Genetic Engineering: The Science… what could go wrong and why?

The Issue
“In school you may have learned the basic components of a cell: the nucleus that contains genetic material, the energy-producing mitochondria, the protective membrane at the outside rim, and the cytoplasm in between.  But within these anatomically simple-looking cells is a complex world; these smart cells employ technologies that scientists have yet fully to fathom.”

GENETIC ENGINEERS ARE USING THEIR LIMITED KNOWLEDGE OF HOW CELLS FUNCTION AS THE BUILDING BLOCKS OF GENETIC ENGINEERING!!! THEY WORK ON THE PRESUMPTION THAT THEY HAVE CORRECT AND TRUSTED INFORMATION!!!

What is Genetic Engineering?
Every living thing; plant, animal or microbe, is made up of microscopic cells, in the centre of which is the nucleus, which controls size, shape & functions in each cell.  Inside the nucleus are genes, tiny chemical structures that store instructions for each cell. Genes are made of DNA: the pattern and operating system for all living things.

Traditional plant and animal breeding mates selected individuals together, generation after generation, in the hope offspring will inherit genes for characteristics like high yield or resistance to disease. Only individuals of similar species can be successfully mated.

Genetic engineering (GE) short-circuits this process. Genes are physically transferred from one living thing into the nucleus of a cell from another. The genes may be of the same or unrelated species. In fact one can be an animal and the other a plant. This can never happen in nature. 

The Concerns (the science is flawed/obsolete!)
The old theory of genetics asserted that each gene is coded for its own single unique protein. Biologists also estimated that the number of proteins in the human body was 100,000 or more. Thus they predicted that there would conveniently be about 100,000 genes in human DNA. When the number of human genes was ultimately tallied and reported on June 26, 2000 , it shocked the scientific world: there were only about 30,000. This figure not only fails to account for the estimated number of proteins, it falls short of explaining the vast quantity of inheritable traits in the human body. Moreover there are weeds with as many as 26,000 genes. Given the one protein-one gene theory, shouldn’t humans have far more genes than a weed? Something seemed terribly wrong.

It turns out that the vast majority of genes do NOT encode for a unique protein. On the contrary, some genes can make many, many proteins. In fact, the current record is set by a single gene from a fruit fly, which can generate up to 38,016 different protein molecules. 

In humans, nearly all genes are theoretically able to make two or more proteins. The number of human genes capable of coding for only a single trait can be counted on your hands.

The fact that a gene creates multiple proteins may explain some of the surprises that keep popping up for genetic engineers, and it is on our list of what could go wrong and why. 

Some examples of what could go wrong and why

Horizontal Gene Transfer & Antibiotic Resistance 

After the foreign genes are blasted into the cells, only a small percentage end up inside the DNA. To figure out which of the thousands of cells on the plate have the foreign gene in their DNA, scientists typically attach an Antibiotic Resistant Marker (ARM) gene to their foreign gene. If this gene package makes it into the DNA, the ARM gene will render that cell invincible to a normally deadly dose of antibiotics.

Thus after the genes are shot into the pile of cells, the cells are all doused with antibiotics. Those that survive got the genes in their DNA. Those that die did not. Only one in thousands survives.

Many scientists are concerned that when humans and animals eat GM food, the ARM genes will transfer into the bacteria found inside the digestive system. This process whereby genes travel from one species to another, is called “horizontal gene transfer”. If the ARM gene moves between species it could result in new and dangerous antibiotic resistant diseases.

The biotech companies assure the public that ARM genes cannot be transferred between food and bacteria in the human gut. They refer to evidence… from animal studies in the 1970s and ‘80s that “failed to find evidence that DNA survived digestion.” When detection techniques became more sensitive starting in the late 1980s, however, animal feeding studies confirmed that DNA not only survives, it is found in the blood, intestinal wall, liver, spleen, and feces and even remains intact in the digestive system for more than five days. DNA can even travel via the placenta into unborn mice. More pertinent, however, is a 2002 study that was dubbed “the world’s first known trial of GM foods on human volunteers.”

Researchers used seven people whose large intestines had previously been removed. Their digestive systems were rerouted out of the body into colostomy bags. In their digestive material “a relatively large proportion of genetically modified DNA survived the passage through” the small intestine. Moreover, in three of the seven subjects, horizontal gene transfer did occur. Some of their digestive bacteria contained the herbicide-resistant gene used in soybeans. Since no increase in gene transfer was detected after subjects ate a meal with GM soy, researchers suggest that the transference might be related to long-term consumption.

“Everyone used to deny that this was possible… It suggests that you can get antibiotic marker genes spreading around the stomach which would compromise antibiotic resistance.”

Bt corn contains an ARM gene that resists the commonly prescribed antibiotic, ampicillin. Scientists worry that this gene’s widespread presence in human and animal food will render ampicillin useless in treating disease. The World Health Organisation, Britain ’s House of Lords, the American Medical Association, and even the Royal Society have all called for a phase-out of the use of ARM genes.

