September 2, 19 15] 



NATURE 



21 



Even without measuring the length of the phago- 

 cyte columns, we may convince ourself that our con- 

 clusion as to calcium promoting the activity of the 

 phagocytes is the correct one. On opening the skin 

 wound, it is immediately seen that in the mineral- 

 watcr-rabbits a much thicker mass of phagocytes is 

 gathered round the tubes than in the pure sodium- 

 chloride-rabbits. The same thing we observed in- 

 variably in all experiments where NaCl-solution con- 

 taining calcium-chloride was injected. 



Taking for granted that phagocytosis is playing 

 a part in defence against microbes, we may infer from 

 the above that an enrichment of our blood, and through 

 this also of the lymph spaces, with small amounts of 

 calcium must have a favourable effect on local and 

 other infections. 



There are manj' experiences supporting this view. 

 I will mention only two examples. In the first place, 

 Sir Lauder Brunton has used with great success 

 chloride of calcium in pneumonia. Other clinicians 

 have also met with success along the same lines; for 

 instance, Crombie, who some years earlier, in the 

 hospital of Calcutta, saw the mortality decrease from 

 386 to 5 per cent. He is inclined to attribute the in- 

 fluence of calcium to an action on the poison excreted 

 by the pneumonia bacteria. But for this there is no 

 evidence. Sir Lauder Brunton has recommended cal- 

 cium for getting amelioration of the heart-action. 

 Ill recovery from pneumonia the amelioration of the 

 heart-action is of the greatest importance. So it was 

 quite rational that the famous clinician and phar- 

 macologist advised calcium for this purpose : in the 

 first place, because it was pointed out by the work 

 of Sydney Ringer that calcium is absolutely necessary 

 for the heart-function, and, on the other hand, 

 Langendorff and Hueck had found that by the injec- 

 tion of calcium into the circulation of a cat the action 

 of the heart was considerably strengthened. 



Sometimes it happens that during surgical opera- 

 tions the heart-beat is stopped by the inhalation of 

 chloroform. The idea occurred to me that in this 

 case calcium might be able to be of good service. 

 Therefore I tried to improve the heart-action by intra- 

 venous injection of calcium in animals, which had 

 been given purposely too much of the anaesthetic. I 

 had no success ; so I began to doubt whether calcium 

 was really capable of stimulating even the normal 

 heart. In a number of experiments I made I found 

 that injection of calcium had no effect on the heart- 

 beat of a normal animal. Studying the original 

 article of Langendorff with renewed attention, I saw 

 that he had performed only one experiment. His 

 great reputation had given his assertion general 

 acceptance, and so it had become a fact in the litera- 

 ture. Obviously the amount of calcium in the normal 

 blood-serum provides already just the optimum quan- 

 tity for the heart function. 



Thus this favourable effect of calcium in pneumonia 

 not being explained by the influence of calcium on 

 the heart, we had to look for another reason. It was 

 therefore most natural to remember the stimulating 

 action of the calcium on phagocytes, which in pneu- 

 monia play such a pref>onderant part. 



My second argument for the probability that calcium 

 i^ of importance in infectious diseases is this: labourers 

 ill limo-kilns do not get tuberculosis; in Holland these 

 v.iirkmen cover any wound they receive with lime. 



The significance of calcium has for some time past 

 n occupying the special attention of biologists and 



tlioiogists in an increasing degree, and 1 shall speak 

 of it further now, and of the cause of the promoting 

 of the activity of the phagocytes in phagocytosis and 

 ( hemotaxis by calcium, only to make one remark. 

 We might be inclined to attribute the increase of the 



NO. 2392, VOL. 96] 



plasticity to a modification in the aggregation of the 

 colloid-protoplasm-particle as a consequence of the 

 electric charge caused by the entering of a number of 

 bi-valent calcium ions into the cells. This explana- 

 tion, however, can scarcely be the correct one here; for 

 experiment shows that other bi-valent kations, namely, 

 barium, strontium, and magnesium, do not augment 

 the amoeboid motion, i.e. of phagocytosis and chemo- 

 taxis. It must be assumed, then, that the action of 

 calcium in this case is based upon a hitherto unknown 

 specific biochemical property of this metal. 



(2) Influence of Iodoform on Phagocytosis. 

 Everyone knows that for the last thirty years iodo- 

 form has been successfully applied in the treatment of 

 wounds and chronic inflammations. At first it was 

 thought that this favourable effect was based upon 

 an antiseptic action, but the idea was relinquished 

 when it was found that lower organisms develop fully 

 in a medium containing iodoform. Then other hypo- 

 theses were suggested, which need not be dvielt on. 

 They are founded mainly on iodine being split off. 

 None of these have proved satisfactory suggestions. 

 For reasons unnecessary to state here, we have raised 

 the question whether the favourable effect of iodoform 

 on local infections may be due to the stimulating 

 effect of this substance on phagocytosis. To answer 

 this question iodoform solutions of different concen- 

 trations in a common salt solution of 09 per cent, 

 were prepared and mixed with a thick suspension of 

 white blood-corpuscles. After having added carbon 

 particles, the mixtures were left to themselves for 

 half an hour in an incubator at 37° C, and then 

 cooled down. Finally, microscopic preparations were 

 made and examined to determine what percentage of 

 the total number of white blood-corpuscles had taken 

 up carbon particles. The following table contains the 

 results of the experiment. 



Concentration of Iodoform Solutions in which the 

 Effect on Phagocytosis is still perceptible. 



Percentage of leucocytes 

 Fluids having taken up carbon 



100 = 44 



NaCl o*9 per cent, (common salt solution j 388 j-43 8 



l38» 



of o'9 per cent.) 



.345 



X 100 = 437 



ri2ix,oo=58-6J 



iodoform to 100,000 NaCl o 9 percent.-^ I'f [S^'^ 



|^£?^xioo = 59-9| 



500,000 



5,000,000 



100 = 522 



.377 



^x 100=61 '4 61-4 

 371 



f20S 



I ^-11 X 100=51 -91 



1445 

 292, 



47 



.52 



?x 100=46*9 1 

 17^x100 = 47-3 I 



37-2 ; 



This table shows that, in the pure salt solution, of 

 the 388 examined leucocytes 171 have taken up carbon, 

 i.e. 44 per cent. In a parallel experiment the per- 

 centage was 437 per cent. Thus the average was 

 438 per cent. In the salt solution containing iodo- 

 form in a proportion i gr. iodoform to loootxi gr. 

 NaCl solution, the percentage in two parallel experi- 

 ments was 586 and 599; average 582 per cent. 

 Evidently the iodoform promoted phagocytosis. 



These and other parallel experiments illustrate also 

 the exactitude of the method. As a matter of course, 

 control experiments have been made in all cases. 



