The Discovery and Importance of Penicillin and the Development of Sulfa Drugs

Overview

The discovery of penicillin in 1928 and sulfanilamide drugs in the 1930s played a major role in treating bacterial diseases and in the creation of today's pharmaceutical industry. These chemical agents, called antibiotics, saved many lives during World War II. Though they were initially remarkable in their treatment of disease, it was soon learned that they could be harmful to humans and that the diseases they treated could become resistant to their action.

Background

Diseases have plagued human beings from the beginning of their appearance on Earth. Causes were unknown, so early humans often blamed these frightening visitations on devils or the will of the gods and frequently thought their appearance was caused by wrong behavior or portended some chaos in the future. Thousands of years later, when man had advanced enough to try to understand disease, visionary doctors suggested that disease was caused by "seeds" that were invisible. That invisibility was overcome beginning in the seventeenth century, when the microscope was invented and curious men began to look at objects through it. A man named Malpighi, an Italian, saw the movement of blood in capillaries. In the 1680s Englishman Robert Hooke (1635-1703) looked through a microscope and drew the first pictures of a cell. Anton van Leeuwenhoek (1632-1723) of Holland discovered microscopic life forms in 1676 that he called animal-cules. He described them so clearly that they can easily be identified today as bacteria, sperm, and blood corpuscles. The structure and understanding of cells was on the verge of being discovered, but nothing more could be done until microscopes were refined two centuries later.

Bacteria were among the first living things on Earth, but their existence was not known until the sixteenth century, and their role in the cycle of life was obscure until the nineteenth century. At the time it was believed that life sprang from non-living matter, a notion called spontaneous generation, and no one knew what a cell was. It was known that diseases came from unseen agents, but doctors did not know what they were. They did know from observation that some diseases spread easily between people with no obvious outside agent. That was the state of affairs in the middle of the nineteenth century.

Louis Pasteur (1822-1895), a French chemist and theoretical scientist, worked on many aspects of matter that had not been understood before the microscope was improved. In 1848 he began working on bacteria and soon was able to show that they were living units. He proved that living things came only from living things. Among his other activities, Pasteur proved that many diseases are caused by living germs that multiply in the body. He invented vaccines and pioneered antiseptics and pasteurization. It was known by then that bacteria caused cholera, tuberculosis, pneumonia, and typhoid fever, among many other diseases. Air, food, and water carry bacteria from one person to another, and antiseptics were perfected to prevent the spread of bacteria.

For thousands of years humans used substances found in common molds to cure skin ailments and other infections. At the time no one knew what these molds contained, but in 1908 a chemist discovered chemicals that had the potential of stopping infections in the same way molds had done. They were called sulfanilomides, or sulfa drugs, but they were ineffective against human bacterial diseases until they were refined and turned into a usable form. Many researchers engaged in trials, experiments, and testing and finally came up with a usable substance in 1930s. Sulfa drugs eliminate bacteria but do not actually kill them. When injected into a group of bacteria, sulfas prevent them from multiplying.

In 1928 Alexander Fleming (1881-1955), a British bacteriologist working at Oxford, was engaged in a program of research on staphylococci, a specific class of bacteria. He noticed a peculiar type of mold in one of his laboratory dishes and showed it to his colleagues. No one knew what it was, nor could Fleming or anyone else reproduce it experimentally. Fleming had no idea what this was nor that it would some day lead to a revolution in medicine. It was not for fifteen years that the nature and importance of penicillin was understood. Ernst Chain (1906-1979) and Howard Florey (1898-1968) came to work at Oxford in the 1930s and began to work with antibiotic substances. Eventually, they were able to identify and purify penicillin, which made it available for use as a drug. Together, Fleming, Chain, and Florey shared the 1945 Nobel Prize in medicine for their discovery.

