FARMED ANIMAL CLONING AND GENETIC ENGINEERING
By Michael W. Fox, B.Vet.Med., Ph.D., D.Sc., M.R.C.V.S.
The farming of animals for human medical and other commercial purposes is being intensified through two new biotechnologies. One is genetic engineering that involves the splicing of alien genes into target animal embryos to create ‘transgenic’ animals, or the deletion of certain genes to create ‘knockout’ genetically modified animals. The other is cloning, that entails taking cells from the desired type of animal, that may be transgenic or a ‘knockout’, or from a conventionally bred genotype possessing such qualities as rapid growth or high milk or wool yield, and inserting the nuclei of these cells into the emptied ova from donor animals of the same species. Once activated by electrical fusion of the nucleus to the egg wall, these embryo -developing ova are inserted into surrogate mothers to be gestated.
Successful gene-splicing techniques and lines of transgenic and knockout animals have been patented by the US government, university-biotechnology industry developers and investors, and most notably by the multinational pharmaceutical and ‘life science’ industries like Monsanto, along with many varieties of transgenic crops, notably corn, cotton, rice, and soya bean.
Advocates for the creation of genetically engineered and cloned animals claim that this new biotechnology is simply an extension of the process of human-directed natural selection for desired genetic traits that began thousands of years ago when animals were first domesticated. Some of these ‘production’ traits, coupled with how these animals are husbanded in crowded ‘factory’ farms, are now recognized as causing a host of animal health, welfare, public health, and economic problems.
Agricultural biotechnologists also contend that their patented transgenic or GM (genetically modified) crops are ‘substantially equivalent’ to conventional crops, and therefore are safe. Investors hope to profit also from the patents they hold on transgenic and cloned animals, just as they seek to monopolize the global market with their patented transgenic seeds.
Critics contend that the creation of transgenic and knockout animals, and cloning, are biologically aberrant (if not abhorrent) technologies that the life science industry and others cannot, from any sound scientific or bioethical basis, claim to be simply an extension of natural selective breeding. Clones are not identical to the original foundation-prototype because of epigenetic environmental influences and different maternal mitochondrial DNA. Likewise, GM crops are substantially different from conventional crops because the biotechnology employed is unnatural, and the consequences unpredictable by virtue of the inherent uncertainties of gene expression related to inaccurate and relatively crude gene-manipulations, and higher incidence of spontaneous mutations.
Animal health and welfare advocates have documented the diseases and suffering that occur as a consequence of natural selective breeding to intensify animal productivity in terms of accelerated growth rates, greater body/flesh mass and higher milk production. Cloning such conventionally bred and genetically engineered animals, often raised under inhumane, intensive/confinement conditions, to create flocks and herds of more productive and profitable livestock is now well under way in several countries.
Commercial aims are directed toward developing animals that have leaner and more meat and healthful fats for human consumption; greater disease resistance, fertility, and fecundity; produce more wool, milk with higher protein, even ‘hypoallergenic’ and ‘infant milk’ high in human lactoferrin; and that produce environmentally less harmful wastes containing lower levels of phosphorus. Pigs with transgenes from spinach, jelly fish, and a marine worm, have been cloned using the spinach gene to lower saturated fats and increase linoleic acid levels in body fat; the jellyfish gene to make the pigs fluorescent, thus serving as a genetic marker; and the nematode worm gene to convert omega 6 fatty acids into more consumer-beneficial omega 3 fatty acids.
The FDA in 2008 announced that the meat and milk from cloned cattle, pigs, is as safe to eat as food from more conventionally bred animals. But concerns over people eating meat and dairy products from cloned animals have nothing to do with any foreseeable risk to consumers. The inherent danger of genetic uniformity in cloned herds selected for production traits that are already linked with various production-related health and welfare problems is a serious ethical issue. Greater genetic uniformity can mean significant economic losses from diseases that become contagious when there is a fatal combination of genetic susceptibility and uniformity. The propagation, by accident or design, of unhealthy traits in cloned and genetically engineered breeds which would result in disease, miscarriages, birth defects etc, have been well documented in the scientific literature. The loss of genetic diversity in the livestock population increasingly displaced and replaced by homozygous clones is a bioethical and potential financial issue that governments and regulatory agencies have not fully addressed.
The treatment and ultimate fate of surrogate and donor cattle and other farmed animals used as mere instruments of biotechnology call for the most rigorous humane standards and their effective enforcement by the US and other governments.
Some of the first farmed animals in non-pharmaceutical production to be cloned have been high-yielding dairy cows. Since animal bioengineers from the US and Japan have collaboratively succeeded in genetically engineered cattle to be resistant to BSE—bovine spongiform encephalopathy, or mad cow disease—animals like theirs may well be the first to be vigorously propagated through artificial insemination and cloning technology. Regardless, BSE was essentially a human-created disease following the livestock industry practice of recycling dead animals back into the food chain in livestock feed.
