11. DRUGS—"SOMETHING OLD AND SOMETHING NEW."

It was the year 1553 B.C. in ancient Egypt. The physician had questioned his patient closely and had recognized the symptoms of constipation. Now he quoted from a papyrus that would be found in a tomb in Thebes, Egypt some 3400 years later and identified by Dr. Georg Ebers.

The physican spoke knowingly to the patient's servants: "Take thou: Fresh dates, one part; sea salt, one part; and sebbet juice, one part. Thou shalt mix them in water, place in an earthen receptacle, and put therein: crushed gengent beans, cook together, cool, and let the patient drink warm. Thereafter let him drink sweet beer."

The Papyrus Ebers, as the historically valuable discovery is called, is the most important and best known of such manu­scripts and is a recording of some 800 prescriptions, with mention of about 700 drugs.

Some of the drugs mentioned in the papyrus still are fa­miliar today: castor oil, opium, olive oil, saffron, acacia, cala­mus, coriander, gentian, and salts of various metals.

Prescriptions in some instances were quite simple. A purge might be a mixture of milk, yeast and honey, or pills made of onion and wormwood. A headache remedy said to be of di­vine origin contained coriander, wormwood, juniper, honey, and opium.

Early Egyptian physicians made extensive use of drugs, but as time went on the trend was to turn more and more to magic and incantations. Thus the Egyptians lost an early advantage in the effort to fight disease.

Before this, an emperor of China, Shen Nung, who lived about 3000 B.C., discovered a large number of drugs and poisons. He is reputed to have written the first Pen Tsao, the Chinese herbal, which has had many subsequent editions that contain descriptions of more than a thousand drugs.

Included among the drugs are such familiar ones as opium, aconite, croton, rhubarb, and inorganic remedies such as iron, sulphur, and arsenic.

Also of ancient Chinese use is a concept of folk medicine called the sympathy cure.

"The hair of the dog that bit you," is the classic example of this type of folk medicine, which, of course, is not limited only to China but is practiced the world over.

The Babylonians, in about 2600 B.C., compounded drugs for illness. Clay tablets of that era have been found that record the symptoms of illness, record a prescription and di­rections for compounding, and include an invocation to the gods.

About 300 B.C. lived one of the greatest Greek philoso­phers and natural scientists, Theophrastus. Not only is he called the "father of botany" because of his work, but his observa­tions and writings concerned with the medical qualities of drugs have earned him the title of "father of pharmacognosy."

For centuries the apothecary and physician were one and the same person. But in the middle of the 8th century the Arabs separated the two arts and the first privately owned drugstores were established in Baghdad.

About 500 years later the separation of pharmacy and medicine came to Europe.

Pharmacology as we know it today actually began in the last century hand in hand with the discoveries brought about by the microscope.

Despite the progress made after 1850 in the medical world, and the introduction of vaccines and new treatments, Ritchie Calder observes in Medicine and Man that in the early 1930s, "over 50 per cent of the drugs in current use had been em­ployed by Arab-speaking physicians in the Middle Ages, and two-thirds of those had been known to the later Greeks."

In 1910 a young medical student was asked to name the ten most important drugs according to his studies.

"I would say: ether, morphine, digitalis, diphtheria anti­toxin, smallpox vaccine, iron, quinine, iodine, alcohol and mercury," the young medic replied accurately.

Thirty-five years later, in 1945, Dr. Morris Fishbein made a similar list of the most important drugs in use. Here is his list: (1) The sulfas, penicillin and other antibiotics. (2) Whole blood, blood plasma and blood derivatives. (3) Quin-acrine and other antimalarial synthetics. (4) Ether and other anesthetics. (5) Digitalis. (6) Arsphenamines. (7) Immuniz­ing agents, specific sera and vaccines. (8) Insulin and liver extract. (9) Hormones. (10) Vitamins.

As we look at a new and rapidly developing world of pharmacology and chemotherapy—usually far too complex for the average layman to understand well—it is almost startling to learn that some of these truly miraculous develop­ments were actually in use thousands of years ago.

The big difference, of course, is that our scientists know why most of our "miracle drugs" work. The ancients did not, and they used them in very crude forms. Antibiotics offer an interesting example.

Three thousand years ago an Indian brave lay gravely wounded after a skirmish with another tribe. An old man carefully inspected the wounds and then applied some mold he had collected. The wounded brave recovered, to go into battle again.

A young Chinese sat patiently with head bowed centuries ago while a Chinese physician dressed a carbuncle on the back of his patient's neck. His medication was a moldy curd obtained from soy beans.

A ruler of ancient India suffered from dysentery. Medical aid was sought. The ruler was treated with a certain type of mushrooms.

An Egyptian papyrus dating from 1500 B.C. lists dozens of curative substances made of molds or yeasts.

Today a schoolboy and his sister learnedly discuss the ill­ness of a playmate.

"They gave Jimmy an antibiotic," the boy says, certain of his word.

