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BULLETIN OF THE 

U^PEPMMFOFAKDDll 



Dtribudon fiom the Bumu of Plant bdoatiy, Wm, A. Tayloc, a 

ud the Buruu of Animal ImWry. A. D. Melnn, Chief. 

May 13. 191 S. 

(PROFESSIONAL PAPER.) 

ZYGADENUS, OR DEATH CAMAS. 

By C. DwiGHT Marsh and A. B. CLiwaox, PhygioiogiaU, Drug-Plant and Poiaowmt- 
Plant InveaUgatione, and Hadleioh Marsh, Veterinary Inapector, Bureau of Ani- 
mal Indnitry. 

INTRODUCTION. 

HISTORICAL 8DMHARY AND REVIEW OF LTTERATURE. 

Chesnut and Wilcox (1901, p. 52)' say that "the earlier explorers 
of the Western, and especially of the Northwestern, United States fre- 
quently mention the poisonous character of the bulbs of one or the 
other of the various species of Zygadenus and refer to them as poison 
camas or poison sego in order to distinguish them from bulbs of two 
other groups of plants, Quamasia and Calochortus, which were com- 
monly known as camas and wild sego and were much xised for food, 
both by the Indians and by travelers. Accounts of the poiaonii^ 
of stock from eating the roots and leaves of various species have but 
recently been sent to this Department." 

This statement, perhaps, covers the knowledge of the subject up 
to that date, although the writers have failed to find much in the 
way of definite statement among the earher writers that can be re- 
ferred to this plant. 

In Wyeth's journal of his second expedition to Oregon (Wyeth, 
1899) occurs this statement: 

16th. Made down the Sandy S. W. by W. 15 milea then 4 S. E. by E. and camped 
on thiB stream bo far the grass is miserable and the honiee are starving and also at last 
night's camp they eat something that has made many of them sick the some thing 
happened two year eince on the next creek weet. 

This happened on June 16, 1834, somewhere between Big Sandy 
Creek and Leckie, in Fremont County, Wyo. The present knowl- 
edge of the botany of that region makes it almost certain that the 
poisonous plant in that place at the time of year mentioned must 

' For th« oamplat« tithe Of works OlM, s« tli« 11>t of Utcnttnre On vtm *^ and 46. 



47698"— BuU. 12&— 15 



2 BULLETIN 125, U. S. DEPARTMENT OF AGRICULTURE. 

have been Zygadeniis. This is the earliest reference to probable 
poisoning by Zygadenns which has been found by the writers. 

Asa Gray (1848) says of Amianthium nuttaUiij now known as 
Zygadenus nuttdUiij ''Crescent cum Kamassa escnlenta, quo bulbi 
nocentes viatoribus saepe confusi sunt.'' 

Hooker (1838) says of Leimanthium nutaUiif which is the same as 
the species mentioned by Gray, '' 'Poison or Death Camass' of 
the Chenooks, from the violent effects of the roots, which create 
vomiting.'' 

Watson (1880) speaks of Zygadenus venenosus as poisonous and 
known to the Indians- as "Death-Camass," and says, on page 184, that 
the bulb of Z. panicvlatus is also poisonous. 

Apparently the Lloyds (1887) were the first to state definitely the 
symptoms produced by the plant in human beings. 

Irish (1889) fed "cammers" to steers without effect. 

Hillman (1893) published a newspaper bulletin calling attention 
to the poisonous character of Zygadenus, and in 1897 he published 
another newspaper bulletin on the same subject. Also, in another 
publication (18976, p. 115), he states that a horse is reported to 
have been made sick by the seeds of Zygadenus paniculatus in hay. 

CoviUe (1897) says that Zygadenus venenosus causes extreme vomit- 
ing and that it is sometimes used by medicine men of the Klamath 
Indians, mixed with the dried roots of Iris missouriensis and a little 
tobacco, to give a person a severe nausea, in order to secure a heavy 
fee for making him well again. 

Chesnut (1902, p. 321-322) tells of the knowledge of this plant 
by the Indians of Mendocino County, Cal., and their use of it for 
medicinal purposes. 

Hunt published an abstract in 1902 announcing the discovery of 
the alkaloid. 

In a copy of McCarthy (1903), apparently annotated by the 
author, the statement is made that Zygadenus glaherrimus and 
Z. leimanthoides are poisonous. 

Nelson (1906) demonstrated by feeding experiments the poisonous 
effect of Zygadenus upon sheep. 

REVIEW OF PHARMACX>LOGICAL WORK.1 

The bulbs of Zygadenus paniculatus were found by Collier (1882) 
to give several alkaloidal reactions, but the first attempts to isolate 
and determine the chemical ajid toxic properties of the poison of 
Zygadenus seem to be those of Reid Hunt,^ special expert of the 
Bureau of Plant Industry in 1901, who worked with the leaves and 
flowering tops of Z. venenosus, ^ Hunt prepared an alcoholic extract 

» The review of pharmacological work was prepared by Dr. Reid Hunt, of the Harvard Medical School, 
s Hunt's results were submitted in a report to the Department in 1901 and also reported at a meeting of 
the American Physiological Society. (Hunt, 1902.) 



ZYGADENUS, OR DEATH CAMAS. 3 

and removed various oily and resinous substances by precipitation 
with water and extraction with petroleum ether. These resinous 
bodies were not toxic. Vejux-Tyrode (1904) later obtained similar 
resinous bodies to which he scribed a high degree of toxicity, but 
Heyl and Hepner (1913) could not confirm this. 

Hunt purified the extract further, and then, by extraction with 
chloroform, obtained an amorphous substance alkaHne to litmus and 
giving the usual alkaloidal reactions. It was very sHghtly soluble in 
water, but readily soluble in dilute acids. When treated with con- 
centrated sulphuric acid this substance dissolved with the formation 
of an orange-yellow solution; the color soon became a blood orange, 
and finally a bright cherry red. This play of colors corresponds 
almost exactly to that caused by cevadin and to that recently 
described by Heyl, Hepner, and Loy (1913) for zygadenin, an 
alkaloid obtained by them from Zygadenus intermedins. Hunt 
found, as did Heyl, Hepner, and Loy later, that the alkaloid was not 
readily extracted with ether. When the alkaloid or mixture of 
alkaloids was further purified, dissolved in ulcohol, and the alcohol 
allowed to evaporate, a clear, glassy residue with a few cubes or 
prisms was obtained. This began to darken at 185° C. At 197° C. 
part of it melted to form a red solution, but all of it did not melt 
until a temperature of 220° C. was reached. It is quite probable that 
this mixture consisted in part of the alkaloid since isolated by Heyl, 
Hepner, and Loy and named by them zygadenin. Zygadenin crys- 
tallizes from alcohol in "orthorhombic blocks" and melts to a red oil 
at 200° to 201° C. Hunt pointed out a nimiber of resemblances and 
also certain differences between the reactions of the alkaloids obtained 
from Zygadenus and those given by cevadin and other veratrin 
alkaloids and concluded that both chemically and pharmacologically 
the two series were closely related. 

Torald SoUman, in a report submitted to the Department of Agri- 
culture in 1903, stated that he could find no poisonous principle in 
Zygadenus other than the alkaloid or mixture of alkaloids found by 
Himt. 

These results were confirmed by Slade (1905) and by Heyl, Hepner, 
and Loy. The latter authors carried the work to the point of 
isolating in pure form an alkaloid which they named zygadenin, 
although the question whether this may not be identical with some 
one of the veratrin alkaloids is, perhaps, stiQ open. It may also be 
doubted whether zygadenin is the most important toxic agent in 
Zygadenus, for these authors quote Mitchell as reporting that "it 
(zygadenin) killg guinea pigs slowly and only in comparatively large 
doses." Hunt found 4 milligrams per kilo of his alkaloidal prepara- 
tion to be fatal to rabbits in an hour or two. SoUman foimd about 
the same amount of cevadin to be fatal. 



4 BULLETIN 125, U. S. DEPARTMENT OF AGRICULTtJBB. 

Hunt found, as did Heyl and Raiford (1911), that the leaves and 
flowering tops contain more of the alkaloid thaja the bulbs. By 
performing an extensive series of experiments on animals with the 
Zjga,demis alkaloids, he found that their action was in all essential 
particulars the same as that of veratrija. They were very irritat. 
ing to the mucous membranes, as was the powdered plant itself; 
they produced an intense burning sensation and a very acrid^ 
bitter taste in the mouth; when appUed to the skin in alcoholic or 
chloroform solution, they caused a burning, painful sensation, but 
the spot later became anaesthetized; they had the typical veratrin 
effect upon the muscles and, as kymograph experiments showed, 
affected the respiration, blood pressure, and heart in the same way 
as does veratrin. It was also shown that the death of animals 
poisoned with Zygadenus was hastened by attempts to arouse them. 
This was attributed to the rapid failure of the respiration, circulation, 
and the muscular system. It was concluded that under laboratory 
conditions (and probably under field conditions) an essential part of 
the treatment should consist in allowing the animals to rest. 

Hunt also isolated the alkaloids from the urine of animals poisoned 
with Zygadenus. He found that they were excreted with the urine 
quite rapidly and demonstrated that under laboratory conditions it 
was often possible to save the life of poisoned animals (rabbits, sheep, 
etc.) by the administration of diuretic drugs (caffein, theobromin, 
sodiosalicylate) . Atropin and strychnin seemed to hasten death. 

Sollman, after satisfying himself that the toxic action of Zygadenus 
is identical with that of veratrin, made a study of poisoning by the 
latter. He found that a single dose often caused prolonged sickness 
and that small, repeated doses caused no tolerance, but increased 
the susceptibility, and suggested demulcents, such as linseed decoc- 
tion, to coimteract the corrosive action on the alimentary tract. 

It is evident from these chemical and pharmacological studies that 
the poisonous properties of Zygadenus are essentially those of vera- 
trin, the indications for treatment being the same in the two cases. 

DESCRIPTION OF ZYGADENUS. 

The genus name Zygadenus is used in this paper as defined in 
Hobinson and Fernald's revision of Gray's Manual and in Coulter and 
Nelson's New Manual of Botany of the Central Rocky Mountains. 
It includes the three genera, Zygadenus, Anticlea, and Toxicoscordion, 
of Britton and Brown's Illustrated Flora. The plants are erect, peren- 
nial, glabrous herbs, growing from a rootstock, or, as in the case of all 
the western species, from a tunicated bulb, with a leafy stem. The 
leaves are grasslike, long, narrow, and keeled. The flowers are green- 
ish yellow or white, borne in a terminal raceme or panicle. This 



ZYGADENUS, OR DEATH CAMAS. ' 5 

raceme varies in the diflferejit species from a^ almost solid head; as 
see^ in Plate I, to a very loose, elongated panicle, there being a con- 
siderable range of variation in the inflorescence within the limits of 
the same species. The perianth is spreading, withering-persistent, 
the sepals bearing one or two glands near the base. The stamens are 
free or attached to the bases of the segments. The capsule is three 
lobed and dehiscent to the base in matm*ity. 

The species of Zygadenus are spring and summer plants. On 
May 8, 1913, in the neighborhood of the Greycliff station, Mont., 
Z. venenosus was about 4 inches high, the largest plants not exceeding 
6 inches, and the flower scape was not visible. On May 11 the plants 
were in bud, and they blossomed through the month of June. Seeds 
were formed the last of June and early in July, and after the middle 
of August the plants had largely disappeared. 

Zygadenus elegans was in full blossom near Red Lodge, Mont., on 
July 20, at an altitude of approximately 6,000 feet. In 1910 Zyga- 
denus coloradensis was in blossom in Colorado at about the same 
time (July 20) at an altitude of about 10,000 feet. 

In Montana, Zygadenus venenosus grows typically at lower levels 
than Z, elegans. As stated by Chesnut, its favorite habitat is in the 
shallow ravines occurring on hillsides. It does not grow abimdantly 
on dry hillsides nor in wet ravines, but it is very commonly found 
in the shallow depressions on the north slopes of bench lands. Z. 
elegans grows at higher levels (Rydberg gives as its limits 6,500 to 
12,500 feet) and in locations where more water is available than is 
necessary for Z. venenosus. While it grows readily on hillsides, it 
reaches its best' development in size in distinctly wet places, some- 
times immediately in contact with rivulets. 

