April 15, 2009 (Vol. 29, No. 8)

Field Could Still Be Derailed by Overhyped Expectations and Trepidation

Synthetic biology, or synbio, has leapt into scientific, commercial, and social discourse with amazing speed. While the term has existed since at least the 1970s, the field emerged in force just five years ago. Today, dozens of companies, thousands of practitioners, and more than $1 billion in investment are making the field an engineering discipline that promises everything from new fuels to new biochemistries, from redefining manufacturing to redefining life itself.

Synthetic biology differs from conventional genetic engineering because it looks not at single genes and the traits or products they provide as proteins, but whole networks of genes that form regulatory and metabolic pathways. Achieving the desired output may arise from increasing the binding affinity of a transcription factor, adjusting codon usage, or overexpressing an enzyme that catalyzes an intermediate step in the reaction.

Current products, or those soon in the marketplace, tweak organisms’ metabolism of isoprenoids to overproduce the antimalarial drug artimisinin, for example, or reroute lipid pathways to produce fuels like biobutanol alongside oils for use in food and cosmetics.

Redesigning the activity of dozens of genes and proteins would have been unthinkable until recently, when advances in DNA sequencing and synthesis technologies made genetic manipulation of ever longer nucleotide strands cheap and easy.

The original Human Genome Project, completed in 2003, cost some $3 billion. Today, Complete Genomics claims it will be able to sequence an entire human genome for $5,000 in 2009, and Pacific BioSciences’, VisiGen’s, and Intelligent Bio-Systems’ plans for $1,000 or even $100 genomes by 2013 no longer seem ambitious. DNA synthesis companies like Blue Heron offer sequences of up to 100,000 bases for $0.40 per bp, and multiple strands have been combined to create wholly synthetic species like Mycoplasma laboratorium.

In addition to creating new species, synthetic biology’s leading edge of researchers is developing stunningly novel biodevices intentionally reminiscent of a catalog of standard electronic parts. For example, Stanford’s Drew Endy developed a method of using the rate of RNA polymerase’s transcription of DNA as an output signal, measured in polymerases per second. Combining biological inverters, oscillators, and other logical components, even undergraduate students are engineering bacteria intended to capture images, detect toxins, and deliver drugs.

The potential of synthetic biology has captured the attention of universities, corporations, and venture investors. At least 23 labs at 10 U.S. universities support graduate work specifically under the synthetic biology rubric; several have undergraduate courses, and dozens more in Europe and Asia are also active. Corporations have made a few investments directly into start-ups, such as Chevron’s funding of Solazyme, while Danisco is developing synbio pathways to biofuels, plastics, rubber, adhesives, and cosmetics. Top VCs are also active, putting hundreds of millions of dollars into fuel and medicine makers.

Synthetic biology companies and applications being developed show a marked trend: the higher up an application is on the scale of life, the further into the future are its hopes of becoming a real product. DNA sequencing and synthesis tools are already battling it out in well-established markets like drug discovery and plant engineering.

Metabolite chemicals and biomolecules, like biofuels made with the help of that DNA, are just starting to be sold today. Engineered cells and cell communities will be useful, simple devices in a few years based on today’s strides in intra- and intercellular signaling. Synthetic tissues and multicellular organisms have at least a decade until commercialization, when we have a better understanding of things like intercellular signaling and hox genes.

The wildest notions in synthetic biology’s envisioned menagerie, however, are pure speculation and won’t be products until sometime beyond 2020.

Synthetic biology’s applications fall inside business, technology, and scientific horizons.

Mark Bunger (mark.bunger@luxre
searchinc.com) is research director at
Lux Research. The firm’s recent report
on Synthetic Biology’s Commercial Roadmap describes how synbio enables disruptive new technologies in energy, healthcare, specialty chemicals, and agriculture. Web: www.luxresearchinc.com.

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