Wonder Drugs

For centuries man has sought cures for disease. Before the recent scientific understanding of the causes of dis­ease, remedies used were generally cho­sen either because of supposed mystical properties in them or because of an observed association between them and improvement in a particular dis­ease condition.
With the discovery of germs and the recognition, late in the nineteenth century, that many a disease is caused by a specific germ, there developed a general impression that the eventual con­quering of germ-produced diseases would consist of discovering the means for killing the responsible germs.

This hope of conquering disease by killing germs began to be realized first in the field of preventive medicine. People correctly reasoned that by keep­ing germs from entering the body they could largely prevent the diseases which these germs produced. Here we have the basic concept of our present methods of sanitation and hygiene, discussed in detail in the previous chapter.

The use of disinfectants for decon­taminating surgical instruments and high heat for sterilizing surgical dress­ings also constitutes part of the pro­gram to prevent disease by destroying germs before they gain access to the human body. These methods of pre-venting surgical infections have been so effective as to prove beyond a doubt that germs can be killed and that many diseases can be prevented by taking precautions against the entry of germs into the body.

The next logical step in applying the growing knowledge of the relationship between germs and disease was to try to treat diseases by killing the offend­ing germs after they had already invaded human tissues. Thus the emphasis shifted from prevention to cure. We have already dealt with immunization's role in this endeavor, a procedure which prevents contraction of disease after exposure. But what if invading germs have already made the patient ill—then what can be done to kill the germs? Such questions impelled medical scientists, beginning several dec­ades ago, to search for drugs which would be effective in controlling infec­tions once they had become estab­lished.
Chemical disinfectants were intro­duced for use in cleansing open wounds. Tincture of iodine became popular as a local application to kill germs when the skin was broken and even in cleansing the torn tissues of a deep wound. Other disinfectant solutions have now come into greater favor than tincture of iodine, but the attempt to kill germs that may enter the tissues when damaged remains standard medi­cal practice.

The real need in trying to cure dis­ease caused by germs was to find a chemical agent which would destroy the germs without damaging the body tissues. Thus the chemical or drug, carried by blood circulation and other body fluids, would kill the germs inside the body without killing the person who harbored the germs. Many sub­stances were known to kill germs and could thus be classed as disinfectants. But most disinfectants when taken into the body were damaging to the tissues as well as to the germs.
In the early decades of the twentieth century several poisonous drugs be­came popular in the treatment of germ-produced diseases. Quinine was one, a drug known to be poisonous and to produce such symptoms as ringing in the ears, loss of hearing, impairment of vision, convulsions, irregularities of the heart, and even collapse and death. But even though poisonous when taken in sizable doses and thus dan­gerous, quinine was able to kill the parasites which cause malaria. Thus, physicians used quinine for the preven­tion and cure of malaria even though they realized the damage it could cause within the human body. Their attempt was to give just enough of the drug to kill the malarial parasite but not quite enough to kill the malaria patient.

A similar approach was made to the treatment of patients with intestinal parasites. The drugs used in such cases, though highly poisonous, were administered in carefully graduated doses within the level of human toler­ance but fatal to the organisms lodged within the intestine.

The most effective drugs in the early part of the century for the treatment of syphilis contained either arsenic or bismuth. Both of these metals are highly poisonous and, even when used in the concentrations necessary to kill the spirochetes which cause syphilis, produced symptoms of mild poisoning. Justification for the use of such preparations was simply that the patient would die prematurely if the syphilitic infection was allowed to go untreated. Even though his life might be short­ened somewhat by the use of - such powerful drugs, this loss was consid­ered better than allowing the syphilis to run its course.
The Sulfonamides
It was in the early 1930's that ru­mors began making their rounds in medical circles that a "wonder drug" was in the offing. Of course medical scientists can't believe rumors. They deal with matters of life and death.


