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In 1938 James and Tate described a tissue phase of P. gallinaceum in chicks which they called the exoerythrocytic phase of the parasite, and in 1945 Hawking succeeded in growing these forms in tissue culture. At the time of writing, similar forms have not been demonstrated in mammalian malaria, but it is likely that they do exist, and that the relapses common in benign malaria are due to their presence.The tissue culture technique has been used as an in vitro method for testing the effect of drugs against the tissue phase of P. gallinaceum. It is hoped that this test can be adapted so that the effect of drugs against the tissue phase of all types of Plasmodia can be investigated. A drug which was active against the tissue phase of the malaria parasite in this test would probably be a causal prophylactic and have a beneficial effect on the relapse rate of benign tertian malaria. METHOD Ten-day-old chicks were injected with sporozoites of P. gallinaceurm and killed [7][8] days later, when they were heavily infected with tissue forms of the parasite. In a typical experiment the spleen from such an infected chick was removed aseptically, minced finely in Tyrode's solution, and set up in Carrel flasks, each of which contained 3-4 coverslips, using the method described by Hawking (1945). The fluid phase consisted of Tyrode's solution containing 20 per cent (v/v) chick serum and 3-4 per cent (v/v) chick embryo extract; 0.05 per cent phenol red was added to indicate changes in the pH of the medium. Penicillin was also added to make a final concentration of 3 units per ml. as an additional safeguard against possible contamination by bacteria. (Later 0.5 unit/ml. was used.) Drugs to be tested were dissolved in Ringer's solution, sterilized by boiling, and appropriate concentrations made by serial dilution. 2.5. ml. volumes of the fluid phase were then run into the flasks containing the infected spleen explants, followed by 0.5 ml. volumes of the drug solutions-the control flasks receiving 0.5 ml. volumes of sterile Ringer solution in place of drug. In this way a series of flasks was set up in which the same infected material was in contact with varying concentrations of several different drugs.Under these conditions the final concentration of the drug in the flasks is less than the nominal concentration owing to the absorptive powers of the plasma and spleen explants used in the course of the experiments; the ratio of the nominal concentration to the final concentration may also vary because the amounts of spleen and plasma used were not

Early types of antibacterial substances were not specifically antibacterial, but were usually toxic to all living cells, and were of value only in so far as they could be employed without serious damage to the host. The search for more suitable antibacterial agents resulted in the preparation and testing of many substances of widely different constitution, and it was from the empirical yet systematic investigations of one such class of chrysoidine dyestuff that knowledge of the activity of sulphanilamide arose. The growing evidence that the antibacterial action of sulphanilyl drugs was due to competition with an enzymic metabolic process suggested to Fildes [1940] a new approach to the problem. This was the design of antibacterial agents by the synthesis of compounds with a close spatial resemblance to substances vital to, or closely associated with, bacterial growth and reproduction. These growth substances include the water-soluble vitamins of the animal world, which now appear to be essential to the life of all growing cells. The method has been recently used in a sufficiently diverse series of independent investigations to confirm the principle [Mcflwain, 1943]. Other compounds which exert a pronounced physiological activity in minute concentration are the animal hormones related to cyclopentanophenanthrene; for example, oestradiol, when injected into an ovariectomized rat of 50 g. body weight in a dose of 02 jig., is capable of doubling the weight of the uterus; with a blood volume of 2 ml., this represents an activity at a concentration of 1 in 107. These compounds are not known to be hormones for the vegetable kingdom, but they are widely distributed in nature and are probably constituents of all growing cells, being found in all plants and bacteria [Aschheimn & Hohlweg, 1933], as well as in all animals. It seems to us that these compounds can readily be incorporated into the living cell, and that such molecules constitute suitable material

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