Search

In order to explain satisfactorily the basic features of cancer a theoretical cause of cancer should be endowed with the following fundamental properties: (1) It should exhibit an affinity for cells and induce them to grow while multiplying along with them. (2) It should be specific for cells so that the same lesion is repeated, yet able to change so that many different lesions are produced. (3) It should be able to remain in a latent state in tissues and be conditioned by genetic and surrounding conditions such as those attending old age. (4) It should be capable of existing either in a free or in an occult state. Viruses fulfill all these requirements. Nevertheless the so-called virus or infectious theory of cancer is not at all popular, most workers favoring endogenous theories. Arguments for and against these doctrines are reviewed, especially those centering on comparisons between bacterial virulence and cell malignancy and the nature of the principles changing bacterial types. The most important argument supporting the virus theory is the undeniable fact that a number of cancers are induced by viruses, of which the most interesting in some respects are those of avian cancer. By studying the phenomena attending the infection of chickens from embryonal life to old age the conclusion is reached that these viruses do not differ fundamentally from ordinary viruses, for in the immature host they induce necrosis instead of neoplasia, and in the cancers they cause in older hosts the virus undergoes a process of degradation manifested first by a depression of the malignancy of the tumor (as indicated by transplantability by cells and metastasis formation) and later by unfilterability of the tumor, that is, masking of the virus. Simultaneously with these events the virus may vary in many forms which cause as many different tumors, as shown when foreign species are infected. These phenomena are discussed in relation, first, to the possible existence in cancers of "unknown etiology" of causative degraded viruses which cannot be demonstrated by ordinary means, and second, to tumor regression. The degraded, masked virus reverts to a vigorous, free form by grafting the tumor into young hosts. This fact together with newer knowledge on contagious lymphomatosis is discussed in relation to the mode of spread of chicken tumors. What has been learned about avian cancer and other types of virus cancer leads to an important question, namely, whether ordinary viruses are capable of inducing cancer under certain conditions. This possibility is discussed and an experimental plan of attack is outlined.

SummarySterile, non-lethal ultrafiltrates of strangulation fluids from humans, dogs, and rats promoted a rapid, lethal E. coli infection in healthy mice by fewer bacteria than was possible with saline suspensions of the same organisms. Cl. welchii and Cl. sordelli, similarly suspended, killed only a small proportion of test mice. Sublethal dosages of several substances that might contribute to the virulence-enhancing activity of strangulation fluids were also studied: E. coli endotoxin enhanced the virulence of Cl. sordelli and E. coli; Cl. welchii exotoxin enhanced only E. coli; bile and mucin enhanced all 3 test microorganisms. Synergism between bacteria of one species and products of another may contribute to the severity of mixed bacterial infections. The identity of the factor in strangulation fluids is unknown. There is as yet no evidence of a role for a bacterial virulence-enhancing factor in the pathophysiology of strangulation intestinal obstruction.

In connection with recent investigations on the spread of bacterial infection among mice, the possible effect of variations in the virulence of the infecting organism has, inevitably, formed one of the problems for study.

ONE of the questions, to which the experimental study of epidemics has as yet given no decisive answer, is the possible significance of variations in bacterial virulence. The experiments here recorded relate to this problem, in the particular case of mouse-typhoid spreading within a closed community. Webster and his co-workers (Webster, 1923, a, b, c, d; 1924, a, b; Webster and Pritchett, 1924) would regard the virulence of any single strain of Bact. aertrycke, the causal organism concerned, as but little variable. While admitting (Webster and Burn, 1928, a, b, c) that variations in virulence may occur in bacteria belonging to this group under the influence of a bacteriophage, they consider that any single strain maintains a constant level of virulence for an indefinite period of time, under any of the usual methods of cultivation, and that variations in virulence are difficult, if not impossible, to induce by any of the methods usually adopted. In particular, they believe that such variations play no significant part in the epidemic spread of disease. Our own experiments, and those of our colleagues (Lockhart, 1926), many of which have not yet been recorded, have convinced us that Bact. aertrycke, when cultivated in the laboratory under various conditions, varies in virulence to a greater degree, and more frequently, than Webster and his colleagues suppose; although our own experience is in accord with theirs, in so far as we have found that a single strain, maintained by massive subculture in a solid medium, and at infrequent intervals, usually maintains its virulence unaltered over months or years. This aspect of the problem will, however, be dealt with more fully in subsequent reports. The present series of experiments is concerned with the epidemic behaviour of strains of appreciably different virulence. With regard to the origin of these strains, we would merely note that they are all derived from strains isolated during the course of the experimental epidemics which we have studied during the past 10 years, and are, so far as we can tell, descendants of the original strain with which we started. Their after-history, as regards the time during which they have been maintained in subculture, and the

