Genetically Modified Foods - the Good, the Bad, and the Ugly

By Dr. Martha Grout
Published in Explore! Magazine, November 6, 2008

Think of the promise - food for all, plentiful supply, resistant to insect pests, high-yield crops, less work for the farmers, more food for the people. It sounds like utopia, doesn’t it? The intentions were good. And the fact that the seed companies made money is also good - that’s how capitalism works. We find a need, fill the need, and are compensated for our labor.

genetically modified foodsIt all started with Mother Nature. Mother Nature has given us all the means to grow, to multiply, and to defend ourselves. Some defense is passive -color of coat like the snow leopards, patterning of spots like certain tropical fish or some butterflies. Other defenses are more active or specific, like claws, teeth, hooves, shells, and a variety of body parts which can be used for defense. Still other organisms have aggressive means of identifying themselves, for example through toxins which are used to immobilize prey. Very tiny organisms have apparently been given the gift of modifying their host’s DNA, to ensure their own survival, like the recently discovered actions of the adenovirus.[1] Sometimes these organisms become incorporated into their very essence of the host - mitochondria, for instance - ensuring the survival of both species. Sometimes the organisms cause the death or significant disruption of function of the host - West Nile virus, for instance - so that in the end, neither the organism nor the host really wins.

gall on plantIt is important to remember that there is always an effect by the aggressor on the defender.

A bacterium called Agrobacterium tumefaciens developed the ability to inject a portion of its DNA into an injured plant, causing the plant to produce the bacterium’s favorite food, a type of amino acid called opines - which are not naturally produced by the plant, nor are they used as food by other species. Another portion of the DNA causes the infected cells to multiple rapidly, causing the growth of a cell mass called a “gall” - found especially on roses, but also on many other plants. A “gall” would be called a “tumor” if it were found in people.

The organic movement in the 1970s encouraged the use of Bacillus thuringensis as a natural pesticide. Organic farmers for years used B thuringensis on their “organic” crops, secure in the knowledge that this bacterium targeted specific organisms, and that it was applied at specific times of the crop’s growth for maximum effect. It was not sprayed indiscriminately over the crops every day, 24 hours a day.

When a gene is inserted by an organism into another organism, this is generally for the purpose of taking over the defender’s protein manufacturing facilities, to produce proteins demanded by the aggressor. The act is not generally considered “consensual” and is often not to the “mutual benefit” of both organisms. One can imagine that the defending organism may produce multiple neurotransmitters - pheromes, hormones, cytokines, etc - in the process of defending itself against the aggressor. If we are of the school which believes that we are what we eat, then we may wish to consider whether we really want to eat organisms - plant or animal - which are engaged in mortal combat.

When genes are inserted for purposes of genetic engineering, two methods are used. One is the “gene gun” method, where the engineered genetic material is simply blasted at the target organism in the hopes that some of it will stick and become incorporated into the genetic material of the target. Another method is the Agrobacterium method, which is thought to insert single copies of genetic material with greater frequency than the gene gun method, and is therefore considered to be safer.[2]

When a gene is designed for insertion, it must be combined with several other genes in order to function in the new insertion site.

gene diagram
Marker - often antibiotic resistance gene
Regulatory sequence - on/off switch - often cauliflower mosaic virus
Coding sequence of the gene to be inserted
Regulatory sequence - termination signal - may be from a pea
Backbone DNA - superfluous genetic material that happens to be attached

A marker gene is used, to determine whether the transgene has actually been inserted into the new cell’s DNA. Often the marker gene is one for antibiotic resistance - that way, when cells are cultured in a medium with antibiotic, only those which include the resistance gene as well as the transgene survive.

A promoter gene is inserted, to ensure that the protein encoded by the transgene is actually expressed. This is the “on-off” switch for the process. A gene from the cauliflower mosaic virus is frequently used. This promoter gene is considered essential, because it is a “constitutive” promoter, driving the production of the protein coded by the inserted gene 24 hours a day, 7 days per week, unaffected by environmental conditions which would normally serve as a feedback mechanism for turning production on and off. The promoter gene is capable of inserting itself, not just into other plants, but also into other bacteria. Thus is it quite capable of turning on unintended genes in the bacteria.

Then follows the gene for the trait desired - production of Bt toxin, or whatever.

Then follows a termination sequence, to tell the genome that the instructions are complete and it can stop reading.

