Hamilton Smith, MD

Scientific Director



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Hamilton Smith, M.D. is a Distinguished Professor at the J. Craig Venter Institute and 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.

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.

Select Publications

Minimal Cells-Real and Imagined.
Cold Spring Harbor perspectives in biology. 2017-12-01; 9.12:
PMID: 28348033
Complete chemical synthesis, assembly, and cloning of a Mycoplasma genitalium genome.
Science (New York, N.Y.). 2008-02-29; 319.5867: 1215-20.
PMID: 18218864
Genome transplantation in bacteria: changing one species to another.
Science (New York, N.Y.). 2007-08-03; 317.5838: 632-8.
PMID: 17600181
Cell-free cloning using phi29 DNA polymerase.
Proceedings of the National Academy of Sciences of the United States of America. 2005-11-29; 102.48: 17332-6.
PMID: 16286637
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. 2003-12-23; 100.26: 15440-5.
PMID: 14657399
Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD, Amanatides PG, Scherer SE, Li PW, Hoskins RA, Galle RF, George RA, Lewis SE, Richards S, Ashburner M, Henderson SN, Sutton GG, Wortman JR, Yandell MD, Zhang Q, Chen LX, Brandon RC, Rogers YH, Blazej RG, Champe M, Pfeiffer BD, Wan KH, Doyle C, Baxter EG, Helt G, Nelson CR, Gabor GL, Abril JF, Agbayani A, An HJ, Andrews-Pfannkoch C, Baldwin D, Ballew RM, Basu A, Baxendale J, Bayraktaroglu L, Beasley EM, Beeson KY, Benos PV, Berman BP, Bhandari D, Bolshakov S, Borkova D, Botchan MR, Bouck J, Brokstein P, Brottier P, Burtis KC, Busam DA, Butler H, Cadieu E, Center A, Chandra I, Cherry JM, Cawley S, Dahlke C, Davenport LB, Davies P, de Pablos B, Delcher A, Deng Z, Mays AD, Dew I, Dietz SM, Dodson K, Doup LE, Downes M, Dugan-Rocha S, Dunkov BC, Dunn P, Durbin KJ, Evangelista CC, Ferraz C, Ferriera S, Fleischmann W, Fosler C, Gabrielian AE, Garg NS, Gelbart WM, Glasser K, Glodek A, Gong F, Gorrell JH, Gu Z, Guan P, Harris M, Harris NL, Harvey D, Heiman TJ, Hernandez JR, Houck J, Hostin D, Houston KA, Howland TJ, Wei MH, Ibegwam C, Jalali M, Kalush F, Karpen GH, Ke Z, Kennison JA, Ketchum KA, Kimmel BE, Kodira CD, Kraft C, Kravitz S, Kulp D, Lai Z, Lasko P, Lei Y, Levitsky AA, Li J, Li Z, Liang Y, Lin X, Liu X, Mattei B, McIntosh TC, McLeod MP, McPherson D, Merkulov G, Milshina NV, Mobarry C, Morris J, Moshrefi A, Mount SM, Moy M, Murphy B, Murphy L, Muzny DM, Nelson DL, Nelson DR, Nelson KA, Nixon K, Nusskern DR, Pacleb JM, Palazzolo M, Pittman GS, Pan S, Pollard J, Puri V, Reese MG, Reinert K, Remington K, Saunders RD, Scheeler F, Shen H, Shue BC, Sidén-Kiamos I, Simpson M, Skupski MP, Smith T, Spier E, Spradling AC, Stapleton M, Strong R, Sun E, Svirskas R, Tector C, Turner R, Venter E, Wang AH, Wang X, Wang ZY, Wassarman DA, Weinstock GM, Weissenbach J, Williams SM, WoodageT, Worley KC, Wu D, Yang S, Yao QA, Ye J, Yeh RF, Zaveri JS, Zhan M, Zhang G, Zhao Q, Zheng L, Zheng XH, Zhong FN, Zhong W, Zhou X, Zhu S, Zhu X, Smith HO, Gibbs RA, Myers EW, Rubin GM, Venter JC
The genome sequence of Drosophila melanogaster.
Science (New York, N.Y.). 2000-03-24; 287.5461: 2185-95.
PMID: 10731132
A new strategy for genome sequencing.
Nature. 1996-05-30; 381.6581: 364-6.
PMID: 8632789
Frequency and distribution of DNA uptake signal sequences in the Haemophilus influenzae Rd genome.
Science (New York, N.Y.). 1995-07-28; 269.5223: 538-40.
PMID: 7542802
A restriction enzyme from Hemophilus influenzae. I. Purification and general properties. 1970.
Biotechnology (Reading, Mass.). 1992-01-01; 24.38-50.
PMID: 1330118
Finding sequence motifs in groups of functionally related proteins.
Proceedings of the National Academy of Sciences of the United States of America. 1990-01-01; 87.2: 826-30.
PMID: 1689055
A restriction enzyme from Hemophilus influenzae. II.
Journal of molecular biology. 1970-07-28; 51.2: 393-409.
PMID: 5312501