In introducing his subject the author pointed out that the following facts suggested the research: - First, that in the course of an experimental investigation on gout in fowls the use of an excessive meat diet had induced a striking hypertrophy of the thyroid and parathyroid glands; and, further, that these changes were not present in the glands of one foul, similarly fed, which was proved to be tuberculous at the postmortem examination. Secondly, the correlation of these facts in the mind of the author with a well-recognised clinical fact in the dietetic treatment of two diseases - gout and tuberculosis - an excessive meat diet being injurious in the former and beneficial in the latter disease. This indicated that the tissues of a gouty subject reacted to a meat diet in a manner different from the tissues of a tuberculous subject, and suggested that an experimental investigation might yield facts which would elucidate the nature of both of these reactions. Thirdly, the present unsatisfactory state of our knowledge of the dietetic treatment of chronic diseases was cited as an additional reason for experimental observations carried out on lower animals. It was probably not too much to say that in the treatment of many diseases in which meat was restricted in amount, no more scientific explanation could be advanced than was involved in the vague and general statement that meat was a "stimulating" food. One object of this research was to ascertain so far as possible, from observations on lower animals, which, if any, organs were "stimulated" by an excessive meat diet. An additional reason for an investigation of this kind was to be found in the view, held by not a few medical men, that there was an important etiological relationship between the increased consumption of animal food - from 3 lbs. per head per annum to over 50 lbs. per head per annum in the past fifty years - and the increasing incidence of certain diseases. The investigation, which was still in progress, was being carried out in the Physiological Laboratory of the University of Edinburgh, and in its conduct the author had secured the co-operation of a number of investigators to whose work reference was made. Some results had already been published, either in the form of preliminary communications or of completed papers; after a reference to the work already published, he recorded in detail the influence of an excessive meat diet on the thyroid gland. Rats were employed as the subjects of experiment, and the observations were extended to more than one generation. Bread and milk was given as a control diet, this being the food in routine use in the laboratory prior to the special diet investigation. A bread-and-milk diet was regarded as a physiological one for tame rats, since, under its use, the young grew rapidly, the young and adults alike appeared to be in perfect health, and the rate of production was very great. The influence of an excessive meat diet on the growth and nutrition of rats of different ages having been fully described in a former paper, little attention was directed to this point beyond describing and illustrating so far as possible the following three points: - (a) The retardation of growth induced by the use of a meat diet when begun in very early life; (b) the prejudicial effects of a meat regime on the reproductive powers; and (c) the high mortality in early life in the second generation of meat-fed subjects. In considering the histological appearances observed in the tissues of meat-fed animals, it was important to bear in mind that in many of the animals there was no external indication of disturbed nutrition. Dealing first with the reproductive system, it was demonstrated from the results obtained by Dr C. 15. Paul that a meat diet markedly arrested the growth of the male reproductive organs when the faulty feeding was begun when the animals were weaned (p. 589). Attention was then directed to the observations of Dr B. P. Watson, who had extended and amplified the author's original observations on the effect of the diet on fertility and lactation. Dr B. P. Watson's observations proved - (1) that a meat diet was decidedly prejudicial to the occurrence of pregnancy when the diet was begun when the animals were from two to four months old; and (2) that, when they had young, they were less able to suckle them, owing to the smaller development of mammary tissue (p. 608). The results of Dr Malcolm Campbell's observations on the minute structure of the uterus were then alluded to and demonstrated. That author had shown that the use of an excessive meat diet in very young animals induced alterations in the minute structure of the uterine mucous membrane of the nature of a fibrosis. This change was, however, not peculiar to a meat diet, but was also observed in animals fed on other unphysiological diets, such as rice or porridge (p. 587). The effects of a meat diet on the osseous system of the progeny of meat-fed rats were then considered. The bones were unduly soft and very vascular; many subjects showed marked curving of the bones with curvature of the spine; in about 15 per cent, of the series there were small whitish nodules in the bony parts of the ribs. Microscopically there was imperfect bone formation with great increase in the size of the medullary cavity, especially in the cranial bones, with proliferation of the marrow cells (p. 590). The occurrence of similar changes in the bones of an infant, aged sixteen