STREPTOMYCIN BRITISH 466 SEPTr. 28, 1946 MEDICAL JOURNAL urbane and witty, was always apt to the occasion with well- of a committee appointed by the Medical Research Council chosen'phrases in good English, whether at the scientific to exploit the pilot-scale production of streptomycin which sessions or at the Banquet in the hotel on the bank of the is being organized by the Ministry of Supply. It is too early to assess accurately the American clinical Rhine. He was ably seconded by the Secretary-General results, but it is almost 100% effective in tularaemia (rabbit of the Academy, Prof. A. Gigon, chief editor of the fever), which though rare in England gives rise to some Schweizerische Medizinische Wochenschrift. It was to 1,000 serious cases a year in U.S.A. In'the residuum of Prof. Gigon that the idea of such a conference occurred, bacterial infections of the urinary tract which are insensi- an idea which he did not relinquish until it took shape; tive to penicillin and / or sulpha drugs considerable suc- and once it had taken shape he did not cease to labour at cess has been reported ranging up to 100% elimination of all the many details of B. proteus and B. pyocyaneus. In tuberculous meningitis organization which make or mar great promise has been shown, though residual nervous or a meeting of this kind. It, is to be hoped that the time will hydrocephalic lesions often remain, and all strains of not be long before we in this country will be able to make Mycobacterium tuberculosis seem sensitive in some degree. a fitting return by entertaining Swiss doctors on British soil. In pulmonary tubd,ulosis, for which.probably the minimal effective trial period may be 5 years, Dr. Corwin Hinshaw (Mayo Clinic) and Dr. Walsh MacDermott (New York) report considerable therapeutic possibilities with strepto- STREPTOMYCIN mycin in extension of Dr. Feldman's Mayo Clinic demon- Antibiotics' are substances elaborated by micro-organisms stration of its value in experiinental guinea-pig infections. which act as antibacterial or antifungal agents. It is (Penicillin will, of course, tend to repel some of the secon- attractive to postulate that these substances are formed by dary bacterial invaders in the tuberculous pulmonary their producers as a defence mechanism. They have often lesion.) Treatment is a great trial to the tuberculous a very marked, specific, antibacterial effect against impor- patient, because it involves at present some six daily injec- tant human pathogens. tions of the equivalent of about 600 mg. of the pure base, Penicillin,2 3 which is a wholly British discovery, is the over perhaps six months. Cost has to be considered, with most successful antibiotic so far exploited therapeutically, the present price of the substance at about $15'a gramme but there remain many organisms pathogenic to man which and the lowest likely price in full production falling to $5 are insensitive to penicillin and the sulpha drugs, or demand a gramme, but if this is weighed against the long sanatorium for effective control of the infection doses so large as to be treatment and even longer subsidy for the patient and his toxic to the host. It is customary to reserve the term anti- dependants it is hardly significant. Dosage is to be cal- biotic for a substance of natural origin and to exclude from culated by dry weight of base, equilibrated against the this designation synthetic antibacterial substances such as standard powder of 1,000 units per mg. potency, but this the sulpha drugs. Gramicidin4 is an antibiotic finding introduces the slight complication that the soluble salts increasing favour in surface wound dressings, but strepto- (hydrochloride 842 units, sulphate 798 units per mg.) have mycin,5 an American discovery, is showing great thera- a lower unitage than the' base. Plague and leprosy are peutic promise in combating Gram-negative bacilli and other diseases in which the effect of streptomycin is being Mycobacterium tuberculosis. Penicillin is a purified meta- investigated. Streptomycin, though rather more costly than bolite of the aerobic culture of the green micro-fungus penicillin, is more stable in aqueous solution and dry form, Penicillium notatum (Westling's original culture was made and it can be heat sterilized. Being relatively stable from the decaying herb hyssop from Norway), and strepto- at acid pH levels it would survive passage through the mycin can be somewhat similarly made by filtration of the stomach, but it has so far not been possible to give effec- product of aerobic culture of the ray fungus, originally tive treatment by mouth (a very desirable route) because isolated from soil, Actinomyces (Streptomyces) griseus adequate concentrations cannot be maintained in the blood, (not to be confused with either the human disease actino- probably owing to simultaneous excretion and absorption