They must possess verified facts before they dare alter their method of treat­ing disease in human subjects.
But in 1936 the rumors were backed up by scientific reports emanating from Germany and France. The reason for the delay in making final announce­ment was that it took time to check results. A new drug must be tried out first in the laboratory. If it passes scrutiny, then, cautiously, it can be tried on humans.
As the exciting story unfolded, it indicated that "prontosil," as used by cer­tain medical scientists in Germany, had prevented the death, laboratory ani­mals infected with streptococci—the germs responsible for many severe in­fections, including many of the skin, one form of meningitis, and the infection accountable for the death of moth­ers following childbirth.

Prontosil is a member of a chemical family of substances developed for use in the dye industry. Sulfanilamide, the original member of this group, had been developed in 1908. A few scattered observations indicated that certain mem­bers of this group of dye substances had the effect of killing bacteria; but, strangely, no research had been done to determine how toxic they might be to living tissues. Now, in the middle 1930's, it was demonstrated that their toxicity was low, meaning that living tissues tolerated these chemicals well, whereas germs were apparently brought under control by their action.

A great deal of professional enthusiasm developed in both the United States and Britain over the hope of curing infections by the use of sulfonamides. In Britain the early successes attended treatment of infections fol­lowing childbirth. In the United States sulfonamides were administered to lab- oratory animals to discover possible dangers in their use. Then they were given cautiously to human patients suffering from various kinds of infection.

In this early use of the sulfonamides enthusiasm ran high. Medical scientists hoped they had found the miracle drug which would prove harmless to the human body but destructive to all or nearly all germs that invade it. There were mixed emotions, then, as the results began to be tabulated and re- ported in medical literature. Cures wrought in certain infections were truly remarkable. Patients with infections caused by the streptococcus germ began to show improvement within a matter of hours, and many cases were practically rid of infection within two or three days. At the same time similar cases without such treatment ended fatally or had to suffer through many days, even weeks, of serious illness.

But it was soon apparent that not all infections responded as dramatically as did those caused by the streptococcus germ. Infections caused by the staph­ylococcus germ were usually reduced by sulfanilamide, but the improvement was not as dramatic as in those caused by the streptococcus.

Pneumonia can be caused by more than one kind of germ, one common type being pneumococcus. Inasmuch as pneumonia was at that time one of the major killers, it had been sincerely hoped that the new drugs would be as helpful in controlling infections by this germ as they had been with others. Gradually the truth dawned, however, that sulfanilamide rendered practically no benefit in the treatment of infections caused by the pneumococcus. It did provide some benefit, however, in the treatment of infections caused by the germ which commonly produced men­ingitis ( the meningococcus) . It also re- lieved infections caused by gonococcus, the bacterium responsible for many cases of venereal disease and other serious infections such as those of the eyes.

Disappointment over sulfanilamide's failure to help in the conquest of pneumoccic pneumonia did not last long. While physicians were gathering data on the advantages and limitations of sulfanilamide, chemists were busy in the laboratory developing chemical modifications of this same preparation. Presently sulfapyridine, another sulfonamide developed in England, proved effective in the control of pneumococcic pneumonia. With the use of this new drug, the mortality rate of this type of pneumonia dropped suddenly from more than 25 percent to a little less than 10 percent. This type of pneumonia was so common that this sharp decline in mortality. represented a say­ing of thousands of lives per year.

Collaboration between physicians and chemists continued, with the result that other sulfonamides soon came into general use, each with its particular advantages and limitations. In addition to sulfapyridine, the list soon included sulfathiazole, sulfadiazine, sulf amera­zine, sulfaguanidine, and sulfasuxidine. These various sulfonamides closely re- semble each other in chemical struc­ture but differ just enough so that some are adapted to the treatment of one in­fection and others to another.
Following the realization that the sulfonamides really were . effective agents in the control of infections, med- ical scientists began to concern them­selves with the question of how the sul­fonamides produced their marvelous results. Previously physicians had been so concerned with finding out what the drugs would do in the control of infections that they had hardly taken time to ask the question, How do they accomplish what they do?

