Although knowledge of principles determining variation is imperfect, some progress has been made and further help may be obtained from some of the newer conceptions about combining affinities regulating normal growth. There are reasons to believe that growth depends on a rhythmic cycle of synthesis, peculiar to living protein, whereby at each successive stage one particular “building stone” is selected for synthesis, with rejection of all others. There is also some evidence that the surface of a growing bacterium passes through periodic phases. Additional light on the activities of the bacterial surface is thrown by the new conception of enzymes which regards them not as fixed chemical entities but as chemico-physical “centres of activity.”

Some of the principles which are gradually coming to light in bacterial variation may ultimately be of assistance in the much more obscure problem of explaining the change from the normal mammalian cell to its malignant variant. I refer in particular to conceptions, which I have discussed in the preceding part of this article, about the mechanism of cellular growth and the nature of a cell's combining affinities.

The analysis of the serological results of blood specimens submitted during the course of the past 2 years for the Widal reaction has been made.

The sera from cases of typhoid and paratyphoid fever were examined in particular for their agglutinin content for the “H” and “O” antigens of B. typhosus and B. paratyphosus B. The results obtained indicate that it is essential to use the “O” antigen of B. typhosus, but no particular advantage has been derived, from the point of view of early diagnosis, from the use of B. paratyphosus B “O” antigen.

A comparison of the value of suitable living and killed antigens has been made. Either type of antigen appears to be equally effective, but for convenience and stability the suspensions issued by the Standards Laboratory, Oxford, have proved entirely satisfactory.

Cases showing the serological difficulties which arise when a mixed specific and non-specific form of B. paratyphosus B “H” antigen is used are described.

The author is indebted to the Medical Eesearch Council for a personal grant, and to Miss N. A. Davidson for much technical assistance.

It does seem clear from the above series of results that of the factors examined in their relation to rickets, etc., the only one of substantial importance is differences in the manner of feeding. The absence of definite association with overcrowding is, certainly, surprising, in spite of the fact that we realise how crude is the measure of this factor which we have had to adopt. If, as we suggest, the personal factor is not a very serious one, the above findings afford at least prima facie evidence of the truth of the assertions made previously, and are certainly sufficient to warrant the prosecution of further field enquiries, on this line, but having greater regard to the obtaining of the necessary information in a form more suitable for detailed analysis.

In this section the influence of five possible factors on the weight of the child has been considered. No one of these can be shown to be of outstanding importance in this respect; but the efficiency of the mother shows the highest and most consistent relationship. Health of mother and those variations of feeding which are considered here as indiscretions have no appreciable influence on infant weight, but the remaining two variables, overcrowding and position of the infant in the family, seem to influence the weight of the child. In the case of overcrowding, the effect is small and only becomes substantial towards the end of the first year. Position of the infant in family, likewise, is of little moment; first and latest-born infants initially seem to have lower than average weights, but towards the end of the first year of life the weights of first-born infants tend to be over average, while those of infants born into already large families still show evidence of inferiority.

Since the early work of Nuttall (1888), Buchner (1889), and others first disclosed the bactericidal property of normal serum, a considerable amount of attention has been devoted to this important biological phenomenon. The literature (which has been reviewed recently by Knorr, 1929) lacks, however, a comprehensive and co-ordinated study of the subject, and in fact presents a good many confusing data in regard to the nature of the active principles concerned and their immunological significance.

1. Rats taken from mixed stock diet and fed synthetic diet containing an excess of magnesium carbonate developed urinary calculi in a large number of cases.

2. The incidence of calculi was much higher in the females.

3. Addition of excess of calcium carbonate to the diet prevented the formation of calculi.

4. Rats previously fed for a short time on the synthetic diet and normal salt mixture did not develop calculi, but suffered from severe catharsis.

5. Rats on mixed stock diet had a more acid caecum and colon than those on synthetic diet.

6. No significant alterations were found in the Ca, Mg or inorganic P of the blood on any of the diets.

7. Extra magnesium, or calcium, or sodium carbonate lowered the urinary phosphate excretion.

8. Extra magnesium or calcium had little effect upon the urinary excretion of the other, but tended in each case to lower the output.

9. Changes in the sex organs brought about by excessive intake of magnesium are described.

The writer wishes to thank Miss V. E. Leader for her watchful care of the rats.

The following investigation was made, at the request of the Mine Rescue Research Committee of the Safety in Mines Research Board, as to the upper limit of temperature at which air can be breathed without distress under various conditions. During the use of self-contained breathing apparatus in rescue work, the air circulating in the apparatus becomes heated and saturated with moisture, and the question arises of the limiting temperature of inspired air that a man can tolerate while resting and while doing work, and which is therefore permissible for an apparatus.