In California and Oregon, Zygadenus venenosus grows in the 
meadows, while Z. paniculatus grows upon the hillsides. Z. veneno- 
sus is more common on north slopes and Z. paniculatus on south 
slopes. 

The species of Zygadenus may grow as more or less scattered indi- 
viduals, but sometimes they are massed together in large areas, 
including, perhaps, several acres, in which, at the time of flowering, 
they seem to be the principal vegetation and give a characteristic 
greenish yellow color to the landscape. 

The species of Zygadenus are distributed very widely in the United 
States and are found as far north as Alaska. They occur most 
abimdantly from the Rocky Mountains west to the Pacific, and their 
importance as stock-poisoning plants is confined almost entirely to this 
part of the United States. Plate I shows the general appearance of 
Zygadenus venenosus. This is an Oregon plant and shows the flowers 
as they appear at the beginning of blossoming. Later, the raceme is 



6 BULLETIN 125, U. S. DEPARTMENT OF AGRICULTURE. 

more extended, as shown in Plate II, which is reproduced from a 
photograph of a Montana plant. Plate III shows the plant after 
the seed is formed. 

COMMON NAMES OF ZYGADENUS. 

The species of Zygadenus are known under a large number of pop- 
ular names. The most common perhaps is death camas. In the 
Northwest perhaps lobeUa is the name used even more generally than 
death camas. Other names are soap plant, alkali grass, water lily, 
squirrel food, wild onion, poison sego, poison sego lily, mystery grass, 
and hog's-potato. Z. glaherrimus is said to be called cow-grass. 

POISONOUS SPECIES OF ZYGADENUS. 

The following species of Zygadenus are said to be poisonous: Z. ^ 
eleganSy Z. falcatusj Z. fremontiij Z. glaherrimus, Z. intermedius, Z. 
mexicanuSy Z. nuttaUiiy Z. paniculatus, Z. venenosus. 

This list is given in accordance with the statements of various 
authors, and no attempt has been made to revise it from the stand- 
point of the systematic botanist. Apparently aU species of this genus 
may be presumed to be poisonous. Even Zygadenus coloradertsis, 
which has been shown not to be injurious to stock in Colorado, has 
the same poisonous principle as the other species, but in smaller 
quantity. 

LOSSES OF UVE STOCK BY ZYGADENUS. 

As already stated, there is reason to think that deaths of cattle and 
horses from Zygadenus poisoning are not numerous. With sheep, 
however, the losses are very heavy, but it is impossible to make even 
an approximate estimate of these losses. It is probable that they 
are much greater than is generally supposed, for in the sheep-grazing 
regions many, perhaps most, of the herders do not know the plant and 
consequently do not recognize it as the cause of illness and death in 
the bands under their charge. The lupines, without any doubt, have 
been blamed for many of the cases of poisoning by Zygadenus. 

Chesnut and Wilcox (1901, p. 53) state that 636 sheep died from 
Zygadenus poisoning in Montana in 1900 and that 3,030 were poisoned. 
In one locahty in Wyoming 500 sheep died out of a total of 1,700 
poisoned, and in one coimty it was said that 20,000 died in 1909. The 
writers of this paper investigated a case in Montana in which 500 sheep 
died within a few hours, the probable cause being Zygadenus. 

There is no doubt that this plant is one of the sources of heaviest 
loss to sheep owners, especially in Wyoming and Montana. There is 
good reason, too, for thinking that many of the losses in Oregon, 
Utah, and California which have been ascribed to other plants were 
really caused by Zygadenus. 




Zygadenus Venenosus from Klamath Aoency, Ores. 



ZvGADENus Venenosus from Montana, rN Bloom. 



ZVGADENUS VENENOSUS FROM MONTANA, fN FHUIT. 



D Position Indicatino 



ZYGADENUS, OR DEATH CAMAS. 7 

ANIMALS POISONED BY ZYGADENUS. 

Swine axe said to eat Zygadenus bulbs with no bad results (Parsons, 
1904, p. 8). 

Cattle are susceptible to the poison and there are reports of result- 
ing deaths. So far as has been learned, however, deaths of cattle 
from this cause are not common, and it is not especially to be feared 
by the cattlemen. ' 

Many cases of horses poisoned by this plant are reported. The 
animals are made very sick, but apparently most of them recover. 
Mr. Uttermohl, of Bigtimber, Mont., who has had considerable expe- 
rience with Zygadenus, is of the opinion that some of those that 
recover are permanently injured. 

Sheep are the animals most frequently poisoned. This is probably 
due in part to a greater susceptibility to the toxic principle of Zyga- 
denus, but very probably it is to a considerable extent due to the way 
in which sheep are managed upon the range. While grazing, they are 
frequently herded rather compactly, so that they eat the forage closely, 
and when passing over a Zygadenus area many of them may eat a 
large quantity of this plant. 

The cases of hmnan poisoning are mostly of children, who find 
the bulbs attractive and sometimes collect them instead of the edible 
camas, species of Calochortus and Camassia. Most of these cases 
recover, but there have been a nunjber of fatalities. 

SYMPTOMS PRODUCED BY ZYGADENUS POISONING. 

With the exception of the work of Chesnut and Wilcox, nothing 
as bieen published in regard to the symptoms exhibited by grazing 
limals. These authors (1901, p. 61) state that the principal 

-mptoms of poisoning in sheep are salivation, nausea, uneasiness, 

aggering, muscular incoordination, paralysis, and convulsions. 

le animals sometimes lie many hours before death. The writers 
ir entioned state also that cattle and horses have spasms. 

Several investigators have mentioned some of the symptoms m 
man. Heller (1909, p. 52) gives the symptoms (quoting from 
Dr. Lee, of Carson) as *' nausea, headache, followed by more or less 
stupor." He states that the heart's action was lessened in frequency, 
while the strength of the pulse remained normal. The respirations 
were almost normal. In another case vomiting was followed by 
the loss of all power of feeling. 

Heyl and Kaiford (1911, p. 64) and Hunt (manuscript) speak 
of the irritating character of the dust when the dry plant is being 
ground, which leads to sneezing on the part of those doing the work. 

The Lloyds (1887) give as symptoms in man '^extreme thirst, con- 
stant vomiting, dilation of the pupil, coma, and inflammation of the 
stomach.'' They also say that one case had very violent convulsions. 



8 BULLETIN 126, U. S. DEPABTMENT OF AGBICULTUBE. 

Chesnut (1902, p. 321) says that the symptoms in poisoned 
Indians are '^burning and smarting in the mouth and esophagus, 
dumbness, nausea, profuse vomiting, foaming at the mouth, dizzi^ 
ness, and mania." 

Mitchell and Smith (1911) experimented with the extract on guinea 
pigs, both by subcutaneous injection and by feeding per os, and found 
salivation, vomiting, excitement, paralysis (first of the hind l^s), 
rapid respiration becoming slow and labored, heightened reflexes, 
spasms, heartbeat slowed, and death, imder fatal dosage, in 20 to 30 
minutes. When injected into dogs imder anaesthesia, the general 
effect was to reduce the rate of heartbeat and respiration and to 
produce marked intestinal peristalsis. The heart stopped before 
the cessation of respiration. 

Hunt, Vejux-Tyrode, and Mitchell and Smith experimented on 
frogs, producing paralysis, which showed itself in an inability to 
draw up the legs readily after extension. Himt considers that it 
produces an effect directly on the muscles as well as on the central 
nervous system. 

Chesnut and Wilcox (1901) and Hunt (manuscript) experi- 
mented with rabbits. Hunt stating that the rabbits exhibited saliva- 
tion, nausea, muscle changes, heightened reflexes, and convulsions. 

Summarizing the published statements in r^ard to the symptoms 
of Zygadenus poisoning, it may be said that the most evident symp- 
toms in the higher animals are salivation, nausea, more or less com- 
plete paralysis, reduced rate of heartbeat and respiration, and con- 
vulsions. The results on frogs are not so marked, as would be ex- 
pected from the less complicated nervous system, and the principal 
thing noticed apparently is paralysis. 

GENERAL STATEMENT OF EXPERIMENTAL WORK. 

Ebq>erimental work upon Zygadenus has been carried on for five 
seasons, in 1909 and 1910 at Mount Carbon, Colo., and in 1912, 1913, 
and 1914 at Greycliff, Mont. Table I gives a summary of these ex- 
periments. In 1909 six head of cattle were fed experimentally on 
Zygadenus colaradensis (Table I, section A). In 1910 a steer and 
four sheep were fed (Table I, sections B and E). In 1912 there were 
18 cases of experimental feeding of Zygadenus venenosus to sheep 
(Table I, section F). In 1913 Zygadenus venenosus from the neigh- 
borhood of the station was fed to 61 sheep. In this section of the 
table are also given the results of one experiment in feeding Zyga- 
denus venenosus from the Stanislaus National Forest, Cal., to a sheep. 
In 1913 Zygadenus degans, collected near Red Lodge, Mont., was 
fed to 6 sheep (Table I, section H). In 1914 there were 110 cases 
of feeding of Zygadenus venenosus to sheep (Table I, section I) and 
five experiments of feeding to sheep Zygadenus elegans from the 



ZYGADENUS, OB DEATH CAMAS. 9 

Fishlake National Forest, Utah (Table I, section J). There were 
also two experimental feedings of Zygadenus fanicndatus from 
Ephraim, Utah (Table I, section K). Three head of cattle in 1913 
were fed upon Zygadenus veneTwsus (Table I, section C), and a horse 
was fed twice upon Zygadenus venenosv^ and once upon Zygadenus 
elegans (Table I, section D). 

So far as possible, the feeding experiments were carried on under 
natm*al conditions. To this end the animals were, ordinarily, de- 
prived of food for about 24 hours, and then the plant to be tested was 
oflFered to them. If they did not eat readily, they were tempted by 
TnJTnng the plant, sometimes ground up, with hay or grain. As it 
was difficult to get any large number of cases by feeding, on accoimt 
of the dislike of the animals to the plant, resort was had to drenchii^ 
and forced feeding. In the drenching experiments, the plant was 
ground and suspended in sufficient water to make the administration 
possible, the drenching being done in most cases with the animal 
upon its haimches. Forced feeding was conducted in some cases 
by placing the plant by hand, a httle at a time, in the animal's 
mouth. In the majority of experiments in forced feeding, however, 
a veterinarian's ordinary balUng gim was used, and the ground material 
was fed as fast as the animal would swallow it. 

The terms imder ''Severity of illness'' are used in the following 
way: 

**Not sick" includes cases in which no symptons appeared. 

"Symptoms" includes cases in which there was slight salivation for a few minutes, 
some regurgitation, some licking of the lips, indicating nausea, or indications of 
uneasiness. 

** Slightly sick" includes those in which salivation was continued for an hour or 
more, with considerable regurgitation. Depression, slightly labored respiration, and 
temperature reduction may occur. 

**Sick** includes cases exhibiting vomiting, weakness, and sometimes hyper- 
sensitiveness and trembling. 

"Very sick " cases were characterized by prostration, extreme respiratory diflBiculty, 
and subnormal temperature. 

47698°— Bull. 125—15 2 



10 



BULLETIN 125, U. S. DEPARTMENT OF AGRICULTURE. 






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20 BULLETIN 125, U. S. DEPABTMENT OF AGRICULTUBE. 

FoUowing are the details of three cases which may be considered 
typical: 

Sheep No. 19S. — This animal (Table I, section G) was a 2-year-old ewe, lent for 
experimental purposes by Mr. Ole Birkeland. She was received at the station on 
May 9, 1913. An attempt was made on May 12 to feed to her the bulbs of Zygademis 
vmenosus ground and mixed with bran. As she would not eat this, a trial was made on 
May 13 of feeding her with Zygadenus tops, but these also she refused to eat; so at 1.40 
p. m. of the same day she was drench^ with 200 grams of Z. vervenosTis bulbs ground 
fine and suspended in water. At 2.35 p. m. she was frothing at the mouth and vomit- 
ing, with violent contractions of the diaphragm and abdominal muscles. She was 
lying down, but was able to stand. At 3.50 p. m. she was still frothing at the mouth, 
but was fairly strong. At 5.30 p. m. her temperature was 101° F. She was fairly strong, 
but acted as though in much discomfort. On May 14, at 7 a. m. she appeared entirely 
normal, and at 8.30 she was turned out to pasture. 

