Horizontal gene transfer from GM crops is unlikely or of no consequence
GM genes can escape into the environment by horizontal gene transfer with potentially serious consequences
Most GM contamination incidents occur through cross-pollination, contamination of seed stocks, or failure to segregate GM from non-GM crops after harvest. But for years, scientists have warned that GM genes could also escape from GM crops into other organisms through a mechanism called horizontal gene transfer (HGT). HGT is the movement of genetic material between unrelated species through a mechanism other than reproduction. Reproduction, in contrast, is known as vertical gene transfer because the genes are passed down through the generations from parent to offspring.
GM proponents and government regulators often claim that, based on available experimental data, HGT is rare. The EU-supported website GMO Compass states, “So far, horizontal gene transfer can only be demonstrated under optimised laboratory conditions.”164 Alternatively, they argue that if it does happen, it does not matter, as GM DNA is no more dangerous than non-GM DNA.
But there are several mechanisms through which HGT can occur, some of which are more likely than others. HGT via some of these mechanisms occurs easily and frequently in nature. The consequences of HGT from GM crops are potentially serious, yet have not been adequately taken into account by regulators.
The basic mechanisms by which HGT could occur are:
- Uptake of GM DNA by bacteria
- Uptake of DNA from the digestive tract into the tissues of the organism
- Transmission of GM DNA via Agrobacterium tumefaciens, a bacterium that is often used to introduce GM genes into plants because of its natural ability to carry and transfer foreign DNA and to infect plants through wounds in their outer layer
- Gene transfer by viruses.
The following sections outline these mechanisms and provide a perspective on the frequency at which these events can occur, as well as their potential impacts.
5.12.1. DNA uptake by bacteria
Bacteria are promiscuous. They are always exchanging DNA between themselves and taking up DNA from their environment. Some of this environmentally acquired DNA can be incorporated to their genome and may be expressed. There are two scenarios in which DNA uptake by bacteria could result in HGT of GM genes.
The first is the transfer of GM DNA from GM food into intestinal bacteria. DNA from a GM plant is released into the intestinal tract of the consumer during digestion. Contrary to frequent claims, GM DNA is not always broken down in digestion and can survive in sufficiently large fragments that can contain intact genes that are potentially biologically active (see 3.1.1, 3.6.2).
Bacteria of many different species are present in the digestive tract, some of which can take up DNA from their environment and incorporate it into their own DNA. In the case of GMOs, this could be problematic. For example, if the GM plant contained a gene for antibiotic resistance, the bacterium could incorporate that antibiotic resistance gene into its genome, and thereby become resistant to the antibiotic. If the bacteria in question happened to be pathogenic (disease-causing), this process would have created an antibiotic-resistant pathogen – a “superbug”.
Since bacteria in the intestinal tract frequently exchange DNA, the creation of a superbug could be a two-stage process. First, the antibiotic resistance gene could initially be taken up and incorporated into a non-pathogenic bacterium in the intestinal tract. Subsequently, if a pathogenic bacterial species becomes part of the intestinal flora, the non-pathogenic bacterium could transfer the antibiotic resistance gene to the pathogenic bacterium, thereby creating a “superbug”.
The transfer of GM genes from food to intestinal bacteria has been documented in a study on humans, which found that the intestinal bacteria of a person whose diet included soy carried sequences unique to the GM soy that was part of their diet.164
The second scenario in which DNA uptake by bacteria could result in HGT of GM genes is the transfer of GM DNA to soil bacteria. Cultivation of transgenic crops leads to the degradation of GM plant material in the environment, liberating GM genes into the soil. Every cubic centimetre of soil contains thousands of different species of bacteria, only a small percentage of which have been identified and characterised. Some of the known soil bacteria can, and do, take up free DNA that may be present in the soil, incorporating that DNA into their genomes.166 This could result in the transfer of GM genes to natural soil bacterial populations. Based on limited currently available data, this type of event has been calculated to be extremely rare.167 However, it has been shown that GM DNA can persist in soil at detectable levels for at least a year,168 increasing the likelihood of HGT.
In addition, we only know a small fraction of the soil bacteria that could potentially take up DNA from their environment.166 Furthermore, if the uptake of a GM gene, for example for antibiotic resistance, gives the bacterium a survival and growth advantage, this can allow them to outcompete other bacterial strains in the presence of widely used antibiotics in agriculture and medicine. Therefore, this initial rare event could still result in a significant environmental and health outcome.169
5.12.2. DNA uptake during digestion of GM foods
A study on mice demonstrated that foreign DNA present in food can be transferred from the digestive tract to the bloodstream of animals that eat the food. This foreign DNA was also found in white blood cells and in the cells of many other tissues of the mice.170 In a separate study, foreign DNA in a diet fed to pregnant mice was found in the organs of their foetuses and newborn offspring. The foreign DNA was believed to have reached the foetus through the placenta.171
It has also been shown that GM DNA in feed can be taken up in the organs of the animals that eat it and can be detected in the meat and fish that people eat.172,173,174,175
Most of the GM DNA in food is fragmented before it reaches the blood or tissues. However, a few copies of GM DNA large enough to contain the sequence of a full and functional gene will also be present in the digestive tract and can be taken up into the blood at lower frequency, where it can be transported by the blood and taken up by cells of some tissues or organs.170 Once taken up by a cell, such a GM gene could be integrated into the DNA of the cell, causing either direct mutation of a host gene function or reprogramming the host cell to produce the protein for which that GM gene codes, or both.
