nature biotechnology volume 26 number 9 september 2008 9 7 5 and disrupt field research that they deem unacceptable. There are important lessons here. First, you don’t conciliate thugs by capitulating to them. Second, the problem would have been avoided entirely, had public policy been crafted intelligently in the first place. And third, when universities permit intimidation to compromise academic freedom and the safety of their faculty and students, they become part of the problem. Henry I Miller The Hoover Institution, 434 Galvez Mall, Stanford University, Stanford, California 94305- 6010, USA. e-mail: miller@hoover.stanford.edu 1. Anonymous. Nat. Biotechnol. 25, 950 (2007). 2. Schiermeier, Q. Nature 453, 263 (2008). for field testing with recombinant DNA– modified plants. In contrast, plants with similar or even identical traits that were created with less precise techniques, such as hybridization or mutagenesis, are subject to no government scrutiny or requirements (or publicity or vandalism) at all. And that applies even to the numerous new plant varieties that result from ‘wide crosses’ with embryo rescue, hybridizations that move genes from one species or genus to another; that is, across what used to be thought of as natural breeding boundaries. If recombinant DNA–modified plants were treated appropriately—that is, no differently from other new varieties—their testing would not need special warning signs or public announcements of test sites. There would be no way for the vandals to target ‘degenerate research’, and allowing persecution of practitioners of certain intellectual approaches, such as the use of the most precise and predictable techniques for genetic modification, the stridency and absolutism of the activists’ pronouncements—and their violent tendencies—will only increase. It is not hard to draw parallels with some of the excesses of intellectual persecution in the 1930s, when the regime’s objections to Entartete Kunst, or ‘degenerate art’, drove out such great minds and innovators as Albert Einstein, Emil Nolde, Max Beckmann, Marc Chagall, Vincent van Gogh, Henri Matisse, Edvard Munch and Pablo Picasso. Those who ignore the mistakes of history are destined to repeat them. But Herr Hormuth has a different take on Germany’s past. In an e-mail to me, he wrote: “If we look at history then we should have also learned that we have to act responsibly with the results and possibilities of scientific research and are accountable to society.” A quite extraordinary statement. Given the existing achievements of recombinant DNA–modified plants—economic benefits to farmers, less use of chemical pesticides, more environment-friendly farming practices—he appears to have a peculiar view of what constitutes acting “responsibly with the results and possibilities of scientific research” and being accountable to society. Could anyone argue seriously that delaying or abandoning a demonstrably safe technology that is environmentally friendly and enhances food (and potentially, biofuel) production is beneficial to society? This time around, the German government is not directly culpable for the current situation, but it certainly has failed to protect freedom of expression and the personal safety and property of plant scientists against assaults by antitechnology activists. (In the United States, such groups have been officially designated as terrorist organizations.) How have we arrived at a position in the 21st century where thugs and vandals dictate the research and syllabus of the academic institutions of a major Western European democracy? One reason is that policy makers in both the European Union (EU) and in individual European countries like Germany have consciously and purposefully chosen not to apply scientific and risk-based regulatory policies to the oversight of recombinant DNA–modified plants. Flying in the face of the scientific consensus—including the EU’s own risk assessments—current EU and national regulations cast a veil of suspicion over agbiotech by requiring case-by-case government environmental assessments Trace and traceability—a call for regulatory harmony To the Editor: Genetically modified (GM) crops were grown commercially in 23 countries in 2007, with a further 29 allowing the import of GM crops for food and/or feed use and release into the environment1. Despite encouraging evidence concerning the positive socioeconomic and environmental benefits brought about by the adoption of GM technology1,2, we wish to highlight the fact that further development is being hampered by a lack of harmonization among national regulatory frameworks relating to research, biosafety and to the trade and use of GM crops. Nowhere is this more apparent than in the laws and regulations governing the tolerance levels for GM material in