{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T13:49:23Z","timestamp":1756993763252},"reference-count":43,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"3563","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1963,4,12]]},"abstract":"<jats:p>The evidence summarized in this article is sufficient to support conclusions as follows.<\/jats:p>\n          <jats:p>1) Antibiotics penetrate rapidly into mammalian cells and inhibit multiplication of susceptible microbes within the cell as promptly and effectively as they inhibit multiplication of such microbes outside the cell. This is consistent with clinical experience.<\/jats:p>\n          <jats:p>\n            2) Death of individual organisms inside mammalian cells bathed in medium containing antibiotics continues over several weeks but may not proceed\n            <jats:italic>pari passu<\/jats:italic>\n            with time. This observation supports the as yet meager clinical data, which suggest that eradication of the typhoid carrier state may be accomplished through antibiotic therapy, provided (i) the proper antibiotic is selected; (ii) it is administered in amounts sufficient to obtain continuous suppression of growth of intracellular organisms; and (iii) the regimen is maintained for 2 or 3 weeks.\n          <\/jats:p>\n          <jats:p>3) The actual cause of death and destruction of intracellular microbes in treated cells remains an enigma. To attribute this to inanition or senescence of the organisms, without describing mechanisms, is to avoid the issue. The hypotheses dealing with inactivation of intracellular microbes by intracellular antimicrobial substances and antibodies deserve to be explored.<\/jats:p>\n          <jats:p>4) Evidence from the ward and laboratory suggests that infected cells can clear themselves of invading pathogens and recover. Although antibiotics have played the major role in demonstrating this in the laboratory, it is possible that they do nothing more than hold the intruders in abeyance while natural defense mechanisms of the cell gain the upper hand. Certainly such cellular mechanisms must provide a potent force for survival; otherwise, why would 98 percent of typhoid patients fail to become chronic carriers?<\/jats:p>\n          <jats:p>5) The continued study of infections, including the carrier state, with a view to understanding the abnormalities created by the multiplying intracellular microbe and the means by which the cell corrects these and eliminates the intruder, should open new vistas in chemotherapy and immunology.<\/jats:p>","DOI":"10.1126\/science.140.3563.153","type":"journal-article","created":{"date-parts":[[2006,10,5]],"date-time":"2006-10-05T09:05:35Z","timestamp":1160039135000},"page":"153-160","source":"Crossref","is-referenced-by-count":11,"title":["Intracellular Infection and the Carrier State"],"prefix":"10.1126","volume":"140","author":[{"given":"Joseph E.","family":"Smadel","sequence":"first","affiliation":[{"name":"Laboratory of Virology and Rickettsiology, Division of Biologics Standards, National Institutes of Health, Bethesda, Md."