Leslie Eleazer Orgel
FRS (12 January 1927 – 27 October 2007) was a British
chemist
A chemist (from Greek ''chēm(ía)'' alchemy; replacing ''chymist'' from Medieval Latin ''alchemist'') is a scientist trained in the study of chemistry. Chemists study the composition of matter and its properties. Chemists carefully describe ...
. He is known for his theories on the
origin of life
In biology, abiogenesis (from a- 'not' + Greek bios 'life' + genesis 'origin') or the origin of life is the natural process by which life has arisen from non-living matter, such as simple organic compounds. The prevailing scientific hypothes ...
.
Biography
Leslie Orgel was born in
London, England
London is the capital and largest city of England and the United Kingdom, with a population of just under 9 million. It stands on the River Thames in south-east England at the head of a estuary down to the North Sea, and has been a major s ...
, on . He received his Bachelor of Arts degree in chemistry with
first-class honours
The British undergraduate degree classification system is a grading structure for undergraduate degrees or bachelor's degrees and integrated master's degrees in the United Kingdom. The system has been applied (sometimes with significant variati ...
from the
University of Oxford
The University of Oxford is a collegiate research university in Oxford, England. There is evidence of teaching as early as 1096, making it the oldest university in the English-speaking world and the world's second-oldest university in contin ...
in 1948. In 1951 he was elected a
Fellow
A fellow is a concept whose exact meaning depends on context.
In learned or professional societies, it refers to a privileged member who is specially elected in recognition of their work and achievements.
Within the context of higher education ...
of
Magdalen College, Oxford and in 1953 was awarded his PhD in chemistry.
Orgel started his career as a
theoretical inorganic
In chemistry, an inorganic compound is typically a chemical compound that lacks carbon–hydrogen bonds, that is, a compound that is not an organic compound. The study of inorganic compounds is a subfield of chemistry known as ''inorganic chemis ...
chemist and continued his studies in this field at Oxford, the
California Institute of Technology
The California Institute of Technology (branded as Caltech or CIT)The university itself only spells its short form as "Caltech"; the institution considers other spellings such a"Cal Tech" and "CalTech" incorrect. The institute is also occasional ...
and the
University of Chicago
The University of Chicago (UChicago, Chicago, U of C, or UChi) is a private university, private research university in Chicago, Illinois. Its main campus is located in Chicago's Hyde Park, Chicago, Hyde Park neighborhood. The University of Chic ...
.
Together with
Sydney Brenner
Sydney Brenner (13 January 1927 – 5 April 2019) was a South African biologist. In 2002, he shared the Nobel Prize in Physiology or Medicine with H. Robert Horvitz and Sir John E. Sulston. Brenner made significant contributions to work ...
,
Jack Dunitz
Jack David Dunitz FRS (29 March 1923 – 12 September 2021) was a British chemist and widely known chemical crystallographer. He was Professor of Chemical Crystallography at the ETH Zurich from 1957 until his official retirement in 1990. He h ...
,
Dorothy Hodgkin
Dorothy Mary Crowfoot Hodgkin (née Crowfoot; 12 May 1910 – 29 July 1994) was a Nobel Prize-winning British chemist who advanced the technique of X-ray crystallography to determine the structure of biomolecules, which became essential ...
, and Beryl M. Oughton he was one of the first people in April 1953 to see the model of the structure of
DNA, constructed by
Francis Crick
Francis Harry Compton Crick (8 June 1916 – 28 July 2004) was an English molecular biologist, biophysicist, and neuroscientist. He, James Watson, Rosalind Franklin, and Maurice Wilkins played crucial roles in deciphering the helical stru ...
and
James Watson
James Dewey Watson (born April 6, 1928) is an American molecular biologist, geneticist, and zoologist. In 1953, he co-authored with Francis Crick the academic paper proposing the double helix structure of the DNA molecule. Watson, Crick and ...
