His chemical experiments led him to the discovery that a valuable substance is obtainable from coal tar which has the property of dissolving india-rubber, and could be used for waterproofing silk and other textile fabrics; an idea which was patented a few months afterwards by Charles Macintosh, of Glasgow (see also Mackintosh).

It was here that he first put into practice his method of clinical teaching, which consisted in having the patients to be operated or prelected upon brought from the ward into a lecture-room or theatre where the students were seated conveniently for seeing and taking notes.

Syme's accession to the clinical chair was marked by two important changes in the conditions of it: the first was that the professor should have the care of surgical patients in the infirmary in right of his professorship, and the second, that attendance on his course should be obligatory on all candidates for the medical degree.

He began practice in London in February 1848; but early in May the same year difficulties with two of his colleagues at Gower Street and a desire to escape from animosity and contention led him to give up his appointment.

As a member of the general medical council called into existence by the act, he made considerable stir in 1868 by an uncompromising statement of doctrines on medical education, which were thought by many to be reactionary; they were, however, merely an attempt to recommend the methods that had been characteristic of Edinburgh teaching since William Cullen's time—namely, a constant reference of facts to principles, the subordination (but not the sacrifice) of technical details to generalities, and the preference of large professional classes and the magnetism of numbers to the tutorial system, which he identified with cramming.

[9] Syme is buried on the upper north-east terrace of St John's Episcopal Churchyard at the east end of Princes Street, Edinburgh.

Syme's character is not inaptly summed up in the dedication to him by his old pupil, John Brown, of the series of essays Locke and Sydenham: Verax, capax, perspicax, sagax, efficax, tenax.

Having grown up as the eldest surviving child of a surgeon, Agnes Syme Lister often assisted her husband's medical research, including taking dictation and case notes.