Dr. Frank Dixon, an immunologist who pioneered the use of radiolabeling in molecular biology, who was among the first to explain how autoimmune diseases worked and who founded the Scripps Research Institute in La Jolla, died Friday at his home in the San Diego community of La Jolla Shores. He was 87.
Dixon had been suffering from aortic stenosis and apparently died of heart failure in his sleep, according to Scripps spokesman Keith McKeown.
"Frank was the model of the modern scientist, demonstrating equal creativity and talent both as an investigator in the laboratory and as the institute's first director," said Dr. Richard A. Lerner, who succeeded him as president of Scripps.
In the postwar years when Dixon began his research, biologists were limited in their ability to trace the course of cellular reactions, relying primarily on their eyes and the microscope. He began his career at Harvard University with Shields Warren, who would become a key player at the Atomic Energy Commission.
Because of Warren's connection to the AEC, Dixon was able to procure radioactive iodine, which was otherwise hard to obtain. He developed techniques to tag proteins and other molecules with it, allowing him to trace their progress through the body of experimental animals and determine where they ended up and in what quantities.
His isotope tracer techniques are still widely used, and researchers now employ a broad variety of isotopes for tracing chemical and biological reactions.
The technique was particularly appropriate for studying a phenomenon then known as serum sickness. In the pre- antibiotic era, one method of treating bacterial infections was to inject the patient with blood serum from animals that had been exposed to the germ.
Antibodies in the serum would destroy the bacteria, but the serum would often produce side effects that included fever, an enlarged spleen, joint pain and rashes. These symptoms are similar to those of several diseases, such as rheumatoid arthritis, rheumatic fever and lupus, and Dixon reasoned that studying serum sickness in animals could provide insight into their origin.
It was already known that the antibodies in the animal serum could bind to specific proteins in the blood, called antigens, forming antigen-antibody complexes. But no one knew what role these complexes played in disease.
Dixon labeled the antigens with radio-iodine and was able to show that the antigen-antibody complexes concentrated at the sites of tissue damage in the body, particularly in the heart, blood vessels, joints and kidneys -- and were presumably the cause of the damage.
In a series of what the Lasker Foundation called "brilliant experimental studies," he determined precisely how this process worked, the quantities required and the role of complement, another component of the immune system.
Subsequently, he and his students were able to show in humans that misguided immunological responses to natural proteins and viruses were the cause of many previously unexplained illnesses.
In particular, they showed that the antigen-antibody complexes could get stuck in the glomeruli of the kidney and attract white blood cells, producing the inflammation typical of lupus. They also showed that the antibodies could attack the kidneys directly, producing anti-glomerular basement membrane disease. They were able to transfer the antibodies responsible for the latter disease to monkeys and make them sick, proving that the antibodies were the source of the disease.
As a result of this work, in 1951 Dixon was named the nation's leading medical researcher under age 35 by the American Assn. for the Advancement of Science. In 1975 he received the Albert Lasker Medical Research Award, frequently a precursor of the Nobel Prize.
In 1961, Dixon was recruited to form a department of experimental pathology at the Scripps Clinic, which was basically a small-town hospital with an allergy clinic. Having visited La Jolla as a teen and finding the climate much more hospitable than his native Minnesota, he was predisposed to accept the offer.
The clinching factors were the freedom from teaching and the lack of administrative duties associated with a medical school.
He lured four faculty members from the University of Pittsburgh to come with him and established a thriving research program, traveling as many as 200 days a year to spread the word about their research and seek new grants.
By 1986, when Dixon formally retired as president of the institute, its funding from the National Institutes of Health was $39 million per year, surpassing the Mayo Clinic and allowing the institute to call itself the largest "independent, nonprofit biomedical research center" in the country.
Dixon supplemented the government funds by making pioneering agreements with Johnson & Johnson and PPG Industries in which Scripps got $10 million per year in research funds from each and the companies gained the rights to discoveries made at the institution.