it on the eighth day. By allowing this to dry and then drawing it across the vesicle again a layer of lymph of double the thickness a single charge would give was placed on one surface. Some of the strips of paper had a single and some a double charge given to them. In using these a piece two lines long was cut off and laid on the abraded spot after being moistened. Where I wished to apply a single charge of lymph to the arms of different individuals whilst this was quite moist a piece of the paper two lines square was charged with the fresh lymph as it flowed and was applied to the abraded surface, which latter was made as nearly as possible to correspond to the size of the paper.

When a double charge was applied the first square of paper, after being allowed to remain on the abraded spot for a given length of time, was removed and another piece, freshly charged, was applied. Small squares of thin ivory were used in a similar manner, but on the whole I prefer the paper.

The object of this mode of proceeding was to ascertain what difference there was in the amount of susceptibility in different individuals and also to determine whether the degree of irritation varied according to the quantity of lymph applied to an abraded surface of a given area. It was for the time being assumed that the power of vaccine lymph did not vary when used whilst fresh. No attempt was made to determine the difference which small variations in the quantity of lymph used would make in the effect produced.

The abrasion of a portion of the skin so as to lay bare, in each case, an area of exactly the same dimensions-or, in other words, an area supplied with a similar number of capillary vessels-proved to be an exceedingly difficult task. So difficult indeed was it that only a very moderate approach to uniformity could be attained. The lancet was the instrument which in most cases had to be used. In some of the cases, however, where I wished to be as exact as possible in the size of the area operated upon, and where the patients were liberal enough to permit the use of a novel apparatus, the cuticle was punctured by a small instru

ment formed by having a number of needles laid together so that the points spread over an area the size of the squares of paper mentioned above, but this method I found was very uncertain. The application of Cantharides to a small portion of the skin might have given uniform results, but I believe that the use of this substance would have been attended with the risk of inducing a greater amount of inflammatory action than could be easily controlled.

As I shall have to show further on, it is not so much the quantity of lymph applied as the more or less perfect manner in which the capillaries are laid bare that determines the degree of inflammatory action.

In both the periods named I was myself a patient, so that I had the opportunity of studying some of the phenomena alluded to a little more closely than I otherwise could have done. The average quantity of lymph used for one vesicle. was about th of a grain (estimated as dry lymph), but I have found that so small a quantity as th of a grain would, if used whilst fresh, produce a full-sized vesicle; but if the lymph is diluted I believe it is possible to make a much smaller quantity than this to suffice.

100

1 500

In operating with the lancet a slip of thin wood, in the centre of which an opening two lines square had been made, was pressed upon the arm, and the lancet was drawn across the skin shown in this opening a given number of times so as to penetrate the cuticle with lines crossing each other at right angles. With a little care, and by using a sharp lancet, tolerably even results could be obtained. Slips of paper perforated in a similar manner answered equally as well as the wood, but were of course not permanent. The squares of paper charged as previously described were applied to these abraded spots.

In the first period the number of persons on whom a normal vesicle was formed was very small. I believe not more than four out of the whole number, and in not one instance do I remember the vaccine fever being set up.

The irritation generally commenced in a very few hours. after the lymph had been applied, but in some cases it would not be felt for two or three days. In the latter case the irrita

tion was generally more severe and more widely spread, and indeed made a nearer approach to the ordinary course of a primary vaccination than is usually seen in re-vaccination. In most instances the vesicles, if such they might be called, arrived at maturity on the fourth or fifth day, and in some few cases as early as the third day.

A curious circumstance occurred in my own case in this first period. I re-vaccinated myself with fresh lymph at the same time that three or four others were operated upon, but whilst in these cases vesicles of a more or less perfect character were formed, no effect was produced upon me. I concluded from this that in all probability I was not susceptible, and that I had to thank the vaccination of my childhood for this immunity. In about four weeks, however, I tried the operation again with lymph obtained from another child, and found that, although the vesicles were very imperfect, I was still susceptible to the action of lymph. In two other instances I have known the same thing to occur. In one of these the patient was suffering from a slight feverish attack of an indefinite character, but of which I was not aware at the time I vaccinated.

