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Biological Chemistry

Advancing Synthetic Biology

Students and researchers come together through events, networking to overcome obstacles

by Britt E. Erickson
July 2, 2012 | A version of this story appeared in Volume 90, Issue 27

BUILDING COMMUNITY
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Credit: iGEM/David Appleyard
Students from around the world compete in the annual iGEM synthetic biology competition.
iGEM 2011 world championship jamboree aerial photo
Credit: iGEM/David Appleyard
Students from around the world compete in the annual iGEM synthetic biology competition.

When some people hear about synthetic biology—an emerging field in which researchers assemble biological parts such as bits of DNA, RNA, and proteins to create organisms with new functionalities—they freak out about the potential for making harmful agents that could wreak havoc.

SEQUENCING VERSUS SYNTHESIS
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The cost of sequencing DNA has fallen significantly since 1990; costs of synthesizing of genetic material have dropped less dramatically.SOURCE: Rob Carlson, Biodesic
A chart showing the difference over time of DNA sequencing, short oligonucleotide synthesis, and gene synthesis prices per base pair.
The cost of sequencing DNA has fallen significantly since 1990; costs of synthesizing of genetic material have dropped less dramatically.SOURCE: Rob Carlson, Biodesic

Safety, security, and public image aren’t the only challenges facing synthetic biology. As researchers get better at building DNA and add more parts to biological registries, limited characterization and standardization of those parts are making it difficult to reproduce and scale up synthesis of organisms. Patents on some of the parts also create barriers to commercialization.

These and other hurdles confronting the field were highlighted last month during a two-day symposium in Washington, D.C., hosted by the U.S. National Academies of Sciences and Engineering in collaboration with the Chinese Academies of Sciences and Engineering, the U.K.’s Royal Society, and the U.K.’s Royal Academy of Engineering. Because there is limited government oversight, researchers feel the need to come together at strategy-setting meetings such as this one.

The meeting was the third in a series of symposia to address challenges associated with synthetic biology. The earlier meetings took place last year in London and Shanghai.

Governments around the world invest in synthetic biology because much of the current work in the field focuses on solving complex global challenges, such as curing diseases, developing biofuels, and boosting crop yields. But many experts predict that such applications are several years away.

The U.S., U.K., and China view synthetic biology as a key driver of innovation and economic growth. By working cooperatively, officials from each of the three countries hope to develop harmonized measurement methods and global approaches to potential safety and security problems, intellectual property (IP) rights, and social and ethical concerns.

To succeed, synthetic biology needs new measurement capabilities and standardization of those capabilities, Marc L. Salit, a research chemist at the National Institute of Standards & Technology, stressed at last month’s meeting. NIST hopes to develop such capabilities, Salit said, “so that two labs can make the same strain that has the same functional performance.”

As a first step, researchers need a library of well-characterized genetic fragments, Salit said. The most widely used registry in synthetic biology—the Registry of Standard Biological Parts, founded in 2003 at Massachusetts Institute of Technology—is a gold mine, said Karmella A. Haynes, a biomedical engineering professor at Arizona State University. But she pointed out that registered biological parts do not carry consistent descriptive data.

Haynes suggested that researchers use a model similar to that of Wikipedia to improve the data in the registry. NIST could play a role in developing the characterization methods for each type of part.

Many instrumentation companies see synthetic biology as the next big wave and are gearing up to provide measurement and informatics tools. To characterize DNA constructs, single cells, and heterogeneous cell populations, researchers need measurement platforms with high sensitivity and high throughput, said Darlene J. S. Solomon, senior vice president and chief technology officer at Agilent Technologies. They also need informatics and software platforms to evaluate what they have built, she added.

The cost of DNA synthesis should continue to come down, and thus hasten research and commercialization of synthetic biology products, Solomon said. But companies will find it difficult to overcome the hurdles to commercialization on their own, she stressed. Solomon recommended the formation of public-private partnerships, such as those in the semiconductor industry, to accelerate investments and to develop a plan for the field’s research and technology needs, including an overall framework for IP.

