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Technology Hopes held high for biotech animals HOW A cloned sheep named Dolly has moved agriculture one step closer to the elusive dream of creating and farming highly productive, disease-resistant animals. Dolly the Finn Dorset lamb hit the headlines in a by frenzy of world Nicole wide publicity earlier this year Baxter, after researchers Kondinin Group at Edinburgh, Scotland, announced they had unlocked the mystery of using genetic engineering to clone adult mammals. But the achievement is only the most recent example of how various gene technologies are being used to provide greater control over animal breeding. For years scientists across the globe have tried to answer the question of why some animals contain ideal characteristics and others do not. It is an age-old jigsaw puzzle with many pieces missing and a substantial amount of uncertainty. Supporters say the breeding method will take away this uncertainty and provide greater control over animal breeding by using genes from completely unrelated organisms. But concerns remain and much needs to be understood before products reach the market. ENGINEERING 16 CSIRO GENETIC Genetic engineering, a major component of biotechnology, is the process used to remove a gene from one organism and insert it into another. The technology is not new. Animals have been selected for genetic superiority and used for breeding ever since people first started to domesticate them. But selective breeding remains slow and does not allow breeders to separate a single production trait from one or more undesirable characteristics. It also fails to allow genes to be transferred between species because of the biological barrier that prevents inter-species breeding. Genetic engineering, and now cloning, give scientists a new way to overcome this barrier, allowing them to introduce genetic material into animals from completely unrelated organisms. Animal genes are going into vegetables, bacterial genes into food crops and human genes into animals. But for all its high-tech science, genetic engineering is no more than a ‘cleaner’ and ‘faster’ road to producing improved animals or plants — one that supplements rather than replaces traditional breeding methods. IT WORKS Making a change to the way an animal looks or how it functions depends on genes and their arrangement within a chemical called deoxyribonucleic acid (DNA). DNA is made of four chemical building blocks which are arranged in pairs and look like a spiral staircase when viewed under a high-powered microscope. These chemical building blocks are the same for all living things and they provide a set of instructions which tell a cell how to make the proteins needed for life. It is this chemical similarity that makes it possible to take a gene from one organism and insert it into another. Scientists locate a useful gene which can be removed, manipulated and reinserted into a new cell where it can operate effectively and give rise to new animal properties. All genes are made of two parts — a portion which contains the information for the gene product and another part which acts as a ‘switch’ to determine in what organism the gene will work and how it will work. Genetic engineering removes the switches normally found on a gene and replaces them with new switches which will tell the gene to work in a different way. There are many ways organisms can have their genes altered and the most common method for animals is by directly inserting a gene into the nucleus of a fertilised egg. Scientists use a very thin glass needle to inject many copies of the gene into the cell to increase the chances of the gene being incorporated into the egg. The altered egg is then transferred into a recipient mother where it grows into a normal but genetically modified animal. If the introduced gene integrates into the existing genetic material the resulting newborn animal will contain the introduced material in all its cells and this animal is known as transgenic. The disadvantage of using this technique is that its success rate is incredibly low. The Microinjection of DNA into a sheep embryo pronucleus 12 hours after fertilisation. FARMING AHEAD No. 69 - September 1997 technique used to produce Dolly — cloning — is different. Cloning allows scientists to fuse cells into eggs emptied of their genetic material and then grow the embryo inside a surrogate mother. One example of the technology’s use in Australia involves cloning Friesian calves using embryonic cells. A Monash University team has produced and developed embryos carrying adult DNA. Their work has resulted in six cloned calves. Despite this, the process is highly inefficient — the researchers at the Roslin Institute in Edinburgh, Scotland, implanted 29 embryos before one successfully divided. But once perfected the technology could have a profound effect on the cattle industry as breeders and farmers seek to produce calves with superior characteristics from both the cow and bull. Another technique, known as superovulation, is being used to collect the thousands of eggs produced in a cow’s ovaries to expand rare stocks or new breeds and increase rapidly the rate of genetic progress. Normally a cow gives birth to only about four to six calves in a lifetime, yet produces more than 75,000 eggs. Down the track it might be possible for superior egg supplies to be stored and used to increase control over developing beef or milk production herds. BENEFITS TO ALL During the next 10 years there will be scores of genetically engineered food products released in what could be a multibillion dollar