' REPORT

OF THE

DIRECTO? OF THE HOSPITAL

7 THE
CORPORATION OF
THE ROCKEFELLER INSTITUTE FOR MEDICAL RESEARCH

' OCTOBER, 193%

 
 

THE HCSPIPAL

The Director of the Hospital submits the following
brief report of the work carried on in the Hospital during the
past year.

At the beginning of the past year the staff consisted
almost entirely of new men. This was due to the fact that sev—
eral of the old men had been calied to positions elsewhere, and
others had left to take part in the war. The new men, however,
very quickly took hold of the work, and all have proved to be
Capable workers. The work in the chemical laboratory has been
reorganized under the direction of Dr. Donald D. Van Slyke.

This has resulted in a marked improvement in the work being car-—
ried on in this department.

During the year several voluntary workers have been
granted the privilege of working in the Hospital and assisting
in the reszarches being carried on.

D>. Gay, Professor of Pathology and Bacteriology in
the University of California, acted as a voluntary assistant for
several months, aiding in the studies concerning lobar pneumonia.
° Dr. Henry F. Moore, (working under a grant from the
National University of Ireland) has worked for several months
in the hospital laboratories studying the effects of optochin in
experimental pneumococous infections in animals.

During the past summer Dr. J.T. Halsey, Professor of
Pharmacology in Tulane University, has worked in the Laborator-
ies ctudying the effect of amyl nitrate on vagus tone.

At the close of the pneumonia season, Dr. Henry Chick—

ering was given leave of absence for six months to work in the

 
 

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Departinent of Pathology ard Bacteriology in the University of
California there he had been appointed a Research Assistant.

ie is assisting in studies concerning typhoid fever, and it is
tLooved that he will bring back new methods of value in furthering
4.2 cork or. pneumonia.

Very few changes are to be made in the personnel of the
ata‘: fort the coming year. Tro new Assistant Resident Physi-
ciais have reen appointed: Dr. Walter W. Palier, formerly Resi-
deat Physician at the Massachusetts General Yospital, Boston, Mas-
sachusetts, and Dr. Reginald Fitz, formerly of the staff of the
Erighaa Hospital and Harvard Medical School, Boston. Both of
these men have already carried on investigations elsewhere, the
former on the question of acidosis, and the latter on the subject
of nephritis.

A brief report on the progress of the work along the
various lincs of investigation follows:-

PNEUMONTA

Epidemiology- Further studies of the pneumococci in the
mouths of normal persons and in the mouths of patients during con=
valescence from pneumonia have shown that pneumococci of the fix-
ed types I, II and III are found only in the mouths of those per-
sons who have lately suffered from an infection with an organism -
of similar type, and in the mouths of normal persons who have
been closely associated with infected persons, in which case the
type of organism found is the same as that causing the infection.
The organisma of the fixed types persist in patients, following .
pneumonia, only during a period of from a few days to three
months. The organisms of the fixed types also spontaneously

disappear from the mouths of contact carriers after a few weeks.

 

 
These new facts are apparently of zreat importance for our know—
ledge of the epidemiology of acute lobar pneumonia, but at pres—
ent it is felt that much care must be taken in interpreting these
facts, and at the present time no final conclusions should be
drawn. They sugzest strongly, hovever, that in the spread of
acute losar pnevmonia, contact infection, either direct or
trrough the intermediation of carriers, plays a very important
rele, and they Give hope that the prevalence of the disease

may be diminished by more strict isolation of the patients,
taouzh the probable large number of carriers may make this

very difficult.

Frequency of Pneumonia due to the Different Types of
Ore@nisms- The type of organism concerned has now been deter-
mined in about five hundred cases, including the cases in this
and other hospitals. The larger statistics confirm the prev-
lous observations that about one third of the cases are due to
organisms of type I, about one third are due to organisms of
type II, a considerably smaller number, 6 to 10 per cent. are
due to pneumococcus type III, while the remainder are due to
organisms of type Iv. The mortality in the Cases due to organ
isms of types I ang II is about 30 per cent. In our experience
cases due to pneumococci of type II are a little more severe than
those due to pneumococci of type I. The mortality in the cases
due to pneumocosci of type III is considerably higher, from 45
to 50 per cent., while the mortality in the cases due to organ-
isms of type IV is much lower, 10 to 12 per cent.