, at the time he and the other scientists were working at Oxford University's Chemistry Department. According to the late Dr. Beryl Oughton, later Rimmer, they all travelled together in two cars once Dorothy Hodgkin announced to them that they were off to Cambridge to see the model of the structure of DNA. All were impressed by the new DNA model, especially Brenner who subsequently worked with Crick; Orgel himself also worked with Crick at the
Salk Institute for Biological Studies
The Salk Institute for Biological Studies is a scientific research institute located in the La Jolla community of San Diego, California, U.S. The independent, non-profit institute was founded in 1960 by Jonas Salk, the developer of the polio vac ...
.
In 1955 he joined the chemistry department at
Cambridge University
, mottoeng = Literal: From here, light and sacred draughts.
Non literal: From this place, we gain enlightenment and precious knowledge.
, established =
, other_name = The Chancellor, Masters and Schola ...
. There he did work in
transition metal
In chemistry, a transition metal (or transition element) is a chemical element in the d-block of the periodic table (groups 3 to 12), though the elements of group 12 (and less often group 3) are sometimes excluded. They are the elements that c ...
chemistry and
ligand field theory
Ligand field theory (LFT) describes the bonding, orbital arrangement, and other characteristics of coordination complexes. It represents an application of molecular orbital theory to transition metal complexes. A transition metal ion has nine vale ...
, published several peer-reviewed journal articles and wrote a textbook entitled ''Transition Metal Chemistry: Ligand Field Theory'' (1960). He developed the
Orgel diagram showing the energies of electronic terms in transition metal complexes.
Orgel formulated his
protein-translation error-catastrophe theory of ageing in 1963, (prior to the use of the term by
Manfred Eigen
Manfred Eigen (; 9 May 1927 – 6 February 2019) was a German biophysical chemist who won the 1967 Nobel Prize in Chemistry for work on measuring fast chemical reactions.
Eigen's research helped solve major problems in physical chemistry and ...
for mutational
error catastrophe) which has since been experimentally challenged.
In 1964, Orgel was appointed senior fellow and research professor at the
Salk Institute for Biological Studies
The Salk Institute for Biological Studies is a scientific research institute located in the La Jolla community of San Diego, California, U.S. The independent, non-profit institute was founded in 1960 by Jonas Salk, the developer of the polio vac ...
in
La Jolla, California
La Jolla ( , ) is a hilly, seaside neighborhood within the city of San Diego, California, United States, occupying of curving coastline along the Pacific Ocean. The population reported in the 2010 census was 46,781.
La Jolla is surrounded on ...
, where he directed the Chemical Evolution Laboratory. He was also an adjunct professor in the Department of Chemistry and Biochemistry at the
University of California, San Diego
The University of California, San Diego (UC San Diego or colloquially, UCSD) is a public university, public Land-grant university, land-grant research university in San Diego, California. Established in 1960 near the pre-existing Scripps Insti ...
, and he was one of five principal investigators in the
NASA
The National Aeronautics and Space Administration (NASA ) is an independent agency of the US federal government responsible for the civil space program, aeronautics research, and space research.
NASA was established in 1958, succeedi ...
-sponsored NSCORT program in
exobiology. Orgel also participated in NASA's
Viking
Vikings ; non, víkingr is the modern name given to seafaring people originally from Scandinavia (present-day Denmark, Norway and Sweden),
who from the late 8th to the late 11th centuries raided, pirated, traded and s ...
Mars Lander Program as a member of the Molecular Analysis Team that designed the
gas chromatography
Gas chromatography (GC) is a common type of chromatography used in analytical chemistry for separating and analyzing compounds that can be vaporized without decomposition. Typical uses of GC include testing the purity of a particular substance, ...
mass spectrometer
Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a '' mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is u ...
instrument that robots took to the planet
Mars
Mars is the fourth planet from the Sun and the second-smallest planet in the Solar System, only being larger than Mercury. In the English language, Mars is named for the Roman god of war. Mars is a terrestrial planet with a thin atmos ...
