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Genetic Engineering

Genetic engineering is the science of altering living things by changing the information encoded in their deoxyribonucleic acid or "DNA". Genetic information is stored in DNA using four different chemicals called adenine, cytosine, guanine and thymine. Abbreviated to the letters "A", "C", "G", and "T", these base chemicals are coupled together to form the linkages or "base pairs" that hold together the two spirals that comprise every DNA molecule.

Any organism's entire genetic sequence is known as its "genome" and contains millions and often billions of DNA base pairs. For example, human DNA contains about three billion. However, rather than working with individual base pairs, genetic engineering is concerned with far larger DNA segments known as genes. The human genome contains about 20,000 to 25,000 distinct genes, and was first mapped by the Human Genome Project. In total, the human genome's three billion chemical base pairs contains about 750Mb of information, which could today be stored in your pocket on a 1Gb USB memory key. This is perhaps interesting to ponder given that an initial major constraint faced by the Human Genome Project was available computer storage capacity.

A Broad Church

Genetic engineering is a very broad discipline that is best broken down into its areas of practical application in order to be most easily understood. At the highest level, genetic engineering can be sub-divided into the creation of genetically modified (GM) plants, animals and micro-organisms, as well as the application of genetic engineering in healthcare, otherwise known as genetic medicine. In turn, genetic medicine may be usefully sub-divided into the fields of genetic testing, pharmacogenetics, and gene therapy.

The following sections provide a brief introduction to GM plants, GM animals, GM micro-organisms, genetic testing, pharmacogenetics and gene therapy. All of these fields involve the study of the genetic traits of a particular species, and/or the alteration or exchange of one or a few genes in order to achieve a desired outcome. Already, however, some scientists are going beyond the genetic modification of one or a few genes in order to create radically different and even entirely artificial life forms. This development goes beyond the scope of what is detailed below, and is covered separately on the synthetic biology page.

GM Plants

All forms of genetic modification (GM) take one or more genes from one species and introduce it into the DNA of another in order to create a "transgenic" organism with different characteristics. So, for example, a plant may be made more resistant to disease, drought or pesticides by introducing a foreign gene from another species into its genome. While many people and organizations still object to such a practice, it is worth remembering that the exchange of genes occurs constantly in the natural world and is the basis of the process of natural selection that keeps us alive.

One of the first GM plants was created at the University of California in 1986. Here, some tobacco plants were transgenically altered with a gene from a firefly to make them bioluminescent. The result was GM tobacco capable of emitting a glow. This very much caught the public imagination, although the intention of the scientists was to allow them to track the successful transfer of genes between species, rather than to harvest glowing plants!

The first commercial GM plant was the Flavr Savr tomato. Created by Calgene, this was licensed for human consumption in 1994. Specifically, Calgene used "gene silencing" technology to shut down the gene that causes tomatoes to rot, so allowing the GM produce to stay firm for longer after harvest. Following the Flavr Savr tomato, a company called Monsanto began to introduce a range of corn and other GM crops. Today, around 90 per cent of the corn, cotton and soybeans grown in the United States are GM. China, Brazil, Argentina, Canada, Paraguay and South Africa also grow large quantities of GM crops. However, despite the improved yields, pesticide resistance and disease resistance than GM offers, across Europe GM crops remain banned.

GM Animals

Transgenic animals have also already been created. Way back in 1986 the first transgenic mice were genetically altered to develop cancer. Since that time the creation of "humanised" transgenic mice and rats for research purposes has also almost become routine, with a company Ozgene having being creating transgenic rodents for over twenty years.

A new breed of "enviropig" has also now been transgenically created by the Guelph Transgenic Pig Research Program to produce a more environmentally-friendly form of manure. Back in 1996, the Roslin Institute in Scotland also successfully managed to clone a sheep called "Dolly" by transplanting an udder cell nucleus from one sheep into an empty egg cell from another. Since that time the same technique has been used to clone pigs, dogs and horses.

Today, we are on the brink of the approval of the first GM creature to enter the human food chain. Created by a company called Aqua Bounty Technologies, the AquAdvantage is a transgenic salmon that has had ocean pout and chinook salmon genes spliced into its DNA. The result is a fish that grows to full size in 18 rather than 36 months. While the pending approval of the AquAdvantage for human consumption may prove controversial, in the face of future food shortages we may well need a whole host of such rapidly-growing animals in order to fend off mass starvation.

GM Micro-organisms

For centuries natural fermentation processes have been used to produce products including cheese, beer and yoghurt. However, since the birth of genetic engineering in the 1970s, genes have also been spliced between micro-organims in order to enable the creation of products using transgenic E.coli bacterium and other micro-organisms. Indeed today, biotechnology is a $200 billion global industry.

Today, transgenic E.coli bacterium are used to produce all manner of things including chymosin (as required in the making of cheese), as well as synthetic insulin, human growth hormones, and first generation bioplastics and biofuels. As detailed on the synthetic biology page, next generation medicines, biofuels and bioplastics are now also on the horizon.

