Steven Albert Benner (born October 23, 1954) has been a professor at
Harvard University
Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of higher le ...
,
ETH Zurich
(colloquially)
, former_name = eidgenössische polytechnische Schule
, image = ETHZ.JPG
, image_size =
, established =
, type = Public
, budget = CHF 1.896 billion (2021)
, rector = Günther Dissertori
, president = Joël Mesot
, ac ...
, and the
University of Florida
The University of Florida (Florida or UF) is a public land-grant research university in Gainesville, Florida. It is a senior member of the State University System of Florida, traces its origins to 1853, and has operated continuously on its ...
where he was the V.T. & Louise Jackson Distinguished Professor of Chemistry. In 2005, he founded The Westheimer Institute of Science and Technology (TWIST) and the Foundation For Applied Molecular Evolution. Benner has also founded the companies EraGen Biosciences and Firebird BioMolecular Sciences LLC.
Benner and his colleagues were the first to synthesize a gene, beginning the field of
synthetic biology
Synthetic biology (SynBio) is a multidisciplinary area of research that seeks to create new biological parts, devices, and systems, or to redesign systems that are already found in nature.
It is a branch of science that encompasses a broad ran ...
. He was instrumental in establishing the field of
paleogenetics Paleogenetics is the study of the past through the examination of preserved genetic material from the remains of ancient organisms. Emile Zuckerkandl and Linus Pauling introduced the term in 1963, long before the sequencing of DNA, in reference to ...
. He is interested in 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 ...
and the chemical conditions and processes needed to produce
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 ...
. Benner has worked with
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, succeeding t ...
to develop detectors for alien genetic materials, using the definition of life developed by the NASA Exobiology Discipline Working Group in 1992, “a self-sustaining chemical system capable of Darwinian evolution”.
Education
Benner attended
Yale University
Yale University is a private research university in New Haven, Connecticut. Established in 1701 as the Collegiate School, it is the third-oldest institution of higher education in the United States and among the most prestigious in the wo ...
, receiving his B.S./M.S. in molecular biophysics and biochemistry in 1976. He then went to
Harvard University
Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of higher le ...
, receiving his Ph.D. in chemistry in 1979.
He worked under the supervision of
Robert Burns Woodward
Robert Burns Woodward (April 10, 1917 – July 8, 1979) was an American organic chemist. He is considered by many to be the most preeminent synthetic organic chemist of the twentieth century, having made many key contributions to the subject, e ...
, completing his thesis work with
Frank Westheimer
Frank Henry Westheimer NAS ForMemRS APS (January 15, 1912 – April 14, 2007) was an American chemist. He taught at the University of Chicago from 1936 to 1954, and at Harvard University from 1953 to 1983, becoming the Morris Loeb Professor of ...
after Woodward's death. His Ph.D. thesis was ''Absolute stereochemistry of acetoacetate decarboxylase, betaine-homocysteine transmethylase, and 3-hydroxybutyrate dehydrogenase.''
Career
After graduating from
Harvard University
Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of higher le ...
, Benner became a fellow at Harvard, receiving the Dreyfus Award for Young Faculty in 1982. He was an assistant professor in the Department of Chemistry at Harvard University from 1982 to 1986.
In 1986, Benner moved to
ETH Zurich
(colloquially)
, former_name = eidgenössische polytechnische Schule
, image = ETHZ.JPG
, image_size =
, established =
, type = Public
, budget = CHF 1.896 billion (2021)
, rector = Günther Dissertori
, president = Joël Mesot
, ac ...
, the Swiss Federal Institute of Technology in Zurich.
He held the positions of associate professor of bio-organic chemistry from 1986 to 1993 and professor of bio-organic chemistry from 1993 to 1996.
By 1996
Benner joined the faculty at the
University of Florida
The University of Florida (Florida or UF) is a public land-grant research university in Gainesville, Florida. It is a senior member of the State University System of Florida, traces its origins to 1853, and has operated continuously on its ...
, as a professor in both chemistry and cell & molecular biology. He was appointed the V.T. & Louise Jackson Distinguished Professor of Chemistry at the University of Florida's Department of Chemistry in 2004.