.
Orgel's lab came across an economical way to make
cytarabine, a compound that is one of today's most commonly used
anti-cancer agents.
Together with
Stanley Miller, Orgel also suggested that
peptide nucleic acids – rather than
ribonucleic acid
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydr ...
s – constituted the first pre-
biotic
Biotics describe living or once living components of a community; for example organisms, such as animals and plants.
Biotic may refer to:
*Life, the condition of living organisms
*Biology, the study of life
* Biotic material, which is derived from ...
systems capable of
self-replication
Self-replication is any behavior of a dynamical system that yields construction of an identical or similar copy of itself. Biological cells, given suitable environments, reproduce by cell division. During cell division, DNA is replicated and c ...
on
early Earth
The early Earth is loosely defined as Earth in its first one billion years, or gigayear (Ga, 109y). The “early Earth” encompasses approximately the first gigayear in the evolution of our planet, from its initial formation in the young Solar S ...
.
His name is popularly known because of
Orgel's rule Orgel's rules are a set of axioms attributed by Francis Crick to the evolutionary biologist Leslie Orgel.
Orgel's First Rule
"Whenever a spontaneous process is too slow or too inefficient a protein will evolve to speed it up or make it more efficie ...
s, credited to him, particularly Orgel's Second Rule: "
Evolution
Evolution is change in the heritable characteristics of biological populations over successive generations. These characteristics are the expressions of genes, which are passed on from parent to offspring during reproduction. Variation ...
is cleverer than you are."
In his book ''The Origins of Life'', Orgel coined the concept of
specified complexity, to describe the criterion by which living organisms are distinguished from non-living matter. He published over three hundred articles in his research areas.
In 1993, Orgel presented at the "What is Life?" Conference at
Trinity College in Dublin, Ireland along with many other prominent scientists exploring origin of life research such as
Manfred Eigen
Manfred Eigen (; 9 May 1927 – 6 February 2019) was a German biophysical chemist who won the 1967 Nobel Prize in Chemistry for work on measuring fast chemical reactions.
Eigen's research helped solve major problems in physical chemistry and ...
,
John Maynard Smith
John Maynard Smith (6 January 1920 – 19 April 2004) was a British theoretical and mathematical evolutionary biologist and geneticist. Originally an aeronautical engineer during the Second World War, he took a second degree in genetics ...
and
Stephen Jay Gould
Stephen Jay Gould (; September 10, 1941 – May 20, 2002) was an American paleontologist, evolutionary biologist, and historian of science. He was one of the most influential and widely read authors of popular science of his generation. Gould s ...
. Orgel's talk was on "Molecular Structure and Disordered Crystals."
Orgel died of pancreatic cancer on 27 October 2007 at the San Diego Hospice & Palliative Care in
San Diego, California
San Diego ( , ; ) is a city on the Pacific Ocean coast of Southern California located immediately adjacent to the Mexico–United States border. With a 2020 population of 1,386,932, it is the List of United States cities by population, eigh ...
.
Research on the origin of life
Nucleobase synthesis
Orgel proposed a novel solution to a problem with
Juan Oro
''Juan'' is a given name, the Spanish and Manx versions of '' John''. It is very common in Spain and in other Spanish-speaking communities around the world and in the Philippines, and also (pronounced differently) in the Isle of Man. In Spanis ...
's proposed mechanism of
nucleobase
Nucleobases, also known as ''nitrogenous bases'' or often simply ''bases'', are nitrogen-containing biological compounds that form nucleosides, which, in turn, are components of nucleotides, with all of these monomers constituting the basic ...
synthesis on the
early Earth
The early Earth is loosely defined as Earth in its first one billion years, or gigayear (Ga, 109y). The “early Earth” encompasses approximately the first gigayear in the evolution of our planet, from its initial formation in the young Solar S ...
