mortality from this disease. The question is one that calls urgently for careful investigation on a large scale, and by mathematicians competent to analyse their results by modern methods.

The study of cancer on the large scale, by statistical methods, has so far led to disappointing results. It would appear at first sight easy to determine, at least the predisposing causes of the disease, by a study of its distribution with regard to the habits and habitat of its victims, their personal history and heredity, but such studies, with hardly an exception, have led to indeterminate results. The investigation of the disease in one district has led to conclusions which appear to be definitely proved, such, for example, as the apparent connexion of cancer with a damp subsoil. This has been studied in other districts, and indeterminate or totally opposite results obtained. As another example, we may quote the question of heredity. That there was a hereditary predisposition to cancer in certain families, and that this predisposition played a part of great importance in the aetiology of the disease, was regarded as proved beyond possibility of doubt; but more recent investigations have shown that previous observers have been largely influenced by coincidences (such, for instance, as the celebrated case of the Buonaparte family), and that, when carefully prepared statistics are examined by modern methods of mathematical analysis, they afford no support to the theory. Indeed, some results obtained at the Middlesex Hospital and analysed by Karl Pearson appear to indicate that a person with a family history of cancer is, if anything, slightly less liable to contract the disease than a person without such a history. But the difficulties in the collection of the data necessary for such investigations are so great that all such conclusions must be received with caution, as Pearson points out. It was the experience of such blind alleys in the study of cancer that led pathologists to turn with relief to the experimental study of the disease, rendered possible by the demonstration of the fact that cancer is inoculable in the lower

Archives of the Middlesex Hospital,' vol. ii (second report from the Cancer Research Laboratories (1904), pp. 104, 127).

animals, provided always that a tumour arising from one animal is inoculated into another of the same species, e.g. a tumour arising from a mouse must be inoculated into a mouse, that from a rat into a rat, and so on. We are here on surer ground, and, admitting that the cancer of the lower animals is of the same nature and governed by the same laws as the disease in man, we may expect results of far greater value from studies of this nature, in which all, or nearly all, of the fallacies incidental to clinical and statistical studies can be avoided. An enormous amount of work has already been accomplished in this direction, of which we shall only give the outline, as it is not of great interest to the general reader.

It is found that for the disease to be transmissible from one animal to another, portions of tissue containing whole cells must be transmitted; if the cells are ground up and filtered the filtrate becomes innocuous. This is quite different from the results obtained in dealing with diseases known to be of bacterial origin, in which such a procedure would simply liberate the bacteria, which would then infect their new host. For the inoculation to succeed, living cells must be inoculated, and the continued growth of the tumour in its new host is simply due to the continued growth and subdivision of these transplanted cells, to which the new host simply supplies nourishment. The inoculations may be carried on from one animal to another, apparently without cessation, thus leading us to the conclusion that, given suitable nourishment, the cancer cell is capable of living and multiplying indefinitely.

The most important results are undoubtedly those which go to show the existence of immunity to cancer; their importance arises from the fact that they afford a gleam of hope, at present perhaps but a feeble one, but still a gleam, that the disease may be prevented or cured in the future.

That natural immunity occurs appears from the fact that the mice of a certain region may be refractory to the cancer from another district: thus with one particular strain of mouse-cancer successful inoculations were obtained in 97 per cent. of cases where Berlin mice were used, in 24 per cent. with Hamburg mice, whilst negative

results were obtained in all cases with animals from Copenhagen and Christiania. But if the mice from Berlin were kept for some time in Norway they became relatively insusceptible, showing that altered surroundings may rapidly cause a profound alteration in an animal's constitution. These results are of the greatest interest in connexion with the statistical study of cancer and its distribution in various localities.