1. In a group of boys, revaccinated 12 years after primary vaccination in infancy, 37 per cent, gave “immune” reactions to vaccine virus.

2. Immune reactions were more than twice as common in those boys with two or more old vaccination scars than those with one.

3. When the number of scars was held constant there was no tendency for groups with large scars to be more immune than those with small scars.

4. The average area of a single old scar was smaller in the “immunes” than in the rest of the group.

5. The substitution of a vaccination technique consisting of one insertion of lymph with a minimum of trauma, for two or three insertions by “crosshatched” scarifications was followed by nearly a threefold fall in the recorded vaccinia morbidity, and a halving of the number of days' sickness attributed to vaccinia.

1. Opinions upon the relationship between anti-rabies immunity and the rabicidal power of rabies-immune serum have been stated.

2. The rabicidal antibody content of the sera of rabbits immunised with etherised virus, living fixed virus and carbolised virus has been determined while at its maximum and compared with the degree of immunity acquired after each method of treatment.

1. In the list showing all substances yet tested in the order of their spermicidal powers, the first four substances are all quinones.

2. In the dihydroxybenzenes and their derivatives, the para-position of the two hydroxyl groups confers high spermicidal powers.

3. In the trihydroxybenzenes and their derivatives, the para-position of two of the three hydroxyl groups confers high spermicidal powers.

4. The introduction of a methyl group into quinones and into the di- and trihydroxybenzenes in certain positions increases the spermicidal power.

5. In the hydroxybenzaldehydes and their derivatives, the ortho-position of the hydroxyl and aldehyde groups confers high spermicidal powers.

6. Among the substances so far tested which may be found to be of practical use are orbhovanillin and methoxytoluquinone. These are highly spermicidal, sufficiently soluble and stable in solution. It remains to be seen whether they are harmless to the vagina.

1. The amount of crystallisable albumin in egg-white and the amount of total globulin in horse serum have been estimated by means of the precipitation reaction. The results are in good agreement with those obtained by other methods.

2. For such estimations it appears advisable to use only antisera prepared against individual proteins.

3. A description of the manufacture and the characteristics of the pure proteins used is appended.

1. Normal “whole” blood and serum-leucocyte mixtures may exert a bactericidal effect when the serum (or plasma) is inactive in this respect, and may possess quantitatively greater bactericidal properties than serum (or plasma), when the latter is active per se, but such effects are relatively weak.

2. Leucocyte suspensions may exhibit an initial bactericidal action on certain bacteria, but this is usually weak and is followed by a pronounced growth-promoting influence on the surviving organisms.

3. Under certain conditions normal “whole” blood and serum-leucocyte mixtures are inferior to serum (or plasma) in bactericidal power. This is observed when the serum (or plasma) is strongly active per se and is due not merely to an inhibition of the bactericidal action of the leucocytes, but also to a lessened effect of the serum-bactericidins.

4. The comparative bactericidal power of normal “whole” blood or serumleucocyte mixtures on the one hand and serum or plasma on the other depends on the activity of the serum; when this is relatively weak, blood shows an enhanced action; when strong, blood is less active.

5. The above findings apply to a wide variety of bacteria irrespectively of biological species.

6. Bacterial extracts possess marked inhibitory properties on the bactericidal action of serum (or plasma), but not to any extent on the bactericidal properties of the leucocytes as evidenced by the approximately equal influence of such extracts on whole blood and serum respectively.

7. Dead bacteria in certain numbers produce inhibition of the bactericidal action of serum (or plasma), but exert a greater inhibitory influence on the reaction of “whole” blood.

8. It is suggested tentatively that when the serum is strongly bactericidal the killed organisms on being phagocyted along with living bacteria interfere with the intracellular destruction of the latter which at the same time are protected from the serum-bactericidins.

9. The paper also includes certain data regarding the time of maximum bactericidal action by serum towards various organisms and the occurrence of growth-promoting action following an initial bactericidal effect.

The occasional occurrence of ”paralytic accidents” during the course of antirabic inoculation is well recognised as an unfortunate complication of that therapeutic measure. The cases have to be distinguished from the rare instances of paralytic rabies in which, usually after extensive bites from rabid wolves, the disease assumes an unusual form and in which the virus can be recovered from the central nervous system. The paralytic accidents on the other hand are in no way related to the date or severity of the original injury—on occasion the suspected animal has later been proved healthy—but are definitely associated in time with the commencement of the treatment; almost all occur within 7–23 days of the first inoculation, and fatal cases show no rabic virus in the nervous structures.

The granular “O” agglutination of human serums from eighty cases of typhoid and paratyphoid B fevers has been titrated with carefully selected killed typhoid “O” and paratyphoid B “O” suspensions of high sensitiveness.

