1. B. bifidus communis, first isolated and described by Tissier, is the predominant organism in the intestinal flora of healthy breast-fed infants in the early weeks of life. In films of the faeces at this period Gram-positive bacilli may constitute almost 99 per cent. of the organisms present.

2. B. bifidus requires fairly strict anaerobic conditions for its isolation in primary culture; but thereafter it grows readily in sub-cultures in the presence of oxygen.

3. B. bifidus is a member of the acid-tolerant group of Gram-positive, faecal organisms. Although closely resembling B. acidophilus, it is distinct from the latter morphologically and also in certain of its cultural characters. The results of agglutination reactions indicate that different strains of B. bifidus are not serologically uniform.

4. Although B. bifidus is a very pleomorphic organism, no evidence was obtained in the present work that it could be changed into an aerobic, spore-bearing bacillus.

5. The predominance of B. bifidus in the intestinal flora of breast-fed infants appears to be closely related to the high degree of acidity of the faeces of these infants. It is probable that the predominance of B. bifidus over other organisms is an important factor in preserving a healthy condition of the intestinal tract in the breast-fed infant.

The geographical distribution of the different species of rat flea is one of the most important factors governing the spread of plague.

Xenopsylla cheopis is the most effective transmitter of both epidemic and epizootic bubonic plague in all parts of the world.

The relative immunity of certain parts of India and Ceylon from plague is to be primarily attributed to the prevalence of an inefficient plague-carrying flea on the rats of these localities, viz. Xenopsylla astia.

Climatic conditions play only a secondary part in limiting the spread of the disease in these relatively plague-free localities.

Plague infection can be maintained in such localities by the importation of cheopis-infested merchandise.

Climate does not exert an equal effect upon the transmitting power of different species of flea.

Numerous attempts to transmit plague from rat to rat by means of X. astia at room temperature during the plague season in Colombo have all failed. X. astia, however, can carry plague from rat to rat under climatic conditions favourable to plague transmission. Continuous transmission of plague from rat to rat has been obtained with X. cheopis in Colombo under exceptionally unfavourable climatic conditions.

Both plague and X. cheopis have a very irregular distribution within limits of Colombo City. The coefficient of correlation between two periods of human plague incidence and percentage of cheopis to total rat fleas of all species in 14 districts of the city is ·95, probable error ± ·02 for both periods.

There is a close relation between premises infested with X. cheopis and premises where plague-infected rats are found.

A three-fold relationship exists between the amount of imported grain, the prevalence of cheopis on rats, and the incidence of plague in the localities where grain is stored in Colombo.

The measures so far devised for combating plague among Oriental populations, tolerant of all forms of animal life, have not proved conspicuously successful.

Due recognition of the importance of the flea species factor should lead to marked improvement in plague preventive measures in many parts of the world.

A rat flea survey of all the principal plague areas, especially the ports, becomes urgently necessary.

The exports from localities where X. cheopis is found to be prevalent upon the rats should be considered actively dangerous when the locality is plague infected, and potentially dangerous even if it is plague free, since the continual importation of cheopis into a locality where this flea is not indigenous may eventually result in the extension of plague infection to a new area.

I agree with Glen Liston and Norman White, that the export of produce, especially grain, from plague-infected ports should be controlled by international agreement.

The limitation of imported cheopis and plague to definite zones in such localities as Colombo greatly facilitates the task of plague prevention, since all available resources can be concentrated simultaneously, or successively, on the infected areas.

In such instances it is possible to mark out the potentially plague-infected zones by the simple and accurate method of surveying the rat fleas.

Ten years have now elapsed since I tentatively put forward the suggestion that the spread of epizootic plague in the East Indies might be governed by the flea species factor. At first I adopted a cautious attitude towards my own hypothesis. I believe that the evidence now available warrants its acceptance by epidemiologists without further hesitation.

If so, the discovery is but further testimony to the essential unity of science in its bearings on the welfare of the human race, for it is the natural outcome of the purely zoological researches of Rothschild and Jordan on the systemics of the Siphonaptera.

