Allergenicity assessment of genetically modified crops--what makes sense?

Goodman RE, Vieths S, Sampson HA, Hill D, Ebisawa M, Taylor SL, van Ree R.

Department of Food Science & Technology, University of Nebraska, Lincoln,
Nebraska, 68583-0955, USA. rgoodman2@unlnotes.unl.edu

GM crops have great potential to improve food quality, increase harvest yields
and decrease dependency on certain chemical pesticides. Before entering the
market their safety needs to be scrutinized. This includes a detailed analysis of
allergenic risks, as the safety of allergic consumers has high priority. However,
not all tests currently being applied to assessing allergenicity have a sound
scientific basis. Recent events with transgenic crops reveal the fallacy of
applying such tests to GM crops.

Publication Types: 
    Research Support, U.S. Gov't, Non-P.H.S.
    Review

PMID: 18183024 [PubMed - indexed for MEDLINE]

2: Nature. 2007 Dec 13;450(7172):928-9.

Showdown for Europe.

Abbott A, Schiermeier Q.

Publication Types: 
    News

PMID: 18075535 [PubMed - indexed for MEDLINE]

3: Nature. 2007 Dec 13;450(7172):921.

Directive action required.

[No authors listed]

Publication Types: 
    Editorial

PMID: 18075528 [PubMed - indexed for MEDLINE]

4: Toxicol Lett. 2007 Dec 10;175(1-3):118-35. Epub 2007 Oct 10.

Zero tolerances in food and animal feed -- are there any scientific alternatives?
A European point of view on an international controversy.

Heberer T, Lahrssen-Wiederholt M, Schafft H, Abraham K, Pzyrembel H, Henning KJ, 
Schauzu M, Braeunig J, Goetz M, Niemann L, Gundert-Remy U, Luch A, Appel B,
Banasiak U, Böl GF, Lampen A, Wittkowski R, Hensel A.

Federal Institute for Risk Assessment, Section 55, - Residues of Medicinal
Products, Diedersdorfer Weg 1, 12277 Berlin, Germany. bfr@bfr.bund.de

A number of zero tolerance provisions are contained in both food and animal feed 
law, e.g. for chemical substances whose occurrence is not permitted or is
directly prohibited in food or animal feed. In the European Union, bans of this
kind were introduced to give consumers and animals the greatest possible
protection from substances with a possible hazard potential within the intendment
of the hazard prevention principles and current precautionary measures. This also
applies to substances for which an acceptable daily intake cannot be derived and 
a maximum residue limit cannot, therefore, be established, e.g. due to missing or
inadequate toxicological data. Zero tolerances are also under discussion as trade
barriers because their use has triggered numerous legal disputes. This paper
draws together the results of an evaluation of alternative risk assessment
methods to be used for the risk assessment of substances to which currently only 
zero tolerances apply. It will demonstrate that, depending on the available
toxicological data, a scientifically sound risk assessment may still be possible.
In this context, the two concepts - margin of exposure and threshold of
toxicological concern - are very promising approaches. Until the scientific and
sociopolitical discussions have been completed, it is essential that the
principle of zero tolerances be upheld, especially for those substances which may
be genotoxic carcinogens. In microbiology, there is no legal room for manoeuvre
with regard to food safety criteria established for reasons of consumer health
protection on the basis of scientific assessments.

PMID: 18024010 [PubMed - indexed for MEDLINE]

5: Anal Bioanal Chem. 2008 Jan;390(1):377-87. Epub 2007 Nov 11.

Detection and characterization of recombinant DNA expressing vip3A-type
insecticidal gene in GMOs--standard single, multiplex and construct-specific PCR 
assays.

Singh CK, Ojha A, Bhatanagar RK, Kachru DN.

Industrial Toxicology Research Centre, Post Box No. 80, M. G. Marg, Lucknow,
226001, Uttar Pradesh, India.

