Curiosity & Collaboration:
The Work of Michael Potter
A New Tool for Immunology:
Plasma Cell Tumors
Born in 1924, in East Orange, New Jersey, Michael Potter spent as much time as he could on the beach as a child, investigating fish, shells, and birds. His father, a lawyer and graphic designer, encouraged his children to explore the world on their own.
After graduating from Princeton University (1945), Potter received his M.D. from the University of Virginia (1949). During the Korean War, he served as a medical officer. In 1954, Potter joined the National Cancer Institute (NCI). During his decades at NCI, he served as chief of the Immunochemistry Section of the Laboratory of Cell Biology and the Laboratory of Genetics. As a chief, he enjoyed independent resources, and could focus on his research without too great of an administrative burden. From the very beginning, he exchanged ideas, material, and work with colleagues.
Potter in his laboratory, May 1976.
“Mike always told us that a Section Chief in the NCI was the best job in science.” —“Biographical Memoir,” Stuart Rudikoff and J. Frederic Mushinski National Academy of Sciences
Courtesy of Michael P. Cancro, Ph.D., University of Pennsylvania
The Road to the Mouse Room
Immunology is the study of how our body fights off foreign invaders, such as viruses and bacteria. Cancer can be viewed as a disease in which our own normal cells turn into abnormal or foreign entities. In the mid-1950s, Michael Potter saw this connection between immunology and cancer. He began to investigate the twin questions of what causes cancer and how antibodies arise in the immune system to attack foreign cells.
“‘There is our animal room, down the hall. Go learn about mice and tumors.’ Needing no further encouragement, Mike proceeded to do just that.”
This is the mouse room of the Carcinogenesis Section in the National Cancer Institute's Laboratory of Biology, led by Lloyd Law, when Potter joined in 1954. Law was among the first to use combination chemotherapy in leukemia. The use of inbred, genetically similar mice enabled scientists to transplant tumors from one mouse to the next and create a continuous line of identical tumors. Such tumor lines allowed researchers such as Potter to study them in depth in a controlled setting.
Photo Credit: National Institutes of Health, Clinical Center Photo Collection
Finding a Plasma Cell Tumor to Study
Potter's research target was tumors of plasma cells (a type of white blood cell) because each tumor produced its own specific antibody, or immunoglobulin, in great quantities. With greater amounts of immunoglobulins, Potter could study broader topics, such as antibody structure, function, and genetics. But first Potter had to find a tumor to study. That’s when luck came into play.
“The mice…arrived the very day in May 1956 we had acquired our first paper electrophoresis apparatus. This had been purchased from Spinco/Beckmann for the large sum of around $300. ... Alvado Campbell and I loaded up the paper electrophoresis strips to fill out the overnight run and put in X5563 serum at the last minute. Then, to our surprise, the X5563 serum proved to be the unusual one. There was the familiar large albumen band, but a large amount of protein remained at the point where the sample had been applied. The first thought was that we had not carried out the procedure properly with this new instrument, but then when the finding was repeated, it was clear that the extra band near the origin was a massive myeloma [plasma cell tumor] protein. I ran across the hall and told [Lloyd Law] about it, announcing, ‘Gold has been struck.’”
This paper electrophoresis strip, separating small proteins from its cell, revealed an antibody expressed by a plasma cell tumor in a mouse carrying the rare tumor X5563. This was Potter's first isolated plasma cell tumor sample to expand into a tumor line.
Finding a Mouse to Grow the Plasma Cell Tumors
Now that he had a tumor, X5563, He needed a mouse to grow it in. Potter’s colleagues Ruth Merwin and Glenn Algire discovered that implanting plastic rings or shavings (and later mineral oil) into mice could induce plasma cell tumors. Luckily, they had used BALB/cAn mice, one of the few inbred mouse strains that is susceptible to developing plasma cell tumors. Potter now had his tumor line and his mouse.
From the Permanent Collection of the
NIH Stetten Museum, Courtesy of Dr. Beverly Mock, NCI
This barrel of mineral oil was used by Potter to induce plasma cell tumors in mice. Rose Lieberman from the National Institute of Allergy and Infectious Diseases had found that mice injected with Freund’s adjuvant, made with mineral oil and antigens, produced large quantities of immunoglobulins. Potter and Lieberman struck a deal: he would do the pathology studies, if she would inject his BALB/c mice with Freund’s adjuvant. Some mice developed plasma cell tumors; so began a collaboration that lasted over 30 years.