At present, this scenario is speculative. Although it is clearly possible to detect transgenic DNA in the tissues of organisms that consume GM feed, no research has been published that shows that the GM DNA is expressed in the tissues of those organisms. It would be expected that if such expression did occur, it would not occur frequently. In order to find out whether such expression events actually occur, it would be necessary to conduct very large-scale studies – though identifying a suitable experimental design would be challenging.
It should be pointed out, however, that although such events may be of low frequency, because of the widespread consumption of GMOs by both humans and animals, the fact that such events are of low frequency does not eliminate them as important to the biosafety assessment of GMOs.
Though the mechanism is still unclear, GM feed has been found to affect the health of animals that eat it. GM DNA from soy was detected in the blood, organs, and milk of goats. An enzyme, lactic dehydrogenase, was found at significantly raised levels in the heart, muscle, and kidneys of young goats fed GM soy.176 This enzyme leaks from damaged cells during immune reactions or injury, so high levels may indicate such problems.
5.12.3. Horizontal gene transfer by Agrobacterium tumefaciens
Agrobacterium tumefaciens (A. tumefaciens) is a soil bacterium that is often used to introduce GM genes into plants.
The introduction of GM genes into plants by infection with A. tumefaciens is carried out by exploiting a Ti plasmid – a small circular molecule of DNA that is naturally found in A. tumefaciens. When A. tumefaciens infects a plant, the Ti plasmid is introduced into the plant cells. Parts of the Ti plasmid may then insert themselves into the DNA of the plant.
Plant biotechnologists have adapted this natural process in order to introduce foreign DNA into plants and thereby produce GM crops. First, the naturally occurring genes of the Ti plasmid in the region that can insert into host plant cell DNA are removed and replaced with the GM gene of choice. The now genetically modified Ti plasmid is then introduced into A. tumefaciens, which in turn is used to infect plant cells. Once inside the plant cell, some of the genetically modified Ti plasmid can insert into host plant cell DNA, thereby permanently altering the genetic makeup of the infected cells.
Although A. tumefaciens is a convenient way of introducing new genes into plants, it can also serve as a vehicle for HGT from the GM plant to other species. This can happen via two mechanisms.
First, residual A. tumefaciens carried in a GM plant could infect plants of other species, thereby carrying the GM gene(s) from the intentionally genetically modified plant into other plants. A. tumefaciens can serve as a vehicle for HGT to hundreds of species of plants, since A. tumefaciens has been found to infect a wide range of plant species.
The second mechanism creates the risk that A. tumefaciens could pass GM genes on to an even wider range of species, including, but not limited to, plants. It consists of certain types of fungi functioning as intermediate hosts in the transfer of transgenes from GM A. tumefaciens to other organisms.
A 2010 study found that under conditions found in nature, A. tumefaciens introduced DNA into a species of disease-causing fungi that is known to infect plants. The study also found that GM DNA sequences in the A. tumefaciens were incorporated into the DNA of the fungi. In other words, the A. tumefaciens was genetically engineering the fungi.
The authors concluded that in cases where a GM plant is infected with fungi, A. tumefaciens in the GM plant could infect the fungi, introducing GM genes into the fungi.177 Such fungi could, in turn, pass the GM genes onto other plants that they infect.
Genetic engineers had previously assumed that A. tumefaciens only infects plants. But this study showed that it can infect fungi, a different class of organism. The study stated, “A. tumefaciens may be able to [genetically] transform non-plant organisms such as fungi in nature, the implications of which are unknown.”177 The authors pointed out that A. tumefaciens is already known to transform – genetically modify – human cells in the laboratory177,178
One of the study’s co-authors, Andy Bailey, a plant pathologist at the University of Bristol, UK, said, “Our work raises the question of whether [A. tumefaciens’s] host range is wider than we had thought – maybe it’s not confined only to plants after all.”179
The implications of this research are that it is possible that GM gene(s), once introduced by A. tumefaciens into a GM crop and released into the environment, could then be introduced into an organism outside the plant kingdom – in this case, a fungus – and genetically modify it. This would be an uncontrolled and uncontrollable process, with unpredictable consequences.