Several assumptions are made in the course of genetic manipulation. First, it is that genetic manipulation is an acceptable way of treating living organisms. This venue is not the proper place for this particular debate. Suffice it to say that farmers have been manipulating the genetic qualities of their crops for thousands of years. However, with the advent of the ability to modify genes rapidly, and to insert them into organisms of not only different species but also different genera, we certainly open the door to the potential for manipulation of human genes by addition of genes derived from other members of other kingdoms whose genetic material split from human countless eons ago. Consider the possibility of inserting the gene for claws into the human genome, to develop better hand-to-hand combat material.

The second assumption is that the gene will be inserted at a place in the genome which can be predetermined, and which does not disrupt the function of any other gene. It is unfortunately not at all clear that genes are inserted in a non-random fashion, obeying the genetic sequences already present in the organism.[3]

The third assumption is that only one copy of the gene will be inserted per cell, or that if multiple copies are inserted, the number of copies has no significant effect on the end product of the cell. Copy number variant has been shown to affect the expression of gene traits, and the manifestation of “genetic” disease in humans.[4] Is there any reason why copy number should not then affect the expression of traits in plants or bacteria?

The fourth assumption is that the marker gene will have no significant effect on the organism into which it is inserted. The technology has made extensive use of antibiotic resistance genes, to be able to determine which organisms have actually taken up the desired DNA. These organisms have then been used to insert the desired gene (along with the antibiotic resistance marker) into recombinant food crops. Thus, the antibiotic resistance marker gene has become widespread, both in the plant crops and in the organisms which ingest them, as well as in the bacteria which live in those organisms. One is certainly led to wonder whether the appearance of multiple-antibiotic resistant bacteria within the past 20 years is somehow related to this widespread genetic manipulation in the last 20 years.

The fifth assumption is that the promoter gene will behave itself - in other words that it will promote only the manufacture of the desired protein, and no other, and that it will not insert itself into any organism other than the one into which it was inserted by the scientists.[5] Alas, once again the assumption has been proven unfounded. The cauliflower mosaic viral promoter is promiscuous, in other words, has been incorporated into DNA of many different species, including other plants, yeasts, and even E coli, thus opening the door to expression of foreign proteins and unexpected systemic effects in living organisms.[6]

The sixth assumption is that the genetic material is stable - in other words once we have succeeded in producing the desired protein (or insecticide, or viral plasmid for vaccine, or whatever), that this protein is stable and will not mutate - or that if it does mutate, that the mutations will be harmless.[7] Once again this assumption is unwarranted. In a study of genetically modified carp, 15% of the inserted genes were found to be changed by mutation, rearrangement or deletion. The abstract of the paper states that “most transgenes were faithfully inherited during the four generations of reproduction”.[8] True, greater than 50% of the genes were faithfully inherited. But 15% were altered in unpredictable ways. This does not appear to qualify as genetic “stability”.

The seventh assumption is that the termination sequence will function correctly. Termination sequences are very specific, and will not function correctly if there is any change in their amino acid sequence.[9] It is not hard to imagine that termination sequences can become non-functional in the face of a 15% mutation rate of inserted genetic material. We may wish to re-think the consequences of producing an insecticide, or a vaccine, or an allergenic protein 24 hours a day 7 days a week without being able to turn it off.

The eighth assumption is that the gene will have only the intended effect on the organism, and will not cause any unintended effects. However, complexity theory, which applies to living organisms, is very clear in its statement that a very small input can have a very large output in a complex system, since every part of the system is responsive to and depends upon every other part of the system. Foreign DNA is extensively methylated, and can cause changes in methylation patterns in areas far removed from the specific area of insertion.[10] Methylation is what activates and de-activates genes. Being unable to predict exactly which genes are modified by the insertion is playing with fire, genetically speaking.

The ninth assumption is that genetically engineered microorganisms (GEMs), because they carried extra plasmids, had an extra burden of genetic information which would somehow cause them not to survive in the “wild” (much like the human variant of Turner’s syndrome, which carries an extra X chromosome and is sterile). Once again, it has been demonstrated that GEMs can survive for long periods of time outside “ideal” laboratory conditions.[11]

The tenth assumption is that because the GEMS were manufactured with crippling mutations (i.e. requirement for specific nutrients which are not normally present in the natural environment) they would not survive even if they were accidentally released. Once again, this has not been the case in the “wild”.[12]

The eleventh assumption is that even if the GEMs were somehow released and survived, the enzymes in the gut which digest DNA would in fact digest the GEMs DNA, so that none of the foreign DNA would survive to make more bacteria or to be incorporated into the host’s DNA. Unfortunately, ingested foreign DNA from an M13 phage has been found in a mouse’s bloodstream, white blood cells, spleen and liver, and even in some organs of the fetuses of mice fed the recombinant product while pregnant.[13,14]

