Report of the 
Scientific Researches 
on the 
Venereal Diseases 
United States Interdepartmental Social Hygiene Board 
The American Social Hygiene Association Report of the 
Scientific Researches 
on the 
Venereal Diseases 
Published by the American Social Hygiene Association by agreement with the 
Unite5*^tates Interdepartmental Social Hygiene Board 
370 Seventh Avenue New York, N. Y. 
1924 PREFATORY NOTE 
This report has been edited with the object of stat- 
ing as concisely and directly as possible the results of 
the Scientific Researches concerning venereal diseases 
that were financed and directed by the U. S. Interde- 
partmental Social Hygiene Board during the years 
1918, 1919, 1920 and 1921. After this time, the Amer- 
ican Social Hygiene Association made grants to some 
of the investigators in order to enable them to complex 
the studies which were well advanced and for whic' 
funds were available. 
These results have an immediate clinical interest 
and should prove of practical value to the busy prac- 
titioner of medicine, whose attention is hereby respect- 
fully called to them. 
Edward L. Keyes, M.D. TABLE OF CONTENTS 
PAGE 
Report on the results achieved under the Scientific Research Fund of the U. S. Inter- 
departmental Social Hygiene Board 7 
Preliminary observations 7 
The Division of Scientific Research: 8 
Functions 8 
Personnel 8 
Comment on results achieved 9 
PART I. 
PART II. 
The researches summarized. 
Strains of gonococci 11 
Gonococcus culture 12 
Gonococcus complement fixation test 16 
Precipitin reaction 16 
Intracutaneous reaction for gonorrhea 16 
Provocative vaccination 16 
Comparative value of smears, cultures, and complement fixation test in the diagnosis 
of chronic gonorrhea 17 
Mercurochrome 18 
Urinary antisepsis following the oral administration of proflavine and acriflavine... 18 
Saligenin 19 
A simplified tissue stain for spirochaeta pallida 19 
The Warthin tissue spirochaeta stain applied to smears 22 
The Warthin stain for spinal fluid 25 
Spirocheturia and syphilitic nephritis 27 
Non-syphilitic rabbit spirochetosis 27 
Diagnosis and culture of spirochaeta 29 
Improvement of dark-field illumination by the interposition of color screens 29 
Aniline black stain for chancre smears 29 
Intravitam dahlia stain for spirochaeta 30 
Spirochaeta culture in defibrinated blood media in partial vacuum 30 
Effect of radium and X-ray upon cultures of spirochaeta 31 
Chemistry of normal and syphilitic, spinal fluid 31 
Diffusion of fluids introduced into the cerebrospinal canal 32 
Effect of treatment upon the lesions of paresis 34 
Source of cerebrospinal fluid 34 
Coincidence of lesions of the cornu with convulsions 35 PAGE 
Unreliability of luetin test 35 
The provoked Wassermann reaction in blood and spinal fluid 35 
Diagnosis of hereditary syphilis by the Wassermann reaction 36 
The nature of syphilitic immunity. Spirocheticidal property of syphilitic immune 
serum. Virulence of spirochaeta during immunity 37 
The latent syphilitic as a carrier 38 
Syphilis as a systemic disease before appearance of the chancre 39 
Neurotropism not shown in familial neurosyphilis 39 
Diagnosis and treatment of early asymptomatic neurosyphilis 39 
The influence of pregnancy on syphilis 11 
Treatment of syphilis: Treatment of neurosyphilis 42 
The effectiveness of the treatment of hereditary syphilis 42 
The effect of syphilis on the families of syphilitics seen in the late stages 44 
Reduction of toxicity and increase in therapeutic effectiveness of arsphenamine. Study 
of new arsenical compounds 44 
Flumerin 46 
Tryparsamide 47 
Syphilis of the innocent 51 
Diagnosis of chancroid by culture 52 
Treatment of chancroid with mercurochrome 53 
PART III. 
References 5+ 
Financial data on scientific research fund 58 
List of publications 59 
List of researches 66 
Advisory Committee for Medical Research on the Venereal Diseases 71 PART I. 
REPORT ON THE RESULTS ACHIEVED UNDER THE 
SCIENTIFIC RESEARCH FUND OF THE U. S. INTER- 
DEPARTMENTAL SOCIAL HYGIENE BOARD 
The United States Interdepartmental Social Hygiene Board was 
authorized by act of Congress on July 6, 1918, to consist of the Secre- 
taries of War, Navy, and the Treasury (or their representatives), and 
the Surgeon Generals of the Army, the Navy, and the Public Health 
Service. The functions of the Board included "medical measures for 
the prevention, treatment, and control of venereal diseases; protective 
social measures primarily directed to the problem of safeguarding the 
Army and Navy; scientific research for the discovery of better medical 
methods for the prevention and treatment of the venereal diseases; 
and educational measures for the discovery or development of better 
educational methods in the prevention of venereal diseases, or for 
psychological or sociological research related thereto." 
This report is concerned with "the scientific research for the dis- 
covery of better medical methods for the prevention and treatment of 
the venereal diseases." 
Preliminary Observations-The story of the national war emer- 
gency that awakened the people of the United States to the grave 
national menace from venereal disease, the impairment in military 
efficiency resulting therefrom, and the necessity of attacking this men- 
ace at its source in the civilian population, may be found in the Con- 
gressional Record (notably in the report of the Sub-committee of the 
Senate on Military Affairs for June 18, 1918) and in the Reports of 
the Interdepartmental Social Hygiene Board for 1920, 1921, 1922. 
It suffices to note here that the summary of scientific research con- 
cerning the venereal diseases detailed in the following pages amply 
supports the statement (in the report for 1922) that "there can be no 
question as to the success of the interrelated medical, social, scientific, 
and educational activities that have been instituted by this board pur- 
suant to congressional authorization and direction. . . . The 
program of medical research stimulated by the United States Inter- 
departmental Social Hygiene Board has stimulated a much larger 
degree of scientific interest in these diseases than ever before. The 
investigation of venereal diseases has been made respectable. Several 
hundred scientific men and women have been led to devote their 
technical skill and their medical knowledge to the problems of treat- 
ment and prevention. Twenty-five of the best equipped of our scien- 
tific institutions have concerned themselves with these researches. 
These activities will not terminate with the withdrawal of govern- 
mental support even though there will be an immediate reduction in 
research activities." 
7 The Division of Scientific Research-The special division for 
scientific research of the Board was organized as follows: 
Functions 
1. Select colleges, universities, other institutions with adequate technical equip- 
ment, personnel, experience in research. 
2. Sift, judge, and estimate value of researches proposed. 
3. Apply rules and regulations of Board as required by law. 
4. Determine sums to be expended on approved researches. 
5. Approve budgets and authorize revisions. 
6. Follow up disbursements and determine value of research work done. 
7. Prepare reports, technical data, memoranda, and bulletins. 
Personnel 
A. Division Staff- 
Chief of Division, Executive Secretary 
Supervising Assistant 1 
Stenographer 1 
Note:-General services furnished this division by- 
Executive office. 
Business office. 
Division of Records, Information, and Planning. 
Personnel Section. 
In January, 1919, the Board adopted the following rules and regu- 
lations to cover appropriations for scientific research as follows: 
1. Appropriations from this fund will be made only to universities, colleges, or 
other suitable institutions that give satisfactory evidence of possessing a 
staff of scientific experts and an equipment of scientific apparatus, sup- 
plies, and resources that will guarantee that the researches undertaken will 
be carried out under approved scientific conditions and in conformity with 
scientific methods. 
2. Appropriations for this fund for scientific research will be made only for 
definite investigations that are described by the proposers in sufficient detail 
to satisfy the Interdepartmental Social Hygiene Board that there is a 
justifiable expectation that these researches "will discover more effective 
medical measures in the prevention and treatment of venereal diseases." 
3. The universities, colleges, or other institutions proposing researches and ask- 
ing for appropriations will furnish information on the following subjects: 
(a) Name of institution requesting appropriation. 
(b) Name, office, and address of official representative of this in- 
stitution. 
(c) Title concisely descriptive of research proposed. 
(d) Laboratory in which research is to be carried out. 
(e) List of more important scientific publications from this labora- 
tory. 
8 (f) Name and concise statement of the scientific training of the 
laboratory chief or director or other individual responsible 
for the scientific policy of the laboratory. 
(g) Laboratory staff, giving names, degrees, etc. 
(h) Laboratory equipment and facilities, with a concise statement 
indicating scientific and working capacity of the laboratory, 
and cooperating laboratories, departments, and agencies. 
(i) Description of research proposed; outline plan in sufficient de- 
tail to show clearly its scientific character and justify the ex- 
pectation that it will discover "more effective medical meas- 
ures in the prevention and treatment of venereal diseases." 
Include references to important scientific investigators, but 
may include salaries for technical assistants. 
(j) Will this institution be able to carry on the research proposed 
if it receives no financial aid from the Interdepartmental 
Social Hygiene Board? 
4. Universities, colleges, and other institutions asking for appropriations will 
furnish the Board with a budget made out on forms supplied by the Board 
and will make an accounting of their disbursements in conformity with the 
rules of the Comptroller of the Treasury of the United States Government. 
The Division of Scientific Research distributed $100,000.00 (ap- 
proximately) a year during the years 1919 and 1920, and during 
1921 distributed $85,000.00 (this last on a 50-50 basis) for 40 scien- 
tific researches in 23 institutions. (See Appendix A.) Two of these 
researches were concerned with chancroid, 14 with gonorrhea, 23 with 
syphilis, and 4 with general problems relating to venereal disease. 
Comment on Results Achieved-As a preface to the detailed 
consideration of the researches endowed by the Interdepartmental 
Board it seems well to discuss several questions that naturally arise 
in connection with the profit to be expected from such endowment 
under other conditions. In other words, do the results of this experi- 
ment in government subvention of laboratory and clinical activities 
encourage the belief that such subvention might profitably be adopted 
by the government as one of its normal functions? 
The actual results of the present experiment tempt one to answer 
in the affirmative. One might pick out almost (but not quite) at 
random a number of contributions on the list, any one of which might 
well be estimated as reimbursing the total governmental expenditure. 
Among those that will most immediately appeal to the practitioner 
of medicine may be mentioned the interpretation and reduction of the 
toxicity of arsphenamine, the great improvement in culture methods 
for the gonococcus and the bacillus of chancroid, and equally startling 
improvement in staining methods for spirochetes in tissue and in 
smears, the first clinical tests of tryparsamide and the support thereby 
of the organotropic as contrasted to the spirotoxic attack upon syphilis, 
the most thorough study that has yet been made of the diagnosis of 
9 chronic gonorrhea in the female, and the series of studies at various 
institutions upon the clinical and pathological problems of hereditary, 
cerebrospinal and familial syphilis. And to these one must add the 
more elusive results, such as the impetus given to the study of the 
problems of venereal disease in institutions all over the country, and 
the final profit to be expected from many of the researches that have 
as yet shown only the prospects of ultimate application to practice. 
In this connection two questions naturally arise. In how far has 
government support furthered the results we claim for it? And what 
further progress is immediately in sight? 
As to the first question, there can be no doubt. The money re- 
quired for these studies was not in sight. At some future date some 
among them would undoubtedly have seen the light; most of them 
would, to say the least, have been indefinitely delayed. But the ques- 
tion was asked at the close of each investigation whether further 
financial support could be made use of for immediate development of 
the problems at hand, and in a surprisingly large proportion of 
instances the reply given indicates that the immediate problems at 
hand have been disposed of, and that the head of the department sees 
no further development of his problem in sight. 
This situation was, of course, not universal. Indeed, it should 
perhaps be insisted upon chiefly because it illustrates so admirably 
the honest spirit in which these investigations were conducted. But 
inasmuch as the best workers of the country were engaged in the work, 
it also suggests that a continuance of the fund, with the inevitable 
insistence of money-especially government money-to get itself 
spent, would have seen a deterioration in the product and a final 
degeneration of the whole mechanism into an official routine quite 
incompatible with free research. The scientific work of the Interde- 
partmental Board was conceived and executed in that spirit of ideal- 
ism on the part of the government officials in charge which was cal- 
culated to meet the scientists on their own ground. That youthful 
idealism wThich the War inspired has gone, and gone with it is the 
probability of reproducing the circumstances necessary to the success- 
ful continuation of this work at the present time. The scientist, like 
the rest of us, must return to the humdrum of peace. 
But to return to our topic; what shall be the evaluation of the 
scientific achievement? Time alone can answer that question. We 
shall not attempt an answer, but refer the curious to the following 
excerpts, summaries and quotations of original publications from 
which to draw their own conclusions. 
10 PART II. 
THE RESEARCHES SUMMARIZED 
Strains of Gonococci-Ever since Torrey in 1907 published his 
conclusion that the gonococcus group embraces a heterogeneous collec- 
tion of types or "strains," few serious efforts have been made to 
determine the serological unity or diversity of these and other strains, 
and such investigations as have been made have resulted in no fixed 
conclusions. Hermanies studied eighty-five strains and divided them 
into six serological groups, forty-one in group 1, thirty-six in group 2 
(with four sub-types), and the rest scattering. 
Torrey and Buckell1 have resumed the study of gonococcus 
strains, using seventy-seven cultures obtained from the most diverse 
sources, anatomical (male urethra, female urethra, cervix, joint, blood, 
eye, and the vagina of infants) as well as geographical (England, 
France, Germany, Belgium, Egypt, Mexico, Panama, and various 
states of the United States). Their analysis by agglutinin absorption 
methods of the serological relationship among these strains indicates 
that they may not be distributed among a number of clear-cut immuno- 
logical types. 
"Although this investigation has not demonstrated the existence of distinct 
immunological types to each of which a considerable number of gonococcus strains 
might be referred, it was found feasible to classify our strains under the three 
general headings of (a) regular, (b) intermediate, and (c) irregular strains. 
"Evidence is submitted which indicates the existence of a marked tendency 
to antigenic lability on the part of the gonococcus. We believe that instability of 
antigenic constitution is a general characteristic of the gonococcus group and that 
the strains exhibiting this tendency may not be segregated into one particular 
type, as suggested by Hermanies. 
"Cross absorption experiments have indicated clearly that no definite sero- 
logical distinction may be drawn between strains isolated from vulvovaginitis in 
children and those from gonorrheal infections in adults (as had been suggested 
by Louise Pearce). 
"Among our regular strains, we have found certain ones which are highly 
generalized from the antigenic standpoint, and which appear to be representative 
of a large part of the gonococcus group. 
"A marked degree of correspondence was noted between strain affinities as 
revealed by agglutinin absorption and complement fixation tests." 
These observations are most important as emanating from the 
author of the well-known "Torrey strains." In 1907, Torrey was 
inclined to group his strains under three types of rather loose consti- 
tution, and this position has been confirmed by his present researches; 
but for practical purposes the great interest in his work attaches to 
his observation that in the fourteen years intervening between the two 
studies, five strains that had been apparently distinct serological enti- 
ties in 1907 had, in 1921, become very closely related as regards their 
11 antigenic constituents; i. e., the antigenic relation of strains is change- 
able (labile). The corrolary to this he also proves; viz., that there 
exists a type (or types) of gonococcus possessing generalized rela- 
tionships and a wide range of antigenic properties fitting it peculiarly 
for vaccine and anti-serum, while other strains are peculiarly suited 
for preparing antigen for the complement fixation test. 
Cook and Stafford2 have also failed to type strains of gonococci 
"by means of the alexin fixation and agglutinin reactions or by means 
of the method of absorption of agglutinins." 
Gonococcus Culture-The difficulties that surround the culture of 
gonococci for diagnostic purposes are well known. These difficulties 
arise both during the transfer of specimens from the patient to the 
laboratory and during the isolation and cultivation of the microor- 
ganism. 
Torrey and Buckell3 have devised the following method whereby 
secretions containing gonococci may be preserved several hours "with 
a minimal risk of loss of viability on the part of the gonococci." 
"One c.c. portions of a mixture of 2 parts of semisolid 'vitamin agar C' 
(see below) and 1 part of ascitic fluid are placed in narrow test tubes (6" x %"). 
This mixture is semifluid in consistency. After the swab has been infected with 
the gonorrheal discharge it is placed in a tube containing this medium, care 
being taken that the swab becomes well moistened with it, and is left there. 
This tube is then placed under the clothing; preferably next to the skin. It is 
advisable, though not essential, to warm the medium slightly just before intro- 
ducing the swab. On reaching the laboratory the tubes containing the swabs 
are placed at once in the incubator. The plates, which should be slightly 
warmed, may be seeded then or the tubes may be left there for three or four 
hours before this is done. Within this period the gonococci apparently do not 
die out at all; in fact, they begin to increase in numbers. The plating, how- 
ever, should not be delayed so long that the contaminating bacteria have an 
opportunity to overgrow the gonococci. Even at room temperature gonococci 
in pus deposited on the surface of an ascitic semisolid agar tube and kept in a 
dimly lighted place have remained viable for a surprisingly long time." Gonococci 
in pus obtained from acute urethritis in the male have been found alive after 
48 hours: after three days they had died. 
"In seeding plates the swabs are applied to only about one-fourth of the 
surface area of the medium. The swab should be rolled so that all parts come 
in contact with the medium. With a platinum loop the other three-fourths of 
the plate surface are now seeded by streaking from the part to which the swab 
was applied. In that way a proper distribution of colonies is likely to be obtained 
on some part of the plate. Before a second plate is seeded the swab should be 
reintroduced into the tube containing inoculated semifluid ascitic agar, and so on 
for each plate." 
The media employed for the isolation of the gonococcus by Torrey 
are the following: 
A. (A modification of Thalmann's medium). Place 1250 gm. of fresh, 
chopped, fat-free veal and 2 liters of distilled water in a pot and bring slowly 
12 to a boil, allowing it to simmer for 20 minutes, with occasional stirring. Strain 
through cotton flannel, cool and remove the fat. Place in a double boiler over a 
saturated brine bath and raise the temperature to about 60° C. Add 20 gm. of 
peptone (Difco), 40 c.c. normal, fresh urine, 10 gm. NaCl, 40 c.c. glycerole and 
36 gm. flaked agar. Allow this to boil for 45 minutes and then adjust the reac- 
tion to pH 6.9, using 10 per cent sodium carbonate, and boil for 20 minutes 
longer. Remove from the brine bath; make up loss from evaporation to 2 liters 
with distilled water. Filter through canton flannel and tube in 10 c.c. amounts. 
Autoclave at about 12 lbs. pressure for 10 minutes. 
In preparing the plates, 5 c.c. of ascitic fluid, free from bile, and 0.5 c.c. 
of a 1:3000 dilution of iodin-green (Grubler) are added to each tube of melted 
medium, just before pouring. The final reaction is generally about pH 7.2. It 
should not be more alkaline than this. 
If to be used in slants, the amount of agar is increased to 40 gm. 
B. (a modification of Huntoon's "hormone" medium). Five hundred gm. 
of fresh, chopped beef heart, free from fat, one whole egg and 1 liter of dis- 
tilled w'ater are placed in a double boiler over a free flame and the temperature 
maintained at 60° C., with constant stirring, for 5 minutes. Fifteen gm. of 
peptone (Difco) and 18 gm. of flaked agar are now added and the temperature 
raised until the mixture assumes a brownish color. The mixture is then made 
slightly alkaline to litmus, using a 10 per cent solution of sodium carbonate. It 
is next placed in a flask, or preferably a coffee pot, and heated to 100° C. in the 
Arnold steam sterilizer for 1 hour. The clot is then separated from the sides 
of the receptacle, and it is replaced in the sterilizer for another hour. It may 
be cleared by centrifuging or by straining through fine wire mesh and then 
through glass wool. A clear medium may often be obtained if the meat residue 
is deposited on the glass wool in a funnel and the fluid portion allowed to percolate 
through several times. Neither cloth, cotton nor any other material with absorp- 
tive properties should be used in clarifying the medium. After filtering the 
reaction is brought to pH 6.8. It is reheated and tubed in 10 c.c. amounts. It 
may be sterilized in the autoclave at 12 lbs. pressure for 10 minutes, but frac- 
tional sterilization at 100° C. flowing steam is preferable. In preparing the 
plates, 5 c.c. of ascitic fluid is added to each tube of melted medium, just before 
pouring. 
Torrey employs the following modification of Medium B for 
carrying stock strains of gonococcus. It is semisolid and contains no 
ascitic or other serous fluid. This medium may be employed for pri- 
mary gonococcus culture (for identification purposes) by the addition 
of about i c. c. of ascitic fluid per tube. 
C. The ingredients are the following: 
Distilled water 1000 c.c. 
Fresh chopped beef heart 500 gm. 
Peptone 10 gm. 
NaCl 5 gm. 
One whole egg 
The same procedures are followed as in the preparation of Medium B, and 
the final reaction is adjusted to pH 6.8. The medium is tubed in about 7 c.c. 
amounts and sterilized in the Arnold sterilizer. 
13 Cook and Stafford report that "gonococcus stock cultures grow 
satisfactorily for all routine work on testicular agar. Chocolate blood 
testicular agar was found to be a useful medium for increasing the 
vitality of a weakly growing culture." They do not give the precise 
method of preparing the media. 
