Genetic modification of farm animals
The genetic modification of plants has become an issue of major public concern. Although the equivalent procedures in animals are much further away from commercial application in food production, they are used experimentally for several purposes.
A brief history of livestock breeding
Humans have been involved in genetic modification of animals, whether knowingly or not, since domestication began about 12,000 years ago. For most of this time genetic modification has been brought about simply by identifying and breeding from animals which best suited human needs for food, clothing, transport or draught power. The increase in the human population in the 18th century led to greater emphasis on 'selective breeding' (picking the best animals to be parents of the next generation) for increased output of animal products such as meat, milk, fibre and eggs.
Many new breeding technologies simply accelerate these conventional selection methods, without directly modifying the animals' genetic make-up. For example, the new and controversial technique of cloning has been used mainly to produce animals with identical copies of existing, naturally occurring, combinations of genes.
What is the purpose of direct genetic modification of animals?
The direct genetic modification of animals has already, or could be, practised for three main purposes:
Scientific and medical research
Genetically modified animals, especially mice, are widely used in scientific research into how animals function. They are also used in research to help understand and develop treatments for both human and animal diseases.Treatment of human disease
Some human proteins used in the treatment of diseases (e.g. cystic fibrosis), are in very short supply. To overcome this problem, genes coding for the production of some human proteins have been transferred into sheep or cattle, enabling these proteins to be produced in the milk of the genetically modified animals. Some proteins produced in this way are now in the late stages of clinical trials. Although still at an experimental stage, the production of animals to provide organs for transplants in humans is another application of direct genetic modification. In this case the modification is aimed at altering the immune system of the animals, so that their organs appear to be of human origin, and are therefore not rejected after transplantation.Production of modified food-producing animals
Potentially, direct genetic modification could be used to enhance the productivity of farm animals, or alter their products e.g. by creating strains which grow faster, which show greater resistance to disease, or which produce novel proteins in their eggs or milk that are beneficial to human health. Such applications are being investigated experimentally in some countries, but the routine use of direct genetic modification in food-producing animals is unlikely in the short to medium term. This is largely because there are few known single genes that have a major effect on economically important characteristics (most characteristics are influenced by many genes). Also, most agricultural products have a relatively low value, and gene transfer methods are inefficient and expensive.
In most countries technologies for the direct genetic modification of animals are strictly controlled. In the UK these procedures are regulated under the Animals Scientific Procedures Act (1986). This requires scientific and ethical justification for each procedure. There is also UK and EU legislation governing the 'contained use' and 'deliberate release' of genetically modified organisms, including animals. This legislation is designed to protect both human health and the environment.
How is direct genetic modification achieved?
Techniques that allow the direct modification of the genes of animals were first established about 20 years ago. There are two main ways in which the genetic makeup of animals can be modified directly:
By altering the expression of existing genes. For example, it is possible to prevent, or knockout, the normal expression of some existing genes. This allows investigations of the function of particular genes. For instance, knockout mice are being widely used in research on cystic fibrosis, breast cancer, colon and other cancers in humans. This approach has not been used to date in farm livestock.
By adding new (foreign) sequences of DNA. Physically inserting the DNA coding for a gene with a desired effect into the DNA of another animal, is termed gene transfer, and the animals receiving the foreign DNA are called transgenic animals. DNA is chemically identical across species, and the genetic codes for producing particular proteins are the same across species. This means that it is possible to transfer genes not only within species, but also between species, and sometimes even between different classes of organism. For instance, bacterial and viral DNA has been introduced to a range of food crops to confer insect and virus resistance.
There are four steps involved in gene transfer:
Identification of a gene with a significant and desirable effect
This is probably the major technical limitation to gene transfer in animals at the moment. Mammals have 50-100,000 genes, but for only a small fraction of these is the function and exact location on the chromosomes known. Since most characteristics of economic importance in farm animals are influenced by many genes, transfer of one or a few genes is only likely to be useful in a few special cases (e.g. adding a gene conferring disease resistance, or significantly altering food quality.)Introducing the DNA coding for the desired gene
This is usually achieved, in mammals, by direct injection of several hundred copies of the foreign DNA sequence into the nucleus of an early stage embryo. In mice, but not in farm livestock, foreign DNA can also be introduced via stem cells. These are cells, such as those found in early embryos, which are capable of developing into any organ or tissue. Transgenic poultry have been created using retroviruses carrying copies of the DNA coding for a new gene. The nuclear transfer technique used recently to produce cloned sheep offers an important new route for the introduction of foreign DNA. Nuclear transfer involves adding a cell from an embryo, or from a cell line maintained in the laboratory, to an unfertilised egg from which the nucleus has been removed. An electric current causes the fusion of the introduced cell and the unfertilised egg, and the new embryo then develops as if newly fertilised. The initial applications of this technique, including the creation of 'Dolly', did not involve genetically modified cells. However, foreign DNA can be introduced to cell lines in the laboratory, and cells that have the desired genetic modification can then be used for nuclear transfer.Regulating expression of the introduced gene
It is clearly vitally important that the right genes get switched on in the right tissues, at the right time. Some early attempts at gene transfer in animals produced undesirable side effects, because genes were introduced without appropriate regulation of expression.Confirming transmission of the transferred gene to the next generation of animals
This is achieved by testing samples of DNA from the offspring, to confirm that the foreign DNA is present.
Ethical issues
The direct genetic modification of plants used in food production has raised public concerns over food safety, environmental risks and socio-economic effects as well as intrinsic concerns about human intervention in nature. There are likely to be additional concerns over direct genetic modification in animals.
Most people accept the use of animals for a range of purposes including food production, providing that the animals are treated humanely. In 1994 the UK government established a committee to consider the ethical implications of the use of new breeding technologies in farm livestock (the 'Banner Committee'), and it has since accepted the major recommendations of that committee. The Banner Committee suggested that the humane use of animals respect three principles:
- some treatments of animals are so harmful that they should never be permitted under any circumstances;
- if a harmful treatment is permitted, the harm it causes must be justified by the good being sought,
- steps should be taken to minimise any harm which is justified by the second principle.
The first principle would exclude the use of technologies, which are regarded as intrinsically objectionable. (There are many new technologies which are not intrinsically objectionable, and which may offer benefits for society or for animals e.g. by improving resistance to disease. Conversely, conventional selection techniques sometimes result in changes which many people regard as objectionable e.g. the extreme breast development, and associated difficulties with natural mating, seen in some strains of turkey.)
Both the creation of genetically modified organisms, and breeding from them, are controlled procedures already in the UK, requiring a licence from the Secretary of State. Before a licence is granted, the likely 'adverse effects' on the animal have to be weighed against the likely benefits of the modification.
It seems appropriate that any analysis of the technical aspects of livestock breeding technologies is accompanied by an analysis of the ethical implications. The framework and recommendations of the Banner Committee provide an important foundation for this, and for a more open dialogue in an area of public concern. In the longer term, this should help to restore public confidence in farming and science, whilst allowing maximum benefit to be derived from those technologies which are considered acceptable.
Acknowledgements
This note was prepared on behalf of BSAS by Prof. Geoff Simm of SAC (Scottish Agricultural College), Edinburgh, telephone 0131 535 3209. The technical advice of Prof. John Clark (Roslin Institute, Edinburgh) and Prof. Bill Hill (University of Edinburgh) is gratefully acknowledged.
For further information please contact the author.
For further copies of this paper, please contact the BSAS office on 0131 445 4508.