Menu
Healthcare, agriculture, and industrial biotechnology. Industrial biotech is growing rapidly due to advances in science and technology, concerns over climate.
Edited by Wim Soetaert and Erick J. Vandamme Industrial Biotechnology
Related Titles Buchholz, Klaus / Collins, John
Hou, C. T., Shaw, J.-F.
Concepts in Biotechnology
Biocatalysis and Bioenergy
History, Science and Business 2010 ISBN: 978-3-527-31766-0
2008 ISBN: 978-0-470-13404-7
Aehle, W. (ed.) Katoh, Shigeo / Yoshida, Fumitake
Enzymes in Industry
Biochemical Engineering
Production and Applications
A Textbook for Engineers, Chemists and Biologists 2009 ISBN: 978-3-527-32536-8
Soetaert, W., Vandamme, E. (eds.)
Biofuels 2009 ISBN: 978-0-470-02674-8
Fessner, W.-D., Anthonsen, T. (eds.)
Modern Biocatalysis Stereoselective and Environmentally Friendly Reactions 2009 ISBN: 978-3-527-32071-4
2007 ISBN: 978-3-527-31689-2
Sheldon, R. A., Arends, I., Hanefeld, U.
Green Chemistry and Catalysis 2007 ISBN: 978-3-527-30715-9
Edited by Wim Soetaert and Erick J. Vandamme
Industrial Biotechnology Sustainable Growth and Economic Success
The Editors Prof. Wim Soetaert Ghent University Department of Biochemical and Microbial Technology Centre of Expertise – Industrial Biotechnology and Biocatalysis Faculty of Bioscience Engineering Coupure links 653 9000 Gent Belgium Prof. Erick J. Vandamme Ghent University Department of Biochemical and Microbial Technology Centre of Expertise – Industrial Biotechnology and Biocatalysis Faculty of Bioscience Engineering Coupure links 653 9000 Gent Belgium
All books published by Wiley-VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate. Library of Congress Card No.: applied for British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library. Bibliographic information published by the Deutsche Nationalbibliothek The Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at 17
33
16
Would buy GM foods if approved by relevant authorities
No, definitely not
40
22
8
22
8
25
30
26
60
7
80
8
7
100
Percentage
Figure 14.4 Percentage of European citizens willing to buy GM food products with particular characteristics. Gaskell et al. [3], Eurobarometer Studies available at: http://www.ec.europa.eu/ research/press/2006/pdf/pr1906_eb_64_3_final_report-may2006_en.pdf.
It can be strongly argued that a reaction towards negative public perceptions does not provide a satisfactory answer. First, a number of social scientists had already pointed out repeatedly that public perception studies are studies of the respondents’ attitudes and that they cannot be extrapolated to behavior [8–12]. More recently this has been supported by a number of studies on actual buying behavior of consumers presented with GM food products [13, 14]. Second, the results of the latest Eurobarometer survey in 2005, but also other (national) studies still showed considerable support for GM food products (Figure 14.4) [3, 15, 16]. In 2005 43% of the EU population supported GM food products. If GM food products were healthier, then even 56% would definitely or probably buy these products. Interestingly, the result for cheaper foods showed that a mere 56% would not or probably not buy GM foods if they were cheaper. This latter result further supports the point that opinion surveys cannot be taken at face value for behaviors. Gaskell et al. [3] suggested that some respondents reacted as citizens rather than consumers, as economics indicate that price is a key determinant in people’s choices. A further interesting point is that price is the only fact consumers can actually ascertain themselves directly. For all the other categories they need to trust some organization (authority, industry, medical research) for the information provided with the food. Whatever the reason, this highlights the doubts about opinion surveys as indicators of actual behavior. Third, and perhaps most convincingly, the sales of products labeled as GM remained constant (orally confirmed by large supermarket chain). Although there
14.3 Public Perceptions of Industrial Biotechnology
was no reduction in sales, food companies continue to replace the GM ingredients of the products with non-GM. For example, in the Netherlands there were more than 120 products with GM ingredients with (voluntary) labels in 1999. By 2007 this number had been reduced to 19 [53]. These considerations strongly suggest that food companies and supermarkets replaced their GM products because they were afraid of emotional actions by environmentalists groups rather than being influenced by fewer people buying GM food or trying to protect people from hypothetical risks. The food companies responded to representation from a minority of consumers and the attendant media publicity, and this resulted in an effective halt to the development of cheaper, more sustainable or healthier food products. What can be done to facilitate a sustainable and accepted introduction of applications from industrial biotechnology? From the perception studies and the reactions of scientists, industries, and governments we also learned some lessons about communication. 14.3.4 Development of Public Interaction
Looking back over the years starting from the first Eurobarometer survey in 1991 on biotechnology we can assess how the results influenced politicians, scientists, and industries. One of the outcomes of these first Eurobarometer studies showed that the public throughout Europe had very little knowledge about biotechnology and indicated that knowledge was linked to support. As a result politicians and biotechnology scientists, aiming to increase the support for biotechnology applications in the early 1990s, started information and education campaigns to educate the public. This one-way communication was based on the belief that if more information were made available then the public would understand the potential benefits and increase their support for biotechnology. This is a good example of the so-called “deficit model” of science communication. However it soon emerged that the brochures, leaflets, lectures, education programmes, etc. did not necessarily increase support [17–20]. It became clear that more information tended to lead to further polarization of opinion, whether positively or negatively. For the 1996 Eurobarometer study on biotechnology a group of science communication experts were invited to help in getting a clearer understanding of public perception. The social scientists chose “perceived use,” “risk,” and “moral acceptability” as determinants of public support. People were asked whether they thought each of six biotechnology applications were useful, risky, morally acceptable and if they should be encouraged. The results led to the conclusion that usefulness is a precondition of support and in no case is a “not useful” application given support. For example, GM food products that are similar to “normal” food products but have a lower production cost are not likely to be accepted. People will accept some risk if the application is useful and morally acceptable. For instance, GM foods containing an important vaccine or new medicines produced by yeast are likely to be accepted. Moral concerns, however, acted as a veto regardless of
467
468
14 Societal Issues in Industrial Biotechnology
Public scientists TV journalists Industry scientists News journalists Medical doctors Environmental orgs Consumer orgs Intellectuals Industry Government Politicians
2 2
Military Religious leaders
0
6 6 5
10
16
28 25 23 21
20
52
32
40
60
Figure 14.5 Responses of European citizens to “Who is best qualified to explain science and technology impacts on society?” from Gaskell et al. [3], Eurobarometer Studies available at: http://www.ec.europa.eu/research/press/2006/pdf/pr1906_eb_64_3_final_report-may2006_en.pdf.
views on risk and use. This is shown by the reluctance displayed about the production of medicines by transgenic animals. A main lesson from the study was the conclusion that “if risk is less significant than moral acceptability, then public concerns are unlikely to be alleviated by technically based reassurances and other policy initiatives dealing solely with risks” [19]. The emphasis on communication certainly shifted to show the benefits of new technology and increased the research on risk assessment, risk communication, and risk perception [21–24]. Adams showed that when risks cannot be controlled by individuals and are vague, for example as a result of scientific uncertainty, confidence decreases and an increased demand for regulation is provoked. So who are the most trusted organizations for providing information on the impact of science and technology? As Figure 14.5 shows, the European public finds public scientists the most qualified to explain science and technology impacts on society and scientists working in industry only slightly less so. By now it had also become widely recognized that acceptance could not be achieved by simply providing information alone. Scientists had not only a role to play but also had to listen to, understand and respond to actual public concerns. The reaction of social scientists, politicians, and industry was to redevelop models of communication, as characterized by the development of a dialog model called the Mode-2 model and the upstream engagement model for communication [25–28]. Discursive models of communication have been advocated by pioneers such as Churchman [29] and Rittel, and in the last few years those approaches have been revived [30, 31].
14.4 Societal Issues in Industrial Biotechnology
Government committees advising on policy measures for technology development started to suggest the involvement of scientists [32–35]. The pressure on scientists to be involved in public communication was further increased by requirements for dissemination and public communication in (inter)nationally funded research projects. Increasingly, project criteria include the dissemination of results to broader audiences, followed by active involvement of stakeholders and demands for public dialogs. These forms of “proactive” communication are now seen as crucial for the implementation of novel technologies.
14.4 Societal Issues in Industrial Biotechnology
The lessons from the biotechnology debate are clear; scientists need to be involved in public communication and such communication needs to address societal issues, involve the stakeholders, etc. Several specially funded projects have been carried out over the years to explore the role of scientists, media, and industry and discuss “best practice” [20, 36]. Training courses have been developed9) [37] and curricula for future scientists revisited. But what are the criteria for these novel forms of communication? 14.4.1 Criteria for Communication
Many academics and industrialists have concluded that biotechnology scientists need to increase their involvement in public communication to achieve greater public support. However, there are other, more urgent reasons to pay attention to communication. Independent of this wish for increased acceptance, these reasons are derived directly from the principles of a democratic society. Public involvement in decision-making processes requires public information and the social contract between society and scientific institutes demands accountability. Based on these arguments posed by present developments in society and biotechnology with its important potential impact, a set of evaluation criteria for public communication may be derived [20]. Political agendas and decisions are subject to voters’ opinions. It is necessary therefore that scientists are accountable to the public about their science and their reasons for doing it so that informed decisions can be made. Scientists also have a moral imperative to communicate with the public as only they have understanding at an early stage of the possible impacts of their science for society, which they need to provide for the joint decision-making process. The complexity of novel 9) A number of courses aimed at scientists and industrialists were developed, such as those by the European Task Force on Public Perception (EU Advanced Course on Bioethics and Public Perceptions; later
adapted to the Kluyver Centre Advanced Course on Strategic Communication in Biotechnology); Netherlands Centre for Society and Genomics; European Molecular Biology Organisation; Wellcome Trust.
469
470
14 Societal Issues in Industrial Biotechnology
technologies often leads people to reject new technologies but as people in a democratic system need to be able to weigh up the pros and cons themselves there is also a social obligation on scientists to provide this understanding. Furthermore, if scientists are contracted by society to develop the solutions for tomorrow’s challenges, then society needs to be able to trust them. Trust acts as a summing device when full understanding is not possible. This is the general situation for modern technologies, and especially for the complexities of biotechnology. Trust is based on confidence and knowledge which is claimed to be maintained by inclusivity, transparency, and information. This relates to both factual information and emotional feelings. A component of the contract and trust is accountability [38]. Scientists are contracted and paid for their work by society via taxation and government. They are accountable to society for the uses and outcomes of that payment. The social need for scientists to be accountable, and thereby maintain trust, is an imperative which follows from the contract between society and science. There are also economic reasons for scientists to communicate with the public. The first relates to the fact that the generation of wealth for the functioning of modern societies wholly depends on science and technology. Biotechnology has been promoted as a major generator of wealth. In order to allow society to make informed decisions about the contribution which biotechnology may make to wealth generation, scientists need to explain its economic impact, that is, its benefits, and its costs, to society. This also includes explanation of the costs and benefits to society if a technology that is scientifically feasible is not pursued. The second economic reason is that scientists have to explain why society must return some of the wealth generated by science to science if science and wealth generation is to continue. As society pays for the publicly funded universities and research institutes, it is in the interest of all academics to communicate about their work. Society decides on the amount and distribution of public funding based on this information. However, with competing calls on limited public funds it is in the biotechnologists’ own interest, as with the members of all academic disciplines, to communicate effectively. The foregoing discussion is based on an idealized view of democracy with full public involvement in the decision-making process. However, the reality in democratic societies is that most people are simply not interested in participating in decision making, which is left to the elected representatives and their staff. They in turn tend to be influenced by communicated opinions and perceived public perceptions while subjected to often intense lobbying by special interest groups, although they are finally answerable to the electorate. Therefore the fact remains that the “silent majority” of the public at large is informed. In order to reach this “silent majority,” public communication activities need to stimulate the interest of the public. Because different groups of people have different competing interests and concerns it is also necessary to know and understand their differing interests and concerns. These are not only related to the scientific and technological information, but also importantly to (bio)ethical, safety, social, and legal issues. Scientists need to be able to understand and respond to these issues. Following from the democratic contract of science with society, these social, moral, and economic reasons dictate that scientists inform and participate in the
14.4 Societal Issues in Industrial Biotechnology Criteria for communication by scientists derived from the social, moral, and economic reasons for communication as partners in a contract between science and society [20].
Table 14.1
Criteria for public communication by scientists to inform the decision-making process: Explain science Explain impact Build trust Listen and respond to ethical, legal and social concerns Interest as many as possible Adapt to changes in society
democratic decision-making process, which includes interaction with the public. As in any contract, good performance is in the interest of the performer. It is argued that communication is an implicit task for scientists, therefore it is in their own interest to do this effectively and it is in the interests of academic institutions to facilitate and organize this process. From the above-mentioned arguments it can be concluded that public communication relates to:
•
the availability of knowledge (information on scientific data; information on potential impact of the implementation of derived technologies in society and information on how judgments are made or can be influenced);
• •
the availability of skills for interaction; and the availability of attitude (to encourage public interest and respond to public interests and concerns).
These requirements lead to the criteria for communication by scientists summarized in Table 14.1. 14.4.2 Novel Approaches to Communication
The application of these criteria for science communication asks for novel forms of communication. Importantly the interaction should be mutual (or two-way) which requires preparedness to listen and understanding of each other’s arguments by both sender and receiver. This is not easy to materialize, especially when we wish to create a solution-oriented dialog. Research on novel forms of communication is therefore looking for models with specific attention for discourse (for example focusing on respecting the symmetry of ignorance which is suggested to lead to systematic stepwise learning dynamics [39, 40] and on methods to increase participation of stakeholders [41–43] and of reaching the “uninterested” public majority through entertainment and emotion [44, 45]). There is no doubt that the transition towards a bio-based society is a very complex design problem, which requires more knowledge than any one single
471
472
14 Societal Issues in Industrial Biotechnology
person can possess and creativity to reach reconciliation of views. As we also strive for changes in consumer behavior, it is important that we combine programmes for sustainable technology and product development with programmes focusing on changes in attitudes and behavior [46] and hence in communication. The following case study of the Kluyver Center for Genomics of Industrial Fermentation will give an example of such an approach. 14.4.3 Three International Workshops Identifying Future Issues in Industrial Biotechnology: A Case Study
One of the most important and perhaps difficult challenges for politicians nowadays is the understanding of ethical, legal, and social concerns in society. In order to fully appreciate the relevant societal issues for applications of industrial biotechnology we need to understand the value systems in our (changing) society, identify present and future stakeholders, and unravel the public and political issues into regulatory, ethical, economic, and safety issues. We also need to understand the roles and responsibilities of all stakeholders so that we can define which organizations can be held responsible for addressing these issues. The Dutch public–private partnership “Kluyver Center for Genomics of Industrial Fermentation”10) has carried out a series of three international workshops to identify, understand, and analyze the possible future societal issues in industrial biotechnology. The workshops form part of the Center’s program on genomics and society and were aimed to inform the development of novel communication activities (for a full account, see ref. [47]). The workshops brought together 25 experts from different disciplines and affiliations (such ethics, microbiology, food sciences, risk perception, cultural management from academia, industry, government, European Commission, etc.) and also aimed to develop a coordinated strategy for public dialog. The first meeting explored the scientific trends in industrial biotechnology and their linked societal issues. The second aimed to identify the organizations involved and responsible for addressing these public concerns. The third and last meeting set out to suggest novel ways of communication and recommend a joint agenda for this approach. In their first meeting in 2004, the expert group related scientific trends such as healthy and personalized foods, novel bio-based materials and biofuels with political incentives for industrial biotechnology, concerns about overregulation and the public’s low awareness but known acceptance of the contained use of microorganisms. On this basis they identified the following “future” issues:
• •
Safety, including questions such as those related to contamination of food products by plants producing pharmaceuticals in coexistence with food crops Land-use with the possible food–energy conflicts, the rise of food prices and the loss of rainforests
10) A government-funded Center of Excellence, see http://www.kluyvercentre.nl for more information.
14.4 Societal Issues in Industrial Biotechnology
• • •
Energetics and eco-efficiency questioning the evidence presented on this complex matter leading to concerns of trust Environmental pressure, including concerns on biodiversity; soil depletion, water constraints, and mono-cultures Economic feasibility with respect to the dependence on oil and linked sugar prices and resulting uncertainty for industrial investment.
The second meeting in 2005 identified the main barriers as preparedness for action; economic interests of stakeholders; coordination of agendas, and clarity on regulations and incentives. The participants recommended clarifying the notion of sustainability and searching for new ways of interaction to interest the public. Additionally they recommended building trust by showing responsibility (and preparedness for action) and the involvement and training of young scientists in dealing with this. Although many of the above-mentioned issues were viewed worthy of further exploration, the group decided to focus on biofuels and sustainability in their final meeting in 2006. They took sustainability as the “core value” and proposed a joint agenda for key stakeholders, with the aim of reducing the use of energy and fossil sources while increasing the use of sustainable sources such as biomass. (Figure 14.6). This consensus approach would bring a single message to the public, underlined by a joint agreement, but at the same time would allow organizations to keep true to their interests, shareholders, or constituencies. With sustainability as a core value, industries and academia could focus on the increase of innovation by using industrial biotechnology. NGOs could stress the importance of reduction of energy use and pollution. And governments could develop measures to stimulate both the increase of innovation and the decrease of energy use and pollution.
Recommendations Sustainability as “core value” and joint agenda: – reduction of use of energy and fossil sources – Increase use sustainable sources NGOs:
reduction of energy use
Academia: Government: Industry:
sustainable applications reduction use,
stimulation sustainability
increase sustainability
Figure 14.6 Recommendations of the international expert group of the Kluyver Center workshop on future issues in industrial biotechnology, Brussels, June 2006.
473
474
14 Societal Issues in Industrial Biotechnology
It was recognized that the adoption of this joint agenda would need further discussion with the stakeholders. Therefore it was proposed that “neutrally based” organizations such as local governing bodies and the European Commission would hold stakeholder meetings. These meetings should aim to openly discuss economic interests, values, and trust relations in order to increase understanding of differing viewpoints and decrease the development of wrong perceptions. The experts further recommended that politicians should focus on the removal of bottlenecks with a view to create uniform regulation. They should also focus on the development of clear incentive procedures. Last but not least, it was recommended that research on the development of novel forms of public communication should be increased with special attention on increasing the level of citizen involvement and responsibility. It is interesting to see that these predictions of the possible future issues of this expert group in June 2006 are the ones presently discussed in the media (Autumn 2007). But what do they entail? 14.4.4 Further Analysis of the Identified Societal Issues Related to Industrial Biotechnology
The first issue, safety, is a well-known phenomenon of our present-day risk-averse society. Although it presents itself as a rational and reasonable concern it is actually something much more than that. To begin with, many scientists claim that there is no known rational scientific basis for concern. They argue that fermentation is something that has been used for centuries and the application of GM techniques provides a more precise method than any previous technique used to improve the microorganisms. So far the many studies on risk assessment have not shown any significant risk from modern industrial engineering biotechnology where the regulated precautionary actions are followed. Neither have we witnessed any great accident since the introduction of industrial GM microorganisms some 30 years ago. Furthermore, there is firm and stringent legislation. The safety of GMOs used in industrial biotechnology depends on the characteristics of the organism and its interaction with the environment into which it is (accidentally) released. Safety legislation generally requires risk analysis that can identify and evaluate potential adverse effects of the GMO(s). Host organisms are chosen for their ability to produce the desired product but also for their inability to grow outside the production unit. If GM (micro) organisms are released for applications in the environment, further safety measures are required to minimize human health and environmental adverse effects. The use of the precautionary principle has enforced a very stringent approach to safety in Europe. A definition of precaution is provided in the UNESCO document The Precautionary Principle, published by the World Commission on the Ethics of Scientific Knowledge and Technology (COMEST) in 2005. The Precautionary Principle United Nations Educational Scientific and Cultural Organization. Printed in France SHS-2005/WS/21 cld/d 20/5/:
14.4 Societal Issues in Industrial Biotechnology
When human activities may lead to morally unacceptable harm that is scientifically plausible but uncertain, actions shall be taken to avoid or diminish that harm. Morally unacceptable harm refers to harm to humans or the environment that is
• • • •
threatening to human life or health, or serious and effectively irreversible, or inequitable to present or future generations, or imposed without adequate consideration of the human rights of those affected.