Erickson and Albert4 prefer testicular blood agar with a reaction 
of pH 7.4-7.8 both for isolation and subsequent cultivation of the 
gonococcus. They give the following formula : 
"Beef testicle from which all connective tissue has been removed is put 
through the meat grinder, weighed and, with twice its weight of distilled water 
added, is infused over night on ice. The following morning the mixture is 
heated in a double boiler to 50° C., allowed to stand for one hour and then 
brought to the boiling point. Let it stand for another hour to let the solid 
particles settle, after which the liquor is decanted off and used as the infusion 
for the preparation of culture media. 
"For the preparation of testicular infusion agar, 2 per cent peptone, 0.5 per 
cent glucose, 0.2 to 0.3 per cent monobasic sodium phosphate and 2.5 per cent 
granular agar are added. This is heated over a flame and stirred constantly 
until the agar is dissolved. The medium is titrated with phenol-red as an 
indicator and the reaction adjusted to pH 7.4 to 7.8; if phenolphthalein is used 
as an indicator, it should be adjusted to a 0.6 reaction. The medium is tubed 
and autoclaved at 15 lbs. for 20 minutes. The titration is checked after steriliza- 
tion. While the tubes are still liquid (just before the agar solidifies) human 
blood in the proportion of 0.5 to 2.5 is added. If human blood is not available, 
defibrinated rabbit's blood (1-2 per cent) may be substituted." 
The conditions favoring maximal growth of the gonococcus have 
been studied by each of the three groups of observers. 
Torrey and Buckell summarize their conclusions as follows: 
"For the optional growth of the gonococcus the reaction of the medium 
should be set close to the point of absolute neutrality; between pH 6.8 and*7.4. 
The reaction range, however, compatible with growth on a semisolid medium 
containing a growth accessory factor was found to extend from pH 5.8 to 8.2. 
"The relation of viability to reaction of the medium was studied. A slightly 
acid reaction was found, on the whole, more favorable than a slightly alkaline 
reaction. The remarkable retention of viability for one year was noted in 
reference to one strain seeded on a semisolid 'hormone' agar (Huntoon) with a 
primary reaction of pH 6.3. 
"No better growth was obtained by the use of a medium containing a high 
concentration of amino acids than when prepared with the specified amount of 
peptone. 
"The presence of glucose does not enhance the growth of the gonococcus. 
"The growth stimulating principle in a medium prepared according to 
Huntoon's method was found to be slightly impaired by exposure in the auto- 
clave to 120° C. for 5 minutes and seriously injured, but not entirely destroyed, 
after 30 minutes at that temperature. 
14 "Abundant moisture in the air of the incubator is a prime requisite for 
the optimal growth of the gonococcus, especially on first isolation, but a reduced 
oxygen tension was not found to be advantageous. 
"Fermentation tests constitute the most valuable single criterion for the 
differentiation of gonococci from other similar gram-negative diplococci. No 
one of 86 gonococcus strains tested split maltose, and all but one fermented glu- 
cose. None of the strains tested on levulose and galactose split these sugars. A 
sugar free, semisolid, ascitic agar medium, with bromthymol-blue as an indicator, 
has proved satisfactory as a base for fermentation tests. Differential readings 
may be made after 18 to 24 hours' incubation. 
"A semisolid, sterilizable medium with a growth accessory factor (Huntoon 
formula) was found admirably adapted for carrying a large collection of 
gonococcus strains. Replantings have not been necessary oftener than once in 
three or four weeks. 
"The plating mediums are described which have been found serviceable in 
the isolation of the gonococcus. One of these mediums is made in some degree 
selective by the incorporation of a dye, iodin-green. For the best results the 
reaction is of prime importance; the final ion concentration should be about 7.2." 
Erickson and Albert summarize as follows: 
"The absence of sodium chloride (from their testicular blood agar medium), 
the proper reaction (pH 7.4-7.8) and moisture content are especially important. 
"Blood or blood serum mixed with the testicular agar or smeared on the 
surface of slanted tubes is necessary for the ready isolation of the gonococcus, 
but is not essential for the securing of growths of stock cultures. 
"Fermentation tests made with solid mediums containing 0.5 per cent glucose 
and phenol-red as an indicator result in a significant primary acidity and sec- 
ondary alkalinity. 
"Reduced oxygen tension is of no practical value for either the isolation or 
subsequent cultivation of the gonococcus. 
"Analine dyes of the violet and green colors tend to inhibit the growth of 
staphylococci more than that of gonococci from cases of mixed infection. Methyl- 
violet added to blood-testicular agar in a proportion of 1:200,000 to 500,000 
appears to be of great value." 
Cook and Stafford2 state that "Environmental requirements of 
the organism included moisture of the atmosphere but not a reduced 
oxygen tension." 
Swartz,5 and Herrold,6 on the other hand, have claimed some 
advantage from growing gonococci in an atmosphere the oxygen ten- 
sion of which is reduced. But Erickson and Albert, after trying the 
methods of Swartz, Herrold, and others and failing to verify the 
advantages claimed for the reduction of oxygen tension, suggest that 
"it is probable that the more satisfactory results attained by certain 
investigators is due, not to a reduced oxygen tension, but to the pres- 
ence of an increased amount of moisture due to the technic used to 
exclude air." 
15 Gonococcus Complement Fixation Test-The studies of Torrey 
and Buckell7 should introduce a new and much needed degree of 
accuracy in the complement fixation test for gonorrhea. Hitherto the 
word "strain" has had only the vaguest significance, and the multipli- 
cation of so-called strains has been quite blind and in large measure 
purposeless insofar as the preparation of a polyvalent antigen was 
concerned. But Torrey and Buckell have shown that their strains 
34 and 41 are so generalized in their antigenic affinities, so nearly 
"supergenococci" in this respect, that they say "If a single antigen is 
employed for diagnostic tests, we would advise using either strain 34 
or 41 alone, or perhaps in combination. It seems very questionable if 
better results would be obtained by combining a large number of 
regular and irregular strains in an attempt to produce a polyvalent 
antigen. In the first place, it is questionable if such an antigen cover- 
ing all the possible variants could be prepared; and, in the second 
place, when a large number of strains each with more or less limited 
affinities and representative of an equal number of so-called types are 
combined in a single antigen, then the antigenic elements of each of 
these types becomes so diluted that, in the dosage permissible, the 
effectiveness of each type would be greatly curtailed. Perhaps the best 
procedure would be to use two separate antigens in each test; one 
prepared with one or two representative strains with generalized 
affinities and good combining qualities, and the other with selected 
irregular strains." 
Precipitin Reaction-Margaret F. Kelley8 proves that the gono- 
coccus precipitin reaction of Robinson and Meader is not applicable 
to the determination of the presence of gonococci. (Herrold obtained 
fairly accurate results with precipitin.) 
Intracutaneous Reaction for Gonorrhea-Cook and Stafford2 
tested 11 persons proven or suspected of harboring gonococci and 18 
controls by cutaneous injection of "gonococcin" and of "meningonoc- 
cin." In general the results were identical for the specific and the non- 
specific vaccination both in the gonorrheal cases and in the controls. 
They conclude that the test is without value. 
Provocative Vaccination-Herrold9 failed to evoke a focal reac- 
tion in the gonorrheal urethra by the subcutaneous injection of gono- 
coccus vaccines. The secretions were cultured 24 hours after the injec- 
tion. Ten cases with negative culture before injection remained 
negative; seven positives remained positive; one positive before injec- 
tion was negative thereafter. 
(It has long ago been shown that a positive complement fixation 
test can not be evoked by vaccination unless the blood has recently 
been positive. Such an evocation therefore means that the patient has 
recently had gonorrhea.) 
16 Comparative Value of Smears, Cultures and Complement 
Fixation Test in the Diagnosis of Chronic Gonorrhea- 
Herrold has tabulated the results of his study of ioo cases of gonor- 
rhea in the male as follows : 
o 
Culture 
Complement 
fixation 
> 5 
Duration of 
infection 
ior 
itis 
Pus cells 
in prostate 
or semen 
Numbe 
cases 
- 
+ 
0 
± 
or 
+ 
+ + 
or 
+ + + + 
Positi 
smes 
2 
to 
6 
mos. 
6 
to 
12 
mos. 
Over 
1 
Year 
Aver- 
age 
mos. 
Anter 
urethr 
Ab- 
sent 
Pre- 
sent 
30 
30 
0 
30 
0 
0 
0 
0 
4 
17 
19 
16 
16 
11 
19 
26 
26 
0 
0 
19 
5 
2 
0 
7 
8 
11 
11 
11 
9 
17 
44 
0 
44 
0 
6 
16 
22 
14 
33 
10 
1 
4 
22 
4 
40 
It is to be noted that he obtained positive smears only in those 
cases showing both positive culture and fixation; that all cases showing 
positive culture had also a positive fixation (though this reaction was 
vigorous only in half the cases) ; that the duration of the infection in 
this positive group averaged four months; that the milder degrees of 
fixation persisted long (sometimes as long as a year) after it was 
impossible to identify gonococci by smear or culture; that pus in the 
prostate or semen is not an evidence of infectiousness. 
But the diagnosis of the presence of gonococci in the cervix or 
urethra of women is a much more complicated matter. Torrey, 
Wilson and Buckell state "that the results of this investigation tend 
to confirm the general impression that neither clinical observations 
alone, cultural tests, gram-stained smears nor fixation tests, as single 
methods of diagnosis, can be relied on as guides to diagnoses of actual 
infection with the gonococcus in cases of suspected gonorrhea in 
women." 
"Considering first clinical observations, we find that 9 of our 29 culturally 
positive cases harbored the gonococcus in the cervix uteri without . . . symptoms 
definite enough to warrant a clinical diagnosis of gonorrhea. Also 7 other cases, 
diagnosed as doubtful gonorrhea, which were culturally negative, gave definitely 
positive complement fixation, and two of them also positive smears. Conversely, 
among 33 cases given a diagnosis of chronic gonorrhea, there were 5 cases in 
which the clinical diagnosis was supported neither by the cultural test nor by 
repeated fixations and smears. . . . 
17 "By way of a general conclusion it may be stated that the smear, cultural 
and complement fixation methods of diagnosis in chronic gonorrhea in women 
have all proven useful, and that their relative values correspond to the order in 
which they are named, the last being the most valuable. Whenever possible, 
however, each test should be carried out, as it is shown that they tend to supple- 
ment each other." 
Mercurochrome-Studies of mercurochrome have been published 
by White,10 its inventor, and Young,11 White and Swartz.12 These 
publications encourage the use of mercurochrome in a great variety of 
infections, because of its singular combination of blandness, antisepsis, 
and deep penetration. 
The authors state that it "has not proved to be vastly superior to 
all other drugs in acute gonorrhea, although certainly quite efficient. 
In chronic infections of the urethra, prostate and vesicles 
its great value has been amply proven. . . . The results obtained 
in many cases of chronic cystitis are remarkable, long standing infec- 
tions often clearing up in a few treatments. The coccus infections are 
more resistant to mercurochrome than the colon bacillus infections. 
Mercurochrome is less irritating and produces less reaction 
in the renal pelvis than silver nitrate solution, while possessing about 
equal germicidal powers, but in some cases both drugs should be used 
alternately and sometimes silver is better. . . . Continued use 
has proven mercurochrome to be a most satisfactory dressing for 
venereal ulcerations and buboes. . . . " It is also recommended 
for general surgical use. 
It is not to be expected that mercurochrome should prove so gener- 
ally efficacious in other hands as it did in those of the first experi- 
menters. It is now chiefly employed as an irrigation for bladders 
infected by the colon bacillus, in the absence of pyelitis. 
Urinary Antisepsis Following the Oral Administration of 
Proflavine and Acriflavine-Davis,13'14 after pointing out that 
hexamthylenamin is the only satisfactory urinary antiseptic we possess, 
and that it has grave inconveniences, such as its irritating qualities, its 
ineffectiveness when the urine is alkaline, and its problematic value at 
the level of the urinary pelvis, shows that "proflavine and acriflavine, 
administered by mouth in o.i gram and even in 0.05 gram dosage, to 
normal individuals is secreted in the urine in sufficient concentration to 
render the latter an unfit culture medium for the colon bacillus and 
staphylococcus, provided the urine is alkaline. . . . This anti- 
septic action becomes evident about two hours after drug-administra- 
tion, and persists for at least eight hours. . . . No claims are 
made for clinical results following the internal administration of these 
dyes. . . . Experimentally, however, the above results constitute 
a distinct step forward, in demonstrating the hitherto theoretical possi- 
bilities offered by the analin dyes." 
18 Saligenin-Hart and Hirschfelder15'16 were inspired by the rela- 
tively low toxicity of phenyl carbinols, the presence of carbinol groups 
in many of the most active natural alkaloids, and the interesting local 
anesthetic and anti-spasmodic properties possessed by phenyl carbinols 
and their esters, to experiment upon the mercurial compounds of this 
group as antiseptics. Much chemical ground has been covered, but no 
striking results applicable to venereal diseases obtained, except that 
Hirshfelder and Wynne17 find that a 4 per cent solution of saligenin 
acts as efficiently as an anesthetic in the female urethra as does a 10 
per cent solution of cocaine. 
A Simplified Tissue Stain for Spirochaeta Pallida-Warthin 
and Starry18 in January, 1920, first described a method whereby the 
Spirochaeta pallida could be demonstrated in ordinary tissue sections; a 
method whereby the old Levaditi method, requiring at least ten days 
for its performance, and the examination of hundreds of sections, the 
hunting for spirochetes becoming a "needle-in-the-haystack affair," was 
superseded. A year later they introduced a further modification of 
their method, simpler, more rapid, more certain. They describe this 
method as follows: 
Warthin and Starry's Silver-Agar Method19 
1. Tissues fixed in neutral formaldehyde. 
2. Embed in paraffin. 
3. Cut, and mount sections on cover-glasses with albumin fixative. 
4. Remove paraffin (xylene, alcohol, water). 
5. Rinse cover-glass with section in 2 per cent silver nitrate; cover wet section 
with another perfectly clean cover-glass, so that they are held together by 
capillary attraction; then place them carefully in a bottle of 2 per cent 
silver nitrate and place in incubator for from thirty minutes to one. 
hour; then remove from the silver nitrate and separate cover-glass. 
6. Place cover-glass with section in this reducing mixture: 
2 per cent silver nitrate solution 3 c.c. 
Warm glycerin 5 c.c. 
Warm 10 per cent aqueous gelatin solution. . 5 c.c. 
Warm 1.5 per cent agar suspension 5 c.c. 
5 per cent aqueous hydroquinone solution.... 2 c.c. 
7. After the section is reduced, remove and rinse in 5 per cent sodium thiosul- 
phate (hyposulphite) solution. 
8. Rinse in distilled water. 
9. Absolute alcohol, xylene, balsam. 
General Considerations.-Fixation should be complete to give the best 
results. Thin slices of tissue, 5 to 7 mm. thick, left in 4 per cent neutral formal- 
dehyde (10 per cent formaldehyde solution) from one to three days give the best 
results. If tissue is put into alcohol before the formaldehyde fixation is com- 
plete, the results are less satisfactory. If the formaldehyde fixation is complete 
it is not necessary to wash the tissue in water before putting it into 96 per cent 
19 alcohol. Some of our best results have been obtained in tissues kept many years 
in 4 per cent formaldehyde. The importance of fixing tissues as soon as removed 
from the body, or as soon as possible after death, must be emphasized again. 
From 96 per cent alcohol the tissue is run through absolute alcohol, two 
changes of xylene and two of 52° C. paraffin. The sections should be cut about 5 
microns thick for the best results, although from 8 to 12 microns give practical sec- 
tions. As they are cut they are floated on warm distilled water that has recently 
been boiled to drive off the air. The under or shiny side of the section is placed on 
the water. When the sections have flattened out on the warm water they are 
caught upon the prepared cover-glasses, the water blotted off, and then dried 
over the flame, or in the drying oven. The cover-glasses should be No. 1 or thin 
No. 2, three-quarter inch squares, or larger if the size of the section requires. 
They must be perfectly clean, free of all dirt and grease. A minimum amount of 
albumin fixative should be spread evenly on the clean cover-glass, so that there 
will not be enough of it to become heavily stained. The prepared cover-glasses 
should be placed on a clean card-board, covered with clean paper and dried in 
the incubator for twelve hours before using. They should not be dried by passing 
through the flame. It is advisable, therefore, to keep a supply of such prepared 
cover-glasses on hand. 
After the mounted paraffin sections have been dried on the cover-glasses, the 
paraffin is removed by heating over the flame and dropping into xylene, followed 
by absolute alcohol and then distilled water. 
The silver impregnation should be carried out in the dark (dark bottles 
covered with black paper). Wide-mouthed bottles with tightly fitting corks 
should be used. The mounted cover-glass is taken from the distilled water, 
rinsed in 2 per cent silver nitrate solution, and then covered with another clean 
cover-glass also wet with the silver solution. The silver solution should always 
be freshly made, and should never be used after it is from 3 to 4 days old. Dur- 
ing this time the same solution may be used over and over again, if kept un- 
contaminated and in the dark bottle. The bottle should contain enough of the 
silver solution so that when the cover-glasses are placed on edge against the side 
of the bottle, it will not completely cover them. The cover-glasses are held 
together by capillary attraction, and if placed against the side of the bottle wet 
and the silver solution then poured in so as not to cover them completely, they 
will be held upright also by capillary attraction, and will not slip apart. The 
bottle is then tightly corked and placed in the incubator for from thirty minutes 
to one hour. After impregnation, the cover-glasses are removed, separated, and 
the mounted section put into the reducing mixture section side up. 
The reducing mixture consists of 3 c.c. of a 2 per cent silver nitrate solu- 
tion, 5 c.c. of warm glycerin, 5 c.c. of a warm 10 per cent gelatin solution, and 
5 c.c. of a 1.5 per cent warm agar suspension, to which mixture from 0.25 to 2 
c.c. of a 5 per cent hydroquinone solution is added just before using. The warm 
glycerin and gelatin solutions and the silver nitrate are first thoroughly mixed, 
then the agar suspension is stirred in with a glass rod, and finally the hydro- 
quinone, just before the sections are placed in the mixture. The agar suspension 
must be carefully made. One and five-tenths gm. of agar cut up into small 
bits is added to 100 c.c. of distilled water and carefully and slowly heated to the 
boiling point, being constantly stirred with a glass rod. When the agar has 
gone into fine suspension, the solution is poured into a bottle, which is corked 
20 lightly and kept on top the paraffin oven. Should the agar become flaky and 
settle out, it must be brought to the boiling point again with constant stirring. 
It should be just thin enough to pour, and not too thin and watery. The glycerin 
and gelatin solutions can also be kept warm on top of the paraffin oven. 
The amount of hydroquinone added to the reducing mixture varies some- 
what with the tissue and the fixation. In general it is best to use as small an 
amount as possible so that the reduction is not too rapid. A slow reduction usu- 
ally gives the best results; but if too slow, precipitates will form and the spiro- 
chetes will not be well stained. Usually from 0.5 to 1 c.c. gives the best re- 
sults ; but in some cases more may be required. After the hydroquinone has 
been added, the mixture is stirred vigorously for a short time. It is then poured 
into a staining dish, and the mounted section removed from the silver solution, 
the cover-glasses separated, and that holding the section immersed in the reducing 
mixture for a number of seconds until reduction is complete. The longer the 
section is in the reducing mixture, the darker it will be. When it becomes a 
light reddish brown it is removed and washed in a 5 per cent sodium thiosulphate 
solution, then rinsed in distilled water, dehydrated in absolute alcohol, cleared 
in pure xylene, and mounted in balsam. When the sections have been properly 
stained they will now be light reddish brown. If a deep brown or black, the 
tissue will be too deeply stained and the spirochetes not sufficiently contrasted. 
Usually the albumin fixative on the cover-glass about the section is stained some- 
what, and this can be rubbed off with a clean cloth, care being taken not to touch 
the section with the cloth. The upper surface of the cover-glass should be 
similarly cleaned. The section, of course, should never be allowed to get dry 
after the paraffin has been removed. 
The use of the second cover-glass during the impregnation in the silver solu- 
tion seems to be an essential feature of the method. We have never been able 
to secure good results by leaving the sections uncovered during impregnation. 
The spirochetes will stain only very faintly or not at all, precipitates more readily 
occur, and the tissue elements are more deeply stained. 
It is important that the alcohol used be pure, and contain no mercuric 
chloride, copper or other metal. Alcohol dehydrated over copper sulphate should 
not be used. The tissues are easily mordanted, and the differentiation of the 
Spirochaeta made difficult or impossible. 
All solutions should be made in distilled water; and all glass-ware must be 
clean. Acid fumes should be avoided. 
