B

EFORE going into the thera

peutic indications for the use of radium in internal medicine

I believe it will be useful to know something about the element itself.

Radium was discovered because of the search by chemists and physicists for a metal or element which would have somewhat the same qualities as the roentgen ray. The roentgen ray was discovered in 1894, and its fluorescent qualities led chemists to believe that there must be some metal that also possessed these fluorescent qualities. It was not long before uranium was isolated in sufficient quantity to show that it contained this substance. A little later a substance known as polonium was isolated by Madame Curie and was named for her native country, Poland. Later it was found that this was only a decay element of radium itself.

Radium was isolated in 1899 by the Curies. What is radium? In itself it has a quality of constantly giving off particles. It decays at a certain rate and in this decay transmutes itself into other elements. One of these elements is the gas helium. The very end-substance of its spontaneous disintegration is a substance which has the chemical and physical qualities of

Read before the American Congress on Internal Medicine, St. Louis, Mo., February 18 to 23, 1924.

lead. From these facts one can see how the discovery of radium upset the chemical and physical world.

The use of radium in medicine dates from the time that Becquerel carried some radium in his vest pocket, and was cautioned by one of his assistants that it might be dangerous. He scoffed at the idea and carried it for a day. A week later a burn appeared on his abdomen, and this incident has gone down in history as the "Becquerel Burn." It was not long before many undertook to see just what physiological effects radium would have, and it was first used in the treatment of disease in 1904.

Radium may be considered as stored up energy. It is the most energized agent we know. When we consider that a gram of radium contains enough energy to lift the largest battleship belonging to the United States Navy out of the water, provided the energy might be liberated at once, we get some idea of its power. This energy cannot be liberated at once, however, by any known method. The half decay period of radium is measured as lasting 1730 years, and the life period is estimated to be millions of years.

The radium atom is not at all stable. It is always breaking up into these other substances, the first of which is radium emanation. Emanation

must be considered a gas. It is composed of alpha, beta and gamma rays. The alpha rays are the first product of the process of decay. They are exceedingly short-lived and they have very little power. They have very little penetration, but they constitute most of the rays. The beta rays are the exceedingly powerful rays of radium and they travel at an enormous rate of speed. We must consider all the energy being distributed by the alpha, beta and gamma rays. The alpha are composed of positively charged helium atoms, the beta of negative, and the gamma are supposed to be nothing else than vibrations caused by the speed of motion of the beta rays. It is estimated that the hard beta rays, the very short ones of radium, travel at a speed equivalent to that of light. In order for the Xray to produce a ray of equivalent rate and speed it would be necessary to construct an apparatus of 2,000,000 volts and a spark gap of 16 feet. Of course, these represent only a small quantity of rays given off from any quantity of radium. The others range from the shortest to the longest beta rays.

Of course, the biologic effects of radium were studied almost as soon as the chemical ones. Take those that apply to medical science. One of the first attempts made was to find out if it had a bactericidal action. In cultures it has. However, in vivo, in case we try to make a practical application, we know that long before the bacteria are destroyed the normal tissue harboring them will be destroyed. For instance, a tuberculous sinus will show a favorable influence if exposed to radium. This favorable

effect is supposed to be due more to the influence of the radium upon the tissues than upon the infecting organism. We know that plant seeds exposed to radium for a given length of time will not grow, and embryos of chickens exposed to radium do not develop at all, or develop abnormally. This has a practical application in medicine, because germinal cells are more susceptible to radium than mature cells.

One of the most important effects is that upon the blood. When it is first exposed to radium we get a leucocytosis. This is followed, if the exposure has been at all excessive, by a leucopenia, and this is what radium workers guard against. People working in radium laboratories should have examinations every three months to find out if blood changes are present. The radium effect upon the red blood cells is interesting, for frequently we find an increase in the red cells and hemoglobin.

How can radium be administered in internal medicine? From these rough. biologic facts you can at once see a number of diseases in which it can be used. There is scarcely any disease in which it has not been tried. It is such a fascinating element, such a magical element, that it has been used in practically every condition, whether indicated or not. The method of administration is very simple. It can be given in any number of ways. We have it in salts, soluble and insoluble. The soluble salt is given by mouth or intravenously. We have the radium gas which is soluble, so it can be taken by mouth or patients can breathe it in "inhalatoriums." The gas has also been given intravenously.

When we come to dosage this has been worked out by innumerable experiments upon animals and patients alike. After it was shown that the health-giving springs of Europe and other countries contained radium their beneficial qualities were ascribed to radium; however, the radium content is so small in amount in these springs that it is inconceivable that any qualities these waters possess might be due to radium. Most of the springs contain from 1 to 30 millicuries of radium per 1,000,000 liters of water. Definite therapeutic effects from radium can be obtained only by giving many thousand times greater doses than are contained in these springs. The daily dose of the soluble radium salts is 4 to 8 micrograms daily. Intravenously, 10 to 100 micrograms are dissolved in 2 cc. of normal salt solution and injections are given seven to ten days apart until 300 micrograms have been given. Emanations, 1.5 to 2 millicuries to the liter of water are given in daily doses of 250 cc. By inhalation, 0.005 to 0.3 microcuries per liter of air are circulated through the inhalatorium. Treatments are usually of one hour's duration. The effects of treatment are usually the same, no matter what method is used.

When rats are injected with large doses of radium or given such by mouth they invariably die. The postmortem findings show fatty degeneration of the liver and fatty degeneration of the kidney cells, with degeneration of the bone marrow. Hemorrhages are commonly found, no matter how radium is administered.

