tity in normal human urine, and increase very much in number in certain infectious diseases.

A third class of substances similar to, but more poisonous than, the ptomains and leucomains has also been found in the living body, and they have been called extractives.

The great source of danger from microbes is believed to be in their poisonous products. In typhoid fever, Asiatic cholera, septicæmia, diphtheria, and some other diseases of this kind, the microbes produce the poisonous alkaloids and spread the infection. In cholera morbus there is a poisonous base called methylguanidin. Four alkaloids have been isolated from the bacillus which causes tetanus; they are called tetanin, tetanotoxin, spasmotoxin, and the fourth not named.

Pasteur believes that hydrophobia is due to a microbe which produces an alkaloid. The microbe itself has not been identified, but a poisonous ptomain has been obtained from the brain of rabbits suffering from the disease, and this ptomain produces the characteristic symptoms.

The comma bacillus of Professor Koch, called so from its resemblance to a comma, is undoubtedly the agent in causing Asiatic cholera. Alkaloids also have been found in the dejections in this disease.

The bacillus typhosus is found in typhoid fever; the alkaloid, however, called typhotoxin, is believed to cause the disease. Malignant pustule, occurring especially in cattle, is due to a microbe called bacillus anthracis; the ptomain is anthracin.

Some ptomains are analogous, chemically, to certain vegetable alkaloids. Again, the same species of microbes will produce different ptomains, according to the organic substance in which they live.

Ptomains which are devoid of oxygen have a strong odor like musk, etc.; this odor is so persistent that, as previously stated, Dr. Gautier recognized it in the guano of prehistoric formation.

It is said that some microbes give rise to soluble ferments called enzymes, products of living protoplasm. Dr. Sheridan Lea has shown that the micrococcus urea secretes a ferment which converts urea into ammonium carbonate. Drs. Roux and Yersin have obtained a soluble poison from the cultivation of the bacillus diphtheriticus, which produces all the symptoms of diphtheria. It is an animal alkaloid, but a special ferment. It is proper, however, to say that the bacillus itself will cause the disease. In the case of the bacillus anthracis, the ferment produced will not cause the disease.

Pasteur has shown that if the blood of animals suffering with anthrax is filtered free from bacilli, the blood will not then cause the disease.

Drs. Lauder Brunton, and Macfadyen have shown by experiment that the microbes which liquefy gelatine do so by means of an enzyme. The enzyme can be isolated and its peptonizing action be demonstrated, apart from the microbes which produce it. For purposes of nutrition, microbes can form ferments adapted to the soil in which they grow.

The real cause of infectious diseases is, therefore, in some cases, the microbe; in others, the alkaloid or ferment, formed or secreted by the microbe. In most cases microbes produce both poisonous alkaloids and special ferments.

A few other interesting substances produced by microbes may be mentioned. The torula cerevisia or yeast plant, acting on sugar in solution, causes a fermentation which results in the production of alcohol and a residue. This is called the alcoholic fermentation. Again, the bacterium aceti produces vinegar in a pure state. The bacterium lactis acting on the sugar in milk produces lactic acid, causing the milk to become sour. All putrefaction results from the action of numberless microbes, the most important of which is the bacterium termo. The bacillus butyricus acting on butter makes it rancid; acting on cheese, causes it to ripen. The bacillus tuberculosis produces cellulose in the blood and tissues of tubercular persons, but does not produce an alkaloid.

Some microbes form pigment on the material in which they live. A few only of these are associated with disease. What is called indigo blue is produced by the action of a bacillus on indican, a substance existing in the indigo plant. This indican has also been found in human urine, especially in cases of intestinal obstruction and ulceration, and in granular kidney. The blue color of sweat is due to microbes. Many of these pigment-forming microbes are found in the air and give rise to patches of color on articles of food. The red spots which sometimes appear, especially on bread, and which in old times were supposed to be blood from the finger of an angry God, are known to be composed of groups of the micrococcus prodigiosus. Yellow milk is due to bacterium xanthinum. The blue color of litmus, used in testing acidity of fluids, is from the action of putrefactive microbes.

Some microbes acting on alkaline sulphates and organic matters in water, as in certain mineral springs, cause the freeing of the sulphur and disengagement of sulphuretted hydrogen.

Many of the lower animals have the power of making themselves phosphorescent. This luminosity is accompanied by the transition of peptones into organized living matter under the influence of free oxygen. This phosphorescence appears to depend on the action of certain microbes.

Experiments have been made to determine how great a degree of heat can be endured by them without being destroyed. The following are some of the results: The bacilli of anthrax and of swine plague were destroyed after exposure for one hour to a boiling temperature. The spores of the bacillus, however, required an exposure of four hours to the same temperature. As it is stated that none of the infectious diseases depend on the spores, it follows that their pathogenic microbes can be destroyed at a temperature of boiling point for one hour. Steam heat will destroy them and their spores in a little over five minutes.

