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A. Introduction At a meeting on psychochemicals arranged by the Battelle Memorial Institute in Columbus, Ohio, on Oct. 13, 1955, Dr. A. C. K. Elliott, of the Montreal Neurological Institute, mentioned the work of Florey. He pointed out that certain dialyzed aqueous brain extracts interfered with peripheral synaptic transmission. 1 One of us (H. A. A.) asked Dr. Elliott whether he knew of the reaction of Siamese fighting fish to LSD-25 2 and suggested that it might be of great importance to study the effect of this brain extract on the reaction of fish. Upon returning to Cold Spring Harbor, a project was set up making beef brain extracts somewhat similar to those described by Florey, with modification of the process so that perchloric acid was at times omitted and lyophilization was utilized throughout. Lyophilization avoids to a certain extent the problem connected with instability in solution. It also provides

A. Introduction It has been shown1,2that 2 mg. of crude beef brain extract per milliliter of water blocks the usual effect of 2μg of LSD-25 per milliliter in the outside liquid on the Siamese fighting fish.* The experiments to be reported here are the study of a blocking effect probably produced by another mechanism: the development of tolerance3to LSD-25 in man by the prior administration for a period of days of a compound similar to LSD-25. This compound, 1-methyl-d-lysergic acid diethylamide (MLD-41), produces in man reactions indistinguishable from LSD-25 but has a higher reaction threshold. It will be shown on the basis of our data that MLD-41 affects both the Siamese fighting fish and man in a manner similar to LSD-25. However, there are important differences; in the fish it is about 1/10 as effective as LSD-25, whereas it is approximately 1/3 as effective in man.

The purpose of this communication is (1) to discuss the errors introduced during the colorimetrie determination of phenolsulphonephthalein in the urine when the color of the dye is obscured by the bile pigments, and (2) to offer a method which permits of fairly accurate estimation of renal function, as expressed by the rate of excretion of phenolsulphonephthalein even though marked jaundice is present. Rowntree and Geraghty 1 noted in their paper, in 1910, that urinary and biliary pigments may be removed from urine by basic lead acetate. No details of the use of this substance were discussed. In 1921 a method was reported by Burwell and Jones, 2 in which it was proposed that the use of a saturated alcoholic solution of zinc acetate precipitated both bile and blood pigments. The following paragraph is a quotation from the paper suggesting the use of zinc acetate. Phenolsulphonephthalein is injected in the usual manner

Whatever the manner in which the normal kidney performs its functions of excreting water, salt, nitrogenous products and foreign dyestuffs like phenolsulphonephthalein, there is not much question that when the kidneys are diseased there is often dissociation of these functions. The importance of the ability of the kidney to excrete phenolsulphonephthalein is particularly emphasized by those cases in which there is a marked diminution of dye excretion while the blood nitrogen figures are normal, or at the upper limit of normal, with the water excretion undiminished. Without discussing the clinical syndromes giving rise to these combinations of expressions of kidney function (not of kidney morphology), it will be assumed that the rate of excretion of phenolsulphonephthalein is one criterion of renal function. 1 And when there is evidence of dysfunction, one method that may aid in estimating diminution of function is the dye excretion. That there is a relationship between obstructive