Even to the present time, the exact means by which the sulfonamides in hibit germs, that cause infection is not known. It seems certain, however, that they bring about conditions within the tissues that retard the growth and re-production of germs that may be pres­ent. Under favorable circumstances germs within the tissues multiply very rapidly. But under the influence of the sulfonamides this rapid multiplication is prevented. Fortunately, however, the body can still produce antibodies to resist the invasion of germs just as well as usual.

Thus far in our story of wonder drugs it probably seems that the sulfon­amides provided a nearly perfect an­swer to the problems of the control of infection. And as yet we have not come to the part of the story relating to the antibiotics, At this point the reader might even ask, Why was it necessary to have any other drugs in addition to the sulfonamides?

No drug is perfect, and the longer the sulfonamides have been used, the more apparent it has become that they have limitations. When used in doses too large for the individual's tolerance, they produce signs of intoxication, meaning that a person can tolerate only so much of the sulfonamides within his body fluids. The limit of tolerance var­ies from one person to another.

The commonest signs of intolerance of the sulfonamides or of an overdose are nausea, vomiting, and mental con­fusion. These signs usually disappear quickly when the drug is reduced or discontinued. Prolonged use of the sulfonamides may interfere with the production of blood cells. Another possible complication is an irritation of the tissues of the kidneys, resulting in a re­duced production of urine. It was soon learned that this effect on the kidneys_ can be largely prevented by requiring the patient to ;drink a larger than usual volume of fluid during the time the sul­fonamides are being taken and by us­ing some chemical substance to keep the urine's reaction from becoming acid.

The sulfonamides continue to be val­uable drugs even though, in the mean­time, antibiotics have been developed. The antibiotics did not replace the sulfonamides in the treatment of disease but only served as a supplement, so that the physician now has more than one effective treatment as he deals with serious infections that affect the human body.

The Antibiotics
Research developments were taking place, even while the sulfonamides were being acclaimed, which soon pro­duced an entirely separate group of wonder drugs—the antibiotics. The story starts in 1928 with an accidental observation made by Sir Alexander Fleming. After serving as a medical officer in World War I, Fleming de voted himself to research in bacteriology at St. Mary's Hospital Medical School in London. One day when ex­amining a culture plate of the staphylococcus germ which had become con­taminated by the growth of mold, he suddenly became fascinated as he ob­served that surrounding the area of the mold was a zone in which no germs were growing.

This caused Fleming to speculate on whether the mold was capable of pro­ducing a substance that was deadly for staphylococcus germs. His subsequent experiments indicated that this was in­deed true. Thus Alexander Fleming became famous as the discoverer of the mold culture which he named penicillin. For this and his continuing re­search in the field, he was awarded the Nobel Prize in 1945.

As far as its application in the treat­ment of germ-produced diseases is concerned, Fleming's discovery lay dormant for eleven years. Then it was, in 1939, that a group of research workers at Oxford University, as they searched for drugs that would supplement the sulfonamides, decided to make a trial run with penicillin. In their experiments on laboratory mice, it proved z surprisingly effective in controlling in­fections caused by the staphylococcus as well as by some other germs. Then, . cautiously, they tried it on human be­ings and were highly gratified to find it effective in controlling certain infec­tions and also remarkably low in toxic­ity for human cells.

Next came the problem of develop­ing ways to produce penicillin in large enough quantities to make it available wherever needed as a medicinal agent. Cooperation between pharmaceutical manufacturers in England and the United States soon resulted in methods of mass production. Its manufacture still uses the processes of mold fermentation, just as in Fleming's laboratory.

In the intervening years, scientists have developed several hundred anti- biotic compounds, all of them related, as far as the structure of their molecules is concerned, to the original penicillin. Most of these have limited uses because they are toxic or because of side effects when used medicinally. Of these, about a score have found important places in the treatment of infec­tions.

Antibiotics are particularly effective in the treatment of infections caused by the staphylococcus germ. They are also useful in combating the pneumo­coccus and the germs that produce the common venereal diseases.

Antibiotic drugs can be administered by mouth and also by either intramuscular or intravenous hypodermic injection. They are used not only in the treatment of infections, but also, very importantly, in the prevention of certain infections. One member of the group (streptomycin) is important in the treatment of tuberculosis.


