The Role of Antibiotics in Nature

PERSPECTIVES IN BIOLOGY AND MEDICINE Volume IV · Number 3 · Spring 1961 THE ROLE OF ANTIBIOTICS IN NATURE SELMAN A. WAKSMAN, Ph.D. * It has long been recognized that natural substrates harbor two kinds of microbes:1 (a) those that are pathogenic, capable of causing diseases in man, animals, and plants, and have to be constantly combated for man to survive; these represent one of the major problems of the human race; (b) those that are saprophytic, non-injurious or even beneficial to man; these are the universal scavengers; they are necessary for the growth of our crops and for a number ofother essential processes. It has also been known for a long time that some of the saprophytic microbes can interfere with the growth ofpathogenic and other microbes; that some can form chemical substances, or antibiotics, that suppress the growth ofpathogenicmicrobes, comprising bacteria, protozoa, andfungi. Thisknowledge remaineduntilveryrecentlymore in the realm ofscientific curiosity than of practical application, although attempts were made at various times to utilize this property for the practical control ofinfectious diseases. The extensive study and utilization of antibiotics in recent years have greatly broadened our understanding of certain living processes, have added vast wealth to our economy, and have almost eliminated fatal consequences of bacterial diseases. The actual producers of these antibiotics, the lowly microbes, frequently considered to be only germs capable of * Institute ofMicrobiology, Rutgers, The State University, New Brunswick, NewJersey. 1 The term "microbe" will be used here in preference to the more generally accepted but cumbersome designations "microorganism" or "microscopic form of life." 27I causing diseases and epidemics, have yielded a great body of knowledge for a better understanding ofcertain natural reactions, for control ofthe activities of injurious microbes, and for improvement of the health of man and animals never before dreamed of. I.Microbes That Produce Antibiotics Microbes capable ofproducing antibiotics are universally distributed— in the air we breathe, in the water we drink, in sewage-disposal systems, and in composts ofplant and animal residues, but mainly in the soil under our feet. Antibiotic-producing organisms are found in practically every group ofmicrobes, but antibiotics are produced primarily by representative forms found among the bacteria, actinomycetes, and fungi. Even within these three groups ofmicrobes, this capacity is largely limited to certain genera, notably Bacillus among the bacteria, Streptomyces amongthe actinomycetes, and Pénicillium and Aspergillus among the fungi. Since the isolation ofpenicillin, and the demonstration ofits great chemotherapeutic properties by Chain et al. in 1940 (1), the most important antibiotics have so far been obtained from various species ofStreptomyces. Beginning with actinomycin in 1940, streptomycin in 1943, then later chloramphenicol, the tetracyclines, neomycin, erythromycin, and various others, this group has yielded some ofthe most important antibiotics now in practical use. Even among these genera, the antibiotic-producing property is characteristic mainly ofcertain species, such as Bacillus subtilis, B. mycoides, and B. brevis; Streptomycesgriseus, S. aureofaciens, S.fradii, S. rimosus, S. erythreus , and certain others in the genus; and Pénicillium notatum, P. chrysogenum, P.griseofulvum, Aspergillusfumigatus, A. clavatus, and certain others among the fungi. And there is considerable variation among the various strains ofthese species. Some give only very low and others much greater yields ofthe same antibiotic. High-yielding strains can be selected by examining numerous freshly isolated cultures, or by treatment of desirable cultures with chemical substances, or by radiation to induce highly potent mutants. The fact that many (not all, however) organisms are resistant to the antibiotics that they produce has been utilized in the search for more potent strains. II.Properties ofAntibiotics The antibiotics themselves are characterized by two distinct properties: (a) their formation by microbes and (b) their ability to inhibit the growth 272 Selman A. Waksman · The Role ofAntibiotics in Nature Perspectives in Biology and Medicine · Spring 1961 ofor kill other microbes. Chemical compounds synthesized in the laboratory that possess antimicrobial properties are not antibiotics unless their production by microbes has beendemonstrated. Antibioticsmay be modified chemically to yield derivatives which possess more desirable properties , such as lower toxicity or greater activity. Certain higher plants and animals may form compounds which are antibiotic-like in nature. Quinine , produced by the cinchona tree, is an illustration ofa plant product, and...