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PATHOGENIC BACTERIA, RICKETTSIAS AND VIRUSES AS SHOWN BY THE ELECTRON MICROSCOPE: Title and subTitle BreakTHEIR RELATIONSHIPS TO IMMUNITY AND CHEMOTHERAPY I. MORPHOLOGY

STUART MUDD, M.D.; THOMAS F. ANDERSON, Ph.D.
[+] Author Affiliations

Owing to lack of space, this article is abbreviated in The Journal by the omission of twenty-six illustrations. The complete article appears in the authors' reprints.

The privilege of republishing certain of the electron micrographs was extended by the authors and the journals cited in the corresponding references in the bibliography and by the Williams and Wilkins Company, Baltimore. The electron pictures, with a few exceptions, were taken at the RCA Research Laboratories. Many courtesies were extended by Dr. V. K. Zworykin and Mr. James Hillier. The pictures of figures 12, 23, 33, 34 and 35 were taken with an RCA type B electron microscope at the Johnson Foundation for Medical Physics, University of Pennsylvania.


PHILADELPHIA

Dr. Mudd was chairman of the Committee on Applications of the Electron Microscope, National Research Council, 1940-1944. Dr. Anderson was RCA Fellow on the Electron Microscope, National Research Council, 1940-1942.


JAMA. 1944;126(9):561-571. doi:10.1001/jama.1944.82850440002010
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Current textbooks, teaching and discussion in bacteriology do not reflect adequate understanding of the structure of the bacterial cell or of the smaller parasitic entities known as rickettsias and viruses. It is a well recognized principle in natural science that understanding of structure is basic to analysis of function. In most areas of the medical sciences this principle is not only accepted as a matter of course but, more important, is expressed in the actual content of these sciences. However, several special circumstances have tended to foster the development of bacteriology without an adequate basis of understanding even of the structure of bacteria. Bacteriology has been pursued primarily for its practical usefulness, only secondarily as a science in its own right; structural details of the bacterial cell are close to, and in many cases beyond, and the structural details of rickettsias and viruses are completely beyond, the limits of resolution

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Mudd, S.; Polevitzky, K.; Anderson, T. F., and Chambers, L. A.:  Bacterial Morphology as Shown by the Electron Microscope: II. The Bacterial Cell Wall in the Genus Bacillus , J. Bact. 42:251-264 ( (Aug.) ) 1941;.
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Mudd, S.; Polevitzky, K.; Anderson, T. F., and Kast, C. C.:  Bacterial Morphology as Shown by the Electron Microscope: III. Cell Wall and Protoplasm in a Strain of Fusobacterium , J. Bact. 44:361-366 ( (Sept.) ) 1942;.
Mudd, S.; Polevitzky, K., and Anderson, T. F.:  Bacterial Morphology as Shown by the Electron Microscope: IV. Structural Differentiation Within the Bacterial Protoplasm , Arch. Path. 34:199-207 ( (July) ) 1942;.
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Marton, L.: The Electron Microscope in Biology: Annual Review of Biochemistry , Stanford University P. O., Calif., Annual Reviews, Inc. 12:587-614, 1943;.
Topley, W. W. C., and Wilson, G. S.: The Principles of Bacteriology and Immunity , ed. 2, Baltimore, William Wood & Co., 1936;, p. 18.
Zworykin, V. K.; Hillier, J., and Vance, A. W.:  An Electron Microscope for Practical Laboratory Service , Tr. American Institute of Electrical Engineers 60:157-161 ( (April) ) 1941;.
Zworykin, V. K., and Hillier, J.:  A Compact High Resolving Power Electron Microscope , J. Applied Physics 14:658-673 ( (Dec.) ) 1943;.
Zworykin, V. K.; Hillier, J., and Vance, A. W.:  Electron Microscope , in Glasser, O.: Medical Physics , Chicago, Year Book Publishers, 1944;.
Anderson, T. F.: The Study of Colloids with the Electron Microscope, from Advances in Colloid Science , New York, Interscience Publishers, Inc., 1942;, vol. 1, pp. 353-390.
Marton, L.:  The Electron Microscope: A New Tool for Bacteriological Research , J. Bact. 41:397-413 ( (March) ) 1941;, figure 6.
