ANTIBIOTIC RESISTANCE IN
GENETICALLY MODIFIED PLANTS

Greenpeace International, September 1998

Some genetically manipulated plants already grown today contain genes which render antibiotics ineffective. These antibiotic resistance genes can be absorbed by pathogenic bacteria in human or animal intestines, and can then no longer be combated by the relevant antibiotics. The Novartis company's genetically modified maize, which was first grown in Europe in 1998 and can already be processed and used in food, should be regarded particularly critically. This maize contains a gene resistant to diverse pencillins frequently used in human medicine. There is a direct danger to health in using such plants as feedstuff or food. They must therefore be banned.

Where does the danger lie?

The increasing failure of antibiotics on account of pathogens being resistant is already a big problem in medicine today. This danger is further exacerbated by genetically modified plants, since the genes can be transferred from the plant to pathogenic bacteria. The gene for antibiotic resistance is to be found in every single cell of the genetically modified plants.

By growing Novartis maize over a large area, billions of these genes would be put into the environment. All research findings to date show that the antibiotic resistance gene is likely to be absorbed in human and animal intestinal bacteria. How likely such a transfer is cannot be reliably determined on the basis of the scientific findings available. What certainly can be said is that genes can be stable in the intestines, that intestinal bacteria are in principle able to absorb genes from the environment into their genetic make-up, and a gene transfer from plants to micro-organisms in soil is possible.

Given the limited scientific evidence available, the claim propounded by the genetic engineering industry - that a gene transfer is extremely unlikely - is unfounded. In view of the enormous number of genes that will be introduced into the environment once Novartis' Bt-maize is grown commercially, we will sooner or later find the resistance genes in pathogens.

Which antibiotics are involved?

The most diverse antibiotic resistance genes are used in genetic engineering. Two of them deserve special mention, because they present a special risk in that they are already on the market in Europe.

Ampicillin
The gene for Ampicillin resistance is contained in the Novartis GM maize already being grown in Europe. It confers resistance not only against Ampicillin but also against a series of pencillins in use, such as Penicillin G, Amoxycillin and Phenoxymethypenicillin. These antibiotics are still the favoured preparations used with illnesses today, and were prescribed in Germany twelve million times in 1996 alone. They are used for tonsillitis, scarlet fever, pneumonia, whooping cough, inflammation of the middle ear, and many other infectious diseases. The gene that confers resistance to Ampicillin is also known as the bla gene.

Amikacin
A genetically manipulated line of potato having the gene resistant to Amikacin (the nptIII gene) is currently in licensing proceedings in Europe. Amikacin is regarded as a 'reserve' antibiotic in human medicine, i.e. at present it is used as little as possible in order than no resistances are produced among bacteria. For this reason the German authorities have declared themselves against the potato varieties being authorised for use as feedstuffs.

Isn't resistance to antibiotics already widespread anyway?

The genetic engineering industry plays down the risk of the spread of billions of antibiotic resistance genes by arguing that a large part of the bacteria in our environment are already resistant to antibiotics; Ampicillin and other penicillins that the bla gene renders ineffective are becoming obsolete. But how is it to be explained that in 1996 these antibiotics were among the those most often prescribed, with 12 million prescriptions being made? Do German doctors only prescribe placebos? No, resistance has spread less and, above all, less evenly than the genetic engineering industry would like to have us believe.

Novartis thus maintains, for example, that some 40-60 per cent of intestinal bacteria are already resistant to Ampicillin and related antibiotics. But analysis of the academic literature shows that intestinal bacteria resistant to Ampicillin are clearly rarer than this. The incidence of resistance to bacteria in general also varies greatly, depending on the kind of bacteria and its host (the person). A sensible health policy ought to aim at combating and stemming the development of antibiotic resistance and not sacrificing antibiotics to an industry oriented towards making profits.

How has the present resistance to antibiotics come into being?

Antibiotic resistance has arisen mainly through lack of care in using antibiotics in human medicine. Antibiotics are prescribed too lightly and not taken by patients over the period prescribed for treatment. In addition poor hygienic conditions in hospitals have encouraged antibiotic resistance to develop.

