Select Committee on European Communities Minutes of Evidence



Dr Michael Antoniou, Senior Lecturer in Molecular Pathology, London, UK

  The greatest claim of those who endorse the use of genetic engineering or modification (GM) in agriculture, is that it is not only a natural extension of traditional breeding methods for the production of new varieties of crops and farm animals but it is also more precise and safer. It is said that GM:

    (i)  simply gives nature a "nudge" speeding it along a pathway that it would take anyway;

    (ii)  by moving a single gene between organisms, the outcomes of GM are more predictable (and therefore more precise and safer) than what occurs in traditional methods;

    (iii)  in molecular chemical terms, DNA is the same in all organisms and therefore poses no great danger when genes are moved between unrelated organisms (e.g., animals to plants).

  However, since technically speaking traditional breeding and GM bear no resemblance to each other, how valid are these claims? The following is a discussion which tries to address this question from a fundamental genetics viewpoint.


  Genes are discrete units of DNA which each individual inherits from its parents. Genes are the blueprints which carry the information for the tens of thousands of proteins which constitute the structures and carry out the biochemical functions of the body of any organism from bacteria to humans. Therefore, what gives each gene its own unique identity is its information content. The fact that all DNA is made of the same chemical units no matter what its source is, from a functional point of view, irrelevant. Life forms are different from one another due to differences in the information content of their genes. Variations between individuals within the population of a given species are also due to subtle differences in the genes which they all have in common.

  Genetics, the study of genes, has two basic components. Firstly, there is the information content of each gene; that is, what gene carries the blueprint for which protein. Secondly, gene function or expression is extremely tightly controlled or regulated. Gene function needs to be controlled because the totality of the genetic information or DNA which is inherited, is retained in all the cells of the body. In other words, the information for the whole organism is present in every part. So, for example, the knowledge for making a kidney is present in the cells of the muscles and vice versa. This basic fact of life was perhaps most dramatically demonstrated with the recent creation of Dolly the cloned sheep. The genetic material for making Dolly was apparently derived from an adult cell from the udder of a ewe clearly showing that the genetic information for making a whole sheep was present in this cell derived from the ewe's mammary gland.


  Each gene occupies its own special place along the DNA molecule which is vital for its correct function. It is vital that the correct families of genes are switched on at the right time and within appropriate cells to ensure that the correct protein and therefore appropriate structure and function, is present in the right place, time and quantity in the body. In order to achieve this, life has evolved sets of sophisticated on-off switches to regulate the expression of genes. It would not only be wasteful but potentially disastrous for genes carrying the information for proteins needed in the liver to be switched on in the cells of the brain.

  In addition, genes are now also known to be organised in distinct groups or families within the DNA in structures called "chromatin domains". It is now clear that the expression and function of genes within a given chromatin domain are closely interdependent and that the function in one domain can influence gene functions within another distant domain. The function of one chromatin domain being influenced by another distantly located gene family can occur by at least two different mechanisms.

  Firstly, one domain may contain genes that possess the information for a special class of proteins (called "transcription factors") that are directly involved in regulating expression of other genes; i.e., genes control the expression of other genes. If the function of these transcription factors is disturbed by a disruption of their genes, then the knock-on effect will be a disturbance in other, perhaps distantly located groups of genes whose activity is dependent on these particular transcription factors.

  Secondly, the still poorly understood phenomenon known as "co-suppression" first described in plants and now also shown to occur in insect and mammalian systems, also demonstrates "action at a distance" between groups of genes that are on separate DNA molecules (chromosomes). When extra copies of a gene that is already present in a plant are introduced by GM, the expected result is that you should get an additive effect; i.e., the more copies of a given gene that you have the more of that protein you should make. However, quite unexpectedly it was discovered that in some cases this GM manipulation can cause a switching off or silencing of genes. Although originally described in plants, co-suppression type activity has now been demonstrated in GM flies and mice.

  Generally, these chromatin domains are turned on and off as needed to provide an intricate, finely balanced state of gene control the complexities of which we are only just beginning to unravel. Nevertheless, tight gene control means, for example, that you will never find liver proteins and functions in your brain or leaf specific processes in the fruit and vice versa!