More information: Esso Oil Can Artifacts page
High-Tech Science, Low-Tech Solution
The Waring Blendor
Potter and Lieberman prepared their Freund’s adjuvant in a common Waring Blendor, as could be found in many kitchens. An adjuvant is a substance that, when mixed with an antigen, can accelerate or prolong an immune response. Freund’s adjuvant keeps an antigen from breaking down quickly and can enhance its effects. More information: Waring Blendor Brand Blender artifacts page
—From the Permanent Collection of the NIH Stetten Museum, Courtesy of Dr. Rose Mage, NIAID
Potter found lesions throughout the skeletons of mice 90 days after they had been transplanted with tumor X5563 (each glass or brass vial holds the complete skeleton of one BALB/c mouse). More information: Mouse Reliquaries artifacts page
From the Permanent Collection of the NIH Stetten Museum, Courtesy of Dr. Beverly Mock, NCI
Photo courtesy of Dr. Michael P. Cancro, University of Pennsylvania
Rose Lieberman and Potter met in 1959 after she gave a lecture on her technique using Freund’s adjuvant to induce ascites, or fluid accumulation, in mice, which included plasma cells. Over the years, she and Potter “wore a path” between her laboratory in Building 10 and his in Building 8. “Rose taught me how to do science,” Potter said (quotes from NIH Record, April 14, 1992, p. 5.)
Lieberman had survived polio when she was four years old, and said, "After those years of being a patient, often in rather bleak circumstances, I vowed to go into medicine, to see if I could change things." She received a B.S. degree in zoology in 1935 from Columbia University, and an M.A. degree in bacteriology in 1937. She began her research career at the Yale School of Medicine, earning the Yale Fluid Research Award in 1949 for correctly identifying an outbreak of infectious lymphocytosis that had been mistaken for leukemia.
Lieberman joined the Laboratory of Clinical Investigation at the National Institute of Allergy and Infectious Diseases (NIAID) in 1952, establishing the first clinical microbiology lab at NIAID. In 1968 she joined the Laboratory of Immunology. Learn more about this remarkable scientist on page 5 of this issue of The NIH Record from 1992
U.S. National Library of Medicine Harold L. Stewart Papers
Known as "The First Lady of Cancer Research," Thelma Dunn’s laboratory was two floors below Potter’s. Dunn, chief of the National Cancer Institute (NCI) Carcinogenics Branch, and Potter searched for rare plasma cell tumors among the many mouse tumors found in their colonies. It was she who gave Potter the idea of inducing plasma cell tumors in larger numbers of mice, using techniques that Ruth Merwin had shown to be feasible. With more tumors to study, his team would be able to more rapidly advance the science.
Dunn was born in Renan, Virginia, the daughter of a public health physician. She did not enroll in elementary school until she was 9 years old and later recalled accompanying her father over nearly impassable trails by horse and mule back and helped him to treat patients. Dunn received her M.D. degree from the University of Virginia in 1926, staying as an instructor until she became a research assistant at the George Washington University School of Medicine from 1936 to 1942.
Dunn came to NCI in 1942. She was one of six U. S. women chosen to visit the U.S.S.R. in May 1958 as a member of the Delegation of American Women Physicians to Russia. In 1959, she was named "Woman of the Year" by the District of Columbia Branch of the American Medical Women's Association. She was also the first women elected President of the American Association for Cancer, Inc.
Read more about her productive life: https://nihrecord.nih.gov/PDF_Archive/1993%20PDFs/19930202.pdf
- The Work of Michael Potter
- I. A New Tool for Immunology: Plasma Cell Tumors
- The Mouse Room in the Laboratory of Biology
- Finding a Plasma Cell Tumor to Study
- Finding a Mouse to Grow the Plasma Cell Tumors
- Significant Collaborations
- II. Antibody Structure, Function, and Genetics
- Matching Immunoglobulins to their Antigens
- What Makes Immunoglobulins Differ Genetically?
- A Structure Identified!
- III. Plasma Cell Tumor Development: A Complex Multi-Step Process
- IV. Legacy of Shared Curiosity
- Exhibit Dedication Video
- Artifacts Index