Antibiotics have also been sacrificed to industrial agriculture's commercial interests. Over half the antibiotics used in the EU end up in animal feed, chiefly to increase yield. In the 1960s scientists discovered virtually by accident that a low dosage of antibiotics resulted in faster growth in animals. The faster growth is thought to be caused by the repression of undesirable germs in the gastro-intestinal tract. This results in a more efficient use of feed, more daily growth, and so a shorter period for fattening. In many conventional businesses it is today routine practice to induce growth in this way. Eight antibiotics are currently still authorised in the EU as feed additives in fattener or for mass production with egg-laying hens. Originally all growth-inducers except for sulphonamide were authorised by the EU. But in the middle of the 1970s authorisation for pencillins and tetracyclines was withdrawn so as not to further jeopardise its therapeutical effectiveness in people. In Sweden there has been a total ban on the use of antimicrobial growth-inducers for this reason since 1986.

Why do genetic engineers need this resistance to antibiotics?

The antibiotic resistance has no function whatsoever in the maize plant in the field. It was only needed in the laboratory for genetic manipulation, as a so-called marker gene. Genetic engineers have to fish out the cell where genetic manipulation has worked from million of cells. The antibiotic resistance serves as an aid in the search to separate the wheat from the chaff. When the cells are treated with the antibiotic after genetic manipulation has been carried out, the natural cells die. Only the cells in which genetically engineered intervention has been successful survive and can be cultivated further, because they are resistant to the antibiotic. It has been possible for years now, however, to make genetically modified plants with no antibiotic resistance genes. There are now methods which remove the antibiotic resistance from the plant afterwards, or from the outset make genetic modifications in such a way that the antibiotic resistance is not transferred to the plants. Marker genes less dangerous than antibiotic resistance genes have also been developed. In other words, the technology is out of date and constitutes an entirely unnecessary risk.

Haven't genetic engineering companies in any case already stopped using antibiotic resistance genes?

Unfortunately not. Although many scientists, authorities and international organisations have for years recommended that antibiotic resistance genes not be used unnecessarily, a number of companies have continued to cling to the outdated technology. Two genetically modified plants containing particularly risky antibiotic resistance genes are for example currently involved in authorisation procedures in Europe. One is the line of maize with a gene for Ampicillin resistance, made by the US genetic engineering company DeKalb, and the other a potato line, produced by the Dutch company, Avebe, which has a gene resistant to Amikacin. Manifestly only an overall ban can move the genetic engineering industry to stop using antibiotic resistance genes.

What do the authorities say about antibiotic resistance?

In Germany the Robert Koch Institute controls the authorisation of genetically engineered plants. It is advised by a scientific committee on biological safety, the ZKBS. Both institutions approved the authorisation of Novartis' maize and deny there is a risk to health from genes resistant to Ampicillin. The ZKBS nonetheless recommended in July 1997 'that in future the genes introduced into genetically modified organisms should as far as possible be confined to genes which are functionally necessary for the modification being striven for'.

In August 1998 the RKI went a step further and did not approve the authorisation of a genetically manipulated line of potatoes for use as feedstuff because it contained resistance to Amikacin. 'Heed [should] on precautionary grounds be paid to the fact that, given a certain pressure on selection, there is a possibility, of low probability, of the horizontal transfer of these genetic properties to micro-organisms in an animal's digestive tract. Unrestricted marketing of these genetically modified potatoes cannot therefore be authorised.' (from the RKI's statement to the EU Commission) The German Federal Department of the Environment is on the other hand more critical towards Novartis' maize, and wrote in a letter to Greenpeace in August 1998: 'In spite of Ampicillin resistance being broadly distributed in micro-organisms in the digestive tract of people and animals, the Department advises against the consumption and feeding of raw products containing the bla gene, on account of Ampicillin's broad spectrum of use, and it calls for a decision as to its use to made along these lines.' (NB. The bla gene is the gene for resistance to Ampicillin.)

Novartis' maize is seen very critically in other European countries. Its import into Austria, Luxembourg and Norway is banned because of the antibiotic resistance. The UK has also declared itself opposed to Novartis' maize being used as feedstuff as long as it contains the gene resistant to Ampicillin.

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