Multiple Myeloma: History and Discovery
The story of multiple myeloma is one of the most instructive in the history of medicine, because for nearly two centuries the disease was visible long before it was understood. A London tradesman's strange urine in the 1840s gave clinical chemistry its first tumor marker; a Ukrainian pathologist's autopsy in 1873 gave the disease its name; a Boston pathologist in 1900 identified the single cell from which it grows; and a chain of twentieth-century discoveries — serum electrophoresis, melphalan, stem-cell transplant, and the proteasome inhibitors — slowly turned a uniformly fatal bone disease into one of the most treatable blood cancers. This page traces that lineage carefully, separating what is firmly documented from what was once only suspected, because the people who read it deserve an honest account of how this knowledge was won.
Table of Contents
- Before the Name: "Softening of the Bones"
- Thomas Alexander McBean and the Peculiar Urine
- Bence Jones Protein: Medicine's First Tumor Marker
- Rustizky, Kahler, and the Naming of the Disease
- James Homer Wright and the Plasma-Cell Origin
- The M-Spike: Electrophoresis and the Monoclonal Protein
- Solving the Bence Jones Riddle: Light Chains
- From Melphalan to the Modern Era
- Legacy and What the History Teaches
- Research Papers and References
- Connections
Before the Name: "Softening of the Bones"
Long before anyone spoke of "multiple myeloma," physicians recognized a baffling and merciless illness in which the bones seemed to dissolve from within. A previously healthy adult would develop deep, gnawing pain in the back, ribs, and pelvis; bones would snap under trivial strain; and the patient would waste away over months or years, growing pale and exhausted, until death. Nineteenth-century doctors filed such cases under the Latin label mollities ossium — "softening of the bones" — a description of the deformed, fragile skeleton rather than an understanding of its cause.
The first reasonably documented case in the medical literature is usually credited to the distinguished London surgeon Samuel Solly, who in 1844 reported the illness of Sarah Newbury, a woman in her late thirties who suffered excruciating bone pain and a cascade of fractures — in her thighs, collarbones, and arm bones — before dying. At autopsy her marrow was found replaced by an abnormal red substance filled with unusual cells. Solly could describe the wreckage but, with the tools of his day, could not name the process that caused it. His report stands as a marker of how the disease appeared to careful observers before the microscope and the chemistry bench transformed what could be known.
It is worth pausing on how dark this period was for patients. There was no diagnosis in the modern sense, no treatment beyond the era's gentle palliatives — Sarah Newbury was reportedly given little more than rhubarb pills and orange-peel infusions — and no framework connecting the crumbling bones, the anemia, and the strange protein soon to be found in the urine. Every thread of that puzzle had been observed by 1844; weaving them into a single disease would take the rest of the century.
Thomas Alexander McBean and the Peculiar Urine
The case that changed everything belonged to Thomas Alexander McBean, a respectable London grocer who in 1845 consulted the physician Dr. William Macintyre with vague but persistent chest, back, and pelvic pain, along with fatigue. Macintyre, an able clinician, noticed something odd: McBean's urine, when heated, behaved unlike any he had seen. The patient's condition deteriorated relentlessly, and he died in 1846; the autopsy revealed the soft, fracture-prone bones of mollities ossium and marrow infiltrated by abnormal cells.
Macintyre had observed that the urine, on gentle heating, turned cloudy and threw down a precipitate — yet on stronger boiling the precipitate redissolved, only to reappear as the sample cooled again. This reversible, temperature-dependent behavior was wholly unlike ordinary albumin, and Macintyre recognized he was looking at a substance that did not fit the chemistry of the day. He preserved samples and, crucially, sent them to one of London's foremost analytical chemists for study. The decision to refer a strange clinical finding to a dedicated chemist is precisely what turned a single sad case into a landmark of laboratory medicine.
It should be noted that priority in this story is layered, and honest history keeps the layers distinct. The bone disease itself had been described by Solly and others; Macintyre clinically characterized McBean and first documented the peculiar heat behavior of his urine; and the chemist to whom he sent the samples — Henry Bence Jones — gave the protein the rigorous analysis that attached his name to it forever. Macintyre published his own account of the case in 1850. Each man contributed a different piece, and collapsing the whole episode into a single "discovery" flattens a more interesting collaboration.
Bence Jones Protein: Medicine's First Tumor Marker
Henry Bence Jones (1813–1873) was a physician-chemist at St George's Hospital in London and one of the early figures who tried to put medicine on a chemical footing. Receiving Macintyre's samples, he confirmed and extended the curious observation: adding acid to McBean's urine produced a precipitate that dissolved on boiling and re-formed on cooling. Bence Jones recognized this heat-soluble urinary protein as something genuinely new, and he published his findings in 1847 (a fuller paper followed in 1848). The substance he characterized has been known ever since as Bence Jones protein.
