Aaron Klug: Architect of the Microscopic World
Sir Aaron Klug (1926–2018) was a titan of 20th-century science whose work bridged the gap between physics, chemistry, and biology. A Nobel laureate and former President of the Royal Society, Klug is best remembered for developing crystallographic electron microscopy and for deciphering the complex structures of viruses and DNA-binding proteins. His career was defined by an uncanny ability to "see" the invisible, turning blurry two-dimensional images into precise three-dimensional models of life’s fundamental machinery.
1. Biography: From the Veld to the Fens
Aaron Klug was born on August 11, 1926, in Zelva, Lithuania, but his family emigrated to Durban, South Africa, when he was just two years old. His early education was shaped by a burgeoning interest in the physical world, leading him to the University of the Witwatersrand in Johannesburg. Though he initially enrolled in medicine, he pivoted to physics and mathematics, earning his BSc in 1945.
After completing an MSc at the University of Cape Town—where he developed a passion for X-ray crystallography—Klug moved to England in 1949. He earned his PhD at Trinity College, Cambridge, studying the properties of steel, but his intellectual curiosity soon drifted toward the "physics of life."
In 1953, a pivotal move took him to Birkbeck College in London. There, he joined the laboratory of the legendary J.D. Bernal and began a transformative collaboration with Rosalind Franklin. Following Franklin’s untimely death in 1958, Klug took over her research group. In 1962, he moved to the newly established Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) in Cambridge. He remained at the LMB for the rest of his career, serving as its Director from 1986 to 1996.
2. Major Contributions: Visualizing the Invisible
Klug’s scientific legacy rests on three pillars of structural biology:
Crystallographic Electron Microscopy
Before Klug, electron microscopy (EM) produced two-dimensional "shadow" images that were often difficult to interpret. Klug realized that by applying the mathematical principles of X-ray diffraction to EM images, one could reconstruct a three-dimensional object from a series of 2D views. This breakthrough allowed scientists to determine the structures of large molecular complexes that were too "floppy" or complex to be crystallized for traditional X-ray analysis.
The Architecture of Viruses
Klug spent decades mapping the structure of the Tobacco Mosaic Virus (TMV). He discovered how the virus’s RNA and protein subunits self-assemble into a precise helical structure. He also solved the structure of the "spherical" (icosahedral) viruses, showing how they are built from geometric arrangements of protein subunits.
The Discovery of Zinc Fingers
In 1985, while studying the transcription of DNA in frogs, Klug’s team discovered a new type of protein motif: the Zinc Finger. These are small, finger-like structures stabilized by a zinc ion that allow proteins to "grip" specific sequences of DNA. This discovery was foundational for the field of gene regulation and laid the groundwork for modern gene-editing technologies like Zinc Finger Nucleases (ZFNs).
3. Notable Publications
Klug authored hundreds of papers, but several stand as landmarks in the history of science:
- "Reconstruction of three dimensional structures from electron micrographs" (1968, Nature): Co-authored with David DeRosier, this paper introduced the mathematical framework for 3D electron microscopy.
- "Structure of the nucleosome core particle at 7 Å resolution" (1977, Nature): This work elucidated how DNA is packaged around histone proteins in the cell nucleus.
- "A central role for RNA in the assembly of tobacco mosaic virus" (1958, Nature): One of his early major papers with Rosalind Franklin, detailing the organization of TMV.
- "A novel protein motif for nucleic acid recognition" (1985, FEBS Letters): The announcement of the discovery of zinc fingers.
4. Awards & Recognition
Klug’s contributions were recognized at the highest levels of global science:
- Nobel Prize in Chemistry (1982): Awarded for his development of crystallographic electron microscopy and his structural elucidation of biologically important nucleic acid-protein complexes.
- Knighthood (1988): Appointed Knight Bachelor by Queen Elizabeth II for services to molecular biology.
- Order of Merit (1995): A prestigious honor limited to only 24 living members.
- President of the Royal Society (1995–2000): During his tenure, he was a vocal advocate for science in the public sphere, particularly regarding genetically modified crops and stem cell research.
- Copley Medal (1985): The Royal Society’s oldest and most prestigious award.
5. Impact & Legacy
Aaron Klug’s impact is visible in every modern structural biology laboratory. His development of 3D reconstruction techniques was the direct precursor to Cryo-Electron Microscopy (Cryo-EM), a field that won the Nobel Prize in 2017 and has revolutionized our ability to see drug targets at the atomic level.
Furthermore, his work on Zinc Fingers opened the door to "programmable" biology. Before CRISPR, Zinc Fingers were the primary tool for targeted genome engineering, and they remain a vital component in the development of gene therapies for diseases like sickle cell anemia and HIV.
6. Collaborations
Klug was a master of the collaborative environment of the MRC LMB.
- Rosalind Franklin: Klug was her closest colleague during her final years. He became her scientific executor, finishing her work on viruses and fiercely defending her role in the discovery of the DNA double helix against early accounts that marginalized her.
- David DeRosier: Together, they pioneered the Fourier-based methods for 3D image reconstruction.
- John Finch: A long-term collaborator at the LMB who worked with Klug on the structural analysis of chromatin and viruses.
- Sydney Brenner & Francis Crick: As a senior figure at the LMB, Klug worked alongside these pioneers, contributing to the intellectual atmosphere that made the laboratory the "Nobel Prize factory."
7. Lesser-Known Facts
- Defender of Franklin: It was Aaron Klug who provided much of the documentary evidence used by biographers to prove that Rosalind Franklin had indeed identified the B-form of DNA and its helical nature before Watson and Crick published their model.
- A Slow Start in Biology: Klug’s transition from physics to biology was initially met with skepticism. When he first applied for a fellowship to work on biological structures, he was told by a senior scientist that
"the time was not yet ripe"
for such a physical approach to biology. - Cultural Scholar: Beyond the lab, Klug was deeply interested in Jewish history and philosophy. He was a polymath who could discuss Talmudic law or the history of Durban with the same rigor he applied to X-ray diffraction patterns.
- Public Policy: As President of the Royal Society, he was instrumental in navigating the UK's "Mad Cow Disease" (BSE) crisis, insisting on transparent, evidence-based communication between scientists and the public.