, which relied on the reaction of five molecules of
hydrogen cyanide
Hydrogen cyanide, sometimes called prussic acid, is a chemical compound with the formula HCN and structure . It is a colorless, extremely poisonous, and flammable liquid that boils slightly above room temperature, at . HCN is produced on a ...
(HCN) to form
adenine
Adenine () (symbol A or Ade) is a nucleobase (a purine derivative). It is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The three others are guanine, cytosine and thymine. Its derivativ ...
. The problem with this was that it would require much more concentrated hydrogen cyanide than evidence suggested was present.
Orgel suggested that the hydrogen cyanide was frozen in solution. This would concentrate HCN molecules in the spaces in between the
crystal lattice
In geometry and crystallography, a Bravais lattice, named after , is an infinite array of discrete points generated by a set of discrete translation operations described in three dimensional space by
: \mathbf = n_1 \mathbf_1 + n_2 \mathbf_2 + n ...
of ice, and also solved the problem of HCN being too
volatile in a liquid water solution.
Nucleoside formation
For
nucleoside
Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar ( ribose or 2'-deoxyribose) whereas a nucleoti ...
(
nucleobase
Nucleobases, also known as ''nitrogenous bases'' or often simply ''bases'', are nitrogen-containing biological compounds that form nucleosides, which, in turn, are components of nucleotides, with all of these monomers constituting the basic ...
+
ribose
Ribose is a simple sugar and carbohydrate with molecular formula C5H10O5 and the linear-form composition H−(C=O)−(CHOH)4−H. The naturally-occurring form, , is a component of the ribonucleotides from which RNA is built, and so this compou ...
sugar) synthesis, Orgel suggested an almost opposite approach, heating a mixture of ribose and the
purine
Purine is a heterocyclic aromatic organic compound that consists of two rings ( pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which include substituted purin ...
nucleobases
hypoxanthine
Hypoxanthine is a naturally occurring purine derivative. It is occasionally found as a constituent of nucleic acids, where it is present in the anticodon of tRNA in the form of its nucleoside inosine. It has a tautomer known as 6-hydroxypurine. H ...
, adenine, and
guanine
Guanine () (symbol G or Gua) is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine ( uracil in RNA). In DNA, guanine is paired with cytosine. The guanine nucleoside is c ...
to dryness in the presence of
magnesium
Magnesium is a chemical element with the symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 of the periodic ...
ions. This reaction puts the
glycosidic bond
A glycosidic bond or glycosidic linkage is a type of covalent bond that joins a carbohydrate (sugar) molecule to another group, which may or may not be another carbohydrate.
A glycosidic bond is formed between the hemiacetal or hemiketal gr ...
in the correct position in two ways: the nucleobase attaches to the correct carbon on ribose, and in the correct orientation (the beta
anomer
In carbohydrate chemistry, a pair of anomers () is a pair of near-identical stereoisomers that differ at only the anomeric carbon, the carbon that bears the aldehyde or ketone functional group in the sugar's open-chain form. However, in order f ...
).
However, the synthesis was later criticised because it only worked most with hypoxanthine, a nucleobase that is not relevant to current life on Earth, and because it was not specific for the ribose sugar and could instead be applied to other sugars.
RNA polymerization
Continuing his work studying the
prebiotic synthesis of
RNA
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
, Orgel explored mechanisms by which inorganic phosphate and nucleotide
phosphoryl group {{unreferenced, date=May 2015
A phosphoryl group is the chemical ion or radical: P+O32−, containing phosphorus and oxygen. (The correct chemical name for this −PO32− group is phosphonato, and phosphono for −PO3H2; as ''phosphoryl'' in ...
s
could be chemically activated for
condensation
Condensation is the change of the state of matter from the gas phase into the liquid phase, and is the reverse of vaporization. The word most often refers to the water cycle. It can also be defined as the change in the state of water vapor ...
into nucleic acid polymers. Starting in the 1960s, Orgel explored a variety of cyanide-based activating agents which could have plausibly been present on a young earth. A
carbodiimide reagent was found to be effective at activating nucleotide
phosphoryl group {{unreferenced, date=May 2015
A phosphoryl group is the chemical ion or radical: P+O32−, containing phosphorus and oxygen. (The correct chemical name for this −PO32− group is phosphonato, and phosphono for −PO3H2; as ''phosphoryl'' in ...
s and promoting the formation of short Adenosine dimers and trimers.
