GENEWATCH
 
SYNTHETIC BIOLOGY: TAKING SHAPE
By Gregor Wolbring
 

Despite its touted developments in the past two years, many people are not aware of synthetic biology, one of the fastest growing subfields of science.   While not itself a technology, it is a research program that uses several different technologies for the purpose of designing biological matter, starting from the base pair level of DNA to higher levels of organization.  The subfield only gained significant visibility recently, with the first synthetic biology conference  taking place on June 10-12, 2004.1-7

The term "synthetic biology" was first used in the scientific literature by Barbara Hobom in her 1980 article "Surgery of genes. At the doorstep of synthetic biology."8  Since then, the research program in synthetic biology has attracted big name investors and prominent scientists.  Microsoft has a new funding initiative as does the Bill & Melinda Gates Foundation.9,10  Beyond Petroleum, BP (formerly British Petroleum) will 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.11-13 BP also invested in Craig Venter's company, Synthetic Genomics, as well as Arizona State University, where the research effort focuses on using a specially optimized photosynthetic bacterium to produce biodiesel.14-15

The market for synthetic biology products and technologies could be one of the fastest growing segments of the life sciences, according to a report by Beachhead.16 Various synthetic biology reports have been published in the last year.3-5,17-20 The Royal Society asked for input into the following topics regarding synthetic biology.21

  • Current research capacity and geographical distribution.
  • Societal implications
  • Ethical concerns
  • Biosecurity risks
  • Implications for the environment
  • Research support and funding
  • Biosafety concerns
  • Education and training
  • Governance and oversight of research
  • Economic considerations for developed and developing countries
  • Intellectual property rights issues for human health
  • Implications for human health
  • Legal issues and implications for regulation (national and international)

With all these activities under way one might still ask, what is synthetic biology?

Defining Synthetic biology

As a field in development, the meaning, scope, processes, raw material used and products envisioned by synthetic biology very significantly among its promoters.5,6,8,22-31 The first definition, dating back to the 1980s, defined synthetic biology as, "the synthesis of artificial forms of life, ...exemplified by the artificial genetic systems."8 R. Rawls credits Eric Kool, Professor of Chemistry at Stanford University for having revived the term at the 2000 American Chemical Society Meeting in San Francisco,  where he described it as "synthetic capability of organic and biological chemistry to design non-natural, synthetic molecules that nevertheless function in biological systems."28 The American synthetic biology community webpage defines  "synbio" (the shorthand term)  as " the design and construction of new biological parts, devices, and systems; and  the re-design of existing, natural biological systems for useful purposes."22 The Committee on Genetic Modification (COGEM), a biosafety expert body to the Dutch Ministry of the Environment, the European Community, the European synbiology project, the Rathenau Institute, a government funded technology assessment think tank in the Netherlands  consisting of academics involved in synbio work  and NGO's such as ETC all define synbio differently.28-35

Synbio activities and anticipated products are as diverse    as the definitions, which apply to all biological life including humans.36-46 Both its definitions and the keyword database of the synthetic biology literature draw a close link between synbio and  biotechnology, bioengineering and genetic engineering.46

   The heterogeneity of the definitions allows for different characterisations of synthetic biology and its relationship to other fields of science and technology such as nanotechnology, biotechnology, biochemistry, computing and engineering. The social issues are defined by the processes and products associated with a particular research program. For example, "The Ilulissat Statement: Synthesizing the Future a vision for the convergence of synthetic biology and nanotechnology" discusses the convergence of nano with synbio.45

Patent Issues Attached to Synthetic biology

Some characterize synbio as "nanobiotechnology."47 Others claim that synthetic biology is nothing more than genetic engineering. However, the bottom up approach of designing genomes from the bases/base pairs to higher levels of biological organization is quite different in its implications from changing a gene here and there. Let's have a look at a few issues.

According to the ETC Group, the Venter Institute has applied for numerous US and Worldwide Patents.50,51 CESAGen, 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, seeks exclusive monopoly on all synthetic genomes.51  It will be interesting to see whether these broad patents will be granted.  ETC states: "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..."50 Ironically, the ETC Group quotes open-science advocate, Dr. Richard Jefferson, founder of BIOS, the  Biological Innovation for Open Society, who believes that "if the patents are granted, Venter might be convinced to surrender them to a 'protected commons' where basic research tools can be used without fees as long as subsequent improvements are made freely available."51-52

It is understandable that many people in the synbio community are against the granting of these patents as it would make their work impossible.48,51 However it is far from clear that the patents will be denied. Countries that accepted Harvard's onco-mouse patent might find it particularly difficult to reject the patent claims of Venter and his company Synthetic Genomics.  However, even if patents on the processes are not granted, one can still apply for patents based on products.

