1. Calculated values of the virtual sterilization time (v.s.t.) have been used in an analysis of the effect of temperature on the concentration exponent of the reaction between phenol and Bact. coli cultures under rigidly standardized conditions.

2. Within the experimental range of temperature and concentration employed, the exponent calculated from the formula Cn × t = K was satisfactorily constant from 20° to 35° C., but it apparently increased at 39° C.

3. This formula is unsatisfactory in that it cannot apply to concentrations near the threshold value without a change in the value of n. Accordingly, a new method of treating these data has been suggested which makes allowance for this threshold or minimum concentration. A corresponding ‘maximum’ concentration has been arbitrarily fixed at which the v.s.t. is 10 min. and the value of (v.s.t. – 10) thus varies from infinity to zero between these concentration limits.

4. Sigmoid curves asymptotic to ordinates at the minimum and maximum concentrations must be obtained when log (v.s.t. – 10) is plotted against concentration and the equation of the Pearl-Verhulst logistic curve, which is of the required type, has been used successfully to express the relationship between v.s.t. and concentration at constant temperature.

5. One of the constants of this formula partakes of the nature of a concentration exponent and this may be constant over the full effective concentration range and for all temperatures.

6. The logistic formula relating v.s.t. to concentration at constant temperature is closely related to that connecting v.s.t. with temperature at constant concentration. The two formulae become interconvertible if certain assumptions are made concerning the relationships between the minimum and maximum concentrations and temperature.

These studies, carried out during the period 1940–2, were undertaken to test the relative merits of hypochlorous acid gas and sprayed solutions of sodium hypochlorite, when these systems are used as aerial disinfectants, and to ascertain the factors determining their efficiencies in this capacity. The ulterior motive was the use of such systems as a counter measure against the danger of air-borne infection. The more practical aspects of their large-scale application, in shelters and other compartments, have been the province of others of our colleagues and will be reported upon separately.

1. In the course of this investigation we have dealt with many cases of refection, but during a period of several years we never obtained the condition except when raw potato starch was the carbohydrate in the synthetic diet. Recently, in the exceptional circumstances described in the text, we have had a few cases with rice starch.

2. Like other authors, we have always found that in refected rats the caeca are always enlarged and their contents the seat of specially great bacterial activity. The nature of the dominant organisms present has varied from case to case, and in one it was apparently a yeast. Nevertheless, there is a suggestion that certain organisms are more potent in promoting refection than others. In rice starch refection, such organisms seem to be present.

3. We have found that the administration of roughage in the manner described can, to a large extent, prevent the establishment of refection. The number of organisms in the caeca is then greatly reduced and the contents indeed may become nearly sterile.

4. Using potato starch as the carbohydrate of the diet, we have had no difficulty in reproducing the results of the early experiments published by one of us (Hopkins, 1912), but we found that to obtain a growth induced by administering very small quantities of milk to vitamin-free diets, the presence of this starch is necessary. Indeed, the growth so promoted calls for the same particularity in the carbohydrate supply as does the establishment of refection.

5. Nevertheless, we have obtained what seems to be conclusive evidence showing that the growth with milk is wholly independent of refection.

6. We have obtained some evidence that potato starch contains growth factors in association with protein which only becomes soluble when liberated by treatment with pepsin HCl. As our experimental results bearing on this, for some reason at present unexplained, have lacked constancy, we can only claim, that they are suggestive.

1. The Introduction (pp. 67–73) describes the course of infant mortality in England and Wales over the past century, and critically reviews arguments advanced to prove that variations in the infant mortality rate (i.m.) are caused by genetic differences with respect to viability.

2. The i.m. in county boroughs shows a 2-yearly cycle of variability, affecting places with high mortalities.

3. We have devised and tested various social indices and have selected five which gave the highest joint covariance with infant mortality in county boroughs during the 11 years 1928–38. These indices are:

H, percentage of families living more than 1 person per room.

U, percentage of men unemployed.

