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Antibiotic Resistance Genes in GM Foods

Introduction

Many genetically modified (GM) plants contain antibiotic resistance marker genes. This briefing shows how these genes might spread, threatening the effectiveness of some of our most important antibiotic drugs.

Antibiotic resistance genes are put into GM plants as tags or markers, so that genetic engineers can tell when they have successfully inserted new traits into a plant. Although it is possible to remove antibiotic resistance marker genes before the plant is released (or to use different marker genes altogether), these precautions are rarely taken.

Concerns

The biggest concern about antibiotic resistance genes is the possibility that they could be transferred to bacteria in the guts of animals or humans, or to bacteria in the environment. Many bacteria have the ability to pick up genes from their surroundings and to pass these genes on to other species of bacteria, including those which cause disease. There is a danger therefore that diseases could become resistant to many important antibiotic drugs.

There is as yet no direct evidence of this transfer from GM food to gut bacteria. However, recent research in the Netherlands, using a model gut, predicted that 6% of the genes from GM tomatoes would survive digestion and pass into the colon. ⁽¹⁾ The researchers considered that the genes could survive for long enough for bacteria to pick them up.

There is also a risk of antibiotic resistance genes being passed from GM crops to bacteria in the soil. Genes are made up of DNA which can be very long lasting in the environment, remaining active for months or even years. In one study, antibiotic resistance genes from GM tobacco survived in soil for 4 months ⁽²⁾. Researchers in 1998 found that, in the laboratory, a species of soil bacteria could pick up antibiotic resistance genes from GM sugar beet mixed into soil ⁽³⁾. Large amounts of GM crops are ploughed back into the soil at the end of each growing season and so there is great potential for such gene transfer to occur.

Getting into the Food Chain

In their report on GM foods the House of Lords Select Committee on the European Communities recommended that antibiotic resistance maker genes “should be phased out as swiftly as possible” ⁽⁴⁾. The British Medical Association recommended in their report on GM crops and food that “there should be a ban on the use of antibiotic resistance marker genes in GM food, as the risk to human health from antibiotic resistance developing in micro-organisms is one of the major public health threats that will be faced in the 21st Century” ⁽⁵⁾. The use of antibiotic resistance genes has also been criticised by the Royal Society, the Advisory Committee on Novel Foods and Processes ⁽⁶⁾ (ACNFP) who are the Government's advisors on GM food safety, and the National Farmers Union ⁽⁷⁾. But despite this consensus, 13 out of 23 applications to the European Union (EU) for approval of GM foods contain antibiotic resistance marker genes. In addition, 12 applications for inclusion on the National Seed List (which enables seed to be sold in the UK) also contain antibiotic resistance marker genes. Details of these can be found in the tables at the end of this briefing.

Antibiotics at Risk

Four different marker genes are used in GM food. They confer resistance to a range of antibiotics used in human and veterinary medicine. The antibiotics at risk include:

• ß-lactam antibiotics - these include many antibiotics in the penicillin family, such as ampicillin and amoxycillin which are used as a first defence against chest infections in humans. They are also widely used in veterinary medicine, eg for treating mastitis in dairy cows. This group of antibiotics is also used against bacteria which commonly cause infections in hospitals.
  
• gentamycin B - used for serious illnesses, such as for treating meningitis and infections of the central nervous system.
  
• neomycin - used in veterinary medicine for gut infections of calves, lambs and domestic pets.
  
• amikacin - reserved for use in the treatment of serious infections which are resistant to gentamycin.
  
• streptomycin - this is used only in the treatment of drug resistant TB.
  
• spectinomycin - this is used only to treat gonorrhoea infections.
  

The risk of transfer of these antibiotic resistance genes is greater in some cases than in others, depending on how the crops have been modified. In some cases the GM crop does not contain a fully functioning gene so it is less likely that bacteria would be able to use it. In other cases, such as Novartis' insect resistant maize, the risk is much higher.

Novartis Maize

Novartis' maize contains a gene which makes the plant resistant to the ß-lactam antibiotics. The gene is structured in such a way that it could be used immediately by any bacteria that picks it up, including disease causing bacteria like E.coli, Salmonella and Shigella. The gene is different to any that occur naturally - it could allow bacteria to be able to break down the antibiotics much more rapidly than they could otherwise. If it spreads to bacteria, this gene could speed up the time it takes for bacteria to become resistant to this group of antibiotics, rendering them ineffective.

The Government's advisory committee on food safety (ACNFP) were so concerned about this that they recommended the gene be removed before entering the food chain. They were particularly concerned that the resistance gene could be transferred to bacteria in the guts of livestock, and from there be passed to bacteria which cause disease in humans ⁽⁸⁾. The committee's advice was accepted by the Government and, along with 12 out of 15 member states, the UK proposed to refuse a European marketing approval for Novartis' maize. Despite this, the European Commission overruled the member states and approved this potentially dangerous crop. Two EU countries, Austria and Luxemburg, have banned the import of Novartis' maize but in the UK it is now being sold in processed food in the shops and in animal feed.

Friends of the Earth's Position

Friends of the Earth believes that no food should enter the human or animal food chain containing an antibiotic resistance marker gene. The Government should refuse approval for any genetically modified organism containing such a gene and use the powers available to them under the EU Directive 90/220/EEC on the Deliberate Release of Genetically Modified Organisms to revoke the marketing consent for any such food and crops.

