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Hamilton Smith, M.D. is a distinguished professor emeritus at the J. Craig Venter Institute and former director of the Synthetic Biology and Bioenergy Group that created the first synthetic cell in 2010 and designed and synthesized the first minimal bacterial genome in 2016. He received an A.B. degree in Mathematics from the University of California, Berkeley in 1952 and the M.D. degree from the Johns Hopkins School of Medicine in 1956. He completed a residency in Internal Medicine in 1962. From 1962-67, he did research on lysogeny in phage P22 at the University of Michigan. In 1967, he was appointed Assistant Professor of Microbiology at Johns Hopkins. In 1970, he discovered the first Type II restriction enzyme, HindII. He received the Nobel Prize in Medicine in 1978 for that work. From 1975 to 1998, he studied the DNA transformation mechanism in Haemophilus Inflluenzae Rd. In 1993, Dr. Smith began his long association with Craig Venter. In 1995, they collaborated to sequence the genome of H. Inflluenzae Rd, and from 1998 to 2002, at Celera Genomics they sequenced Drosophila and the human genome. After leaving Celera, Smith and Venter began their work in synthetic biology.
Related Information
Research Priorities
Deciphering the genetic requirements for minimal bacterial life
- Assignment of genetic functions to unknown genes in the minimal cell by computational, biochemical and genetic methods.
Designing a minimal yeast cell
- Determining non-essential genes by global DNA cassette insertional mutagenesis.
Understanding the mechanism of DNA cassette insertional mutagenesis in yeast
- Genetic and biochemical analysis of the DNA insertion mechanism.
Publications
Publications
Cell. 2022-01-20; 185.2: 345-360.e28.
Fundamental behaviors emerge from simulations of a living minimal cell
International journal of molecular sciences. 2020-09-26; 21.19:
Gross Chromosomal Rearrangements in Kluyveromyces marxianus Revealed by Illumina and Oxford Nanopore Sequencing
Frontiers in molecular biosciences. 2019-11-28; 6.130.
Kinetic Modeling of the Genetic Information Processes in a Minimal Cell
Journal of bacteriology. 2019-10-01; 201.19:
Polar Effects of Transposon Insertion into a Minimal Bacterial Genome
eLife. 2019-01-18; 8.
Essential metabolism for a minimal cell
ACS synthetic biology. 2019-01-15;
Direct transfer of a Mycoplasma mycoides genome to yeast is enhanced by removal of the mycoides glycerol uptake factor gene glpF
ACS synthetic biology. 2018-06-15; 7.6: 1538-1552.
Tuning Gene Activity by Inducible and Targeted Regulation of Gene Expression in Minimal Bacterial Cells
Cold Spring Harbor perspectives in biology. 2017-12-01; 9.12:
Minimal Cells-Real and Imagined
Scientific reports. 2016-08-04; 6.30714.
One step engineering of the small-subunit ribosomal RNA using CRISPR/Cas9
Science (New York, N.Y.). 2016-03-25; 351.6280: aad6253.
Design and synthesis of a minimal bacterial genome
Clinical chemistry. 2015-09-01; 61.9: 1207-8.
The Sequence of the Human Genome
Nature communications. 2015-04-21; 6.6925.
Designer diatom episomes delivered by bacterial conjugation
Genome research. 2015-03-01; 25.3: 435-44.
Bacterial genome reduction using the progressive clustering of deletions via yeast sexual cycling
PLoS biology. 2015-01-20; 13.1: e1002050.
Where next for microbiome research?
International journal of molecular sciences. 2015-01-16; 16.1: 2020-33.
Designed surface residue substitutions in [NiFe] hydrogenase that improve electron transfer characteristics
BMC biochemistry. 2014-06-17; 15.10.
A broad survey reveals substitution tolerance of residues ligating FeS clusters in [NiFe] hydrogenase
Nature protocols. 2014-04-01; 9.4: 743-50.
Transferring whole genomes from bacteria to yeast spheroplasts using entire bacterial cells to reduce DNA shearing
Frontiers in microbiology. 2014-01-01; 5.369.