  Nature has also evolved mechanisms whereby cross breeding can only take place between very closely related species. You can cross a cow with a cow and a sheep with a sheep but you will not have much luck crossing a cow with a sheep. The same principles apply to plants.

  Clearly any technology which aims to manipulate the genetic makeup of a given organism must preserve the natural order and groupings of genes that have evolved to work together over many millions of years. This is indeed the case with traditional breeding methods where different variations of the same genes in their natural context (chromatin domains) are exchanged. This preserves tight control and complex interelationships between genetic functions and their protein products that are vital for integrity of life.


  In order to asses the validity of the claim that GM represents a natural extension of traditional breeding methods, it is important to know how GM ("transgenic") plants and animals are produced.

GM Plants

  As an example, let us see how the herbicide resistant, GM soya was generated. The objective here was to introduce into the soya plants a gene from a common soil bacterium which would allow it to survive when sprayed with the herbicide Roundup. Clearly you cannot "cross" a bacterium with a plant. Therefore, the first step was to grow cells from soya bean plants on plastic dishes in the laboratory. Now, in order to allow the bacterial gene to be able to work once introduced into its new plant host, it had to be linked to a genetic switch combining parts from a cauliflower virus and petunias. (As we discussed above, the bacterial gene's own switch will only work in the bacteria from which it came). This combination of cauliflower virus, petunia and bacterial DNA was then introduced into the soya bean cells growing on the dishes in the laboratory using a procedure known as "biolistics" which employs a device called a "gene gun". In this technique, tiny spheres of gold or tungsten are coated with the DNA one wishes to introduce into the plant cells. These DNA-coated metal articles are then shot at the plant cells using the gene gun at high speed. As a result some of these metal beads enter inside the plant cells carrying the new DNA with them Unfortunately from the point of view of the plant biotechnologist, the efficiency with which the new DNA is taken up by the soya bean cells on the dish is very low. Most of the cells don't take it up at all. So the key is to find those few cells among the many millions on the dish which have taken up the DNA. This is done by using another genetic trick. The introduction of the bacterial gene into the soya bean cells for herbicide resistance, was accompanied by a second gene which confers resistance to an antibiotic (called kanamycin). The soya bean cells were then treated with the antibiotic. The few cells which had taken up the herbicide resistance antibiotic:resistance "marker" gene combination survived and flourished whereas the majority of the cells which had not taken up these genes were simply killed by the antibiotic. Finally, by changing the conditions under which the soya bean cells are grown, the cells clump together to form what is called a callus which in turn starts to put down roots and sprout green shoots. These little "seedlings" are then potted so as to grow into fully mature plants which will carry in all their cells (including those for reproduction; i.e., pollen, etc.) the new bacterial gene. The plant which then displays the best agronomic performance, in this case resistance to herbicide, is then selected for further development (crossing to form new hybrids, etc.).

GM Animals

  The generation of transgenic animals is a no less artificial procedure. Fertilised eggs are first removed from the animal of choice. These eggs are then injected with the genes one wishes to engineer into the animal. The DNA-injected eggs are then returned to the womb of a surrogate mother where they complete their development and are born in due course.

  Therefore, in marked contrast to traditional breeding methods, all transgenic plants and animals start life as individual or groups of cells growing on a plastic dish in a laboratory.


  It is evident from the procedure we just described that with GM there are no holds barred. GM allows the isolation, cutting, joining and transfer of single or multiple genes between totally unrelated organisms circumventing natural species barriers. As a result combinations of genes are produced that would never occur naturally. Transgenic crops containing genes from viruses, bacteria, animals as well as from unrelated plants have been generated. In the case of the herbicide resistant soya beans, the final outcome was the combination of genetic material from four totally unrelated organisms; a cauliflower virus, petunia, bacteria and soya. Furthermore, again as we saw in the case of the GM soya beans, the newly introduced gene units are composed of artificial combinations of genetic material. Another example which illustrates the extreme combinations of genetic material that can be produced, is the introduction of the "anti-freeze" gene from an arctic fish (the sea flounder) into tomatoes, strawberries and potatoes in the hope of producing resistance to frost. As with the bacterial gene in the soya beans, the fish anti-freeze gene is joined to the cauliflower virus genetic switch to allow it to turn on and work in its new host. (The fish genetic switch naturally only works in the fish). All this is in turn coupled to an antibiotic resistance marker gene to allow selection of the newly transformed plants.