non-GM food and in the labeling and traceability of GM products. The definition of what is considered GM and non-GM food varies from country to country, with some nations enshrining precise tolerance targets in their GM regulations and some overlooking this important criterion. The European Union (EU; Brussels) follows the ‘precautionary approach’ and the consumers’ ‘right to know’, with stringent approval, labeling and traceability standards on any food produced from or derived from GM ingredients3. In contrast, US regulations are based on differences in the end product, and include a voluntary safety consultation and voluntary labeling guidelines for GM food4. Most other developed countries, including Japan, Canada, Australia and New Zealand, have introduced regulations that share features of both the EU and US systems4. Developing countries often base their regulatory frameworks on models promoted by developed nations without considering the potential socioeconomic impact of such decisions, and the negative consequences of an overcautious regulatory environment on the health and well-being of their populations. The regulatory frameworks of selected countries are compared in Table 1. In the United States and Canada, as well as Japan and Taiwan, food and feed can be classed as non-GM, even if they contain up to 5% GM material. In contrast, other countries set much lower limits (e.g., 0.9% in the EU or 1% in Australia, New Zealand, South Africa, Brazil and China). The EU actually has a two-tier tolerance policy, with the 0.9% limit applied to approved GM organisms, and a stricter 0.5% limit applied to GM organisms that have yet to be approved, but which have received favorable risk assessments. In many developing countries, there appears to be no established tolerance limit, which calls into question how such countries will distinguish GM and non-GM food and feed. Similarly, this global regulatory discord begs the question of how nominally GM-free food and feed imported from countries with high tolerance will be handled in stricter countries when it may breach local regulations concerning GM tolerance. This inevitably will c o r r e S p o N D e N c e © 2 0 0 8 N a tu re P u b li s h in g G ro u p h tt p :/ /w w w .n a tu re .c o m /n a tu re b io te c h n o lo g y mailto:miller@hoover.stanford.edu 9 7 6 volume 26 number 9 september 2008 nature biotechnology As the prevalence of GM crops continues to grow, we foresee real problems with the trade and use of food and feed if the regulations are not harmonized on a global level. US food exporters and biotech companies have already complained about the EU’s slow and obscure approval process, and bans by individual EU countries on GM products approved by the EU as a whole5. This ongoing dispute has been intensified by by disharmonious regulations concerning the labeling and traceability of GM food. The USA, Canada, Mexico, Argentina, The Philippines and South Africa have voluntary labeling practices, whereas the EU, Australia, New Zealand, China, Chile, Brazil and Taiwan require the mandatory labeling of GM produce. Still other countries, including Bangladesh, Egypt and Kenya, have no requirements for labeling at all. lead to disputes and the impounding of food and feed. The potential confusion caused by these conflicting tolerance levels will only become worse as more countries join the ‘GM club’. It is projected that the number of countries growing GM food and feed commercially will double over the next 10 years in line with the amount of land given over to GM crops1. The potential for conflict is compounded Table 1 Current GM biosafety regulations for selected countries Country Governing bodies/agencies Regulations/laws Product/ process based Transparency Labeling and traceability Tolerance levels Argentina comisión Nacional Asesora de Biotecnología Agropecuaria, Servicio Nacional de Sanidad y calidad Agroalimentaria, Instituto Nacional de Semillas, Direccion Nacional de Mercados Agroalimentarios Law 18284 on Argentine Food codex, Decree 1585/96, Decree 4238, Decree 815/99, resolution 289/97, resolution 511/98, resolution 1265/99 product Yes Voluntary n.d. Australia office of the Gene Technology regulator, Food Standards Australia New Zealand Gene Technology Act 2000, Standard 1.5.2- Food produced Using Gene Technology process Yes Mandatory 1% Bangladesh Ministry of Agriculture, Ministry of Science and Information & communication Technology, Ministry of environment & Forest Draft Biosafety Guidelines product n.d. No labeling regulation n.d. Brazil conselho Nacional de Biosegurança, comissão Técnica Nacional de Biossegurança Biosafety Law Number 11.105 process n.d. Mandatory 1% Burkina Faso National Biosafety Agency Decree 2003-208-/preS/pM/MAecr/ MFB/MecV process No n.d. n.d. canada canadian