October 16th, 1914.

To the klembers of the Corporation
of the Rockef oiler Institute for Medical Research,

Gent lemon: -

The Director of the Hospital has the honor to submit the following

report of the work carried on during the past year.

     When the Hospital was opened it was stated that one of its functions
tight be tho training of men to take part and aid in the changa which was likely

to take place in the toaching of internal medicine.  It is gratifying to know

that thd objact has bean, to a measure, attained, in that a number of the assis-

tants in the Hospital have now beon callod to full-time academic positions in the

teaching of medicine in various univcrsitiee.  Dr. Canby Robinson was called to

Vashington University of St. Louis, to become Assistant Professor of Medicine,

and to aid in organizing the Department of Internal Medicine in the new hospital

of that institution.  Dr. Francis Peabady was called to the Harvard Medical School,

and to the Brigham Hospital, Boston, to become Assistant in Medicine, and Resident

Physician, respectively, in these two institutions.  Finally, Dr. Swift, who has

been Resident Physician of the Hospital, has received and accepted an appointment

as Associate Professor of Medicine in Columbia University, and Dr. Fraser, who has

also been a member of the staff, has been appointed an Instructor in Clinical

Medi tine in the same institution,  All these men are now acting as full-time

instructors in medicine,  While these appointments add to the difficulty of main-

taining the staff at all times on a most efficient basis, yet for the present, at

least, such appointments are gratifying, not only because they show that the

Hospital is able to occupy an important place in training such men, but also


because they offer, an .ns~~rmenti to the younger men who are working in the
                -h-
Hospital with the view of later making an academic career,  In addition ta the

loss of Dr. Swift and Dr. Fraser, the Hospital has also lost Dr. Ellis and Dr.

Zacharias, who have joined the English and German armies respectively. It is

hoped that at the end of the vrar cne or both of them rray return to their :vnrk which

was so suddenly interrupted.

Dr. A. R. Dochez, who has been a member of the Hospital staff since its

organization, and UBS previously on the staff of the Institute Iaboratories, has
been advanced to the position of Resident Physician, to take the place left vacant
by Dr. Swift. The following named men have been appointed to occupy the other

vacant places on the staff:   Dr. Alan Y. Chesney, who formerly sPenf a year in

the Hpospital and during the Past year has been on the staff of the GohxsHopkins

Hospital; Dr. Ross A. Jamieson, who is a graduate of the University of T?oronto,

and has been for the Fast two years on the staff of the Belle- Hospital in this

city, and Dr. ?Franklin C. McIsan, fomsrly professor of phanracology in the Uni-
versity of Oregon. An ImPortant change in the or@nizat$on of the Hospital staff
kas taken Place during the Past year by the appointment of Dr. Donald D. Van Slyke
to tati charge of the chemical Labbmtc+t-y. The orgadzat,io:a of this dsprtl;ent of
the medical work has offered the most serious difficulties, and it has been very

difficult to obtain a rrrul of proper training and scientific inclinati.on to act,

as director of this laboratory. lt is felt and hoped that in Dr. Van SI>-ke the

ideal man for such a position leas been obtained.

                                       .             .
In looking to the future development of the Hospital work, iG is be-

lieved that, with the discovery of new methods which nay be applied practically

in the treatment of disease, definite organized efforts should be &e by the

Hospital, or by the Institute as a whole, to assist

,;ore widespread and efficient operation. This can bs

r;nnsnl practitioners in carrying out new rmthods of

in putting these methods into

lo%~ F'efforts
  6        to assist

tree,t;,lent or by assisting in

c

the srganization of other institutions for carrying out special~~~thods of trE&t-


.

&Tent . The development of this idea could ;ell be one of the function6 of the de-

prtmsnt of Public Health, or the Third Section as suggested by Dr. Prudden.

During the sumwr months just past, owing to the work which v,as go-

ing on adjoining the Hospital, and owing to the fact that the staff v.as so

riaterially reduced, a very srm.11 number of patients have been admitted and the

xork I-ELS been reduced 60 far as possible.   It WZLS not thought advisable to close

the Hospital completely since, in order to obtain support from the public and

modiczl prffession, It is necessary that at all times the Hospital be open for

the examination of patients and for the reception of suitable ones. The following

is a brief review of work carried on in the Hocpital.