In spite of a wide overlapping, due to common factors, a considerable specificity is shown, and this can be utilised in differential diagnosis, especially if due attention is paid to the different levels of “normal” agglutination for the two species.

1. Highly milled parboiled rice was found to be rich in the antineuritic vitamin B1, while roughly milled raw rice was deficient. In estimating the content of vitamin B1 the method of Chick and Roscoe was used.

2. Exact comparison was made of the vitamin B1 potency of two samples of rice, the one raw, the other parboiled, after similar degrees of milling. The vitamin value of the unmilled samples was equal, but when each was highly milled to an equal degree, as judged by weight of polishings removed in a hand rice mill, the parboiled sample retained the vitamin while the raw sample did not.

3. Polishings from parboiled rice were found to contain less vitamin B1 than those from raw rice.

4. Parboiled rice contains more P2O5 than raw rice milled to the same degree.

5. It is probable that when rice is steamed in the process of parboiling, the vitamin B1 and some of the phosphate contained in the germ and pericarp diffuse through the endosperm.

6. The P2O5 content of raw rice is a good index of vitamin B1 value, but in parboiled rice a low percentage of phosphate is compatible with the presence of the vitamin.

Thanks are due to Miss L. M. B. Patterson who kindly made the phosphate estimations recorded in the paper. I am indebted to the Director of Agriculture, British Guiana, for a number of rice samples. The rice mill used was kindly lent by Jackson and Son, 30, Mincing Lane, E.C. 3. I am grateful to Miss Chick for her continued interest in these experiments.

1. Altogether 117 strains of Brucella, belonging to different types and isolated from different parts of the world, have been examined by the thermoagglutination, salt agglutination, acid agglutination, and specific serum agglutination tests.

2. The results obtained by the thermo-agglutination and the serum agglutination tests are in close agreement; there is a fairly high degree of correlation between these tests and the acid agglutination test, and a rather lower correlation with the salt agglutination test.

3. Generally speaking, a strain which is highly thermo-agglutinable is frequently agglutinated by salt, is usually agglutinated strongly by acid, and reacts to a paramelitensis, but not to an abortus serum.

4. A strain which is moderately thermo-agglutinable is seldom agglutinated by salt, is frequently agglutinated by acid, and reacts either with an abortus or a paramelitensis serum, or with both sera.

5. A strain which is not thermo-agglutinable is not agglutinated by salt, seldom reacts markedly to acid agglutination, and is generally agglutinated by an abortus, but not by a paramelitensis serum.

6. There remain, however, a certain number of strains, particularly of the porcine and bovine abortus types which, though non-thermo-agglutinable, inagglutinable by salt, and reacting only with an abortus serum, yet show some degree of acid agglutination.

7. Of the twelve porcine strains examined only one strain was strongly thermo-agglutinable; of the forty-seven bovine strains only two were strongly thermo-agglutinable, a further two showing a milder degree of thermoagglutinability; of the forty-seven melitensis strains eight were strongly, and thirteen were moderately thermo-agglutinable; while of the eleven paramelitensis strains ten were strongly thermo-agglutinable.

8. These results are taken to indicate, in accordance with the suggestion made by certain previous workers, that those strains which are non-thermoagglutinable, are not agglutinated by salt, and are agglutinated by an abortus but not by a paramelitensis serum, represent the smooth form, while those strains which are strongly thermo-agglutinable, are frequently agglutinated by salt, and are agglutinated by a paramelitensis but not by an abortus serum, represent the rough form.

9. If this interpretation is correct it will be noticed that the great majority of the porcine and bovine strains examined were of the smooth type, that nearly half the melitensis strains were partially or completely rough, while all but one of the paramelitensis strains were rough.

10. Whether melitensis strains have a greater tendency than abortus strains to undergo the smooth to rough transformation it is difficult to say with certainty, but the reports in the literature and the observations in the present paper render this probable.

11. By serial passage through broth at 5-day intervals, it is possible to transform smooth strains of all three types into the rough form. This transformation appears to occur more readily and to proceed further in a given time with melitensis than with abortus strains; but since only three strains of each type were examined, the results may have been determined as much by chance selection of strains as by any greater inherent tendency of the strains of the melitensis type to undergo variation.

12. It is clear that none of the tests employed suffices to differentiate individual strains of abortus and melitensis. The thermo-agglutination test and the agglutination test with specific smooth and rough sera do, however, enable a differentiation to be made between smooth and rough strains of all types.

13. In the present paper no attempt has been made to distinguish abortus and melitensis strains by specific agglutination and absorption tests. The general failure of workers hitherto to obtain any clear-cut serological distinction between these types may possibly be due to the fact that many of the strains with which they worked were either partially or completely rough. Since the rough antigen seems to be more or less alike in strains of all types, it is clear that its presence would tend to obscure any difference that might exist between the smooth antigens of the different types. If such a difference does exist it is probable that it will be elicited only by a comparison of absolutely smooth strains.