The judgment of plausibility should be grounded in scientific analysis. Analysis should be ongoing so that chosen actions are subject to review. Uncertainty may apply to, but need not be limited to, causality or the bounds of the possible harm. Actions are interventions that are undertaken before harm occurs that seek to avoid or diminish the harm. Actions should be chosen that are proportional to the seriousness of the potential harm, with consideration of their positive and negative consequences, and with an assessment of the moral implications of both action and inaction. The choice of action should be the result of a participatory process. Companies, and increasingly governments, are now requesting deregulation for certain applications including industrial biotechnology, as the present situation is viewed as disadvantaging economic growth. Many supporters of biotechnology point out that the required risk assessments do not include a comparative risk assessment to existing processes, products, or practices. Additionally there is debate among regulators about the abolition of regulation on processes using GM techniques where the product does not contain any GM. Others claim that including an assessment of the potential benefits of the proposed innovation would create an incentive for beneficial innovation. The request for deregulation stands on a sensitive level with the identified necessity for maintaining trust. Risk perception studies, such as those by Adams ([22], see also [48]) have shown that concerns increase and become less rationally based when people are unfamiliar with the actual risk of a technology or material and when they have no control themselves over its use. It is argued, therefore, that the public concerns related to safety are more likely to spring from an issue of control. It is clear that any scientific uncertainty expressed in the public domain will increase the level of public unease and, indeed, the demand for regulation. But regulation needs to be controlled by someone and that is also why maintaining and building trust has been mentioned as a crucial factor in technology innovation. O’Neill has pointed out, however, that although an increase in regulation and control mechanisms will undoubtedly raise the trustworthiness of the system, it
475
476
14 Societal Issues in Industrial Biotechnology
will not necessarily increase trust in the people who are implementing the novel technology [49]. We urgently need to further understand this relationship and find new ways to deal with scientific uncertainty and with emotive public reactions. We also need to find ways which will build or maintain public trust not only in the scientists who develop the technology (and who already are trusted by the public, see Figure 14.5), but also in those who are responsible for regulating and controlling its uses in society. The second issue, land-use, is probably the one that presently creates the most hype. Recent media reports include emotive terms such as “disgrace,” “crime against humanity,” and “food robbers” in the attack of the production of biomass for non-food materials (usually biofuels). Interestingly, the articles that are positive towards biofuel development are less emotive, perhaps with the exception of Al Gore and his supporters in their claims about the use of these technologies against global warming. In essence this “land issue” is an economic one: land owners have to decide on the basis of returns on investment what they will grow. Their choices may influence food prices, for example if they decide to grow non-food energy crops. However, it will be hard to disentangle the effect of land-use from the overall effect of an increasing demand in biomass. A more emotively expressed area in this issue of land-use is the loss of rainforests and the choices made by poor farmers in developing countries to grow bioenergy crops rather than food crops. As some point out, this may result in more local food crises in already struggling countries but also in a higher income which may enable them to import foods. It is unclear how the economy will develop and what will work best for whom. It is interesting, though, to see how this issue on the use of land is linked to an ethical concern of much broader underlying value. While the increase of safety is often sought by people aiming for a higher level of individual autonomy and choice, the issue of land-use is actually used to support an ideology for all. The ideology includes moral values, linked to a view on the natural world but also to values of democracy, equity for people from developed and less-developed countries, and freedom of handling in less-developed countries. Although their intentions may be very well meant, it is those from Western societies without any land themselves who are usually most concerned with these moral issues of land-use. And their well-meant moral values may differ from those of people living in developing countries, leading to accusations of “neo-colonialism.” Some countries have tried to develop regulations to control the sustainable use of our global land (Cramer Report, 2007)11). However it is necessary to realize that people from Western societies are generally in the highest level of “Maslow’s pyramid”, their basic needs for water, food, housing, healthcare, schooling, and employment are fulfilled. This is not the case in developing countries were sometimes even basic requirements such as food and housing are not yet met. People in these circumstances are not able to concern themselves with issues 11) Project group “Sustainable Production of Biomass” (2007). Testing framework for sustainable biomass. Senternorem, The Hague, Netherlands.
14.4 Societal Issues in Industrial Biotechnology
related to “luxury” problems for next generations, such as loss of rainforest or global warming [50]. It is likely, therefore, that consensus will be difficult to achieve as those most willing to enforce it are generally in a position to be able to afford this, while those in developing countries have more urgent needs to fulfill which may prove counterproductive. The third issue is energetics or eco-efficiency. Presently many impact studies are performed to calculate the ecological footprint in terms of energy and materials produced versus energy and materials used in a global setting. These models aim to predict the best crops for a certain desired product produced in the best (most sustainable) way. Because much of the data needed for the calculation are uncertain and the number of variables included in the calculation differ, the models produce very different outcomes. These results are seriously questioned by scientists, industrialists, and NGOs in (industrial and agricultural) biotechnology who relate to these models as predictors for research investments. This issue therefore relates to the uncertainty of evidence and scientific inquiry. Since the results of these models are often used in public interaction as “proof” of a certain viewpoint, the issue of scientific uncertainty and factual evidence is actually magnified. This undermines public trust in scientists for their ability to produce “rational facts.” The heated debate about the validity of the data may also be perceived by the public in a different way, that is, that parties in debate select and use the “facts” which most suit them because they have an (economic) interest which they wish to advance. Such a perception may further decrease the trust relationships and increase public unease with the technology. The effect of scientific uncertainty of evidence, scientific inquiry, trust, and stakeholder perceptions of interests on public unease and technology development needs further study. The fourth issue, environmental pressure, for example for water and soil depletion, looks like another scientific issue. It could be solved as soon as we know how to work the land in such a way that we do not deplete our soil and use too much water and prevent the loss of biodiversity. For the moment this is again a concern of scientific uncertainty on the best way to handle this issue in the short term while solutions are developed for long-term and higher demands. The abolition of tillage and introduction of drought-resistant crops are used as possible solutions, but some fear that there will never be enough water to produce the total amount of crops needed for a biomass economy. This issue further relates to biodiversity, which is a concern for many years related to GM crops and industrial agriculture. Large agricultural practises using monocultures and herbicides and pesticides are often seen as a threat to the diversity of our global plant (and linked animal) kingdom. Diversity is needed as a source of traits (DNA) for future applications in crops or for pharmaceutical products. Areas rich in diversity of species include rainforests, but also areas in extreme environmental conditions are viewed as important providers of genetic material. Presently seed-banks have been created to maintain the traits of rare or nearly extinct sources. However, it is clear that the
477
478
14 Societal Issues in Industrial Biotechnology
in situ maintenance would be preferable as it would also allow for further evolution and creation of new characteristics. Reduction of herbicides and pesticides by using GM crops and a transition to no-tillage practises may also help to maintain biodiversity. The issue of biodiversity and environmental pressure, however, is not only scientific but is also often related to a deeper underlying view of nature. The arguments used in the heated debates on the supposed loss of monarch butterflies in GM cornfields [51] indicate that those concerned for biodiversity are often refusing scientific solutions, but propose to go back to the “original, natural way” of producing crops (such as in organic farming practices). These views often become emotive in heated debate and lose their science-based rationality [52]. The fifth and final issue presented here is economic feasibility. This clearly is an economic issue for the industry involved and not so much a public issue. It refers to the difficulty of industries to convert to sustainable industrial biotechnology production processes. In order to achieve this, industries need to invest in innovation, manpower, and equipment but they have to decide on these matters in an environment of uncertainty. Oil and feedstock prices fluctuate wildly, innovations are still in development (such as second-generation biofuels), while governmental incentives are not clarified and regulations are still being discussed. Although industries are resourceful in creating ways of balancing these uncertainties against their shareholder values, it is clear that clarification of regulation and decisions on incentives will help to speed up the introduction of sustainable processes. 14.4.5 Other Relevant Studies and Committee Reports
Since the 1980s a whole industry of governmental, intercontinental, multidisciplinary, and multi-stakeholder committees has evolved. It reflects a change in democratic decision-making as many involve more parties in the discussion such as representatives of consumer and patient organizations, NGOs, lay people, etc. Several of these committees have produced very interesting reports, such as the UNESCO report on the precautionary principle (2005) and the Netherlands COGEM12) report “Towards an integrated framework for the assessment of social and ethical issues in modern biotechnology” (2003). Both provide clear definitions and/or procedures for evaluation of the state of the art of governing implementation of biotechnology in society. Other studies have delivered high-profile recommendations (such as the EU-US Consultative Forum13), 2000). The recent Cramer Report12) provides guidelines for sustainable development of biofuels, aiming to avoid the use of rainforests and the use of other less sustainable methods. As the players in the discursive process are extending, it is important to have such sources of information available. These studies and reports will also help us 12) Commissie Genetische Modificatie (COGEM) (2003) Towards an integrated framework for the assessement of social and ethical issues in modern biotechnology. 13) Anonymous. The EU-US Biotechnology Consultative Forum: Find Report, December 2000.
14.5 Smooth Introduction of Acceptable Sustainable Industrial Biotechnology
to understand the social practices around the globe and provide useful suggestions for the implementation of global sustainability. It is also important, however, to acknowledge that different stakeholders use different reports, presenting different views or even “facts.” The choices between sources of information (and trust given to these sources) may play a crucial role in the discussion and needs further investigation.
14.5 Conclusions and Discussion: A Joint Agenda for the Smooth Introduction of Acceptable Sustainable Industrial Biotechnology
We have presented an account of what experts believe the impact will be of industrial biotechnology to our society. We have also showed what (European) citizens think they may support, relying primarily on the Eurobarometer surveys, and have indicated the possible social concerns that may arise from these developments. We have drawn some lessons from the GM food debate which we belief give reason for caution for an overoptimistic view to the acceptability of industrial biotechnology. These lessons taught us that more knowledge does not necessarily result in more support for a developing technology. They also gave us more insight in the risk issue and showed that risk can be overridden by moral values. Through the evidence that European citizens do not disapprove of GM foods we argued that a rational approach (in this case to provide informed choice) can sometimes be overtaken by emotional fear. Finally the perception studies showed that scientists are one of the most trusted professionals by the public. On this basis, but also on the argument that our democratic society has a contract with scientists for which they are accountable we argued that scientists have an important role to play in public interaction on the implementation of novel technologies derived from science. The main argument for caution in the introduction of a bio-based society is that the present debate is not based on rationality of reason and that such emotive context may easily result in equally irrational reactions from politics and industries. However, we have also pointed to the lessons learned from improved involvement of all stakeholders in and responsibility for novel forms of public interaction. This requires preparedness for action, and a preparedness to listen to the arguments and take action on concerns. It also necessitates a reconciliation of interests of all parties, which can be done if all parties adopt sustainability as a core value. This is a challenge for the public because sustainability is not something with a direct impact on the individual. And for many it relates directly to a certain view of the world. In contrast, many novel developments in healthcare are often embraced as direct improvements of people’s quality of life. It is doubtful whether new applications for the environment (and hence for future generations) will be received equally positive by all.
479
480
14 Societal Issues in Industrial Biotechnology
14.5.1 Hurdles and Challenges
Politicians are being challenged to come up with the right incentives and regulation, but they are dependent on trustworthy scientific evidence that supports their action. Unfortunately it is just this scientific evidence that is presently so much at stake in the debate. And the debate increasingly ranges from rational to emotive. Taking a position leads to polarization and political inertion. In order to reconcile different views it is important to find common aims. The experts who came together to discuss future issues in industrial biotechnology concluded that “sustainability” could be taken as a core value. They recommended the development of a joint agenda for all stakeholders involved, taking this notion of sustainability as a core value. However, we conclude that in addition to this core value, we need to make sure that plans also address the basic needs of food, health, housing, and employment. In exploring the issues we have seen that personal views may lead to different positions, which are often not brought into the discussion, and may give rise to emotional claims. This necessitates a willingness to come together and discuss a way to reconcile positions and views. It is good to see that this view is shared by several multi-stakeholder organizations such as the European Platform on Sustainable Chemistry together with the European trade organization EuropaBio, the Directorate Science of the European Commission, the Working Party on Biotechnology of the OECD and the World Wide Fund. They have a challenging time ahead. 14.5.2 Recommendations for Further Studies
As argued in the above text an understanding of public concerns is crucial and encompasses a much broader understanding involving values, economic interests, dealing with uncertainty, trust, and responsibility. We showed that although safety issues can represent a demand for individual autonomy, the land-use issue may represent a deeper underlying ideology for global governance. These values are undoubtedly related to different views on the relation between humans and nature, which can be controversial. The question is whether these controversial views on governance and autonomy are held by the same people and whether discussing these underlying values could help in the search for acceptable solutions for sustainable development. With this understanding we need to develop novel forms of interaction with society. 14.5.3 What Does It Mean for Citizens?
A bio-based society will change the landscape, political powers, and our national incomes – all factors with which citizens will need to come to terms. But as argued
References
above, a joint agenda for increased sustainability also depends on a decrease of energy and material use. This requires a responsibility and change of lifestyle for all and a re-evaluation of everything we do (holidays, sports), use (traveling, packaging, etc.), and eat. In that sense it requires that sustainability will become a moral value.
Acknowledgement
This work was (co)financed by the Kluyver Centre for Genomics of Industrial Fermentation and Centre for Society and Genomics which are part of the Netherlands Genomics Initiative/Netherlands Organisation for Scientific Research.
References 1 Gaskell, G. and Bauer, M.W. (2001) Biotechnology 1996–1999: The Years of Controversy, Science Museum, London. 2 Caesar, W.K., Riese, J., and Seitz, T. (2007) Betting on biofuels. The McKinsey Quarterly, 2, 53–63. 3 Gaskell, G., Allansdottir, A., Allum, N., Corchero, C., Fischler, C., Hampel, J., Jackson, J., Kronberger, N., Mejlgaard, N., Revuelta, G., Schreiner, C., Stares, S., Torgersen, H. and Wagner, W. (2006) Eurobarometer 64.3: Europeans and Biotechnology in 2005: Patterns and Trends, A report to the European Commission’s Directorate-General for Research. 4 European Federation of Biotechnology Task Group on Public Perceptions of Biotechnology and the Kluyver Center for Genomics of Industrial Fermentation (2006) Briefing Paper, Regulating Modern Biotechnology in Europe. 5 Konig, A., Cockburn, A., Crevel, R.W.R., Debruyne, E., Grafstroem, R., Hammerling, U., Kimber, I., Knudsen, I., Kuiper, H.A., Peijnenburg, A., Penninks, A.H., Poulsen, M., Schauzu, M., and Wal, J.M. (2004) Assessment of the safety of foods derived from genetically modified (Gm) crops. Food Chem. Toxicol., 42 (7), 1047–1088. 6 Kuiper, H.A., Konig, A., Kleter, G.A., Hammes, W.P., and Knudsen, I. (2004) Food and chemical toxicology – concluding remarks. Food Chem. Toxicol., 42 (7), 1195–1202.
7 van den Eede, G., Aarts, H.J., Buhk, H.J., Corthier, G., Flint, H.J., Hammes, W., Jacobsen, B., Midtvedt, T., van der Vossen, J., von Wright, A., Wackernagel, W., and Wilcks, A. (2004) The relevance of gene transfer to the safety of food and feed derived from genetically modified (GM) plants. Food Chem. Toxicol., 42 (7), 1127–1156. 8 Ajzen, I. (1991) The theory of planned behavior. Organ. Behav. Hum. Decis. Process, 50, 179–211. 9 Spence, A. and Townsend, E. (2006) Examining consumer behaviour toward genetically modified (GM) food in Britain. Risk Anal., 26 (3), 657–670. 10 Chen, M.F. (2007) Consumer attitudes and purchase intentions in relation to organic foods in Taiwan: moderating effects of food-related personality traits. Food Qual. Pref., 18, 1008–1021. 11 Kalaitzandonakes, N., Marks, L.A., and Vickner, S.S. (2004) Media coverage of biotech foods and influence on consumer choice. Am. J. Agric. Econ., 86 (5), 1238–1246. 12 Paschoud, M. and Sakellaris, G. (2007) Public Attidudes Towards the Industrial Uses of Plants : The Epobio-Survey, CPL Press, Newbury, UK. 13 Powell, D.A., Blaine, K., Morris, S., and Wilson, J. (2003) Agronomic and consumer considerations for Bt and conventional sweet-corn. Br. Food J., 105 (10), 700–713.
481
482
14 Societal Issues in Industrial Biotechnology 14 Cook, A.J., Kerr, G.N., and Moore, K. (2002) Attitudes and intentions towards purchasing GM Food. J. Econ. Psychol., 23 (5), 557–572. 15 Gutteling, J., Hanssen, L., Veer, N., and van der Seydel, E. (2006) Trust in governance and the acceptance of genetically modified food in the Netherlands. Public Underst. Sci., 15, 103–112. 16 Noussair, C., Robin, S., and Ruffieux, B. (2004) Do consumers really refuse to buy genetically modified food? Econ. J., 114, 102–120. 17 Durant, J. (1992) Biotechnology in Public, Science Museum, London. 18 Durant, J., Bauer, M.W., and Gaskell, G. (1998) Biotechnology in the Public Sphere: A European Source Book, Science Museum Publications, London. 19 Gaskell, G., Allum, N., Bauer, M., Durant, J., Allansdottir, A., Bonfadelli, H., Boy, D., de Cheveigné, S., Fjaestad, B., Gutteling, J.M., Hampel, J., Jelsøe, E., Correia Jesuino, J., Kohring, M., Kronberger, N., Midden, C., Hviid Nielsen, T., Przestalski, A., Rusanen, T., Sakellaris, G., Torgersen, H., Twardowski, T., and Wagner, W. (2000) Biotechnology and the European public. Nat. Biotechnol., 18, 935–938. 20 Osseweijer, P. (2006) A Short History of Talking Biotech (Thesis), Vrije Universiteit Amsterdam, Amsterdam. 21 Rip, A., et al. (1995) Managing Technology in Society: The Approach of Constructive Technology Assessment, Pinter Publishers Ltd, London. 22 Adams, J. (1995) Risk, University College London Press, London. 23 Rohrmann, B. (1999) Risk Perception Research: Review and Documentation, No. 48, Jülich Research Centre, Jülich. 24 Renn, O. (1999) A model for an analytic-deliverative process in risk management. Environ. Sci. Technol., 33, 3049–3055. 25 Nowotny, H., Scott, P., and Gibbons, M. (2001) Rethinking Science: Knowledge and the Public in An Age of Uncertainty, Polity Press, London. 26 Marris, C., Wynne, B., Simmons, P., and Weldon, S. (2001) Public Perceptions of Agricultural Biotechnologies in Europe:
27
28
29
30
31
32
33
34
35
36
37
38
39
40
Final Report of the PABE Research Project, University of Lancaster, Lancaster, UK. Wynne, B. (1992) Public understanding of science research: new horizons or hall of mirrors? Public Underst Sci., 1, 37–43. Wynne, B. (2006) Public engagement as a means of restoring publiuc trust in science – hitting the notes, but missing the music? Community Genet., 9, 211–220. Churchman, C.W. (1979) The Systems Approach and Its Enemies, Basic Books, New York. Rith, C., and Dubberly, H. (2007) Why Horst W. J. Rittel matters. Des. Issues, 23 (1), 72–74. Rittel, H.W.J. and Webber, M.R. (2005) Dilemmas in a general theory of planning. Policy Sci., 4 (2), 155–169. House of Lords (2000) Science and Society – Report and Evidence, HMSO, London. POST Parliamentary Office of Science and Technology (2001) Open Channels: Public Dialogue in Science and Technology. Report No. 153. The Royal Society and The Royal Academy of Engineering (2004) Nanoscience and nanotechnologies: opportunities and uncertainties, www.royalsoc.ac.uk/policy (accessed 01–02–2010). The Royal Society (2006) Factors Affecting Science Communication: A Survey of Scientists and Engineers, The Royal Society, London. Moses, V. (2002) Biotechnology: Educating the public, European Commission report. Osseweijer, P. (2001) Course Book EU Advanced Workshop on Bioethics and Pubic Perceptions of Biotechnology, EFB Task Group on Public Perceptions of Biotechnology, Delft, The Netherlands. Munnich, G. (2004) Whom to trust? Public concerns, late modern risks and expert trustworthiness. J. Agric. Environ. Ethics, 17, 113–130. Fischer, G. (2000) Symmetry of Ignorance, Social Creativity, and Meta-Design. Knowledge-Based System, 13 (7–8), 527–537. Ammann, K. and Papazova Ammann, B. (2004) Factors influencing public policy
References
41
42
43
44
45
development in agricultural biotechnology, in Risk Assessment of Transgenic Crops, vol. 9 (ed. S. Shantaram), John Wiley & Sons, Inc., Hoboken, NJ. Slingerland, M.A., Klijn, J.A.E., Jongman, R.H.G., and van der Schans, J.W. (2003) The Unifying Power of Sustainable Development. Towards Balanced Choices between People, Planet and Profit in Agricultural Production Chains and Rural Land Use: The Role of Science, Wageningen University, WUR-report Sustainable Development Wageningen (Report), pp. 1–94. Slingerland, M.A., Traore, K., Kayode, A.P.P., and Mitchikpe, C.E.S. (2006) Fighting Fe deficiency malnutrition in West Africa: an interdisciplinary programme on a food chain approach. Njas-Wageningen J. Life Sci., 53 (3–4), 253–279. Pilemalm, S., Lindell, P.O., Hallberg, N., and Eriksson, H. (2007) Integrating the rational unified process and participatory design for development of socio-technical systems: a user participative approach. Des. Stud., 28 (3), 263–288. Osseweijer, P. (2006) A new model for science communication that takes ethical considerations into account – the three-E model: entertainment, emotion and education. Sci. Eng. Ethics, 12 (4), 591–593. Osseweijer, P. (2006) Imagine projects with a strong emotional appeal. Nature, 444 (7118), 422–422.
46 Klapwijk, R., Knot, M., Quist, J., and Vergragt, P. (2006) Using design orienting scenarios to analyze the interaction between technology, behavior and environment in the sushouse project, in User Behavior and Technology Development, vol. 3 , Springer Netherlands, Dordrecht, pp. 241–252. 47 Schuurbiers, D., Osseweijer, P., and Kinderlerer, J. (2007) Future issues in industrial biotechnology. Biotechnol. J., 2007 (2), 1112–1120. 48 Frewer, L.J., Scholderer, J., and Bredahl, L. (2003) Communicating about the Risks and Benefits of Gentically Mddiefied Foods: The Mediating Role of Trust. Risk Anal., 23 (6), 1117–1133. 49 O’Neill, O. (2002) Autonomy and Trust in Bioethics, Cambridge University Press, Cambridge. 50 Driessen, P. (2003) Eco-Imperialism: Green Power, Black Death, Free Enterprise Press, Washington D.C. 51 Wisniewsky, J.P., Frangne, N., Massonneau, A., and Dumas, C. (2002) Between myth and reality: genetically modified maize, an example of a sizeable scientific controversy. Biochimie, 84 (11), 1095–1103. 52 (2008) Integrated farming: Why organic farmers should use transgenic crops. New Bio technology, 25(2) 101–107. 53 Moses, V., coordinator (2008) Do European Consumers Buy GM Foods? (Final report, part I, II, project no 518435, London, Kings College).