The historical importance of this protein is hard to overstate, and it is often described as the first tumor marker in the history of medicine — a measurable molecule in body fluid whose presence signals a specific cancer. For the first time, a malignancy revealed itself not only through the patient's symptoms or the pathologist's autopsy, but through a simple chemical test that could be run on a sample of urine. The principle that a tumor can betray itself by a substance it sheds into the blood or urine — the foundation of countless modern diagnostic tests — traces in a direct line back to this 1840s London case.
What Bence Jones could not know in 1847 was what his protein actually was. Its true molecular identity — that it consists of free immunoglobulin light chains, fragments of antibody molecules overproduced by the malignant plasma cells — would not be established for more than a century, and that resolution is taken up in a later section. For its time, the achievement was already remarkable: a reproducible chemical fingerprint of a disease that medicine could otherwise neither see nor name.
Rustizky, Kahler, and the Naming of the Disease
For roughly a quarter-century after Bence Jones, the disease still lacked a name that captured its essential nature: multiple tumors growing within the bone marrow. That name arrived in 1873, when the pathologist J. von Rustizky (working in the Russian Empire, associated with Kiev) performed an autopsy in which he found eight separate tumors arising in the bone marrow and, to describe them collectively, coined the term "multiple myeloma." The word fuses the Greek myelos (marrow) with the suffix -oma (tumor); "multiple" captured the scattered, many-sited nature of the disease. In Russia the condition is still sometimes called Rustizky's disease in his honor.
The more famous eponym, however, attached to a different physician. In 1889, Otto Kahler, an internist trained in Prague and working in Vienna, published a detailed and influential account of a patient — a 46-year-old physician named Dr. Loos — who exhibited the full clinical syndrome: skeletal pain, pallor and anemia, albuminuria, and a precipitable urinary protein, all tied together as one coherent disease and correlated with the autopsy findings. Because Kahler's report was so thorough and widely read, the disease became known across much of Europe as Kahler's disease, a name still encountered today.
Why did Kahler's name eclipse Rustizky's, even though Rustizky coined the actual term "multiple myeloma" sixteen years earlier? Historians point to the comparative completeness and reach of the two reports: Rustizky's brief account was not richly illustrated and was not immediately connected by the wider medical community to the growing collection of similar cases, whereas Kahler's detailed clinical-pathological synthesis crystallized the syndrome in physicians' minds. The episode is a recurring pattern in medical history — the name that endures often belongs not to the first observer but to the clearest and most influential expositor. (The condition has carried still other national eponyms; in Italy it has sometimes been called Bozzolo's disease, after Camillo Bozzolo.)
James Homer Wright and the Plasma-Cell Origin
By 1900 the disease had a name, a characteristic urinary protein, and a recognized clinical syndrome — but a fundamental question remained open: which cell, exactly, was the cancer made of? The marrow tumors clearly contained abnormal cells, yet their identity was disputed. The answer came from the American pathologist James Homer Wright (1869–1928) — the same Wright remembered for the Wright stain used to this day on blood smears — who in 1900 reported a 54-year-old man with rib tumors, a skull lesion, anemia, and albuminuria.
Examining the tumor tissue under the microscope, Wright recognized that its cells had the distinctive appearance of plasma cells: cells with an eccentric, off-center nucleus and a characteristic clumped ("clock-face") chromatin pattern. He concluded that the neoplasm arose not from marrow cells in general but specifically from a single cell type, the plasma cell, and he proposed the term "plasma-cell myeloma" — a name still used as a synonym for the disease. This was a conceptual leap: it identified the precise cell of origin and reframed multiple myeloma as a malignancy of the immune system's antibody-producing cells.
Wright's insight tied the whole picture together in a way that would only become fully meaningful decades later. Plasma cells are the body's antibody factories; a cancer of plasma cells is therefore a cancer of cells built to manufacture immunoglobulin. That single fact silently explained the abnormal proteins flooding the blood and urine — the M-spike and the Bence Jones protein — long before the chemistry of antibodies was understood. The plasma-cell origin is the conceptual hinge on which the entire modern understanding of myeloma turns.
