A Tradition of Innovation 3

The first Italian Penicillin

24th May 1947 saw the establishment of SPA (Società Prodotti Antibiotici) by Pharmacologist Dr. Rodolfo Ferrari and microbiologist Carlo Callerio. Now Italy had its own, domestic Penicillin, available both in vials and tablets as SUPERCILLIN and PRONTOCILLIN. SPA stands to this day at the same address in Milan, albeit with the renovation and modernisation expected in its 75 years. Following this success with Penicillin, Rodolfo Ferrari and Carlo Callerio sought to expand the antibiotic portfolio, beginning with Fleming’s earlier discovery, Lysozyme.

Lysozyme’s story at SPA begins

Fruitful initial discussions culminated in a visit to SPA in 1950 after Fleming’s attendance as the guest of honour at the 2nd National Antibiotic Congress held in Milan. From this point, work began to produce high-purity Lysozyme in industrial quantities and expand the applications for which it could be used. SPA’s lysozyme was first marketed as a supplement for enteral feeding, and for the humanisation of cow’s milk. These early findings paved the way for the later development of today’s Lysozyme applications. Mr Pisani, former CEO of SPA fondly recollects:

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“Prof. Ferrari had a vision of the market that reconciled research with the commercial spirit of a true entrepreneur … he knew how to respect and motivate. Both inside and outside the company, he was able to create innovative teamwork for the times, with modern and enlightened governance “

I was entrusted with Lysozyme.
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At this time SPA developed and patented the advanced methods of Lysozyme extraction from eggs on which the foundations of its continued success now stand. Using resin-purification, the quality of SPA’s Lysozyme stood above the competition to become the “gold standard on the market, opening up world markets.” It was with this tremendous momentum in 1983 that Fordras SA was founded in Lugano, Switzerland, where Mr Pisani began coordinating the production, purification, and marketing of lysozyme as an active pharmaceutical ingredient (API).

Applications for Lysozyme emerge

In 1983 work began on understanding the breadth of applications for which Lysozyme could be valuable. Uses in the production of food came first, with the development of a process that entirely prevented the late blowing of cheese. At the time, a significant portion of hard cheeses could not be sold due to hyper-fermentation caused by contaminating Clostridium tyrobutyricum. State-of-the-art approaches were entirely mechanical, including bactofugation and microfiltration. However, spores were still able to evade these attempts, remaining in the curd to begin growth in the cheese during maturation. Mr Pisani recalls the breakthrough application:

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Lysozyme at low dosages of 5PPM, and therefore at a very low cost gave exceptional results on 100% of cheeses
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Today, Lysozyme is trusted to prevent late-blowing defects by 99% of Grana Padano producers in Italy, and over 85% of French hard cheese producers do the same. Its hen egg-white source makes it the perfect natural weapon to protect foods from gram-positive bacterial contaminants, reducing food waste, and ensuring optimal quality. The US market took to these results favourably too, granting it GRAS (generally recognised as safe) status in 1998. Mr. Pisani put it such:

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“ On the US market, the presentation of these results, combined with the total harmlessness of this natural product, gave Lysozyme GRAS status, opening up a potential future market for food preservation. These fortunate results contributed to my being offered the position of CEO which I held until 1994, making me experience SPA and the Ferrari family as my second“
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Fleming believed in Lysozyme

Regardless of Penicillin’s power to combat pathogens harmful to humans, the fame, household name status, and scientific accolades with which Fleming was rewarded; Lysozyme’s discovery remained his proudest achievement. Whether it was the magic of being his first major discovery, or for other reasons we can’t today be sure. We do however have accounts from both VD Allison and his wife, Lady Amalia Fleming, attesting to Fleming’s pride in his discovery of Lysozyme. Indeed, we are not the first to celebrate the anniversary of Lysozyme’s discovery. A conference was held 50 years ago, and it is from the proceedings of this with which we close this instalment in our journey through Lysozyme’s 100-year history. Lady Amalia Fleming recalled:

