From Ancient Mysteries to Modern Breakthroughs: The Fascinating Evolution of Myeloma Through the Ages
When we think about myeloma, we tend to think of modern medicine: bone marrow biopsies, M-proteins, light chains, chemotherapy, stem cell transplants, immunotherapy, CAR-T therapy, and all the other terms that become part of our vocabulary after diagnosis.
But the disease itself is anything but new.
Evidence suggests that a condition consistent with multiple myeloma may have existed thousands of years ago. The story of how doctors eventually recognized, named, diagnosed, and began treating it stretches across centuries.
What Is Multiple Myeloma?
Multiple myeloma is a cancer of plasma cells, a type of white blood cell found in the bone marrow. In myeloma, abnormal plasma cells multiply and can produce abnormal proteins that may be detected in the blood or urine.
As those cells accumulate, they can interfere with the bone marrow's ability to produce healthy blood cells and can affect other parts of the body.
Myeloma can cause anemia, fatigue, bone pain, weakened bones and fractures, kidney problems, high calcium levels, and an increased vulnerability to infections. Some people have few or no symptoms early in the disease, which is one reason myeloma can sometimes be difficult to recognize.
Today we know much more about what causes those problems.
For most of human history, doctors didn't.
Could Myeloma Date Back to Ancient Egypt?
One of the most intriguing chapters in myeloma's history takes us all the way back to ancient Egypt.
Researchers studying human remains from the archaeological site of Qubbet el-Hawa in Aswan identified skeletal changes in an individual who lived roughly 3,800 years ago that researchers considered consistent with multiple myeloma.
The individual appears to have survived with significant disease for some time, suggesting that others may have cared for them as their physical condition deteriorated.
Of course, doctors couldn't perform blood tests, bone marrow biopsies, or protein studies thousands of years later, so we can't diagnose an ancient individual with the certainty possible in a living patient today.
Still, the findings provide fascinating evidence that diseases resembling myeloma may have affected human beings long before medicine had a name for them.
The First Recognized Cases
The modern medical story of myeloma begins in the 1800s.
In 1844, English physician Samuel Solly described the case of Sarah Newbury, a 39-year-old woman who had suffered severe back pain for several years.
Her bones had become extraordinarily fragile. Both femurs fractured while she was being moved, and she died only days later.
At the time, Solly diagnosed her condition as mollities ossium, meaning "softening of the bones."
After her death, examination revealed extensive abnormalities in her skeleton. The cancellous portions of her sternum and femurs had been replaced by a reddish material, and fractures were found in several other bones.
Doctors didn't yet understand what they were seeing, but observations like these were beginning to reveal the characteristics of a disease that would eventually become known as multiple myeloma.
Thomas McBean and a Very Important Urine Sample
Another important early case involved Thomas Alexander McBean, a London tradesman who developed severe bone pain and other symptoms.
His urine contained something unusual.
Physician and chemical pathologist Henry Bence Jones studied the abnormal urinary protein and published his observations in the 1840s.
That protein would eventually become known as Bence Jones protein.
Today, we understand Bence Jones proteins as free immunoglobulin light chains that can be produced by abnormal plasma cells. Their discovery became one of the most important early steps toward understanding and diagnosing multiple myeloma.
Imagine that for a moment.
Doctors didn't have CT scans, PET scans, electrophoresis, free light-chain assays, or bone marrow biopsies.
But someone's urine was beginning to reveal what was happening inside the bone marrow.
Where Did the Name "Multiple Myeloma" Come From?
The disease still needed a name.
In 1873, Russian physician J. von Rustizky described multiple separate tumors within the bone marrow during an autopsy. He used the term multiple myeloma to describe what he observed.
The name stuck.
A few years later, Austrian physician Otto Kahler published a detailed description of a patient with many of the characteristics we now associate with myeloma, including bone pain, anemia, urinary protein, and skeletal abnormalities.
His work became so closely associated with the disease that multiple myeloma was sometimes referred to as Kahler's disease.
Connecting the Protein to the Bone Marrow
By the end of the nineteenth century, researchers were beginning to connect pieces of the puzzle.