P, percentage of occupied males in the Registrar-General's Social Classes IV and V.

F, percentage of women employed on manufacturing processes.

L, latitude.

4. We have computed multiple regression equations involving i.m. and the five indices for each of the 11 years, and two summarizing equations. The regressions plus sampling variance account for about 80% of the total variance in infant mortality. The regression is linear.

5. Latitude does not affect infant mortality in Class I. For this and other reasons we regard the latitude effect as expressing miscellaneous poverty indices omitted from our equations.

6. The regression equations enable us to divide the population into various strata with characteristic average infant mortality rates. These include:

‘Better off’ (all poverty indices = 0) i.m.=23·1

Overcrowded poor i.m. = 108

Unemployed overcrowded poor i.m. = 153

Babies whose mothers work in industry suffer an additional mortality risk of at least 35 per 1000, and possibly more. The figure 23·1 is the i.m. rate that would prevail if our five poverty symptoms could be eliminated.

7. In county boroughs two-thirds of infant deaths would be avoided by the abolition of conditions defined by our indices. Of the preventable deaths, one-third are associated with overcrowding, one-quarter with low-paid occupations, one-fifth with unemployment, and one-eighth with industrial employment of women. In England and Wales, over 250,000 deaths in 11 years, about 63% of the total, can be attributed to adverse social conditions.

We have to thank the Rockefeller Foundation for a personal grant to one of us (J. W.) out of an allocation for research work in Prof. Lancelot Hogben's Department, and the Halley Stewart Trust for a grant for mechanical computing equipment. Our thanks are also due to the various members of the Zoology Department in the University of Birmingham who assisted in computing at various times, and especially to Prof. Hogben for his unfailing interest, advice and support.

1. A quantitative theory has been developed for the reactions between antigens and antibodies, applicable in particular to the precipitin reaction. The theory is equally applicable to unspecific precipitations, for instance the reaction between proteins and protein precipitating agents such as nucleic acids, etc.

2. The theory is based on the concept that the antigen-antibody interaction is governed by the same principles as the dissociation of a polybasic acid, HNT, where the antibody corresponds to the hydrogen ion H, and the antigen to the anion T. In their mutual reactions the antigen G is supposed to be polyvalent and the antibody A monovalent: hence the result of the interaction is a mixture of compounds ANG, AN-1G, …, AG.

3. A mathematical deduction is performed starting from the law of mass action, which leads to expressions for the amounts of total precipitate and its constituents in terms of the quantities of antigen and antibody which were mixed and the known equilibria constants.

4. A numerical example is given for a tetravalent antigen. Three cases are represented in graphical forms: the ‘X case’ without inhibition zones, the ‘Y case’ with one and the ‘Z case’ with two inhibition zones. Certain characteristics are described and the significance of the ‘equivalence point’ is analysed.

5. A discussion deals with the irreversibility in relation to the Danysz phenomenon and the dilution effect, and finally the parameters of the theory are more closely considered.

1. Animals susceptible and naturally immune to plague—Bombay rats and white mice—were infected with Past, pestis and supravital study of white blood cells from the peripheral blood stream carried out. Similar studies were made on white mice injected with (a) pure envelope serum, (b) pure somatic serum, and (c) whole antiplague serum.

2. Different experimental conditions produced different cell pictures with different behaviours of individual cell types, especially the polymorpho-nuclears, the monocytes and the clasmatocytes. These abnormalities were found to bear distinctive relationship to (a) active immunity, (b) passive immunity, and (c) susceptibility on the part of the experimental animal.

3. The value of immunological inferences from this study in relation to plague-serum therapy and plague prophylaxis has been emphasized.

4. The possibility of a better understanding of host-parasite relationships from similar studies in other bacterial infections has been pointed out.

Our thanks are due to Lt.-Col. S. S. Sokhey, I.M.S., Director Haffkine Institute, for his interest in this investigation.