Vegetative insecticidal protein (Vip), a unique class of insecticidal protein, is
now part of transgenic plants for conferring resistance against lepidopteron
pests. In order to address the imminent regulatory need for detection and
labeling of vip3A carrying genetically modified (GM) products, we have developed 
a standard single PCR and a multiplex PCR assay. As far as we are aware, this is 
the first report on PCR-based detection of a vip3A-type gene (vip-s) in
transgenic cotton and tobacco. Our assay involves amplification of a 284-bp
region of the vip-s gene. This assay can possibly detect as many as 20 natural
wild-type isolates bearing a vip3A-like gene and two synthetic genes of vip3A in 
transgenic plants. The limit of detection as established by our assay for GM
trait (vip-s) is 0.1%. Spiking with nontarget DNA originating from diverse plant 
sources had no inhibitory effect on vip-s detection. Since autoclaving of vip-s
bearing GM leaf samples showed no deterioration/interference in detection
efficacy, the assay seems to be suitable for processed food products as well. The
vip-s amplicon identity was reconfirmed by restriction endonuclease assay. The
primer set for vip-s was equally effective in a multiplex PCR assay format
(duplex, triplex and quadruplex), used in conjunction with the primer sets for
the npt-II selectable marker gene, Cauliflower mosaic virus 35S promoter and
nopaline synthetase terminator, enabling concurrent detection of the transgene,
regulatory sequences and marker gene. Further, the entire transgene construct was
amplified using the forward primer of the promoter and the reverse primer of the 
terminator. The resultant amplicon served as a template for nested PCR to confirm
the construct integrity. The method is suitable for screening any vip3A-carrying 
GM plant and food. The availability of a reliable PCR assay method prior to
commercial release of vip3A-based transgenic crops and food would facilitate
rapid and efficient regulatory compliance.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17994293 [PubMed - indexed for MEDLINE]

6: Mol Cells. 2007 Oct 31;24(2):301-6.

Overexpression of Arabidopsis homogentisate phytyltransferase or tocopherol
cyclase elevates vitamin E content by increasing gamma-tocopherol level in
lettuce (Lactuca sativa L.).

Lee K, Lee SM, Park SR, Jung J, Moon JK, Cheong JJ, Kim M.

School of Agricultural Biotechnology and Center for Agricultural Biomaterials,
Seoul National University, Seoul 151-921, Korea.

Tocopherols, essential components of the human diet, are synthesized exclusively 
by photosynthetic organisms. To increase tocopherol content by increasing total
flux to the tocopherol biosynthetic pathway, genes encoding Arabidopsis
homogentisate phytyltransferase (HPT/V-TE2) and tocopherol cyclase (TC/VTE1) were
constitutively overexpressed in lettuce (Lactuca sativa L.). Total tocopherol
content of the transgenic plants overexpressing either of the genes was increased
by more than 2-fold mainly due to an increase in gamma-tocopherol. However,
chlorophyll content in the HPT/VTE2 and TC/VTE1 transgenic lines decreased by up 
to 20% and increased by up to 35%, respectively (P < 0.01). These results
demonstrate that manipulation of the tocopherol biosynthetic pathway can increase
or decrease chlorophyll content depending on the gene introduced.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17978586 [PubMed - indexed for MEDLINE]

7: Ecol Appl. 2007 Oct;17(7):2123-35.

Effect of pollinator abundance on self-fertilization and gene flow: application
to GM Canola.

Hoyle M, Hayter K, Cresswell JE.

PenTAG, Peninsula Medical School, University of Plymouth, Noy Scott House,
Barrack Road, Exeter EX2 5DW, United Kingdom. m.w.hoyle@exeter.ac.uk

