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OCR for page 307
JOHN HOWARD MUELLER
June 13, 1891-February 16, 1954
BY A. M. PAPPENHEIMER, JR.
-
JOHN HOWARD MUELLER was born ~une 13, IS9l, in
Sheffield, Massachusetts, where his father was a Unitarian
minister. After a few years, the family moved to Illinois,
where young Howard received his secondary schooling. He
then attended Illinois Wesleyn University, receiving his B.S.
degree with honors in biology in 1912. Two years as an in-
structor of chemistry at the University of Louisville followed;
he was awarded an M.S. degree in 1914.
While at Louisville he became interested in bacteriology
ant! pathology, and in the summer of 1914 he attenclec} a
summer course in pathology at the College of Physicians and
Surgeons, Columbia University. The instructors in this
course encouraged him to remain as a graduate student at
Columbia, which he clicI. He was awarded an Alonzo Clark
Fellowship in Pathology ant! received his Ph.D. degree in
1916. He worked as assistant pathologist at the Presbyterian
Hospital until war was declared in 1917; he then enlistecI as
a private anct went overseas with the Presbyterian Hospital
Unit to Etretat, France, where he actively participated in the
work that demonstratec! that "trench fever" (like typhus fe-
ver, a rickettsial diseased was transmitted by lice. It was cloubt-
less cluring this period that he became interested in patho-
genic bacteria ant! in their physiology anct metabolism. His
307
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308
BIOGRAPHICAL MEMOIRS
talents were recognized by the Army, and he was commis-
sioned a lieutenant in the Sanitary Corps before the war
ended.
On his return to civilian life in 1919, Mueller was ap-
pointed an instructor in the bacteriology department,
chaired by Hans Zinsser, at the College of Physicians and
Surgeons. There he began his studies on the cultural require-
ments of pathogenic bacteria. Papers I and II of this series
appeared in 1922. In introducing the series, Mueller wrote:
Perhaps the most important results to which success in such a piece of
work might lead, are the applications of the findings to problems of more
general biological importance, particularly to those of animal metabolism.
For, whatever may prove to be the nature of these substances which cause
growth of bacteria, they are largely or entirely components of animal tis-
sue, and it is probable that they are either needed also by the animal body
and supplied by plant or other sources, or else are synthesized by the
animal itself to fill some metabolic requirement. When it is possible to
catalogue the substances required by pathogenic bacteria for growth, it
will probably be found that most of them are either required by, or im-
portant in, animal metabolism, and while many of them will surely be
compounds at present familiar to the physiological chemist, it is equally
probable that some will be new, or at least of hitherto unrecognized im-
portance.
It was not long before his predictions were verified. He
soon found that although he could use an acid hydrolysate
of animal protein supplemented with tryptophane instead
of commercial "peptones"—as a base for growth of Strepto-
coccus hemolyticus, the hydrolysate could not be replaced by a
mixture of the then known amino acids. This led to the frac-
tionation of casein hydrolysate and to the discovery of a new,
ubiquitously distributed sulfur-containing amino acid: meth-
ionine. Mueller's 1923 paper in the journal of Biological Chem-
istry reporting the isolation of the new amino acid from acid
hydrolysates of casein and of ovalbumin and his determina-
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-
~OHN HOWARD MUELLER
309
tion of its elemental composition is an excellent example of
the thoroughness that characterized all of his work. He made
a good many derivatives and carried out the elementary anal-
ysis of each one himself. This lee! to the correct empirical
formula: CHAOS. Only two likely structural formulae
were possible. An organic chemist from Cambridge Univer-
sity suggested to him that the new amino acid might simply
be the ethyl thioether of cysteine. Mueller proceeded to syn-
thesize this thioether and provect that it was not identical with
his new amino acid, the structure of which he stated re-
mainect to be cleterminect.
In the same year as the discovery of methior~ine, Hans
Zinsser was appointed chairman of the Department of Bac-
teriology and Immunology at the Harvard Meclical School
anct asked Mueller to join him as an assistant professor. After
arriving in Boston, Mueller was persuaclect to abandon-
temporarily—his studies on bacterial nutrition. Tnsteact he
joiner! Zinsser in the study of so-callect "residue antigens"
extracted from pneumococci, tubercle bacilli, yeast, and
other microorganisms. These heat-stable, nonprotein anti-
gens were inclepen(lently shown to be polysaccharicles by Av-
ery and his coworkers, whose subsequent brilliant work re-
vealed their role in the pathogenesis of pneumococcal lobar
pneumonia and other bacterial diseases.
