U. S. DEPARTMENT OF AGRICULTURE.
BUREAU OF PLANT INDUSTRY—BULLETIN NO. 129.
B. T. GALLOWAY, Chief of Bureau.

BARIUM, A CAUSE OF THE
LOCO-WEED DISEASE.

BY

ALBERT C. CRAWFORD,

Pharmacologist, Poisonous-Plant Investigations.

Issued August 22, 1908.

WASHINGTON:
GOVERNMENT PRINTING OFFICE.
1908.

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BUREAU OF PLANT INDUSTRY.

• Physiologist and Pathologist, and Chief of Bureau, Beverly T. Galloway.
• Physiologist and Pathologist, and Assistant Chief of Bureau, Albert F. Woods.
• Laboratory of Plant Pathology, Erwin F. Smith, Pathologist in Charge.
• Investigations of Diseases of Fruits, Merton B. Waite, Pathologist in Charge.
• Laboratory of Forest Pathology, Haven Metcalf, Pathologist in Charge.
• Cotton and Truck Diseases and Plant Disease Survey, William A. Orton, Pathologist in Charge.
• Plant Life History Investigations, Walter T. Swingle, Physiologist in Charge.
• Cotton Breeding Investigations, Archibald D. Shamel and Daniel N. Shoemaker, Physiologists in Charge.
• Tobacco Investigations, Archibald D. Shamel, Wightman W. Garner, and Ernest H. Mathewson, in Charge.
• Corn Investigations, Charles P. Hartley, Physiologist in Charge.
• Alkali and Drought Resistant Plant Breeding Investigations, Thomas H. Kearney, Physiologist in Charge.
• Soil Bacteriology and Water Purification Investigations, Karl F. Kellerman, Physiologist in Charge.
• Bionomic Investigations of Tropical and Subtropical Plants, Orator F. Cook, Bionomist in Charge.
• Drug and Poisonous Plant Investigations and Tea Culture Investigations, Rodney H. True, Physiologist in Charge.
• Physical Laboratory, Lyman J. Briggs, Physicist in Charge.
• Crop Technology and Fiber Plant Investigations, Nathan A. Cobb, Crop Technologist in Charge.
• Taxonomic and Range Investigations, Frederick V. Coville, Botanist in Charge.
• Farm Management Investigations, William J. Spillman, Agriculturist in Charge.
• Grain Investigations, Mark Alfred Carleton, Cerealist in Charge.
• Arlington Experimental Farm, Lee C. Corbett, Horticulturist in Charge.
• Vegetable Testing Gardens, William W. Tracy, sr., Superintendent.
• Sugar-Beet Investigations, Charles O. Townsend, Pathologist in Charge.
• Western Agricultural Extension Investigations, Carl S. Scofield, Agriculturist in Charge.
• Dry-Land Agriculture Investigations, E. Channing Chilcott, Agriculturist in Charge.
• Pomological Collections, Gustavus B. Brackett, Pomologist in Charge.
• Field Investigations in Pomology, William A. Taylor and G. Harold Powell, Pomologists in Charge.
• Experimental Gardens and Grounds, Edward N. Byrnes, Superintendent.
• Foreign Seed and Plant Introduction, David Fairchild, Agricultural Explorer in Charge.
• Forage Crop Investigations, Charles V. Piper, Agrostologist in Charge.
• Seed Laboratory, Edgar Brown, Botanist in Charge.
• Grain Standardization, John D. Shanahan, Crop Technologist in Charge.
• Subtropical Laboratory and Garden, Miami, Fla., Ernst A. Bessey, Pathologist in Charge.
• Plant Introduction Garden, Chico, Cal., W. W. Tracy, jr., Assistant Botanist in Charge.
• South Texas Garden, Brownsville, Tex., Edward C. Green, Pomologist in Charge.
• Farmers’ Cooperative Demonstration Work, Seaman A. Knapp, Special Agent in Charge.
• Seed Distribution (Directed by Chief of Bureau), Lisle Morrison, Assistant in General Charge.