483
485
Index a ABE (acetone-butanol-ethanol) process 409, 433 Abraham, Edward P. 12, 13 acarbose 33 Acaryochloris marina 86 accountability 453, 454 acetic acid 1, 26, 297–299 – economic/environmental impact assessments 420, 429, 432–435 acetic acid test for enantioselectivity 165 acetone-butanol-ethanol (ABE) process 409, 433 Acinetobacter baumannii 83 acrylamide 51, 312 Actinobacillus pleuropneumoniae 82, 88 actinomycin D 15, 16 adalimumab (Humira) 44 adhesives, gecko foot hairs 241 adipic acid 420, 429, 432–434 adsorption techniques 285–293, 300, 422 Aedes aegypti 85 aerobic fermentation 134, 140, 421 Aeropyrum pernix 81 affinity chromatography 290 agitated tank fermenters 152 agriculture 35–37 – feed supplementation 203, 204, 354–358 – probiotics 346, 347 Agrobacterium radiobacter – epoxide hydrolase 178 – halohydrin dehalogenase 180 – phosphotriesterase 179 Agrobacterium tumefaciens, N-carbamoylase 179
air, sterilization 140 airlift fermenters 144 alcohols see butanol; ethanol; phenol aldolases – directed evolution 174, 175 – in statin production 317, 318 alternansucrase 351 Amgen Inc. 39, 321 amidase process 319 amino acids – in animal feed 358 – biocatalytic synthesis 20–23, 318–320, 357, 358 – downstream processing 299 – market size 20, 357 L-α-aminoadipic acid 11 7-aminocephalosporanic acid (7-ACA) 13, 308 aminoglycosides 15–17 6-aminopenicillanic acid (6-APA) 11, 308, 309 ampicillin 310 α-amylase – in baking 202, 340, 341 – in detergents 200 – directed evolution 177 – in paper making 204 – in production of resistant starch 353 – in starch hydrolysis 49, 336, 337 β-amylase 177, 202 amyloglucosidase (glucoamylase) 202, 336, 337, 350 amylopectin 336, 341 amylosucrase 353 anaerobic fermentations 134, 421 animal husbandry 36, 37 – feed supplementation 203, 204, 354–358 – probiotics 346, 347
Industrial Biotechnology. Sustainable Growth and Economic Success. Edited by Wim Soetaert and Erick J. Vandamme Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 978-3-527-31442-3
486
Index animals – enzymes derived from 49, 192, 338 – transgenic 47, 48, 356 antibiotics – agricultural uses 36 – biocatalytic synthesis 308–311 – cephalosporins 12–15, 309–311 – historical development 5, 6–20, 77 – penicillins 6–14, 77, 301, 308–311 – purification 301 – resistance to 11, 19, 20 antifoaming agents 146 antifreeze proteins 245, 246 antifungal agents 16, 33 antiglycemic agents 33, 322, 323 antimicrobial peptides 245, 339 antiparasitic agents 18, 36, 37 antiseptics 4 anti-staling agents 341 antitumor agents 35, 42–45 antiviral agents 42, 44 apple juice 203, 345 aqueous two-phase systems (ATPS) see two-phase aqueous systems Aquifex aeolicus 80 Archaeoglobus fulgidus 80 Arcobacter butzleri 86 Arthrobacter sp., hydantoinase and subtilisin 177 ascorbic acid (vitamin C) 24, 25 asexual (non-recombining) evolution 157, 158 Ashbya gossypii 23, 24 aspartame 318, 357, 358 l-aspartic acid 318, 357 Aspergillus fumigatus, phytase 177 Aspergillus nidulans 95 Aspergillus niger – citric acid production 25, 26 – genomics 82, 94 – monoamine oxidase 180 Aspergillus oryzae 95, 140 astaxanthin 301 atorvastatin (Lipitor) 32 – intermediates 172–174 ATP synthase molecular motor 251, 252 Augmentin 15 Autographa californica 47 Avecia Ltd (now NPIL Pharmaceuticals) 316, 317 avermectin 36, 37 azafenidin 313
b Babesia bovis 86 Bacillus spp., Savinase® 177 Bacillus amyloliquefaciens – α-amylase 177, 336 – genomics 86 Bacillus cepacia – biphenyl dioxygenase 178 – toluene monooxygenase 179 Bacillus megaterium, cytochrome P450 174, 178 Bacillus pumilus 86 Bacillus subtilis – esterases 175 – genomics 80, 95 – riboflavin 24 bacterial cell surface display 164, 165 Bacteroides vulgatus 85 baking 202, 340–342 Bartonella tribocorum 87 basiliximab (Simulect) 44 basket bioreactors 227 batch fermentation 135 – environmental conditions 140, 141 – equipment 143–152, 227 – inoculum generation 135, 136 – kinetics 136–138, 141, 142 – media 138–140, 221–227 Bayer Health Care, Miglitol production 322, 323 beer-making 1, 27, 28, 203, 342–344 benzoylformate decarboxylase 179 beta-lactam antibiotics see cephalosporins; penicillins beta-lactam rings 308 bialaphos 36 bifidobacteria, probiotic 346, 347 biocatalysts 211–221, 227 – see also enzymes Biochemical Pathways 75, 76 biocomposites 242, 243 bioconversion see bioreactors; enzymes; fermentation; media; process development biodiesel (VOME) 398–402 biodiversity 405, 406, 460–462 bioethanol see ethanol biofilms 385 biofragrances 30 biofuels – biodiesel 398–402 – butanol 29, 409, 420, 429, 432 – economic/commercial considerations 398–400, 405, 406
Index – ETBE 325, 397, 398, 404, 405 – ethanol see ethanol – public opinion 446 – sustainability 405, 406, 413, 414 – synthesis gas/motor fuel 409–412 biomimicry 238 – gecko foot hairs 241 – nacre 242, 243 – spider silk 239–241 biomineralization 242, 243 bio-oils 410 biopigments 30 bioreactors – full-scale 143–152, 227, 228 – miniature 229, 230 – nano-scale 253, 254 biorefineries 72, 369, 387, 388, 412, 413, 444, 446 biosensors 206, 253 Biostil®2000 process (ethanol production) 297 biosurfactants 302 biotechnology – definitions 64, 236, 443 – history and development 37–41, 77, 78 biotin 21 biotin tyramide labeling 163 biphenyl dioxygenase 178 bipolar membrane electrodialysis 294, 299 bleaching – in the paper industry 379–382 – in the textile industry 204 Bonner, David 11 Borrelia burgdorferi 80 Bradyrhizobium sp. 84 breadmaking 202, 340–342 brewing 1, 27, 28, 203, 342–344 bringer technique 158 Brotzu, G. 12 Brugia malayi 86 BT toxin 37 BtL process for biofuel production 409–412 bubble column fermenters 143 Buchner, Eduard 5, 28 Burkholderia cepacia 170 butanol 6, 29, 409, 420, 429, 432
c CAC (continuous annular chromatography) 292, 293 Caenorhabditis elegans 81 cakes 342 calcium oxalate 385 Campylobacter jejuni jejuni 86
Candida antarctica lipase B 169, 170, 314 Candidatus Cloacamonas acidaminovorans 88 Candidatus Sulcia muelleri 87 Cape, Ronald 39, 40 N-carbamoylase 179 carbapenems 15 carbohydrases see individual enzymes carbohydrates 249 – nanobiotechnology 249, 250 – prebiotic 347–354 – see also cellulose; starch; sugars carbon dioxide – greenhouse gas emissions 405, 414, 426, 429–431, 444 – as a solvent (supercritical fluid) 226, 281, 282 Cargill Dow LLC (polylactic acid) 313, 325 carotenoids 301 carriers for biocatalyst immobilization 218, 219 CASTing (combinatorial active-site saturation testing) 160 cell membranes – disruption techniques 271, 272 – increased permeability 21, 22, 215, 216, 245 – phospholipid structure 248 cellobiohydrolases 371, 382, 408 cellulases – in biofuel production 29, 205, 408, 409 – in detergents 49, 202 – economics of production 196 – in the paper industry 371, 378, 382 – in the textile industry 204 cellulose 371, 406, 407 centrifugation 268–270 cephalexin 310, 311 cephalosporins 12–15, 309–311 cephamycin C 14, 15 Cetus Corporation 39, 40 Chain, Ernst B. 7, 8 cheesemaking 49, 338, 339 chemical industry – bioconversions used in 51, 205, 311–314 – commercial environment 307, 320–332, 417, 418 chemometrics 229 chill haze 343, 344 chiral compounds – biocatalytic synthesis 311, 312, 314–318 – directed evolution of enantioselective enzymes 168–171, 176
487
488
Index – screening assays for enantioselectivity 165, 167 – separation methods 285, 290, 291, 294, 295 Chlamydia trachomatis 81, 88 Chlamydomonas reinhardtii 86 Chlamydophila pneumoniae 81 chlorine, in the paper industry 381 chromatography – continuous 291–293 – countercurrent 283 – molecular imprinting 293, 294 – protein purification 197, 300 – size exclusion 276 – stationary phase systems 286–291 chymosin 49, 338 ciclosporin 33 circular permutation 159 citric acid 6, 25, 26, 297–299, 421 clathrates 248 Clavibacter (Corynebacterium) michiganensis 84, 88 clavulanic acid 15 Clostridium botulinum 84, 85 Clostridium kluyveri 85 Clostridium thermoaceticum 26 Clostridium thermocellum 29 clotting factors 43 cobalamin (vitamin B12) 24 coccidiostats 36 Codexis Inc., statin production 314–316 codon bias 158 cofactor regeneration 214, 215 Cold Spring Harbor Laboratory, patents 77 colony-stimulating factors 43 coloring agents 30, 320–322 combinatorial biosynthesis 18, 19, 205 communication with the general public 451–456, 458, 462–464 compactin (mevastatin) 32 compartmentalization, in flux balance analysis 99, 100 computer software tools – enyzme–substrate reactions 229 – random mutagenesis 159, 160 computers, DNA 252 concentration polarization 273 constant pressure filtration 267 contact lens care products 206 continuous annular chromatography (CAC) 292, 293 continuous feed stirred tank reactors 228 continuous fermentation 135, 195 – assumptions concerning future technology 421
– environmental conditions 140, 141 – equipment 143–149, 151, 152, 228 – kinetics 142, 143 – media 138–140, 221–227 continuous screw fermenters 152 Coprinus cinereus, heme peroxidase 176 corn starch – as a feedstock for industrial production 403, 425, 431 – processing 49, 202, 203, 336, 337 Corynebacterium glutamicum 22, 23, 83, 96 cosmetics see personal care products countercurrent extraction 280, 283 Crick, Francis 37, 38 crossflow filtration 274, 275 crystallization 284, 285, 309, 310, 422 cyanohydrins 319, 320 (R)-4-cyano-3-hydroxybutyric acid 170, 174 cytochrome P450 monooxygenase 174, 178
d dairy products 49, 203, 337–340 – antifreeze proteins in 246 decanter centrifuges 270 decision-making process in democracies 453–455, 462–464 dehydrogenase screening assays 166, 167 deinking 381 Deinococcus radiodurans 81 denim 204, 321 dental care products 206 desferal 33 detergents, enzymes in 49, 50, 200–202 dextran 30, 342 dextransucrases 342, 351, 352 dextrose 336 diastereoisomeric crystallization 285, 309, 310 diauxic growth 138 Dichelobacter nodosus 84 diesel (VOME) 398–402 dietary supplements 346–354 directed evolution 50, 51, 157 – assay systems 161, 162 – – in vitro selection 162, 163 – – in vivo selection 163, 164 – – screening 163–167 – combined with rational protein design 160, 161 – compared with rational protein design 155, 156 – examples – – aldolases 174, 175 – – cytochrome P450 monooxygenase 177
Index – – halohydrin dehalogenase 177, 315, 316 – – hydrolases 168–170 – – nitrilase 170, 171 – mutagenesis methods 157–160 disk stack centrifuges 270 displacement chromatography 289 distillation 277, 422 – ethanol 296, 297 – membrane distillation 277, 278 distribution coefficient 279, 280 Diversa Corporation, statin production 316 DNA, structure 247 DNA computers 252 DNA-modifying enzymes – DNase for cystic fibrosis 43 – in molecular biology 157, 158, 206, 207 DNA shuffling 50, 158, 159 DNA technology see recombinant DNA (rDNA) technology Domagk, Gerhard 5 doramectin 18 doubling times 137 downstream processing 263–265 – economic/environmental impact assessments 421–423 – product groups – – alcohols 296, 297 – – amino acids 299 – – antibiotics 301, 309, 310 – – biosurfactants 302 – – carotenoids 301 – – organic acids 284, 294, 297–299 – – polyhydroxyalkanoates 302 – – proteins 196, 197, 282, 284, 290, 300 – separation techniques 153, 154, 266 – – adsorption 285–293, 300, 422 – – cell disruption 271, 272 – – drying 295, 296 – – electrodialysis 294, 299 – – molecular imprinting 293, 294 – – size-based 269, 272–276, 423 – – solid–liquid 265–271, 274 – – solubility-based 279–285, 297–299, 301, 309, 310, 422 – – volatility-based 276–279, 296, 297, 422, 423 DRIVeR software 159 drying methods 295, 296 DSM 311, 317, 318, 319, 320, 343, 344 DuPont, PDO production 77, 78, 109–111, 325 dyes 320–322
e economics 322–325, 326–330 – biofuels 398–400, 405, 406 – commodity prices 112, 324, 327, 328, 428, 443, 444 – energy use 378, 382, 422 – impact assessments 435, 436 – – methodology 418–422, 426–428 – – results 431–435 – innovation 236, 237 – market sizes 49, 64, 322, 329, 330, 445 – process economics 65, 69, 196, 263, 264, 327, 328, 426, 427 – public engagement with biotechnology 454 ectoine 323 Ehrlich, Paul 4, 5 E.I. Du Pont de Nemours and Company, PDO production 77, 78, 109–111, 325 electrodialysis 294, 299, 422 electropolishing 148 enantioselectivity – biocatalytic synthesis 311, 312 – directed evolution of 168–171, 176 – in screening assays 165, 166 – separation of racemic mixtures 285, 290, 291, 294, 295 endoglucanases 372, 374, 383, 408 endomannanases 373, 374, 384 energy use – in bioconversions 422 – non-renewables 426 – in the paper industry 378, 379 – societal issues 460, 461 entrained-downflow reactors 411 environmental considerations – biodiversity 405, 406, 460–462 – biofuel production 405, 406, 413, 414 – impact assessments 436 – – methodology 418–426 – – results 428–431 – in the paper industry 381–383 – process development 65–67, 69, 226, 326 – sustainability as a core value 457 – waste reduction 325, 326 enzyme inhibitors 31–33 enzymes – design methods 155–160, 197–200 – – assay systems for 161–168, 193 – – examples 168–178 – history of biotechnology 5, 48–51 – immobilization 216–221, 227
489
490
Index – industrial uses 200–207, 254, 255 – production 192–197 – – downstream processing 196, 197, 282, 284, 290, 300 – selection 193, 213 – – production strain 193, 194 – – whole cells vs isolated enzymes 214–216 – see also individual enzymes Epicurian coli XL1-Red 158 epoxide hydrolase 182 Eremothecium ashbyi 23, 24 ergot alkaloids 35 error-prone polymerase chain reaction (epPCR) 157, 158 erythromycins 19 erythropoietin (EPO) 42 Escherichia coli – genomics 80, 88, 91 – as host for recombinant proteins 45, 46, 222 – PDO production 29, 110, 111 eSCRATCHY software 160 eShuffle software 160 esterases – EstA used in selection assays 163 – examples of directed evolution 168, 169, 174, 179 – screening assays for 164–166 – in wood pulp processing 374 esterification of vegetable oils 400, 401 etanercept (Enbrel) 44 ETBE (ethyl-tertiary-butyl-ether) 325, 397, 398, 404, 405 ethanol – as a biofuel 28, 29, 106, 327, 328, 397–400, 404, 405 – economic/environmental impact assessments 420, 421, 429, 432–434 – feedstock 388, 403, 405, 406, 425, 431 – production methods 29, 403, 404, 406–409 – – downstream processing 296, 297 – – history 1, 3, 27–29 – – metabolic models 70–72, 106–108 – production volumes 28, 70, 105, 106, 398 ethene (ethylene) 432–434 ethical concerns 442, 451, 452, 460 – precautionary principle 458, 459 ethyl alcohol see ethanol ethyl lactate 432–434 ethyl tertiary-butyl ether (ETBE) 325, 397, 398, 404, 405
ethylene 432–434 Europe – biofuels 398–400, 402, 405 – GM foods 338, 449, 450 – public opinion 446–452 evaporation 285, 295, 296, 422, 423 Evonik Industries AG, l-tert-leucine synthesis 318, 319 expanded bed chromatography 291, 292 exponential growth kinetics 137, 141, 142 extraction techniques 271, 279–283, 422 – antibiotics 301 – organic acids 299 extremophile enzymes 49, 50, 200
f F0F1 ATP synthase molecular motor 251, 252 factor VIII 43 fatty acid ethyl esters (FAEE) 401 fatty acid methyl esters (FAME) 400, 401 fatty acids 248, 339 FBA (flux balance analysis) 67, 68, 99–105, 107 – see also metabolic flux analysis fed-batch fermentation 135 – environmental conditions 140, 141 – equipment 143–152, 227 – media 138–140, 221–227 – in penicillin production 10, 11 – see also batch fermentation feedstocks 70, 387–388 – for biodiesel 400, 402 – for bioethanol 388, 403, 405, 406, 425, 431 – environmental impact 405, 406, 429–431 – nitrogen in 331 Feigl-Anger assay 167, 168 fermentation – classification 133, 134 – economic/environmental impact assessments 420, 421, 423 – environmental conditions 140, 141 – enzyme production 194–197 – equipment 143–152, 227, 228 – history 1–6, 10, 11, 20 – kinetics 136–138, 141–143 – media 138–140, 221–227 – methodologies 134–136, 194–196 – see also downstream processing fiber engineering in the pulp and paper industry 371, 385–387
Index filtration – problems with antifoaming agents 146 – size-based separation 196, 269, 272–276 – solid–liquid separation 265–268, 274 – sterilization of culture media 139 Finegoldia magna 88 Fischer-Tropsch process 412 Flavobacterium psychrophilum 85 flavor enhancers 20–23, 357 Fleming, Alexander 6, 7 Florey, Howard W. 7 flotation techniques 271 fluidized bed fermenters 144, 145, 228 flux balance analysis (FBA) 67, 68, 99–105, 107 – see also metabolic flux analysis fluxomics – definition 71 – flux balance analysis 67, 68, 99–105, 107 – metabolic flux analysis 108, 110, 111 foaming, in bioreactors 146 focused directed evolution 160, 161, 168 food industry – artificial sweeteners 318, 340, 351, 357, 358 – baking 202, 340–342 – brewing 1, 28, 203, 342–344 – dairy products 49, 203, 246, 337–340 – dietary supplements 346–354 – flavor enhancers 20–23, 357 – fruits 203, 344, 345 – GM food products 338, 442, 446–451 – history 1, 20, 21, 28, 49, 335 – sugar production (from starch) 49, 202, 203, 336, 337 – wine making 1, 28, 203, 345 forestry 369, 370, 406 forward metabolic engineering, definition 71 fractional crystallization 285 fragrances 30 Francisella tularensis tularensis 83 freeze-drying 296 Freundlich isotherm 286 fructooligosaccharides 348 fructose-containing syrup 49, 203, 337 fruit processing 203, 344, 345 fullerenes, in molecular motors (‘nanocars’) 252 functional foods 346–354 Fusarium graminearum 86
g galactooligosaccharides 348–350 β-galactosidase 339, 340, 348–350 gas stripping 277, 422 gasification 411 gecko foot hairs 241 gel filtration (size exclusion chromatography) 276 gene site saturation mutagenesis (GSSM) 170, 171 Genencor International 109 Genentech Inc. 39, 77 genetically modified (GM) foods 338, 442, 443, 446–451 genetics see mutagenesis; recombinant DNA (rDNA) technology genome-scale metabolic models (GSMMs) 72, 90, 104, 105 – ethanol production in S. cerevisiae 106, 107 genome-scale metabolic reconstructed networks 67–90, 115, 116 – M. succiniproducens 93, 114, 115 – organisms studied 91–98 – production 99–104 genomics 71, 77–89 Geobacillus thermodenitrificans 83 germ theory of disease 3, 4 GHG (greenhouse gas) emissions 405, 414, 426, 429–431, 444 Giardia lamblia (intestinalis) 86 gibberellins 36 glucanases – in the animal feed industry 203, 356 – in the brewing industry 203, 342, 343 – endoglucanases 372, 374, 382, 408 – xyloglucanases 372, 386 glucansucrases 350–352 glucoamylase 202, 336, 337, 350 glucocerebrosidase 43 glucomannans 373, 374 α-glucooligosaccharides 350–352 β-glucooligosaccharides 354 glucose 202, 336, 425 glucose isomerase 49, 337 glucose oxidase 206, 341 glucosidases – β-glucosidase 345, 354, 370, 408 – glucoamylase 202, 336, 337, 350 glucuronoyl esterase 374 GLUE software 159 L-glutamate 20–22, 318, 357 glutaryl acylase 179 gluten 341 glycerides 248
491
492
Index glycosidases 345 glycosylation 46 GM (genetically modified) foods 338, 442, 443, 446–451 Gosio, Bartolomeo 34 government policies 444, 445 – on biofuels 106, 399, 400 GRAS (generally recognized as safe) microorganisms 193 Greaves, J.D. 73 greenhouse gas (GHG) emissions 405, 414, 426, 429–431, 444 growth hormone 42 GSMM (genome-scale metabolic models) 72, 90, 104, 105 – ethanol production in S. cerevisiae 106, 107 GSSM (gene site saturation mutagenesis) 170, 171 gut microbiome – genomics 87 – probiotics and 346, 347
