Synthetic biology and ethics: Building public trust
Julian Kinderlerer, President, European Group on Ethics, Professor, Intellectual Property Law, University of Cape Town, South Africa, Professor, Biotechnology & Society, Delft University of Technology, Netherlands
The science of synthetic biology has become of great interest in the last few years, with major studies being commissioned to examine the implications of this new technology.
In 2009, President Barosso, President of the European Commission, requested an Opinion of the European Group on Ethics in Science and New Technologies (EGE) on the ethics of synthetic biology (EGE, 2009). In this request he indicated that “the debate about the legitimacy of engineering new life forms has mainly focused on safety issues and a work on the ethical, legal and social implications that may derive from this specific use of biotechnology is still missing.”
In US President Obama’s letter to the Presidential Commission for the Study of Bioethical Issues (2010), he asked for a consideration of “the potential medical, environmental, security and other benefits of this field of research as well as any potential health, security and other risks.” The issues had been highlighted in May 2010 “by the announcement that scientists at the J. Craig Venter Institute had created the world’s first self-replicating synthetic genome (human-made from chemical parts) in a bacterial cell of a different species” (Gibson et al., 2010).
The European Academies Science Advisory Council (EASAC, 2010) considered the scientific and governance implications of synthetic biology and reported on ‘Realising European Potential in Synthetic Biology: Scientific Opportunities and Good Governance.’ It is therefore clear that the technologies and science involved in what is termed ‘synthetic biology’ are raising major issues, at least within international political circles. Building public confidence in the governance of synthetic biology by following ethical principles and standards is critical. But what are the issues, and why is there concern?
What is Synthetic Biology?
Synthetic biology addresses the design and synthesis of novel biological systems. The EASAC report terms it the ‘engineering of biology’. It is not purely the province of biologists, for it involves input from microbiology, genetics, genomics, chemistry, physics, mechanical and chemical engineering, information technology and computer science. The range of sciences involved identifies an unusual concern – scientists who do not have the expertise or experience in working with biological material may lack the knowledge of the risks and the care needed when handling such material. The EGE considered many different definitions of synthetic biology that have appeared in the literature, and chose to identify the common elements in the definitions rather than attempt an inclusive definition. The concept should include:
- The design of minimal cells/organisms (including minimal genomes);
- The identification and use of biological ‘parts’ (toolkit);
- The construction of totally or partially artificial biological systems.
Either a ‘top-down’ or a ‘bottom-up’ approach is possible. The ‘top-down’ starts with an existing organism and attempts to strip down redundant genetic elements to identify a viable organism with the minimum of genetic information. ‘Bottom-up’ involves the use of an inventory of ‘standard parts’ (for example, the Registry of Standard Biological Parts begun by the Massachusetts Institute of Technology in 2003: http://partsregistry.org/Main_Page) used as building blocks to constitute an organism. The EASAC argues that synthetic biology may be different from genetic modification in that “it more explicitly seeks to model and predict the outcomes of the experiments.” Genetic modification techniques insert a (relatively) small number of genes in order to modify particular traits of the organism. Synthetic biology involves a redesign of the organism both for specific purposes and in order to understand the organism.
Synthetic biology can or has the potential to provide tools that could improve our understanding of biological systems and methods to produce designer organisms for a range of products, such as pharmaceuticals, biofuels, vaccines, new agricultural products or agents for use in the defence industry.
The use of synthetic biology to manufacture new life forms that are then released into the environment may still be in the future, but the insertion of artificial chromosomes into higher life forms may not be fanciful (e.g., see Ananiev et al., 2009; Cavaliere et al., 2009). De novo human artificial chromosomes have been generated in human cells (Basu et al., 2005), which make them ‘potential vectors of gene therapy approaches where there is a need to transfer large sections of the genome’ (EGE, Section 1.5.2, 2009).
What are the Ethical Issues?
The EGE asserted that synthetic biology raises some fundamental ethical questions, requiring a conceptual analysis of life and nature. Should we be designing and manufacturing living organisms at all? In 1999, a group of bioethicists examined these issues before the science had evolved into reality. They concluded that the ideas then prevalent as to what synthetic biology entailed “did not violate fundamental moral precepts or boundaries, but did raise questions about the possible consequences of synthesising new free-living organisms in relation to the concept of life and our relation to it” (Cho et al., 1999; EGE (Section 3.1.2), 2009). Many have argued that the ability to synthesise new, radically changed organisms may change our concepts of ourselves.