At about this time in England, W. E. Gye publishect a series
of papers purporting to show that Rous chicken sarcoma fi~-
trates contained two essential factors, both of which were re-
quired for tumour induction. The first was a substance spe-
cifically affecting certain chicken cells and thereby rendering
them susceptible to transformation to malignancy by a virus.
The same virus was supposedly present in many mammalian
tumours, including human carcinomas. Because the impli-
cations of this work seemed so important at the time, Mueller
attempted unsuccessfully to repeat Gye's experiments. and
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310
BIOGRAPHICAL MEMOIRS
spent several frustrating years working on this problem. In
the end, Gye came to work in Mueller's laboratory, anct in
1929 a joint paper appeared in the Journal of Experimental
Medicine—but with two opposing sets of conclusions: one
written by Gye, the other by Mueller. Subsequent events
prover! Mueller's interpretation of the data to be correct.
After these rather disappointing years, Mueller finally re-
turne(1 to the fielc! that had always been his major interest
since his early work leading to the discovery of methionine.
Papers ~ and II of the series "Studies on the Culture Require-
ments of Bacteria" appeared in the Journal of Bacteriology in
1922; paper ITI did not appear until 1933! Nevertheless, in
1930 when Mueller began his classic studies on the nutrition
of the diphtheria bacillus, bacterial cells were still regarded!
as lowly forms of life that tract little, if any, relationship to the
cells of higher animals and plants. Tissue extractives, inspis-
sated serum, "peptones," etc., were regarclec! as essential for
the cultivation of pathogenic microorganisms, and any no-
tion of bacterial genetics was unheard of. It was not until
1929 that the first enzyme (urease) was crystallized and
shown to be protein.
The decade that followoct must be regarded as the most
fruitful of Mueller's career. He selected the diphtheria bacil-
lus as the organism for his intensive studies. From the very
outset, he recognized the importance of being able to mea-
sure growth quantitatively. Spectrophotometers were not yet
on the market, anct Mueller clecided to use the micro-
Kjelc~hal method! for estimation of growth as bacterial nitro-
gen. Although this method was tedious, it was accurate. It
also gave him a great advantage over others who were begin-
ning to enter the field because it became possible to work out
conditions for maximal yields of the bacteria and their prod-
ucts.
Within a few years the Mueller laboratory had identified
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JOHN HOWARD MUELLER
311
which amino acids were essential for growth of the diphtheria
bacillus and hac! macle the important observation that differ-
ent strains of the same bacillus varied widely in their amino
acid requirements. (For example, if a certain amino acid! was
not needled for growth of a given strain, that strain possessed
the enzymes required for its biosynthesis.) Mueller then went
on to isolate anct identify what he called "accessory" factors.
He isolatec! nicotinic acid from liver anc! shower] that it or
nicotinamide were essential growth factors for all strains of
the diphtheria bacillus being tested. With S. Cohen he iso-
latecl a second factor from liver that proved to be ,13-alanine.
He then showed that pantothenic acid would also satisfy the
,(3-alanine requirement, and others founct cliphtherial strains
that were clependent on pantothenic acid itself for growth.
Soon afterward, both nicotinamide and pantothenic acid
were shown to be part of the vitamin B complex required for
animal nutrition. Finally, in paper X of the series that alv-
peared in 1937, Mueller clescribecT the isolation and identi-
fication of pimelic acid from cow urine, which was required
in trace amounts for growth. Later, after the discovery of
biotin, pimelic acid was shown by du Vigneauc! to be an in-
termecliate in biotin biosynthesis.
Thus, by 1940 the prediction Mueller had made in 1922
had been fully realized, anct the universality of biochemistry
hacl become accepted by everyone. The importance of Muel-
ler's research in helping to bring about this recognition
should not be forgotten. It was his work on bacterial nutrition
that paved the way for the rapid identification of coenzymes
ant} for the eluciclation of the pathways of intermediary me-
tabolism ant] biosynthesis that took place in the 1940s anct
early 1950s. The work on nutrition of the diphtheria bacillus
also had important practical applications in improving the
yielc! ant! quality of the diphtheria toxin used in production
of toxoid for human immunization. By 1941 the diphtherial
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312
BIOGRAPHICAL MEMOIRS
studies were essentially complete, and Mueller turned his ma-
jor attention to the tetanus bacillus and to production of its
toxin. These studies were still in progress at the time of his
death in 1954.
