Dr. Holman recalls that his mentor said, “I’ll take rheumatoid arthritis and you take lupus.” Just like that, Dr. Holman embarked on a line of investigation that ultimately led to identification of anti-nuclear autoantibodies.
Those were exciting times in immunology, when new investigations were disproving the formerly entrenched beliefs that autoantibody formation was not possible. In those times, Dr. Holman encountered the first of many examples in his career of the way in which conceptual changes occur—the “paradigm shift” first explicated by Thomas Kuhn.
The Move to “the Farm”
When Stanford University moved its medical school from San Francisco to Palo Alto (“the farm”), another opportunity arose for him.
“They wanted a clinical faculty that knew both clinical medicine and emerging scientific medicine,” he recalls. “The older, good clinicians didn’t know the science, so they had to seek younger people for the faculty. I got the job because I could do both. It opened up the opportunity to build the department out of young people.”
Edward D. Harris, Jr., MD, the George DeForest Barnett professor emeritus at Stanford University, has been a colleague of Dr. Holman’s since the early 1970s. “One of his most important contributions was recruiting so many very fine clinical scientists to Stanford,” says Dr. Harris, “and then encouraging them to be leaders as well as investigators and clinical teachers. That was pretty unusual at the time.”
Paradigm Shifts
Dr. Holman continued to publish multiple studies on lupus throughout the 1960s, but he was also known for his thoughtful publications on the wider relationships between science, medicine, and society.2
The promise of the earlier discoveries of the anti-nuclear autoantibody, however, was not yielding the hoped-for breakthroughs. “It was becoming clear to us, by about 1970, that we were not going to be able to establish a direct linkage between autoantibodies and disease genesis,” says Dr. Holman.
During the same time period, several treatments for rheumatic diseases—notably, corticosteroids and the early NSAIDs—were allowing people to live much longer with their disease. A different construct for viewing medical treatment was needed.
“The rheumatic diseases were becoming among the first prototypic chronic diseases in which patients continued to live with their handicap,” says Dr. Holman. “We could not use the old standards [i.e., the acute disease model of cure or death] to figure out how well we were affecting patients. We had to come up with new systems for measuring outcome.” He and James Fries, MD, professor of medicine at Stanford, began to analyze long-term data in patients with rheumatic disease. These were the beginnings of the American Rheumatism Association Medical Information System (ARAMIS).