Mudd, S., and Lackman, D. B.:  Bacterial Morphology as Shown by the Electron Microscope: I. Structural Differentiation Within the Streptococcal Cell , J. Bact. 41:415-420 ( (March) ) 1941;.
Mudd, S.; Polevitzky, K.; Anderson, T. F., and Chambers, L. A.:  Bacterial Morphology as Shown by the Electron Microscope: II. The Bacterial Cell Wall in the Genus Bacillus , J. Bact. 42:251-264 ( (Aug.) ) 1941;.
Morton, H. E., and Anderson, T. F.:  The Morphology of Leptospira Icterohemorrhagiae and L. Canicola as Revealed by the Electron Microscope , J. Bact. 45:143-146 ( (Feb.) ) 1943;.
Mudd, S.; Polevitzky, K.; Anderson, T. F., and Kast, C. C.:  Bacterial Morphology as Shown by the Electron Microscope: III. Cell Wall and Protoplasm in a Strain of Fusobacterium , J. Bact. 44:361-366 ( (Sept.) ) 1942;.
Mudd, S.; Polevitzky, K., and Anderson, T. F.:  Bacterial Morphology as Shown by the Electron Microscope: IV. Structural Differentiation Within the Bacterial Protoplasm , Arch. Path. 34:199-207 ( (July) ) 1942;.
Morton, H. E., and Anderson, T. F.:  Electron Microscopic Studies of Biological Reactions: I. Reduction of Potassium Tellurite by Corynebacterium Diphtheriae , Proc. Soc. Exper. Biol. & Med. 46:272-276 ( (Feb.) ) 1941;.
Varney, P. L.:  The Serological Classification of Fusiform Bacilli , J. Bact. 13:275-314 ( (April) ) 1927;.
Hine, M. K., and Bury, G. P.:  Morphological and Cultural Studies of the Genus Fusiformis , J. Bact. 34:517-533 ( (Nov.) ) 1937;.
Knaysi, G., and Mudd, S.:  The Internal Structure of Certain Bacteria as Revealed by the Electron Microscope: A Contribution to the Study of the Bacterial Nucleus , J. Bact. 45:349-359 ( (April) ) 1943;.
Knaysi, G.:  Cytology of Bacteria , Botan. Rev. 4:83-112 ( (Feb.) ) 1938;
 Observations on the Cell Division of Some Yeasts and Bacteria , J. Bact. 41:141-154 ( (Feb.) ) 1941;
Elements of Bacterial Cytology , Ithaca, N. Y., Comstock Publishing Company, 1944;.
Johnson, F. H.:  Observations on the Electron Microscopy of B. Cereus and Tyrothricin Action , J. Bact. 47:551-557 ( (June) ) 1944;.
Mudd, S.; Heinmets, F., and Anderson, T. F.:  Bacterial Morphology as Shown by the Electron Microscope: VI. Capsule, Cell Wall and Inner Protoplasm of Pneumococcus Type III , J. Bact. 46:205-211 ( (Aug.) ) 1943;.
Mudd, S.; Heinmets, F., and Anderson, T. F.:  The Pneumococcal Capsular Swelling Reaction, Studied with the Aid of the Electron Microscope , J. Exper. Med. 78:327-332 ( (Nov.) ) 1943;.
Johnson, F. H., and Dennison, W. L.:  The Volume Change Accompanying the Quellung Reaction of Pneumococci , J. Immunol. 48:317-323 ( (May) ) 1944;.
Mudd, S., and Anderson, T. F.:  Selective "Staining" for Electron Micrography: The Effects of Heavy Metal Salts on Individual Bacterial Cells , J. Exper. Med. 76:103-108 ( (July) ) 1942;.
Pijper Microcinematography of the Agglutination of Typhoid Bacilli , J. Bact. 42:395-409 [ (Sept.) ] 1941;
Wile, U. J., and Kearney, E. B.:  The Morphology of Treponema Pallidum in the Electron Microscope: Demonstration of Flagella , J. A. M. A. 122:167-168 ( (May 15) ) 1943;.
