The history of penicillin, the first antibiotic created in the world – 09/09/2023 – Science

On a cold September day in 1928, English bacteriologist Alexander Fleming returned from vacation to his laboratory at St. Mary’s Hospital in London and found the plaques of bacteria Staphylococcus aureawho was studying, covered in mold.

What could have doomed his research turned out to be one of the most important scientific discoveries of the 20th century—if not mankind: penicillin.

The substance, obtained from the fungus of the genus Penicillium, has bactericidal properties. A year later, the researcher described the finding in a scientific article in the British Journal of Experimental Pathology. A few years later, the drug would become the most important and widely used antibiotic in the world.

Although reports romanticizing the discovery as being 100% incidental are questioned by experts today, it is undeniable that antibiotics were a revolution in medicine at the beginning of the last century.

Widespread infections, the main consequence of wounds in soldiers during both World Wars, were a global health problem, and doctors fought to prevent the death of combatants.

With the discovery of penicillin, treating infections became not only possible, but also achievable within a few days. Almost a century later, penicillin is still used to treat various infections, such as syphilis, bacterial meningitis and strep throat.

“There is a myth that needs to be broken about Fleming’s discovery, which is that this was all completely accidental. This is not true, because he had been studying lysozyme for years, a type of enzyme that has microbial action, so he was looking for a bactericidal agent ; what really was a fortuitous event was the contamination of the material”, explains microbiologist and associate professor at Columbia University (USA), Natália Pasternak.

In his experiment, Fleming described how the area of ​​the Petri dish that contained the fungus had a halo (a kind of circle) where there was no sign of bacterial growth. The bacteria close to the fungus were all dead. Bacterial cells far from the mold were still alive.

Penicillin acts by inhibiting the growth of the bacterial cell wall, essential for the reproduction of the microorganism. Without the cell wall, the structure of the bacteria cannot remain intact and the cells die.

But Fleming, despite describing the mechanism of bactericidal action of penicillin in his 1929 article, never managed to isolate the active compound and purify the substance —an important step for the mass production of the drug.

Those responsible for this feat were two researchers from the University of Oxford, Howard Florey and Ernst Chain, who successfully isolated the penicillin component and managed to send samples for production in the United States in 1940, in the midst of World War II.

The scientists requested samples of penicillin from Fleming, who promptly sent them, and experimented on mice: subjects were infected with a highly contagious strain of Streptococcusand four animals were treated with the fungus, while four others received a placebo substance (control group).

The result was that all treated individuals survived, while mice in the control group died from the infection. The drug’s effectiveness was therefore 100% — and penicillin was announced as the “miracle drug.”

But the strain of fungus used by Fleming did not produce as much substance, which made its extraction difficult. Florey and Chain managed to isolate the compound from another strain, which produced larger quantities of the substance, and were able to send the purified material to produce the drug in a laboratory in the United States. They published the finding in the medical journal The Lancet.

Three years later, an injectable version of penicillin was widely available to treat patients with infections, especially soldiers fighting in war.

Because it is a substance that acts on a component external to human cells — that is, on the agent causing the infection, and not on the infected cells — the side effects of penicillin are practically non-existent. “Of course, there is a very small portion, less than 1%, of the population that is allergic to penicillin, but it is still a very safe and very effective drug,” says Pasternak.

Over time, pharmaceutical companies began to produce penicillin-based or semi-synthetic antibiotics, mixing elements of the original formula with molecules obtained in the laboratory. Penicillin continues to be used, but some broad-spectrum antibiotics, such as amoxicillin and streptomycin, are usually prescribed to combat other infections.

One of the advantages of penicillin would be its low rate of microbial resistance, although Fleming himself warned, in his speech when he received the Nobel Prize in Physiology or Medicine together with Florey and Chain, in 1945, of the probable evolution of drug-resistant strains .

In general, resistance to a drug occurs when, in a generation of bacteria, those that have mutations capable of escaping that mechanism of action are selected. Over generations, that resistant strain becomes the dominant one, and the drug no longer has any effect on the group of bacteria that causes the infection.

“Usually, when you start to have strains resistant to certain antibiotics, that bacteria is not resistant to penicillin because this is not a primary choice to treat several conditions. That is why penicillin remains a good option even today”, points out the microbiologist .

As the emergence of super-resistant bacteria is now considered a global public health problem by the WHO (World Health Organization), it is likely that penicillin will remain a viable option for many years to come.

Its production during the war was essential to guarantee a rapid and effective therapeutic offer for infections. For this reason, penicillin does not have a patent, thus guaranteeing its supply throughout the world by different laboratories.

“In a way, we can draw a parallel with what happened during the Covid pandemic, when there was a global effort to combat a common enemy, Sars-CoV-2, and vaccines had their patents broken,” says Pasternak. “That’s why moments of pandemic and war are also times of great historical and scientific advancement,” he adds.