1. Outbreaks of epidemic disease are common in populations of wild animals, including species little influenced by contact with the diseases of human beings or domestic animals.

2. Such epidemics form one of the commonest factors responsible for fluctuations in numbers of wild mammals.

3. An attempt is made to summarise the available published records of such epidemics (Section II), while certain unpublished records (communicated to me by naturalists) are contained in an Appendix.

4. Little is known of the causes of these epidemics except in the cases of plague and tularaemia.

5. The fluctuations in numbers of some wild mammal populations are sufficiently regular to make the forecasting of epidemics possible. This method is already applicable to wild mice.

6. Mouse periodicities are discussed in detail, with special reference to epidemics and their causes, which are mainly obscure (Section III).

7. Development of the forecasting methods described will make possible the prediction of many other wild mammal epidemics, and render intensive pathological and epidemiological studies more practicable than they have hitherto been.

In eight out of ten occupations associated with exposure to coal gas, tar, pitch or soot the incidence of cancer of the bladder is greater than that found in the general male population, and in five of the ten it is from one and a half to four times as great. Three of these occupations show the highest figures for incidence of cancer of the bladder observed among the forty-six occupations investigated. Various possible sources of error in these figures are discussed, of which the most serious is the smallness of the numbers of deaths involved. The corresponding data for cancer of the prostate give less consistent indications of an occupational liability. The subject needs much further enquiry, but it has seemed best to publish now, without further delay, such material as is available, rather than wait for another long term of years while more data accumulate.

A large, and quite essential, part of this investigation, namely the computing of the population for each occupation recorded on the death certificates, and the calculation of the ratios, has been carried out by members of the staff of the Registrar General, to whom we wish to express our great indebtedness. We have to thank the British Empire Cancer Campaign for a grant which enabled the special enquiry into individual cases to be made, and to record our gratitude to those who assisted so willingly in carrying out this enquiry.

It will, perhaps, be interesting to students of epidemiology to compare with the delicate and complex reactions of an experimental animal population the grosser reactions of a human population. In Australia the materials have been singularly favourable for a demographical study.

The lethal dose of an ordinary pharmacological preparation is expressed in a simple statement of quantity. The lethal dose of a poisonous gas cannot as a rule be so expressed. The majority of such gases are rapidly destroyed in the body, and the building up of a lethal concentration in some critical portion of the organism is a race between the rate at which the gas is inhaled and the rate at which it is destroyed. Even in the cases of such gases as arsenuretted hydrogen which are destroyed only very slowly, and which are therefore cumulative poisons, the attainment of a lethal concentration in the body is a function not only of the concentration of the gas in the atmosphere, but of the time during which that atmosphere is breathed.

The last life table for the Administrative County of London was prepared by Mr King from the census population of 1911 and the deaths in 1910, 1911, 1912, and published in Part I of the Supplement to the 75th Annual Report of the Registrar-General, 1914. The national life tables (No. 9), prepared by Sir Alfred Watson after the census of 1921, included one for “Greater London,” the boundaries of which extend considerably beyond the County Council area and enclose the range of jurisdiction of the Metropolitan Police, so that this table is not geographically comparable with Mr King's 1911 table. The object of the present study was a comparison between the extended method of Mr King and the shorter ones of Drs Brownlee and Snow, to see whether the methods gave comparable results as regards the expectation of life, the question with which the public health worker is mainly concerned. As an example I selected the County of London (census population for 1921, deaths in 1920, 1921, and 1922) as affording, at the same time, an opportunity of making a table comparable with that which Mr King prepared for 1911. Drs Brownlee and Snow have already shown that their methods gave very satisfactory results as judged by the older life tables of this country. This paper will show that similar results have, in the main, been obtained as regards the 1921 experience.

1. An analytical study has been made of the mechanism of natural bactericidal action by the serum of various animals (ox, sheep, horse, rabbit, guinea-pig, rat, man) towards certain organisms (B. typhosus, B. dysenteriae Shiga, B. proteus, V. cholerae) exhibiting the maximum reactivity to this effect.

2. Serum-complement has no bactericidal action per se, and an antibodylike agent invariably acts as an intermediary agent, “sensitising” the particular organism to the action of the complement and capable of being “absorbed” by it from serum at 0° C.