His older sister nods knowingly. "Daddy says it's something like yeast, and molds, and fungus. Like we found growing in the basement that time."

"And antibiotics eat up bacteria," added the brother.

The children are basically correct in their explanation.

When a person's body is attacked by bacteria, white blood cells try to prevent the bacteria from multiplying. If they fail, death results.

The white blood cells can obtain help, if necessary. Certain living organisms, mostly molds, produce antibiotic substances that can check the growth of, or kill, bacteria. When intro­duced into the body of a diseased person fighting bacteria, the antibiotics join forces with the white blood cells and usually help enough to win the battle.

Although some of the ancient peoples were aware of the value of yeasts, mushrooms, and other fungi for medical purpose, the knowledge was subsequently lost over the years until the 20th century.

Pasteur probably observed the actions of antibiotics but did nothing about it. It was not until Dr. Alexander Fleming began to be interested in them, during his work as a bacteri­ologist at the University of London in 1922, that there began the sequence of experimentation that eventually was to lead to the discovery of penicillin. Fleming published a paper on his discovery in 1929, but it drew little attention.

In 1938 interest was aroused again through the work of Professor Howard Florey, a British scientist, and Dr. Ernst Chain. In 1940 they were ready to experiment on animals with penicillin.

Then, in London on a cold, foggy February day in 1940, a husky 43-year-old British policeman lay on a cot in Rad-cliffe Hospital at Oxford University.

He was only half conscious. A doctor glanced at a ther­mometer that read 105 degrees. Grotesque swellings on the policeman's face and neck forced his eyelids shut. He coughed in pain and the spasm left his body weak and drained of strength.

Doctors knew that he suffered from deaded septicemia— blood poisoning that he had contracted from a slight cut made while shaving.

One of the doctors shook his head. The gesture was obvious. The London bobby would not survive under the usual treat­ment.

Consultations were held. There was the possibility that an unusual treatment might miraculously save the man. Every­thing else had been tried, including sulfa drugs. There re­mained a new drug, penicillin, that so far had been used only on experimental animals. It had saved dying animals. Per­haps it could save the man.

Dr. Florey and Dr. Chain took charge of the experiment. With a limited supply of penicillin, they began their injections directly into the blood stream.

On the first day the report was brief and inconclusive: "There is not much change in the patient, but at least he is no worse."

Every two or three hours a relatively large dose of the antibiotic was fed into the patient's blood stream. The doctors waited and watched.

On the second day, the report was: "A slight improvement. Temperature down slightly and facial swelling diminished."

At the end of five days of treatment the sick man appeared to be headed toward recovery. Then came bad news.

"The penicillin supply is exhausted!"

Efforts were hurriedly made to prepare more of the anti­biotic, but it was necessary to halt the injections for a few days. The fever began to mount again. The illness returned in its full assault. Before treatment could be resumed the patient died from an acute infection of the lungs.

Although the doctors had lost their first fight with the new drug, they were not discouraged.

A boy of fifteen was their next patient. This time the doctors had a more adequate supply of the drug. Around the clock, every two hours, a penicillin injection was made directly into the boy's blood stream.

Slowly the infection-induced swelling went down as the antibiotic destroyed the blood-destroying streptococcus. The boy was able to open his eyes. He managed to swallow a little soup. He appeared to be recovering.

But the crucial questions were yet to be answered. Could penicillin destroy all the germs? Could it only arrest the infection, or could it cure it?

The boy recovered and the miracle of antibiotics was a reality.

World War II brought a pressing demand for the drug and pharmaceutical manufacturers went into mass production. During the war penicillin saved thousands of lives. The supply increased dramatically. In 1943 the world's supply was enough to treat about 400 patients. In less than ten years, in 1952, enough was produced to treat 31,000,000 people. Today penicillin is readily available at prices that seem fantastically low compared with the initial penicillin costs.

Since the war the development of new antibiotics has been highly productive. Streptomycin proved to be effective against tubercular meningitis of which only 50 cured cases had previ­ously been known. Terramycin proved to be extremely versa­tile and can be used successfully against 90 per cent of bacteria-caused diseases as compared to penicillin's 40 per cent and streptomycin's 30 per cent. Many antibiotics now are listed in medical references.

A somewhat similar story of modern development may be found in the progress made with the sulfa drugs. Both the sulfas and antibiotics actually come under the classification of chemotherapy.

Fundamentally, the difference between the two types of "miracle drugs" may be easily stated. Antibiotics are sub­stances produced by living organisms, as we have just seen. Sulfa drugs are drugs put together in the laboratory by chemical synthesis.

For years scientists sought a chemical substance capable of killing germs without damaging the body. Countless hours of research were especially devoted to this quest from around 1890 to 1930. The interest was much greater in this field than in antibiotics. Actually, however, the success was limited to the discovery of salvarsan, which was partially successful in treating syphilis.

