14

Hoagland and his associates have been able to devise a suitable method of

accurately estimating these substan;es in the blood of normal and pella-


grous persons.

     Progress in understanding the chemical nature and physiological

action of vitamins and biocatalysts has made desirable an extension of

studies of their function to diseases other than those caused by simple or

mixod deficiencies,  Since the function of vitamins and other essential

catalysts are for the most part mediated through enzyme systems, certain

diseases in which there is reason to suspect changes in the normal enzyme

processes have been selected for study.  Investigations were begun this

year on pseudohypertrophic muscular dystrophy and muscular atrophy, a

group of maladies in which Interruption of normal muscle metabolism is ap-

parent, and on advanced, non-malignant diseases of the liver such as cir-

rhosis, in which a marked depression of hepatic function is known t0  0CCl.W.

Patients with these diseases have been admitted to the Hospital for study

end some interesting facts have been ascertained.  Their exact meaning re-

quires further work.


          PNEUMONIA AND OTHER mSPIRBTORY DISEASES

        Dr. Avery. Dr. Horsfall, and their Associates.

     The outcome of any infectious disease is dependent upon the re-
action between the infecting agent and the host. Factors in the host that

influence this outcome are'spoken of as susceptibility and resistance:

those in the invading agent are collectively designated virulence. Drs.

Avery and Horsfall and their associates have investigated the virulence

of pneu3nococci, organisms that cause ordinary lobar pnsumonia in human be-

ings.  These organisms are made up of a cell body surrounded by a capsule


15

,r covering composed of complex sugars,  It now appears that the manifest

;-Lrxience of encapstiated pneumococci for a particular host species is de-
,sc,sdent upon at least tno distinct and separate properties of the bacte-

i.id. Ct?ll.  One factor seems to reside in the cell body and its influence

is not demonstrable in the absence of a capsule.  The other factor appears

to be intimately associated with the capsule, if indeed it is not actually

the capsule itself, and its influence is without effect in the absence of

the cellular factor,

     Dr. Goebel and his two associates have assisted Dr. Avery in in-
vestigating the complex sugars that surround or encapsulate pneumococci.
To gain further information regarding the chemical nature of the pneumo-

coccus cell, investigations have been carried on concerning an important

constituent of the cell body spoken of as the "heterophile antigen."

Dr. Goebel has shown that the antigen consists of a fatty substance and a

complex sugar.  This work has led Dr. Goebel directly into a war project

for which he now has an OSRD contract.  The problem has to do with the
study of a complex substance obtained from dysentery bacilli which has a
great deal to do with the toxicity of these organisms and which it is
hoped nfll turn out to be a satisfactory immunizing agent if properly pre-

pared.  This substance is said to be a fat-sugar-protein complex.
    The sulfa drugs are being used extensively for the treatment Of

pneumococcal pneumonia.  There are certain substances in body tissues and
fluids and in culture media' which inhibit the action of these drugs. One
of the substances is p-aminobenzoic acid which is active in amounts diffi-
cult to demonstrate by chemical means. Dr. &rick has found a soil bacil-
lus that produces an enzyme which facilitates studies on these inhibiting

substances .


16

     For several years a tyge of pneumonia, which is probably caused

by d virUs and s+:;en c1 as atypical pneumonia, has been recognized.  This

kir,J of pneumonia is becomin g a problem in the armed forces.  With the

outbreak of the war Dr. Avery and Dr. Horsfall secured an OSRD contract

for the investigation of atypical pneumonia.  Since March of this year a

major portion of their time has been devoted to tho problem.  E"any patients

sont to us from the Coast Guard and from the U. S. Naval Hospital in Brook-

lyn have been studied.  Interosting obsorvations have been mado and it is

hopod that something dofinitc will coma out of this work in the near fu-

twc.

PHYS IOLOGY CF BACTGP IA

Dr. Dubos and Associates.

     Dr. Dubos, an agricultural bacteriologist, cane to the Insti-

tute a number of years ago and worked with Dr. Avery for quite a while on

the nature of the capsule of pneumococci.  Dr. Dubos has always been in-

terested in the physiology of bacteria and in the action of substances,

such as enzymes, produced by them.  As reported previously, Dr. Dubos

discovered a soil bacillus that produces substances now spoken of as

gramicidin and tyrocidin which have a lethal action on all Gram-positive

bacteria.  The assistance of Dr. Hot&kiss was obtained by Dr. Dubos in

order to study the chemical nature of these two substances.  During the

past year this work has continued and at present the structures of these

substances are fairly well known.  In addition to this, a great deal has

been learned concerning the effect that these substances have on the

physiological activity of various bacteria.

     During the year, because of the outbreak of the war, Dr. Dubos

became more and more interested in toxic substances derived from Gram-