Synthetic Biology 3.0 by Gregor Wolbring July 15, 2007

My very first column published in May 2006 was called Synthetic Biology 2.0, named after the 2006 conference of the synthetic biology community. The Synthetic Biology 3.0 has just taken place at the Swiss Federal Institute of Technology (ETH) in Zurich, Switzerland, on June 24-26, 2007. This provided an opportunity to reflect on what has happened in the last year, and what did not, with respect to synthetic biology and its discourse.

What Did Happen

New Science

A lot has happened on the science side. The journal Science has just reported on the transformation of one bacterial species into another (see also here and here). And the titles of some of the papers presented at Synthetic Biology 3.0 give an even greater sense of what is going on:

• Synthetic Ecosystems based on Airborne Inter- and Intra-Kingdom Communication;
• Designing Biological Memory and Logic;
• The Quest for a Minimal Cell: a Synthetic Genomics Approach;
• The Semi-Synthetic 'Minimal Cell': a Model for Early Living Cells;
• Metabolic Engineering: Engineering Microbes for Production of Biochemical Products;
• Sense Codon Reassignment as Means of Synthesizing Safe Genetically Engineered Microorganism;
• From Metabolic Engineering to Metabolic Design:
• Embodying Novel Core Metabolisms and Containing Genetic Pollution;
• Production of a Human Artificial Chromosome with a Conditional Centromere; Control and Design of Mammalian Clocks;
• Ab Initio Design of Complete Living Organisms.

Blogs from ETC, the journal Nature and Molecular System Biology highlighted different speakers at the conference.

The conference was highly oversubscribed, an indicator of growing interest in the field. Research is advancing in the design of new metabolic pathways that lead to new product outputs by organisms, and in the design of entirely new organisms from scratch, some of which are based on the traditional genetic code, and others that incorporate bases and base pairs in the genetic code of an organism which do not exist in nature.

New Initiatives

The conference program highlights four initiatives:

• iGEM - the International Genetically Engineered Machine Competition;
• The Synthetic Biology Engineering Research Center - SynBERC ;
• EMERGENCE - a Foundation for Synthetic Biology in Europe; and
• Towards a European Strategy for Synthetic Biology - the TESSY Project.

TESSY aims to establish an expert-based, investigative and participative process for mapping the current state of synthetic biology, assessing its future potential and proposing a European strategy for further development in Europe.

EMERGENCE “intends to establish this coordination on several levels: [i] it will include the majority of European scientists and engineers currently active in the field and reach out to include crucial developments in the USA and Asia via a communication platform; [ii] it will establish the intellectual foundation for Synthetic Biology by recruiting the required competence from neighbouring engineering disciplines; [iii] it will illustrate the power of the Synthetic Biology approach to bioengineering with a demonstrator for a dedicated IT infrastructure; [iv] it will map the most promising approaches to standardizations of procedures and parts; and [v] it will embed the early development of Synthetic Biology into the most meaningful industrial context by exploring the industrial interface. In addressing these aspects, EMERGENCE will provide a firm foundation for Synthetic Biology to prosper in Europe and to fulfil indeed its role as a future engine for economic growth.”

SynBERC -- funded by the National Science Foundation (NSF) -- “is a multi-institution research effort to lay the foundation for the emerging field of synthetic biology. SynBERC aims to develop the understanding and technological tools needed to design biological systems for pharmaceuticals, renewable energy, and other areas where the high costs and long development times of conventional biological approaches are prohibitive. SynBERC is a National Science Foundation Engineering Research Center for synthetic biology, and a program of the California Institute for Quantitative Biomedical Research (QB3).” It has a variety of links to different industries.

iGEM “is an international arena where student teams compete to design and assemble engineered machines using advanced genetic components and technologies.” Teams in the 2006 competition came from 37 schools, predominantly from Europe and North America; however, Africa and Latin America were also present, as well as Turkey and Japan. The winner was a team of eight undergraduates from the University of Ljubljana in Slovenia. In April 2007, a synthetic biology workshop was held in China.

Funding

More happened last year that was not covered in the conference program, such as the Microsoft Research (MSR) new funding initiative for synthetic biology (see also here). The request for proposals allocates $500,000 for two principal areas of synthetic biology research: (1) Re-engineering natural biological pathways to produce interoperable, composable, standard biological parts. Examples include the role of computers in the “specification, simulation, construction and dissemination of biological components or systems of interacting components.” (2) Tools and information repositories relating to the use of DNA in fabricating nanostructures and nanodevices.