On June 14, 1913, she was kept in for feeding, and at 8. 15 a. m. she was fed 100 grams 
of fresh tops of Zygadenus venenosus, which were collected on June 12. At this time 
the plant was in flower. At 4.40 p. m. she was fed 200 grams of the plant, and at 7.40 
p. m. 135 grams. 

On June 16, at 7.10 a. m., she was fed 200 grams; at 6.40 p. m., 200 grams; and at 7.15 
p. m., 250 grams. All the Zygadenus fed on June 16 had been collected on the pre* 
ceding day. 

On June 17, at 6.45 a. m., all the Zygadenus given on the preceding day had been 
eaten. The animal appeared bright, but showed sensitiveness to sudden noises and 
there was some trembling of the surface muscles. At 7 a. m. she was run aroimd the 
corral. It was found that she moved in a stiff-legged manner and was somewhat weak. 
The stiffness was most noticeable in the hind legs. She was licking her lips and rul> 
bing her nose against the fence and moving her head about in a jerky way. At 8.46 
a. m. the symptoms were about the same as at 7. a. m. At this time she was fed 200 
grams of Zygadenus. At 11.30 a. m. and 1.50 p. m. she was fed 100 grams of Zygadenus. 
At 3 p. m. her temperature was 103.8° F. She was more nervous than in the morning 
and her movements were somewhat more stiff. The jerking movements were more 
pronoimced and continuous. All the Zygadenus which had been previously given 
had been eaten. At 8 p. m. the symptoms as noted at 3 o'clock still continued She 
was fed a little alfalfa. 

On June 18, at 6.45 a. m., the sheep was trembling almost constantly, with frequent 
spasmodic movements. Her legs were stiff as she walked about, and there was some 
lack of control. She was dejected and dull and without appetite. At 9 a. m. she 
was given 5 grams of tannic acid. At 9.40 she was given 4 ounces of Epsom salts in 
solution. At 10.30 a. m. she was put in a metabolism cage, in order to collect the 
excretions. At 2 p. m. she seemed to be decidedly better, and continued in about the 
same condition throughout the afternoon. 

On June 19, at 6.30 a. m., the animal trembled, but showed no other symptoms. 
She had not urinated since being placed in the metabolism cage at 10.30 a. m. on the 
preceding day. At 8 a. m. she was taken out of the cage and fed some alfalfa. The 
general appearance of the animal was better than on the preceding day, but she was 
stiU imsteady in her gait and exhibited trembling of the surface muscles. At 1 p. m. 
she defecated as the result of the dose of magnesiiun sulphate given on the preceding 
day, and this defecation continued in a mild diarrhea. At 3 p. m. she urinated for 
the first time after being placed in the metabolism cage. At this time her respiration 
was 148, and she seemed in general to be worse. At 8 p. m. she was given 1 gram of 
diuretin in solution, and returned to the metabolism cage. During the afternoon the 
animal seemed to be gradually getting worse. When standing, her hind legs were 



ZYGADENU8, OR DEATH CAMAS. 21 

drawn forward under her. The muscles of the legs were twitching almost continu- 
ously, and it was with difficulty that she could get up and down. 

On Jime 20, at 6.30 a. m., there were about 1) pints of urine which had accumulated 
through the night. This was preserved in alcohol, and a chemical examination 
showed that it contained the alkaloids of Zygadenus. The diarrhea still continued. 
The general condition of the animal was nearly the same as the preceding night, except 
that she appeared a little stronger. She was taken out of the cage and fed alfalfa. 
At 2 p. m. she was somewhat better than in the morning and had an appetite, although 
she still preferred to lie down. At this time she was given 1 gram of diuretin in solu- 
tion. At 7.50 p. m. she was much better, standing in a more normal manner and with 
no noticeable trembling. On Jime 22 she was turned out, apparently all right. 

On July 15, 1913, the sheep was again kept in for feeding, 'and on July 16, at 10.30 
a.m., she was given 200 grams of the mature heads of Zygadenus venenostLS, consisting of 
pods and seeds, groimd and mixed in btan. 

On July 17, at 9.25 a. m., she was fed 270 grams prepared as the day before, and at 
1.25 p. m. she was fed 180 grams. At 7.45 p. m. she was fed 210 grams. At the time of 
the last feeding she showed the effects of the poisoning. She did not move with the 
usual freedom, and there was some twitching of the surface muscles of the body. 

On July 18, at 9.50 a. m., she was fed 235 grams. At 6.30 p. m. she was fed 220 
grams. During the day there was little change in the condition of the animal. 

On July 19, at 7 a. m., the symptoms were much more pronounced than the preceding 
night. There was stiffness of movement of the 1^2;s, licking of the lips, and slight 
trembling. This stiffness and accompanying clumsiness were more pronounced in 
the hind legs. At 9 a. m. she was fed 255 grams and at 3 p. m. 195 grams. At this 
time the animal was considerably weaker than in the morning. 

On July 20, at 8.45 a. m., all the Zygadenus given on the preceding day had been 
eaten, and the general condition of the animal was about the same as on the preceding 
night. She moved with some difficulty and with marked stiffness of the legs. There 
was trembling of the surface muscles accompanied by some shaking of the head and 
licking of the lips. She was unusually sensitive to noise, as she was easily startled, 
and at such times there were sudden contractions of the body muscles. She had much 
difficulty in raising her feet sufficiently to get over elevations of 3 or 4 inches. 

On July 21, at-3 p. m., the animal had improved in its general condition, although 
the symptoms were still well marked. These did not differ from those seen earlier in 
the sickness, but were less pronoxmced. 

On July 22, at 7 a. m., the animal moved about fairly well, but there was some 
trembling of the surface muscles, especially in the shoulders. She improved during 
the day and at 7 p. m. seemed to be quite normal. On July 23, at 7.55 a. m., she 
was turned out to pasture, appearing strong and active and showing no symptoms 
except some slight trembling when handled. 

Sfieep No. 160, — ^This animal (Table I, section F) was a ewe lent by Mr. Ole Birke- 
land on June 20, 1912. On July 19, 1912, she was taken in for feeding with Zygadenus 
venenosus. At 11 .05 a. m. her respiration was 28, pulse 26, and temperature 105® F. At 
11.25 a. m. she was drenched with 125 grams of the seed heads of Zygadenus venenosus 
suspended in water. These seed heads included the pods and seeds. At 11.35 a. m. 
there was a little frothing at the mouth. At 11 .40 a. m. her respiration was very rapid 
and irr^ular. It would run as high as 200 per minute for perhaps 50 respirations, 
then stop, only to be resumed at the same rapid rate. At this time the animal had 
vomited. At 12.55 her pulse was 95 and very variable; her temperature was 104® F. 
At 1 p. m. her respiration was 200 or more and the heart action regular and strong. 
She was then given a solution of potassium permanganate. At 1.17 p. m. she was 
getting weaker on her legs. She would start to lie down and nearly fall, but would 
get on her feet after a minute or two and then lie down again. Her respiration was 
about 180 per nunute. At 1.30 p. m. her respiration was still rapid, the mucous 



22 BULLETIN 125, U. S. DEPARTMENT OF AGRICULTTJBE. 

membranes of the mouth somewhat cyanotic, and the ears drooped. At 1.47 p. m. 
she was given subcutaneously 8 grams of caffein. At 1.49 p. m. she threw her head 
up and held her breath for about a quarter of a minute. She repeated this action 
several times. At 2.03 p. m., her temperature was 100® F. The animal seemed 
somewhat stronger. Her respiration was still variable, running as high as 180 per 
minute. Her puke was about 80. She was still frothing at the mouth and apx)eared 
to be in pain. At 2.20 p. m. she had a hard time to breathe. She shook her head, 
staggered about, and lay down . Her respiration was slow and labored . At 2 .22 p . m. 
her respiration was getting more rapid. At 2,23 p. m. the animal seemed to be in 
great pain; her breathing nearly stopped for a minute, but started again in a panting 
manner. Her respiration continued irregular, first fast and then slow and labored. 
At 3 p. m. her temperature was 100.2® F. and her respiration 84, but not afi labored 
as at 2.03 p. m. She was still frothing at the mouth. Her pulse was 96 and strong. 
At 3.30 p. m. her respiration was 160. She fell upon her knees, struggled to get on 
her feet again, but finally lay down. At 4.15 p. m. she was groaning more or less and 
staggered as she attempted to walk. Her respiration was 90. At 4.30 p. m. die was 
lying down and her respiration was very nearly normal. Her temperature was 99.1® F. 
At 5 p. m. she was down again and in pain, groaning continuously, her respiration 
slower than for some time previous, the rate being about 60 per minute . At 5 .04 p . m. 
the animal was lying sprawled out upon her belly. Her respiration was 168. At 
5.38 p. m. she appeared very stupid, almost as if sleepy. She was given subcutane- 
ously 6 grains of caffein sodiobenzoate . At 5 .45 p . m . her temperature was 99 .4® F. , her 
respiration 120 and very variable, and her pulse 96. At 7.10 p. m. her temperature 
was 99.7® F. Her respiration Was slow and variable. After expiration there would be 
a pause followed by two short and shallow inspirations close together. These Woidd 
be followed by a long inspiration, then a full expiration accompanied by a groan. 
This was repeated over and over again, the whole cycle taking about 20 seconds. The 
animal on the whole seemed to be brighter than at 6 p. m. 

At 8 p. m. the animal was given 5 grains of caffein sodiobenzoate. Her temperatuie 
was 100.8® F., respiration 10, and pulse 120. At 10 p. m. her temperature was 100.2® 
F., pulse 120, and respiration 4. The inspiration was deep and the expiratton was 
accompanied by a groan. At 10.55 p. m. her temperature was 100® F. At 11.15 p.m. 
her respiration was 18 and pulse 108. Her general condition was unchanged. 

On July 20, at 7 a. m., the animal's pulse was 100, temperature 100.8® F., and resi»- 
ration 11 . She was then lying with her head bent under her body and would probably 
have died in that position had die not been relieved. She seemed at this timfe mncon- 
Bcious. At 8.45 a. m. her temperature was 100.6® F, pulse 84, and respiration 12. At 
10 a. m. her respiration was 10, and her pulse 84. The animal was in a comatose con- 
dition. At 10.50 a. m, her respiration seemed to be getting more shallow. At 11.15 
a. m. she seemed somewhat brighter than earHer in the day. At 12 m. her temperature 
was 102.6® F., respiration 12, and pulse 108. During the afternoon rfie had been lying 
in practically the same position, with her head slightly raised, resting upon a su'pport. 
She was too weak to move herself at all. At 3 p. m. her respiration was 12. At 3.30 
she was given subcutaneously 10 c. c. of whisky. At 4.20 p. m. her temperature was 
102.8® F., respiration 36, and pulse 116. At 8.05 p. m. she was given subcutaneously 
5 c. c. of whisky. At 9.30 p. m. her temperature was 104.6® F., respiration 18, and 
pulse 120. 

On July 21, at 5.45 a. m., she was found in practically the same condition as the 
preceding night. At 6.45 a. m. her temperature was 104® F., respiration 24, and pulse 
148, and Weak. At 9.50 a. m. she was given subcutaneously 5 drops of fluid extract of 
digitalis in 8 c. c. of whisky. At 10.15 a. m. her pulse was somewhat stronger than 
before the digitalis was given. At 11 a. m. her pulse was 102, temperature 104.6® F., 
and respiration 48. At 3 1 .15 a. m. her respiration was fairly deep, but was somewhat 



ZYGADENUS, OB DEATH OAMAS. 23 

spasmodic. Her pulse was weak. At 11.45 a.m. her respiration was 68. At 9.30 p.m. 
her temperature was 106.3° F., respiration 24, and pulse 120, but weak. The animal 
was given subcutaneously 3 drops of fluid extract of digitalis in 6 c. c. of whisky. 
During the day there had been very Httle change in her condition. She lay in a 
coma, from which she did not rouse herself except occasionally to shake the flies 
from her ears. Her position had been changed from time to time by the attendants. 
She was foimd dead on the morning of July 22. 

At the autopsy the venous blood vessels were found congested and the lungs were 
congested, as were the liver and kidneys. There was considerable inflammation of 
the walls of the fourth stomach and of the whole length of the intestines. Sections 
of the kidney showed that the capillaries were much congested, and there was some 
degeneration of the tubule walls. Sections of the liver showed acute congestion, and 
the same condition was noticed in the sections of the lung. 