Mudd, S.; Polevitzky, K., and Anderson, T. F.:  Bacterial Morphology as Shown by the Electron Microscope: V. Treponema Pallidum, T. Macrodentium and T. Microdentium , J. Bact. 46:15-24 ( (July) ) 1943;
Wile, U. J.; Picard, R. G., and Kearny, E. B.:  The Morphology of Spirochaeta Pallida in the Electron Microscope , J. A. M. A. 119:880-881 ( (July 11) ) 1942;.
Morton, H. E., and Anderson, T. F.:  Some Morphologic Features of the Nichols Strain of Treponema Pallidum as Revealed by the Electron Microscope , Am. J. Syph., Gonor. & Ven. Dis. 26:565-573 ( (Sept.) ) 1942;.
Meirowsky, E.:  Spirochaeta pallida, Schaudinn, nebst Bemerkungen über den Entwicklungskreis der Spirochäten , München. med. Wchnschr. 77:429-430 ( (March) ) 1930;.
Ingraham, N. R., Jr.:  The Life History of the Treponema Pallidum: A Critical Review of the Literature , Am. J. Syph. 16:155-189 ( (April) ) 1932;.
Manouélian, Y.:  Etude morphologique de Spirochaeta pallida: modes de division; spirochétogène syphilitique , Ann. Inst. Pasteur 64:439-455 ( (May) ) 1940;.
Lancefield, R. C.:  Studies on the Antigenic Composition of Group A Hemolytic Streptococci: I. Effects of Proteolytic Enzymes on Streptococcal Cells , J. Exper. Med. 78:465-476 ( (Dec.) ) 1943;.
Lancefield, R. C.:  Type Specific Antigens M and T of Matt and Glossy Variants of Group A Hemolytic Streptococci , J. Exper. Med. 71:: 521-537 ( (April) ) 1940;.
Lancefield, R. C., and Stewart, W. A.:  Studies on the Antigenic Composition of Group A Hemolytic Streptococci: II. The Occurrence of Strains in a Given Type Containing M but no T Antigen , J. Exper. Med. 79:79-88 ( (Jan.) ) 1944;.
Lancefield, R. C.:  A Serological Differentiation of Human and Other Groups of Hemolytic Streptococci , J. Exper. Med. 57:571-595 ( (April) ) 1933;.
Zittle, C. A., and Harris, T. N.:  The Antigenic Structure of Hemolytic Streptococci of Lancefield Group A: X. The Purification and Certain Properties of the Group Specific Polysaccharide , J. Biol. Chem. 142:823-833 ( (Feb.) ) 1942;.
Lancefield, R. C.:  The Antigenic Complex of Streptococcus Hemolyticus: II. Chemical and Immunological Properties of the Protein Fractions , J. Exper. Med. 47:469-480 ( (March) ) 1928;.
Mudd, S., and Wiener, M.:  The Antigenic Structure of Hemolytic Streptococci of Lancefield Group A.: XI. Relationships of the Nucleoproteins of Some Species of Streptococci and Pneumococci , J. Immunol. 45:21-28 ( (Sept.) ) 1942;.
Sevag, M. G.; Smolens, J., and Lackman, D. B.:  The Nucleic Acid Content and Distribution in Streptococcus Pyogenes , J. Biol. Chem. 134:523-529 ( (July) ) 1940;.
Bernheimer, A. W., and Pappenheimer, A. M., Jr.:  Factors Necessary for Massive Growth of Group A Hemolytic Streptococcus , J. Bact. 43:481-494 ( (April) ) 1942;.
Bernheimer, A. W.; Gillman, W.; Hottle, G. A., and Pappenheimer, A. M., Jr.:  An Improved Medium for the Cultivation of Hemolytic Streptococcus , J. Bact. 43:495-498 ( (April) ) 1942;.
Kendall, F. E.; Heidelberger, M., and Dawson, M. H.:  A Serologically Inactive Polysaccharide Elaborated by Mucoid Strains of Group A Hemolytic Streptococcus , J. Biol. Chem. 118:61-69 ( (March) ) 1937;.
Kass, E. H., and Seastone, C. V.:  The Role of the Mucoid Polysaccharide (Hyaluronic Acid) in the Virulence of Group A Hemolytic Streptococci , J. Exper. Med. 79:319-330 ( (March) ) 1944;.