Cross-pollination from fields of transgenic crops is of great public concern.
Although cross-pollination in commercial canola (Brassica napus) fields has been 
empirically measured, field trials are expensive and do not identify the causes
of cross-pollination. Therefore, theoretical models can be valuable because they 
can provide estimates of cross-pollination at any given site and time. We present
a general analytical model of field-to-field gene flow due to the following
competing mechanisms: the wind, bees, and autonomous pollination. We parameterize
the model for the particular case of field-to-field cross-pollination of
genetically modified (GM) canola via the wind and via bumble bees (Bombus spp.)
and honey bees (Apis mellifera). We make extensive use of the large data set of
bee densities collected during the recent U.K. Farm Scale Evaluations. We predict
that canola approaches almost full seed set without pollinators and that
autonomous pollination is responsible for > or = 25% of seed set, irrespective of
pollinator abundance. We do not predict the relative contribution of bees vs. the
wind in landscape-scale gene flow in canola. However, under model assumptions, we
predict that the maximum field-to-field gene flow due to bumble bees is 0.04% and
0.13% below the current EU limit for adventitious GM presence for winter- and
spring-sown canola, respectively. We predict that gene flow due to bees is
approximately 3.1 times higher at 20% compared to 100% male-fertility, and due to
the wind, 1.3 times higher at 20% compared to 100% male-fertility, for both
winter- and spring-sown canola. Bumble bee-mediated gene flow is approximately
2.7 times higher and wind-mediated gene flow approximately 1.7 times lower in
spring-sown than in winter-sown canola, regardless of the degree of
male-sterility. The model of cross-pollination due to the wind most closely
predicted three previously published observations: field-to-field gene flow is
low; gene flow increases with the proportion of plants that are male-sterile; and
gene flow is higher in winter- than in spring-sown canola. Our results therefore 
suggest that the wind, not bees, is the main vector of long-distance gene flow in
canola.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17974346 [PubMed - indexed for MEDLINE]

8: Int J Toxicol. 2007 Sep-Oct;26(5):389-99.

Strategies to evaluate the safety of bioengineered foods.

Delaney B.

Pioneer Hi-Bred International, Inc., DuPont Agriculture and Nutrition, Johnston, 
Iowa 50131-0550, USA. bryan.delaney@pioneer.com

A number of genetically modified (GM) crops bioengineered to express agronomic
traits including herbicide resistance and insect tolerance have been
commercialized. Safety studies conducted for the whole grains and food and feed
fractions obtained from GM crops (i.e., bioengineered foods) bear similarities to
and distinctive differences from those applied to substances intentionally added 
to foods (e.g., food ingredients). Similarities are apparent in common animal
models, route of exposure, duration, and response variables typically assessed in
toxicology studies. However, because of differences in the nutritional and
physical properties of food ingredients and bioengineered foods and in the
fundamental goals of the overall safety assessment strategies for these different
classes of substances, there are recognizable differences in the individual
components of the safety assessment process. The fundamental strategic difference
is that the process for food ingredients is structured toward quantitative risk
assessment whereas that for bioengineered foods is structured for the purpose of 
qualitative risk assessment. The strategy for safety assessment of bioengineered 
foods focuses on evaluating the safety of the transgenic proteins used to impart 
the desired trait or traits and to demonstrate compositional similarity between
the grains of GM and non-GM comparator crops using analytical chemistry and, in
some cases, feeding studies. Despite these differences, the similarities in the
design of safety studies conducted with bioengineered foods should be recognized 
by toxicologists. The current paper reviews the basic principles of safety
assessment for bioengineered foods and compares them with the testing strategies 
applied to typical food ingredients. From this comparison it can be seen that the
strategies used to assess the safety of bioengineered foods are at least as
robust as that used to assess the safety of typical food ingredients.

Publication Types: 
    Review

PMID: 17963126 [PubMed - indexed for MEDLINE]

9: Risk Anal. 2007 Aug;27(4):935-46.

An empirical test of competing theories of hazard-related trust: the case of GM
food.

Allum N.

Department of Sociology, University of Surrey, Guildford, UK.
n.allum@surrey.ac.uk

Few scholars doubt the importance of trust in explaining variation in public
perception of technological risk. Relatively little, however, is known about the 
particular types of judgments that people use in granting or withholding trust.
This article presents findings from an empirical study that explores several
dimensions of trust relevant for citizens' judgments of scientists involved in
the development of GM food. The relationship between particular dimensions of
trust and perceptions of GM food risk is also explored, using structural equation
modeling. Results suggest that trust judgments based on the perception of shared 
values are most important in relation to GM food risk, but that judgments about
scientists' technical competence are also important.

