ABC of Genetic Engineering

Genetics: The ABC of Genetic Engineering

Before examining the ethical issues involved in genetic engineering it might help to outline briefly, and in a very simplified way, what is involved. Genetic engineering is a by-product of the relatively young science of genetics. The science emerged out of the pioneering work of the Austrian Augustinian priest, Gregory Mendel (1822-1884). In a paper published in 1865 Experiments with Plant Hybrids Mendel developed a theory of organic inheritance from his work on crossing garden peas that exhibited different characteristics like tallness or shortness, the presence or absence of colour in the blossoms (green or yellow), round or wrinkled and so on. In crossing the tall with the short variety of peas one might expect that the offspring might be of medium size. This is not so. Mendel discovered the dominance of certain traits or dominant genes over others genes that are called recessive. He postulated that in succeeding generations hybrid offspring appear to exhibit dominant and recessive genes in a specific ratio. For example sometimes the specific characteristic of shortness appears in one generation and is not found in the next generation but appears again in the third generation. Mendel’s experiments and laws help us to understand what is happening. According to his insight, when a recessive gene is paired with a dominant gene, the recessive gene cannot express itself and therefore will have no perceptible effect. In the next generation, however, the recessive gene of shortness might be pair with another recessive gene and therefore it will express itself and have a perceptible effect giving rise to a short plant.

Unfortunately, Mendel’s work remained unrecognised for decades, until in the early 1900s various other scientists like Hugo De Vries, William Bateson and Karl Correns independently obtained results similar to his. When these scientists checked the biological literature they found that Mendel had experimented with peas and published a theoretical understanding of the data 30 years previously.

By the 1920s genetics was being used to help plant breeders improve plants. In the 1930s scientists began to explore the similarities between quantum physics and genetics. Erwin Schrodinger’s book What is Life? published in 1934 gave new impetus to this research and brought modern physics and biology to bear on genetics. On the negative side genetics got a bad name in the late 1930s and 1940s because it was misused by scientists and doctors who were promoting eugenics in Germany and elsewhere.

Even a short account of the history of genetics would be incomplete without mentioning the work of the great Russian geneticist Nikoloi Vavilov. He travelled all over the world between 1916 and 1940 studying crop diversity and establishing one of the most extensive collections of seeds. In a small area of Ethiopia he found hundreds of varieties of wheat which are only found in that place. Vavilov used his knowledge of genetics to pinpoint the places in the world where humans first cultivated particular wild crops like wheat, maize and potatoes. He also mapped out the areas in the world which are rich in biodiversity the islands in South East Asia and Peru.

The science of genetics took another leap forward in the 1950s when two young scientists, James Watson and Francis Crick, discovered the physical make up of deoxyribonucleic acid (DNA), the fundamental molecule of life. They discovered that the structure of DNA was like a double helix. The two strands were twisted around each other like a spiral staircase with bars extending across the connecting strands. These units, composed of four different chemical nucleotides, arrange themselves in a variety of patterns that form the genes. It is the precise ordering of the chemical base in the DNA molecule that makes each life form unique. In the light of Watson’s and Crick’s discovery, biologists began to realise that they could change or modify life forms.

But this discovery, though crucial, was not sufficient to enable scientists to cut up, delete, or recombine genes. They needed tools to cut the genes and then they required a suitable mode of conveyance or vectors to insert the genetic material into another organism. The cutting tools were discovered in a group of enzymes that are called ‘restriction enzymes’. They have the ability as part of their own defence mechanism, to splice up DNA. The vector is also composed of genetic material like specific types of viruses or plasmids from bacteria. This genetic vector will carry the genetic element across the cell membrane of an embryo of the host organism in order to introduce the foreign gene into the target cell’s genome. The process is quite imprecise. It often happens that the integration of the foreign gene takes place at unpredictable places in the chromosomes of the host organism resulting in the fact that only a small number of the target cells will integrate the foreign gene successfully. It is necessary therefore to be able to select the cells that have successfully taken up the foreign gene. Until recently the most common way of doing this was to use antibiotics to kill the cells that have not integrated the foreign gene. Cells that have taken up the foreign gene will survive because they possess the resistant marker gene.

The first genetically engineered organism appeared in 1973 when Drs Stanley Cohen and Annie Ghang inserted genes from a South African clawed toad into a bacterium – e-coli. When the e-coli reproduced themselves they also reproduced the toad gene that had been inserted into the bacterium.

Today plants and animals with genes taken from completely unrelated species are being engineered in the laboratories of biotechnology companies and released into the environment. There is genuine worry about genetic pollution. In October 2001 researchers from the University of California found that one of the oldest varieties of maize in world had been contaminated by genetically engineered maize in Mexico. This is a very worrying development as Mexico is the genetic home of maize. The UN Food and Agriculture Organisation is worried that genetically engineered crops may pollute the gene pool of conventional relatives in the same area.

