Blockchain Papers

Jason MacLean

No abstract is available for this record.

Jane Qiu

The amount of arable land per person in China is only about 40% of the global average. In the next two decades, the country will need to produce 30–50% more food to meet the demand of its growing population. It's a daunting task for an agricultural sector that has long been plagued by pest infestation, crop diseases, soil pollution and degradation, water shortage and labour efflux—which will be exacerbated by climate change. To secure food supply, China is increasingly looking to genetic modification (GM) technology. In 2008, it rolled out a 12-year, 25 billion yuan (US$3.7 billion) programme to promote the research and development of GM technology. Six years on, Chinese scientists lament about the slow progress and public misconceptions, whereas some social scientists and non-government organizations are concerned that GM proponents are missing the forest for the trees. In a forum chaired by National Science Review's executive associate editor Mu-ming Poo, five panellists from diverse backgrounds locked horns over a myriad of issues of GM technology. Bing Liu Social Scientist at Tsinghua University in Beijing Baorong Lu Ecologist at Fudan University in Shanghai, a member of National Committee on the Biosafety of Agricultural Genetically Modified Organisms (NCBAGMO) Lanying Zhang Coordinator of the non-government organization Farmer Seed Network in Beijing Yunlong Zhou Researcher at Ministry of Agriculture's Centre for Science and Technology Development in Beijing, a member of NCBAGMO Zhen Zhu Geneticist at Chinese Academy of Sciences’ Institute of Genetics and Developmental Biology in Beijing Mu-ming Poo (Chair) Neurobiologist at Chinese Academy of Sciences' Institute of Neuroscience in Shanghai Poo: What's the stance of the Chinese government on GM technology? Zhu: Food security in China is extremely pressing at the moment. With a growing population, it's only going to get worse in the future. This is why the No.1 Document—central government's first policy document of the year—in the past consecutive years invariably focused on agriculture issues, with particular mention of seed industry and GM technology. The government really sees GM technology as central for feeding its people, and has invested heavily on its research and development. Lu: This is in line with the rapid development of GM technology around the world. The cultivation area of GM crops has reached 175.2 million hectares in 2013, constituting over 11% of global farmlands, up by 3% compared with the previous year. Zhu: There has been a lot of progress in GM research in China: hundreds of field trials of GM crops have been approved and conducted, and half a dozen have been approved for commercial production. In 2009, the government awarded safety certificates to two GM rice varieties, but it's unlikely that they will make their way to the market. The commercial cultivation of GM crops in China has been stagnated for years—since the great success of Bt cotton. Lu: Indeed. At 4.2 million hectares, China ranked sixth in 2013 in the cultivation area of GM crops, mostly Bt cotton—after the USA, Brazil, Argentina, India and Canada—dropping from the fourth place 10 years ago. Even in Pakistan and South Africa, which have much less land mass than China, the cultivation area of GM crops reached nearly 3 million hectares last year. China is in danger of being left behind by the rest of the world. Zhu: This will have serious implications for food security. China imports nearly 70 million tonnes of GM corn, soybean and rapeseed a year, about 12% of China's total production of all crops. If we do not get a significant boost from GM technology, our reliance on imports will continue to rise. This is a grave matter of food security. Poo: Why has the commercialization of GM crops been so slow in China despite the major government push? Zhou: The public concerns for ethical and biosafety issues are the main reason. We develop GM crops to serve consumers. Even if they are safe, it'd be no good if nobody buys them. The government is reluctant to grant further approval for commercial production unless there is a sea change in public mood. Poo: There've been fierce debates in China about GM crops, which are increasingly polarized. What are the underlying reasons? Lu: In the past five years, the public attitude has shifted from being more or less neutral to being negative. We did a survey recently and found that most people don't really know what GM technology is about, but oppose their commercialization. As scientists, we haven't done a good job in communicating the importance of GM crops to the public. Zhu: The public debates on GM crops are a sign of progress, illustrating China's improving democracy. Compared to a few decades ago, people demand a greater say in important public policies, especially about the environment they live in and the food they eat. But they should listen to the experts—scientists and economists—about the value of GM technology and how safe it is. Zhou: Scientific and technological breakthroughs are often controversial at the beginning. China's economic development has reached a stage in which basic livelihood is not a problem for most people. The public are really concerned if it's safe to eat GM foods—not only for themselves but also for future generations—and whether GM crops could damage the environment. When the public hasn't received proper information, they are more likely to be influenced by scaremongering claims that GM crops are unsafe than those that support them. Zhang: The public are also concerned whether GM technology will make farmers and national food production heavily rely on a small number of biotech companies, and what impact they will have on local cultivars, traditional farming practices and indigenous knowledge. Another issue is that people want to retain their right to choose what they eat, especially when staple food is concerned. This is a basic autonomy that must be respected. They simply cannot and would not accept to have GM foods, especially GM rice, imposed upon them. This is why compulsory labelling is absolutely essential. China is losing ground in the international race of transgenic technology. —Zhen Zhu Liu: The debates about GM crops are not just about science or economics. Rather, it concerns a myriad of issues, including the role of science in society, ethics, culture, tradition and even religion. A main problem is that China still uses the outdated science-communication approach in which scientists tell the public about their findings, which the public passively understand and accept. This is highly problematic and rarely effective. A better approach is to have a dialogue between experts and multiple stakeholders and involve diverse perspectives and opinions. Poo: This discussion is very interesting. We really need to have more interactive dialogues involving multiple stakeholders, not just the public being told by the scientists. There is a lack of intelligent debates in the Chinese media—most are one-sided, either supporting or opposing GM—which is partly to blame for fuelling the polarization. Liu: The fierce GM debates also result from a serious mistrust on the experts. Scientists have been saying that GM crops are safe, but this hasn't persuaded the public. Some people wonder if those scientists are part of an interest group conspiring to benefit financially from the commercialization of GM crops. This suspicion has been exacerbated by the fact that there is a lack of transparency in terms of who the committee members are, how the assessment is done, how the decisions of commercialization are reached and whether different opinions are considered. Zhu: I agree we need to adopt a more interactive approach when engaging with the