18

prevents denudation is the same as the new factor essential for the growth

of rats.  Further work is being conducted on this subject.


                  Pneumonia

    Since the opening of the hospital, Dr. Cole and later Dr. Avery
and his associates have been intereeted In reepiratory diseases, partlcu-

larly lobar pneumonia.  Mach of the fundamental work on this disease has

been conducted in the Rockefeller Hospital, and as a result of this activi-
ty a method of treating the malady by immune serum was elaborated, At first

the Berum was made in horese.  Later Dr. Qoodner end Dr. Horsfall showed
that serum prepared In rabbits poeeessed qualities superior to thoee of

ant ipneuntococcal horse serum.  For a few years the treatment of pneumonia
by antlpneumococcal rabbit serum gave highly satisfactory results and this
serum would have been universally used within a short time if it had not
been for the appearance upon the scene of eulfapyridlne. The relative
chaapnesa of the drug and the ease with which practislng physfcians oan ad-
minister it orally made it obvious that within a abort time thle or some
closely related drug would for the most part supplant the u8e of serum in

the treatment of pneumonia.  As a matter of fact this bae already OCCuTred~
    Despite the obviouB value of the new drugs, Bulfapyridine and
sulfathiaaole, Dr. Avery and hie aseociatee believe that there is still use,
under certain conditiona, for antipneumococcal rabbit serum, particularly
when it is employed In combination with the drugs.  Type III pneumonia iB
one Of the mOBt fatal and al.80 one of the most difficult diSeaSeB t0 treat.
During the years 1936-38 26 patients `with Type III pneumonia were treated
with antipneumococcal rabbit serum alone and seven of these died, a mor-

tality rate of 27 per cent.  In the past two years only one patient has died


19

In a group of 20 treated with the combination of serum and sulfapyridine, a

mortality rate of 5 per cent.

     The Introduction of sulfapyrldine in the treatment of pneumonia

naturally created interest in many centers of research in regard to how this

particular drug acts as a ourative agent.  Does it act directly upon the

pneumococcus or Indirectly through changes In the physiology of the patient?

Dr. Avery and his associates have attacked this problem by gradually accli-

matizing pneumococci to concentrations of sulfapyridine that would ordinarl-

ly be lethal for these organisms.  After this acclimatization has taken

place, the pneumococci morphologically, immunologically, and In regard to

virulence appear unchanged.  On the other hand, it was easily shown that

the drug-fast etralns had undergone marked physiological alterations in that
certain of their enzyme systems (systems having to do with metaboliem) had

been suppressed.

     Almost from the time that sulfapyridine was introduced into the

physiclansts armamentarlum it was notioed that It would not act upon pneumo-

cocci in collections of pue in the pleural cavity or in localized abscesses

in other parts of the body.  A number of explanationa have been offered for
the inefflcaoy of the drwg under euah oonditiona. Dr. Ma&sod on Dr,,, Avery's
eervioe hm ehoun that .rt. least one reaau why the dnrg is impotent under

the aonditlonr mentioned %a,.that $a purQsat materials there oaoIare a eubm
stanoe nhioh markedly inhlbita the baoterlcldal action of the drmg in: the

test tube. - Thie eubrtanoe hae been irolated and partially purified; but its

nature is a8 yet not known: further work fe being conduoted along t&se

linee.

    When the sulfonamide drugs more or less supplanted the UB0 of im-

mune serum in the treatment of pneumonia, it appeared for a short time that


20

the work on pneumonia at the Rockefeller Hospital might, be forgotten or
overshadowed by the striking results obtained with the drug. Fortunately,

however, Drs. Dubos and Hot&kiss have kept the Hospital in the front line
of chemotherapeutic attack against Infectious diseases by the discovery,
purification, and crystallization of a new chemical substance capable of
attacking all gram-positive organisms so far tested.  (The bat terial world

is divided into two parts on the basis of the manner in which different
microorganisms react to a stain devised by Professor Christian Gram;  those

organisms that retain the stain are said to be gram-positive, while those
not retaining It are classified as gram-negative.)
    The substance mentioned has been obtained from a gram-positive

soil bacillus ;  in fact from this soil bacillus there have been extracted
several substances which are highly active against gram-positive organisms,

e.g., pneumococci, ma streptococci, when tests are carried out in test

tubes.  One of the BUbStBnCeS, which has been crystallized and Is Called
gramicldin, kills gram-positive organisms both in the teet tube and in mice.