Sheep No. 197.— This animal (Table I, section G) was a ewe 2 years old, lent by 
Mr. Ole Birkeland on May 9, 1913. An unsuccessful attempt was made to feed Zyga- 
derms venenostis tops to her on May 12. 

On May 26, at 11.25 a. m., she was drenched with 178 grams of Zygadenua venenosta 
tops suspended in water. These plants were collected on May 23. At 11.40 a. m. 
she was frothing at the mouth. At 11.45 a. m. she was given a drench of 1 gram of 
diuretin and 0.455 gram of caffein citrate. At 11.50 a. m. she was vomiting, and when 
observed at 12 m. the vomiting was continuing. At 12.05 p. m. her respiration was 
getting irregular and deeper. At 12.30 p. m. her respiration was extremely fast and 
she was panting. At this time she was vi(^ently nauseated and threw herself down 
two or three times and then jerked about in a e^asmodic manner. At 12.40 p. m., 
being extremely nauseated she was trying to vomit, throwing herself down, and the 
spasmodic movements were followed by quick, panting respiration. At 12.45 p. m. 
her respiration was about 200. She showed weakness in her legs. At 1.15 p. m. she 
repeated the spasmodic movements which had been noticed at 12.30 and 12.40 p. m., 
evidently struggling to get breath. She threw her head from side to side and ran the 
length of the corral, throwing herself upon the ground and rising again as though 
having a fit. The mucous membranes of the mouth were cyanotic. These move- 
ments were repeated a little later. At 1.30 p. m. she was given a dose of 5 c. c. of gin. 
Another struggle for breath f(^owed, and it was noted after this struggle that her 
heart action was very rapid and strong. The beat was audible to the observers. 
Five c. c. more of gin were given subcutaneously. At 1.36 p. m. she was lying upon 
her side. Her respiration was 160. At 1.40 p. m. she had another struggle for breath, 
throwing herself about violently, even throwing herself over upon her back. These 
struggles were repeated at 1.49 and at 1.53 p. m. The mucous membrane of the 
mouth at both times was very markedly cyanotic. At 1.55 p. m. she was given 5 c. c. 
of gin. At this time she was still strong.enough to get on her feet. She was urinating 
freely. At 1.59 p. m. she passed through another spasmodic attempt to breathe. 
At 2.02 p. m. her pulse was about 200. At 2.06 p. m. there was a spasmodic struggle 
for breatli. At 2.10 p. m. the anunal was breathing with very great difScuIty. Am- 
monia was used to stimulate her respiration. Her pulse was 130. At 2.45 p. m. she had 
great difficulty in respiration, but at this time it was not accompanied by a spasmodic 
struggle. At 3.06 p. m. she had another spasmodic struggle, and ammonia was used 
as a stimulant. At 3.30 p. m. her respiration some of the time was very rapid, becom- 
ing as high as 200 per minute. Then it slowed down and became labored. On the 
whole the quimal at this time seemed somewhat better. At 3.39 p. m. she made a 
struggle to get upon her feet but was unable to do so. Her respiration at this time 
was variable and very labored, the breathing being followed by quick, panting efforts. 
At 4.10 p. m. her respiration nearly stopped. She was stimulated with ammonia. 
At 4.15 p. m. anmionia was again used. At 4.45 p. m. her respiration was 132. At 



24 BULLETIN 125, U. S. DEPARTMENT OF AGRICULTURE. 

5.19 p. m. the animal was upon her side. Her respiration was labored, but seemed 
somewhat stronger. Her condition remained very nearly Hie same until 6 p. m. 
At 6.30 p. m. she was foimd dead. 

The autopsy showed that the lungs were slightly congested; the inner walls of the 
ileum were congested and the venous blood vessels, generally speaking, were fuU. 
It was evident that death had occurred from respiratory paralysis. 

The detailed report of the examination of the internal organs by Dr. Mohler, of the 
Bureau of Animal Industry, is as follows: 

Kidney (cortex and medulla). — ^Many of the intertubular capillaries in the laby- 
rinth of the cortex and some Malpighian bodies show a marked distention, but not 
sufficiently pronounced to be called congestion. There is also a general distention of 
many of the convoluted tubules and the interstices between the capsule of Bowman 
and glomeruli with a serous, oedematous exudate. This latter has distended the 
tubules and compressed the renal epithelial cells, many of which, having become 
atrophic from pressure, disintegrated and desquamated into the lumen of the tube. 
While these changes are quite marked in the convoluted tubules, the oedema, des- 
quamation, and d^eneration are absent in the straight portions of the uriniferouB 
tubules of the medulla. The distention of the capillaries, however, is present ev^ 
in the medulla. No interstitial alterations are present. 

Lung, — ^The characteristic lesion is the intense congestion of the entire organ, the 
presence of small lobular sureas of consolidation, and occasional minute oedematous 
areas. The laiger pulmonary and bronchial vessels are all overdistended, but the 
interfundibular capillaries show not only overdistention but also diapedesis and 
outwandering of the leucocytes. No such capillary hemorrhages or poollike accumu- 
lations of the blood can be seen in this lung as were previously observed in lung 716. 
The bronchial tubes and the smaller bronchi are unaltered . There is no peribronchitis 
present, although the bronchial blood vessels have all participated in the distention 
of the other vessels of the limg. 

Kidney, — ^No acute inflammatory changes present. Evidences of a slight subacute 
catarrhal nephritis accompanied by mild degenerative changes in the renal cells in 
the cortical portion of the kidney. No interstitial changes present. 

Liver. — ^Moderate amount of physiological fatty infiltration and a slight congestion of 
the intralobular capillaries between the liver cords, but no diapedesis of red blood 
cells or outwandering of leucocytes. The hepatic cells proper show a slight amount 
of cloudy swelling in isolated lobules. No interstitial changes present. 

Ileum. — Shows a slight increase in the adenoid tissue in the mucosa and slight 
fullness of the blood vessels in the submucosa. There is, however, no congestion^ 
desquamation, or degeneration present. 

SYMPTOMS IN SHEEP OBSERVED AT THE^ GREYCUFF STATION. 

The very large number of cases of illness and death observed at 
the Greycliflf station furnished an opportunity for a fairly complete 
picture of the symptoms produced by Zygadenus poisoning. The 
symptoms were noted in detail, and the description that follows is 
drawn from a summarized statement formulated from these notes. 

SALIVATION. 

GeneraUy salivation, or frothing at the mouth, was the first 
noticeable symptom and continued through the acute period of the 
illness. It was not invariably present; sometimes it did not appear, 
especially in the fed cases. It was seen in nearly all the drenched 



ZYGADENUS, OR DEATH CAMAS. 25 

cases, and was rarely absent when the attack was acute. The saliva- 
tion was in many cases accompanied by grinding of the teeth. Plate 
IV, figure 1, of sheep No. 160, and Plate IV, figure 2, of sheep No. 192, 
illustrate this stage of the illness. 

NAUSEA. 

Nausea was very pronounced in nearly all cases, and frequently 
resulted in violent vomiting, this vomiting, like the salivation, being 
largely confined to the acute stage of the illness. 

PULSE. 

Routine observations upon the pulse were made in a large number 
of cases. The rate of the pulse is, of course, very variable imder 
normal conditions. When taken before the experimental feeding it 
varied from 52 to 144, although in most cases it was between 60 and 
100. Generally speaking, when the intoxication was not acute there 
was very little change from what would be expected in normal 
variations either in the rate or character of the pulse. In the severer 
cases, especially in those that ended fatally, the rate was from 125 
to 200. While in three cases of sheep not imder the influence of a 
toxic substance the pulse was 144, this condition is imusual; and 
in a general way it seems to be true that if the rate runs much above 
130 a fatal termination of the illness is likely to follow. In the 
severe cases the pulse was weak and sometimes intermittent. 

TEMPERATURE. 

Temperature observations were made in detail in a lai^e number 
of cases. It was considered necessary to get the average of a con- 
siderable number, inasmuch as there is in sheep quite a range of 
variability under normal conditions and also a considerable difference 
in individuals. The extreme range of temperature was from 97.4° 
to 105.7° F. From the cases of 1914, 64 records were made. Of 
these, 8 showed no marked change, 14 exhibited an increase, and 42 
a decrease, and the decrease ordinarily was not very great but in 
some few cases was down to between 97° and 98° F. It is evident 
that, in general, intoxication by Zygadenus is accompanied by depres- 
sion of temperature. In some few cases, ill which there were no 
other symptoms of poisoning, a lowering of temperature was noticed; 
this, however, was not sufficiently general so that it could be con- 
sidered diagnostic in the absence of other symptoms. Curves are 
given (figs. 1 and 2) of sheep 282 and 291. These, it should be stated, 
are not average cases, but they may be considered typical of cases 
in which the lowering of temperature is more marked. 



26 



BULLETIN 126, V. S. DEPARTMENT OF AGBICULTUEE. 



RESPIRATION. 



The rate of respiration had an extremely wide range of variation. 
Quite uniformly in the acute stages of the poisoning, the rate waa 
very rapid, running in some cases as high as 250 per minute. After 
this period the rate was very much reduced, falling to normal or below, 



k^o^ 



« ^ ^ 5! V Hi <^ 



■ .1 ■ ill r I ii» I i ■ 1 




Fig. 1.— Curve of temperature of sheep No. 282. 



and the animal sometimes lay for hours breathing most of the time 
in a slow and labored fashion. This period of comparative quiet might 
be interrupted, sometimes frequently, by times of rapid breathing, 
accompanied by panting and followed quickly by a very slow rate. 
Sometimes, in severe cases, there were times when the animal threw 



/OS 



^ 



f04 






/Of 



is 



/oo 



>?. A/. 1 

<»> 5 ^ 5! N M 



> %> <0 



5 




FiQ. 2.— Curve of temperature of sheep No. 291 . 



itself about violently, fighting for oxygen. This condition lasted for 
perhaps two or three minutes and was succeeded by a period of quiet, 
which was soon broken by another struggle. During these struggles 
the mucous membranes of the mouth were frequently cyanotic. 
The struggles were spasmodic, and when authors state that poisoned 
animals have spasms or convulsions, it is to be presumed that they 



ZTGADBNTTS, OB DEATH CAMAS. 



27 



£00 



/90 



/SO 



/70 



/eo 



J50 



sao 



refer to this condition. It should be noted, however, that in the 
cases observed at the Greycliff station there was no indication of any- 
special tonic or clonic contraction of the muscles; the violent move- 
naents of the animals were simply those caused by distress from 
dyspnoea. 

Figure 3 gives the curve of respiration for sheep No. 174 and may 
be considered typical of the average fatal case. The sheep was 
drenched at 12 o'clock 
iioon and died at 1 1 . 1 5 
p.m. The respiratory 
rate rose to 200 be- 
tween 2 and 3 o'clock, 
when the animal had 
one of the spasmodic 
struggles for breath. 
It then fell to 9 and 
remained low, with 
comparatively slight 
variations, untU the 
time of death. 

Figure 4 gives the 
curve of respiration 
of sheep No. 160, a 
prolonged case. This 
animal was drenched 
with Zygadenus , at 
11.25 a. m., July 19, 
and died during the 
night of July 21. The 
respiration ahnost im- 
mediately after the 
dose was given ran 
up to 200 and during 
the afternoon varied 
between 60 and 168. 
In the evening it fell, and after that time the maximum noticed was 
68, but most of the time it was near 20 or 30. 



I 



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Fig. 3.— Curve of respiration of sheep No. 174. 



MUSCULAR WEAKNESS. 



In all cases of any severity muscular weakness was noticeable. 
Early in the illness the animals staggered, and in the more serious 
cases not only could not rise, but lay flat upon the ground. This 
weakness was most pronounced in the forelegs. Plate V, figure 1, 
shows this condition of weakness in the forelegs in sheep No. 162, 
while Plate V, figure 2, shows the same animal down. Plate VI, 



28 



BULLETIN 125, V. S. DEPARTMENT OF AGBICULTURE. 



figure 1, shows sheep No. 174 when down and very sick. This picture 
was taken just before a spasmodic struggle for breath. 