Hans Zinsser died in 1940 anct shortly thereafter Howard
Mueller was appointed to succeed him as head of the cle-
partment. Mueller was one of those rare inclividuals who con-
tinuect to work with his own hands even after becoming chair-
man of a large department at a major university. He was an
early riser, and daybreak usually found him at the bench.
Several hours later, soon after his elevated research associate
ant! friend Pauline Miller had arrived, Mueller was ready to
leave the laboratory for his office to pursue his administrative
duties. He took his obligations toward the department, to-
ward the teaching of medical students, and toward his clinical
associates very seriously. He was interested in all aspects of
infectious disease and felt that his own research should be
medically oriented with ultimate practical applications. And
indeed, in audition to its fundamental scientific importance,
much of his work die! have important practical application in
· · . . · . - ~
immunization and In diagnosis.
Mueller was a man of great generosity who had impec-
cable integrity particularly with regard to scientific accu-
racy and an unusual capacity for brushing aside all that was
irrelevant in order to get at the core of the matter. He had
no use for the sham, the half-truth, or the pretentious. Those
who knew him well were always impressed by his moclesty-
inueea, he user! to refer to himself as only "a high school
chemist." Yet as pointer! out in the "Minute" on his life that
was read to the faculty of medicine of Harvard University
following his death: "Howard Mueller belongs among the
scientific 'elite' as Kirtley Mather has recently defined them-
that is among those who actively seek insight and meaning,
whose minds are constantly on the alert to the possibility of
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JOHN HOWARD MUELLER
313
new generalizations anc! new relationships as distinguishecl
from those who merely know how to clo that which they have
been trained to do." No better example of his remarkable
insight can be given than his reaction to the 1944 discovery
by Avery, Macleocl, and McCarty that the rough-to-smooth
transformation could be induced by DNA. In his chapter on
the chemistry and metabolism of bacteria, which was written
in that same year for the Annual Review of Biochemistry, Muel-
ler wrote (the italics are mine):
In other words it appears that a polymer of a nucleic acid may be
incorporated into a living, degraded cell, and will endow the cells with a
property never previously possessed, namely, the ability to produce a cap-
sule composed of a complex polysaccharide entirely different in structure
from that produced by the smooth organism from which the degraded
form was originally derived. When thus induced the function is perma-
nent, and the nucleic acid itself is also reproduced in cell division. The
importance of these observations can scarcely be overestimated and stim-
ulates speculation concerning such matters as the chemical basis for spec-
ificity in nucleic acids, and the genetic implications presented by the ability
to induce permanent mutation in a cell by the introduction of a chemical
substance. Such speculation may well include considerations of the relation
of this phenomenon to the sequence of events following the introduction
of a filterable virus (or a bacteriophage particle) into a susceptible cell.
Mueller wrote those worcts at a time when recombination in
bacteria was unknown, microbial genetics did not exist, and
no one had previously spoken of mutations in connection
with bacteria.
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314
BIOGRAPHICAL MEMOIRS
B IBLIOGRAPHY
1920-1921
Growth-determining substances in bacteriological culture media.
Proc. Soc. Exp. Biol. Med., 18:225-28.
Observations on bacterial metabolism. Proc. Soc. Exp. Biol. Med.,
18: 14-17.
1921-1922
A new sulphur-containing amino acid isolated from casein. Proc.
Soc. Exp. Biol. Med., 19:161-63.
1922
Studies on cultural requirements of bacteria. I. I. Bacteriol.,7 :309-
24.
Studies on cultural requirements in bacteria. II. I. Bacterial.,
7:325-38.
1923
A new sulfur-containing amino-acid isolated from the hydrolytic
products of protein. I Biol. Chem., 56: 157-69.
A new sulfur-containing amino-acid isolated from the hydrolytic
products of protein. II. Sulfur excretion after ingestion. T. Biol.
Chem., 58:373 -75.
1924
With I. Tomcsik. The chemical nature of residue antigen prepared
from yeast. J. Exp. Med., 40:343-52.
With M. Wayman and H. Zinsser. A preliminary report on the
chemical composition of residue antigen. Proc. Soc. Exp. Biol.
Med., 21:241-43.
1925
With H. Zinsser. On the nature of bacterial allergies. l. Exp. Med.,
41:159.
A chemical study of tuberculin. Proc. Soc. Exp. Biol. Med.,22:209-
11.