The Antibiotic Resistance Genes

GM plants contain genes which confer resistance to many antibiotics including neomycin, kanamycin, spectinomycin, amikacin, gentamycin B and ß-lactam antibiotics such as ampicillin. Table one [below] and table two show those GM crops which may enter the food chain and which contain antibiotic resistance genes

Table one

Ref	Company	Crop	Antibiotic Resistance	Approval For	UK position	EU Decision
C/UK/94/M1/1	Plant Genetic Systems (PGS)	Glufosinate tolerant oilseed rape	aph(3')-II neomycin/ gentamycin B kanamycin	seed only	approved	Approved 06/02/98
C/F/94/11-03	Novartis	Insect resistant, glufosinate tolerant maize	bla TEM-1 (bacterial promoter) beta-lactamase	growing for food & feed	against approval	Approved 5/2/97
C/F/95/05-01 A	PGS	Glufosinate tolerant oilseed rape	aph(3')-II neomycin/ gentamycin B kanamycin	growing for food & feed	approved	Awaiting consent
C/UK/95/M5/1	AgrEvo	Glufosinate tolerant oilseed rape	neomycin	growing for food & feed	approved	9/6/98
C/F/95/12-07	AgrEvo	glufosinate tolerant maize	partial bla TEM-1 beta-lactamase	growing for food & feed	approved	Awaiting consent
C/F/95/12-01/B	Pioneer Hi-Bred	insect resistant, glyphosate tolerant maize	aph(3')-II (bacterial promoter) neomycin/ gentamycin B kanamycin	growing for food & feed	concern about antibiotic resistance	Commission decision pending
C/NL/94/25-A	Bejo Zaden BV	Glufosinate tolerant chicory	aph(3')-II kanamycin/ gentamycin B neomycin	growing for food & feed	not approved	Commission decision pending
C/NL/96/10	AVEBE	altered starch content potato	aph(3')-II aph(3')-III neomycin/ gentamycin B kanamycin amikacin	growing for industrial starch & feed	not approved for feed	Commission decision pending rejected by Scientific Committee
C/ES/96/01	Zeneca	improved processing tomato	aph(3')-II neomycin/ gentamycin B kanamycin	growing for food & feed	under consideration	Commission decision pending
C/ES/96/02	Monsanto	insect resistant cotton	aph(3')-II ant (3'')-Ia kanamycin/ gentamycin B spectinomycin	growing for industry & feed	under consideration	Commission decision pending
C/ES/97/01	Monsanto	insect resistant cotton	aph(3')-II ant (3'')-Ia kanamycin/ gentamycin B spectinomycin	growing for industry & feed	under consideration	Commission decision pending
C/ES/96/35/01	Amylogene	altered starch potato	aph(3')-II neomycin/ gentamycin B kanamycin	seed potato production starch for industry and feed	under consideration	Commission decision pending
C/NL/97/17	Dekalb Genetics	insect resistant maize	bla TEM-1 (bacterial promoter) beta-lactamase	seed production food and feed	under consideration	Commission decision pending

Table two [back to text]

Crop	National List Applicant	Antibiotic Resistance	Estimated National List Decision
herbicide tolerant sugar beet 2 varieties	Kleinwanzlebe ner Saatzucht, Germany (developed by AgrEvo)	Kanamycin/ gentamycin B neomycin	April 2000
herbicide tolerant maize 2 varieties	Van der Have, Netherlands (developed by AgrEvo)	partial beta-lactamase	February 2000
oil modified oilseed rape 2 varieties	Calgene Inc., USA	kanamycin/ gentamycin B neomycin	November 1999
herbicide tolerant spring oilseed rape 4 varieties	Plant Genetic Systems, Belgium	neomycin / kanamycin/ gentamycin B	from early 1999
herbicide tolerant winter oilseed rape 2 varieties	Plant Genetic Systems, Belgium	neomycin / kanamycin/ gentamycin B	November 2000

April 1999.

The Real Food Campaign
Friends of the Earth
26-28, Underwood Street
LONDON
N1  7JQ
Email - info@foe.co.uk
Website - www.foe.co.uk

Notes

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Footnote: 1 [Back to text]
J.M.B.M. van der Vossen et al. 1998. “Development and application of an in vitro intestinal tract model for safety evaluation of genetically modified foods” in Food Safety Evaluation of Genetically Modified Foods as a Basis for Market Introduction. pp.81-99. Ministry of Economic Affairs, P.O. Box 20101, 2500 EC The Hague, The Netherlands.

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Footnote: 2 [Back to text]
Widmer, R.J. Seidler and L.S. Watrud. 1996. “Sensitive detection of transgenic plant marker gene persistence in soil microcosms” Molecular Ecology. 5, pp. 603-613

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Footnote: 3 [Back to text]
Frank Gebhard and Kornelia Smalla. 1998. “Transformation of Acinetobacter sp. Strain BD413 by Transgenic Sugar Beet DNA”. Applied Environmental Microbiology, pp. 1550-1554, Vol 64, No. 4

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Footnote: 4 [Back to text]
House of Lords Select Committee on the European Communities. 1998 “EC Regulation of Genetic Modification in Agriculture”: para 184.

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Footnote: 5 [Back to text]
British Medical Association. 1999 “The Impact of the Genetic Modification on Agriculture, Food and Health- An Interim Statement”: p.13.

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Footnote: 6 [Back to text]
Advisory Committee on Novel Foods and Processes. 1996, “Annual Report 1996”: page 18.

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Footnote: 7 [Back to text]
Report of the National Farmer Union Biotechnology Working Group 1998.: para 6.5.

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Footnote: 8 [Back to text]
Advisory Committee on Novel Foods and Processes. 1996, op cit: page 145.