public. The right to choose is also very important, and we are not saying that we will force people to eat certain things just because they are safe. But we can't ignore the harsh reality: the demand for food supply is overwhelming; a lot of people still live below the poverty line in many parts of the world. As we overemphasize the importance of the right to choose, aren't we depriving people's right to basic livelihood? Isn't that something we should take into consideration in our ethical debates? Zhou: It's unlikely that we will be able to persuade everybody. So who should make the decision? I think government and international organizations must take a lead on this. Otherwise we'd be going nowhere if we have to consider the opinions of every individual. It's as much about the respect for individual's rights as the collective interest. Lu: There is a lot of misinformation floating around, which contributes to some public anxieties about GM crops. For instance, most people don't realize that compulsory labelling is required for all products derived from GM crops according to the Chinese biosafety regulations. GM rice would be labelled, too, so consumers would always have the choice. Zhu: The GM debates touch upon many issues. But the most fundamental question we must consider before anything else is: are GM crops safe? The answer must be based on solid scientific evidence. Poo: So what have we learned about the potential impact of GM crops on human health? Zhu: The world has been consuming foods derived from GM crops for nearly 20 years and there have been no safety issues. Zhou: China imports 70 million tonnes of GM corn, soybean and rapeseed a year. GM foods have long got into our food chain. Liu: I don't think it's appropriate to make a sweeping statement about the biosafety of GM crops in general. It really depends on which GM crops you are talking about. If Bt rice turns out to be harmful, its large-scale cultivation and commercialization would have unthinkable consequences. — Bing Liu Zhu: That's true. GM is a technology. It's neutral. Whether it's safe or not depends on what kind of genes you introduce to crops. If you have a GM toxin, of course it won't be safe. Lu: Indeed. We cannot say all GM crops are safe before biosafety assessment. Biosafety must be assessed on a case-by-case basis—which is one of the fundamental principles in biosafety evaluation in China and around the world. GM technology is not that much different from traditional breeding, but is more targeted, efficient and can cross species reproductive barriers. There are mainly two types of GM crops that have been commercialized in the world: one is genetically modified to produce a protein made by the bacterium Bacillus thuringiensis (Bt) that can kill a type of pests belonging to the lepidopteran order and the other is modified to produce an enzyme called EPSP synthase that can protect plants from herbicides. Extensive research and nearly 20 years of commercial cultivation have really shown that neither Bt nor EPSP crop has any adverse impact on health and environment. Zhang: I don't think the picture is as black and white as you portrayed. In 2012, a study led by French scientist Gilles-Eric Seralini and published in Food and Chemical Toxicology showed that EPSP maize caused tumours and other serious diseases in rats after two years of feeding experiments. In a controversial move, the journal retracted the paper a year later on the grounds that ‘no definitive conclusions can be reached’. It was republished this June by Environmental Sciences Europe, another peer-review journal. I don't think there is a consensus within the scientific community. Zhu: The Seralini study, along with other similar research, has been widely refuted by mainstream scientists. Until now, there is simply no solid evidence that GM foods could pose any threat to human or animal health. Liu: I agree with Zhang: the health impacts of GM crops are still an open question. Most of the existing GM crops are either used as animal feeds or consumed after having been processed. None of them has been directly consumed to the extent as rice is in China. So even if no health issue has emerged so far, this does not mean that Bt rice would be safe. No country in the world—not even the USA—has commercialized a GM staple crop. Zhang: The pest-resistant protein Bt is a toxin. The Bt pesticides are also derived from the same chemical. I think the public anxiety over Bt rice is understandable. Liu: I certainly don't think that those three-month rat experiments are sufficient to reassure the public that eating toxin-containing rice three times a day for their entire life would be safe. If Bt rice turns out to be harmful, its large-scale cultivation would have unthinkable consequences. Zhu: I think you are holding an impossible standard for biosafety studies. If three months of animal experiments are not enough, how long a duration would assure you? Two years, 50 years or 500 years? If one demands such stringent proof, there would be no hope for any technology. Zhou: The issues of staple crops have attracted a lot of public attention. But I don't think, as a staple crop, GM rice is a special case from the point of view of biosafety. China takes biosafety issues very seriously, which was why it took 15 years to approve the two Bt rice varieties. It has also dedicated 40% of the funding of the major GM programme, billions of yuans, to biosafety research. Liu: We should be extremely cautious about GM rice. Is the issue of food supply so pressing that we must subject one billion people to the biggest human experiment in history? There are several historical examples, in which new inventions, such as pesticides, seemed wonderful at the time but has turned out to be harmful. They are cautionary tales for GM technology. Lu: No technology is absolutely safe, and so we should balance the risks and benefits of GM crops. As pointed out by the Chinese proverb: when we face two benefits, choose the greater one; when we face two evils, choose the lesser one. Poo: What could GM crops do to environment and biodiversity? Lu: One worry is whether Bt toxin, which aims at killing target pests, could also affect neutral or beneficial insects—the so-called non-target effects. There has been a lot of research around the world, and most studies show little impact. Another concern regards gene flow—that is, whether the transgene could get into unmodified, wild or weedy relatives through cross-pollination. We have done a lot of research on Bt rice in the past 15 years. Because rice produces seeds strictly through self-pollination, the efficiency of gene flow to rice crops is extremely It would be even if you have a between GM and rice. The efficiency of gene flow to wild rice is but we haven't found any significant adverse with the Bt Zhu: There are some issues with GM cotton. For instance, the first Bt is to but the of non-target pests, such as of the after a few years and the main Scientists have the of GM with two are to Liu: that the widely used gene into weedy rice, could make the plants and more in the of the This is a of the GM crops could have on the environment. It's because any gene flow to weedy rice is the transgene to and subject to But of studies are rarely in debates about the biosafety of GM crops. Poo: GM crops have any on environment or Zhu: GM technology can pollution caused by of pesticides and GM crops have the of Scientists are GM crops that can take up and much more so less would be There could also be GM that are to and crop diseases and can in Lu: At the we have two we either rely on pesticides, at and more with serious impacts on health and or we pest-resistant crops. We must risks and benefits in this kind of Liu: I that we have a lot of with such as those caused by pesticides and But are we