Sir Aaron Klug, OM
Scientist who developed new ways of determining the structure of large molecules like chromosomes
SIR AARON KLUG, OM, who has died aged 92, won the 1982 Nobel Prize in Chemistry for his development of crystallographic electron microscopy and his work in charting the infinitely complex structures of chromosomes, the body’s largest molecules.
Human genes are made of nucleic acids such as DNA (deoxyribonucleic acid). The acids are too small to be seen with an ordinary microscope and too large to be studied by examining them under X-rays.
During the 1960s, while studying the structure of the tobacco mosaic virus using X-ray crystallography, Klug developed a new image-processing technique and found a way to use the electron microscope, a tool much more powerful than an ordinary microscope, to determine the arrangement of atoms in large molecules.
He then used the technique to examine viruses, nucleic acids and chromosomes, which consist of genes (made of nucleic acids) intertwined with proteins. Chromosomes contain a small protein core called a nucleosome, and Klug showed that the nucleosome looks like “a sardine can with DNA wrapped around it”.
Klug’s achievement in unravelling the structure of chromosomes was seen as of crucial importance in advancing understanding of the nature of cancer.
Aaron Klug was born to Yiddishspeaking Jewish parents on August 11 1926 in Zelvas, Lithuania. His father, Lazar, was a saddler and cattle herder. Aaron remembered nothing of his early youth because, as life got more difficult for Jews in Lithuania, the family fled to Durban, South Africa, when he was two.
He was educated at Durban High School, where, he recalled that “the bright boys specialised in Latin, the not so bright in science and the rest managed with geography or the like”. Klug did not feel a strong call to any one subject, but read voraciously and began to find science interesting. It was the book Microbe Hunters by Paul de Kruif, well-known in its time, which influenced him to apply to study Medicine at university as a way into microbiology.
Aged just 15 he won a scholarship to the University of Witwatersrand in Johannesburg, where he took the pre-medical course and, in his second year, studied biochemistry. Later he moved to chemistry, physics and mathematics, finally taking a science degree.
By that time he had decided to specialise in physics and went on to do an MSC at the University of Cape Town, which was then offering scholarships in return for demonstrations in laboratory classes. After graduation he stayed on and worked on the X-ray analysis of small organic compounds.
During this time, Klug developed a strong interest in the structure of matter and how it is organised. Supported by an 1851 Exhibition Scholarship and also by a research studentship to Trinity College, Cambridge, in 1949 he went to the Cavendish Laboratory wanting to do some “unorthodox” X-ray crystallography. Unfortunately the relevant Medical Research Council unit was full; instead, his PHD was obtained in solid state physics under D R Hartree.
After taking his PHD, Klug spent a year in the Colloid Science department in Cambridge, working with F J W Roughton, who had asked Hartree for someone to help him tackle the problem of absorption by simultaneous diffusion and chemical reaction – a chemical process which occurs in many biological and physiological situations, including when oxygen enters a red blood cell.
This work stimulated his interest in biology and he decided that he really wanted to work on the X-ray analysis of biological molecules. He obtained a Nuffield Fellowship to work in JD Bernal’s department at Birkbeck College in London and moved there at the end of 1953. He joined a project on the protein ribonuclease, but shortly afterwards met the crystallographer Rosalind Franklin, who had moved to Birkbeck earlier and had begun working on the tobacco mosaic virus.
Her X-ray photographs of molecules fascinated him and he decided to take up the study of the virus. Within four years, working with Kenneth Holmes and John Finch, he was able to map out the general outline of its structure. During this time he met Francis Crick, and together they published a paper on diffraction by helical structures.
After Rosalind Franklin’s untimely death in 1958, Klug became leader of the virus group and extended its work to spherical viruses. In 1962 they moved to the newly built Medical Research Council Laboratory of Molecular Biology in Cambridge, under the leadership of Max Perutz, where Klug became joint head of the division of Structural Studies in 1978 and director of the laboratory in 1986.
Klug’s group continued to work on the structure of viruses and on the assembly of the tobacco mosaic virus. The interests of the group soon diversified to include work on the structure of DNA and ribonucleic acid (RNA). The crystal structure of RNA was established in 1974, and in 1995 Klug’s team solved the structure of a molecule known as ribozyme, which attacks and breaks down the bonds in ribonucleic acid, allowing viruses and faulty genes to replicate.
This work led to the establishment of several biotech companies, and Klug was also instrumental in the establishment of the Sanger Centre (now the Wellcome Sanger Institute) in Cambridge, a spin-off of the MRC laboratory founded as a Dnasequencing centre to participate in the Human Genome Project. Klug gave much encouragement behind the scenes to the project, which eventually led to the sequencing of the human genome. In later life Klug led a research group on gene expression.
Over his years in Cambridge, Klug was actively involved in the teaching of undergraduates and supervising research students, and was particularly encouraging to female scientists. He became director of studies in Natural Science at Peterhouse.
A staunch supporter of, and frequent visitor to, the state of Israel, where an Aaron Klug Integrated Centre for Biomolecular Structure and Function was founded in his honour at the Ben-gurion University of the Negev, Klug’s Judaism was important to him, if mainly for its traditional social and ritual aspects, and he attended synagogue.
He was elected a Fellow of the Royal Society in 1969 and was its president between 1995 and 2000. He was knighted in 1988 and appointed to the Order of Merit in 1995.
In 1948 he married Liebe Bobrow, a dancer and choreographer whom he had met in Cape Town. She survives him with a son. Another son predeceased him in 2000.
Sir Aaron Klug, OM, born August 11 1926, died November 20 2018