Men engaged in slaughtering and dressing meat show a higher incidence of Brucella abortus agglutinins than those in similar age and sex groups who are otherwise employed, where titres of 1 in 20 and upwards are observed.

This applies especially to men who deal with cattle and sheep; no such increased incidence has been noted in men dealing with pigs.

It would seem that a titre in the vicinity of 1 in 40 serves to indicate evidence of Brucella infection definitely greater than that likely to be found in the generality of the community.

In a semi-closed institution, Greenwich Hospital School:

1. There was no constant relation between the prevalence of cases and carriers of virulent, or avirulent, diphtheria bacilli.

2. Carrier rates showed a seasonal periodicity with a maximum in the autumn and a minimum in the winter school term.

3. High rates for carriers of virulent bacilli were found in the absence of clinical diphtheria and presence of numerous Schick susceptibles.

4. As much as 40 per cent. of a random sample of healthy boys, none of whom contracted diphtheria, were discovered to harbour diphtheria bacilli (M.D.)1 within 1 year, during which the average carrier rate in the sample was 6·8 per cent.

5. The carrier rate for avirulent diphtheria bacilli, among boys recently infected with virulent, was three times the expected rate.

6. The carrier rate for virulent diphtheria bacilli, among boys recently infected with avirulent, was no higher than the expected rate.

7. The frequency of avirulent diphtheria bacilli infections was twice as great among Schick susceptibles as among Schick immunes.

8. Carriers of virulent bacilli (with five exceptions) were always found to have Schick-negative reactions, in spite of their being more frequent among the junior members of the institution.

9. Carriers of avirulent diphtheria bacilli were as common among the senior as the junior Schick-immune members of the school.

10. Carriers of avirulent bacilli were less frequently found in those Schick-susceptible members of the community who were most quickly immunised by artificial diphtheria antigens.

11. The hypothesis that, when a Schick susceptible is infected with virulent diphtheria bacilli, the latter often acquire avirulence, could satisfactorily explain many anomalies in the distribution of latent infection with diphtheria bacilli and Schick immunity.

[Since this article went to press I have received a reprint from A. Garrido-Morales and 0. Costa (“ The Mechanism of Natural Immunity to Diphtheria,” Amer. J. Hyg. (1931), 14, 89), who describe the distribution of diphtheria carrier infection and Schick immunity in a school at San Juan, Porto Rico. In the main their results parallel those obtained at G.H.S. The most important difference between the tropical and G.H.S. observations was found in a sample of children, who were Schick tested and swabbed synchronously, in which the frequency of virulent carrier infections was greater among Schick susceptibles than Schick immunes. (However, only 9 T.C.D. infections were found among 642 children, but 5 of these were discovered among the 194 Schick susceptibles in this group.)—S. F. D.]

As a result of the extensive investigations in America and on the Continent into the relationship of Br. abortus to undulant fever in man, attention in this country has been directed to cases of fever due to obscure causes, with the result that an increasing number of cases of undulant fever are being reported. So far, however, the cases in Great Britain appear to be less numerous than those in the United States and in Denmark where every effort has been directed to tracing sources of infection and where the conclusion has been reached that, although a certain number are infected by contact with the secretions and carcasses of infected animals, many infections occur through ingesting milk containing Br. abortus.

1. “Normal” agglutinins for B. typhosus and B. paratyphosus B appear to be conclusively of the O type.

2. Such agglutinins appear to be of consistently low titre and are absent in many sera.

3. Normal agglutinins for B. paratyphosus A have not been encountered.

4. O agglutinins are readily produced by inoculation of a T.A.B. vaccine, and may rise to as high titres as those encountered during an enteric infection.

5. It is impossible to fix any limit for residual O agglutinins in inoculated persons.

6. The value of examining for O agglutinins in enteric cases is confirmed.

7. Some fallacies of a purely qualitative method are pointed out, and a plea is made for the inclusion of the principles of qualitative receptor analysis in a quantitative Widal.

Experiments were carried out on rabbits, guinea-pigs and monkeys to test the immunity produced by vaccinia virus killed with heat, phenol or formalin. Before use, the vaccines were rigorously tested for their inactivity by a method of inoculation and triple passage in series. The test of immunity was quantitative.

The rabbit experiments gave equivocal results but indicated that a slight immunity was produced in some cases. In guinea-pigs more success was obtained: they could be protected against one to ten minimal infecting doses and showed a partial immunity to stronger tests. Monkeys were only tried in one experiment in which a weak vaccine was used. This did not protect them.

The superiority of guinea-pigs for this kind of work is discussed as also the bearing of the results obtained with them on the nature of immunity to vaccinia virus.