In 1898, Weber proposed that the bone marrow was the source of Bence Jones protein.
That connection was important.
The strange substance appearing in patients' urine wasn't simply a kidney problem. Researchers were beginning to understand that what they were finding in the urine was connected to abnormalities occurring within the bone marrow.
Over the following decades, scientists continued investigating that relationship.
Researchers studying patients with Bence Jones proteins increasingly suspected that these proteins were being produced by abnormal cells within the marrow.
Slowly, myeloma was becoming understandable not simply as a disease that destroyed bones, but as a disease involving abnormal plasma cells and the proteins they produced.
Kappa and Lambda Enter the Story
Another major breakthrough came from studying Bence Jones proteins themselves.
In the early twentieth century, researchers discovered that these proteins weren't all identical. They could be separated into two major groups.
Those groups eventually became what we know today as kappa (κ) and lambda (λ) light chains.
Later research helped establish the relationship between Bence Jones proteins, immunoglobulins, and the abnormal proteins produced in multiple myeloma.
In 1956, Leonard Korngold and Rose Lipari demonstrated important relationships between Bence Jones proteins and myeloma proteins. Their names live on in the terminology we still use today: kappa and lambda.
Further work on antibody structure helped scientists understand heavy and light chains and ultimately gave physicians much better tools for identifying and monitoring monoclonal proteins.
For today's myeloma patient, words like kappa, lambda, M-protein, and light chains can quickly become part of everyday life.
It took generations of researchers to figure out what those words actually represented.
And Then There Were the Treatments...
Understanding the disease was only half the battle.
Treating it was another matter entirely.
Early attempts at treating people with myeloma included remedies that sound almost unbelievable today: rhubarb, leeches, quinine, iron preparations, opiates, and various other treatments aimed primarily at relieving symptoms.
Doctors were doing what they could with the knowledge they had.
By the twentieth century, researchers began experimenting with medications that they hoped might actually control the disease.
One of those was urethane.
Beginning in the 1940s, urethane was used as a treatment for myeloma, and early reports suggested that some patients experienced improvements in bone pain, hemoglobin levels, or abnormal protein measurements.
For a time, it appeared promising.
Unfortunately, further study told a very different story.
Urethane could cause significant toxicity, including nausea, vomiting, weight loss, blood abnormalities, and liver damage. It was also found to be carcinogenic.
More importantly, controlled studies failed to show the survival benefit physicians had hoped for.
In one study comparing urethane with placebo in patients with symptomatic myeloma, the patients receiving placebo actually had a better median survival.
It was another reminder of something medical science would learn repeatedly:
A treatment can appear to work without actually helping people live longer.
At that time, options for patients with myeloma remained extremely limited, and survival after diagnosis was often measured in months rather than years.
That makes what happened next even more remarkable.
From Months to Years
The history of multiple myeloma is really a story of people slowly putting together pieces of an enormous puzzle.
One doctor noticed unusual bones.
Another studied a strange protein in urine.
Someone else connected that protein to bone marrow.
Researchers identified plasma cells.
Others discovered immunoglobulin heavy and light chains.
Eventually, scientists began understanding the biology driving the disease itself.
And each discovery gave the next generation something to build upon.
Today, we have treatments those early physicians couldn't possibly have imagined: proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, stem cell transplantation, bispecific antibodies, CAR-T cell therapy, and other approaches that continue to change the outlook for people living with myeloma.
We still don't have all the answers.
Multiple myeloma remains a serious and complex disease, and patients can have very different experiences with it. But we've traveled an extraordinary distance from the days when physicians could only document fragile bones and wonder what had happened.
And the Story Isn't Over
I find the history of myeloma fascinating because it puts today's medicine into perspective.
Every blood test we have today exists because someone asked a question.
Every treatment exists because someone tried something, studied what happened, learned from failures, and tried again.
Even the words kappa and lambda on a lab report have a history.
For patients, those discoveries aren't simply interesting pieces of medical trivia. They represent generations of work that have turned a disease once measured in months into one that many people now live with for years.
And we're not finished.
If the history of myeloma has taught us anything, it's that today's breakthrough can become tomorrow's starting point.
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