Ten years ago, the late Dr John Brownlee published in The Lancet a preliminary note giving the reasons which led him to conclude, provisionally, that epidemics of influenza tended to occur at intervals of approximately 33 weeks. In the following year two other short notes were published in the same journal by Mr Spear and by Dr Stallybrass. Dr Stallybrass, from an analysis of Liverpool data (not very fully set out in his paper), confirmed Brownlee's conclusion, but Mr Spear, using the London data, criticised Brownlee's inferences and methods, pointing out—inter alia—that an interval between successive epidemics of the order of 52 weeks agreed better with the observations than an interval of 33 weeks or a multiple thereof. In an appendix to the Report on the Pandemic of Influenza 1918–19 issued by the Ministry of Health, Dr Brownlee reaffirmed his original contentions, published some further collateral evidence and replied to Mr Spear's methodological criticism. That was, I think, the end of Dr Brownlee's connection with the subject; to his death he retained, I think, a half-serious faith in the 33 weeks' rule but did not regard the matter as of sufficient epidemiological interest to justify further investigation.

The nitroso-bacterium inoculated into sterile urine does not produce nitrites. If, however, urine be added to an active culture of this microorganism nitrites are rapidly developed.

A nitroso-bacterium culture developed in bulk in peat and chalk can be used as a urinal. After passing through this urinal all ammonia in urine appears to have been converted into ammonium nitrite and nitrate. No odour is noticeable when left to evaporate at either 37° C. or at room temperature.

Urine rendered ammoniacal before use and then sterilised is also a good medium for the growth of the nitroso-bacterium.

The nitroso-bacterium is difficult to isolate because (1) when colonies are developed on a dilution plate, sufficiently spaced to allow of certainty in subculture, nitrification only rarely takes place in the sub-culture, and when it does take place some months are required for the production of a measurable amount of nitrite, and (2) the nitroso-bacterium usually grows in association with some other more rapidly growing species. The colonies of this other microorganism often appear to be pure, but when growth has proceeded for some days individual colonies of the nitroso-bacterium may appear in a certain percentage of the plates.

1. The incidence produced during 1926 by two epidemics of diphtheria, in a remote and unsalted country district, was equivalent to 30 years of the London endemic morbidity.

2. The cases arose in two distinct groups. An autumn outbreak with a definite concentration of infection on the school age, and probably disseminated by droplet infection, followed by an epidemic in the succeeding spring which was more severe, probably milk-borne, and in which the frequency of cases was higher among infants and adults than school children.

3. The effect of a long drive over bad roads caused a deterioration of the diluted toxin which was used for a Schick test investigation. The use of this toxin led at first to false conclusions regarding the immunity of the children, since it only caused reactions in the most susceptible members of the community.

4. As a result of retesting with a fully potent toxin it was estimated that the figure of 40 per cent. susceptible which was found with the weak toxin would have been about 80, if full strength toxin had been used.

5. The attempt to immunise actively those children who had reacted to the weak Schick toxin was found to have failed in 72 per cent. of a group which was retested 7 months later. The prophylactic course was identical with one which had succeeded in inducing Schick immunity, within 4 months, in 100 per cent. of the susceptible children in the Dunedin orphanages.

6. The slow rate of immunisation at Kaitangata is attributed to two causes, (a) the low original herd immunity of the district, (b) the selection by the weak toxin of only the most sensitive reactors which were almost certainly the most “unresponsive” members of the total Schick positive population.

7. By a comparison of the rate of response to a small dose of toxin-anti-toxin mixture, in those positive Schick reactors (a) who had, and (b) who had not, received previous prophylactic injections, it was shown that the principle of “primary and secondary” antigenic stimuli held good for human subjects, as well as for experimental animals.

8. Careful examination of the known data led to the conclusion that the air-borne autumn epidemic had increased the herd immunity of the population, in spite of the fact that the subsequent milk-borne spring outbreak produced as high a morbidity and a more severe type of diphtheria.