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__ “At the time of his Lysozyme studies, Fleming himself, the introvert, was unable to hide his excitement. His rich imagination and the dreams which he kept so cautiously to himself overpowered him, and he expounded a stream of wonderful hypotheses. The six papers which he wrote about lysozyme show perhaps more than any of his other works the brilliance of his mind. … Fleming had high respect for natural defence mechanisms, and he kept this respect to the end in spite of the miraculous achievements of his penicillin and all the other antibiotics. … Fleming believed in Lysozyme. He believed that it was bound to have a great future he had discovered it and had done marvellous work on it. Other scientists would follow the path he had opened. Others would purify it, advance it. With absolute confidence, he used to say, “We shall hear more about lysozyme. Your work has made Fleming’s prophecy come true“
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Early examples of SPA’s Supercillin vials. Photo Credit: Wikimedia commons.

SPA’s lysozyme, LISOZIMA, in 250mg and 75mg variants.

Alexander Fleming examines SPA’s Lysozyme display at the 2nd National Antibiotic Congress held in Milan, 1950. Credit: Public Domain, Wikimedia commons

100 years of Lysozyme

2022 marks 100 years since news of Lysozyme’s discovery reached the Royal Society. Let us take you on the journey of this 100-years story:

100 years of Lysozyme | Episode III Instalment 3

Lysozyme leads the way for DeepMind’s AlphaFold

Lysozyme contributed directly to our understanding of the structure-function relationship of proteins. It was the first solved structure that established the concept that the 3D shape of a  protein[...]


100 years of Lysozyme | Episode I Instalment 1

A beginning for Lysozyme

Bioseutica® group has been producing lysozyme from hen egg-white since the 1950s, a history spanning nearly 75 years. But lysozyme’s story doesn’t begin with us. For that, we must look back to the earliest human use of egg-white[...]


100 years of Lysozyme | Episode I Instalment 2

Thus ended collection of tears

The second instalment of our 100 Years of Lysozyme series is now live. This week we discover how the abundance of Lysozyme in eggs was first discovered (hint: it wasn’t in the supermarket)[...]


100 years of Lysozyme | Episode I Instalment 3

Not a great lecturer

Fleming’s shyness, his being, “not a great lecturer” as acknowledged by Allison, may in part account for the poor reception received at the first reading of the initial paper describing lysozyme[...]


100 years of Lysozyme | Episode I Instalment 4

Try £ 3

From 3p for tears to £3 for Picassos; in this instalment, we uncover how Alexander Fleming’s eye and contributions had an immeasurable impact on medicine and science in the 20th century[...]


100 years of Lysozyme | Episode II Instalment 1

A Tradition of Innovation

The aftermath of the war has left Italy economically devastated like the rest of the European countries. In Milan another Ferrari begins production, but this time of Penicillin.[...]


100 years of Lysozyme | Episode II Instalment 2

A Tradition of Innovation 2

The death of their first trial patient through the insufficient supply of Penicillin drove Florey, Chain, and their research assistant Heatley, forward with inspired momentum.[...]


100 years of Lysozyme | Episode II Instalment 3

A Tradition of Innovation 3

24th May 1947 saw the establishment of SPA (Società Prodotti Antibiotici) by Pharmacologist Dr. Rodolfo Ferrari and microbiologist Carlo Callerio. Now Italy had its own, domestic Penicillin[...]


100 years of Lysozyme | Episode III Instalment 1

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To most of us, if at least those reading, I hope, Lysozyme is best known as a potent, natural antimicrobial. This is evidently its primary purpose for the hen's egg, making[...]


100 years of Lysozyme | Episode III Instalment 2

Finding the structure

Sir. William Bragg and Sir. Lawrence Bragg shared the Nobel Prize in 1915 for their work on analysing crystal structures using X-Rays. This award is notable not only as it was the first and [...]