Benner left University of Florida in late December 2005 to found The Westheimer Institute of Science and Technology (TWIST) in Honor of
Frank Westheimer
Frank Henry Westheimer NAS ForMemRS APS (January 15, 1912 – April 14, 2007) was an American chemist. He taught at the University of Chicago from 1936 to 1954, and at Harvard University from 1953 to 1983, becoming the Morris Loeb Professor of ...
. It is part of the Foundation For Applied Molecular Evolution (FfAME) in
Alachua, Florida
Alachua ( ) is the second-largest city in Alachua County, Florida and the third-largest in North Central Florida. According to the 2020 census, the city's population was 10,574. The city is part of the Gainesville metropolitan area, which had a ...
, which Benner founded in 2001.
Benner founded EraGen Biosciences in 1999. The company was acquired by Luminex in 2011.
He founded Firebird BioMolecular Sciences LLC in 2005.
Research
Benner's research falls into four major areas:
# expanding the genetic alphabet by synthesizing artificial structures
# pre-biotic chemistry, the recreation of the chemical origin of life
# paleogenetics, the study of ancient proteins from long-extinct species
# detection of extraterrestrial life
The Benner laboratory is an originator of the field of "
synthetic biology
Synthetic biology (SynBio) is a multidisciplinary area of research that seeks to create new biological parts, devices, and systems, or to redesign systems that are already found in nature.
It is a branch of science that encompasses a broad ran ...
", which seeks to generate, by
chemical synthesis
As a topic of chemistry, chemical synthesis (or combination) is the artificial execution of chemical reactions to obtain one or several products. This occurs by physical and chemical manipulations usually involving one or more reactions. In moder ...
, molecules that reproduce the complex behavior of living systems, including their genetics, inheritance, and evolution. Some high points of past work in chemical genetics are listed below.
Gene synthesis
In 1984, Benner's laboratory at Harvard was the first to report the chemical synthesis of a gene encoding an enzyme,
following Khorana's synthesis of a shorter gene for
tRNA
Transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA) is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes), that serves as the physical link between the mRNA and the amino ac ...
in 1970.
This was the first designed gene of any kind, a pioneering achievement that laid the groundwork for
protein engineering
Protein engineering is the process of developing useful or valuable proteins. It is a young discipline, with much research taking place into the understanding of protein folding and recognition for protein design principles. It has been used to imp ...
.
The design strategies introduced in this synthesis are now widely used to support protein engineering.
Artificial genetic systems
Efforts toward the goal of artificial genetic systems were first reported by Benner and coworkers in 1989, when they developed the first unnatural
base pair
A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
.
Benner and his colleagues have since developed a six-letter artificially expanded genetic information system called
Artificially Expanded Genetic Information System
Artificially Expanded Genetic Information System (AEGIS) is a synthetic DNA analog experiment that uses some unnatural base pairs from the laboratories of the Foundation for Applied Molecular Evolution in Gainesville, Florida. AEGIS is a NASA-fu ...
(AEGIS) which includes two additional nonstandard nucleotides (Z and P) in addition to the four standard nucleotides (G, A, C, and T).
AEGIS has its own supporting molecular biology.
It enables the synthesis of proteins with more than the naturally-encoded 20 amino acids, and provides insight into how nucleic acids form duplex structures, how proteins interact with nucleic acids,
and how alternative genetic systems might appear in non-terran life.
Benner is one of a number of researchers, including Eric T. Kool, Floyd E. Romesberg, Ichiro Hirao, Mitsuhiko Shionoya and Andrew Ellington, who have created an extended alphabet of synthetic bases that can be incorporated into DNA (as well as RNA) using Watson-Crick bonding (as well as non-Watson-Crick bonding). While most of these synthetic bases are derivatives of the A, C, G, T bases, some are different. While some are in Watson-Crick pairs (A/T, C/G), some are self complementing (X/X). Thus the genetic alphabet has been expanded.
The number of possible nucleotide triplets, or
codons
The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...
