Letter from Colin M. MacLeod to United States Army, Office of the Surgeon General
During World War II Heidelberger developed a simple vaccine against pneumococcal pneumonia, like other infectious diseases
a serious health threat among soldiers. The Pneumonia Commission of the Board for the Investigation and Control of Influenza
and Other Infectious Diseases within the Office of the Surgeon General of the U.S. Army, headed by Colin MacLeod, a microbiologist
and co-discoverer of the genetic properties of DNA, organized a trial of the vaccine in 1944, as described in this memorandum.
The trial, carried out among 20,000 trainees at an air base in Sioux Falls, South Dakota, proved that a vaccine made from
a mixture of purified capsular polysaccharides from four different types of pneumococcus was effective against the disease.
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1944-07-03 (July 3, 1944)
MacLeod, Colin M.
United States Army. Office of the Surgeon General
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Medical Subject Headings (MeSH):
Clinical Trials as Topic
Antigens and Antibodies: Heidelberger and The Rise of Quantitative Immunochemistry, 1928-1954
To: The Surgeon General, War Department (through Chief, Preventive Medicine Section)
Subject: Antipneumococcal Immunization at Sioux Falls Air Base, Sioux Falls, South Dakota
1. A meeting was held at 204 East 72nd Street, New York, New York on June 19th, 1944 to discuss the program. The following
were present: Drs. Michael Heidelberger, Paul Beeson and Colin MacLeod (Pneumonia Commission, Board for the Investigation
of Epidemic Diseases in the Army); Captain Richard Hodges, M. C., Epidemiologist at Sioux Falls Air Base; Dr. Ruth Pauli,
Laboratory Consultant, Office of the Air surgeon.
2. Captain Hodges reviewed briefly the respiratory disease picture at Sioux Falls over the past 20 months. Pneumococcal
Pneumonia has been epidemic throughout the period. Of the pneumococcal types, Type II has been consistently the most important,
causing 30-45% of the cases. Types I, V and VII have each been responsible for about 10% of the cases. Since February 1944,
85% of the cases have been typed, prior to that time 45% had been typed. Capitan Hodges pointed out that during the sulfadiazine
prophylaxis experiment of the past winter and spring the incidence of pneumococcal pneumonia was affected considerably less
than streptococcal disease.
Plan of Study
A. Epidemiological observations: Carrier Incidence: It is planned to carry out a pro-immunization survey for the presence
of pneumococci at the post. This will be started about August 1st with immunization beginning about September 15th, 1944.
The carrier incidence will be determined in the following groups:
a. Permanent personnel (300 subjects)
b. New arrivals (300 subjects)
c. Members of teaching groups in relation to length of stay on the post (600)
The technique proposed is as follows: Throat swabs (tonsillar fauces and pharyngeal wall) will be inoculated immediately
into Avery tubes and on the surface of blood ager plates. The Avery tubes will be incubated for 4-8 hours, and 015 cc of
culture then inoculated intraperitoncally in mice. After the death of the mice, direct typing will be carried out on the
peritoneal exudates. The heart blood will be cultured on blood agar. Media will be prepared from fresh meat. Rabbit blood
will be used. The blood egar plates streaked from the original throat swab will be incubated for 24 hours and then examined
particularly for pneumococci and hemolytic streptococci.
Following immunization the carrier incidence of pneumococci is to be observed for the duration of the study. It is anticipated
that 50-100 cultures ban be handled each week in addition to the other work.
Mode of spread G pneumococci: In addition to routine carrier studies as outlined above, carrier studies are also to be made
a. personnel of barracks where cases of pneumonia have occurred.
b. persons with upper respiratory infections. (This does not infer that pneumcoccus is responsible for cases of u. r. i.,
but the carrier incidence may increase under such circumstances or the number of pnoumocozci increase in throat of individuals
with u. r. i.)
In addition, the presence and persistence of pneumococci in barracks dust and blankets will be studied.
Antibody studies: It is considered important to measure antibody for pneumcoccus Type I, II, V and VII before and after immunization.