PMID: 17958502 [PubMed - indexed for MEDLINE]

10: J AOAC Int. 2007 Sep-Oct;90(5):1513-6.

Development of agricultural biotechnology and biosafety regulations used to
assess the safety of genetically modified crops in Iran.

Mousavi A, Malboobi MA, Esmailzadeh NS.

National Institute of Genetic Engineering and Biotechnology, P.O. Box 14155-6343,
Tehran, 1417863171, Iran. m-amir@nrcgeb.ac.ir

Rapid progress in the application of biotechnological methodologies and
development of genetically modified crops in Iran necessitated intensive efforts 
to establish proper organizations and prepare required rules and regulations at
the national level to ensure safe application of biotechnology in all pertinent
aspects. Practically, preparation of a national biotechnology strategic plan in
the country coincided with development of a national biosafety framework that was
the basis for the drafted biosafety law. Although biosafety measures were
observed by researchers voluntarily, the establishment of national biosafety
organizations since the year 2000 built a great capacity to deal with biosafety
issues in the present and future time, particularly with respect to food and
agricultural biotechnology.

Publication Types: 
    Review

PMID: 17956001 [PubMed - indexed for MEDLINE]

11: J AOAC Int. 2007 Sep-Oct;90(5):1500-7.

Development of agriculture biotechnology in Pakistan.

Zafar Y.

Pakistan Atomic Energy Commission, Agriculture and Biotechnology Division, PO Box
No. 1114, Islamabad, Pakistan. y_zafar@yahoo.com

Agriculture plays an important role in the national economy of Pakistan, where
most of the rapidly increasing population resides in rural areas and depends on
agriculture for subsistence. Biotechnology has considerable potential for
promoting the efficiency of crop improvement, food production, and poverty
reduction. Use of modern biotechnology started in Pakistan since 1985. Currently,
there are 29 biotech centers/institutes in the country. However, few centers have
appropriate physical facilities and trained manpower to develop genetically
modified (GM) crops. Most of the activities have been on rice and cotton, which
are among the top 5 crops of Pakistan. Biotic (virus/bacterial/insect) and
abiotic (salt) resistant and quality (male sterility) genes have already been
incorporated in some crop plants. Despite acquiring capacity to produce
transgenic plants, no GM crops, either produced locally or imported, have been
released in the country. Pakistan is signatory to the World Trade Organization,
Convention on Biological Diversity, and Cartagena protocols. Several legislations
under the Agreement on Trade-Related Aspects of Intellectual Property Rights have
been promulgated in the country. National Biosafety Guidelines have been
promulgated in April 2005. The Plant Breeders Rights Act, Amendment in Seed
Act-1976, and Geographical Indication for Goods are still passing through
discussion, evaluation, and analysis phases. Meanwhile, an illegal GM crop
(cotton) has already sneaked into farmer's field. Concerted and coordinated
efforts are needed among various ministries for implementation of regulation and 
capacity building for import/export and local handling of GM crops. Pakistan
could easily benefit from the experience of Asian countries, especially China and
India, where conditions are similar and the agriculture sector is almost like
that of Pakistan. Thus, the exchange of information and experiences is important 
among these nations.

PMID: 17955999 [PubMed - indexed for MEDLINE]

12: J AOAC Int. 2007 Sep-Oct;90(5):1492-9.

Application of current allergy assessment guidelines to next-generation
biotechnology-derived crops.

Bannon GA, Martino-Catt S.

