thesis of growth-promoting Β vitamins in the intestinal tract. Obviously, the complete answer is still forthcoming. A n i m a l G r o w t h Promotion Yields Extra Farm Profits
The broiler on the left, which did not receive Aureomycin, has had its growth stunted by disease, while the one on the right, exposed to the same conditions but receiving a feed containing Aureomycin, is a healthy, well developed bird. Antibiotic-fed chickens grow 10 to 15% faster on 10% less food per pound of weight gain during a given period
For Antibiotics, Uses Galore In the nonpharmaceutical field, antibiotics offer immense possibilities in the growing of plants and animals COME
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•^ growing so rapidly these days that even people most glowingly optimistic from the start are still rubbing their eyes in utter disbelief. Especially im pressive has been the field of anti biotics. Although these products were virtually unknown 15 years ago, sales in 1953 reached 1,470,000 p o u n d s - a jump of 39% since 1951. However striking may be the record for antibiotics in general, the real tor rent of activity is in the applications for antibiotics outside of human medi cine, particularly in animal growth stimulation. Sales of antibiotics for animal feed supplements in 1953 hit 391,000 pounds—a 100% increase since 1951. Last year, sales of antibiotics for animal feeds (on a poundage basis, 27% of total antibiotic sales) were valued at a sizable $19.4 million. Actually, nonpharmaceutical or in dustrial uses for antibiotics in many areas (plant disease control, food pres ervation, industrial fermentation) are just on the threshold of development. To date over 3500 different antibiotic materials have been isolated and in vestigated. Although most of these 4640
are of no practical value because of low potency or high toxicity, there's no telling what antibiotic may eventu ally emerge as the preferred product in a leading industrial application. For the present, however, the antibiotics most widely used nonpharmaceutically are also those most widely employed in human medicine: penicillin, streptomy cin, Aureomycin, Terramycin, and bacitracin. Far and away the biggest single non pharmaceutical use for antibiotics is in the promotion of animal growth, an application that some experts regard as one of this century's most significant advances in animal nutrition. How antibiotics stimulate growth is one of those questions that will con tinue to intrigue scientists for years to come. Most widely accepted theory is that antibiotics reduce the level of growth-stunting subclinical disease present in almost all animals. Some researchers suggest that antibiotics stimulate growth by destroying micro organisms that consume part of the animal's food supply or that impede the internal absorption of nutrients. Others find that antibiotics accelerate the syn
Tests show that antibiotic-fed chick ens grow 10 to 15% faster. Partly because the animals are healthier and are thus able to use their food more efficiently, feed consumption is cut by 10%. At the same time, mor tality rates are reduced appreciably. In poultry feeds, the preferred anti biotics are penicillin, Aureomycin, and Terramycin. Although penicillin is ac tive against fewer different types of microorganisms than Aureomycin, Ter ramycin, and other broad-spectrum an tibiotics, it is the most widely used antibiotic in the feeding of chickens, mainly because of its high specific effectiveness and low cost. Today, vir tually all broiler chickens are fed anti biotic rations. In the U. S., almost all turkeys are now receiving antibiotics, mainly penicillin and Aureomycin. Here, the effect is even more pro nounced than with chickens, probably because turkeys are more susceptible to disease. Antibiotic-fed turkeys are 15 to 2 0 % heavier at the customary market age. In addition, early mor tality is cut from the usual 25% to less than 10%. Another major use for antibiotics is in swine feeding. Most widely used products are Aureomycin, Terramycin, and penicillin, which give a growth kick of about 10 to 20%, most notice able in younger animals. At the same time, about 5 to 10% less feed is re quired per pound of weight gain', and the animals are far less susceptible to enteritis and other major swine dis eases. Today, an estimated 60% of all pigs in the U. S. receive antibiotic feeds; in the Midwest, the figure is about 90%. Less widespread is the use of anti biotic feeds in the diets of ruminants. Actually dairy and beef calves that have not begun to ruminate respond to antibiotics in much the same way as do nonruminants. Growth improvement in dairy calves during the first four months is about 10 to 25%. Control animals, on the other hand, eventually reach the same weight. Chief advan tage of antibiotics is their ability to minimize illness and death among young animals. Currently, about 4 0 % of all dairy calves are receiving anti biotics, primarily Aureomycin and Terramycin. Significant Increases M a d e I n A v e r a g e Dosage Levels
In animal growth stimulation, a fore most development today is the feeding