  This is clearly a great technological advance. However, the manipulation and transfer of DNA from one organism to another by GM can only be carried out with any degree of precision in lower forms of life such as bacteria and yeast although complications may arise even in these cases resulting from biochemical disturbances. The generation of transgenic plants and animals is currently an imperfect technique. Once injected into the cells of the organism, the introduced gene is randomly incorporated or spliced into the DNA of its new plant or animal host. As a result the normal order of genes within the chromatin domains is disrupted.

  There is a further complication in the case of plants. As discussed already, the genetic engineering of plant cells is a very inefficient process. We saw how in order to identify the few plant cells in the laboratory culture that have permanently assimilated the new genes, the plant biotechnologist has to rely on the presence of an antibiotic marker gene. This approach is used in the production of all GM plants. As one can see this method totally depends on the function of the antibiotic resistance gene. This gene must be assimilated in a manner that will allow it to be switched on, otherwise the cells will die once treated with the antibiotic.

  As we discussed above, regions of DNA (chromatin domains) can be switched off ("inactive") or expressing genes ("active") as part of vital, normal genetic control mechanisms. Since the incorporation of the new genes into the host DNA in GM technology is a random affair totally beyond the control of the genetic engineer, the antibiotic resistance gene can be incorporated into either silent or active DNA. If the antibiotic resistance gene is incorporated into silent DNA it will not be switched on and therefore the cell will die in the presence of the antibiotic. If on the other hand the antibiotic resistance gene is assimilated in active DNA, it will be switched on and the cells will survive antibiotic treatment. However, by definition, active DNA is a region where other genes are already switched on and trying to function. The random incorporation of a foreign gene into the already active domain will therefore always risk disrupting the balanced functioning of the host genes. It was previously thought that host gene functions would only be disturbed if the foreign gene spliced into the middle of another gene or into the genetic switch region which controls its expression. However, it is now known that the functions of genes within a given chromatin domain are interdependent and in many cases genes within a family grouping compete for common "master" control switches called "locus control regions"). This latest model of gene organisation and function predicts that the mere presence of another gene introduced by GM into a given chromatin domain, will compete with the host genes and disrupt their balanced function. Therefore, by relying on the selection of the transformed plant cells by the function of an antibiotic resistance gene, the biotechnologist in turn selects for events where the new genes have been spliced into regions of DNA where other genes are trying to function, therefore maximising the degree of disruption to normal host gene function. This in turn maximises the degree of biochemical disturbance resulting from the disrupted gene function. Therefore, GM of animals and especially plants, always results in a loss, to a lesser or greater degree, of the tight genetic control and balanced functioning which is retained through conventional cross breeding. With GM, host genes can be silenced (rendered inactive) or inappropriately activated resulting in either a deficiency in a given protein(s) or the presence of the wrong protein(s) in the wrong place or in the wrong quantity or all these combined.

  In addition, it is assumed that the introduced gene will behave in exactly the same way in its new host as it does in its native environment which frequently will not be the case. Gene and protein functions have evolved over millions of years to work together in any given organism. the anti-freeze gene/protein in the arctic sea flounder has evolved to work together with the other genes/proteins in this fish. It is purely an assumption that it will work in exactly the same way with no unwanted side effects in its new hosts where it will now be surrounded by plant proteins.

  These effects combine to always produce a totally unpredictable disturbance in host genetic function as well as in that of the introduced gene. These phenomena which are technically called "position effects", complicate the production of every GM crop or animal. Of the several tens of individual plants or animals that will be produced with the same genes, only a few will meet the agricultural performance criteria that are being sought. This is because in each individual the foreign gene is spliced into a different location in the host DNA. Plants or animals with gross defects can always be spotted and discarded. However, subtle changes in host biochemistry that will always accompany the desired effects and which in addition to producing variable agronomic performance under different soil and climatic conditions can result in the production of novel toxins, allergens as well as adversely affecting nutritional value, are on the whole ignored by the producers of these GM organisms.


