Hyperkeratos is 273 in the warmer months, and should graduation from the University of Pennsyl- either be sent to slaughter or treated to vania in ig2§^ he was employed by the destroy the carrier state. Pennsylvania Bureau of Animal Industry. He received the degree of master of science JOHN G. LOTZE is a parasitologist in the from Cornell University in igjj and served Animal Disease and Parasite Research as zoo veterinarian for the Staten Island Branch and has been doing research on Zoological Society for a number of years. protozoan diseases of livestock at the Agri- T. O. ROB Y is a veterinarian in the Ani- cultural Research Center^ Beltsüille, since mal Disease and Parasite Research Branch, igjS. He has conducted investigations par- and is working principally on the comple- ticularly on anaplasmosis of cattle and coc- ment fixation test for anaplasmosis. He has cidiosis of sheep and goats. Dr. Lotze is a degrees form Michigan State University and graduate of Miami University and Ohio Auburn Polytechnic Institute. Before joining State University. the Department of Agriculture in ig^2, Dr. DANIEL W. GATES is a veterinarian in Roby was a practitioner for 2 years, was in the Viral and Rickeitsial Disease Section of the Veterinary Corps of the United States the Animal Disease and Parasite Branch of Army for j years, and worked as a virologist the Agricultural Research Service. Following at I. E. du Pont de Nemours Co. for ^years^

Hyperkeratosis

AUBREY M. LEE

A NEW and strange disease of cattle less than 6 months old. About 50 to 60 was first seen and reported by Dr. percent of older calves died. The mor- Peter Olafson, of the New York State tality in adult cattle was 10 to 35 Veterinary Gollege, in 1941. It was percent. called , or X-disease—• In Texas the disease was diagnosed "X" being a symbol for the unknown in 53 counties by 1950. In Wisconsin and "hyperkeratosis" indicating the in June 1952 we had reports of i ,085 increased amount of , or horny cases among cattle on 268 premises; material, that develops on of the an estimated 10,000 calves died in the neck, shoulders, and withers in chronic winter of 1952. In Illinois 33 herds cases. were affected. Tennessee reported This ailment was reported in 10 more than 3,000 cattle had died or States in 1946. A year later it was had to be slaughtered before 1952 known to exist in 27 States. Officials because of the hyperkeratosis. About of the Department of Agriculture and 20,000 animals were affected in Texas of Southeastern States in 1948 investi- and 5,000 in Oklahoma in the winter gated 26 afifccted herds in 20 counties of 1952-1953- in Alabama, Florida, Georgia, Ten- The disease then had been diagnosed nessee, and Virginia. They found an and reported in 35 States, and in 4 average loss of 4,200 dollars per herd. more States it had been suspected in The disease was causing an esti- a herd or two. No new cases of hyper- mated loss of 2 million to 4 million of cattle were reported to the dollars a year by 1949. Deaths were Department of Agriculture in 1954 or highest—up to 80 percent—in calves 1955—an indication that it had been 360304°—56 19 274 Yearbook of Agriculture 1956 eradicated or reduced to the extent treme lowering of blood plasma vita- that it was no longer important to the min A in hyperkeratosis could predis- livestock industry. pose to secondary bacterial infections, such as abscess formation, and inflam- SYMPTOMS usually start with listless- mations of some of the internal organs. ncss, depression, excessive secretion of The symptoms vary according to the tears, drooling of saliva and a watery amount of the toxic or poisonous sub- discharge from the nose, and loss of stance the animal eats or touches and flesh. A rapid drop in blood plasma the duration of the exposure. The con- A often to very low levels may centration of the toxic substance in the occur. feed or in the compound that the ani- Often there also develops loss of con- mal comes in contact with will also dition, emaciation, a variable appe- cause variations in some symptom-s. tite, intermittent diarrhea, and a dry, Other factors, such as age, individual scurfy skin. Raised areas, or wartlike difl'erences, rations, and the material lesions, often are found on the floor of in which the toxic principle is suspend- the mouth and on the dental pad, hard ed, may determine which symptoms palate, lips, tongue, gums, and the are shown and which form the disease inside of the cheeks. They have been takes. found also on the muzzle,, the margins Research workers applied know^n of the nostrils, and the lining of the hyperkeratosis-producing substances in esophagus. diluted form locally to the skin of cattle. If the animal survives those systemic Little or none of the general systemic efl'ects and does not die from secondary efí'ects were produced, but a typical bacterial infection, pneumonia, or in- definite hyperkeratosis of the skin