68 SECTIONAL ADDRESSES 



A consideration of these papers suggested that in any comparisons of 

 amoebicides with emetine in vitro the effect of acidity should be studied, 

 particularly when the amcEbicides are to be administered orally, and that 

 tests should be carried out at a^H value of 6-2 or 6-3. 



Under these conditions T.A.D.D. is three to five times as efficient as 

 emetine. Moreover, when blood is added to the medium even at p\i 

 values otherwise favouring emetine, T.A.D.D. and emetine are of very 

 similar amcebicidal value, the former at times showing a definite 

 superiority. 



The toxicity of T.A.D.D. to mice has been compared with that of 

 emetine with the following results : 



Median Lethal Dose mg.jg. 

 Oral. Subcut. Intraven. 



ax-Tetra-«-amyl- 



diaminodecane 



dihydrochloride . 0-45 0-35 0-04 



Emetine 



dihydrochloride . 0-04 c-o6 0-013 



It has thus only one-tenth of the toxicity of emetine when administered 

 orally to mice, and one-sixth on subcutaneous injection. Its therapeutic 

 index is therefore much more favourable than that of emetine, and it 

 appeared to be an exceptionally promising compound for clinical trial 

 in conditions of ill-health due to infestation with Entamoeba histolytica. 

 At this point, it was recommended to and accepted by the Therapeutic 

 Trials Committee of the Medical Research Council for clincial trial. It 

 was tried clinically by Prof. Warrington Yorke, F.R.S., who has 

 kindly allowed me to state his results. He finds that T.A.D.D. has some 

 action in amoebic dysentery, when administered orally, but is not suffi- 

 ciently active to be of any real value. Unfortunately, it cannot be given 

 intramuscularly, subcutaneously or intravenously as it is intensely 

 irritating. 



It appears, therefore, that the comparison of the amcebicidal values of 

 emetine and T.A.D.D. with a faintly alkaline medium gives a better 

 indication of their relative clinical value than the comparison in a slightly 

 acid medium. This knowledge will be of value in further work on the 

 subject. 



The foregoing account of investigations in chemotherapy indicates the 

 enormous amount of chemical and biological work involved in attempts 

 to evolve new drugs for the treatment of disease. Investigations of this 

 type involve the team-work of a group of chemists and biologists before 

 the selected product reaches the clinicians, and in the present case I 

 should like to pay special tribute to the parts taken in it by Mr. Coulthard 

 on the bacteriological side and Mr. Levene on the chemical side. Only 

 a limited number of private concerns have the facilities for such co- 

 operation, and it is therefore very satisfactory to know that work of this 

 character is being carried out under public auspices, such as the in- 

 vestigations into anti-malarials directed by Prof. Robinson under the 

 Chemotherapy Sub-committee of the Medical Research Council, and those 



