Part 1

TRANSCRIBER NOTES:

Words in italics are indicated with an underscore (_) at the begining and end. Words in bold are indicated with an equal sign (=) at the begining and end. Subscripts contained in chemical notations are indicated as _{ }.

The table on page 32 has been modified to fit by the use of keys to replace some of the information.

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.

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.

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_.

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_.

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_.

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

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]

* * * * *

FOOTNOTES:

[1] Stalker, M. The "Loco" Plant and Its Effect on Animals. Bur. Animal Industry, 3d Ann. Rept. (1886), p. 271. 1887.

[2] Bur. Animal Industry, 6th and 7th Ann. Repts. (1889 and 1890), p. 272. 1891.

[3] Day, M. G. Loco-Weed. In F. P. Foster's Reference-Book of Practical Therapeutics, vol. 1, p. 587. 1896.

[4] O'Brine, D. Progress Bulletin on the Loco and Larkspur. Colo. State Agric. Coll. Bul. 25, p. 18. 1893.

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

[6] Fletcher, J. Experimental Farms Reports for 1892, p. 148. 1893.

=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]

* * * * *

FOOTNOTES:

[5] Fletcher, J. Evidence Before the Select Standing Committee on Agriculture and Colonization. Ottawa, 1905, p. 53.

[7] Sayre, L. E. Loco Weed. Amer. Vet. Rev., vol. 11, p. 555. 1887.--Stalker, M. The "Loco" Plant and Its Effect on Animals. Bur. Animal Industry, 3d Ann. Report. (1886), p. 271. 1887.

[8] Eastwood, A. The Loco Weeds. Zoe, vol. 3, p. 53. 1892.

[9] Chesnut, V. K. Preliminary Catalogue of Plants Poisonous to Stock. Bur. Animal Industry, 15th Ann. Rept. (1898), p. 404.

[10] Williams, T. A. Some Plants Injurious to Stock. S. Dak. Agric. Coll. and Exper. Sta. Bul. 33, p. 21. 1893.

[11] Givens, A. J. Loco or Crazy Weed. Med. Century, vol. 1, p. 22. 1893.

[12] Eastwood, A., l. c. 1892.

[13] Sayre, L. E. Loco Weed. Amer. Vet. Rev., vol. 11, p. 555. 1887.

[14] Amer. Pharm. Assoc. Proc. for 1879, vol. 27, p. 611. 1880.

[15] Kelsey, F. D. Another Loco Plant. Bot. Gaz., vol. 14, p. 20. 1889.

[16] Sayre, L. E. Loco Weed. Kans. State Board Agric., 5th Bienn. Rept., p. 209. 1887.

[17] Anderson, F. W. Poisonous Plants and the Symptoms They Produce. Bot. Gaz., vol. 14, p. 180. 1889.--Pammel, L. H. Loco Weeds. Vis Medicatrix, vol. 1, p. 44. 1891.

[18] Stalker, M. The "Loco" Plant and Its Effect on Animals. Bur. Animal Industry, 3d Ann. Rept. (1886), p. 275. 1887.--Anderson, F. W. Poisonous Plants and the Symptoms They Produce. Bot. Gaz., vol. 14, p. 180. 1889.

NOTE.--The symptoms described in Janvier's interesting story, "In Old Mexico" (Scribner's Magazine, vol. 1, p. 67, 1887), would coincide with those due to some member of the nightshade family (probably _Datura stramonium_). See also Pilgrim, C. W., Does the Loco Weed Produce Insanity? in Proc. Amer. Medico-Psycholog. Assoc., vol. 5, p. 167. 1898.

[19] Sayre, L. E. Loco Weed. Kans. State Board Agric., 5th Bienn. Rept., p. 209. 1887.

[20] Stalker, M. The "Loco" Plant and Its Effect on Animals. Bur. Animal Industry, 3d Ann. Rept. (1886), p. 272. 1887.

[21] Mayo, N. S. Loco. The Industrialist, vol. 30, p. 473. 1904.

[22] Science, vol. 9, p. 32. 1887.

[23] Hayes, M. H. Veterinary Notes for Horse Owners, London, 1903, p. 425.--Compare Woronin, M. Ueber die Taumelgetreide in Süd-Ussurien. Bot. Zeit., vol. 49, p. 80. 1891.

[24] Chesnut, V. K., and Wilcox, E. V. Stock-Poisoning Plants of Montana. U. S. Dept. Agric., Div. Bot., Bul. 26, p. 88. 1901.

NOTE.--The wide distribution of these plants is claimed to be partly due to the buffalo. See Blankinship, J. W., The Loco and Some Other Poisonous Plants in Montana, in Mont. Agric. Exper. Sta. Bul. 45, p. 79. 1903.

=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.