Since Gruber and Nicolle expressed the opinion that the agglutination of bacteria by specific immune sera was due to the surfaces of the bacteria becoming viscous under the influence of the specific sera, many theories have been advanced aiming at a more complete explanation of the reaction. Bordet (1899) considered that the agglutinins by uniting with the agglutinable substances lead to changes in molecular attraction between the elements affected, either as among themselves, or between them and the surrounding fluid. He distinguished the two phases of the reaction, (1) the interaction between the agglutinin and the bacteria, and (2) the agglomeration of the bacteria.

(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 condition of Pyrexia, associated with the febrile state, is a phenomenon which has been noted from the very earliest times, but only since the latter half of the last century has the experimental method been brought in to determine the cause of a phenomenon which had previously been a field of speculation only. The very old ideas can be passed over, but in the last century Johannes Müller regarded fever as a reflex process while Virchow (1853) looked upon fever as a neurosis—the condition being considered analogous to a paralytic state, a failure of the control of the vital functions of the body—while it is interesting to note that Traube (1855, 1864) and Traube and Jochman (1855) at this time determined an increase in the elimination of nitrogen from the body in fever. Both Virchow and Traube assumed the existence of a fever-producing agent, but did not proceed to elucidate its nature or origin.

In a former communication (1) we showed that a substance acting as complement is present in milk under both normal and abnormal conditions, and that this substance displays characteristics which lend a certain amount of doubt as to its true complementary nature. Expression was also given to the idea, that the haemolytic system—heated ox-serum + guinea-pig corpuscles—is of a peculiarly sensitive character in regard to ox-complement in the presence of milk.

This subject was first considered statistically by the late Dr Farr. It is one of the brilliant attempts to extract the real meaning of figures so frequent in his work, but though this theory has not shared in the complete neglect that has been the lot of his attempt to put a quantitative measure to the course of epidemics, it has suffered as much from the kind of patronage with which it is usually discussed. On at least one of the great medical officers of health of his time, however,— the late Dr J. B. Russell—the theory exercised a strong fascination. My own copy of Fare's Vital Statistics came from Dr Russell's library, and the whole passage referring to the law is lined with his characteristic nervous pencil marks, while in much of his work on vital statistics the influence can easily be traced.

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.

Actinomycotic lesions in tissues from a consecutive series of forty-four oxen slaughtered in this country have been examined and compared with fifty specimens imported chiefly from Argentina.

The British cases can be divided into two groups, according as the specific granules do not or do contain Gram-staining organisms.

The first group, characterised by the presence of granules consisting of clubs without Gram-staining organisms, contains 40 cases. In these the lesions were situated in the cheek, palate, tongue, or lymphatic glands in relation to the mouth and pharynx. From twenty-three of the forty cases, cultures of a non-Gram-staining organism were obtained, which were identical in their characters on nutrient agar plates and in shake glucose agar tubes; and five of the strains were found identical when tested on a large series of differential media. One of the cultures was inoculated into a calf, and produced a local lesion with the characters of a natural lesion.

This first group shows complete identity in the histological features and in the anatomical distribution of the disease with Actinobacillosis described by Lignières and Spitz in Argentina. The bacillus obtained has the characters of the Actinobacillus, except that the production of typical granules in the peritoneal cavity of guinea-pigs, described by Lignières and Spitz, has not been demonstrated.

All the imported specimens which were examined microscopically exhibited the characters of the lesions of this first group, but the causal organism was not obtained in pure culture.

The second group contains the remaining four British cases. The specific granules were composed of clubs and Gram-staining organisms, including branching filaments. The lesions were situated in each case in the inferior maxilla. The investigation of the biological characters of the organisms concerned is still in progress.

These results show that Actinobacillosis is widespread in the world, and forms a considerable proportion of the cases of disease in oxen known under the name of Actinomycosis.

1. The chain of evidence incriminating the house fly as a disseminator of typhoid fever is at present fairly complete, but many of the links are weak and not thoroughly strengthened by experimentation.

2. The bulk of experimental work has hitherto been done under highly unnatural and artificial circumstances and the results so obtained cannot be accepted unreservedly as giving a correct view of conditions in nature.

3. The experiments described in the present paper show that flies can ingest typhoid bacilli from natural matter, i.e. human faeces and urine, and carry them for a certain period of time.

4. There is no evidence to show that the typhoid bacilli multiply in the house fly. On the contrary the evidence goes to show that they are not adapted for prolonged life on or in the fly.

5. It thus follows that the house fly is a purely mechanical carrier of the typhoid bacillus and is not a natural “host” in the strict sense of the term.

6. Many bacilli closely resembling B. typhosus in cultural characteristics appear to be natural or, at least, common inhabitants of the intestine of the house fly. These are extremely likely to be mistaken for B. typhosus unless the most stringent tests are employed.

7. As might be expected there is evidence to show that a process of bacterial selection occurs in the fly's intestine. Some bacteria appear to flourish but others are rapidly eliminated. Among the latter must be numbered B. typhosus.

I have to thank my colleagues at the Lister Institute, particularly Dr Ledingham, Dr Henderson Smith and Dr Petrie, for much valuable help and advice during the course of these investigations. To Prof. Bainbridge, Dr Arkwright, Dr Penfold and Dr Macalister my thanks are also due, inasmuch as they helped to smooth over many difficulties both theoretical and practical.