3. This sensitising agent is stable at 55° C. but labile at 60°–65° C. In this respect it resembles natural haemolysins and agglutinins, but contrasts with the more stable immune antibodies and the more labile natural complement-fixing antibodies (for bacterial antigens). It is resident mainly in the carbonic-acid-insoluble fraction of the serum. It is present in the serum of young animals before certain other natural antibodies have developed.

4. Absorption tests demonstrate the high degree of specificity of these natural bactericidal antibodies for particular bacteria.

5. A non-specific extracellular substance occurs in bacterial cultures which may neutralise or inhibit these antibodies, and interfere with their sensitising action even at 0° C.

6. This substance is liberated in large amount in cultures heated at high temperatures (120° C). It can be removed by repeated washing of growths in saline solution. It may inactivate a bactericidal antibody in heated serum, though not in fresh unheated serum, and may inactivate a particular antibody in the serum of one animal species but not in another. Strains of bacteria vary in their production of this substance.

7. The observations submitted in this paper, correlated with previous studies of natural antibodies by the authors and others, indicate that immune antibodies have their precursors specifically differentiated in the serum of normal animals and that, in general, immune antibodies are not substances formed de novo.

1. By means of the Old Standard bismuth sulphite medium B. typhosus was cultivated 44 times out of 50 examinations of the stools of 50 typhoid fever patients and convalescents.

2. By means of the same medium B. paratyphosus B was cultivated 22 times out of 27 examinations of the stools of 27 different cases of paratyphoid fever.

3. In 13 examinations of Belfast sewage in different months during 1928 and 1929, by means of the Old Standard sulphite media, B. typhosus was isolated on 10 occasions. In two examinations of Lisburn sewage B. typhosus was isolated. Although no special search for B. paratyphosus B was undertaken, this organism was isolated on two occasions from Belfast sewage. The viability of B. typhosus and B. paratyphosus B in sewage is longer than was suggested by the work of previous observers. It has been possible to cultivate B. typhosus and B. paratyphosus B from the deposit of sewage stored in a bottle at room temperature for 3 weeks. On one occasion B. typhosus was found alive at the end of 5 weeks.

4. On two occasions water from the River Lagan was examined, and on one of these B. typhosus and B. paratyphosus B were cultivated.

5. For the isolation of the B. enteritidis Gaertner the media gave good results in the examination of faeces from cases of food-poisoning.

1. A technique is described for comparing the spermicidal powers of pessaries, using human sperms.

2. Those pessaries which do not contain cocoa-butter are more spermicidal than those that do.

3. Quinine and lactic acid pessaries, in cocoa-butter vehicles, are almost without effect upon sperms.

4. There is more than ten times as much quinine bisulphate in a quinine pessary as suffices to kill all sperms in half an hour, but the cocoa-butter prevents its action in some way which is not at present understood.

5. Semori is the most spermicidal pessary of the nine investigated. Even at one-tenth of the concentration at which it is normally used, it kills every sperm or nearly every sperm in half an hour.

6. Even if the foam-producing substances are omitted, semori remains effective.

7. The minute quinine urea hydrochloride pessary is nearly as effective as semori, but the absence of foam-producing substances in this pessary limits its usefulness.

8. Speton relies for its spermicidal power wholly upon its foam-producing substances. Its supposedly active substance, sodium dichlorylsulphamidbenzoate, is without effect upon sperms.

While investigating the effects of silica dust and coal dust respectively in the production of respiratory disease in coal miners, we have been struck by the sharp contrast between silicotic coal miners in South Wales as compared with silicotic gold miners in South Africa in their respective liability to pulmonary tuberculosis. Coal miners have always been noted for their relatively low tuberculosis mortality, while gold miners and other workers in hard rock, but exempt from simultaneous exposure to coal dust, are conspicuous for their marked liability to fatal pulmonary tuberculosis in late middle age. And yet the recent findings of Cummins and Sladden (1930) and of the Medical Staff of the Welsh National Memorial Association (1930) indicate that both in the pathological, histological and chemical characters of the lungs of Welsh coal miners and in the X-ray appearances observed in long-service colliers of over forty years of age, there is nothing to distinguish them from Band gold miners suffering from silicosis except the added presence of large amounts of coal dust in the lung tissue of coal miners and their relatively low tuberculosis mortality. This contrast has been discussed by one of us (S.L.C.) in a recent paper (1931) and the suggestion made that the well-known adsorption power of finely divided carbon particles for colloidal substances might be a factor in reducing the liability of the coal miner to pulmonary tuberculosis.