These results were quite dramatic.  However, when the material was used in

dogs, it was soon found that the toxicity of the new chemical for this
species of animal was greater than for the mouse, and that experimental
pneumonia in dogs oould not be successfully combatted by the material In

its preeent form. ,Thees findings prevented the Immediate UBB of. the drug
for the treatment of pneumonia In human beings.

Dseplte the faot that gramioldia~ in its present state is not

SatiBfaCtOry for the treatment of pneumonia in human beings, the enthusiasm

of the workers haa not been dampened, because they realize that they pas-
888s a new lead for the chemotherapeutic treatment of infectious diSSaSf3B

in general.  This realization has induced them to continue their work on


              I
21     J .'

the chemical structure of the substance, with the result that considerable         ;
                                                                           /

information concerning the size and constituents of molecules of the ma-

terial has been obtained.  At the present time it is known that gramici-

din is essentially a polypeptide to which is linked a fatty acid chain.

This knowledge regarding gramicidln has already caused the workers to seek

similar substances with bactericidal action, and a number have been found,

     Although gramicldin has no immediate value in the treatment of

pneumonia, its employment by means of local application may have a wide-

spread use in the treatment of wounds and local infections.  Indeed, sev-

era1 workers In this country and abroad are Investigating whether gramici-

din Is of value in the treatment of war wounds. Rirthermore, Dr. Dubos and

Dr. Little of the Princeton branch of The Rockefeller Institute have shown

that gramicidln, when administered locally In small amounts of a bland oil,

is valuable in the treatment of mastitis of cows. Dr. John Mohler of the

Bureau of Animal Industry, because of results obtained in the Walker Gordon

cows, has become interested In this method of treating a disease of great

economic importance,

     Dr. Goodner, on Dr. Avery's service, has been investigating mech-

anisms of resistance to infeotion other than those covered by the term an-

tibody or immune SUbBhnOe in abruIn.  He bellsvea that,the physiological            . .
                                                                           i
                                                                           . .
                                                                           i,

atate of an animal plays a part in natural resistance and that this physio-

logical state is influenced by diet.  By feeding mice unaccustomed diets

he was able to show that certain vegetables, fruits, grains and herbs pos-

sess something which increases the resistance of mice to pneumococoal in-

factions, while other substances of a similar nature do not. The nature of

the substance or substances possessed by the effective foods has not been

definitely determined.


22

    For a number of years workers in Dr. Avery's laboratory have been
interested in the chemical constitution of the CapSUl8 or the covering Of

the pneumococcus.  The capsule is a very important part of this microor-
ganism, because it determines Its type specificity and also is essential

for its disease-producing characteristics.  Information obtained during the'
course of a number of years regarding the chemical constitution of the cap-
sules of eeveral types of pneumococci has shown that they are composed of

complex sugare.  Tne capsule of Typo III pnoumococcus has been difficult to
analyze, but it is believed that during tho past year Dre. Goobol and Adams

have at last dotormined Its structure.

Rheumatic Fever

     Dr. Swift and his associates for a number of years have been en-
deavoring to find the cause of rheumatic fever and have been collecting
data which eventually will permit of an accurate description of the natural

history of the disease.  Many ideas regarding the cause of this malady have

been set forth:  the most generally accepted one is that the hemolytic

streptococcus plays an important role.  Notwithstanding the general belief
that the etreptococcua is the inciting agent, a number of workers from time

to time have sought other agenta,  For Instance, a f iltrable virus has been

proposed as the cause,  Because of Dr, A. B. Sabin's recent work on the oc-
currence of pleuropneumonla-like microorganisms in mice, which produce in
this species a multiple arthritis possessing certain of the characteristics
of human rheumatic fever, Dr, Swift and his associates attempted to find
out whether a similar microorganism was responsible for the human malady.
At first it was believed that it was possible to isolate pleuropneumonia-
like organisms from rheumatic fever patients. Much excitement was caused,