h Haemophilus influenzae 80, 93 haloalkane dehalogenase 179 Halobacterium salinarum 88 halohydrin dehalogenase 173, 180, 315, 316 Hansch parameter 224 health issues 325, 326, 458–460 Heatley, Norman 7, 8 Helicobacter pylori 80, 81, 93 hemicellulases 373, 374 hemicelluloses 373, 377 Hemiselmis andersenii 87 herbicides 35, 36, 313 Herceptin (trastuzumab) 44 Herminiimonas (Cenibacterium) arsenicoxydans 83 HETP (height equivalent to a theoretical plate) 288, 289 hexenuronic acid 379 hexose oxidase 341 high fructose corn syrup (HFCS) 49, 203, 337 high-throughput screening (HTS) 161–168, 193 homogenization of cells 271, 272 human growth hormone (hGH) 42 humans, genomics 86, 97 hydantoinase 177, 310 hydrocyclones 270 hydrogenation of vegetable oils 402 hydrolase screening assays 164–166
hydrophobic interaction chromatography 290 hydroxy-ectoine 323 hydroxynitrile lyases 167, 168, 320 d-hydroxyphenylglycine 309, 310 Hyperthermus butylicus 82
i ice cream 246 ice-structuring proteins 245, 246 idiolites (secondary metabolites) 30–35, 138 – see also antibiotics imatinib (Gleevec) 45 immobilization of biocatalysts 216–221, 227 immunosuppressants 33, 34 immunotherapy – immunization 4, 51 – interferons 42 – monoclonal antibodies 35, 44 in situ product recovery 264, 265, 270 in vitro evolution see directed evolution in vitro selection techniques for mutants 162, 163 in vivo selection techniques for mutants 164, 165 inclusion bodies 45, 46 indigotin 320–322 industrial biotechnology, definitions 64, 443 industrial systems biology 67–72, 104, 105, 115–117 – bioethanol (S. cerevisiae) 105–108 – definition 71 – genomic research 77–89 – PDO (E. coli) 109–111 – succinic acid (M. succiniciproducens) 112–115 – see also genome-scale metabolic reconstructed networks infliximab (Remicade) 44 ink removal from waste paper 383 inoculum generation 135, 136 insect cells, in rDNA technology 47 insecticides 36, 37, 319 insulin 41, 42 interfacial catalysis 223 interferons 42 interleukins 43 inulin 348 inverse metabolic engineering 71, 72 ion exchange chromatography 290 ion exchange membranes 294
Index ionic liquids, as bioconversion media 224, 225 IP6 (myo-inositol hexakisphosphate) 354–355 isomaltooligosaccharides 350 ITCHY (incremental truncation for the creation of hybrid enzymes) 159 iterative saturation mutagenesis (ISM) 160 ivermectin 37
j jackets, for bioreactors 148 Janthinobacterium sp. 85 Johnson, Marvin 10
k Kaneka Corporation 310, 316 ketoreductases 314–317 kinesins 251, 252 kinetics – batch fermentation 136–138, 141, 142 – continuous fermentation 142, 143 – microbial growth and metabolism 73–75 Kluyver, Albert Jan 73 Kluyver Center for Genomics of Industrial Fermentation, workshops 456–458 Koch, Robert 3 koji fermentations 1, 141, 149–151 König reaction 167 kraft cooking of wood pulp 372, 376–378 Krebs, Hans A. 75, 76 Kyoto Protocol 444
l Laccaria bicolor 87 laccase-mediator system (LMS) 379, 381, 382 laccases 204, 254, 255, 375, 379 lactase (β-galactosidase) 339, 340, 348–350 lactic acid 27, 297–299 – economic/environmental impact assessments 420, 429, 433 Lactifit® 350 Lactobacillus spp. 27 – genome 87 – GSMMs 95 – probiotics 346, 347 Lactococcus lactis 82, 95 lactose 339, 340 lactosucrose 340 lag phases in batch fermentation 136, 138 land use for biomass production 405, 426, 430, 431, 444, 460 Langmuir isotherm 286
laundry detergents, enzymes in 49, 50, 200–202 leather industry 205 Leeuwenhoek, Antonie van 1, 2 l-tert-leucine 318, 319 Leuconostoc citreum 88 life cycle assessments 423–426, 428–431 lignin – bleaching 379–382 – composition of lignocellulosic biomass 368, 369, 373, 407 – oxidative enzymes 373–375 lignin peroxidases (LiPs) 374 lignocellulosic biomass – composition 371–373, 407 – as a feedstock 387, 388, 406, 425, 429–431 – production of biofuels from 205, 406–412 – see also paper and pulp industry lipases 222, 254, 314 – in cheesemaking 50, 339 – directed evolution 168–170, 175 – in the paper industry 379 – screening assays for 165 lipids 247–249 Lipitor (atorvastatin) 32 – intermediates 170–172 lipoxygenase 341 lipstatin 33 LMS (laccase-mediator system) 379, 381, 382 log phase growth 137, 141, 142 lovastatin (mevinolin) 48 l-lysine 11, 22, 23, 318, 358 Lysinibacillus sphaericus 88 lysozyme 272, 339
m Macaca mulatta 83 macrolides 19 Malassezia globosa 87 maleic anhydride 112 malting 342, 343 maltose 337 mammalian cells, in rDNA technology 47 manganese-dependent peroxidase (MnP) 374, 375 mannanases – in the animal feed industry 357 – in the paper industry 372, 373, 383 Mannheimia succiniproducens 93, 113–115 marine microbial/plankton communities 83, 86 mass balance analysis 101–103
493
494
Index materials science 238 – gecko foot hairs 241 – immobilization of biocatalysts 218, 219 – nacre 242, 243 – nanoparticles 219, 237, 238 – spider silk 239–241 media – fermentation 138, 139 – non-aqueous 221–227 – sterilization of 139, 140 MEGAWHOP technique 158 membrane separation methods – adsorption 290 – chiral separation 294, 295 – distillation/pervaporation 277–279 – electrodialysis 294, 299 – filtration 267, 268, 272–276 – in the future 422 – perstraction 281 membranes, cellular see cell membranes metabolic control analysis 99 metabolic engineering 63, 67–69, 115–117 – definition 71 – ethanol (S. cerevisiae) 70–72, 105–108 – genomics 77–89 – lysine (C. glutamicum) 22, 23 – PDO (E. coli) 109–111 – research history of microbial metabolism 73–76 – succinic acid (M. succiniproducens) 112–115 metabolic flux analysis (MFA) 75 – ethanol production (S. cerevisiae) 108 – PDO production (E. coli) 110, 111 metabolomics, definition 71 metagenomics, definition 71 Metallosphaera sedula 84 Methanobrevibacter smithii 84 Methanocaldococcus jannaschii 80 Methanococcus jannaschii 94 methanogenic archaeon RC-I 83 Methanosarcina barkeri 97 Methanothermobacter thermoautotrophicus 80 methionine 357 mevastatin (compactin) 32 mevinolim (lovastatin) 32 micelles 248, 249 microbiology, history 1–20, 73–76 Microcystis aeruginosa 87 microfiltration 267, 268, 274 microscale processing 229, 280 Miglitol 322, 323 milk processing 49, 203, 337–340
modeling techniques – in process development 229 – random mutagenesis 159, 160 – see also genome-scale metabolic models molds 46, 47 – see also Aspergillus; Penicillium molecular evolution see directed evolution molecular imprinting 293, 294 molecular modeling 229 molecular motors 250–252 monensin 36 monoamine oxidase 180 monoclonal antibodies, therapeutic 35, 44 Monod, Jacques 75 Monodelphis domestica 84 monomer production 51, 312–314 – see also 1,3-propanediol monoseptic fermentations 134 Monosiga brevicollis 103 monosodium glutamate (MSG) 20–22, 357 moral concerns 442, 451, 452, 460 – morally unacceptable harm 458, 459 mother of pearl (nacre) 242, 243 mouse (Mus musculus) 98 moving bed chromatography 291, 292 MRSA (methicillin-resistant S. aureus) 20, 96 Mullis, Cary 40 mutagenesis – focused directed evolution 160, 161 – random 50, 51, 73 – – assay systems for 161–168, 193 – – examples of directed evolution 168–180 – – methods used in directed evolution 157–160, 170, 171 – – software evaluation tools 159, 160 – – strain selection for antibiotic production 9, 17–19 – site-directed 50, 156, 170, 199 mutator strains 158 Mycobacterium tuberculosis 80, 96 mycophenolic acid 34 Mycoplasma genitalium 80 Mycoplasma pneumoniae 80 myo-inositol hexakisphosphate (IP6) 354, 355
n nacre 242, 243 nanobiotechnology 255, 256 – biomimicry of materials 238–243 – bioreactors 253, 254 – biosensors 206, 253 – commercial development 237, 239, 246
Index – definition 236 – molecular building blocks 235, 236, 243–250 – nanomachines 250–252 – scaffolds 255 nanofiltration 274, 275 nanoparticles 219, 237, 238 naphthalene dioxygenase 321, 322 NatureWorks plant (Nebraska) 314 Neisseria meningitidis 87 Nematostella vectensis 86 neomycin 16 Newton, Guy G.F. 12 NextBtL process for biofuel production 402 Nitratiruptor sp. 85 nitrilases – examples of directed evolution 170, 171, 180 – in statin production 316 nitrile hydratase 312, 313 nitrogen – in feedstocks 331 – in fermentation media 138 non-renewable energy use (NREU) 426 NPIL Pharmaceuticals (formerly Avecia), statin production 316, 317 nucleotides 23, 247 nystose 349
o oil prices 112, 324, 327, 328 oligosaccharides, prebiotic 347–354 OptKnock process (metabolic engineering) 117 oral microbial communities 84 orange juice 203, 345 organic acids 25–27 – downstream processing 284, 294, 297–299 – economic/environmental impact assessments 420, 429, 432, 433, 434, 435 – see also individual acids organic solvents – as bioconversion media 221–224 – in downstream processing 279–281, 283, 284, 299 Orientia (Rickettsia) tsutsugamushi 84 Orlistat 33 Ostreococcus lucimarinus 84 oxalate-removing enzymes 385 oxidases – in baking 341, 342 – in the paper industry 372–374, 378, 386 – see also laccases; peroxidases
oxidation, biocatalytic 311, 312 oxidoreductase screening assays 166, 167 oxygen, in fermentation 138, 140, 146 oxygenase screening assays 167
p packed-bed columns 286–291 palivizumab (Synagis) 44 paper and pulp industry 369–370 – bleaching 379–382 – enzymes used 204, 370–375, 377–380, 382, 383 – equipment cleaning 385 – fiber engineering 369, 385–387 – paper making 382, 383 – pulping 376–379 – recycling 383, 385 Parabacteroides distasonis 85 partitioning allocation procedure 424, 425 Pasteur, Louis 2–5 patents 77, 78 PCPP (production cost plus profits) analysis 426, 427, 431–435 PDO see 1,3-propanediol pectinases 203, 344, 345, 383 PEDEL software 159 PEG (polyethylene glycol) 282, 283 penicillins – history 6–14, 77 – purification 301 – synthesis 308–311 Penicillium spp. 7, 9, 10 pentose sugars 77, 107, 108, 409 peptides 243–245 permeability of cell membranes 21, 22, 215, 216, 245 peroxidases 166, 167, 174 – in the paper industry 374, 375 personal care products 30, 206, 323, 324 perstraction 281 pervaporation 278, 279, 297, 422 phage display 161 pharmaceutical industry 4, 5, 39–41, 322–324 – discovery of new compounds using combinatorial biosynthesis 18, 19, 205 – products 31–35, 41–45, 314–318 – see also antibiotics PHAs see polyhydroxyalkanoates phenol 330, 331 phenotypic phase planes (PhPP) 103, 104 – S. cerevisiae 106 l-phenylalanine 318, 357 d-phenylglycine 309, 310
495
496
Index phosphatases see phosphotriesterases; phytases phosphoketolase pathway 108 phospholipases 170, 342 phospholipids 248 phosphotriesterases 179 Physcomitrella patens patens 88 phytases 50, 177, 344 – in animal feed 203, 204, 354–356 Pichia pastoris 46 Pichia stipitis 82 pigs 354–356 pitch (resin) 204, 380 PLA (polylactic acid) 313, 325, 328, 432, 434 plants – enzymes derived from 49, 192 – transgenic 48 Plasmodium falciparum 93 plastics, biodegradable 30 – economic/environmental impact assessments 328, 420, 429, 432–434 – production methods 313, 314 – public support for 446 plug flow fermenters 135, 143, 227, 228 polishing of bioreactors 148, 149 polyethylene glycol (PEG) 282, 283 polyhydroxyalkanoates (PHAs) 30, 302 – economic/environmental impact assessments 420, 429, 432–434 polylactic acid (PLA) 313, 325, 328, 432, 434 polymerase chain reaction (PCR) 40, 157, 158 polymers 29, 30, 212, 213 – economic considerations 326–328 – hybridized with peptides/proteins 246 – production methods 312–314 polynucleotides, self-assembly 247 polytrimethylene terephthalate (PTT, 3G+) 30, 429, 433, 434 poultry 36, 203, 347, 354–356 pravastatin 32 prebiotics 347–354 precautionary principle 458, 459 precipitation 284, 298, 422 pressure, in bioreactors 146 primary metabolites 138 – see also amino acids probiotics 346, 347 process development 65–70, 105, 211–213, 228–230 process economics 65, 69, 196, 263–264, 327, 328, 426–427
process flow diagrams 418, 419 Prochlorococcus marinus 82, 83, 86 production cost plus profits (PCPP) analysis 426, 427, 431–435 1,3-propanediol (PDO) 29, 77, 78, 109–111, 313, 314 – economic/environmental impact assessments 420, 429, 432–434 ProSAR technique 160, 161 proteases – in brewing 343, 344 – in the dairy industry 339 – in the leather industry 205 protein engineering see directed evolution; rational protein design proteomics, definition 71 Pseudomonas sp., glutaryl acylase 181 Pseudomonas aeruginosa, lipases 168, 169, 176 Pseudomonas diminuta, phosphotriesterase 181 Pseudomonas fluorescens, esterases 169, 176 Pseudomonas pseudoalcaligenes, biphenyl dioxygenase 178 Pseudomonas putida, benzoylformate decarboxylase 181 public perception of biotechnology 441, 442, 445–451, 463, 464 – scientific communication affecting 451–456 Pulley, H.C. 73 pullulanase 202, 336, 350 pulp industry see paper and pulp industry Purdue Research Foundation, patents 77 purification see downstream processing pyrethroids 319 Pyrococcus horikoshii (shinkaj) 80 pyrolysis 410, 411
q Quick E screening assay 165, 166 QuikChange™ technique 156, 158 quinolones 17
r RACHITT (random chimeragenesis on transient template) 158, 159 RaMuS software 160 rapamycin (sirolimus) 33, 34 rational protein design 155–157, 199, 200 – combined with directed evolution 160, 161
Index raw materials see feedstocks reactive extraction 281 recombinant DNA (rDNA) technology – DNA-modifying enzymes used in 206, 207 – enzymes 49–51, 198, 199 – history of 18, 39–41, 49, 50, 78 – host cells 45–48 – pharmaceuticals 41–45 – see also genetically modified (GM) foods Recordati S.p.A. 310 recycling, paper 383, 385 rennet 49, 338 resins – as bioconversion media 225, 226 – pitch hydrolysis 204, 378 resistant starch (RS) 352–354 retuximab (Rituxan) 44 reverse osmosis 274–276 reversed phase chromatography 290 Rhizobium etli 97 Rhizopus oryzae, lactic acid 27 Rhodococcus sp., haloalkane dehalogenase 179 riboflavin (vitamin B2) 23, 24 l-ribulose 30 Rich, Alexander 37, 38 Rickettsia prowazekii 81 Rickettsia rickettsii 88 risk assessment 458–460 RNA 247 – double-stranded 37–39 rotary disk fermenters 151 rotary drum fermenters 152 rotary drum vacuum filters 268 Rovabio™ Excel 357 Rubrivivax gelatinosus 82
s Saccharomyces cerevisiae – ethanol production 28, 106–108 – genomics 70–72, 80, 90, 91, 92, 106, 107 – glycosylation 46 – lipid metabolism 117 Saccharopolyspora erythraea 83 safety issues 325, 326, 458–460 Salinispora tropica 83 salting out 284 scaffolds, for tissue reconstruction 255 SCFs see supercritical fluids screening assays for mutants 164–168 scroll centrifuges 270 SDM (site-directed mutagenesis) 50, 156, 170, 199
secondary metabolites 30–35, 138 – see also antibiotics seed fermenters 136 self-sufficiency see sustainability sexual evolution (recombination) 158, 159 silk (spider) 239–241 simulated moving bed chromatography 291, 292 simvastatin (Zocor) 32 SIRCH software 160 sirolimus 33, 34 site-directed mutagenesis (SDM) 50, 156, 170, 199 size exclusion chromatography 276 skincare products 323, 324 slime control 385 societal issues – biodiversity 405, 406, 460–462 – changes associated with shift from oil to biomass 443, 444 – communication with the public 451–456, 458, 462–464 – decision-making process 453–455, 462–464 – economics 445, 454, 462 – energy use 460, 461 – government policies 106, 399, 400, 444, 445 – Kluyver Center workshops 456–458 – land use 405, 444, 460 – public perception of biotechnology 441, 442, 445–451 – safety 325, 326, 458–460 software see computer software tools soil microbial communities 85 solid-phase screening assays 164 solid-state fermentation 133, 141 – enzyme production 195, 196 – equipment 149–152 solvents – as bioconversion media 221–224 – in downstream processing 279–281, 283, 284, 299 Sorangium cellulosum 87 Sorona™ 313 soybean, β-amylase 177 spider silk 239–241 spinosyns 37 spontaneous generation, theory of 2, 3 spray-drying 296 Staphylococcus aureus – genome sequences 84, 85, 87 – methicillin-resistant 20, 96 – phospholipases 170
497
498
Index starch – as a feedstock for industrial production 403, 425, 431 – processing 49, 202, 203, 336, 337 – resistant 352–354 starter cultures 135 static bed fermenters 151 statins 31–33, 314–318 steam explosion process 407 steel, for fermenters 148, 152 StEP (staggered extension process) 158 sterilization, of fermentation media 139, 140 stickies (in paper recycling) 383, 385 stirred tank fermenters 143, 227 – continuous feed 228 Stokes’ law 268, 269 Streptococcus sanguinis 82 Streptococcus suis 83 streptogramins 19, 20 Streptomyces coelicolor 94 streptomycin 16 submerged fermentation 133, 134 – environmental conditions 140, 141 – enzyme production 194, 195 – equipment 143–149 – media 138–140, 221–227 subtilisin 177 succinic acid 112–115, 297–299 – economic/environmental impact assessments 420, 429, 432–434 sugar cane 425 sugars 30 – commodity prices 328, 428 – economic/environmental impact assessments 425, 428, 429–431 – as raw materials for bioethanol 403 – see also individual sugars Sulfurovum sp. 85 supercritical fluids (SCFs) – as bioconversion media 226, 227 – product extraction using 281, 282 supersaturation 285 sustainability 65–67, 69, 457 – biofuel production 405, 406, 413, 414 – see also environmental considerations sweeteners, artificial 318, 340, 351, 357, 356 Synechocystis sp. 80 Synercid 19, 20 synthesis gas 409–412 system expansion allocation procedure 424 systems biology 51, 52, 71 – see also industrial systems biology
t tacrolimus 34 tau-fluvalinate 319 taxol 35 telithromycin 19 temperature control in fermentation 140, 141 tetracyclines 20 textile industry 204 – see also detergents thermal stability in enzymes 49, 50, 200 thermochemical pathway of biofuel production 409–412 Thermotoga maritima 81 Thermotoga neapolitana, xylose isomerase 178 thienamycin 15 l-threonine 23, 358 tigecycline 20 tissue engineering 255 tissue plasminogen activator (tPA) 42, 43, 48 toluene monooxygenase 177 toothpaste 206 torrefaction 411 training, in communication 453 transcriptomics 71, 107 transglutaminase 339 trastuzumab (Herceptin) 44 Traube, Moritz 5, 28 tray fermenters 149–151 Treponema pallidum pallidum 80 Trichoderma reesei, xylanase 177, 200 trickle-bed fermenters 145 triglycerides 248, 378 trust 450, 453, 454, 459, 460 l-tryptophan 358 tunnel fermenters 151 two-phase aqueous systems – as bioconversion media 225 – extraction using 271, 282, 283 two-phase aqueous–SCF systems 281, 282 two-phase aqueous–solvent systems 279–281, 283, 299 two-phase solid–gas systems 226
u ultrafiltration 196, 272–274 Umezawa, Hamao 31 USA – biofuels 28, 105, 106, 399 – biotechnology companies 39–41 – genomic research funds 89 Ustilago maydis 82
Index
v vaccines 4, 51 vacuum distillation 277 vacuum filtration 267, 268 d-valine 319 van Leeuwenhoek, Antonie 1, 2 Vanderwaltozyma polyspora 86 vegetable oil methyl esters (VOME) (biodiesel) 398–402 versatile peroxidase (VP) 375 Vesicomyosocius okutanii 84 vinegar 1, 26 – see also acetic acid vitamins 23–25 Vitis vinifera 86, 87 VOME (vegetable oil methyl esters) (biodiesel) 398–402
wood see lignocellulosic biomass Woodruff, H. Boyd 16 wound healing 255
x x-omics 71, 72, 104, 105 xanthan 29, 30 Xanthomonas campestris campestris 88 xylanases – in animal feed 203, 356 – in baking 202, 341 – genetically engineered 177, 200 – in the paper industry 373, 380–382 xyloglucanases 374, 386 xyloglucans 386, 387 xylooligosaccharides 354 xylose, bioethanol from 77, 107, 108 xylose isomerase 178
w Waksman, Selman A. 15, 16 water purification 274–276 water use in the paper industry 383 Watson, James D. 37, 38 Weizmann, Chaim 6 wine making 203, 345 – history 1, 27, 28 – V. vinifera genome 86, 87
y 382,
yeasts 27, 28, 46 – see also Saccharomyces cerevisiae Yersinia pseudotuberculosis 85 yield from multistep procedures 153
z zeaxanthin 301 Zocor (simvastatin)
32
499
Related Titles Buchholz, Klaus / Collins, John
Hou, C. T., Shaw, J.-F.