Instrumentalisation of organisms, already prevalent, is taken beyond that which some believe acceptable, especially if this were to be extended to higher organisms (Sommerville, 2007). These fundamental concerns of theologians and ethicists relate to our understanding of ourselves and our relation to other organisms.
Ethical issues identified by the various reports already cited include Biosafety. The safe use of organisms depends on our understanding of them in the environment in which they are placed. Genetically modified organisms (GMOs) have already raised many safety concerns and all countries that use them or refuse to allow their use have instituted risk assessment procedures (insofar as it is possible) to assure that the introduction into the environment is as safe as it can be; at least as safe as those organisms already in the environment. The safety assessments depend on the characteristics of the organism already in use plus those traits that are newly introduced into the organism. How is it possible to assess the risk of an organism that has been significantly altered, way beyond the changes introduced into GMOs?
The risks have to be addressed in order to permit the use of these new organisms responsibly. The Nuffield Council on Bioethics’ discussion paper, ‘The Use of Genetically Modified Crops in Developing Countries’ (2003), stressed a possible interpretation of the precautionary approach and its application in the governance of biotechnology (which is required for those countries that are members of the Cartagena Protocol on Biosafety (2000)). This approach, which depends on the likelihood of serious and irreversible risks, shifts the burden of proof from those potentially exposed to the hazards of a new technology to those who want to introduce it. The EGE raises a concern at the dangers of potentially harmful organisms being accidentally or inadvertently released into our environment, in part because of the range of practitioners of these new technologies.
Biosecurity is a major issue; it is already possible to use published sequences of letha
l viruses to deliberately manufacture them for maleficent use. Synthetic organisms engineered to produce toxins are therefore an obvious concern. “The literature on bio-war and the use of bioengineering for bio-defence, bio-offence and terrorism shows the potential of this technology, which may be amplified by synthetic biology” (EGE, 2009, see also Crosby, 1986; Endicott and Hagerman, 1998; Keith, 1999; Mangold and Goldberg, 1999; Alibek and Handelman, 2000; Preston, 2002; Orent, 2004; Woods, 2005).
The Principle of Justice is analysed in the EGE Opinion (EGE, 2008) and the US Commission’s Report (Presidential Commission for the Study of Bioethical Issues, 2010). It relates to the role of the State in protecting and advancing human rights and includes a need to consider the technology divide, particularly between developed and developing countries. The Principle requires the addressing of intergenerational justice, the need to conserve the environment and natural resources. New technologies are invariably used by, and arguably, controlled by the scientifically advanced countries. This may impact on the ability of those in less advanced and developing countries to benefit from these technologies or even control them within their territories. The costs of using the technologies may be high, and the costs of not using them may also be high if the effect is to compete with that that they produce.
The issue of the patenting of new life forms then becomes critical, as it may enhance their use in developed countries (through the availability of funding) whilst ensuring that their use in poorer areas of the world is deterred through high cost.
The ethical use of patents for synthetic life forms has also been the topic of major discussion. A live organism is patentable if it has markedly different characteristics from a comparable organisms found in nature. Many patent laws forbid patenting if the commercial exploitation of the invention is contrary to morality. Can it be argued that the commercial exploitation of a new life form expressly designed for commercial purposes is contrary to morality? Probably not. Few argue with the ability to patent microorganisms as long as they meet the requirements of patent law. Many are concerned at the patenting of higher life forms, such as mice or plants, and it has been affirmed in many jurisdictions that the human body cannot constitute a patentable invention. The European Union’s Directive 98/44 (1998) indicates that modifying the genetic identity of animals that is likely to cause suffering without any substantial medical benefit in terms of research, prevention, diagnosis or therapy to man or animals must be excluded from patentability. More general issues relating to patents and ethics are mentioned in Fossey’s article on the ethics of research innovations (2008).
There are no new ethical issues identified by published works in relation to synthetic biology. However, synthetic biology does provide ethical challenges that need to be addressed.
