The field of synthetic biology took a step forward last week with the news that researchers at the J. Craig Venter Institute (JVCI, Rockville, MD), a genomic-research organization founded and headed by J. Craig Venter, who helped map the human genome, had successfully constructed the first self-replicating synthetic cell. The work lays the possibility for advancing the technology one day into developing pharmaceuticals, vaccines, biofuels, and other industrial products.

The significance of the work is that is showed a “proof of principle that genomes can be designed in the computer, chemically made in the laboratory, and transplanted into a recipient cell to produce a new self-replicating cell controlled only by the synthetic genome,” according to a JVCI press release. The researchers recently published their work online in Science (1). The researchers used several procedures they had developed during the past several years to synthesize a genome and transplant it into a recipient cell.

The researchers designed, synthesized and assemblied the 1.08 million base pair Mycoplasma mycoides JCVI-syn1.0 genome starting from digitized genome-sequence information and transplanted it into a Mycoplasma capricolum recipient cell to create new Mycoplasma mycoides cells that are controlled only by the synthetic chromosome (1). The only DNA in the cells is the designed synthetic DNA sequence, including what the authors referred to as “watermark” sequences and other designed genetic variations as well as mutations acquired during the building process. The new cells exhibit the phenotype expected by the authors and are capable of continuous self-replication (1).

The researchers said their work represented the construction of the largest synthetic molecule of a defined structure–almost double the size of a previously reported synthetically produced DNA molecule, according to the JCVI release. With this proof of principle, JVCI will work on creating an organism that contains the minimal genome required to sustain itself and its replication, to be used as platform for analyzing the function of every essential gene in a cell, according to the JVCI release.

The researchers used DNA units made according to JCVI’s specifications by Blue Heron Biotechnology (Bothell, WA), a biotechnology company specializing in synthesizing DNA. Synthetic Genomics (SGI, La Jolla, CA), a company cofounded by Venter, provided nearly $30 million in funding for the research. SGI has a $600-million agreement with ExxonMobil to develop biofuels from algae. SGI and ExxonMobil formed a long-term research and development alliance in 2009 focused on finding and optimizing (through synthetic genome techniques and other more traditional metabolic engineering techniques) algae to produce biological crude oil replacements.

The work of Venter and his team is without question a scientific accomplishment, but the real challenge lies ahead in one day eventually being able to adapt the technology cost-effectively and at a large-scale. The researchers envision that the knowledge gained by constructing this first self-replicating synthetic cell, coupled with decreasing costs for DNA synthesis, will give rise to wider use of the technology to be applied in the development of a range of therapeutic and industrial products. However, it is not yet clear given the time and cost to design new organisms using the technology, whether the technology will indeed be a better approach than using conventional genetic-engineering techniques.

The technology also raises bioethical and other concerns. Following the announcement last week President Barack Obama directed the Presidential Commission for the Study of Bioethical Issues to examine potential medical, environmental, security, and other benefits as well as any potential health, security, or other risks and to report back to him within six months.

In its release, JCVI said it continues to work with bioethicists, outside policy groups, legislative members and staff, and the public to encourage discussion and understanding about the societal implications of their work and the field of synthetic genomics generally. JVCI conducted a study with the Center for Strategic & International Studies and the Massachusetts Institute of Technology, with a grant funded by the Alfred P. Sloan Foundation, to examine the risks and benefits of this emerging technology, as well as possible safeguards to prevent abuse, including bioterrorism. In December of 2008, JCVI received funding from the Alfred P. Sloan Foundation to examine ethical and societal concerns associated with the developing science of synthetic genomics.

As the feasibility of applying the technology and concerns over its use are debated, it is still useful to take a moment to recognize the scientific accomplishment and consider its potential.

Reference

1. D.G. Gibson et al., “Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome,” Science, online May 20, 2010, DOI: 10.1126/science.1190719.