Recent evidence in the field of antibiotics does not bear out this distinction. In differentiating between these two terms, the suggestion that the term "antagonism" be applied to the complex unfavorable effects of one living system upon another, when the mechanism involved is not yet clearly understood; and that the term "antibiosis" be used to describe the phenomena of specific selective activities of chemical substances, or antibiotic agents, produced by one organism upon another, appears to have greater justification.

Gradually there evolved the concept of antibiotics, or those agents that are produced by micro-organisms and that have the capacity of inhibiting the growth and destroying bacteria and other micro-organisms. More important yet is the practical application of some of these antibiotics in the control of human and animal infections. The action of antibiotics against bacteria and other micro-organisms, as distinct from the common antiseptics and disinfectants, is selective in nature, that is, the antibiotics act upon some bacteria and not at all, or to only a limited extent, upon other bacteria. Some act readily upon fungi and others do not. Some are readily soluble in water and others are not. Antibiotics also vary greatly in their toxicity to animals. Because of these characteristics, certain antibiotics have remarkable chemotherapeutic Properties and can be used for the control of various bacterial diseases 41 man and in animals.

The most important property of antibiotics is their selective action upon bacteria and other cells of lower and higher forms of life. Because of this, they may be active upon bacteria, without affecting the host cells. Although some 100 antibiotics have now been isolated, only 3 have so far found definite practical application. This small percentage of agents having chemotherapeutic potentialities is due to several factors: Some substances are too toxic to animal tissues; some leave undesirable aftereffects in the animal body; some are inactivated by blood or tissue constituents of the body; some are not very active and are inferior to others that possess greater activity.

The organisms that produce the three important antibiotics, tyrothricin, penicillin, and streptomycin, represent typical soil forms, namely, Bacillus brevis, Penicillium notatum-chrysogenum, and Streptomyces griseus, respectively. Although these organisms may also be found in other substrates, the soil may be considered as their natural habitat.

Tyrothricin is produced by a group of aerobic spore-forming bacteria belonging to the B. brevis group. Although many other soil bacteria, notably strains of the spore formers B. mycoides, B. subtilis and B. mesentericus, as well as various non-spore-formers (Pseudomonas aeruginosa), are also capable of producing antibacterial substances, these differ greatly in their chemical composition, antibacterial action, and in vivo activity. A number of antibiotics have now been isolated from soil bacteria, in addition to tyrothricin. It is sufficient to mention subtilin, simplexin, bacillin, pyocyanase, and pyocyanin. Tyrothricin is the best known. It is a polypeptide, or rather a group of polypeptides, several of which have been crystallized, notably gramicidin, tyrocidine, and gramicidin S. Tyrothricin is not soluble in water, but is soluble in alcohol. It acts largely against gram-positive bacteria, but since it is hemolytic, it can be used only for topical and not for parenteral. administration. It is utilized for the treatment of a variety of infections caused by gram-positive bacteria, such as various streptococci and staphylococci, that cause carbuncles and other skin eruptions, sinus infections, and cattle mastitis.

Penicillin is produced by a large number of fungi belonging to the genera Aspergillus and Penicillium. For manufacturing purposes, however, only certain strains of P. notatum and P. chrysogenum are used. The ability to form penicillin is characteristic of both of these species, although different strains vary greatly as regards the quantitative production and the chemical nature of the penicillin type. These fungi are widely distributed in the soil. In 1916, for example, strains of P. notatum and P. chrysogenum were isolated from a variety of soils collected from New Jersey, Louisiana, Colorado, North Dakota, and Puerto Rico. Penicillin is active only against certain bacteria. The soil contains many organisms capable of destroying penicillin, and it is produced on artificial media only under special conditions of culture. It is highly improbable therefore that penicillin is formed in a natural soil and, even if traces of it are produced, that it is of any significance in the survival of the fungi producing it.

The utilization of specific strains of fungi for the production of penicillin became the high mark of chemotherapy during the Second World War. Many infections caused by various gram-positive and certain gram-negative bacteria were brought under control. It is sufficient to mention the various staphylococcal and streptococcal diseases, the pneumococcal, meningococcal, gonococcal, and clostridia) infections; as well as syphilis, anthrax, actinomycosis, and a variety of others. Penicillin is nontoxic and can be used liberally in the treatment of these and other infections.

Streptomycin is produced by certain strains of an organism known as Streptomyces griseus, belonging to the actinomycetes. As opposed to that of penicillin production, the property of forming streptomycin is characteristic not of the genus Streptomyces, nor of the species of S. griseus, but only of certain strains of this organism. Other species of the genus Streptomyces are also capable of producing antibiotics, but these are markedly different from streptomycin in their physical and chemical properties, antibacterial action, and in vivo activity. The closest antibiotic to streptomycin is streptothricin, produced by S. lavendulae, another soil species. This substance is much more toxic to animals than is streptomycin.

Streptomycin is active against a variety of gram-negative and gram-positive bacteria not affected by penicillin, including Mycobacterium tuberculosis. It is not very toxic to animals and can be administered parenterally for the treatment of a number of infections, including those of the urinary tract, tularemia, pertussis, typhoid, and tuberculosis. It can also be used orally for the elimination of certain bacteria in the digestive system. It is not active against viruses and fungi and has only a limited effect on anaerobic bacteria.

THE AUTHOR

Selman A. Waksman is a microbiologist at the New Jersey Agricultural Experiment Station, New Brunswick, N. J.