Editor, J. E. Rockwell.
Chief Clerk, James E. Jones.

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POISONOUS-PLANT INVESTIGATIONS.
SCIENTIFIC STAFF.

Rodney H. True, Physiologist in Charge.

• C. Dwight Marsh, Expert in Charge of Field Investigations.
• Albert C. Crawford, Pharmacologist.
• Arthur B. Clawson, Expert in Field Investigations.
• Ivar Tidestrom, Assistant Botanist, in Cooperation with Forest Service.

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LETTER OF TRANSMITTAL.

U. S. Department of Agriculture,

Bureau of Plant Industry,
Office of the Chief,
Washington, D. C., April 10, 1908.

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. While many have doubted any causal relation between the plants in question and the stock losses, the reality of the damage has remained and has seemed to require a thoroughgoing sifting of the evidence concerning the part played by the plants. Accordingly, in the spring of 1905 a station for the experimental study of the problem was established at Hugo, Colo., in charge of Dr. C. Dwight Marsh, Expert, in cooperation with the Colorado Agricultural Experiment Station. Later a further feeding experiment was undertaken at Imperial, Nebr., in cooperation with the Nebraska Agricultural Experiment Station. Parallel with the feeding work in the field, laboratory work, designed to test under laboratory conditions the poisonous action of the plants from given areas, was undertaken at Washington by Dr. A. C. Crawford, Pharmacologist. A further phase of his part of the work was an attempt to ascertain the nature of such poisonous substance or substances as might occur in the loco plants.

In both of these lines of work Doctor Crawford has been successful, and the technical results of his work are here collected.

Respectfully,

B. T. Galloway,
Chief of Bureau.

Hon. James Wilson,
Secretary of Agriculture.

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INTRODUCTORY STATEMENT.

A scientific understanding of the so-called loco-weed disease has been demanded and sought after for several decades for most practical purposes, but, in spite of the great amount of attention which this problem has received, no general agreement has been found among the results obtained. 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. Not only did this confusion characterize the field aspect of the matter, but the situation viewed from the

standpoint of laboratory study was also much obscured. Some investigators claimed to have separated poisonous substances of various sorts from the loco weeds, while others of equal scientific standing denied the presence of any poisonous substance in the plants under general suspicion—the so-called loco weeds.

In view of the great seriousness of the loco situation from the standpoint of the stock interests, an active campaign both in the line of feeding experiments in the field and laboratory study at Washington was undertaken by the Office of Poisonous-Plant Investigations of the Bureau of Plant Industry.

The feeding experiments carried out at Hugo, Colo., in cooperation with the Colorado Agricultural Experiment Station, before the close of the first season developed evidence that there was in reality such a thing as a loco disease. The investigator in charge was enabled to describe the disease in its most important manifestations and made it possible to sift the facts from the large number of contradictory statements in the literature.

The laboratory work, undertaken and carried on simultaneously, consisted of a pharmacological study, under laboratory conditions and with the usual laboratory subjects, of the action of plant material sent in from the field. The acute phase of loco-weed poisoning, as well as a more prolonged type of the disease, was studied. In plants found in this preliminary feeding to be harmful, the poisonous principle was sought, with the very striking results fully described in this paper. The demonstration of the presence of barium in the plants was followed by barium feeding, with the production of symptoms which agreed with those produced in the laboratory with loco extracts and in the field experiments with the loco plants as seen growing on the range. By comparing these laboratory results with those produced in connection with the field work, it became possible to sift the wheat from the chaff in the mass of contradictory evidence detailed in the literature of this subject.

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. It opens up most important problems concerning the soils and the relation of the flora to them. It should be borne in mind that although barium is shown to be chiefly responsible for the poisonous properties of loco weeds in eastern Colorado, it is entirely possible that in other regions other substances may be equally or even more significant. This discovery also seems likely to provide a basis for a rational treatment of locoed stock. Unfortunately, the discovery of the fact that barium is the poisonous constituent of loco weeds came too late to aid in the search for remedial measures on the range during the period covered by this report, but those empirically arrived at have received additional support from these laboratory results.

