Part 10

Power and Cambier summed up their conclusions by stating that both the Astragalus and the Crotalaria contain very small amounts of toxic alkaloids, to which they believe the symptoms of poisoning produced were due. Their work from a chemical standpoint is excellent, but from a pharmacological point of view seems to be deficient; in fact, Power does not claim to be a pharmacologist. What would seem to be the proper course would have been to test for themselves the action of the plant on various animals and, after deciding which reacted most characteristically, test, after various precipitations, both the precipitates and filtrates on various animals to see whether the original symptoms and pathological lesions could be produced. They failed, however, to test their mother substance. It is well recognized that plants grown under varying conditions and on different soils vary in the amount of the physiologically active principle they contain.

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

Certain of these precipitates were also later examined physiologically by O'Brine. He also found the resin precipitated from an alcoholic extract of the plant and also the alcoholic extract from 2.2 pounds of the dried Astragalus mollissimus to be physiologically inactive.

Oatman, using Power and Cambier's method with alfalfa (Medicago sativa), obtained a noncrystalline mass which when given in 0.1 gram dose caused frothing at the mouth in a kitten, but no serious symptoms. This 0.1 gram represented about 5 pounds of powdered leaves and tops of the plants.

Since the appearance of Power and Cambier's work Sayre has published various papers on the loco weeds in the Transactions of the Kansas Academy of Sciences for 1903-4, vol. 19, p. 194, 1905; 1901-2, vol. 18, p. 141; Seventh Biennial Report of the State Board of Agriculture of Kansas, vol. 12, p. 97, 1891; Journal of the Kansas Medical Society, vol. 4, pp. 222 and 241, 1904, etc. He has contributed nothing especially new, but says that "the old theory that an alkaloidal poison is secreted in the plant causing the loco trouble has not been found tenable," but wishes to be understood that he does not discredit the ground for the opinion that in some mysterious way certain disorders occur in cattle in connection with what is commonly called loco-weed. He suggests that this connection might be somewhat similar to the relationship between the disorder caused by over-feeding half-starved animals on clover or alfalfa and has had the plant analyzed as to its nutritive value, giving the table in the Transactions of the Kansas Academy of Sciences, vol. 19, p. 194. He makes the suggestion that any injurious action the plants may have might be due to the fine, hair-like projections on the plant which mechanically set up irritation. This supposition can be thrown out at once by the experiment of Day and others, who induced symptoms in animals by extracts of the plant, and by the fact that other coarse plants do not act similarly. This fine, hair-like material was found to constitute about 33 per cent of the plant on grinding. But Sayre himself does not seem to be positive as to any conclusion. He, like O'Brine and others, has obtained alkaloidal reactions from the plant, but states he has obtained similar ones from alfalfa. At one time he said:

I do not consider loco directly or indirectly the cause of the condition, but am of the opinion that what is called "locoed" is, first, congestion of the brain and spinal marrow (causing blindness and first symptoms), and, second, softening to a greater or less extent. These terms describing the alleged symptoms of "locoism" might occur in well recognized diseases resulting from brain lesions, which latter occur in so-called forage poisoning and poisoning from foul drinking water, etc.

We are not prepared to affirm or deny that the loco-weed produces a train of symptoms characteristic of the plant.

Again Sayre states:

It seems not unreasonable to suppose that the peculiar condition of the animals of the plains, when they gorge themselves with this highly nitrogenous weed, has something to do with the disease. A condition of malnutrition may set in and give rise to the rapid growth of a toxic-producing micro-organism or an irritating principle. This principle may be capable of cultivation and of producing disease artificially. Be this as it may, we feel warranted in saying that the so-called poison is a development within the animal, not a product preexisting in the weed itself.

Sayre also suggests the possibility of the plants producing hydro-cyanic acid, which, it is well known, occurs in sorghum. In the Journal of the Kansas Medical Society (vol. 4, p. 243), he claims to have isolated a crystalline body, but this he has not tested physiologically. Sayre especially deserves credit for keeping the loco investigation alive, and no doubt his change in position is due to his lack of facilities for pharmacological testing.

Carl Ruedi fed rabbits daily by a stomach tube with 10 c.c. of an extract (unstated strength) of Astragalus mollissimus and recorded the following results:

After only five injections one of the rabbits died, and the post-mortem showed to a nicety the congestion of the whole tract of the vena portæ and the anæmia of the brain. I put six rabbits under the influence of loco, and the effect was marked, but not rapid, if not given in very concentrated solutions. The solutions were prepared differently, and each of the rabbits had its own preparation, but the effect was nearly the same. In the beginning loco acts as a stimulant; the animals get lively, hilarious, running about; cleaning themselves, etc. This lasts about eight hours, then they become very quiet, sit in a corner of a box, and one can do with them pretty nearly what one likes; they do not move from the place, or just run into another corner, to fall back into the same complacent reverie. One can leave the door open and hammer away at the box, but they do not show any inclination to run away. During the excitement, however, they become fierce, and I had once the opportunity to watch one of the drollest things possible: One of the rabbits, two hours after dosing it, got loose and ran under a porch. A heavy tomcat came near this hole, and commenced sniffing about; this offended the rabbit highly, and it jumped on the neck of the cat, bit it through the skin, and the cat ran screaming away. When the animals are first under the influence of moderate doses of loco, they suffer greatly from hyperæsthesia of the cutaneous nerves; when one touches them with a stick while lying in a corner, without hurting them, one sees the platysma working away very forcibly, and sometimes they utter sounds of pain. According to my experiments the loco-weed works slowly but surely; as soon as the anæmia of the brain sets in, the animals act in every respect mad like; one hour they are excitable, and then again dull and languid as can be. The rabbits eat, when well, very quickly, and whenever they have opportunity; not so the locoed rabbit; he eats slowly for a minute or two, then he goes into a corner and meditates, comes forward to nibble at a carrot or a piece of cabbage, but he never eats greedily, and does not steal it from the mouth of his neighbor, or only very exceptionally. I observed these rabbits for ten days; they did not die, because I gave them weaker solutions; but they all became very ill, and as I had to leave the park I killed them with the needle inserted into the medulla oblongata, and made the post-mortem. In all of these cases I found great congestion in the abdomen, and marked anæmia of the brain. The congestion of the vena portæ commences certainly very early, but still the first symptoms are the nervous symptoms, first as excitants, then depressing or sedative, with a marked hyperæsthesia of the cutaneous nerves.

