Chapter I: 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.

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.[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.

* * * * *

FOOTNOTES:

[25] Kingsley, B. F. The Loco Plant. Daniel's Texas Medical
Journal, vol. 3, p. 522. 1888.

[26] Schwartzkopff, O. The Effects of "Loco-Weed." Amer. Vet.
Rev., vol. 12, p. 162. 1888.

[27] McCullaugh, F. A. Locoed Horses. Journ. Comp. Med. &
Vet. Archives, vol. 13, p. 435. 1892.

[28] Eastwood, A. The Loco Weeds. Zoe, vol. 3, p. 57. 1892.

[29] Vasey, G. Plants Poisonous to Cattle in California.
Report of Commissioner of Agriculture for 1874, p. 159. 1875.

[30] Vasey, G., l. c., p. 159.

[31] Nockolds, C. Poisoning by Loco Weed. Amer. Vet. Rev.,
vol. 20, p. 570. 1896-7.

[32] Patterson, A. H. Starvation OEdema. Med. Rev., vol.
56, p. 715, 1899.

[33] Vasey, G. Botanical Notes, Monthly Reports of Dept.
Agriculture for 1873, p. 504. 1874.

[34] Anderson, F. W. Poisonous Plants and the Symptoms They
Produce. Bot. Gaz., vol. 14, p. 180. 1889.

[35] Schwartzkopff, O. The Effects of "Loco-Weed." Amer. Vet.
Rev., vol. 12, p. 161. 1888.

[36] Wilcox, T. E. Treatment of "Loco" Poisoning in Idaho
Territory. Med. Rec., vol. 31, p. 268. 1887.

[37] Mayo, N. S. Some Observations Upon Loco. Kans. State
Agric. Coll. Bul. 35, p. 118. 1893.

[38] McCullaugh, F. A. Locoed Horses. Journ. Comp. Med. and
Vet. Archives, vol. 13, p. 436. 1892.

[39] O'Brine, D. Progress Bulletin on the Loco and Larkspur.
Colo. State Agric. Coll. Bul. 25, p. 12. 1893.

[40] Knowles, M. E. Loco Poisoning. Breeders' Gaz., vol. 39,
p. 973. 1901.--Sayre, L. E. Loco Weed. Kans. State Board of
Agric., 5th Bienn. Rept., p. 211. 1887.--Ruedi, C. Loco Weed.
Trans. Colo. State Med. Soc., p. 422. 1895.

[41] Miller, C. H. The Loco Weed: Its Probable Usefulness as
an Emmenagogue. Southern Clinic, vol. 11, p. 269. 1888.

[42] Vasey, G. Botanical Notes. Monthly Reports of Dept.
Agriculture for 1873, p. 504. 1874.

[43] Parker, W. T. The Loco-Weed. Science, vol. 23, p. 101.
1894.

[44] Vasey, G. Botanical Notes. Monthly Reports of Dept.
Agriculture for 1874, p. 513. 1875.

[45] Anderson, F. W. Poisonous Plants and the Symptoms They
Produce. Bot. Gaz., vol. 14, p. 180. 1889.

[46] Sayre, L. E. Loco Weed. Proc. Amer. Pharm. Assoc., vol.
36, p. 111. 1888.

[47] Nockolds, C. Poisoning by Loco Weed. Amer. Vet. Rev.,
vol. 20, p. 570. 1896-7.

[48] Knowles, M. E. Loco Poisoning. Breeders' Gaz., vol. 39,
p. 972. 1901.

[49] Vasey, G. Botanical Notes. Monthly Reports of Dept.
Agriculture for 1873, p. 504. 1874.

[50] Stalker, M. The "Loco" Plant and Its Effect on Animals.
Bur. Animal Industry, 3d Ann. Rept. (1886), p. 272.
1887.--Nockolds, C. Poisoning by Loco Weed. Amer. Vet. Rev.,
vol. 20, p. 570. 1896-7.--Maisch, J. M. Poisonous Species of
Astragalus. Amer. Journ. Pharm., vol. 51, p. 239. 1879.

[51] Nockolds, C. Poisoning by Loco Weed. Amer. Vet. Rev.,
vol. 20, p. 570. 1896-7.

[52] Stalker, M., l. c., p. 273.

[53] Stalker, M., l. c., p. 274.

[54] Ruedi, C. Loco Weed (Astragalus Mollissimus): A
Toxico-Chemical Study. Trans. Colo. State Med. Soc., 1895, p.
417.

