The observation itself
In September 1928, in a laboratory at St Mary’s Hospital in London, the bacteriologist Alexander Fleming examined a culture plate on which staphylococcus bacteria had been growing. A blue-green mold had also grown on the plate, and the bacterial colonies near it looked clear and ghostlike, as if dissolved. Away from the mold, the colonies were normal. Something from the mold appeared to be diffusing through the jelly-like growth medium and stopping or destroying the bacteria nearby.
This page is a history of that laboratory observation and its scientific meaning. It is not medical advice.
Reading the plate
Bacteriologists of the period also routinely examined stained samples under a compound microscope. A culture plate is a shallow dish with a layer of nutrient jelly, often agar. Bacteria spread on it grow as visible colonies, and the pattern of growth can show whether anything is affecting them. An empty zone around a spot is called a zone of inhibition, and it is still used in laboratories to compare antibacterial substances.
The zone around Fleming’s mold told him three things.
- The mold released a substance into its surroundings, since the effect extended beyond the mold itself.
- The substance was active against at least some bacteria, and was strong enough to be seen.
- The effect could be tested again, by growing the mold in a liquid and trying the resulting broth on other bacteria.
Fleming did that. He grew the mold in broth, and he tested what he called mold juice against many kinds of bacteria. It halted the growth of a number of them, including some responsible for common wound infections, while others were unaffected. That selectivity was important: it suggested the substance acted on particular types of bacteria, not on every living cell.
Antibiosis and competition
The idea that microbes can inhibit each other was not entirely new. Researchers in the late 1800s had seen cases where one kind of bacterium or mold stopped another from growing, and the term antibiosis, meaning “against life”, was in use by the early 1900s. Penicillin did not create the concept, but it was a very clear example.
Biologists later explained the effect as a kind of chemical competition. Molds and bacteria share soil, food and surfaces, and many species make compounds that hamper their neighbors. Penicillin interferes with the way many bacteria build their outer cell wall, so growing bacteria are weakened and burst. Human cells do not have the same kind of wall, which helps explain why the substance was not harmful to white blood cells in Fleming’s tests. This mechanism was worked out in the decades after the discovery, not in 1928.
Naming the mold
The mold was identified in 1928 as a Penicillium, a genus of common molds that are found on spoiled fruit and bread. The species was long described as Penicillium notatum, and later taxonomic work put the strain in the species now called Penicillium rubens. Names like this changed because the classification of molds has been revised repeatedly.
What the experiments did not show
The 1928 results were suggestive but limited, and it helps to be clear about what was missing.
- Fleming did not have a pure substance. His broth contained many things, and the active material could not easily be separated.
- The active material was unstable and lost its strength over a short time.
- There was no evidence yet about how it behaved inside a living body, or how a dose might be controlled.
For these reasons, he published the finding in 1929 and used the mold mainly as a laboratory tool. It also fits into the wider story of medical instruments and laboratory methods that built up around bacteriology. Penicillin helped separate some kinds of bacteria from others in mixed cultures, which was practical for bacteriologists even before it was a drug.
A pause of about a decade
For roughly ten years the substance remained a laboratory curiosity. Chemists attempted to concentrate it, but the compound was difficult to purify with the methods available in the 1930s. Interest in antibacterial drugs was also being drawn elsewhere. The sulfonamide drugs, introduced in the middle of the 1930s, showed that chemicals could act against bacterial infections in the body, which revived attention toward systematic searches for antibacterial agents.
The way purified penicillin was ultimately produced and tested is told in the story of the Oxford work and, separately, in the history of its wartime manufacture. The point of this chapter is narrower: the 1928 dish demonstrated that a living organism could make an antibacterial substance in a form that was easy to observe.
What the discovery taught scientists
Several lessons came out of the early observation, and they shaped later research.
- Natural sources, such as molds and soil organisms, can hold useful antibacterial compounds. This prompted later large-scale searches of soil microbes.
- Selective action is possible: a substance can affect some bacteria and spare animal cells.
- Careful observation matters. A contaminated plate is often thrown away. Recognizing the pattern as significant was the contribution that history credits to Fleming.
- A finding alone is not a medicine. Purification, testing and manufacturing are separate achievements, carried out by other people.