Ruedi made an attempt to isolate the active principle and separated a base, which he calls "locoin," from an ether shaking. This base, however, he found to be physiologically inactive, but believes the activity to be due to a body which he calls "loco-acid," which is present in the mother liquid after the shaking with ether. He, however, has not obtained this in any degree of purity and gives no chemical data to substantiate this statement save that the fluid was acid.

Experiments made at the University of Pennsylvania with certain loco plants on cats, dogs, and rabbits proved negative.

Other experiments on rabbits have been made by Doctor Lewis. These rabbits were fed on the leaves, stem, and whole plant, and also extracts of one of the loco plants (presumably Astragalus mollissimus) for one or two months, without producing any noticeable effect.

This uncertainty in the results of the investigation as to the cause of the loco disease turned the attention of observers into other lines. President Ingersoll, of the State Agricultural College of Colorado, in his autopsies on sheep was struck by the presence of tapeworms (Taenia expansa) in the gall duct and small intestines. He apparently tried to prove a relationship between the tapeworms and the locoed condition by feeding the extract of a loco plant to sheep, and thus showing its harmlessness. He prepared a decoction from 20 pounds of loco plant (the species was not stated) and boiled this down from 12 gallons to 1 quart. This concentrated extract was fed in three days to a bottle-fed lamb; this lamb showed no symptoms, although kept under observation for two weeks. This theory of the causation of loco by worms was also considered by Curtice, and later brought forward by Steele and Marshall. This idea is very suggestive when considered in relation to the etiology of bothriocephalous anæmia.

Others, again, have claimed that the disease is due to a parasite found upon the loco plants, but all specimens examined by entomologists proved to be harmless.

Lloyd, from his study of the subject, says:

From first to last I have failed in obtaining a characteristic proximate principle, either from the fresh or dried plant. The disease called loco was as murky as the milk sickness so prevalent in the new settlements of Indiana and Kentucky in early days, and, like the numberless herbs that have been presumed to produce that obscure peculiar disease, milk sickness, loco was unresponsive to my chemistry.

It may be safely said that if a specimen of the plant were to be examined in the ordinary manner by a chemist who had no idea of its importance he would report that it did not contain a characteristic proximate constituent.

Can it be that an admixture of loco and some undetermined plant or earth infected with bacteria taken with the roots, each innocuous under other conditions, can by digestion together in the stomach and intestines result in the production of a poison?

To sum up, it seems to the writer that the poison of loco is a product, and not an educt.

But Lloyd adds, in speaking of the reports of various experts and ranchmen:

Their description concerning its toxic action on animals agreed, and it was folly to argue that so many observers from so many sections of the country could be misled. There must be an undetermined something behind the loco-weed.

In 1893 O'Brine, from Colorado, and Mayo, from Kansas, reported on their work with the loco plants. O'Brine failed to isolate any alkaloidal or other poisonous body, and his feeding experiments on himself and on rabbits having failed, he sums up in despair: "The more I examine the loco question, the more I am persuaded that we must look for some other cause besides the loco-weed." At the end of his report he gives some ash analyses but fails to interpret them. He also fails to give details as to the method of obtaining and estimating his ash. O'Brine's ash analyses are as follows:

KEY TO ASH ANALYSIS: A = SiO{2}. B = Fe{2}O{3} and Al{2}O{3}. C = CaO. D = MgO. E = K{2}O. F = Na{2}O. G = H{2}SO{4} H = Cl. I = P{2}O{5}. J = CO{2}

------+-----+-----+-----+-----+----+-----+----+----+----+----+-----+ Plant.|Total| | | | | | | | | | | |ash. | A | B | C | D | E | F | G | H | I | J | ------+-----+-----+-----+-----+----+-----+----+----+----+----+-----+ AM |12.15|32.77|16.26| 6.05|3.11|13.30|3.21|3.9 |0.47|6.12|10.55| | | | | | | | | | | | | AL |13.52|17.08|12.21|14.27|2.62|17.26|5.75|3.22|3.87|3.30|17.37| | | | | | | | | | | | | AC |12.36| 7.82| 5.97|12.10|3.55|23.35|3.38|5.56|9.0 |4.67|20.62| | | | | | | | | | | | | ------+-----+-----+-----+-----+----+-----+----+----+----+----+-----+ KEY TO PLANTS: AM = Astragalus mollissimus (whole plant) AL = Aragallus lamberti (whole plant) AS = Astragalus caryocarpus

These analyses are evidently incorrect, as O'Brine estimates a carbon content of 4.13 per cent for the first, and for the second 2.22 per cent, showing incomplete combustion.