1. Several strains of the influenza bacillus were grown under varying conditions for many months in order to ascertain whether morphology and colonial appearances could be permanently modified.

2. It was found that a modification in morphology occurred in all the strains studied.

3. Typical coccobacillary forms were changed to atypical long-curved forms.

4. The reverse change from atypical was also observed but was not so frequent, nor, when it occurred, was it so constant.

5. The change took place most readily after growth in a flask of Fildes' broth for several weeks or months at 37° C.

6. There was found to be a definite association between morphology and colonial form. The typical strains produced smooth colonies, while the atypical gave rough colonies, or colonies very much smaller than those produced by the typical.

7. When the change in morphology took place the change in colonial form occurred at the same time.

8. The biochemical characters remained on the whole unchanged.

9. One hundred and forty strains were examined for their fermentation reactions. The sugars most frequently fermented were dextrose, maltose and sucrose.

10. The atypicals were more active fermenters than the typicals.

11. 63·9 per cent. of the typicals, and 18 per cent. of the atypicals, gave a positive indol reaction.

12. Although the ability to grow on X or V alone affords an important differential criterion within this group, great care is necessary in interpreting the results obtained, especially in the case of those strains which grow on V in the absence of X. Different yeast preparations may give very different results in this respect.

13. All the strains tested were non-haemolytic.

The work described in this paper is based, very largely, on the work of Dean and Webb (1926), and the methods used in the various experiments are similar to those described by them. The results are discussed in two parts. The first is concerned with the mixture of different specimens of anti-horse serum, and with the relationship of the antibody in one specimen to the antibody in another. The second part deals with the nature of the reaction between antigen and antibody in the serum precipitation reaction. The two parts are dependent on each other, and the subject of the second suggested itself whilst the work on the first was in progress. The order in which the work is described is mostly that in which it was done. Nevertheless, conclusions arrived at in one part are, in one or two cases, of importance in the consideration of the other part, and vice versa. A question as to the possibility of strengthening the ratio of an antiserum by the addition of another antiserum led to the earlier experiments.

Epidemic encephalitis made its appearance in Glasgow in 1918, although it was only in 1919 that its prevalence was such as to lead to its recognition. It recurred annually till 1924, and, during this period, the change in the clinical features from year to year suggested that it had passed through an evolutionary phase. While ocular symptoms were probably the features most common to all epidemics, prolonged lethargy and somnolence characterised the earlier cases; choreiform and myoclonic movements were more prevalent in 1920 and in 1921, while in 1924 there appeared for the first time a considerable proportion of cases with spinal signs and symptoms, which simulated acute attacks of insular sclerosis.

Hides and calf skins cured with marine salts, especially if kept under conditions of warmth and moisture, tend to develop on the flesh side large areas of brick-red coloration. Similar red colorations have, for many years, been noted as occurring in similar conditions on salted fish, and a number of investigations have been made as to their cause, the first recorded being that of Farlow (1878). Following him were Mauriac (1886), Ewart (1887), Layet (1887), Le Dantec (1891) and, in recent years, Harrison and Kennedy (1922), Browne (1921–22) and Cloake (1923). All these workers have agreed in attributing the red coloration on salted fish to the growth of one or several species of redcoloured organisms, and the more recent workers (Harrison and Kennedy, Browne, Cloake) trace these organisms to the sea salt used in curing the fish, and find them to be chromogenic bacteria only capable of growth in a high concentration of salt. Clayton and Gibbs (1927) have examined many solar brines and salts, and have found that “they almost invariably contain microorganisms which only exist and develop in the presence of abundance of common salt.” Sturges and Heidemann (1923, 1924) have isolated many saltloving organisms from meat-curing solutions, and Le Fèvre and Round (1919) from the brine of pickled cucumber.