Building Public Trust
Genetically modified organisms were first introduced onto the market towards the end of the 1980s. In 1986, the Organisation for Economic Cooperation and Development published its manual ‘Recombinant DNA Safety Considerations’ (OECD, 1986), known as ‘the Blue Book’, which (arguably) is the basis for much of the national and international regulatory structure for assessing the safety of genetically modified organisms around the world. The UK had formulated regulations in relation to the contained use of GMOs in the early 1980s under the guidance of the Advisory Committee on Genetic Modification, a committee that advised the Health and Safety Executive, and the USA introduced a coordinated framework for regulation of Biotechnology in 1986 (US Office of Science and Technology Policy, 1986) in part to add to the earlier guidelines formulated by the National Institutes of Health (1986; see also current version, 2011). All of these documents presumed that there were risks associated with the new technologies that had to be addressed through some sort of statutory or voluntary regulation.
During the 1990s, much discussion took place as to whether an international treaty was needed to ensure the safe use of these organisms. In 2000, the Cartagena Protocol to the Convention on Biological Diversity was adopted (Cartagena Protocol on Biosafety, 2000). This treaty now has 160 Member Countries, surprisingly excluding the countries that are the prime producers of genetically modified crops (James, 2010) and Article 1 specifically addresses the safe transfer, handling and use of living modified organisms resulting from modern biotechnology.
There has, therefore, been a presumption that GMOs are likely to have adverse effects on the environment and/or on human health. Most scientists assert that there have been no observable adverse effects, and current non-transgenic technologies pose greater threats to human health and the environment than those GMOs currently on the market. Nevertheless, in many countries around the world there are concerns and the public appears to have chosen not to accept these products. In other countries, notably the USA, Canada, Argentina and Brazil that grow these crops almost to the exclusion of their non-GMO equivalents, little public concern has been noted.
Since public concerns on GMOs remain, the introduction of the products of synthetic biology, where the modification is much greater, could elicit at least the same level of concern. The type of products, the scale and speed of their introduction into the market and into the environment, and the manner in which the ethical issues are addressed is likely to impact on the extent of their acceptance. Care is needed to involve the public in discussions and decisions in relation to the development and use of synthetic biology products (and processes). This is crucial. Building confidence in the governance and use of synthetic biology could go a long way to assuring the acceptability of the products if they meet the necessary public safety requirements and environmental standards. Scientists and governments must adhere to the highest ethical principles and standards with respect to this evolving scientific and technological advance.
Alibek, K. and Handelman, S. 2000. Biohazard: The Chilling True Story of the Largest Covert Biological Weapons Program in the World – Told from Inside by the Man Who Ran it. Delta, New York USA. ISBN 0-385-33496-6.
Ananiev, E.V., Wu, C.C., Chamberlin, M.A., Svitashev, S., Schwartz, C., Gordon-Kamm, W. and Tingey, S. 2009. Artificial chromosome formation in maize (Zea mays L.). Chromosoma 118: 157-177.
Basu, J., Compitello, G., Stromberg, G., Willard, H.F. and Bokkelen, G. van. 2005. Efficient assembly of de novo human artificial chromosomes from large genomic loci. BMC Biotechnology 5: 21, doi:10.1186/1472-6750-5-21.
Cartagena Protocol on Biosafety. 2000. Cartagena Protocol on Biosafety to the Convention on Biological Diversity. http://www.cbd.int/doc/legal/cartagena-protocol-en.pdf
Cavaliere, F.M., Scoarughi, G.L. and Cimmino, C. 2009. Interspecific transfer of mammalian artificial chromosomes between farm animals. Chromosome Research 17: 507-517.
Cho, M.K., Magnus, D., Caplan, A.L. and Ethics of Genomics Group. 1999. Ethical considerations in synthesising a minimal genome. Science 286: 2087–2090. http://www.sciencemag.org/content/286/5447/2087.short
Crosby, A.W. 1986. Ecological Imperialism: The Biological Expansion of Europe, 900-1900. Cambridge University Press, New York, USA. ISBN 0521456908.
EASAC. 2010. Realising European Potential in Synthetic Biology: Scientific Opportunities and Good Governance. European Academies Science Advisory Council Policy Report 13, Brussels, Belgium. ISBN: 978-3-8047-2866-0. http://www.easac.eu/fileadmin/PDF_s/reports_statements/Synthetic%20Biology%20report.pdf
EGE. 2008. Ethics of Modern Developments in Agricultural Technologies. The European Group on Ethics in Science and New Technologies to the European Commission, Brussels, Belgium.