Rescue of mutant fitness defects using in vitro reconstituted designer transposons in Mycoplasma mycoides
Journal of biological engineering. 2013-12-10; 7.1: 30.
Assembly of eukaryotic algal chromosomes in yeast
Journal of biological engineering. 2013-07-02; 7.1: 17.
Dual organism design cycle reveals small subunit substitutions that improve [NiFe] hydrogenase hydrogen evolution
Nature methods. 2013-05-01; 10.5: 410-2.
Direct transfer of whole genomes from bacteria to yeast
Nucleic acids research. 2012-11-01; 40.20: 10375-83.
Sequence analysis of a complete 1.66 Mb Prochlorococcus marinus MED4 genome cloned in yeast
ACS synthetic biology. 2012-07-20; 1.7: 267-73.
Assembly of large, high G+C bacterial DNA fragments in yeast
ACS synthetic biology. 2012-01-20; 1.1: 22-8.
Cloning the Acholeplasma laidlawii PG-8A genome in Saccharomyces cerevisiae as a yeast centromeric plasmid
FEMS microbiology letters. 2011-09-01; 322.2: 180-7.
Genetic analysis of the Alteromonas macleodii [NiFe]-hydrogenase
Microbiology (Reading, England). 2011-05-01; 157.Pt 5: 1363-74.
Heterologous expression of Alteromonas macleodii and Thiocapsa roseopersicina [NiFe] hydrogenases in Escherichia coli
Biotechnology letters. 2011-03-01; 33.3: 549-55.
Single-step linker-based combinatorial assembly of promoter and gene cassettes for pathway engineering
Applied and environmental microbiology. 2011-03-01; 77.6: 1990-8.
[NiFe] hydrogenase from Alteromonas macleodii with unusual stability in the presence of oxygen and high temperature
Nature methods. 2010-11-01; 7.11: 901-3.
Chemical synthesis of the mouse mitochondrial genome
Science (New York, N.Y.). 2010-07-02; 329.5987: 52-6.
Creation of a bacterial cell controlled by a chemically synthesized genome
Nucleic acids research. 2010-05-01; 38.8: 2558-69.
Cloning whole bacterial genomes in yeast
Journal of molecular evolution. 2009-10-01; 69.4: 360-71.
The evolution of RecD outside of the RecBCD complex
Science (New York, N.Y.). 2009-09-25; 325.5948: 1693-6.
Creating bacterial strains from genomes that have been cloned and engineered in yeast
Applied and environmental microbiology. 2009-09-01; 75.18: 5821-30.
Discovery of [NiFe] hydrogenase genes in metagenomic DNA: cloning and heterologous expression in Thiocapsa roseopersicina
Nature methods. 2009-05-01; 6.5: 343-5.
Enzymatic assembly of DNA molecules up to several hundred kilobases
Molecular systems biology. 2009-01-01; 5.330.
A systems biology tour de force for a near-minimal bacterium
Proceedings of the National Academy of Sciences of the United States of America. 2008-12-23; 105.51: 20404-9.
One-step assembly in yeast of 25 overlapping DNA fragments to form a complete synthetic Mycoplasma genitalium genome
Science (New York, N.Y.). 2008-02-29; 319.5867: 1215-20.
Complete chemical synthesis, assembly, and cloning of a Mycoplasma genitalium genome
Science (New York, N.Y.). 2007-08-03; 317.5838: 632-8.
Genome transplantation in bacteria: changing one species to another
PLoS biology. 2007-03-01; 5.3: e77.
The Sorcerer II Global Ocean Sampling expedition: northwest Atlantic through eastern tropical Pacific
Proceedings of the National Academy of Sciences of the United States of America. 2006-01-10; 103.2: 425-30.
Essential genes of a minimal bacterium
Proceedings of the National Academy of Sciences of the United States of America. 2005-11-29; 102.48: 17332-6.
Cell-free cloning using phi29 DNA polymerase
Science (New York, N.Y.). 2004-04-02; 304.5667: 66-74.
Environmental genome shotgun sequencing of the Sargasso Sea
Proceedings of the National Academy of Sciences of the United States of America. 2003-12-23; 100.26: 15440-5.