really a of either GM crops or those there other we should a little and how we have got into such a before what we should Zhang: A lot of agricultural issues are in decades of farming such as of pesticides and land which have out and the of to and A on GM crops is a for and the Liu: I we need to take a approach agricultural The of GM technology to is just the than the The of which can just as much as is a case in farmers are on pesticides, the same as I the transgenic GM to and will other In the USA, the benefits of GM crops have also because have mostly to farming Zhang: GM technology is not a for food production. on GM could also further for improving traditional and farming Zhou: No one is saying that GM technology is a for all agriculture It's a that we cannot not to take GM is not the only for such as pest infestation, but it's the main up to Poo: What are the impact of GM crops on traditional agriculture and One I have in is GM it was in the USA, farmers growing traditional have China must consider of issues if it is to GM crops on a Zhang: farmers I of GM technology. When I told them that if they GM crops they have to seeds every year, they really worry about their autonomy and Lu: We should take into consideration interest. But as we get into a the traditional farming approach of and is way to large-scale This is a global not an issue to GM technology. Zhou: I also the seeds if they rice or and have to get supply from seed with technology. farming has always been in and but I don't think is a Lu: I think Bt really how GM technology could impact it was in the production nearly because of pest The was and of farmers year. The of Bt has really the has a lot of labour and A study led by of Chinese Academy of Sciences’ Centre for Chinese Agricultural showed that by yuan per No technology is absolutely safe and so we should balance the risks and benefits of GM crops. Lu Zhang: The benefits of Bt are They most significant in the first a few years after Bt was but to as pests and farmers on This is by the fact that Bt is more to diseases and their seeds are several times more than traditional Liu: is a major only the seeds but also of and are all by it's about who and the food supply of billion population. Zhu: the of GM products would be able to get sufficient from the and would always on government the of between China and would if we do not develop Poo: and of GM crop research trials is to their development and public has it been The in which at the Academy of Sciences field trials of GM crops has serious Zhou: China has a of and on GM technology such as basic research, field commercial food and compulsory They are all in line with international and The government takes biosafety evaluation very The National Biosafety between five government of experts on public environment food safety and Liu: The issue at is not only about having a good but also It's similar to China has a very good on but many and are have that the of GM crops is not Zhang: Indeed. GM seeds have been found at local in several because of GM rice has also been for years. to by China's of and the for Food and found times of GM rice in food products from China. panellists the importance of GM technology in but this could be for China's food The debates should all stakeholders and take diverse opinions and perspectives into Zhang Liu: In the are genetically to produce a of to the efficiency of of to after of the rice approval or from the This is just another of and Zhang: of GM crops is also for and the of But I just don't that China is able to face up to such on a Poo: We are out of their Zhu: GM crops are safe and China is losing ground in the international race of transgenic technology. We should to science and and be engaging in and the great The food shortage that we must Lu: There is no We should balance risks and benefits, the greater benefit and the lesser The potential risks of GM crops can be to Zhou: The of GM technology is on The Chinese government will take and consider public when important it's about the most out of this technology and at the same time risks as much as we Liu: We should be extremely cautious and potential risks when over the commercialization of GM crops, especially GM rice. The national biosafety committee should be much more about its members and The public has a right to Zhang: The GM debates are not just about science and technology. A lot of social issues are also such as ethics, culture, tradition and The debates should all stakeholders and take diverse opinions and perspectives into

Henry‐York Steiner, Claire Halpin, Joseph M. Jez, John Kough · 8 authors

Plant breeding has a long history of developing varieties with desirable traits in response to the needs of both growers and consumers. Although the bases for most of these traits are not known genetically or biochemically, conventional breeding combines these multiple traits to create new hybrids and stable varieties that are safe and not generally subject to safety assessment. With the advent of genetic engineering, a tool for incorporating additional traits has become available to plant breeders. The safe application of genetic engineering to food and feed crops is widely acknowledged as a useful tool in addressing global agricultural challenges, including population growth and climate change. As used here, the term genetically engineered (GE) stack refers to a plant in which two or more transgenic events (i.e. single-locus insertions) that have been separately assessed for safety have been combined by conventional breeding (Table I). In recent years, increasing numbers of GE stacks have been planted, the first of which offered combinations of insect and herbicide tolerance genes to combat a wider range of pests and weeds than covered by the single events (Que et al., 2010; James, 2011). Two main questions arise when considering the food and feed safety of GE stacks: (1) does incorporation of more than one event increase genomic instability, and (2) can potential interactions between the products of the combined events impact safety? A related paper considered the stacking of events in light of the plasticity of plant genomes and concluded that enhanced genetic instability from a transgene or from common sequences in two or more transgenes is remote (Weber et al., 2012). This paper addresses the second question of potential interactions between events and their products combined in a stack, reviews the basic principles of plant breeding and its history of safe use, and extends these principles to the feed and food safety of events combined through the same processes used in conventional breeding of non-GE plants. Potential environmental impacts are outside the scope of food and feed safety. The new varieties developed through modern biotechnology are identified by a number of terms, including genetically modified (GM), GE, transgenic, biotech, recombinant, and plants with novel traits. The term GE is used here as defined by Weber et al. (2012). For these reasons, the term GE is preferred over the term GM. There are many methods encompassed by the general term conventional breeding, including wide crosses and selection, mutagenesis, and somaclonal variation. When the parental species are not closely related, the cross may be facilitated by embryo rescue, somatic hybridization, or x-ray-induced translocations. The term interaction, as used in this paper, refers to an effect, such as a new or modified metabolic activity, resulting from a combination of transgenes. An example of an interaction is protein-protein binding resulting in a novel effect only seen with a specific combination of proteins, for instance, protein cofactors or subunits for the same enzymatic complex or subcellular metabolic binding reaction. Examples can also include a direct metabolic interaction