EGE. 2009. Ethics of Synthetic Biology. The European Group on Ethics in Science and New Technologies to the European Commission, Opinion No 25, Brussels, Belgium. ISBN 978-92-79-13829-4. http://ec.europa.eu/european_group_ethics/docs/opinion25_en.pdf
Endicott, S. and Hagerman, E. 1998. The United States and Biological Warfare: Secrets from the Early Cold War and Korea. Indiana University Press, Bloomington, IN, USA. ISBN 0253334721.
European Union (1998) Directive 98/44/EC of the European Parliament and of the Council of 6 July 1998 on the Legal Protection of Biotechnological Inventions.
Fossey, A. 2008. Research ethics and agricultural innovations. CTA Knowledge for Development Dossiers. http://knowledge.cta.int/index.php/en/Dossiers/S-T-Issues-in-Perspective/Science-and-ethics/Articles/Research-ethics-and-agricultural-innovations
Gibson, D.G.; Glass, J.I., Lartigue, C., Noskov, V.N., Chuang, R.Y., Algire, M.A. et al. 2010. Creation of a bacterial cell controlled by a chemically synthesized genome. Science 329: 52-56. http://www.sciencemag.org/content/329/5987/52.full
James, C. (2010) Global Status of Commercialized Biotech/GM Crops: 2010. ISAAA. Metro Manila, Philippines. ISBN 978-1-892456-49-4.
Keith, J. 1999. Biowarfare in America, Illuminet Press, Lilburn, GA, USA. ISBN 1-881532-21-6.
Mangold, T. and Goldberg, J. 1999. Plague Wars: a True Story of Biological Warfare, Macmillan, London, UK. ISBN 0-333-71614-0.
National Institutes of Health. 1986. NIH Guidelines for Research Involving Recombinant DNA Molecules, Federal Register, May 7, 1986 51 FR 16958. Washington, D.C., USA.
National Institutes of Health. 2011. NIH guidelines for research involving recombinant DNA molecules. Washington, D.C., USA. http://oba.od.nih.gov/oba/rac/Guidelines/NIH_Guidelines.pdf
Nuffield Council on Bioethics. 2003. The use of GM crops in developing countries: a follow-up discussion paper. http://www.nuffieldbioethics.org/fileLibrary/pdf/GM_Crops_Discussion_Paper_2004.pdf.
OECD. 1986. Recombinant DNA Safety Considerations. Organisation for Economic Co-operation and Development, Paris, France. http://www.biosafety.be/cu/BSL_Ressources/PDF/M00032689.pdf.
Office of Science and Technology Policy. 1986. Coordinated Framework for Regulation of Biotechnology. Office of Science and Technology Policy, Washington, D.C., USA. http://usbiotechreg.nbii.gov/CoordinatedFrameworkForRegulationOfBiotechnology1986.pdf
Orent, W. 2004. Plague, The Mysterious Past and Terrifying Future of the World’s Most Dangerous Disease. Simon & Schuster, Inc., New York, NY, USA. ISBN 0-7432-3685-8.
Presidential Commission for the Study of Bioethical Issues. 2010. New Directions – The Ethics of Synthetic Biology and Emerging Technologies. Washington, D.C., USA. http://www.bioethics.gov/documents/synthetic-biology/PCSBI-Synthetic-Biology-Report-12.16.10.pdf
Preston, R. 2002. The Demon in the Freezer. Random House, New York, NY, USA. ISBN: 978-0-553-75655-5.
Sommerville, M. 2007. Creating the ethics of synthetic biology. Ottawa Citizen, June 14, 2007. http://www2.canada.com/ottawacitizen/news/opinion/story.html?id=936d1e43-3dc3-48a2-bee5-b3164f6f4517.
Woods, J.B. (ed.). 2005. USAMRIID’s Medical Management of Biological Casualties Handbook, 6th edition, US Army Medical Institute of Infectious Diseases, Fort Detrick, MD, USA. http://www.usamriid.army.mil/education/bluebookpdf/USAMRIID%20BlueBook%206th%20Edition%20-%20Sep%202006.pdf
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