, available in protein synthesis depends on the number of nucleotides available. The standard alphabet (G, A, C, and T) yields 4
3 = 64 possible codons, while an expanded DNA alphabet with 9 DNA bases would have 9
3 = 729 possible codons, many of them synthetic codons. For these codons to be useful,
Aminoacyl tRNA synthetase
An aminoacyl-tRNA synthetase (aaRS or ARS), also called tRNA-ligase, is an enzyme that attaches the appropriate amino acid onto its corresponding tRNA. It does so by catalyzing the transesterification of a specific cognate amino acid or its pre ...
has been created such that tRNA can code for the possibly synthetic amino acid to be coupled with its corresponding synthetic anti-codon. Brenner has described such a system which uses synthetic iso-C/iso-G DNA which uses the synthetic DNA codon
so-C/A/Gwhich he calls the 65th codon. Synthetic mRNA with synthetic anti-codon
so-G/U/Cwith synthetic aminoacyl-tRNA synthetase results in an ''in vivo'' experiment that can code for a synthetic amino acid incorporated into synthetic polypeptides (synthetic
proteomics
Proteomics is the large-scale study of proteins. Proteins are vital parts of living organisms, with many functions such as the formation of structural fibers of muscle tissue, enzymatic digestion of food, or synthesis and replication of DNA. In ...
).
A "second generation" model for nucleic acids
Benner has used synthetic organic chemistry and biophysics to create a "second generation" model for nucleic acid structure. The first generation model of DNA was proposed by
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 ...
and
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 struc ...
, based on crystallized X-ray structures being studied by
Rosalind Franklin
Rosalind Elsie Franklin (25 July 192016 April 1958) was a British chemist and X-ray crystallographer whose work was central to the understanding of the molecular structures of DNA (deoxyribonucleic acid), RNA (ribonucleic acid), viruses, co ...
. According to the
double-helix model, DNA is composed of two complementary strands of nucleotides coiled around each other.
Benner's model emphasizes the role of the sugar and phosphate backbone in the genetic molecular recognition event. The poly-anionic backbone is important in creating the extended structure that helps DNA to replicate.
In 2004, Benner reported the first successful attempt to design an artificial DNA-like molecule capable of reproducing itself.
Genome sequencing and protein structure prediction
In the late 1980s, Benner recognized the potential for genome sequencing projects to generate millions of sequences and enable researchers to do extensive mapping of molecular structures in organic chemistry. In the early 1990s, Benner met
Gaston Gonnet
Gaston H. Gonnet is a Uruguayan Canadian computer scientist and entrepreneur. He is best known for his contributions to the Maple computer algebra system and the creation of a digital version of the Oxford English Dictionary.
Education and ear ...
, beginning a collaboration that applied Gonnet's tools for text searching to the management of protein sequences.
In 1990, in collaboration with
Gaston Gonnet
Gaston H. Gonnet is a Uruguayan Canadian computer scientist and entrepreneur. He is best known for his contributions to the Maple computer algebra system and the creation of a digital version of the Oxford English Dictionary.
Education and ear ...
, the Benner laboratory introduced the DARWIN bioinformatics workbench. DARWIN (Data Analysis and Retrieval With Indexed Nucleic acid-peptide sequences) was a high-level programming environment for examining genomic sequences. It supported the matching of genomic sequences in databases, and generated information that showed how natural proteins could divergently evolve under functional constraints by accumulating mutations, insertions, and deletions.
Building on Darwin, the Benner laboratory provided tools to predict the three dimensional structure of proteins from sequence data. Information about known protein structures was collected and marketed as a commercial database, the Master Catalog, by Benner's startup EraGen.
The use of multiple sequence information to predict secondary structure of proteins became popular as a result of the work of Benner and Gerloff.
Predictions of protein secondary structure by Benner and colleagues achieved high accuracy.
It became possible to model protein folds, detect distant homologs, enable structural genomics, and join protein sequence, structure, and function. Further, this work suggested limits to structure prediction by homology, defining what can and cannot be done with this strategy.