industry around the world. The effects of these products will be felt at every link in the food and fibre chain. For consumers, the technology could mean a cleaner environment, a reliable food supply and more nutritional food products. Understandably, many consumers are concerned about feeding antibiotics to food animals, the presence of drug and hormone residues in milk, meat and eggs and the effects of chemicals on the environment. Already, genetic engineering is addressing these concerns by producing animals with in-built disease resistance, improved wool production, faster growth, whiter wool and higher protein milk. For the processing industry, the technology will allow speedier production of drugs using animals as bioreactors (manufacturers of pharmaceuticals), fewer off-cuts and less spoilage as food products are transported from the paddock to the plate. On farms, genetically engineered animals with in-built resistance to disease could decrease animal health costs, reduce environmental hazards and improve animal production on existing land — vital for meeting the needs of a growing world population and conserving the world’s FARMING AHEAD No. 69 - September 1997 rainforests and animal habitats. Specific rural applications of animal genetic engineering include: • vaccines to improve stock health; • altering the make-up of milk, meat and wool; • breeding disease-resistant animals; • improved plant digestibility; and • superior animal production. To remain competitive, and even survive, the pressure is on to make additional gains by increasing animal growth rates and reducing stock losses from disease. It is believed genetic engineering will allow farmers to compete with overseas competitors, many of which already have embraced the technology to sustain farm production. Supporters claim genetic engineering has endless possibilities as farmers strive to overcome the quality and disease problems unique to Australian agriculture. Tender wool, flystrike and poor quality pastures are major challenges facing the livestock industries in Australia but solutions are on the horizon if research proves successful. The new cloning technologies pioneered on Dolly also may mean sheep producers could clone top lambs and dairy farmers could clone high production cows, making it possible to produce more meat and milk from smaller flocks and herds. But despite the immense potential of the technology concerns remain as scientists and consumers consider the benefits and risks of the new technology. ETHICAL CONCERNS The cloning of Dolly unleashed a wave of concern among the community that similar technology soon would be used to clone adult humans. In the United States, President Bill Clinton responded to the Dolly breakthrough by banning all human cloning research. But the question must be raised of whether the work will move elsewhere, after all, a black market exists for almost all illegal products available today. This issue is less clear cut in most Australian states other than Victoria. In Victoria, human cloning is prohibited by legislation on infertility treatment and embryo experiments. And in states where no legislation exists, cloning appears to clash with guidelines prepared by the National Health and Medical Research Council. Apart from ethical dilemmas, most of the concern about animal genetic engineering surrounds its safety and suitability for human consumption. The recent push for agricultural industry groups to become quality assured has brought to the fore consumers’ demands for high quality and safe food. In many cases genetic engineering will eliminate the need to administer veterinary products by creating in-built resistance to disease in the animal but uncertainty remains about the possible ill-effects on human health. Some consumer groups opposed to the release of modified foods believe there is no way to ensure modified products are safe to eat. They claim safety testing can never provide a complete guarantee about a product’s safety. For example, tests extending over three years may fail to detect harmful effects that require five years to emerge. Supporters of the technology refute this claim by arguing that there are legislative checks and a substantial time period in place to test biotech products before their release. Several countries, including Australia, have addressed the question of safety, and a wide range of regulatory regimes currently operate. These vary from a very liberal approach in Italy to extremely strict regulations in Germany, Denmark, Canada, the United Kingdom, the US and Australia. In Australia the method of modifying animals is standardised and a production process is established. The product is tested in trials on several animals of varying ages and different environments and in a range of locations, and then under ‘natural’ conditions using normal management practices. In the case of the cattle tick vaccine more than 18,000 cattle were vaccinated during the trial period. Added to the research time are a set of regulatory checks. These include permission from the Australian Quarantine and Inspection Service if any imports of biological products are to be made and permission from the Genetic Manipulation Advisory Committee to manufacture a genetically engineered product. Finally permission needs to be obtained from the National Registration Authority to market the product. Another concern voiced frequently by various groups is that gene manipulation could transfer allergenic properties from the donor organism to the modified organism. These fears have been echoed by the medical community. One example of this is the epidemic