British chemist
Leslie Eleazer Orgel
FRS
[1]
(12 January 1927 ? 27 October 2007) was a British
chemist
. He is known for his theories on the
origin of life
.
Biography
[
edit
]
Leslie Orgel was born in
London, England
, on
(
1927-01-12
)
12 January 1927. He received his Bachelor of Arts degree in chemistry with
first-class honours
from the
University of Oxford
in 1948. In 1951 he was elected a
Fellow
of
Magdalen College, Oxford
and in 1953 was awarded his PhD in chemistry.
Orgel started his career as a
theoretical
inorganic
chemist and continued his studies in this field at Oxford, the
California Institute of Technology
, and the
University of Chicago
.
Together with
Sydney Brenner
,
Jack Dunitz
,
Dorothy Hodgkin
, 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
and
James Watson
, at the time he and the other scientists were working at Oxford University's Chemistry Department.
[2]
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
.
[3]
In 1955 he joined the chemistry department at
Cambridge University
. There he did work in
transition metal
chemistry and
ligand field theory
, 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 aging in 1963,
[4]
(prior to the use of the term by
Manfred Eigen
for mutational
error catastrophe
) which has since been experimentally challenged.
[5]
In 1964, Orgel was appointed senior fellow and research professor at the
Salk Institute for Biological Studies
in
La Jolla, California
, 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
, and he was one of five principal investigators in the
NASA
-sponsored NSCORT program in
exobiology
. Orgel also participated in NASA's
Viking
Mars Lander Program as a member of the Molecular Analysis Team that designed the
gas chromatography
mass spectrometer
instrument that robots took to the planet
Mars
.
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 acids
? constituted the first pre-
biotic
systems capable of
self-replication
on
early Earth
.
His name is popularly known because of
Orgel's rules
, credited to him, particularly Orgel's Second Rule: "
Evolution
is cleverer than you are."
[6]
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 the origin of life research such as
Manfred Eigen
,
John Maynard Smith
and
Stephen Jay Gould
. Orgel's talk was on "Molecular Structure and Disordered Crystals."
[7]
Orgel died of pancreatic cancer on 27 October 2007 at the San Diego Hospice & Palliative Care in
San Diego, California
.
Research on the origin of life
[
edit
]
Nucleobase synthesis
[
edit
]
Orgel proposed a novel solution to a problem with
Juan Oro
's proposed mechanism of
nucleobase
synthesis on the
early Earth
, which relied on the reaction of five molecules of
hydrogen cyanide
(HCN) to form
adenine
. 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.
[8]
This would concentrate HCN molecules in the spaces in between the
crystal lattice
of ice, and also solve the problem of HCN being too
volatile
in a liquid water solution.
Nucleoside formation
[
edit
]
For
nucleoside
(
nucleobase
+
ribose
sugar) synthesis, Orgel suggested an almost opposite approach, heating a mixture of ribose and the
purine
nucleobases
hypoxanthine
, adenine, and
guanine
to dryness in the presence of
magnesium
ions.
[9]
This reaction puts the
glycosidic bond
in the correct position in two ways: the nucleobase attaches to the correct carbon on ribose, and in the correct orientation (the beta
anomer
).
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
[
edit
]
Continuing his work studying the
prebiotic synthesis
of
RNA
, Orgel explored mechanisms by which inorganic phosphate
[10]
and nucleotide
phosphoryl groups
[11]
could be chemically activated for
condensation
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 groups
and promoting the formation of short Adenosine dimers and trimers.
[12]
In 2018, John D. Sutherland and co-workers proposed that
methyl isocyanide
and
acetaldehyde
could combine to form a pre-biotic phosphate activating agent which could plausibly have formed under early-earth conditions.
[13]
Orgel also theorised that one single strand of RNA could have been the
template
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.
[11]
They further discovered that the divalent metal cation used to catalyze the reaction influenced the
regiochemistry
of the inter-nucleotide linkage.
[14]
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.
[15]
In the absence of
montmorillonite
, the primer was capped through the formation of a 5’ adenosine
pyrophosphate
.
The oligonucleotide products in early studies were typically characterized through a combination of
14
C
radiolabeling
,
gel electrophoresis
, and paper
electrophoresis
. Enzymatic digestion was used to differentiate
regioisomers
.
[12]
The advent of
HPLC
allowed the characterization of long oligomers of guanosine.
[14]
Directed panspermia
[
edit
]
Though he later downplayed the hypothesis, Orgel, along with
Francis Crick
, proposed a detailed
panspermia
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.
[16]
They proposed a design for the spaceship that aliens could have used to seed life on Earth.
RNA world
[
edit
]
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.
[17]
This view would be developed and shaped into the now widely accepted
RNA world
hypothesis.
Almost thirty years later, Orgel wrote a lengthy review of the RNA World hypothesis.
[18]
This review highlighted many proposed syntheses for RNA and its parts in
abiotic
conditions, noted the significance of the discovery of
ribozymes
(RNA molecules that function as
enzymes
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."
[18]
Awards
[
edit
]
Books
[
edit
]
- 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
[
edit
]
- ^
Dunitz, Jack D.; Joyce, Gerald F. (1 December 2013).
"Leslie Eleazer Orgel. 12 January 1927 ? 27 October 2007"
.
Biographical Memoirs of Fellows of the Royal Society
.
59
: 277?289.
doi
:
10.1098/rsbm.2013.0002
.
ISSN
0080-4606
.
- ^
Judson, Horace Freeland (2013).
The Eighth Day of Creation: Makers of the Revolution in Biology
. Cold Spring Harbor, New York: CSH Press. p. 238.