Even more important, from its possible bearing on the question of the prevention and curative treatment of the disease, are the observations which prove that the development of an acquired immunity to mousecancer is possible; in other words, that mice can be successfully vaccinated against the disease. This was first shown by Ehrlich, who found that if mice were inoculated with a non-virulent strain of the disease, kept for a week or so, and then re-inoculated with a virulent strain, but few of them became affected. This, of course is entirely comparable with what takes place in the infective diseases, such as small-pox, anthrax, and the like, in which it is possible to confer protection against the virulent disease by inoculation of the same disease in a harmless form. The importance of these observations, as harbingers of hope from the future, may perhaps not be at once apparent to the non-medical mind. It arises from the fact that natural recovery from the infective diseases arises solely in virtue of the fact that the patient becomes immune to the germ which causes the disease. Thus in pneumonia, for example, at the outset and during the course of the disease, the patient is not immune, and the causal agent (the pneumococcus) flourishes and produces its poison. But during this period many important processes, some fairly well known, but some hardly guessed at, are taking place in the blood and tissues of the patient; he is mobilising his defensive forces, and after a time these are so well developed that they are able to cope successfully with the invader, the pneumococcus is destroyed, and the patient recovers. Now it is important to realise that medical treatment is useful only in so far as it encourages the development of this acquired immunity. With a few exceptions (the most important of which is the use of quinine in malaria, in which case

the drug appears to act as a direct antiseptic, killing the germ in the blood) medical remedies have no direct action on the disease, but, by supporting the patient's strength, and in other ways, encourage the development of immunity. Where this is not produced naturally, medical treatment is useless; this is the case in leprosy, and in hydrophobia when once the disease is developed. The importance of these observations on mouse-cancer lies in the fact that they remove cancer from the class of diseases to which immunity cannot be acquired. A mouse can be immunised against cancer; may we not hope the same for man in the future? or may we not hope that the methods of vaccine-therapy, by which patients are now immunised against various diseases whilst actually suffering therefrom, may be found to be applicable in the case of cancer also, and a curative method devised by which a patient actually affected may be immuned and the disease cured? Considerations of this nature justify the very full and careful investigation which the question is receiving from the Imperial Cancer Research Fund. They have opened up entirely new avenues by which the great problem may be approached; and whilst it is easy, in view of past experiences, to be too sanguine, it really seems as though the researches on mouse-cancer may afford a clue to the labyrinth.

Bashford and others have shown that acquired immunity to mouse-cancer may be produced in many ways. It occurs after spontaneous cure of a cancer; after an unsuccessful inoculation of the disease; after the injection of red-blood corpuscles (but not of the serum) of an animal of the same species, but not of other species; after the injection of emulsions of the cells of the skin and other organs.

It would lead us too far to discuss the results of these experiments further. We may point out that they have, so far, afforded but little direct light as to the nature and cause of the disease. They are all consistent with the parasitic theory, postulating the existence of a parasite living entirely in the animal cells which it stimulates to active division, and experience of other diseases shows that the existence of a parasite of such a nature is quite possible. Indeed, some of the analogies of the mouse-cancer with infective diseases have led

some to deny that the former is cancer at all. Thus it seems certain that cages in which mice affected with cancer have been kept may harbour the disease and infect other mice, whilst the disease as it occurs in man is not believed to be infectious or contagious according to the most recent views of the best authorities. As far as structure is concerned, there is no doubt that the disease, as it affects mice, is typical cancer; some of its clinical characters may render it a little uncertain, and make us careful how we apply the recent discoveries to the human disease. On the whole, it appears probable that the mouse-cancer is a true cancer, but experience with another form of disease in the lower animals (the so-called infective sarcoma of dogs, now known not to be a malignant tumour), in which pathologists were led astray in the past, shows us the danger of accepting histological structure in the identification of malignant disease. The subject of mouse-cancer cries out for further investigation, but it is in the highest degree desirable that it should not interfere with the study of the disease as it affects man, or that laboratory work should lead to the neglect of statistical, clinical, and other researches.

The researches on cancer on the lower animals have not at present dealt at all with the actual cause of the disease, i.e. with the agent which induces the cancer-cell to start dividing. This still remains unknown. We do know, however, in a few cases, the conditions under which this unknown cause comes into operation. Of these the most important is chronic inflammation or irritation; the frequency with which cancer of the lower lip can be traced to the use of a short (and therefore hot) clay pipe is an old and well-known example. Another, and even more striking one, is the Kangri cancer, which affects the lower part of the abdomen. It is common in the inhabitants of Cashmere, and is due to their habit of carrying an earthenware pot full of burning charcoal under their robes for the sake of warmth. A good many other cases might be quoted, and chronic inflammation must be recognised as one of the most important causes of cancer. Whether it is a predisposing cause only, that is to say, whether it simply lowers the resistance of the region and allows the actual causal agent to act, or whether cells irritated for a sufficiently long period may become