Transgenic farm animals are already being cloned to create flocks and herds for ‘gene pharming’, many carrying human genes that make them produce various novel proteins in their milk, like antithrombin 111 and alpha-trypsin that the pharmaceutical industry seeks to profit by. The animals are called mammary bioreactors. The global market for such recombinant proteins from domestic animals is expected to reach US&18.6 billion by 2013, but similar proteins from transgenic pharm crops producing pharmacologically active proteins may lower this figure considerably. Genetically altered farm animals are also being created to serve as organ donors for humans; to produce human blood substitutes, and to produce monoclonal and polyclonal antibodies. Models of human diseases have also been created in transgenic animals, like Denmark’s cloned pigs that have genes for Alzheimer’s disease.
HEALTH AND WELFARE CONCERNS
The incorporation of other species’ genes into farm animals, like the human growth hormone gene into pigs, can have so called multiple deleterious pleiotropic effects. These unforeseen consequences on transgenic animals’ development and physiology include abnormal and excessive bone growth (acromegaly), arthritis, skin and eye problems, peptic ulcers, pneumonia, pericarditis and diarrhea (implying impaired immune systems) as well as decreased male libido and disruption of estrus cycles. Inserted/spliced genes may be ‘overexpressed’, meaning overactive and produce excessive amounts of certain proteins like growth hormone, or create an ‘insertional mutation’ problem, disrupting the functions of other genes and organ systems. These Russian roulette-like adverse consequences of genetic engineering can result in serious health problems later in life if they do not cause fetal deformities and pre- or early postnatal death. Many transgenic creations are either still-born or are resorbed by the mother; or soon after birth they die from internal organ failure or circulatory, or immune system collapse. This is especially so with cloned animals, the success rate being extremely low in terms of survivability.
For example, a US Dept of Agriculture research experiment to create cows resistant to mastitis had a success rate of 1.5 percent, 8 calves being born from 330 transgenic cloned ova, only eight of these being gestated to term as live calves. Three of these died before maturity.
Cloning can result in abnormally large fetuses that can mean suffering and death for the mothers. Abnormal placentas, deformed still-born fetuses and live offspring with defective lungs, hearts, brains, kidneys, immune systems, and suffering from circulatory problems, deformed faces, feet and tendons, intestinal blockages and diabetes have been documented. Cloning seems more likely to cause problems when the cloned animals have been previously subjected to genetic engineering. Yet it is only through cloning that productive flocks and herds can be quickly built from one or two ‘founder’ transgenic/knockout stock.
The incorporation of cloned farm animals into conventional, industrial agriculture is ethically, economically and environmentally unacceptable. This is because it is being directed primarily toward making confinement-raised farmed animals (and aquatic species on fish farms, notably transgenic salmon) more productive than ever. This is a myth because the industrialized factory farming of animals is not only inhumane and environmentally damaging; it is also not sustainable economically or ecologically.
It is blight across most rural landscapes throughout much of the industrial world, and, according to a recent report by the United Nation’s FAO, (Food and Agriculture Organization), it is the number one culprit in global warming, when coupled with the enormous global population of livestock that are creating desert wastelands from over-stocking and over-grazing in less developed countries. Health and environmental experts, conservationists and economists are calling for a reduction in livestock numbers globally, and for more sustainable, organic and ecological farming practices, including more humane and ‘free range’ animal production methods. They see no place for cloned livestock and agricultural bioengineering if there is to be a viable future for sustainable agriculture.
The Western market and unhealthy appetite for animal products as a dietary staple, that the inhumane farm animal industry promotes through government subsidies and price supports at tax payer’s expense, is now being exported to many developing countries at great cost to their natural biodiversity, traditional, sustainable farming practices, and to environmental and public health. We should all ask what farm animal cloning and genetic engineering have to do with feeding the poor and hungry, and in developing a sustainable and socially just agriculture locally and globally, to feed the starving millions of our kind, without further sacrifice of biodiversity, the Earth’s wild plant and animal species, and most precious communities, notably those recognized by the UN as Global Biosphere Reserves.
All countries importing genetically engineered seeds, and foods and animal feeds derived there from, as well as meat and dairy products from cloned animals, should, for the above bioethical, scientifically verifiable, environmental, and economic reasons, immediately boycott this market sector of agricultural and animal production biotechnology: And cease and desist from further endeavors to develop their own animal and plant biotechnologies that are no substitute for humane, sustainable, socially just, ecologically sound and environmentally beneficial food and fiber production methods.
