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Most people know Alexander Fleming for the mouldy dish of 1928. Seven years earlier, he found something odder in his own runny nose: an enzyme, lysozyme, that breaks bacteria open. It was useless against dangerous germs, but it taught him what an unexpected bacteria-free patch on a culture plate could mean.
How did Alexander Fleming discover lysozyme?
In late 1921 Fleming had a cold and decided to culture a sample of his own nasal mucus, according to Claudia Kalb's account in Scientific American. His research student, V. D. Allison, saw Fleming marvelling over the dish and later described it: near the blob of nasal mucus there were no bacteria.
Fleming's own report, published in 1922 in the Proceedings of the Royal Society B, describes the nasal secretion of a patient with acute coryza (a heavy cold) being cultured every day on blood agar plates. For three days almost nothing grew. On the fourth day, a plate showed many small colonies of large Gram-positive cocci. Fleming called this microbe *Micrococcus lysodeikticus*, and it was the one his new substance dissolved most clearly.
He described that substance as present in the tissues and secretions of the body and "capable of rapidly dissolving certain bacteria". Because it behaved like a ferment, the old word for an enzyme, he named it lysozyme.
Where is lysozyme found, and how did Fleming test it?
Once the nose had given a result, Fleming widened the search. The Scientific American account lists tears, saliva, sputum, blood serum, semen, pus and fluid from ovarian cysts, and all of them tested positive. To get enough tears, the team squeezed lemon peel in front of their eyes, and laboratory attendants were paid three pence per sample. Lysozyme also turned up in turnips, egg whites, and tissues from rabbits, dogs and guinea pigs.
A 2017 review by Ragland and Criss in PLOS Pathogens reports lysozyme in blood and liver, in secretions including tears, urine, saliva and milk, and at mucosal surfaces.
How does lysozyme kill bacteria?
Most bacteria are wrapped in a cell wall made of peptidoglycan, a mesh of sugar chains cross-linked by short peptides. Lysozyme hydrolyses the β-1,4 glycosidic bond between two alternating sugars in that mesh, N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG), according to the Ragland and Criss review. Because it breaks a bond using water, lysozyme belongs to the hydrolases, one of the six enzyme classes you learn in school biology.
The same review explains why it works better on some bacteria than others. Gram-positive bacteria have a thick layer of peptidoglycan exposed on the outside. In Gram-negative bacteria, the layer is thinner and sits behind an outer membrane that blocks molecules larger than about 650 Da, and human lysozyme is about 14.7 kDa. That is the same wall difference behind the Gram stain that sorts bacteria into two groups.
Why didn't lysozyme become a medicine like penicillin?
Lysozyme only worked well against bacteria that are harmless to people and was ineffective against deadly ones such as staphylococci, Scientific American reports. When Fleming presented it at the Medical Research Club in December 1921, nobody asked a single question.
The work still mattered. The same account says lysozyme primed Fleming to recognise the potential of the Penicillium mould that landed in his dish in 1928. His penicillin paper of 1929 is reprinted in the Bulletin of the World Health Organization. In 1945 he shared the Nobel Prize in Physiology or Medicine with Ernst Boris Chain and Howard Florey for the discovery of penicillin and its curative effect.
What can you learn from Fleming's runny nose?
Worked answer. Suppose an exam asks: why is lysozyme in tears more effective against Gram-positive than Gram-negative bacteria?
Lysozyme is a hydrolase that breaks the β-1,4 bond between NAM and NAG in peptidoglycan.
Gram-positive bacteria have a thick peptidoglycan layer on the outside, so the enzyme reaches it directly.
Gram-negative bacteria have a thin layer behind an outer membrane that keeps out large molecules such as lysozyme.
If any of these steps feels shaky, the Fermi Concept Library gives every concept in biology and chemistry its own lesson, so you can trace cell walls back to their sugars.
The odd-result habit. Fleming's lysozyme work follows a pattern you can use in any practical:
Write down what you expected before you look at the result.
Record what you actually saw, even if it looks like a mistake.
Ask what would have to be true for that result to happen.
Change one thing and repeat, as Fleming moved from mucus to tears to egg white.
Find where it stops working; lysozyme's limit with staphylococci was as useful to know as its success.
If you are revising how the body keeps germs out, our guide to pathogens, immunity and vaccines puts barriers like tears and saliva in context.