Our experience has taught us that not all formaldehyde-fixed tissues react 
to the silver impregnation method in the same way. Controls show that, with 
the same solutions and same conditions otherwise, some tissues appear granular, 
some a bright yellow, and others brown or black, while others will not stain at 
all. We believe that these differences in staining reactions are in part due 
to slight differences in fixation, contamination of the formaldehyde, etc., 
giving rise to differences in the process of reduction. We have found 
that by changing the reaction of the tissue before staining, it is often 
possible in such cases to affect the tissue conditions to such an extent that good 
staining results can be obtained. The best results have been obtained by the 
use of a 1 per cent solution of uranium or copper nitrate, or a 0.5 per cent solu- 
tion of ferric alum. This is accomplished by placing the sections, from water, 
21 after the removal of the paraffin, in one of these solutions for several minutes, 
and then washing thoroughly in distilled water before putting them into the 
silver solution. These solutions do not act uniformly in all cases. Uranium 
nitrate usually gives the best results, as, after its use, the tissue elements do not 
stain so deeply, leaving the spirochetes better differentiated. Copper nitrate and 
ferric alum have given especially good results in isolated cases of poor formal- 
dehyde fixation. If the tissues are well fixed in formaldehyde, it is not necessary 
to use any one of these reagents, and they should be tried only when the method 
proper does not yield good results. 
Aside from the use of the second cover-glass to cover the section during the 
impregnation, the successful operation of the method depends on the reduction 
process. This can be controlled to a great degree by varying the amount of 
hydroquinone and also by the temperature. After a little experience in judging 
the color obtained by reduction there should be no trouble in obtaining sufficiently 
good stains for diagnostic purposes. With a little more skill obtained by practice, 
the most beautiful preparations can easily be obtained. Any failures or incon- 
stant results are due to differences in the physical condition of the reducing 
mixture, or in the fixation of the tissue. 
The Warthin Tissue-Spirochaeta Stain Applied to Smears- 
Warthin and Starry20 have adapted the above stain for use with 
smears of secretions or other fluids containing spirochetes. They very 
justly observe that the darkfield and India ink methods are not wholly 
reliable in inexpert hands even for the diagnosis of genital lesions, and 
are often misleading even to the expert in the diagnosis of lesions 
about the mouth. They cite cases and depict spirochetes resembling 
the pallida and commonly found about the mouth, in support of their 
contention. They describe the method as follows: 
Method for Silver-Impregnation of Spirochetes in Smears on Cover-Glasses: 
1. Prepare smears on No. 1 cover-glasses. 
2. Dry thoroughly in the air. 
3. Place in absolute alcohol 3-5 minutes. 
4. Wash in distilled water. 
(If hydrogen peroxide is used to clear background, the smear is placed in 
concentrated hydrogen peroxide for 5-20 minutes, and then washed thoroughly 
in a distilled water.) 
5. Rinse cover-glass with smear in 2 per cent^ silver nitrate. Cover the smear 
side with another perfectly clean cover-glass also rinsed in the silver 
nitrate solution. Place the adherent pair of cover-glasses carefully, so as 
not to separate them in a bottle of 2 per cent silver nitrate, and place in 
an incubator for 1-2 hours; then remove the cover-glasses from the silver 
nitrate solution and separate them. 
6. Place the cover-glass with the smeared side up in the following mixture: 
2 per cent silver nitrate solution 3 c.c. 
Warm 10 per cent aqueous gelatin solution. . 5 c.c. 
Warm glycerol 5 c.c. 
Warm 1.5 per cent agar suspension 5 c.c. 
5 per cent aqueous hydroquinone solution. ... 2 c.c. 
22 7. After the solution is reduced remove and rinse in 5 per cent sodium thio- 
sulphate solution. 
8. Rinse in distilled water. 
9. Absolute alcohol, xylol, balsam. 
Discussion of the Method.-Clean cover glasses are essential. The 
cover-glass smears are prepared in the usual way. It is important that they be 
thoroughly dried in the air before attempting to stain them. Long exposure to 
air does not affect the staining quality if they are protected from dust and dirt. 
Dried smears containing Leptospira icteroides stained readily after standing 4 
weeks. After drying, the smears are placed in absolute alcohol for 3-5 minutes, 
and are then washed with 2 changes of distilled water. It is essential that no 
other method of fixation than drying in air followed by absolute alcohol be used. 
The silver-impregnation is carried out in wide-mouthed dark bottles fitted 
with tightly fitting corks. The smear is taken from the distilled water, and rinsed 
in 2 per cent silver nitrate solution; the smeared side is then covered with another 
perfectly clean cover-glass also rinsed in the silver nitrate solution, so that the 
wet cover-glasses adhere. The silver nitrate solution should be fresh, not over 
6-7 days old. During this time the silver nitrate solution can be used over and 
over if kept in the dark bottle and free from contamination. The adhering pair 
of cover-glasses are put into the bottle so that they stand on edge against the 
side of the bottle, and enough silver nitrate is poured into the bottle to come 
about half way up the cover-glasses. If round bottles are used a small meniscus 
is formed between the cover-glasses and the side of the bottle, thus holding them 
in place. It is a good routine measure always to place the smeared cover-glass 
next to the wall of the bottle, so that there will be no danger of getting the 
cover-glasses mixed and placing the wrong one in the reducing mixture. 
The reducing mixture is prepared by mixing the silver nitrate solution, 
gelatin and glycerol in order. This mixture is thoroughly stirred, and the agar 
suspension stirred in last. The hydroquinone solution is added just before using. 
About 2 c.c. give the best results. If the reduction takes place too rapidly add 
less, if too slowly, add more. The agar suspension should be carefully made as 
follows: One and a half gm. of agar are broken up fine, and placed in 20-30 
c.c. of distilled water, and allowed to soak for a few minutes until the agar is 
saturated with water. The excess is then poured off and the agar washed with 
several changes of distilled water; 100 c.c. of distilled water is then added; and 
it is carefully brought to the boiling point with constant stirring. When the 
agar has gone into fine suspension the mixture is poured into a clean bottle, 
corked and allowed to cool. As the agar thickens it is occasionally shaken, and 
when it begins to set it is thoroughly broken up by violent shaking. It is then 
placed on top of the paraffin oven, after which it will remain a thick heavy mix- 
ture just fluid enough barely to run. All of the solutions used should be made 
up in clean porcelain or glass ware, and not in metal containers. 
The hydroquinone is added just before using. After it has been added 
the mixture is stirred vigorously for a short time, when it is poured into staining 
dishes, and the smears removed from the silver nitrate solution, the cover-glasses 
separated, and the one having the smear is immersed in the reducing mixture 
for a number of seconds (30 seconds to 2 minutes) until the reduction is com- 
plete. The smears turn a light brown; if very thin they may scarcely change 
23 color. When reduced, the smears are removed and placed in a 5 per cent sodium 
thiosulphate solution for a few seconds. They are then rinsed in water, de- 
hydrated in absolute alcohol, cleared in xylol and mounted in balsam. The longer 
the smears are in the reducing fluid the darker they are; it is, therefore, advisable 
to leave them in it until the reduction is nearly or wholly completed. 
The use of the extra cover-glass in the silver solution seems to be essential. 
Good results are rarely obtained if the smear is left uncovered, as the serum 
and cellular elements of the smear take a deep brown stain and the spirochetes 
are usually indistinguishable. 
It is essential that all the reagents used be chemically pure and free from 
all contamination. The alcohol must be pure; if it contains phenol, mercuric 
chlorides, etc., the smears are easily mordanted, and the staining of the spirochetes 
becomes difficult. 
The spirochetes in the stained smears should appear black against a light 
background. In heavy smears with much serum or cell material we have found 
it of great advantage to use hydrogen peroxide to clear up the background. Be- 
tween steps 4 and 5 of the method the cover-glass is placed in concentrated 
hydrogen peroxide for 5 to 20 minutes. It is then washed in two changes of 
distilled water before proceeding with the silver-impregnation in No. 5. In 
smears made from macerated liver we have found it possible to secure nearly 
colorless backgrounds for the spirochetes. The hydrogen peroxide must be pure 
and free from such impurities as barium chloride and other substances commonly 
found in commercial hydrogen peroxide. We have found that put up in pure 
form in slightly acidulated water, made by Parke, Davis and Co., to be satis- 
factory. With care the same solution can be used over and over for several 
weeks. 
The Spirochaeta are increased in apparent size by this method, particularly 
insofar as their thickness is concerned. The precipitation of silver is chiefly a 
surface reaction on the Spirochaeta. There is apparently some difference between 
different forms of spirochetes with relation to the intensity of this precipitation. 
The spirochetes of syphilis, relapsing fever, mouth and smegma precipitate silver 
much more intensely than Spirochaeta icterohaemorrhagica and Leptospira icter- 
oides, and the thickness of the first named group is increased proportionately, 
that of Spirochaeta obermeieri about three times. This magnification of the size 
of the organisms is of the greatest advantage in diagnostic work, as every mor- 
phologic detail of the organism is proportionately increased in size and intensity 
and differential morphological characteristics are accentuated. The number, 
size and character of the turns of the organisms are easily determined, more so 
than by any other method. 
The stained smears are not always permanent. After 4-6 weeks some of 
them fade, while others have retained their original intensity for a year and 
longer. We have found this fading particularly marked in the case of Leptospira 
icteroides. When for purposes of record it is desirable to make permanent prepa- 
rations we have found that the smears made according to our method can be 
stabilized and, so far as our present experience goes, made permanent by toning 
with gold chloride. We have found Perrin's1 method very satisfactory. After 
the smears are stained they are washed in a solution of sodium hyposulphite, then 
with distilled water and then toned in the following solution: 
1Arch. f. Dermat. u. Syphilis, 1920, 21, p. 354. 
24 Ammonium sulphocyanide 6.25 gm. 
Tartaric or citric acid 50 gm. 
Sodium chloride 1.25 gm. 
Distilled water 2.50 c.c. 
Solution of gold chloride (1:100) 6.25 c.c. 
After a short time in this solution (5-15 minutes) the stain turns to a blue- 
black color. The smears are then washed in distilled water, dehydrated and 
cleared, and mounted in balsam. 
We believe that our method of demonstrating spirochetes in cover-glass 
smears by silver-agar silver impregnation is the surest and safest diagnostic method 
yet devised. It should replace the use of the dark-field and the India-ink method 
in the diagnosis of syphilis. The morphologic details of Spirochaeta pallida and 
the mouth and smegma organisms so often mistaken for it by workers using the 
dark-field or India-ink method, are so accentuated that differential diagnosis is 
made much easier. The India-ink method is especially dangerous for inexperi- 
enced workers. If spirochetes are present in the smear they will be stained by 
our method if directions are followed. The method is not formidable as it may 
seem because of the full directions given. It is easily acquired by laboratory 
workers. Aside from the time required for silver-impregnation in the incubator, 
it is a relatively short method, and a large number of smears can be kept going 
in different bottles at the same time. For bacteriologists and laboratory workers 
engaged in spirochete studies this method is of the greatest advantage in recover- 
ing organisms from the organs of inoculated animals, or from the blood or urine. 
It lends itself particularly well to the laboratory study of Spirochaeta ictero- 
haemorrhagica and Leptospira icteroides. Nevertheless, it is in its application 
to the clinical diagnosis of syphilis that it possesses its greatest value. 
The Warthin Stain for Spinal Fluid-Warthin, Wanstrom and 
Buffington21 have adapted the above method to the demonstration of 
Spirochaeta pallida in the spinal fluid by means of coagula obtained 
by the Altzheimer method, by the following technic: 
1. Four parts of spinal fluid and eight parts of 96 per cent alcohol are 
centrifuged, at first at a low rate of speed for a long time, and then at a high rate 
of speed for a short time to pack the clot more firmly. 
2. When a firm clot is obtained, the alcohol is poured off and replaced by 
10 per cent neutral formaldehyde solution. Small clots are left in the formal- 
dehyde solution for at least thirty hours; larger clots, for three days. In the 
formaldehyde solution the clot becomes firmer and can be handled with ease, 
as if it were a piece of tissue. 
3. The clot is then run through the routine method of embedding in 
paraffin: through dehydration in absolute alcohol, a half hour in two changes of 
pure xylol, one-half hour in paraffin No. 1, and twelve hours in paraffin No. 2. 
A paraffin melting at 52° C. is used. Embedding and blocking are carried out 
in the usual way for tissues. 
4. Sections of the embedded clot are cut at from 5 to 7 microns. As the 
sections are cut they are floated on warm, freshly boiled distilled water until per- 
fectly flat and smooth. They are then caught up on cover-glasses on which a 
minimum amount of albumin fixative has previously been spread and dried in the 
incubator. No. 1 or thin No. 2 cover-glasses should be used. 
25 5. The cover-glasses mounted with sections are now dried, and the paraffin 
removed from the sections by successive immersion in xylol, 96 per cent alcohol 
and distilled water. 
6. From the distilled water the mounted cover-glass is placed in a con- 
centrated hydrogen-peroxide solution for from ten to fifteen minutes. It is then 
thoroughly washed in distilled water. 
7. The mounted cover-glass is then taken from the distilled water and 
rinsed in 2 per cent silver nitrate solution; the wet section is then covered with 
another perfectly clean cover-glass wet with the 2 per cent silver nitrate solution 
so that the two cover-glasses are held together by capillary attraction. The wet 
adherent cover-glasses are then placed on edge in a dark bottle, holding the 
cover-glasses against the side of the bottle so that they are held by capillary at- 
traction while a 2 per cent solution of silver nitrate is poured into the bottle until 
the cover-glasses are nearly, but not quite, covered by the solution. The bottle 
is then tightly corked and placed in the incubator for one hour. The silver solu- 
tion should always be freshly made; it should not be more than three days old. 
8. After impregnation the cover-glasses are removed, separated and the 
mounted section placed section side up in the reducing fluid as follows: 
2 per cent silver nitrate solution 3 c.c. 
Warm glycerin 5 c.c. 
Warm 10 per cent aqueous gelatin solution 5 c.c. 
Warm 1.5 per cent agar suspension 5 c.c. 
5 per cent aqueous hydroquinone solution 0.8-1.0 c.c. 
The sections are reduced for from one to five minutes until the mixture 
becomes dark brown, when the background of the section is light tan or grayish 
tan. The reduction depends on the temperature and exposure to light, being 
slower in the dark at lower temperatures. 
9. After reduction is complete, the sections are rinsed in 5 per cent sodium 
hyposulphite solution, and then in distilled water. 
10. The sections are then dehydrated in absolute alcohol, cleared in xylol 
and mounted in balsam. 
The spirochetes should appear black against a grayish tan background. 
Nothing else is black except the nuclei of the white cells and the red blood cells. 
These are brownish black, and not the gray-black of the spirochetes. There are 
no fibrillae of any nature in these clots that are stained black, so that there is no 
danger of confusion. In the sections prepared by the aluminum-cream method, 
clumps of thick black rods larger than bacilli occur, probably crystalline forma- 
tions. Morphologically, these are easily distinguishable from spirochetes. 
As a rule, the spinal fluid coagula yielded about ten to fifteen seven-micron 
sections. Six sections of each block were examined in a routine manner. If 
positive findings were made in these, no other sections were examined in that 
case. If the six routine sections proved negative, ten or more-all of the sections 
obtainable from the clot-were examined. The fact that the spirochetes were 
usually found in one or two sections and fairly close together may be explained 
by the action of the centrifuge. The spirochetes present in the spinal fluid are 
undoubtedly concentrated in the same portion of the coagulum. 
More fragments of spirochetes were found than well-preserved ones, and the 
whole organisms showed twisting, entangled forms, straightening of coils, granu- 
26 lar appearance and fragmentation as the result of the centrifugation. The 
staining reaction is, however, characteristic and the morphologic characters are 
usually sufficiently well preserved to permit identification. We accepted only 
well-preserved forms as positive. There is a marked tendency for the spirochetes 
to fragment into pieces of from two to three coils. Acquaintance with these 
fragmented forms leads us to believe that they are sufficiently characteristic to 
possess diagnostic value. There is nothing else in the spinal fluid coagula that 
will stain with the silver method or that resembles these fragments morpho- 
logically. 
Spirocheturia and Syphilitic Nephritis-Warthin22 has applied 
the methods described above to the study of syphilitic nephritis and 
of the urine passed during the existence of this lesion. He finds that 
the organisms are excreted chiefly through the convoluted tubules, 
occasion degeneration of these, and are themselves mostly destroyed 
within these tubules. He concludes : 
Spirocheturia appears to be a striking phenomenon of the entire group of 
spirochetal infections. The elimination of the spirochetes through the kidneys 
with the production of associated renal lesions appears to constitute a family 
characteristic insofar as the known types of the organisms have been studied 
thoroughly. It is best known in the case of infectious jaundice, and in this 
disease is a factor of considerable diagnostic value. 
Syphilitic spirocheturia occurs in the stage of septicemic syphilis, in both the 
congenital and acquired infections. Spirochaeta pallida (as are Spirochaeta ictero- 
haemorrhagica), may be excreted in enormous numbers through the convoluted 
tubules. During such excretion through the kidneys the Spirochaeta of syphilis 
suffers greater destruction than does the icterogenic parasite, so that fewer 
spirochetes may reach the urine in syphilis than in infectious jaundice. The 
demonstration of the occurrence of syphilitic spirocheturia is, therefore, not 
likely to possess such diagnostic value as that of icterogenic spirocheturia. 
It seems probable that spirocheturia is more likely to occur when the spiro- 
chetes in the blood stream are exposed to the action of antibodies or spirocheticidal 
drugs. Further, spirocheturia in any degree, both in the case of syphilis and 
infectious jaundice, appears to be associated with definite degenerative lesions 
of the epithelium of the convoluted tubules. Such lesions may make the tubules 
more pervious to the passage of the spirochetes. 
Non-Syphilitic Rabbit Spirochetosis-In a profusely illustrated 
contribution, Warthin, Buffington and Wanstrom23 disclose the results 
of "a more detailed study of the cuniculi disease than has yet been 
made." They note the discovery of non-syphilitic rabbit spirochetosis 
by Ross in 1912, and quote subsequent observers to the effect that the 
disease closely resembles rabbit syphilis, and its organism is indis- 
tinguishable from the pallida. 
The material consisted of 18 rabbits inoculated from one source. 
Stains were made by the Warthin methods. They sum up their con- 
clusions as follows: 
The study of 18 rabbits infected with Spirochaeta cuniculi shows that the 
27 spirochetosis produced by this organism is a superficial lesion, papillomatous or 
condylomatous in character, limited to the mucous membranes or skin, and 
spreading by continuity or contiguity or auto-inoculation, and transmissible by 
inoculation, contact, and coitus. The lesions are essentially epithelial and not 
vascular, limited to the epithelial surface and upper portion of the sub-epithelial 
tissues, with marked hyperplasia of the epithelium and papillary layer. A well- 
developed lesion is essentially a condyloma, and does not suggest a chancre histo- 
logically. No evidence of systemic infection was found. No lesions containing 
the spirochetes were found in any of the internal organs. The general health 
of the infected animals remained good except in the case of intercurrent infections. 
The Wassermann reaction was negative. No general immunity was developed. 
The local lesions, when protected from trauma or local irritation, showed a 
tendency to resolve and become slight scaly latent lesions, from which spirochetes 
could still be obtained in numbers by scarification, and which, through trauma, 
could be revivified into more active and extensive lesions. 
From the lesions the spirochetes can be easily obtained by cover-glass smears 
of the surface, or by scarification. The organism is most easily and best demon- 
strated in cover-glass smears stained by the Warthin-Starry silver-agar method 
for cover-glass smears. In such preparations, its morphologic characteristics are 
more clearly seen than they can be in the dark-field or by other staining methods; 
and to one acquainted with both forms there should be no danger of confusing 
cuniculi with pallida. In sections of the tissue lesions, the spirochetes may also 
be easily stained by the Warthin-Starry silver-agar method, but they are less 
satisfactorily demonstrated in rabbit tissues than is pallida in human tissues. In 
the tissue, cuniculi lie in thickly crowded and entangled masses on and in the 
epithelium, and just below it. They are not found in numbers very deep in 
the tissue. Their localization is essentially an epithelial one, and not a vascular 
one. Their entrance into the blood stream is accidental and occasional. No 
generalized spirochetemia and spirochetosis occurs in this infection. No colon- 
ization of cuniculi in any of the internal organs was found. Because of the 
genital lesions, urine and semen are easily contaminated; but no evidence of any 
true spirocheturia is as yet forthcoming. 
Cuniculi spirochetosis is, therefore, a local disease of epithelial surfaces, the 
clinical course and local and general pathology of which do not in any way 
resemble those of syphilis. It should not be called "rabbit syphilis," and the term 
paralues cuniculi should also be discarded. The spontaneous rabbit disease can 
be easily differentiated from pallida infections by its morphology, as shown in 
silver-agar cover-glass smears, and by the pathology of the lesions. 
Nevertheless, it is disconcerting to find that there is a Spirochaeta infection 
of rabbits, apparently widespread throughout the world, caused by a Spirochaeta 
that resembles pallida sufficiently closely to make possible the occurrence of 
mistaken identifications of the one for the other, in the case of any worker who 
is not acquainted with the two organisms and their differential diagnosis. It is 
unfortunately true that the great mass of experimental work on the transmission 
of human syphilis to the rabbit has been carried out in such ignorance of the 
spontaneous rabbit disease, and the value of that work now becomes legitimately 
doubtful. It is extremely likely that mistakes have been made. Now that the 
knowledge of this primary rabbit spirochetosis has been obtained, the possibility 
of future error should disappear with intimate acquaintance with the cuniculi 
28 organism. It will, however, be necessary to repeat much of the work in this new 
light, particularly that concerned with the production of rabbit syphilis from 
paretic brains and human semen, and the production of reinfection and super- 
infection, immunity and cure. Too many important deductions have been made 
from rabbit experimental work to admit of any doubt being allowed to remain 
as to their accuracy. 