Meyer, K.; Dubos, R., and Smyth, E. M.:  The Hydrolysis of the Polysaccharide Acids of Vitreous Humor, of Umbilical Cord and of Streptococcus by the Autolytic Enzyme of Pneumococcus , J. Biol. Chem. 118:71-78 ( (March) ) 1937;.
Dick, G. F., and Dick, Gladys H.:  A Skin Test for Susceptibility to Scarlet Fever , J. A. M. A. 82:265-266 ( (Jan. 26) ) 1924;.
Dochez, A. R., and Sherman, L.:  The Significance of Streptococcus Hemolyticus in Scarlet Fever , J. A. M. A. 82:542-544 ( (Feb. 16) ) 1924;.
Hottle, G. A., and Pappenheimer, A. M., Jr.:  A Quantitative Study of the Scarlet Fever Toxin-Antitoxin Flocculation Reaction , J. Exper. Med. 74:545-556 ( (Dec.) ) 1941;.
Smytne, C. V., and Harris, T. N.:  Some Properties of a Hemolysin Produced by Group A β-Hemolytic Streptococci , J. Immunol. 38:283-300 ( (April) ) 1940;.
Tillett, W. S., and Garner, R. L.:  The Fibrinolytic Activity of Hemolytic Streptococci , J. Exper. Med. 58:485-502 ( (Oct.) ) 1933;.
Milstone, H.:  A Factor in Normal Human Blood Which Participates in Streptococcal Fibrinolysis , J. Immunol. 42:109-116 ( (Oct.) ) 1941;.
Meyer, K.; Chaffee, E.; Hobby, G. L., and Dawson, M. H.:  Hyaluronidases of Bacterial and Animal Origin , J. Exper. Med. 73:309-328 ( (March) ) 1941;.
Chain, E., and Duthie, E. S.:  Identity of Hyaluronidase and Spreading Factor , Brit. J. Exper. Path. 21:324-338 ( (Dec.) ) 1940;.
McClean, D.:  The Capsulation of Streptococci and Its Relation to Diffusion Factor (Hyaluronidase) , J. Path. & Bact. 53:13-27 ( (July) ) 1941;.
Harris, T. N.:  A Lethal Agent Produced by the Hemolytic Streptococcus , J. Bact. 43:739-748 ( (June) ) 1942;.
Sevag, M. G.; Smolens, J., and Stern, K. G.:  Isolation and Properties of Pigmented Heavy Particles from Streptococcus Pyogenes , J. Biol. Chem. 139:925-941 ( (June) ) 1941;.
Stern, K. G.:  Studies on Macromolecular Particles Endowed with Specific Biological Activity, from Frontiers in Cytochemistry , Biological Symposia 10:291-321, Lancaster, Pa., 1943;.
Luria, S. E.; Delbrück, M., and Anderson, T. F.:  Electron Microscope Studies of Bacterial Viruses , J. Bact. 46:57-77 ( (July) ) 1943;.
Richards, A. G., Jr.; Steinback, H. B., and Anderson, T. F.:  Electron Microscope Studies of Squid Giant Nerve Axoplasm , J. Cell. & Comp. Physiol. 21:129-143 ( (April) ) 1943;.
Pinkerton, H.:  The Pathogenic Rickettsiae, with Particular Reference to Their Nature, Biologic Properties and Classification , Bact. Rev. 6:37-78 ( (March) ) 1942;.
Plotz, H.; Smadel, J. E.; Anderson, T. F., and Chambers, L. A.:  Morphological Structure of Rickettsiae , J. Exper. Med. 77:355-358 ( (April) ) 1943;.
Weiss, L. J.:  Electron Micrographs of Rickettsiae of Typhus Fever , J. Immunol. 47:353-357 ( (Nov.) ) 1943;.
Sabin, A. B.:  The Filtrable Micro-Organisms of the Pleuropneumonia Group , Bact. Rev. 5:1-66 ( (March) ) 1941;.
Weiss, L. J.:  Electron Micrographs of Pleuropneumonia-like Organisms , J. Bact. 47:523-533 ( (June) ) 1944;.
Dienes, L., and Smith, W. E.:  The Significance of Pleomorphism in Bacteroides Strains , J. Bact. 48:125-153 ( (Aug.) ) 1944;.
Hesselbrock, W., and Foshay, L.:  The Morphology of Bacterium Tularense , J. Bact. , to be published.