In previous papers (1922, 1924) we have investigated the capacity possessed by certain micro-organisms of reducing sulphites to sulphides, and have applied it (1) to the differentiation of bacteria, and (2) to the bacterioscopic analysis of water.

The “chronic irritation” theory still retains its interest, though it has not yet provided a thoroughly satisfactory explanation of the origin of that stimulus to growth which causes normal tissue to become malignant. If employed with caution, ideas borrowed from bacteriological work on “transmissible autolysis” may be contributory in the search for the explanation which is desired.

It is important to maintain a careful distinction between the initiation and the continued propagation of the malignant variant.

It seems hazardous to assume that one can apply as immediately valid for cancer those ideas about the natural and acquired resistance of the host which are current in bacteriological literature. On the other hand, it is not suggested that such ideas should be discarded but rather that they should be regarded as suggesting alternative possibilities, none of which can be definitely excluded.

Analogies with immunological reactions to foreign protein (bacterial or animal) certainly suggest the possibility that the cure of cancer may be found in discovery of “the right antibody for the right antigen”; but it is not clear how far such analogies can be accepted as being entirely appropriate; still, owing to the likelihood that new kinds of antigens and antibodies will be discovered, continued search for these factors in cancer is of high importance.

In the present article, which is a sequel to a former discussion on stimulants to bacterial variation, I have considered whether the idea of a stimulus to the production of non-viable variants may be regarded as of immunological interest in relation to the therapeutic problem of cancer.

I have endeavoured to show that this idea is worth consideration, provided that its importance is not exaggerated and that it is correlated with better established data about the principles of immunity.

The blood picture in rubella is characterised by the presence of numerous plasma and Türk cells and by the absence of toxic changes in the neutrophilic leucocytes.

Plasma cells occur also in scarlatina and in measles but with less regularity and, as a rule, in smaller numbers, but these diseases are always associated with “toxic” changes in the neutrophilic cells.

Such haematological features must be considered in relation with the clinical findings because plasma cells and toxic changes in the neutrophiles may occur in entirely different conditions, e.g. in association with the lympho cytosis following almost any acute infective malady.

The haematological method would probably find its greatest application in those cases in which the characters of the rash are not sufficiently well developed to enable a diagnosis to be made in the usual way.

Acknowledgments. My investigations were carried out at the Institute of Pathology of Charing Cross Hospital Medical School, and I am much indebted to the Director, Dr Piney, for assistance and advice, and to Dr Whittaker of the Metropolitan Asylums Board for access to clinical material. Moreover, financial assistance has been afforded by The Virol Research Scholarship which I hold.

Summarising our results, and considering their probable significance, we should draw the following conclusions.

Our observations do not suggest that the dissemination of a bacteriophage is likely to have been the cause of the sudden decrease in the excretion rate of B. aertrycke, which was observed among the population at risk during the epidemic previously recorded (Topley, Ayrton and Lewis, 1924).

Our results are completely at variance with those recorded by d'Herelle in the case of fowl typhoid, a disease which shows many points of similarity to enteric infection in mice. The observations we have recorded do not suggest that the presence of the bacteriophage will, in itself, prevent the epidemic spread of infection, check an epidemic when it has once started, or appreciably reduce the mortality among the population at risk. In the light of these results we cannot share d'Herelle's optimism as to the probable results of the wholesale administration of the lytic principle in a public water supply. We do not suggest that the Twort-d'Herelle phenomenon has no significance in the epidemic spread of disease, but it does not appear to us that the problem is the simple and straightforward one envisaged by d'Herelle.

The results of the last experiment of this series are in substantial agreement with d'Herelle's experiments on barbone in cattle, so far as they concern the action of the lytic filtrate in causing an immunising response, though we have not obtained such strikingly uniform and satisfactory results.

We would note, in conclusion, that we have not yet tested the effect of the administration of the lytic principle, by injection, during the course of an experimental epidemic.