Generating a synthetic genome by whole genome assembly: phiX174 bacteriophage from synthetic oligonucleotides
Proceedings of the National Academy of Sciences of the United States of America. 2003-03-18; 100.6: 3025-6.
The independence of our genome assemblies
Nature biotechnology. 2002-11-01; 20.11: 1118-23.
Genome sequence of the dissimilatory metal ion-reducing bacterium Shewanella oneidensis
Science (New York, N.Y.). 2002-10-04; 298.5591: 129-49.
The genome sequence of the malaria mosquito Anopheles gambiae
Nature. 2002-10-03; 419.6906: 512-9.
Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium yoelii yoelii
Nature. 2002-10-03; 419.6906: 531-4.
Sequence of Plasmodium falciparum chromosomes 2, 10, 11 and 14
Science (New York, N.Y.). 2002-05-31; 296.5573: 1661-71.
A comparison of whole-genome shotgun-derived mouse chromosome 16 and the human genome
Proceedings of the National Academy of Sciences of the United States of America. 2002-04-02; 99.7: 4145-6.
On the sequencing and assembly of the human genome
Science (New York, N.Y.). 2001-07-20; 293.5529: 498-506.
Complete genome sequence of a virulent isolate of Streptococcus pneumoniae
Science (New York, N.Y.). 2001-02-16; 291.5507: 1304-51.
The sequence of the human genome
Journal of molecular biology. 2000-08-04; 301.1: 27-33.
Prediction of transcription terminators in bacterial genomes
Nature. 2000-08-03; 406.6795: 477-83.
DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae
Science (New York, N.Y.). 2000-03-24; 287.5461: 2185-95.
The genome sequence of Drosophila melanogaster
Science (New York, N.Y.). 2000-03-10; 287.5459: 1809-15.
Complete genome sequence of Neisseria meningitidis serogroup B strain MC58
Science (New York, N.Y.). 1999-12-10; 286.5447: 2165-9.
Global transposon mutagenesis and a minimal Mycoplasma genome
Science (New York, N.Y.). 1999-11-19; 286.5444: 1571-7.
Genome sequence of the radioresistant bacterium Deinococcus radiodurans R1
Research in microbiology. 1999-11-01; 150.9-10: 603-16.
DNA uptake signal sequences in naturally transformable bacteria
Parassitologia. 1999-09-01; 41.1-3: 69-75.
The malaria genome sequencing project: complete sequence of Plasmodium falciparum chromosome 2
Nature. 1999-05-27; 399.6734: 323-9.
Evidence for lateral gene transfer between Archaea and bacteria from genome sequence of Thermotoga maritima
Science (New York, N.Y.). 1998-11-06; 282.5391: 1126-32.
Chromosome 2 sequence of the human malaria parasite Plasmodium falciparum
Science (New York, N.Y.). 1998-07-17; 281.5375: 375-88.
Complete genome sequence of Treponema pallidum, the syphilis spirochete
Science (New York, N.Y.). 1998-06-05; 280.5369: 1540-2.
Shotgun sequencing of the human genome
Journal of bacteriology. 1998-02-01; 180.3: 746-8.
A new transformation-deficient mutant of Haemophilus influenzae Rd with normal DNA uptake
Nature. 1997-12-11; 390.6660: 580-6.
Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi
Journal of bacteriology. 1997-12-01; 179.23: 7315-20.
In vitro Tn7 mutagenesis of Haemophilus influenzae Rd and characterization of the role of atpA in transformation
Nature. 1997-11-27; 390.6658: 364-70.
The complete genome sequence of the hyperthermophilic, sulphate-reducing archaeon Archaeoglobus fulgidus
Nature. 1997-08-07; 388.6642: 539-47.
The complete genome sequence of the gastric pathogen Helicobacter pylori
Nature. 1996-05-30; 381.6581: 364-6.
A new strategy for genome sequencing
Science (New York, N.Y.). 1995-10-20; 270.5235: 397-403.
The minimal gene complement of Mycoplasma genitalium
Science (New York, N.Y.). 1995-07-28; 269.5223: 496-512.