Concepts in Biotechnology
Biocatalysis and Bioenergy
History, Science and Business 2010 ISBN: 978-3-527-31766-0
2008 ISBN: 978-0-470-13404-7
Aehle, W. (ed.) Katoh, Shigeo / Yoshida, Fumitake
Enzymes in Industry
Biochemical Engineering
Production and Applications
A Textbook for Engineers, Chemists and Biologists 2009 ISBN: 978-3-527-32536-8
Soetaert, W., Vandamme, E. (eds.)
Biofuels 2009 ISBN: 978-0-470-02674-8
Fessner, W.-D., Anthonsen, T. (eds.)
Modern Biocatalysis Stereoselective and Environmentally Friendly Reactions 2009 ISBN: 978-3-527-32071-4
2007 ISBN: 978-3-527-31689-2
Sheldon, R. A., Arends, I., Hanefeld, U.
Green Chemistry and Catalysis 2007 ISBN: 978-3-527-30715-9
Edited by Wim Soetaert and Erick J. Vandamme
Industrial Biotechnology Sustainable Growth and Economic Success
The Editors Prof. Wim Soetaert Ghent University Department of Biochemical and Microbial Technology Centre of Expertise – Industrial Biotechnology and Biocatalysis Faculty of Bioscience Engineering Coupure links 653 9000 Gent Belgium Prof. Erick J. Vandamme Ghent University Department of Biochemical and Microbial Technology Centre of Expertise – Industrial Biotechnology and Biocatalysis Faculty of Bioscience Engineering Coupure links 653 9000 Gent Belgium
All books published by Wiley-VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate. Library of Congress Card No.: applied for British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library. Bibliographic information published by the Deutsche Nationalbibliothek The Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at
33
16
Would buy GM foods if approved by relevant authorities
No, definitely not
40
22
8
22
8
25
30
26
60
7
80
8
7
100
Percentage
Figure 14.4 Percentage of European citizens willing to buy GM food products with particular characteristics. Gaskell et al. [3], Eurobarometer Studies available at: http://www.ec.europa.eu/ research/press/2006/pdf/pr1906_eb_64_3_final_report-may2006_en.pdf.
It can be strongly argued that a reaction towards negative public perceptions does not provide a satisfactory answer. First, a number of social scientists had already pointed out repeatedly that public perception studies are studies of the respondents’ attitudes and that they cannot be extrapolated to behavior [8–12]. More recently this has been supported by a number of studies on actual buying behavior of consumers presented with GM food products [13, 14]. Second, the results of the latest Eurobarometer survey in 2005, but also other (national) studies still showed considerable support for GM food products (Figure 14.4) [3, 15, 16]. In 2005 43% of the EU population supported GM food products. If GM food products were healthier, then even 56% would definitely or probably buy these products. Interestingly, the result for cheaper foods showed that a mere 56% would not or probably not buy GM foods if they were cheaper. This latter result further supports the point that opinion surveys cannot be taken at face value for behaviors. Gaskell et al. [3] suggested that some respondents reacted as citizens rather than consumers, as economics indicate that price is a key determinant in people’s choices. A further interesting point is that price is the only fact consumers can actually ascertain themselves directly. For all the other categories they need to trust some organization (authority, industry, medical research) for the information provided with the food. Whatever the reason, this highlights the doubts about opinion surveys as indicators of actual behavior. Third, and perhaps most convincingly, the sales of products labeled as GM remained constant (orally confirmed by large supermarket chain). Although there
14.3 Public Perceptions of Industrial Biotechnology
was no reduction in sales, food companies continue to replace the GM ingredients of the products with non-GM. For example, in the Netherlands there were more than 120 products with GM ingredients with (voluntary) labels in 1999. By 2007 this number had been reduced to 19 [53]. These considerations strongly suggest that food companies and supermarkets replaced their GM products because they were afraid of emotional actions by environmentalists groups rather than being influenced by fewer people buying GM food or trying to protect people from hypothetical risks. The food companies responded to representation from a minority of consumers and the attendant media publicity, and this resulted in an effective halt to the development of cheaper, more sustainable or healthier food products. What can be done to facilitate a sustainable and accepted introduction of applications from industrial biotechnology? From the perception studies and the reactions of scientists, industries, and governments we also learned some lessons about communication. 14.3.4 Development of Public Interaction
Looking back over the years starting from the first Eurobarometer survey in 1991 on biotechnology we can assess how the results influenced politicians, scientists, and industries. One of the outcomes of these first Eurobarometer studies showed that the public throughout Europe had very little knowledge about biotechnology and indicated that knowledge was linked to support. As a result politicians and biotechnology scientists, aiming to increase the support for biotechnology applications in the early 1990s, started information and education campaigns to educate the public. This one-way communication was based on the belief that if more information were made available then the public would understand the potential benefits and increase their support for biotechnology. This is a good example of the so-called “deficit model” of science communication. However it soon emerged that the brochures, leaflets, lectures, education programmes, etc. did not necessarily increase support [17–20]. It became clear that more information tended to lead to further polarization of opinion, whether positively or negatively. For the 1996 Eurobarometer study on biotechnology a group of science communication experts were invited to help in getting a clearer understanding of public perception. The social scientists chose “perceived use,” “risk,” and “moral acceptability” as determinants of public support. People were asked whether they thought each of six biotechnology applications were useful, risky, morally acceptable and if they should be encouraged. The results led to the conclusion that usefulness is a precondition of support and in no case is a “not useful” application given support. For example, GM food products that are similar to “normal” food products but have a lower production cost are not likely to be accepted. People will accept some risk if the application is useful and morally acceptable. For instance, GM foods containing an important vaccine or new medicines produced by yeast are likely to be accepted. Moral concerns, however, acted as a veto regardless of
467
468
14 Societal Issues in Industrial Biotechnology
Public scientists TV journalists Industry scientists News journalists Medical doctors Environmental orgs Consumer orgs Intellectuals Industry Government Politicians
2 2
Military Religious leaders
0
6 6 5
10
16
28 25 23 21
20
52
32
40
60
Figure 14.5 Responses of European citizens to “Who is best qualified to explain science and technology impacts on society?” from Gaskell et al. [3], Eurobarometer Studies available at: http://www.ec.europa.eu/research/press/2006/pdf/pr1906_eb_64_3_final_report-may2006_en.pdf.
views on risk and use. This is shown by the reluctance displayed about the production of medicines by transgenic animals. A main lesson from the study was the conclusion that “if risk is less significant than moral acceptability, then public concerns are unlikely to be alleviated by technically based reassurances and other policy initiatives dealing solely with risks” [19]. The emphasis on communication certainly shifted to show the benefits of new technology and increased the research on risk assessment, risk communication, and risk perception [21–24]. Adams showed that when risks cannot be controlled by individuals and are vague, for example as a result of scientific uncertainty, confidence decreases and an increased demand for regulation is provoked. So who are the most trusted organizations for providing information on the impact of science and technology? As Figure 14.5 shows, the European public finds public scientists the most qualified to explain science and technology impacts on society and scientists working in industry only slightly less so. By now it had also become widely recognized that acceptance could not be achieved by simply providing information alone. Scientists had not only a role to play but also had to listen to, understand and respond to actual public concerns. The reaction of social scientists, politicians, and industry was to redevelop models of communication, as characterized by the development of a dialog model called the Mode-2 model and the upstream engagement model for communication [25–28]. Discursive models of communication have been advocated by pioneers such as Churchman [29] and Rittel, and in the last few years those approaches have been revived [30, 31].
14.4 Societal Issues in Industrial Biotechnology
Government committees advising on policy measures for technology development started to suggest the involvement of scientists [32–35]. The pressure on scientists to be involved in public communication was further increased by requirements for dissemination and public communication in (inter)nationally funded research projects. Increasingly, project criteria include the dissemination of results to broader audiences, followed by active involvement of stakeholders and demands for public dialogs. These forms of “proactive” communication are now seen as crucial for the implementation of novel technologies.
14.4 Societal Issues in Industrial Biotechnology
The lessons from the biotechnology debate are clear; scientists need to be involved in public communication and such communication needs to address societal issues, involve the stakeholders, etc. Several specially funded projects have been carried out over the years to explore the role of scientists, media, and industry and discuss “best practice” [20, 36]. Training courses have been developed9) [37] and curricula for future scientists revisited. But what are the criteria for these novel forms of communication? 14.4.1 Criteria for Communication
Many academics and industrialists have concluded that biotechnology scientists need to increase their involvement in public communication to achieve greater public support. However, there are other, more urgent reasons to pay attention to communication. Independent of this wish for increased acceptance, these reasons are derived directly from the principles of a democratic society. Public involvement in decision-making processes requires public information and the social contract between society and scientific institutes demands accountability. Based on these arguments posed by present developments in society and biotechnology with its important potential impact, a set of evaluation criteria for public communication may be derived [20]. Political agendas and decisions are subject to voters’ opinions. It is necessary therefore that scientists are accountable to the public about their science and their reasons for doing it so that informed decisions can be made. Scientists also have a moral imperative to communicate with the public as only they have understanding at an early stage of the possible impacts of their science for society, which they need to provide for the joint decision-making process. The complexity of novel 9) A number of courses aimed at scientists and industrialists were developed, such as those by the European Task Force on Public Perception (EU Advanced Course on Bioethics and Public Perceptions; later
adapted to the Kluyver Centre Advanced Course on Strategic Communication in Biotechnology); Netherlands Centre for Society and Genomics; European Molecular Biology Organisation; Wellcome Trust.
469
470
14 Societal Issues in Industrial Biotechnology
technologies often leads people to reject new technologies but as people in a democratic system need to be able to weigh up the pros and cons themselves there is also a social obligation on scientists to provide this understanding. Furthermore, if scientists are contracted by society to develop the solutions for tomorrow’s challenges, then society needs to be able to trust them. Trust acts as a summing device when full understanding is not possible. This is the general situation for modern technologies, and especially for the complexities of biotechnology. Trust is based on confidence and knowledge which is claimed to be maintained by inclusivity, transparency, and information. This relates to both factual information and emotional feelings. A component of the contract and trust is accountability [38]. Scientists are contracted and paid for their work by society via taxation and government. They are accountable to society for the uses and outcomes of that payment. The social need for scientists to be accountable, and thereby maintain trust, is an imperative which follows from the contract between society and science. There are also economic reasons for scientists to communicate with the public. The first relates to the fact that the generation of wealth for the functioning of modern societies wholly depends on science and technology. Biotechnology has been promoted as a major generator of wealth. In order to allow society to make informed decisions about the contribution which biotechnology may make to wealth generation, scientists need to explain its economic impact, that is, its benefits, and its costs, to society. This also includes explanation of the costs and benefits to society if a technology that is scientifically feasible is not pursued. The second economic reason is that scientists have to explain why society must return some of the wealth generated by science to science if science and wealth generation is to continue. As society pays for the publicly funded universities and research institutes, it is in the interest of all academics to communicate about their work. Society decides on the amount and distribution of public funding based on this information. However, with competing calls on limited public funds it is in the biotechnologists’ own interest, as with the members of all academic disciplines, to communicate effectively. The foregoing discussion is based on an idealized view of democracy with full public involvement in the decision-making process. However, the reality in democratic societies is that most people are simply not interested in participating in decision making, which is left to the elected representatives and their staff. They in turn tend to be influenced by communicated opinions and perceived public perceptions while subjected to often intense lobbying by special interest groups, although they are finally answerable to the electorate. Therefore the fact remains that the “silent majority” of the public at large is informed. In order to reach this “silent majority,” public communication activities need to stimulate the interest of the public. Because different groups of people have different competing interests and concerns it is also necessary to know and understand their differing interests and concerns. These are not only related to the scientific and technological information, but also importantly to (bio)ethical, safety, social, and legal issues. Scientists need to be able to understand and respond to these issues. Following from the democratic contract of science with society, these social, moral, and economic reasons dictate that scientists inform and participate in the
14.4 Societal Issues in Industrial Biotechnology Criteria for communication by scientists derived from the social, moral, and economic reasons for communication as partners in a contract between science and society [20].
Table 14.1
Criteria for public communication by scientists to inform the decision-making process: Explain science Explain impact Build trust Listen and respond to ethical, legal and social concerns Interest as many as possible Adapt to changes in society
democratic decision-making process, which includes interaction with the public. As in any contract, good performance is in the interest of the performer. It is argued that communication is an implicit task for scientists, therefore it is in their own interest to do this effectively and it is in the interests of academic institutions to facilitate and organize this process. From the above-mentioned arguments it can be concluded that public communication relates to:
•
the availability of knowledge (information on scientific data; information on potential impact of the implementation of derived technologies in society and information on how judgments are made or can be influenced);
• •
the availability of skills for interaction; and the availability of attitude (to encourage public interest and respond to public interests and concerns).
These requirements lead to the criteria for communication by scientists summarized in Table 14.1. 14.4.2 Novel Approaches to Communication
The application of these criteria for science communication asks for novel forms of communication. Importantly the interaction should be mutual (or two-way) which requires preparedness to listen and understanding of each other’s arguments by both sender and receiver. This is not easy to materialize, especially when we wish to create a solution-oriented dialog. Research on novel forms of communication is therefore looking for models with specific attention for discourse (for example focusing on respecting the symmetry of ignorance which is suggested to lead to systematic stepwise learning dynamics [39, 40] and on methods to increase participation of stakeholders [41–43] and of reaching the “uninterested” public majority through entertainment and emotion [44, 45]). There is no doubt that the transition towards a bio-based society is a very complex design problem, which requires more knowledge than any one single
471
472
14 Societal Issues in Industrial Biotechnology
person can possess and creativity to reach reconciliation of views. As we also strive for changes in consumer behavior, it is important that we combine programmes for sustainable technology and product development with programmes focusing on changes in attitudes and behavior [46] and hence in communication. The following case study of the Kluyver Center for Genomics of Industrial Fermentation will give an example of such an approach. 14.4.3 Three International Workshops Identifying Future Issues in Industrial Biotechnology: A Case Study
One of the most important and perhaps difficult challenges for politicians nowadays is the understanding of ethical, legal, and social concerns in society. In order to fully appreciate the relevant societal issues for applications of industrial biotechnology we need to understand the value systems in our (changing) society, identify present and future stakeholders, and unravel the public and political issues into regulatory, ethical, economic, and safety issues. We also need to understand the roles and responsibilities of all stakeholders so that we can define which organizations can be held responsible for addressing these issues. The Dutch public–private partnership “Kluyver Center for Genomics of Industrial Fermentation”10) has carried out a series of three international workshops to identify, understand, and analyze the possible future societal issues in industrial biotechnology. The workshops form part of the Center’s program on genomics and society and were aimed to inform the development of novel communication activities (for a full account, see ref. [47]). The workshops brought together 25 experts from different disciplines and affiliations (such ethics, microbiology, food sciences, risk perception, cultural management from academia, industry, government, European Commission, etc.) and also aimed to develop a coordinated strategy for public dialog. The first meeting explored the scientific trends in industrial biotechnology and their linked societal issues. The second aimed to identify the organizations involved and responsible for addressing these public concerns. The third and last meeting set out to suggest novel ways of communication and recommend a joint agenda for this approach. In their first meeting in 2004, the expert group related scientific trends such as healthy and personalized foods, novel bio-based materials and biofuels with political incentives for industrial biotechnology, concerns about overregulation and the public’s low awareness but known acceptance of the contained use of microorganisms. On this basis they identified the following “future” issues:
• •
Safety, including questions such as those related to contamination of food products by plants producing pharmaceuticals in coexistence with food crops Land-use with the possible food–energy conflicts, the rise of food prices and the loss of rainforests
10) A government-funded Center of Excellence, see http://www.kluyvercentre.nl for more information.
14.4 Societal Issues in Industrial Biotechnology
• • •
Energetics and eco-efficiency questioning the evidence presented on this complex matter leading to concerns of trust Environmental pressure, including concerns on biodiversity; soil depletion, water constraints, and mono-cultures Economic feasibility with respect to the dependence on oil and linked sugar prices and resulting uncertainty for industrial investment.
The second meeting in 2005 identified the main barriers as preparedness for action; economic interests of stakeholders; coordination of agendas, and clarity on regulations and incentives. The participants recommended clarifying the notion of sustainability and searching for new ways of interaction to interest the public. Additionally they recommended building trust by showing responsibility (and preparedness for action) and the involvement and training of young scientists in dealing with this. Although many of the above-mentioned issues were viewed worthy of further exploration, the group decided to focus on biofuels and sustainability in their final meeting in 2006. They took sustainability as the “core value” and proposed a joint agenda for key stakeholders, with the aim of reducing the use of energy and fossil sources while increasing the use of sustainable sources such as biomass. (Figure 14.6). This consensus approach would bring a single message to the public, underlined by a joint agreement, but at the same time would allow organizations to keep true to their interests, shareholders, or constituencies. With sustainability as a core value, industries and academia could focus on the increase of innovation by using industrial biotechnology. NGOs could stress the importance of reduction of energy use and pollution. And governments could develop measures to stimulate both the increase of innovation and the decrease of energy use and pollution.
Recommendations Sustainability as “core value” and joint agenda: – reduction of use of energy and fossil sources – Increase use sustainable sources NGOs:
reduction of energy use
Academia: Government: Industry:
sustainable applications reduction use,
stimulation sustainability
increase sustainability
Figure 14.6 Recommendations of the international expert group of the Kluyver Center workshop on future issues in industrial biotechnology, Brussels, June 2006.
473
474
14 Societal Issues in Industrial Biotechnology
It was recognized that the adoption of this joint agenda would need further discussion with the stakeholders. Therefore it was proposed that “neutrally based” organizations such as local governing bodies and the European Commission would hold stakeholder meetings. These meetings should aim to openly discuss economic interests, values, and trust relations in order to increase understanding of differing viewpoints and decrease the development of wrong perceptions. The experts further recommended that politicians should focus on the removal of bottlenecks with a view to create uniform regulation. They should also focus on the development of clear incentive procedures. Last but not least, it was recommended that research on the development of novel forms of public communication should be increased with special attention on increasing the level of citizen involvement and responsibility. It is interesting to see that these predictions of the possible future issues of this expert group in June 2006 are the ones presently discussed in the media (Autumn 2007). But what do they entail? 14.4.4 Further Analysis of the Identified Societal Issues Related to Industrial Biotechnology
The first issue, safety, is a well-known phenomenon of our present-day risk-averse society. Although it presents itself as a rational and reasonable concern it is actually something much more than that. To begin with, many scientists claim that there is no known rational scientific basis for concern. They argue that fermentation is something that has been used for centuries and the application of GM techniques provides a more precise method than any previous technique used to improve the microorganisms. So far the many studies on risk assessment have not shown any significant risk from modern industrial engineering biotechnology where the regulated precautionary actions are followed. Neither have we witnessed any great accident since the introduction of industrial GM microorganisms some 30 years ago. Furthermore, there is firm and stringent legislation. The safety of GMOs used in industrial biotechnology depends on the characteristics of the organism and its interaction with the environment into which it is (accidentally) released. Safety legislation generally requires risk analysis that can identify and evaluate potential adverse effects of the GMO(s). Host organisms are chosen for their ability to produce the desired product but also for their inability to grow outside the production unit. If GM (micro) organisms are released for applications in the environment, further safety measures are required to minimize human health and environmental adverse effects. The use of the precautionary principle has enforced a very stringent approach to safety in Europe. A definition of precaution is provided in the UNESCO document The Precautionary Principle, published by the World Commission on the Ethics of Scientific Knowledge and Technology (COMEST) in 2005. The Precautionary Principle United Nations Educational Scientific and Cultural Organization. Printed in France SHS-2005/WS/21 cld/d 20/5/:
14.4 Societal Issues in Industrial Biotechnology
When human activities may lead to morally unacceptable harm that is scientifically plausible but uncertain, actions shall be taken to avoid or diminish that harm. Morally unacceptable harm refers to harm to humans or the environment that is
• • • •
threatening to human life or health, or serious and effectively irreversible, or inequitable to present or future generations, or imposed without adequate consideration of the human rights of those affected.
