Malcolm. — Experiments on Tutin and Tutu Poisoning. 249 



much the same way and with practically the same results as Dr. Fitchett 

 and myself. He found, as we did, that tutin is extremely toxic, the lethal 

 dose to guinea-pigs and rabbits being a few milligrams per kilogram body- 

 weight, and that it is not readily destroyed — e.g., it withstands treatment 

 with acids, and does not lose its properties on standing. Like ourselves, 

 he failed to produce immunity to its action. A large part of his work was 

 done on the fate of tutin in the tissues, and his most striking assertion is 

 that the tutin can be localized in the brain. From our experiments Fitchett 

 and myself had come to the conclusion that tutin attacks the nerve-centres, 

 but Foid goes further and says he is able to prove its existence in the brain 

 as a " detoxified " body which reduces Fehling's solution after being hydro- 

 lyzed with HC1. I have repeated his experiments, following his method 

 so far as I can gather it from his paper, but I have not succeeded in getting 

 a positive result. The same problem had presented itself to me before 

 I saw Ford's paper, and I had already done some of the experiments he 

 describes — e.g., I also found that brain-tissue from a recently killed animal 

 does not diminish the toxic power of tutin (Exp. 226). 



Recent Experiments on the Fate of Tutin in the Body. 



Our previous work on this point had led to no positive conclusions. We 

 found no evidence for the existence of tutin in the urine or in the milk of 

 rabbits. We believed we had some evidence of accumulation of the drug, 

 as successive sublethal doses proved fatal (see Exp. 13 in Fitchett's paper), 

 but we suggested that th.o facts might be explained in another way — viz., 

 that the vital mechanisms became more and more susceptible to the. action 

 of the drug. 



In considering the possible fate of a poison in the body several possi- 

 bilities present themselves : (a) The poison may remain unchanged and 

 become uniformly distributed throughout the tissues ; (b) it may remain 

 unchanged, but some tissues may have more and some less ; (c) it may 

 be changed into some other substance which may be uniformly or irre- 

 gularly distributed. Besides these possibilities, the poison may be excreted 

 more or less rapidly in changed or unchanged form ; in the case of tutin 

 this is unlikely, at least so far as the unchanged poison is concerned (see 

 previous papers). Concerning the other possibilities, all that one can say 

 at present is that experiments show that (a) is unlikely — e.g., Expe. 238 

 and 240 show that the extract of relatively large amounts of muscle has 

 no toxic effect. This fact is of considerable practical importance to sheep- 

 farmers, for I believe it would be quite safe to feed the dogs on the meat 

 of sheep accidentally poisoned by tutu. 



Besides the muscles, I have examined the liver, blood, and brain of 

 animals after administration of large doses — larger relatively than is likely 

 to occur in stock spontaneously eating the tutu-plant — but I have not 

 been able to detect any evidence of its presence in any tissue except blood 

 and brain, and in those instances only in traces. 



In examining the tissues for presence of tutin two methods presented 

 themselves — that used by Ford, in which the tissue is examined for a 

 reducing substance after hydrolyzing ; and, secondly, the biological method, 

 in which the toxicity of extracts of the tissue is examined. As already 

 stated, I was unable to obtain Dr. Ford's results, and accordingly made use 

 of the second method to a greater extent. The tissue was usually dried, 

 care being taken that the reaction was acid ; the dried material was ex- 



