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Jul 13, 2010

Synthetic Biology—The Devil Is in the Financial Details

Oil companies’ significant investments have made biofuels the mainstay of R&D.

Synthetic Biology—The Devil Is in the Financial Details

© Orlando Florin Rosu - Fotolia.com

  • In an appearance March 10 on Comedy Central's "The Colbert Report," Jay D. Keasling, Ph.D., chemical and biomolecular engineering professor at UC Berkeley, explained how he and his colleagues at the Joint BioEnergy Institute were persuading yeast to make ethanol instead of alcohol from sugar. In response to host Stephen Colbert's suggestion that he was (and is) a mad scientist, Dr. Keasling replied that the same yeast that we use to produce beer and bread will soon be fueling our cars and planes. 

    The last laugh is definitely on Colbert, as Dr. Keasling’s synthetic biology company Amyris has developed fuels with properties superior to those of existing renewable alternatives. In 2009, the company announced that the EPA had obtained its No Compromise™ diesel fuel, making it the first hydrocarbon-based fuel made from plant-derived resources to be registered for commercial sale.

    Amyris also developed a semisynthetic form of artemisinin, a key ingredient in first-line malaria treatments, in a project funded by a grant from the Bill and Melinda Gates foundation. Amyris, however, handed over a royalty-free license to this technology to sanofi-aventis for the manufacture and commercialization of artemisinin-based drugs with a goal of market availability by 2012.

    Technological advances and huge investments have fueled this segment, which has the potential to reach $2.4 billion by 2013. A lion’s share of the money has come from oil companies. Amyris and other synthetic biology enterprises like Synthetic Genomics (SGI) have thus focused on producing alternative fuels despite first products that were potential pharmaceuticals. Both Amyris’ and Synthetic Genomics’ deal-making activities reflect those investments, as does the industry’s current leadership.

  • Following the Money

    James Collins, Ph.D., a professor of biomedical engineering at Boston University and a Howard Hughes Medical Institute investigator told GEN that alternative fuels has become the “killer app” for synthetic biology. The good news was that they brought attention to the field and a lot of funding into it. The bad news was that biofuels detracted the focus from other fields like new therapeutics development. “In my view, the amount of money thrown at alternative fuels resulted in recruitment of a majority of talented scientists into bioenergy at a critical time for the field.”

    Amyris was founded in 2003 and has since raised more than $244 million in private funding including $138.6 million on June 23, 2010. Its first CEO, John G. Melo, was previously president of U.S. fuels for BP. The firm says that it has about six corporate partnerships including one that resulted in an affiliate of French oil and gas giant Total SA becoming its largest stockholder.

    SGI was founded in 2005 by J. Craig Venter, Ph.D., Hamilton Smith, M.D., who shared the Nobel Prize in 1978 for physiology or medicine, Juan Enriquez, and David Kiernan. In 2007, BP reportedly made a substantial equity investment in the company as part of a R&D deal. Synthetic Genomics was to study the gene sequences of microbes that live within hydrocarbons and develop biological conversion processes that could lead to cleaner energy production and improved recovery rates. In retrospect, the deal should have focused on oil-eating, not fuel-making, microbes.

    Exxon Mobil made its first major investment in greenhouse gas reducing biofuels in 2009 via a $600 million partnership also with Synthetic Genomics to develop transportation fuels from algae. And technology companies wanting broader franchises in synthetic biology have been putting money into SGI, the latest being Life Technologies. On June 2, Life Technologies said that it had made an equity investment in SGI. 

    About two months before inking the deal with SGI, Life Technologies purchased about 59% of Germany’s Geneart, which concentrates on DNA engineering and processing. It provides custom gene-synthesis and gene-optimization services to its customers. Life Technologies now owns a 74% stake in that company.

    The SGI investment, in particular, extends Life Technologies footprint beyond tools and services to the basic science behind creating synthetic life forms. Peter Dansky, Life Technologies’ president of molecular biology systems, told GEN that the move reflects the company’s openness to expanding its business model. “It’s pretty unlikely we’ll be setting up biofuel pumps, but we think there are significant evolving spaces for applications that we can play in.

    “We’ve typically been a research tool oriented company, so why are we making investments beyond the tool stage? First of all, our roots are in research but our mission is to apply life sciences to improve human conditions. An example of this in the medical world is molecular diagnostics. Our tools are increasingly applied in molecular diagnostics, and we think this analogy holds in synthetic biology.”

    Dansky noted that the firm’s investment in SGI speaks to where Life Technologies believes there’s an opportunity. “Our interest is being on the leading edge and in touch with thought leaders.  It’s not about their business model.”

  • Will Good Science Prevail?

    Governments as well as private industry have also increased investments in synthetic biology. The Woodrow Wilson Center’s Synthetic Biology Project found that the U.S. government has spent around $430 million on research related to synthetic biology since 2005, with the Department of Energy funding a majority of the research. By comparison, the analysis indicated that the EU and three individual European countries—The Netherlands, U.K., and Germany—spent approximately $160 million during the same period.

    And the reality of fuel factory microbes may be somewhat closer to realization with the J. Craig Venter Institute (JCVI) reporting in May that it had created a synthetic organism. The project consumed $40 million, a team of 20 people, and about 12 years to complete. SGI has provided JCVI with nearly $30 million in funding since 2005. 

    Dr. Venter and his team reported that they had assembled a 1.08 mega base pair Mycoplasma mycoides JCVI-syn1.0 genome using digitized genome sequence information. The scientists transplanted the genome into a M. capricolum recipient cell to create new M. mycoides cells controlled only by the synthetic chromosome.

    Is the bug that Dr. Venter built a parlor trick or a real technological road map for producing worker bee bacteria that can provide new drugs, sources for scarce drugs, safer fuels, and address the messes made by oil companies? Plenty of skeptics, while thoroughly impressed with the remarkable technical achievement in producing the new organism, have raised some practical issues. One significant issue remains the unpredictable results of introducing either novel genetic sequences or whole new genomes into non-native hosts.

    The new bacterial cell, nicknamed Synthia, certainly focused the President’s and Congress’ attention on synthetic bio. President Obama, almost immediately following the JCVI’s announcement, called for the Presidential Commission for the Study of Bioethical Issues to “undertake, as its first order of business, a study of the implications of this scientific milestone to identify appropriate ethical boundaries and minimize possible risks associated with the breakthrough.” The committee is expected to deliver a report within about four months.

    Ultimately, it is hoped that calm heads and good science will prevail over the sort of fear-mongering stuff that appeared for example, in a June 3 online edition of the Daily Mail, that seems to have created its own artificial life forms with the headline “Scientist Accused of Playing God After Creating Artificial Life by Making Designer Microbe from Scratch—But Could It Wipe Out Humanity?” How many wrong ideas could you pack into one headline? 


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