Henry Bence Jones – physician, chemist, scientist and biographer: A man for all seasons

The name Bence Jones is recognized today as the name of a protein excreted by patients with multiple myeloma. It is ironic that Bence Jones was not the first to describe the characteristics of the protein, but he recognized its place in the diagnosis of myeloma when he wrote, `I need hardly remark on the importance of seeking for this oxide of albumen in other cases of mollities ossium' (Bence Jones, 1847). J. F. Heller (1846) had described a protein in the urine that precipitated when warmed a little above 508C, and then disappeared on further heating. Although Heller did not recognize the precipitation of the protein when the urine was cooled, it is almost certain that this was Bence Jones protein. He differentiated this new protein from albumin and casein. It should be noted that the term `albumen' had been introduced less than a decade earlier. Both Thomas Watson, a well-known physician in London, and William Macintyre had sent a urine sample from a patient, Thomas Alexander McBean, to Henry Bence Jones. Dr Macintyre had examined the patient's urine on 30 October 1845 because the patient had had oedema 4 months earlier. Macintyre's examination revealed no sugar, but the urine was opaque, acid and of high density, and its specific gravity was 1 ́035. The urine, when heated, was found to `abound in animal matter.' A precipitate developed after the addition of nitric acid. The precipitate `underwent complete solution on the application of heat, but again consolidated on cooling' (Macintyre, 1850). The next day, Dr Watson sent a urine sample and the following note to Henry Bence Jones, a 31-year-old physician at St. George's Hospital, who had already established a reputation as a clinical chemist. Saturday, Nov. 1st 1845 Dear Dr Jones, The tube contains urine of very high specific gravity. When boiled it becomes slightly opaque. On the addition of nitric acid, it effervesces, assumes a reddish hue, and becomes quite clear; but as it cools, assumes the consistence and appearance which you see. Heat reliquifies it. What is it? Dr Macintyre, a 53-year-old Harley Street consultant and physician to the Metropolitan Convalescent Institution and to the Western General Dispensary, St. Marylebone, had cared for the patient, Thomas Alexander McBean, intermittently for over a year. In September 1844, McBean jumped out of an underground cavern on his country holiday and `instantly felt as if something had snapped or given way within the chest, and for some minutes he lay in intense agony unable to stir' (Macintyre, 1850). Macintyre applied a strengthening plaster to his chest. This was of only temporary benefit. He was subsequently treated with the removal of a pound of blood and application of leeches, and his pain resolved. He had a relapse during the spring of 1845 and responded well to a course of steel and quinine. He again had a relapse and was cared for by Macintyre and Watson, but his disease progressed and he died on 1 January 1846 (Kyle, 2000). An autopsy revealed soft and brittle bones that were filled with a `gelatiniform substance' (Macintyre, 1850). Microscopic examination of the bone marrow revealed cells with the features of plasma cells (Dalrymple, 1846). Bence Jones noted that the addition of nitric acid produced a precipitate that was redissolved by heat and formed again on cooling, an observation which confirmed the findings of Watson and Macintyre. Jones concluded that the protein was an `oxide of albumen' and from the ultimate analysis was the `hydrated deutoxide of albumen' (Bence Jones, 1847, 1848). He believed that chlorine was responsible for the formation of this protein. He calculated that there were 66 ́97 parts of hydrated deutoxide of albumin per 1000 parts of urine, and this amount was equivalent to the protein of albumin in normal blood. Thus, every ounce of urine contained the same amount of protein as an equal quantity of blood (Bence Jones, 1847, 1848). Some have suggested that the term `multiple myeloma' should be designated as McBean's disease with Macintyre's proteinuria. Although Bence Jones was not the first to recognize the heat properties of the urine, he recognized its importance in patients with skeletal disease.