One German chemist, Dr. P. Gelomo, was on a new trail, however, and in 1908 he formed a compound derived from a complicated substance called para-amino-benzene-sulfona-mide.

Shortly after World War I the drug was developed in Germany as a cure for African sleeping sickness. In another 15 years or so the drug was known to be effective against other diseases, including scarlet fever, blood poisoning, and pneumonia.

For a rather short time the huge German dye trust, I. G. Farben, held an exclusive patent on the drug which was known then as Prontosil.

Two chemists at the Pasteur Institute in Paris brought about an end to the monopoly when they discovered that half of the molecular structure of Prontosil was not essential to the drug's efficacy. The rest of the molecule actually did the job of killing off the streptococci family. This substance was easily synthesized and was known as "sulfanilamide," and it was not patented.

The Farben monopoly was broken. The era of the "sulfa" drugs began. Since then the sulfas have gained an important place in the battle against disease.

Even so, the age of miracle drugs still was hardly upon us. Within recent memory of most of us are other new develop­ments in chemotherapy and medical fields. They form a never-ending flow of news from our great medical centers, schools, pharmaceutical firms, governmental research projects, foundations, and the other scenes of medical, chemotherapy, and other science activities.

Hormones have gone far beyond the first major news value when insulin—a hormone—came to the aid of diabetics. Among other hormones, two widely and more recently known hormones are cortisone, produced by the adrenal glands— and ACTH, produced by the pituitary gland and sent to the adrenals to stimulate their production of the cortisone.

Cortisone has been used fairly extensively for skin dis­orders, forms of asthma, and arthritis, which also has been helped in some instances by ACTH.

These hormones are known by name to many thousands of persons, and probably represent the whole meaning of hor­mones to many. Actually the field of hormones is extensive and much more complete than many of us may realize. For instance, from news about hormones comes another name that more and more finds its way into headlines: steroid.

What are steroids? What do they do?

In chemotherapy a scientist may readily explain that steroid is a group name for compounds that contain a hydrogenated cyclopentophenanthrenering system.

Interpreting the steroid into layman's language, we might do it in this way:

A sex hormone called estradiol helps make a woman a woman. A sex hormone called testosterone helps make a man a man. Both of these hormones are in a group of substances called steroids.

Steroids enable man and woman to express love physically. Our reproductive organs are entirely under their influence. Steroids fight many diseases for us. They control our ability to withstand stress. Steroids are responsible for our ability to maintain a mineral balance necessary to life. Their functions include creation of sexual desire and sexual development, the distribution of fat, the maintenance of vigor, stimulation of the growth of hair, regulating a body's salt-water balance and blood-sugar level, preparing women for and supporting preg­nancies.

Master control of hormones rests with the pituitary gland, which controls the steroid glands, which, in turn, release their hormones into the blood stream.

At present, steroid drugs are classified into two categories. Corticosteroids (cortisone is one) come from the cortex— skin—of the adrenal glands. Sex hormones (such as estradiol and testosterone) come from the gonads or sex glands.

Each is effective in treating certain diseases.

Corticosteroids are used in treating infectious hepatitis and cirrhosis of the liver, certain types of anemia and leukemia, arthritis, diabetes, tuberculosis, allergies, asthma, eye and skin inflammations, and a previously untreatable disease called ulcerative colitis.

Female Sex Hormones and their synthetic associates are used to treat prostate cancer in men, to test for pregnancy, to help women who are prone to miscarriage give birth to healthy babies, to aid in keeping skin healthy, to relieve en­gorged breasts after childbirth.

Male Sex Hormones aid elderly men remain active, help underdeveloped boys to become men, and are used to fight breast cancer in women. In a refined form they help women through the menopause. They help people resist listlessness, convalescents to put on flesh.

The future of steroids in medical care looms exciting as researchers continue new experiments, synthetic variations, and elimination of some side effects that have not been satis­factory in the use of steroids.

Here are reports on progress in steroid development with the promises for the near future:

Infection. New clues indicate that steroids fight or retard the growth of fungi and bacteria. Experiments now are being made to develop steroid antibiotics.

Cancer. Steroids presently compose the largest segment of new drugs being tried by the Cancer Chemotherapy National Service Center. Fifty have progressed far enough to be tried in human clinical studies.

Birth Control. Powerful, synthetic forms of the steroid progesterone have proved to be effective as a contraceptive by halting ovulation. Studies made among women in Puerto Rico showed 100 per cent effectiveness in protection against contraception by this method.

Heart. While the controversy about cholesterol as a fac­tor in heart disease seems to be drawing to a positive conclu­sion, scientists at the University of Southern California Medical School and at Michael Reese Hospital in Chicago have demonstrated that men who have suffered a heart attack can keep their cholesterol levels low with a daily dose of the female hormone estradiol. A male hormone, androtesterone, also is reported to accomplish the same thing. It also has been demonstrated that steroids can regulate the heart's beat and lower blood pressure.

