The stability of the biological reagents used in routine immunological procedures is a matter of practical interest to the public health worker, and an attempt has been made in the following research to estimate the period during which the diluted toxin used in the Schick test for the estimation of susceptibility to diphtheria remains potent. In the early days of Schick testing, although Leete (1920) reported that a diluted toxin retained its potency for as long as 5 weeks, it has hitherto been considered inadvisable to use a toxin at a longer interval than 48 hours after it had been diluted to its proper strength. Glenny, Waddington and Pope (1928) and O'Brien, Okell and Parish (1928) have introduced a new diluent consisting of a solution of a combination of crystal borax 57, boric acid 84 and sodium chloride 99 parts. A 1·5 per cent, solution of this mixture is now used as a diluent and has the effect of sustaining the potency of the diluted toxin over a greater period of time. In our work over 400 persons have been tested with toxins made up according to this formula, a comparison being made in each individual between the reactions elicited by an aged toxin, stored for varying periods at room temperature or in the cold room, with those produced by a fresh toxin. Enough toxin was made up at the beginning of the experiment to last over a considerable period of time, samples being sent to us by post periodically together with batches of freshly diluted toxin. The testing of reagents was carried out immediately on receipt, the lower age groups being selected in any series of individuals as being likely to give the largest number of reactors. The actual testing was performed practically throughout by one of us (J. C. J. McEntee) so as to maintain uniformity of technique. Each pair of toxins was controlled by a single injection of inactivated toxin and the results were scrutinised at the 4th and 10th days, a record of the comparative intensities of the positives being made at the same time. The results are recorded in Table I.

B. dysenteriae (Sonne Type III) may be separated from the dispar group by the fact that it is indol negative and zylose negative. It is usually inagglutinable when freshly isolated but will remove all agglutinins from a Sonne serum. B. dysenteriae (Sonne Type III) is a serological entity and can readily be distinguished from B. dysenteriae Flexner and from the dispar group. Eleven strains of B. dysenteriae (Sonne Type III) have been isolated and examined, along with standard cultures of this group of organisms.

Invisible infective agents may be divided into: (1) true, ultramicroscopic, living viruses, which do not arise de novo and, so far as is known, are not ubiquitous; (2) transmissible infective agents which arise de novo and are propagated through living cells, but are not themselves living organisms; (3) stimulants to variation which arise de novo, are not transmissible, and are not living organisms.

Class (1) is not represented in malignant disease. “Bacteriophage” is a representative of class (2); very probably the infective agent of fowl sarcoma comes under the same category, and possibly some important human diseases of doubtful aetiology. There is no satisfactory evidence that mammalian malignant disease is related to class (2); its causation, according to the “chronic irritation” theory, must be attributed to influences comprised within class (3).

The stimulants to variation in class (3) depend for their effectiveness upon the unstable energy of living matter. The changes which they produce are “biological” in the sense that they are changes of chemical constitution which could not be obtained without the aid of vital processes.

Regulation of normal growth in the animal body means regulation of the cell's facilities for obtaining energy. I think it is misleading to regard it as a forceful restraint (or stimulus) upon the cell's inherent capacity for unlimited growth.

The assumption, borrowed from “natural immunity” towards bacteria, that there is in the animal body a natural principle which destroys frequently occurring foci of incipient malignancy is also unsubstantiated and misleading.

During the latent period, certain cells, which subsequently grow into a neoplasm, lose their capacity to respond to inhibitory systemic influences. This change is brought about by local and not by systemic causes.

As regards the special class of tumour derived from cells which have been displaced in foetal life, long residence in an abnormal situation does not appear to be equivalent to the ordinary latent period; but it may have had the effect of increasing their susceptibility, so that, if exposed to chronic irritation, the cells would more readily lapse into the latent period predisposing to malignancy.

It is known that the various tissues of the animal body differ in their degree of susceptibility to the precancerous change. This is a cellular characteristic; so also is the difference in the susceptibility of one animal as compared with another. It is not a question of difference in a hypothetical humoral property of “systemic resistance.”

On the termination of the latent period by a fresh stimulus to proliferation, certain cells commence active growth and are incapable of responding to systemic inhibitory influences. These conditions seem sufficient for the origin of an innocent neoplasm. But something more is required to explain malignancy, because the malignant cell is essentially different from the cells in a benign tumour.

