570 



SCIENCE 



[N. S. Vol. XXVIII. No. 721 



THE LOCO-WEED DISEASE 

 For several decades the loco-weed disease 

 lias been a subject of much interest both 

 practical and theoretical — ^practical because it 

 is the cause of extensive losses of live stock 

 in the western half of the United States, 

 theoretical because to the pharmacologist it 

 has offered an unusually puzzling and tan- 

 talizing problem which has hitherto baffled all 

 attempts at solution. 



By far the most important contribution 

 ever made to the subject has recently appeared 

 as a bulletin of the Bureau of Plant In- 

 dustry, United States Department of Agri- 

 culture, by A. 0. Crawford.' In order to 

 appreciate the significance of this piece of 

 work, which is one of the most important con- 

 tributions to pharmacology ever made in this 

 country, it is necessary to recall the state of 

 knowledge concerning " loco " when Crawford 

 began his investigations. The condition has 

 been known for at least sixty years; the 

 United States Department of Agriculture 

 began to investigate it in 1873 and has re- 

 turned to the problem at frequent intervals 

 since. In addition it has been the subject of 

 study by a number of state institutions and 

 by many private individuals. The condition 

 has usually been ascribed to the eating of cer- 

 tain plants; most commonly various species 

 of Aragallus and Astragalus were held re- 

 sponsible for it. All efforts to obtain a 

 poisonous substance from these plants had, 

 however, failed. Most experimenters had been 

 unable to produce any poisonous effects what- 

 ever, when the plants or their extracts were 

 administered to animals; Professor Sayre 

 stated that he had sent thousands of pounds 

 of the dried plants to various investigators in 

 America and Europe, but all reports were 

 negative as to pharmacological activity. The 

 condition was ascribed by some to the me- 

 chanical action of fine hairs on the plant, by 

 others to bacteria associated with the plants; 

 others denied any causal relation between the 

 plant and the condition and attributed the 

 latter to malnutrition, helminthiasis, etc. 



^ " Barium, A Cause of the Loco-weed Disease," 

 Bull. 129, Bureau of Plant Industry. 



The few who had seen poisonous effects from 

 the plants seemed inclined to the belief that a 

 poisonous substance was actually present, but 

 that it was too unstable to admit of isolation 

 except under the most favorable conditions of 

 work. 



Thus when Crawford began his work in 

 1905 it was still a matter of controversy 

 whether the plants he was to study were 

 poisonous or not. Field experiments carried 

 out independently by C. D. Marsh and 

 laboratory experiments by Crawford soon 

 showed definitely that it is possible to pro- 

 duce sickness and death by the administra- 

 tion of certain of the plants. The first step 

 having been thus taken, Crawford attacked 

 the problem of the nature of the poisonous 

 substance. Seldom has a pharmacologist been 

 confronted with a more difficult problem; the 

 few clues from the work of the last twenty- 

 five years proved absolutely misleading. It is 

 impossible to give the details, but a brief out- 

 line will indicate what an amount of the most 

 painstaking work was necessary before suc- 

 cess was finally achieved. Having determined 

 the amount of plant necessary to kill a rabbit 

 of a certain weight, Crawford proceeded to the 

 chemical examination controlling each step by 

 experiments on animals. One group of 

 poisons after another — volatile poisons, alka- 

 loids, glucosides, organic acids, toxalbumins — 

 were excluded. The first encouragement came 

 when it was found that the toxicity was not 

 destroyed by boiling. This was followed by 

 the surprising discovery that the ash of the 

 plant was poisonous ; if any conclusion was to 

 be drawn from the work of previous writers 

 it was that the poisonous substance — if such 

 were present at all — was so unstable that it 

 did not withstand even drying! 



After the discovery that the ash was toxic 

 there were still many difficulties. The ash 

 was very complex but Crawford systematically 

 separated it into many fractions, testing each 

 physiologically. In this way all of the com- 

 mon heavy metals were excluded; the ash 

 however, contained small amounts of zir- 

 conium, titanium, etc. All of these as well 

 as beryllium, thorium, thallium, had to be 