The judgment of plausibility should be grounded in scientific analysis. Analysis should be ongoing so that chosen actions are subject to review. Uncertainty may apply to, but need not be limited to, causality or the bounds of the possible harm. Actions are interventions that are undertaken before harm occurs that seek to avoid or diminish the harm. Actions should be chosen that are proportional to the seriousness of the potential harm, with consideration of their positive and negative consequences, and with an assessment of the moral implications of both action and inaction. The choice of action should be the result of a participatory process. Companies, and increasingly governments, are now requesting deregulation for certain applications including industrial biotechnology, as the present situation is viewed as disadvantaging economic growth. Many supporters of biotechnology point out that the required risk assessments do not include a comparative risk assessment to existing processes, products, or practices. Additionally there is debate among regulators about the abolition of regulation on processes using GM techniques where the product does not contain any GM. Others claim that including an assessment of the potential benefits of the proposed innovation would create an incentive for beneficial innovation. The request for deregulation stands on a sensitive level with the identified necessity for maintaining trust. Risk perception studies, such as those by Adams ([22], see also [48]) have shown that concerns increase and become less rationally based when people are unfamiliar with the actual risk of a technology or material and when they have no control themselves over its use. It is argued, therefore, that the public concerns related to safety are more likely to spring from an issue of control. It is clear that any scientific uncertainty expressed in the public domain will increase the level of public unease and, indeed, the demand for regulation. But regulation needs to be controlled by someone and that is also why maintaining and building trust has been mentioned as a crucial factor in technology innovation. O’Neill has pointed out, however, that although an increase in regulation and control mechanisms will undoubtedly raise the trustworthiness of the system, it
475
476
14 Societal Issues in Industrial Biotechnology
will not necessarily increase trust in the people who are implementing the novel technology [49]. We urgently need to further understand this relationship and find new ways to deal with scientific uncertainty and with emotive public reactions. We also need to find ways which will build or maintain public trust not only in the scientists who develop the technology (and who already are trusted by the public, see Figure 14.5), but also in those who are responsible for regulating and controlling its uses in society. The second issue, land-use, is probably the one that presently creates the most hype. Recent media reports include emotive terms such as “disgrace,” “crime against humanity,” and “food robbers” in the attack of the production of biomass for non-food materials (usually biofuels). Interestingly, the articles that are positive towards biofuel development are less emotive, perhaps with the exception of Al Gore and his supporters in their claims about the use of these technologies against global warming. In essence this “land issue” is an economic one: land owners have to decide on the basis of returns on investment what they will grow. Their choices may influence food prices, for example if they decide to grow non-food energy crops. However, it will be hard to disentangle the effect of land-use from the overall effect of an increasing demand in biomass. A more emotively expressed area in this issue of land-use is the loss of rainforests and the choices made by poor farmers in developing countries to grow bioenergy crops rather than food crops. As some point out, this may result in more local food crises in already struggling countries but also in a higher income which may enable them to import foods. It is unclear how the economy will develop and what will work best for whom. It is interesting, though, to see how this issue on the use of land is linked to an ethical concern of much broader underlying value. While the increase of safety is often sought by people aiming for a higher level of individual autonomy and choice, the issue of land-use is actually used to support an ideology for all. The ideology includes moral values, linked to a view on the natural world but also to values of democracy, equity for people from developed and less-developed countries, and freedom of handling in less-developed countries. Although their intentions may be very well meant, it is those from Western societies without any land themselves who are usually most concerned with these moral issues of land-use. And their well-meant moral values may differ from those of people living in developing countries, leading to accusations of “neo-colonialism.” Some countries have tried to develop regulations to control the sustainable use of our global land (Cramer Report, 2007)11). However it is necessary to realize that people from Western societies are generally in the highest level of “Maslow’s pyramid”, their basic needs for water, food, housing, healthcare, schooling, and employment are fulfilled. This is not the case in developing countries were sometimes even basic requirements such as food and housing are not yet met. People in these circumstances are not able to concern themselves with issues 11) Project group “Sustainable Production of Biomass” (2007). Testing framework for sustainable biomass. Senternorem, The Hague, Netherlands.
14.4 Societal Issues in Industrial Biotechnology
related to “luxury” problems for next generations, such as loss of rainforest or global warming [50]. It is likely, therefore, that consensus will be difficult to achieve as those most willing to enforce it are generally in a position to be able to afford this, while those in developing countries have more urgent needs to fulfill which may prove counterproductive. The third issue is energetics or eco-efficiency. Presently many impact studies are performed to calculate the ecological footprint in terms of energy and materials produced versus energy and materials used in a global setting. These models aim to predict the best crops for a certain desired product produced in the best (most sustainable) way. Because much of the data needed for the calculation are uncertain and the number of variables included in the calculation differ, the models produce very different outcomes. These results are seriously questioned by scientists, industrialists, and NGOs in (industrial and agricultural) biotechnology who relate to these models as predictors for research investments. This issue therefore relates to the uncertainty of evidence and scientific inquiry. Since the results of these models are often used in public interaction as “proof” of a certain viewpoint, the issue of scientific uncertainty and factual evidence is actually magnified. This undermines public trust in scientists for their ability to produce “rational facts.” The heated debate about the validity of the data may also be perceived by the public in a different way, that is, that parties in debate select and use the “facts” which most suit them because they have an (economic) interest which they wish to advance. Such a perception may further decrease the trust relationships and increase public unease with the technology. The effect of scientific uncertainty of evidence, scientific inquiry, trust, and stakeholder perceptions of interests on public unease and technology development needs further study. The fourth issue, environmental pressure, for example for water and soil depletion, looks like another scientific issue. It could be solved as soon as we know how to work the land in such a way that we do not deplete our soil and use too much water and prevent the loss of biodiversity. For the moment this is again a concern of scientific uncertainty on the best way to handle this issue in the short term while solutions are developed for long-term and higher demands. The abolition of tillage and introduction of drought-resistant crops are used as possible solutions, but some fear that there will never be enough water to produce the total amount of crops needed for a biomass economy. This issue further relates to biodiversity, which is a concern for many years related to GM crops and industrial agriculture. Large agricultural practises using monocultures and herbicides and pesticides are often seen as a threat to the diversity of our global plant (and linked animal) kingdom. Diversity is needed as a source of traits (DNA) for future applications in crops or for pharmaceutical products. Areas rich in diversity of species include rainforests, but also areas in extreme environmental conditions are viewed as important providers of genetic material. Presently seed-banks have been created to maintain the traits of rare or nearly extinct sources. However, it is clear that the
477
478
14 Societal Issues in Industrial Biotechnology
in situ maintenance would be preferable as it would also allow for further evolution and creation of new characteristics. Reduction of herbicides and pesticides by using GM crops and a transition to no-tillage practises may also help to maintain biodiversity. The issue of biodiversity and environmental pressure, however, is not only scientific but is also often related to a deeper underlying view of nature. The arguments used in the heated debates on the supposed loss of monarch butterflies in GM cornfields [51] indicate that those concerned for biodiversity are often refusing scientific solutions, but propose to go back to the “original, natural way” of producing crops (such as in organic farming practices). These views often become emotive in heated debate and lose their science-based rationality [52]. The fifth and final issue presented here is economic feasibility. This clearly is an economic issue for the industry involved and not so much a public issue. It refers to the difficulty of industries to convert to sustainable industrial biotechnology production processes. In order to achieve this, industries need to invest in innovation, manpower, and equipment but they have to decide on these matters in an environment of uncertainty. Oil and feedstock prices fluctuate wildly, innovations are still in development (such as second-generation biofuels), while governmental incentives are not clarified and regulations are still being discussed. Although industries are resourceful in creating ways of balancing these uncertainties against their shareholder values, it is clear that clarification of regulation and decisions on incentives will help to speed up the introduction of sustainable processes. 14.4.5 Other Relevant Studies and Committee Reports
Since the 1980s a whole industry of governmental, intercontinental, multidisciplinary, and multi-stakeholder committees has evolved. It reflects a change in democratic decision-making as many involve more parties in the discussion such as representatives of consumer and patient organizations, NGOs, lay people, etc. Several of these committees have produced very interesting reports, such as the UNESCO report on the precautionary principle (2005) and the Netherlands COGEM12) report “Towards an integrated framework for the assessment of social and ethical issues in modern biotechnology” (2003). Both provide clear definitions and/or procedures for evaluation of the state of the art of governing implementation of biotechnology in society. Other studies have delivered high-profile recommendations (such as the EU-US Consultative Forum13), 2000). The recent Cramer Report12) provides guidelines for sustainable development of biofuels, aiming to avoid the use of rainforests and the use of other less sustainable methods. As the players in the discursive process are extending, it is important to have such sources of information available. These studies and reports will also help us 12) Commissie Genetische Modificatie (COGEM) (2003) Towards an integrated framework for the assessement of social and ethical issues in modern biotechnology. 13) Anonymous. The EU-US Biotechnology Consultative Forum: Find Report, December 2000.
14.5 Smooth Introduction of Acceptable Sustainable Industrial Biotechnology
to understand the social practices around the globe and provide useful suggestions for the implementation of global sustainability. It is also important, however, to acknowledge that different stakeholders use different reports, presenting different views or even “facts.” The choices between sources of information (and trust given to these sources) may play a crucial role in the discussion and needs further investigation.
14.5 Conclusions and Discussion: A Joint Agenda for the Smooth Introduction of Acceptable Sustainable Industrial Biotechnology
We have presented an account of what experts believe the impact will be of industrial biotechnology to our society. We have also showed what (European) citizens think they may support, relying primarily on the Eurobarometer surveys, and have indicated the possible social concerns that may arise from these developments. We have drawn some lessons from the GM food debate which we belief give reason for caution for an overoptimistic view to the acceptability of industrial biotechnology. These lessons taught us that more knowledge does not necessarily result in more support for a developing technology. They also gave us more insight in the risk issue and showed that risk can be overridden by moral values. Through the evidence that European citizens do not disapprove of GM foods we argued that a rational approach (in this case to provide informed choice) can sometimes be overtaken by emotional fear. Finally the perception studies showed that scientists are one of the most trusted professionals by the public. On this basis, but also on the argument that our democratic society has a contract with scientists for which they are accountable we argued that scientists have an important role to play in public interaction on the implementation of novel technologies derived from science. The main argument for caution in the introduction of a bio-based society is that the present debate is not based on rationality of reason and that such emotive context may easily result in equally irrational reactions from politics and industries. However, we have also pointed to the lessons learned from improved involvement of all stakeholders in and responsibility for novel forms of public interaction. This requires preparedness for action, and a preparedness to listen to the arguments and take action on concerns. It also necessitates a reconciliation of interests of all parties, which can be done if all parties adopt sustainability as a core value. This is a challenge for the public because sustainability is not something with a direct impact on the individual. And for many it relates directly to a certain view of the world. In contrast, many novel developments in healthcare are often embraced as direct improvements of people’s quality of life. It is doubtful whether new applications for the environment (and hence for future generations) will be received equally positive by all.
479
480
14 Societal Issues in Industrial Biotechnology
14.5.1 Hurdles and Challenges
Politicians are being challenged to come up with the right incentives and regulation, but they are dependent on trustworthy scientific evidence that supports their action. Unfortunately it is just this scientific evidence that is presently so much at stake in the debate. And the debate increasingly ranges from rational to emotive. Taking a position leads to polarization and political inertion. In order to reconcile different views it is important to find common aims. The experts who came together to discuss future issues in industrial biotechnology concluded that “sustainability” could be taken as a core value. They recommended the development of a joint agenda for all stakeholders involved, taking this notion of sustainability as a core value. However, we conclude that in addition to this core value, we need to make sure that plans also address the basic needs of food, health, housing, and employment. In exploring the issues we have seen that personal views may lead to different positions, which are often not brought into the discussion, and may give rise to emotional claims. This necessitates a willingness to come together and discuss a way to reconcile positions and views. It is good to see that this view is shared by several multi-stakeholder organizations such as the European Platform on Sustainable Chemistry together with the European trade organization EuropaBio, the Directorate Science of the European Commission, the Working Party on Biotechnology of the OECD and the World Wide Fund. They have a challenging time ahead. 14.5.2 Recommendations for Further Studies
As argued in the above text an understanding of public concerns is crucial and encompasses a much broader understanding involving values, economic interests, dealing with uncertainty, trust, and responsibility. We showed that although safety issues can represent a demand for individual autonomy, the land-use issue may represent a deeper underlying ideology for global governance. These values are undoubtedly related to different views on the relation between humans and nature, which can be controversial. The question is whether these controversial views on governance and autonomy are held by the same people and whether discussing these underlying values could help in the search for acceptable solutions for sustainable development. With this understanding we need to develop novel forms of interaction with society. 14.5.3 What Does It Mean for Citizens?
A bio-based society will change the landscape, political powers, and our national incomes – all factors with which citizens will need to come to terms. But as argued
References
above, a joint agenda for increased sustainability also depends on a decrease of energy and material use. This requires a responsibility and change of lifestyle for all and a re-evaluation of everything we do (holidays, sports), use (traveling, packaging, etc.), and eat. In that sense it requires that sustainability will become a moral value.
Acknowledgement
This work was (co)financed by the Kluyver Centre for Genomics of Industrial Fermentation and Centre for Society and Genomics which are part of the Netherlands Genomics Initiative/Netherlands Organisation for Scientific Research.
References 1 Gaskell, G. and Bauer, M.W. (2001) Biotechnology 1996–1999: The Years of Controversy, Science Museum, London. 2 Caesar, W.K., Riese, J., and Seitz, T. (2007) Betting on biofuels. The McKinsey Quarterly, 2, 53–63. 3 Gaskell, G., Allansdottir, A., Allum, N., Corchero, C., Fischler, C., Hampel, J., Jackson, J., Kronberger, N., Mejlgaard, N., Revuelta, G., Schreiner, C., Stares, S., Torgersen, H. and Wagner, W. (2006) Eurobarometer 64.3: Europeans and Biotechnology in 2005: Patterns and Trends, A report to the European Commission’s Directorate-General for Research. 4 European Federation of Biotechnology Task Group on Public Perceptions of Biotechnology and the Kluyver Center for Genomics of Industrial Fermentation (2006) Briefing Paper, Regulating Modern Biotechnology in Europe. 5 Konig, A., Cockburn, A., Crevel, R.W.R., Debruyne, E., Grafstroem, R., Hammerling, U., Kimber, I., Knudsen, I., Kuiper, H.A., Peijnenburg, A., Penninks, A.H., Poulsen, M., Schauzu, M., and Wal, J.M. (2004) Assessment of the safety of foods derived from genetically modified (Gm) crops. Food Chem. Toxicol., 42 (7), 1047–1088. 6 Kuiper, H.A., Konig, A., Kleter, G.A., Hammes, W.P., and Knudsen, I. (2004) Food and chemical toxicology – concluding remarks. Food Chem. Toxicol., 42 (7), 1195–1202.
7 van den Eede, G., Aarts, H.J., Buhk, H.J., Corthier, G., Flint, H.J., Hammes, W., Jacobsen, B., Midtvedt, T., van der Vossen, J., von Wright, A., Wackernagel, W., and Wilcks, A. (2004) The relevance of gene transfer to the safety of food and feed derived from genetically modified (GM) plants. Food Chem. Toxicol., 42 (7), 1127–1156. 8 Ajzen, I. (1991) The theory of planned behavior. Organ. Behav. Hum. Decis. Process, 50, 179–211. 9 Spence, A. and Townsend, E. (2006) Examining consumer behaviour toward genetically modified (GM) food in Britain. Risk Anal., 26 (3), 657–670. 10 Chen, M.F. (2007) Consumer attitudes and purchase intentions in relation to organic foods in Taiwan: moderating effects of food-related personality traits. Food Qual. Pref., 18, 1008–1021. 11 Kalaitzandonakes, N., Marks, L.A., and Vickner, S.S. (2004) Media coverage of biotech foods and influence on consumer choice. Am. J. Agric. Econ., 86 (5), 1238–1246. 12 Paschoud, M. and Sakellaris, G. (2007) Public Attidudes Towards the Industrial Uses of Plants : The Epobio-Survey, CPL Press, Newbury, UK. 13 Powell, D.A., Blaine, K., Morris, S., and Wilson, J. (2003) Agronomic and consumer considerations for Bt and conventional sweet-corn. Br. Food J., 105 (10), 700–713.
481
482
14 Societal Issues in Industrial Biotechnology 14 Cook, A.J., Kerr, G.N., and Moore, K. (2002) Attitudes and intentions towards purchasing GM Food. J. Econ. Psychol., 23 (5), 557–572. 15 Gutteling, J., Hanssen, L., Veer, N., and van der Seydel, E. (2006) Trust in governance and the acceptance of genetically modified food in the Netherlands. Public Underst. Sci., 15, 103–112. 16 Noussair, C., Robin, S., and Ruffieux, B. (2004) Do consumers really refuse to buy genetically modified food? Econ. J., 114, 102–120. 17 Durant, J. (1992) Biotechnology in Public, Science Museum, London. 18 Durant, J., Bauer, M.W., and Gaskell, G. (1998) Biotechnology in the Public Sphere: A European Source Book, Science Museum Publications, London. 19 Gaskell, G., Allum, N., Bauer, M., Durant, J., Allansdottir, A., Bonfadelli, H., Boy, D., de Cheveigné, S., Fjaestad, B., Gutteling, J.M., Hampel, J., Jelsøe, E., Correia Jesuino, J., Kohring, M., Kronberger, N., Midden, C., Hviid Nielsen, T., Przestalski, A., Rusanen, T., Sakellaris, G., Torgersen, H., Twardowski, T., and Wagner, W. (2000) Biotechnology and the European public. Nat. Biotechnol., 18, 935–938. 20 Osseweijer, P. (2006) A Short History of Talking Biotech (Thesis), Vrije Universiteit Amsterdam, Amsterdam. 21 Rip, A., et al. (1995) Managing Technology in Society: The Approach of Constructive Technology Assessment, Pinter Publishers Ltd, London. 22 Adams, J. (1995) Risk, University College London Press, London. 23 Rohrmann, B. (1999) Risk Perception Research: Review and Documentation, No. 48, Jülich Research Centre, Jülich. 24 Renn, O. (1999) A model for an analytic-deliverative process in risk management. Environ. Sci. Technol., 33, 3049–3055. 25 Nowotny, H., Scott, P., and Gibbons, M. (2001) Rethinking Science: Knowledge and the Public in An Age of Uncertainty, Polity Press, London. 26 Marris, C., Wynne, B., Simmons, P., and Weldon, S. (2001) Public Perceptions of Agricultural Biotechnologies in Europe:
27
28
29
30
31
32
33
34
35
36
37
38
39
40
Final Report of the PABE Research Project, University of Lancaster, Lancaster, UK. Wynne, B. (1992) Public understanding of science research: new horizons or hall of mirrors? Public Underst Sci., 1, 37–43. Wynne, B. (2006) Public engagement as a means of restoring publiuc trust in science – hitting the notes, but missing the music? Community Genet., 9, 211–220. Churchman, C.W. (1979) The Systems Approach and Its Enemies, Basic Books, New York. Rith, C., and Dubberly, H. (2007) Why Horst W. J. Rittel matters. Des. Issues, 23 (1), 72–74. Rittel, H.W.J. and Webber, M.R. (2005) Dilemmas in a general theory of planning. Policy Sci., 4 (2), 155–169. House of Lords (2000) Science and Society – Report and Evidence, HMSO, London. POST Parliamentary Office of Science and Technology (2001) Open Channels: Public Dialogue in Science and Technology. Report No. 153. The Royal Society and The Royal Academy of Engineering (2004) Nanoscience and nanotechnologies: opportunities and uncertainties, www.royalsoc.ac.uk/policy (accessed 01–02–2010). The Royal Society (2006) Factors Affecting Science Communication: A Survey of Scientists and Engineers, The Royal Society, London. Moses, V. (2002) Biotechnology: Educating the public, European Commission report. Osseweijer, P. (2001) Course Book EU Advanced Workshop on Bioethics and Pubic Perceptions of Biotechnology, EFB Task Group on Public Perceptions of Biotechnology, Delft, The Netherlands. Munnich, G. (2004) Whom to trust? Public concerns, late modern risks and expert trustworthiness. J. Agric. Environ. Ethics, 17, 113–130. Fischer, G. (2000) Symmetry of Ignorance, Social Creativity, and Meta-Design. Knowledge-Based System, 13 (7–8), 527–537. Ammann, K. and Papazova Ammann, B. (2004) Factors influencing public policy
References
41
42
43
44
45
development in agricultural biotechnology, in Risk Assessment of Transgenic Crops, vol. 9 (ed. S. Shantaram), John Wiley & Sons, Inc., Hoboken, NJ. Slingerland, M.A., Klijn, J.A.E., Jongman, R.H.G., and van der Schans, J.W. (2003) The Unifying Power of Sustainable Development. Towards Balanced Choices between People, Planet and Profit in Agricultural Production Chains and Rural Land Use: The Role of Science, Wageningen University, WUR-report Sustainable Development Wageningen (Report), pp. 1–94. Slingerland, M.A., Traore, K., Kayode, A.P.P., and Mitchikpe, C.E.S. (2006) Fighting Fe deficiency malnutrition in West Africa: an interdisciplinary programme on a food chain approach. Njas-Wageningen J. Life Sci., 53 (3–4), 253–279. Pilemalm, S., Lindell, P.O., Hallberg, N., and Eriksson, H. (2007) Integrating the rational unified process and participatory design for development of socio-technical systems: a user participative approach. Des. Stud., 28 (3), 263–288. Osseweijer, P. (2006) A new model for science communication that takes ethical considerations into account – the three-E model: entertainment, emotion and education. Sci. Eng. Ethics, 12 (4), 591–593. Osseweijer, P. (2006) Imagine projects with a strong emotional appeal. Nature, 444 (7118), 422–422.
46 Klapwijk, R., Knot, M., Quist, J., and Vergragt, P. (2006) Using design orienting scenarios to analyze the interaction between technology, behavior and environment in the sushouse project, in User Behavior and Technology Development, vol. 3 , Springer Netherlands, Dordrecht, pp. 241–252. 47 Schuurbiers, D., Osseweijer, P., and Kinderlerer, J. (2007) Future issues in industrial biotechnology. Biotechnol. J., 2007 (2), 1112–1120. 48 Frewer, L.J., Scholderer, J., and Bredahl, L. (2003) Communicating about the Risks and Benefits of Gentically Mddiefied Foods: The Mediating Role of Trust. Risk Anal., 23 (6), 1117–1133. 49 O’Neill, O. (2002) Autonomy and Trust in Bioethics, Cambridge University Press, Cambridge. 50 Driessen, P. (2003) Eco-Imperialism: Green Power, Black Death, Free Enterprise Press, Washington D.C. 51 Wisniewsky, J.P., Frangne, N., Massonneau, A., and Dumas, C. (2002) Between myth and reality: genetically modified maize, an example of a sizeable scientific controversy. Biochimie, 84 (11), 1095–1103. 52 (2008) Integrated farming: Why organic farmers should use transgenic crops. New Bio technology, 25(2) 101–107. 53 Moses, V., coordinator (2008) Do European Consumers Buy GM Foods? (Final report, part I, II, project no 518435, London, Kings College).