On the other hand, many microbes will withstand a temperature of 90° F. without losing vitality, if the air is dry. Tubercle bacilli after being dried for three or four months may still be alive. Other microbes have been known to endure a tropical temperature in dry air for as much as three years. This endurance of heat and dryness is comparable to that of some of the lower animals. For instance, the anguillula has been found alive after two years desiccation ; rotifers after four years, and some eel-worms after 30 years. ability to endure cold has already been mentioned.

The

The action of electricity on microbes has been very little studied. Experiments show that the electric current is detrimental, and it is known that after a thunder-storm the microbes in the air are fewer than at any other time. Light is beneficial to some, detrimental to others. The same as to gases. Microbes which require free oxygen are called aërobic; the others anaërobic; but all require oxygen in some form. Compressed oxygen diminishes or destroys their vitality.

The condition of not being susceptible to infectious disease is called immunity. It is either natural or acquired. Some microbes will produce disease in some animals and not in others. The bacilli of anthrax will cause the disease in sheep and in man, but not in cats, dogs, or pigs. The bacillus of septicemia, or what is commonly called blood-poisoning, will produce the disease in housemice, but not in field-mice. These are cases of natural immunity. The acquired form is shown when an animal has an infectious disease, recovers, and then for a longer or shorter time it is not sus

ceptible to another attack. The theory is that the microbes have consumed some element in the body which is essential to their growth and development. The body is, therefore, unfit to sustain a second crop, the soil is exhausted; and until this absent condition is restored the body is protected against another seizure of the disease.

Again, this constituent may be exhausted by a microbe which is less vigorous and destructive than the one which causes the disease, and, if this is done, then the introduction of the more vigorous one will fail to find anything to grow upon, and the individual is thus protected. This is the explanation of vaccination. The attenuated virus is a protection against the more poisonous virus.

This theory of exhaustion, as it is called, does not explain all the facts in the case; and the antidote theory of Klebs explains them more fully. His theory supposes that the microbes produce a substance which is poisonous to themselves in case they should reënter the same person at a subsequent time. There is some direct evidence in support of this theory.

The acquired form of immunity may be subdivided into that of acclimatization and that of inoculation.

People of tropical climates are less susceptible to the malarial fevers, etc., of their country than are strangers. This is acclimatization.

Vaccination, or protective inoculation, is the introduction into the system of a milder or weaker virus than that which produces the disease. In this way it is a protective in small-pox, yellow fever, splenic fever, chicken cholera, hydrophobia, swine fever, cattle plague, acute septicemia, etc. There is no such protection, however, in such diseases as tuberculosis, pneumonia, erysipelas, malarial fever, relapsing fever, and breakbone fever. I have included tuberculosis here because I do not think, as yet, the inoculation of tuberculin, the modified virus of tuberculosis, has been proved to be a protection against the disease. In erysipelas, pneumonia, etc., one attack of the disease, so far from being protective against another, appears to increase the susceptibility.

The proportion of deaths from small-pox in 1,000 deaths from all causes is one-twentieth now what it was before vaccination was introduced. Deaths from splenic fever are one-twenty-fourth what they were before inoculation of the attenuated virus was practiced, and in hydrophobia, one-twenty-third. Some work has been done. in inoculating against diphtheria.

I must pass over the discussion of how this milder virus is obtained and say something about germicides or microbe-destroyers; also called necrophytes. Two expressions are used in this connection which need to be explained. The word antiseptic is used, meaning against poison. Anything that retards or prevents the development of a poison is antiseptic. The same substance, if used in sufficient strength, may become an actual destroyer of germs. This we call a germicide.

There are many chemical agents which are antiseptic and germicidal. It would be very desirable, so far as microbe diseases are concerned, to be able to introduce into an animal, its blood, etc., this destructive chemical agent. The difficulty, however, is to use such germicide in sufficient strength to destroy the microbe and yet not injure the patient. It would be the height of therapeutic success if we could inject into the blood by means of a hypodermic syringe a little appropriate fluid and so stop the progress or prevent the development of an infectious disease-say, typhoid fever-by killing the microbes; or when the disease is caused by a poisonous alkaloid or special ferment, it would be desirable to neutralize these by some chemical agent and thus abort the disease. The destruction of the microbes in the first instance would, of course, prevent the formation of the alkaloids or ferments. I mention only a few of the more prominent of these microbe-destroyers.

The salts of mercury, especially the mercuric chloride or corrosive sublimate. A solution of this salt, one part in 1,000 to 5,000 of water, will destroy the most resisting organism in a few minutes. There is a difference of opinion as to whether such solution will destroy the spores, although the weight of evidence seems to favor the opinion that it will. This salt has been and is still very extensively used in surgery, midwifery, and ophthalmia of the new-born. Iodine is a germicide and has been used hypodermically in splenic fever. In consumption also it has been used to diminish the number of bacilli and prevent the formation of spores, though its inhalation causes irritation and cough.

Sodium chloride, common table salt, is said to destroy the comma or cholera bacilli, but the microbes of typhoid fever, tubercle, cattle plague, etc., may remain in common salt for months without losing the power of growth and reproduction. The salting of meats, therefore, may be ineffectual in preventing the development of pathogenic microbes.

Sulphuretted hydrogen destroys the bacillus tuberculosis and is