M & B 693 TO THE RESCUE

New Zealand Listener, Volume 10, Issue 238, 14 January 1944, Page 4

M & B 693 TO THE RESCUE

Mr. Churchill is sixty-nine years of age and for the second time in twelve months has just recovered from pneumonia. Four years before the war his chances of recovery would have been very slender. His life was saved, as have been the lives of thousands of other pneumonia patients, by a sulphonamide drug, M & B 693, discovered in 1938 by Dr. Ewens. Dr. Ewens and Dr. Lionel Whitby, the bacteriologist who helped to prove M & B 693’s value, both came to the BBC studios after his first illness and told the first complete story of their discovery. The text of this we here reproduce in full,

R. WINSTON CHURCHILL has recently recovered in almost record time from what used to be a serious and dangerous illness-pneumonia. But since the discovery of the drug capable of destroying the pneumonia germ while it is actually at work in the body of the patient, this disease has lost a goodly Proportion of the terror it used to inspire in both doctor and patient. What pneumonia used to be we can best explain by asking you to imagine yourself in the lecture theatre of a large hospital. The year is 1935. Professor McPherson is addressing the students. His subject is pneumonia .. . "Now, gentlemen, you will have read in your textbooks that the mortality of pneumonia is high. Young people stand pneumonia better than old, because in this disease there is a great strain on the heart-and the heart tends to get weaker as you get older. The death rate in people over sixty varies between sixty and eighty per cent. You see what this means-that you may lose eight out of ten of your elderly patients who develop this disease. "If you look at the charts given in your textbooks on medicine you will see that the temperature begins to rise, going up perhaps a couple of degrees each night, and perhaps down a degree in the morning. It’s a queer fact that the crisis in pneumonia arrives on odd days-the fifth, seventh, ninth, or eleventh day of the disease. And it’s at the crisis, or shortly after, that you will. know whether your patient is’ going to surVive or whether he is going to die. But whatever happens he is going to be a very sick man for a week or two, and you will be wise not to let him get about for some weeks afterwards; for Pneumonia, gentlemen, is a very exhausting disease. "And now, ‘as to treatment. I regret to inform you that there is little you can do except to treat the symptoms. This is not to say that your services are useless in this disease. Far from it. Constant watch on the part of the doctor and most careful nursing will go a long way to turn the scales in your favour. There is, of course, a serum which can be used, but I advise you to rely mainly on warm poultices to the chest, stimulants for the heart, oxygen for the breathing if it is bad, and such liquid nourishment as the patient can take." That was the picture of pneumonia as it was known to the doctors until the year 1938. That year saw the birth of an amazing drug. It came from the laboratories of Messrs. May and Baker, and was discovered by Dr. Ewens and those assisting him in the laboratory. Now hear what Dr. Ewens himself has to say about his discovery of a drug which has done more than any other single medicine to reduce the mortality of pneumonia. By Dr. Ewens "The first of these sulphonamide drugs was discovered in Germany in 1935. This product, a red dye, was called prontosil rubrum. It had been found to have a curative effect in infections caused by a microbe, streptococcus pyogenes, which is responsible for such diseases as that generally known. as blood poisoning, for the dangerous fever. which sometimes follows childbirth, for septic wounds, erysipelas, and many others. "This discovery opened up a new field of research, since for the first time a

pure chemical substance had been shown to be capable of overcoming bacterial infection in man. The next advance came very soon afterwards, this time from France. A group of workers in the famous Pasteur Institute of Paris

showed that prontosil rubrum was broken down in the body to a much simpler substance which possessed practically all the curative properties of the original substance from which it was formed. It was not a new substance: it had been prepared as long ago as in 1908, but it was only now shown to possess these almost miraculous properties. The substance is now known as sulphanilamide, and at the present time is the most widely used of all the sulphonamide drugs. For the treatment of wounds in the fighting forces in the present war it has proved of immense value. "In the research laboratories with which I have been associated for many years as director, we, in. the early part of 1936, began work to try to find products of similar type which could be regarded as an improvement on sulphanilamide itself, either by reason of being less harmful to the patient-because all powerful drugs are liable to produce undesirable side-effects, especially if misused, and the sulphonamides are no ex-ception-or because they might be found to be curative against other bacteria which were not effectively dealt with by those already known. "In research of this kind, a team of workers, each playing his own’ part, is