The Synbio Discourse

As with bio and nano, the synbio discourse  presents  the same problems of determining what applications are developed and who gets to decide how those applications are used.53 The synbio discourse does not involve the majority of the world, such as the poor, indigenous peoples, disabled people and other marginalized populations. Proponents of synbio steer it away from social risk discourse, trying to link it solely to risks to medical and environmental health, as well as biological security. The recent report titled "Synthetic Genomics: Options for Governance," from the Craig Venter Institute (JCVI), the Center for Strategic & International Studies (CSIS), and the Massachusetts Institute of Technology (MIT) is an example of this. ***********54  Their focus fits with the self regulation and general libertarian perspective proposed by the synbio actors such as the International Consortium for Polynucleotide Synthesis (ICPS).55

The self regulation proposal raises some serious questions.

  • Considering the framework for governmental oversight of recombinant DNA technology, why should government regulation not extend to DNA synthesis?
  • Are there no issues related to other synbio applications, which according to the report include 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 synbio  initiative actually ensure any kind of biosecurity, even in the limited sense of pathogens and weapons?
  • Is self-regulation of synbio development feasible in a global context?

Ethics

Some people might contend that synbio needs its own "synbio ethics." Others are convinced it can be dealt with under conventional bioethics. Do we really need a converging-technology ethics or an application-based ethics?  Regardless of which system of ethics will be used, synbio work should lead to increased discussions about the societal implications of pursuing synthetic biology.56

Indeed, in 1999 a group of ethicists  wrote in Science  that Venter's work on the minimal genome does not cross any moral boundaries.57 However, the same bioethicists raised questions that should be answered before the technology advances further.  It has been over eight years since publication of the article and those questions have not been answered.49 The bioethicists stated,  among other things, that:

"Long-established techniques for manipulating DNA are continually being refined, extended, and combined in new ways for new ends. The prospect of constructing minimal and new genomes does not violate any fundamental moral precepts or boundaries but does raise questions that are essential to consider before the technology advances further. How does work on minimal genomes and the creation of new free-living organisms change how we frame ideas of life and our relationship to it? How can the technology be used for the benefit of all, and what can be done in law and social policy to ensure that outcome?"57

The 1999 Science article is a reminder of the pre-Asilomar letters in the early 1970s by Maxine Singer and Paul Berg that asked the scientific community to voluntarily pause on certain recombinant DNA research until the key questions are answered.  In contrast, the 1999 Science paper leaves the impression that there is no reason not to go full speed ahead with the research even as the ethical questions remain unanswered.49

Conclusion

Research into synbio technologies have progressed rapidly in the last year, but consideration of its social implications has moved at a snail's pace, if at all. We see some NGO's involved in the discourse. However , far more people are involved in GM Food activism than in synthetic biology.  The discourse also exhibits the same problems as the nano and bio discourse in general by being myopic in the issues it covers and the people involved.

So far international agencies and 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,  have not given any statements and guidance.58

It would be short-sighted to debate whether synbio is something truly new or merely a variant of existing biotechnology.  Even if an argument can be made that it is derivative from established technologies, its vision is bolder and its applications involve many more technologies beyond genetic engineering to achieve its goal.  It would also be short-sighted to debate whether the old ethics can deal with it or whether we need a new ethical approach. Does it pose unique ethical questions? The current ethical discourses do not address social risks of technology in a way that meets the needs of the marginalized majority of the world.  Perhaps synbio offers a way to jumpstart this discussion.

Synthetic biology is yet another scientific initiative that promises solutions to nearly every medical, social and environmental problem.  Technologies are replacing one another at an ever-increasing rate to offer solutions for the same set of problems. We often read about the top ten developments in science and technology, including those in nano, bio, regenerative medicine, the personalized genome and so on.59 There is no equivalent discussion about the top ten social solutions needed.

In the final analysis we need to revamp the entire discourse of science and technology policy and not just focus on synbio. Otherwise, social concerns over synthetic biology will muddle along, never reaching the core issues of sustainable living, narrowing health disparities, meeting the basic needs of underserved populations, and reforming science's hubris with regard to understanding and appreciating complex systems.


