During the last few years much has been written both for and against the usefulness of radium as a therapeutic agent in the treatment of malignant growths. The observations along this line have been chiefly clinical, made, that is, upon tumors in man, where it was impossible to control the results with any degree of accuracy. Each investigator has developed a different method of applying and filtering rays, so that much confusion has arisen in regard to the most satisfactory method of applying these rays and the manner of employing them in order to obtain the best results.

Two years ago investigations were begun along this line in the Crocker Fund laboratory, using transplantable animal tumors, in which the results can be controlled with a far greater degree of accuracy than is possible in the human subject. The outcome of these experiments has been published in full elsewhere (1).

Little attention has been paid in the work already done, however, to the effect of radium upon the isolated cells of mammalian tissue. Yet it is here that the action of the radium rays is exerted for good or ill, and it is essential to know just what takes place within the confines of the cell exposed to the influence of this element. It was in order to clear up this phase of the question, therefore, that the following work was undertaken.

The employment of in vitro cultures of cells growing in plasma offers a convenient method for observing growing tissue, and this, therefore, was chosen as the most suitable means for studying the changes produced by radium upon the individual cells. In all the work which has appeared since radium has been obtained in sufficient quantities to allow of its general use, practically no observations have been made previous to 1914 upon the action of radium rays on living mammalian tissue grown outside the host. As early as 1911, however, Wedd and Russ (2) reported a series of experiments in which a transplantable tumor was removed from the mouse in which it had grown, kept moist between mica sheets during exposure to radium, and then inoculated into mice; it was found that no growth resulted from the grafts, provided they had been radiumized for a sufficient length of time. Several years later, Wassermann (3) published the results of his work along the same line. He, however, exposed pieces of tumor tissue suspended in Ringer's solution to the radium rays and inoculated these fragments into animals, but did not try to grow the cells outside of the body. He formulated from his results the hypothesis, that following radium therapy there results a nuclear but not a cellular death. No observations were made, however, on the growing cells themselves, a circumstance which rendered his deductions of less value than they might otherwise have been. In this same year, however, Price Jones and Mottram (4) undertook to expose pieces of transplantable mouse and rat carcinomata to the action of radium rays. After the exposure, plasma cultures were made of the tissue and twenty-four hours later there was observed an extrusion of spindle cells which had been uninfluenced in their ameboid activity by the beta or gamma rays. The alteration in the power of these cells to divide, as shown by the decrease in the number of mitotic figures, was regarded by them, however, as evidence of a profound effect exercised by the radium rays upon the growth of tumors. Their results partially corroborated Wassermann's hypothesis concerning the increase in the size of the growth, which he had suggested was due to an ameboid outwandering of the cells and not to any true mitotic division. In other words, Wassermann believed, though he had not made any observations upon tissue growing in vitro, that the proliferative power of the cells was destroyed by the action of the radium rays, but that the cells were not killed, being left, rather, in a purely vegetative condition. Whether this was the case or not still remained undecided, and the evident importance of the question stimulated the undertaking of further experiments along the same line, which are here reported. The first tissue used was that of the embryo chick heart, as it can be kept alive and growing for a long period by the method of culture set forth by Carrel (5). The fact that this muscle continues to beat for a long time after its removal made it peculiarly favorable for this work; for were the heart to continue to beat this would be a conclusive indication that the culture was still alive, even though there was no evidence of an outgrowth of those new cells which are regarded by Carrel and most investigators as connective tissue elements. The method used was simple, and followed fairly closely the technic already described by Carrel and others. Hearts were removed from chicks which had been incubated for from five to seven days, cut into small pieces about 0.001 gram in weight, and some two or three dozen such fragments suspended in a hanging drop of Ringer's solution on a cover slip sealed with paraffin over a hollow slide. The cultures to be treated with radium were then covered with 0.4 mm. of brass, upon which the radium tubes were placed, and thus exposed to the action of 100 mgm. of radium for one-half and two hours respectively. In a previous series of experiments (1), it had been found that the lethal point of small pieces of tissue, where the unfiltered rays were concerned, was twenty, fifteen, and ten minutes for 17, 83, and 100 mgm. of radium respectively. When the alpha and soft beta rays were removed by filtration with 0.4 mm. of brass, three hours, one hour, and forty-five minutes respectively, were required for 17, 83, and 100 mgm. to kill; whereas when only the gamma and secondary beta rays were employed, twenty hours were necessary for 17 mgm. of radium, and about seven hours for both the 83 and 100 mgm., to cause death.

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