In many cases in which the animals were strong enough to remain 
on their feet, the gait was peculiarly stiff l^ged. Both fore and hind 
limbs were affected, but the condition was most pronounced in the 
hind legs. Sometimes the hind legs were moved less readily, approxi- 
mating, perhaps, the condition noticed by other writers in laboratory 
experiments. These symptoms were especially noticeable in the 
cases in which the animals were fed and were not very sick. 



5 





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Fig. 4.— Curve of respiration of sheep No. 160. 



TREMBLING AND HEIGHTENED REFLEXES. 



The fed cases generally exhibited trembling and a sensitiveness to 
sudden noises or movements. A blow upon the corral fence was fol- 
lowed by a sudden start on the part of the animal, or a hght blow upon 
the animal was followed by a quick reflex movement. This con- 
dition was not noticed in the drenched cases and seems to be more 
characteristic of prolonged iflnesses. As stated before, this symp- 
tom of heightened reflexes had been noted by both Chesnut and 
Hunt. 

COMA. 

While, as already noted under the head of respiration, death 
resulted from respiratory failure and was frequently preceded by 
spasmodic attacks of dyspnoea, there were other cases in which the 
animals lay quietly hour after hour, and sometimes even for days, 
with labored breathing, in a condition of coma which ended in 



Fig. 1— Sheep No. 168 at 1,30 P. M„ Showing Weakness in Fohelegs. 



Fig. 2.— Sheep No. 168 at 5.45 p. m., when Unable to Rise. 



FiQ. 2.— Sheep No. 161, Down Almost Two Houits a 



ZYGADENUS, OR DEATH CAMAS. 29 

death without any exhibition of spasms. Plate VI, figure 2, shows 
sheep No. 161 in this condition of coma. Sheep that are poisoned 
on the range are more apt to be in this condition of prolonged coma 
than to show the more violent symptoms of dyspnoea exhibited by 
animals that are drenched or forcibly fed. 

SYMPTOMS IN HORSES AND CATTLE. 

No results on horses were reached in the experimental work at 
Greycliff . From conversations with stockmen who have had experi- 
ence with horses poisoned by Zygadenus, it appears that, in general, 
the symptoms resemble those exhibited in sheep. 

In the cases of the two head of cattle which showed symptoms, the 
experiment was carried only to the point of proving the toxic effect 
of the plant, tod no attempt was made to get a complete symptomatic 
picture. The animals became uneasy, displayed heightened reflexes, 
and one dragged the hind legs slightly. So far as they went, the 
symptoms were Uke those observed in sheep. 

AUTOPSIES. 

Autopsies were made on four cases in 1912, six in 1913, and seven 
in 1914. Of the cases in 1913, sheep No. 186, while showing distinct 
symptoms of Zygadenus poisoning, died as the result of the admin- 
istration of morphin. 

The appearances presented by these animals at the autopsies were 
quite xmiform, though not aUke in all details. In six cases there 
was epicarditis. In nearly all, the inner wall of the ileum was 
hyperaemic or congested, and in aU but one the lungs were congested. 
The kidneys were congested and more or less degenerated in most 
cases. Generally the heart was in systole, the contraction being 
most marked in the left ventricle. 

Generally speaking, then, the post-mortem appearances may be 
stated as including inflanunation of the inner wall of the ileum and 
occasionally of the fourth stomach and large intestines, the heart 
in systole, congestion of the limgs, and congestion and more or less 
degeneration of the kidneys. Possibly the condition of epicarditis 
may be considered typical, although it was not noted in all the 
cases. 

The preserved material from the autopsies was examined by Dr. 
Mohler, and the following smnmarized statement of the pathological 
findings and the inferences to be drawn has been furnished by him: 

The most conspicuous phenomenon shown in all six cases was the high capillary 
blood pressure, manifested principally in those organs which eliminated the active 
principle of the ingested substance, that is, kidneys, lungs, and liver, being also shown 
to a less extent in the intestine. 

In the kidney the changes in the capillary varix were fullness to overdistention, 
which was accompanied by outwandering of leucocytes, diapedesis of the red blood 



30 



BULLETIN 125, V. S. DEPARTMENT OF AGRICULTUBE. 



corpuscles, and all the phenomena of a congestion or an acute or subacute inflanunae- 
tion. Occasional ruptures of the capillary vessels were noted, forming poollike capil- 
lary hemorrhages. 

The distention of the capillaries in some instances had brought about cloudy swell- 
ing, or the early stage of degeneration of the renal epithelium, which in some instances 
had become desquamated. The supporting or interstitial tissue was not affected. 

In the lung the high capillary pressure is even more manifest than in the kidney, 
owing to the presence of a greater number of capillaries. The variations were from 
moderate fullness to overdistention, followed by inflammation in the more acute 
cases, resulting in localized areas of cedema where the serimi had oozed out and filled 
one or more lobules of the lung. 

In spite of the fact that the fullness, congestion, and inflammation were more marked 
in the lung than in the kidneys, the degenerative changes and the desquamation of 
the pulmonary epithelium were less evident and not as frequent, ow;ing to the greater 
resistance of the pulmonary cells. WhiJje no interstitial changes were present in 
the kidney, slight interstitial changes in the lungs were present in the peribronchial 
areas in some of the cases. In others, the interstitial changes were also present in 
the visceral pleura. 

In the liver the vascular changes were either entirely absent or so slight as not to 
deserve any mention, but the epithelial changes were quite marked, owing to the 
more delicate composition of the cytoplasm. The absence of vascular changes indi- 
cates that the elimination by this organ is but very slight and that the metabolic 
function is quite able to take care of any of the irritant products that may have reached 
the liver. 

In the intestine the vascular changes are likewise very slight. 

TOXIC AND LETHAL DOSE OF ZYGADENUS YEN^^OSUS FOR SEBEMP. 

The very large number of feeding experiments with sheep at Grey- 
cliff made it possible to detennine the toxic and lethal dose with con- 
siderable accuracy. Inasmuch as very Uttle has been known in 
regard to the toxic dose of Zygadenus for sheep, the results of these 
cases are especially interesting. Table II summarizes the nonfatal 
cases, showing their number and the quantities of the plant neces- 
sary to produce illness. 

Table II. — Nonfatal cases of poisoning of sheep by Zygadenus venenosus at Qreydiffy 

Mont., in 1912, 1913, and 1914. 



Feeding experiments. 



Season of 1912: 

Drenched with leaves, stems, and fruit 

Drenched with stems and leaves «. 

Drenched with stems, fruit, and some leaves 

Drenched with fruit 

Season of 1913: 

Fed on leaves 

Drenched with leaves 

Drenched with bulbs 

Drenched with leaves and buds 

Drenched with buds and flowers 

Fed on leaves and flowers 

Drenched with leaves and flowers 

Fed on leaves, flowers, and fruit 

Fed on seed heads 

Fed on seeds 



Number 
of cases. 



2 
1 
2 
5 

4 
8 
3 
1 
1 
G 
2 
2 
1 
3 



Quantity used per 100 pounds of 



Maximum. 



Pounds. 
1.324 



.771 
.264 

2.1 

.747 
.612 



4.6 

.496 
7.188 
5.597 

.241 



Minimum. 



Pounds. 
0.79 



.33 
.141 

.893 
.385 
.517 



1.728 

.495 

3.155 



.092 



Average. 



Pounds. 

1x057 

.33 

.55 

.228 

1.607 
.5746 
.5746 
.555 
.389 

2. 75ia 
.4955 

5. 1715 

5.597 
.1613 



ZY6ADENUS, OB DEATH CAMAS. 



31 



Table II. — Nonfatal cases of poisoning of sheep by Zygadenus venenosui at Greycliff^ 

M<mt., in 1912, 1913, avd i9i4— Continued. 



Feeding experiments. 



Seaaon of 1914: 

F(H-ced feeding of leaves 

Forced feeding of leaves and some yovais buds 

Fed on leaves, some yomig buds, and a few flowers.. 
Forced feed&ig of leaves, stems, flowers, and buds- 
Material collected near the station. 

Cabfai Corral collections 

Fed on leaves, stems, flowers, and buds 

Forced ibeding of leaves, st^ns, and flowers (Cabin 

Corral collections) 

Forced feeding of leaves, stems, flowers, and young 

fruit 

Forced feeding of very youn^ seed heads 

Fcntsed feeding of seed heads, some fully developed 

and others half developed 

Fcvoed feeding of half-developed seed heads (Cabin 

Corral collections) 

Fwced feeding of nearly developed seed heads 

F(»ced feeding of fully developed seed heads 

Fcvoed feeding of ripening seacl heads 

Forced feeding of pods with seeds removed 

Forced iieeding of seeds 



Number 
of oases. 



2 
2 
1 

8 

4 
1 

9 

4 
1 



3 
6 
18 
2 
1 
2 



Quantity used per 100 pounds of 



tea per i 
anunal. 



M' ^ytnm m 



Pounds. 
0.662 
.499 



.197 



Minimum. 



Pounds. 
0.661 
.550 



.622 
1.963 


.405 
1.436 


2.756 
.992 


.902 
.757 






1.754 
1.323 

.741 


1.543 
.881 
.440 
.740 



.110 



Average. 



Pounds. 
0.6615 
.5245 
1.643 

.5405 
1.789 
1.912 

1.712 

.851 
1.543 

1.432 

1.69 
1.175 
.859 
.7415 
.540 
.153 



Table III summarizes the fatal cases in the three seasons. 

Tablb III. — Fatal cases of poisoning of sheep by Zygadenus venenosus at Grey cliff, 

Mont., 1912, 191S, and 1914^ 



Feeding exi>eriments. 



Season of 1912: 

Drenched with fruit 

Season of 1913: 

Fed on leaves 

Drenched with leaves 

Drenched with leaves and flowers 

Season of 1914: 

Forced feeding of leaves, stems, and flowers. 

Forced iieeding of fullv developed seed heads 

Forced feeding of seeos 



Number 
of cases. 



1 
4 
1 

1 
2 

3 



Quantity used per 100 x>ounds of 
iimal. 



ani 



Maximum. 



Pounds. 
0.853 



.746 



.991 
.220 



Mitilrnnm . 



Pounds. 
0.299 



.384 



.882 

.199 



Average. 



Pounds, 
0.571 

1.307 
.537 
.550 

.544 
.936 
.213 



As these feedings were carried on during the season as long as the 
plants could be obtained and as it was practically impossible to have 
any considerable number of cases at one time, it is evident that the 
number of cases imder any given set of conditions must have been 
small. As a matter of fact, none of the cases of 1912 were strictly 
comparable with those of 1913. Consequently, the actual averages 
of dosage were based on a comparatively small number of cases. 

In 1914, there was a much larger number of cases, and some stages 
of the plant were fed upon which no experiments were made in the 
preceding years. Even in this year, however, there were only a few 
cases in which the experiments were imder identical conditions. 



82 BULLETIN 125, XT. S. DEPABTMBNT OP AGBICULTUBB. 

In the compOation of Tables 11 and HI some of the cases have been 
exclu4ed. In Table 11 all cases in which the remedy given was 
clearly eiOfective were excluded, for some of these received what would 
have been a lethal dose had it not been for the remedy. In Table III 
cases were excluded which were known to have received much more 
than a lethal dose. The imiformity of dosage in 1914 is explained by 
the fact that the preceding work had shown clearly that the toxic 
dose was not far from 0.5 poimd, and the experiments were made on 
this basis. It should be noted, too, that most of the work of the 
summer of 1914 was with reference to the experimental use of reme- 
dies, so that the quantity of the plant administered was estimated 
to be sufficient not simply to produce symptoms, but to make the 
animal very sick, in order to get a fair test of the remedy. Hence, 
the average figiu*es for the toxic dose will be rather high. 

The "forced feeding'' cases of 1914 can be fairly compared with the 
''drenched'' cases of 1912 and 1913, as the difference between the 
two methods is mainly in the fact that in forced feeding no water is 
used while in drenching considerable water is necessary as a vehicle 
for the weed. 

The age of the animal played a comparatively small part in these 
experiments, as aU the animals were mature, most of them being 2 
years old or older. 