that would inhibit or activate components in a metabolic pathway shared by the proteins newly combined in the GE stack or components of independent metabolic pathways that indirectly interact by way of a common metabolite. Thus, interactions within GE stacks generally refer to the metabolic or physiochemical interplay between the products of transgenes or between the product of one transgene and the second gene, rather than between the two genes themselves. Conventional breeding has a long history of safe use despite the presence of antinutritional factors, toxins, and allergens in crops. There is no evidence that a random genomic change in a crop has resulted in a novel food or feed safety issue (Weber et al., 2012). Historically, humans have selected desirable traits that arise from the crop’s genomic plasticity and interactions between genes. As breeding became more advanced, new methods were applied to select and combine desired traits, which also modify the genome as a consequence. Plants produce a multitude of metabolites that provide various functions. These include signaling activities in response to environmental stress or attack from plant pathogens and pests. Some metabolites have beneficial effects, while others are toxic when fed at high levels to sensitive animal species (Ames et al., 1990). Although particular metabolites tend to be specific to some plant families, there are metabolites of concern in a number of common food and feed crops, including apple (Malus domestica), apricot (Prunus armeniaca), Brassica spp., celery (Apium graveolens), cucumber (Cucumis sativus), lima bean (Phaseolus lunatus), potato (Solanum tuberosum), cherry (Prunus avium or Prunus cerasus), and sorghum (Sorghum bicolor; Beier, 1990; D’Mello et al., 1991; Stewart, 2009). Examples of such metabolites include alkaloids, lectins, glucosinolates, furanocoumarins, cyanoglucosides, nicotines, and phytoestrogens. Some of these can impart bitter taste, and conventional breeding has repeatedly reduced their levels to acceptable concentrations (Drewnowski and Gomez-Carneros, 2000). There are few documented cases in which breeding led to an unacceptable level of a metabolite. Following reports of bitter taste, the potato var Lenape, which was developed from a cross of potato to a wild Solanum species, was found to contain doubled levels of glycoalkaloids (Anonymous, 1970). The only other documented incident of unacceptable metabolite levels associated with plant breeding is that of a disease-resistant celery containing elevated levels of furanocoumarins, which may have contributed to dermatitis among grocery store personnel (Berkley et al., 1986; Seligman et al., 1987). The environment can also play a role in impacting furanocoumarin levels; a later report of dermatitis among celery harvesters in southern Israel was attributed to delayed harvest, and hence more mature plants being handled, due to the Gulf War (Finkelstein et al., 1994). Similarly, reports of toxic squash (Rymal et al., 1984) and zucchini (Herrington, 1983) appear to have been limited to individual plants within otherwise widely grown varieties, suggesting the higher toxin levels were due to environmental conditions or mutations. Despite these few instances, these crops remain safe for food or feed use. Although breeders recombine tens of thousands of genes with virtually infinite potential interactions, to our knowledge, there has never been a report of a completely novel toxin or allergen appearing in a genus as a result of conventional breeding. The development of an interspecific somatic hybrid of potato (S. tuberosum and Solanum brevidens) containing demissidine (Laurila et al., 1996) has often been cited as proof that novel toxins can arise during breeding. In fact, Jadhav et al. (1981) documented the presence of demissidine in potato more than a decade before it was found in the hybrid. To guard against unexpected increases in levels of known toxins, breeders have instituted screens for these compounds in new varieties before they are released. Examples include cotton (Gossypium hirsutum), potato, lima bean, and canola (Brassica napus), because they contain known compounds that can impact food or feed safety. However, breeders cannot and do not screen for de novo compounds. Hundreds of thousands of varieties have been bred without the emergence of any novel allergens or toxins, indicating that the likelihood of such events is virtually zero (Stevens, 1974). Improved crop varieties produced by conventional breeding are the cornerstone of food production in the world today. Thus, the ways in which risks are managed during conventional breeding of non-GE crops, which includes testing for any known concerns, sets the framework for the food and feed safety assessment of GE stacks. As is the case for any other new variety or hybrid, GE stacks are only considered for market introduction if the combined traits have met the intended thresholds for efficacy and stability. Newly developed GE events undergo rigorous safety assessments by the developer and by regulatory agencies prior to their commercial release. These assessments evaluate the impact of both intended and potential unintended effects on food, feed, and other aspects of crop safety. Assessment criteria and objectives are based on national priorities and on international standards, such as those of the Joint Food Standards Program of the Food and Agriculture Organization of the United Nations and the World Health Organization (FAO/WHO, 1996, 2000), as well as Codex Alimentarius Commission recommendations for conducting food safety assessments of GE crops (Codex Alimentarius Commission, 2009). Codex principles and guidance are widely followed for single events. The key components of GE crop safety assessments include (1) descriptive information on the transgenes and inserted recombinant DNA; (2) detailed characterization of the DNA insert relative to the native genome, in planta concentration and stability of the products of the transgene(s), analysis of plant phenotype, and descriptive information such as efficacy, mechanism or mode of action of the new trait(s), and crop management considerations; (3) evaluation of the safety of the products of the transgene(s) in the context of common commercial crop practices and uses; and (4) comparative safety assessment for suitability as food and/or feed. Such analyses might include a determination of expression levels of known allergens and toxins, and overall composition, including nutrients, antinutrients, and selected metabolites for that crop (FAO/WHO, 1996, 2000; Cellini et al., 2004; Codex Alimentarius Commission, 2009; Thomas et al., 2009). Assessments of nutrient composition and agronomic characteristics, as well as an assessment of potential allergenicity and toxicity, are widely recognized as significant components of GE crop safety assessments (FAO/WHO, 1996, 2000; Metcalfe et al., 1996; Kuiper et al., 2001; Cellini et al., 2004; Delaney et al., 2008; Codex Alimentarius Commission, 2009; Thomas et al., 2009). Differences between the GE crop and appropriate comparators are evaluated in terms of biological relevance, magnitude of difference, exposure, and impact on food or feed safety to determine the need for further investigation. The comparators may include a closely related non-GE variety and other commercial GE and non-GE varieties. The International Life Sciences Institute’s Crop Composition Database (http://www.cropcomposition.org; International Life Sciences Institute, 2006) may also serve as a reference for comparison for some crops (Ridley et al., 2004). These holistic analyses also take into account interactions of the transgenes with endogenous genes and their products. Agriculturally important plants express approximately 25,000 to 50,000 genes at any given