It is not so long ago that the germ theory of disease was promulgated, or rather that particular group of microscopic germs known as Bacteria. The discoveries of Louis Pasteur and Robert Koch which led them to associate such disease processes as Cholera, Tuberculosis, Anthrax in animals, Typhoid Fever and Pneumonia with definite plant organisms brought with them the thought that by the use of powerful chemical poisons these organisms could be destroyed in the body and so the disease arrested. The effort was made to introduce germicides and antiseptics into the wounds and render the germs incapable of growth. This was the beginning of antiseptic surgery. It led surgeons to operate without fear on internal organs, on the brain. Then came other experiments to show that the germs themselves created poisons or antipoisons, and the antipoisons or antitoxins were more effective in destroying or neutralizing the germ poisons than the most powerful drugs. Thus we discovered the Antitoxin of Diphtheria which according to the most careful investigators has reduced the mortality from this disease greatly.

Later researches show that the cells of the body can be educated to throw off some poisons or sensitized to others by the use of vaccines, especially prepared poisons from cultures of the disease germs themselves, and some very wonderful results have been obtained in the treatment of boils and abscesses and other pus diseases, using gradually increased doses of the products of the very bacteria that cause the malady. In Malaria, Yellow Fever, Sleeping sickness of Africa and Syphilis, the greatest plague of civilization, we find a different causative agent. Here the organism is of an animal nature, very minute but like the larger parasites, like the Tape Worm and Ameba it undergoes a transformation in the body or requires an intermediate host like that of the mosquito or Tsetse fly, and only after a certain period of development causes a poisoning of the entire system of the individual finally attacked. A mosquito may bite a yellow fever or malarial patient and take into its body the parasites which there undergo changes and finally ripen and a person so bitten is liable to contract the disease. But another species of mosquito will not convey the organism, nor will the disease be transmitted to one person from another without the intervention of the mosquito. There is something in a certain species of insect which is required to complete the chain to make the organism active.

For years Quinine was given in Malaria without knowing why. The natives of South America used the Peruvian Bark or Cinchona tree bark against the chills and ague and when malaria first appeared in Europe, the remedy went with it. We now know that Quinine, the active principal of Cinchona, has a poisoning action on the parasites that cause malaria and if given at a time when they are present in

the blood it can destroy or so paralyze the germs that the healthy blood cells can resist their further advance. Acting in the same line Arsenic was found effective in the Sleeping Sickness against the Trypanosomes of that disease but the arsenic had to be given at certain times and in large doses. In experimenting with different drugs to find one sufficiently potent, Ehrlich, a German plodder of the most patient kind, has now opened up a new philosophy in the treatment of disease and it holds out endless hopes and creates countless speculations. For thirty years this German has gone on theorizing and experimenting, discovering hundreds of by-products, some very useful and others of no value, and working on to secure a drug so powerful that it would quickly annihilate the parasites and not harm the body. This substance must in some way have an attraction for the germ so as to anchor it or fix it somehow as a fly is fixed on sticky paper, and yet not affect the body cells. Of the thousands of preparations tried especially in the disease known as Sleeping Sickness, the most active ones were found in three groups, the Arsenicals, the Azo dyestuffs and the Triphenol dyestuffs, many of these belonging to what is known as the Aniline dyes, out of which have come so many valuable chemicals. Animal experiments were conducted on a large scale. The Trypanosomes that cause the Sleeping Sickness kill mice in three days. It was found that several arsenic and aniline combinations affected the parasites when the drug was given internally but did not kill them outside of the body so by further research a drug was found identical with the ones as it appeared in the body and this one was powerfully active in the test tube as well as by mouth. A new fact was now noticed, that if small doses of the new drug were given, not enough to free the animal entirely from the parasites, the parasites became immune and could not be affected by doses large enough to kill the animal itself. And this particular immune breed of germs would remain so though propagated through 300 normal animals, and for a year or more. This means that unless the dose was sufficiently large to kill all the germs at short notice, it would be impossible to act on those that remained and they would eventually triumph. The researches were then continued to find a still more powerful agent so as to act on those that resisted. Arsacetin was the name given to the other chemical; finally Salvarsan, the 606th drug tried, seemed to fulfill most of the indications powerful enough to destroy the parasites in one or two doses and yet not affect the body seriously. But it is not so much in the sleeping sickness as in Syphilis, a highly infectious disease due to a similar parasite, that this chemical or group of chemicals have come to be employed. Syphilis is a disease spread by one person to another in numberless ways, as a rule it is attributed to an immoral