The M-Spike: Electrophoresis and the Monoclonal Protein
The next great advance was a tool rather than a single case. In 1937, the Swedish biochemist Arne Tiselius reported a refined method of protein electrophoresis — separating serum proteins by their movement in an electric field — which resolved the blood's globulins into distinct alpha, beta, and gamma fractions. Tiselius would receive the 1948 Nobel Prize in Chemistry for this body of work. His technique gave medicine, for the first time, a way to see the protein composition of the blood as a profile of peaks.
Applied to myeloma, electrophoresis revealed something striking. Instead of the broad, smooth hump that normal, diverse antibodies produce in the gamma region, the serum of a myeloma patient showed a tall, narrow spike — the now-famous "M-spike" or M-protein ("M" for monoclonal). That sharp peak is the visible signature of a single clone of plasma cells churning out one identical antibody in enormous quantity. Here Wright's 1900 insight and Tiselius's 1937 method finally met: a cancer descended from one plasma cell makes one antibody, and electrophoresis renders that monoclonal flood as a single spike.
The M-spike transformed myeloma from a disease diagnosed mainly at autopsy into one that could be detected, measured, and monitored in living patients through a blood or urine test. Serum and urine protein electrophoresis remain, to this day, central to diagnosing the disease and tracking its response to treatment — a direct working descendant of Tiselius's apparatus. The concept also clarified a wider family of conditions, including the related disorder Waldenstrom's macroglobulinemia, in which a monoclonal protein is similarly produced.
Solving the Bence Jones Riddle: Light Chains
For more than a hundred years, Bence Jones protein remained a useful clinical curiosity whose deeper nature was unknown. The resolution came only after the structure of the antibody molecule itself was worked out — the achievement, in the late 1950s and 1960s, of immunologists including Gerald Edelman and Rodney Porter, who showed that an immunoglobulin is built from paired heavy chains and light chains. Edelman and Porter shared the 1972 Nobel Prize in Physiology or Medicine for elucidating antibody structure.
With the antibody's architecture in hand, the century-old puzzle dissolved. In 1962, Gerald Edelman and Joseph Gally demonstrated that Bence Jones protein is composed of free immunoglobulin light chains — the very light-chain subunits of antibodies, produced in excess by the malignant plasma-cell clone and small enough to be filtered by the kidney and spill into the urine. The strange heat-soluble substance Bence Jones had characterized in 1847 was, at last, identified: a fragment of an antibody, shed by a cancer of antibody-making cells.
This closing of the loop is one of the most satisfying arcs in medicine. The plasma-cell origin (Wright, 1900), the monoclonal protein made visible by electrophoresis (Tiselius, 1937), and the molecular identity of the Bence Jones protein (Edelman and Gally, 1962) are three windows onto one truth: multiple myeloma is the unchecked proliferation of a single antibody-producing plasma cell, and the abnormal proteins it sheds — in serum and urine — are the diagnostic fingerprints earlier physicians detected without being able to explain them. Free light chains in serum can now be measured directly, refining diagnosis still further.
From Melphalan to the Modern Era
For all the diagnostic progress, multiple myeloma remained essentially untreatable until the second half of the twentieth century. The first real chemotherapy arrived in the early 1960s with melphalan, an alkylating agent (developed from nitrogen-mustard chemistry, with early work by Larionov and colleagues and clinical evaluation advanced by investigators including Daniel Bergsagel). When melphalan was later combined with the corticosteroid prednisone, the pairing became the standard of care for decades and extended median survival into the range of a few years — a modest but genuine first victory against a previously hopeless disease.
The next leap was the idea of giving much higher doses of melphalan and then rescuing the patient's wiped-out marrow with a transplant of blood-forming stem cells. High-dose melphalan was pioneered by Tim McElwain and Ray Powles in 1983, and the strategy of high-dose therapy supported by autologous stem-cell transplantation was developed through the mid-1980s by Bart Barlogie and others, ultimately becoming a cornerstone of treatment for eligible patients. For the first time, deep and durable remissions became achievable in a substantial fraction of patients.
The modern transformation arrived around the turn of the twenty-first century with two new drug classes that exploit the peculiar biology of the antibody-overproducing plasma cell. The proteasome inhibitor bortezomib (Velcade) — the first of its kind — was approved by the U.S. FDA in May 2003 for multiple myeloma; it works by blocking the cell's protein-disposal machinery, which the protein-stuffed myeloma cell depends on heavily. In parallel, the immunomodulatory drugs — thalidomide and its more refined successor lenalidomide (with pomalidomide later) — reshaped therapy from another direction. Together with monoclonal antibodies (such as daratumumab) and, most recently, CAR T-cell and bispecific-antibody therapies, these agents have turned myeloma into one of the most treatable blood cancers, with survival measured today in many years rather than months. It remains, with rare exception, not curable — but the trajectory from Solly's rhubarb pills to targeted immunotherapy is one of the steepest in oncology.