Diagnosis and Culture of Spirochaeta-Rosenberger and Fanz24 
have published as one communication five distinct studies concerning 
the recognition of Spirochaeta pallida, its culture, and the effect of 
various dyes and physical agents suggested for its destruction, as 
follows: 
Improvement of Dark-Field Illumination by the Interposi- 
tion of Color Screens-They have experimented with various 
screens and solutions in the effort to cut off the eye-fatiguing ultra- 
violet rays in the intense light of the dark field illumination. Their 
greatest success was attained by the use of the following: 
(1) Acriflavine solution, 1-5000, in flat culture flasks (3*4" wide and 
deep). The only disadvantage in the use of this solution is that it deteriorates 
slightly and requires filtration after several weeks. "The intense scintillating, 
dazzling white light from the four hundred watt dark field lamp was so mellowed 
by the removal of chemic rays that the motile bodies of Treponema pallidum 
were readily seen in more detail and could be viewed and studied for very long 
periods of time without optical discomfort." 
(2) The No. 8K2 Kodak filter. These filters are stable, but must be placed 
as far as possible from the source of light, for "due to the peculiarity in mount- 
ing with the balsam, they cannot be kept in the heat of the dark field lamp over 
a prolonged or unreasonable period of time." 
(3) The No. 1 Beta-Naphtholdisulphonic Acid Kodak filter. This is in- 
ferior to (2), but inasmuch as it gives a white light, is better adapted for the 
examination of stained specimens. 
Analine Black Stain for Chancre Smears- 
"There are observers who believe that the dark field illumination is the only 
and best method for recognizing the Treponema pallidum, but we believe that 
'the analine black method, devised by Fanz,' is equally efficient." The technique 
is described as follows: 
Solution No. 1 (Analine Oil Water).-"Analine oil water is made by 
adding 1% c.c. pure oil to 100 c.c. of water, shaking thoroughly and filtering." 
Solution No. 2 (Oxidizing Reagent).-"The oxidizing reagent is made by 
adding 5 c.c. concentrated sulphuric acid and 15 grams of C.P. potassium bi- 
chromate to 375 c.c. of distilled water." 
Technic.-The serum is obtained, free from blood, and spread upon a slide 
in the usual manner. "Thinness of the preparation is the keynote to success. 
Fixation is then accomplished by gently heating the slides about six to eight 
inches above the flame of a Bunsen burner. Four to six slides will ensure a 
correct diagnosis. After fixation and drying, each of the slides should be covered 
with 10 drops of solution No. 1, while still slightly warm. Solution No. 1 is 
29 allowed to 'soak in' to the suspected preparation for about two minutes; then 
Solution No. 2 is added in equal amount. This is allowed to remain for five 
or six minutes to oxidize the analine which the presumed organism has absorbed. 
During the action of the oxidizing solution the color changes steadily from 
orange to green, dark green, and then to metallic blue black, with the formation 
of a scum over the surface of the stain. Washing is the next step, and is 
accomplished by flushing the slide thoroughly and vigorously under a faucet of 
running water. After drying the slides thoroughly, immersion oil may be directly 
applied and the slides studied under the twelfth inch objective. The organism 
is seen on a delicate blue background containing precipitated granules of stain, 
varying in number according to the expertness of the technician and the thorough- 
ness of the washing. The Treponema appears as a black, opaque structure 
displaying its specific morphology in detail. Allied organisms, particularly the 
Spirochaeta ref ringens, can be readily differentiated; blood corpuscles and epi- 
thelial cells are likewise stained an opaque black of varying intensity." 
Intravitam Dahlia Stain for Spirochaeta-Intravitam staining 
consists in drying the stain first on a perfectly cleaned slide and then 
adding a drop of chancre secretion, applying cover-glass and oil im- 
mersion. The Treponemata are first seen colorless and motile, then 
absorbing the color, and finally dead and stained. Dahlia was found 
to give the best results. "Slides were thinly coated with a one to two 
per cent (1-2 per cent) alcohol solution of the color, permitted to dry 
and stored for use. Suspensions of several strains of the organism 
were dropped on the area of stain, covered with a cover-glass and ex- 
amined under the twelfth inch objective. The organism gradually 
absorbed the stain, being apparent in five minutes. After fifteen min- 
utes had elapsed the organism was seen to exhibit clear definition and 
an utter lack of motility.'' 
SpirochaeTxA Culture in Defibrinated Blood Media in Partial 
Vacuum- 
"The underlying principle of the various important methods of Treponema 
culture is to furnish a condition of partial anaerobiosis or diminished oxygen 
tension brought about by addition of tissue, either fresh or sterilized by heat, 
having the property to absorb oxygen gradually in small amount. On analyzing 
this principle it occurred to the writers that in all probability the reducing prop- 
erty of the tissue was due in part to the red blood cells therein contained." 
Defibrinated blood or blood hydrocele agar (ij4 per cent agar 
Jelly, two parts; hydrocele fluid, one part; to 10 c.c. of this add 1 c.c. 
of sterile defibrinated rabbit blood) is placed in sterile tubes 20 cm. 
long by cm. in diameter. The organism is next introduced by 
means of a special needle (12 bore; 27 cm. long) attached to a 10 c.c. 
syringe. The tube is softened and partially drawn out over a Bunsen 
burner, its contained air exhausted to as near a vacuum as possible by 
an air pump, the tube sealed and further reduction of the oxygen ten- 
sion entrusted to the red cells of the medium. 
The authors have found this technic successful and believe it a 
30 valuable simplification of older methods. They have also devised an 
apparatus whereby several tubes may be handled at once, and the 
vacuum obtained by pump and corpuscles further increased by oxygen 
absorption through automatic mixture of pyrogallol with 25 per cent 
sodium hydroxide solution. 
Effect of Radium and X-Ray Upon Cultures of Spirochaeta 
-The so-called "erythema" dose, whether of radium or of X-Ray, 
failed to inhibit growth or propagation of Spirochaeta pallida. 
Chemistry of Normal and Syphilitic Spinal Fluid-Egerer- 
Seham and Nixon25 sum up their comparative studies in the chemistry 
of the blood and cerebrospinal fluid with the remark that "In the 
cerebrospinal fluid of syphilis no constant deviation from normal is 
encountered in sugar, creatinin or urea content, in acid base equilib- 
rium, in specific gravity or in enzymatic activity." Their tables, giving 
the results recorded by various observers are worthy of reproduction. 
Table No. 1 shows the per cent of sugar in normal spinal fluid as follows: 
Author 
Per cent of sugar 
0.0555 
0.0188 
Claud Bernard 
0.0188 
Mastrezat 
0.048-0.53 
....(20 cases) 
Kopetzki 
0.046 
... (8 cases ; Benedict's method).... 
Hopkins 
0.060-0.075 
... . (Bang's method) 
Jaksch 
0.06-0.08 
....(20 cases) 
Schloss and Schroeder 
0.054-0.139 
....(Children; Lewis and Benedict) 
Kraus and Corneille 
O.O55-O.11O 
....(22 cases; above method) 
Levinson 
......0.064-0.09 
....(5 cases) 
Egerer-Seham and Nixon... 
0.045-0.095 
....(9 cases; above method) 
"The creatinin value in normal spinal fluid varies from 0.45 to 2.20 mg. 
for 100 c.c. of spinal fluid." 
Date 
Author 
Urea per 100 c.c. 
1896.. 
. . Cavazzani 
9.8 mg 
1896.. 
. . Thiery 
13.5 mg 
1904.. 
..Widal and Froin 
0.015-0.025 per cent 
1906.. 
. .Fraenkel 
0.543 per cent Urea N 
1912.. 
.. Mestrezat 
0.06-1 per cent 
..Leopold and Bernhard 
7.0-13.5 mg 
1914.. 
.. Gumprecht 
0.012 per cent in spinal fluid of cow 
1916.. 
..Kahn 
14-33.32 in 100 c.c. Urea N 
1916.. 
..Folin 
6.25-20.75 Urea N 
1921.. 
. .Egerer-Seham and Nixon 
9.87 mg 
Table No. 11 records the urea content of cerebrospinal fluid: 
"Under normal conditions the carbon dioxide carrying capacity of the cere- 
brospinal fluid is somewhat lower than that of the blood, while in acidosis it is 
greater, in some instances at least. Whether or not this indicates the operation 
of a mechanism for the protection of the nervous system is not yet clear." 
"The diastasic activity of cerebrospinal fluid is 21.9 per cent of that of the 
blood." Lipase was found only twice in 26 spinal fluids examined. 
31 Table No. 26 records the specific gravity of spinal fluid: 
Author 
Specific gravity 
Ch. Richet 
1.006 
Ch. Robin 
1.005 
Toison and Lenoble 
1.007 
Lassaigne 
1.008 
Marcet 
1.006 
Cheritier 
1.002 
Widal and Sicaire 
1.004 
Quinke 
1.006-1.007 
Egerer-Seham and Nixon 
1.0086 
Nixon and Naito26 have by their studies advanced our understanding of the 
nature of the Wassermann and colloidal gold reactions. They summarize their 
observations as follows: 
"The globulin fraction in syphilitic serum contains the active substance in 
the Wassermann reaction. The filtrability of globulin in syphilitic serum by the 
ultrafilter was less than that in the normal serum." 
"The lessened filtrability of the globulin in syphilitic serum they explain in 
part by the increased ease of absorption of the Wassermann positive globulin, 
possibly in part by an increase in size of this globulin, and its instability as com- 
pared with the normal globulin. 
"Positive colloidal gold reactions are due to the presence of precipitating 
substances. 
"Both precipitating and protecting substances are present in pathologic 
cerebrospinal fluid. 
"Curves in Zones I, II, and III are due to varying amounts and propor- 
tions of the precipitating and protecting substances. 
"Albumin and globulin may possess both precipitating and protecting power. 
"Ultrafiltrates or syphilitic and non-syphilitic serums give curves that are 
more or less similar, but there tends to be a greater difference between the zones 
of reduction of the original and filtered serum in syphilitic than in normal cases. 
"The protecting substance is decreased to a greater degree by ultrafiltration 
than the precipitating substance. 
"Changes in the state of the protein modify precipitating and protecting 
powers. 
"The salt solution used in the gold test partially neutralizes the protective 
action." 
Diffusion of Fluids Introduced Into the Cerebrospinal 
Canal-Solomon, Thompson, and Pfeiffer27 summarize our knowl- 
edge as to the formation and resorption of the cerebrospinal fluid as 
follows: "In conditions of normal health, cerebrospinal fluid is con- 
stantly being formed in the cerebral ventricles in considerable amounts. 
This fluid is absorbed in large part in the subarachnoid spaces, arriving 
there by a course through the acqueduct of Sylvius and the foramina of 
Luschka and Magendie." Thus, there is a flow of cerebrospinal fluid 
from cerebral ventricles toward the subarachnoid space, which flow is 
32 rendered irregular by the proven influence of heart beat, respiration, 
etc. The principles governing the diffusion of solutions through the 
cerebrospinal fluid are not well understood; indeed the observations 
upon which those principles must be based are singularly at variance. 
Thus Schmorl reported that out of seven cases of paresis with the 
usual positive Wassermann reaction in the spinal fluid only one showed 
a positive Wassermann reaction in the fluid obtained from the ven- 
tricles. Cushing showed differences in the sugar content of spinal and 
ventricular fluid. Solomon found differences in the gold reaction. 
Dahlstrom and Wideroe confirmed the observation of Schmorl. Gold- 
mann, Kramer and Horbatsky have each shown that certain injected 
dyes diffuse but slowly from the point of injection. 
On the other hand Dandy and Blackfan showed that neutral 
phenolsulphonephthalein injected into the lateral ventricle appears in 
the lumbar spinal fluid in two to three minutes, and vice versa. It 
was in one case excreted by the kidneys as rapidly as though it had 
been injected intravenously. Weston failed to confirm these diffusion 
findings, but they have been confirmed by Dahlstrom and Wideroe, 
and by the authors of this monograph, who have carried the experi- 
ment one step further, and noted not only the diffusion of a dye, but 
also the diffusion of serum. They find a striking difference in results. 
The dye diffuses rapidly, the serum sinks toward the bottom of the 
cerebrospinal column, and if mixed with dye carries this with it. 
"Under ordinary conditions it is probable that there is not very much 
movement from one locus to another of the substances introduced into 
the cerebrospinal fluid. The movement of the introduced substances 
may depend either on the circulation of the cerebrospinal fluid or, 
what is more probable, on a diffusion of the substances due to osmotic 
and specific gravity effects. . . . We may, therefore, assume 
that when the blood serum is introduced into the subarachnoid space, 
it will tend to reach the lowest portion of the cerebrospinal fluid 
system by a slow diffusion process. On the contrary, there is no evi- 
dence to show that there is sufficient active circulation of the cerebro- 
spinal fluid to displace the blood serum in a direction contrary to grav- 
ity. . . . It is to be assumed that a certain amount of the blood 
serum introduced intraspinally will make its way out into the general 
circulation from the spinal subarachnoid space. Under conditions in 
which intraspinal therapy is usually given for neurosyphilis and epi- 
demic cerebrospinal meningitis, a large part of the subarachnoid space, 
surrounding the cerebral cortex and the greater part of the cerebral 
ventricular space, is at a higher level than the lumbar subarachnoid 
space. It is, therefore, to be assumed that the blood serum (injected) 
does not reach the ventricles or the cerebral cortex in any great 
amount, particularly as effort is usually made to introduce the serum 
into the spinal spaces under a comparatively low pressure. On the 
33 other hand, serum introduced into the superior portion of the anterior 
horn of the lateral ventricle should tend to diffuse in the caudal direc- 
tion because the superior portion of the anterior horn of the lateral 
ventricle is at a higher level than the lumbar subarachnoid space. 
In order to reach the.base of the brain, the point of election for intro- 
duction of serum is the cisterna magna. For therapeutic purposes, 
blood serum should be introduced as near as possible to the area in 
which its effects are desired." 
Effect of Treatment Upon the Lesions of Paresis-"In order 
to determine whether antisyphilitic treatment produces any effect on 
the paretic process," Solomon and Taft28 instituted a study of brains 
from cases of general paresis that came to autopsy. There were 27 
brains of treated patients and 15 brains of patients not treated since 
the onset of paresis. Inasmuch as the parenchymatous, vascular, and 
neuroglia changes characteristic of the lesion are organized no con- 
clusions were drawn from the fact that these were unaffected. But the 
observations showed that the plasma cell infiltrate of the perivascular 
spaces, and the accompanying lymphocytosis were so often reduced in 
amount that from the observation of the tissue it was often possible 
to state that a certain case had received treatment. The pial inflam- 
mation was also influenced. 
They further noted that the Wassermann reaction and cell count 
sometimes became negative during treatment, and that the cell count 
does not give a true indication of the amount or extent of cerebral 
meningitis. 
They found that intraventricular injections of arsphenamized 
serum ordinarily produce no injurious effect upon the choroid plexus 
or ependymal lining of the ventricles, but note that the clinical benefit 
derived from this treatment was no more than might perhaps have 
been had without it. 
Source of Cerebrospinal Fluid-Taft29 noted in the course of his 
studies of paretic brains that the choroid plexus showed certain 
changes, not characteristic of paresis, but bearing upon the question of 
the method whereby the choroid produces the cerebrospinal fluid. He 
found a progressive fibrous change "beginning with general increase of 
connective tissue, followed by obliteration of capillaries, with forma- 
tion of fibrous tufts, in which calcium salts are deposited, and final 
cystic conditions of the plexus. At this stage the capillaries have 
entirely disappeared, but the ependymal cells remain and are little 
changed morphologically." There is no lack of cerebrospinal fluid in 
paretic brains. Indeed the ventricles are often dilated. Yet with the 
disappearance of the choroid capillaries it is difficult to understand 
how this fluid is produced by filtration, as is commonly believed to be 
the case. 
34 Coincidence of Lesions of the Cornu With Convulsions- 
Taft30 has found confirmation of the relation of sclerosis of the cornu 
ammonis to convulsions in his study of paretic brains. Of the 50 cases 
studied histologically, 19 had a history of convulsions and all showed 
this sclerosis, the cells within the corpus dentatum being particularly 
affected. One other case showed sclerosis of the cornu, but the corpus 
dentatum was spared, and the history showed no convulsions. 
Unreliability of Luetin Test-Alderson31 notes that the luetin 
test is very generally depended upon in California as an important 
(and by some as an infallible) test of the presence of active syphilis. 
He himself found the original luetin, supplied by Noguchi, a useful 
agent. His results at that time confirmed the claims of Noguchi that 
luetin test is always positive in tertiary syphilis, usually positive in 
latent syphilis and usually positive in congenital syphilis. He quotes 
many confirmatory reports, but notes its ready deterioration and 
quotes Pusey: "It is only useful when one is using a supply of luetin 
which has been tried out and is of known reliability. As furnished 
commercially now with only sufficient suspension in a single supply for 
one or two tests, it is, I believe, unreliable." 
He accordingly made a series of luetin tests upon 40 syphilitics 
and 7 non-syphilitics, using the freshest luetin available. He used 
three samples of luetin, and "there were so many luetin failures in our 
series of selected cases (63 negative, 21 positive, 3 doubtful) that 
were clinically and serologically positive that we fear that luetin pur- 
chased in the market here may be inert." 
The Provoked Wassermann Reaction in Blood and in Spinal 
Fluid-Shepardson32 has studied the provoked Wassermann reaction. 
Though reporting a provoked positive, i.e., a reversal from negative 
to positive, occurring after an interval of from two to fifteen days 
following the administration of arsphenamine (average dose 0.3 to 0.4 
gm.), he calls attention to the report of Strickler, Munson, and Sid- 
lock (J. A. M. A., 1448, Ixxv, 1920), who obtained provoked Was- 
sermann reactions in 16 out of 30 patients believed to be non-syphilitic, 
following injection of arsphenamine; and concludes that "we believe 
that an equally valuable and less time consuming procedure is to have 
the patient return for repeated Wassermanns (to be done by both the 
ice-box and water-bath methods) at varying intervals depending upon 
the clinical indications and history." 
Solomon and Klauder33 report six cases illustrating the reversal of 
Wassermann reaction from negative to positive in the spinal fluid dur- 
ing the course of treatment of late cerebrospinal syphilis. (They 
noted no instance of provoked blood Wassermann in this series.) 
The gold curve reacted sometimes in the direction taken by the 
Wassermann reaction, sometimes in the opposite direction. The Was- 
sermann reaction was sometimes provoked by a series of intravenous. 
35 treatment, sometimes by intraspinal treatment. One of the patients 
was 36 years old and has recently had a fleeting hemiplegia and had 
been treated thereafter for syphilis, though he gave no history of the 
disease. He was admitted to the hospital suffering from headache, 
loss of memory, and an occasional slight speech defect. Mentally he 
seemed euphoric, but a searching examination, including spinal fluid 
examination, revealed no abnormalities other than slightly more active 
bicipital and patellar reflexes on the left side. 
A provocative injection of arsphenamine was given. The blood 
Wassermann remained negative after twenty-four, forty-eight, and 
seventy-two hours; but later the spinal fluid became positive (with 1 
c.c. and 0.8 c.c.) there were 53 cells per cu. millimeter; globulin pres- 
ent; albumin in excess; gold curve 244333000. The positive result of 
the provocative injection thus established the diagnosis. 
Diagnosis of Hereditary Syphilis by the Wassermann Re- 
action-Jeans and Cooke34 have studied the diagnosis of hereditary 
syphilis, and certain related items, such as the effect of treatment of 
the syphilitic mother in the prevention of hereditary syphilis. They 
studied the placenta grossly and microscopically and the Wasserman 
reaction of the umbilical cord blood of 2030 unselected infants. They 
then examined the blood of 389 of these infants after they had 
reached the second month of life, and concluded that the diagnosis of 
hereditary syphilis could be made in only 27 per cent from examina- 
tion of the placenta, while from the Wassermann reaction of the cord 
blood 63 per cent could be diagnosed. They deduce an incidence of 
hereditary syphilis among the colored race in St. Louis of 15 per cent 
as against 1.8 per cent for the poorer whites, and less than 1 per cent 
for the well-to-do; a total incidence of hereditary syphilis for the city 
of 3 per cent. • 
They further observe that "syphilitic infants at birth have Was- 
sermann reactions in the following proportion: 37 per cent negative, 
18 per cent weakly positive and 45 per cent strongly positive. After 
the first few weeks or months all syphilitic children have strongly 
positive Wassermann reactions; yet syphilitic infants over two months 
of age fail to show clinical evidence of the disease at the first examina- 
tion in 50 per cent of instances. 