This is a particularly difficult branch of the subject to investigate. It might be thought at first sight that the death rates at different age periods might be compared, and this is often done; but when it is noted that the death rates at different age periods are organically connected, it is obvious that such a comparison is statistical or actuarial and completely neglects the biology of the subject. To illustrate the problem a diagram is given. This is constructed on a principle open to objection, but, if that is remembered, it illustrates a number of points. The healthy district life table H2 has been taken as a standard of comparison. Now a healthy district life table labours under certain disadvantages. A district may, as the Register General says, be excluded because it contains an institution drawing its inmates from a wider district. This is not a serious objection. A more serious objection is the fact that whether deaths which might be considered to belong to the district are returned to it or not, the result is equally unsatisfactory. Everyone who has had practical experience knows many instances in which it is impossible to allocate a death to the district to which it properly belongs. When all is balanced, I think that probably on the whole the healthy districts get credit for more than their share of deaths, that is, for more deaths than would occur if there was no process of intermingling of town and country. For one death the town gets credit for, the country gets credit for another, in the one case some old person dying of a cancer in a hospital, in the other, some poor young person, who having tried city life, returns broken, to die of phthisis or some similar disease. Thus a healthy district life table is open to objection as a criterion. It is, however, for the purpose at present required, the only one at our disposal.

In a previous paper (1912) a rough analysis of certain statistical data was made which seemed to show that the age of the parent at the birth of the offspring was a factor in its susceptibility to the Zymotic Diseases.

Although plague broke out in India in 1896, it was not until a period of 18 years had elapsed that it reached Ceylon, notwithstanding the close proximity and the daily intercourse which takes place between the two countries. It is not surprising that this prolonged immunity, coupled with the example of the failure of the disease to thrive in such places as Madras, Singapore and other maritime towns within the tropical belt, should have created in the minds of the public in Colombo a feeling of considerable security as regards invasion by this disease, and that when it was announced that plague had at last broken out, there was the usual scepticism expressed as to the accuracy of the diagnosis. The advent of plague in Ceylon has already been announced by Castellani and Philip (1914).

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.

Fifty-six cases examined for Dysentery bacilli. All save one were clinically dysentery, and all save two were negative for amoebae and other protozoa.

Twenty cases (35·7%) yielded dysentery-like bacilli.

From these twenty cases thirty-six organisms were isolated and studied. Of these—

Six corresponded with no familiar pathogenic organism.

Six resembled B. Shiga. Two agreed completely both by fermentation and agglutination. One also gave typical fermentation and agglutination results but was at first a motile organism, although in later generations it became non-motile. The other three are less definitely Shiga bacilli.

Five were mannite-fermenting organisms but only one agreed very closely in its fermentation reactions with B. Flexner and it was not agglutinated by Flexner serum.

Sixteen cultures from ten separate cases corresponded closely with Morgan's bacillus.

Eight of these agreed completely in their characters with Morgan's No. 1 bacillus.

Three differed only from Morgan's No. 1 in being non-motile.

Five presented characters intermediate between those of Morgan's No. 1 and Bowman's “Bac. S.”

Of six cases yielding Morgan's bacillus, agglutination with the patient's own serum was positive in five.

Three cultures showed affinities with the Bac. enteritidis.

Polyvalent anti-dysenteric serum treatment tried on a considerable number of cases was a complete failure.

In recent years it has been found that in vitro many ferments, etc., lose their power of action at a rate corresponding to the monomolecular reaction, i.e. if the amount of the substance present at the beginning is denoted by unity, and, if after a certain period of time only one half of the substance remains active, then it may be predicted that at the end of an equal period of time, one half of one half, or only one quarter of the original amount, will still retain its power of a.ction. It is not necessary to give examples, they are sufficiently well known.

The material on which this enquiry is based consisted of tuberculous tissue, pus, or fluid obtained from the sources specified in Table II, pp. 260–268.

In a large number of cases the curves which describe the rate at which ferments, antibodies, etc., disappear in the body accord in form with the equations of physical chemistry, but not so as to be readily interpretable. If one molecule, two molecules, etc., take part in a reaction then it is clear that the indices in the equations must bear certain relations to whole numbers. Failure to conform to these relations seems at first sight to imply that a fraction of a molecule takes part in a reaction, but this is not necessarily the case. Such a failure has been found to appear when the curves of many vital phenomena, e.g. the disappearance of agglutins in an organism, are fitted to physico-chemical equations. A possible meaning, however, can easily be seen.

Seventeen cases were examined, the disease affecting the genital organs in nine instances (seven testes, one salpinx, one prostate) and the urinary tract in eight.

The bacilli obtained were of “human” type in fourteen cases and “bovine” in three.

The three “bovine” cases were affections of the kidney in persons aged, respectively, 25, 19 and 20 years.

The following conclusions of practical value to those engaged in serum concentration can be drawn from the experimental work described above:

(1) An end product containing not more than 20% of protein and having a potency of 8 or 10 times that of the original can be obtained as a matter of routine where the pooled antidiphtheritic sera has a unitage not greater than 500, and where the heat denaturation is of the order of 40%.

(2) By the fractional precipitation methods at present employed for the concentration of antitoxic sera for therapeutic use the degree of concentration of high potency sera cannot be taken beyond the limit of about 22,500 units of antitoxin per gramme of protein in the end product.

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.