Legacy and What the History Teaches
The arc of multiple myeloma compresses, in a single disease, much of the method of modern medicine. A careful clinician noticed an anomaly (Macintyre); a chemist refused to let it pass unexplained (Bence Jones); pathologists named the disease and found its cell of origin (Rustizky, Kahler, Wright); a physicist-chemist gave it a measurable signature (Tiselius); molecular biologists decoded the abnormal protein (Edelman, Porter, Gally); and pharmacologists, step by step, built treatments that work (melphalan, transplant, bortezomib, the immunomodulators). No single person "discovered" multiple myeloma; it was assembled, observation by observation, over a hundred and sixty years.
The history also carries a quiet lesson about honesty in science. Bence Jones is rightly famous, but his protein was first seen in Macintyre's clinic; Kahler's name is on the disease, but Rustizky coined the term; the urinary protein was a tumor marker for a century before anyone could say what it was. Good medical history resists the urge to award a tidy single credit and instead honors the chain — including the patients, Sarah Newbury and Thomas McBean among them, whose illnesses and whose preserved samples made the knowledge possible.
For a patient or family living with myeloma today, this lineage is more than antiquarian interest. The same Bence Jones protein, the same M-spike, and the same plasma-cell biology that nineteenth-century doctors stumbled upon are the very things a modern hematologist measures to diagnose the disease, gauge its burden, and confirm that treatment is working. The detailed contemporary picture — symptoms, staging, current therapy, and supportive care — is covered on the main Multiple Myeloma page; this history exists to show how hard-won, and how human, that knowledge has been.
Research Papers and References
The references below combine peer-reviewed historical reviews of multiple myeloma with curated PubMed topic-search links into the primary and secondary literature. Nineteenth-century primary reports (Solly 1844; Macintyre 1850; Bence Jones 1847–48; Rustizky 1873; Kahler 1889; Wright 1900) are named in the article as historical sources; the modern reviews below reconstruct and cite them. Each link opens at its source (publisher DOI or the National Library of Medicine) in a new tab.
- Kyle RA. Multiple myeloma: how did it begin? Mayo Clinic Proceedings. 1994;69(7):680-683. — PubMed 8015334
- Kyle RA, Steensma DP. History of multiple myeloma. Recent Results in Cancer Research. 2011;183:3-23. — doi:10.1007/978-3-540-85772-3_1
- Ribatti D. A historical perspective on milestones in multiple myeloma research. European Journal of Haematology. 2018;100(3):221-228. — doi:10.1111/ejh.13003
- Rosenfeld L. Henry Bence Jones (1813-1873): the best "chemical doctor" in London. Clinical Chemistry. 1987;33(9):1687-1692. — PubMed 3304739
- Clamp JR. Some aspects of the first recorded case of multiple myeloma. The Lancet. 1967;2(7530):1354-1356. — PubMed 4168480
- Kyle RA. Henry Bence Jones — physician, chemist, scientist and biographer: a man for all seasons. British Journal of Haematology. 2001;115(1):13-18. — doi:10.1046/j.1365-2141.2001.03061.x
- Edelman GM, Gally JA. The nature of Bence-Jones proteins: chemical similarities to polypeptide chains of myeloma globulins and normal gamma-globulins. Journal of Experimental Medicine. 1962;116(2):207-227. — doi:10.1084/jem.116.2.207
- Kyle RA, Rajkumar SV. Multiple myeloma. Blood. 2008;111(6):2962-2972. — doi:10.1182/blood-2007-10-078022
- Multiple myeloma — history and historical milestones (PubMed topic search) — PubMed: multiple myeloma history milestones
- Bence Jones protein — discovery and free light chains (PubMed topic search) — PubMed: Bence Jones protein and light chains
- Tiselius and serum protein electrophoresis — the M-protein (PubMed topic search) — PubMed: electrophoresis and the M-protein
- Melphalan therapy for multiple myeloma (historical) (PubMed topic search) — PubMed: melphalan therapy for myeloma
- High-dose melphalan and autologous stem-cell transplantation (PubMed topic search) — PubMed: high-dose melphalan and stem-cell transplant
- Bortezomib and proteasome inhibitors in multiple myeloma (PubMed topic search) — PubMed: bortezomib and proteasome inhibitors
External Authoritative Resources
- National Cancer Institute — Plasma Cell Neoplasms / Myeloma
- NCI Dictionary of Cancer Terms — Bence Jones protein
- PubMed — All research on the history of multiple myeloma