Best known for his discovery of Waldenströms
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.
Waldenströms 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.
Waldenströms 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
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
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
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 Waldenströms macroglobulinemia
related to excess of monoclonal immunoglobulin M.
This research led to Waldenströms 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 Waldenströms
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 Waldenströms 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 Waldenströms 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
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. Waldenströms contributions to medicine had been
so significant, he said repeatedly, I am only a clinician.
by Jason Harris
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