A shot in the arm: Swetha Sivakumar writes on the penicillin pushers

We don’t often think of fungi in pharma, but that is, of course, where penicillin comes from.

The antibiotic substance earned three of its discoverers — Alexander Fleming, Howard Florey and Ernst Boris Chain — the 1945 Nobel in Medicine. But I want to tell you the fascinating story of why that list should have been longer. (When will the Nobel committee do away with this unfair rule of threes?)

It all began, as we know, with Fleming, a Scottish bacteriologist working at St Mary’s Hospital in London. He ran a lab there that was famously messy. He even used the mess to create art. He carefully arranged different bacterial species in petri dishes, then left for the day or weekend and returned excited to see the colourful designs they had formed.

This was in the 1920s. At one point, he returned from a vacation to this riotous lab to find that some petri dishes he’d left unwashed now housed a blue-green fungal mold. And, he noticed, there were no bacterial colonies around this mold.

The green stuff, he realised, had anti-bacterial properties.

Excited, he wrote up a paper and published his findings, in 1929. The paper went largely unnoticed. Fleming wasn’t a great speaker or writer. Aside from which, he was still struggling to isolate pure penicillin from the mold, because it was so unstable and broke down so quickly.

Those who did learn of his discovery dismissed the green stuff as an interesting yet impractical substance.

The world moved on. As for Fleming, this, in fact, is where his role ended.

A decade later, in 1939, Howard Florey, an Australian pathologist at Oxford University, applied for funding for penicillin research. He too would struggle to isolate the substance without destroying the mold.

A team led by him and the English biochemist Norman Heatley did eventually manage to isolate enough to begin animal and human trials. A researcher on this team, the German-British Ernst Boris Chain discovered exactly how penicillin worked: killing bacteria by breaking down their cell walls, and preventing them from building new ones.

Soon after, the world’s first penicillin shot was administered to a patient: an Oxford policeman Albert Alexander who had developed a severe infection after scratching his eye while gardening.

A day after Alexander received his first dose, of 200 mg, his condition improved dramatically. But he had been prescribed small doses every three hours, and the drug still wasn’t easy to produce. The limited supply ran out, and he eventually died a few weeks later (as he would have without the drug, and as so many did before it was discovered).

Today, hardy molds are grown in bulk, in fermentation tanks, and the fluid culture is used to make antibiotics. Back then, amid the war, despite the lives it could save in battle, Florey was unable to get anyone to help him mass-produce the drug.

Tired of waiting, he eventually decided to try his luck in the US, where resources were less strained. But in order to mass-produce, he needed a powerful strain that multiplied quickly, and he didn’t have one.

The US Department of Agriculture (USDA) offered to help. This is where it gets really interesting.

The penicillin most of the world uses today can be traced to early efforts with Penicillium chrysogenum, which was discovered by USDA researcher Mary Hunt (nicknamed Moldy Mary), in 1943.

She was part of the USDA team that was hunting everywhere for penicillin Florey could use. Researchers had even asked the US Army to fly soil samples home from wherever in the world they were posted. Mary, as part of her research, scoured local produce markets, salvaging moldy fruits and vegetables for the lab. It was during one such excursion that she found a hardy new strain, growing on a cantaloupe.

Penicillium chrysogenum yielded much more pure penicillin per gm than anything that had been tried before. Within three years, American production went from zero to 100 billion units a month (a unit of penicillin is 0.6 microgrammes). By 1951, production soared to 25 trillion to 30 trillion units a month.

Today, penicillin is just one of hundreds of antibiotic compounds used to battle infections in humans and animals. Its development remains one of the greatest success stories in medicine.

Yet, even in his Nobel Prize acceptance speech, Fleming had warned that improper use could render it ineffective. He warned that overprescribing it, using it for the wrong reasons, or not using enough could lead to bacteria developing resistance too.

The term “antibiotic resistance”, in fact, is almost as old as penicillin itself.

Escalating levels of such resistance are now considered an urgent public health threat. For so many reasons, watch what you put in your mouth.

(To reach Swetha Sivakumar with questions or feedback, email upgrademyfood@gmail.com)