Thus the work in field and laboratory, undertaken after repeated attempts and discouraging failures by others, has yielded results to persistent scientific research and promises practical aid to the now suffering live-stock interests. The results of the laboratory work are presented in this bulletin.

Rodney H. True,
Physiologist in Charge.

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CONTENTS.

Page. Geographical distribution of the loco-weed disease and allied conditions 9 Plants associated with the locoed condition 10 Clinical symptoms of locoed animals as described in literature 12 Conditions similar to loco-weed poisoning in other parts of the world 16 Pathological conditions in locoed animals as described on the range 18 Historical sketch of loco investigations from a pharmacological standpoint 19 Notes on various members of the loco-weed family 35 Laboratory experiments—physiological 36 Experiments on rabbits 36 Acute cases 36 Chronic cases 38 Pregnant animals 42 Subcutaneous injections 43 Summary of feeding experiments on rabbits 44 Experiments on sheep 44 Laboratory experiments—chemical 46 Effect of the aqueous extract of ashed loco plants 49 Total ash determinations of loco

plants 54 Barium determinations in the ash of loco plants 55 Analysis of soils 57 Feeding experiments with barium salts on animals in the laboratory 57 Barium poisoning in man 62 Pathological lesions in experimental barium poisoning 65 Toxicity of various aqueous extracts of loco plants 66 Theoretical antidote for loco-weed poisoning 71 Action of barium on domestic and farm animals 72 Application of the results of these investigations to the range 74 Conclusions 75 Index 77

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BARIUM, A CAUSE OF THE LOCO-WEED
DISEASE.

GEOGRAPHICAL DISTRIBUTION OF THE LOCO-WEED DISEASE
AND ALLIED CONDITIONS.

In our Western States there is a marked annual loss of stock due to various causes. Some of these animals die in a condition known as ‘locoed,’ a term derived from the Spanish word “loco,” meaning foolish or crazy.

This disorder extends from Montana to Texas and Mexico, and from Kansas and Nebraska to California.[1]

In 1898 the United States Department of Agriculture sent out, under the immediate direction of Mr. V. K. Chesnut, a request for information concerning the ravages of the loco disease. It was found that in the ten States of California, Colorado, Kansas, Montana, Nebraska, New Mexico, North Dakota, Oklahoma, Texas, and Wyoming the loss in 1898 was $144,850. Of this amount, $117,300 was attributed to Colorado alone; in fact, the disorder spread so that this State expended more than $200,000 in two years and over $425,000 in a period of nine years in attempts to eradicate the loco plants, the supposed cause of the trouble.[2]

The loss in one area of 35 by 120 miles in southwestern Kansas amounted to 25,000 cattle in 1883.[3] This loss in stock has been so great that the raising of horses has of necessity been abandoned in certain areas on account of the prevalence of these loco weeds.

It is difficult to obtain accurate data, as the ranchmen believe that any information as to the prevalence of the disorder would interfere with the value of their stock.[4]

Dr. James Fletcher, of the Central Experimental Farm, Ottawa, Canada, testified before the Select Standing Committee on Agriculture and Colonization that he had never seen a case in the North-west of a Canadian bred animal being locoed, although the loco plants were prevalent. He explained this absence of loco disease by the abundance of grass on the range, because of which the animals do not acquire the habit of eating loco plants.[5] Cases have been reported, however, in Manitoba.[6]

class="label">[5] Fletcher, J. Evidence Before the Select Standing Comminttee on Agriculture and Colonization. Ottawas, 1905, p. 53.

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PLANTS ASSOCIATED WITH THE LOCOED CONDITION.