[55] Blankinship, J. W. Loco and Some Other Poisonous Plants
in Montana. Mont. Agric. Exper. Sta. Bul. 45, p. 81. 1903.

[56] Blankinship, J. W., l. c.

[57] Day, M. G. Loco-Weed. In F. P. Foster's Reference Book
of Practical Therapeutics, vol. 1, p. 588. 1896.--Pilgrim, C.
W. Does the Loco-Weed Produce Insanity? Proc. Amer.
Medico-Psycholog. Assoc., vol. 5, p. 167. 1898.

[58] Schuchardt, B. Die Loco-Krankheit der Pferde und des
Rindviehs. Deutsch. Zeits. f. Thiermed., vol. 18, p. 405.
1892.--Parker, W. T. Loco-Weed. Science, vol. 23, p. 101.
1894.

[59] McCullaugh, F. A. Locoed Horses. Journ. Comp. Med. and
Vet. Archives, vol. 13, p. 435. 1892.

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

[61] Stalker, M. The "Loco" Plant and Its Effect on Animals.
Bur. Animal Industry, 3d Ann. Rept. (1886), p. 272.
1887.--See also Linfield, F. B. Sheep Feeding, in Mont.
Agric. Coll. Exper. Sta. Bul., 59. 1905.--Special Report on
Diseases of Cattle. Bur. Animal Industry, 1904, p.
66.--Wilcox, E. V. Plant Poisoning of Stock in Montana. Bur.
Animal Industry, 17th Ann. Rept., p. 115. 1900.

[62] Stalker, M., l. c., p. 275.

=CONDITIONS SIMILAR TO LOCO-WEED POISONING IN OTHER PARTS OF THE WORLD.=

According to Maiden[63] a condition similar to loco is met with among animals in Australia and is there believed to be due to eating various species of Swainsona.[64] As Maiden says, "Its effect on sheep is well known; they separate from the flock, wander about listlessly, and are known to the shepherds as 'pea-eaters' or 'indigo-eaters.' When once a sheep takes to eating this plant it seldom or never fattens, and may be said to be lost to its owner." Horses, after eating this herb, "were exceptionally difficult to catch, and it was observed how strange they appeared. Their eyes were staring out of their heads and they were prancing against trees and stumps. The second day two out of nine died, and five others had to be left at the camp."

Martin[65] experimentally studied these cases of intoxication and sums up his work as follows:

1. That one can by feeding sheep upon Darling pea reproduce all the
symptoms which are attributed by pastoralists to this cause.
Briefly stated these symptoms are: Stupidity, loss of alertness and
an agonized expression, followed by stiffness and slight staggering
and frequently trembling of the head or limbs. Later, clumsiness
and unsteadiness ensue, which slowly advance until the animal often
falls down. In this stage, the action of the animal in running over
small obstacles is characteristic. It jumps over a twig as if it
were a foot in height. When first it commences to tumble about, it
is able more or less readily to regain its feet, but in the
advanced stage of the disease this is impossible and, after
exhausting itself in efforts to do so, it remains lying down until
it dies. During the whole time the sheep become progressively more
bloodless, and in advanced cases the blood when shed appears to the
naked eye lighter in color. It contains fewer red blood-cells
(about two-thirds to one-half the usual number). (The corpuscles
were estimated in several cases by means of a hæmocytometer.) All
these symptoms are much aggravated by driving. Thus, an animal in
which the symptoms are little marked may exhibit them in a striking
degree after being driven. In addition to the above the teeth
(especially in young sheep) frequently become loose, and
consequently displaced or even dislodged.

2. That the time which elapses before the onset of definite
symptoms is three to four weeks in sheep of 2 to 3 years old. (It
is probable, however, that with younger animals the time is
shorter.)

3. That under the conditions of the experiment, the animals
survived about three months. They lived, however, an invalid's
life. Everything was brought to them, and it is improbable that if
feeding exclusively upon the pea, and left to shift for themselves
in the paddocks, they would survive more than two months.

4. That if a sheep be returned to proper fodder after one month to
six weeks feeding upon the pea, and before the symptoms are fully
established, it may recover completely.

5. That when once the paralytic symptoms are established it will
not recover; but if returned to proper food, will remain in much
the same condition, becoming neither better nor worse.

6. That Darling pea contains a very fair amount of nourishing
material so that animals may, provided they eat it readily, retain
their condition on it for some weeks, until the poisonous principle
contained has had time to exert its effects.