Mental Disorders. Exploration of corticosteroids in this field is now in progress in the hopes that they may be useful in reversing the "mixed-up" metabolisms of mental illnesses.

TRANQUILIZERS—No review of modern drugs would be complete without reference to tranquilizers, although they will be discussed again elsewhere in this book.

Most of us have at least an idea of what tranquilizers are. They are discussed by people who use them, mentioned in the fast patter of comedians, sought by those who are nervous and jittery, and prescribed for the mentally ill, persons in stress, postoperative cases, nausea, childbirth, emotional ex­haustion, alcoholics painfully trying to sober up.

Actually, any tranquilizer is one of a large and diverse group of drugs which have no pharmacological property common to all.

Most frequently they are associated with the term "mental drugs" because they are used extensively in the field of mental disorders.

The effect of such a drug is by no means new. For 30 centuries physicians in India have used rauwolfia to treat insanity as well as other illnesses including fever, dysentery, headaches, and blindness. When it was successfully used to lower blood pressure by an Indian physician, Dr. Rustom Jal Vakil, he wrote a report in 1949 for a British medical journal. In Boston, Dr. Robert Wilkins saw the report and tried it on hypertensive patients. He noticed that the drug had a remarkable calming effect upon anxious patients.

Dr. Emil Schlitter, a chemist employed by the international pharmaceutical firm, Ciba, chemically broke down rauwolfia and after much labor isolated pure crystals of reserpine, one of the rauwolfia alkaloids one thousand times more potent than the root. The brand name is Serpasil, used to reduce blood pressure and to tranquilize.

Other researchers took up the hunt. More tranquilizers resulted, such as meprobamate, more commonly known as Miltown, which is classed as a muscle relaxant.

Experiments with chlorpromazine led to a large and grow­ing group of potent tranquilizers called phenothiazine deriva­tives.

Not only are tranquilizers used to aid people, but they are extremely useful in working with animals, fowls, and fish. They encourage chickens to grow larger on less feed, and to lay eggs with thicker shells. They protect turkeys against fatal bursting of the heart's major artery which is quite common in flighty, restless flocks. They enable zoo keepers to quiet wild animals. They have calmed huge fish in tanks when they are on display.

Many of them actually might serve dual purposes. As Donald G. Cooley writes in Today's Health, Nov. 1960: "Many of these drugs, if they had been developed before 'peace of mind' and 'tranquilizer' became everyday terms, would have been classified as very valuable new muscle relaxants, sedatives, antihistamines, antinauseants, anticon-vulsants, antispasmodics, or potentiators of anesthetics."

To most persons, however, they are popularly known simply as "tranquilizers" and they have aroused keen and widespread public interest.

A word of warning might well be voiced here.

"The tranquilizers should never be used except under medical supervision," Dr. George S. Stevenson, medical con­sultant to the National Association for Mental Health cau­tions. "In some cases, their use is definitely not desirable, and it takes medical judgment to determine when those conditions exist. Because the drugs have proved so valuable in certain cases, the temptation is to use them when they are not appropriate."

ENZYMES—When antibiotics were introduced they fre­quently were called the "wonder drugs." The steroids have been called the "miracle drugs."

In this progression of adjectives we might now find place for a "miracle of miracles"—the enzymes.

Writing for the September, 1960 issue of Today's Health, a magazine published by the American Medical Association, J. D. Ratcliff says: "Enzyme is the hottest word in research laboratories today. Mark it well. Enzymes are nature's chem­ists. All activity of living things depends on them—the green­ing of leaves in the spring, the bolt from an electric eel, the wagging of a dog's tail, the illumination of a firefly. Every­thing you are and everything you do traces inevitably back to enzyme action."

A standard definition of enzyme reads: "Any number of complex organic substances, as diastase, pepsin, etc., capable of transforming by catalytic action some other compound; a soluble ferment."

Enzymes are protein molecules found in all living things. For some reason, as yet not certainly understood, they per­form astounding chemical transformations.

A small amount of enzyme that travels with sperm dis­solves a small entrance for the sperm into the female egg to bring about conception.

The hormone insulin, of such importance to the diabetic, is produced in the normal body by enzymes. Our digestion depends upon enzymes. These enzymes convert foods into substances which can be absorbed into the blood stream and taken where needed in the body. One enzyme, invertase, is said to be able to break down a million times its own weight in sugar without losing its overwhelming capacity for work and activity! A pound of the enzyme pepsin can digest 30 tons of meat in a few hours.

They are meticulous workers, too. One as yet unknown enzyme in the liver transforms a substance called phenylala-nine into another substance, tyrosine. The difference between these two substances is only one atom of oxygen.

More than 650 different enzymes are known to exist in the body, and scientists believe that many more will be discov­ered. They also estimate that the smallest cell—of the trillions of cells we have in our bodies—contains at least 100,000 enzyme particles.

Some enzymes convert a fragment of food into a form that, in turn, undergoes additional chemical reactions to produce a true "miracle of miracles"—ATP, which is the shortened term for adenosine triphosphate.