About the actual cause of the change to malignancy one can only offer conjectures. I have suggested a way in which the change may possibly be produced through the agency of the local endothelium and the autogenous formation of antibodies.

On taking a broad view, the change into the malignant variant is not something unique; equally remarkable changes are to be found in the properties of bacteria. In both cases the facts have to be accepted, at present, without satisfactory explanation of the conditions which gave rise to them. One finds with bacteria that degradation or “roughness” may be a phase preparatory to the acquirement of new properties, just as the degradation of cells in the latent period seems to be a requisite preparation for acquiring the new property of malignancy. But the actual steps involved in the change from a bacterial saprophyte to an invasive parasite are as difficult to understand as are the processes involved in the conversion of a normal animal cell into its malignant variant.

Throughout the study of cancer it is very desirable to maintain a clear distinction between cause and effect. For example, the enzymes peculiar to cancer are not the cause of cancer but the effect of the biological change which produced the cancerous cell.

The results of an inquiry into colds and slight influenza—held by me with the obliging collaboration of 7000 informants in the Netherlands from September 1925 till June 1926—do not contradict the hypothesis propounded in the introduction, that various respiratory diseases depend upon a disturbance in the thermo-regulation, in consequence of which the body becomes receptive to commensal infection.

In the first place a proportionally equal number of colds was reported at the same time from the various parts of the country during the period of observation, while the increase and the decrease of these colds ran parallel to the falling and rising of the temperature of the air. Further, when calculating the figures from large and from small families, it was proved that the members of small families have no lesser chance of infection than the members of large families.

This joint result tells against the contagiousness of colds in the period of observation.

The outbreak in September stood alone; the preceding period had not been marked by a low average temperature but by a series of cold nights. During the following month the occurrence of colds was accompanied by the mortality from old age and by the joint mortality from bronchitis and pneumonia.

An increased mortality from pneumonia in March–April, linked up with a moderate lowering of the temperature of the air, was not accompanied by “old-age mortality” and only moderately by “colds” it went together however with an increased mortality from influenza. The influenza cases of the inquiry too had increased by that period of time. So the influenza showed itself as a parasitic infection, which takes its own epidemic course. Still the possibility remains of the virus, at times of reigning influenza, having also widely spread among the healthy. At any rate the idea that catching cold reduces resistance to influenza or pneumonia is supported by the data.

The opinion obtained from the results of the inquiry, that most colds and pneumonia, as well as many cases in which old age has been given as the cause of death, are founded on a disturbance of the thermo-regulation, has drawn attention to physiological oscillations of the temperature of the body in relation to that of the temperature of the air. As the thermo-regulating system is not able to fix the temperature of the body completely, even under normal conditions, but allows a certain poikilothermia, it is clear that by a considerable drop in the temperature of the air these oscillations of the temperature of the body become so large that they may cause a disturbance.

The prophylaxis of the diseases from catching cold will have to be directed towards the application of “passive” prophylactics (for preserving and supplying heat by imminent cooling), as well as of “active” prophylactics (raising the production of heat by the body).

1. In B. typhosus, B. paratyphosus A and B, and B. enteritidis Gärtner, low concentrations of phenol and formaldehyde produce a definite inhibition of the 0 agglutination, while the H agglutination is unaltered—a fact already established many years ago in the case of B. proteus X 19.

2. Alcohol, even in high concentrations, has no such inhibitory effect.

3. Therefore, suspensions preserved in the usual way with phenol or formalin are not adequate reagents for the qualitative serum analysis in enteric fevers or for the usual diagnosis test in typhus fever.

4. Phenol and formalin suspensions are responsible for negative results of the Widal test in cases of enteric fevers which show only the 0 immune body in the serum; such cases form a considerable percentage of the total especially in typhoid fever.

5. As a routine measure in the diagnosis of enteric fevers, it is suggested that two preserved suspensions of each organism be used:

(1) an alcoholic suspension (like that of Bien and Sonntag in typhus fever) as a reagent for the 0 agglutinin, and

(2) the usual phenol or formalin suspension as a reagent for the H agglutinin.

6. The nature of the described phenomenon of inhibition is not, as yet, entirely clear.

1. No evidence was found of the presence of furunculosis in trout farms. Over 100 trout from four farms in S. England were examined with entirely negative results.