life, but once contracted, the virtuous and innocent are continuously menaced by the person affected. Thousands of children come into the world with it, thousands of women through marriage are the innocent victims of their husbands' carelessness. The dentist and the doctor are frequently infected by patients. The common drinking cup, the habit of using another's pipe, promiscuous kissing on the lips where the early symptons of the disease are often found are some of the not unusual ways the disease is spread. The disease is a most terrible one in many instances, for not only does it produce severe and lasting deformities in the flesh and bones, but it injures the nervous system, leading later on to Locomotor Ataxia, Paresis and Insanity. Many cases are curable if promptly seen, carefully treated and the patient gives himself over entirely to the treatment which is never much less than three years. Thus if a remedy could be found that would permanently destroy the parasites of syphilis in one dose, destroy them so as to prevent their dangerous action on the nervous system it would be one of the greatest achievements of modern medicine. Before anything was promised and first after numerous animal experiments were made to prove the drug potent and not dangerous, Ehrlich distributed among the noted surgeons of the world about 40,000 doses-two physicians being the first to have the drug tried on themselves. These doses were tried on the acutely affected persons and those chronically ill as a result of the disease, and soon glowing reports were obtained everywhere as to the wonderful action of this chemical in curing sores and symptons in a few days that under other treatment required months to heal. Thousands of cases have now been treated with Salvarsan, 14,000 up to last year. Within two years over 1000 original articles have been published in medical literature besides a large number of reports on this one drug. There have been some deaths among the number treated, there have also been many among those untreated. The enthusiasm over this new method is not so great as it first was because there are relapses and the older remedies must be called upon to help out, but while the whole subject is still on trial, the achievement so far is miraculous.

The same sort of treatment is being taken up with other diseases and no doubt we may yet expect some potent chemical to overcome the toxin of Tuberculosis.

The prevention of disease is always of more importance than the cure. And the education of the public, or children even, that there are such diseases and that such diseases can be prevented by proper care of the afflicted and by living in accordance with the best knowledge on the subject, this, though apparently a slow and thankless task will in the end achieve more than the attempts to cure the countless victims.

The treatment by this new remedy can only be carried out successfully in connection with laboratory tests of the blood for the purpose of establishing whether or not the parasites are active and also to control the treatment. The laboratory test is a very delicate and complex one and very few persons are sufficiently equipped to undertake it. Some charlatans in order to impose on the credulous and suffering claimed to use the remedy almost before it had been placed on the market.

Salvarsan is chemically,

Dioxy-diamido-arseno-benzene-dihydrochloride.

It contains about 34 per cent. arsenic-the ordinary arsenious acid contains 75 per cent. The fatal dose of arsenic is about 2 grains, medical dose 1-30 to 1-5. The fatal dose of Salvarsan is 150 grains, the average dose 9 grains. Sodium Cacodilyate contains 30 per cent. arsenic; 10 grains failed to kill a rabbit. Thus the toxic properties depend on the solubility and fixing power with cells. We may probably expect further advances along this line, i. e. to find drugs that enter into combinations with the cells of plants and animals so that they are unable to fix themselves to the blood cells and tissue cells of the body and unable to resist the destructive action of the body juices or natural resistance growers.

An interesting phenomenon noticed in experimenting with serums is that serums instead of causing immunity cause an increased sensitiveness to a second dose. This has been called Anaphylaxis or the opposite of prophylaxis. Some diseases there are that render the body more susceptible to a second attack although there are many diseases that do the opposite, one attack conferring immunity from a second. In the experiments with drugs this discovery will be taken account of. We often say that the drugs have lost their effect, the body tolerates larger quantities, in the first case the disease germs have developed protecting cells and are no longer sensitive to the same strength of drug and in the second place the body has developed a tolerance or immunity and is less sensitive. Other drugs make the body more sensitive after a time. There is what was formerly called

an accumulative action but what may come to be explained by this increased sensitiveness, amounting in some instances to actual poisoning.

Thus we have germ products that tend to make the body safe against an attack of disease, like vaccine of cow-pox against smallpox, typhoid vaccine against typhoid fever. We have the antitoxins to neutralize the direct poison like the diphtheria. We have the other vaccines that aim to stimulate the activity of the protecting body cells so that they will overcome the germs themselves when present, and lastly we have drugs, in themselves powerful poisons, to paralyze or destroy the animal parasites after they have gained entrance into the body. The action of many of these products is still purely experimental. The position of Salvarsan like that of Tuberculin is by no means established, but the union of chemistry with Biology is a great advance in treatment. The Bacteriologist is no longer a mere Botanist. He must have a profound knowledge of the highest and most complex forms of chemistry. It is not sufficient to know that a certain germ is a poison or that a certain drug is a poison, but we are wanting to know how it attacks the cells, how it fixes itself and hinders or destroys life. Much patient research is still called for. Many isolated facts are known and we believe we stand a little nearer to the great mystery of life than did our forefathers.

Reforestration in Pennsylvania.

By J. H. West

Certain localities produce a certain kind of trees and some of the other varieties will not thrive in those localities. Canada producing a luxuriance of Coniferous trees has a very small amount of Oak which for some reason does not thrive there. Sections to the south and west produce some varieties to the exclusion of others. But such is not the case with Pennsylvania. Like the mother of a large family whose instinctive ways and means for the protection, sustenance and comfort of her flock are without number and limit, so our state is almost without limit in her adaptation for nurturing a great variety of trees.

With her ear at the wavelets of the Great Lakes, and her feet at the brink of the Atlantic in the Chesapeake Bay she has, as her right, the edge of the Mississippi Valley region, at her left the Piedmont region and within these four extremities is contained the thoracic section of the Appalachian Mountain system.

There is not a feature of North Temperate Zone climate that is not found in some part of Penna., and this may be in some measure responsible for the great variety of trees that flourish in the State.