[For] those suffering under the thraldom of the vice [of opium eating] … it is well to avoid undue harshness with the patient; and it should be carefully remembered, that in many instances the sufferers are more objects of pity than of blame.

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.

In not a few the [opium-eating] habit has crept upon them almost unconsciously, during the medicinal use of opiates to soothe pain, to remove sleeplessness, or to arrest protracted bowel-complaint. The risk of this evil should therefore be carefully borne in mind, for life-long misery has often been caused by undue laxity in the prescribing of opiates.

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 possible that in ten years’ time penicillin itself will be a back number and will be replaced by something better. It is quite certain though that to displace penicillin any newcomer will have to be very, very good.

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.

The active agent is readily filterable and the name “penicillin” has been given to filtrates of broth cultures of the mould. … It is suggested that it may be an efficient antiseptic for application to, or injection into, areas infected with penicillin-sensitive microbes.

The greatest possibility of evil in self-medication [with penicillin] is the use of too-small doses, so that, instead of clearing up the infection, the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bred out which can be passed on to other individuals and perhaps from there to others until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save. In such a case the thoughtless person playing with penicillin treatment is morally responsible for the death of the man who finally succumbs to infection with the penicillin-resistant organism. I hope this evil can be averted.

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.

You do not know what you will find, you may set out to find one thing and end up by discovering something entirely different.

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.'

Applied research generates improvements, not breakthroughs. Great scientific advances spring from pure research. Even scientists renowned for their “useful” applied discoveries often achieved success only when they abandoned their ostensible applied-science goal and allowed their minds to soar—as when Alexander Fleming, “just playing about,” refrained from throwing away green molds that had ruined his experiment, studied them, and discovered penicillin. Or when C. A. Clarke, a physician affiliated with the University of Liverpool, became intrigued in the 1950s by genetically created color patterns that emerged when he cross-bred butterflies as a hobby. His fascination led him—“by the pleasant route of pursuing idle curiosity”—to the successful idea for preventing the sometimes fatal anemia that threatened babies born of a positive-Rhesus-factor father and a negative-Rhesus-factor mother.

The history of penicillin is one of the disgraces of medical research. Fleming published his classic paper in the British Journal of Experimental Pathology for June, 1929, but it was not until 1939 that Florey followed up the clue. An antiseptic which is almost ideal, inasmuch as it has no toxic effects, was allowed to slumber for ten years. Had it not been for the exigencies of the present war it might be slumbering still.