REPORT

OF THE

~IRECTfYl Op ?H!Z HOSPITAL

"0 THE

CORPORATTON OF

THE ROCKEFELLER TN3TI'FUTE FOR MEDTCAL RESEARCH

OCTOBER, 192tIi


THE   I-ICSPfPA L.

     The Director of the Hospital submits the following
Srief repcrt 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 ha9 left to take part in the war.   The near 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.
Tnis has resulted in a marked Improvement in the work being car-
ried on in this department.

      During the year several voluntary workera have been
granted the privilege of working in the Hospital and assisting
in the reasarches being carried on,

        Dr. 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 pneumooocous infections in animals.

&ring the past summer Dr. J.T. Halsey, Professor of

Phar~iaCOlOgy  in Tulane University, has worked in the laborator-

ies E$-tiyirig the effect of amy3. nitrate on vagus tone.

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

erfng was given leave of absence for ePx months to work in the


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Departnent oI' Pztilologf ar.ci Bacteriology in the University of
California iThere he had beet appointed a Research Assistant.
;ib is asslsti-g I-n ;tudies concerning typhoid fever, and it is

i::,2,ri that he nil1 bring bac'l: ne:-; methods of value in furthering

1;. 2 :-clrk or. pneumonia.

      Very fe;i changes are to be made in the personnel of the

st.l^C fc: the ccc,ink; year.   ~TO nen Assistant Resident Physi-

ciz-1s ha-;e bacn a.pk>ointed:  Dr. Valter V. Paliaer, formerly Resi-
5c.-,f, PkLysician at the Massachusetts General Zlospital, Boston, Mas-
sazhusetts, and Dr. Reginald Fitz, formerly of the staff of the

Erighai?: Hospital and Harvard Medical School, Boston.   Both of

these men have already carried on investigations elsei-rhere, 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 lir?c3 of investigation folloi7s:-

rno:J-ths of

            PNEUi!!lOXIA

Epidemiolom-  Further studies of the pneumococci in the
normal persons and in the mouths of patients during co*

valescence from pneumonia have shorn that pneumococci of the fix-
ed types I, II and III are found only in the mouths of those per-
sons who have lattily suffered from an infection with an organism-

of similar type, and in the mouths of normal persons wh.o have
been closely associated with infected persons, in which case the
type of organism found is the same as that causing the infection.
The organisms of the fixed types persist in patients, following.

E;neumonia, only during a period of from a few days to three

months.  The cr,anisms of the fixed types also spontaneously
diazqpear from the mouths of contact carriers after a few weeks.


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These neLT facts are apparently of peat importance for OUT know-
ledge of the epidemiology of acute lobar pneumonia, but at pres-

ent it is felt that rzuch care must be taken in interpreting these
facts, and at the present time no final conclusions should be

d r zwn .  They suggest strongly, ho.-iever, that in the spread of

az.Ate lo';ar pnellzonie, cor,tact infection, either direct or

tt-. r o-~$2 the intermediation of carriers, plajrs a very important

rcle, azd they give hope that the prevalence of the disease

r,:lt;r be da v- -o.,inis`ned by more strict isolation of the patients,
t'noxgh the probable large number of carriers rray make'this

very difficult.

     Frequency of Pneumonia due to the Different Types of

Or gan i 8m0-  The type of org`anism concerned has nom been deter-
-mined in about five hundred cases,  including the cases in this

and other hospitals.   The larger statistics confirm the prev-
icus 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 $0 pneumococcus type III, while the remainder are due to

organisms 0I" type IV.  The mortality in the cases due to organ-
isms of types I and 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 pneumoco;=ci 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 lcmver, 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-


                                          -4.

veloped so that it can now be carried out in any laboratory.
';"ne only difficuity -,vhich has arisen has been associated with the
Determination of type of certain organisms, small in number,
:-&lch give an atypical or incomplete agglutination reaction with
se:-m of t;Te II.   Ten such strains kave now been found and have
lorzed the basis of a thorough study made by Dr. Avsry,   His
s'iuAi:r has oh&n that all these organisms undoubted1.J belong to
typa II, and all are acted upon by the type II serum.   However

these organisms difr^er somer;hat in their i~;;ru~ity reactions from
the typical type II organisms, and also differ arzong themselves,
              .

so Cat it has been possible to subdivide these organisms into
szvzral grcupe.

      Specific Treatment.-   The results obtained in the
             _. -.-             -_
treatment v,rith intnune serum of cases due to organisms of type II

LEiV2 not been as good as we had hoped for.   The serum treatment

cf szses due to pneumococci of type I,

satisfactory.   Forty-eight such cases

immtlne serum,   Of these, four died.

however, has proved very

have been treated with

Of the four fatal cases*

hOmeT:er, one

embol i sm,  an

only treated

fore death.

to have been

died suddenly during convalescence from pulmo&ary
accidental complication, and two of the oases were

when they were almost "in extremism, a few hours be-
This leaves only one case th& can be considered
treated with any hope of success, and this was treat-

ed only on the 5th and 6th days, the patient dying on the 6th

clay.   The results obtained, therefore, are in marked contrast
to the results &n the untreated cases due to organisms of type
:; in ?.Afch the mortality is 25 or 30 per cent.   While, there-

Ice a the results obtained in the treatment of cases due to or-


                                    ? .;rj
                                                                    ;`  . . i

                                         -5
ganisms of type 1 have been encouraging, nevertheless efforts

are being made to improve the efficacy of the serum in this type

SC cases,  and also tc render immune serum effective In the cases

riue to other fixed types of organisms.