Genetic Testing

Ever since the completion of the Human Genome Project, hopes have been high for the application of genetic engineering in healthcare. While progress has been slower than the media anticipated -- and the role of most of the genes in human DNA is far from understood -- already more than 1,000 human genetic tests are available. These enable couples who conceive a child using in vitro fertilization (IVF) to have embryos screened for the genetic mutations that cause cystic fibrosis, sickle cell disease, spinal muscular atrophy, and a range of other conditions. It is also now possible to obtain a genetic test for many conditions over the Internet, with the process now as straight-forward as point, click and spit.

Major research is also underway into the genetics of cancer. For example the International Cancer Genome Consortium has been set up to generate genetic data on up to fifty of the most common types of cancer. In time, this work should allow doctors to test for and diagnose cancers based on their genetic characteristics. Further into the future, cancer gene therapies may also result.

Since the Human Genome Project, was fully completed in 2003, scientists have learned that the role of individual genes in human DNA is far more complex than first thought. Not least, the "expression" (or level of activation) of a gene has been found to be as least as medically important as gene composition. Significant progress in genetic testing -- let alone genetic treatments -- are therefore likely to require doctors to be able to test patients for far more than mutations in one or a few genes. Fortunately, this is also likely to become possible, and relatively soon.

When the Human Genome Project was fully completed in 2003, the sequencing of an individual human genome took thirteen years and cost three billion dollars. Yet today, a Californian company called Illumina can already sequence an individual human genome in eight days for about $10,000. By the middle of this decade, a company called Pacific Biosciences is already predicting that it will be able to sequence an individual human genome in fifteen minutes for less than $1,000. What this incredible progress will make possible is a whole new approach to medicine called pharmacogenetics.

Pharmacogenetics

Pharmacogenetics -- also known as pharmacogenomics -- is the study of how genes influence a person's response to drugs. It has always been obvious that different people respond differently to the same medication. However, it has usually not been known why. The promise of pharmacogenetics is to alter this situation by allowing doctors to select treatments based on the genetic makeup of each individual patient.

Pharmacogenetics will also allow prescriptions to be calculated based on a person's genetics rather than purely their weight and age. Vaccines will also be able to be genetically targeted, with different strains for different patient DNA profiles. In addition, pharmacogenetics will allow medicines that work very well in some people but cause major side effects in others to be safely brought to market as it will be known who will react badly to them and who will not.

Before widespread, individual genome sequencing becomes routine, a critical pharmacogenetic technology is likely to be the gene chip. Gene chips are medical sensors about the size of a matchbox, and feature a tiny "DNA microarray". Every square on this grid contains a particular DNA snippet. When a sample of patient DNA comes into contact with the gene chip this causes some of its squares to illuminate, so revealing the level of activation of particular genes. By examining the gene chip under a microscope a patient's genetic suitability for certain drugs can thereby be assessed. Experimental gene chips are already available from suppliers including Affymetrix.

Gene Therapy

The ultimate goal of genetic medicine is to cure health complaints at the genetic level. Potentially, several mechanisms exist that could be used to insert additional or replacement genes into a patient's DNA. These include the use of gene transfer agent viruses known as "vectors" to deliver therapeutic genes to target patient cells. Alternatively, therapeutic genes may be coated with artificial liposomes. These fatty substances adhere to the surface of cells and may therefore encourage attached genes to enter into them.

Gene therapy trials have been taking place for over a decade. For example, a baby called Rhys Evans who suffered from an immunodeficiency called X-SCID received a gene therapy treatment way back in 2001. While this was successful, other human trails have resulted in serious side effects -- such as leukemia -- and even some patient deaths. In 2008, a significant success was reported using gene therapy to cure inherited blindness. However, gene therapies for most conditions probably remain many decades away.

The World of the Designer Baby

Gene therapy and related genetic engineering research in human beings is currently tightly regulated (if to very different degrees in different parts of the world). However, we already live in the world of the designer baby, with IVF now widely used to help some couples conceive. Indeed, in the UK, about one child in fifty is now born as a result of IVF. Babies conceived via IVF are also routinely screened for genetic diseases. With certain embryos then consciously selected for implantation, human choices are thereby already being made regarding the characteristics of resultant children. A company called The Fertility Institutes in the United States also already offers parents a "gender selection program". The technology also now exists to enable a baby's hair and eye colour to be screened for and selected via IVF. While this is not yet commercially available, it may well become so in the future.

Genetic engineering is a science in its infancy that faces not just highly complex technical hurdles, but also significant bioethical debates. Genetically modified crops that offer improved yields and high disease resistance may well be the answer to food shortages. However, they also raise understandable fears including the risk of genetic cross-contamination and the potential abuse of monopoly power as parts of the "natural" world start to become patented and controlled by Big Business. Human genetic modification is even more contentious. Indeed, it has been hypothesised that a "eugenics gap" may emerge between nations if different countries (such as China and the United States) continue to take very different ethical stances in respect of the research and practice of future human generic engineering.

More information on genetic engineering can be found in my book 25 Things You Need to Know About the Future. A list of genetic modification (GM) web references can be found here, while a list of genetic medicine references from the book can be found here.

Genetics Man

Genetic engineering alters life itself by changing the information encoded
in its DNA.

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