Changes of nuclear structure in bacteria have been studied by means of the hydrochloric acid-Giemsa method which produces brilliantly stained specimens and can be carried out with almost the same ease as some of the ordinary routine staining techniques.

The nuclear changes in the four spore-bearing organisms studied are outlined in Text-fig. III, to which the following numbers refer. The dumbbell bodies which are dispersed in the cells of the young growth (1) become alined in the long axis of the cell (2) where they eventually fuse into an axial nuclear cylinder (3, 4). These cells divide up into fusion cells of approximately the same length (5). The development of the ‘chromosome’ stage (1) into the fusion cell (5) is the first step in the process of sporulation. During its further development the fusion cell or spore mother cell divides twice (6, 7), with the result that it is segregated into four structures which often assume dumbbell shape. Therefore the chromatin cylinder of the individual spore mother cell seems to be equivalent to four nuclear elements one of which functions as the spore ‘chromosome’ (‘nucleus’?), whereas the remaining three disintegrate (8, 9). The ripe spore (9) representing, as it does, the smallest cell unit contains one nuclear structure only.

Therefore the two main features in spore formation of bacteria appear to be (1) a fusion of the dumbbell bodies into an axial chromatin rod (‘autogamy’?), (2) a reduction partition which is reminiscent of, though not corresponding to, the more complicated phenomenon of meiosis in the higher organisms. The sporulation, as outlined in this paper, gives new proof of the important part played by the chromatinic dumbbell bodies (‘chromosomes’) in the developmental cycle of spore-bearing organisms. The fusion cell with its axial chromatin cylinder has for the first time been proved to have a progressive functional significance as a stage in a nuclear cycle. The particular mode of fusion followed by reduction partition suggests that the chromatinic dumbbell bodies may be concerned with the transmission of the hereditary characters in bacteria.

1. Avian tubercle bacilli were cultivated in centri- fuged embryo extract in large hanging-drop preparations.

2. Small groups of individual bacilli were studied undisturbed on a warm stage for several days.

3. The cultures grew very actively and several types of reproduction were observed, all of which were modifications of what was arbitrarily termed the ‘standard’ type.

4. In the ‘standard’ life cycle, which was that most commonly seen, the bacillus elongates during the first 24 hr. to form a filament several times its original length; this divides repeatedly to form a bunch of 20–30 filaments which on the 2nd or 3rd day break down into short rods, which continue to multiply slowly by ordinary binary fission. If the bacilli are subcultivated in fresh embryo extract the cycle is repeated but not otherwise.

5. Three forms of slow growth were seen: (a) The bacillus elongates, though very slowly, to form a long filament which does not divide. (b) The bacillus elongates to about twice its original length and then divides by simple binary fission, (c) The bacillus elongates and segments into short rods, but the intermediate stage of filamentous proliferation is greatly restricted.

6. Bacilli floating freely in the surface film of the drop often form what we have termed a ‘raft’ colony. In this form of development elongation of the rods and filamentous proliferation occur, but the return to the original short form is gradual and incomplete. The organisms grow in one plane and are arranged in a tidy mosaic.

7. The development of ‘mycelial’ forms was studied. A minority of the long filaments formed by the elongation of the rod-shaped bacilli do not break up into strings of daughter rods but continue to elongate rapidly into abnormally long threads; small buds appear at intervals along the thread and grow into primary branches on which secondary and tertiary branches form in the same way: finally a complex branching ‘mycelium’ is produced.

8. The ‘standard’ life cycle appears to be characteristic of rapid initial growth. The wide differences between our results and those of Kahn are probably due, at least in part, to the different cultural conditions used in the two investigations.