Though we have, in former papers (1915, 1916, 1920), given details of the apparatus we used in producing sterilisation of milk by the electric current, it will be a convenience to readers to repeat some facts in regard to the arrangements of the electrodes and electrical circuit. The quantity of current used depends on the size of the apparatus, arid the voltage is normally between 3000 and 4000. The alternating current is carried by the milk and is applied by means of three copper electrodes, ⅛th of an inch thick, each enclosed in a glass electrode chamber.

Since the birth-rate is persistently diminishing, interest in the laws by which nativity is governed is steadily increasing. This interest became still more intense when, on account of the war, a large number of human lives were destroyed, causing a decrease of population in many countries. Those who fell in this war happened to be men in the prime of life, a fact which manifested itself after the war in a decreased number of births, apart from the temporary increase of births in consequence of the return of the mobilised men to their native towns.

Owing, in our opinion, to faulty classification and terminology of bacterial types, it is very common, especially on the Continent and, to a lesser extent, in U.S.A., to ascribe outbreaks of food poisoning to B. paratyphosus B, the common cause of paratyphoid fever. If such a conception is true, it is obvious that B. paratyphosus B can at one time cause paratyhpoid fever, at another an outbreak of food poisoning. Further, one would expect in outbreaks of either condition that some cases would be of the one clinical type while others would exhibit the other. In particular in outbreaks of paratyphoid fever in which the vehicle of infection was some form of food, it is to be anticipated, on this view, that a considerable proportion of the cases would be of acute food poisoning type.

The German social statistician Sombart rightly asserts that in many cases we obtain a sharper and better impression by limiting our investigations to the conditions prevailing in a single year-class than by taking several ageclasses together, which are always in some respects heterogeneous.

1. A short account is given of the occurrence of plague epidemics in wild mammals other than “domestic” rats and mice. Enough is now known to show that such epidemics are often of great practical importance.

2. The method by which most rodents regulate their numbers is as follows: increase in numbers over several years up to a point at which an epidemic of some sort occurs, which kills off a large proportion of the population. Increase then takes place again, and is followed by another epidemic, and so on indefinitely.

3. These periodic fluctuations are probably controlled by widespread climatic fluctuations, the best evidence for this being that in certain cases the former run synchronously in widely separated countries.

4. There appears to be a dominant short period in fluctuation of three to four years, and a larger movement of period ten to eleven years, both in North America and Europe. The fact that the 11-year sunspot cycle roughly corresponds with the larger movement is significant.

5. The data available from Eastern Asia suggest that there too, small mammals fluctuate periodically in numbers, and with similar periods to those of North America and Europe. There is also some evidence that the maxima of the 10–11-year fluctuations coincide in Eastern Asia and in North America, just as those of the 3–4-year period coincide in Northern Canada, Greenland and Norway.

6. Evidence is given that the plague marmot (Arctomys bobac), and other rodents carrying plague, are liable to these fluctuations. If this proves to be true, it may be possible, when fuller data are available, to forecast with some accuracy the years of epidemics among these animals, and if this can be done we shall have some means of gauging the likelihood of the occurrence of plague outbreaks in the human population of those regions.

7. The available data are admittedly fragmentary, but it is probable that between the years 1931 and 1934 epidemics among A. bobac in Transbaikalia and Mongolia will be severe, and that these events will lead to an increase of plague mortality in man.

In the Goulstonian Lectures, delivered in 1919, one of us (W. W. C. T.) discussed the possibility of attacking epidemiological problems by the method of direct experiment, and reported a few preliminary observations on the spread of enteric infection among mice. Since then a series of reports have been published dealing with the investigation of particular problems along these lines (Topley, 1921 a and b, 1922 a and b, 1923, Topley and Wilson, 1923 a and b, Topley and Ayrton, 1924 a, b and c, Topley, Ayrton and Lewis, 1924 a and b, Topley, Wilson and Lewis, 1925).