Implications of horizontal gene transfer through A. tumefaciens
Could A. tumefaciens transfer GM genes from a GM plant to another organism under realistic farming conditions? The answer depends on whether any A. tumefaciens carrying GM genes remains in the GM crop that is planted in open fields. Genetic engineers use antibiotics to try to remove the A. tumefaciens from the GM plant after the initial GM transformation process is complete in the laboratory. But this process has been found to be unreliable and incomplete:
- A study on GM brassicas, potato and blackberry found that the use of three antibiotics failed to completely remove A. tumefaciens. Instead, the A. tumefaciens contamination levels increased from 12 to 16 weeks after the GM transformation process and the A. tumefaciens was still detected 6 months after transformation.180
- A study on GM conifers found that residual A. tumefaciens remained in the trees 12 months after the genetic transformation but were not detected after this time in the same plants.181
However, these experiments only examined the first GM plant clones. In the GM development process, such GM clones go through a long process of back-crossing and propagation with the best-performing non-GM or GM plant relatives in order to try to produce a GM plant that performs well in the field and expresses the desired traits. The important question is whether A. tumefaciens carrying GM genes survives this back-crossing and propagation process and remains in the final GM plant that is commercialised.
To the best of our knowledge there have been no studies to assess whether any A. tumefaciens remains in the final commercialised GM plant. The study on GM conifers examined the initial GM clones that were grown on, not plants that had been cross-bred and propagated over several generations, as GM crops are before they are commercialised, so it does not provide an answer to this question.
However, this question should be answered before a GM variety is commercialised, in order to avoid unwanted consequences that could be caused by residual A. tumefaciens in the final GM plant. Examples of consequences that should be excluded are the transfer of insecticidal properties to bacteria, or of herbicide tolerance to other crops or wild plants. The study discussed above (5.12.3) shows that the introduction of GM genes into crop plants could have consequences to organisms outside the plant kingdom, through the mechanism of infection by fungi carrying A. tumefaciens, which in turn carry GM genes.177
The consequences of such HGT for human and animal health and the environment are not predictable, but are potentially serious. The health and environmental risk assessment for any GM variety must demonstrate that the GM plants have been completely cleared of GM A. tumefaciens before they are approved for commercialisation.
5.12.4. Gene transfer by viruses
Viruses are efficient at transferring genes from one organism to another and in effect are able to carry out HGT. Scientists have made use of this capacity to create viral gene transfer vectors that are frequently used in research to introduce GM genes into other organisms. Such vectors based on plant viruses have also been developed to generate GM crops, though no crops produced with this approach have been commercialised to date.182,183
The viral vectors that are used to generate GM crops are designed to prevent the uncontrolled transfer of genetic material. However, because the long time period during which virally engineered crops would be propagated in the environment, and the large number of humans and livestock that would be exposed to this GM genetic material, there is a real, though small, risk that unintended modifications could occur that could lead to virus-mediated HGT – with unpredictable effects.
Another potential risk of virus-mediated HGT comes from GM crops engineered to contain a virus gene, in particular those carrying information for a viral “coat” protein. This is done in an attempt to confer resistance of the crop from actual infection and damage by the family of ‘wild’ virus from which the viral GM gene was derived. However, it has been suggested that if a GM crop containing a viral gene of this type was infected by the viruses, it may result in exchange of genetic material between the GM viral gene in the plant and the infecting virus, through a process known as recombination. This can potentially result in a new more potent (“virulent”) strain of virus.184,185
The reasons for these concerns are as follows. The GM viral gene will be present in every single cell of the crop. As a result, the large-scale cultivation of such a viral GM gene-containing crop will result in an extremely high concentration of particular viral genes in fields. It has been suggested that this provides an unprecedented opportunity for genetic material recombination events to take place between an infecting virus and GM viral genes in the crop, thereby increasing the risk of new, mutated, and potentially more virulent strains of virus being produced.185
Such viral mutation with increased virulence has been shown to occur under laboratory conditions.186,187
To date only two GM crops engineered with genes from viruses have been commercialised: a variety of squash grown in the USA and Mexico,188,189 and papaya cultivated in Hawaii.190 There are no reports of any investigations to see if any new viral strains have arisen by recombination in these two crops. Interestingly, and quite unexpectedly, although the GM squash was resistant to viral infection, it was found to be prone to bacterial wilt disease following attack by beetles.191
5.12.5. Overall assessment of the risks of HGT by the above methods
HGT events of all types are of very low probability of occurrence. The method with the highest probability of occurring is DNA uptake by bacteria in either the environment or the digestive tract. There is good evidence that this has already happened in the intestinal bacteria of humans who consume GM soy.
The other scenarios are of significantly lower probability. However, given the extremely wide distribution of GM crops and their intended use over decades, these low probabilities translate into the likelihood that HGT events could actually occur even via the mechanisms that are expected to take place at lower probabilities.
Therefore, the negative impacts and risks associated with HGT must be taken into account in considering the overall biosafety of any GM crop.