This will be done in Dr. Heidelberger's laboratory in New York by the quantitative precipitin technique. Bleedings before
immunization, will be obtained about September 1, 1944.
a. permanent personnel, both those carrying epidemic types and non-carriers (20 subjects)
b. new arrivals (50 subjects)
c. teaching groups (60 subjects)
Six - eight weeks after immunization, antibody studies will be carried out on 60 subjects. This will be repeated after 4
months on as many of the subjects as are still available.
In addition to these studies, antibody determinations will be made on patients recovered from pneumonia, blood to be drawn
on the day of discharge and two months later.
For the antibody studies bleedings of 40 cc are necessary. The serum is to be separated under sterile conditions, and preserved
by the addition of merthiolate in final concentration of 1:5000. The specimens will then be sent to Dr. Heidelberger.
B. Immunization with Polysaccharides: Selection of subjects:
a. Half of each of the two teaching groups at the time the study is begun.
b. Half of the new arrivals assigned to each teaching group during the course of the study.
Dosage of Polysaccharides: .06 mgm of each of the polysaccharides of
pneumococcus Type I, II and V, made up in 0.5% phenolized saline, Borkofeld filtered. Dose to be contained in 2.0 cc and
to be administered subcutaneously. Thu solutions of polysaccharide are to be prepared by E. R. Squibb and Co. from polysaccharides
originally prepared by them for the Pneumonia Commission and sent to Dr. Heidelberger. Arrangements for the above have already
been made. Those polysaccharides have bean used by Dr. Heidelberger in the preliminary experimental work. The solutions
will be tested for sterility by Squibb before release. They will be dispensed in 100 cc and 30 cc vials capped with rubber
diaphragms. 12 liters of solution are being prepared. If present tests on Type VII polysaccharide, kindly supplied by Dr.
Augustus B. Wadsworth, are satisfactory, 0.1 mg of this polysaccharide will also be included in the mixture, keeping the final
volume at 1 cc. The inclusion of the Type VII polysaccharide, however, is not considered essential to the success of the
Estimation of antibody response: Bleedings will be taken on 60 subjects
6-8 weeks after immunization. This will be repeated 4 months after immunization on as many of the original 60 as are still
C. Studies of epidemic strains: It is possible that the epidemic strains, particularly Type II may have certain distinctive
properties, especially the ability to persist in the pharynx of normal individuals. To study this aspect of the problem,
10 strains of each of Type I, II, V and VII will be obtained from carriers, shipped immediately to Dr. MacLeod in Now York
where they will be lyophilized following a minimum number of transfers in artificial media. As opportunity is presented,
these strains will be tested for their ability to persist in the pharynx of normal individuals following experimental introduction.
D. Laboratory space and Equipment: With the assistance of Dr. Ruth Pauli, a list of laboratory equipment was prepared.
The items have been ordered by the Office of the Air Surgeon and should be available at Sioux Falls by July 15, 1944. Laboratory
space is being provided. It is recommended that one end of the laboratory be partitioned to provide space for mice and rabbits.
An outside animal room is not considered necessary. Mice for pneumococcal isolation will be purchased from the funds of the
E. Personnel for the Study: Dr. Ruth Pauli plans going to Sioux Falls on or about July 15th to set up the laboratory and
train the technical assistants in pneumococcal isolation and typing. Dr. Pauli expects to stay at Sioux Falls until the laboratory
side of the study is operating smoothly. Three enlisted technical assistants formerly at Buckley Field have been assigned
to this project; in addition, a civilian technician, export in typing and presently at Sioux Falls, has been requested.
General supervision of the study is to be undertaken by Dr. MacLeod and Dr. Beeson of the Pneumonia Commission, though it
is not expected that either will be able to be present continuously throughout the period of the study. Dr. MacLeod plans
to go to Sioux Falls early in August; Dr. Beeson in September. Direct supervision of the program is to be in the hands of
Captain Richard Hodges, M. C., Epidemiologist at Sioux Falls.
Colin M. MacLeod, M. D.
Director, Commission on Pneumonia
Board for the Investigation and Control of Influenza and Other Epidemic Diseases in the United States Army