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"221","reference":[{"issue":"5","key":"e_1_2_1_1_1","first-page":"57","year":"1957","unstructured":"BODIAN, D, NEW YORK ACADEMY OF SCIENCES SPECIAL PUBLICATION 5 57 (1957).","journal-title":"NEW YORK ACADEMY OF SCIENCES SPECIAL PUBLICATION"},{"key":"e_1_2_1_2_1","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1128\/jb.73.1.56-62.1957","volume":"73","year":"1957","unstructured":"BOVARNICK, M.R., REVERSIBLE INACTIVATION OF TYPHUS RICKETTSIAE AT 0-C, JOURNAL OF BACTERIOLOGY 73: 56 (1957).","journal-title":"JOURNAL OF BACTERIOLOGY"},{"key":"e_1_2_1_3_1","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1085\/jgp.38.2.169","volume":"38","year":"1954","unstructured":"BOVARNICK, M.R., REVERSIBLE INACTIVATION OF TYPHUS RICKETTSIAE .1. INACTIVATION BY FREEZING, JOURNAL OF GENERAL PHYSIOLOGY 38: 169 (1954).","journal-title":"JOURNAL OF GENERAL PHYSIOLOGY"},{"key":"e_1_2_1_4_1","doi-asserted-by":"crossref","first-page":"475","DOI":"10.4049\/jimmunol.76.6.475","volume":"76","year":"1956","unstructured":"BOZEMAN, F.M., STUDY ON THE GROWTH OF RICKETTSIAE .1. A TISSUE CULTURE SYSTEM FOR QUANTITATIVE ESTIMATIONS OF RICKETTSIA-TSUTSUGAMUSHI, JOURNAL OF IMMUNOLOGY 76: 475 (1956).","journal-title":"JOURNAL OF IMMUNOLOGY"},{"key":"e_1_2_1_5_1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1084\/jem.74.3.213","volume":"74","year":"1941","unstructured":"BUDDINGH, G.J., Observations on the infection of chick embryos with Bacterium tularense, Brucella, and Pasteurella pestis, JOURNAL OF EXPERIMENTAL MEDICINE 74: 213 (1941).","journal-title":"JOURNAL OF EXPERIMENTAL MEDICINE"},{"key":"e_1_2_1_6_1","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1126\/science.127.3293.282","volume":"127","year":"1958","unstructured":"COHN, Z.A., UNSTABLE NUCLEIC ACIDS OF RICKETTSIA-MOOSERI, SCIENCE 127: 282 (1958).","journal-title":"SCIENCE"},{"key":"e_1_2_1_7_1","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1084\/jem.110.6.853","volume":"110","year":"1959","unstructured":"FREIMER, E.H., STUDIES OF L-FORMS AND PROTOPLASTS OF GROUP-A STREPTOCOCCI .1. ISOLATION, GROWTH, AND BACTERIOLOGIC CHARACTERISTICS, JOURNAL OF EXPERIMENTAL MEDICINE 110: 853 (1959).","journal-title":"JOURNAL OF EXPERIMENTAL MEDICINE"},{"key":"e_1_2_1_8_1","first-page":"36","volume":"1","year":"1958","unstructured":"GINSBERG, H.S., THE SIGNIFICANCE OF THE VIRAL CARRIER STATE IN TISSUE CULTURE SYSTEMS, PROGRESS IN MEDICAL VIROLOGY 1: 36 (1958).","journal-title":"PROGRESS IN MEDICAL VIROLOGY"},{"key":"e_1_2_1_9_1","first-page":"149","volume":"13","year":"1937","unstructured":"GOODPASTURE, E, The problem of infection as presented by bacterial invasion of the chorio-allantoic membrane of chick embryos, AMERICAN JOURNAL OF PATHOLOGY 13: 149 (1937).","journal-title":"AMERICAN JOURNAL OF PATHOLOGY"},{"key":"e_1_2_1_10_1","first-page":"175","volume":"13","year":"1937","unstructured":"GOODPASTURE, E.W., Concerning the pathogenesis of typhoid fever, AMERICAN JOURNAL OF PATHOLOGY 13: 175 (1937).","journal-title":"AMERICAN JOURNAL OF PATHOLOGY"},{"key":"e_1_2_1_11_1","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1084\/jem.108.4.537","volume":"108","year":"1958","unstructured":"HENLE, G, STUDIES ON PERSISTENT INFECTIONS OF TISSUE CULTURES .1. GENERAL ASPECTS OF THE SYSTEM, JOURNAL