THE SERENDIPITY OF THE SCIENTIFIC METHOD: DISCOVERING DRUGS

The discoveries in science are not always determined by the strict formulation and testing of a formal hypothesis. Quite often, they involve serendipity and the luck of being in the right place and time, followed by a curiosity and willingness to change the direction of an experiment. This is especially true in the field of drug discoveries. The first antibiotic, penicillin, was discovered in the late 1920s by Dr. Alexander Fleming, who found a mold colony growing on a culture of bacteria that was wiping out the bacteria. He isolated the active ingredient that eventually launched the era of antibiotics. The search for new drugs to treat infections and cancer has been a continuous focus since that time. Even though the detailed science of testing a drug and working out its chemical structure and action required sophisticated scientific technology, the first and most important part of discovery often lies in a keen eye and an open mind.

            In 1987, Dr. Michael Zasloff, a physician and molecular biologist, was doing research in gene expression, using African clawed frogs as a source of eggs. After performing surgery on the frogs and routinely placing them back in a nonsterile aquarium, he was surprised to notice that most of the time the frogs did not get infected or die. If the animal had been a mammal such as a mouse, it would probably not have survived the nonsterile surgery. This led him to conclude that the frog’s skin must provide some form of natural protection. He observed that when the skin was stimulated by injury or irritants, it formed a thick white coating in a few moments that reminded him of a self-made “bandage” over the wound. He took a section of skin and extracted the components that were responsible for killing the microbes. His tests showed that they were small proteins called peptides, which he named magainins, after the Hebrew word for shield. Within 6 months of these finding, Dr. Zasloff made the decision to completely change the subject of his research and started up a new biotechnology company (Magainin Pharmaceuticals) to explore the therapeutic potential for magainins as well as other frog peptides.

            The initial tests on this new class of drugs would indicate that they do indeed destroy a variety of bacteria as well as fungi, protozoa, and viruses. Although they are toxic to human cells too, this makes them a possible candidate for cancer treatment. Currently the drugs are being synthesized and tested in the lab for effectiveness and safety. Dr. Zasloff’s intriguing observation and subsequent experiments had the impact of opening up a whole new area of biology: isolating antimicrobic peptides form multicellular organisms. Additional studies have shown that these compounds are widespread among amphibians, fish, birds, mammals, and plants. A number of companies are involved in developing applications for animal peptides. This discovery has been well timed, since resistance among microorganisms to traditional is a continuing problem.