9. The practical lessons which may be learnt from this study are: (a) That unless a special buffered diluent is used, the toxin used for Schick testing must be freshly diluted near the place where it is to be used, (b) Active immunisation of remote unsalted communities against diphtheria requires more time, and more intensive courses of prophylactic, than areas where diphtheria has been endemic for some years, (c) In such places with a low original herd immunity, it is essential, even more than in endemic centres, never to omit retesting those who have been inoculated, in order to be certain that any attempt made to induce active immunity to diphtheria may be successful. (d) Estimations of the relative efficiency of diphtheria prophylactics, which are based on the rapidity with which samples of children become immune, are worthless unless all the observations have been made in the same environment on groups having the same original herd immunity, (e) An immunity, good enough to withstand droplet infection in a day school environment, may be broken down by massive doses of diphtheria bacilli in milk.

10. The study of outbreaks of disease in communities which are not too large to prevent a complete supervision of the whole population and environment, enable one to visualise imaginary mechanisms of infection very much more easily than in large populous areas, where so many more factors have to be left unexamined, or remain unsuspected. The hypotheses, perhaps better termed surmises, which the facts suggest, are only intended to be purely tentative and temporary. Their practical value is that they indicate to the investigator a plan of campaign and suggest what to look for, in the lucky event of his ever again meeting with a similar combination of circumstances. In epidemiology in general, as illustrated by this particular instance, opportunities arise and pass, often never to recur, and much is missed, or left undone that might have been done, if only the knowledge and hints gained during the passage of the epidemic itself had been known before its advent.

The work described in this paper was commenced in 1926 in order to demonstrate whether or no infections with the M. catarrhalis afford positive reactions with gonococcal antigens. It had already been shown that an antigen of M. catarrhalis might react with the sera from gonococcal infections. Later it was decided to investigate aberrant forms of M. catarrhalis and allied organisms and also to test whether sera which react very strongly to the Wassermann reaction might also react non-specifically to the Gonococcal Complement Fixation test, possibly to such a degree as to detract from the value of the latter. Such a non-specific reaction might be of the nature of a group fixation (the Wassermann being not anti-spirochactal but probably anti-lipoidal), or to adventitious substances introduced in the preparation of the gonococcal extracts from cultures derived from patients with secondary syphilis.

From 72 cases of pyrexial illness, occurring in British Guiana, an organism has been isolated which has the cultural and serological reactions of B. para-typhosus C (Hirschfeld). It seems probable that enteric fever, due to infection with this organism, is now endemic in the Colony, and is an important cause of sickness and death.

(1) A modern pressure steam steriliser is thoroughly tested systematically.

(2) The experiences gained by the different methods employed are compared.

(3) It is shown that if steam is forced through the objects to be sterilised, the penetration through and the heating of the materials are practically effected in the time it takes to fill the oven. A bucket containing four surgeons' smocks and placed in accordance with the new principle, is thus heated in 5 minutes from 24° C. to 126° C. in all layers, by steam at 134° C. (2 atm. pressure). The same bucket placed in current steam at 134° C. with space for the steam to stream round about the bucket, as in ordinary sterilisers, is to be steamed for 40 minutes to get the thermometers in the contents to register over 125° C. In the first case, the samples of earth used are sterile after 5 minutes, in the second, after 30 minutes.

(4) In a series of orientating and purely provisional experiments, it is also proved that a smock bucket can be sterilised throughout at a low temperature, by formaldehyde-aqueous vapours, when these are sucked through the smocks, in accordance with the new principle.

The culture of organisms in a stagnant liquid medium, which is the normal method employed when the products of their metabolism are studied, has obvious disadvantages. The medium is constantly varying in its constituents and physical characteristics; prominent variations are oxygen tension, pH, food supplies and surface tension, and growth phase of the organism. Experimenters are constantly occupied in preparing nutritive media bearing closer analogy to living tissue fluids; but strangely enough little attention has been directed to maintaining the dynamic conditions obtaining when infection takes place. Yet such conditions may greatly modify the metabolism and general pathological activity of the organism.

