In 1928, the discovery of ‘mold juice’ would go on to save 500 million lives

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Although penicillin was discovered on September 28, 1928 by Andrew Fleming, a British physician and professor of bacteriology at St. Mary’s Hospital in London, it took fourteen years for the first civilian patient to receive treatment. Such a long delay to deliver what Popular Science called one of 1943’s top ten “triumphs in medicine” of all time seems unconscionable. In the decades since, it has been estimated that penicillin has saved more than 500 million lives. But word of Fleming’s discovery was slow to spread, the therapeutic implications weren’t entirely clear, and penicillin turned out to be quite difficult to manufacture. 

Fleming, who admittedly discovered penicillin by chance, is reported to have said, “When I woke up just after dawn on September 28, 1928, I certainly didn’t plan to revolutionize all medicine by discovering the world’s first antibiotic, or bacteria killer. But I guess that was exactly what I did.” 

He had been conducting experiments with common staphylococcal bacteria, or staph, but left an uncovered petri dish by an open window during a vacation in Scotland. When he returned, the dish looked different. It had the usual clusters of bacterial colonies, except for one spot covered in mold. “In the broth,” Fleming later wrote, “the mould grows on the surface as a white fluffy growth changing in a few days to a dark green felted mass.” Around the “felted mass” the broth was clear—nearby bacterial colonies seemed to have been killed by mold secretions.

Fleming continued to experiment with what he called “mold juice,” eventually isolating the Penicillium fungus as the bacteria slayer. He published his findings in 1929 in the British Journal of Pathology with only passing reference to the ramifications penicillin might have to treat patients suffering from serious infections such as pneumonia, scarlet fever, gonorrhea, or meningitis. Fleming seemed more focused on its implications for helping scientists who study bacteria. “In addition to its possible use in the treatment of bacterial infections,” he wrote, “penicillin is certainly useful to the bacteriologist for its power of inhibiting unwanted microbes in bacterial cultures so that penicillin insensitive bacteria can be readily isolated.” 

A decade after Fleming published his work, Howard Florey, Ernst Chain and others at Oxford University sought ways to manufacture penicillin at scale, which meant cultivating massive quantities of Penicillium. But they struggled to grow enough mold. Their production was so scant, in fact, that they ran out of penicillin while treating their first patient, Albert Alexander, in 1941. Without the medication, Alexander, who had been improving, ultimately died. It wasn’t until Florey recruited help from the US Department of Agriculture and US-based pharmaceutical companies like Pfizer, Lilly, and Merck that mass production began in earnest. 

When, in 1943, Popular Science named penicillin as one of the top ten medicines in history, the contributing writer and physician, Iago Galdston, cited its superior infection-fighting performance when compared with the leading antibacterial treatment, sulfa drugs: “Penicillin operates, as the sulfonamides do not, in the presence of pus and tissue fluids.” Until then, no drugs existed that could fight “long-established infections,” which, as Galdston wrote, made penicillin particularly valuable. But even in 1943, penicillin was hard to come by. Galdston lamented, “Unfortunately we cannot as yet produce penicillin in large quantities, and what is being produced has been preempted by the Government for military use.” At the time, a single dose of penicillin cost $20 ($364 in 2024). By the time World War II ended in 1945, a dose of penicillin cost $.55 ($10 today) and was readily available in the US. 

Looking back, Popular Science’s 1943 Top Ten List seems particularly prescient. In addition to penicillin, the new and emerging treatments that Galdston cited included vitamins and the importance of nutrition, hormone therapy to treat cancer and other disorders, and psychosomatic treatment, or the growing awareness that psychiatric disorders could manifest in physical symptoms and vice versa. Despite such medical blockbusters, it may be Galdston’s final item that has had the most profound effect on medicine: “Biological Thinking.” Galdston defined biological thinking as an acknowledgment that “the basis of well-being lies in achieving the best possible adjustment between the individual and his physical and emotional environment.” Today, we take for granted that excess stress from factors such as jobs, relationships, and finances, can make us sick, but in 1943 the idea was novel.

