Albert Cornelius Crawford

“ The practical importance of the discovery of the true nature of the active poisonous principle of the loco weeds is very great. It not only sheds light on the loco situation and enables one to explain many hitherto inexplicable things, but it also adds much to our knowledge of barium in its medical bearings. ”

“ The amount of barium found in various species of loco plants will no doubt vary, and perhaps the pharmacological test on rabbits as the writer has used it may have to be modified for such plants, so that at present the wisest plan to test these plants is to determine their barium content and also make the physiological test, as has been proposed, and if the barium content runs low, say below 0.11 per cent of the ash, in plants yielding from 12 to 18 per cent of ash, then to increase the number of feedings on the rabbit. ”

“ The field investigations have given such contradictory evidence that until the Bureau of Plant Industry of the Department of Agriculture turned its attention to the matter the whole subject of the loco disease was regarded by many as a kind of delusion and the existence of a distinct entity was freely doubted. ”

“ No actual experiments have yet been made with cattle by feeding small doses of the pure salt.
No doubt more of the pure barium salts will be required to produce symptoms of poisoning in animals than would be necessary in the case of the form of barium found in the plant, as in the loco-weed the barium is probably better protected from precipitation than are the barium salts when dissolved in water alone. ”

“ The fact that treatment of the loco-weed extract with a few drops of sulphuric acid, which will remove the barium, renders these extracts harmless, and even apparently nutritious, would suggest the theoretical antidotal treatment to be with sulphates, in the form, perhaps, of epsom salts, but perhaps alkaline bicarbonates may be present in the stomach, either due to lessened acidity of the stomach or from drinking alkaline waters, in which case the precipitation of the barium by sulphates would presumably be interfered with, and thus the treatment be rendered ineffectual. ”

“ The animals may remain with the herd, but they often wander away. Stalker records the following observations:
I have seen a single animal miles away from any other individual of the herd, carefully searching as if for some lost object, and when a loco plant is found he would devour every morsel of it with the greatest relish. As soon as one plant was eaten he would immediately go in search of more, apparently oblivious to everything but the intoxication afforded by his one favorite article of food. [50]
All of Nockolds’s animals which were locoed were mares more than 6 years of age. ”

“ No doubt on ranges where a large number of loco plants are eaten, with little other food, plants with a very low barium content may be poisonous, but if large amounts of other food are fed the writer would expect few, if any, serious results.
As the writer’s work has been confined to the laboratory side of the loco-weed investigations no feeding experiments with barium salts have been made by him on large animals. Such experiments should, of course, be made under range conditions; that is, where the water and food supply is deficient. ”

“ The fact that the aqueous extract of 500 grams of the fresh Astragalus mollissimus, or of 200 grams (in some cases 100 grams) of the dried plant, when fed by mouth, would regularly kill a rabbit weighing about 907 grams, with certain definite clinical symptoms and pathological lesions, was at first arbitrarily selected as our test [Pg 47] to aid in the isolation of the active principle. Later the production of chronic symptoms by the aqueous extract or digestion of 200 grams of these dried plants given in doses of 100 grams each on two successive days was considered essential. ”

“ When 400 grams of the dried and powdered plant were fed in substance the result was merely to increase the appetite. The organic acid obtained from 4 ounces of the plant was also found to be inert.
Kennedy did not state in what season the plant was collected and from what locality it was obtained, but says simply that the plant extract was inactive to a dog, a carnivorous animal, and that therefore the plant is nonpoisonous. He adds that death might be due to the tough fibers and indigestible character of the plant. ”

“ In the case of Crotalaria, Power and Cambier had before them the experiment of Stalker, in which he reproduced the disorder by feeding the plant extract to horses, yet they claimed that the body which they administered was the active principle, merely because it produced some frothing at the mouth and salivation in a kitten. The percentage of active principle they found would be too small to account for the symptoms, except in the case of a very active compound. ”

“ There must be an undetermined something behind the loco weed. [131]
In 1893 O’Brine, from Colorado, and Mayo, from Kansas, reported on their work with the loco plants. O’Brine failed to isolate any alkaloidal or other poisonous body, and his feeding experiments on himself and on rabbits having failed, he sums up in despair: “The more I examine the loco question, the more I am persuaded that we must look for some other cause besides the loco-weed.” ”

“ These terms describing the alleged symptoms of “locoism” might occur in well recognized diseases resulting from brain lesions, which latter occur in so-called forage poisoning and poisoning from foul drinking water, etc.
We are not prepared to affirm or deny that the loco-weed produces a train of symptoms characteristic of the plant. [116]
Again Sayre states:
It seems not unreasonable to suppose that the peculiar condition of the animals of the plains, when they gorge themselves with this highly nitrogenous weed, has something to do with the disease. ”

