Aaron Klug
(1926 - )
Aaron Klug was born on August 11, 1926, in Zelvas, Lithuania; however, his family
moved two years later to Durban, South
Africa. During primary school, Klug read the book Microbe Hunters
by Paul de Kruif, which influenced him to study medicine and microbiology
at the University of Witwatersrand in Johannesburg.
After graduating, Klug pursued research in physics
and crystallography (the experimental science of determining the arrangement
of atoms in solids) at the University of Cape Town, where he received
his masters in science. Klug remained at the university to continue
studying X-ray analysis of small organic compounds. It was during this
period that Klug developed a deep interest in the composition and organization
of matter.
In 1949, Klug moved to England to study at the Trinity
College Cavendish Laboratory in Cambridge. Klug received his doctorate
in 1953 from the university. At the end of 1953, Klug moved to London to work with Rosalind Franklin in John Bernal’s department in
Birkbeck College. Together, Franklin and Klug tackled the uncertainties
surrounding tobacco mosaic virus (RNA virus that affects plants) and
outlined the molecular structure of the virus.
After Franklin died in 1958, Klug continued his research
on viruses, now expanding to spherical viruses. In 1962, Klug and his
team of assistants returned to Cambridge to work in the newly built
Laboratory of Molecular Biology. Between 1986 and 1996, Klug was elected
to director of the Laboratory.
At the lab, Klug used techniques from X-ray diffraction,
microscopy, and structural modeling to develop crystallographic electron
microscopy. This form of microscopy takes two-dimensional images of
crystals from different angles and combines them to produce three-dimensional
image reconstruction of the target. This allowed Klug to produce three-dimensional
structures of viruses. Aaron Klug received the Nobel
Prize for Chemistry in 1982 for his development in crystallographic
electron microscopy.
Klug has also worked on revealing the structure of
the DNA-protein complex, chromatin. Also in 1974, Klug and his collaborators
were the first to collect crystals of a transfer RNA and determine its
structure.
Klug has chaired the Israel Academy of Sciences and
sat on the advisory committee of the Weizman
Institute, at Hebrew University. In 1988, Klug was knighted by Queen
Elizabeth.
The following press release
from the Royal Swedish Academy of Sciences
describes Klug's work:
Life is a chemical phenomenon. Living organisms are
the most complicated of all chemical systems in the universe. In contrast
to the dead matter which surrounds us, life is characterized by a high
degree of order and organization. The building blocks of the cell are
to a large extent giant molecules (macromolecules) in which thousands
of atoms occupy a unique arrangement in space specific for each substance.
The cell also contains ordered structures, organelles, which are large
aggregates of different macromolecules, and many important biochemical
functions are associated with such molecular aggregates. As examples
may be mentioned that the chemical machinery of heridity is localized
in the cell nucleus, and other organelles, mitochondria, are the power
stations of the cell, producing energy by combustion.
The goal of biochemistry is to explain a biological
function on the basis of chemical structure. An important step in biochemical
research is consequently the isolation and structure determination of
the macromolecular components of the cell and of the functional aggregates
formed from them. Pure chemical substances can often be obtained in
the form of crystals, in which the position of the constituent atoms
and molecules is repeated in a periodic fashion, and in this case there
is a general method available for determination of structure. This method
is based on an interpretation of the specific pattern which is created,
when X-rays are scattered from atoms in a periodic arrangement. The
principle of X-ray diffraction is old and was awarded with the Nobel
Prize in physics already in 1915. Not until much later was the method
sufficiently developed for the determination of the structure of biological
macromolecules. Max Perutz and John Kendrew were awarded the 1962 Nobel
Prize in chemistry for their investigations on the structure of proteins
by X-ray diffraction.
Complicated molecular aggregates, such as membranes,
muscle fibres and chromosomes, can generally not be obtained as highly
ordered, three-dimensional crystals suitable for structural determination
by X-ray diffraction. Aaron Klug, who has been awarded this year's Nobel
Prize in chemistry, has developed a method for the structural determination
of biologically functional molecular aggregates. His technique is based
on an ingenious combination of electron microscopy with principles from
diffraction methods.
Electron microscopy has
long been used to obtain a two-dimensional
picture of biological objects. The power
of the method to give a clear picture of
the structure is, however, limited by several
factors. The molecules of life consist
mainly of light atoms, which makes the
picture lacking in contrast. Increased
contrast can be achieved with long exposure
times, but this entails the danger that
the structure is destroyed by radiation
damage. Instead the contrast is generally
improved by "staining" with heavy
metals, which can also lead to a distortion
of the structure.
Klug has shown that pictures of biological objects
seemingly lacking in contrast often contain a large amount of structural
information, which can be made available by a mathematical manipulation
of the original picture. His method allows electron microscope pictures
of high quality to be obtained with very low radiation doses and without
the use of heavy metal stains. In this way changes in the sample are
minimized, so that the electron microscope picture at high resolution
is a true representation of the original biological structure. The method
gives a two-dimensional projection of the sample only, but Klug has
shown that a three-dimensional reconstruction of the object can be obtained
by collecting pictures in several different directions of projection.
The method of Klug makes it possible to determine structures
at high resolution of functionally important molecular aggregates. Klug
himself has chiefly investigated complexes between nucleic acids and
proteins, the key substances of life. One nucleic acid, DNA, is carrier
of the traits of heredity in the chromosome of the cell nucleus, and
it forms giant complexes with specific proteins, histones. Less complicated
nucleic acid-protein complexes are found in viruses, which can be said
to be genetic material without a cell of its own. Klug has used the
whole arsenal of structural chemistry, including his own method, to
investigate the structure of several viruses, e.g. tobacco mosaic virus
(TMV). His structural investigations snow that TMV contains a long thread
of nucleic acid which is arranged in the form of a helix through interaction
with as many as 2130 identical protein molecules. Klug's structural
investigations have also given a detailed picture of the formation of
the virus particle from a mixture of its nucleic acid and protein constituents.
In this way he has illuminated a very important biochemical principle,
namely the spontaneous formation of complicated functional molecular
aggregates from the molecular components.
The DNA-protein complex of cell nuclei, chromatin,
is condensed to chromosomes during cell division. In a given cell only
a part of the genetic message in DNA is transcribed, a fact which must
also be related to structural changes in the chromatin. Knowledge of
chromatin structure is consequently of great importance for an understanding
of the control functions of the cell.
Chromatin is too large a molecular aggregate to allow
a direct structural determination even by the method of Klug. With his
co-workers, Klug has, however, succeeded in breaking down chromatin
to fragments which are small enough to be studied by X-ray diffraction
and electron microscopy. Klug has then been able to construct a model
for the chromosomes based on his knowledge of the structure of the fragment.
Klug's investigations of biochemical structures have
yielded a detailed picture of the functional arrangements in biologically
important nucleic acid-protein complexes. They have already provided
clues to the problem of cell differentiation, since the transcription
of the genetic message in a cell is under structural control. Continued
structural investigations of chromatin will, in a long-term perspective,
undoubtedly be of crucial importance for our understanding of the nature
of cancer, in which the control of the growth and division of cells
by the genetic material no longer functions.
Sources: Wikipedia;
"Aaron
Klug Autobiography"; Weizman
Institute; Press release: "The
1982 Nobel Prize in Chemistry" |