In a recent report (Topley, Wilson and Lewis, 1925) we described some observations on the rôle of the Twort-d'Herelle phenomenon in the epidemic spread of mouse-typhoid. In the experiments there recorded the lytic filtrate was administered by the mouth. The results obtained did not suggest that such administration exerted any appreciable influence on the spread of disease. It was shown, in a separate series of experiments, that intraperitoneal inoculation of such a filtrate afforded a marked degree of protection against subsequent inoculation of living cultures of B. aertrycke, provided that sufficient time had elapsed to allow of an immunising response, that no immediate protection was afforded by the inoculation of the lytic filtrate, and that neither immediate protection, nor subsequent immunisation, was afforded by the administration of the lytic filtrate by the mouth.

Enquiries have frequently been received at the National Institute for Research in Dairying concerning the efficiency of the Fermentation-Reductase Test as a method for the grading of milk, and the suggestion has been made that this test, which is now in use in some European countries, might with advantage be substituted for the standard methods of counting bacteria and demonstrating the presence or absence of B. coli, which at present form the basis for the grading of milk in England. A study of this question was therefore undertaken, and since similar enquiries are still being received, it is thought advisable to publish a résumé of the results that have already been obtained.

The question of non-specific formation of antibodies is of considerable theoretical and practical importance, and is closely related to the problem of “non-specific immunisation” which has attracted attention in therapeutics during recent years.

When diphtheria toxin is injected in a suitable form and in sufficient quantity into an animal, antitoxin will presently appear in the blood. If the injection be made into an animal that has not previously received a stimulus there is a latent period of about three weeks before any antitoxin can be detected. The amount present in the blood gradually increases, reaching a maximum about eight weeks after the injection, and then a gradual fall in level of antitoxic content is seen. If, however, the same amount of the same antigen be injected into a previously treated animal, antitoxin appears in the circulation at a far greater rate. The latent period is only three days, and the maximum antitoxin level is reached in about eight days. The maximum level reached is from 10 to 100 times that reached after an injection into a normal animal. The two types of response are illustrated in Charts 1 and 2 and also in Chart 3, which shows the antitoxic content of a horse after two separate injections of a toxin antitoxin mixture. There is a great contrast between the extent and rapidity of the antitoxic response on the two occasions.

The incidence of goitre among school-children in New Zealand has been determined by the examinations made by one of us (Hercus) and by the officers of the School Medical Service, of over 80,000 children. The proportion of men of military age who were unfitted for active service on account of goitre was ascertained during the examination of over 135,000 recruits by the Military Medical Boards in the years 1916–1918. Additional information has also been derived from hospital records, by the number of operations for goitre.

The amount of iodine has been determined in nearly five hundred samples of soil, obtained from all parts of New Zealand, together with samples of a number of waters from mineral springs and town supplies.

In order to ascertain whether any relation exists between the amount of iodine in the soil of any district (considered as a soil of plant food, and therefore indirectly of human food), we have divided the Dominion into thirty-three districts, each homogeneous as far as possible in its geological and geographical circumstances, and have ascertained the average amount of iodine in soil and average incidence of goitre among school-children within each district, utilising certain defined methods of soil-analysis and diagnosis of goitre. It is proved that the following relation is approximately true throughout: viz, percentage incidence of goitre among school-children is equal to 6 plus the quotient of 360 divided by the amount of iodine in ten million parts of soil, so long as this does not exceed 50, assuming defined methods of medical examination and chemical analysis. When the soil is abnormally rich in iodine the constant 6 must be diminished. Further (though the records are here less complete), the relation between the average amount of iodine in the soil and the percentage of military recruits medically rejected on account of goitre is of the same general nature, the latter figure being about one-twentieth of the incidence among school-children, though this proportion must also be diminished in regions in which iodine is particularly abundant.

Approximately, therefore, the incidence of the disease is inversely proportional to the amount of iodine in the soil. Further, where, though the incidence of goitre is low, the amount of iodine in the soil is abnormally low, we have proved that it is present in the water supply in greater amounts than usual, and the daily intake of iodine among the inhabitants of such a district is thereby maintained. Further, regions in which the average amount of soiliodine is low are also those in which goitre is most frequently seen amongst the domestic animals.