With D. E. Smith and S. Litarczek. "Residue antigen" from a strain
of Friedlander bacillus. Proc. Soc. Exp. Biol. Med., 22:373-74.
OCR for page 315
JOHN HOWARD MUELLER
315
Chemical studies on tuberculin. Proc. Natl. Acad. Sci. USA, 11 :23-
25.
1926
Observations on Gye's work with the Rous sarcoma. Proc. Soc. Exp.
Biol. Med., 23:704.
A chemical study of the specific elements of tuberculin. I. I. Exp.
Med., 43: 1-8.
A chemical study of the specific elements of tuberculin. II. The
preparation of residue antigen from old tuberculin. l. Exp.
Med., 43:9-12.
1927
The virus problem in transplantable tumors. (Abstract.) I. Bacte-
riol., 13:26.
An experimental study of Gye's cancer theory. I. Exp. Med.,
45:243-62.
1928
With H. Zinsser. Antigenic properties of the bacterial cell and an-
tibody reactions. In: The Newer Knowledge of Bacteriology and Im-
munology, ed. E. O. Jordan and I. S. Falk, pp. 721-32. Chicago:
University of Chicago Press.
The effect of oxidation of filtrates on a chicken sarcoma (chicken
tumor I-Rous). I. Exp. Med., 48:343-49.
The oxidative destruction of the agent of the chicken tumor I
(Rous). Science, 68:88-89.
1929
With W. F. Gye. An experimental study of the etiology of chicken
sarcoma I (Rous). I. Exp. Med., 49:195.
1931
With L. Whitman. An improved method for the detection of hemo-
lytic streptococcus carriers. I. Bacteriol., 21:219-23.
The effect of alexin in virus-antivirus mixtures. I. Immunol.,
20: 17-23.
OCR for page 316
316
BIOGRAPHICAL MEMOIRS
1932
With K. S. Klise. Agglutination of hemolytic streptococci. (Ab-
stract.) I. Bacteriol., 23:83.
With K. S. Klise. Mass cultures of Streptococcus hemolyticus in broth.
Proc. Soc. Exp. Biol. Med., 29:454-55.
With S. Sturgis. Prevention of blood coagulation by cysteine. Sci-
ence, 75:140.
With K. S. Klise. A method for the agglutination of hemolytic
streptococci. i. Immunol., 22:53-59.
1933
With K. S. Klise, E. F. Porter, and A. Graybiel. Studies on cultural
requirements of bacteria. III. The diphtheria bacillus. I. Bac-
teriol., 25:509-19.
With K. S. Klise. An agglutinative classification of the hemolytic
streptococci of scarlet fever. J. Infect. Dis., 52:139-45.
1934
Amino acids required by the diphtheria bacillus for growth. Proc.
Soc. Exp. Biol. Med., 32:318-20.
1935
Studies on cultural requirements of bacteria. IV. Quantitative es-
timation of bacterial growth. I. Bacteriol., 29:383-87.
Studies on cultural requirements of bacteria. V. The diphtheria
bacillus. J. Bacteriol., 29:515-30.
Studies on cultural requirements of bacteria. VI. The diphtheria
bacillus. I. Bacteriol., 30:513 -24.
With I. Kapnick. Studies on cultural requirements of bacteria. VII.
Amino acid requirements for the Park-Williams no. 8 strain of
diphtheria. J. Bacteriol., 30:525-34.
Methionine as an impurity in natural leucine preparations. Sci-
ence, 81 :50-51.
1936
Studies on cultural requirements of bacteria. VIII Utilization of
glutamic acid by the diphtheria bacillus. J. Bacteriol., 32:207-
10.
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JOHN HOWARD MUELLER
1937
317
With Y. Subbarow. Studies on cultural requirements of bacteria.
IX. Tissue extractives in the growth of the diphtheria bacillus.
I. Bacteriol., 34: 153 -61.
Studies on cultural requirements of bacteria. X. Pimelic acid as a
growth stimulant for C. diphtheriae. ]. Bacteriol., 34: 163-78.
With S. Cohen. Beta alanine as a growth accessory for the diph-
theria bacillus . I. B. acteriol ., 34: 381 - 86.
Nicotinic acid as a growth accessory substance for the diphtheria
bacillus. I. Bacteriol., 34:429-41.
Pimelic acid as a growth accessory for the diphtheria bacillus. l.
Biol. Chem., 119: 121-31.