The experimental method for, and analysis of, more than 300 determinations of air influx rates into two unheated ‘closed rooms’ of opposite aspects each fitted (a) with wall grating, or (b) with flue, are described. The average relative efficacy for all observed wind velocities of (a) of 50 sq.in. to (b) of 15 sq.in., so far as facilitating natural ventilation in the rooms used, is found to be 1·0. The analysis reveals definite and complex relations between influx rate and wind velocity. A correlation is made with data from other sources, principally photographs of the flow forms of air streaming past grounded house models, and a theory is advanced to explain the broad features of the observations. Comparison with similar published work is made, and the fundamental necessity of simultaneous measurement of the speed and direction of the main wind stream is stressed. The advantage of the flue and the importance of openings, other than those in the room concerned, are pointed out.

The author wishes to record that the investigation was commenced at the instigation of Mr Dean Chandler, to whom he is indebted for en-couragement to publish the results of the further examination of the data obtained. He desires also to acknowledge the enthusiastic interest in the experimental work which his colleagues of the Physical Laboratory displayed throughout the investigation.

The measurements of the wind velocity, so essential to the completeness of the observations, frequently necessitated the scaling of roofs in snow, rain and gale, yet at no time were they neglected.

The author thanks Dr E. V. Evans, General Manager and Director of the South Metropolitan Gas Co., for granting permission to publish the paper.

1. In the period 1923–39, more than one-fifth of all deaths in the age group 0-2 years in the Administrative County of London are recorded as having been caused by bronchitis or broncho-pneumonia. It is very unlikely that the returns have been exaggerated by more than 10–15% through the inclusion of deaths from secondary broncho-pneumonia following measles, whooping cough or influenza. In the 8 years in which measles epidemics occurred, the peak of the measles mortality was from 2 to 17 weeks after, and never before, that of the mortality from broncho-pneumonia.

2. The winter rise in mortality from broncho-pneumonia is not associated with any comparable increase in the carrier rates for pneumococci and haemolytic streptococci.

3. The broncho-pneumonia mortality of infants in the Metropolitan Boroughs is strongly correlated with sub-standard housing incidence, social index and percentage below the poverty line. The relatively small value found for the coefficient of regression between broncho-pneumonia mortality and sub-standard housing may be due to the less rigorous winter temperatures occurring in the more overcrowded central areas.

4. Low external temperature appears to be the most important predisposing cause of fatal broncho-pneumonia in infants; their weekly death-rate from this disease in mid-winter is about seven times that in the late summer. This great seasonal fluctuation in mortality is also found for persons over 55 years in the Administrative County, and for persons of all ages in both the urban and rural districts of the Home Counties.

5. The weekly mortalities of infants from broncho-pneumonia in the Administrative County are most strongly correlated with low temperatures 2 weeks earlier. The two variables are so associated that the mortality rises sharply when the mean temperature of the coldest day of the week falls below 40° F. There is no indication that low temperatures in the spring are associated with higher death-rates from broncho-pneumonia than the same temperatures in the autumn, so that the data provide no support for the supposition that susceptibility increases during the winter in consequence of the progressive depletion in the body of protective nutrient substances.

6. Possible measures to reduce the mortality of infants from broncho-pneumonia are discussed.

The quantitative theory for the interaction between antigen and antibody presented in the previous paper has been compared with some experimental precipitin reactions published in the literature. These reactions include Type VIII pneumococcus polysaccharide-homologous (horse) antibody, egg albumin-(rabbit) anti-egg albumin and diphtheria toxin-(horse) antitoxin.

1. The general course of the experimental precipitation curves (total amount of precipitate, amounts of precipitated antigen and antibody) corresponded well to the theoretical type curves. Hence it may be concluded that the precipitates may be composed of mixtures of compounds of the types AG, A2G, A3G, …, ANG in accordance with the law of mass action. In the cases with ‘inhibition zones’, however, AG, or ANG, or both (and perhaps several more compounds) retain the same solubility as the free antigen (G) and free antibody (A).

2. With regard to the location of the ‘equivalence zones’, experiment and theory also showed a satisfactory agreement.

3. A hypothesis on the velocity of flocculation in the precipitin reaction is presented and compared with some recent results. The relation between the immunological concepts ‘equivalence (neutral) point’, ‘optimum point’ and ‘maximum precipitation point’ is also discussed.