Practical genotyping tools
Benner's approach opened new perspectives on how nucleic acids work, as well as tools for diagnostics and nanotechnology. The FDA has approved products that use AEGIS DNA in human diagnostics. These monitor the loads of virus in patients infected with
hepatitis B
Hepatitis B is an infectious disease caused by the ''Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection.
Many people have no symptoms during an initial infection. Fo ...
,
hepatitis C
Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, a ...
and
HIV
The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
.
AEGIS has been the basis of the development of tools for multiplexed detection of genetic markers such as cancer cells
and single nucleotide polymorphisms in patient samples. These tools will allow personalized medicine using "
point-of-care
Clinical point of care (POC) is the point in time when clinicians deliver healthcare products and services to patients at the time of care.
Clinical documentation
Clinical documentation is a record of the critical thinking and judgment of a health ...
" genetic analysis,
as well as research tools that measure the level of individual mRNA molecules within single processes of single living neurons.
Interpretive proteomics
Interpreting genomic data and projecting back to a common genetic ancestor, "Luca", the Benner laboratory has introduced tools that analyze patterns of conservation and variation using structural biology, study variation in these patterns across different branches of an evolutionary tree, and correlate events in the genetic record with events in the history of the biosphere known from geology and fossils. From this have emerged examples showing how the roles of biomolecules in contemporary life can be understood through models of the historical past.
Experimental paleogenetics
Benner was an originator of the field of experimental
paleogenetics Paleogenetics is the study of the past through the examination of preserved genetic material from the remains of ancient organisms. Emile Zuckerkandl and Linus Pauling introduced the term in 1963, long before the sequencing of DNA, in reference to ...
, where genes and proteins from ancient organisms are resurrected using bioinformatics and recombinant DNA technology.
Experimental work on ancient proteins has tested hypotheses about the evolution of complex biological functions, including the biochemistry of ruminant digestion,
the
thermophily of ancient bacteria, and the interaction between plants, fruits, and fungi at the time of the
Cretaceous extinction
The Cretaceous ( ) is a geological period that lasted from about 145 to 66 million years ago (Mya). It is the third and final period of the Mesozoic Era, as well as the longest. At around 79 million years, it is the longest geological period of th ...
.
These develop our understanding of biological behavior that extends from the molecule to the cell to the organism, ecosystem, and planet, sometimes referred to as planetary biology.
Astrobiology
Benner is deeply interested in 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 ...
, and the conditions necessary to support an
RNA-world model in which self-replicating RNA is a precursor to life on Earth. He has identified
calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...
,
borate
A borate is any of several boron oxyanions, negative ions consisting of boron and oxygen, such as orthoborate , metaborate , or tetraborate ; or any salt with such anions, such as sodium metaborate, and disodium tetraborate . The name also refe ...
, and
molybdenum
Molybdenum is a chemical element with the symbol Mo and atomic number 42 which is located in period 5 and group 6. The name is from Neo-Latin ''molybdaenum'', which is based on Ancient Greek ', meaning lead, since its ores were confused with lea ...
as important to the successful formation of carbohydrates and the stabilization of RNA.
He suggested that 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 (planet), Mercury. In the English language, Mars is named for the Mars (mythology), Roman god of war. Mars is a terr ...
may have had more desirable conditions than Earth for the initial production of RNA,
but more recently agreed that models of early Earth showing dry land and intermittent water, developed by Stephen Mojzsis, present sufficient conditions for RNA development.
The Benner group has worked to identify molecular structures likely to be universal features of living systems regardless of their genesis, and not likely products of non-biological processes. These are "
biosignature
A biosignature (sometimes called chemical fossil or molecular fossil) is any substance – such as an element, isotope, or molecule – or phenomenon that provides scientific evidence of past or present life. Measurable attribute ...
s", both for terrean-like life and for "weird" life forms.
References
{{DEFAULTSORT:Benner, Steven A.
University of Florida faculty
21st-century American chemists
American molecular biologists
Living people
1954 births
Harvard University alumni
Astrobiologists
Synthetic biologists