mycosis or with streptococci). It was found, by its isolator from the gut. Waksman's collaborators,6 to have a wide and intense It is important to stress that a complete and final opinion potency in animals, and after a very few months of on the therapeutic value of streptomycin, particularly in scattered American biochemical effort the pure base and tuberculous infections, cannot be expected yet, and that crystalline salts were- prepared. It is thought significant streptomycin is unlikely to be available either in America that penicillin-an acidic substance-should have maximal or England for use outside the official trials for some time. action on Gram-positive bacteria and that streptomycin- The unwary philosopher may ask himself whether, with a base-should have maximal action on the Gram-negative streptomycin complementary to penicillin, there will be series. any pathogenic bacteria for human beings to die of in the The pharmacological development of streptomycin in Brave New World. America is proving very like that of penicillin in England, and, as the first few clinical observations with crude con- centrates showed such promise, the American Streptomycin CIVILIAN DEATHS FROM AIR BOMBARDMENT Clinical Trials Committee, under the chairmanship of The Statistical Bulletin of the Metropolitan Life Insurance Dr. Chester Keefer (Harvard), has been set up to control Company for July, 1946, contains a useful article, under location and method of clinical trials and to assess results the above heading, which summarizes the available data. before the general release of the substance. The Com- British civilian loss of life amounted to something over mittee buy the entire output (some 35 kg. a month in 60,000 deaths, more than two-thirds in the first " blitz" May, 1946) of the ten firms who have subscribed $500,000 between August, 1940, and June, 1941. French losses were to the Committee for this purchase. Similar controlled almost as heavy, nearly 54,000, more than two-thirds of clinical trials are about to start in England under the aegis them in 1944. In proportion to population the Netherlands I Oxford, A. E., " Antibiotics," Annual Review Biochemistry, 1945, 14, 749. suffered more than any other ally; 30,000 are estimated to 2 Fleming, A., Brit. J. exp. Path., 1929, 10, 226. 3 Florey, H. W., et al., Lancet, 1940, 2, 226. have perished in the dastardly raid on Rotterdam. No 4 Dubos, R. J., J. exp. Med., 1939, 70, 1. figures seem to have been available with respect to Russia 5 Waksman, S. A., et al., Proc. Soc. exp. Biol., 1944, 55, 66. 6 Waksman, S. A., et al., Science, 1944, 100, 103.. and Poland; Norway lost 1,000 lives. The Axis Powers BRITISH SEPT. 28, 1946 ~ DR. OLIN WEST MEDICAL JOURNAL 467 paid heavily for their choice. The United States Strategic infectious disease from mattresses filled with dirty rag flock, Bombing Survey estimates German losses at over half a but the risk may be assumed to exist. In any case it is un- million, and Japanese losses as between 360,000 and desirable that anyone should have to sleep on unclean 375,000; the two atomic bombs are thought to have killed bedding. There is also a risk to the health of the about one-third of this total, 105,000 to 120,000; but the workers who handle the flock, apart from the presence most destructive single raid is thought to have been that on of vermin in it. Tokyo on March 9, 1945-the estimate is 85,000. These An attempt to control this material was made in the Rag are statistics of deaths alone. In time a medical and statis- Flock Act, 1911; the Rag Flock Amendment Act, 1928; tical study of all the effects of air raids, mental as well and the Public Health (London) Act, 1936 (Section 136); as corporal, will no doubt be made. The psychological but an inadequate definition of rag flock and too small effects have been, perhaps, less serious than was expected penalties for contravention of the law have defeated the before the attacks began, but a comprehensive study intention of these Acts. An Interdepartmental Committee requires leisure. was therefore set up in 1938 to make recommendations to ensure proper cleanliness of rag flock used for the manu- facture of upholstery, bedding, and other household furni- DR. OLIN WEST ture in Great Britain. Its report and recommendations are The centenary session of the American Medical Associa- now published.' These include the registration of all tion will be held in Atlantic City in June next year. Already premises used for the manufacture of rag flock and inspec- plans are afoot to make it " the greatest medical assem- tion by local authorities. It is further suggested that it blage that the world has ever known." At its annual meet- would be wise to apply these regulations to premises in ing, which took place this year at San Francisco, the House which any kind of filling material is used.