Some examples of Genetically Engineered Organisms

A company called Calgene developed a genetically engineered tomato called Flavr Savr in the US and Europe. This tomato was approved by the US Food and Drug Administration (FDA) in May 1997. The goal of the experiment was to extend the shelf life of the tomato that is marketed under the brand name of "McGregor". Calgene invested a whopping $95 million in the process which involved isolating a gene that encodes for an enzyme involved in the ripening process. Having discovered the enzyme the technologist blocked its expression.

As a result the tomato will take a few days to ripen on the vine and still maintain its firmness during shipping. As consequences the unfortunate consumer will be duped into believing that the tomato is much fresher than it is. Extending the shelf-life means that the crop can be grown much further away from the retail outlet. For example, it is now possible to grow the tomatoes in places like Central America where the labour and environmental laws are much less strict than those in the United States. Calgene has already been in touch with Mexican growers with a view to producing Flavr Savr on their lands

Scientists have also attempted to create leaner and more cost effective pork through genetically engineered pigs even though the animals experienced extensive arthritis. They can re-engineer the genetic blueprint of an animal or plant in order to create a "super animal" or a higher yielding plant. On the medical, side genetic engineering has created the first patented mammal, called the OncoMouse. This creature was genetically engineered with a human gene to express cancer in the mammary gland. It is now possible to create new transgenetic viruses, bacteria, plants or animals that can be used to secrete in the milk or blood large quantities of inexpensive drugs or chemicals suitable for human use. As we will see these are just a few examples of the wide range of transgenetic plants and animals that are now available.

A Brief outline of Some Technical Elements of Biotechnology

Dr. Mae-Wan Ho, a geneticist opposed to genetic engineering, argues that genetic engineering is a crude and imprecise operation and consequently is inherently hazardous to health and biodiversity. First the geneticist has to identify the gene or gene sequence which expresses the desired trait. Next a carrying agent or vector that will carry the desired gene into the target genome needs to be assembled. The vector is often a plasmid. This is a small DNA ring common to bacteria as additional DNA other than their own chromosomes. The most common is the Ti-plasmid for the bacteria agrobacterium tumefaciens. Several genetic elements are spliced together within the vector. There is the gene or gene sequence. This crucial element is followed by the promoter. This will enable the new gene to become expressed. In other words it will produce the protein for which it is coded. In order to be sure that the target cell has successfully incorporated the new gene it has been found necessary to include a resistance marker gene. And finally the biotechnologist completes the construct with a terminating or regulatory gene.

One common example of this process is found in plants that are genetically engineered to be resistant to the herbicide "Round-up-Ready. The gene construct comes from the soil bacterium agrobacterium sp.. The chloroplast targeting sequence is from the wall cress. The promoter from the figwort mosaic virus and a terminal sequence is from the common pea.

Several techniques are used to transfer the new genetic material to the target plant. One way is for the Ti-plasmid from a pathogenic bacteria to infect the cells of the target plant. Other is called electrophoresis. This involves using an electric field to force the new genetic material into the target plant. Sometimes thousands of gold bullets coated with the genetic material are loaded in a gene gun and fired into the cells of the target plants.

This final operation in the genetic engineering process is to determine whether the target plants have taken up the new genetic material. After describing the four steps above it is easy to see why genetic engineering, at least at present, is imprecise and inefficient. The integration of the foreign genetic material can take place at unpredictable locations in the chromosomes of the target organism. For that reason it is necessary to determine which cells have successfully incorporated the new genetic material. This is done by using antibiotics to kill all the targeted cells that have not integrated the foreign genetic material. Cells that have integrated the foreign genes will survive since they possess the antibiotic resistance marker gene.

It ought to be clear from this sequence that the insertion of a foreign gene into the host genome is a complex and random process, not under the control of the genetic engineer. It is through the use of artificial vectors that the horizontal gene transfer is achieved. The transferred gene can give rise to random genetic effects including cancer. This is why Mae Wan-Ho believes that the technology will contribute to an increase in the frequency of horizontal transfer of those genes that are responsible for virulence and antibiotic resistance, and allow them to recombine to generate new pathogens[1].

Such fears are dismissed by other geneticists, but even if there is a remote chance of this happening the whole genetic engineering enterprise should be put on hold until independent scientific research has addressed these issues over a considerable period of time. The mechanistic bias of conventional genetic engineering that each gene articulates for a particular trait took a bit of a hammering when the mapping of the human genome project was completed. Scientists had predicted that humans would possess 100,000 genes based on the number of proteins humans must synthesize in order to be human. Scientists were surprised when they only discovered 30,000 genes. It now appears that the mechanism of gene expression is much more complex and complicated than has been assumed in orthodoxy genetics. In fact we know that proteins are not made directly from the instructions on the DNA. What happens is that the relevant gene is copied initially on to a short-lived nucleic acid call RNA. This molecule then provides a kind of template on which the protein is built [2]. Yet genetic engineering still operates with the belief that a single trait can be transferred in a rather simplistic way[3].