Non-syphilitic infants may give a weakly positive Wassermann 
reaction at birth which becomes negative later, but never give strongly 
positive reactions at birth or at any other time. All mothers of such 
non-syphilitic infants as give weakly positive Wassermann reactions 
have themselves reactions of equal or greater intensity than their 
infants. In these instances the fixing substances are probably trans- 
mitted from the mother to the infant without transmission of the 
infection." 
36 In the older children with active hereditary untreated syphilis they 
also find the Wassermann reaction positive, except in the course of 
interstitial keratitis. 
Such a doctrine is quite revolutionary. Accepted authorities on 
hereditary syphilis take a much more conservative stand on the merits 
of the Wassermann reaction as a diagnostic measure in hereditary 
syphilis, though as a rule according it more importance than for late 
acquired syphilis. There is seemingly a very human possibility of 
error in all Wassermann reactions. 
The Nature of Syphilitic Immunity: Spirocheticidal Prop- 
erty of Syphilitic Immune Serum: Virulence of Spirochaeta 
During Immunity-The researches of Engman and Eberson35'36 
have convinced them that "latent infections connote a balance between 
the antibodies of the individual and the invading parasites. Thus the 
presence of Spirochaeta pallida in the human or animal body at certain 
times need not imply disease, but rather a latent stage in which the 
spirochetes are able to survive in the immunized body." 
Their observations have established the communicability of syphilis 
during latency, but have not shown the relative infectiousness of 
latent as compared to active syphilitics. 
During latency they found no diminution of virulence of Spiroch- 
aeta (though they recognize that such may exist). 
They observed spirocheticidal properties in the blood serum of 
latent syphilitics, of sufficient strength to protect rabbits when injected 
in combination with virulent strains of Spirochaeta (control injections 
showed that non-syphilitic serum possessed no such protective prop- 
erties). 
This protective property was shared by sera obtained from syphili- 
tics whose disease dated back from three to twenty-five years, some 
of whom had received treatment, while others had not; some of whom 
had positive Wassermann reactions, while others had not. 
In the rabbit it was found that this spirocheticidal property of the 
serum developed in the course of six months to a year after infection, 
"In the rabbit, as in man, protective substances are found at a time 
when the infection has attained a relatively latent state. The presence 
of these substances in given sera apparently depends on the stage of 
infection. When definite latency has been established the serum 
appears to protect against experimental inoculation, whereas the serum 
from cases of early syphilis, or those in which true latency has not 
been attained is not spirocheticidal. 
"Sera developed in rabbits by strains of Spirochaeta pallida from 
latent sources manifested a wide range of protective properties, as 
shown by the inhibitive effect upon heterologous as well as homologous 
strains. Sera from latent cases behaved in a similar manner." 
37 Chancre strains, on the contrary, did not protect from heterologous 
inoculation. 
The treatment that renders the Wassermann reaction negative 
does not seem to diminish the protective spirocheticidal quality of the 
blood serum. 
"By analogy with the trypanosome and spirillary diseases and the 
carrier state of certain well-known infections, syphilis offers immunity 
phenomena which tend to explain latency on the basis of a blood im- 
munity which is progressively developed from a tissue immunity. 
"The mechanism by which immunity develops in syphilis would 
seem to be an elaboration of antibodies commencing at the time when 
the initial lesion is present and continuing as a progressive extension 
of local immunity from one group of tissues to another until the 
immune substances are absorbed by the blood stream." Hence the 
relative innocuousness of the latent Spirochaeta to its host, though its 
actual virulence may remain undiminished. 
Though the protective value of serum immunity is thus of the 
greatest import to the syphilitic, and an instructive phenomenon in 
the laboratory, no practical application of this phenomenon to human 
therapy has been developed. 
The Latent Syphilitic as a Carrier-Eberson and Engman37 
note thirty-eight previous attempts to infect rabbits by the injection 
of blood obtained from patients regarded as latent syphilitics with 
four positive results; but in each of these the syphilis may have been 
active at the time of injection. 
Under the classification of latent syphilis were admitted patients 
with a positive Wassermann reaction and patients with visceral or 
cerebrospinal syphilis. Indeed they seem to have excluded only re- 
cently infected persons, those under active treatment and those who 
had recently shown lesions of the skin or mucous membranes. There 
were thus included fifteen per cent of 500 clinic cases. 
Inoculations were made into rabbit's testicles of (1) defibrinated 
blood, (2) semen, (3) spinal fluid, (4) emulsion of (inguinal) nodes, 
(5) nasal washings, and (6) tonsils. The rabbits injected with tonsil 
emulsion promptly died of streptococcus septicemia. The results of 
the remaining injections are tabulated as follows: 
Material 
Number injected 
Positive inoculations 
Blood 
73 
0 
Blood (incubated) 
36 
0 
Spinal fluid 
31 
0 
Nasal washings 
24 
6 
Inguinal nodes 
14 
3 
Semen 
17 
2 
Testes (postmortem) 
2 
0 
38 Infective material from inguinal nodes was obtained from one 
patient whose syphilis dated back at least eleven years, infective semen 
from one whose syphilis dated back thirteen years, the remaining 
"takes" were from patients whose syphilis was one year old. 
"It appears from this investigation that the blood and other body 
fluids, excepting semen, are not infectious in latent syphilis, or if so, 
but rarely." 
Syphilis a Systemic Disease Before Appearance of Chancre- 
Engman and Eberson38 have corroborated the observation that the 
Spirochaeta pallida appears in the blood and lymph nodes within 
seven days of inoculation and 23 to 26 days prior to the appearance 
of any initial lesion, and that the organism may be recovered from 
the blood stream up to 26 days: thereafter it abides in the lymph 
nodes, whence it may be recovered long after it has disappeared from 
the chancre. Hence these observers stoutly oppose the excision of 
chancre, believing this lesion to be a protective reaction. They also 
call attention to the resistance to treatment of the spirochetes in lym- 
phoid tissue; hence the need for prolonged specific intensive therapy 
of the disease. 
Neurotropism Not Shown in Familial Neurosyphilis-The 
studies of familial neurosyphilis by Moore and Keidel and the discus- 
sion of one of these contributions when read before the Section on 
Medicine of the American Medical Association, shows that the ques- 
tion of the existence of a special neurotropic strain of Spirochaeta, as 
suggested some years ago by Reasoner, is still unsettled. No clinic 
has yet been able to confirm by observation of the behavior of the 
disease in human beings the laboratory observations that suggested 
neurotropism in animals. 
Diagnosis and Treatment of Early Asymptomatic Neuro- 
syphilis-Keidel and Moore,39'40'41 and Moore42'43 independently, 
have attempted a classification of those cases of early syphilis that 
show changes in the cerebrospinal fluid productive of no symptoms, 
or only "manifested by mild symptoms or slight physical signs, not of 
themselves diagnostic of central nervous system damage. Patients in 
this group may complain of headache, neuralgic pains, insomnia, ver- 
tigo, or 'nervousness,' or may have no symptoms." The physical 
signs are "slight pupillary abnormalities (myosis, mydriasis, aniscoria, 
irregularity, or sluggish light reaction), and exaggeration, sluggishness 
or inequalities of the reflexes" not pathognomonic of syphilis. 
"Such asymptomatic neurosyphilis constitutes the largest group of 
early neurosyphilis (76.6 per cent of 352 patients), and passes totally 
undiagnosed unless routine spinal puncture is resorted to. Early spinal 
puncture should be a routine part of the treatment of every case of 
syphilis, for thus only can the gravest lesions in the nervous system 
39 be foreseen at a time when it is still possible by treatment to avert the 
development of such lesions." 
Keidel and Moore perform spinal puncture after one or two 
routine courses of arsphenamine have been administered-not before 
this, for fear of exciting infection of the cerebrospinal fluid by spiro- 
chetes circulating in the blood. 
For purposes of diagnosis and treatment they classify these asymp- 
tomatic neurosyphilitics into three groups based upon their spinal 
fluid changes, and corresponding to their response to various types of 
treatment, as follows: 
Group I includes those patients whose spinal fluid shows a cell count of 
no more than 20 (usually less than 10), a slight increase in globulin (by Pandy's 
test), negative Wassermann reaction, and negative colloidal gold and mastic 
tests. Routine antisyphilitic treatment almost always suffices to clear up the 
signs and prevent the symptoms of such cases. The authors insist that the treat- 
ment of syphilis should be continuous and not intermittent. They begin with 
a course of eight doses of arsphenamine; then (beginning just before the last 
dose of the arsphenamine course) four weeks of inunctions; then three more courses 
of arsphenamine injections consisting of six injections in each course and with a 
lengthening interval (up to twelve weeks) so that the four courses cover a 
year of treatment, with intervals (of 26 weeks in all) during which inunctions 
are given. If the blood Wassermann was positive at the time treatment was 
begun, another course of arsphenamine is given after an interval of two months 
of inunctions. For cases showing the above type of cerebrospinal fluid changes 
no more than the above treatment is usually necessary to reduce the findings to 
normal. 
Group II includes those patients whose cells are more than 10 and less 
than 100, usually less than 50; whose globulin content is on the whole greater 
than in group I; whose spinal fluid Wassermann reaction is either negative or 
mildly positive; whose colloidal gold test is of the "syphilitic" type (maximum in 
the third to the sixth tube; e. g., 1123332100 or 2445522100), whose mastic 
curve varies between the "syphilitic" and the "paretic." 
Group III includes those cases whose cell count is high (50 to 200) ; whose 
globulin is high; whose spinal fluid Wassermann is positive in 0.2 c.c. or less; 
whose colloidal gold and mastic tests are usually paretic. Such cases are not 
controlled by the routine antisyphilitic treatment, even of such persistence and 
intensity as outlined above. They must be subjected to intraspinal treatment (or 
to some substitute for this.-Ed.). 
Manifestly, therefore, intraspinal treatment should not be employed for 
cases that fall into Groups I and II until and unless they fail to respond to the 
usual antisyphilitic treatment; but should be employed in the treatment of cases 
that fall into Group III as early as possible, so as to avert the gravest forms of 
neurosyphilis. 
The summary of Moore's paper contains several items of cardinal interest. 
"1. It has been shown that early invasion of the central nervous system in 
syphilis is common, occurring in 16.4 per cent of a series of 352 patients with 
40 primary or secondary syphilis. Of 94 early neurosyphilitics, 72 were asympto- 
matic, and were detected only by the routine application of spinal puncture. 
"2. Early asymptomatic syphilis may be divided into three sub-groups on 
the basis of the spinal fluid findings and the response of the various groups to 
treatment. 
"3. Invasion of the central nervous system probably occurs in the majority 
of all patients with syphilis and, unless the course of the disease is influenced 
from without (by treatment), this invasion takes place in most instances within 
the first year after infection. The ability of the invading organisms to produce 
clinical neurosyphilis probably depends on the defense mechanism of the individual 
patient. . . . 
"4. Early asymptomatic neurosyphilis is more common in the white race 
than in negroes, but is equally frequent in men and women of either. 
"5. Prolonged regular treatment influences favorably the incidence of early 
asymptomatic neurosyphilis. Irregular and lapsing treatment, on the other hand 
markedly increases its incidence. 
"6. A study of this material from the standpoint of strains of Treponema 
pallidum furnishes no support to the theory of the existence of a neurotropic 
strain of the organism. 
"7. . . . An appreciation of the (minor subjective and objective neuro- 
logic) signs, and of the significance of a persistent positive blood Wassermann 
reaction in treated patients, furnishes a clinical aid for the recognition of neuro- 
logic invasion. 
"8. Spinal puncture is an indispensible routine procedure in the management 
of early syphilis. Unless it is employed many patients will be discharged as 
cured who are nevertheless candidates for clinical neurosyphilis. It should be 
performed as a routine after the first or second course of arsphenamine, and unless 
a lapse in treatment occurs, need not be repeated (if negative) until the end of 
treatment and the probation period. 
"9. All three groups of asymptomatic neurosyphilis may be serologically and 
clinically "cured" by appropriate methods of treatment. 
"10. Early asymptomatic neurosyphilis is the forerunner of clinical neuro- 
syphilis. ..." 
The Influence of Pregnancy on Syphilis-The previously pub- 
lished work of Brown and Pearce (Am. J. of Syph., IV, 593) showing 
that in animals the course of syphilis is markedly affected by pregnancy 
has given the long awaited explanation of the clinical suppression of 
the disease in the pregnant woman. Moore44 states that "A study of 
the pregnant woman, now in progress, has convinced us that the usual 
early manifestations of syphilis are markedly altered by the occur- 
rence of pregnancy. A woman infected at or shortly after the time 
of concention usually does not develop a chancre or secondary syphilis. 
When infection takes place late in pregnancy, on the other hand, the 
usual course of events may follow, but is often much delayed." 
He further shows that "In women with late syphilis (of more 
than one year's duration) the incidence of abnormal spinal fluids is 
41 twice as high in a group of sterile women as in a group in which one 
or more pregnancies have occurred since infection. 
"Multiparae seem to be less liable to late asymptomatic syphilis 
than primiparae. 
"Pregnancy is one factor which may partially account for the 
comparative freedom of women from neurosyphilis." 
Treatment of Syphilis-Treatment of Neurosyphilis- 
Hoffman and Lyon45 as a result of their study of the toleration of 
rabbits to arsphenamine injected intravenously find that visceral injury 
usually begins in the liver rather than in the kidney. Human syph- 
ilitics tolerate bi-weekly administration of neoarsphenamine in quan- 
tities paralleling the rabbit dosage without clinical hepatitis or neph- 
ritis. The bi-weekly dosage permits an increase in total tolerated 
dosage of 30 to 40 per cent more neoarsphenamine than by present 
methods. This schedule calls for 1.2 to 1.4 gm. neoarsphenamine 
weekly to individuals weighing more than 150 pounds. On account 
of the brief residence of the drug in the tissues it becomes apparent 
that the more frequent the administration of the drug and the greater 
the dosage, short of visceral damage, the nearer is the approach to 
the ideal treatment. 
They also call attention to the observations of Merthens to the 
effect that 50 per cent of all persons have meninges impermeable to 
blood borne arsphenamine. Thus every other case requires some 
method of conveying the drug to the meninges. 
They suggest the following plan of investigation as preliminary 
to the treatment of cerebrospinal syphilis: 
1. Intravenous injection of arsphenamine or neoarsphenamine followed in 50 
minutes by withdrawal of 40 c.c. of cerebrospinal fluid. 
2. Test the cerebrospinal fluid for arsenic by Gutzeit's method. If arsenic 
is present intravenous therapy is presumably adequate for the case in question. 
3. If arsenic cannot be detected, treat the patient (at another time) by the 
method of Corbus; injecting intravenously a pypertonic salt solution, and 6 hours 
later injecting intravenously neoarsphenamine. Fifty minutes later the cerebro- 
spinal fluid is again tested for arsenic. If present the Corbus plan of treatment 
is pursued. 
4. If arsenic is again absent, a second puncture an hour later may show 
arsenic. 
5. If arsenic then fails to show, intraspinal therapy is required. 
The Effectiveness of the Treatment of Hereditary Syphilis 
-White and Veeder46 have investigated the social and clinical data 
in relation to 443 children (among 396 families) with hereditary syph- 
ilis, and also the effect of treatment upon the disease. They have 
attempted to evaluate the dividend to be expected in the form of 
economic physical result from the therapeutic attack upon hereditary 
42 syphilis. They feel that their results are on the whole unsatisfactory, 
and believe that the only adequate attack upon hereditary syphilis is 
that upon the syphilitic mother. 
Their conclusions are as follows: 
"This study was undertaken with the purpose in view of determining 
whether or not the end-results of the intensive work with hereditary syphilis 
during the period 1912-1920 were of such a nature that future work along the 
same line is indicated or justified. During this period 443 patients with the 
disease were observed and followed with adequate hospital, clinic, and social 
service facilities available at all times. It is impossible to state the exact cost but 
when the time and salaries of physicians and social workers, equipment, drugs, etc., 
are considered we are justified in estimating it at many thousands of dollars. 
"From the social standpoint we have found the group as a whole unsatis- 
factory and difficult to deal with. Lack of interest on the part of parents has 
led a large part of our material to discontinue treatment long before dismissal 
by the physician. While here and there families have been encountered who have 
cooperated most satisfactorily, their number is far overshadowed by the group of 
uncooperative. Thus, out of 230 living patients in whom end-results are known, 
only 52 followed out a thorough course of treatment; while 95 were absolutely 
uncooperative. A middle group of 83 cases continued treatment with a fair 
degree of regularity for a time, but dropped away before discharge. Allowing 
for the 78 deaths' in the group there are still left 125 patients who for one 
reason or another were lost track of and a large per cent must be included with 
the group of "uncooperative." In our experience, in spite of thorough and in- 
tensive follow-up work, only a third of the hereditary syphilitic patients were 
given the benefit of a satisfactory or fairly satisfactory course of treatment, and 
we question whether this figure can be improved under ordinary conditions. 
"In discussing the results of medical treatment two viewpoints must be 
considered: first, the results of treatment in the individual case of hereditary 
syphilis; and secondly, the results of treatment for the group of 443 cases as a 
whole. So far as the individual case is concerned our results show that a given 
case has a fair chance of clinical and serological recovery or improvement; that 
such recovery or improvement may seemingly take place on little or practically 
no treatment, but that the chances for cure or improvement are very much 
better for a case thoroughly treated with arsenicals and mercury than for one 
poorly treated. The earlier the treatment is started the better the result. If 
the given case has either serological or clinical evidence of involvement of the 
central nervous system, the chances for recovery or improvement are poor. One 
is justified, therefore, in treating a case of hereditary syphilis thoroughly with 
the expectation that it will be benefited. 
"As regards the group as a whole the results have been disappointing. The 
infant mortality rate is three times the rate for infants from all diseases. This 
is despite treatment and is seemingly dependent upon the extent to which the 
infant's nutrition and metabolic function have been impaired. Further, approxi- 
mately one-third of the cases have had involvement of the central nervous system 
and as a group these have shown little improvement. Although active lesions in 
these cases have been checked, the residue of the infection leaves a child who as 
a rule belongs to the socially unfit. Considering the group of 308 cases whose 
43 end-results are known we quote them briefly as follows: Cured or recovered, 67 
or 22 per cent; improved, 108 or 35 per cent; unimproved, 55 or 17 per cent; 
died, 78 or 25 per cent. Thus we find that in our entire group, regardless of 
the amount of treatment received, 43 per cent were either unimproved or died. 
Despite the intensive work during this period only 22 per cent of our cases are 
known to have been cured or recovered. 
"Certainly this cannot be considered a brilliant showing. While one is 
justified in urging thorough treatment in the individual case, our group results 
clearly show that from a social or group standpoint the treatment of hereditary 
syphilis in the infant or child leaves much to be desired. The problem is best 
attacked by reaching the syphilitic woman or mother before and during preg- 
nancy. This is all the more apparent when one takes into consideration the 
fetal mortality. While by no means advocating the neglect of the syphilitic 
child, we feel that the results to be obtained are so poor as a whole that our 
efforts should be directed much more to the prenatal clinic than to the pediatric 
clinic." 
The Effect of Syphilis on the Families of Syphilitics Seen in 
the Late Stages-previous investigations-Previous investiga- 
tions either refer to syphilitics seen in the early stages or do not cover 
so large a group. 
material studied-Families of 555 patients seen by H. C. and 
M. H. Solomon47 at the Psychopathic Hospital with positive Wasser- 
mann reactions (only 236 of the mothers gave positive reactions). 
RESULTS-1. Whether the disease shows itself as paresis, cerebro- 
spinal syphilis or visceral syphilis without involvement of the central 
nervous system, the problems affecting the family are the same. 
2. At least one-fifth of the families of syphilitics have one or 
more syphilitic members in addition to the original syphilitic parent. 
3. Between one-third and one-fourth of the families of syphilitics 
have never given birth to a living child, while only one-tenth of normal 
families remain childless. 
4. More than one-third of the syphilitic families have accidents 
to pregnancies; i.e., abortions, miscarriages or stillbirths (about twice 
the normal). 
5. The birth rate in syphilitic families is 2.05 per family (as 
compared to a normal of 3.8 per family). 
6. Two-thirds of these families show defects as to children (ster- 
ility, accidents to pregnancy and syphilitic children). 
7. Between one in twelve and one in six of the children examined 
show syphilitic involvement. 
Reduction of Toxicity and Increase in Therapeutic Effec- 
tiveness of Arsphenamine-Study of New Arsenical Com, 
POUNDS-The toxicity of arsphenamine has been searchingly studied 
during the last five years by many independent observers connected 
44 with laboratories where arsphenamine was in process of manufacture. 