ATP is a high-energy phosphate compound that is really the energy source for most of the body's action. It supplies energy for heat production and muscle activity. Raise an arm, blink an eye, take a breath—ATP provides the energy for the action.

Enzymes also produce acetylcholine which makes possible the transmission of messages across nerve junctions. When its job has been done, it must be immediately destroyed to prevent the heart from stopping. Another enzyme does this in a few thousandths of a second, according to the experts.

These "miracles of miracles" are being put to work medi­cally. They are used for infant burns and diarrhea. They have been used with success in obtaining pregnancies. Enzymes have been used to dissolve blood clots; to clean contaminated wounds.

The lack of specific enzymes in the body, researchers now believe, may be responsible for some diseases—in the pan­creas, for instance, as noted in diabetes. Consequently much experimentation, research, and conjecture is being made about the role of enzymes in all types of disease, including cancer. All in all, some 40 or more diseases have been tied to enzyme disorders.

Ratcliff sums it up: "Many top researchers are today con­vinced that enzymes hold the key to virtually all health problems—from heart disease, to gout, to insanity."

OUR DRUG SUPPLY—One could hardly be abreast of the news in the preceding two years or so and not know that the source of our drug supply has also been a source of national news, including the reports from a Congressional investiga­tion.

All of the pros and cons of problems involving our drug supply are not expressed solely on a national scale. The problems find expression in almost every community in the country.

Recently a young man and his wife shopped in a large self-service drugstore.

"I need some empirin," the young wife said. She reached for a bottle containing 100 of the tablets and looked at the price tag.

"How much?" asked the husband.

"A dollar and thirty-five cents—there are one hundred in the bottle. It's probably the best buy in the larger bottle like this."

"Let's take a look," the husband said. "The fellows at the office were talking about it." He reached to the shelf and took down another bottle. "This is P-A-C put out by another company. Let's check the formulas." He read off the ingredi­ents and their strength in the compounds.

"Why, they're the samel" the wife exclaimed. "How much are those?"

"Seventy-two cents a hundred."

"Here's another, Jack. It's called APC. I think this drug chain makes it itself. Let's compare formulas." She read from the label. "The same?" she asked.

The husband nodded. "The same. How much?"

"Fifty-four cents!"

The husband shook his head, with a puzzled frown. "Some­times, honey, I wonder what makes . . ."

Even as the couple compared prices in the serve-yourself section, a gray-haired pharmacist in the back of the store studied a prescription handed to him by an old friend.

"Pete," he said, "how well do you know your doctor?"

"As well as I know you, Jim. You know that. You and Doc are friends, too."

"Well, next time tell him to use the generic name instead of the brand name."

"What's the difference?"

"The generic name is the Latin for the specific formula the doctor wants to prescribe. The brand name is the name in ordinary English. You know what a brand name is."

"Sure. But why the fuss? So it's called one thing in Latin and something else by brand name? What's the difference to me?"

"In this case twenty-five cents a pill. They're expensive enough, at any rate, but if I use the brand name he wrote, it's fifty cents a pill. Four other firms put out the same thing under other brand names for as low as twenty-five cents."

"Same thing?"

"Exactly the same formula—the same generic name. If he had prescribed by that generic name I could sell you the twenty-five cent brand. But he didn't. He prescribed the expensive brand name. That's what I have to sell you. I can't legally substitute ..."

Another druggist listened patiently to the complaints of a housewife about her drug bill.

"Mrs. Leith, I know the bill seems high. Some of the new antibiotics and steroids come high. But they kept your daughter out of the hospital. Once, she would have been there for probably two weeks . . . with all the accompanying expense. These new drugs cleared up the trouble in three days and you kept her right at home. I know that thirty dollars seems high for drugs—but you probably saved a hospital bill of two or three hundred dollars."

The housewife looked doubtful, and then said: "But Mrs. Thompson had penicillin for almost a week and it was a lot less than this!"

"I know, but they can manufacture that for much less now.

The drugs prescribed for your daughter are relatively new."

"Well, maybe so ... but I certainly don't understand it!"

The druggist shrugged a little hopelessly. Sometimes he wasn't certain that he understood it, either.

Probably 85 per cent of the drugs he dispersed now were unknown 10 or 15 years ago. Sometimes he shuddered to think how vast his inventory had grown in his almost hopeless effort to keep up with the new drugs that doctors might prescribe.

More and more, it seemed, medicine was becoming a science of specifics—a particular drug or formula for each ill­ness or variation of an illness. The language of pharmacy was becoming so complex that it was almost impossible to re­member the vast array of generic names and complex formulas except by brand names. He didn't wonder that doctors used brand names.

On the other hand, he could also sympathize with his customers. Actually, Mrs. Leith's bill would have been about half of what it was if the doctor had prescribed by a generic name. The brand name he had chosen was the most expensive on the market for that particular drug.