time. The safety assessment evaluates the GE crop phenotype, which includes interactions between the event and the host genome that may impact safety. Once the safety assessment is completed, conventional breeding is used to incorporate the event into different genetic backgrounds, without undergoing additional assessment. The developer of the resulting food and feed products is, however, responsible for the safety of those products and for meeting all relevant statutory and regulatory requirements, as is the case for all foods and feeds. Even within a single genus having species that differ in ploidy level, the number of genes within a plant can vary. For example, some 400 genes are not common in the historically important maize (Zea mays) inbreds B73 and Mo17; each of these genes is found in B73 but not in Mo17 or vice versa (Springer et al., 2009; Lai et al., 2010). Similarly, of the approximately 46,000 of genes in soybean (Glycine max), 856 genes were present in some but not all of the soybean genotypes tested (Lam et al., 2010). Of the two potato genotypes with sequenced genomes, 275 genes are found in only one or the other et al., 2011). Thus, different non-GE genotypes in novel combinations in novel interactions, but no safety have been this of novel interactions is to be by the stacking of transgenes. Despite the genetic in crop most regulatory agencies do not new non-GE varieties developed by conventional breeding there is a known safety concern or associated with the new variety of and Food and of the Food on Organization and Health Food This is based on the that conventional breeding is as As defined conventional breeding traits from genetic interactions of genes and their products are in breeding to produce new crop varieties. In plant breeders through crosses that combine different different et al., in some different genes et al., 2011). However, the are from and among have the that might be in et al., et al., et al., and et al., these that thousands of interactions are when genomes are combined by breeding. these interactions have led to which has been selected by plant breeders to desirable traits et al., 2010). these interactions of genes have a long history of food and feed the bases of these interactions are the information to a specific interactions between endogenous genes in conventional breeding do not to direct As information and methods to complex become it may be to such when GE events by breeding, it is to interactions between the events within the GE stack in a and can be developed for those specific with the historically used in conventional breeding to new traits into crop such as wide hybridization, genetic engineering a direct of a DNA that a specific into a the methods by which individual events are combined to produce a GE stack are to those used to combine multiple traits in new conventional crop varieties and two GE does not any in the genome is by two non-GE (Weber et al., the safety assessments for the individual events are to the GE The only safety question that the individual event assessments do not is that of interactions between the products of the combined transgenes. Two questions on the potential of interactions between the events in a particular GE (1) does a potential interaction between the products in each single event in the GE stack, and (2) would the potential interaction result in a food and feed safety In other are there of engineered and any interactions between these that might create A safety assessment of a crop produced by conventional breeding of parental into a GE stack can incorporate a that addresses interactions of the transgene products are and if they might food and feed safety. A for this is in which the overall development of a for potential interactions, with the and of the crop of the single and the prior food and feed safety assessments on the products. The question in the assessment is it or that the transgene expression products of the single events interact in the The only of interaction different in a GE stack from that seen in conventional breeding of non-GE plants is a metabolic or physiochemical interaction from the combination of the transgene products. other interactions are to those in bred non-GE plants. A for the safety assessment of a food and feed crop with a GE stack produced by conventional breeding of two or more events. if it is that novel interactions in the GE stack, can the interaction impact the safety of the GE This is a if there is no for a potential interaction, or if a potential interaction that does not the prior safety assessments on the individual events are for the GE a can be developed for an interaction that may food or feed further questions on the and of the A number of relevant be considered to a the presence and of interactions to a potential safety Although the of questions on the transgenes in the GE stack, these questions be to food and feed safety. Examples of questions that can be to a are in these questions on direct product interactions, expression and metabolic products of the transgenes. The same to genes expression of other such as transgenic and to the of endogenous genes. these of transgenes may expression of of other the and of by each transgene would be documented before each single event is used in be from the of the specific effects of each many products of conventional breeding of non-GE plants on known to have been from in or from et al., 2010). To the that conventional breeding has plants with associated with or in factors, there is no that metabolite have resulted in any novel to food or feed safety. In or there has not been the of novel toxins related to these metabolic of the specific of transgenes being assessment of the combined information from the single events can or a for The need for further safety assessment of the potential interaction is evaluated on a Examples of the can be used to at safety assessment are An interaction between the products of transgenes is not the single events combined in a GE stack proteins that are not known to interact or that on different metabolic pathways with no known or common metabolite between GE stacks that combine insect and herbicide tolerance are an In these crops, insect is by one or more genes toxin proteins from that are not native to but have a general history of safe use in the food as in conventional and and in GE crops. The proteins no known metabolic in plants and are in the or to tolerance is by a that an of a or that a that the of the herbicide For a herbicide tolerance stack, is there a that an interaction between these events The GE stack does not create a new The herbicide tolerance may or may not serve a metabolic in the and insect As herbicide tolerance may be engineered to be and in the or both and the protein herbicide tolerance be found in the same of the two transgenic traits the of interaction in the GE however, these proteins are not related, are not in the same metabolic and no common there is no biological pathway in which these products would or indirectly there is no or for the interaction of these proteins or their products in the GE stack that the need for a new safety evaluation The same to the stacking of transgenic with other transgenes in crops with events that have a safety assessment. the transgenes are not in the same or their products are not to the same there would be no new food or feed safety if the transgenic event the of endogenous there is no for a food or feed safety on an of the of some event combinations may have the potential to produce products that at For example, if individual events produce within metabolic pathways or produce that can for the same in a GE stack, a potential for interaction to the number of interactions, there are only a of direct interactions between metabolic and metabolic which are as