Pneumonia.

           During the period since the last report eighty cases of

pneumonia have been treated. Numerous studies have been made on these patients

lrcm various points of view by Dr.  Cole, Dr. Dochez, Dr. Avary and Dr. Chickering.

The results obtained rray be classified under the following haaJ.6:

       &faction and Epidemiology.  Studies 1ave been rrada of the types of

pneurnococci occuring in normal mouth6 and in the mouths of patients convalescent

from pneumonia. In the mouth of only one normal parson have pneumocci of the fix&

types I, II, and III been found. This parson VW  the wife of a patient suffering

frcxn pnaumonia due to pneumococci of type II. In her mouth pneumococci of type II.

wra fourd. Studies of wtients conalescent from pneumonia have shown that pnau-

mococci of the type found during the Disease us~lly persist in the mouth6 for

from one to several weeks. Iater than this they are not found. Only pna-umococci of

the non-specific type IV. are then present.  During the present summer Dr. Iyle

has carried out a study of the types of pneumococci present in the mouths of

patients suffering from tuberculosis. Among fifty cases, in two, pneUmOOOCCi of

type I. were present; In no other cases were pneumococci of the fixad types found.

These s&dies indicate that in casa6 of pneumonia, except possibly thoat due to

organism6 of type IV., infection probably occurs from without, though there are

probably contributing factors in etiology.

In no case has direct evidence been obtained of transference of one

orgazdsm of one type into those of another type. It is probable, however, that in

the evolution of the pathogenic types such transforamLtions have occurred. That this

evolution rray have bean along different lines in different parts of the world is

ahown by the fact that in South Africa a type of pneumococci is present which has

iJOt been met with here,  and this type  is there fairly wide sprea;l. A si;-all

%2ker LJ~ organisms have beei? sent to us from South Africa. The four types fo&

i
I







:


           A
                                     * -

l;ere are among them and in addition a fifth type, as mentioned.

        Careful study of the organism isolated from each case of pnau-            ! .I

                                                                           L "

monia  coming under our observation has been made. The results confirm our pre-               i
                                                                           !
                                                                           ,' ?

vious report in regard to the relative frequency and severity of cases due to the

lifferant types of pneumococci. Studies concerning the occurrence of pneumococci

of different typos in cases of pneumonia have also been made with our assistance

in tkle Brigham Fospital at Boston, the Pennsylvania Hospital in philadalp'nia, and

the Detroit Caner-al Hospital.

        Dr. Chickering has studied the agglutinating power of patients'

sarum for paumococci of different types. The results afford further proof of the

specificity of the different types and their relations to the disease. In the

blood of patients with infections due to organisms of type IV. only the hoiAologou

organism is agglutinated. In the blood from ptiants with infections due to ore


; 3xis of types I. ati II. only organisms of the corresponding type are agglutinated.

A,:glutins Pave us~lly disappeared from the blood within a few weeks after tha end

of the disease. In the cases where they haVf3 persisted there has eXiStad sor;.a

specific complication, as delayed resolution or empyama.
                                             I

             Treatment with serum.   Further studias in the treatment of

cases have confirmed the opinion previously held in regard to the efficacy cf

irnnine serum in the treatment of cases due to organism6 of type I. In regard to

the serum offactive against organisms of type II. ou$ previous anticipations

have not bean entirely confirmed. During the past winter we had several very

severe cases due to organism6 of type II,  in which the serum seemed to have little

or no effect. A study of the serum then being used showed that it was much less

effective, as tested by protective power in aninrsls, then ~66 the serum which lid

previously been used. While, therefore, the results were not necessarily dis-

couraging, except as reprds the statistical study being mde, nevertheless,

--._


v;hen it is realized that 1ti 1s very difficult to obtain and keep the serum of

type II. at its highest efficiency it is evident tha t the complications in the way

of carrying out effective treatment witn tne II.  serum are bound to be considerable

An attempt ha$ been trade to render this serum more effective by con-

centrating it, but the results as detemined from experimental stuiies are not en-