      Concentration of the serum has not proved, at present,

cf practical importance.   The attempts at concentration, hay-

ever, especially the studies carried on by Dr. Gay and Dr. Chick-

zririg, have yieldo d results of great theoretical interest, By
-::is r:iethod it 3as been possible to obtain the irnnune substances


G f  tke serum in a fluid containing an almost negligible amount

of t'r,e other serum constituents.   The preparation so formed also

G:or.tains some of the bacterial substance, and may, therefore, be

of value in stimulating active irrmUni&jt,   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 imrzmization 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 ant;$meningitis serum.   The method

has not yet been tried on horses, but it is planned to immunize
:lorses according to this method during the coming winter and to

test t2.e serum so obtained on patients.

       @tochin.-  Experimental studies concerning optochin
(thylhydr ocuprein) have been undertaken to determine whether,

                                                  .


1

                                       ,' I:'?  - I   !
                                              i '.:L,!         /


                                                                 .       -6-
by combining t;,lis drug with a~rum, the results would justify
the employment of thi a combined met'nod of treatment in the
ceaea due to organisms of type II in which treatment with


acru3 Acne has not proved satisfactory.   This drug is a de-
rivative of quinine, F;aa diecovered by Professor Norgenroth, and
has been employed in Germany in the treatment of a limited nun+

her or` patients nith pneumonia.   Judgirig from ';he reports, the

results o2';ainsd from trantment tvith this drug have been auggeat-
iv-8, 5ut 20: s+,zilal,-.   lhe drug, hmever, has been said to
hzvc a definite specific action on pneumococci, both in the
animal. body and in the teat tube.   To control these obaervationa
Dr. Moore has carried on studies of this drug, first in the lab-

0rLtpry cf Dr. F'lexnzr, and later in t;e laboratory of the Hoapi-
tal.  He has found that the drug haa a definite specific bac-

tercidal action for pneumorlocci in the test tube, and that when

administered to infected animals it ha6 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 t&is drug is combined with treatment with in+
mune serum, the drug is able to increase the curative value of

the serum, i.e. a more intense grade of infection can be auc-
ceasfully treated when the drug is combined with the aerum than

,

when the aerum alone is employed.   Dr. Moore has studied var-
ious preparations of the drug and has made us quite familiar

with the effect of t'ne drug, so that now me are prepared to go

ahead rnd test its value in increasing the effectivetieaa of im-

;gm-e Ser'J-` of
            -- A ty?e II in cases of infection due to organisms of
type Ii, and it is plzLned to do t'nis 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. Dochex and Dr, Avery have shoivn that the immune

ser.&l has a depressing action on the metabolic activities of the

%zc:?ria.   Tkia is one of the actions of immune serum which has

been little studied, but which may be of considerable importance.
They have named t.113 form of activity "antibiasti;."   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 pneurnococci

are transplanted to new medium.   These studies are still in

progress, but results 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 actio@. of inxnune

serum.  These studies are also in progress.

SYPHIr.iY&

ft was hoped that before this time a complete report

of the studies concerning syphfli8 of the central nervous system
could have been published `in the form of a monograph.   The de-

parture of Dr. Ellis for the war, h&ever, and the fact that Dr.
Swift severed his connection with the Instltute staff, have

necessitated a delay in its appearance.   However, during the

past year the patients pr eviously treated have been under ob-

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


or bein,; admitted to the Prea$:-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 ago.   During the year, Dr. Swift

had little time to devot= r, to the preparation of the material, but
during the su'Tpner ha apest moat of his time at this Hospital, get-

tin,- the matezial ready for publication and it is hoped that the

monograph Clay appear this fail.
     The method of treatment of tajes by intraspinal injec-

tions ol" salvarsanized serum has been quits extensively erzploycd

clsc:;hncre.   Many of the  observers have been enthusiastic as to

it3 value;  othera have been doubtful.   It is felt by those v;ho
have c.uri& cn and observed the :;-ork in this Hospital that the
reason for the adverse opinions v;hich have appeared has been that
the method has been very inadequately and unv;isely employed. In-
stead oi' employing the method as described here, many have em-
ployed mcdifications, 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 indicates that the meth-
od is of very great value in the treatment of locomotor ataxia,
It is believed that the publication of the monograph will permit
an accurate estimate of t'ne exact value of the method, and furnish
a reliable glide. for those who undertake this form of treatment.

IXABETES.

In the report to the corp'oration one year ago, it was


stated that the work on diabetes had consisted mainly in experimental studies

on dogs, carried cut by Dr. Allen, and In the treatment of a limited number

of patients along liner suggested by the experimental studies.  During the

past year the na2ber of patlentr trusted has been largely increased. The

direct care of tlm patients has been mainly under the IaaEsdlate supervision

of Dr. Stillman, while Dr. Allen baa devoted his time largely to ths ccntinua-

ticn of hle experimental studies.  The rmthol of treatment introduced by

Dr. Allon has received very wide attention by the medical profession, and Is

be lng widely employed.  Among thcso men in this country whc have had the largest

experience in diabetes, and are boat able to judge, the concensus of opinion

is that an important contribution to the method of treatment of diabetes has boar


made.  The only question that her been raieed In regard to the method of treat-

ment devised hsre is as to whether or not the principle upon which it is based

is new.  Thie is of 1 it tie importance, hcwevor, einoo, through the s tudisr that

have been made and through the new fact8 determinid, Tt hae been possible to

apply the principle In a way that' haa not been done beeore, and in a manner

to greatly improve the treatment of porsone suffering from this sericus disease.

The patisntr admitted to this Hospital for treatment have been only those of the

mc8 t aevoro typo, mainly young people and children, and tba 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