Penicillin remains one of the most widely prescribed antibiotics. And producing penicillin still requires growing mold, but pharmaceutical companies have perfected the manufacturing process, growing Penicillium in deep fermentation tanks not unlike those used in breweries. But these tanks produce something even more valuable than beer—Fleming’s “mold juice.” 

Popular Science, December 1943:

Ten New Triumphs in Medicine

MAGIC DRUGS, INGENIOUS INSTRUMENTS, WIDER KNOWLEDGE MARK THE RAPID ADVANCEMENT OF THE LAST THREE DECADES
By IAGO GALDSTON, M. D. Author of “Progress in Medicine” and “Behind the Sulfa Drugs”

Within the short span of the past 30 discoveries have developed in the field of medicine than in any comparable period during the entire history of the science. In times past, important discoveries often were followed by long periods of little or no progressive medical thinking. Today, discoveries of the utmost importance are following quickly on each other’s heels.

Among these inventions and discoveries is an instrument with a moving pen, which can “take dictation” from a patient’s brain. The record of electrical brain waves that this amazing secretary takes down is read by the surgeon for indications of brain disorders. Another is a drug so powerful that one part in 25 million parts of water will stop the growth of bacteria. Still another has revolutionized the science of diagnosis, and has completely recast the modern physician’s approach to the problem of healing.

In this writer’s judgment, 10 of the greatest medical discoveries and inventions of recent years are: The sulfonamides; penicillin; the vitamins; the sex hormones; the relation of the sex hormones to cancer; the electro-encephalograph; the electron microscope; psychosomatic medicine; brief therapy; and biological thinking.

The Sulfonamides

The sulfonamides are without doubt the best known of the recent medical discoveries. And justly so, for no single group of com- pounds has proved as effective as this one in preventing and treating such a large number of diseases. Pneumonia, gonorrhea, erysipelas, childbed fever, many forms of bloodstream infection, trachoma, septic sore throat, urinary infections, meningococcus meningitis, chancroid, gas gangrene, actinomycosis, anthrax, scarlet fever, impetigo -these are but some of the conditions effectively treated with one or another of the sulfonamide compounds.

Equally remarkable and numerous are the applications of the sulfonamides in the prevention of infection. Since their first use in this respect, the lives of countless men wounded in battle have been saved. The sulfonamides have also extended the scope of surgery, heretofore limited by the threat of infection supervening upon operations in contaminated regions. They are reducing the incidence of serious complications which in times past frequently followed on simple infections. There is, however, one particular aspect of the discovery of the sulfonamides which overshadows even its great practical results. The sulfonamides have given new life to the science of chemotherapy-the treatment of internal disease with chemicals. Chemotherapy got off to a great start when Paul Ehrlich discovered Salvarsan in 910 although for the next 25 years little new appeared on the chemotherapeutic scene. Then in 1935 came Prontosil, and later the sulfonamides, and the whole picture changed. But what changed most was the concept of chemotherapy itself. Paul Ehrlich and practically all of his followers thought of chemotherapy in terms of “magic bullets,” that is, in terms of protoplasmic poisons which would kill germs, but not the human body. Unfortunately few such selective poisons were found. Most of the protoplasmic poisons proved as likely to injure the victim as the at- tacking germs. Then when Prontosil and the sulfonamides were found to be so amazingly effective against bacteria, the old theories of chemotherapy had to be recast, for the sulfonamides do not belong to the class of protoplasmic poisons. In fact, the sulfonamides are not even bactericidal, that is, they do not directly kill germs. They are, however, bacteriostatic: they arrest the development of germs by interfering with their metabolism. By thus weakening the germs, they make it possible for them to be overcome by the body’s own defenses.

Today, research follows the path of germ metabolism, and seeks to discover how that metabolism may be adversely affected by means of chemical agents. It is this new rational basis for chemotherapy that warrants our hope of finding chemicals with which to cure tuberculosis, leprosy, malaria, and other germ and virus diseases not affected by the sulfonamides.

Penicillin

Hot on the heels of the sulfonamides came the discovery of penicillin, a chemotherapeutic agent in many respects superior to the sul- fonamides. This powerful new drug is derived from a fungus called Penicillium notatum. In 1929, this fungus, or mold, was an unwelcome in- truder into some staphylococcus cultures with which the English bacteriologist Prof. A. Fleming had been experimenting for quite some time. Fleming acutely observed then that wherever the fungus grew, the germs did not, and he reasoned that the fungus and the germs did not get along well together. He studied the matter further and found his reasoning correct.