The condition known as “locoed” is popularly believed to be due to eating various plants, especially the members of the Astragalus and Aragallus genera of the Leguminosæ, or pea family, but particularly to Astragalus mollissimus and Aragallus lamberti. These plants have therefore received the name “loco plants,”[7] or crazy weed. But others, as Astragalus mortoni,[8] A. hornii, A. lentiginosus, A. pattersoni,[9] A. nuttallianus, A. missouriensis, A. lotifloras, A. bisulcatus, A. haydenianus,[10] A. tridactylicus,[11] Crotalaria sagittalis, Lotus americanus,[12] Sophora sericea, Caprioides aureum, Aragallus deflexa,[13] A. campestris,[14] A. lagopus,[15] Malvastrum coccineum, Amaranthus graecizans, and Rhamnus lanceolata, are considered by some as loco plants.[16] In other places Stipa vaseyi, Leucocrinum montanum, Fritillaria pudica, Zygadenus elegans,[17] and even species of Delphinium are considered loco plants, so widely has this name been used.

In Mexico the term “locoed” embraces a condition due to the action of Cannabis sativa and various members of the nightshade family. This term has been much abused and has been made to embrace many groups of symptoms. In fact, if an animal dies while showing more or less stupor it is said to be locoed.[18] The early Spanish settlers seemed to be unfamiliar with the disease, or at least of any causative relation between the plant and the disease. The Spanish name for Astragalus mollissimus was “Garbanzillo,” from its resemblance to Garbanzo (Cicer arietinum), which is used in Spain as a food.[19] The term as applied to this condition seems to be of comparatively recent origin.[20]

A somewhat similar condition to the loco in stock is sometimes attributed by the ranchmen of our Western States to eating various sages.[21] In Texas the loco disease is known as “grass staggers.”[22]

Hayes[23] has described as follows a condition known as grass staggers, which apparently has little resemblance to loco and is supposed to be due to eating overripe grass, especially rye.

The symptoms, generally, take two or three days to become developed. The animal gradually becomes more or less unconscious and paralyzed and staggers if forced to walk. Although he may have great difficulty in keeping on his legs, he is extremely averse from going down and leans for support against any convenient object. He breathes in a snoring manner. The mucous membranes are tinged with yellow. Convulsions, or spasms, like those of tetanus, may come on.

Recovery may be expected in cases which are not marked by extreme symptoms.

If animals are not regularly salted, they visit salt deposits and eat the alkalis. This some sheepmen believe to be the cause of the locoed condition, but this is disproved by the occurrence of locoed animals in ranges without salt. Others modify this view by claiming that the vitiation in taste from eating these alkalis leads to a desire for the loco weeds and thus to the locoed condition.[24]

id="Footnote_8_9"/>[8] Eastwood, A. The Loco Weeds. Zoe, vol. 3, p. 53. 1892.

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CLINICAL SYMPTOMS OF LOCOED ANIMALS AS DESCRIBED IN LITERATURE.

The animals usually affected are sheep, horses, cattle, mules,[25] donkeys,[26] and goats. It is claimed that practically all herbivorous animals are liable to the disease, even antelopes being affected.[27] Hogs are said to be unaffected,[28] but definite information is lacking. Cows seem to be less sensitive to this form of intoxication.[29] The condition is usually a chronic one, although acute cases are said to occur at times. The symptoms consist of digestive disturbances, associated with emaciation and various symptoms suggesting lesions in the nervous system, central or peripheral. 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.

All of Nockolds’s animals, however, were constipated and the stools were covered with mucus.[31] The dependent portions of the body may swell, simply as an expression of the anæmia.[32] Sometimes there are symptoms indicating acute pain,[33] the animals running about as if affected with colic. They may belch and their abdomens swell. Some claim that the animals are markedly salivated so that the saliva trickles from their mouths. In other cases the mouth may be dry.[34] The eyes may be rolled up so that the whites alone show. In some cases the pupil has been noted to be dilated, as in atropine poisoning,[35] but Wilcox states that they are contracted as after the use of eserine.[36] The temperature of the animal falls from 1/2 degree to 1-1/2 degrees F. below normal.[37] Tetanic symptoms may occur,[38] or the muscles of the mouth and tongue becoming paralyzed may interfere with mastication. When water is offered to the animal, it gazes stupidly at it and may not drink for days. One of the symptoms noted is the loss of power to back properly.[39] Cows during the first two or three months of gestation are almost sure to abort.[40] This is claimed by Knowles, however, to be due to malnutrition. As a result of these observations, suggesting some uterine action, the drug has been proposed as an emmenagogue.[41]

