In 1844, Mr. Thomas Alexander McBean,a 45-year-old London grocer, developedsevere chest pains following a minor accident. His pain was relieved by a plastercast, but recurred a month later, and continued without cease until his death in 1846.

His ddctor had conducted a urinalysis,and had noted a strange opacity uponboiling. The opacity disappeared with theaddition of nitric acid, but reappearedupon cooling.

On November 1, 1845, the urine samplewas sent to Henry Bence Jones along witha note asking, “¿�Whatis it?―Bence Jones,then a 31-year-old physician, proceededto identify the protein as the “¿�hydrateddeutoxide of albumen.― He was able todescribe the protein's precipitation attemperatures between 45°and 70°C., andto note that it redissolved at heats bothabove and below. When a post-mortemon the patient revealed softening of thecancellous bones, Bence Jones was led totheconclusionthatthiswas a hithertoundescribeddisease,“¿�essentiallymalignantin nature,― affecting the “¿�osseoussystem.―Today, these findings are acknowledgedto be the first recorded case of multiplemyeloma —¿�and thepuzzlingsubstanceinthe urine has ever after been known as theBence-Jonesprotein.

Bence Jones was born at ThoringtonHall, England on December 31, 1813. Heattended Trinity College,. Cambridge,studying divinity and hoping to take theholy orders, but changed his mind in favor

of joining a relative who was a merchantin Liverpool. Finally, after six months'work dispensingmedicinesin a hospitalapothecary, he decided to become a doctor and received, in succession, an A.B. in1836,an A.M. ii@1842,an M.B. in1845and an M.D. in 1849.

On leaving Cambridge, he continuedhis medical training at St. George's Hospital in London, and studied chemistrywith Thomas Graham, one of the foremost chemists of his day, at UniversityCollege. In 1841, he visited Germany, andcontinued his chemical studies with Liebig.He became licentiate of the Royal College of Physicians in 1842, and fellowin 1849.

From 1846 until 1860, Bence Jones wasAssistant Surgeon, and later Surgeon, toSt. George's Hospital. Thomas Huxley,the famed biologist (and grandfather ofAldous), was especially appreciative ofthe care, and stated in his autobiography,“¿�InApril another good friend, BenceJones, lent the invalid (Huxley) his homeat Folkstone for three months.― CharlesDarwin, too, was a friend and patient.The Life and Letters of Charles Darwingives the following description of Jones'treatment: “¿�.. . toward the close of theyear [1865] Darwin began to recover underthe care of the late Dr. Bence Jones whodieted him severely and as he (Darwin) expressed it, ‘¿�halfstarved him to death.'―Herbert Spencer, the social-Darwinist,wrote of him in An Autobiography:

VOL. 28, NO. 1JANUARY/FEBRUARY1978 47

Henry Bence Jones(1813-1873)

“¿�Speakingof drugs, Bence Jones said thatthere is scarcely one which may not underdifferent conditions produce opposite effects.― And Michael Faraday was stillanother loyal admirer. In 1870, BenceJones published a biography of the scientist in two volumes.

Bence Jones ‘¿�wasalso a chemist, and inan age when i@hedescription of diseasewas often-a mere catalogue of symptoms,he devoted himself to applying chemistry

‘¿�totherapeutics. This can readily be seenfrom the titles of some of his papers:“¿�AnimalChemistry in its Application toStomach and Renal Diseases,― (1850),“¿�Lectureson Some of the Applications ofChemistry and Mechanics to Pathologyand Therapeutics,― (1867), and “¿�CroonianLectures on Matter and Force,― (1868).But what makes Jones' synthesis of purescience and clinical practice even morestriking is that they were carried on simultaneously. It is said that he began laboratory work each day at dawn, and spentafternoons and evenings doing his roundsat?the hospital. It was only when compelledby warnings of a serious cardiac lesionthat he curtailed his clinical work, anddevoted himself wholly to scientificstudies.

In addition to his description of whatwe now call the Bence-Jones protein, hewas also the first to describe the occurrence of xanthine in urine. He did an extensive analysis of kidney stones as well:in noting the appearance of a cystinecalculus, he made medical history bydescribing its sulphur content.

Bence Jones' early work in understanding multiple myeloma has, of course, beenadded to in the century following hisdeath. Today, we know that his protein isfound in 70 percent ofall patients afflictedwith the disease. Fihdings have beenrecofddd in greater detail, including@re- -cognition ‘¿�ofmore localized plasmacytomas. And in 1944, Waldenstroin describedmacroglobinemia, leading the study of thedisease into the fields of immunology andmolecular biology. But Henry Bence Jonesremains a pioneer among physicians ofthe nineteenth century, for it was his workwhich brought to bear the results ofchemical research upon the clinical aspectsof disease.

1846: AUTOPSY AN!) HISTOLOGY

The 1846 death certificate of ThomasMcBean listed “¿�atrophyfrom albuminuria― as the cause of death. Although we know today that this wasa case of mWtiple myeloma, the original diagnosis was not unreasonable,for in those days, “¿�al'buminuria―wasused as a non-specific term, and included proteinuriaas well.

-. The autopsy revealed significant

findings in the ribs, the sternum, andthe cervical, thoracic and lumbarvertebrae. These bones were soft andeasily breakable; their interior hadbecome red, sodden, and @‘¿�gelatiniform.―

John Dalrymple, surgeon to theOpthalmic Hospital, performed ahistological examination, and decribed the nucleated cells which madeup most of this softened mass. Henoted that although they were ofvarious sizes and shapes, many wererounded, and that even the smallercells' were “¿�oneand a half to. twicelarger than the-average blood cell-orblood disc―(red blood cell). The larger, less evenly rounded cells,. .he noted, had two and frequently threenuclei.

This is a plausible, if incomplete,description of malignant plasma cellswith multinucleated forms. ButDalrymple, Bence Jones and the otherphysicians involved considered thisdisease to be a malignant bone disorder. They were at a loss, however,to understand why the tumor remained only inside the bone, andthought finally that the limited lifespanoLthe.nucleated cells must inturn havèTimited the mass of thetumor.

@*1odern -science has found thatplasmacytomas as part of multiplemycloma can occur in soft tissue aswell, but it is rare, and more cornmonly confined to bone. Yet the reason for this,-'fir@t, pondered in 1846,remains today an unanswered question.

48 CA-A CANCER.dOURNALFORCLINICIANS