These plants, if fed with other herbage, do not seem to be injurious and apparently lose their harmful action upon being cultivated.[66] As long as salt is properly fed the animals will not eat this plant[67] and are said to suffer no effects from it. Physiological study has shown the presence of a body with marked sudorific power which causes rapid emaciation in frogs.[68]

It has been claimed that these symptoms are due to the presence of a narcotic poison in the plant.[69] Post-mortem examinations were negative save for the presence of a peripheral neuritis.[70]

* * * * *

FOOTNOTES:

[63] Maiden, J. H. Plants Reputed to be Poisonous to Stock in
Australia. Dept. Agric., New South Wales, Misc. Pub. No. 477,
pp. 15, 16. 1901.

[64] Notes on Some American and Australian Plants Injurious
to Stock. Agric. Gaz., New South Wales, vol. 4, p. 677.
1894.--Notes on Weeds. The Darling Pea. Agric. Gaz., New
South Wales, vol. 3, p. 330. 1893.

[65] Martin, C. J. Report on an Investigation into the
Effects of Darling Pea (Swainsona Galegifolia) upon Sheep.
Agric. Gaz., New South Wales, vol. 8, p. 366. 1898.

[66] Woolls, W. On the Forage-Plants Indigenous in New South
Wales. Linn. Soc., New South Wales, Proc., vol. 7, pp.
315-316. 1882.

[67] Guthrie, F. B., and Turner, F. Supposed Poisonous Plant.
Agric. Gaz., New South Wales, vol. 4, p. 86. 1894.

[68] Bailey, F. M., and Gordon, P. R. Plants Reputed
Poisonous and Injurious to Stock, Brisbane, 1887, p. 25.

[69] Guthrie, F. B., and Turner, F. Supposed Poisonous Plant.
Agric. Gaz., New South Wales, vol. 4, p. 87. 1894.

[70] Martin, C. J. Report on the Investigation into the
Effects of Darling Pea (Swainsona Galegifolia) upon Sheep.
Agric. Gaz., New South Wales, vol. 8, p. 367. 1898. (Further
literature on the indigo disease will be found in Bailey, F.
M., and Gordon, P. R. Plants Reputed Poisonous and Injurious
to Stock, Brisbane, 1887, p. 25).

NOTE.--In Canada a chronic disease associated with cirrhosis
of the liver results from eating ragwort, or _Senecio
jacobaea_. See Dept. of Agriculture, Canada, Rept. of
Veterinary Director General, 1905, Ottawa, 1906, p. 31.--In
South Africa a disorder known as nenta appears in goats after
eating certain plants, especially _Cotyledon ventricosa_. See
Hutcheon, D., Nenta, in Agric. Journ. Cape of Good Hope, vol.
14, p. 862. 1899.

=PATHOLOGICAL CONDITIONS IN LOCOED ANIMALS AS DESCRIBED ON THE RANGE.=

The pathological features as described by previous writers are a softening and ulceration of the stomach walls[71] and a degeneration of the walls of the intestines with or without perforations. The peritoneum may be found inflamed.[72] The peritoneum and omentum in one case (cow), reported by Sayre, were covered with small nodules. These were probably tubercular in origin. The colon in one horse was found enormously distended, while the coecum and small intestines were normal,[73] save that the walls appeared thin.

Ulcers have been found at times in the kidneys, but were probably secondary in origin, as other cases are reported with normal kidneys. Faville has found in some cases amyloid degeneration. The pancreas and spleen are reported normal. The abdominal cavity may contain a slight effusion.[74] The liver has been found cirrhotic, and at times shows tubercular lesions of a secondary nature. The inner coat of the bladder has been found softened, and in sheep the bladder may be markedly distended at the autopsy. The cerebral membranes are congested and perhaps adherent,[75] and there may be blood clots over the longitudinal sinus or at the base of the brain. Effusions have been especially noted around the medulla. The arachnoid has also shown slight congestion, and in other cases the membranes showed a slight thickening. The middle ventricle was found filled with yellow serum, while the fourth ventricle contained a hemorrhagic effusion,[76] and the base of the brain was covered by a clot. The hemorrhage may become organized and the brain be held to the membranes by tough organized fibers. In many cases serous effusion is present in the lateral ventricles. The arachnoid space is also in some cases similarly filled. Microscopic examination of the brain in the case of a steer showed atrophy of Purkinjie's cells.[77]