Code Scramblers  
To make a protein, the DNA uses its unique genetic code to write a prescription for its chief assistant, RNA. The RNA fills the prescription by creating and assembling amino acids. The amino acids form the protein. But in some cases, before RNA fills the prescription for the protein, along come the spliceosomes (code scramblers), a group of molecules that cut up the RNA, rearrange it and then reassemble it. 

The code scramblers can rearrange a single RNA code in many, many ways, “creating hundreds and even thousands of different proteins from a single gene.” As long as the scientists were absolutely sure that a single gene created one and only one protein, then they could confidently insert that gene in a new species and be sure that it would create that unique protein. The scientists were absolutely sure; but they were wrong.

Will the code scrambler ignore the foreign gene? Or will the code scramblers try to switch around its prescription and accidentally create a protein that might be toxic, or allergenic, or the source of a new disease? It’s hard to say; hard to say since no-one generally tests for this… the biotech industry would rather make the assumption that their foreign gene will somehow avoid the host organism’s scramblers. If not, genetic engineering would be way too risky.

Position Effects
When a foreign gene makes it into the DNA, there is no telling where along the strand it will end up. The inserted gene could disrupt any number of naturally expressed traits depending on where it lands. For example, when scientists inserted a foreign gene into a plant from the mustard family, the plant’s ability to crossbreed with related species varied depending on where in the DNA the gene was located.

Similarly, the location of a foreign gene can dictate how well it does its job. In some locations it will not produce its protein at all; in others, it will produce too little. These location-specific changes are called “position effect” – a kind of genetic Russian roulette.

Gene Silencing
One common position effect is that either the foreign gene or the native genes in their vicinity get shut off; they are no longer able to produce their protein. This common and unpredictable occurrence is called “gene silencing”.

One way that a native gene can get permanently disabled is if the foreign gene ends up right in the middle of it. This happened in one experiment and the mouse embryos ended up dying.

Silencing native genes can result in all sorts of unpredictable outcomes. For example, in his testimony before the United States Environmental Protection Agency (EPA), Michael Hansen of the Consumers Union warned that if the process of genetic engineering “turned off” a native gene whose job was to prevent “the expression of some toxin, the net result of the insertion would be to increase the level of that toxin.”

Environmental Influences
Scientists observed gene silencing when genetically engineering petunia plants. The inserted foreign gene was designed to express salmon red. Scientists expected virtually all the flowers to bloom with the same red colour. Instead, the flowers varied in both colour and pattern. The variation was due to the silencing of the foreign genes in some of the plants. Which plants had silenced foreign genes depended on the position effect – where in the DNA those foreign genes ended up.

In this experiment, however, there was another factor influencing the plants. The colour of those petunia flowers inexplicably changed during the season. More of the foreign genes were switched off as the season progressed. Here, the changes in gene expression were apparently linked to environmental changes. 

A list of even more things that could go wrong…

• Hitchhikers
• Unexpected add-on molecules.
• Chaperones
• Unpredictability of relationship between chaperone protein (which folds other proteins) and foreign proteins, e.g. insecticide gene.
• Messing up the host’s normal DNA
• Method of gene transfer may result in unintended structural consequences, resulting in instability of plant’s genetic make up.
• Turning on genes at random
• The effects of inserting a foreign gene requiring a promoter (cauliflower mosaic virus – CaMV) which is permanently on causes unpredictable proteins to be produced. Can create flood of proteins which are totally inappropriate.
• Hot spots
• Studies show the promoter creates a hot spot in the DNA. This means that the whole DNA section can become unstable, causing breaks in the strand or exchanges of genes with other chromosomes.
• Waking sleeping viruses
• Historically acquired dormant viruses within the DNA structure are in danger of being reactivated. Horizontal gene transfer of the CaMV promoter has    the potential to reactivate dormant viruses or create new viruses.
• Synthetic genes
• Naive assumptions that synthetic genes, which are used pervasively behave the same as natural genes.
• Genetic disposition
• For reasons not well understood, inserting the same gene into different varieties of the same plant species can have widely varying results. The unpredictable influence of genetic disposition is not usually addressed in safety studies
• Complex unpredictable interactions
• Altered proteins can activate or deactivate genes. With each change new interactions can begin setting off further changes. These types of unpredicted chain reactions can have toxic effects.
• Rearranged codes
• Sometimes the process of genetic engineering results in a rearranged sequence of unpredictable genetic information.
• Gene stacking – organisms which are genetically engineered for MORE that one trait.
• Nutritional problems – Changes in the DNA – both intended and accidental – can influence a plant’s nutritional content. Cows fed GM Roundup Ready soy, for example, produced milk with increased fat content.
• Allergens
• Unknown allergens may result from foreign genes and proteins never before part o the human food supply.
• Human error, etc…

• Lipton, Bruce, Ph.D. (2005) The Biology of Belief. Mountain of Love/Elite Books
• Smith, Jeffrey M. (2003) Seeds of Deception. Yes! Books