References and further reading

1. Wolbring, G, Synthetic Biology 2.0, http://www.innovationwatch.com/choiceisyours/choiceisyours.2006.05.30.htm, 2006.,The Choice is Yours Column at Innovationwatch.com

2. Wolbring, G, Synthetic Biology 3.0, http://www.innovationwatch.com/choiceisyours/choiceisyours-2007-07-15.htm, 2007.,Innovationwatch.com webpage

3. ETC Group. Extreme Genetic Engineering: An Introduction  to Synthetic  Biology, 2007, http://www.etcgroup.org/upload/publication/602/01/synbioreportweb.pdf,

4. European Commission 6th Framework Programme, NEST-New and Emerging Science and Technology. Synbiology: An Analysis of Synthetic Biology Research in Europe and North America, 2006, http://www2.spi.pt/synbiology/documents/news/D8%20-%20Synthetic%20Biology%20Research%20Assessment.pdf

5. Huib de Vriend and Rinie van Est. Constructing Life Early social reflections on the emerging field of synthetic biology, 2006, 10: 90-77364-11-0,

6. Synthetic biology community, Brief Definitions of Synthetic Biology, http://openwetware.org/wiki/Synthetic_Society/Distinguishing_and_defining_Synthetic_Biology#Brief_Definitions_of_Synthetic_Biology, 2007.,Openwetware

7. Synthetic biology community, Synthetic Biology 1.0 The First International Meeting on Synthetic Biology June 10-12, 2004

at the Massachusetts Institute of Technology Cambridge, MA, http://syntheticbiology.org/

Synthetic_Biology_1.0.html, 2007.,Synthetic biology community

8. Hobom B.Gene surgery: on the threshold of synthetic biology (1980) Medizinische Klinik 75, 24 834-841, http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&list_uids=6160378&cmd=Retrieve&indexed=google,

9. Microsoft, Computational Challenges in Synthetic Biology 2006 Awards, http://research.microsoft.com/ur/us/fundingopps/RFPs/Synthetic_Biology_Awards_2006.aspx, 2006.,Microsoft webpage

10. Michael Kanellos,.Gates foundation to promote synthetic biology, 2004, ZDnet News, http://news.zdnet.com/2100-9596_22-5489245.html .

11. Faculty Forum on the Energy Biosciences Institute, Faculty Forum on the Energy Biosciences Institute, http://webcast.berkeley.edu/event_details.php?webcastid=19207&p=1&ipp=15&category=, 2007.,UC Berkeley

12. Richard Brenneman,  News Analysis: GMO Research Dominates BP-UC Partnership, http://www.berkeleydailyplanet.com/article.cfm?issue=03-06-07&storyID=26481, 2007.,Berkeley Daily Planet

13. Brendan Maher, Rabble Rousing 3.0 (Surprise, Berkeley is the Source of the Upheaval), http://blogs.nature.com/news/blog/2007/06/rabble_rousing_30_surprise_ber.html, 2007.,Nature Newsblog

14. Michael Kanellos, Oil giant BP invests in microbe specialist, http://msn-cnet.com.com/Oil+giant+BP+invests+in+microbe+specialist/2100-11395_3-6191159.html, 2007.,CNET webpage

15. Joe Caspermeyer, ASU launches renewable biofuel research initiative with BP and SFAz, http://www.biodesign.asu.edu/news/asu-launches-renewable-biofuel-research-initiative-with-bp-and-sfaz, 2007.,Arizona State University

16. Beachhead, Synthetic Biology, A New Paradigm for Biological Discovery, http://www.beachhead.com, 2007, http://news.biocompare.com/newsstory.asp?id=117177.,Biocompare webpage

17. Synbiology: An Analysis of Synthetic Biology Research in Europeand North America project. SYNBIOLOGY An Analysis of Synthetic Biology Research in Europe and North America Final Report on Analysis of Synthetic Biology Sector, 2006, http://www2.spi.pt/synbiology/documents/news/D11%20-%20Final%20Report.pdf, SYNBIOLOGYAn Analysis of Synthetic Biology Research in Europe andNorth AmericaFinal Report on Analysis of Synthetic Biology Sector,

18. European Commission 6th Framework Programme, NEST-New and Emerging Science and Technology, 6th Framework Programme Anticipating scientific and technological needs NEST New and Emerging Science and Technology  Reference Document on  Synthetic Biology 2004/5-NEST-PATHFINDER INITIATIVES, 2004,.http://www.eurosfaire.prd.fr/nest/documents/pdf/PATH_synthetic_biology_2004.pdf.,European Community

