"Work in creating a synthetic chromosome/genome will give us a better understanding of basic cellular processes. Genome composition, regulatory circuits, signaling pathways and numerous other aspects of organism gene and protein function will be better understood through construction of a synthetic genome. Not only will this basic research lead to better understanding of these pathways and components in the particular organisms, but also better understanding of human biology. The ability to construct synthetic genomes may lead to extraordinary advances in our ability to engineer microorganisms for many vital energy and environmental purposes."
- J. Craig Venter, 2003
synthetic genomics: a new era in research
In the last two decades the field of genomics has undergone a revolution. Scientific discoveries have come at a dazzling pace. These breakthroughs were made possible by advances in the underlying enabling technologies such as high-throughput DNA sequencing, high-performance computing, and bioinformatics. Many of these advances are directly attributable to the innovation of Dr. Venter and his teams. With the genomes of more than 300 organisms and millions of newly discovered genes readily available, genes now have the potential to be the design components of the future world economy.
Synthetic Genomics, Inc. seeks to lead the world in its ability to design, synthesize and assemble specifically engineered cell level bio-factories. The ability to make extensive changes to the DNA of a chromosome, assemble it, and insert it into an organism is in its infancy, and the capability to assemble chromosome length strands of DNA will be key to the success of the company. Synthetic Genomics, Inc. is developing new scientific processes to enable industry to design and test desired genetic modifications. Using the genome as a bio-factory, a custom designed, modular “cassette” system will be developed so that the organism executes specific molecular functions. Synthetically produced organisms with reduced or reoriented metabolic needs will enable new, powerful, and more direct methods of bio-engineered industrial production. After designing and producing a synthetic chromosome, the team plans to develop a proof of concept in either of two bio-energy applications—hydrogen or ethanol. We believe that the synthetic chromosome, and eventually a synthetic cell, will become an integral tool for the energy industry.
the genesis of the company
In the mid 1990’s Drs. Venter and Smith in collaboration with Dr. Clyde Hutchison, began work at The Institute for Genomic Research (TIGR) on what was termed the “minimal genome project”. The research centered on the very small genome of Mycoplasma genitalium, a bacterium that primarily causes urinary tract infections in humans. With only 517 genes, the research team, led by Dr. Hutchison, surmised that perhaps they could ascertain which of these were essential to sustain the life of the organism. After using a technique pioneered by Dr. Hutchison called global transposon mutagenesis, the team was able to knock out non-essential genes and get to a core set of 265 to 350 genes that were needed to sustain life. However, most of those genes were of unknown function. The results were tantalizing both for what was learned and how much still remained to be learned. In 2002, Dr. Venter established the synthetic biology and biological energy groups, led by Dr. Smith at the Venter Institute, to continue this and other follow-on research. The work at the Venter Institute culminated in the successful synthesis of Phi-X174 in 2003. In just 14 days the team was able to completely and accurately assemble the Phi-X174 using synthetic segments of DNA. This was a proof of principal that gave the team encouragement to pursue this work in a commercial setting and led to the founding of Synthetic Genomics, Inc. in spring of 2005.
the science of synthetic genomics
The science at Synthetic Genomics, Inc. is building on the research of Drs. Venter and Smith and the team at the Venter Institute, a non-profit research institute with approximately 200 staff and scientists with expertise in genomics, microbiology, human and evolutionary biology, bioinformatics, high-throughput DNA sequencing, environmental biology, information technology, biological energy and synthetic biology. The founders of Synthetic Genomics, Inc. believe now is an opportune time to develop biologically-based software. Scientists at the Venter Institute have made significant progress in building synthetic chromosomes. In 2003, they successfully built in vitro a fully synthetic Phi-X174 chromosome in just two weeks. This substantial scientific breakthrough is a necessary first step in the ability to create highly engineered, efficient bio-production capabilities.
The initial step for the Company will be to develop a minimal genome that can provide an operating system for biologically-based software. Work has been ongoing at Synthetic Genomics, Inc. in conjunction with the Venter Institute, to remove genes from simple organisms to identify the minimum set of genes necessary for an organism to survive in a controlled environment. Synthetic Genomics, Inc. intends to synthesize the proposed minimal genome, add the desired biological capabilities, and insert it into an environment that allows metabolic activity and replication – the creation of a synthetic cell.
applications for the science
At Synthetic Genomics, Inc. we believe there are potentially limitless applications for synthetic biology/genomics, everything from energy to chemicals to pharmaceuticals. In the near-term, we think that synthetic genomics has applications in the areas of cleaner and more efficient energy production, specifically in the production of ethanol and hydrogen. It is widely accepted that the need for non-petrochemical fuel sources is growing and will continue to grow in the future. According to the U.S. Department of Energy (DOE), total carbon dioxide emissions in the United States and its territories were 5,870.2 million metric tons in 2003, the most recent year for statistics. Even more sobering is the fact that since 1990, total U.S. carbon dioxide emissions have increased by an average of 1.3 percent per year. There is a clear environmental need to reduce greenhouse gas emissions, as well as growing geopolitical security concerns regarding the continued U.S. dependence on imported oil. To this end, biofuels could save an estimated $20 billion per year on fuel costs over the next 50 years, decrease greenhouse emissions by 1.7 billon tons per year and reduce America’s dependence on foreign oil.
The Synthetic Genomics, Inc. business team is also developing an in-depth market analysis for the various other potential applications, and intend to use market needs to direct and drive scientific discovery and thus applications.
Smith HO, Hutchison CA, Pfannkoch C, Venter JC. 2003. Generating a Synthetic Genome by Whole Genome Assembly: phiX174 Bacteriophage from Synthetic Oligonucleotides. Proc Natl Acad Sci USA 100: 15440-15445.
Hutchison, CA, et al, 1999. Global Transposon Mutagenesis and a Minimal Mycoplasma Genome. Science 286, 2165
Cho, MK, et al. 1999 Ethical Considerations in Synthesizing a Minimal Genome. Science 286, 2087