Actually, these substances should be called penicillins, as nature produces many different types and more than one type has been produced in bacteriology labs. Many are active and effective against specific bacteria and many are unusable because they are destroyed in the human body. It took ten more years to prove how they did their work. It was known that penicillin was different from sulfas. Both are chemical agents, but where sulfas prevent disease cells from multiplying, penicillin damages the walls of those cells.

Impact

The effect of sulfas and penicillins on stopping diseases, infections, and their spread was electrifying. There had previously been no compound or medicine that could prevent the diseases caused by bacteria. Only after a connection was made between living cells and chemical components was it possible to produce these new medicines. Sulfas were demonstrated to be instrumental in saving many lives, and scientists finally did produce a penicillin, administered by mouth, that was used to treat soldiers during World War II. Because of their rapid effectiveness, a great deal of publicity was given to these drugs. This high visibility caused them to be hailed as "miracle drugs."

The sudden appearance of these compounds created myriad consequences in the modern world. They provided hope that many debilitating and life threatening diseases could be prevented or cured. Another effect was to revolutionize medicine by changing treatment and prognosis of many diseases. Their appearance also changed and expanded experiments into the chemical properties of natural substances. This led to the creation of chemical substitutes or synthetic replicas to act in similar ways. This visibility also created a realization that other fields could benefit from the same kind of research and that there might be substances that could affect viruses, fungi, and other disease-causing agents the same way. This greatly amplified research in microbiology and bacteriology and drew many more practitioners to these fields.

One disappointing fact that became clear by the middle of the century arose from the administration of the drugs. It was soon evident that chemical agents have side effects in the human body. Penicillins, for instance, cause allergic reactions or extreme hypersensitivity in some people. They can cause skin rashes, hives, and other allergies as well as anaphylactic shock, which can result in death. It was also discovered that those allergic to one form of penicillin are allergic to all of them. Sulfas, too, were discovered to be damaging to human kidneys. The "wonder drugs" had definite limits. Far from reducing the use of these drugs, the knowledge led to the creation of synthetic drugs. It also caused the medical profession and drug makers to take more care to determine possible side effects before the drugs were marketed. Successful synthetic penicillins are absorbed into the blood more quickly than the original while maintaining the ability to kill bacteria.

An unexpected discovery in the use of these chemical agents came when it was seen that some strains of bacteria became resistant to a particular strain of penicillin. Scientists thus had to work toward producing new substances.

The use of these drugs has been dubbed "chemotherapy"—that is, the treatment of disease by chemicals. Antibacterial chemicals are selectively toxic only to the infected cells and are designed not to harm healthy cells. The chemists who create these medicines have done so because the drugs do not exist in nature. They have been able to do so because of another exceedingly important impact of the creation of antibiotics. It has been said that it was the creation of sulfas and penicillins that created the pharmaceutical industry, one of the largest and most profitable industries in today's world. Drug companies existed before the 1930s, of course, but were much smaller and made such compounds as prescription medicines, aspirin, and antacid pills.

After the invention of the penicillins and sulfas, pharmaceutical companies expanded, hired researchers, and gave them the time, space, and money to do necessary research into refining products or searching for new ones. Because of the newly understood connection between disease and chemistry, these companies greatly expanded their ability to find the drugs that were needed and to extend their capability to produce these drugs and make them available for everyone.

Today, sulfa drugs and penicillin are no longer the premier substances they once were. Many other clinically useful antibiotics are now now produced. Most treat bacteria, while others work against fungi and protozoa. None are effective against viruses. Scientists were disappointed when they discovered that the much-praised sulfa drugs and penicillin could not cure all diseases. But the drugs were augmented by new techniques and new substances. The emergence of new antibiotics has come about because of the availability of funding for scientific testing and investigation. So, one more impact of the emergence of penicillin and sulfa drugs is that they stimulated further study and led to better understanding of the drugs. It also produced further knowledge about the physiology of the human body and its relation to chemical agents, which in turn has led to the availability of safer medicines.

LYNDALL B. LANDAUER