In 2018, John D. Sutherland and co-workers proposed that
methyl isocyanide and
acetaldehyde
Acetaldehyde (IUPAC systematic name ethanal) is an organic chemical compound with the formula CH3 CHO, sometimes abbreviated by chemists as MeCHO (Me = methyl). It is a colorless liquid or gas, boiling near room temperature. It is one of the ...
could combine to form a pre-biotic phosphate activating agent which could plausibly have formed under early-earth conditions.
Orgel also theorised that one single strand of RNA could have been the
template
Template may refer to:
Tools
* Die (manufacturing), used to cut or shape material
* Mold, in a molding process
* Stencil, a pattern or overlay used in graphic arts (drawing, painting, etc.) and sewing to replicate letters, shapes or designs
Co ...
for the first life on Earth and that these
imidazole-activated nucleotides could have used this RNA template strand to polymerise and
replicate. Lohrmann and Orgel reported that the
phosphorimidazolide derivative of adenosine monophosphate (in which a phosphoryl group oxygen is substituted by an imidazole ring) forms short adenosine oligomers in the presence of poly-uridine templates.
They further discovered that the divalent metal cation used to catalyze the reaction influenced the
regiochemistry of the inter-nucleotide linkage.
Pb
2+ gave primarily 5’-2’ linked nucleotides while Zn
2+ gave primarily 5’-3’ linked nucleotides from guanosine phosphorimidazolides in the presence of a poly-cytidine template.
Montmorillonite clay was also shown to promote the polymerization of adenosine phosphorimidazolide into oligonucleotides tens of bases in length starting from a poly-adenosine 10-mer primer. In the absence of
montmorillonite, the primer was capped through the formation of a 5’ adenosine
pyrophosphate
In chemistry, pyrophosphates are phosphorus oxyanions that contain two phosphorus atoms in a P–O–P linkage. A number of pyrophosphate salts exist, such as disodium pyrophosphate (Na2H2P2O7) and tetrasodium pyrophosphate (Na4P2O7), among o ...
.
The oligonucleotide products in early studies were typically characterized through a combination of
14C
radiolabeling
A radioactive tracer, radiotracer, or radioactive label is a chemical compound in which one or more atoms have been replaced by a radionuclide so by virtue of its radioactive decay it can be used to explore the mechanism of chemical reactions by tr ...
,
gel electrophoresis
Gel electrophoresis is a method for separation and analysis of biomacromolecules ( DNA, RNA, proteins, etc.) and their fragments, based on their size and charge. It is used in clinical chemistry to separate proteins by charge or size (IEF ...
, and paper
electrophoresis
Electrophoresis, from Ancient Greek ἤλεκτρον (ḗlektron, "amber") and φόρησις (phórēsis, "the act of bearing"), is the motion of dispersed particles relative to a fluid under the influence of a spatially uniform electric f ...
. Enzymatic digestion was used to differentiate
regioisomer
In chemistry, a structural isomer (or constitutional isomer in the IUPAC nomenclature) of a compound is another compound whose molecule has the same number of atoms of each element, but with logically distinct bonds between them. The term metam ...
s.
The advent of
HPLC
High-performance liquid chromatography (HPLC), formerly referred to as high-pressure liquid chromatography, is a technique in analytical chemistry used to separate, identify, and quantify each component in a mixture. It relies on pumps to pa ...
allowed the characterization of long oligomers of guanosine.