19. European Commission 6th Framework Programme, NEST-New and Emerging Science and Technology. Synthetic Biology Applying Engineering to Biology Report of a NEST High-Level Expert Group, 2005, http://www.cordis.lu/nest/home.html,

20. Sam Bradbrook. HSE Horizon Scanning Intelligence Group Short Report Synthetic biology, 2007, http://www.hse.gov.uk/horizons/synthetic.pdf,

21. Royal Society, UK, Synthetic biology: Call for views, http://www.royalsoc.ac.uk, 2007,. http://www.royalsoc.ac.uk/downloaddoc.asp?id=4297.,Royal Society

22. Synthetic biology community webpage, http://syntheticbiology.org/, 2007.,Synthetic biology community

23. European Commission FrameworkProgramme 6. SYNBIOLOGY. An Analysis of Synthetic Biology Research in Europe and North America., 2005, http://www2.spi.pt/synbiology/documents/SYNBIOLOGY_Literature_And_Statistical_Review.pdf ,

24. Bhutkar, A.Synthetic Biology: Navigating the Challenges Ahead (2005) THE JOURNAL OF BIOLAW & BUSINESS 8, 2 19-29www.openwetware.org/images/0/02/Aj_bhutkar_synth_bio_jbb_2005.pdf ,

25. Paras Chopraa, a. A. K.Engineering Life through Synthetic Biology (2006) In Silico Biology 6, 401-410http://www.paraschopra.com/publications/synbio/synbio_review.pdf,

26. A Michael Sismour & Steven A BennerSynthetic Biology (2007) Expert Opin. Biol. Ther 5, 11 1409-1411http://www.ffame.org/sbenner/eobt5.1409-1414.pdf,

27. A Michael Sismour & Steven A BennerSynthetic Biology (2005) Expert Opin. Biol. Ther 5, 11 1409-1411http://www.ffame.org/sbenner/eobt5.1409-1414.pdf,

28. Rawls, R.'Synthetic Biology' Makes Its Debut (2000) hemical and engineering news 78, 17 49-53, http://www.stanford.edu/group/kool/,

29. Philip BallSynthetic biology:  Starting from scratch (2004) Nature, http://www.nature.com/news/2004/041004/pf/431624a_pf.html

30. Ray, T.An evolutionary approach to synthetic biology: Zen and the art of creating life (1995) Artificial Life 1, 1/2 195-226, http://www.his.atr.jp/~ray/pubs/zen/,

31. Brent, R.A partnership between biology and engineering (2004) Nature Biotechnology 22, 1211-1214

32. COGEM. Synthetische biologie. Een onderzoeksveld met voortschrijdende gevolgen., 2006, http://www.cogem.net/pdfdb/advies/CGM060228-03.pdf ,

33. Synbiology project. SYNBIOLOGY An Analysis of Synthetic Biology Research in Europe and North America Europe/North America Comparative Assessment, 2006, 

34. Benner, S. A. &. S. M. A.Synthetic biology (2005) Nature Reviews Genetics 6, 533 543

35. Christian KRASSNIG, PATHFINDER initiative on Synthetic Biology , 2005,.http://www.eurosfaire.prd.fr/nest/documents/pdf/3-Synthetic_Biology_brokerage_event_6-12-2005.pdf.,Eurosfaire webpage

36. Oliver Morton, Life Reinvented, http://www.wired.com/wired/archive/13.01/mit.html , 2005.,Wired Magazine

37. Synthetic biology community, Synthetic Biology Applications, http://syntheticbiology.org/Applications.html, 2007, http://openwetware.org/wiki/Keasling:_Synthetic_Biology_Class.,Synthetic biology community

38. Institute for the Future, The Future of Science and Technology, 2005-2055; Promising Applications of Synthetic Biology, http://humanitieslab.stanford.edu/2/282, 2007, http://humanitieslab.stanford.edu/deltascan/Home.,Institute for the Future,

39. Synbiology, Synthetic biology info, http://www.synthetic-biology.info/links.html, 2007.,Synbiology webpage (Europe)

40. Tara O'Toole, Hearing on "Project BioShield Reauthorization Issues", ,Center for Biosecurity

41. Jay Keasling, (2006) in Frontiers of Engineering: Reports on Leading-Edge Engineering from the 2005 Symposium  (National Academy of Engineering, Ed.) pp 83-89, National Academy of Engineering. http://www.nap.edu/catalog/11577.html 

42. Directorate-General for ResearchDirectorate S - Implementation of the 'Ideas' Programme,.SYNTHETIC BIOLOGY A NEST PATHFINDER INITIATIVE, 2007, RTD Infoftp://ftp.cordis.europa.eu/pub/nest/docs/5-nest-synthetic-080507.pdf.