Researchers who want to commercialize synthetic biology products do not have an industry trade association to help them chart a path forward. Such a group could create a road map that provides customers of synthetic biology, such as pharmaceutical companies and the chemical industry, with information about technology trends, said Jason Kelly, a cofounder of the Boston-based start-up Ginkgo BioWorks.

Like Solomon, Kelly points to the semiconductor industry’s success for ideas. That industry lets customers know what they can expect to see in the next two to three years, so they can plan ahead for the products, Kelly said. A synthetic biology industry group could do the same, providing key industry statistics such as the percentage of global fermentation capacity that is currently occupied, so that customers can plan ahead to use the technology, he added.

An industry group could also help researchers navigate IP rights. Synthetic biologists often run into problems because not all genetically encoded functions in a registry are free to use. Just determining which ones have patent protection and which ones do not can be prohibitively expensive for a small company, particularly when tens, hundreds, or even thousands of biological parts go into a commercial product.

“For the most part, through either a de facto research exemption or a series of licensing agreements, we’ve been able to disseminate the use of these parts for nonprofits, educational purposes, and research,” said Linda Kahl, head of the ownership, sharing, access, and innovation systems project at Stanford University’s Synthetic Biology Engineering Research Center. But problems arise when researchers “want to be able to use these parts for commercial purposes,” she noted.

As the cost of DNA synthesis drops, researchers will no longer need to get parts from a registry, Kahl predicted. They will simply obtain the sequence information and pay a company to synthesize the part, she said. When that happens, she warned, DNA synthesis companies may unknowingly infringe patents.

To make it easier to identify biological parts that are covered by IP rights, researchers should register such rights in a clearinghouse, said Mark A. Lemley, a law professor at Stanford.

Another concern related to the field’s decentralized nature is that synthetic biology is progressing with limited government oversight. As a result, researchers rely on social media and annual gatherings to build a sense of what is right and wrong. Robert C. Wells, head of the biotechnology unit in the Directorate for Science, Technology & Industry at the Organisation for Economic Cooperation & Development, characterized the field’s ethos as stemming from “a culture of values as opposed to a culture of compliance.”

One of the most successful community-building efforts for synthetic biology has been the International Genetically Engineered Machine (iGEM) competition. The event started at MIT in 2004 as a summer competition for undergraduate students.

Students design their own biological pieces and combine them with parts in the Registry of Standard Biological Parts to make novel organisms. The teams compete at regional jamborees, and some of them go on to a world championship.

The iGEM competition has grown from five undergraduate teams in 2004 to 190 undergraduate teams this year. In addition, 40 high school teams and 15 entrepreneurship teams, made up of undergraduate and graduate students, will compete this year. The entrepreneurship teams, which are new this year, develop business plans and economic models, as well as focusing on regulations and policies.

Altogether, more than 10,000 people worldwide have participated in an iGEM competition, said Meagan Lizarazo, vice president and chief operating officer of the iGEM Foundation, an independent nonprofit organization that spun out of MIT this year. In addition, more than 200 academic research labs have signed up to use iGEM Foundation resources, such as the registry of biological parts, she noted.

The annual event has become more than a competition to build the niftiest genetically engineered machine. Participants have to consider the social, ethical, safety, security, and IP aspects of synthetic biology. As a result, the competition has built a community that understands the broader implications of their work and the importance of collaboration, said Sohi Rastegar, a senior adviser for emerging technologies and interdisciplinary research at the National Science Foundation. “Hands-on training in synthetic biology has been taking place even before NSF makes serious investments in it,” he remarked.

Researchers at the meeting used words like “awesome,” “unique,” and “wonderful” to describe the iGEM competition, but some people said it needs to cost less and be scaled up so that more students can participate. Each team spends an average of $30,000 to $50,000 on its iGEM project, Lizarazo estimated.

Having a vehicle such as the iGEM competition to impart a sense of values is important because synthetic biology is likely to have applications that fall under the jurisdiction of multiple regulatory agencies, Wells pointed out. “It is hard to imagine a governance structure that would overarch all of the areas,” he said. Governing the field, he said, will be “more about the values than about the day-to-day regulations.” ◾

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