Food Inspection Agency consumer packaging & Labeling Act, Feeds Act, Fertilizers Act, Food & Drugs Act, Health of Animals Act, Seeds Act, plant protection Act product Yes Voluntarya 5% Health canada Food & Drugs Act, canadian environmental protection Act, pest control products Act environment canada canadian environmental protection Act chile Advisory committee for the release of Transgenics (Ministry of Agriculture, Agricultural and Livestock Service, National Agricultural research Institute, National commission on Scientific and Technical research) resolution of exemption 1927/93 Decree- Law 3554/81 n.d. n.d. Mandatory n.d. china Administration for Quality Supervision, Inspection and Quarantine State environmental protection Administration, Ministry of Science and Technology, Ministry of commerce, Ministry of Health Under discussion process n.d. Mandatory 1% egypt National Biosafety committee No proper biosafety regulation but Ministerial decree No. 1648 (1998) is for commercialization of imported products; National Biosafety committee guidelines occur, however, not legally binding process n.d. No labeling required (no framework) Not estab- lished eU Member states’ competent authorities and european commission eU Directive 2001/18/ec (2001), ec regulation 258/97 (1997) process Yes Mandatoryb 0.9%; 0.5% food and feed India Ministry of environment & Forests, Department of Biotechnology epA 1986 &1989 rules process Yes proposed legis- lation for man- datory labeling occurs n.d. Japan Ministry of Agriculture, Forestry and Fisheries, Ministry of Health, Labor and Welfare, Ministry of the environment, Ministry of education, culture, Sports, Science and Technology Law concerning the conservation & Sustainable Use of Biological Diversity through regulations on the Use of LMos, Food Sanitation Law, Feed Safety Law process Yes Mandatory for selected prod- ucts 5% (continued) c o r r e S p o N D e N c e © 2 0 0 8 N a tu re P u b li s h in g G ro u p h tt p :/ /w w w .n a tu re .c o m /n a tu re b io te c h n o lo g y nature biotechnology volume 26 number 9 september 2008 9 7 7 earned $27 billion from the technology, split almost equally between developed and developing countries2. As well as direct economic benefits, GM crops reduce pesticide use, and reduce the use of fossil fuels in agriculture2. These benefits could be lost, or curtailed, if the regulations in different parts of the world are not brought into line, or at least made mutually compatible. It is also important to base the global regulations on scientific principles rather than unrealistic expectations of risk avoidance. Currently, many countries have in place regulations that erect unnecessary hurdles to the further development of the technology, especially banning GM products all together, even after they have been approved as safe by European Food Safety Authority (Parma, Italy), the EU’s own regulatory agency on GM6. Developing countries have also been drawn into this dispute as both sides try to win their support. Many developing countries have banned GM products owing to consumer and environmental concerns, only to find themselves excluded from markets and refused financial support from industrialized nations to conduct research and build human capital for biotech activities. In the decade since GM crops were first adopted, it is estimated that farmers have the EU’s introduction of mandatory labeling. The role of the World Trade Organization’s (Geneva) legal framework regarding trade in GM products (the Sanitary and Phytosanitary Agreement, and the Agreement on Technical Barriers to Trade; http://www. wto.org has played a significant role in stifling the opportunities offered by GM products. Strict labeling, identity preservation and import requirements impose additional costs and reduce public confidence, which in turn affects trade. The decline in US corn exports to the EU has been blamed on the EU’s strict approval and labeling requirements, with some EU countries Table 1 Current GM biosafety regulations for selected countries (continued) Country Governing bodies/agencies Regulations/laws Product/ process based Transparency Labeling and traceability Tolerance levels Kenya National Biosafety committee, National environmental Management Authority, Kenya Bureau of Standards, Kenya Animal plant Health Inspectorate Services, Kenya Standing committee on Imports and exports, public Health Department, Department of Veterinary Services, pest control products Board Kenyan Draft Biosafety Bill of 2003, eMcA Act process Yes No labeling addressed in draft bill Not estab- lished Mexico Secretaria de Agricultura, Ganaderia, Desarrollo rural, pesca y Alimentacion, Secretaría de medio ambiente y recursos naturales, Secretaria de Salud, comision Federal para la proteccion contra riesgos