OF EXPERIMENTAL MEDICINE 108: 537 (1958).","journal-title":"JOURNAL OF EXPERIMENTAL MEDICINE"},{"key":"e_1_2_1_12_1","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1084\/jem.110.4.525","volume":"110","year":"1959","unstructured":"HENLE, W, STUDIES ON PERSISTENT INFECTIONS OF TISSUE CULTURES .4. EVIDENCE FOR THE PRODUCTION OF AN INTERFERON IN MCN-CELLS BY MYXOVIRUSES, JOURNAL OF EXPERIMENTAL MEDICINE 110: 525 (1959).","journal-title":"JOURNAL OF EXPERIMENTAL MEDICINE"},{"key":"e_1_2_1_13_1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1128\/br.24.1.133-140.1960","volume":"24","year":"1960","unstructured":"HIRSCH, J.G., ANTIMICROBIAL FACTORS IN TISSUES AND PHAGOCYTIC CELLS, BACTERIOLOGICAL REVIEWS 24: 133 (1960).","journal-title":"BACTERIOLOGICAL REVIEWS"},{"key":"e_1_2_1_14_1","first-page":"1031","volume":"76","year":"1957","unstructured":"HOBBY, G.L., INVITRO ACTION OF ANTITUBERCULOUS AGENTS AGAINST MULTIPLYING AND NON-MULTIPLYING MICROBIAL CELLS, AMERICAN REVIEW OF TUBERCULOSIS AND PULMONARY DISEASES 76: 1031 (1957).","journal-title":"AMERICAN REVIEW OF TUBERCULOSIS AND PULMONARY DISEASES"},{"key":"e_1_2_1_15_1","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1111\/j.1749-6632.1950.tb42158.x","volume":"53","year":"1950","unstructured":"HOBBY, G.L., THE ANTIMICROBIAL ACTION OF TERRAMYCIN, ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 53: 266 (1950).","journal-title":"ANNALS OF THE NEW YORK ACADEMY OF SCIENCES"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-56-14643"},{"key":"e_1_2_1_17_1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.4049\/jimmunol.82.2.161","volume":"82","year":"1959","unstructured":"HOPPS, H.E., STUDY ON THE GROWTH OF RICKETTSIAE .3. INFLUENCE OF EXTRACELLULAR ENVIRONMENT ON THE GROWTH OF RICKETTSIA-TSUTSUGAMUSHI IN TISSUE CULTURE CELLS, JOURNAL OF IMMUNOLOGY 82: 161 (1959).","journal-title":"JOURNAL OF IMMUNOLOGY"},{"key":"e_1_2_1_18_1","doi-asserted-by":"crossref","first-page":"172","DOI":"10.4049\/jimmunol.82.2.172","volume":"82","year":"1959","unstructured":"HOPPS, H.E., STUDY ON THE GROWTH OF RICKETTSIAE .4. EFFECT OF CHLORAMPHENICOL AND SEVERAL METABOLIC INHIBITORS ON THE MULTIPLICATION OF RICKETTSIA-TSUTSUGAMUSHI IN TISSUE CULTURE CELLS, JOURNAL OF IMMUNOLOGY 82: 172 (1959).","journal-title":"JOURNAL OF IMMUNOLOGY"},{"key":"e_1_2_1_19_1","doi-asserted-by":"crossref","first-page":"162","DOI":"10.4049\/jimmunol.87.2.162","volume":"87","year":"1961","unstructured":"HOPPS, H.E., EFFECT OF ANTIBIOTICS ON INTRACELLULAR SALMONELLA TYPHOSA .2. ELIMINATION OF INFECTION BY PROLONGED TREATMENT, JOURNAL OF IMMUNOLOGY 87: 162 (1961).","journal-title":"JOURNAL OF IMMUNOLOGY"},{"key":"e_1_2_1_20_1","first-page":"117","volume":"2","year":"1961","unstructured":"Isaacs, A., Perspectives In Virology 2: 117 (1961).","journal-title":"Perspectives In Virology"},{"key":"e_1_2_1_21_1","first-page":"292","volume":"6","year":"1959","unstructured":"JERSILD, T, ANTIBIOTIC MEDICINE & CLINICAL THERAPY 6: 292 (1959).","journal-title":"ANTIBIOTIC MEDICINE & CLINICAL THERAPY"},{"key":"e_1_2_1_22_1","unstructured":"Kundin W. D. Arch. Ges. Virusforsch. in press."