ISBN
978-0-879694-78-4
.
- ^
Olby, Robert,
Francis Crick: Hunter of Life's Secrets,
Cold Spring Harbor Laboratory Press, 2009, Chapter 10, p. 181
ISBN
978-0-87969-798-3
- ^
Orgel, Leslie E. (1963).
"The maintenance of the accuracy of protein synthesis and its relevance to ageing"
.
Proc. Natl. Acad. Sci. USA
.
49
(4): 517?521.
Bibcode
:
1963PNAS...49..517O
.
doi
:
10.1073/pnas.49.4.517
.
PMC
299893
.
PMID
13940312
.
- ^
Michael R. Rose
(1991).
Evolutionary Biology of Aging
. New York, NY:
Oxford University Press
. pp.
147?152
.
ISBN
978-0-19-506133-8
.
- ^
Dunitz, Jack D.; Joyce, Gerald F. (2013).
"Leslie E. Orgel"
(PDF)
.
Biographical Memoirs of the National Academy of Sciences
: 11.
- ^
Rice, Fredric L.
"WHAT IS LIFE? The next fifty years Trinity College, Dublin, Ireland September 20th ? 22nd"
.
icr.provocation.net
. Retrieved
18 November
2016
.
- ^
Sanchez, R.; Ferris, J.; Orgel, L. E. (1 July 1966). "Conditions for purine synthesis: did prebiotic synthesis occur at low temperatures?".
Science
.
153
(3731): 72?73.
Bibcode
:
1966Sci...153...72S
.
doi
:
10.1126/science.153.3731.72
.
ISSN
0036-8075
.
PMID
5938419
.
S2CID
31527498
.
- ^
Fuller, William D.; Sanchez, Robert A.; Orgel, Leslie E. (14 June 1972). "Studies in prebiotic synthesis".
Journal of Molecular Biology
.
67
(1): 25?33.
doi
:
10.1016/0022-2836(72)90383-X
.
PMID
4339529
.
- ^
Lohrmann, R.; Orgel, Leslie (1968). "Prebiotic Synthesis: Phosphorylation in Aqueous Solution".
Science
.
161
(3836). American Association for the Advancement of Science: 64?66.
Bibcode
:
1968Sci...161...64L
.
doi
:
10.1126/science.161.3836.64
.
JSTOR
1724394
.
PMID
5655266
.
S2CID
13005451
.
- ^
a
b
Weimann, B.; Lohrmann, R.; Orgel, Leslie; Schneider-Bernloher, H.; Sulston, J. (1968). "Template-Directed Synthesis with Adenosine-5'-Phosphorimidazolide".
Science
.
161
(3839). American Association for the Advancement of Science: 387.
Bibcode
:
1968Sci...161..387W
.
doi
:
10.1126/science.161.3839.387
.
JSTOR
1724244
.
PMID
5661298
.
S2CID
35649008
.
- ^
a
b
Sulston, J.; Lohrmann, R.; Orgel, Leslie; Miles, H. (1968).
"Nonenzymatic Synthesis of Oligoadenylates on a Polyuridie Acid Template"
.
Proceedings of the National Academy of Sciences of the United States of America
.
59
(3): 726?733.
Bibcode
:
1968PNAS...59..726S
.
doi
:
10.1073/pnas.59.3.726
.
PMC
224735
.
PMID
5238657
.
- ^
Mariani, Angelica; Russell, David; Javelle, Thomas; Sutherland, John (2018).
"A Light-Releasable Potentially Prebiotic Nucleotide Activating Agent"
.
Journal of the American Chemical Society
.
140
(28): 8657?8661.
doi
:
10.1021/jacs.8b05189
.
PMC
6152610
.
PMID
29965757
.
- ^
a
b
Lohrmann, R.; Bridson, P.; Orgel, Leslie (1980). "Efficient Metal-Ion Catalyzed Template-Directed Oligonucleotide Synthesis".
Science
.
208
(4451). American Association for the Advancement of Science: 1464?1465.
Bibcode
:
1980Sci...208.1464L
.
doi
:
10.1126/science.6247762
.
JSTOR
1684687
.
PMID
6247762
.
- ^
Ferris, James; Hill, Aubrey; Liu, Rihe; Orgel, Leslie (1996). "Synthesis of Long Prebiotic Oligomers on Mineral Surfaces".
Nature
.
381
(6577): 59?61.
Bibcode
:
1996Natur.381...59F
.
doi
:
10.1038/381059a0
.
hdl
:
2060/19980119839
.
PMID
8609988
.
S2CID
4351826
.
- ^
Crick, F. H. C.; Orgel, L. E. (1 July 1973). "Directed panspermia".
Icarus
.
19
(3): 341?346.
Bibcode
:
1973Icar...19..341C
.
doi
:
10.1016/0019-1035(73)90110-3
.
- ^
Joyce, Gerald F. (2007). "Obituary: Leslie Orgel (1927?2007)".
Nature
.
450
(7170): 627.
Bibcode
:
2007Natur.450..627J
.
doi
:
10.1038/450627a
.
PMID
18046392
.
S2CID
5439488
.
- ^
a
b
Orgel, Leslie E (1 January 2004). "Prebiotic Chemistry and the Origin of the RNA World".
Critical Reviews in Biochemistry and Molecular Biology
.
39
(2): 99?123.
CiteSeerX
10.1.1.537.7679
.
doi
:
10.1080/10409230490460765
.
ISSN
1040-9238
.
PMID
15217990
.
S2CID
4939632
.
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