483
485
Index a ABE (acetone-butanol-ethanol) process 409, 433 Abraham, Edward P. 12, 13 acarbose 33 Acaryochloris marina 86 accountability 453, 454 acetic acid 1, 26, 297–299 – economic/environmental impact assessments 420, 429, 432–435 acetic acid test for enantioselectivity 165 acetone-butanol-ethanol (ABE) process 409, 433 Acinetobacter baumannii 83 acrylamide 51, 312 Actinobacillus pleuropneumoniae 82, 88 actinomycin D 15, 16 adalimumab (Humira) 44 adhesives, gecko foot hairs 241 adipic acid 420, 429, 432–434 adsorption techniques 285–293, 300, 422 Aedes aegypti 85 aerobic fermentation 134, 140, 421 Aeropyrum pernix 81 affinity chromatography 290 agitated tank fermenters 152 agriculture 35–37 – feed supplementation 203, 204, 354–358 – probiotics 346, 347 Agrobacterium radiobacter – epoxide hydrolase 178 – halohydrin dehalogenase 180 – phosphotriesterase 179 Agrobacterium tumefaciens, N-carbamoylase 179
air, sterilization 140 airlift fermenters 144 alcohols see butanol; ethanol; phenol aldolases – directed evolution 174, 175 – in statin production 317, 318 alternansucrase 351 Amgen Inc. 39, 321 amidase process 319 amino acids – in animal feed 358 – biocatalytic synthesis 20–23, 318–320, 357, 358 – downstream processing 299 – market size 20, 357 L-α-aminoadipic acid 11 7-aminocephalosporanic acid (7-ACA) 13, 308 aminoglycosides 15–17 6-aminopenicillanic acid (6-APA) 11, 308, 309 ampicillin 310 α-amylase – in baking 202, 340, 341 – in detergents 200 – directed evolution 177 – in paper making 204 – in production of resistant starch 353 – in starch hydrolysis 49, 336, 337 β-amylase 177, 202 amyloglucosidase (glucoamylase) 202, 336, 337, 350 amylopectin 336, 341 amylosucrase 353 anaerobic fermentations 134, 421 animal husbandry 36, 37 – feed supplementation 203, 204, 354–358 – probiotics 346, 347
Industrial Biotechnology. Sustainable Growth and Economic Success. Edited by Wim Soetaert and Erick J. Vandamme Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 978-3-527-31442-3
486
Index animals – enzymes derived from 49, 192, 338 – transgenic 47, 48, 356 antibiotics – agricultural uses 36 – biocatalytic synthesis 308–311 – cephalosporins 12–15, 309–311 – historical development 5, 6–20, 77 – penicillins 6–14, 77, 301, 308–311 – purification 301 – resistance to 11, 19, 20 antifoaming agents 146 antifreeze proteins 245, 246 antifungal agents 16, 33 antiglycemic agents 33, 322, 323 antimicrobial peptides 245, 339 antiparasitic agents 18, 36, 37 antiseptics 4 anti-staling agents 341 antitumor agents 35, 42–45 antiviral agents 42, 44 apple juice 203, 345 aqueous two-phase systems (ATPS) see two-phase aqueous systems Aquifex aeolicus 80 Archaeoglobus fulgidus 80 Arcobacter butzleri 86 Arthrobacter sp., hydantoinase and subtilisin 177 ascorbic acid (vitamin C) 24, 25 asexual (non-recombining) evolution 157, 158 Ashbya gossypii 23, 24 aspartame 318, 357, 358 l-aspartic acid 318, 357 Aspergillus fumigatus, phytase 177 Aspergillus nidulans 95 Aspergillus niger – citric acid production 25, 26 – genomics 82, 94 – monoamine oxidase 180 Aspergillus oryzae 95, 140 astaxanthin 301 atorvastatin (Lipitor) 32 – intermediates 172–174 ATP synthase molecular motor 251, 252 Augmentin 15 Autographa californica 47 Avecia Ltd (now NPIL Pharmaceuticals) 316, 317 avermectin 36, 37 azafenidin 313
b Babesia bovis 86 Bacillus spp., Savinase® 177 Bacillus amyloliquefaciens – α-amylase 177, 336 – genomics 86 Bacillus cepacia – biphenyl dioxygenase 178 – toluene monooxygenase 179 Bacillus megaterium, cytochrome P450 174, 178 Bacillus pumilus 86 Bacillus subtilis – esterases 175 – genomics 80, 95 – riboflavin 24 bacterial cell surface display 164, 165 Bacteroides vulgatus 85 baking 202, 340–342 Bartonella tribocorum 87 basiliximab (Simulect) 44 basket bioreactors 227 batch fermentation 135 – environmental conditions 140, 141 – equipment 143–152, 227 – inoculum generation 135, 136 – kinetics 136–138, 141, 142 – media 138–140, 221–227 Bayer Health Care, Miglitol production 322, 323 beer-making 1, 27, 28, 203, 342–344 benzoylformate decarboxylase 179 beta-lactam antibiotics see cephalosporins; penicillins beta-lactam rings 308 bialaphos 36 bifidobacteria, probiotic 346, 347 biocatalysts 211–221, 227 – see also enzymes Biochemical Pathways 75, 76 biocomposites 242, 243 bioconversion see bioreactors; enzymes; fermentation; media; process development biodiesel (VOME) 398–402 biodiversity 405, 406, 460–462 bioethanol see ethanol biofilms 385 biofragrances 30 biofuels – biodiesel 398–402 – butanol 29, 409, 420, 429, 432 – economic/commercial considerations 398–400, 405, 406
Index – ETBE 325, 397, 398, 404, 405 – ethanol see ethanol – public opinion 446 – sustainability 405, 406, 413, 414 – synthesis gas/motor fuel 409–412 biomimicry 238 – gecko foot hairs 241 – nacre 242, 243 – spider silk 239–241 biomineralization 242, 243 bio-oils 410 biopigments 30 bioreactors – full-scale 143–152, 227, 228 – miniature 229, 230 – nano-scale 253, 254 biorefineries 72, 369, 387, 388, 412, 413, 444, 446 biosensors 206, 253 Biostil®2000 process (ethanol production) 297 biosurfactants 302 biotechnology – definitions 64, 236, 443 – history and development 37–41, 77, 78 biotin 21 biotin tyramide labeling 163 biphenyl dioxygenase 178 bipolar membrane electrodialysis 294, 299 bleaching – in the paper industry 379–382 – in the textile industry 204 Bonner, David 11 Borrelia burgdorferi 80 Bradyrhizobium sp. 84 breadmaking 202, 340–342 brewing 1, 27, 28, 203, 342–344 bringer technique 158 Brotzu, G. 12 Brugia malayi 86 BT toxin 37 BtL process for biofuel production 409–412 bubble column fermenters 143 Buchner, Eduard 5, 28 Burkholderia cepacia 170 butanol 6, 29, 409, 420, 429, 432
c CAC (continuous annular chromatography) 292, 293 Caenorhabditis elegans 81 cakes 342 calcium oxalate 385 Campylobacter jejuni jejuni 86
Candida antarctica lipase B 169, 170, 314 Candidatus Cloacamonas acidaminovorans 88 Candidatus Sulcia muelleri 87 Cape, Ronald 39, 40 N-carbamoylase 179 carbapenems 15 carbohydrases see individual enzymes carbohydrates 249 – nanobiotechnology 249, 250 – prebiotic 347–354 – see also cellulose; starch; sugars carbon dioxide – greenhouse gas emissions 405, 414, 426, 429–431, 444 – as a solvent (supercritical fluid) 226, 281, 282 Cargill Dow LLC (polylactic acid) 313, 325 carotenoids 301 carriers for biocatalyst immobilization 218, 219 CASTing (combinatorial active-site saturation testing) 160 cell membranes – disruption techniques 271, 272 – increased permeability 21, 22, 215, 216, 245 – phospholipid structure 248 cellobiohydrolases 371, 382, 408 cellulases – in biofuel production 29, 205, 408, 409 – in detergents 49, 202 – economics of production 196 – in the paper industry 371, 378, 382 – in the textile industry 204 cellulose 371, 406, 407 centrifugation 268–270 cephalexin 310, 311 cephalosporins 12–15, 309–311 cephamycin C 14, 15 Cetus Corporation 39, 40 Chain, Ernst B. 7, 8 cheesemaking 49, 338, 339 chemical industry – bioconversions used in 51, 205, 311–314 – commercial environment 307, 320–332, 417, 418 chemometrics 229 chill haze 343, 344 chiral compounds – biocatalytic synthesis 311, 312, 314–318 – directed evolution of enantioselective enzymes 168–171, 176
487
488
Index – screening assays for enantioselectivity 165, 167 – separation methods 285, 290, 291, 294, 295 Chlamydia trachomatis 81, 88 Chlamydomonas reinhardtii 86 Chlamydophila pneumoniae 81 chlorine, in the paper industry 381 chromatography – continuous 291–293 – countercurrent 283 – molecular imprinting 293, 294 – protein purification 197, 300 – size exclusion 276 – stationary phase systems 286–291 chymosin 49, 338 ciclosporin 33 circular permutation 159 citric acid 6, 25, 26, 297–299, 421 clathrates 248 Clavibacter (Corynebacterium) michiganensis 84, 88 clavulanic acid 15 Clostridium botulinum 84, 85 Clostridium kluyveri 85 Clostridium thermoaceticum 26 Clostridium thermocellum 29 clotting factors 43 cobalamin (vitamin B12) 24 coccidiostats 36 Codexis Inc., statin production 314–316 codon bias 158 cofactor regeneration 214, 215 Cold Spring Harbor Laboratory, patents 77 colony-stimulating factors 43 coloring agents 30, 320–322 combinatorial biosynthesis 18, 19, 205 communication with the general public 451–456, 458, 462–464 compactin (mevastatin) 32 compartmentalization, in flux balance analysis 99, 100 computer software tools – enyzme–substrate reactions 229 – random mutagenesis 159, 160 computers, DNA 252 concentration polarization 273 constant pressure filtration 267 contact lens care products 206 continuous annular chromatography (CAC) 292, 293 continuous feed stirred tank reactors 228 continuous fermentation 135, 195 – assumptions concerning future technology 421
– environmental conditions 140, 141 – equipment 143–149, 151, 152, 228 – kinetics 142, 143 – media 138–140, 221–227 continuous screw fermenters 152 Coprinus cinereus, heme peroxidase 176 corn starch – as a feedstock for industrial production 403, 425, 431 – processing 49, 202, 203, 336, 337 Corynebacterium glutamicum 22, 23, 83, 96 cosmetics see personal care products countercurrent extraction 280, 283 Crick, Francis 37, 38 crossflow filtration 274, 275 crystallization 284, 285, 309, 310, 422 cyanohydrins 319, 320 (R)-4-cyano-3-hydroxybutyric acid 170, 174 cytochrome P450 monooxygenase 174, 178
d dairy products 49, 203, 337–340 – antifreeze proteins in 246 decanter centrifuges 270 decision-making process in democracies 453–455, 462–464 dehydrogenase screening assays 166, 167 deinking 381 Deinococcus radiodurans 81 denim 204, 321 dental care products 206 desferal 33 detergents, enzymes in 49, 50, 200–202 dextran 30, 342 dextransucrases 342, 351, 352 dextrose 336 diastereoisomeric crystallization 285, 309, 310 diauxic growth 138 Dichelobacter nodosus 84 diesel (VOME) 398–402 dietary supplements 346–354 directed evolution 50, 51, 157 – assay systems 161, 162 – – in vitro selection 162, 163 – – in vivo selection 163, 164 – – screening 163–167 – combined with rational protein design 160, 161 – compared with rational protein design 155, 156 – examples – – aldolases 174, 175 – – cytochrome P450 monooxygenase 177
Index – – halohydrin dehalogenase 177, 315, 316 – – hydrolases 168–170 – – nitrilase 170, 171 – mutagenesis methods 157–160 disk stack centrifuges 270 displacement chromatography 289 distillation 277, 422 – ethanol 296, 297 – membrane distillation 277, 278 distribution coefficient 279, 280 Diversa Corporation, statin production 316 DNA, structure 247 DNA computers 252 DNA-modifying enzymes – DNase for cystic fibrosis 43 – in molecular biology 157, 158, 206, 207 DNA shuffling 50, 158, 159 DNA technology see recombinant DNA (rDNA) technology Domagk, Gerhard 5 doramectin 18 doubling times 137 downstream processing 263–265 – economic/environmental impact assessments 421–423 – product groups – – alcohols 296, 297 – – amino acids 299 – – antibiotics 301, 309, 310 – – biosurfactants 302 – – carotenoids 301 – – organic acids 284, 294, 297–299 – – polyhydroxyalkanoates 302 – – proteins 196, 197, 282, 284, 290, 300 – separation techniques 153, 154, 266 – – adsorption 285–293, 300, 422 – – cell disruption 271, 272 – – drying 295, 296 – – electrodialysis 294, 299 – – molecular imprinting 293, 294 – – size-based 269, 272–276, 423 – – solid–liquid 265–271, 274 – – solubility-based 279–285, 297–299, 301, 309, 310, 422 – – volatility-based 276–279, 296, 297, 422, 423 DRIVeR software 159 drying methods 295, 296 DSM 311, 317, 318, 319, 320, 343, 344 DuPont, PDO production 77, 78, 109–111, 325 dyes 320–322
e economics 322–325, 326–330 – biofuels 398–400, 405, 406 – commodity prices 112, 324, 327, 328, 428, 443, 444 – energy use 378, 382, 422 – impact assessments 435, 436 – – methodology 418–422, 426–428 – – results 431–435 – innovation 236, 237 – market sizes 49, 64, 322, 329, 330, 445 – process economics 65, 69, 196, 263, 264, 327, 328, 426, 427 – public engagement with biotechnology 454 ectoine 323 Ehrlich, Paul 4, 5 E.I. Du Pont de Nemours and Company, PDO production 77, 78, 109–111, 325 electrodialysis 294, 299, 422 electropolishing 148 enantioselectivity – biocatalytic synthesis 311, 312 – directed evolution of 168–171, 176 – in screening assays 165, 166 – separation of racemic mixtures 285, 290, 291, 294, 295 endoglucanases 372, 374, 383, 408 endomannanases 373, 374, 384 energy use – in bioconversions 422 – non-renewables 426 – in the paper industry 378, 379 – societal issues 460, 461 entrained-downflow reactors 411 environmental considerations – biodiversity 405, 406, 460–462 – biofuel production 405, 406, 413, 414 – impact assessments 436 – – methodology 418–426 – – results 428–431 – in the paper industry 381–383 – process development 65–67, 69, 226, 326 – sustainability as a core value 457 – waste reduction 325, 326 enzyme inhibitors 31–33 enzymes – design methods 155–160, 197–200 – – assay systems for 161–168, 193 – – examples 168–178 – history of biotechnology 5, 48–51 – immobilization 216–221, 227
489
490
Index – industrial uses 200–207, 254, 255 – production 192–197 – – downstream processing 196, 197, 282, 284, 290, 300 – selection 193, 213 – – production strain 193, 194 – – whole cells vs isolated enzymes 214–216 – see also individual enzymes Epicurian coli XL1-Red 158 epoxide hydrolase 182 Eremothecium ashbyi 23, 24 ergot alkaloids 35 error-prone polymerase chain reaction (epPCR) 157, 158 erythromycins 19 erythropoietin (EPO) 42 Escherichia coli – genomics 80, 88, 91 – as host for recombinant proteins 45, 46, 222 – PDO production 29, 110, 111 eSCRATCHY software 160 eShuffle software 160 esterases – EstA used in selection assays 163 – examples of directed evolution 168, 169, 174, 179 – screening assays for 164–166 – in wood pulp processing 374 esterification of vegetable oils 400, 401 etanercept (Enbrel) 44 ETBE (ethyl-tertiary-butyl-ether) 325, 397, 398, 404, 405 ethanol – as a biofuel 28, 29, 106, 327, 328, 397–400, 404, 405 – economic/environmental impact assessments 420, 421, 429, 432–434 – feedstock 388, 403, 405, 406, 425, 431 – production methods 29, 403, 404, 406–409 – – downstream processing 296, 297 – – history 1, 3, 27–29 – – metabolic models 70–72, 106–108 – production volumes 28, 70, 105, 106, 398 ethene (ethylene) 432–434 ethical concerns 442, 451, 452, 460 – precautionary principle 458, 459 ethyl alcohol see ethanol ethyl lactate 432–434 ethyl tertiary-butyl ether (ETBE) 325, 397, 398, 404, 405
ethylene 432–434 Europe – biofuels 398–400, 402, 405 – GM foods 338, 449, 450 – public opinion 446–452 evaporation 285, 295, 296, 422, 423 Evonik Industries AG, l-tert-leucine synthesis 318, 319 expanded bed chromatography 291, 292 exponential growth kinetics 137, 141, 142 extraction techniques 271, 279–283, 422 – antibiotics 301 – organic acids 299 extremophile enzymes 49, 50, 200
f F0F1 ATP synthase molecular motor 251, 252 factor VIII 43 fatty acid ethyl esters (FAEE) 401 fatty acid methyl esters (FAME) 400, 401 fatty acids 248, 339 FBA (flux balance analysis) 67, 68, 99–105, 107 – see also metabolic flux analysis fed-batch fermentation 135 – environmental conditions 140, 141 – equipment 143–152, 227 – media 138–140, 221–227 – in penicillin production 10, 11 – see also batch fermentation feedstocks 70, 387–388 – for biodiesel 400, 402 – for bioethanol 388, 403, 405, 406, 425, 431 – environmental impact 405, 406, 429–431 – nitrogen in 331 Feigl-Anger assay 167, 168 fermentation – classification 133, 134 – economic/environmental impact assessments 420, 421, 423 – environmental conditions 140, 141 – enzyme production 194–197 – equipment 143–152, 227, 228 – history 1–6, 10, 11, 20 – kinetics 136–138, 141–143 – media 138–140, 221–227 – methodologies 134–136, 194–196 – see also downstream processing fiber engineering in the pulp and paper industry 371, 385–387
Index filtration – problems with antifoaming agents 146 – size-based separation 196, 269, 272–276 – solid–liquid separation 265–268, 274 – sterilization of culture media 139 Finegoldia magna 88 Fischer-Tropsch process 412 Flavobacterium psychrophilum 85 flavor enhancers 20–23, 357 Fleming, Alexander 6, 7 Florey, Howard W. 7 flotation techniques 271 fluidized bed fermenters 144, 145, 228 flux balance analysis (FBA) 67, 68, 99–105, 107 – see also metabolic flux analysis fluxomics – definition 71 – flux balance analysis 67, 68, 99–105, 107 – metabolic flux analysis 108, 110, 111 foaming, in bioreactors 146 focused directed evolution 160, 161, 168 food industry – artificial sweeteners 318, 340, 351, 357, 358 – baking 202, 340–342 – brewing 1, 28, 203, 342–344 – dairy products 49, 203, 246, 337–340 – dietary supplements 346–354 – flavor enhancers 20–23, 357 – fruits 203, 344, 345 – GM food products 338, 442, 446–451 – history 1, 20, 21, 28, 49, 335 – sugar production (from starch) 49, 202, 203, 336, 337 – wine making 1, 28, 203, 345 forestry 369, 370, 406 forward metabolic engineering, definition 71 fractional crystallization 285 fragrances 30 Francisella tularensis tularensis 83 freeze-drying 296 Freundlich isotherm 286 fructooligosaccharides 348 fructose-containing syrup 49, 203, 337 fruit processing 203, 344, 345 fullerenes, in molecular motors (‘nanocars’) 252 functional foods 346–354 Fusarium graminearum 86
g galactooligosaccharides 348–350 β-galactosidase 339, 340, 348–350 gas stripping 277, 422 gasification 411 gecko foot hairs 241 gel filtration (size exclusion chromatography) 276 gene site saturation mutagenesis (GSSM) 170, 171 Genencor International 109 Genentech Inc. 39, 77 genetically modified (GM) foods 338, 442, 443, 446–451 genetics see mutagenesis; recombinant DNA (rDNA) technology genome-scale metabolic models (GSMMs) 72, 90, 104, 105 – ethanol production in S. cerevisiae 106, 107 genome-scale metabolic reconstructed networks 67–90, 115, 116 – M. succiniproducens 93, 114, 115 – organisms studied 91–98 – production 99–104 genomics 71, 77–89 Geobacillus thermodenitrificans 83 germ theory of disease 3, 4 GHG (greenhouse gas) emissions 405, 414, 426, 429–431, 444 Giardia lamblia (intestinalis) 86 gibberellins 36 glucanases – in the animal feed industry 203, 356 – in the brewing industry 203, 342, 343 – endoglucanases 372, 374, 382, 408 – xyloglucanases 372, 386 glucansucrases 350–352 glucoamylase 202, 336, 337, 350 glucocerebrosidase 43 glucomannans 373, 374 α-glucooligosaccharides 350–352 β-glucooligosaccharides 354 glucose 202, 336, 425 glucose isomerase 49, 337 glucose oxidase 206, 341 glucosidases – β-glucosidase 345, 354, 370, 408 – glucoamylase 202, 336, 337, 350 glucuronoyl esterase 374 GLUE software 159 L-glutamate 20–22, 318, 357 glutaryl acylase 179 gluten 341 glycerides 248
491
492
Index glycosidases 345 glycosylation 46 GM (genetically modified) foods 338, 442, 443, 446–451 Gosio, Bartolomeo 34 government policies 444, 445 – on biofuels 106, 399, 400 GRAS (generally recognized as safe) microorganisms 193 Greaves, J.D. 73 greenhouse gas (GHG) emissions 405, 414, 426, 429–431, 444 growth hormone 42 GSMM (genome-scale metabolic models) 72, 90, 104, 105 – ethanol production in S. cerevisiae 106, 107 GSSM (gene site saturation mutagenesis) 170, 171 gut microbiome – genomics 87 – probiotics and 346, 347