The result of these investigations has been to throw a good deal of 
light upon the chemical construction of the drug as well as upon its 
toxicity. Among those contributing are those which have been fost- 
ered by the Interdepartmental Board grants. At Harvard under the 
direction of Professor Reid Hunt,48 Walter Christiansen49 has pub- 
lished thirteen contributions upon a simplified method of producing 
relatively non-toxic arsphenamine, and concerning the toxicity of 
arsphenamine and its relations to the sulphur group. Professor Lewis 
in reviewing the work of Christiansen comments as follows: 
"Christiansen states that relatively toxic or non-toxic products may be 
obtained from either of the three commercially feasible processes of manufacture 
of arsphenamine. The addition of so much as 5 per cent of such probable im- 
purities as 4, 3, 5-HO (02N) 2-C6H2 AsO3H2, or a mixture of 2, 5-and 2, 3- 
HO (02N) C6H3AsO3H2 before reduction, caused but a slight variation in 
the toxicity of arsphenamine. Methods of forming the dihydrochloride from the 
base were not responsible for the variations, which Christiansen finally considers 
as dependent upon the conditions of reducing the parent 4, 3-HO (O2N)-C 
6H4AsO3H2. He obtained products of low toxicity using hypophosphorous acid 
as a reducing agent. In subsequent articles Christiansen concludes that there is 
no direct relation between the total sulphur and the toxicity, and searchingly dis- 
cusses toxic types in general. Hunt cites three distinct toxic types: (a) prepara- 
tions the toxicity of which was due to the presence of amino-p-hydroxyphenyl- 
arsenous oxide (arsenoxide) ; (b) preparations the toxicity of which seemed to 
be due to the presence in the manufactured product of toxic substances other than 
arsenoxide; (c) those toxic on account of the presence of easily destroyable toxic 
principles. 
Type (a) were not encountered commercially but were demonstrable in the 
laboratory. No toxic substance of type (b) was isolated but their occurrence is 
probable. Warming and in some cases standing at room temperature reduced 
the toxicity of type (c). Unique and unexplainable toxic types were also en- 
countered." 
Adams, Palmer50 and Johnson51 have exhaustively studied the 
chemistry of arsphenamine. To quote Lewis again "Adams and 
Palmer have compared the action of arsine and the substituted arsines 
with the corresponding nitrogen compounds. They were able to con- 
dense phenylarsine, the analogue of aniline, with aldehydes. Primary 
aromatic arsines react with aldehydes in three ways according to the 
conditions-i.e., R. AsH2 + R CHO R As (CHOHR) 2; R AsH2 
+ 4R CHO (R CHO AsR) 2 + 2R CH2OH (Adams regards this 
product as a phenyl substituted heterocyclic ring of arsenic, carbon 
and oxygen) ; R AsH2 + 2R CHO R - AS - R -f- R CH2OH. 
"Quick and Adams52 have also exhaustively studied the prepara- 
tion of aliphatic arsinic and arsinic acids, and aliphatic aromatic arsinic 
acids. These authors have improved upon Meyer's method of arse- 
nating aliphatic compounds using alkyl bromides and chlorides instead 
45 of the iodides and employing water as a solvent. Thus, the reducing 
effect of the liberated hydriodic acid on the arsonic acid is avoided 
on the one hand, and the formation of ether greatly lessened on the 
other. The arsinic acids are prepared from the arsonic acids by reduc- 
tion with sulphur dioxide, in hydrochloric acid solution, to the alky- 
Miochlorarsines, which are then treated with sodium hydroxide and 
the alkyl halide." 
Both of these groups of observers have made excursions into the 
building up of new compounds of arsenic and Professor Lewis53 him- 
self, in connection with Lowry and Bergein with Cheetham and Hamil- 
ton have built up and studied the therapeutic properties of new organic 
compounds of arsenic. Thus far, unfortunately, it is not known that 
any of these new drugs are calculated to surplant the older ones. 
As a commentary upon the results of these investigations it has 
been concluded by one observer that "the field of organic arsenic has 
been fairly well investigated by Ehrlich and by American chemists. 
The arsphenamines have proven to be satisfactory spirocheticides, 
their principal weakness lying in their low degree of penetrability, 
rather than in their germicidal activity. Therefore it would appear 
that resources, invested in studies for improving the manner of con- 
veying the arsphenamines to syphilitic tissues or binding them therein 
for long periods of time, promise more success than might be expected 
from synthesizing new arsenic compounds." 
Flumerin-White, Hill, Moore, and Young54 have developed and 
studied the therapeutic effects of this new drug for the treatment of 
syphilis. Their comment and conclusions are given in full. 
The evaluation of the worth of any new drug in medicine, and particularly 
in the treatment of syphilis, is a difficult problem, which must be approached 
with the utmost caution. In this instance, it is fraught with special difficulties. 
It is obvious that flumerin cannot be compared with the arsphenamines. No 
strictly comparable studies with other mercurials, especially so far as rabbit 
syphilis is concerned, have been carried out. It is not permissible to conclude, 
because the single dose therapeutic ratio of this drug is the same as that of other 
mercurials, and because a quantity of flumerin from eight to twenty times 
greater than other mercurials can be safely employed, that the actual therapeutic 
activity of flumerin is, therefore, proportionally greater. Therapeutic activity 
depends on many other factors, chief among which may be mentioned the penetra- 
bility of a given drug, and its ultimate fate in the body. No comparisons are 
therefore attempted and it is given only as our clinical impression that flumerin 
is, from the standpoints of toxicity and therapeutic activity, superior to the 
soluble mercurial salts in general use by the intravenous route. 
No attempts have as yet been made to employ the drug by the intramuscu- 
lar route. For the present, and until adequate experimentation shall have demon- 
strated the limitation of toxicity, the factor of freedom from pain and the 
relative value of this route as compared to the intravenous route, we do not 
advise its use. 
46 From the standpoint of the clinical results, it should be pointed out that, 
as yet, we have given only small doses of the drug. The results obtained in 
rabbit syphilis indicate the desirability of employing doses larger than 3 mg. 
per kilogram. The few instances in which we have recently administered 4 or 5 
mg. per kilogram indicate that the effect of the drug on lesions and on the 
Wassermann reaction is enhanced. Attempts to increase the dosage must, how- 
ever, be carried out cautiously and under adequate control. No attempt is made 
to suggest the ultimate place which this drug may attain in the treatment of 
syphilis. It is not available for general distribution, and, for the present at least, 
permission will not be granted for its commercial manufacture. 
This paper deals with a new soluble mercurial drug of low toxicity and of 
remarkably non-irritating character when injected intravenously. The complete 
chemical name-hydroxymercurifluorscein-has been shortened to flumerin. This 
drug is effective in eradicating experimental syphilis in rabbits in doses which 
are well tolerated. Even in large doses, it causes little or no clinical injury to 
the kidneys of animals. In ninety-six human cases, definite proof of its value as 
an antisyphilitic drug has been given. 
Doses containing from eight to twenty times the amount of mercury present 
in the therapeutic dose of other mercurial drugs commonly used intravenously 
have been given with impunity, and the maximum dose which may be employed 
serially in the human being has not yet been determined. 
The therapeutic effect of the drug has been shown in primary, secondary 
and tertiary syphilis by the resolution of lesions and the reversal of positive blood 
Wassermann reactions. The number of cases treated is sufficient to demonstrate 
that this mercurial is of value, but is too small to permit the allocation of the 
drug to a definite place in the therapy of syphilis. 
Tryparsamide-Lorenz, Loevenhart, Bleckwenn and Hodges55 have 
reported with some enthusiasm on what may prove to be the greatest 
contribution to the therapy of syphilis since Ehrlich. They were given 
the opportunity by the Rockefeller Institute to experiment with try- 
parsamide on patients suffering from syphilis of the nervous system. 
Tryparsamide is the sodium salt of N-Phenyl-glycineamid-p-ar- 
sonic acid, CaH4 (NHCH2 CONH). AsO.OH.ONa) was first 
made by Jacobs and Heidelberger in 1915. "The biologic action of 
this substance has been studied experimentally by Brown and Pearce in 
normal animals and in animals infected with trypanosomes and with 
the spirochetes of relapsing fever and of syphilis. Tryparsamide has 
also been used in a comparatively small group of patients for the 
treatment of syphilis other than that of the central nervous system, 
first by Louise Pearce and later by Keidel and Moore; and at the 
time our investigation began it was about to be tested by Dr. Pearce 
in the treatment of human trypanosomiasis." 
The work done by the observers had shown that doses as large as 
5 gm. could usually be administered with safety, though its adminis- 
tration (even in smaller doses) may be followed by blindness, which 
our authors speak of as a transient amblyopia, but which has else- 
where proven permanent. 
47 Indeed it should be said at the beginning that the observations 
thus far made unite in warning those who use the drug that it has the 
toxic effect. 
The conclusions of Lorenz, Loevenhart, Bleckwenn, and Hodges 
have been confirmed and the general problem of the relation of try- 
parsamide to syphilis more intimately studied by Moore, Robinson 
and Keidel. The therapeutics of the new drug may be described as 
follows: 
toxicology-Tryparsamide, like other concentrated arsenicals, causes blindness 
if given in overdose. This blindness is "apparently a typical toxic amblyopia, due 
to retrobulbar neuritis, and quite similar to the effects of atoxyl." (Moore.) 
"When tryparsamide was used in 5 gram doses at weekly intervals, we found 
that after four or five such administrations approximately 40 per cent of our 
patients complained of dimness of vision. This condition was transient in all 
except two cases, and disappeared as soon as the drug was stopped. In the two 
cases in which the condition was persistent the patients were far advanced 
paretics who had had abnormal eyegrounds before treatment." (Lorenz). 
"Impairment of vision developed in Pearce's experience only in patients with 
moderately or markedly advanced trypanosomiasis of the central nervous system 
and not at all in the early stages of the disease. The phenomenon seemed to 
depend further on the size of the dose given, the upper limit of safety apparently 
ranging from 50 to 80 mg. per kilogram and on the spacing of the injections. 
An interval shorter than one week was especially likely to be followed by visual 
disturbance. The transient blurring of vision was usually mild in degree, though 
in four patients it was marked. On withdrawal of the drug there was always 
improvement, though in a few instances there was definite residual impairment of 
vision. 
"Early in our own experience with syphilitic patients the same difficulty was 
encountered. Fourteen patients among about 150 treated have complained of 
dimness of vision during tryparasamide treatment. In ten of these the visual 
impairment was slight in degree and cleared up at once when the drug was 
stopped. In one a patient whose original lesion was syphilitic neuroretinitis, 
there was a slight permanent visual defect; while in three instances disturbance of 
vision was severe and there was a marked residuum. All of these fourteen patients 
had neurosyphilis, and in three there was preexisting disease of the optic nerve. 
We have not seen an instance of amblyopia in early or late syphilis without 
involvement of the central nervous system. . . . Eleven neurosyphilitic 
patients, accepted for treatment on the basis of objectively normal eyes, have 
developed mild and transient amblyopia, often preceded for a few hours or days 
by the complaint of flashes or glimmering of light before the eyes, a phenomenon 
apparently dependent on irritation of the nerve or retina. This bore no par- 
ticular relation to the dose employed. One instance occurred after four injec- 
tions, the first of 0.5 gm., the rest of 1 gm. each. Several have developed after 
a few weekly injections of 2 gm., and in one of these there was permanent 
residual damage. In some of our mild cases we have found, as did Pearce in 
Africa, that it was possible to begin the tdrug'again, after complete disappearance 
of the mild disturbance, and to reach the initial level of dosage without recrud- 
escence of symptoms." 
48 Comment on the above statements is all but superfluous. Personal report 
to the editor from two, other sources amply confirms the fact that tryparsamide, 
as at present manufactured, may cause permanent blindness even when admin- 
istered in small doses to patients showing no lesion of the eye or optic nerve that 
our methods of clinical examination can detect. Hence the accepted rules: 
Tryparsamide should be administered only to patients whose eyes have been 
proven free from disease by skilled ophthalmological examination. 
Patients taking the drug must be warned to report any flashes or glimmering 
before the eyes, and such report should be made the signal for stopping the ad- 
ministration of the drug, even though no objective signs of disease of the eye 
appear. 
administration-Tryparsamide is administered intravenously. "Our practice 
during the past year has been to dissolve 3 gm. of tryparsamide in 10 c.c. of 
sterile freshly distilled water, and to inject the total amount intravenously. 
This solution is given at intervals of one week and for periods of eight weeks." 
Nine intramuscular injections of salycylate of mercury are interspersed with the 
intravenous injections, followed by "a rest, period of from five to eight weeks, 
when a similar course is repeated," and if necessary, a third. (Lorenz.) 
"Treatment should be begun cautiously, the initial dose 1 gm., the second 
2 gm., and the third and subsequent doses never more than 3 gm. At the 
slightest complaint of flashes of light or 'glimmering vision,' or of blurred or dim 
vision, the drug should be immediately discontinued." (Moore.) 
The inconvenience following injection is reported to be negligible, far less 
than that which follows injection of arsphenamine. 
tryparsamide in early syphilis-Moore treated eight cases, seven with early 
secondary syphilis, one with a seronegative chancre. From two to five injections 
were given without demonstrable effect upon the lesions, or disappearance of sur- 
face organisms. 
tryparsamide in late syphilis-Moore treated 24 patients with late syphilis, 
some with lesions, some with only a positive Wassermann reaction and obtained 
only the most negligible results. Then the cases were put upon the ordinary 
arsphenamine treatment and many of them immediately responded, showing the 
tryparsamide to be definitely inferior to the established forms of treatment. 
trypasamide in early neurosyphilis-Moore treated three cases. The symp- 
toms of one case became worse, the spinal fluid picture of two other (asympto- 
matic) cases was improved, but one of these developed a secondary skin eruption 
while under the tryparsamide treatment. Hence "satisfactory results having 
been obtained with the arsphenamines, it seems inadvisable to substitute a weaker 
spirochetecidal agent." 
tryparsamide in late neurosyphilis-The type of case experimented upon 
by Lorenz and his co-workers was wholly different from those treated by Moore 
and his co-workers. The former group treated institutionalized patients, the 
majority of whom had definite psychoses, and about half of whom were advanced 
general paralytics; moreover none of them had been treated for syphilis during 
the six months preceding the administration of tryparsamide. The latter group 
was made up of clinic patients, some of whom had had prolonged and recent 
antisyphilitic treatment. The Lorenz group treated 97 cases with a definite 
routine (described above) of tryparsamide and salicylate of mercury. The Moore 
49 group treated 40 cases of alternating courses of tryparsamide and inunctions of 
mercury, varying the dosage and the length of the course from time to time. Yet 
their results are in substantial agreement, as shown in the accompanying table 
(from Moore). 
"In the whole group of patients there was only one in whom some improve- 
ment in the fluid did not occur as a result of tryparsamide therapy. 
"From the clinical standpoint, ten patients were regarded as arrested, and 
seventeen as improved by previous treatment. These results were bettered by 
tryparsamide. Of eight previously untreated patients, five are regarded as arrested, 
two improved, and only one as unimproved. From the previously treated group, 
twenty-two are considered to be arrested, three improved, and four unimproved. 
Six of our patients have remained well for as long as three years following the 
institution of tryparsamide. 
"With regard to the blood Wassermann reaction, a curious phenomenon is 
observed. In fourteen instances, the test was negative when tryparsamide was 
begun, and remained so. In eleven, it was positive at the start of treatment, 
but in only two of these was any change toward the negative phase apparent as 
the result of treatment. In four patients, the blood Wassermann reaction was 
negative when tryparsamide was started, and became completely positive during 
the course, even though in the same patients the spinal fluid was simultaneously 
changing toward negative. The same type of response was seen in patients with 
tertiary syphilis, as mentioned above. 
"In this point only do our results differ from those of Lorenz and his asso- 
ciates. So far as clinical and cerebrospinal fluid results are concerned, the per- 
centages are surprisingly close. The Wisconsin group, however, obtained a 
reduction or a reversal of the blood Wassermann reaction in 98.7 per cent of 
their cases, as compared with only 26.6 per cent in our material. The explana- 
tion for this variance is not clear to us. The only essential difference in treat- 
ment is that the Wisconsin workers employed a somewhat larger unit dose of 
tryparsamide plus mercuric salicylate in combination with it, while we used 
tryparsamide either alone or (in a few cases) in combination with an arsphe- 
namine." 
the effect of tryparsamide ON nutrition-"In common with others who 
have worked with this drug, we have been struck by the fact that some patients 
gained markedly in weight and the general physical condition improved. We 
have definite information available regarding the weight curves during a single 
course of tryparsamide (from four to eighteen doses) in fifty patients. In twelve 
there was no gain or loss; in nine, a slight loss in weight occurred during treat- 
ment (minimum 1 kg.; maximum 9 kg., the latter in a general aralytic whose 
clinical course was rapidly down-hill, average loss 3 kg.). Twenty-nine patients, 
however, gained in weight during their treatment, the average gain being 5 kg. 
In a few instances we have employed the drug solely for its tonic effect, some- 
times with startling results. For example, a girl with congenital syphilis, age 
24, weighed 41.8 kg. at the beginning and end of the first course of arsphenamine. 
During the subsequent four weeks she was given a weekly injection of 1 gm. of 
tryparsamide, with no other change in therapy, diet or mode of living. In these 
four weeks she gained 5.9 kg. (13 pounds) and has maintained this gain during 
the following year. In about half the cases of this type, a satisfactory gain in 
weight has followed the use of the drug; in the other half apparently similar 
50 clinically, no gain has resulted. The question apparently hinges on factors with 
which we are as yet unfamiliar." 
summary-"The place of tryparsamide in syphilotherapy has still to be defined. 
Our experience indicates its value in certain types of neurosyphilis, and together 
with the results of the Wisconsin workers, leads us to think it a more effective 
drug than any other now at our disposal. In other forms of syphilis, in which 
the nervous system is not involved, we have seen no evidence that the drug is of 
any value, except for its tonic effect in undernourished patients. It appears to 
be contraindicated in early syphilis because of its comparatively feeble spiro- 
cheticidal activity. In tertiary and latent syphilis, also, our experience leads us 
to believe that it is inferior to the arsphenamines, and that, if used at all in this 
stage of the disease, it should not replace the arsphenamines or mercury, but only 
supplement them. For the present, therefore, its use should, we think, be re- 
stricted to neurosyphilis, and, possibly, to cardiovascular syphilis. It is empha- 
sized that the use of tryparsamide is to be avoided in all cases in which optic 
nerve impairment already exists, and it is recommended that during tryparsamide 
administration close attention be given to the fundus of the eye and the sight." 
(Moore et al.) 
Syphilis of the Innocent-Under the above title Harry C. and 
Maida H. Solomon56 have published a volume of 239 pages, the sub- 
title of which is "A Study of the Social Effects of Syphilis on the 
Family and the Community; with 152 illustrative cases." The volume 
is divided into chapters on "The Individual," "The Mate," "The 
Child," "The Family," "The Community," and covers the subject of 
the social aspects of syphilis in a full and judicial manner that has 
rarely been equalled. This is due to the method of approach, which 
is to quote all prominent authorities, giving their opinions as well as 
their statistics, and to reduce the authors' own comments to a mini- 
mum. The personal element is thus almost wholly eliminated and the 
reader is charmed from one page to another by the fascinating inter- 
play of opposed opinion. Yet the whole is so judiciously edited that 
the volume might be entrusted to the hands of an uninformed person 
with less danger of ensuing harm than any such book we have read. 
The utmost limit of reticence is reached when the authors, after six 
pages of quotation of the "Opinion of Various Authorities on the 
Marriage of a Syphilitic," state merely that "it is evident that all 
these opinions allow a great lattitude in the interpretation of the 
term 'non-contagiousness.' It is also clear that the time element is 
brought in as a more important factor than a negative Wassermann 
reaction"-a wise conclusion, indeed, and a most temperate one, which 
they then proceed to illustrate by the case of a neurosyphilitic who 
married on the strength of a negative Wassermann reaction. 
This volume is an admirable treatise on the social problems of 
syphilis. Though there is scarcely any strictly new and unpublished 
material between its covers, there is much to fascinate, much to inform 
even the expert. 
51 Diagnosis of Chancroid by Culture-Teague and Deibert57'58 
have improved the culture of the Ducrey bacillus to such a degree 
that it can be used "with as much ease and almost as much certainty as 
the familiar culture of the diphtheria bacillus." 
They submitted to culture the secretions from 274 sores of the 
male genitals, obtaining 140 cultures positive for Ducrey, and 134 
negative. In the majority of cases the culture was taken the first time 
the patient entered the clinic, and without interrupting the routine 
treatment of the clinic. The authors estimate the accuracy of the 
method as "probably above 90 per cent," and cite a series of 32 cases 
examined at the United States Marine Hospital Clinic by Traynor 
with 22 positive and 10 negative results. 
The medium employed is clotted blood; the technic as follows: 
"A rabbit is bled from the heart with a sterile 20 c.c. syringe and the 
blood is distributed in amounts slightly less than 1 c.c. in test tubes 
about 100 mm. long and 10 mm. in diameter. The blood is allowed 
to clot at room temperature, is then heated for five minutes at 55°C. 
and is either used at once or is kept in the ice box overnight and used 
on the following day. We found that instead of heating the clotted 
blood equally good results were obtained when the tubes were simply 
kept in the ice box for from three to five days before they were used." 