Much of the wondering, and many of the questions about drugs, began to receive a vast and public airing when Con­gress, through the Kefauver Committee hearings, forced open the door that has kept much of the drug industry operation from public scrutiny.

During 1960 the accusations and denials flew hot and heavy. In May of that year Dr. Arthur H. Fleming, Secretary of Health, Education and Welfare, demanded the resignation of Dr. Henry A. Welch, director of the Antibiotics Division of the U. S. Food and Drug Administration, over disclosure of Dr. Welch's private income from sources dependent on the makers of the drugs over which Dr. Welch had responsibilities in governmental regulation.

In June, 1960, a committee to review policies and proce­dures used by the Food and Drug Administration was ap­pointed by the President of the National Academy of Sciences at the request of Dr. Fleming.

Upshot of much of this is echoed in a news story in Science Magazine, November 25, 1960, which has a subheadline that reads simply: "Regulating the Drug Industry: Reports Ask for Reform While the Industry Leaders Ask for Trademark Pro­tection."

In the face of sometimes confusing news reports, opinions, and conjecture, the public may well want pertinent questions about the drug industry answered.

For one thing, the question is frequently asked: "What is meant by the ethical drug industry? What is meant by pro-prietory drugs?"

"Ethical" drug firms manufacture prescription drugs, and— in the main—advertise only to the medical profession. Non-prescription, over-the-counter drugs are known as "proprie-tory" drugs.

The "proprietory" drug business in the nation is huge— around a billion dollars a year—and accounts for some 12 billion aspirin tablets annually, cold pills and an extensive list of products, including more than 7 million pounds of vitamins every year.

Even greater than the proprietory business, is the nation's "ethical" prescription business, measuring up to about a $2 billion cost to the public each year.

It is estimated that 1,080 prescriptions are filled every minute in the 56,000 drugstores in the nation.

One of the strange—and disturbing—facts about this truly tremendous business is suggested by Consumer Report Maga­zine, July, 1960: "Consumers only pay for the prescription drugs they use. They do not exercise any choice in their purchase. There is, in fact, no other product or service neces­sary to the maintenance of life that so completely escapes the exercise of consumer sovereignty as does the prescription drug in the circumstances under which it is sold today."

Not long before this observation was made, LIFE Magazine did a dramatic coverage of the problem in an article entitled "Big Pill Bill to Swallow." LIFE concluded its article with these words: "The present excitement stirred up by the Senate hearings may make the drug companies reduce their prices. But in the long run it is up to better informed consumers to insist on being less captive and to pressure the doctors into using a finer discrimination. Until then the consumer will go on digging deep into his pocketbook when he needs a prescrip­tion filled."

Why do drugs cost so much? Who gets the money?

Some pertinent answers of experts disclose that in 1959 the net income to drug companies after taxes was $343 million. It is observed that the average cost of prescription drugs has trebled since 1940. More than a fourth of the $16.4 billions we spend annually for medical care goes into drugs and appliances.

Profits in the industry almost dwarf other great industries. Annually the pharmaceutical industry averages 22 to 25 per cent of its net worth. The U. S. manufacturing average is 11 per cent.

Before taxes, average profit in the industry was 19.9 per cent compared with only 7.4 per cent for manufacturing generally.

One ethical drug concern was bought for $29 million in 1952. It earned profits of $32 million in less than six years. If you had purchased stock in another firm for $9,900 in 1948, your stock would have been worth $244,013 by the end of 1959, and you would have received $20,000 in divi­dends.

More than one thousand firms in the "ethical" category of the industry produce drugs that are sold only by prescription. Twenty of them account for 90 per cent of the annual sales, mostly to pharmacists and wholesalers.

The "ethical" drug business has a sales method distinctly its own. During the last 10 years or so it has changed drastically from what it once was.

There was a time when the drug firm supplied what the doctors wanted. Now the industry tells the doctors what they should want and use.

Salesmen for the drug firms are called "detail men." It is their business to call on the medical profession and promote and sell the drugs made by their firms. All the techniques of modern salesmanship, promotion, and advertising are used to parallel the detail man's efforts.

Direct mail is one of the big mainstays in drug promotion. An average doctor is reported to receive about 5,000 promo­tional mailings a year. He may receive anywhere from a few dollars' worth of samples up to 40 or 50 dollars' worth a day. The postage charges for such mailings are estimated to be about $12 million a year, and the samples are estimated to cost about $68 million. Experts say that ethical drug com­panies spend $750 million on promotion of their products, and use 15,000 detail men to sell their wares.

The retail druggist tries to keep up with the new demands. About 10 years ago a druggist might have stocked about 400 drug items to maintain a good business. Today he must stock nearly 2,000. New products are coming steadily. There were about 400 new items in 1959.

Are all these many products the offshoot of real medical progress? Many authoritative sources say they are not. Dr. Claude Forkner, professor of clinical medicine at Cornell University, says that there are only three or four useful sulfonamide preparations but 200 different brand-name sul-fonamide products produced by ethical drug firms. Of 130 antihistamine products, three or four are basic. There are eight or ten hematinic drugs (some doctors say only one— ferrous sulphate—is reliable) and 300 preparations on the market.