essential. The chemists have to devise and prepare new products; the bacteridlogists have to find out whether these products prevent the growth of various kinds of bacteria when grown artificially, or cure animals which have been infected with one or other of these germs; the pharmacologists have to examine the products in order to see what effects they have on the body, and to tell us whether they are safe to use. "By studying the effects produced by various alterations in the formula, the chemists were finally led, towards the end of 1937, to the preparation of the product now known as sulphapyridine, or, more popularly, M & B 693. "Since this discovery of sulphapyridine some hundreds, if not thousands, of new sulphonamide compounds have been prepared and tested, some by ourselves, but mainly by workers in the U.S.A. A few have already been found to be as effective as sulphapyridine and additional advantages have been claimed for their employment. One of these, sulphathiazole, first prepared by us in 1938, is already widely used. Other will doubtless follow." As Dr. Ewens told you, this drug had to be thoroughly tested before it was safe to use it on the human being. He has told you that he enlisted the help of a distinguished bacteriologist. Dr. Whitby will now tell how he helped to Prove the efficacy of this new discovery and to establish a suitable dosage. By Dr. Lionel Whitby, C.V.0., M.C., M.D., F.R.C.P. | "The sulphonamide group of drugs first came into prominence in medicine when Domagk, the German chemist, announced the remarkable effect of a patented compound called prontosil. This he had found of life-saving value in the treatment of puerperal or child-bed fever. "The secret of Domagk’s complicated compound was soon discovered. Its virtue was due to a relatively simple substance which it contained. When this was known, the whole world was free to try to improve upon the simple basic substance that is now known as sulphanilamide. From 1935 onwards, literally thousands of new, but similarly constituted substances have been tested. This with a view to making improvements. But of all the many substances tested, only a few have been found to be as effective, still less to be-a definite improvement. The greatest advances were in 1938 when the compounds known as M & B 693 and M & B 760 were synthesised, assessed, and their activities proved. The cryptic letters and the numbers refer to the great British firm of May and Baker, whose research chemists gave serial numbers to the Many compounds they made. But of course, it was medical men, first in the laboratory and then in the words of hospitals, who carried out the assessments and obtained the proof of activity. This vital side of the work is delicate, difficult, and fundamentally important. "The two M & B compounds were a great advance on the parent substance, sulphanilamide, because they were not only more powerful against the germs affected by the parent compounds, but were also active against the germ of pneumonia and another frequently fatal organism, the staphylococcus. These (continued on next page)

The Drug That Saved Mr. Churchill's Life

(continued from previous page) last two germs are not affected by the parent substance, sulphanilamide. Scientists have always been curious as to how these drugs act. If they could but propound some reasohable theory they would be in a position to forecast the probable activity of new compounds, rather than simply submitting them to a process of trial and error. "The mode of action is now known. To put it picturesquely, it would Seem that these drugs are closely related to some of the essential foodstuffs of certain germs. These germs seize upon the chemical, thinking they are getting a good meal, and do not discover the mistake until too late. Fed with this unsatisfying food, the germs tend to die

of starvation. At least, they are unable to multiply quickly, and when this is so there is every chance for the natural defence mechanisms of the body to overcome the infection. "This knowledge is of first importance when using these drugs in the treatment of disease. As the drugs imitate germ foodstuffs they can only be effective against the particular germs whose foodstuffs they imitate. They are not, therefore, of any use for every unknown fever; they will only cure fever when they are so constituted that they can trap the particular germ causing the fever. The haphazard use of these drugs for every little cough or cold or unknown illness is unwarranted, futile, and wasteful. "The next point is that the drugs must be used in full and proper doseeither full doses or none at all is the best maxim. What these drugs do they do quickly-in a matter of five, seven, or, at most, ten days. If the drug has not shown evidence of working by then it will not work at all. "The drugs are not without danger, particularly if used over long periods in small and ineffective doses. Their administration must always‘ be closely supervised by a medical man. During treatment the patient must have plenty of simple fluids so that he has a free kidney action and can wash the drug out of his system without clogging up his kidneys. Nor should reliance be placed on the drug alone. All the well-tried and reliable methods of treatment for keeping the patient in good and fit condition must never be neglected." And that is what the two men most responsible for this epoch-making discovery have to say about their work. Yoa will not fail to compare the typical case-history of pneumonia in 1935 with the recent illness of our Prime Minister. For him there was no seventh, ninth, or eleventh day crisis, because, as you know, he was treated by this new drug -and within twenty-four or forty-eight hours of taking it the temperature usually becomes normal. We are told that the Prime Minister worked throughout his illness and must therefore assume that there was never deep anxiety, thanks to M & B 693.