From these cases I conclude that there may be a condition of the organism which at times renders the patient unsusceptible to the action of lymph for the time being, whilst there are other patients who are susceptible to the action of one lymph and not to another. Of the exact nature of the

condition which gives these results I can offer no explanation, and it is important to mention here that it is only in re-vaccinated cases that this condition has been seen.

In this first period fully one fourth of those operated upon seemed to be quite insusceptible to the action of vaccine lymph; whilst about an equal number were very slightly susceptible. In all these cases it was the rule to make two abrasions, and curiously enough whilst one vesicle would, in some cases, be more or less perfect, the other would be quite abortive although both abrasions had been treated in exactly the same manner, charge of lymph was applied double one was applied to the

In some few cases a single to one abrasion, whilst a other, but not in any case

could I say that the degree of inflammatory action bore an exact relation to the quantity of lymph applied. In one instance no difference was perceptible.

In 1871 the number of successful cases was much greater than in 1864 and 1865. Whilst in the latter period not less than one in four proved to be entirely insusceptible, in the former period not more than one in ten seemed to be so. In some cases the susceptibility seemed to be very small indeed, but in others the vesicles were as well-formed as in any primary vaccination. In these cases it would have been interesting to have tried whether the lymph would have afforded as complete protection, if used for other patients, as that obtained from a primary vaccination. The feeling that it was my duty to do that which I knew would give the most complete protection prevented me trying any experiments of this kind; but I do not doubt that lymph obtained in this way would be quite efficacious.

In primary vaccinations there is, as every one knows, a period of quiescence, so far as external signs are concerned, between the insertion of the lymph and the formation of the vesicle. In first vaccinations this period may extend to the seventh or eighth day; in re-vaccination it is generally much shorter, rarely going beyond the second or third day, and sometimes not lasting more than twenty-four hours. This stage of incubation was longest in those cases which were most severe, and in which the vesicle approached most nearly to the character of the vesicle of a primary vaccination; but I could not say that this period of quiescence was as long in any case as it usually is in the latter.

In some cases sores were formed which kept up a constant discharge of thin puriform lymph for ten days or a fortnight after the usual period of healing was past. In two of these cases there had been a previous attack of syphilis, and in these the wound enlarged to quite double the size of the vesicle first formed; rendering it necessary to have them dressed with a stimulating lotion before the healing process would commence. Had it not been that twenty-five to thirty other patients were re-vaccinated along with the two mentioned above, and in whom no untoward appearances

were seen, I should have been inclined to suspect that the lymph used was unhealthy, and this leads me to observe that in some cases of primary vaccination, where I have known that a specific taint has existed in one or other parent, I have had similar trouble with the vaccination in the child.

In

As a rule those who were full fleshed or inclined to obesity suffered more severely than those of spare habit, but some even of the latter had a smart febrile attack. one case this was attended with a slight tendency to delirium. In my own case the vesicles began to appear in about forty-eight hours after the lymph had been applied, and at the end of the fourth day I began to have a sense of chilliness, with aching pains in the spine and weariness over the whole body. The sleep was fitful and disturbed for a couple of nights. The vesicles were small and not very perfectly developed and arrived at maturity on the sixth day. For about two days the arm was very painful and tender to the touch. During the night the pain and burning sensation around the abrasions were quite severe enough to keep one awake if the arm was not kept elevated a little above the body and in an easy position. After the seventh day the symptoms gradually abated, but there was one symptom which in my case was the first to appear and the last to depart. I allude to the peculiar stinging sensation felt in or around the abraded spots. This was so sharp and sudden at times that one forgot all about the vaccination and grasped the arm suddenly in order to get rid of it. I believe that this sensation is very common amongst those who have been re-vaccinated, for I found on inquiry that a very large number of my patients complained of the same thing. My reason for drawing attention to it, however, is to mention that as it lessened in intensity in the area affected by the vaccination it seemed to spread itself over the whole of the upper and lower limb of the same side. The sensation was at times felt in the foot or the hand so distinctly that it seemed almost as if it might be the prelude to partial anesthesia.

It was often very troublesome long after the vaccinated