Substitution of p-alanine, nicotinic acid, and pimelic acid for meat
extract in growth of diphtheria bacillus. Proc. Soc. Exp. Biol.
Med., 36:706-8.
Nicotinic acid as a growth accessory for the diphtheria bacillus. I.
Biol. Chem., 120:219-24.
Pimelic acid as a growth accessory factor for a strain of the diph-
theria bacillus. Science, 85:502.
With A. M. Pappenheimer, fir., and S. Cohen. Production of potent
diphtherial toxin on a medium of chemically defined composi-
tion. Proc. Soc. Exp. Biol. Med., 36:795-96.
1938
The replacement of meat infusion by known substances in the cul-
tivation of Corynebacterium dipEtheriae. (Abstract.) I. Bacteriol.,
35:7-8.
A synthetic medium for the cultivation of C. diphtheriae. ]. Bacte-
riol., 36:499-515.
The utilization of carnosine by the diphtheria bacillus. I. Biol.
Chem., 123:421.
With A. Klotz. Pantothenic acid as a growth factor for the diphthe-
ria bacillus. l. Am. Chem. Soc., 60:3086-87.
1939
Factors concerned in formation of toxin by the diphtheria bacillus.
(Abstract.) In: Third International Congress for Microbiology, Ab-
stracts of Communications, p. 203. International Association for
Microbiology.
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318
BIOGRAPHICAL MEMOIRS
A simplified formula for diphtheria toxin broth. I. Immunol.,
37: 103-12.
An unidentified growth factor for certain strains of the diphtheria
bacillus. Proc. Soc. Exp. Biol. Med., 40:632-33.
1940
Physical and chemical properties of filterable viruses. In: Virus and
Rickettsial Diseases with Especial Consideration of Their Public Health
Significance, pp. 65-88. Cambridge, Mass.: Harvard University
Press.
With P. A. Miller. Tetanus toxin production on a simplified me-
dium. Proc. Soc. Exp. Biol. Med., 43:389-90.
With i. C. Snyder. Nutritional factors concerned with colony de-
velopment of C. dipAtheriae. Proc. Soc. Exp. Biol. Med., 45:243.
With S. Cohen. Oleic acid in colony development of C. diphtheriae.
Proc. Soc. Exp. Biol. Med., 45:244.
Hans Zinsser ~ 1878 - 1940~. J. Bacteriol., 40: 747-53.
Nutrition of the diphtheria bacillus. Bacteriol. Rev., 4:97-134.
1941
With P. A. Miller. Production of diphtheric toxin of high potency
(100 Lf) on a reproducible medium. J. Immunol., 40:21-32.
With E. R. Johnson. Acid hydrolysates of casein to replace peptone
in the preparation of bacteriological merlin ~ Tmm,~nn1
40:33-38.
~ . %,, . in, ~ . .,
With P. A. Miller. A modification of Rosenthal's chromium-sulfuric
acid method for anaerobic cultures. I. Bacteriol., 41:301-3.
With S. Cohen and J. C. Snyder. Factors concerned in the growth
of Cornyebacterium diphtherial from minute inocula. J. Bacteriol.,
41 :581-91.
With E. B. Schoenbach and I. F. Enders. The apparent effect of
tyrothrycin on Streptococcus hemolyticus in the rhinopharynx of
carriers. Science, 94:217-18.
The influence of iron on the production of diphtheria toxin. l.
Immunol., 42:343.
With J. Hinton. A protein-free medium for primary isolation of
the gonococcus and meningococcus. Proc. Soc. Exp. Biol. Med.,
48:330-33.
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JOHN HOWARD MUELLER
1942
319
With O. F. Cox and M. McDermott. Delayed planting of gonococ-
cus cultures: Preliminary report. Vener. Dis. Info., 23:226-27.
With I. Hinton and P. A. Miller. Growth requirements of Neisseria.
(Abstract.) I. Bacteriol., 43: 100.
With P. A. Miller. Growth1 requirements of Clostridium tetani. J. Bac-
teriol., 43:763 -72.
With P. A. Miller. Folic acid in the growth of Cl. tetani. Proc. Soc.
Exp. Biol. Med., 49:211-12.
1943
With R. E. Feeney and P. A. Miller. Growth requirements of Clos-
tridium tetani. II. Factors exhausted by growth of the organism.
I. Bacteriol., 46:559-62.
With R. E. Feeney and P. A. Miller. Growth requirements of Clos-
tridium tetani. III. A "synthetic" medium. J. Bacteriol., 46:563-
71.