In sheep the post-mortem examination showed paleness, anæmia of the muscles, and great distention of the abdomen. The intestines were found filled with gases, and the mesenteric blood vessels filled with blood. No peritonitis, or ascites, or ecchymoses in the mucous membranes were noted in the autopsies made on sheep by Ruedi. The liver has been seen enlarged. In sheep the brain was anæmic. Microscopically the brain showed atrophy and the Purkinjie's cells disappeared or their processes atrophied. In these sheep the brain was so anæmic that the distinction between the gray and the white matter was hard to define.[78] The membranes of the cord have been found inflamed and adherent, but the spinal cord was usually normal.[79] In some cases, however, the spinal cord has been found softened[80] and oedematous. The arteries of the limbs were gorged with blood,[81] and at the same time there was a collection of serum in the abdominal cavity. Death is thought to be due to starvation.[82] In other words, the pathological condition, according to published accounts, shows little that is characteristic save some action on the gastro-intestinal tract.

* * * * *

FOOTNOTES:

[71] Anderson, F. W. Poisonous Plants and the Symptoms They
Produce. Bot. Gaz., vol. 14, p. 180. 1889.

[72] Sayre, L. E. Loco Weed. Amer. Vet. Rev., vol. 11, p.
558. 1887.

[73] O'Brine, D. Progress Bulletin on the Loco and Larkspur.
Colo. State Agric. Coll. Bul. 25, p. 12. 1893.

[74] Faville, in O'Brine, D. Progress Bulletin on the Loco
and Larkspur. Colo. State Agric. Coll. Bul. 25, p. 11. 1893.

[75] Sayre, L. E. Loco Weed. Amer. Vet. Rev., vol. 11, p.
559. 1887.

[76] Stalker, M. The "Loco" Plant and Its Effect on Animals.
Bur. Animal Industry, 3d Ann. Rept. (1886), p. 274.
1887--Sayre, L. E. Loco-Weed. Amer. Pharm. Assoc. Proc., vol.
38, p. 108. 1890.--O'Brine, D. Progress Bulletin on the Loco
and Larkspur. Colo. State Agric. Coll. Bul. 25, pp. 16, 17.
1893.

[77] Mayo, N. S., l. c., p. 118.

[78] Ruedi, C. Loco Weed (Astragalus Mollissimus): A
Toxico-Chemical Study. Trans. Colo. State Med. Soc., 1895, p.
418.

[79] Sayre, L. E. Loco Weed. Amer. Vet. Rev., vol. 11, p.
559. 1887.

[80] O'Brine, D. Progress Bulletin on the Loco and Larkspur.
Colo. State Agric. Coll. Bul. 25, p. 12. 1893.--Klench, J. P.
Rattleweed or Loco Disease. Amer. Vet. Rev., vol 12, p. 399.
1888.

[81] Anderson, F. W. Poisonous Plants and the Symptoms They
Produce. Bot. Gaz., vol. 14, p. 180. 1889.

[82] McCullaugh, F. A. Locoed Horses. Journ. Comp. Med. and
Vet. Archives, vol. 13, p. 436. 1892.

=HISTORICAL SKETCH OF LOCO INVESTIGATIONS FROM A PHARMACOLOGICAL STANDPOINT.=

During the western immigration of 1849 the Indians along the Missouri River described to the immigrants a plant (_Astragalus mollissimus_) producing death in horses and cattle, which was preceded by various forms of excitement.[83]

The attention of the United States Department of Agriculture was first called to the toxic action of the loco plants in 1873, when specimens of the plants, which were identified as _Astragalus hornii_ and _A. lentiginosus_,[84] were sent from California by Mr. O. B. Ormsby, with the statement that they were poisonous to stock, especially to horses. Mrs. J. S. Whipple also corroborated this information. The botanist of the Department, Dr. George Vasey,[85] published a note and requested further information concerning the plants. These notes were enlarged by a similar contribution by Dr. P. Moffat on _Aragallus lamberti_.[86] The following year Vasey reported with more fullness, and his description of the action of the plants is substantially what we find in most of the books of to-day.

In 1876 Lemmon[87] noted that _Astragalus mortoni_ was "a deadly sheep poison." At the same time Rothrock,[88] botanist of the United States Geographical Survey under Lieutenant Wheeler, described these plants, and Kellogg,[89] a botanist in California, reported that _Astragalus menziesii_ was causing great losses in horses, sheep, and cattle and claimed that the stockmen had been familiar with this disorder for at least ten or fifteen years. This report of Kellogg was followed by that of Rothrock[90] in 1877.

