Kimishige Ishizaka

Immunologist, allergy expert and researcher

Dr kim is hi ge is hiz aka, an immunologist whose experimental work–including transforming himself into a human pin cushion — identified the antibodies that trigger wheezing, itching, rashes and other allergic reactions, died on 6 July in Yamagata, Japan. He was 92.

His death was announced by the La Jolla Institute for Allergy and Immunology in California, where he had been scientific director and president.

By developing a better understanding of what causes severe allergic reactions in hypersensitive individuals, Ishizaka and his wife, Teruko Ishizaka, a research immunologist, laid the groundwork in the mid-1960s for advances in monitoring, treating and preventing such conditions as asthma, hay fever and drug and food allergies.

More recently, he cautioned in an interview in the book “History of Allergy” (2014) that the number of allergy patients had been increasing in developed countries, apparently as a result of environmental factors like air conditioning, heating and exposure to certain products.

He said the increase might also be attributed to what is called the “hygiene hypothesis,” which posits that more children develop allergies because they are exposed in infancy to fewer allergens than in the past.

For decades, researchers had been studying reagin, an antibody implicated in hyperallergic reactions. Ishizaka asked his colleagues to inject solutions of the molecule into his back. At the time, he and his wife were working at the Children’s Asthma Research Institute and Hospital (now National Jewish Health) in Denver, where Ishizaka eventually became chief of immunology.

The injections prompted him to produce more antibodies, the blood proteins that attack foreign substances entering the body. His team first identified Immunoglobulin E or IGE antibodies, which are rare compared to other antibodies but trigger the most inflammatory reactions.

Ishizaka not only identified the antibody but also deciphered how it worked – through a lock-and-key binding factor, which connects one end of the antibody to the offending foreign substance and the other end to a white blood cell called a mast cell. Normally, once the foreign substance, the antibody and the mast cell are linked, the mast cell secretes histamine and another chemical. That causes an individual to cough or sneeze and expel the pollen or other allergen.

In a person suffering from allergies, though, too much IGE stimulates an extra release of histamine, a compound that causes dilation of capillaries. That, in turn, results in excessive sneezing and other symptoms, including some that could be more serious.

Ishizaka’s team published its findings in 1966.

In 1969, the Ishizaka team and another headed by SGO Johansson and Hans Bennich in Uppsala, Sweden, collaborated in publishing similar findings.

For nearly two decades, beginning in 1970, the Ishizakas conducted research at Johns Hopkins University, where Ishizaka was an assistant professor of biology, medicine and microbiology. In 1989, he was named scientific director of the then-new La Jolla Institute; he became its president in 1991. He retired in 1996 and returned to Japan, settling in Yamagata, his wife’s hometown, in northern Japan.

Ishizaka, who was known as Kimi, was born on 3 December, 1925, in Tokyo to Koki and Kiku Ishizaka. His father was a career soldier who retired in 1933 as a lieutenant general.

Kimishige Ishizaka intended to become a physician but was captivated by immunology while taking a summer course in college. He received his medical degree in 1948 from the University of Tokyo, where he was also awarded a doctorate.

In 1949, he married Teruko Matsuura, who survives him along with their son, Yutaka Ishizaka.

From 1953 to 1962, Ishizaka headed the immunoserology division of the serology department at the Japanese National Institute of Health, spending part of that time as a research fellow at the California Institute of Technology. In 1962, he and his wife were recruited to study human allergies at the research institute in Denver.

During one experiment while he was working there, he injected antibodies into his right arm.

Although he had never had a severe allergic reaction before, he developed a rash that was diagnosed as atopy, a hypersensitivity more common in patients with a family history of asthma or hay fever. The rash subsided after a week.

Ishizaka and his wife wrote scores of articles together and shared several prizes for their research on IGE.

In 1984-85, he was the first foreign-born individual elected to serve as president of the American Association of Immunologists. In 2000, he won the Japan Prize from the Science and Technology Foundation of Japan.

SAM ROBERTS