Monsanto Co., Global Regulatory Sciences, 800 N. Lindbergh Blvd, St. Louis, MO
63167, USA. gary.a.bannan@monsanto.com

In any single day, our immune systems are exposed to thousands of different
proteins from the environment and the food we eat. In a portion of the human
population, some of those proteins will stimulate the immune systems to
synthesize immunoglobulin E in an allergenic response. The discrepancy between
the vast numbers of proteins we encounter and the limited number of proteins that
actually become allergens have led scientists on a quest to discover what unique 
features exist that make proteins destined to be allergens. The information
gained from these studies has led to an allergy assessment strategy that
characterizes the potential allergenicity of biotechnology products prior to
their commercialization. This testing strategy appears to be effective as shown
by the fact that there have been no clinically documented food allergic reactions
to any of the biotechnology proteins introduced into food crops, to date. The
next generation of biotechnology products will most likely contain more complex
traits, including nutritionally enhanced food crops, and the question arises as
to whether the current allergy assessment strategy will be sufficient to protect 
the health of the consuming public. In this paper, we discuss general allergen
characteristics in order to better understand how proteins become allergens,
summarize the current allergy assessment process, evaluate the different aspects 
of this process for their adequacy in determining the allergenic potential of
engineered functional foods, and, finally, we assess the possibility of new
technologies having a positive impact on the allergy assessment of nutritionally 
enhanced crops.

Publication Types: 
    Review

PMID: 17955998 [PubMed - indexed for MEDLINE]

13: J AOAC Int. 2007 Sep-Oct;90(5):1480-91.

An overview of methods for assessment of iron bioavailability from foods
nutritionally enhanced through biotechnology.

Cockell KA.

Health Canada, Nutrition Research Division, Food Directorate, 2203C Banting
Research Centre, 251 Sir Frederick Banting Driveway, Ottawa, ON, Canada.
kevin_cockell@hc-sc.gc.ca

Iron deficiency and iron deficiency anemia continue to be significant public
health problems worldwide. While supplementation and fortification have been
viable means to improve iron nutriture of the population in developed countries, 
they may be less successful in developing regions for a number of reasons,
including complexities in distribution and consumer compliance. Biofortification 
of staple crops, through conventional plant breeding strategies or modern methods
of biotechnology, provides an alternative approach that may be more sustainable
once initial investments have been made. Three types of biofortification
strategies are being essayed, singly or in combination: increasing the total iron
content of edible portions of the plant, decreasing the levels of inhibitors of
iron absorption, and increasing the levels of factors that enhance iron
absorption. Bioavailability is a key concept in iron nutrition, particularly for 
nonheme iron such as is found in these biofortified foods. An overview is
presented of methods for evaluation of iron bioavailability from foods
nutritionally enhanced through biotechnology.

PMID: 17955997 [PubMed - indexed for MEDLINE]

14: J AOAC Int. 2007 Sep-Oct;90(5):1470-9.

Nutritional and safety assessments of foods and feeds nutritionally improved
through biotechnology: lysine maize as a case study.

Glenn KC.

Monsanto Co., 800 North Lindbergh Blvd, E3NB, St. Louis, MO 63167, USA.
kevin.c.glenn@monsanto.com

During the last decade, the area of biotech crops modified for agronomic input
traits (e.g., herbicide tolerance and insect protection) has increased to 90
million halyear, grown by over 8 million farmers in a total of 17 countries. As
adoption of these improved agronomic trait biotech crops has grown, so has
interest in biotech crops that have improved nutritional characteristics for use 
as feed and food. A previous publication by the International Life Sciences
Institute (ILSI) reported on the principles and concepts proposed for the
nutritional and safety assessments of foods and feeds nutritionally improved
through biotechnology. In this paper, the guidelines and principles recommended
in the earlier publication are discussed relative to a specific case study,
Lysine maize. Lysine maize is a feed ingredient with enhanced nutritional
characteristics for poultry and swine and provides an alternative to the need for
addition of supplemental lysine to some diets for these animals. The 2004 Task
Force of the ILSI has also applied the concepts from that report to 4 other case 
studies: sweet potato enriched in provitamin A (2 examples, one using
biotechnology and one using conventional breeding); Golden Rice 2; double-embryo 
maize; and ASP-1 enhanced protein sweet potato.

PMID: 17955996 [PubMed - indexed for MEDLINE]

15: Appl Environ Microbiol. 2007 Dec;73(24):8012-7. Epub 2007 Oct 12.

Effect of feeding cows genetically modified maize on the bacterial community in
the bovine rumen.

Wiedemann S, Gürtler P, Albrecht C.

