1. Statistical evidence and animal experiment have alike proved carbolised killed anti-rabies vaccine to be of undoubted efficacy in both pre-infectional and post-infectional treatment. Statistical evidence is furnished by the results of treatment of 90,000 patients, while experimental proof rests partly on the resistance shown by immunised animals to artificial infections with street virus, and partly on an estimation of degree and duration of rabicidal properties in their sera.

2. The Bordet-Gengou reaction is of no value as a qualitative or quantitative test for the estimation of anti-rabies immunity.

3. The efficacy of killed carbolised vaccine and probably of other antirabies vaccines is largely dependent on the concentration of the dosage and the period within which it is administered. Better results follow the giving of small doses over a number of days than the giving of larger doses over a shorter period.

4. It is impossible to reduce below a certain limit the time over which the total quantity of vaccine ordinarily sufficient for complete immunisation can be usefully administered.

5. The effect on rabbits of the subcutaneous injection of fresh-fixed virus is dependent on the quantity of virus introduced and on the duration of its period of administration. Few inoculations are more likely to cause death than several; repeated inoculations ordinarily confer immunity. Immunity thus acquired must have been produced within 11 or 12 days.

The final choice of a suitable dilution of a given toxin will be made, partly from the difficult comparison with other known toxins, but mainly from the results of clinical observations in patients in the early stage of scarlet fever and in convalescents.

It is difficult to titrate scarlet fever toxin with accuracy. It will probably be found that by careful choice of subject and by several readings of the reactions at different intervals after the injection, one can differentiate between toxins of values x and 2x.

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 prominence recently given to the Rous sarcoma has increased the confusion of hypotheses about malignancy. With a view to clarification, one may say that there are three simple hypotheses of outstanding importance, viz.: (1) the living virus hypothesis, which regards living viruses as the actual and effective cause of both the avian and the mammalian disease; (2) the autogenous enzyme hypothesis, which ascribes both diseases to the development within living cells of an ens malignitatis resembling an enzyme rather than a virus; and (3) the “chronic irritation” hypothesis, which explains mammalian malignancy on this principle and considers fowl sarcoma to be of a different nature.

Recently conflicting statements have been published in various countries on the prevalence and increased mortality from cancer, i.e. malignant disease in general. Statistics show a definite upward trend in the annual death rate from cancer, but opinions differ as to whether the increased mortality represents the actual increase in the incidence of the disease or is explained by such factors as the increased average age at death, improved methods of diagnosis and more careful records of the cause of death.

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.

Under warm weather conditions, contamination from milking machine rubber parts can be effectively controlled by simple, practicable methods. Milk drawn by machines so treated is equal in sanitary quality to that produced by careful hand milking.

The chloramine-brine treatment proved to be quite as effective as the hot water treatment in controlling bacterial contamination, while superior from the standpoint of economy and simplicity.

Charts, illustrating observations over several years, have been published by Hamer (1908–10) for London, by Niven (1910) for Birmingham and by Hope (1920–21) for Liverpool, which show that in the third quarter of the year the summer diarrhoea death curve usually reaches its maximum about a fortnight after the curve representing the numbers of flies caught in traps has reached its highest point.

It is impossible to say with certainty that the outbreak of illness in Manchester was due to ergot, but the evidence available strongly supports the view that ergot was the cause. The train of symptoms and pathological changes, though not necessarily peculiar to ergot poisoning, are strongly suggestive of this origin and this conclusion is reinforced by the fact that all the sufferers consumed rye bread made from rye which contained a significant proportion of ergot. The ergot isolated from this rye, after being kept for many months under conditions which were unfavourable for the preservation of its toxic properties, was found at the expiration of this period to contain some toxin and the amount found was consistent with the ergot having been highly active when fresh and therefore quite capable of causing the outbreak of illness which developed at a period shortly after the harvest when the toxic properties of ergot are greatest.

As a result of my inquiry the following facts of interest have emerged:

1. A considerable quantity of rye is grown in England and Wales and more than half of it is allowed to ripen. The districts in which most of it is grown are Yorkshire, Lancashire, Cheshire, Monmouth and Essex. Rye in this country is seldom, if ever, free from ergot and the degree of infection varies from year to year in each district according to the season, weather, seed and other conditions.