Sanitarios, comisión Intersecretarial de Bioseguridad de los organismos Genéticamente Modificados Biosafety Law of Genetically Modified organisms (2005) process Yes Mandatory n.d. New Zealand environmental risk Management Authority, New Zealand Food Safety Authority, Food Standards Australia New Zealand, Ministry of Agriculture and Forestry The Hazardous Substances & New organisms Act 1996 (HSNo Act) process Yes Mandatory 1% Nigeria Federal Ministry of environment, National Biosafety committee Nigeria Biosafety Guidelines, Draft biosafety bill process Yes (planned in draft bill) Mandatory as planned in draft n.d. South Africa executive council of Genetically Modified organisms, Department of Agriculture, Department of environment and Tourism, Department of Health GMo Act, 1997 (Act No. 15 of 1997), amended 2007; National Biodiversity Act product Yes Voluntary 1% Taiwan Taiwan Department of Health; council of Agriculture Article 14 of the Law Governing Food Sanitation product Yes Mandatory 5% The philippines National committee on Biosafety of the philippines (Departments of Agriculture, Science and Technology, Health, and environment and Natural resources), Institutional Biosafety committee e.o. 430 (1990) DA-A.o. No. 8 (2002) product Yes Voluntary 5% UK Health and Safety executive, Department for environment, Food, and rural Affairs Directive 2001/18/ec process Yes Mandatory c Food Standards Agency, Advisory committee on releases to the environment regulation (ec) No 1829/2003 USA US Department of Agriculture Federal plant protection Act product Yes Voluntarya 5% environmental protection Agency Federal Insecticide Fungicide and rodenticide Act, Federal Food Drug and cosmetic Act, Toxic Substances control Act Food and Drug Administration Federal Food Drug and cosmetic Act Zambia National Biosafety Authority, Scientific Advisory committeed National Biotechnology & Biosafety Bill process Yes n.d. n.d. aLabeling required if safety concerns (allergenic, change in nutritional composition) exist. bLabeling required at a 0.9% threshold for approved GM organisms or 0.5% for GM organisms given a favorable risk assessment but not yet approved (called ‘adventitious presence’) and 0% for unapproved GMos. cTo be established by the biosafety bill, however, the parliamentary committee on education, Science and Technology currently is in rule. dLabeling is required of seeds used for planting—the characteristics of the acquired genetic combination, implications with regard to special conditions and growing requirements, and changes in reproductive and productive characteristics should be stated. n.d., not disclosed. c o r r e S p o N D e N c e © 2 0 0 8 N a tu re P u b li s h in g G ro u p h tt p :/ /w w w .n a tu re .c o m /n a tu re b io te c h n o lo g y 9 7 8 volume 26 number 9 september 2008 nature biotechnology have neglected to consult a comparative pathologist during the evaluation of such manuscripts. One must wonder whether such a practice would be allowed if a submitted manuscript contained complex statistical analyses and no statistician was involved during the preparation or review of the manuscript, or crystallography was used to resolve a molecular structure but no expert was asked to check the X-ray diffraction data. Yet, it appears that when it comes to evaluation of human tissues and genetically engineered mouse (GEM) phenotypes, which is no less complex than statistics or X-ray diffraction, unvalidated1 DIY pathology’ has become common— and frequently accepted—practice2. We have previously noted the dwindling number of comparative pathologist- scientists who are qualified to coordinate and critique the pathological interpretation and the basic science in a manuscript3,4. There is an urgent need to make use of existing experts and encourage the growth of this discipline5. We recognize that a qualified expert may not be available for journal editors in some instances. However, when a pathologist-scientist who can review the entire manuscript is not available, both journal editors and grant study sections should, at least, seek the expert opinion of a pathologist to perform a fact and/or quality check of the pathology data, without necessarily commenting on the basic science. Implementing such a policy routinely during manuscript reviews in Nature journals would have an immense positive impact for the future health of scientific research. We, a group of concerned investigator-pathologists, have formed a nonprofit educational foundation, Center for Genomic Pathology (CGP; Davis, CA, USA; http://www. ctrgenpath.org/) to address these issues. We invite others who are interested in this issue to participate in a comprehensive debate to develop standards for the manuscript and the grant review process involving human and genetically engineered mouse tissues and use of pathology in research. We note that this letter represents a consensus opinion of the faculty of CGP and other cosigners below. Tan A Ince1, Jerrold M Ward2, Victor E Valli3, Dennis Sgroi4, Alexander Yu Nikitin5, Massimo Loda1,6, Stephen M Griffey7, Christopher P Crum1, James M Crawford8, Roderick T Bronson9 & Robert D Cardiff10 1Department of Pathology, Harvard Medical School, Division of Women’s and Perinatal 1Departament de Produccio Vegetal I Ciencia Forestal, University of Lleida, Avenue Alcalde Rovira Roure 177, E-25198 Lleida, Spain. 