Foshay, L., and Hesselbrock, W.:  Some Observations on the Filtrability of Bacterium Tularense , J. Bact. , to be published.
Smith, W. E., and Mudd, S.: To be published.
Rivers, T. M.: Viruses and Virus Diseases (Lane Medical Lectures) , Stanford University, Calif., Stanford University Press, 1939;.
Rives, T. M.: Virus Diseases, with Particular Reference to Vaccinia, from Virus Diseases , by Members of the Rockefeller Institute for Medical Research, Ithaca, N. Y., Cornell University Press, 1943;, pp. 3-31.
Green, R. H.; Anderson, T. F., and Smadel, J. E.:  Morphological Structure of the Virus of Vaccinia , J. Exper. Med. 75:651-656 ( (June) ) 1942;.
Woodruft, A. M., and Goodpasture, E. W.:  The Susceptibility of the Chorioallantoic Membrane of Chick Embryos to Infection with the Fowl Pox Virus , Am. J. Path. 7:209-222 ( (May) ) 1931;.
Scott, J. P.:  Swine Influenza, 13th International Veterinary Congress , Zurich-Interlaken 1:479-490, 1938;.
Henle, W., and Chambers, L. A.:  The Serological Activity of Extraembryonic Fluids of Chick Infected with Virus of Influenza A , Proc. Soc. Exper. Biol. & Med. 46:713-717 ( (April) ) 1941;.
Burnet, F. M.:  Growth of Influenza Virus in the Allantoic Cavity of the Chick Embryo , Australian J. Exper. Biol. & M. Sc. 19:291-295 ( (Dec.) ) 1941;.
Nigg, C.; Wilson, D. E., and Crowley, J. H.:  Studies on the Cultivation of Influenza Virus , Am. J. Hyg., Sect. B 34:138-147 ( (Nov.) ) 1941;.
Burnet and Bull ( Changes in Influenza Virus Associated-with Adaptation to Passage in Chick Embryos , Australian J. Exper. Biol. & M. Sc. 21:55-69 [ (June) ] 1943;
Chambers, L. A., and Henle, W.:  Studies on the Nature of the Virus of Influenza: I. The Dispersion of the Virus of Influenza A in Tissue Emulsions and in Extraembryonic Fluids of the Chick , J. Exper. Med. 77:251-264 ( (March) ) 1943;.
Chambers, L. A.; Henle, W.; Lauffer, M. A., and Anderson, T. F.:  Studies on the Nature of the Virus of Influenza: II. The Size of the Infectious Unit in Influenza A , J. Exper. Med. 77:265-276 ( (March) ) 1943;.
Friedewald, W. F., and Pickels, E. G.:  Size of Infective Particle and Hemagglutinin of Influenza Virus as Determined by Centrifugal Analysis , Proc. Soc. Exper. Biol. & Med. 52:261-262 ( (March) ) 1943;.
Taylor, A. R.; Sharp, D. G.; Beard, D.; Beard, J. W.; Dingle, J. H., and Feller, A. E.:  Isolation and Characterization of Influenza A Virus (PR 8 Strain) , J. Immunol. 47:261-282 ( (Sept.) ) 1943;.
Sharp, D. G.; Taylor, A. R.; McLean, I. W., Jr.; Beard, D.; Beard, J. W.; Feller, A. E., and Dingle, J. H.:  Isolation and Characterization of Influenza Virus B (Lee Strain) , J. Immunol. 48:129-153 ( (Feb.) ) 1944;.
Sharp, D. G.; Taylor, A. R.; McLean, I. W., Jr.; Beard D., and Beard, J. W.:  Density and Size of Influenza Virus A (PR 8 Strain) in Solution , Science 100:151-153 ( (Aug. 18) ) 1944;.
Stanley, W. M.:  An Evaluation of Methods for the Concentration and Purification of Influenza Virus , J. Exper. Med. 79:255-266 ( (March) ) 1944;.
Stanley, W. M.:  The Size of Influenza Virus , J. Exper. Med. 79:267-283 ( (March) ) 1944;.
Friedewald, W. F., and Pickels, E. G.:  Centrifugation and Ultrafiltration Studies on Allantoic Fluid Preparations of Influenza Virus , J. Exper. Med. 79:301-317 ( (March) ) 1944;.