43. The Economist,. Synthetic biology Life 2.0, 2006, The Economist, http://www.economist.com/science/displaystory.cfm?story_id=7854314.

44. Neil Savage, Building Better Biofuels Startup LS9 is developing microbes that produce hydrocarbons, http://www.technologyreview.com/Biztech/18827/, 2007, http://synthesis.typepad.com/synthesis/2007/06/the_need_for_fu.html.,Technol Rev

45. Robert Austin, Philip Ball, Angela Belcher, David Bensimon, Steven Chu, Cees Dekker, Freeman Dyson, Drew Endy, Scott Fraser, John Glass, Robert Hazen, Joe Howard, Jay Keasling, Hiroaki Kitano, Paul McEuen, Petra Schwille, Ehud Shapiro, and Julie Theriot, The Ilulissat Statement Synthesizing the Future a vision for the convergence of synthetic biology and nanotechnology Kavli Futures Symposium 'The merging of bio and nano: towards cyborg cells', ,Kavli Foundation Webpage

46. European Commission 6th Framework Programme, NEST-New and Emerging Science and Technology Synbiology, Keyword Database of the synthetic biology literature , http://www.synthetic-biology.info/, 2007, http://www2.spi.pt/synbiology/.,Synbiology webpage (Europe)

47. Michael Anisimov, Interview with Dr. Alan Goldstein, http://lifeboat.com/ex/interview.alan.h.goldstein, 2007, http://lifeboat.com/ex/i.nanobot.,Lifeboatfoumndation webpage

48. Wolbring, G.Bio-tech, NanoBio-Tech, SynBio-tech, NanoSynBio-tech? The changing face of biotech law? (Part I) (2007) Journal of International Biotechnology Law 4, 4 177-186

49. Wolbring, G.Bio-tech, NanoBio-Tech, SynBio-tech, NanoSynBio-tech? The changing face of biotech law? (Part II) (2007) Journal of International Biotechnology Law 4, 6 221-227

50.  ETC Group, Patenting Pandora's Bug: Goodbye, Dolly...Hello, Synthia! J. Craig Venter Institute Seeks Monopoly Patents on the World's First-Ever Human-Made Life Form, http://www.etcgroup.org/en/materials/publications.html?pub_id=631, 2007,.http://www.etcgroup.org/upload/publication/pdf_file/631,  http://www.etcgroup.org/upload/publication/pdf_file2/631.,ETC Group webpage

51. ETC Group, Extreme Monopoly: Venter's Team Makes Vast Patent Grab on Synthetic Genomes, http://www.etcgroup.org/_page24?pub_id=665, 2007.,

52.Cambia, BIOS Homepage,

             http://www.bios.net/daisy/bios/home.html, 2007.,Cambia

53. Wolbring, G.Nano-engagement: For Whom? By Whom? With Whom? for what? What Risk? Medical Health? Environmental? Social? (2007) Journal of Health and Development (India) accepted,

54. Craig Venter Institute (JCVI), the Center for Strategic & International Studies CSIS and the Massachusetts Institute of Technology MIT. Synthetic Genomics: Options for Governance, 2007, http://www.jcvi.org/research/synthetic-genomics-report/, http://www.jcvi.org/research/synthetic-genomics-report/media/synthetic-genomics-report.pdf, http://www.jcvi.org/press/news/news_2007_10_17.php

55. Hans Bügl et. al., A Practical Perspective on DNA Synthesis and Biological Security  (2006) Nat Biotechnol 25, 6 607-627, http://pgen.us/ICPS.htm, http://pgen.us/PPDSS.htm, http://pgen.us/PPDSS.htm

56. Carole Lartigue, et.al, Genome Transplantation in Bacteria: Changing One Species to Another (2007) Science Express 10 126, http://www.sciencemag.org/cgi/content/abstract/1144622,

57. Mildred K. Cho, et. al. G.Ethical Considerations in Synthesizing a Minimal Genome (1999) Science 286, 5447 2087-2090, http://www.sciencemag.org/cgi/content/summary/286/5447/2087,

58. Wolbring, G, NBICS and the Convention on Biological Diversity, http://politicsofhealth.org/wol/2007-06-30.htm, 2007.,Healhwrights webpage

59. Wolbring, G, Which NBICS For What, When?, http://politicsofhealth.org/wol/2007-09-30.doc, 2007.,Innovationwatch.com webpage

 
 
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