With P. A. Miller. Large-scale production of tentanal toxin on a
peptone-free medium. J. Immunol., 47:15-22.
The relation of the carrier to epidemic meningitis. Ann. Intern.
Med., 18:974-77.
With L. R. Seidman and P. A. Miller. A comparison of antigenicities
of hydrolysate and peptone tetanus toxoids in the guinea pig.
i. Clin. Invest., 22:321-24.
With E. B. Schoenbach and I. I. ~ezukawicz. Conversion of hydrol-
ysate tetanus toxin to toxoid. l. Clin. Invest., 22:319-20.
With E. B. Schoenbach, l. l. ~ezukawicz, and P. A. Miller. Produc-
tion of tetanus toxin on peptone-free media. l. Clin. Invest.,
22:315-18.
With L. R. Seidman and P. A. Miller. Antitoxin response in man to
tetanus toxoids. }. Clin. Invest., 22:325-28.
1943-1944
Nutrition of the single cell: Its applications in medical bacteriology.
Harvey Lect. Ser. 39: 143-61.
1944
With R. G. Gould and L. W. Kane. On the growth requirements of
Neisseria gonorrhoeae. ]. Bacteriol., 47: 287-92.
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320
BIOGRAPHICAL MEMOIRS
With O. F. Cox and M. A. Kinney. Methods of transporting gono-
cocci to laboratories for cultural studies. Vener. Dis. Info.,
25:207-9.
1945
The chemistry and metabolism of bacteria. Annul Rev. Biochem.,
14:733-48.
With P. A. Miller. Production of tetanal toxin. I. Immunol.,50:377-
84.
1946
Graduate training in bacteriology. (Abstract.) J. Bacteriol., 51:630.
With P. A. Miller. A new tellurite plating medium and some com-
ments on the laboratory "diagnosis" of diphtheria. I. Bacteriol.,
51 :743-50.
With H. L. Ley, Jr. On the isolation from agar of an inhibitor for
Neisseria gonorrhoeae. ]. Bacteriol., 52:453-60.
1947
With F. S. Cheever. Epidemic diarrhea! disease of suckling mice;
manifestations, epidemiology, and attempts to transmit disease.
I. Exp. Med., 85:405-16.
With P. A. Miller. Factors influencing the production of tetanal
toxin. I. Immunol., 56: 143-47.
1948
With P. A. Miller. Factors affecting the production of tetanus toxin:
Temperature. I. Bacteriol., 55:421-23.
With S. Lavin and L. E. Farr. Shaking device for multiple contain-
ers. Proc. Soc. Exp. Biol. Med., 68:99-100.
With F. S. Cheever. Epidemic diarrhea! disease of suckling mice;
effect of strain, litter, and season upon incidence of disease. I.
Exp. Med., 88:309-16.
With P. A. Miller and E. M. Lerner. Factors influencing the pro-
duction of tetanus toxin: Gaseous products of growth. i. Bac-
teriol., 56:97-98.
With P. A. Miller. Unidentified nutrients in tetanus toxin produc-
tion. J. Bacteriol., 56:219 -33.
OCR for page 321
JOHN HOWARD MUELLER
1949
321
With P. A. Miller. Inhibition of tetanus toxin formation by D-serine.
}.Am.Chem.Soc.,71:1865.
With P. A. Miller. Glutamine in the production of tetanus toxin. I.
Biol. Chem., 181 :39-41.
1950
The use of thick paper for chromatography. Science, 112:405-6.
With W. L. Aycock. Meningococcus carrier rates and meningitis
incidence. Bacteriol. Rev., 14: 115-60.
1951
With H. E. Umbarger. Isoleucine and valine metabolism of Esche-
r?chia coli. I. Growth studies on amino acid-deficient mutants. I.
Biol. Chem., 189:277 - 85.
With R. M. Drew. A chemically defined medium suitable for the
production of high titer diphtheriae toxin. I. Bacteriol., 62:
549-59.
1954
With P. A. Miller. Variable factors influencing the production of
tetanus toxin. J. Bacteriol., 67:271-77.
With N. H. Fisek and P. A. Miller. Muscle extractives in the pro-
duction of tetanus toxin. I. Bacteriol., 67: 329-34.
1955
With P. A. Miller. Separation from tryptic digests of casein of some
acid-labile components essential in tetanus toxin formation. i.
Bacteriol., 69:634-42.
Representative terms from entire chapter:
howard mueller