It will be noticed that when the plant was given in the form of a 
drench or by forced feeding, the dosage, as would be expected, was 
considerably less than when it was given with food. An examination 
of the complete table of feeding (Table I) shows also very clearly that 
the size of the dose varied inversely with the time during which the 
material was eaten. In a large niunber of cases in which the plant 
was given with food, the feeding extended over two or more days. 
In those cases the dosage was considerably greater than when the 
material was fed in a single day. It may be assumed that if the 
same quantity of the plant which was received in a drench could 
have been fed within a short period of time, the effect would have 
been the same. 

The average dose which produced illness when administered in the 
form of a drench or by forced feeding was practically the same for 
aU parts of the plant except the pods and seed. It appears that the 
plants are less toxic at the time when the pods are forming, which may 
be due, in part at least, to the diminished toxicity of the leaves as they 
dry up. It is not clear, however, from this work, that the leaves lose 
any appreciable amount of toxicity, and the more probable explana- 
tion is that the pods at this time are only slightly toxic. In the single 
experiment of feeding pods without seeds, the dosage was about like 
that of other parts of the plants, but it is probable from the detailed 
history of this experiment that this is not a fair representative of such 

^ses. 



ZYGADENUS, OB DEATH CAMAS. 33 

The seeds are very much more poisonous than any other part of the 
plant. Heyl, Loy, Knight, and Prien (1912, p. 17) give the results of 
determinations of alkaloids in different parts of the plant. Their 
statement is obscure and contradictory, but apparently they reach 
the conclusion that the bulbs and leaves contain approximately the 
same quantity of the alkaloid, the roots much less, and the flowers 
about twice as much as the bulbs and leaves. This compares very 
weU with the results of the experimental feeding at GreychflF, except 
that it did not appear that the flowers were more toxic than other 
parts of the plant. 

Table II gives the maximum and minimum dosage, and it will 
be noticed that there is a considerable range of variation between 
these two. The individual peculiarities of the animal in cases of 
poisoning doubtless must be taken into account, and the detailed 
table of the experiments shows that in some cases a larger quantity 
of plant than that which this table indicates to be toxic may be 
administered without effect. In most of the cases, however, where 
the larger amoimt was used, the feeding was distributed over a 
longer time. 

In general, the experiments seem to indicate that when any part 
of the plant except the seed is used the toxic dose varies from 1.6 
poimds per hundredweight of animal to 5.6 poimds, this wide range 
of variation being accoimted for by the more or less extended time 
of feeding. In the drenching and forced-feeding experiments, more 
uniform results were reached, showing that the toxic dose of aU parts 
of the plant, except the seed, is not far from 0.5 poimd per himdred- 
weight of animal. 

There is considerable difference in the items of the summarized 
tables in the exactness of the averages, and some explanation is 
necessary to indicate their actual value. 

In thft feeding of leaves in 1914, there were three cases, two 
becoming sick. The third case received 0.661 poimd without symp- 
toms, the same quantity that was received by No. 282, which became 
sick. It seems probable, then, that the average figure 0.6615 must 
be pretty close to the toxic limit. In the feeding of ''leaves and some 
young buds'' in 1914, while the minimum of sick cases received 0.499 
poimd, another animal received 0.551 pound without ill effect; it is 
evident that the toxic limit must be not far from 0.5 poimd. In the 
feeding of eight cases on "leaves, stems, flowers, and buds," with 
material collected near the station, the toxic limit was practically the 
same as in the preceding cases. A perusal of Table II shows that 
during the growth of the seed heads the toxicity was reduced and 
that the fuUy developed seed heads were somewhat less toxic than 
the plant in the earher stages. 



34 BULLETIN 125, U. S. DEPABTMENT OF AGRICULTURE. 

In the two cases of forced feeding of seeds in 1914 the average toxic 
dose was 0.153 pound; inasmuch as the animal receiving the maxi- 
mum amount was very sick, the actual toxic limit must be consid- 
ered to be close to the minimum figure of 0.11 pound. It will be 
noticed that the cases of feeding of seeds in 1513 had practically the 
same average dose as the cases of forced feeding in 1914; this is 
accounted for by the fact that these animals ate the seed in such a 
short time that the results were similar to those from forced feeding. 

It is interesting to note in Table III that the lethal dose is only 
slightly larger than the toxic dose. 

In transferring these results to the probable dosage when sheep 
are range fed, the feeding habits of the sheep must be taken into 
consideration. In the corrals the sheep do not, as a rule, eat as 
readily as when on the range. When the sheep in a band are grazing 
together, both imitation and jealousy aflFect the quantity of any plant 
which a sheep eats in a given time; so it is reasonable to suppose 
that if feed is short and Zygadenus fairly abundant, sheep may eat 
much more in a short time than they would under corral conditions. 
Under such circumstances, the dosage might approximate that of 
the drenching experiments. Therefore, it appears probable that 
animals feeding on the range might, because of the more rapid eating, 
be poisoned with much less than when in corrals. 

EXPERIMENTS WITH HORSES AND CATTLE. 

Three experiments were made of feeding Zygadenus to a horse, 
as shown in Table I (section D), Z. venenosus being used in two tests 
and Z. elegans in one. The smallest quantity fed in these experi- 
ments was 12.1 poimds per 1,000 poimds of weight, and the largest 
was 15 pounds. In each instance the feeding was extended through 
several days, and the feeding of 15 pounds extended through 6 days. 
If the quantity necessary to poison a horse should be in the same 
proportion to its weight as that required to poison a sheep, it would 
be, according to our dosage, at least between 11 and 12 poimds, and 
probably much more. It may be presumed, therefore, that in these 
cases the amoimt fed was not suflBlcient to produce toxic effects. 
There is, however, abundance of evidence that horses are poisoned 
by Zygadenus, although not ordinarily with fatal results. 

Section C of Table I shows the results of feeding Zygadenus 
venenosus to three cattle. Two of these animals, both of which 
received leaves and flowers, showed symptoms of poisoning, one 
on 58 pounds per 1,000 poimds of weight and the other on 46.5 
pounds per 1,000 pounds of weight. In these cattle, therefore, 
the average toxic dose was 52.25 pounds, which was fed in an average 
of 6i days. This compares fairly well with the results reached with 



ZYGADENXTS, OB DEATH CAMAS. 35 

sheep and would indicate that the toxic dose for cattle, computed 
in terms of the weight of the animal, does not diflfer materially 
from the toxic dose for sheep. 

COMPARATIVE TOXICITY OF DIFFERENT SPECIES OF ZYGADENUS. 

In the course of the experiments, four species of Zygadenus were 
used, Z. venenosus, Z, elegans, Z. paniculatiLS, and Z. coloradensis, by 
far the greater part of the work being done with Z. venenosfus. The 
number of experiments with Z. elegans and Z. paniculatus was very 
small, and the material, especially in the case of Z. paniculatusy had 
been shipped a long distance, so that there was some question of the 
water content of the plant. Apparently, however, Z. elegans and Z. 
paniculatus do not differ materially in toxicity from Z. venenosfus. 
Z. coloradensis, however, produced no toxic effects whatever with 
the exception of slight symptoms in one sheep, although the plant 
was fed in quantities several times as great as the toxic dose of Z. 
venenosus. 

It is evident that in the feeding of cattle with Zygadenus coloraden- 
sis at Mount Carbon in 1909, the results of which are given in Table I, 
the quantities fed were too small to produce results, even if the 
plants were as poisonous as Z. venenosus. In the experiment of 
1910, however, a large quantity was fed, and sufficiently large 
quantities in single days to produce symptoms of poisoning if the 
plant were as toxic as Z. venenosus. 

In this connection it should be added that Dr. C. L. Alsberg made 
a laboratory examination of the Colorado plants and found in them 
a very small quantity of alkaloid. It would appear, then, that the 
form which is identified by some botanists as Z. coloradensis contains 
the same toxic substance as the other form, but that this substance 
is present in so small a quantity that it is unlikely that it ever 
produces toxic effects on domestic animals. While it is not in the 
province of this paper to discuss the systematic relations of plants, it 
may be suggested that this difference of toxicity between Z. elegans 
and Z. coloradensis may indicate a valid specific distinction between 
these two forms which are so closely related that by some botanists 
they are considered identical. 

DOES TOXICITY VARY WITH LOCALITY? 

The collections of Zygadenus venenosus with which experiments 
were made were obtained at the '* Station" (by which is understood 
the region within a radius of 2 miles of the station), at an elevation 
of about 4,050 feet; at ^^Greycliff," 2i to 3 miles distant from the 
station, at an elevation of .about 3,920 feet; and at '* Cabin Corral'' 
and * 'George Hughes's '' Gocations from 4 to 7 miles from the station), 
at an elevation of something over 5,000 feet. Material of this species 



36 BULLETIN 125, U. S. DEPABTMENT OP AGRICULTURE. 

was also used from Avery, Cal., collected at an elevation of 3,500 feet. 
The material of Z. elegans was from two localities, from near Red 
Lodge, Mont., at an elevation between 5,500 and 6,000 feet, and from 
the Fishlake National Forest, Utah, at an elevation of something 
over 9,000 feet. The Z. paniculatus material was collected near 
Ephraim, Utah, at an elevation between 5,500 and 6,000 feet. All 
the Z. coloradensis material was collected within 4 or 5 miles of the 
Momit Carbon station, at an elevation of something over 10,000 feet. 

As has been stated already, the lack of toxic properties in Zygadenus 
coloradensis is assumed to be characteristic of the species. The experi- 
ments with Z. elegans and Z. paniculatus were few in number, and 
too much importance must not be attached to the results. Appar- 
ently, however, not only did they have, practically, the same toxicity 
as the Z. venenosus collected near the station, but there was no evident 
difference between the Z. elegans of Montana and that collected in 
Utah. The Z. venenosus, collected in California gave the same results 
as that produced by material from the neighborhood of the Greycliff 
station. 

An entirely unexplained variation in toxicity was exhibited by 
material collected at Cabin Corral, about 5 miles from the station and 
at a greater elevation of about a thousand feet. When Table II 
was being compiled, it was noticed that the cases receiving ^'forced 
feeding of leaves stems, flowers, and buds'' fell into two distinct 
divisions, one with an average dosage of 0.5495 pound and the other 
with an average of 1.789 pounds. This difference was so marked 
that the two sets were separated in the summary. In searching for 
some possible explanation of this difference, it was found that all 
the cases with the larger dosage were treated with material collected 
at Cabin Corral. Note was then made of the other items in this table 
which were collected in this locality, and a glance at the table will 
show that in the other cases the Cabin-Corral material showed much 
less toxicity. It has been entirely impossible to explain this difference. 
The number of cases would seem to make it certain that this result 
was not due to an error of experimentation. There are no local 
conditions to account for it. The George Hughes place, at which 
collections were made giving the same results as those produced by 
the station material, is situated at about the same distance from the 
camp as Cabin Corral, at about the same elevation, and it has the 
same soil conditions. The question of the correlation of variation 
in toxicity with changes in altitude was raised, but the experiments do 
not indicate anv such relation. The fact that the Cabin-Corral mate- 
rial was less toxic is nevertheless substantiated, and it would appear 
that while Zygadenus venenosus, Z. elegans, and Z. paniculatus have 
ordinarily the same degree of toxicity wherever grown, there is a pos- 
sibility of marked variation. 



ZYGADENUS, OB DEATH CAMAS. 37 

EFFECT OF REPEATED FEEDING IN PRODUCING IMMUNITY OR IN- 
CREASED SUSCEPTIBILITY. 

During the course of the experimental work at Greycliff a number 
of sheep were treated with Zygadenus several times during the 
same season. It was important to decide whether a sheep after 
having been poisoned once was more or less likely to be affected a 
second time. A careful analysis of the results showed that no effect 
either of immunity or of increased susceptibility was produced. 
The fact that an animal had suffered from poisoning once neither 
lessened the effect of another dose, nor, on the other hand, was the 
sheep any more likely to suffer from a second experience. 

REMEDIES. 

Because of the heavy losses of sheep from Zygadenus poisoning 
it was deemed important to investigate thoroughly the possibility 
of finding some remedial measures to reduce the number of deaths. 
To this end a large number of experiments were made, as can be seen 
by an examination of the table giving the summarized accouat of the 
work. 