Pieces of stiff iron wire, gauge 18, about 5%" long are bent upon them- 
selves at one end for about Ten or twelve of these wires are placed in a 6" 
test tube and are heated in the dry sterilizer. The patient is told to remove the 
dressing, if he has one, and a bit of the pus from the ulcer is picked up with the 
bent end of the sterile wire, the latter having first been rubbed gently over the 
base of the ulcer or its undermined edge. The pus is then transferred to a tube 
of clotted blood and is quickly distributed in the serum by passing the wire several 
times around the clot. A second tube is inoculated in the same way with a 
fresh wire. After from 20 to 24 hours' incubation at 37°C. the serum around 
the clot is thoroughly stirred with a platinum loop and then a smear is made 
and stained by Gram's method. Examination with the oil-immersion lens shows 
characteristic chains of small Gram-negative bacilli, sometimes apparently in pure 
culture, sometimes together with Gram-positive cocci or bacilli. If these char- 
acteristic chains are present it is stated that the culture is positive for Ducrey 
bacilli. 
Positive cultures have been repeatedly obtained from lesions under treat- 
ment by argyrol, iodoform and other drugs. It was not found profitable either 
to use a larger number of tubes than two, or to cleanse the ulcer with salt solu- 
tion. Human blood was not found as effective a culture medium as rabbit blood. 
Cultures negative after 24 hours were reexamined after 48 hours. Though 
a few late positives were thus obtained the authors advise that as routine the 
report should be made after the first examination at the end of 24 hours. 
They give the following three characteristics of the Ducrey bacillus: (1) 
It is a small Gram-negative bacillus growing in characteristic long chains and 
tangles in clotted rabbit blood ; (2) it forms on blood agar characteristic colonies 
52 that readily glide over the surface of the medium; (3) it does not grow on any 
of the ordinary laboratory media with the exception of blood agar." 
Secondary cultures may be carried on blood agar plates. The authors 
recognize that blood has been previously used for the culture of the bacillus of 
chancroid, but claim the first demonstration of the practicability of the method 
for routine diagnosis. 
Treatment of Chancroid With Mercurochrome-Young, 
White, and Swartz11 advise the use of "a starch paste containing 5 per 
cent of mercurochrome -220 by weight," the sore being dressed only 
once daily. "In all of the cases, the sores cleaned off in from one to 
four days, and presented a healthy healing surface." Thereafter, 
boric acid ointment and silver nitrate were applied to granulations. 
"Tables giving length of time required for complete healing are not 
included, as many of the patients left the clinic after the sore was 
partly healed." 
In a later publication they quote Bowman as using 1 to 2 per cent 
pastes with excellent results, "all the sores immediately cleaning off 
and healing in from six to twenty days, without contraction of compli- 
cations"; and themselves state that venereal ulcerations, when dressed 
with mercurochrome, "almost without exception . . . promptly 
become cleaner and the granulations healthy looking." 
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Hill, Moore and Young, Journal of American Medical Association, 79:877-82, 
September 9, 1922. 
55. "The treatment of central nervous system syphilis with a new arsenical," by W. F. 
Lorenz, M. D., Wisconsin Medical Journal, 20:336-37, December, 1921. 
56. "Syphilis of the innocent," by United States Interdepartmental Social Hygiene 
Board, 1922. 
57. "The value of the cultural method in the diagnosis of chancroid," by Oscar Teague 
and Olin Deibert, Journal of Urology, 4:543-50, December, 1920. 
58. "Some observations on the bacillus of Unna-Ducrey," by Oscar Teague and Olin 
Deibert, Journal of Medical Research, 43:61-75, January/March, 1922. 
57 FINANCIAL DATA ON SCIENTIFIC RESEARCH FUND 
Amount of appropriation. 
Assisting 
State and institution. 
1921, 50-50 ap- 
propriation 
Num- 
ber 
of re- 
search- 
es. 
Scien- 
tists 
in 
charge. 
profes- 
sors, 
techni- 
cians, 
social 
workers, 
etc. 
1919 
1920 
From 
Gov- 
ern- 
ment. 
From 
insti- 
tution. 
California: 
Leland Stanford University 
$7,200 
$885 
3,875 
$1,200 
$1,200 
3 
4 
8 
University of California 
1 
1 
2 
Connecticut, Yale University 
4,000 
2 
2 
4 
Illinois: 
John McCormick Institute 
3,000 
6,000 
3,500 
1 
1 
8 
Northwestern University 
6,000 
2,500 
6,800 
2,480 
9,000 
8,000 
6,000 
2,500 
6,800 
2,480 
9,000 
8,000 
2 
2 
5 
University of Illinois 
1 
1 
4 
Indiana, The South Bend Clinic 
2 
2 
5 
Iowa, University of Iowa 
5,320 
19,050 
10,000 
13,200 
1 
1 
3 
Maryland, Johns Hopkins University. . . 
Massachusetts: 
Harvard University 
19,050 
7,000 
6 
2 
6 
1 
13 
1 
Boston Psychiatric Institute 
2 
1 
5 
Michigan, University of Michigan 
6,000 
1 
1 
4 
Minnesota, University of Minnesota. . . . 
8,250 
3,000 
9,000 
4,000 
3 
4 
5 
Missouri: 
St. Louis University 
1,500 
1,500 
1 
1 
2 
Washington University 
13,200 
5,000 
4,000 
2,500 
5,000 
2,500 
5,000 
4 
3 
10 
Nebraska, University of Nebraska 
2 
1 
5 
New York: 
Columbia (College of Physicians and 
Surgeons).. 
4,200 
1 
1 
2 
Cornell University 
7,440 
1 
1 
2 
New York University and Bellevue 
Hospital 
5,400 
1 
1 
4 
Union University, Albany Medical 
College 
4,380 
1,550 
2,500 
8,000 
2 
3 
6 
Pennsylvania: 
Woman's Medical College 
1 
2 
4 
Jefferson Medical College 
1 
2 
3 
14 
Wisconsin, University of Wisconsin 
12,000 
6,800 
6,800 
2 
1 
Total (14 States, 23 institutions). . 
96,570 
103,430 
43 
44 
115 
Note.-The tabulated number of persons engaged in these researches refers to trained personnel, and does 
not include clerks, dieners, etc. 
[Board began making appropriations for researches in March, 1919] 
SUMMARY. 
Number of researches started during fiscal year 1919 25 
Number of researches started during fiscal year 1920 11 
Number of old researches extended during fiscal year 1920 11 
Number of new researches started during fiscal year 1921 4 
Number of old researches extended during fiscal year 1921 11 
Number of institutions represented in the 43 researches 23 
Number of States represented 14 
Number of scientists in direct charge of investigations 44 
Number of trained assistants (professors, technicians, social workers) 115 
Board's appropriations for scientific researches, 1919 $96,570 
Board's appropriations for scientific researches, 1920 $103,430 
Board's appropriations for scientific researches (50-50 plan), 1921 $85,000 
Institutions' appropriations to match board's allotment, 1921 $85,000 
Joint appropriation for scientific researches, 1921 $170,000 
Number of researches completed 4 
Number of reports published, 1921 20 
58 LIST OF PUBLICATIONS CONCERNING THE RESEARCHES UNDER GRANT 
OF THE SCIENTIFIC FUND OF THE UNITED STATES INTER- 
DEPARTMENTAL SOCIAL HYGIENE BOARD 
Boston Psychopathic Hospital 
"A study of the economic status of forty-one paretic patients and their families," by 
Harry C. Solomon and Maida H. Solomon. Reprinted from Mental Hygiene, 
5:556-65, July, 1921. 
"The effects of syphilis on the families of syphilitics seen in the late stages," by H. C. 
Solomon, M. D., and M. H. Solomon, B. S., Social Hygiene, 6:469-86, October, 1920. 
"The incidence of sclerosis of the cornu ammonis and convulsions in general paresis," 
by A. E. Taft. Reprinted from the Journal of Neurology and Psychopathology, 
2:221-23, November, 1921. 
"A study of the gonococcus and gonococcal infections," by M. W. Cook and D. D. Staf- 
ford. Reprinted from the Journal of Infectious Diseases, 29:561-76, December, 1921. 
University of California 
"Some observations on the bacillus of Unna-Ducrey," by Oscar Teague and Olin Deibert, 
Journal of Medical Research, 43:61-75, January/March, 1922. 
"The value of the cultural method in the diagnosis of chancroid," by Oscar Teague and 
Olin Deibert. Reprinted from the Journal of Urology, 4:543-50, December, 1920. 
Columbia University, College of Physicians and Surgeons 
Cornell University Medical College 
"A serological study of the gonococcus group," by John C. Torrey and George T. Buckell. 
Reprinted from the Journal of Immunology, 7:305-59, July, 1922. 
"Comparative value from the public health standpoint, of smears, cultures and com- 
plement fixation in the diagnosis of chronic gonorrhea in women," by J. C. Torrey, 
M. A. Wilson and G. T. Buckell. Reprinted from Journal of Infectious Diseases, 
31:148-58, August, 1922. 
"Cultural methods for the gonococcus," by J. C. Torrey and G. T. Buckell, Journal of 
Infectious Diseases, 31:125-47, August, 1922. 
Harvard Medical School 
"Hypophosphorous acid preparation of arsphenamine. (3,3'-Diamino-4,4'-Dihydroxy- 
arsenobenzene dihydrochloride-)," by Walter G. Christiansen. Reprinted from 
the Journal of the American Chemical Society, 42:2402-5, November, 1920. 
"Indirect reduction of 3-amino-4-hydroxyphenyl-arsonic acid to arsphenamine," by Walter 
G. Christiansen. Reprinted from the Journal of the American Chemical Society, 
43:370-75, February, 1921. 
"Purifying sodium hydrosulfite; a modification of Jellinek's method," by Walter G. 
Christiansen and Arthur J. Norton. From the Journal of Industrial and Engineer- 
ing Chemistry, 14:1126-28, December, 1922. 
"Some factors relating to the toxic action of arsphenamine," by Reid Hunt, M. D. Re- 
print from the Journal of the American Medical Association, 76:854-59, March 
26, 1921. 
"The arsonation of ortho- and meta-cresol," by Walter G. Christiansen. From the 
Journal of the American Chemical Society, 45:800-4, March, 1923. 
"The arsonation of phenol," by W. G. Christiansen and A. J. Norton, Journal of the 
American Chemical Society, 45:2188-92, September, 1923. 
59 "Some derivatives of arsphenamine," by W. G. Christiansen, Journal of the American 
Chemical Society, 45:2182-88, September, 1923. 
"Observations on the properties of arsphenamine," by W. G. Christiansen, Journal of 
American Chemical Society, 45:1807-11, July, 1923. 
"The hemolytic properties of arsphenamine and fifteen allied compounds," by G. P. 
Grabfield. Reprinted from the Journal of Pharmacology and Experimental Thera- 
peutics, 19:343-52, June, 1922. 
"The relation between the mode of synthesis and toxicity of arsphenamine and related 
compounds," by Walter G. Christiansen. From the Journal of the American Chemi- 
cal Society, 43:2202-10, October, 1921. 
"The sulfur content of arsphenamine and its relation to the mode of synthesis and the 
toxicity, I," by Walter G. Christiansen, Journal of the American Chemical Society, 
44:847-54, April, 1922. 
"The sulfur content of arsphenamine and its relation to the mode of synthesis and the 
toxicity. II," by Walter G. Christiansen. From the Journal of the American 
Chemical Society, 44:854-59, April, 1922. 
"The sulfur content of arsphenamine and its relation to the mode of synthesis and the 
toxicity. Ill," by Walter G. Christiansen. From the Journal of the American 
Chemical Society, 44:2334-42, October, 1922. 
"The sulfur content of arsphenamine and its relation to the mode of synthesis and the 
toxicity. IV," by Walter G. Christiansen, Journal of the American Chemical 
Society, 45:1316-21, May, 1923. 
"N,N'-Diamethylenesulfurous acid-3,3'-Diamino-4,4'-Dihydroxy-Azobenzene: a nitrogen 
compound analogous to sulfarsphenamine," by W. G. Christiansen, Journal of the 
American Chemical Society, 46:497-503, February, 1924. 
University of Illinois 
"Aliphatic arsonic and arsinic acids, and aliphatic-aromatic arsinic acids," by A. J. 
Quick and Roger Adams. Reprint from the Journal of the American Chemical 
Society, 44:805-16, April, 1922. 
"Arsenated arylamino alcohols," by C. W. Rodewald with Roger Adams, Journal of 
American Chemical Society. 
"Arsenated derivatives of cinchoninic acid. I," by Katharine Ogden with Roger Adams, 
Journal of the American Chemical Society. 
"Arsenated derivatives of cinchoninic acid. II," by H. O. Calvery with Roger Adams, 
Journal of the American Chemical Society. 
"Diarsono-diphenyl and derivatives," by W. W. Bauer with Roger Adams, Journal of 
the American Chemical Society, 46:1925-31, August, 1924. 
"Arsenated derivatives of phenyldiketopyrrolidines," by J. R. Johnson with Roger Adams, 
Journal of the American Chemical Society, 45:1307-15, May, 1923. 
"Arsenated derivatives of siphenyldiketopyrrolidines. II," by C. W. Rodewald, I. A. 
Koten and Roger Adams, Journal of the American Chemical Society. 
"2 phenylquinoline-4-carboxylic acid-6-arsonic acid," by J. R. Johnson and Roger Adams. 
Reprinted from the Journal of the American Chemical Society, 43:2255-57, Octo- 
ber, 1921. 
"The reactions of the arsines. Preliminary paper. Condensation of primary arsines 
with aldehydes," by Roger Adams and Charles Shattuck Palmer. Reprint from 
the Journal of the American Chemical Society, 42:2375-78, November, 1920. 
"The reactions of the arsines. II. Condensation of aromatic primary arsines with alde- 
hydes," by Charles Shattuck Palmer with Roger Adams, Journal of the American 
Chemical Society, 44:1356-82, June, 1922. 
60 University of Iowa 
"Cultivation of the gonococcus," by Mary J. Erickson and Henry Albert. Reprinted 
from the Journal of Infectious Diseases, 30:268-78, March, 1922. 
Johns Hopkins University 
"A new germicide for use in the genito-urinary tract: mercurochrome-220," by Hugh H. 
Young, Edwin C. White and Ernest O. Swartz. Reprinted from the Journal of 
the American Medical Association, 73:1483-91, November 15, 1919. 
"Further clinical studies on the use of mercurochrome-as a general germicide," by H. 
H. Young, E. C. White and E. O. Swartz, Journal of Urology, 5 :353-88, April, 
1921, and Journal of the American Medical Association, 77:93-98, July 9, 1921. 
"Culture method for the gonococcus," by E. O. Swartz, Journal of Urology, 4:325- 
45, 1920. 
"A new culture method for the gonococcus," by E. O. Swartz, M. D. Report of experi- 
mental studies, Journal of Urology, 4:325-45, August, 1920. 
"Certain cultural characteristics of the gonococcus," by E. O. Swartz, A. T. Shohl and 
D. M. Davis, Johns Hopkins Hospital Bulletin, 31:449-52, December, 1920. 
"The testing of germicidal substances against the gonococcus," by D. M. Davis and E. O. 
Swartz, Journal of Infectious Diseases, 27:591-601, December, 1920. 
"The action on the gonococcus of sodium oleate, alone and in combination with other 
drugs," by D. M. Davis and E. O. Swartz, Journal of Urology, 4:409-18, Octo- 
ber, 1920. 
"Mercury derivatives of phthaleins," by Edwin C. White, Ph.D., Journal of American 
Chemical Society, 42:2355-66, November, 1920. 
"The action on the gonococcus of various drugs commonly used in the prophylaxis and 
and treatment of gonorrhea," by E. O. Swartz and D. M. Davis, Journal of Urology, 
5:235-47, March, 1921. 
"Action of mercurochrome-220 on the gonococcus," by E. O. Swartz, M. D., and D. M. 
Davis, M. D., Journal of the American Medical Association, 76:844-46, March 
26, 1921. 
"A further discussion of germicides and presentation of the new germicide-Meroxyl," 
by H. H. Young, M. D., and Edwin C. White, Ph.D., Surgery, Gynecology and 
Obstetrics, 36:508-21, April, 1923. 
"A psychological study of motion pictures in relation to venereal disease campaigns," 
by Karl S. Lashley and John B. Watson, Washington, United States Interdepart- 
mental Social Hygiene Board, 1922, 88 p. 
' Studies in asymptomatic neurosyphilis. I. A tentative classification of early asymp- 
tomatic neurosyphilis," by A. Keidel, M. D., and J. E. Moore, M. D., Archives of 
Neurology and Psychiatry, 6:284-91, September, 1921. 
"Studies in asymptomatic neurosyphilis. II. The classification, prognosis and treatment 
of early asymptomatic neurosyphilis," by J. E. Moore, M. D., Johns Hopkins Hos- 
pital Bulletin, 33:231-46, July, 1922. 
"Studies in asymptomatic neurosyphilis. III. The apparent influence of pregnancy on 
the incidence of neurosyphilis in women," by J. E. Moore, Archives of Internal 
Medicine, 30:548-54, November, 1922. 
"Studies in asymptomatic neurosyphilis. IV. The apparent role of immunity in the 
genesis of neurosyphilis," by A. Keidel, Journal of the American Medical Associa- 
tion, 79:874-76, September 9, 1922. 
61 "Studies in familial neurosyphilis. I. Conjugal neurosyphilis," by J. E. Moore, M. D., 
and A. Keidel, M. D., Journal of the American Medical Association, 77:1-7, July 
2, 1921. 
"Studies in familial neurosyphilis. II. Familial neurosyphilis from various extra familial 
sources: a clinical contribution to the question of neurotropism," by J. E. Moore 
and A. Keidel, Journal of the American Medical Association, 80:818-20, March 
24, 1923. 
"Studies on the the influence of pregnancy in syphilis. I. The course of syphilitic infec- 
tion in pregnant women," by J. E. Moore, M. D. Johns Hopkins Hospital Bulletin, 
34:89-99, March, 1923. 
John McCormick Institute for Infectious Diseases 
"A simplified plate method of partial oxygen tension in the cultivation of the gonococ- 
cus," by Russel D. Herrold. Reprinted from the Journal of the American Medical 
Association, 74:1716-17, June 19, 1920. 
"Determination of cure in gonorrheal infection of the male," by Russel D. Herrold, M. D. 
Reprinted from the Journal of the American Medical Association, 76:225-27, Jan- 
uary 22, 1921. 
Leland Stanford Junior University 
"Rectal injection of massive doses of neo-arsphenamin," by Henry G. Mehrtens. Re- 
printed from the Journal of the American Medical Association, 76:574-76, Feb- 
ruary 26, 1921. 
Massachusetts Psychiatric Institute 
"Provocative reactions in the cerebrospinal fluid in neurosyphilis," by Harry C. Solomon. 
Reprinted from Archives of Dermatology and Syphilology, 2:679-91, December, 1920. 
"The social worker's approach to the family of the syphilitic," by Maida Herman Solo- 
mon. Reprint from Hospital Social Service, 3:442-52, June, 1921. 
University of Michigan 
"A study of rabbit spirochetosis," by Dr. A. S. Warthin, Dr. Ruth Wanstrom, Estella 
Buffington, Journal of Infectious Diseases, 32:315-32, May, 1923. 
"A more rapid and improved method of demonstrating spirochetes in tissues," by A. 
Scott Warthin and Allen C. Starry. Reprint from the American Journal of 
Syphilis, 4:97-103, January, 1920. 
"The cultivation of Spirochaeta cuniculi," by Estella Buffington. (This work still in 
progress.) 
"The demonstration of spirochaeta pallida in aortic lesions," by Dr. A. S. Warthin. (In 
process of publication.) 
"Syphilis of the umbilical cord," by Dr. A. S. Warthin. (Will be published during the 
summer.) 
"Occurrence and staining of leptospira icteroides in guinea-pigs inoculated experimentally, 
with a study of the lesions produced," by R. C. Wanstrom, Journal of Infectious 
Diseases, 34:110-16, February, 1924. 
"Application of the Warthin-Starry silver-agar method to the demonstration of spiro- 
chaeta pallida in the spinal fluid by means of coagula obtained by the alzkeimer 
method," by A. S. Warthin, M. D., Ruth C. Wanstrom, M. D., and Estella Buf- 
fington, Archives of Dermatology and Syphilology, 8:461-68, October, 1923. 
"Second improved method for the demonstration of spirochaeta pallida in the tissues," 
by A. Scott Warthin and Allen C. Starry. Reprinted from the Journal of Ameri- 
can Medical Association, 76:234-37, January 22, 1921. 
62 "Segundo metodo perfeccionado para la demonstracion del espiroqueto palido en los 
tejidos," by Dr. A. S. Warthin and Dr. A. C. Starry. Reprinted from the Journal 
of the American Medical Association, 5:307-10, Marzol, 1921. (Edicion en 
Espanola.) 
"Improved methods for staining Spirochaeta pallida in tissue," by Dr. A. S. Warthin 
and Dr. A. C. Starry. Reprinted from Society for Experimental Biology and Medi- 
cine, Proceedings, v. 18, p. 82-84, 1920/21. 
"The excretion of spirochaeta pallida through the kidneys," by A. Scott Warthin. Re- 
printed from the Journal of Infectious Diseases, 30:569-91, June, 1922. 
"The staining of spirochaetes in cover-glass smears by the silver-agar method," by A. S. 
Warthin and A. C. Starry. Reprinted from the Journal of Infectious Diseases, 
30:592-600, June, 1922. 
