WASHINGTON — Noel R. Rose, whose experiments in the 1950s helped launch the study of autoimmune diseases and whose decades of research and teaching led colleagues to call him the ‘‘father of autoimmunity,’’ died July 30 at a hospital in Boston. He was 92.
He died after a stroke, said his son David.
Dr. Rose began his investigations when the idea of autoimmune disease — that the body’s immune system can produce illnesses by attacking its own cells — was considered preposterous. Today, largely because of Dr. Rose’s early groundwork in the field, more than 80 autoimmune diseases have been identified, including Type 1 diabetes, multiple sclerosis, and rheumatoid arthritis, affecting more than 20 million Americans, a disproportionate percentage of whom are women.
‘‘Add them up and the number of people with these diseases is very high,’’ Dr, Rose told The Washington Post in 1995. ‘‘Autoimmune diseases are one of the big three, meaning cancer, heart disease, and autoimmune disease.’’
Beginning in 1951, Dr. Rose became a medical researcher and instructor at what was then the University of Buffalo, working in a laboratory led by immunologist Ernest Witebsky, who had fled Nazi Germany in the 1930s.
Witebsky, who studied the properties of different blood types, was interested in how antigens entered the body and triggered an immune response from naturally produced antibodies. It was how the body healed itself: Harmful viruses and other invasive organisms were identified and vanquished by the immune system.
Witebsky’s academic mentor in Germany had been a student of Paul Ehrlich, a Nobel laureate who died in 1915. Ehrlich made major discoveries in immunology and, at the turn of the 20th century, coined a term that became well known in the field: horror autotoxicus, or the dread of self-poisoning. It represented the notion that the body could not destroy itself.
Decades later in Witebsky’s laboratory in Buffalo, Dr. Rose became a third-generation scientific descendant of Ehrlich, and the first to challenge his prevailing idea, which had hardened into doctrine.
Witebsky suggested that Dr. Rose study thyroglobulin, a protein found in the thyroid gland. Dr. Rose extracted the protein from various mammals, including humans, horses, and pigs, treated it with a substance to induce an immune response, then injected it in laboratory rabbits. The rabbits produced antibodies to fight off the foreign protein, even though it was structurally similar to the rabbits’ own thyroglobulin.
Next, Dr. Rose used thyroglobulin obtained from other rabbits and came up with the same results — the experimental rabbits produced an immune response to ward off thyroiditis, or inflammation of the thyroid gland.
Finally, at Witebsky’s behest, Dr. Rose extracted small amounts of thyroglobulin from living rabbits, then devised innovative methods to inject the protein back into the same animals. He developed sensitive tests to measure the antibody response, if any.
To his surprise, he discovered that the rabbits produced antibodies to fight off the invading antigen, even though it was derived from their own bodies.
‘‘Is it actually possible that an animal can respond to its own antigen?’’ Dr. Rose told the Johns Hopkins University Gazette in 2014, recalling his sense of wonder at the time.
Because the experiment upset the commonly held ideas propounded by Ehrlich and others, Witebsky ordered Dr. Rose to repeat it again and again. Every time, the results were the same.
‘‘We finally realized that we had essentially induced an autoimmune disease experimentally,’’ Dr. Rose told the Gazette. ‘‘That changed the world.’’
He and Witebsky wrote a paper in 1956, but it was rejected during peer reviews by other scientists who refused to believe their findings could be true. The paper was finally published several years later, after British researchers conducted similar experiments.
‘‘At first, the immunologic world was suspicious of this whole business,’’ Dr. Rose said in a 2019 interview with Brigham Clinical & Research News. ‘‘To take one of the basic dogmas of immunology — horror autotoxicus — and turn it on its head, well . . . but eventually people bought into it.’’
Meanwhile, Dr. Rose and Witebsky began to compare their results with blood samples from human patients with Hashimoto’s disease — a form of thyroid inflammation that had, at the time, no known cause. They found that the human patients had developed antibodies that resembled those found in the experimental rabbits injected with their own thyroglobulin.
‘‘You have fulfilled the postulates,’’ Witebsky told Dr. Rose, ‘‘and proven that a human disease can be caused by autoimmunity.’’
They stated their findings about Hashimoto’s disease in the Journal of the American Medical Association in 1957, years before their paper about the original experiments that led to the breakthrough was published. Since then, the range of autoimmune diseases has grown to include Graves’ disease (or hyperthyroidism), scleroderma, lupus, inflammatory bowel disease, and psoriatic arthritis.
In 2015, Dr. Rose retired from Johns Hopkins and moved to Massachusetts, where he had a joint appointment to lecture at Harvard Medical School and work in the pathology department of Brigham and Women’s Hospital until his death.
‘‘In every aspect,’’ George Tsokos, a Harvard Medical School professor, said in the June issue of the publication the Scientist, Dr. Rose ‘‘is the father of autoimmunity. The man opened a whole chapter in the book of medicine.’’
Noel Richard Rose was born Dec. 3, 1927, in Stamford, Conn. His mother was a teacher, his father a physician who served in the medical corps during World War II. He later developed a specialty in treating patients with rheumatic fever, now considered an autoimmune disease.
Aside from his father, Dr. Rose was strongly influenced by a seventh-grade teacher who brought his microscope to the classroom.
‘‘I became enraptured with the idea that there is another world around us that we don’t see,’’ Dr. Rose told the Scientist earlier this year. ‘‘It was something that raised my curiosity from the beginning and has been the theme of most of my career.’’
Despite working 20 hours a week, Dr. Rose completed his bachelor’s degree in zoology at Yale University in three years, graduating in 1948. At the University of Pennsylvania, he received a master’s degree in 1949 and a doctorate in 1951, both in microbiology.
While working in the laboratory and teaching courses, Dr. Rose graduated from medical school in 1964 from what is now called the University at Buffalo, part of the State University of New York system.
From 1973 to 1982, when he was a professor at the medical school of Wayne State University in Detroit, Dr. Rose made major advances in understanding genetic links to autoimmune diseases.
After joining Johns Hopkins University in 1982, Dr. Rose chaired the department of immunology and infectious diseases at the School of Public Health. He became the founding director of the Johns Hopkins Center for Autoimmune Disease Research, which he founded in 1999.
Dr. Rose published almost 900 scientific papers and helped write or edit more than 20 books, including a textbook, ‘‘The Autoimmune Diseases,’’ which has had multiple editions.
He leaves his wife of 69 years, Deborah Harber Rose of Brookline, Mass; four children, Alison Rose Weinstock of Weston, Mass.; David Rose of Waterloo, Ontario, Bethany Rose Kramer of Framingham, Mass.; and Jonathan Rose of Romeo, Mich.; 10 grandchildren; and five great-grandchildren.