southern California. 14th AnnualAnnouncement. 1898-1900.

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