Mayo experimented with alcoholic and aqueous extracts of dried Astragalus mollissimus on guinea pigs, with negative results, and was first led to deny a relationship between the disease and the plants. Later, as a result of the post-mortem findings, he was convinced that his first conclusion was wrong and that "the disease is certainly the result of animals feeding upon the loco-weed." Mayo says:
A careful survey of the experiments performed and observations noted leads me to the opinion that the disease known as "loco" is the result of malnutrition, or a gradual starvation, caused by the animals eating the plants known as "loco weeds," either Astragalus mollissimus or Aragallus lamberti. If there is a narcotic principle in the plant, chemists have failed to find it and a fluid extract does not possess it, and a ton of the plant eaten by an animal ought to contain enough of the poisonous properties to destroy an animal.
Kobert has also tested the activity of Astragalus mollissimus and says, "Ich fand Astragalus mollissimus ziemlich unwirksam."
Doctor McEackran fed dried Astragalus mollissimus and Aragallus lamberti mixed with feed to a stabled animal for two months without result. (Animal not stated). Similar negative experiments are reported from the State of Washington, but the amounts used were too small to form any conclusions.
Mr. V. K. Chesnut has busied himself with the loco problem, but mainly in an executive capacity, his own efforts being directed to the study of the relation of the loco plants to the disease on the range. He has done no laboratory work. Chesnut and Wilcox made numerous autopsies on sheep and experiments on animals. They claimed that an extract of Aragallus spicatus produced some slight narcotic action in rabbits. Their pathological examinations failed to show any characteristic lesion, but they state that the cerebral membranes were in all cases slightly congested. They deny any causative relationship to the presence of worms or with feeding upon alkalis. They believe that sheep are more likely to become locoed if not salted regularly. Chesnut describes one case in which a lamb became locoed by nursing from a locoed mother.
In 1901 Reid Hunt, at that time a special agent of the United States Department of Agriculture, studied the loco question in Montana, working mainly with Aragallus spicatus. He moistened the ground-up plant with 93 per cent ethyl alcohol and then percolated it until exhausted. This extract was evaporated and taken up with water so that 1 c.c. of the solution corresponded to 10 grams of the plant. This was fed to an active young rabbit weighing 490 grams, 6 c.c. being fed by the mouth and followed in about an hour by 10 c.c. more, and two hours after this by 15 c.c. This rabbit showed no symptoms during the following day. The next day it was very dull and there was marked muscular weakness, as the rabbit's legs were spread wide apart and his nose rested on the ground. Later respiration became very slow and the pupils were dilated. The paralytic symptoms increased and finally, after a convulsive movement, the animal died, thirty-six hours after the first feeding. Hunt merely states of the post-mortem examination that the stomach was well filled and that the "walls seem normal."
Hunt tried to isolate an active principle by the Dragendorff method, but failed to obtain any physiologically active shakings. He tried hypodermic injections of 80 per cent alcohol extractions of the fresh green plant, and after the injection of an extract corresponding to 60 grams of the fresh plant there was no effect produced. He tried to induce symptoms by feeding the plant itself to rabbits, but was unsuccessful, as the rabbits refused to eat the plant. He was not able to induce symptoms with the extracts of the dried plant.
Marshall studied the loco question with regard to sheep and practically denies the existence of a locoed condition due to eating the loco plants, but believes the condition due to bad feeding, parasitism, etc. He lays great stress upon the presence of worms, but fails to see that they may be merely a secondary infection superimposed upon an already morbid condition produced by eating the plants. Others have claimed that the cause is an insect living upon the loco plants. Others, again, have suggested an analogy with trypanosome disorders.
Chesnut has held the view that many of the cases of so-called locoed sheep were really due to parasites, but that there was a true locoed condition due to eating the loco weeds.
The lack of agreement in the results of the investigators has caused many to doubt any positive relation between the plant and the disease, and even as late as 1904 Payne practically says these diseases are due to lack of nutrition and not to the loco plant. The matter has been summed up in a recent work as follows:
Though many chemists have sought for the constituents, none have been able to locate the active properties, the trace of alkaloids, resins, volatile and fixed oils having each in turn been found destitute of it. Yet the poisonous properties are fully established by field observations. The destructiveness of these plants to stock is so great as to have probably caused upward of a million dollars loss in the aggregate, and large bounties have been offered by State governments for an effective method of avoiding such losses. It is considered very probable that the poisonous constituent is albuminoidal.
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FOOTNOTES:
Storke, B. F. The Loco Weed. Med. Current, vol. 8, p. 155. 1892.--Kellogg, A. California and Colorado "Loco" Poisons. Cal. Acad. Sci. Proc. for 1875, vol. 6, p. 3. 1876.
NOTE.--The very early reports of these loco plants were purely botanical. See Torrey, J., Botany, in Report on the United States and Mexican Boundary Survey, by W. H. Emory, vol. 2, p. 56, 1859; also Botanical Register, London, vol. 13, pl. 1054, 1827.
Vasey, G. Plants Poisonous to Cattle in California. Rept. of Commissioner of Agriculture for 1874, p. 159. 1875.
Vasey, G. Botanical Notes. Monthly Reports of Dept. Agriculture for 1873, p. 503. 1874.
Vasey, G. Botanical Notes. Monthly Reports of Dept. Agriculture for 1874, p. 513. 1875.
Brewer, W. H., and Watson, S. Geological Survey of California, Botany, vol. 1, p. 155. 1876.
Rothrock, J. T. Notes on Economic Botany, in G. M. Wheeler's Report upon U. S. Geographical Surveys West of the One Hundredth Meridian, vol. 6, p. 43. 1878.
Kellogg, A. California and Colorado Loco Poisons. Cal. Academy of Sciences, Proc., 1875, vol. 6, p. 3. 1876.
Rothrock, J. T. Poisonous Properties of the Leguminosæ. Acad. of Nat. Sci., Phila., Proc., vol. 29, p. 274. 1877.
Prescott, A. B. Laboratory Notes--A Partial Analysis of the Oxytropis Lamberti. Amer. Journ. Pharm., vol. 50, p. 564. 1878.
Rept. of Commissioner of Agriculture for 1878, p. 134. 1879.
Rept. of Commissioner of Agriculture for 1879, pp. 89, 90. 1880.
Rept. of Commissioner of Agriculture for 1886, p. 75. 1887. Rept. of Commissioner of Agriculture for 1884, p. 123. 1884.
Rothrock, J. T. Notes on Economic Botany, in G. M. Wheeler's Report upon U. S. Geographical Surveys West of the One Hundredth Meridian, vol. 6, p. 43. 1878.
Gibbons, H. Poisonous Effects of Crotalaria--Vulgo Rattle Weed, Loco Weed. Pacific Med. and Surg. Journ., vol. 21, p. 496. 1878-79.
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