2. Of eighteen live trout taken from the Kennet, three were carrying the B. salmonicida in their blood. All three were in poor condition but alive and active, and two of them were so-called “black fish”.

3. Bacteriological analyses of Kennet water at eleven selected points were carried out in the month of August. They revealed no serious pollution nor any definite relationship between high bacterial content and the disease.

4. Laboratory experiments to test pathogenicity of B. salmonicida appear to show:

(a) That the bacillus is lethal to goldfish when injected into the muscle but not necessarily so when rubbed into a skin wound.

(b) That in the case of gobies infection from water polluted with pure broth cultures of B. salmonicida is possible and may cause death in about fifteen days after the introduction of the culture.

(c) That fish (gobies) which had survived the last experiment for a period of six weeks were capable of infecting healthy “contacts”, when kept with them in fresh running water.

5. A few laboratory experiments on the behaviour of B. salmonicida in sewage appeared to indicate that the bacillus persists longer in tap and distilled water than in crude sewage and sewage effluent.

6. Specimens of fish (salmon and trout) infected with furunculosis were also received during the summer from the Rivers Lledr (Wales), Lyon (Scotland) and a private hatchery on the Test at Whitchurch. The conditions in the two latter cases suggested that the outbreak was mainly due to carriers.

7. Measures suggested in the case of infected streams are: avoidance of over-stocking, bacteriological scrutiny of source of fresh stocks, removal of sick and ill-conditioned fish, and sewage control.

In January 1923, after the publication of The Epidemiology of Botulism by Dr K. F. Meyer and his colleagues in America, and after the publication of the official report to the Scottish Board of Health on the Loch Maree tragedy, it seemed obvious that an accurate knowledge of the distribution of the Bacillus botulinus in Scotland was very desirable. Dr Meyer had shown that this was an organism which lived in the soil, and he had already published the results of the bacteriological examination of a great number of soils in America and other countries. None of them, however, came from Scotland. I therefore suggested to the Scottish Board of Health that they should ask the Medical Research Council to undertake such an examination, and offered my own services for the purpose of collecting soils from all the Scottish counties. The Board at once agreed, and the Medical Research Council on having the request put to them also at once agreed and appointed Professor Basil Buxton, F.R.C.V.S., to undertake the bacteriological investigation. Prof. Buxton and myself arranged exactly the kind of samples which should be taken, and the method of taking them, and he supplied me from time to time with a number of sterilised containers into which samples of soil were put and forwarded to him for examination.

Skin tests made with the toxin obtained from Tunnicliff's strain of green producing streptococcus on normal individuals, and on cases prior to and after an attack of measles did not give any definite positive evidence of the etiological relationship of this organism to measles. Further, an attack of measles did not produce any apparent increase in the antitoxic content of a patient's serum for this toxin.

In a previous paper (Williams and Hoy, 1927) it was shown that living and virulent tubercle bacilli could be demonstrated in the faeces of six apparently healthy cows from among a total of 391 which were examined. All these cows were living the normal life of the herds in which they were discovered, and three of them were brought to the Institute in order that a study might be made of the frequency with which tubercle bacilli could be found in their faeces.

We hope that this summary of our researches will be sufficient to make clear the nature of the danger spoken of at the beginning of this article. We see that certain bodies, not poisons in themselves in the usual sense of the word, can provoke physiological disorders and organic lesions, the etiology of which remains generally unnoticed, when they are absorbed daily for months and years. Such products are most certainly responsible for many illnesses, the frequence of which augments with the alimentary conditions imposed upon us by modern civilisation in a manner inexplicable beforehand.

Our object will have been attained if we succeed in attracting the attention of physicians and hygienists to certain problems, the study of which is perhaps not very attractive but the solution of which is of considerable practical interest.

In view of the number of cases of epidermal cancer, especially cancer of the scrotum, which have occurred amongst cotton mule spinners within recent years, constituting this the foremost occupational cancer in our country, it may be opportune to investigate the exact duration of employment in the mule rooms that would seem to be necessary before the disease manifests itself. How long must the individuals be exposed to the action of the cancerinducing influence before the cancerous response is elicited? The Departmental Committee on Mule Spinners' Cancer having found that the “influence” or agent in this case is mineral oil, which Leitch has proved experimentally to have cancer-producing properties, how long does it take to act?