through a a potential interaction does not that food or feed safety would be a of metabolites in plant pathways have been to have a role other than as in plant et al., 2000). An example a potential interaction within a pathway that does not impact food or feed safety can be found in the A in is the for and James, The product of the is used for Plant are of two subunits and two The two subunits are by different genes. In a GE stack, one event would an engineered of of higher levels of and the second event would an engineered of also of higher levels of In both single the level of is due to an level of from the would be in these traits to for an effect on In this example, the two genes would be for their direct genes expression and the proteins are in the same metabolic pathway and the same enzymatic interaction between the transgenes in these events is for the intended effect of further in a GE In this the GE stack does not a new pathway or metabolites only and effects are there is no potential impact on food or feed safety. is to a safety issue from a GE example which are produced plant metabolites in plant can be into and become toxic by by a and they in the plant response to from pests and pathogens et al., The is in the the is in the or In some the and its are in but to the of and no toxin is present in However, from insect and of enzymatic of the in the a toxic to the In this event the level of a particular that is present in the plant at resulting in a variety with to pests and Although event the level of this particular the is if found within the range of levels in this would no food or feed safety during the safety assessment of event which is also in a variety with a with enhanced that is to a The of this transgene into a host plant with levels of the particular of this no because the inserted the for toxin The safety assessment of each individual event would be to include an analysis of the safety of the event various environmental the of that enzymatic of the in the to produce a toxic would have been evaluated during the safety assessment of the individual events. However, for the of the combination of these two it is that this be more closely in the event than been with the individual events In such an additional assessment of the GE stack would be In over a of plant breeding, there are no known de novo effects from the breeding which has conventional plant breeding with a history of safety for food and feed. effects have have been can be between endogenous genes in a conventional breeding and transgenes by conventional breeding The between the endogenous genes combined conventional breeding and transgenes combined through conventional breeding is the of the transgenes and their products. This the development of food and feed safety. A safety assessment for a food or feed crop produced by conventional breeding of GE events first the likelihood of interactions if they do they might safety. the events are to no additional assessment be to a safety determination for the GE stack, because each individual event has independent safety When interactions are to the effects can be based on and safety assessment of the individual parental events. When there is a biological to an interaction, the of the interactions be evaluated to determine if there be an impact on food or feed safety. there is no impact of the interaction on food or feed no additional testing be to the GE if the identified interaction be to impact food or feed the GE stack would a food and feed on the specific interaction The need for such a further assessment and the used be on a on the specific interaction identified and into account the Codex Alimentarius principles for safety assessment (Codex Alimentarius Commission, 2009). International Life Sciences International Food and Plant and and and for and during the The also International Life Sciences and for their in this to also the of and in the of this The and would also to the for in the and for many and de de and of Standards Commission on of of of of Food and of and of of of Agriculture and and Plant Food and of and and genetically engineered genetically modified

Henk van den Belt

On May 20, 1999, Nature published a brief report on an experiment performed by researchers at Cornell University that indicated that pollen from genetically modified (GM) Bt corn (Zea mays) could kill the larvae of monarch butterflies (Danaus plexippus). In laboratory tests, caterpillars fed milkweed (Asclepias curassavica) leaves dusted with pollen from a Bt corn hybrid showed retarded growth and increased mortality. “These results,” the authors stated, “have potentially profound implications for the conservation of monarch butterflies” (Losey et al., 1999). In a press release announcing the publication in Nature, the principal investigator on the Cornell study, John Losey, had expressed due caution: “Pollen from Bt-corn could represent a serious risk to populations of monarchs and other butterflies, but we can't predict how serious the risk is until we have a lot more data. And we can't forget that Bt-corn and other transgenic crops have a huge potential for reducing pesticide use and increasing yields. This study is just the first step, we need to do more research and then objectively weigh the risks versus the benefits of this new technology” (Cornell News, 1999). Such caution was wasted on Greenpeace International. The day the findings of the Cornell study were published it already demanded that authorities in the United States, Argentina, Canada, and the European Union take immediate action and prohibit the growing of genetically engineered maize crops. The environmentalist nongovernmental organization (NGO) reiterated its earlier call for a ban on all releases of genetically modified organisms (GMOs). Less than a month later, in a media-oriented action, members of Greenpeace dressed up as butterflies confronted a meeting of European Union environment ministers held in Luxembourg, carrying banners demanding “Give butterflies a chance.” In Europe, their campaign apparently found resonance among the authorities: The European Commission decided to freeze the approval process for new Bt maize varieties. The Cornell study did not show that monarch butterfly populations in the wild were actually endangered by Bt corn. However, when Monsanto and Novartis, the companies that sold Bt corn at that time, correctly pointed out that the detrimental effects had so far only been shown in the laboratory, Greenpeace branded them as irresponsible. A spokesperson declared: “Such reactions are the precise opposite to precaution and follow the same pattern of denial these companies have employed for decades, when health and environmental effects of their chemical pesticides were exposed. However, in the case of these GMOs we are talking about living toxins that can reproduce in nature and transmit their dangerous traits to wild species. We cannot consider GMOs harmless until harmful effects are fully proven (sic)” (Greenpeace, 1999a). (The last sentence is obviously a—Freudian?