In 1876 a specimen of _Aragallus lamberti_ was sent from Colorado to Professor Prescott, of the University of Michigan, under the name of "crazy weed," with the statement that it was poisonous to horses and cattle and that, while the Mexicans often used it in making beer, it sometimes caused symptoms in men. His pupil, Miss Watson, undertook a study of its chemical properties. She failed to isolate any pure chemical compound, but claimed that in the root there was a body giving alkaloidal reactions and that there was also a resinous body present. Another of his pupils, W. R. Birdsall, took the ground-up root himself in doses of 20 grains at various intervals for several days and later 40-grain doses in one and a half hours, but without experiencing any marked symptoms except colicky pains. A kitten also was given about one and a half ounces of the fluid extract without effect. Prescott[91] sums up by saying that "it would seem that the dried ground root possesses no poisonous properties." The work of Miss Watson was considered of sufficient importance to be abstracted in the Annual Report of the Commissioner of Agriculture for 1878 (1879), page 134.

Gradually the Department of Agriculture became more and more interested in this subject, and Peter Collier, chief chemist, in 1878, examined the roots and leaves of _Aragallus lamberti_ for alkaloids, but found none.[92]

In 1880 Peter Collier published a proximate analysis of _Astragalus mollissimus_ made by Francis A. Wentz, of Kansas. His investigations showed it to have an ash content of 6.76 per cent, while the _Aragallus lamberti_, analyzed by L. F. Dyrenforth, of Chicago, showed an ash content of 4.32 per cent. Collier[93] sums up by saying:

From the additional work done at this Department it seems probable
that the deleterious effects observed from animals eating this
plant may be due principally to the fact that the sweet taste
causes cattle to reject more nutritious food and strive to subsist
upon the Oxytropis only. 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. Again, it seems
probable that the plant may contain much larger proportions of
alkaloid at certain stages in its development than at others, or
the seeds may prove to be the most injurious portion.

The departmental work was continued by further short notices by Vasey[94] in 1884, 1886, and 1887, and by the report of Stalker in 1887. This report by Stalker is still the best description on the clinical side of the question.

Rothrock,[95] meeting the loco plants in his survey work, describes their effects on animals as follows:

Certain it is, however, that, once commenced, they continue it,
passing through temporary intoxication to a complete nervous and
muscular wreck in the later stages, when it has developed into a
fully marked disease which terminates in death from starvation or
inability to digest a more nourishing food. The animal toward the
last becomes stupid or wild, or even vicious, or, again, acting as
though attacked with "blind staggers."

Under the name of Crotalaria, H. Gibbons,[96] in 1879, refers to a plant growing in California which it was claimed was producing characteristic symptoms of poisoning in horses and sheep. This plant Professor Maisch afterwards identified as _Aragallus lamberti_.

Dr. Isaac Ott[97] undertook the physiological study of the question and used an alcoholic extract of _Astragalus mollissimus_. He found from its action on frogs, rabbits, and cats that the plant had decided physiological action, as follows:

(1) It decreases the irritability of the motor nerves.

(2) Greatly affects the sensory ganglia of the central nervous
system, preventing them from readily receiving impressions.

(3) Has a spinal tetanic action.

(4) Kills mainly by arrest of the heart.

(5) Increases the salivary secretion.

(6) Has a stupefying action on the brain.

(7) Reduces the cardiac force and frequency.

(8) Temporarily increases arterial tension, but finally decreases
it.

(9) It greatly dilates the pupil.

Doctor Stockman, in England, about this time tried the action of the aqueous and alcoholic extracts of the dried _Astragalus mollissimus_ sent from Texas. He experimented with frogs and rabbits in increasing doses, but without result.[98]

In 1888 Hill reported that a species of Astragalus was acting detrimentally on cattle, goats, and sheep in Cyprus and that these animals fell down as if intoxicated, and also that the natives in time of great drought feed their cattle with this plant mixed with straw, but that they were always made sick until they became used to it.

In 1885 Professor Sayre, of the University of Kansas, undertook the investigation of the loco question. His first report was made in the Transactions of the Kansas Academy of Sciences for 1885, and his reports have been continued at various periods up to 1904. 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. He has, however, done some work on the pure chemistry of the plant and found that the plant contained 10 per cent of moisture and yielded 12.01 per cent of ash. Of this ash, 25 per cent was soluble in water, while 50.6 per cent was soluble in HCl. The insoluble portion consisted largely of silica. He found CaO, K_{2}O, MgO, Al_{2}O_{3}, and Fe_{2}O_{3}, with the acid radicals SO_{3}, Cl, P_{2}O_{5}, CO_{2}, and SiO_{2}.[100] Although Sayre claims that the plant is physiologically inactive, he tried by chemical means to isolate a physiologically active body and, naturally enough under the circumstances, failed to find one. He claims that while the plant might give alkaloid reactions, he was unable to isolate this body in a pure state, and that alfalfa reacted similarly.

