Emil L. Smith dies at 97; biochemist advanced protein research

Biochemist Emil L. Smith, who pioneered the process of determining the structure of proteins, played a key role in bringing UCLA’s department of biological chemistry to national prominence, and led the first scientific delegation to China, has died. He was 97.

FOR THE RECORD: A headline on an earlier version of this article incorrectly gave Smith’s age as 98.

Smith died May 31 at the Ronald Reagan UCLA Medical Center from complications of a heart attack he had two months earlier.

“Emil Smith was one of the true pioneers in the development of protein chemistry, particularly in the immediate decades following World War II,” said biochemist Ralph Bradshaw of UC Irvine. His work “was instrumental in providing some of the earliest evidence for Darwinian evolution” of proteins.

Proteins are composed of long strings of amino acids, and determining the sequence of those components reveals much about the molecule’s function. Today, automated machines can crank out such a sequence in a few days, but when Smith was working, it was a tedious, time-consuming process that required removing each amino acid sequentially and identifying it, using elaborate chemical techniques.

In the late 1950s, while Smith was at the University of Utah, he and Emanuel Margoliash determined the sequence of cytochrome c, which transports electrons, allowing cells to burn fuels and extract energy. It is a relatively simple molecule, composed of only 104 amino acids. Sequencing the same molecule from other mammals, Smith and his colleagues found that the human molecule was identical to that of the chimpanzee and differed from that of the rhesus monkey at only two positions along the amino acid chain, while it differed from horse cytochrome c at 12 positions.

Based in large part on this work, Emile Zuckerkandl and Linus Pauling of Caltech proposed the idea of a molecular clock, arguing that such changes in proteins -- and hence in the genes that serve as their blueprints -- occur at a fairly constant rate. Thus, rhesus monkeys and humans diverged from a common ancestor much more recently than did humans and horses.

In 1969, after Smith had moved to UCLA, he and James Bonner worked out the amino acid sequence of histone H4, one of the five proteins that are found in chromosomes. They showed that the proteins from cows and from the pea plant differed at only two positions despite 2 billion years of evolution, suggesting that almost every part of this protein served a critical function.

Smith and his colleagues also determined the sequences of the plant proteinase papain, the subtilisins enzymes and several glutamate dehydrogenases.

Emil L. Smith was born July 5, 1911, in New York, the son of Russian immigrants. Unlike many prominent scientists, he did not have an early interest in the discipline. “I was a late starter and came to science largely by accident,” he later said. In high school, he described himself as an indifferent student who frittered away much of his time playing jazz saxophone with various orchestras.

He was a good enough student, however, that he enrolled in a pre-med curriculum at Columbia University at age 16, and was steered into science in his sophomore year by two gifted teachers who sparked his interest in biology and organic chemistry. He supported himself during his college years playing the sax and met his future wife, the former Esther Press, at a New Year’s Eve gig. He received his bachelor’s degree in 1931 and his doctorate in chemistry in 1936, also from Columbia.

After a two-year term as an instructor at Columbia, he went to Cambridge University on a Guggenheim fellowship and worked on the chlorophyll-protein complex until he was forced to return by the outbreak of war. He spent the war years at E.R. Squibb & Sons in New Brunswick, N.J., working on the production of purified proteins from blood plasma for use by the armed forces.

While at the University of Utah, he spearheaded the writing of the classic textbook “Principles of Biochemistry” with Abraham White, Philip Handler and DeWitt Stetten. The book was known familiarly as “White, Handler and Smith” and went through seven editions, with the last published in 1983.

In 1963, Smith was recruited to chair the department of physiological chemistry at UCLA’s then-new School of Medicine, promptly renaming it the department of biological chemistry to reflect the field’s importance to medicine. Because of his recruitment, the department “immediately jumped several notches in stature,” said Irving Zabin, a professor emeritus from the department. “He led the department by example, by consultation, by encouragement, and by persuasion when necessary.”

In 1965, Smith founded the Molecular Biology Institute at UCLA with fellow chemist Paul Boyer.

One of Smith’s proudest moments was his selection by President Nixon to lead the first scientific delegation to the People’s Republic of China in 1973. The group met with Premier Chou En-lai and helped to establish open communication between scientists in these countries for the first time.

He retired from active teaching in 1979 and closed down his laboratory. “He felt strongly that, after nearly 50 years of research, whatever he was going to do he had done,” said his son, Dr. Jeffrey B. Smith of UCLA.

Smith was preceded in death by his wife and his brother Bernard, the literary critic and producer of the films “Elmer Gantry” and “Cheyenne Autumn.” He is survived by his sons, J. Donald of Cambridge, Mass., and Jeffrey of Santa Monica, both of whom followed him into research.

thomas.maugh@latimes.com