2. Rye bread is eaten to a large extent (in Liverpool and Manchester at any rate) by Jews, and rye for these towns is obtained almost exclusively from Lancashire and Yorkshire.

3. The rye grain is usually not treated in any way before milling, that is to say, no attempt is made to remove any ergot which may be present; it is ground into meal in the condition in which it comes from the threshing machine.

4. On the assumption that some of the rye consumed in Manchester contained 1 per cent. of ergot, a half-pound loaf of bread of which this rye is a constituent would contain 4 to 5 grains of ergot. Although this is a relatively small dose, it is possible that if consumed over lengthy periods, especially if the ergot were in an actively toxic state, pathological conditions might ensue.

5. The samples of rye actually examined by the Public Analyst were not found to be toxic. This may possibly be accounted for on the ground that the method employed for extracting the toxin was not satisfactory, or to the fact that the ergot examined was at least six months old, by which time it would normally have lost most if not all of its toxicity.

6. Damp weather favours the growth of ergot and the climatic conditions of the summer of 1927 were just those most suited to the development of ergot. It is probable therefore that the rye crop was heavily infected and the ergot rich in toxins.

The clinical characters of the outbreak, so far as they have been recorded, strongly support the view that ergot was responsible; all the necessary factors and conditions for the production of illness were present and it is not surprising that it occurred.

In view of the potential danger the obvious preventive measures to which I have already referred should be put into operation. Rye crops should be grown with such precautions as to reduce the risk of ergot infection to a minimum. Millers of rye for human consumption should install the necessary machinery to remove, so far as possible, any small proportion of ergot which the rye may contain.

A method has been devised whereby the potency of any given carcinogenic agent can be compared with that of a standard agent. This is called the standard carcinogenic potency of the agent (P.). The relative potency of the agent (R.P.), calculated from P., permits one to estimate the effect on the agent of different chemical treatments, dilutions, etc., the percentage increase or decrease in activity of the agent being at once shown. A unit of carcino-genicity (U.C.) has been established, and a concentration of 500 carcinogenic units per cubic centimetre is considered to induce the maximum relative response on animals when the agent is applied twice a week. These standards have been devised as a natural sequence to the accumulation of a vast amount of experimental data the correlation of which necessitated some expedient more rapid and covering a wider field than the graphs formerly utilized.

Typhoid fever is one of the prevailing endemic diseases of Palestine. In 1925 and 1926 epidemic outbreaks of considerable magnitude occurred in various parts of the country (Kligler, 1927). As a part of a general programme of the study of the epidemiology of this disease, we have attempted to ascertain the incidence of typhoid carriers in a general population group. Owing to the large number of typhoid cases which occurred there in 1925 and 1926, Afule, a village of some 1200 inhabitants, was chosen as a desirable spot for such an investigation.

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.

This paper is written from the practical point of view of a laboratory worker who is daily in direct contact with the cases submitted to him for diagnosis. Its purpose is to prove the inefficiency of the Widal reaction as a diagnostic test, and to urge its replacement by a more satisfactory method. Such a method is to be found in the application of the discoveries and theories on agglutination of Weil and Felix (1920), Felix (1924 and 1929), and Felix and Olitzki (1928 and 1929).

No hygienist has any doubt that diseases of the intestinal tract, especially the enteric fevers, may be spread by the consumption of shellfish. Clinical experience, often repeated, led to this conclusion long before the bacteriologist had been able to detect the presence of the causative organism in the shellfish. In fact it is only within the past year that definite proof has been afforded by the exceedingly valuable work of Wilson (1928), who found B. typhosus in cockles taken from Belfast Lough.

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.

A series of spontaneous epidemics of a paratyphoid infection among guinea-pigs is described. It is shown that an epidemic may result from the introduction of a fresh susceptible population into an infected area and vice versa. Such epidemics developed only when the new population was exposed during certain months. The bringing in of a fresh population at the end of November was not followed at the time by an epidemic outbreak; the epidemic did not occur until the following July.