Environmental impact assessment has been based on the latter three assumptions, all three of which have been proven to be incorrect. Horizontal gene transfer and recombination is almost certainly one of the greatest threats to public health facing us today. Antiobiotic resistance marker genes are inserted into nearly all recombinant DNA. Since the advent of serious genetic engineering and widespread use of genetically engineered food crops, we have seen increasing antibiotic resistance, and even resistance to multiple antibiotics within the same organism, creating an ever-increasing inability to treat infectious diseases, and resulting in ever-increasing morbidity and mortality related to infectious diseases. One wonders whether these events are simply coincidental, or whether there might perhaps be a causative connection.

In summary, the idea behind genetic manipulation of crops is sound. To increase the world’s food supply, with less use of pesticides and higher yield of crop is an admirable goal. The manifestation of the end product appears to be less than ideal. The use of pesticides has increased, the resistance of the target organisms to the manipulated genes has increased, allergenicity has increased. And in the meantime, scientists who have attempted to slow the spread of these genetically engineered crops into the public domain have been ignored, or even fired from their positions, in an apparent attempt to silence them. One wonders about the necessity of creating a “seed bank” in the Arctic Circle, if the crops are indeed as safe as agribusiness assures us they are.

Martha M Grout, MD, MD(H) leads a team of talented associates at the Arizona Center for Advanced Medicine in Scottsdale, Arizona. She graduated from the Medical College of Pennsylvania in 1971 and practiced Emergency Medicine for many years as a Board Certified specialist. After extensive further training, she obtained her homeopathic license in the State of Arizona in 1997. She is firmly committed to the idea that not only does all healing come from within (and above), but also that we can help the healing along, using a variety of different methods. She became intrigued by the idea of genetic modification of crops, because it seemed like such an interesting idea, at least in theory. This paper is a result of some of her explorations into the field of genetic modification of our foods.

[1] Ferrari R, Pellegrini M et al. Epigenetic Reprogramming by Adenovirus e1a. Science (22 August 2008) 321;5892:1086 - 1088.[2][3] Ambrosi A, Cattoglio C, Di Serio C (2008) Retroviral Integration Process in the Human Genome: Is It Really Non-Random? A New Statistical Approach. PLoS Comput Biol 4(8): e1000144. doi:10.1371/journal.pcbi.1000144[4] Estivill X, Armengol L 2007 Copy Number Variants and Common Disorders: Filling the Gaps and Exploring Complexity in Genome-Wide Association Studies. PLoS Genetics 3(10): e190 doi:10.1371/journal.pgen.0030190[5] Assaad FF, Signer ER. Cauliflower mosaic virus P35S promoter activity in Escherichia coli. Mol Gen Genet. 1990 Sep;223(3):517-20. [6] Ewen SWB, Pusztai A. Effect of diets containing genetically modified potatoes expressing Galanthus nivalis lectin on rat small intestine. The Lancet 354 (October 16, 1999). [7] Doerfler W, Remus R et al. The fate of foreign DNA in mammalian cells and organisms. Dev Biol (Basel). 2001;106:89-97. [8] Wu B, Sun YH et al. Characterization of transgene integration pattern in F4 hGH-transgenic common carp (Cyprinus carpio L.). Cell Res. 2005 Jun;15(6):447-54. [9] He B, Kukarin A et al. Characterization of an Unusual, Sequence-specific Termination Signal for T7 RNA Polymerase. J Biol Chem, Vol. 273, Issue 30, 18802-18811, July 24, 1998. [10] Doerfler W. A new concept in (adenoviral) oncogenesis: integration of foreign DNA and its consequences. Biochim Biophys Acta. 1996 Oct 9;1288(2):F79-99. [11] Cremers HCJ, Groot HF. Survival of E.coli K12 on laboratory coats made of 100% cotton. RIVM Rapport 719102009. [12] Ibid. [13] Schubbert R, Hohlweg U et al. On the fate of orally ingested foreign DNA in mice: chromosomal association and placental transmission to the fetus. Mol Gen Genet. 1998 Oct;259(6):569-76. [14] Schubbert R, Lettmann C et al. Ingested foreign (phage M13) DNA survives transiently in the gastrointestinal tract and enters the bloodstream of mice. Mol Gen Genet. 1994 Mar;242(5):495-504.
Genetically Modified Foods - the Good, the Bad, and the Ugly