It has been shown by Hunt that the poisonous principle of Zyga- 
denus is excreted in the urine, and this has been verified by the 
authors in the cases of some of the sheep used in the Greycliff experi- 
ments. Hunt concluded that the logical remedy is some diuretic 
which will insure excretion rapid enough to prevent serious effects 
from the poisoning, and his experiments seem to substantiate this 
position. He also advised the use of permanganate of potash 
administered per os to destroy the alkaloid in the stomach. 

The experimental work on remedies in 1912 was based upon these 
conclusions of Hunt. Later, a number of remedies were used in the 
hope that some method might be found sufficiently simple to be used 
under range conditions. 'Hiis work was carried on for three summers 
in order to get the average of a considerable number of cases, and 
a brief statement of the results of the more important experiments 
follows. 

CAFFEIN AND DIUBETIN. 

The Conclusions reached by Hunt led to a series of experiments 
with caffein. In 1912, caffein sodiobenzoate was administered to 
five animals subcutaneously; in two of these cases potassium perman- 
ganate was also used, and in one tannic acid. It was evident that 
by the use of this drug the excretion of urine was increased, but the 
observers could not see that any marked improvement followed in 
the condition of the animals. In the summer of 1913, diuretin and 
caffein citrate were given per os in four cases, of which one died and 
three recovered. In these cases, as in those of the preceding year. 



38 BULLETIN 125, U. S. DEPARTMENT OF AGRICULTURE. 

there was no evidence of any good result. All these experiments had 
been with single doses. In 1914 two animals were treated, one 
with two doses of 10 grains each of caffein sodiobenzoate adminis- 
tered subcutaneously, and one with three doses of 5 grains each. 
One of these animals died and one recovered, but in neither case 
could it be seen that the remedy was advantageous. It seemed to 
be clear that while caflEein might be considered a logical remedy it 
failed in practical application. 

STSTCHNIN. 

Although the work of Hunt quite clearly indicated that strychnin 
was not beneficial, it seemed best to try a few experiments to see 
whether, by its stimulating effect, it might not aid in relieving the 
depression of the animals. Six cases were treated by subcutaneous 
injections. In two of these cases eserin was also used, and in one 
case gin. There was an apparently beneficial effect in one case, but 
a study of all fails to show any good results which, could be fairly 
considered as due to strychnm. 

ESEBIN, EPSOM SALTS, LINSEED OIL. 

With the idea that relief might be brought about by an increase in 
intestinal elimination, eserin was administered subcutaneously, and 
Epsom salts and linseed oil per os; no reduction of toxic symptoms 
could be seen. 

CHARCOAL. 

Dr. SoUman suggested to the writers that charcoal, by adsorption, 
might be beneficial. Three experiments were made with this, in 
one case combined with linseed oil. No beneficial results followed. 

WmSKY AND DIGIFALIS. 

In some cases of extreme depression whisky seemed to have an 
effect m bridgmg over a period when death might otherwise have 
followed. The same thing is true of digitalis, which in one or two 
cases may have saved the life of the patient. Neither drug, however, 
had any marked effect. It can only be said that if the symptoms of 
the animal are carefully watched, times will be found when whisky 
or digitalis may be administered advantageously. Inasmuch as the 
life of the individual sheep is of small importance, these remedies are 
of little practical use. 

POTASSIUM PERMANGANATE. 

Especial Interest attaches to the experiments with potassium 
permanganate, since it is the remedy that has been most commonly 
recommended for plant poisoning. The dosage advised for a mature 
sheep has been 5 to 9 grains. This was used at first in the experi- 
mental work, and when no beneficial results appeared it was increased 



ZYGADENUS, OR DEATH CAMAS. 39 

to 30 grains, but still with no evidence of a reduction of the toxic 
effect. In two cases, 15 grains were introduced directly into the 
rumen with no better results. 

Because of this lack of success it was deemed best to try mixing 
the permanganate with the Zygadenus before administration to see 
if the alkaloid would be destroyed in vitro. On May 19, 1913, two 
sheep of equal weight, Nos. 184 and 191, were each drenched with 
0.586 pound of Zygadenus venenosus in water. In the dose given to 
No. 191 there were dissolved 7i grains of potassium permanganate 
and 7i grains of aluminum sulphate. Both animab were sick, and 
there was no recognizable difference in the degree of illness. The 
experiment tended to show that the administration of the potassium 
permanganate was without any definite effect upon the toxicity of the 
plant, but a similar experiment on July 11, 1914, on sheep No. 253 
showed quite clearly that the dosage of the former experiment was 
insufficient. In this case 0.441 pound of seed heads of Z. venenosus 
was mixed in water with 15 grains of potassium permanganate and 
15 grains of aluminum sulphate and the mixture allowed to stand for 
20 minutes before being administered. The sheep displayed no 
symptoms of poisoning, although other cases of the same date 
receiving the same quantity of Zygadenus, with no remedy, showed 
distinct symptoms. It seemed clear that a sufficient quantity of 
permanganate will diminish the toxicity of the plant, when mixed 
with it before administration. When given after symptoms of poison- 
ing are exhibited, however, the remedy is of no value. This, too, has 
been demonstrated by practical experience upon the range. Potas- 
sium permanganate has been used by many sheep owners in Montana, 
and it is the almost universal testimony that it is worthless. 

TANNIC ACro. 

Sheep No. 206, on Jime 4, 1913, was drenched with 0.43 pound of 
Zygadenus tops, including leaves and flowers. To this drench were 
added three grams of tannic acid. The animal showed no signs of 
illness. On May 29 a sheep was made sick on 0.389 pound, and on 
May 30 one was made sick on 0.385 pound and one died on 0.384 
pound. It seems fair to presume, therefore, that the tannic acid had 
been of benefit to sheep No. 206. 

Sheep No. 210, on June 6, 1913, was drenched with 0.496 pound of 
leaves and flowers of Zygademis venenosus to which 3 grams of tannic 
acid had been added. On the same date sheep No. 209 received 0.495 
pound of the same material, but without the tannic acid. Both 
animals were sick and recovered, but it was the impression of the 
observers that sheep No. 210 was not as sick as sheep No. 209. 

On Jime 7, 1913, sheep Nos. 212 and 213 were each drenched with 
0.55 poimd of leaves and flowers of Zygadenus venenosus. In the 



40 BULLETIN 125, U. S. DEPARTMENT OP AGRICULTTJBE. 

drench given to No. 212 were included 4 grams of tannic add. This 
sheep had no symptoms of iUnesS; while No. 213 died 1 hour and 17 min- 
utes after the administration of the drench. These two sheep were of 
very nearly equal weight and the dose was the same (0.55 poxmd) per 
hundredweight of animal. There was every reason to expect similar 
results except for the effect of the tannic acid. Difference of indi- 
vidual susceptibihty would seem to be eliminated in this instance, in 
which one animal died and the other showed no symptoms of poisoning. 

Dining the season of 1913, four animals which had been fed on 
Zygadenus venenosus were given doses of tannic acid after toxic 
symptoms were well developed. All of these animals recovered. 
These cases, however, were not connected up with control cases, 
and it is possible that all would have recovered without any remedial 
aid. 

The general result of all the experiments in 1913 with tannic acid 
indicated that it can be used with beneficial results. The experiments 
seemed also to indicate very clearly that, in vitro, the tannic acid was 
much more effective than potassium permaganate as an antidote for 
the Zygadenus alkaloid. 

In 1914, a large nimiber of cases were treated with tannic acid, 
in order to try it out thoroughly. In most of these experiments one 
or more control animals were used. Where the tannic acid was 
administered in a single dose, in 19 cases, there were only two deaths: 
in mc^t of these cal, however, the Zygadenus was not given in a 
quantity necessarily fatal. 

A study of the cases in which there was a control shows apparently 
beneficial results in some instances. For example, sheep Nos. 249 
and 251 received the same quantity of Zygadenus on July 9; No. 249 
died, while No. 251, which received a dose of tannic acid, lived. 

Sheep Nos. 229 and 235 were fed the same quantity of Zygadenus 
on June 3. No. 229 was treated with tannic acid and was not so sick 
as No. 235. On the other hand, Nos. 239 and 256 were fed on Jxme 
16 with the same quantity, and No. 239, which received the tannic 
acid, had more marked symptoms than No. 256. Sheep Nos. 269, 
255, and 282 were fed the same quantity of Zygadenus on Jime 15 
and Jime 16. Tannic acid was administered to Nos. 269 and 282; 
both of these animals were sick, while No. 255 exhibited no symp- 
toms. A consideration of all these cases shows that tannic acid in 
single doses can not be considered an effective remedy, although 
under favorable conditions some oases may be benefited. 

SODIUM BICARBONATE. 

It was suggested by Mr. O. F. Black that, inasmuch as alkaloids 
are, to a large extent, insoluble in an alkaline solution, sodium bicar- 
bonate might serve to prevent the solution and absorption of the 



ZYGADENUS, OB DEATH CAMAS. • 41 

poisonous principle of Zygadenus and thus prove valuable as a medic- 
inal remedy. This was used only in repeated doses, and the results 
will be discussed under the next head. 

REPEATED DOSES OF TANNIC ACTO AND SODIUM BICARBONATE. 

Inasmuch as tannio acid is a recognized remedial agent for poison- 
ing by alkaloids, it seemed strange that so little benefit followed 
its use. In seeking for an explanation, it occurred to the writers 
that it might be accounted for by the fact that, because of the char- 
acter of a ruminant's stomachs, the remedy does not actually come in 
contact with any considerable quantity of the poisonous substance. 
The first stomach of a ruminant always contains a large quantity of 
material. When an animal feeds upon a poisonous plant, the ma- 
terial taken up goes to the first stomach ; some of this, after macera- 
tion, proceeds to the third and fourth stomachs, while another part 
goes on only after rumination. If the remedy is given in the form of a 
drench, it will be distributed in all the stomachs, although ordinarily 
the larger part of the drench goes directly to the third and fourth 
stomachs. That part of the drench which goes to the fourth stomach, 
we can assume, takes effect on the alkaloid which has arrived at that 
part of the digestive canal. The portion of the drench which stops 
in the first stomach meets a mass of organic matter, in which it is 
lost; there is no reason to think that any antidote for an alkaloid 
will have any selective effect, so as to attack the Zygadenus alkaloid 
rather than the midtitude of other substances in the stomach with 
which it can unite. The only hope of destroying the alkaloid under 
such circumstances would be by flooding the firet stomach with the 
antidote, and that is practically impossible. So even when the anti- 
dote is introduced by a canula directly into the first stomach, it would 
be impracticable to use a quantity sufficient to produce any marked 
effect. 

On the other hand, inasmuch as no absorption takes place in the 
stomachs, if the antidote could meet the poisonous material as it 
passes through the fourth stomach good results might be expected. 
On the basis of this conclusion, it seemed best to the writers to try 
the effect of antidotes repeated at frequent intervals; it was thought 
that if the antidote coidd reach the fourth stomach frequently 
enough to catch the alkaloid as it passed from the first stomach and 
render it more or less innocuous before passing into the intestine, the 
remedy might be distinctly beneficial. 

Four experiments of this character were conducted with tannic 
acid, all with controk, which received no remedy but were fed with 
the same quantity of Zygadenus. The tannic acid was given in doses 
of 1 and 2 grains, repeated at intervals varying from 10 to 30 min- 
utes, or longer in some cases, at the latter part of the experiment. 



42 BULLETIN 125, U. S. DEPARTMENT OF AGRICULTURE. 

The total time of treatment varied from 4 to 7i hours, and the total 
quantity of tannic acid given varied from 14 to 16 grams. The 
doses and intervals were as follows: 

Sheep No. 263: 9 doses, 1 gram each, once in 10 minutes; 2 doses, 1 gram each, once 
in 30 minutes; 1 dose, 1 gram, in 20 minutes; 2 doses, 1 gram each, once in 30 minutes. 
Total, 14 grams. 

Sheep No. 216: 7 doses, 2 grams each, once in 30 minutes. Total, 14 grams. 

Sheep No. 267: 5 doses, 1 gram each, once in 10 minutes; 3 doses, 1 gram each, once 
in 15 minutes; 8 doses, 1 gram each, once in 30 minutes. Total, 16 grams. 

Sheep No. 291: 3 doses, 2 grams each, once in 30 minutes; 1 dose, 2 grams, in 60 
minutes; 1 dose, 2 grams, in 30 minutes; 2 doses, 2 grams each, once in 60 minutes; 
1 dose, 2 grams, in 3 hours. Total, 16 grams. 