GM and Traditional Breeding Methods Are Worlds Apart

  The proponents of the use of GM in agriculture argue that mankind has been selecting and manipulating plant and animal food stocks for millennia and that this new technology is simply the next stage in this process. However, we have seen:

    —  Technically speaking, GM and traditional breeding methods bear no resemblance to each other.

    —  GM plants and animals start out life in a laboratory culture dish.

    —  GM employs totally artificial units of genetic material which are introduced into plant and animal cells using chemical, mechanical or bacterial methods.

    —  GM always results in disruptions to the natural order of genes within the host DNA.

    —  GM also brings about combinations of genes that would never occur naturally.

  Clearly these procedures are worlds apart when compared to cross fertilisation between closely related species.

  The totally artificial nature of GM does not automatically make it dangerous. It is the imprecision in the manner by which genes are combined and the unpredictability in how the introduced gene will interact within its new environment which results in uncertainty. The balanced gene functions that have evolved together and which are preserved with traditional methods, are lost with GM.


  Genes have evolved to exist and work in families within the context of a given species. With traditional breeding which can take place only between closely related organisms, these natural groupings of genes are preserved. Given these basic principles of life, the claim that the reductionist approach of GM, which moves one or a few genes between unrelated organisms, is a precise technology is highly questionable. What makes these assertions even more disputable, is that by selecting for the function of the foreign gene and looking only at the desired agronomic performance as an end point, GM always results in a disruption in the natural genetic order of the host. Therefore, from the standpoint of the fundamental principles of genetics and the limitations in the technology, GM is neither more precise nor a natural extension of traditional cross breeding methods. If anything the opposite would appear to be true. GM violates the laws of genetics while traditional methods work within and make the best use of the well established laws of genetics that have been laid down over millions of years of evolution.

  Therefore GM foods possess new and unique safety considerations both in terms of health and to the environment. It would appear to be quite erroneous to view GM technology from purely an agriculture performance perspective upon which the current claims of precision and safety are based.

  The availability of safe, sustainable, natural methods of breeding and husbandry utilising the many thousands of different varieties of any given food crop, makes the risks associated with GM foods simply not worth taking. These risks are even less acceptable when one takes into account the fact that once released into the environment, genetic mistakes/pollution cannot be contained, cleaned up or recalled like a chemical spill or a BSE epidemic but will be passed on to all future generations indefinitely.


  Dillon, N and Grosveld, F 1994, Chromatin domains as potential units of eukaryotic gene function, Curr. Opin. Genet. Develop. 4: 260-264.

  Dillon, N et al. (1997) The effect of distance on long-range chromatin interactions. Molecular Cell 1: 131-140.

  Felsenfeld G 1992, Chromatin as an essential part of the transcriptional mechanism. Nature 355: 219-224.

  Wijgerde, M, Grosveld, F and Fraser, P (1995) Transcription complex stability and chromatin dynamics in vivo. Nature 377: 209-213.

  Palmiter R D and Brinster, R (1986) Ann. Rev. Genet. 20: 465.

  Flavell, R B (1994) Inactivation of gene expression in plants as a consequence of specific sequence duplication. Proc. Natl. Acad. Sci USA 91: 3490-3496.

  Mayeno, A N and Gleich, G L (1994) Eosinophilia-myalgia syndrome and tryptophan production: a cautionary tale. Trends in Biotechnology 12: 346-352.

  Inose T and Kousaku, M (1995) Enhanced accumulation of toxic compounds in yeast cells having high glycolytic activity: a case study on the safety of genetically engineered yeast. International Journal Food Science Technology 30: 141-146.

  Mandel, M A et al. (1992) Manipulation of flower structure in transgenic tobacco. Cell 71: 133-143.

  Hirel B, Marsolier, M C, Hoarav, A, Hoarav, J, Brangeon, J, Shafer, R and Verma, D P S (1992) Forcing expression of a soybean root glutamine synthetase gene in tobacco leaves induces a native gene encoding cytosolic enzyme. Plant Molecular Biology 20: 207-218.

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