Though there are certain points as yet unexplained, the whole body of facts is too large, and the relationship too consistent, to be fortuitous. We believe, therefore, that the hypothesis that goitre is caused by a deficiency of iodine in the diet has been fully sustained by the present investigation. Reasons have been deduced also for believing that a relation holds between the incidence of goitre and the distribution of geological formations (as determining the nature of the soil) in New Zealand, Switzerland, and perhaps in other countries.

Further, a study has been made of the prophylactic treatment of schoolchildren in New Zealand, by administering small amounts of iodine weekly. This has hitherto had fairly good results. We believe that the best method of prophylaxis, considered on physiological grounds, as well as those of efficiency and economy, would be daily ingestion of minute amounts of iodine, obtained by the utilisation for all culinary and table purposes of an iodised salt, in which 1 part of potassium iodide had been added to 200,000 of sodium chloride—the method which has been attended by such satisfactory results in Switzerland. This would afford the minimum amount of 0·005 mg. per day, which seems necessary for the functional requirements of the thyroid gland, while it would be far too small to have any ill-effects in the production of hyperthyroidism.

A consideration also has been given to the source of the iodine in soils and natural waters in the light of our own analyses and those of previous investigators, especially Dr Th. v. Fellenberg, whose work has been of the greatest assistance to us.

Any conclusions that are reached in such an enquiry as this can only be put forward very tentatively, for they are based (1) upon limited data which cannot be free entirely from error, and (2) upon the averaging of individual results drawn, it is true, from the same class, but from families varying considerably in economic status. For this reason, without much further investigation, any generalisation would be out of place, and the conclusions summarised below are put forward not as definite results but only as indications of the actual facts.

(1) In view of the fact that minimum wage legislation for agricultural workers is being introduced in answer to the statements that the economic status of these workers is deplorably low, it is important to bring forward any facts relating to the actual condition of the rural families.

(2) For an investigation of these conditions, Essex (rural districts) was chosen as the field of enquiry in 1923, and for purposes of comparison and confirmation of results earlier rural investigations have been utilised.

(3) A study of the experimental work on metabolism suggests that the agricultural labourer would certainly need a gross amount of at least 3300 calories per day, and that this assumption will not be likely to err on the side of excess.

(4) The Essex studies of 1923 give a mean value of 2872 calories per man value per day and only 17 per cent. of the families secure over 3300 calories per man per day.

(5) This result is not at variance with the conclusions reached in earlier investigations in rural areas, and the suggestion accordingly is that underfeeding is, to some extent, present in the rural areas. (Lusk writes “it is evident… that one may reduce the basal requirement of energy by undernutrition, and that this process may largely economise food, but that to accomplish a given amount of work a fixed amount of food-fuel is required, irrespective of the nutritive condition of the organism.”)

(6) This under-feeding occurs although nearly three-quarters of the total income is spent on food (leaving a very small amount for other essentials and practically nothing for non-essentials), and although the diet is substantially increased by the consumption of home produce. Without the latter the diet would be seriously deficient.

(7) In the Essex studies nearly one-third of the money spent on food was devoted to bread and flour.

(8) On the other hand, in comparison with urban studies, the rural diet compares very favourably with that of urban workers possessed of a higher money income.

(9) This advantage to the rural family is gained by (a) a larger percentage expenditure on food; (b) a less varied diet containing a substantially smaller amount of meats and hence less animal protein; a substantially larger amount of breadstuffs and hence more carbohydrates in place of fats1; (c) by the consumption of home produce, which, however, entails, in its turn, a lengthening of the day's work and increased needs for food. Without this home produce the diets would compare very unfavourably with those of the urban workers studied. With it, the Vitamine content, as well as the energy value of the diet, must be substantially increased.

(10) In spite of the diet being low there is little evidence of malnutrition amoung the rural children of Essex, and their physique is better, age for age, than that of urban children, living on a diet equivalent or superior in energy value. Other factors, especially the “racial” factor and the “fresh air and sunlight” factor, however, must exert such an influence that the efficacy of the diets cannot be satisfactorily measured by a comparison of heights and weights.