The investigation on animals was continued by Kennedy.[101] He administered an infusion of 1/2 ounce of green _Astragalus mollissimus_ to a fasting dog weighing 23 pounds, but there were no symptoms after 12 hours. A decoction of 1 ounce of the green plant and one of 4 ounces of the dried plant were likewise without action. Extracts with hydrochloric acid were also inactive. 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. He overlooks, however, the fact that the plant might vary in its toxicity, and he infers from the experiments on carnivorous animals that these results would hold good for herbivora, yet he does not claim that carnivora become locoed in nature.

Kennedy found that the plant lost 80 per cent in weight on drying and that the water extract which represented 30.6 per cent of the powdered and dried plant contained magnesium sulphate and sodium chlorid, tannic acid, gum, coloring matter, an extractive, and a "peculiar organic acid." The ashed plant yielded 20 per cent of ash, consisting of magnesium sulphate, sodium chlorid, alumina, silica, and a trace of iron. "The abundant precipitate produced by the alkaline hydrates, potassium, sodium, and ammonium was found to consist of magnesium hydrate, an abundance of this base being present in the plant." Kennedy also obtained alkaloidal reactions, but failed to isolate the body giving these reactions.

In 1889 the investigations were greatly stimulated by the report of Doctor Day,[102] then of the University of Michigan. She claimed that she was able to produce marked physiological symptoms, using both _Astragalus mollissimus_ and _Aragallus lamberti_ in her work. She administered daily 60 to 70 c.c. of a decoction[103] of the plants to kittens, together with abundant milk and other food. She states that in two days--

The kittens became less active, the coat grew rough, appetite for
ordinary food diminished and fondness for the "loco" increased,
diarrhea came on, and retching and vomiting occasionally occurred.
The expression became peculiar and characteristic. Emaciation and
the above symptoms progressively increased until the eighteenth
day, when periods of convulsive excitement supervened. At times the
convulsions were tetanic in character; frothing at the mouth and
throwing the head backward as in opisthotonus were marked. At other
times the kitten would stand on its hind legs and strike the air
with its forepaws, then fall backward and throw itself from side to
side. These periods of excitement were followed by perfect quiet,
the only apparent sign of life being the respiratory movements.
After a short interval of quiet the convulsive movements would
recur. These alternate periods of excitement and quiet lasted
thirty-six hours, when the posterior extremities became paralyzed,
and the kitten died about two hours afterward. There was no
apparent loss of consciousness before death.

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. By the twelfth day the cat was wasted almost to
a skeleton, and was correspondingly weak. Paralysis of the hind
limbs came on, and the cat died on the thirteenth day. There were
no periods of excitement in this case.

These cats developed a craving for the decoction and "would beg for it as an ordinary kitten does for milk, and when supplied would lie down contented."

Doctor Day made controls with healthy animals under the same conditions, with the exception that they received no loco plant. She also fed a young wild jack rabbit on milk and grass for a few days and then substituted fresh loco plants for grass.

At first the "loco" was refused, but after two or three days the
"loco" was eaten with as much relish as the grass had been. After
ten days of the milk and "loco" diet the rabbit was found dead,
with the head thrown back and the stomach ruptured.

Subcutaneous injections of the concentrated decoction caused
nervous twitchings in frogs and kittens, and if large amounts were
used death followed in from one to two hours from paralysis of the
heart. The same symptoms were produced in frogs by the injection of
an alcoholic extract of the residue left after the evaporation to
dryness of the decoction.

In other words, Doctor Day was able to produce a chronic form of loco poisoning with the characteristic symptoms so often described save in the occurrence of diarrhea. Diarrhea is not usually noted on the range. Sayre had already reported an ulcerated condition of the intestines of a locoed cow similar to that described by Doctor Day as occurring in cats. Doctor Day urged that the reason previous experimenters failed to produce symptoms was that they had used too small an amount of the plant and that by systematic feeding to healthy cats cases of loco disease may be produced.

Storke states that "Dr. V. C. Vaughan, of the University of Michigan, has since fully corroborated Dr. Day's views."[104]