PASADENA, Calif.-Giuseppe Attardi, whose work linked degenerative diseases and aging to genetic mutations, died at his home in Altadena on Saturday, April 5. He was 84 years old.

Attardi, the California Institute of Technology’s Steele Professor of Molecular Biology, was among the first scientists to delve into the processes through which DNA’s information is transferred. He identified all the genes of the DNA in human mitochondria–often called the powerhouses of biological cells. He then developed techniques for investigating genetic diseases, including Alzheimer’s, and aging in general, which he discovered is associated with changes in mitochondrial DNA (mtDNA).

Born in 1923 in Vicari, Italy, a town of less than 3,000 people in the Province of Palermo, Attardi earned an MD from the University of Padua in 1947. He remained there for almost 10 years as an assistant professor in the Institute for Histology and General Embryology.
During those years, he also visited the Karolinska Institute in Stockholm, Sweden, as a research fellow in cell research and genetics, and the Washington University in St. Louis School of Medicine as a Fulbright Fellow.

Still on the Fulbright Fellowship, Attardi arrived at Caltech in 1959. He was appointed associate professor of molecular biology four years later. It was at Caltech that Attardi turned his interests to mitochondria, establishing that mtDNA is an active, working genome.
This spurred research into the organelle’s genetic machinery.

David Chan, an associate professor of biology and Attardi’s colleague and friend, credits Attardi with being a leading figure in identifying the products and functions of the mitochondrial genome.
Attardi and a student developed a technique in which they replaced the mtDNA of a human cell line with the mtDNA from diseased cells.
This allowed them to distinguish the roles of mtDNA and the genome of the nucleus–where the rest of a cell’s DNA resides–in causing the disease. With this technique, they could also examine the relationship between changes in mtDNA and changes in cell function caused by the disease. “Many labs have used his approach to understand how mutations in mtDNA diseases affect mitochondrial function,” Chan says.

“Giuseppe was one of the founders of what is now a central and still-expanding area of molecular cell biology,” adds Attardi’s colleague and friend Gottfried Schatz, emeritus professor of biochemistry at the University of Basel’s Biozentrum, in Switzerland.
“His unique insights bore magnificent fruits with the landmark description of the transcription map of mammalian mtDNA, as well as the precise characterization of the mechanism of mitochondrial diseases and the dynamics of human mitochondrial genomes.”

In recent years, researchers in Attardi’s lab at Caltech have focused on how mtDNA replicates, and on detecting mutations that result from aging, and what affects those mutations have. The team discovered that older people carry a significantly greater number of genetic defects in a specific region of their mtDNA, suggesting that cell aging begins in the mitochondria.

“He has been a central figure in mitochondrial research for several decades. One of the things I will always remember about him is his constant excitement for all types of biological questions,” Chan says. “I think his intense curiosity is one reason he accomplished so much as a scientist.”

Schatz adds, “To him, science was everything and he never tired of discussing the latest experiments. Yet he also embodied a vanishing breed of scientists whom I would define as ‘gentlemen intellectuals.’
He had a superb grasp of European history and world culture, had mastered French and German at a very high level of proficiency, and even in his most spirited discussions refrained from personal invective or overt aggression. To me, he was an example of how science can keep us young in spirit, and ennoble us.”

During his career, Attardi garnered several distinctions. They include two Guggenheim Fellowships; election to the National Academy of Sciences; the Antonio Feltrinelli International Prize for Medicine from the Accademia Nazionale dei Lincei; a degree of doctor honoris causa from the University of Zaragoza, Spain; the Passano Foundation Award in 2000; and the Gairdner Foundation International Prize.

Attardi is survived by his wife and fellow researcher, Anne Chomyn, a senior research fellow, emeritus, at Caltech; a son, Luigi Attardi, of Rome; a daughter, Laura Attardi, of Palo Alto, who is a professor of cancer biology at Stanford University; and a grandson, Marcello Attardi, of Palo Alto.

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Elisabeth Nadin, science writer
Caltech Media Relations