Jan Waldenström: ‘I am only a clinician’

Waldenström produced seminal discoveries in monoclonal gammopathies and macroglobulinemia.

Best known for his discovery of Waldenström’s macroglobulinemia, Jan Gosta Waldenström, MD, also made significant contributions to the exploration of porphyria, paraneoplastic phenomena and the carcinoid syndrome. Those who knew him, though, said he was as skilled in the classroom, the clinic and the art gallery as he was in the lab.

Waldenström was born in Stockholm, Sweden in 1906. He was the grandson of a professor of internal medicine and the son of a professor of orthopedic surgery. He earned his MD from the University of Uppsala before studying organic chemistry at The Technical University of Munich, Germany under the direction of Nobel Laureate Hans Fischer, MD.

Waldenström’s work with Fischer led to the publication of the monograph “Studien Über Porphyric” in 1939. Along with co-author Bo Vahlquist, MD, Waldenström introduced the term “porphobilinogen” to describe a chromogen substance that is an intermediate in the biosynthesis of heme and porphyrins. Representing an error of metabolism, porphobilinogen appears in the urine of people with porphyria.

Jan Gosta Waldenström Photo Courtesy of RA Kyle

Waldenström returned to Uppsala after only a year and became a professor of theoretical medicine there in 1941. He was named professor of practical medicine at the University of Lund and physician in chief at Malmö General Hospital three years later. He was later tapped to head the department of internal medicine at Malmö and held that position until he retired in 1972.

Discovery of Waldenström’s macroglobulinemia

Waldenström’s most famous achievement is his work involving a condition that would later bear his name. The condition, also known as lymphoplasmacytic lymphoma, is a rare, chronic plasma cell neoplasm that affects plasma cells and lymphocytes. Robert A. Kyle, MD, and Kenneth C. Anderson, MD, recounted the process of uncovering the disease in a tribute to Waldenström published in the journal Blood in 1997.

In 1944, Waldenström described two patients with oronasal bleeding, lymphadenopathy, normochromic anemia, increased erythrocyte sedimentation rate, thrombocytopenia, hypoalbuminemia, low serum fibrinogen and increased numbers of lymphoid cells in the bone marrow. He also noted prolonged bleeding after lymph node biopsy and bone marrow aspiration, lobar pneumonia and retinal hemorrhages.

The condition differed from multiple myeloma because bone radiographs were normal and patients were not experiencing bone pain. Moreover, excess cells in the bone marrow in these patients were lymphoid, not plasma cells as in his patients with multiple myeloma. In these two patients, he noted the poor quality of the blood and bone marrow smears, presumably from the hyperproteinemia.

Kyle and Anderson said Waldenström “observed an abnormally large amount of a homogeneous globulin with a sedimentation coefficient of 19 S and 20 S, corresponding to a molecular weight of more than 1,000,000.” He theorized that the protein was one giant molecule rather than a collection of smaller globulin molecules, an idea that remains characteristic of the clinical presentation and lab abnormalities of Waldenström’s macroglobulinemia related to excess of monoclonal immunoglobulin M.

This research led to Waldenström’s development of the concept of monoclonal vs. polyclonal gammopathies, first presented in 1961. Kyle told HemOnc Today that Waldenström discovered that patients with a monoclonal gammopathy either had a malignant lesion or a potentially malignant lesion whereas patients with a polyclonal increase in immunoglobulins had a reactive or an inflammatory process.

“He was known far and wide for these studies and was considered the seminal person throughout his career in monoclonal gammopathies,” Kyle said. “In my opinion, he should have received a Nobel Prize for his work on either monoclonal gammopathies or Waldenström’s macroglobulinemia.”

From art to botany to travel

For all his academic and medical accolades, Waldenström was a man of catholic intellectual pursuits and spoke four languages. Claus A. Pierach, MD, wrote about a visit to Waldenström’s home: “the walls decorated with art by Munch, Rodin and Braque, his bookshelves overflowing with old botanical folios. A drive with him through the Swedish countryside was a living lesson in history as he described the various castles and churches en route. Entering one of these magnificent edifices revealed how warmly the custodians greeted an old friend.”

Kyle, professor of medicine, laboratory medicine and pathology at the Mayo Clinic in Rochester, Minn., and an internationally renowned hematologist and researcher in his own right, first met Waldenström in the 1960s. The men remained friends for more than 30 years until Waldenström’s death in 1996 at the age of 90.

“He was never at the bench, so to speak, manipulating test tubes and running instruments,” Kyle said. “His research was more clinical research in which he saw patients and saw things no one else had seen in them.”

Neil Abramson, MD, wrote about his time hosting Waldenström while Abramson was doing his hematology fellowship at Harvard Medical School.

“During this visit, I took Dr. Waldenström on teaching rounds daily, which was a most pleasant experience for patients and a great educational opportunity for house officers, nursing staff and students,” Abramson wrote in Clinical Hematology/Oncology Newsletter. “Although Dr. Waldenström’s contributions to medicine had been so significant, he said repeatedly, ‘I am only a clinician.’” – by Jason Harris

For more information:

• Abramson N. I am only a clinician. Clinical Hematology/Oncology Newsletter website. http://community.e-baptisthealth.com/services/bci/educational/docs/Iamonlyaclinician.pdf. Accessed March 3, 2009.
• Blood. 1997;89:4245-4247.
• Pierach CA. Jan Waldenström: an oslerian life. Ask Osleriana: A Searchable Database website. http://asksam.com/cgi-bin/as_web6.exe?Command=DocName&File=Osleriana&Name=2005-29%20Jan%20Waldenstrom%3A%20An%20Oslerian%20Life. Accessed March 3, 2009.
• Leuk Res. 2007;31:435-438.