During the years since antibiotics have come into use, many varieties of germs have become resistant to these drugs. This is one of the facts that has urged medical scientists to develop other forms of antibiotics. When a certain germ becomes resistant to one member of the antibiotic group, an­other member which differs slightly in its chemical structure may still be effective.
Another complication seriously af­fecting the usefulness of antibiotics is that a small percentage of persons develop an allergic reaction by which, after they have received some such drug on a previous occasion, they manifest a dangerous sensitivity to its sub­sequent use. Physicians now test a patient for sensitivity before administering certain antibiotics.

Anticancer Agents
Another frontier along which medical science is making progress is the development of chemical substances helpful in the control of some types of cancer. Popular reports on these chemicals have sometimes given the false impression that they are "cancer cures." But when we understand the means by which these anticancer agents act, we recognize that they are only ad­juncts to the longer-established meth­ods of treating cancer and that they do not cure the disease but rather merely increase the survival time of the cancer patient.

These are chemicals which combine with certain constituents within the cells of the cancerous tissue in a way that prevents the growth and multiplication of these cells. We must recog­nize, however, that a chemical power­ful enough to have this effect on the cells of cancer will also have adetri- mental effect on normal cells.
Anticancer agents are limited, for practical purposes, to certain types of cancer. They are valuable in many cases of childhood leukemia, also in chronic leukemia occurring in adults when used in combination with X-ray therapy. They have also prolonged life in cases of multiple myeloma. They have been used beneficially as adjuncts to other methods of treatment in selected cases of other forms of cancer.
It has already been implied that these anticancer agents may harm nor­mal tissues of the body. Tissues which usually suffer most are those that pro­duce the body's blood cells. Thus seri­ous anemia may develop.

Drugs Which Influence the Brain
Two other groups of drugs which deserve mention in this chapter are the tranquilizers and the antidepressants—those that relax mental processes and those that stimulate them. The development of these drugs has greatly in­fluenced the methods of treating per­sons with mental disorders. Depressed cases often benefit by the proper use of antidepressant drugs—those that whip up the mental processes. In similar fashion, patients who develop panic, fear, hostility, and delusions may be helped by the appropriate use of tranquilizers.

Many persons with mental illness can now be treated without having to go to a mental hospital. Other cases still have to be admitted, but the time spent in the hospital is greatly reduced. It must be emphasized, however, that the particular effect of any one of these drugs on a certain individual is difficult to predict. Possible side effects may be undesirable. Use of some drugs of this group may develop pathological dependence in the patient. Some may cause harmful effects on the liver, on the blood-forming organs, or in the brain itself. Some have the effect of raising the blood pressure.
Important as these drugs are, then, in the treatment of mental illness, they must be used only under the supervision of a physician skilled in this area of medical practice.

Conclusion
Treatment of disease by the use of drugs has undergone a remarkable rev­olution. At the beginning of the pres­ent century medicines used for treat­ing disease were chosen empirically. In most cases the exact effect of the drug on the human body was not known, the medicine being used only because of its supposed beneficial influence or because of its relief of symptoms.

Now that medical science has ad­vanced to the place that cause-and-­effect relationships serve as the basis for the treatment for illness, the use of drugs is based on combating the cause rather than on merely relieving symptoms. Most drugs in use today are those of known effect on the body's tissues and fluids. This does not mean, however, that modern drugs are always safe. Many have marked effects on the functions of the tissues and organs of the body. In many cases a delicate balance exists between beneficial effects and harmful side effects. Reactions Differ from person to person.

The wonder drugs have prolonged millions of lives, certainly , a cause for gratitude. But the same drugs which, when used appropriately, may be life­saving can, on the other hand, if used indiscriminately, produce great harm and even death. Physicians trained in chemistry, pharmacology, and modern methods of therapeutics are the only ones in a position to make available to a patient the benefits of the wonder drugs. For the layman, therefore, the only safe policy to follow is to avoid self-medication.