The method devised for the rapid determination of the

type of organism Concerned in any individual case has been de-

 

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veloped so that it can now be carried out in any laboratory.
The only Gifficuity which has arisen has been associated with the.
determination of type of certain organisms, small in number,
“hich give an atypical or incomplete agglutination reaction with
Serum of time IT, Ten such strains have now been found and have
sormed the basis ofa thorough Study made by Dr, Aver;. His
study has shown that all these organisms unaouvtedly belong to
typ? II, and all are acted upon ty the type ITI Serum, However
these Organisms differ somewhat in their immunity reactions from
the typical type II organisms, and also differ among themselves,
SO that it has been possible to subdivide these orgarisms into
Sevoral grcups.

Specific Treatment.- The results obtained in the
treatment with immune serum of Cases due to organisms of type II
have not been as good as we had hoped for. The serum treatment
cf cases due to pneumococci of type I, however, has proved very
Satisfactory, Forty-eight such sases have been treated with
immune serum, Of these, four died, Of the four fatal cases,
however, one died suddenly during Gonvalescence from pulmohary
embolism, an accidental complication, and two of the cases were
only treated when they were almost rin extremis", a fey hours be-
fore death, This leaves Only one case that can be considered
to have been treated with any hope of success, and this was treat-
ed only on the 5th and 6th days, the patient dying on the 6th
aay. The results obtained, therefore, are in marked contrast
to the results on the untreated cases due to organisms of type
<, in which the mortality is 25 or 30 per cent. While, there-

fore, the Tesults obtained in the treatment of Casés due to or—

 

 

 

 
ganisms of type I have been encouraging, nevertheless efforts
are being made to improve the efficacy of the serum in this type
cr cases, and also tc render immune serum effective in the cases
jue to other fixed types of organisms.

Concentration of the serum has not proved, at present,
of practical importance. The attempts at concentration, how
ever, especially the studies carried on by Dr. Gay and Dr. Chick—
2ring, have yielded results of great theoretical interest. By
-.is methed it has been possible to obtain the immune substances
of the serum in a fluid containing an almost negligible amount
of tne other serum constituents. The preparation so formed also
cortains some of the bacterial substance, and may, therefore, be
of value in stimulating active immunitt, The therapeutic value
of this preparation is not yet determined, but it is being tested
in a small number of patients.

The attempt to produce a better serum by employing a
different method of immunization of the horses seems at present
to be more promising than the method of improving its quality by
concentration, By injecting smaller animals daily with mixtures
of immune serum and bacteria, better sera have been obtained than
could be obtained by the old method, These results are similar
to those obtained during the present year by Dr. Flexner and Dr.
Amoss in the preparation of antimeningitis serum. The method
has not yet been tried on horses, but it is planned to immunize
norses according to this method during the coming winter and to
test the serum so obtained on patients.

Optochin.= Experimental studies concerning optochin

ones

(sthylhydrocuprein) have been undertaken to determine whether,

 

 

 
 

 

by combining this drug with serum, the results would justify

the employment of this combined method of treatment in the

ceases due to organisms of type II in which treatment with

scerua elcne has not proved satisfactory. This drug is a de-
rivative of quinine, was discovered by Professor Morgenroth, and
has been eimiployed in Germany in the treatment of a limited num
ver ot patients with pneumonia. Judging from the reports, the
results octained from treatment with this drug have been suggest-—
ive, Sut not striking. The drug, however, has been said tc

have a definite specific action on pneumococci, both ir the
animal tody and in the test tube. To control these observations
Dr. Moore has carried on studies of this drug, first in the lab—
oz~etory cit Dr. Flexner, and later in she laboratory of the Hospi-
tal. He nas found that the drug has a definite specific bac-
tercidal action for pneumococci in the test tube, and that when
administered to infected animals it has a definite curative val-
ue. This curative effect is not very satisfactory, however,
since the curative dose is very close to the toxic dose. When

the treatment with this drug is combined with treatment with im-
mune serum, the drug is able to increase the curative value of
the serum, i.e. a more intense grade of infection can be suc-—
cessfully treated when the drug is combined with the serum than
when the serum alone is employed. Dr. Moore has studied var—
ious preparations of the drug and has made us quite familiar

witn the effect of the drug, so that now we are prepared to go
aheai and test its value in inoreasing the effectiveitess of im-
mune sérun of tvpe IT in cases of infection due to organisms of
type IT, and it is planned to do this during the coming winter.

