What do the marmalade you put on your toast and the vitamin you perhaps take at the same time have in common? Both have an ingredient called citric acid, an ubiquitous, weak organic acid. Indeed, citric acid is the molecule that led to the technology which enabled the mass production of penicillin.
Citric acid is a naturally occurring molecule found most concentrated, as the name might suggest, in citrus fruit. Today citric acid is a commodity chemical produced and consumed throughout the world, across a range of industries. As an antioxidant and acidifier it can be used to preserve and enhance flavours and aromas in a range of food products, can be used as an environmentally benign cleaning agent as it is biodegradable, and is an ingredient in many pharmaceuticals, cosmetics and toiletries as it is readily metabolized and eliminated from the body.
Citric acid was first isolated and crystallized from lemon juice in 1784 by the Swedish chemist Wilhelm Scheele. Due to its remarkable properties, its use spread rapidly throughout the 19th century. In this period, the acid was produced on an industrial scale, just as the chemist Scheele did, by extracting it directly from concentrated lemon juice, by precipitating calcium citrate and then recovering citric acid using dilute sulfuric acid.[i]
The downsides of this method were purely efficiency based – even the most citric acid heavy of citrus fruits – the lemon – has only 7-9% citric acid concentration, to make a kg of citric acid requires more than 500 lemons[ii]. This left the door open for disruption.
Through the 19th century, Italy provided the raw ingredients for almost the entire world supply of citric acid, as production came directly from the citrus fruit crops in its Southern regions. The production of citric acid in Italy grew from 12,000 tons in 1906 to 17,500 in 1916 – which would prove to be its peak.[iii]
Snapping at the heels of the citrus-fruit-based citric acid industry were both chemical synthesis and fermentation solutions. The science had been around since 1893 when Carl Wehmer discovered that citric acid could be produced by the fermentation of a sugar-based substrate by a microorganism, Penicillium. However, he failed to produce it on a truly industrial scale mainly due to contamination issues with the open tray system he was using.
Another microorganism, Aspergillus niger was also found to turn sugar into citric acid, and the investigations of this microorganism by the American food chemist James Currie would prove to be pivotal, as he showed a way to get significantly higher yields of citric acid using it.[iv],[v]
As usual with these types of disruption, while the technology and science were there, it also needed to be economically viable. As is often the case it took an outside event – or in this case a few – to catalyse this.
The interruption of exports of calcium citrate (the key precursor for citric acid) from Italy following World War I was coupled with increasing worldwide demand for citrus fruit as the Spanish Flu pandemic took hold. In the US, lemon prices rose by 50% from 20¢ a dozen to 30¢ a dozen.[vi] Together these led to higher and more volatile prices across all parts of the citric acid supply chain. This led to a small chemical company in the US, Charles Pfizer & Co, to search for an alternative supply. They hired Currie with the bold aim of producing citric acid without citrus fruits.
With Currie on board, Pfizer opened a pilot plant to produce citric acid via fermentation – which they called SUCIAC – Sugar Under Conversion to Citric Acid. The success of this pilot plant meant that in 1926, when the first large scale industrial plant opened, the output of citric acid using fermentation technology outpaced that from lemons and limes. In its first year of production, this plant produced more than 50% of the world’s supply of citric acid, and by 1929, Pfizer no longer used lemons and limes for its citric acid production. All 10 million pounds were being produced by fermentation.[vii] This was a fast business-to-business, ingredient-led disruption.
Indeed, part of this swift disruption was due to the far cheaper cost – the price of citric acid fell by more than half, from $1.25 to 40¢ per pound in about five years.[viii] By 1930, 90% of citric acid was made using fermentation and improvements to the process have continued to this day.
The expertise that Pfizer developed in fermentation from the production of citric acid proved to be pivotal. Not only was it applied in the production of a variety of other acids like gluconic acid (used as a food preservative and cleanser) and ascorbic acid (Vitamin C), but ultimately it was this knowledge that led to Pfizer’s success in the large-scale production of penicillin during World War II. In fact, most of the penicillin that went ashore with Allied forces on D-Day came from Pfizer’s Brooklyn facility.
Today, we are benefitting from the knock-on impacts as Pfizer was one of the first companies to roll out their Covid-19 vaccine. And it all started with a microbe that could ferment sugar into a really useful ingredient. Since then, of course, we have improved our fermentation methods which has helped enable the rise of Precision Fermentation.
Today, more than 2 million tonnes of citric acid is produced every year by fermentation, and organic acids like citric acid are the third largest category of fermentation products globally, behind antibiotics and amino acids.[i]
[i] Ciriminna, R., Meneguzzo, F., Delisi, R. et al. Citric acid: emerging applications of key biotechnology industrial product. Chemistry Central Journal 11, 22 (2017).
[ii] Molinari, Ettore, “Treatise on General and Industrial Chemistry,” 2nd ed., Part I, pp. 412-19, London, J. and A. Churchill, 1920.
[iv] Zahorsky B. U.S. Patent 1913; 1065358.
[v] Currie JN. The citric acid fermentation of Aspergillus niger. J Biol Chem. 1917; 31:15–37.
[vii] Lombardino, J.G. A brief history of Pfizer Central Research. Bull. Hist. Chem. 2000; 25:1
[viii] Prices for citric acid in the US found in here: Citric Acid Industry P. A. Wells and H. T. Herrick. Industrial & Engineering Chemistry 1938 30 (3), 255-262. A few sources (like here), cite the price of citric acid falling from $1.20 per lb to 20 cents 5 years later, however this was not sourced.