—slip of the tongue and should be read: “We cannot consider GMOs harmless until the absence of harmful effects is fully proven.”) For Greenpeace, not just monarchs were supposed to be endangered. The NGO drew up a list of over 100 species of butterflies that it believed could be harmed by GM maize. It accused biotech companies and regulatory authorities of fully ignoring these risks (Greenpeace, 1999b). More recent field research performed in the American Midwest, however, seems to indicate that monarch butterfly populations are hardly affected, if at all, by the large-scale cultivation of Bt maize in this region (Ortman et al., 2001). The monarch butterfly case is only one among many occasions in which the so-called Precautionary Principle (PP) has been invoked to advocate preventative action to forestall possible harm even before the likelihood or the possible extent of the latter has been scientifically well established. This principle is highly contested. With many other environmentalist NGOs, Greenpeace champions its adoption as a central principle of international law against tenacious opposition from the United States, Canada, and Australia (Greenpeace, 2002). The principle is also at issue in recent World Trade Organization trade disputes between the United States and the European Union. But why does the PP play such a central role? The PP is an outgrowth of increased environmentalist awareness since the 1970s. The conviction took hold that humanity finds itself in a historically unprecedented situation in which our technological capacity and the potential scale of our actions far exceed our predictive knowledge. According to the German philosopher Hans Jonas, this discrepancy between the ability to foresee and the power to act itself assumes ethical importance and asks for humility and responsible restraint on our part. Jonas maintains that it is possible to extract from this situation of profound scientific uncertainty a rule or principle of decision making that is itself not uncertain at all, namely the rule “to give in matters of a certain magnitude—those with apocalyptic potential—greater weight to the prognosis of doom than to that of bliss” (Jonas, 1984). The supreme moral imperative in the new age, Jonas holds, is that humankind may not put its own existence and survival at stake in the wager of technological progress. If we want to find a philosophical basis for the PP, we must look for it in Jonas' book on the imperative of responsibility (although he himself did not use the expression PP). Environmentalists often hold that modern biotechnology has “apocalyptic potential” because it tampers with the basic processes of life. If we release GMOs into the environment, the ultimate consequences for the natural flora and fauna are extremely hard to predict but may well be irreversible. However, many environmentalists, just like Jonas, believe that we possess a decision rule or principle for dealing with fundamental scientific uncertainty that is itself not the least uncertain. That rule is the PP. Thus, in almost any debate, it seems that the PP can be brought in as a trump card to override all other considerations and arguments. But what exactly is the PP? Proponents of the PP assert that the principle is already “enshrined” in such international agreements as the Convention on Biological Diversity and the Cartagena Protocol on Biosafety, but existing definitions of it are at best partial and incomplete. In the context of dealing with environmental hazards, the Rio Declaration of 1992 presented the following formulation of what a precautionary approach entails: “Where there are threats of serious or irreversible damage, lack of full scientific certainty shall not be used as a reason for postponing cost-effective measures to prevent environmental degradation.” A well-known definition of the PP was spelled out in a January 1998 meeting at Wingspread in Racine, Wisconsin. The Wingspread Statement summarized the principle thus: “When an activity raises threats of harm to human health or the environment, precautionary measures should be taken even if some cause and effect relationships are not fully established scientifically” (Raffensberger and Tickner, 1999). Definitions such as these beg many questions. Is there ever full scientific certainty? Do we need a minimal threshold of scientific certainty or plausibility before we may (or should) undertake preventative action? And do we really know how to prevent harm if we are so much ignorant about the underlying cause-effect relationships? The definitions that are currently on offer fail to spell out the precise conditions that have to be fulfilled before the PP may be invoked or the nature of the preventative action that has to be taken. The types of action suggested range from implementing a ban, imposing a moratorium while further research is conducted, allowing the potentially harmful activity to proceed while closely monitoring its effects, to just conducting more research. The PP does not have a very precise meaning as long as such crucial aspects are left largely unanswered. In practice, however, the PP is often given a more definite meaning by reducing it to an absurdity. Normally, no minimal threshold of plausibility is specified as a “triggering” condition, so that even the slightest indication that a particular product or activity might possibly produce some harm to human health or the environment will suffice to invoke the principle. And just as often no other preventative action is contemplated than an outright ban on the incriminated product or activity. The intervention of Greenpeace in the monarch butterfly case seems to fit this pattern. Closely linked to various versions of the PP is the idea of reversing the onus of proof. Thus, the adherents of the Wingspread Statement declare that “the applicant or proponent of an activity or process or chemical needs to demonstrate that the environment and public health will be safe. The proof must shift to the party or entity that will benefit from the activity and that is most likely to have the information” (Raffensberger and Tickner, 1999). Greenpeace also holds that effective implementation of the PP requires a shift in the burden of proof (Greenpeace, 2001). Shifting the burden of proof seems a fairly straightforward way to ensure, as Jonas demanded, that greater weight will be given to the “prognosis of doom” than to the “prognosis of bliss.” Before looking into the proper assignment of the burden of proof, we must first examine more closely the underlying justification for the strong version of the PP. Why should the prospect of harmful effects of a new technology take precedence over the prospect of beneficial effects, quite apart from the inherent likelihood of each of these possibilities? The obvious answer seems to be that such a priority is defensible only when the harmful effects are of such magnitude that they carry catastrophic (or, as Jonas would say, “apocalyptic”) potential. The infinite costs of a possible catastrophic outcome necessarily outweigh even the slightest probability of its occurrence. This type of reasoning exhibits a remarkable resemblance to a well-known example of a “zero-infinity dilemma,” namely Pascal's famous “wager.” When it comes to wagering on the existence of God, the 17th century French philosopher argued incisively in his Pensées that it is better to be safe than sorry (Haller, 2000; Graham, 2002; Manson, 2002). Given an unknown but nonzero probability of God's existence and the infinity of the reward of an eternal life, the rational option would be to conduct one's earthly life as if God exists. Alas, Pascal's reasoning contains a fatal flaw. His argument is vulnerable to the “many gods” objection (Manson, 2002). Consider the possible existence of another deity than God, say Odin. If Odin is jealous, he will resent our worship of God, and we will have to pay an infinite price for our mistake. Never mind that Odin's existence may not seem likely or plausible to us. It is sufficient that we cannot exclude the possibility that he exists with absolute certainty. Therefore, the very same logic of Pascal's wager would lead us to adopt the opposite conclusion not to worship God. Pascal's argument, then, cannot be valid. If the wager argument is not valid, the strong version of the PP (which Manson dubs the “catastrophe principle”) cannot be valid either. Take the application of this principle to the problem of global warming. Environmentalists often argue that even if it is not conclusively established that the emission of carbon dioxide