h Haemophilus influenzae 80, 93 haloalkane dehalogenase 179 Halobacterium salinarum 88 halohydrin dehalogenase 173, 180, 315, 316 Hansch parameter 224 health issues 325, 326, 458–460 Heatley, Norman 7, 8 Helicobacter pylori 80, 81, 93 hemicellulases 373, 374 hemicelluloses 373, 377 Hemiselmis andersenii 87 herbicides 35, 36, 313 Herceptin (trastuzumab) 44 Herminiimonas (Cenibacterium) arsenicoxydans 83 HETP (height equivalent to a theoretical plate) 288, 289 hexenuronic acid 379 hexose oxidase 341 high fructose corn syrup (HFCS) 49, 203, 337 high-throughput screening (HTS) 161–168, 193 homogenization of cells 271, 272 human growth hormone (hGH) 42 humans, genomics 86, 97 hydantoinase 177, 310 hydrocyclones 270 hydrogenation of vegetable oils 402 hydrolase screening assays 164–166
hydrophobic interaction chromatography 290 hydroxy-ectoine 323 hydroxynitrile lyases 167, 168, 320 d-hydroxyphenylglycine 309, 310 Hyperthermus butylicus 82
i ice cream 246 ice-structuring proteins 245, 246 idiolites (secondary metabolites) 30–35, 138 – see also antibiotics imatinib (Gleevec) 45 immobilization of biocatalysts 216–221, 227 immunosuppressants 33, 34 immunotherapy – immunization 4, 51 – interferons 42 – monoclonal antibodies 35, 44 in situ product recovery 264, 265, 270 in vitro evolution see directed evolution in vitro selection techniques for mutants 162, 163 in vivo selection techniques for mutants 164, 165 inclusion bodies 45, 46 indigotin 320–322 industrial biotechnology, definitions 64, 443 industrial systems biology 67–72, 104, 105, 115–117 – bioethanol (S. cerevisiae) 105–108 – definition 71 – genomic research 77–89 – PDO (E. coli) 109–111 – succinic acid (M. succiniciproducens) 112–115 – see also genome-scale metabolic reconstructed networks infliximab (Remicade) 44 ink removal from waste paper 383 inoculum generation 135, 136 insect cells, in rDNA technology 47 insecticides 36, 37, 319 insulin 41, 42 interfacial catalysis 223 interferons 42 interleukins 43 inulin 348 inverse metabolic engineering 71, 72 ion exchange chromatography 290 ion exchange membranes 294
Index ionic liquids, as bioconversion media 224, 225 IP6 (myo-inositol hexakisphosphate) 354–355 isomaltooligosaccharides 350 ITCHY (incremental truncation for the creation of hybrid enzymes) 159 iterative saturation mutagenesis (ISM) 160 ivermectin 37
j jackets, for bioreactors 148 Janthinobacterium sp. 85 Johnson, Marvin 10
k Kaneka Corporation 310, 316 ketoreductases 314–317 kinesins 251, 252 kinetics – batch fermentation 136–138, 141, 142 – continuous fermentation 142, 143 – microbial growth and metabolism 73–75 Kluyver, Albert Jan 73 Kluyver Center for Genomics of Industrial Fermentation, workshops 456–458 Koch, Robert 3 koji fermentations 1, 141, 149–151 König reaction 167 kraft cooking of wood pulp 372, 376–378 Krebs, Hans A. 75, 76 Kyoto Protocol 444
l Laccaria bicolor 87 laccase-mediator system (LMS) 379, 381, 382 laccases 204, 254, 255, 375, 379 lactase (β-galactosidase) 339, 340, 348–350 lactic acid 27, 297–299 – economic/environmental impact assessments 420, 429, 433 Lactifit® 350 Lactobacillus spp. 27 – genome 87 – GSMMs 95 – probiotics 346, 347 Lactococcus lactis 82, 95 lactose 339, 340 lactosucrose 340 lag phases in batch fermentation 136, 138 land use for biomass production 405, 426, 430, 431, 444, 460 Langmuir isotherm 286
laundry detergents, enzymes in 49, 50, 200–202 leather industry 205 Leeuwenhoek, Antonie van 1, 2 l-tert-leucine 318, 319 Leuconostoc citreum 88 life cycle assessments 423–426, 428–431 lignin – bleaching 379–382 – composition of lignocellulosic biomass 368, 369, 373, 407 – oxidative enzymes 373–375 lignin peroxidases (LiPs) 374 lignocellulosic biomass – composition 371–373, 407 – as a feedstock 387, 388, 406, 425, 429–431 – production of biofuels from 205, 406–412 – see also paper and pulp industry lipases 222, 254, 314 – in cheesemaking 50, 339 – directed evolution 168–170, 175 – in the paper industry 379 – screening assays for 165 lipids 247–249 Lipitor (atorvastatin) 32 – intermediates 170–172 lipoxygenase 341 lipstatin 33 LMS (laccase-mediator system) 379, 381, 382 log phase growth 137, 141, 142 lovastatin (mevinolin) 48 l-lysine 11, 22, 23, 318, 358 Lysinibacillus sphaericus 88 lysozyme 272, 339
m Macaca mulatta 83 macrolides 19 Malassezia globosa 87 maleic anhydride 112 malting 342, 343 maltose 337 mammalian cells, in rDNA technology 47 manganese-dependent peroxidase (MnP) 374, 375 mannanases – in the animal feed industry 357 – in the paper industry 372, 373, 383 Mannheimia succiniproducens 93, 113–115 marine microbial/plankton communities 83, 86 mass balance analysis 101–103
493
494
Index materials science 238 – gecko foot hairs 241 – immobilization of biocatalysts 218, 219 – nacre 242, 243 – nanoparticles 219, 237, 238 – spider silk 239–241 media – fermentation 138, 139 – non-aqueous 221–227 – sterilization of 139, 140 MEGAWHOP technique 158 membrane separation methods – adsorption 290 – chiral separation 294, 295 – distillation/pervaporation 277–279 – electrodialysis 294, 299 – filtration 267, 268, 272–276 – in the future 422 – perstraction 281 membranes, cellular see cell membranes metabolic control analysis 99 metabolic engineering 63, 67–69, 115–117 – definition 71 – ethanol (S. cerevisiae) 70–72, 105–108 – genomics 77–89 – lysine (C. glutamicum) 22, 23 – PDO (E. coli) 109–111 – research history of microbial metabolism 73–76 – succinic acid (M. succiniproducens) 112–115 metabolic flux analysis (MFA) 75 – ethanol production (S. cerevisiae) 108 – PDO production (E. coli) 110, 111 metabolomics, definition 71 metagenomics, definition 71 Metallosphaera sedula 84 Methanobrevibacter smithii 84 Methanocaldococcus jannaschii 80 Methanococcus jannaschii 94 methanogenic archaeon RC-I 83 Methanosarcina barkeri 97 Methanothermobacter thermoautotrophicus 80 methionine 357 mevastatin (compactin) 32 mevinolim (lovastatin) 32 micelles 248, 249 microbiology, history 1–20, 73–76 Microcystis aeruginosa 87 microfiltration 267, 268, 274 microscale processing 229, 280 Miglitol 322, 323 milk processing 49, 203, 337–340
modeling techniques – in process development 229 – random mutagenesis 159, 160 – see also genome-scale metabolic models molds 46, 47 – see also Aspergillus; Penicillium molecular evolution see directed evolution molecular imprinting 293, 294 molecular modeling 229 molecular motors 250–252 monensin 36 monoamine oxidase 180 monoclonal antibodies, therapeutic 35, 44 Monod, Jacques 75 Monodelphis domestica 84 monomer production 51, 312–314 – see also 1,3-propanediol monoseptic fermentations 134 Monosiga brevicollis 103 monosodium glutamate (MSG) 20–22, 357 moral concerns 442, 451, 452, 460 – morally unacceptable harm 458, 459 mother of pearl (nacre) 242, 243 mouse (Mus musculus) 98 moving bed chromatography 291, 292 MRSA (methicillin-resistant S. aureus) 20, 96 Mullis, Cary 40 mutagenesis – focused directed evolution 160, 161 – random 50, 51, 73 – – assay systems for 161–168, 193 – – examples of directed evolution 168–180 – – methods used in directed evolution 157–160, 170, 171 – – software evaluation tools 159, 160 – – strain selection for antibiotic production 9, 17–19 – site-directed 50, 156, 170, 199 mutator strains 158 Mycobacterium tuberculosis 80, 96 mycophenolic acid 34 Mycoplasma genitalium 80 Mycoplasma pneumoniae 80 myo-inositol hexakisphosphate (IP6) 354, 355
n nacre 242, 243 nanobiotechnology 255, 256 – biomimicry of materials 238–243 – bioreactors 253, 254 – biosensors 206, 253 – commercial development 237, 239, 246
Index – definition 236 – molecular building blocks 235, 236, 243–250 – nanomachines 250–252 – scaffolds 255 nanofiltration 274, 275 nanoparticles 219, 237, 238 naphthalene dioxygenase 321, 322 NatureWorks plant (Nebraska) 314 Neisseria meningitidis 87 Nematostella vectensis 86 neomycin 16 Newton, Guy G.F. 12 NextBtL process for biofuel production 402 Nitratiruptor sp. 85 nitrilases – examples of directed evolution 170, 171, 180 – in statin production 316 nitrile hydratase 312, 313 nitrogen – in feedstocks 331 – in fermentation media 138 non-renewable energy use (NREU) 426 NPIL Pharmaceuticals (formerly Avecia), statin production 316, 317 nucleotides 23, 247 nystose 349
o oil prices 112, 324, 327, 328 oligosaccharides, prebiotic 347–354 OptKnock process (metabolic engineering) 117 oral microbial communities 84 orange juice 203, 345 organic acids 25–27 – downstream processing 284, 294, 297–299 – economic/environmental impact assessments 420, 429, 432, 433, 434, 435 – see also individual acids organic solvents – as bioconversion media 221–224 – in downstream processing 279–281, 283, 284, 299 Orientia (Rickettsia) tsutsugamushi 84 Orlistat 33 Ostreococcus lucimarinus 84 oxalate-removing enzymes 385 oxidases – in baking 341, 342 – in the paper industry 372–374, 378, 386 – see also laccases; peroxidases
oxidation, biocatalytic 311, 312 oxidoreductase screening assays 166, 167 oxygen, in fermentation 138, 140, 146 oxygenase screening assays 167
p packed-bed columns 286–291 palivizumab (Synagis) 44 paper and pulp industry 369–370 – bleaching 379–382 – enzymes used 204, 370–375, 377–380, 382, 383 – equipment cleaning 385 – fiber engineering 369, 385–387 – paper making 382, 383 – pulping 376–379 – recycling 383, 385 Parabacteroides distasonis 85 partitioning allocation procedure 424, 425 Pasteur, Louis 2–5 patents 77, 78 PCPP (production cost plus profits) analysis 426, 427, 431–435 PDO see 1,3-propanediol pectinases 203, 344, 345, 383 PEDEL software 159 PEG (polyethylene glycol) 282, 283 penicillins – history 6–14, 77 – purification 301 – synthesis 308–311 Penicillium spp. 7, 9, 10 pentose sugars 77, 107, 108, 409 peptides 243–245 permeability of cell membranes 21, 22, 215, 216, 245 peroxidases 166, 167, 174 – in the paper industry 374, 375 personal care products 30, 206, 323, 324 perstraction 281 pervaporation 278, 279, 297, 422 phage display 161 pharmaceutical industry 4, 5, 39–41, 322–324 – discovery of new compounds using combinatorial biosynthesis 18, 19, 205 – products 31–35, 41–45, 314–318 – see also antibiotics PHAs see polyhydroxyalkanoates phenol 330, 331 phenotypic phase planes (PhPP) 103, 104 – S. cerevisiae 106 l-phenylalanine 318, 357 d-phenylglycine 309, 310
495
496
Index phosphatases see phosphotriesterases; phytases phosphoketolase pathway 108 phospholipases 170, 342 phospholipids 248 phosphotriesterases 179 Physcomitrella patens patens 88 phytases 50, 177, 344 – in animal feed 203, 204, 354–356 Pichia pastoris 46 Pichia stipitis 82 pigs 354–356 pitch (resin) 204, 380 PLA (polylactic acid) 313, 325, 328, 432, 434 plants – enzymes derived from 49, 192 – transgenic 48 Plasmodium falciparum 93 plastics, biodegradable 30 – economic/environmental impact assessments 328, 420, 429, 432–434 – production methods 313, 314 – public support for 446 plug flow fermenters 135, 143, 227, 228 polishing of bioreactors 148, 149 polyethylene glycol (PEG) 282, 283 polyhydroxyalkanoates (PHAs) 30, 302 – economic/environmental impact assessments 420, 429, 432–434 polylactic acid (PLA) 313, 325, 328, 432, 434 polymerase chain reaction (PCR) 40, 157, 158 polymers 29, 30, 212, 213 – economic considerations 326–328 – hybridized with peptides/proteins 246 – production methods 312–314 polynucleotides, self-assembly 247 polytrimethylene terephthalate (PTT, 3G+) 30, 429, 433, 434 poultry 36, 203, 347, 354–356 pravastatin 32 prebiotics 347–354 precautionary principle 458, 459 precipitation 284, 298, 422 pressure, in bioreactors 146 primary metabolites 138 – see also amino acids probiotics 346, 347 process development 65–70, 105, 211–213, 228–230 process economics 65, 69, 196, 263–264, 327, 328, 426–427
process flow diagrams 418, 419 Prochlorococcus marinus 82, 83, 86 production cost plus profits (PCPP) analysis 426, 427, 431–435 1,3-propanediol (PDO) 29, 77, 78, 109–111, 313, 314 – economic/environmental impact assessments 420, 429, 432–434 ProSAR technique 160, 161 proteases – in brewing 343, 344 – in the dairy industry 339 – in the leather industry 205 protein engineering see directed evolution; rational protein design proteomics, definition 71 Pseudomonas sp., glutaryl acylase 181 Pseudomonas aeruginosa, lipases 168, 169, 176 Pseudomonas diminuta, phosphotriesterase 181 Pseudomonas fluorescens, esterases 169, 176 Pseudomonas pseudoalcaligenes, biphenyl dioxygenase 178 Pseudomonas putida, benzoylformate decarboxylase 181 public perception of biotechnology 441, 442, 445–451, 463, 464 – scientific communication affecting 451–456 Pulley, H.C. 73 pullulanase 202, 336, 350 pulp industry see paper and pulp industry Purdue Research Foundation, patents 77 purification see downstream processing pyrethroids 319 Pyrococcus horikoshii (shinkaj) 80 pyrolysis 410, 411
q Quick E screening assay 165, 166 QuikChange™ technique 156, 158 quinolones 17
r RACHITT (random chimeragenesis on transient template) 158, 159 RaMuS software 160 rapamycin (sirolimus) 33, 34 rational protein design 155–157, 199, 200 – combined with directed evolution 160, 161
Index raw materials see feedstocks reactive extraction 281 recombinant DNA (rDNA) technology – DNA-modifying enzymes used in 206, 207 – enzymes 49–51, 198, 199 – history of 18, 39–41, 49, 50, 78 – host cells 45–48 – pharmaceuticals 41–45 – see also genetically modified (GM) foods Recordati S.p.A. 310 recycling, paper 383, 385 rennet 49, 338 resins – as bioconversion media 225, 226 – pitch hydrolysis 204, 378 resistant starch (RS) 352–354 retuximab (Rituxan) 44 reverse osmosis 274–276 reversed phase chromatography 290 Rhizobium etli 97 Rhizopus oryzae, lactic acid 27 Rhodococcus sp., haloalkane dehalogenase 179 riboflavin (vitamin B2) 23, 24 l-ribulose 30 Rich, Alexander 37, 38 Rickettsia prowazekii 81 Rickettsia rickettsii 88 risk assessment 458–460 RNA 247 – double-stranded 37–39 rotary disk fermenters 151 rotary drum fermenters 152 rotary drum vacuum filters 268 Rovabio™ Excel 357 Rubrivivax gelatinosus 82
s Saccharomyces cerevisiae – ethanol production 28, 106–108 – genomics 70–72, 80, 90, 91, 92, 106, 107 – glycosylation 46 – lipid metabolism 117 Saccharopolyspora erythraea 83 safety issues 325, 326, 458–460 Salinispora tropica 83 salting out 284 scaffolds, for tissue reconstruction 255 SCFs see supercritical fluids screening assays for mutants 164–168 scroll centrifuges 270 SDM (site-directed mutagenesis) 50, 156, 170, 199
secondary metabolites 30–35, 138 – see also antibiotics seed fermenters 136 self-sufficiency see sustainability sexual evolution (recombination) 158, 159 silk (spider) 239–241 simulated moving bed chromatography 291, 292 simvastatin (Zocor) 32 SIRCH software 160 sirolimus 33, 34 site-directed mutagenesis (SDM) 50, 156, 170, 199 size exclusion chromatography 276 skincare products 323, 324 slime control 385 societal issues – biodiversity 405, 406, 460–462 – changes associated with shift from oil to biomass 443, 444 – communication with the public 451–456, 458, 462–464 – decision-making process 453–455, 462–464 – economics 445, 454, 462 – energy use 460, 461 – government policies 106, 399, 400, 444, 445 – Kluyver Center workshops 456–458 – land use 405, 444, 460 – public perception of biotechnology 441, 442, 445–451 – safety 325, 326, 458–460 software see computer software tools soil microbial communities 85 solid-phase screening assays 164 solid-state fermentation 133, 141 – enzyme production 195, 196 – equipment 149–152 solvents – as bioconversion media 221–224 – in downstream processing 279–281, 283, 284, 299 Sorangium cellulosum 87 Sorona™ 313 soybean, β-amylase 177 spider silk 239–241 spinosyns 37 spontaneous generation, theory of 2, 3 spray-drying 296 Staphylococcus aureus – genome sequences 84, 85, 87 – methicillin-resistant 20, 96 – phospholipases 170
497
498
Index starch – as a feedstock for industrial production 403, 425, 431 – processing 49, 202, 203, 336, 337 – resistant 352–354 starter cultures 135 static bed fermenters 151 statins 31–33, 314–318 steam explosion process 407 steel, for fermenters 148, 152 StEP (staggered extension process) 158 sterilization, of fermentation media 139, 140 stickies (in paper recycling) 383, 385 stirred tank fermenters 143, 227 – continuous feed 228 Stokes’ law 268, 269 Streptococcus sanguinis 82 Streptococcus suis 83 streptogramins 19, 20 Streptomyces coelicolor 94 streptomycin 16 submerged fermentation 133, 134 – environmental conditions 140, 141 – enzyme production 194, 195 – equipment 143–149 – media 138–140, 221–227 subtilisin 177 succinic acid 112–115, 297–299 – economic/environmental impact assessments 420, 429, 432–434 sugar cane 425 sugars 30 – commodity prices 328, 428 – economic/environmental impact assessments 425, 428, 429–431 – as raw materials for bioethanol 403 – see also individual sugars Sulfurovum sp. 85 supercritical fluids (SCFs) – as bioconversion media 226, 227 – product extraction using 281, 282 supersaturation 285 sustainability 65–67, 69, 457 – biofuel production 405, 406, 413, 414 – see also environmental considerations sweeteners, artificial 318, 340, 351, 357, 356 Synechocystis sp. 80 Synercid 19, 20 synthesis gas 409–412 system expansion allocation procedure 424 systems biology 51, 52, 71 – see also industrial systems biology
t tacrolimus 34 tau-fluvalinate 319 taxol 35 telithromycin 19 temperature control in fermentation 140, 141 tetracyclines 20 textile industry 204 – see also detergents thermal stability in enzymes 49, 50, 200 thermochemical pathway of biofuel production 409–412 Thermotoga maritima 81 Thermotoga neapolitana, xylose isomerase 178 thienamycin 15 l-threonine 23, 358 tigecycline 20 tissue engineering 255 tissue plasminogen activator (tPA) 42, 43, 48 toluene monooxygenase 177 toothpaste 206 torrefaction 411 training, in communication 453 transcriptomics 71, 107 transglutaminase 339 trastuzumab (Herceptin) 44 Traube, Moritz 5, 28 tray fermenters 149–151 Treponema pallidum pallidum 80 Trichoderma reesei, xylanase 177, 200 trickle-bed fermenters 145 triglycerides 248, 378 trust 450, 453, 454, 459, 460 l-tryptophan 358 tunnel fermenters 151 two-phase aqueous systems – as bioconversion media 225 – extraction using 271, 282, 283 two-phase aqueous–SCF systems 281, 282 two-phase aqueous–solvent systems 279–281, 283, 299 two-phase solid–gas systems 226
u ultrafiltration 196, 272–274 Umezawa, Hamao 31 USA – biofuels 28, 105, 106, 399 – biotechnology companies 39–41 – genomic research funds 89 Ustilago maydis 82
Index
v vaccines 4, 51 vacuum distillation 277 vacuum filtration 267, 268 d-valine 319 van Leeuwenhoek, Antonie 1, 2 Vanderwaltozyma polyspora 86 vegetable oil methyl esters (VOME) (biodiesel) 398–402 versatile peroxidase (VP) 375 Vesicomyosocius okutanii 84 vinegar 1, 26 – see also acetic acid vitamins 23–25 Vitis vinifera 86, 87 VOME (vegetable oil methyl esters) (biodiesel) 398–402
wood see lignocellulosic biomass Woodruff, H. Boyd 16 wound healing 255
x x-omics 71, 72, 104, 105 xanthan 29, 30 Xanthomonas campestris campestris 88 xylanases – in animal feed 203, 356 – in baking 202, 341 – genetically engineered 177, 200 – in the paper industry 373, 380–382 xyloglucanases 374, 386 xyloglucans 386, 387 xylooligosaccharides 354 xylose, bioethanol from 77, 107, 108 xylose isomerase 178
w Waksman, Selman A. 15, 16 water purification 274–276 water use in the paper industry 383 Watson, James D. 37, 38 Weizmann, Chaim 6 wine making 203, 345 – history 1, 27, 28 – V. vinifera genome 86, 87
y 382,
yeasts 27, 28, 46 – see also Saccharomyces cerevisiae Yersinia pseudotuberculosis 85 yield from multistep procedures 153
z zeaxanthin 301 Zocor (simvastatin)
32
499