Taylor, A. R.; Sharp, D. G.; McLean, I. W., Jr.; Beard, D.; Beard, J. W.; Dingle, J. H., and Feller, A. E.:  Purification and Character of the Swine Influenza Virus , J. Immunol. 48:361-379 ( (June) ) 1944;.
Knight, C. A.:  A Sedimentable Component of Allantoic Fluid and Its Relationship to Influenza Viruses , J. Exper. Med. 80:83-100 ( (Aug.) ) 1944;.
Taylor, A. R.; Sharp, D. G.; Beard, D., and Beard, J. W.:  Isolation and Properties of the Equine Encephalomyelitis Virus (Eastern Strain) , J. Infect. Dis. 72:31-41 ( (Jan.) -Feb.) 1943;
 Electron Micrography of the Eastern Strain Equine Encephalomyelitis Virus , Proc. Soc. Exper. Biol. & Med. 51:332-334 ( (Dec.) ) 1942;.
By "organization," in the sense used, is meant differentiation and localization of components of structure which are not merely structural units or "building stones" of a single molecule.
Sharp, D. G.; Taylor, A. R.; Beard, D., and Beard, J. W.:  Electron Micrography of the Western Strain Equine Encephalomyelitis Virus , Proc. Soc. Exper. Biol. & Med. 51:206-207 ( (Nov.) ) 1942;.
Sharp, D. G.; Taylor, A. R.; Beard, D., and Beard, J. W.:  Study of the Papilloma Virus Protein with the Electron Microscope , Proc. Soc. Exper. Biol. & Med. 50:205-207 ( (June) ) 1942;.
Glaser, R. W., and Stanley, W. M.:  Biochemical Studies on the Virus and the Inclusion Bodies of Silkworm Jaundice , J. Exper. Med. 77:451-466 ( (May) ) 1943;.
von Ardenne, M., and Pyl, G.:  Versuche zur Abbildung des Maulund Klauenseuche-Virus mit dem Universal-Elektronenmikroskop , Naturwissenschaften 28:531-532 ( (Aug. 16) ) 1940;.
Krueger, A. P., and Scribner, E. Jane:  The Bacteriophage, Its Nature and Its Therapeutic Use , J. A. M. A. 116:2160-2167 ( (May 10) ), 2269-2277 (May 17) 1941;.
Ruska, H.:  Die Sichtbarmachung der Bakteriophagen Lyse im Uebermikroskop , Naturwissenschaften 28:45 ( (Jan.) ) 1940;.
Kausche, G. A., and Pfankuch, E.:  Isolierung und übermikroskopische Abbildung eines Bakteriophagen , Naturwissenschaften 28:46 ( (Jan.) ) 1940;.
Luria, S. E., and Anderson, T. F.:  The Identification and Characterization of Bacteriophages with the Electron Microscope , Proc. Nat. Acad. Sc. 28:127-130 ( (April) ) 1942;.
Baylor, M. R. B.; Severens, J. M., and Clark, G. L.:  Electron Microscope Studies of the Bacteriophage of Salmonella Pullorum , J. Bact. 47:277-282 ( (March) ) 1944;.
Anderson, T. F.:  The Effect of Sonic Vibration, Ultraviolet Light and pH on the Bacteriophage Virus , Report to 1st Annual Meeting of Electron Microscope Society of America, New York, Jan. 14, 1944 .
Bernal, J. D., and Fankuchen, I.:  X-Ray and Crystallographic Studies of Plant Virus Preparations , J. Gen. Physiol. 25:111-165 ( (Sept.) ) 1941;.
Stanley, W. M.:  Chemical Structure and the Mutation of Viruses , in Virus Diseases , Ithaca, N. Y., Cornell University Press, 1943;.
Stanley, W. M., and Anderson. T. F.:  Electron Micrographs of Protein Molecules , J. Biol. Chem. 146:25-30 ( (Nov.) ) 1942;
Stanley, W. M., and Anderson, T. F.:  A Study of Purified Viruses with the Electron Microscope , J. Biol. Chem. 139:325-338 ( (May) ) 1941;.
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To understand the clinical management of acute heart failure syndromes.
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