*

 

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The pneumonia studies also have yielded other results

which are at present of only theoretical importance, though it

is hoped to make practical application of certain of them. In
the investigation of the mode of action of the immune serum, for
instance, Dr. Dochez and Dr. Avery have shown that the immune
serun has a depressing action on the metabolic activities of the
bacteria. Tais is one of the actions of immune serum which has
been little studied. tut which may be ot considerable importance.
They have named tais form of activity "antibiastis," Dr. Ches—
ney has made studies concerning the rate of growth of pneumococci
and has investigated further the question of the so-called "bac-
terial lag", or the delayed growth which occurs when pneumococci
are transplanted to new medium. These studies are still in
progress, but resuits have already been obtained which may be

of general biological Significance. Observations have also
been made which indicate that inflammatory exudates induced by
pneumococci have an inhibiting effect on the actiori of immune

serum, These studies are also in progress.

SYPHILIS,

It was hoped that before this time a complete report
of the studies concerning syphilis of the central nervous system
Could have been published in the form of a monograph. The de-
parture of Dr. Ellis for the war, however, and the fact that Dr.
Swift severed his connection with the Institute staff, have
necessitatec a delay in its appearance. However, during the

past year the patients previously treated have been under ob-

servation, either returning here to be studied by Dr. Stillman,

 
 

 

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or beins admitted to the Presn;terian Hospital for study by Dr.
Swift. The study of these patients, therefore, when it does
appear, will be more Complete than would have been the case,

had it been published a year aco. During the year, Dr. Swift

had little time to devote to the preparation of the material, but
during the summer he spent most of his time at this Hospital, get~
sing the material ready for publication and it is hoped that the
monograph may appear this fail.

The method of sreatment of tabes oy intraspinecl injec-
tions of salvarsanized serum has been quite extensively employed
elsewhere. Many of the observers have been enthusiastic as to
its value; others have been doubtful. It is felt by those tho
nave carried cn anc. observed the work in this Hospital that the
reason for the adverse opinions which have appeared has been that
the method hag been very inadequately and unwisely employed. Inu
stead of employing the method as described here, many have er
ployed modifications, which have rendered it impossible for the
observers to Judge of the value of the procedure, It has always
been realized that the method was technically difficult, and that
it was necessary to Carry out the treatment over prolonged per—
iods of time, in order to obtain results. When the method is
rightly carried out, the experience here indicateg that the meth-
od is of very &reat value in the treatment of locomotor ataxia,
It is believed that the publication of the monograph will permit
an accurate estimate of the exact value of the method, and furnish

a reliable guide: for those who undertake this form of treatment.

DIABETES,

In the report to the corporation one year ago, it was
 

AY ne meen

stated that the work on diabetes had consisted mainly in experimental studies
on dogs, carried out by Dr. Allen, and in the treatment of a limited number
of patients along lines suggested by the experimental studies. During the
past year the number of patients treated has been largely increased. The
direct care of the patients has been mainly under the dmrediate supervision
of Dr. Stillman, while Dr. Allen has devoted his time largely to the continua-
tion of hie experimental stuiies. The methoi of treatment introduced by
Dr. Allen has received very wide attention by the medical profession, and is
being widely employed. Among those men in this country who have had the largest
experience in diabetes, and are best able to judge, the concensus of opinion
is that an important contribution to the method of treatment of diabetes has bem
made. ‘The only question that has been raised in regard to the method of treat-
ment devised here is as to whether or not the principle upon which it is based
is new. This is of little importance, however, aince, through the studies that
have been made and through the new facts determined, it has been possible to
apply the principle in a way that has not been done before, and in a manner
to greatly improve the treatment of persons suffering from this serious disease.
The patients admitted to this Hospital for treatment have been only those of the
most severe type, mainly young people and children, and the results obtained
have been very satisfactory.

Dr. Allen has continued his study of experimental diabetes in
dogs in an effort to learn more of the essential nature of the condition. The
effects of cold, exercise, feeding, etc. on the utilization of sugar, both

by normal and by depancreatized