326
JOURNAL OF CHEMICAL EDUCATION LITERATURE CITED
(1) (2) (3)
BEILSTEIN, "Handbuch der organischel1 Chemie," 4th ed. J. Springer, Berlin, 1920, Vol. 2, p. 167. BERTHELOT, Ann. chim. phys., (6), 7, 410-26 (1886). BICHQWSKY AND ROSSINI. "Thermochemistry of chemical substances," Reinhold Publishing Company, New York, 1936.
(4) (5)
(6) (7)
BOUZAT, Ann. chim. phys., (7), 29, 305-83 (1903). "Handbook of chemistry and physics," 21st ed., Chemical Rubber Publishing Company, Cleveland, Ohio, 1936. "International critical tables," McGraw-Hill Publishing Company, New York, 1929, Vol. V. VARET, Ann. chim. phys.• (7),8,79-141 (1896).
Penicillin PENICILLIN, the latest of the "wonder drugs" to attain popular notice, is as yet more of a problem than a solution. Although clinical tests of penicillin and other therapeutic substances of microbial origin are still far from complete, it is apparent now that penicillin is particularly useful against many infections previously resistant to treatment and appears to be non-toxic. The problem, one for the microbiologist and the chemist rather than the physician, lies in producing the penicillin and preventing its deterioration. There are recent indications that both of these may be solved in the not too distant future. The existence of penicillin, which is produced by a common mold, Penicillium notatum, was first noted accidently in England in 1929, when the mold contaminated some culture plates during a search for an influenza-causing organism and was observed to inhibit the growth of some other organisms. Broth cultures of the mold were found to contain an antibacterial substance, later named penicillin, but even yet not isolated or chemically identified. The first discovery was not followed up at the time, but in recent years there has been a recrudescence of interest in penicillin, as well as investigations of other antibacterial substances produced by molds and bacteria. Some of these other substances have proved promising including one called gramicidin, now produced at low cost and used in veterinary medicine, but most have had disadvantages such as toxicity and insolubility. At present penicillin still appears the most valuable of these substances. A great virtue of penicillin is its lack of toxicity as compared with the sulfonamides, which often cause reactions. In addition penicillin has been found highly effective against the pus-causing bacteria, which commonly inhabit the surface of the skin and against which the sulfonamide drugs are only moderately effective. These organisms are responsible for many minor infections, such as pimples and boils, but are also one of the most frequent sources of serious infection in wounds and burns. Staphylococcus infection has been a major cause of death and invalidism in previous wars and also is a frequent cause of the bone infection, osteomyelitis. Recently several cases of staphylococcus infection of the blood where the sulfonamides had failed and a fatal outcome seemed probable were rapic11y cleared up by penicillin. Penicillin is also effective against streptococcus, pneumococcus, and some other organisms, but here the need for a new drug
is less because of the efficacy of the sulfonamides which are now available. Although penicillin is effective in extremely high dilution in preventing the development of many disease-producing organisms, it produces no injurious effect on other living cells: Penicillin shares with the sulfonamide drugs an advantage over such commonly used antiseptics as iodine, silver nitrate, and bichloride of mercury in that when applied locally it is not fixed at the surface of the wound and may penetrate to the actual sites of bacterial multiplication. Penicillin may also be injected into the blood stream or beneath the skin, as well as used locally on wounds, without injuring the normal processes of the body or preventing the growth of new cells, which is necessary in the repair of wounds and burns. The sulfonamide drugs are inhibited in their action by the presence of pus, which is formed by staphylococci, but penicillin is apparently unaffected by pus or any body fluid. Because of these highly desirable properties, there has been great clinical interest in penicillin and doctors would be glad to try it in a large number of cases. Its production from mold, however, is a difficult and space-consuming operation. Large areas of mold must be cultivated and tremendous quantities of exceedingly dilute penicillin-containing culture fluid have to be extracted. The yield varies most unpredictably with slight changes or even with no detectable change in the nature of the culture medium. Until recently, there has not been enough penicillin even for limited clinical tests, but a newly developed process has made it available in larger quantities. Research recently reported in Science indicates that reacting some common alcohols with the most unstable portion of the penicillin molecule produces a more stable compound. This modified penicillin is only weakly antibacterial in the test tube; but so far seems comparable to penicillin in activity in a living organism. Eventually complete synthesis of penicillin may be possible, but this will have to await further knowledge of its molcular structure. This bas been the object of intensive research for several years and now may be near realization. A recent article in the British Journal of Experimental Pathology indicates that penicillin may be a complex member of the very large aromatic, or coal-tar, group of compounds. It is PQssible that penicillin may eventually be synthesized from coal-tar-derived compounds.
-Industrial Bulletin of Arthur D. Little, Inc.