},{"key":"e_1_2_1_23_1","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1128\/jb.75.5.567-576.1958","volume":"75","year":"1958","unstructured":"LANDMAN, O.E., QUANTITATIVE CONVERSION OF CELLS AND PROTOPLASTS OF PROTEUS-MIRABILIS AND ESCHERICHIA-COLI TO THE L-FORM, JOURNAL OF BACTERIOLOGY 75: 567 (1958).","journal-title":"JOURNAL OF BACTERIOLOGY"},{"key":"e_1_2_1_24_1","first-page":"303","volume":"56","year":"1952","unstructured":"LEY, H.L., IMMUNIZATION AGAINST SCRUB TYPHUS .4. LIVING KARP VACCINE AND CHEMOPROPHYLAXIS IN VOLUNTEERS, AMERICAN JOURNAL OF HYGIENE 56: 303 (1952).","journal-title":"AMERICAN JOURNAL OF HYGIENE"},{"key":"e_1_2_1_25_1","doi-asserted-by":"crossref","first-page":"485","DOI":"10.2307\/4590490","volume":"74","year":"1959","unstructured":"MCDERMOTT, W, INAPPARENT INFECTION - RELATION OF LATENT AND DORMANT INFECTIONS TO MICROBIAL PERSISTENCE, PUBLIC HEALTH REPORTS 74: 485 (1959).","journal-title":"PUBLIC HEALTH REPORTS"},{"key":"e_1_2_1_26_1","first-page":"112","year":"1958","unstructured":"Morgan, H. R., Symposium on Latency and Masking in Viral and Rickettsial Infections: 112 (1958).","journal-title":"Symposium on Latency and Masking in Viral and Rickettsial Infections"},{"key":"e_1_2_1_27_1","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1056\/NEJM195203062461001","volume":"246","year":"1952","unstructured":"MURRAY, E.S., EPIDEMIC-TYPHUS ANTIBODIES IN HUMAN SUBJECTS IN BOSTON, MASSACHUSETTS, NEW ENGLAND JOURNAL OF MEDICINE 246: 355 (1952).","journal-title":"NEW ENGLAND JOURNAL OF MEDICINE"},{"key":"e_1_2_1_28_1","first-page":"310","volume":"30","year":"1961","unstructured":"NICOL, C.G., WORLD MED 30: 310 (1961).","journal-title":"WORLD MED"},{"key":"e_1_2_1_29_1","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.2307\/4590319","volume":"73","year":"1958","unstructured":"OCONNOR, M, EFFICACY OF CHLORAMPHENICOL THERAPY FOR TYPHOID CARRIERS, PUBLIC HEALTH REPORTS 73: 1039 (1958).","journal-title":"PUBLIC HEALTH REPORTS"},{"key":"e_1_2_1_30_1","first-page":"593","volume":"32","year":"1953","unstructured":"PARKER, R. T., JOURNAL OF CLINICAL INVESTIGATION 32: 593 (1953).","journal-title":"JOURNAL OF CLINICAL INVESTIGATION"},{"key":"e_1_2_1_31_1","first-page":"67","year":"1958","unstructured":"PRICE, W.H., AMERICAN JOURNAL OF HYGIENE: 67: 154 (1958).","journal-title":"AMERICAN JOURNAL OF HYGIENE"},{"key":"e_1_2_1_32_1","first-page":"154","volume":"67","year":"1958","unstructured":"PRICE, W.H., ECOLOGIC STUDIES ON THE INTEREPIDEMIC SURVIVAL OF LOUSE-BORNE EPIDEMIC TYPHUS FEVER, AMERICAN JOURNAL OF HYGIENE 67: 154 (1958).","journal-title":"AMERICAN JOURNAL OF HYGIENE"},{"key":"e_1_2_1_33_1","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/0042-6822(57)90030-2","volume":"3","year":"1957","unstructured":"SCHAECHTER, M, STUDY ON THE GROWTH OF RICKETTSIAE .2. MORPHOLOGIC OBSERVATIONS OF LIVING RICKETTSIAE IN TISSUE CULTURE CELLS, VIROLOGY 3: 160 (1957).","journal-title":"VIROLOGY"},{"key":"e_1_2_1_34_1","doi-asserted-by":"crossref","first-page":"979","DOI":"10.7326\/0003-4819-42-5-979","volume":"42","year":"1955","unstructured":"SCHAEFER, G.L., INCIDENCE OF EPIDEMIC TYPHUS ANTIBODIES IN INDIVIDUALS BORN IN EASTERN EUROPE, ANNALS OF INTERNAL MEDICINE 42: 979 (1955).","journal-title":"ANNALS OF INTERNAL