Bacteriologists are not in a position to disregard the limitations recognised by the physiologists. Precise data which are not available from experiments are far from sufficient to explain the properties of living matter; they must be supplemented by vaguer conceptions about the functions of a cell, its internal organisation and its susceptibility to stimulative or inhibitory agencies—conceptions which cannot yet be translated into recognised chemical substances and physical properties. One must therefore start by recognising that bacterial virulence, being dependent on vital processes, cannot be fully explained in chemico-physical terms.

The course of development of lesions in pulmonary tuberculosis varies, depending on the nature of infiltration and the position of the affected lung field. As a rule, the prognosis of the disease is influenced by such conditions as individual resistance, the bacterial virulence and the number of bacilli in the infection; but in some cases with a certain type and/or situation of infiltration, the infection is destined to get worse in spite of any other various individual conditions. One such case is that in which the lesion is in the upper left lung field.Apical lesions ordinarily have good prognosis, but a cavity in the apical field makes the lesion take a turn for the worse. The upper left location of the lesion is more serious than cavitation of the infiltration; that is, the upper left lesion will not only have poor prognosis, even if it has no cavity, but will also exert influence on the course of the lesion in the opposite right field if such exists. Generally, cases with TBB-positive sputum in culture show a tendency to worsen more than those with negative sputum; and the TBB-positive sputum is found most frequently in upper-left lesion cases and left cavity cases. Consequently, patients of left infiltration type with cavity and with bacilli-positive sputum will be most poor in prognosis. Cases in which sputum is found to be TBB-positive in smear tests are more serious than those in which the positive occurs only in culture tests. However, the occurence of cavity or concormitant lesion is of more serious import than bacillary findings, as factors related to prognosis of the disease. In particular these factors seriously affect the course of the left apical lesion; and it has been found that smear findings themselves are closely related with the presence of cavity in the lesion. As to haemoptysis, its seriousness depends on the stage in the clinical course in which it occurs. Haemoptysis, after chemotherapy has been applied to some degree, is a bad sign. When haemoptysis occurs in the middle and late stages of cases with left cavity, such cases will become more serious in the long run.

The source of bacterial contamination leading to infection of clean operative wounds has long been a point of discussion among surgeons. Although many possible sources of contamination have been identified, the significance of each has been difficult to assess because of a wide variability in host resistance and bacterial virulence. The epidemiology of this problem has been under study in our laboratories for several years. These studies have shown that organisms which cause infections in clean operative wounds are seldom found in the air of the operating room1or in the noses and throats of personnel. Relatively small numbers of these organisms ordinarily gain access to clean surgical wounds through the air providing the operating room is relatively clean and accepted masking techniques are used.2These bacteria, however, are found in large numbers in the hospitalized patients who harbor an established infection1and in an occasional carrier.

emerges from a study of infections with gramnegative bacteria is that whether such bacteria can grow in a host and therefore appear virulent depends, in the final analysis, on whether they can be phagocytosed and killed by the cells of the host. The ultimate and decisive event that signals the beginning of the end for bacteria is phagocytosis and for this to happen efficiently and rapidly requires the presence of specific antibody, which may be free or bound to the surfaces of the cells. This seems to be acceptable as true whether one espouses the cause of humoral immunity or that of cell-mediated immunity or even if one takes the more reasonable compromise view, that both humoral and cellular elements are inseparably involved. The fact that living attenuated bacteria are more efficient promoters of an increased state of resistance to many bacterial infections should not alter this belief in the fundamental importance of phagocytosis. Indeed, it is now clear that the in