de- flammation of the intestines, the typi- veloped. The scientists found, however, cal skin hyperkeratosis develops slowly. that the systemic efl'ects developed if Then there develops gradually an ac- the material were fed or given inter- cumulation of hard, kcratinous ma- nally and that the skin hyperkeratosis terial, which makes the skin thick, in- developed from this internal adminis- elastic, and wrinkled. The deep fissures tration, although usually it took 6 and bold folds formed in the skin be- weeks to 2 months or longer. Calves come so hard that they are not reduc- died with the acute—rapid—form of ible by stretching with the hands. The the disease before skin changes ap- skin feels more like a hide than a skin. peared. Hair on the afl'ected skin gets thin or disappears entirely. The sides of the THE INTERNAL changes or lesions in neck, shoulders, and withers are af- the internal organs that are most fected most commonly. Skin on the characteristic of hyperkeratosis are inner surface of the thigh, the udder, swellings on the inside lining of the gall and scrotum, the convex surface of the bladder, gall duct, and the large bile ear,- the dewlap, and the sides also may ducts. Characteristic changes of the be afí'ected. Almost all the skin of the small bile ducts of the liver commonly body and sometimes the skin of the occur. The pancreas, liver, kidneys, legs may be afl'ectcd in extreme chronic and reproductive organs may be af- cases. fected. The intestines, may become in- A few herds, free of brucellosis but flamed, and the inside lining of the severely afí'ected with bovine hyper- fourth, or true, stomach, especially keratosis, have had abortions and still- near the intestinal opening, may have born calves and greatly reduced milk reddened areas, flat erosions, and small secretion. In some experimentally pro- ulcers. duced cases of hyperkeratosis in preg- nant cows, abortion took place and SCIENTISTS in i8 States in 1949-1953 milk flow dropped markedly. The ex- undertook research in a cooperative Hyperkeratosis 275 project with the Department of Agri- ence in Europe in May 1950 learned culture to find the cause of hyperkera- of a disease condition in cattle pro- tosis. They had to start from scratch. duced experimentally at the Han- They had only a few theories to begin nover Veterinary College in Ger- with. many. It seemed to be like the bovine They had to study practically the hyperkeratosis in the United States. whole environment of the affected In Germany the condition had been cattle—soils, plant life, fertilizers, bac- caused by a particular tank carlot of a terial flora of the rumen, livestock commercial wood preservative. Some feeds, viruses. of the v/ood from a barn at Hannover Drs. A. G.Johnson and W. O. Rob- and some of the preservative with inson, of the Department of Agricul- which it had been treated 2 years pre- ture, established that soil, plants, and viously were taken to Cornell Univer- fertilizers were not factors. sity and Pennsylvania State Univer- Dr. W. O. Gibbons, of Alabama sity for study. Polytechnic Institute, did extensive Dr. William Hansel, Dr. Olafson, survey work and proved that DDT did and Dr. Kenneth McEntee, of Cor- not cause the disease. nell University, and Drs. Bortree and Dr. William Sippel, of the Georgia Miller produced hyperkeratosis with Coastal Plain Experiment Station, Dr. both the wood preservative and the Dennis Sikes, of the University of Ten- wood in April 1951. They found the nessee, and Dr. Hubert Schmidt, of disease produced was the same as ex- the Texas Agricultural and Mechani- isted on farms in this country and as cal College, demonstrated that the had been produced experimentally disease was not caused by a virus and with pellets, breadcrumbs, and tim- was not infectious. They also proved othy hay. that road oils and American wood pre- Drs. Olafson, Hansel, and McEntee servatives did not cause it. began studies of the place of vitamin Dr. Carl Olson, Jr., of the University A in hyperkeratosis produced experi- of Nebraska, in 1950 produced hyper- mentally by breadcrumbs and by the keratosis experimentally in cattle with German wood preservative. They a pelleted feed that had been suspected found that the blood plasma vitamin because of being connected with an A was lower than had previously been outbreak. produced experimentally—as low as Dr. Peter Olafson, of Cornell Uni- 3 and 4 micrograms per 100 milli- versity, produced it by feeding a par- liters. Dr. Miller and Dr. P. H. Phil- ticular lot of suspected breadcrumbs lips, of the University of Wisconsin, from the slicers in a commercial bakery later confirmed the finding, which was which were being fed to cattle and of value in studies in nutrition and in found the toxic substance was elimi- the research program to determine if nated in the milk. a suspected causative agent should be Dr. R. C. Miller and Dr. A. L. Bor- studied further. tree, of