(1) Inoculation of pathologically active crusts on guinea-pigs caused no reaction, and in this respect a marked difference was demonstrated clinically between the disease of which the crusts were a product, and vaccinia.

(2) On calves the disease tended to show some vaccino-variolal relationship, from the appearance of its vesicles, but it appeared to be distinct on the one hand from vaccinia, and from variola on the other.

(3) Calf experiments, two only in number, suggested that vaccinia and variola failed to protect against Australian disease, and that Australian disease failed to protect against vaccinia or variola.

(4) On monkeys the vesicles of Australian disease were undistinguishable in appearance from those of vaccinia or variola, but the evidence for immunity relationship between Australian disease and vaccinia and variola was of the slightest; Australian disease affording no protection against vaccinia or variola, vaccinia possibly protecting against Australian disease in 25 per cent, of the cases, and variola possibly protecting against Australian disease in 40 per cent, of the cases. Vaccinia protected against variola in 100 per cent, of the cases, and variola against vaccinia in 50 per cent, of the cases.

The determination of the presence or absence of B. coli in a drinking water is universally regarded as the estimation of most value in determining its safety or as grounds for its condemnation. Valuable as this estimation is it is desirable that, if possible, it should be reinforced and confirmed by the determination of the presence or absence of other organisms. In particular it would be of extreme value and importance if the isolation of other selected organisms could be used to throw light upon two points in regard to which evidence is either lacking or indefinite at the present time. These two matters are the question as to whether ascertained contamination is of human or animal origin and as to the probable date of any contamination shown to be present. The B. coli enumeration does throw considerable light upon the latter, but none upon the former point.

Since Forssman (1911) discovered a heterologous haemolysin obtained by immunising rabbit against guinea-pig organs—kidney, liver, etc.—and having the property of dissolving sheep blood corpuscles but not those of the guinea-pig, many authors have devoted their time to this subject, and to the elucidation of the relationship between antigen and antibody.

By using watery extracts of mouse tumours and guinea-pig kidney, and alcoholic goat erythrocyte extract, it has been shown that mouse tumour, guinea-pig kidney and goat erythrocyte antisera contain complement fixing antibodies for all three extracts, although the reaction is most evident when the homologous antigens are employed.

Goat erythrocyte antiserum agglutinates goat blood corpuscles strongly while guinea-pig kidney and mouse tumour sera do not contain haemagglutinin at all. Haemagglutination is therefore not to be regarded as a prelude to haemolysis; the antibodies for both processes can exist independently of one another. It has thus been seen that mouse tumour, guinea-pig kidney and goat erythrocytes have in common the property of producing, when inoculated into the rabbit, besides haemolytic amboceptors, complement fixing antibodies, but receptors for goat haemagglutinins cannot be found in either guinea-pig kidney or mouse tumours.

For his advice and assistance in carrying out this work I desire to thank Dr Schütze.

In January, 1914, Dr J. H. Reford, Uganda Medical Staff, reported the discovery, in the blood of a dog belonging to a European missionary, of a trypanosome showing marked morphological resemblance to the human parasite, the so-called Trypanosome rhodesiense. The dog had made a single journey through the morsitans belt south of Masindi. It died after a short and severe illness characterised by marked emaciation and keratitis. Dr Reford recognised a certain number of trypanosomes in which the nucleus was displaced posteriorly, and also sundry irregular, more or less rounded-off forms. Miss Robertson, who had just completed a tour in this same fly belt, examined some of Dr Reford's slides and expressed her agreement with his view as to the affinities of the organism to the Rhodesian trypanosome. As she had not met with any trypanosomes of the gambiense-brucei group during her experiments in the same district, Miss Robertson, in a report to the Principal Medical Officer dated 20th January, 1914, laid considerable stress on the importance of the find and discussed at some length the pros and cons of the arrival of the dreaded South African organism in this already overburdened Protectorate.

The method for the concentration of antitoxic sera suggested in this communication and now being used in this laboratory, presents a further step towards the desired goal, viz. the preparation, on a commercial scale for general therapeutic use, of antitoxic sera with a minimal amount of attendant protein.

In the concentration of sera on a large scale by the routine methods hitherto published the final products have shown a protein content of about 18 to 20 % with a potency per c.c. four to five times that of the original serum. The above described method yields, as a matter of routine, a final product with a protein content of about 17 to 19% and with a potency per c.c. as much as nine times that of the original serum. With the use of better processes the potency might be higher still.

It is worth while to concentrate by this method plasma or sera in which the unitage is so low that hitherto they would have been discarded as having too low a potency for use even after concentration.

The patient will receive a relatively higher percentage of antitoxic units per gram of protein than if the sera had been concentrated by other methods, for by this method the removal of 70% of the total proteins is ensured.

The heat denaturation of the proteins during the prolonged heating of the serum and consequent diminution of protein relatively to antitoxin may serve to minimise troubles with serum sickness.

In the British Medical Journal, Dec. 18, 1915, there is a letter by Mr Benians, in which he refers to the Toxic Bodies of the Bacillus of Malignant Oedema, and discusses the production of aromatic bodies by the action of bacteria on proteins. He also speculates as to the cause of the lessened production of indol in peptone culture media containing glucose, glycerine and other similar bodies. As the metabolic activities of some bacteria decompose these substances with the production of acid, Mr Benians wonders whether it is this acidity which so modifies the action of the proteolytic ferment that cultures, which, in the ordinary course of events are very foul remain sweet when glucose is present.