1. The laboratory findings in a series of 215 cases of enteric fever are described and discussed, with special reference to early diagnosis.

2. In the majority of the cases reviewed, the leucocyte count was about the lower level of normal limits, though considerable variation both upwards and downwards occurred.

3. Blood culture was a very satisfactory and early method of diagnosis; the method used is described fully.

4. Certain variations from normal in the behaviour of the organisms were encountered and are described.

5. Bact. faecalis alkaligenes was isolated from blood culture in five cases in which enteric group organisms were also isolated from blood, faeces or urine and in three which were clinically enteric fever. The relation of these observations to the possibility of primary Bact. faecalis alkaligenes septicaemia is noted.

6. Seventeen cases were fatal. The causes of death are described.

1. The virtual sterilization time (v.s.t.) has been used as a measure of the rate of disinfection of Bact. coli cultures by phenol under carefully standardized conditions, and the relationship between this rate and temperature at five phenol concentrations has been examined.

2. The graphs of log (v.s.t.) against temperature reveal that the formula t×θT = A, as usually employed for the calculation of the temperature coefficient of the rate of disinfection, has only a limited applicability for these data. θ and Q10 increased with temperature especially at high concentrations, and at the lowest concentration there was a tendency for them to increase again as the temperature was reduced below a certain point.

3. The other general type of formula, t(T –α)b = a, used for the calculation of biological temperature coefficients, is also of very limited value when applied to these data since b increases with temperature at all concentrations.

4. The magnitude of these temperature coefficients and their manner of variation are considered in relation to previously published data by other authors and the way in which θ should theoretically vary with temperature is discussed.

Measurement of ventilation, is of importance both in the design and control of heating and ventilating systems. In addition, the rates of ventilation actually obtaining constitute an important factor in any quantitative studies of air-borne infection. Measurements of ventilation have, however, not been made as often as was desirable: partly, at least, owing to the lack of a convenient method.

1. An analysis of the complement-fixation reaction in influenza has been made by the use of chess-board experiments in which serial dilutions of antigen are tested against serial dilutions of serum with a constant dose of complement.

2. The reaction has been shown to be a complex one, involving two different antigens, the virus elementary body and the soluble antigen.

3. The soluble antigens of all strains of influenza virus A are identical, and different from the antigen of virus B.

4. The elementary body is a complex of several different antigens, and differences in antigenic structure can be detected between different strains of virus A. All elementary body preparations, however, contain soluble antigen which may be an intrinsic part of the elementary body or may be adsorbed.

5. The most suitable antigen for use in epidemiological studies is one containing chiefly soluble antigen, and a description is given of the method of preparation and use of such an antigen derived from infected mouse-lung tissue.

The author wishes to express his indebtedness to Dr C. H. Andrewes for some of the strains of influenza virus used in this work.

A total of 1040 individuals has been examined for the typhoid carrier state by the O, H and Vi agglutination tests. Some observations have been made upon the technique of the Vi test.

Estimation of the O and H agglutinins proved unsuitable as a preliminary test owing to the high proportion of positive reactors. The Vi test, in contrast, gave a positive result in only a small percentage of those tested and brought the cultural work subsequently required within practical limits. All positive reactors were examined by cultural methods, and in no case were the organisms of enteric fever recovered.

The relative merits of the various tests available for the detection of carriers are discussed and certain tentative conclusions are expressed.

1. A study has been made of different types of coliform bacteria with particular reference to (a) their ability to ferment lactose in MacConkey broth at different temperatures, and (b) the effect of using different temperatures of incubation for the indol, methyl-red, V.P., and citrate tests.

2. It was found that 97% of the cultures of Bact. coli (indol positive, methyl-red positive, V.P. negative, citrate negative) examined could ferment lactose with production of acid and gas between 40 and 44° C. The number was not appreciably reduced at 45° C. but was markedly reduced at 46° C. 28% of the cultures of Bact. coli (indol negative, methyl-red positive, V.P. negative, citrate negative) and 15% of Bact. aerogenes (indol negative, methyl-red negative, V.P. positive, citrate positive) were found to be positive at 44° C.