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of higher dosages of antibiotics. Although the conventional level was previously about 2 to 10 grams of antibiotic per ton of feed, the trend now is in the direction of 5 0 grams or more per ton. This high-level feeding results not only in the desired growth stimulation, but also in a lower incidence of clinical disease. How far this trend will go is anybody's guess, although, at dosage levels of about 100 grams per ton, a farmer has done just about all he can do in growth stimulation with antibiotics. For people concerned about whether the feeding of antibiotics to animals means that humans are being gratuitously drugged at the dinner table, researchers have an answer. They say that, even by use of the most sensitive analytical techniques available, no antibiotic can be detected in the meat of animals fed growth stimulation levels of these compounds. Growth responses with antibiotics are possible in a great many different animals—cats, dogs, horses, rabbits, hamsters, chinchillas, mink, pheasants, and even tropical fish. Some feed manufacturers are already adding antibiotics to their dry dog foods. Insects aren't being ignored either. Abbott Labs finds that when bees are fed its antibiotic, fumagillin, honey production is boosted by more than 25%. Investigators at the Institute of Science in Bangalore, India, report that when silkworms are fed diets containing Aureomycin plus amino acids they turn out 8 to 14% more silk. In the prevention and cure of specific animal diseases, antibiotics continue to play a vital role. They're widely used against chronic respiratory disease in chickens, sinusitis in turkeys, scours in calves. Infectious enteritis, which causes more losses than all other swine diseases combined, can he sharply reduced if not completely eliminated by antibiotics. At therapeutic dosages, animal feeds ordinarily contain about 200 grams of antibiotic per ton, which is appreciably above the growth stimulation level. Apart from their use in feeds, antibiotics may also be administered orally (via drinking water, for example) or by injection.
experimental use on 100,000 fruit trees. Substantial quantities of streptomycin have been distributed by Merck, Squibb, and other companies for extensive agricultural testing throughout the nation. Tests have been under w a y on the use of antibiotics in the control of bacterial spot of tomatoes and p e p pers, blight of walnuts, soft rot of potatoes. A key advantage of some antibiotics is their ability to act systemically. Conventional pesticides (with a few notable exceptions) merely coat the plant and thus have no effect on disease organisms inside. On the other hand, some of today's leading antibiotics, once they're absorbed by the plant, are diffused throughout the plant interior, where they cannot be washed away by rain. This opens the possibility that fruit growers, instead of rushing out with spray equipment after every rainstorm, may, in the future, b e able to control specific plant diseases far more effectively by the use of regular, well timed schedules of antibiotic treatments. Among the antibiotics offering greatest promise in plant disease control today is streptomycin, sometimes used with Terramycin in an effort to minimize the growth of resistant bacteria. Other antibiotics have also been tested on plants, with varying degrees of success—not only conventional antibiotics such as Aureomycin and penicillin, but also such less familiar ones as actidione, griseofulvin, helixin, thiolutin, and viridin. In the future, antibiotics may find one of their biggest outlets in orchards
jplagued with fireblight of apple, pear, o r p&ach trees. So destructive is fireblight that, except in some northern areas of the U . S., it is virtually impossible to grow Bartlett pears commercially east of the Rockies. Availability of antibiotic sprays may extend tzremeradously the pear-growing areas of fcheTJ. S. Until very recently, use of streptomycin or streptomycin-Terramycin sprays to control fireblight was considered a perfectly splendid idea, but much too costly—compared to the cost o f copper-lime dust, Bordeaux mixture, o r other chemical treatments. However, latest tests by John C . Dunegan o f the Department of Agriculture, Peter A . AJ1C of t h e University of California, and others demonstrate that, when concentrations of antibiotic much lower than those previously tested are txsed, higHly effective control is achieved at a cost that is n o w economically attractive. Antifungal Agent Effective Against Cherry Leaf Spot The only commercial antibiotic d e v e l o p e d exclusively for plant disease Cîontrol is Upjohn s actidione, which is also t h e only commercial antibiotic with auntifuriigal properties. (Pfizer's thiohutin i s antifungal, but is still experinoental.) Actidione is used primarily sts a postharvest spray against cherry leaf s p o t and a s a n antifungal agent o>n golf course turf. Partly because of ifcs higlh toxicity ( a modest overdose iriay severely injure the p l a n t ) , actid-ione> Bias found only limited application t o date·
A water spray containing a combination of streptomycin and Terramycin is applied to fruit trees. Department of Agriculture scientists report that the spray can be used successfully to control fireblight, a century-old x>1ague> of orchards—particularly on pears