The technique of detecting diphtheria bacillus carriers has found little recognition in the literature of diphtheria.

A method of detecting diphtheria carriers by single swabbings is described.

The method is somewhat elaborate but is highly efficient.

The results which may be obtained with it are discussed.

Its application in certain specific cases is briefly considered.

1. A technique for comparing the spermicidal powers of pure substances is described in detail. It is hoped that this may be accepted as the standard technique for the purpose.

2. The killing concentration of each substance is determined by this technique. The killing concentration is defined as the lowest concentration, in the series 2, 1, ½, ¼ per cent., etc., which suffices to kill every guinea-pig sperm suspended in glucose-saline solution in half an hour at the temperature of the body in four consecutive experiments, the majority of the control sperms being moderately or very active.

3. 36 substances have been graded by this technique.

4. Mercuric chloride and formaldehyde were found to be the most spermicidal substances. The killing concentration of each per cent.

5. Hexyl resorcin kills at per cent., soaps at per cent.

6. Formaldehyde and hexyl resorcin, among other substances, seem likely to be useful as contraceptives.

7. The significance of the high spermicidal power of soaps is discussed.

8. Quinine bisulphate and chinosol, which are perhaps more commonly used as contraceptives than any other substances, only kill at ½ per cent.

9. Certain very poisonous substances have very slight spermicidal powers. This applies to potassium cyanide, prussic acid and strychnine hydrochloride.

10. Foaming mixtures, consisting of acids and sodium bicarbonate, could probably be used alone as contraceptives.

11. The acrosome is the part of the sperm most vulnerable to spermicides. It tends to swell up and burst.

12. Sperms are very susceptible to changes in osmotic pressure.

13. It is the hydrogen ions and not the anions of acids that kill sperms.

14. The suggestion that tribasic acids would be found to be more spermicidal than dibasic, and dibasic than monobasic, is not substantiated.

15. Substances which reduce surface tension are often effective spermicides.

16. The characters of the ideal chemical contraceptive are discussed.

17. The need for co-operation in research in chemical contraception is stressed.

We all recognise that some diseases are more “catching” than others. Every mother knows that measles is very catching and most people set aside a group of common complaints, measles, mumps, whooping-cough, scarlet fever, diphtheria—perhaps roughly in that order—as catching complaints. Then again, still keeping ourselves within the circle of ideas of educated non-medical people, one has such complaints as common colds or influenza which one thinks of as running through a house indeed but does not put quite into the measles category, as one feels that factors determine the spread other than mere proximity to a sick person. Lastly, one has some illnesses, gonorrhoea would be a fair example, which everybody recognises to be spread wholly by contagion, almost always by a particular method of contagion, but does not regard as catching at all in the sense that measles and whooping-cough are catching. When we enquire into the reasons of these opinions they will be found, I think, to be these.

1. Sera from 500 patients, mostly natives of East Africa, were tested by the Kahn and Wassermann tests, under conditions described.

2. Clinical data were available in the case of 448 specimens. The results of tests upon 230 sera from cases believed to be yaws and syphilis and 218 cases believed not to be yaws and syphilis are discussed. In 46 of the 230 cases, treatment had previously been given.

3. In interpreting results, the resolutions of the League of Nations' Conference on the Serodiagnosis of Syphilis were strictly followed.

4. In the performance of the tests recognised standard methods were used.

5. The two tests correlated exactly in 96·4 per cent. of all cases.

6. The Kahn test was the more sensitive to yaws and syphilis.

7. The Wassermann test alone gave one non-specific reaction.

8. The reagents used in the Kahn test did not deteriorate when kept for two months at room temperature.

9. It is suggested that although the use of both tests is preferable when practicable, the Kahn test alone is a reliable diagnostic measure in the tropics.

The following dusts produce a fibrosis in the guinea-pig's lung, and are therefore to be classed as dusts whose inhalation in industry would be attended by risks of pneumoconiosis. The most deadly of all dusts examined was precipitated silica. Less dangerous, but all producing fibrosis, were the following, arranged in order of decreasing toxicity: flint, slate, aluminium hydroxide, precipitated chalk, magnesium carbonate and carborundum. In the concentrations used in the experiments calcspar and emery were border-line dusts, indicating that their inhalation in any considerable quantity would cause fibrosis. Wood charcoal inhaled in large amount produces a slight fibrosis, and must, therefore, be placed on the “dangerous” list. Colloidal coal, when inhaled in massive amounts, is potentially dangerous, while shale under similar conditions is rather more dangerous.

