Although all the vital processes which take place in the body are in a great measure co-operative and interdependent, that of metabolism, with its indispensable function of elimination is conspicuous in its importance. The property of casting off unabsorbable materials and the chemical substances resulting from digestive processes is one which all living things possess. It is observed in the most primitive forms of animal and plant life, and the process becomes more and more complex as we ascend in the scale of creatures, attaining its greatest intricacy in the human body. Unicellular animals exhibit biological phenomena in their simplest form, but as yet we are unable to explain the features we may observe - the changes which take place in the cytoplasm, the chemical and dynamic forces which perpetuate cell life, the substances cast off as the result of food assimilation or the environmental changes which the organism induces by its existence. But although we cannot examine protoplasm chemically and thus interpret movements and process which may be seen, we are able to study the excreta from the tissues of higher animal forms, and determine by experiment their physical and physiological properties.

Wherever there are living things the process of appropriating food from the environment, assimilating a part of it and casting off the residue constantly goes on. Through the microscope we may see the slowly moving amoeba surround food masses, retain them for a time, and then cast them off as containing no further nutriment. This residue contains more than indigestible refuse, there is also metamorphosed food material. If fish are confined in a limited space with no egress for their waste products they soon die, even if their food is yet unconsumed. If animals or human beings are likewise confined, and no provision is made for the admission of fresh air, they too die and with symptoms of narcotic poisoning. Air once breathed is poisonous and the organism is killed by that which is cast off from its own lungs. If bacteria are cultivated in nutrient media their multiplication continues until a time when their growth ceases, even if there remains a surplus of nutriment. The media are found to contain a substance which is unfavorable to the growth of germs which is clearly the result of the metamorphosis of the nutrient media by the bacteria. They too cast off a substance which is harmful to themselves. If the kidneys, through destructive processes in their substance or obstruction of their efferent ducts are unable to perform their eliminative functions, the animal soon dies, and with clinical phenomena which are fairly constant in different animals. If obstruction of the bowel lumen occurs and an organism is unable to eliminate fecal residues, poisonous symptoms soon ensue and unless the condition be relieved they terminate in death. In the tissues, if waste materials are retained too long, cellular death and lesions result, for if a cell is not separated from the products of its metabolism its life cannot continue. For example, if the ducts of the pancreas become occluded and its specific secretion finds no outlet, pancreatitis and necrosis is likely to occur. These facts are illustrative of a biological truth, that the end-products of metabolism are harmful to the organism from which they proceed, and to the resulting phenomena the appropriate name of auto-intoxication or self-poisoning has been given.

The variety of definitions given for this state is a testimony to the difficulty of obtaining one terse yet comprehensive. It is "the poisoning of an organism by matter produced within itself" to be sure, but this is too broad a conception since the toxins of all infectious diseases are produced within the organism, yet the toxemia of tuberculosis, diphtheria, or tetanus, cannot properly be classified as intrinsic. It is also "that form of self-poisoning in which neither wound nor gross pathological lesions exist, but poisons elaborated within the system are not excreted with proper activity, and the system at large is injured." This is open to the objection that it implies that these poisons are pathological products, while some of them are produced normally. One might coin a definition: Autointoxication is the poisoning of an organism by the retention of its metabolism end-products which normally are excreted; but this too is incomplete since it does not include, as it should, those poisons elaborated in deranged functions. Intestinal fermentation and putrefaction are not normal, constipation is not physiological, and the retention of bile from duct stenosis is distinctly pathological, so it is evident that other than normal excretions are concerned. For it is impossible to conceive any perversion of function without variation in the specific product of such function, and the greater the departure from the normal, the more abnormal do the excreta become, and, as we shall see, the more poisonous. So we must add to our coined definition that these materials are of two kinds, those that are regularly formed in the system, and those formed in abnormal states where there is perverted or disordered function.

There is a tendency with many writers to include all the specific infectious diseases in the class of auto-genetic disorders, a thing which, to the writer's mind, extends its scope far beyond its proper boundaries. The conception of the prefix "auto" should be that of inherent or intrinsic substances - those which originate in or are elaborated within the system. In diphtheria, for example, we have a poison elaborated within the body, but in no way related to it, as truly extrinsic as would be any poison administered by another individual. In death from this disease the toxin kills, as would a drug, through its effect upon vital nerves, the anatomical structures of which are visibly changed, and not through a true self-poisoning. The principals of auto-intoxication may apply in the case, affecting the course of the disease, and failure of the emunctories may be an important factor in dissolution, yet it is not within the scope of the subject according to our accepted definition. Non-pathogenic bacteria, upon whose action so many of the factors of auto-intoxication depend, are to be found normally in the alimentary tract, which is not true of pathogenic species. To more completely explain this important difference we may compare mussel poisoning with intestinal putrefaction in which poisonous diamins are formed in the intestinal lumen. In the former, the mussel contains a preformed poison when ingested, and it will cause symptoms shortly after ingestion as would a drug. On the other hand, if a normal and - innocuous food remains in the intestinal tract for any length of time, it is to be expected that it would be wrought upon by the intestinal bacteria, its nucleins become metamorphosed and harmful substances liberated from them. Thus protesting against too broad an application of the term we must add that this subject is often confused with auto-infection.