Frequently the "new" products are not really as new as believed. More than two-thirds of the new drugs launched every year, experts observe, are combinations of ingredients already available. One year there was an excellent example of this when there was available 30 mixtures of two anti­biotics, 20 combinations of three, eight combinations of four, and four combinations of five antibiotics. Back in 1943 no antibiotics were available under trade names. Today more than 100 are sold under almost 600 trade names. Yet, with few exceptions, there is no reason for using any of these mixtures.

Obviously it is possible for firms to profitably exploit drugs of dubious therapeutic superiority, and drugs that may be merely variants of drugs produced by other firms.

The pressure on a doctor to keep up with this onslaught of drugs and information about them is almost staggering. When he feels called upon to write a prescription for one of the newer drugs, he faces a decision.

"Small gifts do not, of course, induce a doctor to prescribe a particular drug. Nor do tender attentions at conventions, cocktail parties, or tours of company facilities or the stock exchange," writes Alek A. Rozental in Harper's Magazine, May, 1960.

"But a doctor would rather prescribe a drug put out by a large than a small company and the proof of bigness is exten­sive advertising and a large corps of detail men. That is why Equanil, which is identical with Miltown, outsells its com­petitor two to one, why Merck had to merge with Sharp and Dohme, why Pfizer, lacking detail men, in 1950 had to spend $4 million on its Terramycin 'blitz.' Small firms producing identical products must confine themselves to the limited institutional market. As a result, two-thirds of the drugs sold by prescription are put out by only fifteen firms, armed with trade names and trade marks."

He also calls attention to the fact that although the sick person foots the bill, the target of drug promotion is the prescribing physician who seldom knows the price of the drug nor is likely to worry about cost if he is convinced that it is indicated.

Actually what are some of the costs of brand-name drugs compared with costs for the same drugs under a generic or chemical name?

A price list from a discount drugstore shows these differ­ences in prices per hundred tablets.

1.  Brand name: Cortone Acetate (25mg.), for arthritis $14.95
Generic name: Cortisone Acetate          7.60

2.  Brand name: Meticorten (5 mg.), for arthritis  20.95
Generic name: Prednisone                   3.95

3.  Oreton Methyl (25 mg.), for male hormone deficiency 20.40
Generic name: Methyl Testosterone       5.20

Such examples may be found many times over in other comparisons between brand-name prices and generic-name prices for the same drugs.

In March, 1960, Connecticut's state welfare department issued a list of 25 trade-named drugs most commonly prescribed for welfare recipients, and ordered doctors to prescribe by generic name "whenever possible."

It was anticipated that savings would average 50 per cent. Some of the sample differences in wholesale prices were quoted by Time Magazine, March 14, 1960: "Dexedrine, $2.65 per 100 v. dextroamphetamine, 444; Rubramin, $3.33 per 100 v. B-12, $1.85; Pentids, $1.27 for twelve tablets v. buffered penicillin G, $2.75 per 100. Retail prices would be about in the same proportion. All drugs sold by chemical name must meet the same Government standards of purity and potency as brand-named items."

Dr. Harold Pierce, medical director of the welfare depart­ment, suggests: "If welfare recipients get drugs for less, why shouldn't the other 98 per cent of the general public?"

For those who believe their doctors may be interested in prescribing by chemical name, or simply wish to be able to check costs for themselves in this area of comparison, the Connecticut list of drugs follows:

CHEMICAL NAME BRAND NAME

USE

Piperazine citrate       Antepar   Worm Infestation

Bacitracin ointment    Baciguent Skin infection

Butabarbital sodium   Butisol sodium     Sedation
Dioctyl sodium

sulfosuccinate            Colace     Bowel difficulty
Methamphetamine

hydrochloride            Desoxyn  Stimulant
Dextro-amphetamine

sulfate                       Dexedrine sulfate Stimulate

Digitoxin           Digitaline Nativelle Heart stimulant

Ferrous sulfate           Feosol     Iron deficiency

Erythromycin             Ilotycin    Antibiotic
Methenamine

mandelate                  Mandelamine       Urinary antiseptic
Magnesium-Aluminum

hydroxides                Maalox    Antacid

Prednisolone             Meticortelone      Arthritis, etc.

Prednisone                Meticorten           Arthritis, etc.