Directed panspermia
Though he later downplayed the hypothesis, Orgel, along with
Francis Crick
Francis Harry Compton Crick (8 June 1916 – 28 July 2004) was an English molecular biologist, biophysicist, and neuroscientist. He, James Watson, Rosalind Franklin, and Maurice Wilkins played crucial roles in deciphering the helical stru ...
, proposed a detailed
panspermia
Panspermia () is the hypothesis, first proposed in the 5th century BCE by the Greek philosopher Anaxagoras, that life exists throughout the Universe, distributed by space dust, meteoroids, asteroids, comets, and planetoids, as well as by space ...
scenario for the origin of life on Earth, going so far as to suggest that life on Earth was designed by an
alien species and sent to Earth. They proposed a design for the spaceship that aliens could have used to seed life on Earth.
RNA world
In the late 1960s, Orgel proposed that life was based on RNA before it was based on DNA or proteins. His theory included genes based on RNA and RNA enzymes.
This view would be developed and shaped into the now widely accepted
RNA world
The RNA world is a hypothetical stage in the evolutionary history of life on Earth, in which self-replicating RNA molecules proliferated before the evolution of DNA and proteins. The term also refers to the hypothesis that posits the existenc ...
hypothesis.
Almost thirty years later, Orgel wrote a lengthy review of the RNA World hypothesis.
This review highlighted many proposed syntheses for RNA and its parts in
abiotic conditions, noted the significance of the discovery of
ribozyme
Ribozymes (ribonucleic acid enzymes) are RNA molecules that have the ability to catalyze specific biochemical reactions, including RNA splicing in gene expression, similar to the action of protein enzymes. The 1982 discovery of ribozymes demonst ...
s (RNA molecules that function as
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...
s just as Orgel had once predicted) and at the same time, demonstrated nucleic acid polymers with alternatives to ribose such as
threose nucleic acid (TNA) and
peptide nucleic acid (PNA).
In conclusion, Orgel wrote, "One must recognize that, despite considerable progress, the problem of the origin of the RNA World is far from being solved."
Awards
*Elected to the
National Academy of Sciences
The National Academy of Sciences (NAS) is a United States nonprofit, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the Nat ...
in 1990.
*Elected as a
Fellow
A fellow is a concept whose exact meaning depends on context.
In learned or professional societies, it refers to a privileged member who is specially elected in recognition of their work and achievements.
Within the context of higher education ...
of the
Royal Society of London
The Royal Society, formally The Royal Society of London for Improving Natural Knowledge, is a learned society and the United Kingdom's national academy of sciences. The society fulfils a number of roles: promoting science and its benefits, re ...
in 1962.
*
American Academy of Arts and Sciences
The American Academy of Arts and Sciences (abbreviation: AAA&S) is one of the oldest learned societies in the United States. It was founded in 1780 during the American Revolution by John Adams, John Hancock, James Bowdoin, Andrew Oliver, ...
Books
*Leslie E. Orgel, ''An Introduction to Transition-Metal Chemistry. The Ligand Field Theory'', 1961
*Leslie E. Orgel, ''The Origins of Life: Molecules and Natural Selection'', 1973
*Leslie E. Orgel and Stanley L. Miller, ''The Origins of Life on the Earth'', 1974
References
External links
Register of the Leslie Orgel Papers at UCSDThe Implausibility of Metabolic Cycles on the Prebiotic EarthLeslie Orgel's obituary on the Salk Institute website*LA Times
"Leslie Orgel, 80; chemist was father of the RNA world theory of the origin of life" 31 October 2007
"Leslie Orgel dies" ''
The Scientist'', 1 November 2007
{{DEFAULTSORT:Orgel, Leslie
Members of the United States National Academy of Sciences
British chemists
Inorganic chemists
Members of the University of Cambridge Department of Chemistry
Fellows of the American Academy of Arts and Sciences
Fellows of Magdalen College, Oxford
Fellows of the Royal Society
1927 births
2007 deaths
Panspermia
Origin of life
Salk Institute for Biological Studies people