Scientific Standards and the Regulation of Genetically Modified Insects

Experimental releases of genetically modified (GM) insects are reportedly being evaluated in various countries, including Brazil, the Cayman Islands (United Kingdom), France, Guatemala, India, Malaysia, Mexico, Panama, Philippines, Singapore, Thailand, the United States of America, and Vietnam. GM mosquitoes (Aedes aegypti) have already been released for field trials into inhabited areas in the Cayman Islands (2009–?), Malaysia (2010–2011), and Brazil (2011–2012). Here, we assess the regulatory process in the first three countries permitting releases (Malaysia, US, and the Cayman Islands) in terms of pre-release transparency and scientific quality. We find that, despite 14 US government–funded field trials over the last 9 years (on a moth pest of cotton), there has been no scientific publication of experimental data, and in only two instances have permit applications been published. The world's first environmental impact statement (EIS) on GM insects, produced by US authorities in 2008, is found to be scientifically deficient on the basis that (1) most consideration of environmental risk is too generic to be scientifically meaningful; (2) it relies on unpublished data to establish central scientific points; and (3) of the approximately 170 scientific publications cited, the endorsement of the majority of novel transgenic approaches is based on just two laboratory studies in only one of the four species covered by the document. We find that it is not possible to determine from documents publically available prior to the start of releases if obvious hazards of the particular GM mosquitoes released in Malaysia, the Cayman Islands, and Brazil received expert examination. Simple regulatory measures are proposed that would build public confidence and stimulate the independent experimental studies that environmental risk assessments require. Finally, a checklist is provided to assist the general public, journalists, and lawmakers in determining, from documents issued by regulators prior to the start of releases, whether permit approval is likely to have a scientifically high quality basi

Checklist for assessing the scientific quality of approvals for un-caged field trials, based on the examination of documents made publically available by regulators prior to the start of releases.

<p>Citations given in the above checklist are intended to provide for non-specialist readers a small number of relevant passages from national laws, international agreements, scientific literature, or regulatory guidelines.</p

Global extent of legislation relating to living genetically modified organisms by 2010.

<p>One hundred and sixty governments are parties to the Cartagena Protocol on Biosafety, and ten that are not parties have chosen to submit documents to the Biosafety Clearing-House (an instrument set up under the Cartagena Protocol) relating to “National Laws, Regulations and Guidelines” governing the release or transportation of living GM organisms. Of the remaining countries, the US, Israel, and Singapore are known to have specific laws regulating living GM organisms (all the above countries and categories are colored in blue). Consequently, countries and territories colored blue have at least some specific laws governing the release or transportation of living GM organisms. For the remaining 21 countries that are not parties to the Cartagena Protocol on Biosafety and some overseas or disputed territories, it is unclear if they have any relevant laws (colored yellow). The locations of field trials mentioned in the text are indicated by arrows. Malaysia and the US both have comprehensive, specific legislation, and Malaysia is also a party to the Cartagena Protocol on Biosafety. While the UK is a party to the Cartagena Protocol on Biosafety, the Cayman Islands (which are a UK overseas territory) has not become a party to the protocol despite encouragement to do so by the UK government <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0001502#pntd.0001502-Countess3" target="_blank">[78]</a>, <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0001502#pntd.0001502-Countess4" target="_blank">[112]</a>. A quote from a senior researcher of the research institute conducting the field trial in 2009 <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0001502#pntd.0001502-Nightingale1" target="_blank">[9]</a> confirms that the Cayman Islands had no enacted legislation relating to living GM organisms (only draft legislation is mentioned <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0001502#pntd.0001502-Cayman3" target="_blank">[113]</a>). See <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0001502#pntd.0001502.s006" target="_blank">Supporting File S6</a> for additional map details.</p

Twelve novel HGD gene variants identified in 99 alkaptonuria patients: focus on ‘black bone disease’ in Italy

Alkaptonuria (AKU) is an autosomal recessive disorder caused by mutations in homogentisate-1,2-dioxygenase (HGD) gene leading to the deficiency of HGD enzyme activity. The DevelopAKUre project is underway to test nitisinone as a specific treatment to counteract this derangement of the phenylalanine-tyrosine catabolic pathway. We analysed DNA of 40 AKU patients enrolled for SONIA1, the first study in DevelopAKUre, and of 59 other AKU patients sent to our laboratory for molecular diagnostics. We identified 12 novel DNA variants: one was identified in patients from Brazil (c.557T>A), Slovakia (c.500C>T) and France (c.440T>C), three in patients from India (c.469+6T>C, c.650–85A>G, c.158G>A), and six in patients from Italy (c.742A>G, c.614G>A, c.1057A>C, c.752G>A, c.119A>C, c.926G>T). Thus, the total number of potential AKU-causing variants found in 380 patients reported in the HGD mutation database is now 129. Using mCSM and DUET, computational approaches based on the protein 3D structure, the novel missense variants are predicted to affect the activity of the enzyme by three mechanisms: decrease of stability of individual protomers, disruption of protomer-protomer interactions or modification of residues in the region of the active site. We also present an overview of AKU in Italy, where so far about 60 AKU cases are known and DNA analysis has been reported for 34 of them. In this rather small group, 26 different HGD variants affecting function were described, indicating rather high heterogeneity. Twelve of these variants seem to be specific for Italy