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

(La Jolla, California)—December 22, 2020—Hamilton O. Smith, M.D., Nobel Laureate, distinguished professor and scientific director of the J. Craig Venter Institute (JCVI) Synthetic Biology Group, is retiring  from daily duties at the Institute effective December 31, 2020. Dr. Smith will continue advancing JCVI’s mission through authorship and an advisory role as a professor emeritus.

Reflecting on this moment, J. Craig Venter, Ph.D. said, “It has been an honor of a lifetime to work alongside Ham. Our chance meeting nearly three decades ago changed my life, the trajectory of my work, and the arc of genomic science in profound ways that cannot be overstated. When we met, Ham was on the verge or retirement. Little did each of us know that his greatest – our greatest – work was yet to come. I am forever grateful to my best friend for his immeasurable contributions to JCVI.”

Dr. Smith first began collaborating with Dr. Venter in 1993, while at Johns Hopkins University School of Medicine. At the time, the U.S. government-funded effort to sequence the genome of the bacterium Escherichia coli was advancing very slowly, even with hundreds of scientists enlisted in the project.

With the E. coli project hanging in the background, Dr. Smith proposed sequencing a complete organism and Dr. Venter jumped at the opportunity. The team at the precursor organization of JCVI, The Institute for Genomic Research (TIGR), then dove into the task of sequencing the genome of the bacterium Haemophilus influenzae.

While sequencing the genome of an entire organism is now routine, at the time it was extremely ambitious, and unclear if it was even possible. Segments of DNA had been read on the order of hundreds or thousands of base pairs previously, but to sequence H. influenzae’s 1.8 million base pairs, would require a radical, new approach: whole genome shotgun sequencing at scale never attempted. This innovation led to the first genome sequence of a cellular organism, inexpensively and rapidly.

H. influenzae is the same organism in which Dr. Smith discovered restriction enzymes in the late 1960s, leading to him jointly receiving a Nobel Prize in Physiology or Medicine in 1978. He officially joined TIGR in 1997 to continue sequencing many of the first complete genomes.

“Ham was critical to the success of sequencing many of these early genomes, including Thermotoga maritima, where challenges in genome library construction and highly repetitive genomic elements were often encountered,” recalls Karen Nelson, Ph.D., JCVI president and first author on the T. maritima paper. As an extremophile, interest in the organism initially stemmed from its ability to thrive in hot springs and hydrothermal vents but expanded as the team discovered evidence, for the first time, of lateral gene transfer between two branches of life in its DNA: Archaea and bacteria.

In 1998, Drs. Smith and Venter, along with others left TIGR to form a new company, Celera Genomics. Their principal goal was to sequence the human genome and successfully completed the first draft in 2001. As had been done previously at TIGR, the team employed shotgun sequencing to dramatically accelerate the pace of discovery. This strategy in turn forced the hand of the public Human Genome Project to adopt the method, and is now the industry standard approach.

Following the completion of sequencing the human genome, Dr. Venter founded a series of nonprofits, which eventually became part of JCVI. Dr. Smith joined the Institute for Biological Energy Alternatives (IBEA) in 2002 as Scientific Director where the team had an eye towards the future: synthetic biology. Following the pattern, the team’s goals were ambitious, and included deciphering a basic set of genes necessary for life and learning how to build custom genomes.

The first step came in 2003 with the proof-of-concept synthesis of phi X 174 (ΦX174), significantly advancing methods to improve the speed and accuracy of genomic synthesis. Researchers assembled the 5,386 bp bacteriophage (a virus that attacks bacteria) from short, single strands of commercially synthesized DNA.

Building on this success, JCVI’s synthetic biology team, headed by Drs. Smith and Venter, now set their sights on something much larger: constructing a synthetic bacterial cell. This project came in several significant steps, including: bacterial genome transplantation in 2007, developing the first synthetic bacterial genome in 2008, and booting up the first self-replicating, synthetic bacterial cell in 2010.

The tools for grand scale engineering of biology generated by the JCVI synthetic biology team catalyzed much of the current biotechnology revolution. During the intense period of work on the synthetic cell, Drs. Venter and Smith also co-founded a commercial company, Synthetic Genomics, Inc. (SGI) to commercialize the advances of the basic science research in synthetic biology at JCVI. Dr. Smith was on the board of directors of SGI for several years.

Now having the tools to boot up a cell, the team began working backwards, peeling off genes from the organism Mycoplasma mycoides to identify a set of minimal genes necessary to sustain a living, dividing cell. In 2016, after nearly 20 years, this quest came to an end with the announcement of the very first minimal cell, JCVI-syn3.0, containing only 473 genes. Work on the minimal cell and its applications continue today at JCVI and at more than forty academic labs who are using this simple bacterium to investigate the first principles of cellular life.

Dr. Smith also previously served on JCVI’s board of trustees from 1999 to 2013.

The weight of Dr. Smith’s scientific achievement is matched by few in history. He is one of the true scientific giants.

A new fund, the Hamilton O. Smith Fund, has been set up to honor Dr. Smith. Donors to the fund will help enable new research, support individual scientists, and allow for naming opportunities at the JCVI La Jolla Sustainable Lab.

About J. Craig Venter Institute

The J. Craig Venter Institute (JCVI) is a not-for-profit research institute in Rockville, Maryland and La Jolla, California. dedicated to the advancement of the science of genomics; the understanding of its implications for society; and communication of those results to the scientific community, the public, and policymakers. Founded by J. Craig Venter, PhD, the JCVI is home to approximately 200 scientists and staff with expertise in human and evolutionary biology, genetics, bioinformatics/informatics, information technology, high-throughput DNA sequencing, genomic and environmental policy research, and public education in science and science policy. The JCVI is a 501(c)(3) organization. For additional information, please visit www.JCVI.org.

Media Contact

Matthew LaPointe, [email protected], 301-795-7918