and other gases causes an enhanced greenhouse effect, the mere prospect of an ecological catastrophe due to such a scenario should lead us to drastically curb our emissions of greenhouse gases now. By the same logic, however, one could conjure up the possibility of a coming ice age. The mere prospect of this equally catastrophic scenario should then induce us to avert this outcome by stepping up the emission of greenhouse gases. Thus, the strong version of the PP would lead to contradictory recommendations (compare with Graham, 2002). In a similar way, it could be argued that this principle commits us to each of two contradictory policies: (a) We must not develop GM crops, and (b) We must develop GM crops. The first alternative is argued vehemently by many environmentalists who appeal to the PP. To support the second possibility, Gary Comstock conjures up a dramatic scenario in which people are forced to seize upon the remaining reserves of nature in a desperate effort to overcome food shortages resulting from global warming. He then argues, in the style of the environmentalists, that “lack of full scientific certainty that GM crops will prevent environmental degradation shall not be used as a reason for postponing this potentially cost-effective measure” (Comstock, 2000). Therefore, the strong version of the PP is untenable. But what about the proposed shifting of the onus of proof toward those who advocate a new technology or activity? Reversing the burden of proof would amount to substituting the maxim “guilty until proven innocent” for the age-old legal principle “innocent until proven guilty.” Biotech enthusiasts and antiregulationists resent this departure from what they consider time-honored legal sanity (Miller and Conko, 2000). They are prone to counter the frequent invocation of the PP with an equally insistent demand of “sound science.” The same opposition is also at the center of the present World Trade Organization trade disputes between the United States and the European Union and their disagreement on the regulation of GM crops. One side claims the moral high ground, whereas the other side attempts to seize the scientific high ground. The situation is highly polarized because various economic and political interests are at stake (Fig. 1). Wheat (Triticum aestivum) fields in the Palouse region of the state of Washington in the United States. The polarized discussion about the PP and the adoption of GM crops has become a proxy for everything that Europeans and environmentalists in other countries don't like about modern agriculture. The rejection of agricultural biotechnology may perhaps be tolerated as a European indulgence but hardly makes sense on a global scale. The critics of the PP assert that the burden that environmentalists and regulators want to impose on the proponents of new technologies tends to be unbearable (Miller and Conko, 2000). In the name of absolute safety, the latter are asked nothing less than to demonstrate conclusively that the new technologies they advocate offer no possible harm. This is a formidable, perhaps even logically impossible, task. You cannot prove a negative (compare with Wildavsky, 1995). Moreover, a risk-free world is not a real option. Thus, a consistent application of the PP would in the final analysis stifle all innovation. A closer analysis of what is involved in applying the classical principle “innocent until proven guilty,” however, reveals that the situation need not be as black and white as it seems at first sight. Take the paradigm case of criminal justice. There are two main ways in which a miscarriage of justice can come about. Either the suspect did not commit the crime, but the verdict found him guilty; or the suspect did commit the crime, but the verdict found him not guilty. In a civilized system of justice, the risks of the first type of error are minimized as far as possible. That is what is meant by the phrase “innocent until proven guilty.” The system contains safeguards and precautions in the form of high standards of proof so as to ensure that a suspect will be condemned for a certain criminal offense only if it has been established “beyond reasonable doubt” that he in fact committed the alleged offense. Alas, there is a price to be paid for this cautious and civilized approach, namely the possibly large number of wrongdoers who have to be acquitted due to “lack of sufficient proof.” To a certain extent, the risks of the two types of error are inversely related. We may to the risk of an by demanding ever more standards of proof but only at the of increasing the risk of Therefore, we must that there is an involved in the of our system of criminal justice. We may to our standards as high as we but a must be the system will become by making it to sentence on the of there is a similar to be between the of a type or a type the of when it is in fact or to the when in fact it is By a we a particular this should on our of the and with of the two types of The analysis that the at issue is not just to burden of proof. as we for more or less standards of proof, an of In other the burden we want to put on the of one or the other party more or less on we our standards of proof more or less This may us to from the polarized opposition of PP versus In most companies to GM crops have to their to for health effects and environmental This can be more or less The of those who by “sound is a fully risk However, it is only possible to this in more and such as or are at then the expression “sound is because it the that necessarily into the of of and between type and type In other or more ecological effects are at the of the fully risk is of “sound will be to such less straightforward as or risks that can be However, as the proponents of the PP are in lack of of harm is not of lack of harm. If we are really about such hazards, we can put in effort to more about their plausibility or It would be to our with an appeal to “sound science.” A recent European on the release of GMOs into the environment that any that to or a transgenic should carry out a environmental risk into immediate and 2001). This new regulation of GM crops much further than some American also argue for a more approach et al., 2001). The new European a burden of proof on biotech companies to or not they are to take that burden on their will on the definition of a or for conducting environmental risk The to be is that the on these companies will become them at the of regulatory and for of environmental This will be enhanced by the fact that the of the has been by the PP and that regulatory authorities may give to the of GMOs only they have been that the release will be safe for human health and the The fairly of the environmental risk need not be in if of play for the regulation of GM crops can be More is also about the that have to be taken into in The outcome of the is for on or not in are taken as a or or not a strong to as a option is 2001). The and of a Bt maize hybrid or any other transgenic might be quite in than in the United States. Europeans are to because their countries lack of and other of regulatory at holds that the in on GM is not about safety, but is in fact a proxy for a on how should be 2001). GM crops have become a for all that Europeans don't like in modern agriculture. a for and a rejection of agricultural biotechnology perhaps may be tolerated as a European the prospect hardly makes sense on a global scale. this is what Greenpeace us as a the NGO us a serious answer to the of how to a growing world and natural the of modern biotechnology (compare with 1999). We can even press the environmentalist organization by the Thus, it that the polarized on the PP is just a proxy for a on the of world agriculture.

Anthony Trewavas, Christopher J. Leaver

No abstract is available for this record.