The use of farm animals as medical models of human diseases, and as sources of new pharmaceutical and other medical products from livers to hearts for ‘xenotransplantation’ into humans, raises a host of scientific and ethical questions. It may not be a sustainable or effective path for medicine to take, profitability not withstanding. From a bioethical perspective it puts the human in the role of genetic parasite, which, from a cultural and evolutionary perspective, may not make for a better or desirable future.
GENE “EDITING”-THE NEW TECHNOLOGY
Using what is called CRISPR/Cas9 gene editing technology (which enables multiple genes to be altered simultaneously) scientists in China have created two beagles that lack some or all of the muscle-inhibiting protein myostatin, resulting in dogs with larger-than-normal muscles. Dogs now join the list of species that have been genetically edited, including pigs, goats, monkeys, rabbits and rats. Using this technology, dwarf “micropigs” have been produced for medical research in China and may be the first gene-edited animals sold as pets. Gene-edited herds of pigs to serve as organ donors for humans, along with more varieties of animal disease models and possible gene editing of human embryos for medical reasons are on the horizon here in the U.S. and in animal laboratories in other countries. These activities raise profound ethical concerns. Like it or not, the age of bioengineering cybergenetics is upon us. Genetically edited animals often have genetic and developmental abnormalities and new diseases which cannot be justified for the novel pet trade or for reasons culinary and commercial.
Chinese biotechnology firm Boyalife and South Korea’s Sooam Biotech have built the world’s largest animal gene-editing and cloning facility in China. Cloning of farmed animals is permitted and considered consumer-safe by the U.S. government but is prohibited by the European parliament for animal welfare reasons. (The ban does not cover cloning for research purposes, nor does it prevent efforts to clone endangered species).
The Chinese facility will raise and sell dogs, racehorses and “improved” cattle for the rising market demand for beef. The news sparked questions about the ethics of cloning companion animals (costing $100,000 per dog) with already high numbers of stray dogs. Claiming this new technology will help save endangered species is a publicity stunt to gain public acceptance. Genetically engineered and cloned endangered species would be virtual, not real species. Their natural genomes call for the protection and restoration of their natural environments that resonate epigenetically to maintain species integrity, vitality, generational adaptability and well-being.
Two calves have been genetically edited to ensure they won’t grow horns, improving safety, eliminating the need to remove horns and making it easier to fit the animals in pens and trucks. The result should be healthier cows, safer humans and lower costs, those in the industry say. The Holsteins at the University of California at Davis, are part of a new line of research using gene editing in food animals aimed at reducing disease and improving agriculture practices. The Sacramento Bee (Calif.) (tiered subscription model) (12/20’2015)
Bacterial DNA mistakenly edited into hornless cattle genome Bacterial DNA that includes a gene conferring antibiotic resistance was inadvertently integrated into the genome of cattle genetically edited to lack horns, and though some experts say the mistake is not harmful, it dooms the chances of FDA approval. The finding raises concerns of unintended side effects in genome-editing treatments being tested in people with a rare disease. MIT Technology Review online (free registration) (8/29/2019). See also https://www.gmwatch.org/en/news/latest-news/19084 Gene-edited hornless cattle: Flaws in the genome overlooked “No matter how “precise” the initial gene-editing event is in terms of location, undesirable outcomes can occur at the intended site stemming from the DNA repair processes that follow the cutting of the DNA by the editing tool. No research has been carried out on the possible consequences for animal health, or whether these additional genes are biologically active.
As the experts from the FDA point out, the errors caused by the genetic engineering technique are unlikely to be isolated cases. They suspect that such errors are “under reported or overlooked”.
The FDA scientists highlight several reasons why Recombinetics failed to detect these errors in its screening methods and recommend procedures that should be followed in future in order to provide a more accurate picture.
According to GMWatch, given that the the POLLED gene-editing event is present in every cell of the animal, the antibiotic resistance genes will also be present in every cell. If these genes are active, they will produce a body-wide antibiotic resistance which can render these medicines ineffective when used to combat pathogenic bacterial infections in the animals. This factor invalidates any claims of animal welfare benefits from producing gene-edited POLLED cattle.
The new research exposes much of the hype around gene-edited animals as false and misleading. For example, an article published by UC Davis Dept of Animal Science about the animal scientist and promoter of gene-edited animals, Alison Van Eenennaam, begins, “Gene editing — one of the newest and most promising tools of biotechnology — enables animal breeders to make beneficial genetic changes, without bringing along unwanted genetic changes.” Yet “unwanted genetic changes” from gene editing are exactly what the FDA scientists found”.
