New Tools Fuel Progress on Development of Genetically Engineered Farm Animals
Bob Holmes, New Scientist Magazine
Genetically Engineered Farm Animals
Genetically modified farm animals cold provide us with more nutritious meat, eggs and milk, causing fewer pollution problems
Unless you live in
The main reason is that the genetic engineering of animals -- with the exception of mice -- has been a slow, tedious process needing a lot of money and not a little luck. Behind the scenes, though, a quiet revolution has been taking place. Thanks to a set of new tricks and tools, modifying animals is becoming a lot easier and more precise. That is not only going to transform research, it could also transform the meat and eggs you eat and the milk you drink.
The first transgenic animals were produced by injecting DNA into eggs, implanting the eggs in animals and then waiting weeks or months to see if any offspring had incorporated the extra DNA. Often, fewer than 1 in 100 had, making this a long, expensive process.
"That's just really inefficient," says
In mice, geneticists found a way round this problem: producing cells with the desired modification first, before growing entire animals. The researchers alter the DNA in embryonic stem cells growing in a dish, then inject successfully modified cells into embryos. This yields chimeras with a mixture of cells that can be bred to produce mice in which all the cells are modified. It has become cheap and easy: there are now many millions of GM mice in labs worldwide, including extraordinary creations like the "supermouse" capable of running twice as far as normal, "brainbow" mice whose neurons light up in different colours and even mice that do not fear cats.
Saved by the clones
It is not yet possible to grow embryonic stem cells from other animals -- except, since last year, rats -- so this technique does not work for other species. However, improvements in cloning mean that for many species ordinary cells can be altered, and entire animals then produced by cloning cells with the desired modification.
At the same time, biologists have developed more efficient ways of adding DNA to cells, by hijacking natural genetic engineers such as viruses, and jumping genes capable of "copying and pasting" themselves. All these advances mean the effort and cost needed to produce GM animals has decreased a hundredfold, says Fahrenkrug.
Researchers are also developing far more precise ways of altering DNA, rather than relying on random insertion. One promising new tool is the zinc finger nuclease: a DNA-cutting enzyme attached to a "zinc finger" that can be customized to bind to specific DNA sequences. Zinc finger nucleases allow engineers to cut a cell's DNA at a preselected spot. When the cell attempts to mend the cut, it often leaves out a few DNA letters or incorporates a few extra ones, so this method can be used to destroy, or knock out, specific genes.
"This will revolutionize genetic engineering of animals," says
What's more, in theory, if you also add a bit of DNA flanked by sequences matching those on either side of the cut, the cell should sometimes be tricked into repairing the cut by splicing in the added DNA, a process known as homologous repair. In other words, the extra DNA is added exactly where you want it. Rumor has it that researchers at the biotech company
The ability to easily and precisely modify animals will undoubtedly lead to huge pay-offs in research and medicine. Whether it will transform the animal products we consume is less clear.
Ultimately, the adoption of GM farm animals may hinge on public opinion and the demand for the benefits they can offer. That demand may be felt most urgently in countries such as
So in 20 years' time will GM animals be as widespread as their botanic counterparts are now? "Technologically, nothing is standing in our way," says Fahrenkrug. "Really, the issue is coming down to: What are you going to make?"
Genetic engineering is now a standard technique in the production of many protein-based drugs. Human insulin, for example, has long been produced by cultures of bacteria carrying the human insulin gene. Pharmaceutical companies are eager to turn animals into drug factories, too. That's because animal cells alter many of their proteins by tacking on sugars and other "decorations," an extra step that bacteria cannot perform. As a result, many proteins -- most importantly, antibodies -- work much better if they are made in animal cells.
One such animal-produced protein has already been approved for clinical use by the
Many others are under development. The Dutch company
Don't expect a cow to walk up to your restaurant table and offer you a prime cut anytime soon. Nonetheless, genetically modified farm animals could provide us with more nutritious meat, milk and eggs, while causing fewer pollution problems and perhaps suffering less, too.
Pigs whose muscles are enriched with omega-3s have already been created, and researchers are exploring similar options with milk. Meanwhile, a team at the
"They're obviously very interested. They consume half of the world's pork," says Fahrenkrug. A similar effort under way in fish could reduce pollution from fish farms.
Animals could also be modified to reduce disease risk. Hematech, of
Welfare could be improved, too. Cows have been modified to produce a compound that protects them against udder infections, for example. Engineering could also end the quick slaughter of half of all offspring of dairy cattle and laying hens, whose owners have little use for male animals. This could perhaps be done by inserting genes on a bull's Y chromosome to cripple male-producing sperm.
"The idea has been around for 15 years, but now the efficiency of making transgenics is so high that this problem will be solved within the next couple of years," says Fahrenkrug, whose group is one of about 10 worldwide working on the issue.
Many people die waiting for organ transplants. Animals could provide an unlimited supply, if only the human immune system did not reject them. So geneticists have been working for years to create pigs whose organs lack the molecules that trigger rejection, such as alpha 1,3-galactosyltransferase. The race is gathering momentum.
Already, a team led by
"Occasionally you get the 180 days, but not on a regular basis," says Niemann.
Meanwhile, Fahrenkrug and his colleagues are working on another major barrier to pig-to-human transplantation: the presence of dormant viruses within the pig genome that could, in theory, reawaken and infect a human recipient. Fahrenkrug has added a gene for a human antiviral protein into pigs in the hope that it will suppress the viruses. If it works, the likely first application will be transplants of insulin-producing islet cells from pigs to humans.
"This is personal issue for me," says Fahrenkrug. "I have friend and family members that have died from the complications of diabetes."
We have around 23,500 genes. What do they all do, and which gene variants contribute to common diseases? By disabling genes to see what happens, geneticists can work out what they do. Until recently, however, this was possible only in mice, which are not always the best animals to use. Now genes can be "knocked out" in an ever-growing range of animals.
PETS IN ALL COLORS
The first genetically modified pet to go on sale was a medaka, or rice fish, with a green fluorescent jellyfish gene, launched in
It was swiftly followed by the GloFish, a zebrafish with fluorescent genes from jellyfish or corals that has become a popular aquarium fish in the U.S. and parts of
Several years ago, there was talk of genetically engineering cats and dogs that people would not be allergic to. That never happened, but new methods would make knocking out the relevant genes much easier if attempted today.
While there are valid reasons to be concerned about the welfare of GM pets, conventional breeding can also produce deformities, as seen in many dog breeds.
You can "knock out" genes in the cells of many animals now. The new techniques are being used to create animals that are a big improvement on the mouse "models" used to study human diseases today.
"Not only is this low-hanging fruit, it is easier politically to deal with," says Fahrenkrug. "Most people are OK with this kind of work. The bigger issues are the agricultural ones."
Fahrenkrug's team has created pigs with high cholesterol by deleting a protein that mops up LDL cholesterol. Since the heart and arteries of pigs are roughly the same size as those of humans, the modified pigs are a realistic testbed for stents and other devices to keep blocked arteries open.
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