Large-Scale Tests Under W a y In Control of Plant Diseases Focus of a vast amount of research effort these days is the use of antibiotics in plant disease control. In quite a few such applications, antibiotics received their first large-scale trials this year. As part of its mass orchard testing program, Pfizer early this year distributed enough Agri-Mycin (a mixture of streptomycin and Terramycin) for VOLUME
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In the growing of beans for seed, so great is the hazard of bacterial diseases that this crop is only produced commercially in the U. S. in blight-free areas of Idaho and California. Bean growers are pinning high hopes on antibiotics. John W. Mitchell and William J. Zaumeyer of the Department of Agriculture have demonstrated that halo blight of beans can be successfully controlled with sprays of streptomycin sulfate or dihvdrostreptomycin sulfate. Research on the control of common blight is still in progress. Antibiotics are also being explored for possible use in protecting seeds against disease microorganisms in the soil or in the seed itself. Thiolutin has recently been shown to be effective on oat grains. Much research in this field is also being done with streptomycin, which one day may find widespread use in warding off diseases of pea, tomato, cucumber, barley, and cotton seeds. Of special importance to flower growers is the recent discovery of the effectiveness of streptomycin in controlling bacterial wilt of chrysanthemums—the first successful application of antibiotics to the growing of ornamentals. As reported by Robert S. Robison and coworkers at the N e w Jersey Agricultural Experiment Station, control is achieved by soaking the ends of chrysanthemum cuttings in a dilute aqueous solution of streptomycin. Since cuttings of this type are supplied by a relatively few growers in the U. S., their adoption of this technique could have a far-flung effect on the control of chrysanthemum bacterial wilt. Antibiotic Use in Food Preservation Awaits Official G o v e r n m e n t Sanction
A field bustling with activity these days is the preservation of foods with antibiotics. Addition of even trace quantities of these drugs might have a phenomenal effect in curbing food deterioration. It must be emphasized, however, that antibiotics are not now being used in foods. In February last year, the Department of Health, Education, and Welfare stated that antibiotics in foods for human use "may be deemed an adulteration" and thus may b e illegal. The official statement further declared that antibiotics used as food preservatives constitute a "public health hazard." In the first place, they might cause some people to become acutely sensitive to these drugs. Furthermore, they might promote the emergence of resistant strains of disease-causing microorganisms and thus destroy the effectiveness of antibiotics in human medicine. In March this year, a top spokesman for the Food and Drug Administration issued a policy-making report indicat4642
ing that the Government's views are changing. Nowhere in this report are antibiotics flatly denounced as public health hazards. On the contrary, it states that the official position might b e revised if "evidence shows that the use of these drugs as preservatives in a given food is safe and is essential to the production of the food." H o w far the Government will go in allowing antibiotics to be used in foods is a hotly controversial issue right at the moment. Of course, in an area as vital as the safeguarding of public health, the Government must proceed with extreme caution. One possibility, however, is that the Government may allow antibiotics to be used where it can be clearly demonstrated that the antibiotic is not present in the food when it reaches the consumer, or where the antibiotic is destroyed in cooking. Meanwhile, research on the use of antibiotics in food preservation moves rapidly ahead. Antibiotics, which as far back as 1946 were being investigated for use in the preservation of milk, are today being suggested as preservatives of everything from cream puffs and shrimp to cheese and eviscerated chickens. Especially promising is the use of antibiotics in the preservation of fish. H. L. A. Tarr and coworkers at Canada's Pacific Fisheries Experimental Station, after testing 15 different antibiotics, find that the most effective in fish preservation is Aureomycin, used either as an aqueous dip or incorporated into flaked ice. When fish is packed in ice containing merely 1 to 4 p.p.m. of Aureomycin, spoilage is significantly reduced at a cost of less than 0.1 cent per pound of fish. The Streptomycin has been used successfully to control bacterial wilt in chrysanthemums at New Jersey Agricultural Experiment Station by Robert S. Robison and coworkers. Here Robison assays streptomycin activity in chrysanthemum tissue