The observed seasonal occurrence was not due to a change in virulence. The strains isolated at the end of the 1926 epidemic did not differ in virulence from those cultivated at the height of the 1927 epidemic.

The guinea-pig may remain a carrier for a long time whilst eliminating bacteria in the faecal discharges only intermittently and in small numbers. In general, even in the case of infected animals, the discharge of pathogenic bacteria is relatively small, except a few days before death.

Attention is called to the parallelism between the seasonal prevalence of human typhoid epidemics in this country and the epidemics of paratyphoid observed in our guinea-pig stock.

It is pointed out that a sound theory of the epidemiology of certain diseases must take into account the seasonal variation in host susceptibility.

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. During the summer months 1928–9 an epizootic occurred in De Aar and neighbouring districts among small veld rodents, mainly affecting Namaqua gerbilles (Desmodillus auricularis).

2. Many of the animals dying showed a haemorrhagic septicaemia, the causative organism of which appeared to be a Pasteurella rather smaller in size than Pasteurella (Bacillus) pestis.

3. In a considerable proportion of the animals found dead there was no obvious septicaemia.

4. A description is given of the Pasteurella, which is believed to be a hitherto undescribed species, and for which the name Pasteurella desmodilli is suggested.

5. This organism was found to be highly pathogenic for rabbits, less so for guinea-pigs and mice, and non-pathogenic for rats and fowls.

6. It was found by Rhodes to be highly pathogenic for Lobengula gerbilles (Tatera lobengulae) from Cape Town, but for animals of this species from Johannesburg it proved to be much less virulent, and even when it killed them there was frequently no septicaemia.

7. The above observation seems to indicate the presence of a considerable degree of immunity among the Johannesburg lobengulas, as compared with those from Cape Town.

8. It is suggested that a similar condition of partial immunity among the Namaqua gerbilles (for which there is other evidence adduced) might account for the finding of many of them dead without obvious septicaemia.

9. The existence of this disease introduces a complication in the diagnosis of plague among veld rodents.

In the December issue of this Journal Peller (1928) presented a critical analysis of my paper (1927). His criticism is both general and specific. The general criticism requires no comment on my part. Polemics have no place in English scientific literature. Any contribution which contains an idea and stimulates thought and investigation is, in my opinion, of sufficient interest to warrant publication, provided the data presented are accurate.

Some comment, however brief, is required because the specific remarks create an impression that not only are the deductions wrong, but that the data on which they are based are inaccurate.

(1) Of 71 cases of malignant growths the Shaw-Mackenzie test was positive in 49, doubtful in 5 and negative in 17. Epitheliomata of the skin all gave negative results, and some cases which had been treated with lead, X-rays or radium, and some cases of advanced inoperable carcinoma in old people also gave negatives.

(2) In 102 cases of various diseases other than growths (malignant or otherwise) negatives were obtained in 65 cases while 19 were doubtful and 18 were definitely positive. The chief conditions likely to give wrong "positives" are venereal disease, heart cases, nephritis, pulmonary tuberculosis, pregnancy and menstruation.

(3) Cloudy sera do not always clear on incubation with co-enzyme of pancreatic lipase, and unless such clearing takes place they should be discarded, as a high percentage of false positive results occurs in these instances.

(4) A 1 per cent, solution of cholin hydrochloride gave very similar results to the carcinoma extract.

I am deeply indebted to the following for supplying me with material, either serum or tumours, and without whose kind co-operation the work could not have been carried out: Dr Cooke, Addenbrooke's Hospital, Cambridge; Dr Varrier-Jones and Dr L. Stott, Papworth Hall, Cambridge; Dr L. King, Cancer Hospital, Fulham Road; Dr Piney, Charing Cross Hospital; Dr Perrin, Dr J. R. Marrack and Dr Sybil Robinson, London Hospital; Professor McIntosh, Middlesex Hospital; Professor F. R. Fraser and Professor G. E. Gask, St Bartholomew's Hospital; Dr Alport, St Mary's Hospital; Professor Maclean and Dr Osmond, St Thomas' Hospital; Professor Choyce, University College Hospital.

I also have to thank Professor Ellis, of the London Hospital, for kindly allowing me to work in the research laboratory on several occasions.