Genetic modification, also called genetic engineering, is the process of changing the DNA of an organism, such as a bacterium or plant or animal. These changes can be as small as inserting or deleting a few DNA ‘letters’ in the organism’s genome (its complete set of DNA) to adding a new gene from a different species.
Genetic modification is not the same as cloning. Cloning creates an exact copy of all or part of an organism’s DNA, while genetic modification makes changes to existing DNA to create a new, modified version of the genome.
There are many reasons why a scientist would want to produce a GM animal. Altering the sequence of individual genes can tell us a lot about how that gene works, how it is controlled and how it interacts with biological processes in the animal. Many GM animals are used as models of human and animal disease to help scientists discover new treatments and therapies.
Some researchers at The Roslin Institute use GM animals for one or both of these reasons, and others are interested in using GM animals to increase the productivity of livestock animals, such as pigs and chickens. Using GM technology allows our scientists to introduce beneficial characteristics into a livestock breed much more quickly than by normal selective breeding. They can also add traits that could not be added by selective breeding alone (for an example of this, see FAQ 6).
The process of genetic modification itself is not harmful to animals. Some changes, particularly those found in disease models, can be potentially harmful to the animal but these changes are only ever made when there is a very strong case that the research will benefit human or animal health. The Roslin Institute takes the welfare of its animals very seriously and all of our animal research is carried out under strict Home Office regulations.
There are several different methods that scientists can use to create a GM animal. The newest and most powerful technology is that of genome editors (see FAQ 5). Whichever method is used, GM mammals, such as sheep or pigs, can be produced by two different methods;
Stem cells can also be genetically modified and used to make a GM mammal, however so far scientists have only successfully isolated stem cells from a few species, including mice and rats.
Birds can also be genetically modified. GM chickens are produced at The Roslin Institute by the injection of special cells called primordial germ cells (PGCs). PGCs can be genetically modified in the lab before being injected into a chick embryo. Once in the embryo, the modified PGCs will form GM sperm or egg cells and breeding two adult chickens that have these modified cells produces a fully GM chicken.
Genome editors act like a pair of scissors, cutting DNA at a specific target position. Scientists can use genome editors to modify the DNA either by inserting a new DNA sequence at the cut site using a template, or by allowing the cell to repair the cut on its own, which often introduces small random changes at the cutting site. These changes can be as small as adding or removing a single base from an animal’s genome. The latest versions of genome editors are capable of introducing the intended mutation into an animal’s DNA without having any so called ‘off-target’ effects elsewhere in the genome.
Genome editors are easy to use, highly efficient and can be made to target any DNA sequence, which means that they are rapidly becoming a very popular method of genetic modification. Although there are several different types of genome editor, the CRISPR/Cas9 system is the most commonly used. In February 2016, the HFEA granted approval to researchers at The Crick Institute to use the CRISPR/Cas9 system in human embryos as part of their research into the early stages of embryo development. These embryos will only be grown in a laboratory and will not be transplanted into a woman to develop further.
Many types of GM animals have been produced at The Roslin Institute – examples of some of our projects are below:
Flu-resistant chickens – In the first half of 2015, avian influenza, or bird flu, was responsible for almost $390 million of losses in the US alone. Research at The Roslin Institute and Cambridge University has developed chickens which do not transmit bird flu. The chickens were genetically modified to produce a small RNA molecule which mimics the structure of the flu virus and binds to proteins which are involved in viral reproduction. When the GM chickens are infected with bird flu, virus replication is blocked. Although the modified chickens themselves can still become infected and succumb to flu, they do not pass the virus on to other birds. We are continuing the project to try to develop chickens which not only prevent transmission of the virus, but are also resistant to flu themselves.
More productive sheep – Genome editing technology is being used at The Roslin Institute to increase the productivity of sheep bred for the meat industry. Naturally-occurring mutations that stop a gene called myostatin from functioning have shown that animals with these mutations have up to 20% more muscle mass compared to animals without the mutations. Animals with myostatin mutations convert feed to muscle more efficiently, reducing the amount of resources needed to produce meat. The meat from these animals is also of a higher quality and is healthier, containing less fat.
These mutations have already been bred into livestock breeds, such as Belgian Blue cattle, but it can take up to 50 years of selective breeding to produce new breeds with myostatin mutations. Research at The Roslin Institute is using genome editors to accurately and efficiently introduce these mutations into sheep to increase their muscle mass. As part of this work, the first genome edited sheep was created in 2013.
Disease-resistant pigs – African Swine Fever virus (ASFV) is a fatal disease of pigs, originally found in sub-Saharan Africa but now spreading into Europe. In 2014 it was reported to have infected pigs in Eastern Europe for the first time and has now spread as far west as Poland. Pigs infected with ASFV die within two weeks of infection as a result of overstimulation of their immune system, but wild pig species in Africa, such as the warthog, are not affected by ASFV. Because wild African pigs and domestic European pigs cannot breed, genome editors are being used to make European pigs more resistant to ASFV.
Scientists at The Roslin Institute have identified a gene called RELA, which is involved in the immune system and could be modified to produce ASFV-resistant pigs. As part of this work, the Roslin team produced the world’s first genome edited pig, known as Pig 26, in 2013. Pig 26 had a single DNA ‘letter’ missing from its RELA gene; a powerful demonstration of the accuracy of genome editors. Current research is trying to replace a section of the pig RELA gene with the equivalent section from the warthog to make pigs which are resistant to ASFV.
There is no reason to think that the process of genetic modification in food products would be unsafe in any way. However, each new GM plant or animal food product would have to be rigorously tested on a case-by-case basis to ensure that the inserted or modified DNA sequences don’t inadvertently produce any harmful substances, such as toxins or allergens.
Any attempt to introduce genetically modified livestock into the food chain would have to be fully assessed and approved by the appropriate authorities such as the Food and Drug Administration (FDA) in the US or the European Food Safety Authority in Europe. The FDA have recently approved the AquAdvantage salmon as the first GM animal fit for human consumption, but products from GM animals will only make it onto supermarket shelves if there is public demand for them.