Whole-genome random sequencing and assembly of Haemophilus influenzae Rd
Science (New York, N.Y.). 1995-07-28; 269.5223: 538-40.
Frequency and distribution of DNA uptake signal sequences in the Haemophilus influenzae Rd genome
Biotechnology (Reading, Mass.). 1992-01-01; 24.38-50.
A restriction enzyme from Hemophilus influenzae. I. Purification and general properties. 1970
Proceedings of the National Academy of Sciences of the United States of America. 1990-01-01; 87.2: 826-30.
Finding sequence motifs in groups of functionally related proteins
Journal of molecular biology. 1970-07-28; 51.2: 393-409.
A restriction enzyme from Hemophilus influenzae. II
Video
News
Remembering Hamilton O. Smith
Reading the blueprint of life
Hamilton O. Smith, M.D., Synthetic Biology Pioneer and Nobel Laureate, to Step Down from Daily Duties at J. Craig Venter Institute
Dr. Smith will maintain advisory role as professor emeritus
After saving countless lives, Nobel laureate Hamilton Smith retires as his own health falters
He has been a fixture in San Diego science for decades
J. Craig Venter Institute Education Program Fosters Learning Opportunities with Salisbury University Students and Faculty
Teams at Venter Institute and Synthetic Genomics, Inc. Successfully Engineer 16S rRNA using One Step Process Combining CRISPR/Cas9 Systems and Yeast Recombination Machinery
Unlocking the Mysteries of the Microbiome
First Minimal Synthetic Bacterial Cell Designed and Constructed by Scientists at Venter Institute and Synthetic Genomics, Inc.
Cell, JCVI-syn3.0, was minimized to just 473 genes
JCVI Gala “2015: A Genome Odyssey” Celebrates Discovery
Johns Hopkins Announces Inaugural Recipient of Hamilton Smith Award for Innovative Research
Guest Speakers Marlo Gottfurcht Longstreet and Dean Ornish Inspire Guests at JCVI‘s “Life at the Speed of Light” Gala
JCVI Researchers, as Part of NIH Human Microbiome Project Consortium, Publish Papers Detailing the Variety and Abundance of Microbes Living on and in the Human Body
Study Represents Largest Group of Healthy Individuals Studied to Date
JCVI also Details its Metagenomics Reports (METAREP) Open Source Bioinformatics Tool
First Self-Replicating, Synthetic Bacterial Cell Constructed by J. Craig Venter Institute Researchers
Scientist Spotlight: Hamilton O. Smith and Clyde A. Hutchison III
J. Craig Venter Institute Researchers Clone and Engineer Bacterial Genomes in Yeast and Transplant Genomes Back into Bacterial Cells
New methods allow for the rapid engineering of bacterial chromosomes and the creation of extensively modified bacterial species; should also play key role in boot up of synthetic cell
Venter Institute Scientists Create First Synthetic Bacterial Genome
Publication Represents Largest Chemically Defined Structure Synthesized in the Lab
Team Completes Second Step in Three Step Process to Create Synthetic Organism
JCVI Scientists Publish First Bacterial Genome Transplantation Changing One Species to Another
Research is important step in further advancing field of synthetic genomics
His Royal Highness Prince Andrew, The Duke of York, to Tour J. Craig Venter Institute
J. Craig Venter Announces Consolidation of Three Research Organizations Into One New Not-For-Profit Organization — The J. Craig Venter Institute
The Center for Advancement of Genomics (TCAG), Institute for Biological Energy Alternatives (IBEA), and J. Craig Venter Science Foundation Joint Technology Center (JTC) consolidated to form J. Craig Venter Institute
IBEA Researchers Make Significant Advance in Methodology Toward Goal of a Synthetic Genome
Group Synthesizes Biologically Active Genome of Bacteriophage φX174
IBEA research, funded by Dept. of Energy, is an important advance toward the goal of a completely synthetic genome that could aid in carbon sequestration and energy production
IBEA Receives $3 Million Dept. of Energy Grant for Synthetic Genome Development
Hamilton Smith, M.D., Nobel Laureate, Named Scientific Director of IBEA