Institute of Biochemistry and Molecular Medicine, University of Bern, Buehlstr.
28, CH-3012 Bern, Switzerland. christiane.albrecht@mci.unibe.ch

Rumen-cannulated cows (n = 4) were fed successively silage made from either
conventional or genetically modified (GM) maize. Results revealed no effects of
GM maize on the dynamics of six ruminal bacterial strains (investigated by
real-time PCR) compared to the conventional maize silage.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17933942 [PubMed - indexed for MEDLINE]

16: Vet Res Commun. 2007 Aug;31 Suppl 1:385-8.

Detection of genetically modified organisms in food: comparison among three
different DNA extraction methods.

Vodret B, Milia M, Orani MG, Serratrice G, Mancuso MR.

Zooprofilattic Institute of Sardinia, Feed Hygiene Unit, Sassari, Italy.
bruna.vodret@izs-sardegna.it

PMID: 17682920 [PubMed - indexed for MEDLINE]

17: Nat Biotechnol. 2007 Oct;25(10):1065-6.

Europe's anti-GM stance to presage animal feed shortage?

Mitchell P.

Publication Types: 
    News

PMID: 17921975 [PubMed - indexed for MEDLINE]

18: Food Chem Toxicol. 2007 Nov;45(11):2073-85. Epub 2007 Aug 30.

Report of an Expert Panel on the reanalysis by of a 90-day study conducted by
Monsanto in support of the safety of a genetically modified corn variety (MON
863).

Doull J, Gaylor D, Greim HA, Lovell DP, Lynch B, Munro IC.

Pharmacology, Toxicology and Therapeutics, Division of Toxicology, Department of 
Pharmacology, The University of Kansas Medical Center, 1018A Briedenthal
Building, 3901 Rainbow Boulevard, Kansas City, KS 66160-7417, USA.

MON 863, a genetically engineered corn variety that contains the gene for
modified Bacillus thuringiensis Cry3Bb1 protein to protect against corn rootworm,
was tested in a 90-day toxicity study as part of the process to gain regulatory
approval. This study was reanalyzed by Séralini et al. who contended that the
study showed possible hepatorenal effects of MON 863. An Expert Panel was
convened to assess the original study results as analyzed by the Monsanto Company
and the reanalysis conducted by Séralini et al. The Expert Panel concludes that
the Séralini et al. reanalysis provided no evidence to indicate that MON 863 was 
associated with adverse effects in the 90-day rat study. In each case,
statistical findings reported by both Monsanto and Séralini et al. were
considered to be unrelated to treatment or of no biological or clinical
importance because they failed to demonstrate a dose-response relationship,
reproducibility over time, association with other relevant changes (e.g.,
histopathology), occurrence in both sexes, difference outside the normal range of
variation, or biological plausibility with respect to cause-and-effect. The
Séralini et al. reanalysis does not advance any new scientific data to indicate
that MON 863 caused adverse effects in the 90-day rat study.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17900781 [PubMed - indexed for MEDLINE]

19: Nat Biotechnol. 2007 Sep;25(9):981-7.

Comment in:
    Nat Biotechnol. 2007 Dec;25(12):1351-4; author reply 1359-60.    Nat Biotechnol. 2007 Dec;25(12):1354-5; author reply 1359-60.    Nat Biotechnol. 2007 Dec;25(12):1355-6; author reply 1359-60.    Nat Biotechnol. 2007 Dec;25(12):1355; author reply 1359-60.    Nat Biotechnol. 2007 Dec;25(12):1355; author reply 1359-60.    Nat Biotechnol. 2007 Dec;25(12):1356-8.    Nat Biotechnol. 2007 Dec;25(12):1356; author reply 1359-60.

GM soybeans and health safety--a controversy reexamined.

Marshall A.

PMID: 17846624 [PubMed - indexed for MEDLINE]

20: Nature. 2007 Sep 6;449(7158):9.

Biotech crop rules get rewrite.

Marris E.

Publication Types: 
    News

PMID: 17805261 [PubMed - indexed for MEDLINE]

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