months, suffering from an obscure disease, whose mother was tuberculous and had been treated for a prolonged period prior to and during gestation with a diet containing a great excess of meat, was then referred to. Mention was made of the results of the investigations of Mr G. W. Watson, L.D.S., and Mr J. H. Gibbs, who found that, notwithstanding the very imperfect state of development of the cranial bones, the teeth showed no noteworthy histological change (p. 577). Reference was then made to the observations of the author in conjunction with Dr G. Lyon, which were not yet published, and which showed that there was a hypertrophy of the kidneys in meat-fed animals, and also that a meat diet threw a marked strain on the secreting cells of the kidney, this being indicated by the alteration in the size and arrangement of the granules of the cells, as revealed by special staining methods (p. 578). With regard to the thyroid gland, reference was made to a preliminary communicat'on published by him in the Proceedings of the Physiological Society in 1904, in which it was shown that the use of a meat diet in young rats induced, as a rule, distinct histological changes in the thyroid gland (ten out of twelve subjects). In the past two years these observations had been extended, and particular attention had been devoted to the histological appearances of the gland in the progeny of rats that had been fed on a meat diet. Attention had also been directed to the appearances of the gland during lactation and to its normal structure as seen in wild rats. The glands of sixty-five animals - second generation of meat-fed rats - were examined, with fifty control bread-and-milk-fed subjects. The ages varied from one day to three months, thirty-five of the series being under three weeks old and unweaned at the time of death. The majority of the meat-fed rats died; the others were killed. As an additional control for the animals which succumbed, a series of sixteen young animals of similar age, which died as a result of feeding on other unphysiological diets (rice and porridge), where employed. The histological appearances of the thyroid gland of the meat-fed rats differed from those of the controls. In ten out of the sixty-five the histological changes were slight and did not exceed those occasionally present in bread-and-milk-fed animals. The remainder showed marked changes, which could be classified in the following three groups: - 1. Great congestion of the gland with absence of colloid and little or no attempt at vesicle formation, the gland being in an embryonic state. This appearance was only observed in animals which died in the first few weeks; it was observed in twelve of the series. 2. An increase in the amount of the colloid, far in excess of that obtaining in bread-and-milk-fed subjects, with thinning of the walls of the vesicles from pressure. This appearance was most pronounced in animals which had apparently adapted themselves to the diet, and whose weight and general nutrition were above the average of meat-fed subjects. This appearance was present in eighteen of the series. 3. A diminution or entire absence of colloid with the degeneration and shedding of the secreting cells. This condition was specially marked in animals the general nutrition of which was obviously defective. The majority of these animals died. This series included twenty-six animals. The result of this investigation confirmed the author's earlier observations in showing that an excessive meat diet induces structural changes in the thyroid gland. The appearances proved, to his satisfaction, that a meat diet at first stimulated and later exhausted the functional activity of the gland. Special attention was directed to the modification in structure acquired by the young of the animals fed on an excessive meat diet. The opinion was expressed that conditions comparable to those described would be found if looked for in thyroid glands of children, and that many symptoms of disease in young children were associated with, and dependent on, an impaired functional activity of the thyroid gland which the child had "inherited" from his parents. Some evidence in support of this view was advanced in the form of a section of the thyroid gland of the infant, aged sixteen months, previously referred to, whose mother had been fed on an excessive meat diet. In this gland the intrrvesicular glandular tissue was much less in amount than in the glands of infants of the same age which were apparently normal, the general microscopic appearances of the gland vividly recalling the picture in some of the meat-fed animals. In conclusion, the author drew attention to the importance of the main facts which the investigation had elicited - viz., (1) that an excessive meat diet modifies the structure and function of some important organs, notably the reproductive glands, thyroid gland, and kidney; and (2) that some of these modifications were acquired by the offspring, in which they were present in an accentuated degree, and were in them associated with an increased susceptibility to disease. His clinical experience led him to the view that there was at the present time in this country an increased susceptibility to disease, which was the result in great part of changes in the tissues comparable in their nature and origin to those described in this communication.
1 Paper read by Chalmers Watson before the Pathological Society of London, Lancet, vol. ii., 1906.