SEARCH FOR ANTIBIOTICS: SCRP:ENIXC; PROCRAMS 



27 



agents, Chain (1!).")8) made the following 

 comment: "In the absence of any line of 

 rational approach to the problem of tumour 

 therapy, any new substance with any sort 

 of biological activity is tested by someone 

 with iTgard to its possible inhibitory effect 

 on tumours; there is no prima facie scientific 

 case at all why antibiotics in particular could 

 be expected to act against tumours. Bac- 

 terial infections and malignant tumours ha\'e 

 nothing in common except that in some very 

 superficial resemblance phenomena of growth 

 are involved in both diseases." 



Antiviral and Antiphagc Surreus 



In a recent review of antibiotics, Al)ra- 

 ham (1959), one of the pioneers in the field, 

 stated: "In some laboratories they [screen- 

 ing programs] also aimed at the discovery of 

 substances that will selectively inhibit the 

 growth of tumor cells or viruses, though 

 there is so far little evidence to indicate that 

 they will have much success in this field." 



In a summary of an early sur\'ey dealing 

 with the problem of antiviral agents, Jones 

 and associates (194.")) reported that they 

 tested loO organisms, comprising bacteria, 

 fungi, and actinomycetes, isolated from 

 composts, manures, soils, drainage ma- 

 terial, as well as from soil enriched with 

 A'irus concentrates, for their ability to in- 

 activate viruses. Only three of these or- 

 ganisms gave any indication of possible 

 inactivation of fowl ])ox \irus, and in one 

 case, of the laryngotracheitis virus. An ac- 

 tive principle was isolated from a culture of 

 one of these organisms; the substance pro\XKl 

 to be actinomycin. The other two virus- 

 inactivating organisms were less extensively 

 studied. 



A number of substances capable of modify- 

 ing or controlling viral infections have been 

 described in recent years. A l)eneficial effect 

 was found to be exerted on pre\-iously in- 

 fected hosts, such as chick embryos. These 

 compounds included certain bacterial poly- 

 saccharides, hexamidine, pectin, tannic acid, 



tea extracts, crude penicillin, and viscosin. A 

 preparation obtained from a strain of 

 Streptomyces lavendulae and designated as 

 ehrlichin also had an injurious effect upon 

 influenza virus (Groupe et ai, ]9ol ). 



Unfortunately, none of the above ob- 

 servations, or others of a similar nature, led 

 to any practical developments as potential 

 therapeutic agents in viral diseases. Actino- 

 mycin recei\'ed no further consideration be- 

 cause of its highly toxic effect upon animals. 

 Different investigators, constrained by the 

 difficulties involved in the use of animal and 

 plant viruses for this type of investigation, 

 devoted their attention to the bacterial 

 \-iruses or l)acteriophages (Schatz and Jones, 

 1947; Asheshov et a!., 1949, 1952; Hamada, 

 1957; Smejkal, 1960), on the assumption that 

 if one were successful in obtaining antiphage 

 agents, he would be dealing with mechanisms 

 similar to those that might be destructive to 

 the ultramicroscopic intracellular agents 

 affecting higher forms of life. Several prep- 

 arations were actually found to be effective 

 against phages, l)ut they were totally in- 

 active for animal viruses. 



In an effort to find drugs that would 

 possess antix'iral properties, Dickinson (1953) 

 suggested the following po.'^sibilities: (1) 

 direct inactivation of the extracellular virus; 

 (2) prevention of adsorption of virus on the 

 cell or of its penetration into the cell; (3) 

 inhibition of multiplication of intracellular 

 virus; (4) prevention of release of the virus 

 from infected host cells. 



Hermann and Rosselet (19()()) proposed a 

 procedure bv which paper chromatograms 

 of antiviral agents are de^'eloped by apply- 

 ing them to virus-infected, agar-overlay, 

 chick embryo cell tissue cultures. The 

 plaque-free zones produced indicate the 

 location of the active material on the paper 

 chromatogram. The biological activity of 

 several antiviral agents could thus be 

 demonstrated. As little as 1 jug of an anti- 

 biotic (W 122) produced large placiue-free 

 zones when a paper chromatogram was ap- 