outbreak of the disease eosinophilia-myalgia syndrome which arose in the US and other countries during 1989. The symptoms of the disease include abnormally high counts of white blood cells which at the time resulted in about 1500 cases reported and more than a dozen deaths. To control muscle pain, the victims had taken a particular batch of synthetic L-tryptophan, a harmless amino acid found naturally in food. It is thought this batch of L-tryptophan, produced from a genetically engineered bacteria, became contaminated. Supporters of genetic engineering, on the other hand, argue that many of the proteins produced by gene expression are common to a large range of organisms and are unlikely to trigger allergic reactions. They also claim these factors are tested for during the 17 Technology research process and evaluated by various regulatory checks in each country. In the case of food additives, unlike whole foods, strict laws exist where they are evaluated before use and their presence in a food is clearly shown on the label. While it is too early to say whether engineered animals and their products will produce similar illeffects there is no doubt price and customer perception will have a big role to play. LEAN PIGS SPARK OUTCRY Perhaps the best example of how customer perception can affect the success of biotech foods was when Adelaide-based company, Bresatec, made moves to slaughter some of its transgenic pigs for human consumption during 1994. The pigs had been genetically modified to grow faster when fed a diet high in zinc. Although the pigs were not deemed unsafe by the Australian and New Zealand Food Authority, staff of the Australian Consumers Association held a demonstration to protest against the possible slaughtering of the pigs for human consumption. A company in Corowa, New South Wales, also protested the move by refusing to process the pigs at its abattoir. Bresatec crumbled under the public pressure, and although free to slaughter the pigs, it withdrew all plans to do so because it alledgedly wanted some type of official stamp of approval from the National Food Authority. Like other areas within the food and fibre industry, this event showed how marketing and consumer perceptions ultimately will decide the fate of genetically engineered products. Negative perceptions of genetically engineered products could decrease market size until the public understands the merits of these products and their safety is confirmed. One suggested solution to allay the safety fears surrounding genetically engineered foods is to legislate for mandatory labelling. Appropriately labelled foods would allow consumers to choose for themselves whether or not to accept the risk. Health officials also could trace the source of any problems more easily within appropriately labelled products. TO LABEL OR NOT TO LABEL Many manufacturers of biotech foods claim there is no need to label products because humans have eaten plant and animal DNA for millions of years and the introduced material is no different from its original source. There is some concern that labelling could cause consumer alarm, deterring them from buying a product because they think there is something wrong with it. Nonetheless, others argue that appropriate labelling would help build consumer understanding, confidence and maintain a vital and healthy market. The public does have some right to know and various surveys within Australia have confirmed the need for appropriate labelling. According to a 1994 survey carried out by the Department of Industry, Science and Technology, the Australian public broadly supports the notion of genetic engineering. The survey showed a vast majority of Australians would wear clothes made from genetically engineered cotton (77%) and eat genetically engineered cooking oil (60%), tomatoes (61%) and pork (56%). But respondents wanted products clearly labelled so they could choose for themselves whether or not to use them. In the case of genetically engineered animals, it is quite likely people will be impressed with improved meat, milk and fibre quality of biotech products. As engineered animals and their products are released onto the market farmers and consumers will have to make certain value judgements on a range of ethical issues and at times other moral, social or even political aspects will come into the equation. The decisions concerning animal genetics will be difficult and will be overcome only by extensive education and discussion. Nevertheless, it is clear genetic engineering will play a vital role in agriculture of the future. The research yet required is substantial, longterm and costly, but it is only a matter of time before transgenic livestock is used successfully to improve production on Australian farms. Acknowledgements: Kevin Ward, CSIRO, and Marion Seymour, Kondinin Group. But labelling remains one of the most contentious issues in the area of genetic engineering and legislation varies according to individual countries. Some supermarkets in the UK banned the sale of genetically engineered foods despite the presence of labels. Similarly, grocers in Switzerland have erected signs to inform customers that food has been modified genetically because labelling laws have lagged behind the release of biotech products. Opponents to mandatory labelling believe there is no definite line between where labelling is justified and where it is not. There have been calls in Australia to label cheese made from genetically modified organisms, despite the fact that the cheese itself does not contain any introduced genetic material. FARMING AHEAD No. 69 - September 1997 19