Here a person adds another focus of germ infection to those already existing. A patient with typhoid fever may inflict wounds upon himself while in delirium and these abrasions, being infected from his nails, may become abscesses or pustules. A convalescent typhoid may become reinfected through his urine which may contain the bacillus in pure culture, illustrating also the importance of urinary disinfection. Gonorrheal ophthalmia may be transplanted from the genital focus, or a patient with pulmonary tuberculosis may swallow the sputum and in this way infect the alimentary tract, producing tuberculosis of the intestine and peritoneum.

Whenever any function of the human organism fails in its specific action, organic equilibrium is disturbed in a measure proportionate to such failure; and this disturbance is transient if compensation is established by increased action of other organs, permanent if they fail to perform this added duty or if there is actual destruction of tissue. This is particularly true of those organs of the body concerned in the elimination of the excreta, the retention of which causes poisoning.

Intoxications manifest themselves in a great variety of ways, according to the toxic power of the substance itself, its degree of concentration, the part of the body with which it is brought in contact, and the susceptibility of the individual. This susceptibility may be some pre-existing lesion or anatomical anomaly, it may be mental instability from heredity, the precise philosophy of which we do not know, or it may be a group of factors into which enter the diet, habits and personality of the individual. Or the predisposition may itself be the result of a morbid process and it may only remain for the added influence of another force to precipitate or develop its activity. For a substance may require combination with another before its toxic powers may be developed, and materials may circulate in the system without injury, causing cellular damage only when brought into contact with some particular part or its emanations. For example, when normal bile comes in contact with the tissue of the pancreas marked necrotic changes result; and when peptones and albumoses are introduced into the blood stream they induce cytolysis and other hemic changes.

The investigation of a large number of cases of auto-intoxication shows that no clinical symptoms may result until the cells of a part have been under the influence of autogenous poisons for a long time, and in this we find a resemblance to disease in general, for it is a well-known truth that pathological conditions may progress for some time without pain or subjective symptoms unless there is irritation of some sensory nerve. And unless the toxic agencies at work are of the major grade of poisons there may be but few manifestations or perhaps none, until the degree of concen tration is great enough for cumulative action. The intrinsic poisons of the body spend their force chiefly upon the nervous and circulatory systems as will be shown in Part II.

A disease may both cause auto-intoxication and be caused by it. We know that nephritis may be caused by endogenous as well as exogenous poisons circulating in the blood stream, and with this nephritis comes decreased functional power and failure of elimination proportional to such loss. This necessarily produces intoxication whenever accumulation becomes great enough to produce toxemia. Gastric dilitation is increased by the fermentation which its original dependency occasions, and the effect of auto-toxins upon the mind predisposes to errors of judgment and dietary indiscretions which promote the continuance of the underlying cause. We have reason to believe that cirrhosis of the liver is caused by intrinsic systemic poisons and from the peculiarly important place this organ occupies in the animal economy any failure in its activity predisposes to the elaboration of intestinal auto-toxins.

The autogenous, like other poisons may cause marked and severe symptoms lasting for a short time and be acute, or they may be insidious in their action, endure for a longer time and become chronic. It is to be regretted that there are so few studies as to the experimental administration for extended periods of time, of substances known to cause self-poisoning, and until such investigations are made we shall not know to what extent they enter into the etiology of chronic conditions, a matter clinically of equal importance with the acute.

The most convincing arguments in the study of endogenous poisons are analagous to those which Koch formulated in his celebrated studies of the bacteria. The substance is first found associated with a diseased state, it is next administered to a healthy organism and produces a state similar to that from which it was derived, and lastly it is obtained from the individual experimented upon. Such cogent reasoning is almost direct proof, and in a great many cases of experiment with metabolic end-products all of these stipulations are satisfied. For example, indol, which is representative of a class of sub-oxidation bodies, has been found in the urine and feces of persons suffering with nervous disorders of a neurasthenic nature; experimental poisonings with indol produces similar symptoms and the material may be recovered from the individual experimented upon. In the same way it is found that the administration of uric acid will produce migrim, and that following an attack the alkalinity of the blood is lessened and the urine contains this acid in increased amount. And so the scientific aspect of this subject is built not upon conjecture but upon actual experiment and conclusions reasonably drawn from such investigations.