“ After the administration per os, much of the barium must be carried off in the diarrheal stools. A number of deaths in horses have been attributed to the use of this agent. No doubt the presence of sulphates, etc., derived from the food would render the barium insoluble in the gastro-intestinal tract, and this would explain the lack of poisonous action in certain of the cases in which large doses of barium proved harmless.
Husard and Biron administered daily doses of 8 grams of barium chlorid to one horse, and the same amount of barium carbonate to a second horse, for several days. ”

“ One sample of the soil from near Hugo, Colo., from which the Aragallus lamberti was collected, was examined by the Bureau of Soils, and that Bureau reported the absence of barium and zirconium, at least of any recognizable by the chemical methods used, so that it can not be said that the barium came from any soil accidentally mixed with the ash. Traces of titanium were, however, found. Evidently the plant must collect minimal quantities of these elements from the soil and store them. ”

“ The animals lose their appetite from the first, begin to emaciate, and show symptoms of malnutrition and starvation. The head trembles, the gait becomes feeble and uncertain, the eyes become sunken and have a “flat, glassy look.” [30] There is a general sluggishness, muscular incoordination, and difficulty in motion; finally all control of the limbs is lost and the animal is unable to stand; the coat becomes rough and loses its luster, and, in fact, all the typical symptoms of starvation appear. In some cases diarrhea is also present. ”

“ But even the treatment of acute cases of barium poisoning in man is not always successful, even when sulphates combined with symptomatic treatment are employed. The conditions under which the sulphates fail to precipitate barium must be considered. At present it seems best to rely on preventive measures rather than on antidotal treatment.
(7) Loco plants grown on certain soils are inactive pharmacologically and contain no barium. ”

“ It is important that the ash of plants, especially those grown on uncultivated soil, as on our unirrigated plains, be examined for various metals, using methods similar to those by which rocks are now analyzed in the laboratory of the United States Geological Survey. ”

“ Their work from a chemical standpoint is excellent, but from a pharmacological point of view seems to be deficient; in fact, Power does not claim to be a pharmacologist. What would seem to be the proper course would have been to test for themselves the action of the plant on various animals and, after deciding which reacted most characteristically, test, after various precipitations, both the precipitates and filtrates on various animals to see whether the original symptoms and pathological lesions could be produced. ”

“ As a rule the loco plants are refused by animals save when there is lack of other food, although at times animals have shown the keenest relish for these plants, rejected all other forage, and devoted their whole attention to searching for the loco plants. ”

“ Hillebrand [182] has called attention to the fact that the igneous rocks of the Rocky Mountains showed a higher percentage of barium than rock from other portions of the United States, so that under these conditions one might expect the presence of barium in plants growing in this region. A sample of Aragallus lamberti and one of Astragalus mollissimus were sent to the Bureau of Chemistry for spectroscopic examination for various elements and they reported traces of barium in each. ”

“ The post-mortem examination revealed the presence of ulcers in the stomach and duodenum. Some of the ulcers had nearly perforated the walls of the stomach and duodenum. The heart was in diastole; brain and myel appeared normal. As might be expected from the emaciated condition, the entire body was anæmic.
In a second case 60 to 70 cubic centimeters of a more concentrated decoction were fed daily, with other food as before, to a vigorous adult cat. The symptoms of inactivity, loss of appetite, rough coat, diarrhea, and the peculiar expression of countenance were as in the first case. ”

“ Evidently the barium in these dried plants had been converted into an insoluble form by drying or by some peculiarity of its metabolism, and was not extracted by water, but could be extracted by digesting the plants with the combined digestive ferments, pepsin and pancreatin. ”

“ The results of his experiments on various animals—dogs, cats, and frogs [99] —have been entirely negative. He administered alcoholic preparations to himself and took them until they became too nauseous to continue, and found they produced absolutely no symptoms besides the nausea. He suggests, however, that if the plant really is poisonous it is due to its fine hairs, which might mechanically cause death. Sayre has stated that he has sent thousands of pounds of the dried loco plants to various investigators in America and Europe, but all reports were negative as to pharmacological activity. ”

“ 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 [141] 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. ”

“ Sir: I have the honor to transmit herewith the manuscript of a technical bulletin entitled “Barium, a Cause of the Loco-Weed Disease,” prepared by Dr. A. C. Crawford, Pharmacologist, under the direction of Dr. Rodney H. True, Physiologist in Charge of Poisonous-Plant Investigations, and to recommend that it be published as Bulletin No. 129 of the series of this Bureau.
For many years the stockmen in many parts of the West have reported disastrous consequences following the eating of so-called loco weeds characteristic of the regions involved. ”

“ This plant is mechanically a very unfit substance for food, being of a tough, fibrous, and indigestible character. It is possible that, when the animal becomes somewhat enfeebled by lack of proper nourishment, the small amount of alkaloid may have a direct poisonous action. ”