Jay Keasling at UC Berkeley received $42 million from Bill Gates to create living microfactories that manufacture a powerful antimalaria agent.

Beyond Petroleum BP (formerly British Petroleum) agreed to give $500 million over the next ten years to a group headed by the University of California at Berkeley for research into alternative energy, biofuels and synthetic biology (see also here).The consequences of this deal are also covered by the blog of the journal Nature covering the synbio conference.

News from the synbio community can be found here.

Patents

According to ETC Group, the Venter Institute has applied for a US Patent (number 20070122826) which claims exclusive ownership of a set of essential genes, and a synthetic “free-living organism that can grow and replicate” that is made using those genes. The Institute has also filed an international patent application at the World Intellectual Property Organization (WIPO number WO2007047148, published April 27, 2007) which names more than 100 countries where it may seek monopoly patents.

It will be interesting to see whether this patent will be granted. ETC Group reports: “The patent application explains that the inventors arrived at their minimal genome by determining which genes are essential and which are not. Remarkably, their patent application claims any synthetically-constructed organism that lacks at least 55 of 101 genes that they’ve determined are non-essential. “All synthetic biologists developing functionalized microbes are going to have to pay close attention to the claim on a ‘non-essential’ set of genes……”

This patent and the numerous other patents applied for raise the question whether the ‘synthetic biology of the future’ will indeed be as ‘open source’ as often stated. One wonders how synthetic biology patenting will impact initiatives such as the biological commons of the Cambia project.

On the one hand, one reads from a member of the synbio community: “Biological engineering has been held back because many of the most effective biological parts (promoters, genes, plasmids, etc.) have been patented and are available only to companies that can afford the royalty payments. This has not only increased the cost of drug development, but also hampered the development of new biological solutions to problems that may not have significant monetary payoffs (basically, anything other than drug development). Open-source biological parts, devices, and eventually whole cells would reduce the cost of engineering biological systems, make biological engineering more predictable, and encourage the development of novel biological solutions to some of our most challenging problems. The development of open-source biological technology would improve awareness of, and minimize possible future biological risks, in the same way that open-source software tends to promote a constructive and responsive community of users and developers.”

On the other hand, many members of the synbio community have started companies and are trying to expand their patent collections. (For a piece on economics of synbio which covers the issue of open source in life sciences see here.)

Patents with sweeping scope were granted in the early days of nanotechnology, and this is already leading to problems. Will the synbio field end up with the same dynamic?

Reports on Synthetic Biology

A variety of reports on synthetic biology have been published in the last year, including:

• Extreme Genetic Engineering: An Introduction to Synthetic Biology by ETC Group, that covers synthetic biology for a variety of years.
• The Rathenau Institute report on synthetic biology. The Institute is an independent body funded by the Ministry of Education, Culture and Science in the Netherlands. Administratively, the institute falls under the Royal Netherlands Academy of Arts and Sciences (KNAW). It Institute carries out research in the development of science and technology.
• Bio-era’s Genome Synthesis and Design Futures report. (free pdf - registration required).
• Synthetic Biology:Applying Engineering to Biology. Report of a NEST High-Level Expert Group NEST (New and Energing Science and Technology -- a research activity under the European Community’s 6th Framework Programme).
• HSE Horizon Scanning Intelligence Group Short Report on Synthetic biology
• SYNBIOLOGY An Analysis of Synthetic Biology Research in Europe and North America (more documents here).

The Royal Society of the United Kingdom is considering undertaking a project on synthetic biology and is soliciting opinions until August 27, 2007.
Other documents are listed on the synbio community wiki.

What Has Not Really Happened

My column Synthetic Biology 2.0 highlighted among other issues the concerns of NGOs with respect to medical health, and environmental and social safety issues whereby the synbio community only recognizes problems in regard to biosecurity issues. A lot of these issues are covered in the ETC report Extreme Genetic Engineering, the Rathenau Institute report and this news item. For security issues surrounding synthetic biology and other biological issues see here.

The positions of the NGOs and synthetic biology community seem to be far apart in regard to the risk assessment, with the NGOs demanding governmental and global regulation of the synbio field, and the synbio community proposing self-regulation. The synbio community issued a Declaration at the Second International Meeting on Synthetic Biology which they later rejected at their own meeting.