However, since the fungus was not antagonistic to all germs, but only to certain ones, he employed it to eliminate from groups of mixed germs those to which penicillin was antagonistic. But that was as far as the matter went at the time.

With the discovery of the sulfonamides it was natural for the scientists to turn their attention once again to the penicillium mold. Another English scientist, Prof. H. W. Florey, in 1940 extracted from the penicillium mold a brown powder-like substance. He found it to be an extraordinarily powerful drug, effective against a larger variety of infections than are the sulfonamides.

Though but recently discovered, penicillin has already been subjected to numerous trials. Unlike the sulfonamides, which operate by diminishing the growth of bacteria, it has been found to kill bacteria or stop their growth entirely. But it will work in many cases where the sulfa drugs have proved useless or only partially effective. Penicillin operates, as the sulfonamides do not, in the presence of pus and tissue fluids. This renders it particularly valuable in the treatment of such conditions as osteomyelitis, empyema, infected compound fractures, and wounds and burns with long-established infections. Penicillin is superior in undermining the yellow pus-producing bacteria, the staphylococcus aureus, and many infections caused by cocci. And the user of penicillin suffers no toxic effects such as are sometimes experienced when sulfa drugs have been employed.

Unfortunately we cannot as yet produce penicillin in large quantities, and what is being produced has been preempted by the Government for military use. There is, however, no reason to doubt that the chemists will before long succeed in crystallizing it and reproducing it artificially.

The Vitamins

The vitamins represent a major medical discovery of an order different from any of those thus far described. Biology and medicine have been radically affected by their discovery. Until vitamins were discovered, the conviction prevailed among medical men that there wasn’t much one could do about health except to prevent disease. Doctors preached personal hygiene in terms of rest, cleanliness, exercise, fresh air, and good food. But they did so in the belief that they could only preserve health, which for any given individual was more or less fixed. For the rest, attention was focused on “fighting infection” by such means as vaccines, serums, antiseptics, and so forth.

With the development of the modern science of nutrition, of which the vitamins are an important segment, we learned that one could be not sick, but at the same time not healthy, as in the case of “subclinical conditions,” in which the patient is not manifestly ill, but also is far from well. We also discovered that susceptibility to many types of disease, including infections, was due to malnutrition, and that growth, de- velopment, and aging were profoundly influenced by the quantity and quality of the foods eaten.

As our knowledge of nutrition increases, and as that knowledge is applied to the everyday diet of people, we are bound to see a reduction in the incidence of disease, and an improvement in physical growth and wellbeing.

The Sex Hormones

The discovery of the sex hormones is one of the achievements of modern medicine on which the public is comparatively unin- formed. Yet it is truly a tremendous accomplishment.

It was a bright hunch that led to the discovery of the female sex hormone. When an ovum (egg) ripens in the ovary, it is surrounded by a minute quantity of a yellowish fluid, known as the liquor folliculi. No one thought to investigate the function of that fluid until 1922, when Edgar Allen, Ph.D., of St. Louis, and his wife obtained buckets of ovaries from a meat-packing plant and, working on their kitchen table, carefully drew off the fluid from the follicles. Soon they had enough of it to enable their coworker, Dr. E. A. Doisy, to purify it and determine its chemical constitution. This made possible the crystallization of the female hormone in 1929. In 1936 it was reproduced artificially. The discovery of the male hormone, which is credited to L. C. McGee, of Chicago, took place in 1927.

The sex hormones have proved enormously useful in the treatment of a variety of disturbances, including those of the sexual and reproductive functions. From this discovery was derived the original Aschheim-Zondek test for pregnancy.

The most important result of the discovery of sex hormones, however, is the light it has thrown upon the complicated structures and operations of the glands of internal secretion. These glands affect growth, development, metabolism, sexual function, reproduction; in fact, all phases of the “inner activities” of the human body.

