Nobel Prize-winning scientist Aaron Klug, who led MRC LMB, dies at 92

A Nobel Laureate who led the MRC Laboratory of Molecular Biology in Cambridge for a decade has died at the age of 92.

Professor Sir Aaron Klug won the 1982 Nobel Prize in Chemistry for developing crystallographic electron microscopy.

His work was instrumental in revealing the structures of complex biological molecules, including viruses, tRNA, chromatin and zinc fingers.

Aaron was director of the LMB from 1986-96, was knighted in 1988 appointed a member of the Order of Merit in 1995. A fellow of The Royal Society from 1969, he served as its president from 1995 to 2000.

He died on Tuesday, November 20 and his funeral took place at Cambridge City Cemetery on Monday November 26.

Nobel Prize winner Richard Henderson, who followed in Prof Klug’s footsteps as joint head of structural studies on the LMB and later as its director, said: “Aaron had a unique ability to see the strong and weak points in the experimental observations made by his colleagues and to inspire them to carry out more rigorous and adventurous research than they might have done without his incisive analysis.”

Tony Crowther, who collaborated with Aaron on image analysis, added: “Aaron was a strong but fair critic, whose insights on contentious scientific matters generally proved to be correct.”

Born in Zelvas, Lithuania on August 11, 1926, Aaron moved with his family to Durban, South Africa, when he was two.

He completed a BSc at the University of Witwatersrand in 1945 and an MSc at the University of Cape Town in 1946 and was initially drawn to a medical career before quickly switching to studying chemistry, physics and mathematics.

He became a junior lecturer in Cape Town’s physics department and worked on X-ray analysis of small organic compounds.

Developing a strong interest in the structure and organisation of matter, he came to Cambridge in 1949 as a research student at the Cavendish Laboratory of Physics under the supervision of D R Hartree. He was awarded his PhD in 1953 on ‘The kinetics of phase changes in solids’.

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Aaron became a Nuffield fellow in the crystallography laboratory at Birkbeck College, London, where he met Rosalind Franklin, who was working on the structure of tobacco mosaic virus.

He recalled: “I was able to interpret some of Franklin’s beautiful X-ray diffraction patterns of the virus particle. From then on, my fate was sealed.”

After her death in 1958, he became head of the virus research project and took over her group. Discussions were under way for the group to move to the LMB.

In 1962, Aaron joined the LMB’s structural studies division, continuing to work on the structure of TMV and looking at the structures of spherical viruses. He became head of the division in 1977.

He coined the term ‘self-assembly’ to describe how the instructions for viruses are built into the individual units from which the structure is composed.

His research employed X-ray diffraction and then electron microscopy, assisted by John Finch.

Close study of electron micrographs of viruses led to crystallographic electron microscopy being developed and quantitative methods for their analysis. This led to general methods for calculating three-dimensional maps of specimens, which were taken up worldwide and helped to establish the rules governing structure and self-assembly of viruses.

Moving on to work involving DNA and RNA, his group were the first to determine a number of key structures, such as the crystal structure of yeast phenylalanine tRNA in 1974, and then a hammerhead ribozyme RNA.

After discussions with Francis Crick, he analysed the nucleosome core and higher order structures, aiding an understanding of how DNA is packed in chromosomes.

Work on transcription factor binding to DNA enabled the discovery in 1985 of zinc finger proteins, which bind specific DNA sequences using arrays of ‘fingers’, each of which interacts with a run of three or four base pairs.

Thanks to their modular nature, it has been possible to design synthetic proteins with a range of specificities, leading to the prospect of targeted therapies for a wide range of diseases.

Aaron also championed large-scale DNA sequencing, and as director of the LMB supported the work of John Sulston and colleagues in this field. He played a vital role in establishing what is now the Sanger Institute, which was key to the Human Genome Project.

Aaron was also key to the LMB starting work on neurodegenerative disease. Michel Goedert worked with him on the role of the tau protein, which is implicated in Alzheimer’s disease.

“Aaron always said that curiosity was the most important quality for a scientist and that one had to live in interesting times,” he said.

Actively involved in teaching undergraduates and supervising research students, Aaron was director of studies in nature sciences at his college, Peterhouse, for many years. Aaron continued as an emeritus scientist until 2012, when he retired from the LMB.

When asked about the laboratory, he said: “In a factory you know what you’re going to make. Here, we plant things that grow and mature. It takes a long time.”