MEDICINE"},{"key":"e_1_2_1_35_1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1085\/jgp.45.4.143","volume":"45","year":"1962","unstructured":"SHOPE, R.E., ARE ANIMAL TUMOR VIRUSES ALWAYS VIRUS-LIKE, JOURNAL OF GENERAL PHYSIOLOGY 45: 143 (1962).","journal-title":"JOURNAL OF GENERAL PHYSIOLOGY"},{"key":"e_1_2_1_36_1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1085\/jgp.45.4.143","volume":"45","year":"1962","unstructured":"SHOPE, R. E., JOURNAL OF GENERAL PHYSIOLOGY 45: 143 (1962).","journal-title":"JOURNAL OF GENERAL PHYSIOLOGY"},{"key":"e_1_2_1_37_1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.4049\/jimmunol.87.2.153","volume":"87","year":"1961","unstructured":"SHOWACRE, J.L., EFFECT OF ANTIBIOTICS ON INTRACELLULAR SALMONELLA TYPHOSA .1. DEMONSTRATION BY PHASE MICROSCOPY OF PROMPT INHIBITION OF INTRACELLULAR MULTIPLICATION, JOURNAL OF IMMUNOLOGY 87: 153 (1961).","journal-title":"JOURNAL OF IMMUNOLOGY"},{"key":"e_1_2_1_38_1","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1128\/br.21.4.273-294.1957","volume":"21","year":"1957","unstructured":"SKARNES, R.C., ANTIMICROBIAL FACTORS OF NORMAL TISSUES AND FLUIDS, BACTERIOLOGICAL REVIEWS 21: 273 (1957).","journal-title":"BACTERIOLOGICAL REVIEWS"},{"key":"e_1_2_1_39_1","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1172\/JCI102154","volume":"28","year":"1949","unstructured":"SMADEL, J.E., CHLORAMPHENICOL (CHLOROMYCETIN) IN THE TREATMENT OF TSUTSUGAMUSHI DISEASE (SCRUB TYPHUS), JOURNAL OF CLINICAL INVESTIGATION 28: 1196 (1949).","journal-title":"JOURNAL OF CLINICAL INVESTIGATION"},{"key":"e_1_2_1_40_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4049\/jimmunol.84.1.1","volume":"84","year":"1960","unstructured":"SMADEL, J.E., SOME ASPECTS OF INTRACELLULAR INFECTIONS, JOURNAL OF IMMUNOLOGY 84: 1 (1960).","journal-title":"JOURNAL OF IMMUNOLOGY"},{"key":"e_1_2_1_41_1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1128\/br.22.1.46-73.1958","volume":"22","year":"1958","unstructured":"WILKINSON, J.F., THE EXTRACELLULAR POLYSACCHARIDES OF BACTERIA, BACTERIOLOGICAL REVIEWS 22: 46 (1958).","journal-title":"BACTERIOLOGICAL REVIEWS"},{"key":"e_1_2_1_42_1","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1172\/JCI102238","volume":"29","year":"1950","unstructured":"WOODWARD, T.E., CHLORAMPHENICOL AND OTHER ANTIBIOTICS IN THE TREATMENT OF TYPHOID FEVER AND TYPHOID CARRIERS, JOURNAL OF CLINICAL INVESTIGATION 29: 87 (1950).","journal-title":"JOURNAL OF CLINICAL INVESTIGATION"},{"key":"e_1_2_1_43_1","unstructured":"Woodward T. E. Science Technology and Developments 6 (1963)."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.140.3563.153","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T03:50:26Z","timestamp":1704945026000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.140.3563.153"}},"subtitle":["The path of clinical investigation leads from bench to bed and back again."],"short-title":[],"issued":{"date-parts":[[1963,4,12]]},"references-count":43,"journal-issue":{"issue":"3563","published-print":{"date-parts":[[1963,4,12]]}},"alternative-id":["10.1126\/science.140.3563.153"],"URL":"https:\/\/doi.org\/10.1126\/science.140.3563.153","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1963,4,12]]}}}