Haematite, talc, and molecular mixtures of soluble silica with aluminium hydroxide and magnesium carbonate respectively were not found to cause any permanent lesions in the lung.

The deductions to be drawn from this work are:

1. All inhaled particles are rapidly ingested by certain individual cells belonging to the alveolar epithelium.

2. These cells (dust cells or phagocytes) remain in the lung parenchyma until they have ingested an amount of dust constituting the cell's saturation load. This load varies with different dusts.

3. A cell having attained its saturation load becomes sooner or later detached from the alveolar wall and either migrates into the lymphatics or becomes free in the alveolus. In the former case it passes into the pulmonary lymphoid tissue and thence to the bronchial lymph glands. In the latter case it passes up the bronchial tree to be either coughed out or swallowed.

4. Dust cells which speedily leave the alveolar wall are principally eliminated by the bronchi.

5. In the case of a dust cell being eliminated from the lung via the lymphatics, it may be arrested in the periatrial lymphatics on account of its bulk. The dam thus produced offers obstruction to the passage of other dust cells shed into the alveoli. Groups of free dust cells in the obstructed alveoli form plaques, which degenerate and liberate their dust. This is again ingested, and the irritation caused by such a process may lead to fibrosis.

6. The continued presence of dust-laden cells in the lymphatics may set up a foreign body irritation, with resulting fibrosis.

7. Most inhaled particles contain soluble matter to at least a very small extent. The solute may be either harmlessly active or toxic. If the former, the cell is stimulated to detach itself from the alveolar wall, and so remove the dust. If the latter, the solute effects the viability of the phagocyte, which becomes less able to detach itself. At the same time the solute diffuses into the neighbouring tissues, with irritation to them, and consequent fibrosis.

8. The more soluble form of a substance causes greater pulmonary damage than the less soluble. The solute, therefore, plays a large part in the determination of damage.

9. While many dusts cause pulmonary fibrosis, silica is the dust par excellence predisposing to tuberculosis. This is doubtless due to its influence in forming a medium suitable not only for the survival but the proliferation of the tubercle bacillus in the lung (Kettle, private communication). The harmful effects of soluble silica may be neutralised by simultaneous administration of basic dusts such as aluminium hydroxide or magnesium carbonate, though the latter are themselves harmful when inhaled alone. It is suggested that their respective solutes combine to form monosilicate. Monosilicates do not appear to have any harmful effect on the lung.

10. Heavy inhalations of any dust are liable to cause pulmonary damage.

11. The intensity of the initial pulmonary reaction to a dust is very generally in inverse ratio to the degree of eventual damage caused by the dust.

1. The Weil-Felix reaction in a series of forty-five cases of tsutsugamushi disease (type Schüffner) is recorded.

2. The agglutination reaction was negative in fifteen cases, the other thirty showing a positive reaction with the “Kingsbury” strain of B. proteus X.

3. The Weil-Felix reaction is not regarded as an adequate method for differentiating tsutsugamushi disease from scrub typhus, since high titres (1 in 1000) occur in a considerable proportion of cases of tsutsugamushi disease.

4. In the present state of our knowledge of the two diseases it is recommended that they should be separated according to the presence or absence of a primary ulcer and bubo.

In the last memoir of this series (Greenwood, Topley and Wilson, 1931) we discussed at some length the modifications of the course of herd sickness effected by immunisation of entrants to the herds. Briefly, these were our conclusions: efficient artificial immunisation (the criteria of efficiency being the usual standardising methods of a laboratory) confers a considerable temporary advantage upon mice entering an infected herd. The risk of death during the period of herd life when the rate of mortality is especially high is greatly reduced, so that when one has the case of a herd or group temporarily exposed to special risks, the value of the expedient is very great. But no method of artificial immunisation we have tried will render the immunised animals impervious to the risks which their membership of the herd entails.