The World Health Organization defines genetically modified organisms (GMOs) as “organisms in which the genetic material (DNA) has been altered in a way that does not occur naturally”.1 European legislation is more specific, defining GMOs as organisms in which “the genetic material has been altered in a way that does not occur naturally by mating and/or natural recombination”.2
Typically genetic engineering involves manipulating an organism’s genetic material (genome) in the laboratory by the insertion of one or more new pieces of DNA or by the modification of one or more of the base unit letters of the genetic code. This re-programmes the cells of the genetically modified organism to make a new protein or to modify the structure and function of an existing protein. Genetic modification (GM) confers new properties or “traits” that are not naturally present in the organism. Among the manipulations included within GM are:
- Transferring of genes from related and/or totally unrelated organisms
- Modifying information in a gene (“gene editing”)
- Moving, deleting, or multiplying genes within a living organism
- Splicing together pieces of existing genes, or constructing new ones.
When incorporated into the DNA of an organism, genetically modified genes modify the functional characteristics – the traits – of an organism. The most common traits in the GM crops currently on the market are the expression of proteins designed to kill insects that try to eat the crop or to make the crop tolerant to an herbicide. However, in theory, the new proteins expressed in GM crops could have a wide range of functions.
What is DNA?
DNA stands for deoxyribonucleic acid.DNA molecules are found in the nucleus of every cell. Within the DNA molecule are segments called genes, which can number in the tens of thousands. Genes contain the instructions that guide the development and functioning of all known living organisms and viruses.
The main role of DNA is the storage of biological information. Information stored within genes is expressed as physical characteristics or traits, such as height, dark skin, red hair, or blue eyes.
There are four subunits of the DNA molecule, called “bases”. These are the “letters” of the genetic alphabet. Information is stored in DNA in the sequence of these letters, just as information is stored on this page in the sequence of the letters of our 26-letter alphabet.
Each gene is a specific sequence of genetic letters and can be likened to a blueprint, recipe, or code for a specific protein or set of proteins. The genome of an organism is the collection of all the genes needed to construct, either directly or indirectly, all components of the organism’s cells.
Most genes encode information for proteins, which can function in any of four different ways:
- As the structural building blocks of an organism’s body, forming physical structures such as cell walls and organs
- As enzymes – proteins that catalyze the biochemical reactions needed to maintain life
- As intracellular signalling and regulatory molecules, controlling the function of genes, metabolic pathways, cells and organs
- As regulatory molecules or peptide hormones that govern many physiological processes from outside the cells.
The latest estimates indicate that humans have around 21,000 different genes that code for proteins, roughly the same number as a fruit fly. Crop plants, on the other hand, such as rice, wheat, maize and soybeans, contain 30,000–50,000 genes. Clearly, the information content rather than the quantity of genes is most important in determining the characteristics of an organism.
Regions of DNA that contain protein-encoding genes constitute only a small proportion of the DNA present in any human, animal or plant (approximately 3–5%). Until recently the non-coding DNA was thought to be largely non-functional and was referred to by some scientists as “junk DNA”. But it has now been discovered that “junk DNA” is far from non-functional and contains thousands of elements that are vital for the control of gene function.
It also used to be thought that one gene coded for one protein. However, since the number of protein functions in humans and other mammals is estimated at more than 200,000, it is clear that there must be ways of obtaining more than one protein from a given gene. It is now known that most genes (at least 60%) encode for more than one protein.
Furthermore, more and more proteins are being found to be localized to multiple sites within cells and organs and to perform more than one function. Many cellular functions are now known to be performed by groups of proteins clustered together. So a large diversity of cellular and organ functions can be obtained from a limited number of genes.
Finally, it is worth noting that many genes do not encode proteins. Rather, they produce ribonucleic acid (RNA) copies of themselves of various sizes. These RNA molecules perform structural, regulatory, and catalytic roles, and are involved in vital cellular processes, including the manufacture of proteins and controlling the function of other genes. For example, RNA molecules can control how much of a certain protein is made from a given gene.
In summary, it is now obvious that gene organisation within DNA is not random and that control of gene function consists of a finely balanced, highly complex network of interactions, which scientists do not fully understand. It is also evident that, because the genes of an organism are an interconnected network, a single disturbance in gene organisation or function can affect multiple gene systems, with serious downstream consequences in terms of the cellular function and health of the organism.
It is also important to keep in mind that because of the complexity of gene systems, the effects of even a single disturbance are not predictable. This is illustrated by the fact that altering a single letter of the genetic code of a single gene can be a significant step leading to cancer, a disease that involves alterations in the function of multiple genes, proteins and cellular systems. Except in a few circumstances, every cell of an organism (human, animal, plant) contains the whole genome of that organism: that is, the total collection of genetic information specifying, either directly or indirectly, all aspects of the structure and function of the organism.
When cells multiply and reproduce themselves, the total genome is duplicated (“DNA replication”) before the cell divides. The complete genome is passed on to both “daughter” cells. The manufacture of all types of proteins from the information contained in genes is a multistep series of reactions:
- The corresponding genes are copied into messenger ribonucleic acid (mRNA), a process known as transcription.
- After transcription, the mRNA is transported out of the cell’s nucleus to its outer compartment, known as the cytoplasm.
- Once in the cytoplasm, the genetic information within mRNA is decoded or “translated” to build the desired proteins.
This process is summarized in what is known as the central dogma of molecular biology: DNA makes RNA makes protein.
Genetic engineering theory and practice
Just as magnetic tape can be used to store electronic information such as music or video, DNA stores genetic information. And just as a sound engineer cuts and splices magnetic tape to make a complete recording of a song, genetic engineers use the techniques of genetic modification or genetic engineering to cut and splice DNA. They use these techniques to isolate, modify and move DNA and the genetic information it carries between both related and unrelated organisms.
The central concept of genetic engineering is that by cutting and splicing the DNA of an organism, new functions, characteristics, or traits can be introduced into that organism. The assumption is that the resulting organism will be identical to the non-genetically modified original, except that it will have the new trait that is conferred by the new gene introduced by the genetic engineer.
This is a simple and elegant concept. But the actual practice of genetic engineering is not so simple and elegant. The genetic engineering process is not precise or predictable. Genes do not function as isolated units but interact with each other and their environment in complex ways that are not well understood or predictable. The genetic engineering process can disrupt the host organism’s genome or genetic functioning in unexpected ways, resulting in unpredictable and unintended changes in the function and structure of the genetically modified organism. This in turn can result in the presence of unexpected toxins or allergens or altered nutritional value and the engineered organism can have unexpected and harmful effects on the environment.
- World Health Organization (WHO). 20 questions on genetically modified foods. 2002. Available at: http://www.who.int/foodsafety/publications/biotech/20questions/en/index.html.
- European Parliament and Council. Directive 2001/18/EC of the European Parliament and of the Council of 12 March 2001 on the deliberate release into the environment of genetically modified organisms and repealing Council Directive 90/220/EEC. Off J Eur Communities. 2001:1–38.