Aaron Klug, 92, Dies; His 3-D Images of Bodily Molecules Won a Nobel

Aaron Klug, who won the Nobel Prize in Chemistry in 1982 for devising ways to create three-dimensional images of biological molecules like proteins and DNA, died on Nov. 20. He was 92.

His death was reported by British newspapers and by the Medical Research Council’s Laboratory of Molecular Biology in Cambridge, England, where Dr. Klug had worked for decades. It did not say where he died.

Trained as a physicist, Dr. Klug — Lithuanian-born and raised in South Africa — became interested in the 1960s in how techniques to discern the structure of crystals could be applied to biology. Initially he bounced X-rays off biological molecules, but in the mid-1960s he switched to electrons.

Electron microscopy can make out tiny features as small as atoms, but it requires that samples be placed in a vacuum — an unfriendly environment for almost all components of living organisms.

Dr. Klug and his collaborators worked around that issue by using heavy metals to encase the molecules. In an interview, Richard Henderson, a colleague of Dr. Klug’s at the Laboratory of Molecular Biology, explained the process:

“You did a mold like a plaster of Paris mold of your hand, and then you could determine the structure of the plaster of Paris, and then, by implication, you’d find out the structure of what was inside it. That’s what they did in the ′60s.”

By making electron images from different directions, Dr. Klug was able to construct three-dimensional images.

X-rays, not electron microscopy, was the primary method to decipher protein structures until recent years, when researchers figured out that freezing the molecules could preserve their structure. Dr. Klug was not involved with the latest advances, but “the mathematics behind it is the same mathematics that was developed in the ′60s by Aaron Klug,” Dr. Henderson said.

The Nobel committee cited Dr. Klug “for his development of crystallographic electron microscopy and his structural elucidation of biologically important nucleic acid-protein complexes.”

Aaron Klug was born in Lithuania on Aug. 11, 1926. When he was 2, his family emigrated to South Africa, a more welcoming environment for Jews at the time. He enrolled at the University of the Witwatersrand in Johannesburg at the age of 15.

After graduating with a bachelor of science degree, he obtained a master’s degree at the University of Cape Town and then moved to England in 1949 to study at the University of Cambridge. He finished a doctorate there in 1953.

Dr. Klug, whose research had focused mostly on bouncing X-rays off crystals to determine their structure, had received an offer of a postdoctoral fellowship in Philadelphia at the Johnson Foundation for Medical Physics. He e was denied a visa, however, because a student organization he had belonged to in South Africa was deemed Communist. Instead he took a position at Birkbeck College in London to work on studying proteins using X-ray crystallography.

There he met Rosalind Franklin, whose X-ray images of DNA were crucial to Francis Crick and James D. Watson’s figuring out the double helical structure of the molecule in the early 1950s.

When Dr. Klug encountered her, in 1954, she was applying the same techniques to viruses, and the images enchanted Dr. Klug.

“That determined, really, my scientific career, because up to then I hadn’t had a firm idea of what I wanted to do,” he said in an interview for the Nobel Foundation in 2001. He switched to studying the structures of viruses.

Dr. Klug joined the Laboratory of Molecular Biology in 1962 and started working on the electron microscopy techniques.

He also moved on to other topics of research, spending six to eight years on one before switching to another. “I think he quite liked the challenge of having some completely new problem to work on,” Dr. Henderson said.

Dr. Klug was at the forefront of determining the structure of transfer RNA, a type of RNA molecule that helps decode the instructions for producing a protein. He studied chromatin, which holds the long strands of DNA in tight packages within a nucleus, and he discovered “zinc fingers,” molecular motifs that can bind to specific DNA sequences. He also studied tangles of proteins associated with Alzheimer’s disease.

Dr. Klug acknowledged that he preferred being a pioneer in his research as opposed to expanding on others’ work.

“Almost everything I’ve worked on, after I started, other people moved in and did all sorts of useful work,” he told the Nobel Foundation. “But by then I’d moved on to something else, because people jump in when they see something good and spoil the fun, really.”

Dr. Klug was director of the laboratory from 1986 to 1996 and played a key role in establishing what is now the Wellcome Sanger Institute in England, which completed about a third of the sequencing of the Human Genome Project. He was president of the Royal Society, the world’s oldest scientific organization, from 1995 to 2000. He was knighted in 1988.

In a tribute, Venki Ramakrishnan, president of the Royal Society, called Dr. Klug a “giant of 20th-century molecular biology who made fundamental contributions to the development of methods to decipher and thus understand complex biological structures.”

Dr. Klug is survived by his wife of 70 years, Liebe; a son, David; and four grandchildren. Another son, Adam, died in 2000.

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