The psychical symptoms are shown by errors of judgment. The animal becomes dull and spiritless and wanders about half dazed. The mental dullness passes into stupor. This dull, stupid condition has been compared to intoxication with opium. If the locoed horse is led across a stick lying on the ground he often jumps high as if it were a great obstacle. The animal may now have maniacal attacks, during which he rears and may fall backward,[42] and makes unreasonable jumps and other unexpected movements, thus rendering himself dangerous to man.[43] Other symptoms due to disturbances of the central nervous system are hallucinations of various sorts. Though the optic nerve itself is apparently not affected, the animal will stare at an object for a long time without any apparent comprehension of its nature. This disturbance in the visual function McCullaugh claims to be one of the first symptoms of this disease. The animal seems to lose all idea of distance, as he will butt against an obstruction as if oblivious of its presence. Any sudden or violent motion made before him may cause him to fall. According to some, the animal loses the sense which guides him in finding water. A cow may fail to recognize her calf.[44] There is more or less loss of control of the limbs[45] and tremors;[46] the feet are lifted abnormally high when trotting, and, if crowded, the animal falls headlong and will jump over little hollows as if they were wide ditches.[47] The horse may shy without apparent cause and kick at imaginary objects,[48] and, in fact, the reasoning powers seem to be lost. These attacks are brought on by sudden excitement or when crossing water.[49] There may be cutaneous hyperæsthesia.

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.

tag="{http://www.w3.org/1999/xhtml}a">[50]

All of Nockolds’s animals which were locoed were mares more than 6 years of age.[51]

According to Stalker there is a passive type in which the animal shows symptoms only on being disturbed; the animal then becomes unmanageable. This happens even with old, well-broken saddle horses.[52]

There are few published reports as to the symptoms occurring in sheep which are locoed. Stalker[53] says sheep “become loco-eaters, grow stupid, emaciated, and eventually die.” One of the few descriptions of the symptoms is that of Ruedi,[54] in which he claims that the symptoms in sheep are those comparable to the symptoms of cerebro-spinal meningitis except that there is an absence of fever. Ruedi speaks of sheep “lying flat on the ground, not able to stand, and not able even to lift their heads to drink the offered water; the head and the vertebra in opisthotonus position; the four legs stretched out and stiff; breathing was stertorous, pulse slow, abdomen much distended, diarrhea present. * * * The heart * * * was very slow and insufficient.” The teeth (in sheep) may blacken and fall out.[55]

It is mainly the young animals, such as lambs and colts, that are affected, probably due to the fact that their attention is more easily directed to the flower of the loco[56] plants. It is claimed (on slight evidence) that men have become locoed. The symptoms in them are nausea and headache.[57]

Schuchardt[58] has called attention to the resemblance of the symptoms in locoed animals to those which occur in so-called lathyrism, but most observers in this country have especially marked the resemblance of the symptoms to those induced by the habitual use of narcotic drugs.[59]

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.[60]

Stalker says that animals not too long addicted to the use of these plants, if confined, soon lose their taste for them (after two or three months),[61] although old loco eaters do not readily lose the habit. Stalker also says that “it is to be presumed that the plant is possessed of some toxic property that has a specific effect on the nervous centers, and that these effects have a marked tendency to remain permanent.”[62]

The fundamental character of the disorder seems to be a progressing anæmia. The interpretation of psychical symptoms in herbivora, and especially on the range, must often be fallacious.