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Genetic engineering

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Genetic engineering: hopes and fears

Genetic engineering can be used in three main types of organism: micro-organisms, plants, and animals.

The most well-known examples of genetically engineered micro-organisms produce therapeutic proteins for medical treatments, but recombinant bacteria have also been developed that can extract metal from ore. This type of genetic engineering is well established and the risks are well controlled. Few people express any concerns about the use of genetically modified (GM) microorganisms to make human medicines or vaccines. Unfortunately, the biochemistry of prokaryotes means that there is a limit to the complexity of the molecules they can make – so microorganisms cannot solve all of our medical problems.

Transgenic plants are also relatively common. Many crops are grown in the US with a specific herbicide or pesticide resistant gene added. For example, 85% of the soy beans grown in the US, and 98% of the soy beans grown in Argentina are GM crops. Organisations such as the International Rice Research Institute (IRRI) are working to develop strains of rice which are resistant to extreme weather conditions resulting from climate change such as flooding or dryness. Making crop plants more efficient, or more nutritious, through genetic modification, offers a way of meeting the food needs of the ever-growing human population.

Scientists are also looking to develop nutritionally enriched strains of rice and other staple foods such as cassava and sweet potatoes. These offer a way of preventing some of the many deficiency diseases which have devastating impacts on the health of millions of people around the world (see paragraph on golden rice). GM plants also have the potential to deliver medicines in a way which is particularly valuable in the developing world. Work is well underway on growing GM plants which contain specific drugs, vaccines and even monoclonal antibodies. Over 3 million people die every year from vaccine-preventable diseases, mainly in the developing world – if a locally grown food crop can be engineered to deliver the vaccines which are needed, many lives could be saved.

Another category of transgenic plants are the biopharm crops, which contain a substance of medical value that could replace a pharmaceutical product. For example, genetically modified plants are being produced that contain vaccines. In future these vaccines should be inexpensive, easy to deliver to remote areas and could even be orally administered without specialist technology. However, there are concerns that wildlife could be poisoned by eating biopharm crops. Recombinant vaccines have already been produced in micro-organisms: yeast is used to produce a vaccine for hepatitis B. A specific protein on the surface of the hepatitis B virus triggers an immune response when it infects humans; this protein is produced by genetically engineered yeast cells grown in culture, from which the protein can be easily extracted and purified. This is relatively cheap and safe - the virus is not present when the protein is produced and so there is no chance of an accidental infection, unlike the previous method of producing a vaccine which involved purifying the blood of humans and animals infected with the disease. However it is hard to get enough vaccine from the yeast cells. GM potatoes which can grow the hepatitis B vaccine are now being investigated.

In spite of many years of safe use of GM crops such as soy beans, some people still have concerns about these new biotechnologies, including fears that:

  • wildlife could be poisoned though the overuse of herbicides on genetically engineered herbicide-resistant crops.

  • the herbicide-resistant transgene could transfer to weeds, creating ‘super weeds’.

  • the genetically engineered crops themselves could become superweeds by growing out of control.

Some people think the use of genetically engineered crops promotes industrial farming, and creates large populations of identical genetically engineered organisms with the same unknown disease susceptibilities. Others are worried about the health risks: will new allergens be created (perhaps by inserting nut genes into other crops)? People wonder if it is possible that new toxins will be produced as inactive toxin production pathways become activated by gene insertion. Some crops are genetically engineered to be able to withstand high concentrations of toxic metal in soil and resist herbicides – but perhaps they will have high concentrations of these in their edible tissues and therefore be poisonous?

Of course, concerns must be investigated, and the use of GM plants constantly monitored, but once evidence is available to show that the process appears safe, it should be taken on board to benefit those in need. The use of GM plants generally, and especially in medicines, is well summarised in this paper from the Journal of the Royal Society of Medicine.

Biopharm – the production of medicines from biological systems – doesn’t just need GM microorganisms and plants. There is also a growing role for transgenic animals.


Mouse engineering

Mice are incredibly useful tools for scientists investigating how healthy human beings work, and what happens in disease. There are three main ways in which mice have been manipulated to make them more useful as human models:


1. Selective breeding

Careful inbreeding has led to strains of mice which are genetically stable for specific characteristics. They are not clones, but they are genetically almost identical. Scientists have about 100 strains of mice available to them, each with a particular genetic makeup and in some cases a particular tendency to develop diseases such as cancer.


2. Transgenic mice

These are genetically engineered mice which have foreign DNA such as DNA from human cells inserted into their genome. So for example, the mouse may make a different protein. This technique allows scientists to investigate the function and regulation of specific genes, and investigate human diseases such as Alzheimer’s disease. Two main techniques are used to make transgenic mice. In one, the new gene is added to a fertilised ovum, so the whole mouse which develops is transgenic. In the other, the new gene is added to embryonic stem cells which are then added to a host embryo, which is almost always a different coloured strain of mouse. The mouse which results is known as a chimera, because it is a mixture of two organisms. Some of the eggs and sperm will carry the engineered genes so by breeding these mice scientists can produce a strain with the engineered genes present in every cell of the body.


3. Knockout mice

Knockout mice are becoming increasingly important as disease models. Gene editing enables scientists to inactivate or ‘knock out’ specific genes in mouse embryonic stem cells. These cells are grown on and then injected into early mouse embryos. The resulting mice have some knockout cells and some normal cells. As with transgenic mice, researchers then cross breed to achieve homozygous knockout mice. These mice have been developed to mimic human diseases including different types of cancerobesity, heart disease, arthritis, diabetes, Parkinson’s disease and ageing. There are limitations – sometimes a gene affects different tissues or behaviours in mice to those it controls in humans. But the potential value of knockout mice is both increasing our understanding of disease and finding effective treatments.

Mice are surprisingly similar to people – almost every gene in the human genome has an equivalent in the mouse genome.

A chimeric mouse with its offspring. Chimera mice are named after the chimeras of Greek legends, mythical beasts with a lion’s head, a goat’s body and a serpent’s tail!

As with GM plants, there are concerns about the use of GM animals in medical research. Some people raise concerns based around animal welfare: whether pain will be inflicted on transgenic animals, the large number of animals required for genetic experiments and the invasive procedures carried out on them. The extent to which GM blurs the line between species is also of concern to many people. Some of the ethical concerns are related to how humans will use (or misuse) the technology: will it be accessed by those whose quality of life will directly benefit, or by those who will gain only economically?

Genetic engineering in humans is already occurring in the form of somatic gene therapy. This is a way of treating a genetic disorder, but it only works if the gene causing the disease is known, and if the replacement of this gene is likely to work as a treatment. A number of different processes are covered under the name ‘gene therapy’: replacing a mutated copy of a gene with a healthy one, inactivating a malfunctioning copy of the gene, or introducing an entirely new gene into a cell. Somatic gene therapy only alters the genetic material of the affected tissues in the patient; germ cell therapy results in the genetic change being inherited by the patient’s descendants, so many people believe this should be banned until more is known about the technology. Somatic cell therapy isn’t just restricted to treating genetic disorders: it has been proposed that athletes from many different sports might be tempted to use ‘gene doping’ to gain a competitive edge.

At the moment gene therapy is in its infancy. Success stories are just beginning to emerge. If we can get it right, gene therapy of both plants, animals and humans could play a huge role in the future of medicine.

Muscular dystrophy – the importance of animal models