Pennsylvania State University, Cattle will eat grease from machin- induced the disease by feeding a cer- ery and grease cans. Dr. Wilson B. tain cutting of timothy hay that had Bell, of Virginia Polytechnic Institute, been fed to cattle on a farm where the found in 1951 that a lubricant or disease had caused heavy losses. grease recovered from a farm on which All the experiments were made under the disease had occurred and a similar rigid controls, so there was no question product purchased on the market pro- but that each particular lot of the duced hyperkeratosis. With the co- three products contained something operation and help of the company that caused or brought on the disease. that made it, he fed this serial number Dr. H. W. Schoening, of the De- of grease minus its various chemical partment of Agriculture, at a confer- additives. 276 Yearbook of Agriculture 1956 Soon afterwards he found the item Dr. Bell prepared a good livestock in the grease that made it produce feed. He pelleted one-half of it in a hyperkeratosis was highly chlorinated machine greased with a lubricant that naphthalene. Dr. Sikes, at the Uni- did not contain highly chlorinated versity of Tennessee, at the same time naphthalene. For the other half the was feeding several chemicals used in pellet machine was lubricated with a greases and also found that highly grease that contained 3 percent of chlorinated naphthalene produced hy- highly chlorinated naphthalene. The perkeratosis. pellets made when the machine was N. R. Ellis, R. E. Davis, and Ivan greased with the lubricant that did not Lindahl, of the Department of Agri- contain highly chlorinated naphtha- culture at Beltsville, Md., investigated lene were not toxic to the calves to a feed mill of the kind that is com- which they were fed. The pellets made monly used in this country. The when the machine was lubricated with directions for operating it called for a grease which contained highly chlo- the use of grease every 12 hours of rinated naphthalene produced hyper- operation. The grease lubricated the keratosis in calves. The first pellets bearings of the rollers that force the made following the lubrication were feed against the die plate. The end of highly toxic, but the ones made just the shaft is in contact with loose feed, before lubrication were only slightly and provision is made that the grease toxic. will work out from the bearing in Oil companies and feed manufac- order that feed and dirt will not get turers, warned of the danger, did what into the bearings. The workers con- they could to keep the damaging addi- cluded that the grease used as replace- tive away from livestock and livestock ment every 2 hours went into the feeds. pellets. The men at Cornell University AUBREY M. LEE became head of the started working on the breadcrumbs Noninfectious Diseases Section of the Ani' in an effort to find the chemical as mal Disease and Parasite Research Branchy soon as they proved the breadcrumbs Agricultural Research Service^ in 1952. He would produce hyperkeratosis. The received a degree in veterinary medicine at test itself had to be developed and Kansas State College in 1922 and master of perfected. It required expensive equip- science in iggo at Ohio State University. ment and much time. They developed He joined the Department of Agriculture in a testing method and identified highly igS^. He has served with the Brucellosis chlorinated naphthalene as the con- and Tuberculosis Eradication Division and taminant in the breadcrumbs and also with the Pathological Division, in the German wood preservative. For further reading: They later cooperated and worked Wilson B. Bell: Further Studies on the Produc- closely with several industries con- tion of Bovine Hyperkeratosis by the Administration cerned in the production of pellets of a Lubricant, Virginia Journal of Science that were causing hyperkeratosis in (new series), volume 3, pages 169-177. 1952. Wilson B. Bell: The Relative Toxicity oj the Texas. One large corporation bought Chlorinated Naphthalenes in Experimentally Pro- expensive special equipment and set a duced Bovine Hyperkeratosis (X-Disease), Veter- large staff of chemists to work on the inary Medicine, volume 48, pages 135-140. problem. Highly chlorinated naph- 1953. W. Hansel, P. Olafson, and Kenneth thalene was found and identified in McEntce: Bovine Hyperkeratosis Studies on a the pellets and in the grease used to German Wood Preservative, Cornell Veteri- lubricate the pellet machines. Dr. narian, volume 43, pages 311-324. 1953. Roger P. Link and Dr. E. F. Reber, of W. Hansel, P. Olafson, and K. McEntce: The Isolation and Identification oj the Causative the University of Illinois, later identi- Agent of Bovine Hyperkeratosis {X-Disease) From fied this chemical in pellets that pro- a Processed Wheat Concentrate, Cornell Veter- duced hyperkeratosis in Illinois. inarian, volume 45, pages 94-101. 1955.