A drop from the nose of Fleming, who had a cold, fell onto an agar plate where large yellow colonies of a contaminant had grown, and lysosyme was discovered. He made this important discovery because when he saw that the colonies of the contaminant were fading, his mind went straight to the right cause of the phenomenon he was observing—that the drop from his nose contained a lytic substance. And also immediately, he thought that this substance might be present in many secretions and tissues of the body. And he found this was so—the substance was in tears, saliva, leucocytes, skin, fingernails, mother's milk—thus very widely distributed in amounts and also in plants.

A good gulp of hot whisky at bedtime—it’s not very scientific, but it helps.
Response when questioned about the common cold.

For the birth of something new, there has to be a happening. Newton saw an apple fall; James Watt watched a kettle boil; Roentgen fogged some photographic plates. And these people knew enough to translate ordinary happenings into something new...

I have been trying to point out that in our lives chance may have an astonishing influence and, if I may offer advice to the young laboratory worker, it would be this—never neglect an extraordinary appearance or happening. It may be—usually is, in fact—a false alarm that leads to nothing, but may on the other hand be the clue provided by fate to lead you to some important advance.

In my first publication I might have claimed that I had come to the conclusion, as a result of serious study of the literature and deep thought, that valuable antibacterial substances were made by moulds and that I set out to investigate the problem. That would have been untrue and I preferred to tell the truth that penicillin started as a chance observation. My only merit is that I did not neglect the observation and that I pursued the subject as a bacteriologist. My publication in 1929 was the starting-point of the work of others who developed penicillin especially in the chemical field.

It has been demonstrated that a species of penicillium produces in culture a very powerful antibacterial substance which affects different bacteria in different degrees. Generally speaking it may be said that the least sensitive bacteria are the Gram-negative bacilli, and the most susceptible are the pyogenic cocci ... In addition to its possible use in the treatment of bacterial infections penicillin is certainly useful... for its power of inhibiting unwanted microbes in bacterial cultures so that penicillin insensitive bacteria can readily be isolated.

It is the lone worker who makes the first advance in a subject: the details may be worked out by a team, but the prime idea is due to the enterprise, thought, and perception of an individual.

It was astonishing that for some considerable distance around the mould growth the staphococcal colonies were undergoing lysis. What had formerly been a well-grown colony was now a faint shadow of its former self...I was sufficiently interested to pursue the subject.
[Sep 1928, the first observation of penicillin. Lysis is the dissolution or destruction of cells.]

One sometimes finds what one is not looking for.

While working with staphylococcus variants a number of culture-plates were set aside on the laboratory bench and examined from time to time. In the examinations these plates were necessarily exposed to the air and they became contaminated with various micro-organisms. It was noticed that around a large colony of a contaminating mould the staphylococcus colonies became transparent and were obviously undergoing lysis. Subcultures of this mould were made and experiments conducted with a view to ascertaining something of the properties of the bacteriolytic substance which had evidently been formed in the mould culture and which had diffused into the surrounding medium. It was found that broth in which the mould had been grown at room temperature for one or two weeks had acquired marked inhibitory, bacteriocidal and bacteriolytic properties to many of the more common pathogenic bacteria.

I doubt that Fleming could have obtained a grant for the discovery of penicillin on that basis [a requirement for highly detailed research plans] because he could not have said, 'I propose to have an accident in a culture so that it will be spoiled by a mould falling on it, and I propose to recognize the possibility of extracting an antibiotic from this mould.'