The Relation of the Sex Hormones to Cancer

Cancer of the prostate is one of the most common types of malignancy affecting men. This type of cancer is difficult to discover in its early stages, and tends to spread so work of uniformly close tolerances is performed rapidly that, in actual experience, less than five percent of such cases can be successfully treated surgically.

In 1941, Dr. C. Huggins, of the University of Chicago, advanced the idea that the prostate cancer cells require the male hormone for their continued existence, even as the normal prostate cells do. He and his associates reasoned from this that castration or else the “neutralization” of the male hormone by means of the female hormone should adversely affect the prostate cancer growths. He, and others after him, tried the latter treatment. The results were astonishing. Although the cancer is not cured, most of the patients benefit enormously. Pain disappears, nutrition improves, appetite returns, and strength is regained. The original cancer growth in the prostate, and those that have spread to other parts of the body, regress so that many sufferers are enabled to carry on their normal activities in comfort. This treatment of prostatic cancer is vastly superior to any previously available. But the greatest value of the discovery is that it has stimulated many scientists to study the relation of the sex hormones to cancer in general.

The Electro-Encephalograph

This recent invention is a sleuthing machine for tracking down the mysterious ways of the brain. Working by means of vacuum tubes similar to those used in a radio, it picks up “brain waves”-electrical impulses generated in the head by brain function. These currents, which have distinguishing characteristics, are visibly recorded by a moving pen. Since a brain suffering from some organic ailment sends out waves differing from those generated by a normal one, the record set down by the electro-encephalograph can be read by the brain surgeon for indications of such dis- orders as brain tumors and epilepsy. This useful diagnostic instrument promises to be of great value in the study of the physiology of the nervous system, and of the dynamics of drugs employed for their effects on the nervous system.

The Electron Microscope

The electron microscope likewise promises to prove a great research instrument. The ordinary microscope cannot magnify an object beyond approximately 2,000 diameters, this limitation being imposed by the wavelength of light. The electron microscope, however, can magnify objects from 50,000 to a 100,000 diameters. It can, therefore, be readily seen how this extremely powerful instrument has opened up new and vast fields of research in bacteriology and biochemistry. We are now able to obtain a really intimate insight into the structure of both living and nonliving matter, and, most interestingly, of that “in-between” matter known as the viruses, which are responsible for such destructive diseases as smallpox, influenza, and infantile paralysis.

Psychosomatic Medicine

One of the more interesting developments of psychiatry goes by the name of psychosomatic medicine. It represents the fusion of orthodox clinical medicine with the best in psychiatric knowledge. It teaches the important lesson, in an irrefutable way, that there is no disorder of the soma (the body) without some involvement of the psyche (the mind and the emotions), and conversely, that psychiatric disorders have their somatic (physical) components. In some instances, indeed, physical symptoms are the only tangible manifestations of what is primarily a psychiatric condition. This insight into the interplay of psyche and soma has made possible a much more effective treatment of many conditions which in times past could be treated only superficially. It also enables the physician to anticipate, and by appropriate action to prevent, the development of a variety of physical and emotional strains and disorders.

Brief Therapy

Related to psychiatry is the new experimental development of brief therapy. The objective of these experiments is, simply, brevity of treatment. Most of the techniques of psychiatric therapy as practiced today are lengthy and therefore costly. Far too many persons who require treatment cannot afford it. And there are not enough trained psychiatrists available to meet the needs. To correct these deficiencies, studies, conferences, and experiments are being conducted to develop techniques of psychotherapy that will be effective but less time-consuming.

Biological Thinking

Finally we come to that development in present-day medicine which blankets all others: the ability to think biologically. Today the physician thinks of his patient in terms of his many environmental relationships–his job, his marriage, his friends, his education, his degree of success, and so forth. A short while ago, however, the physician thought of his patient only in terms of his complaints, of the symptoms or disorders he discovered and of the specific remedies he could use in the treatment of “the case.” In fact, the physician was more concerned with the “case”-with the disease afflicting the patient-than with the patient himself.

Today, we know that to effect a permanent cure, the contributory as well as the primary factors must be considered and dealt with; that, in substance, the basis of well-being lies in achieving the best possible adjustment between the individual and his physical and emotional environment.

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