CoInaging. It is quito pQssib3e t3 Cause considerable concentration of the irx,;pme

su!xtances since 3.11 the protective substances have been fomd to be in the globulin

i

1
I
1

iraction of the cerun. Vnen the prcVtaztivo powor of concentrated serum is tested ,

hol!:ever, the possibility  of obtail;ing greater clLative effects fror;l its usa does

:.ot sea~n probable. 'lb reason for this is as follovis. Serum of type 1. protects

5ice against 0.1 C.C. of culture when 0. 2 c.c. of serum is us&. It is found,

!:ov;ever, that, no wtter how much ths amount of t'nis serum be increased, evea if

U c.c. be used instead of 0. 2 C.C. , the mount of culture protected against can

Kc3ver be more than 0.1 C.C.  This holds good for concentrated as well as not con-

centrated serum and has been found almost constantly true in a very large number

3f experiments. In the case of serum type II. this limit of dosage is st,lll. lower.

0.2 C.C. of serum never protects against more than 0.61 c.c. of culture, and no

greater amount of culture can be protected against, no rratter how lnrg3 the
             cam 02

amount of serum. Inprganisxns of type III. even the smallest amount nf cLltue can-

not be protected apinst by ime serum, using even the largest amoxnta 02 serum,

       The facts as stated render it evident that, in addition to the irrmne

body, probably a second factor which must be supplied by the body itself, bs

necessary. In infections due to organisms of type I. t&s secon;l factor is probably

not required in large ampunts. At any rate, by increasing the amount of immune

body, the demxnd on the organism probably II&Y be reduced. In the case of infection

due to organism of type II. the requirement of this second factg;r is greater and

xan very large amounts of irxnune body will not supply this deficiency. In the


of infection due to organisms of type II. the requirement of this second factor is

greater and even very large amounts of immune body will not supply this deficiency.
In the case of infections due to organisms of type III. apparently the unimrnunized
anirral is almost entirely unable to supply this deficient factor.  The next step
in obtaining a method of cure for this disease must consist in determining the nature
of this additional factor and methods for stimulating the body to produce it.
     The studies so far rrade of the groups of pneumococci causing pneumonia
indicate the following arrangement as regards pthogenicity ana irrmunity.  First,

group IV. in which the pthogenio effects are only slight; the ptients infect&
practically all recover. Immunity against these organisms can very readily be ob-
trrined but the practical dlffiatitv in the efficient use of the serum consists in

the fact that these organisms differ among themselves, each one possessing specific

1332nological characteristics.  @xt come organisms of type I. which are found in
                                                                           I
ZLS~S of pneumonia of moderate severity and which constitute the etiological agents
in the largest group of the cases of pneumonia. The organisms of this group are all
alike inrsunologically and a high degree of specific immunity can be obtained in an-

11:a IS , the serum of these anirrals apparently being most effective in protection and
cure. It is in this group of cases that it is felt that serum treatment is most

affective. Next come organisms of group II.  These organisms possess a still hi&r

grade of pthogenicity; the infections caused by them are more severe and the mortal-

ity is higher.  A high grade of active ixrrrunity may be obtained for these organi&ns
but the passive immunity obtained by employing the serum of these iwnmiaed aninals
is conside:ably less effective in protection, ati probably in cure, than is Chat
obtained from the serum produced by the inoculation of organisms of type I.  Iastly,

wp&ms of type III. so-called Pneumococous mu~osus type, which probably possess

the highest grade of pthogenicity of any of these organisms, causing infections in

>Bn of extreme severity and with a very high mortality. Active immunity can also be

;';bined by the inoculation of org&nisms of thishype, but passive irrnunity in this


i:roup is entirely lacking, the serum has no efficacy whatever.

       The rasults of treatment indicate that much has alreaQ been acccxnplish-

~1 with mses of type I. and it is hoped that this alone nay ux3ke a rraterial reduc _

tlon in the total rrxxtality from pneumonia. The chief effort is now being directed

to improving the treatment of cases due to organisms of type II.  Little can be

hoped for, at present, as regards  any form of effective specific therapy against

orenisms of type III.