The question of the relationship of the virulent diphtheria bacillus to avirulent forms of similar morphology and fermentative properties has always attracted the interest of bacteriologists. Practically all careful observers agree that avirulent bacilli can never become virulent either in vivo or in vitro. It has been also the experience of most observers that no virulent strain can be made avirulent by laboratory methods. Crowell (1926) and Cowan (1927) have however reported that they had succeeded in isolating avirulent variants from a pure culture of a virulent strain. From the nature of Crowell's experiment, which only records one such change, it seems possible that he may have chanced on a true biological (i.e. uncontrolled) variation, but Cowan suggests that it might be possible to isolate with some degree of regularity “rough” avirulent colonies from virulent cultures. As Cowan points out the procedure is both lengthy and difficult. My own experiments in this direction have been entirely negative, although I have on many occasions tried to isolate avirulent variants from virulent cultures by colony selection and other methods. I have not even been successful with the cultures with which Miss Cowan worked and which she very kindly put at my disposal. Individual colonies of the Park 8 strain have been also tested on more than 700 occasions and have always proved fully virulent when pure. Passage both through a large variety of artificial media and through animals failed to engender avirulent variants.

1. There is a lower percentage of positive Wassermanns in cases of malignant disease than in a similar population of non-malignant cases. If buccal cancers are excluded, the percentage is half that in non-malignant cases.

2. Cancer of the tongue and buccal cavity, in which a high percentage of positive Wassermanns is found, is almost confined to males and is probably due less to syphilitic infection than to some factor such as smoking.

3. There is a low percentage of syphilis in cancer of the digestive tract, except in cases of cancer of the stomach, and the incidence diminishes from mouth to anus.

4. Syphilis does not appear to be a factor of importance in cancer of the glandular organs, nor, apart from the lip, in the production of cutaneous cancer.

5. In general, from the above figures there is no evidence that syphilis plays any direct or very important part in the production of cancer.

The spermicidal powers of the various chemical contraceptives sold to the public have never previously been compared, and no one has been in a position to say that one spermicide is preferable to another. The only literature on the subject consists of the pamphlets issued by the makers of the different pessaries, and these give little or no information on the length of time taken to kill sperms at stated concentrations. The Birth Control Investigation Committee therefore asked me to undertake this investigation. The work was financed by the Committee, and carried out, with Prof. Goodrich's permission, in the Department of Zoology and Comparative Anatomy at Oxford.

A statistical analysis has been made of the figures collected during the last eight years in the Edinburgh area, relating to asthmatic patients who presented themselves for examination in certain departments of the Edinburgh Royal Infirmary. The figures for males and females are considered separately, and refer to the numbers of individuals who presented themselves at various, ages, and in whom the disease first manifested itself at various earlier ages. In all, complete records were obtained of 193 males and 167 females. For convenience the ages are grouped in five-year periods.

It has been shown that the figures in the case of females agree well with the assumption that asthmatics, no matter at what age they are first affected, gradually cease to suffer from the disease, or at least fail to report for examination, at a rate which is constant and independent of age. In the case of males the agreement between theory and observation is not as good as in the case of the females, but much of the discrepancy results from two or three obviously aberrant figures. Of every 100 asthmatics at any age it would appear that approximately 7 females, or 8 males as the case may be, are transferred to a non-complaining category every year. The absence of complaint may be due to death from asthma, or recovery, or to some other cause, as for example, that by repeated experience the individual learns how to avoid conditions which precipitate an attack.

On this assumption the relative rates of incidence (P) of the disease at various ages have been calculated for males and for females. Both curves fall during adolescence, rise to a maximum, and then gradually fall, but the male curve lags behind the female curve. From these figures the rates of attack amongst the potential asthmatics (p) have been calculated both for males and for females. The curves fall during adolescence, then rise, remaining practically constant until about 45 years of age, when a rise occurs towards unity. For the further analysis of these curves larger numbers of figures will be necessary, in order that confidence may be placed in the results.

In 1927 we undertook certain work at the request of the Medical Research Council, as part of an international investigation into the standardisation of scarlet fever reagents promoted by the Health Organisation of the League of Nations. The laboratory work was carried out by the late Dr G. R. James, and his untimely death caused the suspension of the research. A great many observations, however, had been made. Since many of these have a general interest, and since up to the time of writing no completely satisfactory experimental method of assay has been devised, we have no hesitation in adding to the volume of evidence that is accumulating with regard to the methods at present in use.