Another self regulation proposal was floated -- this time by the International Consortium for Polynucleotide Synthesis (ICPS) -- which was published in Nature Biotechnology in June 2007 .and commented on June 22 in Science magazine. Both publications appeared just before the 3.0 Conference. It was authored by companies from the United States, Germany, Austria and South Korea, some university affiliated academics and the United States Federal Bureau of Investigation.

The proposal relates to screening of the sale of DNA synthesis products and focuses on ‘biosecurity,’ as in pathogens and weapons. It is beyond the scope of this column to highlight all of the issues associated with the proposal. I urge the reader to read it, and leave the reader just with a few questions:

• As we had a framework for governmental oversight of recombinant DNA technology (mentioned in the proposal) why should government regulation not be extended to DNA synthesis?
• Are there no issues related to other synbio applications -- which according to the proposal are biological production of energy, biosynthesis of bulk and fine chemicals, bio-based manufacturing of materials, biological information processing, environmental sensing and remediation, agriculture, and human health and medicine?
• As “improvements to the process and commercialization of DNA synthesis” will make the process less and less expensive, and will increase its availability, can the proposal actually ensure any kind of biosecurity, even in the limited sense of pathogens and weapons?
• Is self-regulation really feasible for a global scenario?

Synthetic Biology 3.0 offered several sessions on the topic of security, safety and ethics (which I called synbio-ethics in my Synthetic Biology 2.0 column):

• Parallel Session: Biosafety and Biosecurity: Public Perception; Synthetic Genomics: Biosafety, Biosecurity, and Governance; Riding a Roller-Coaster: Policy, Public and Science Interactions in Synthetic Biology; Biosecurity Implications of DNA Synthesis and Synthetic Biology
• Gautam Mukunda, Boston University; Synthetic Biology and Biosafety: Insight into Control Mechanisms on Worldwide Distribution of Synthetic DNA from an Industrial Perspective
• Parallel Session: Synthetic Biology and Ethics: Debating the Ethics of Synthetic Biology: Transcending the Current Impasse

SYNBIOSAFE is a scientific project that is fully supported by the European Commission´s 6th framework programme. It is the first European project to conduct research on the safety and ethical aspects of synthetic biology. It aims to proactively stimulate a debate on these issues. SynBERC -- a USA synbio project -- covers some social issues in Thrust 4: “Thrust 4 examines synthetic biology within a frame of human practices, with reciprocal emphasis on ways that economic, political, and cultural forces may condition the development of synthetic biology and on ways that synthetic biology may significantly inform human security, health, and welfare through the new objects that it brings into the world.”

Much more is needed in my view. The SBELSI (synbio-ethical, legal, social implications) are still rather underrepresented at the conference and in the synbio discourse. Civil society and NGOs are no more involved now than they were a year ago.

The Choice is Yours

Synbio has progressed rapidly in the last year; however, consideration of its social implications has moved at a much slower pace.. It will be interesting to see whether some guidance will come from international bodies such as those involved in the Convention for Biological Diversity -- a convention which by the nature of its language covers the scope and processes of synbio (see my column from June 30th).

It also appears that synbio is suffering from the hyperbole and sales pitches that plague so many scientific endeavours. With a multitude of new and emerging technologies in need of funding, researchers try to outdo each other in promising solutions to every problem that has some visibility.

It will be interesting to see what happens between now and Synthetic Biology 4.0 -- planned for October 2008 in Asia, perhaps in Hong Kong. There are many issues I think people need to become knowledgeable about in a hurry. From what has been reported from the Synbio 3.0 Conference in three different blogs -- namely ETC (especially this part), the journal Nature, and the molecular system biology blog -- things are moving very fast.

Gregor Wolbring is a biochemist, bioethicist, disability/vari-ability/ability studies scholar, and health policy and science and technology governance researcher at the University of Calgary. He is a member of the Center for Nanotechnology and Society at Arizona State University; Part Time Professor at Faculty of Law, University of Ottawa, Canada; Member CAC/ISO - Canadian Advisory Committees for the International Organization for Standardization section TC229 Nanotechnologies; Member of the editorial team for the Nanotechnology for Development portal of the Development Gateway Foundation; Chair of the Bioethics Taskforce of Disabled People's International; and former Member of the Executive of the Canadian Commission for UNESCO (2003-2007 maximum terms served). He publishes the Bioethics, Culture and Disability website, moderates a weblog for the International Network for Social Research on Disability, and authors a weblog on NBICS and its social implications.