Pentobarbital sodium Nembutal sodium Sedation

Chloral hydrate          Noctec    Sedation

Penicillin G                Pentids    Antibiotic
Pentaerythritol

tetranitrate                 Peritrate   Angina pectoris
Rauwolfia serpentina

root                           Raudixin  High blood pressure

Vitamin B-12            Rubramin Pernicious anemia

Secobarbital sodium  Seconal sodium    Sedati6n

Reserpine                  Serpasil   High blood pressure

Vitamin B Complex Sur-Bex     Vitamin deficiency

Therapeutic multiple

vitamins            Theragran;

Unicap Therapeutic Vitamin deficiency
Mephenesin                      Tolserol  Muscle relaxant

The ethical drug industry maintains that one reason for high prices is the cost of research. During the hearings con­cerned with the problem, Dr. James E. Bowes of the Uni­versity of Utah disclosed that the companies spend more on advertising than they do for research.

In the Health Hucksters, Ralph Lee Smith writes: "Seventy-five per cent of medical research done in the United States is not done by private firms. About half of all such research is financed by the federal government, and 25 per cent is financed by various foundations and private nonprofit sources. The remaining 25 per cent is done by the drug companies, which, however, probably do the bulk of research on actual drugs."

Dr. Frederick H. Meyers, associate professor of pharma­cology at the University of California touches upon another phase of the industry's research by calling it "me-too research —the quest for patentable variations on things which already are selling well." Bluntly he adds and is quoted in Life: "Extraordinarily few important new drugs have been origi­nated by American drug houses. Most of the major discov­eries have been made either in other countries or by inde­pendent, nondrug-company investigators here in the U. S."

Already beset by drug problems, the nation was confronted by another one in 1960 when a drug counterfeiting racket was evidently uncovered.

Parade, a Sunday newspaper supplement, covered the racket in part with these words: "An insidious racket that threatens the health of every man, woman, and child is spreading throughout America. The racket is a flourishing under-the-counter trade in fake and diluted drugs, stamped with the counterfeit trademark of reputable firms."

The AMA News a newspaper published by the American Medical Association in its August 8, 1960 issue carries a well-illustrated story of a raid on one of the counterfeiters in Hoboken, N. J. Trademarks said to be copied by the raided firm (General Pharmacal Co.) included those of Ciba's Serpasil, Schering's Meticorten, Warner-Chilcott's Tedral, Wallace's Miltown, Wyeth's Equanil, Merck Sharp & Dohme's Hyrdro-diuril, and Smith Kline & French's Dexedrine.

Significantly the story, entitled "Raid Uncovers Bogus Drugs" is immediately followed by a story headlined "Physi­cians' Assurance—Integrity of Drug Maker" covering state­ments and thoughts of Francis Boyer, chairman of the board of Smith Kline & French Laboratories, given to the New Jersey Pharmaceutical Association.

Boyer said that "the alleged enormous saving in price" that is claimed by those who would have MDs prescribe by generic names "is largely an assumption unsupported by facts."

Doing away with pharmaceutical trademarks would require a greatly enlarged Food and Drug Administration "in an attempt to enforce universal quality," he stated.

Eliminating the patent system in the pharmaceutical field would, in Boyer's opinion, remove "all incentive for the manufacturer to create new products or improve existing ones . . . just as in Italy, where the absence of patent protection has produced organized product piracy rather than pharma­ceutical research."

Commenting on the counterfeiting racket, Science Maga­zine, November 25, 1960, observed:

"In fact, as far as FDA officials can tell, the racket does not necessarily, or even normally, involve either fake or diluted drugs. It stems from the situation of which the Kefauver Committee made so much: that a great many drugs are sold at a modest price under their generic narnes (e.g. reserpine) and at a much higher price under their trade names (e.g. Serpasil, the trade name under which CIBA sells reserpine)."

Parade, on January 15, 1961 ran a follow-up story to their first story and quoted Deputy Commissioner John L. Harvey of the Food and Drug Administration as stating: "An FDA survey now going on indicates that drug counterfeiting may be on the increase. Retail druggists have been warned to insist on sealed manufacturers' packaging and to be on the alert for suspicious drug marketing practices which may suggest that the drugs involved are counterfeit. This is a serious threat to the public health."

In the article Parade announced that the District of Columbia Pharmaceutical Association had taken the initiative in an effort to solicit the aid of pharmacists across the country in a crusade to stop the counterfeiting, and had organized a National Committee Against Counterfeit Drugs. In the pro­gram, according to the magazine article: "Pharmacists will sign a 'Pledge of Ethical Practice' and agree to forfeit a $10,000 bond if, knowingly, that pledge is broken. Those who sign will be issued blue-and-white seals as a symbol of the purity of their pharmacies."

Perhaps one of the most objective observations about the whole drug situation, as viewed in 1960 and 1961, is well expressed by Rozental in his Harper's article:

"There are real advantages in a vigorous drug industry, however sharp its selling methods and however taxing its pricing policies. No regulated firm is likely to send a team of scientists into a jungle to search for a drug, or to explore new approaches to old diseases. Some way must be found to eliminate current practices without destroying the initiative of the drug companies. The question is how."

So the problems concerning the ethical drug business, drug costs, governmental regulation, and what will happen to the consumer's frequently inadequate medical budget is by no means settled.

It is to be hoped that under public pressure a satisfactory solution may be found.

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