fish itself picks up only a negligible amount of antibiotic. I n fact, a person would have t o eat a staggering 5 to 10 tons of cooked, antibiotic-treated fish before he would consume the equivalent of one daily therapeutic dose. Antibiotics such as Aureomycin and Terramycin might also g o a long way in preserving meat. Pioneering work in this field has been done by Fred E. Deatherage and coworkers at Ohio State University, who find that injection of Aureomycin into whole carcasses of beef greatly retards spoilage even in the absence of refrigeration. Chickens and ground beef can likewise be preserved b y treatment with antibiotics, which not only maintain the freshness of the meat but also increase its tenderness. An important future use for antibiotics may be in the preservation of vegetables. USDA's Wilson L. Smith, Jr., finds that sprays or dips of 0.1% aqueous streptomycin sulfate, by retarding the action of soft-rot bacteria, can add at least two days to the shelf life of fresh spinach. H e also reports that packaged, unrefrigerated cole slaw, which darkens appreciably in one day, remains salable for at least three days when treated with 0.1% streptomycin sulfate. Antibiotics Find Tough Sledding In Suggested Use i n Food Canning
Back in 1949, reports from USDA's Western Regional Research Laboratory that antibiotics might b e just the answer to some of the toughest unsolved problems of the canning industry touched off a splurge of headlines. For years, canners have been seeking ways of reducing temperatures and time cycles in their food sterilization operations. Lower temperatures would mean less degradation of foods and the possibility that some foods, such as cauliflower and Brussels sprouts, could at last be commercially canned. After studying a variety of antibiotics, WRRL researchers found that subtilin was by far the most promising. Because of its high activity against heat-resistant bacteria, subtilin appeared to be the open-sesame to sterilization at mild temperatures. Subsequent work, however, has shown that, since subtilin cannot b e counted on to destroy all the bacteria, it's a case of close-but-no-cigar. The requirements of die canning industry are unusually rigorous. If only one spore of a dangerous organism survives, a can of food may puff up like a football in a matter of hours, and the contents may be lethal. Demand for 100% bacterial kill is so severe that (Continued
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One of the few areas in which anti ^womotf^r^iisTrUAi _^^^^^M biotics are actually being used i n in dustry is in the production of beer, whiskey, and edible and baker's yeast. ^^^^^f^RRBRRVl^RV*\2j^^MÉi^^^B^^^^^^^l Such antibiotics as polymyxin, Aureomycin, and Terramycin are finding widespread use in fermentation opera tions to prevent the growth of un wanted bacteria, particularly those that cause off-flavors b y producing lactic acid. By suppressing bacterial action, antibiotics also accelerate the conver sion of starches to alcohol and, a t the same time, increase yields. r—WELLS L A B O R A T O R I E S , I N C . — Λ Over the years, chemists have sought 28 Concourt· East, Journal Square vigorously to develop numerous other Jersey City 6# Now Jersey industrial applications for antibiotics. Telephones » £ « o M S S w 2-1907 CONSULTANTS · RESEARCH · TESTING Studies have been made of the use of MICROMOUMICAL: Industrial, Food, Medical, Pobllc Health. Biological deterioration investigations and antibiotics to prevent mildew of rope, preservation specialists. cloth, and electrical insulation, to sup BIOCHEMISTRY. ANALYTICAL AND ORGANIC CHEMISTRY. Toxicity· pathology, physiology. Human ana press scum formation in paper mills animal testing facilities. Operate Test Beauty Shop. and tanneries, to retard mold growth in floor waxes, to prevent marine foul MASS SPECTROMETER ing with antibiotic paints. Over ANAlYTICAl I Complex Mixtures whelming evidence to date, however, LABORATORY I Isotope Assays is that, in these applications, anti SERVICE I Leak Detection biotics cannot as yet begin to compete Consolidated Engineering economically with the inorganic or or CORPORATION ganic compounds already available. 100 NO. SIERRA MADRE VILLA. PASADENA 15, CAUP. There's no telling, of course, how this picture might change as the price of antibiotics declines or perhaps as lowcost synergists are developed that per mit the same job to be done with much I ^^^H ^^HL^I A S S O C I A T E S less antibiotic. • P J^I^^VV CONSULTANTS Β^^Φβ'Γ INDUSTRIES In the broad field of nonpharma H y . " / ' : ' ^ ^ J . ' ^ E A New Products and Processes ceutical uses for antibiotics, a host of R4 r -^>rÇ^^^^ ^fl C o m p l e t e T e c h n i c a l a n d unsolved problems still remain. Are \^^^2jf^f^^\^^^M n o m iAve c S eN rvices. 27E c opqrk l^S^^S^a^HB ° - -Y- 17 the advantages possible with antibiotics ||BEKÉat3grJtdMEBEML ELdorado 5-1430 | actually worth the cost? Can anti biotics b e used with complete safety SCHWARZKOPF to humans, animals, and plants? Will MICROANALYTICAL LABORATORY Routine Analysis Within One Week antibiotics in agriculture, perhaps by Microdetermination of Carbon-hydrogen, upsetting nature's balance, create more Oxygen, Nitrogen, Halogens, Sulfur, problems than they solve? Can alto Phosphorus. Alkoxyl, Acetyl, Amino, gether new antibiotics be developed Molecular weight and Other Analyses. 56-19 37th Ave., Woodside 77, L. Ι., Ν . Υ. that are uniquely effective i n special Telephone: HAvemoycr 9-6248 nonpharmaceutical applications? Are resistant bacterial strains likely to de s i N c r j 8 7Q Food Ingredient & New Drug Studies velop that in a few years will make existing antibiotics totally useless? Researchers aren't intimidated by questions such as these. They're busily seeking answers—answers that could profoundly affect the lives of millions in this Antibiotic Age.
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