University of Minnesota Medical School 
"Does the introduction of an ethoxy group into aromatic compounds increase their bac- 
tericidal action upon the pneumococcus and the gonococcus?" by A. D. Hirsch- 
felder and L. J. Paukow, Society for Experimental Biology and Medicine, Proceed- 
ings, v. 19, p. 64-67, 1921/22. 
"Comparative studies in the chemistry of blood and cerebrospinal fluid," by Greta Egerer- 
Seham and G. E. Nixon. Reprinted from the Archives of Internal Medicine, 
28:561-85, November, 1921. 
"Methods used in determining the electric conductivity of solutions," by J. F. McClendon. 
Reprinted from the Journal of Biological Chemistry, 43:317-22, September, 1920. 
"The pharmacological action of some ethers and esters of saligenin," by A. D. Hirsch- 
felder and H. H. Hensen, Society for Experimental Biology and Medicine, Pro- 
ceedings, v. 19, p. 145-48, 1921/22. 
"Mercury compounds of some phenol carbinols," by M. C. Hart and A. D. Hirschfelder. 
Reprinted from the Journal of the American Chemical Society, 43:2678-86, Decem- 
ber, 1920. 
"Saligenin as a local anesthetic for the female urethra," by A. D. Hirschfelder and H. M. 
N. Wynne. Reprinted from the Journal of the American Medical Association, 
75:1770, December 25, 1920. 
"Some derivatives of saligenin," by M. C. Hart and A. D. Hirschfelder. Reprinted from 
the Journal of the American Chemical Society, 43:1688-93, July, 1921. 
"Studies of cerebrospinal fluid and blood of syphilitic and normal persons, with special 
reference to the immunity reactions and the colloidal gold test on the original and 
ultrafiltered fluids and serums," by C. E. Nixon, M. D., and Korchi Naito, M. D. 
Reprinted from Archives of Internal Medicine, 30:182-215, August, 1922. 
"Further observations on acriflavine in gonorrhea," by Dr. Edwin Davis, Nebraska State 
Medical Journal, 5:19-23, January, 1920. (Problems under investigation.) 
"Urinary antisepsis, a study of the antiseptic properties and the renal excretion of 204 
anilin dyes," by Dr. Edwin G. Davis, American Journal of the Medical Sciences, 
161:251-67, February, 1921. 
"Urinary antisepsis-The secretion of antiseptic urine by man following the oral ad- 
ministration of proflavine and acriflavine-preliminary report," by Edwin G. 
Davis. Reprinted from Journal of Urology, 5:215-33, March, 1921. 
University of Nebraska Medical College 
University of Nevada 
"Cultivation of the gonococcus," by M. J. Erickson and Henry Albert, Journal of Infec- 
tious Diseases, 30:268-78, March, 1922. 
63 Northwestern University 
"Arsenated benzophenone and its derivatives. II," by W. Lee Lewis and H. C. Cheetham 
Journal of the American Chemical Society, 45:510-15, February, 1923. 
"Arsenated benzanilide and its derivatives," by W. Lee Lewis and C. S. Hamilton, 
Journal of the American Chemical Society, 45:757-62, March, 1923. 
"Arsenated benzophenone and its derivatives," by W. Lee Lewis and H. C. Cheetham. 
Reprinted from the Journal of the American Chemical Society, 43:2117-21, Sep- 
tember, 1921. 
"7-Chloro-7,12-dihydro-y-benzo-pennarsazin and some of its derivatives," by W. Lee 
Lewis and C. S. Hamilton. Reprinted from the Journal of the American Chemical 
Society, 43:2218-23, October, 1921. 
"Some derivatives of phenoxarsin," by W. Lee Lewis, C. D. Lowry and F. H. Bergeim. 
Reprinted from the Journal of the American Chemical Society, 43 :891-96, April, 1921. 
"Recent developments in the organic chemistry of arsenic," by W. Lee Lewis, Industrial 
and Engineering Chemistry, 15:17-19, January, 1923. 
"The preparation of phenylimido-phosgene, and the chlorination of formanilide," by R. 
S. Bly, G. A. Perkins and W. Lee Lewis, Journal of the American Chemical 
Society, 44:2896-2903, December, 1922. 
"Some mercury derivatives of phenol ethers," by F. C. Whitmore and E. B. Middleton, 
Journal of the American Chemical Society, 45:1753-55, July, 1923. 
"Reaction of alkali halides with mercury derivatives of phenol," by F. C. Whitmore and 
E. B. Middleton, Journal of the American Chemical Society, 43:619-24, March, 1921. 
"Cultivation and isolation of the gonococci," by R. A. Kinsella, G. O. Broun and O. 
Garcia, Journal of Infectious Diseases, 32:1-7, January, 1923. 
St. Louis University School of Medicine 
Stanford University Medical School 
"Preliminary report on an investigation of the 'provocative Wassermann' controlled by 
the ice-box method," by Ruth T. Shepardson. Reprinted from the California State 
Journal of Medicine, 20:80-83, March, 1922. 
"Value of tests with commercial luetin," by H. E. Alderson, M. D. Reprinted from the 
Archives of Dermatology and Syphilology, 5:592-600, May, 1922. 
Tulane University 
"A method for the concentration of cells and bacteria in prostatic secretion," by Dr. 
Foster M. Johns, Journal of the American Medical Association, 80:463-64, Feb- 
ruary 17, 1923. 
Union University Medical School 
''Cholesterol and cholesterol esters in blood showing a positive Wassermann reaction," 
by A. Knudson, T. Ordway and H. Ferguson, Society for Experimental Biology 
and Medicine, Proceedings, v. 18, p. 229-30, 1920/21. 
Washington University School of Medicine 
"A biologic study of latency in syphilis: general considerations: latency-A biologic 
reaction," by Martin F. Engman, M. D., and Frederick Eberson. Reprinted from 
the Archives of Dermatology and Syphilology, 3:347-71, April, 1921. 
64 "A study of the incidence of hereditary syphilis," by P. C. Jeans and J. V. Cooke. Re- 
printed from the American Journal of Diseases of Children, 22:402-11, October, 1921. 
"The transmission of syphilis to the second generation," by J. V. Cooke and P. C. Jeans. 
Reprinted from the American Journal of Syphilis, 6:569-85, October, 1922. (In- 
direct result of the Social Hygiene Board grant.) 
"Dissemination of spirochaeta pallida in experimental syphilis," by Frederick Eberson. 
Reprinted from Archives of Dermatology and Syphilology, 3:111-16, February, 1921. 
"Immunity studies in experimental syphilis," by Frederick Eberson. Reprinted from 
Archives of Dermatology and Syphilology, 3:775-87, June, 1921. (Infectivity and 
survival of spirochaeta pallida in rabbits with observations on some strains from 
latent syphilis.) 
"An experimental investigation of the latent syphilitic as a carrier," by Drs. M. F. 
Engman and F. Eberson, Journal of American Medical Association, 76:160-66, 
January 15, 1921. Preliminary communication. 
"A study of the incidence of hereditary syphilis," by Dr. P. C. Jeans and Dr. J. V. Cooke, 
American Journal of Diseases of Children, 22:402-11, October, 1921. 
"A study of 443 cases of hereditary syphilis with especial reference to the results of 
treatment," by Dr. Park J. White and Dr. B. S. Veeder, American Journal of 
Syphilis, 6:353-91, July, 1922. Part I. Social and clinical data. Part II. End 
results of treatment. 
"Immunity studies in experimental syphilis. (Spirocheticidal properties of serums in 
latent and experimental syphilis) with some observations on immunity," by Fred- 
erick Eberson. Reprinted from Archives of Dermatology and Syphilology, 4:490- 
511, October, 1921. 
"The transmission of complement-fixing substances from mother to child," by J. V. Cooke, 
American Review of Tuberculosis, 6:127-33, April, 1922. (Result of a study of 
the incidence of hereditary syphilis, and is therefore an indirect result of the 
Social Hygiene Board grant.) 
"An improved method for the preparation of primary arsanilic acid," by H. C. Cheetham 
and John H. Schmidt. Reprinted from the Journal of the American Chemical 
Society, 42:828-29, April, 1920. 
"An automatic pipetting device," by W. F. Lorenz, Journal of Laboratory and Clinical 
Medicine, 7:54-57, October, 1921. 
"The relation of chemical constitution of certain organic arsenical compounds to their 
action on the optic tract," by A. G. Young and A. S. Loevenhart, Journal of Phar- 
macology and Experimental Therapeutics, 23:107-26, March, 1924. 
"The therapeutic use of tryparsamide in neuro-syphilis," by W. F. Lorenz, A. S. Loeven- 
hart, W. J. Bleckwenn and F. J. Hodges, Journal of American Medical Associa- 
tion, 80:1487-1502, May 26, 1923. 
"The treatment of central nervous system syphilis with a new arsenical," by W. F. 
Lorenz, M. D., Wisconsin Medical Journal, 20:336-37, December, 1921. 
University of Wisconsin Medical School 
65 LIST OF THE SCIENTIFIC RESEARCHES THAT HAVE BEEN AIDED BY THE 
UNITED STATES INTERDEPARTMENTAL SOCIAL HYGIENE BOARD 
California, Berkeley 
University of California 
Drs. Frederick Gay, Marjorie Cook 
"Classification of gonococci and fixation reaction in gonorrhea." 
California, Stanford University 
Leland Stanford University Medical School 
Drs. H. G. Mehrtens, Wm. McKay, Mr. A. Motzkau, Mr. C. A. McArthur, Mr. P. 
S. Williams 
"The permeability of the meninges to antisyphilitic drugs-an attempt to increase 
their permeability." 
Leland Stanford University Medical School 
Drs. H. E. Anderson, H. E. Coe 
"An investigation into more effective methods of treating syphilis." 
Leland Stanford University Medical School 
Dr. H. G. Mehrtens 
"Quantitative estimation of arsenic in the spinal fluid following irritation of the 
meninges and intravenous injection of trysparsamide." 
Leland Stanford University Medical School 
Dr. William Ophuls 
"An investigation into more effective treatment in acute and chronic gonorrhea." 
Connecticut, New Haven 
Yale University Medical School 
Dr. George H. Smith 
"An intensive study of methods for the isolation and identification of the gono- 
coccus with a view to the determination of the homogeniety and heterogeniety of 
strains and their etiological relationships." 
Yale University Medical School 
Drs. M. C. Winternitz, Theodore S. Moise 
"Serological reactions on experimental syphilitic infection of the rabbit." 
Yale University Medical School 
Drs. M. C. Winternitz, F. P. McNamara, Sidney Moise 
"The demonstration of the syphilitic nature of unusual lesions encountered at the 
post mortem table." 
Illinois, Evanston 
Northwestern University 
Dr. Frank Whitmore, Messrs. Vergil E. Meharg, Edmund B. Middleton 
(a) "Synthesis of new organic compounds of mercury for use in treatment of 
syphilis of the central nervous system." 
(b) "Synthesis of new substances of the general type R- HG-O. OO, R' with vari- 
ations to make new drugs more suited to their use in syphilis and gonorrhea." 
Northwestern University 
Dr. W. Lee Lewis, Messrs. C. D. Lowry, Frank H. Bergein, Harold C. Cheetham, 
C. S. Hamilton 
"A synthesis of organic compounds containing arsenic of possible value in the 
treatment of syphilis of the central nervous system." 
66 Illinois, Urbana 
University of Illinois 
Dr. Roger Adams, Messrs. J. R. Johnson, C. S. Palmer, J. L. Hall 
"The preparation of new organic compounds which may have therapeutic value." 
Illinois, Chicago 
John McCormick Institute for Infectious Diseases 
Drs. L. Hektoen, R. D. Herrold 
"An investigation for the establishment, if possible, of a better and more definite 
standard of cure in gonorrheal infection in the male by means of improved 
methods of cultivation of the gonococcus, improvement in the provocative test, 
and by means of correlation of the results of fixation and other serologic tests." 
Indiana, South Bend 
The Clinic 
Drs. R. V. Hoffman, M. W. Lyon 
"(1) The relation of the Wassermann reaction to the complete and incomplete 
sterilization of syphilitic tissues; (2) An attempt to sterilize syphilitic tissue by 
constant saturation of the blood with drugs in tolerable doses." 
Iowa, Iowa City 
Iowa University (College of Medicine) 
Drs. Henry Albert, Mary Erickson 
"A selective medium for the isolation and cultivation of the gonococcus." 
Maryland, Baltimore 
Johns Hopkins University 
"(1) Studies in asymptomatic neurosyphilis; (2) Studies in familial neurosyphilis, 
and (3) Studies in the treatment of syphilis." 
Johns Hopkins University 
Drs. Hugh H. Young, E. O. Swartz, E. C. White 
(a) "Manufacture and investigation of a series of penetrating dyes in the treat- 
ment of chancroids." 
Drs. Hugh H. Young, D. M. Davis 
(b) "Experimental study of various methods of venereal prophylaxis with the ob- 
ject of developing simpler technic, more efficient and less expensive drugs." 
Drs. Hugh H. Young, E. C. White 
(c) "Development of new synthetic drugs for the treatment of gonorrhea." 
Drs. Hugh H. Young, E. C. White, J. F. Moore 
(d) "The manufacture and investigation of a series of new organic compounds in 
the treatment of syphilis." 
Johns Hopkins University 
Dr. J. Whitridge Williams 
"1. The operation of a clinic for the scientific study and treatment of patients 
suffering from syphilis; (2) Study of available data now accumulated concerning 
presence of syphilis in families; (3) Study of positive Wassermann reactions 
among different groups of patients; (4) The effect of syphilis on prenatal and 
infant mortality." 
Johns Hopkins University 
Karl S. Lashley and John B. Watson 
"A psychological study of motion pictures in relation to venereal disease campaigns." 
Dr. J. Whitridge Williams 
"A comparative application and analysis of some of the more popular forms of 
treatment for syphilis." 
67 "Studies of the treatment of syphilis in families, with special reference to its 
prenatal application." 
Massachusetts, Boston 
Massachusetts State Psychiatric Institute 
Dr. Harry C. Solomon 
"An investigation of the changes produced in the central nervous system by the 
treatment of neurosyphilis." 
Massachusetts State Psychiatric Institute 
Dr. Harry C. Solomon 
"Research on the family of the syphilitic (Social and economic effects of syphilis 
in special relation to the family)." 
Massachusetts State Psychiatric Institute 
Dr. Harry C. Solomon 
"The clinical results in the treatment of general paresis. (Summary of results 
obtained in the treatment of general paresis at the Boston Psychopathic Hospital 
and state institutions of Massachusetts for a period of seven years)." 
Massachusetts, Cambridge 
Harvard University Medical School 
Dr. Reid Hunt, Mr. W. G. Christiansen 
"An investigation of the properties contributing to the toxity of arsphenamine, 
neoarsphenamine, and analogous products." 
Harvard University Medical School 
Dr. Reid Hunt, Mr. W. G. Christiansen x 
"An investigation of methods for preparing safer, cheaper and also new arsenicals 
in the treatment of syphilis." 
Michigan, Ann Arbor 
University of Michigan 
Dr. A. S. Warthin, Mr. Allen C. Starry 
"A research for an improved method of demonstrating the Spirochaeta pallida in 
human tissues." 
Minnesota, Minneapolis 
University of Minnesota Medical School 
Dr. A. D. Hirschfelder, Mr. Merrill C. Hart, Mr. F. J. Eucera 
"Investigation of phenol-alcohol derivatives in relation to their antisepsis and 
chemo-therapy of the gonococcus and spirochaeta." 
University of Minnesota Medical School 
Dr. C. E. Nixon 
"An investigation of the chemical and physical properties of the cerebrospinal 
fluid in the luetic and non-luetic." 
University of Minnesota Medical School 
Drs. W. P. Larson, J. M. McClendon 
"A study of the permeability of bacterial membranes particularly the organisms 
of venereal disease." 
Missouri, St. Louis 
Washington University School of Medicine 
Dr. Borden S. Veeder 
"A study of hereditary syphilis with particular reference to the progress of the 
disease in the individual and the effect of the treatment." 
68 Washington University School of Medicine 
Dr. F. C. Jeans 
"A study of hereditary transmission of syphilis." 
Washington University School of Medicine 
Dr. M. F. Engman, F. Eberson 
"A laboratory (biological) investigation of the latent syphilitic as a carrier." 
Washington University School of Medicine 
Drs. White and Veeder 
"Problems in prevention, immunity and treatment of syphilis, based upon observa- 
tions made in a study of the latent syphilitic as a carrier." 
St. Louis University School of Medicine 
Dr. R. A. Kinsella 
"Studies in the bacteriology of the gonococcus-its growth peculiarities, immunizing 
properties, classification, and its mode of infecting experimental animals." 
Nebraska, Lincoln 
University of Nebraska Medical College 
Dr. Edwin G. Davis 
"(1) Investigation relative to the development of an internal urinary antiseptic; 
(2) Investigation of the value of certain anilin dyes in the treatment of gonorrhea." 
University of Nebraska Medical College 
Dr. Edwin G. Davis 
"The clinical value of the various acridin dyes for the purpose of internal urinary 
antiseptsis." 
University of Nebraska Medical College 
Dr. Edwin G. Davis 
"The relative value of the various brands of acriflavine in treatment of gonorrhea." 
New York, New York 
Cornell University Medical School 
Dr. John C. Torrey 
"A seriological study of the gonococcus group." 
Columbia University College of Physicians and Surgeons 
Drs. Hans Zinsser, Oscar Teague, Mr. Olin Deibert 
"Studies of the etiology of chancroids with special reference to bacteriology, diag- 
nosis and serum reactions." 
American Social Hygiene Association 
"An attempt to evaluate the results developed from the scientific researches on 
venereal disease problems which are now being carried on in this country." 
Albany Medical Department of Union University 
Drs. George S. Graham, W. M. Baldwin 
"An attempt to produce generalized infection in lower animals with treponema 
pallidum of gonococcus." 
Albany Medical Department of Union University 
Drs. Thomas Ordway, Dr. Arthur Knudson 
"Studies on the nature of the Wassermann reaction." 
Albany Medical Department of Union University 
Drs. G. S. Graham, W. M. Baldwin 
"A study of the effect of radiant energy upon experimental syphilis in the rabbit." 
69 New York University and Bellevue Hospital Medical College 
Drs. Wm. Park, Noble, Frankel 
"Improvement in methods for determining infection as employed in cultures and 
complement fixation in subacute and chronic gonorrhea, and results of frequent 
tests in cases under treatment and detention." 
Pennsylvania, Philadelphia 
Jefferson Medical College 
Drs. Randle C. Rosenberger, John I. Fanz 
"A series of studies for the recognition and diagnosis of treponema pallidum in 
venereal diseases, and the effect of various drugs and materials, as germicidal 
agents against treponema pallidum." 
Woman's Medical College of Pennsylvania 
Dr. Bertha Meine, Dr. Rose Hirschler 
"A serological study of syphilis in pregnant women and new-born children with 
reference to the efficacy of methods of diagnosis and treatment." 
Wisconsin, Madison 
University of Wisconsin Medical School 
Drs. A. S. Loevenhart, H. C. Bradley, P. F. Clark, W. S. Stoval, W. F. Lorenz 
"An attempt to prepare mercurial and arsenical compounds which have a pre- 
dilection for the central nervous system, in the hope of finding drugs more useful 
than any known in the treatment of syphilis of the central nervous system." 
70 THE AMERICAN SOCIAL HYGIENE ASSOCIATION 
advisory committee for 
MEDICAL RESEARCH ON THE VENEREAL DISEASES 
Edward L. Keyes, M.D., Chairman, New York, N. Y. 
Maurice A. Bigelow, Ph.D., New York, N. Y. 
Wade H. Brown, M.D., New York, N. Y. 
Walter M. Brunet, M.D., New York, N. Y. 
Charles F. Craig, M.D., Washington, D. C. 
Hugh S. Cumming, M.D., Washington, D. C. 
John A. Fordyce, M.D., New York, N. Y. 
Frederick P. Gay, M.D., Berkeley, Calif. 
Robert V. Hoffman, M.D., South Bend, Ind. 
Reid Hunt, M. D., Boston, Mass. 
Merritte W. Ireland, M.D., Washington, D. C. 
George W. McCoy, M.D., Washington, D. C. 
Henry J. Nichols, M.D., Washington, D. C. 
William Ophuls, M.D., San Francisco, Calif. 
William H. Park, M.D., New York, N. Y. 
Mazyck P. Ravenel, M.D., Columbia, Mo. 
Thomas W. Salmon, M.D., New York, N. Y. 
William F. Snow, M.D., New York, N. Y. 
Edward R. Stitt, M.D., Washington, D. C. 
John H. Stokes, M.D., Philadelphia, Pa. 
Thomas A. Storey, M.D., New York, N. Y. 
John C. Torrey, Ph.D., New York, N. Y. 
Victor C. Vaughan, M.D., Chicago, Ill. 
William H. Welch, M.D., Baltimore, Md. 
Milton C. Winternitz, M.D., New Haven, Conn. 
Hugh H. Young, M.D., Baltimore, Md. 
Hans Zinsser, M.D., Boston, Mass. 
71