2Department of Biology, University of York, Heslington, York YO10 5DD, UK. 3Department of Biology, Calvin College, 1726 Knollcrest Circle, S.E., Grand Rapids, Michigan 49546-4403, USA. 4Institucio Catalana de Recerca i Estudis Avancats, Passeig Lluís Companys, 08018, Barcelona, Spain. e-mail: christou@pvcf.udl.cat 1. James, c. ISAAA Brief No. 37. (ISAAA, Ithaca, NY, USA, 2007). 2. Brookes, G. & Barfoot, p. ISAAA Brief No. 36. (ISAAA, Ithaca, NY, USA, 2006). 3. Gruère, G.p. Food Policy 31, 148–161 (2006). 4. carter, c.A. & Gruère, G.p. in Regulating Agricultural Biotechnology. Economics and Policies (eds. Just, r., Alston, J.M. & Zilberman, D.) 459–480 (Springer publishing, New York, USA, 2006). 5. Fransen, L., La Vina, A., Dayrit, F., Gatlabayan, L., Santosa, D.A. & Adiwibowo, S. Integrating Socio- Economic Considerations into Biosafety Decisions: The Role of Public Participation (World resources Institute White paper, WrI, Washington, Dc, USA, 2005). 6. Bernauer, T. Genes, Trade and Regulation: The Seeds of Conflict in Food Biotechnology (princeton University press, princeton, NJ, USA, 2003). 7. christou p. & Twyman, r.M. Nutrition Res. Rev. 17, 23–42 (2004). 8. Bernauer, T. Intl. J. Biotechnol. 7, 7–28 (2005). developing countries where the benefits are most needed7. Several policy tools have been used to accommodate, reduce or eliminate international regulatory diversity8. One realistic approach is ‘mutual recognition’, where countries agree to recognize each other’s regulations; for example, the US and EU could agree to allow imports of each other’s products (GM and conventional) produced and marketed under home regulations, giving consumers on both sides of the Atlantic the choice. Perhaps if Europe and the US were to show such leadership, this type of compromise could be rolled out globally. Whatever the case, as more and more countries cultivate GM varieties, and national and international bodies continue to promulgate diverging regulatory approaches, there is little doubt that a more harmonious future for GM food and feed regulation would be in the interests of all. Koreen Ramessar1, Teresa Capell1, Richard M Twyman2, Hector Quemada3 & Paul Christou1,4 Do-it-yourself (DIY) pathology To the Editor: An exchange of correspondence in your November issue highlighted the importance of precise terminology for pathology data and terminology in scientific research and literature1. In the past few decades, several developments in technology have significantly increased the use of pathology in basic and translational research. For example, the development of genetically engineered mice has resulted in the creation of an ever-increasing variety of murine disease models. And more recently, availability of new technologies, such as mRNA expression arrays and tissue microarrays, has allowed basic researchers to work with patient tissue samples. Even so, the application of these technologies appears to have outpaced our ability to properly evaluate the resulting data2. The systematic analysis of disease phenotypes in mice, and their correlation with human disease, requires expertise in ‘comparative pathology’, encompassing training both in mouse and human gross anatomy, microscopic analysis of tissues (histopathology and immunopathology) and disease mechanisms (pathobiology), which even the most accomplished basic or clinical scientists frequently lack2. Formal training in one field of pathology might prepare one to become a self-taught expert in another field of pathology. However, we find it unlikely that one can become an expert pathologist with no prior formal training. Those of us with comparative pathology expertise have collectively noted that numerous tissue-based research studies have been published over the past decade without a pathologist among the authors, collaborators or consultants2. Furthermore, based on the frequently inaccurate use of pathology terms and misinterpretation of data in many of these studies, it appears that not only the authors but also the reviewers and editors often c o r r e S p o N D e N c e © 2 0 0 8 N a tu re P u b li s h in g G ro u p h tt p :/ /w w w .n a tu re .c o m /n a tu re b io te c h n o lo g y http://www.ctrgenpath.org/ http://www.ctrgenpath.org/