AU these animals recovered and were not as sick as the controls, 
Nos. 269 and 294. Sheep No. 291 suffered more than the others, 
but the tannic acid in this case was administered later in the illness, 
after a course of small doses of Epsom salts had failed to produce 
any effect. All these animals and the controls were given Zygadenus 
collected on the same date. The experiments were considered to 
prove conclusively that repeated doses of tannic acid are beneficial. 

A similar set of experiments was conducted with sodium bicarbon- 
ate. Seven animals were used, and all, with one exception, were fed 
Zygadenus material collected on the. same date, and in the excep- 
tional case the material was collected only a few days later. Doses 
of sodium bicarbonate of 2 and 4 grains were given at intervals vary- 
ing from 15 to 60 minutes. The total time of treatment was from 
2i to 5 hours, and the total amount of sodium carbonate given varied 
from 20 to 48 grains. The doses and intervals were as follows: 

Sheep No. 246: 10 doses, 4 grams each, once in 30 minutes. Total, 40 grams. 

Sheep No. 259: 8 doses, 4 grams each, once in 15 minutes; 4 doses, 4 grams each, 
once in 30 minutes. Total, 48 grams. 

Sheep No. 264: 6 doses, 4 grams each, once in 60 minutes. Total, 24 grams. 

Sheep No. 292: 10 doses, 4 grams each, once in 30 minutes. Total, 40 grams. 

Sheep No. 293: 4 doses, 4 grams each, once in 30 minutes; 2 doses, 2 grams each, 
once in 30 minutes. Total, 20 grams. 

Sheep No. 277: 5 doses, 4 grams each, once in 30 minutes; 2 doses, 2 grams each, 
once in 30 minutes; 1 dose, 2 grams, after 1^ hours. Total, 26 grams. 

Sheep No. 240: 3 doses, 8 grams each, once in 60 minutes; 2 doses, 4 grams each, 
once in 60 minutes. Total, 32 grams. 

Of these animals all recovered but one. No. 264. This sheep re- 
ceived a total of 24 grains, given at hour intervals. No. 240 also 
received the remedy at hour intervals and recovered very slowly, 
being unable to stand on the morning after the poisonous dose had 
been given. All the other cases, except No. 277, recovered rather 
quickly. No. 277 was as slow as No. 240, although the doses of 
sodium bicarbonate were given frequently, and the total amount was 



ZYGADENUS, OR DEATH CAMAS. 43 

greater than that given to No. 264 and to No. 293, which recovered. 
If we exclude No. 277, it would appear clear that sodium carbonate 
given in sufficiently frequent doses is distinctly beneficial. The Zyga- 
denus in the case of No. 277 was given in three doses, and it is pos- 
sible that there was some accumulative effect, which may explain in 
part the slow recovery. 

The general conclusion from the experiments with sodium bicar- 
bonate is that if the remedy is given at frequent intervals it will prove 
distinctly beneficial. The dose should be 4 grams, and this should 
be repeated as often as every 30 minutes. 

These experiments with repeated doses of tannic acid and sodiunj 
bicarbonate were interesting from a theoretical standpoint and indi- 
cate a line of treatment which can be used successfully with valuable 
animals. It is evident, however, that remedies used in this way can 
not be recommended for the ordinary band of sheep, for the expense 
of the treatment would be greater than the value of the animals. 

No experiments of repeated doses were made with potassium per- 
manganate; but it is probable that it could be used successfully, 
although the general trend of the experimental work is to indicate 
that the potassium permanganate is not, as a remedy, so efficient as 
tannic acid and sodium bicarbonate. 

BLEEDING. 

It is customary among sheep herders to bleed sheep poisoned by 
Zygadenus, the favorite place being the angular artery and vein of 
the eye. Although there seems to be no logical reason for this prac- 
tice, it seemed wise to try it, and three sheep were treated in this 
way; two of the three died, and no beneficial result appeared in any 

of the cases. 

METHODS OF PREVENTING LOSSES. 

The most obvious thing to do is, of course, to keep the animals 
from eating the plant. With this end in view, it is important that 
all herders should be taught to recognize Zygadenus. When the 
plant is in flower this is not at all difficult, but it has been a matter of 
surprise to find to what extent, amoi^ the herders and sheep owners, 
the plant is not known, even at this stage. Before flowering, its 
grassHke leaves are not so easily recognized, but there is no reason 
why a fairly intelUgent man should not be taught to know it even then. 
If one knows the plant in the preflowering and flowering stages, he 
will readily recognize it in the later dried-up condition, when, it will 
be remembered, it is fully as dai^erous as earUer in the season. 

When the plant is recognized care should be taken that the sheep 
do not have an opportunity to eat any large quantity of it. If 
it be necessary to drive the sheep over a patch of Zygadenus, the 
herder should take the precaution to have the band well fed before 



44 BULLETIN 125, U. S. DEPABTMENT OF AGBICULTXJBB. 

making the drive. If hungry sheep come upon a thick growth of Zyga- 
denuS; some of them, in their haste to satisfy their hunger, are almost 
certain to become poisoned, while if already well fed they are likely 
to choose their food with more care and to eat less of the Zygadenus. 

Special care should be used early in the season, not because the 
plant is more poisonous at that time, but because, on account of the 
dry condition of other forage, it is more likely to be eaten. Later 
in the season sheep are less likely to eat a lai^e quantity, because of 
the greater abundance of other food. As a matter of fact, most of the 
cases of extensive poisoning have occurred before the flowering of 
the plant. 

If sheep become poisoned, they should be kept as quiet as possible. 
Any attempt to make them move about is likely to have disastrous 
results. 

So far as remedies are concerned, none has been foimd so far that 
gives much promise of being really useful. The experimental work 
at Greycliff shows that repeated doses of tannic acid or sodium 
bicarbonate wiU aid in recovery, but this method of treatment is not 
practically possible for animals upon the range. 

GENERAL SUMMARY. 

Zygadenus grows abundantly on many of the stock ranges of the 
West and is one of the most important sources of loss to sheepmen. 
Apparently all species of Zygadenus are poisonous. The plants are 
poisonous through the whole season of their growth, but the tops are 
somewhat more poisonous at the time of flowering. The toxicity of 
the bulbs and tops is about the same, while the seeds are much more 
toxic than other parts of the plant. Cases of poisoning are more 
Ukely to occur before the maturity of the plant, because at that time 
other forage is scanty. 

The tolc dose varies according to the conditions of feedmg. In 
drenched animals it may be put at about one-half a pound for an 
animal weighing a hundred pounds. In fed animals it varied from 
1.6 pounds to 5.6 pounds. 

The poisonous principle is an alkaloid or alkaloids aUied to veratrin 
and cevadin. 

Sheep, cattle, and horses are poisoned by the plant, but the fatali- 
ties are almost entirely confined to sheep. 

The principal symptoms are salivation, nausea, muscular weakness, 
coma, and sometimes attacks of dyspnoea. 

To prevent losses, it is important to recognize the plant and avoid 
grazing upon it. If animals become sick they should be iept quiet, 
and under this treatment many will recover. There is no satisfac- 
tory medical remedy. 



LITERATURE CITED. 

Brttton, N. L., and Brown, Addison. 

1913. Illustrated Flora of the Northern United States, Canada, and the British 
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Chesnut, V. K. 

1902. Plants used by the Indians of Mendocino County, Calif omia. Contri- 
butions, U. S. National Herbarium, v. 7, p. 321-322, 327. 

and Wilcox, E. V. 

1901. The stock-poisoning plants of Montana; a preliminary report. U. S. De- 
partment of Agriculture, Division of Botany, Bulletin 26, p. 51-64, pi. 1. 

Collier, Peter. 

1882. Proximate analysis of Zygadenus paniculatus. Report, pj. S.] Commis- 
sioner of Agricidture, 1881/82, p. 647-548. 

Coulter, J. M. 

[1909.] New Manual of Botany of the Central Rocky Moimtains . . . rev. by 
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COVILLE, F. V. 

1897. Notes on the plants used by the Klamath Indians of Oregon. Contribu- 
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Gray, Asa. 

1848. Melanthacearum Americae Septentrionalis revisio. Annals, Lyceum of 
Natural History, New York, v. 4, p. 124. 



[1908.] Gray*s New Manual of Botany, ed. 7, rev. by B. L. Robinson and M. L. 
^ Femald. New York, Cincinnati, p. 284. 

Heller, A. A. 

1909. The death camus. Muhlenbergia, v. 5, no. 3, p. 50-52. 

Hbyl, F. W., and Hepner, F. E. 

1913. Some constituents of the leaves of Zygadenus intermedins. III. Journal, 
American Chemical Society, v. 35, no. 6, p. 803-811. 

and LoY, S. K. 

[1912.] Zygadenine. The crystalline alkaloid of Zygadenus intermedins. Sec- 
ond paper. Wyoming Agricultural Experiment Station, 22d Annual Report, 
1911/12, p. 51-57, 2 fig. 



1913. Zygadenine. The crystallin alkaloid of Zygadenus intermedins. Journal, 
American Chemical Society, v. 35, no. 3, p. 258-262, 2 fig. See also Wyoming 
Agricultural Experiment Station, Bulletin 101. 

— LoY, S. K., Knight, H. G., and Prien, O. L. 

1912. The chemical examination of death camas. Wyoming Agricultural Experi- 
ment Station, Bulletin 94, 31 p., 3 fig. 

and Raiford, Charles. 



[1911.] Analysis of Zygadenus intermedins. First paper. Wyoming Agricul- 
tural Experiment Station, 2l8t Annual Report, 1910/11, p. 62-69. See also 
Journal, American Chemical Society, v. 33, no. 2, p. 206-211, 1911. 

45 



46 BULLETIN 125, U. S. DEPARTMENT OF AGRICULTXJBE. 

HiLLMAN, F. H. 

1893. A poisonous plant. Nevada Agricultural Experiment Station, Newspaper 
Bulletin 5, 1 p., 1 fig. 



1897a. A dangerous range plant. Nevada Agricultural Experiment Station, 
Newspaper Bulletin 21, 1 p., 1 fig. 



18976. Nevada weeds. III. Nevada and other weed seeds. Nevada Agricul- 
tural Experiment Station, Bulletin 38, p. 114-116, fig. 116-117. 

Hooker, W. J. 

1838. Flora Boreali-Americana ... v. 2, London, p. 177. 

Hunt, Reid. 

1902. Experiments with Zygadenus venenosus (poison camass). American Jour- 
^nal of Physiology, v. 6, p. xix. 

Irish, P. H. 

1889. Plants poisonous to stock. Or^on Agricultural Experiment Station, Bulle- 
tin 3, p. 25-26. 

Lloyd, J. U., and Lloyd, C. G. 

1887. Zygadenus nuttallii: the death camoss of the West. American Druggist, 
V. 16, no. 8, p. 141. 

McCarthy, Gerald. 

1903. The poisonous plants of North Caroling. Report, Commissioner of Agricul- 
ture, North Carolina, 1902, p. 167. 

Mitchell, P. H., and Smith, George. 

1911. Physiological effects of alkaloids of Zygadenus intermedins. American 
Journal of Physiology, v. 28, no. 6, p. 318-329, 3 fig. 

Nelson, S. B. 

1906. Feeding wild plants to sheep. Washington Agricultural Experiment Sta- 
tion, Bulletin 73, p. 61-54, 1 fig. 

Parsons, Mary E. 

1904. The Wild Flowers of California . . . illustrated by Margaret W. Buck. San 
Francisco, p. 6-8, 1 fig. 

Slade, H. B. 

1903. Some conditions of stock poisoning in Idaho. Idaho Agricultural Experi- 
ment Station, Bulletin 37, p. 181-183, 1 pi. 



1905. Some alkaloids of the death camas. American Journal of Pharmacy, v. 77, 
no. 6, p. 262-264. 

Vbjux-Tyrode. 

1904. The composition of Zygadenus venenosus and the pharmacological action 
of its active principle. Journal of Medical Research, v. 11 (n. s. v. 6), no. 2, 
p. 399-402. 

Watson, Sereno. 

1880. Botany. [Geological Survey of California.] v. 2, Cambridge, Mass., p. 183. 

Wyeth, N.J. 

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Oregon, v. 1, pt. 3/6., p. 225. 



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