3. The adoption of a temperature of incubation of 30°C. for the V.P. test as advocated by Levine (1941) and the use of O'Meara's test showed that many cultures previously regarded as unable to produce acetylmethylcarbinol were in fact able to do so. Employing a temperature of 30°C. for 5, or in some cases 7, days for the methyl-red test, it was found that with nearly all the cultures tested there was an inverse correlation between the results of the methyl-red test and those of the V.P. test. With these modifications in technique some cultures originally designated as Intermediate type I were found to have reactions corresponding with those of Bact. aerogenes type I. Similarly, many cultures originally classified as Intermediate type II should have been typed as Bact. aerogenes type II.

4. It was found that all cultures of Intermediate type I classified as such by the new technique were incapable of using the nitrogen of uric acid for growth, but that the majority produced hydrogen sulphide. Cultures of Bact. aerogenes type II, on the other hand, grew well in uric acid medium, but produced no hydrogen sulphide.

The investigation described in this paper was carried out by the Freshwater Biological Association, as part of the programme of the Water Pollution Research Board of the Department of Scientific and Industrial Research. The paper is published by permission of the Department.

The Schick test was carried out on 500 recently confined women and their new-born infants. The Schick reaction was positive in as many as 73 % of the mothers and in 60 % of their infants. The infants were positive reactors in 82% of all the cases in which their mothers were positive.

The reaction of the new-born infants was, as a rule, weaker than that of the mothers. It often happened that when the mother's reaction was faintly positive, her infant's reaction was negative.

When the mothers had been immunized with diphtheria toxoid, the overwhelming majority of both the mothers and their new-born infants were negative. Immunization of Schick-positive women with diphtheria toxoid during pregnancy is recommended as a preventive of diphtheria in infancy, as by this means the antitoxin level of the new-born infant can be raised.

We wish to acknowledge our indebtedness to Jörgen Lövset, M.D., chief physician, Hospital for Gynaecology and Obstetrics, Bergen, Norway, for permission to use the material for this investigation.

1. In vitro experiments carried out by a modified Rideal-Walker technique showed the superiority of CTAB over chlorine and chloroxylenol disinfectants against Str. agalactiae.

2. The disinfectant action of 1 % CTAB persisted on the surface of dry hands and cows' teats for a period of at least 3 hr. Subsequent moistening of the hands with milk reduced the efficiency of this disinfectant.

3. For the prevention of dissemination of Str. agalactiae by means of milkers' hands and at the same time to reduce the incidence of infection on the surface of teats, a lanette wax-oil base containing 1 % CTAB was tested. It was found that the inclusion in the cream base of CTAB did not reduce its bactericidal efficiency.

From three patients suffering from gastro-enteritis, non-mannite-fermenting, dysentery-like organisms were isolated which showed marked serological relationship to X, Y and P119 strains of B. dysenteriae Flexner.

In carbohydrate peptone-water media the organism fermented glucose without production of gas. In Lemco broth, however, both acid and gas were produced from glucose. The only other carbohydrate which was fermented was saccharose, but fermentation was weak and occurred only when incubation was prolonged for several days.

The organism possesses the group antigen common to the whole Flexner group and also a new type specific antigen of its own. Therefore it must be regarded as a new, non-mannite-fermenting member of the Flexner group of dysentery organism.

This work was undertaken at the instigation of Prof. P. L. Sutherland, to whom I am indebted for assistance and advice in the preparation of this paper. My thanks are due to Mr S. J. Denyer, Chief Technician, who isolated the first strain and referred it for further examination. I also thank Mr Gordon Denton for technical assistance.

Subcultures of all three strains have been sent to the National Collection of Type Cultures in London. Samples of the specific antiserum may be obtained from this laboratory.