In the human being where do we find the radium distributed? In the bones, the liver, blood vessels and

spleen. It has been recovered from these tissues in cancer cases treated by exceedingly large doses of radium. The interesting fact is that the tumor tissue contains no more radium than the normal tissue. It is found most frequently in the bones, then the liver, along the blood vessels and the spleen, in the order named.

Radium given by mouth is mostly excreted by the intestines, some by the kidneys. When breathed in, it is eliminated by the lungs and partly in the urine. in the urine. Gas acts much more rapidly than the element. Gas acts in four hours, the others in about eight to ten days. When it is taken by mouth 25 to 35 per cent remains in the body for four or five days; intravenously, 55 to 65 per cent remains. If you wish to maintain 50 micrograms in the body, give an injection of about 50 micrograms intravenously, and after ten days give 2 micrograms by mouth every few days.

The general physiological effects reported from the use of radium are quite amusing because, depending upon the enthusiasm of the therapist, we get such different results. If we tell the patients that they are having this great element and that it is very rare, a certain type of patient will feel much better after the first teaspoonful. Some patients say they feel "fine" and there will be a slight increase in the output of urine, a general laxative effect and the general change is an improvement in the disease they are being treated for. In another type of case the patient will have quite a different reaction. Some patients will have a tired feeling, will want to sleep all the time, while others will have intense excitement

re

and sleeplessness. These are actions that are reported and I think we may admit that we may get them from any drug which carries with it the fancy name radium has today. There is a diuresis, sometimes a slightly laxative effect. The blood pressure is usually decreased and it may remain decreased over a long period of time. This is particularly This is particularly true in gouty and arthritic patients. The theory has been advanced that this is due to the antagonistic action of radium on the vaso-constricting element of the adrenals.

I have said that radium has been used in almost every condition. The diseases in which it is of real value are, first, anemia accompanied by great increase of leukocytes, especially with an enlarged spleen. In splenomyelogenous leukemia it has a very favorable effect even after other things have failed. Where the splenic irradiation has reduced the leucocytes very markedly, there is general improvement in the condition. This is true whether or not the spleen has been removed. The enlarged thymus responds to radium as to no other agent. It is superior to X-ray because its action is much more prompt. Also, there is no excitement and the patient does not have to be moved to receive treatment. In the lymphatic leukemias it has value. In Hodgkin's disease it has an almost magical effect. It is astonishing to see the large nodes in Hodgkin's disease melt away within a few days so that they can hardly be felt. In toxic goiter radium occupies about the same position as X-ray. There are men who think radium a great therapeutic agent in toxic goiter,

while others think it is of no value whatever. I believe in goiter where general medical measures have failed and where surgery is considered too dangerous, that radium is of value.

The diseases of metabolism are the ones we are particularly interested in and we find that in arthritis deformans favorable results have been reported, but the most promising cases are the chronic arthritides in which no bone changes have occurred. In gout accompanied by high blood pressure radium should be tried. It has been used in myalgia, neuralgia and neuritis, and with high blood pressure it certainly is of value. In certain chronic suppurative processes, nephritis and diabetes, it may be used.

In various types of anemia it is of great value. In psoriasis and scleroderma many favorable reports have been made and it is worth trying. In general carcinomatosis its use internally is not to be recommended, although we cannot say positively that it does or does not do any good.

Radium, as I see it, belongs to those therapeutic agents which are going to take great deal of time and thorough investigation before their scope can be properly defined. When we consider that we have had it about twenty years and that it has occupied the limelight so persistently, I think we can all look upon it with the hope that a drug which is so powerful, whose administration is so simple, and whose cost, when given in such minute quantities internally, is reasonable, may in the future be proved to be of real value, especially in certain metabolic diseases.

THE FUNCTIONS OF THE CONGRESS

T

HE primary function of the

Congress is to give yearly a

short, but intensive, course in post-graduate medicine in one of the large medical centers of the country. As the place of meeting is not fixed in one city, but moves in succession from year to year through the most important cities, those, who attend the Congress, are brought within a few years, into touch with the chief centers of medical instruction and investigation of our country. The advantages of such a peripatetic Congress are very great. It affords an opportunity to feel the individual atmosphere of each of our most prominent medical schools and hospitals and to come into contact with the men who constitute the medical groups connected with these. Each medical center has its own individual flavor, its different history and traditions, its own conceptions of medical education, and its especial interests in medical research. Each eity has men who have made good in medicine, who have made important contributions to medical knowledge, or have had an unusual experience in some line of clinical work. To meet these men personally, to see their laboratories or clinics, to hear from their own lips the story of their work, to see their methods of work is a stimulating experience and the physician who makes use of this opportunity cannot

help but go back to his own work with an added store of knowledge, and a reactivation of mental activity, coupled with a rejuvenation of enthusiasm. These are the objects of all post-graduate education in medicine and the Congress can be an effective and important medium in supplying such an education. It offers just what the medical generations of the last century had to go abroad to secure. The earlier stimuli to scientific work in medicine in this country came from the men who visited the medical schools and hospitals of Europe and came into contact with the creative minds there. Returning home, their own work and teaching showed the fruits of such contact and inspiration. Their experiences became the founda

tion of American medical research and

teaching which today have come to such a ripe fruition. Today our own schools can offer the contact with creative minds, with a wealth of clinical material unsurpassed in any part of the civilized world, and an unequalled material equipment in buildings and apparatus, and, above all, a wonderful accomplishment in the field of medical research. The greatest medical discoveries of the last ten years-insulin and the cause of scarlet fever-belong to America. The Congress offers, then, with a minimum of expense and time, the opportunity of such educational contact with the best in medicine that our country possesses.