More than a century elapsed between the first description of a case of pernicious anemia, by Combe, of Edinburgh, in 1822, and the investigations of Castle and his colleagues, which mark the beginning of our present understanding of the disease. This paper gives an account of the work carried out during that period in defining and investigating the condition.
A paper1 entitled "History of a Case of Anaemia," read by Combe, on May 1, 1822, contains the first authentic description of a case of pernicious anemia. The patient was a corn merchant's servant, aged 47 years, who had always enjoyed perfect health. When Combe was first consulted he was immediately struck by the man's peculiar appearance. "His face, lips and the whole extent of the surface, were of a deadly pale color . . . his motions and speech were languid; he complained much of weakness.