During the year 1915, Drs F. Griffith, W. M. Scott and I have been investigating the meningococcus in the Board's Pathological Laboratory with the object of providing information which may be of service to the Board, particularly with reference to the carrier problem.

Simple agglutination tests divided into two main groups a series of 34 meningococci obtained from the cerebro-spinal fluid of cases of meningitis during the recent epidemic.

Certain of these strains of meningococci, which were either not agglutinated or only slightly by any of the sera employed, could be placed in one or other of the groups by the demonstration of their agglutinogenic capacity.

Certain individual strains in each of the groups were agglutinated to a less degree than the homologous strain, and certain strains were agglutinated by sera of both groups.

For further evidence as to specific relationship resort was made to agglutinin absorption experiments.

While the question, as to whether meningococci can be divided into independent groups by means of agglutinin absorption tests, must, at this stage of the investigation, remain open, the experiments detailed above indicate that variations in absorptive capacity between individual strains of meningococci are analogous to, though not in actual correspondence with, variations in agglutinability.

The non-contact naso-pharyngeal strains, culturally identical with meningococci, exhibited in relation to monovalent agglutinating sera prepared with cerebro-spinal meningococci, the same tendency to grouping as the cerebro-spinal strains and similar variations in agglutinability. The 28 non-contact strains, which have been investigated serologically, reacted to the following extent with one or other of the above-mentioned meningococcus immune sera:—5 showed complete agglutination in 1:400 or over, 10 in 1:200 or over, 6 in 1:100; 7 were not completely agglutinated in dilutions higher than 1:50. The first-mentioned 5 absorbed, from the respective agglutinating sera, the agglutinins for the homologous strains. From one of these 5, N.P. 10, a serum was prepared which was found to agglutinate strains in Group II. Of the 16 strains which agglutinated with meningococeus sera between 1:100 and 1:400, a few were tested as to their absorptive capacity in relation to two sera and, as will be seen from the absorption tables, showed evidence of agglutinin absorption. The absorption, though slight in amount, was equal to that occurring with the same sera treated with certain cerebro-spinal strains. The remaining 7 strains, which were agglutinated feebly by the meningococeus sera employed, are being subjected to further investigation (1) as to their agglutinability in relation to other cerebro-spinal meningococeus sera, (2) as to their capacity for producing agglutinating sera for cerebro-spinal meningococci. Taken as a whole, the serological results afford indication of a division of meningococci into two groups with some overlapping of each.

The theoretical explanation may be that the antigenic substance of the meningococeus contains one or other of two specific components, A and B, and sometimes contains both components, one of the two then being present in greater amount than the other. Consequently some strains produce sera with agglutinins of the A class alone; others create agglutinins of the B class alone; others produce both A and B agglutinins, with preponderance in some cases of A and in other cases of B. As regards agglutinability, again, some strains are capable of combining with A alone, others with B alone, and others with both A and B, but to a greater degree with the one than with the other.

Comparing the capacity of an individual strain for producing agglutinin with its capacity for combining with agglutinin, I find that in some cases these two capacities appear to coincide. But this is not a general rule. For example, a strain may have limited capacity for combining with agglutinin, but much greater capacity for producing agglutinin; again, it may combine with A alone, or mainly with A, but produce agglutinins in which B preponderates over A.

Absorption experiments, again, show that whilst there is sometimes a correspondence between capacity to absorb and capacity to create, or combine with, specific agglutinin, this correspondence is not a general rule.

These last two considerations show that the characteristics of different strains of meningococci, while affording a basis for division into groups, are closely inter-related, and, in fact, are connected by inseparable links, which appear to make it impossible to effect a definite cleavage between the one group and the other.

The above observations have been suggested by the results so far obtained, but further work on this subject is in progress, with special reference to the identification of the meningococcus in the naso-pharynx.

(1) The maximum period during which meningococci may be isolated from the naso-pharynx of convalescents exceeds three months.

(2) Meningococci were isolated from the naso-pharynx and proved identical with those isolated from the spinal fluid of the same patient in seven cases.

(3) In two of these cases the type of meningococcus found in the naso-pharynx at first resembled exactly that found in the spinal canal of the same patient, and later was persistently replaced by a meningococcus differing markedly in serological reactions from the spinal strain.

(4) Micro-organisms indistinguishable from meningococci by microscopical and cultural methods (including fermentation tests) were found in the naso-pharynx in 22% of 138 individuals, non-contacts, from an urban population (Lambeth out-patients).

(5) With 63% of these organisms the serological tests confirmed their identity with or close relationship to meningococci; they agglutinated specifically with anti-meningococcus serum and exhibited a tendency to fall into the same serological groups as the spinal strains.

(6) Their agglutinating properties were not, in general, so strongly marked with the sera used as those of the known pathogenic strains but they showed definite absorption of the specific agglutinm. They appeared to differ from the majority of the spinal strains not in the quality but in the quantitative intensity of their specific affinities: some spinal strains, however, resembled them in this.

(7) Thus, in 13·7% of the 138 non-contacts micro-organisms were found in the naso-pharynx indistinguishable by any test from strains of meningococci known to have caused meningitis: these are regarded by the writer as meningococci and the individuals harbouring them as meningococcus-carriers.