Subjecting animals to gene editing and other genetic biotechnologies should be strictly regulated and limited to clinically justifiable veterinary medical purposes for the benefit of the animals. Putting human benefits first is another turn of the screw that will only intensify an increasingly parasitic relationship manipulating and exploiting the genomes of other species to direct evolutionary and other biological processes toward our own selfish ends rather than seeing progress in the light of a more compassionate and mutually enhancing relationship based on respect for all life. A UK firm working with the University of Missouri used gene-editing technology to produce swine resistant to porcine reproductive and respiratory syndrome virus, a potentially fatal immune disease that costs the US swine industry $700 million annually. The process isn’t commercialized yet, but should be within about five years, analysts said. The research findings were published in Nature Biotechnology. Reuters (12/8/2015)
In a paper published *Jan. 31,2017, scientists from the Northwest A&F University in Shaanxi, China demonstrated they have made healthy baby cows that have been modified to be more resilient against bovine tuberculosis (TB)—with no adverse side effects.“When you want to insert a new gene into a mammalian genome, the difficulty can be finding the best place in the genome to insert the gene,” Yong Zhang, a bioinformaticist and the lead author of the paper, said in a statement. He and his team meticulously combed through the cow genome and found a place where they thought they may be able to insert another copy of a gene called NRAMP1, which occurs naturally in cows. This gene has been associated with being able to resist infection from bovine TB; by adding a second copy, the researchers thought they could vamp up this resistance. They used CRISPR-Cas9 technology to insert the extra copy of NRAMP1 into 11 young cow embryos before inserting them back into cows to gestate as usual. After the healthy calves were born, the researchers exposed them to bovine TB. The cattle, who didn’t appear to have any other health consequences as a result of being modified, didn’t get sick, and their immune systems seemed less bothered by the bacteria than cows that hadn’t been altered. Although they’re still not totally resistant to bovine TB (NRAMP1 is just one gene that helps with cattle immunity), more resistance is better against the devastating infection.( Single Cas9 nickase induced generation of NRAMP1 knockin cattle with reduced off-target effects. Yuanpeng Gao et al Genome Biology2017 18:13).
Gene-edited chickens could help prevent influenza pandemics Scientists are using CRISPR gene editing to make chickens immune to avian influenza by removing parts of a key viral protein. If successful, the engineered chickens could be a “buffer between wild birds and humans” and could prevent influenza pandemics, project co-leader Wendy Barclay said. Reuters (1/21/2019)
Groups create task force to study gene editing in livestock
The Association of American Veterinary Medical Colleges and the Association of Public and Land-Grant Universities has set up a task force to develop policy and regulatory recommendations for genetically modifying livestock. Full Story: Drovers (6⁄11 2020).
This entire industry is built on the science-driven hubris and hoped for profitability and improved animal productivity in the absence of bioethical considerations of long-term consequences on animal wellbeing and the environmental costs of animal-derived foods rather than nutritious plant-based foods as the main components of a more healthful human diet.
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From CAB ABSTRACTS: Measuring biotechnology employees’ ethical attitudes towards a controversial transgenic cattle project: the Ethical Valence Matrix. Small, B. H., Fisher, M. W. Journal of Agricultural & Environmental Ethics,. 18:495-508. 2005.
Author Affiliation: Social Research Unit, AgResearch Ltd, Ruakura Research Centre, Hamilton, New Zealand.
Abstract: What is the relationship between biotechnology employees’ beliefs about the moral outcomes of a controversial transgenic research project and their attitudes of acceptance towards the project? To answer this question, employees (n=466) of a New Zealand company, AgResearch Ltd., were surveyed regarding a project to create transgenic cattle containing a synthetic copy of the human myelin basic protein gene (hMBP). Although diversity existed amongst employees’ attitudes of acceptance, they were generally: in favor of the project, believed that it should be allowed to proceed to completion, and that it is acceptable to use transgenic cattle to produce medicines for humans. These three items were aggregated to form a project acceptance score. Scales were developed to measure respondents’ beliefs about the moral outcomes of the project for identified stakeholders in terms of the four principles of common morality (benefit, non-harm, justice, and autonomy). These data were statistically aggregated into an Ethical Valence Matrix for the project. The respondents’ project Ethical Valence Scores correlated significantly with their project acceptance scores (r=0.64, p<0.001), accounting for 41% of the variance in respondents’ acceptance attitudes. Of the four principles, non-harm had the strongest correlation with attitude to the project (r=0.59), followed by benefit and justice (both r=0.54), then autonomy (r=0.44). These results indicate that beliefs about the moral outcomes of a research project, in terms of the four principles approach, are strongly related to, and may be significant determinants of, attitudes to the research project. This suggests that, for employees of a biotechnology organization, ethical reasoning could be a central mechanism for the evaluation of the acceptability of a project. We propose that the Ethical Valence Matrix may be used as a tool to measure ethical attitudes towards controversial issues, providing a metric for comparison of perceived ethical consequences for multiple stakeholder groups and for the evaluation and comparison of the ethical consequences of competing alternative issues or projects. The tool could be used to measure both public and special interest groups’ ethical attitudes and results used for the development of socially responsible policy or by science organizations as a democratizing decision aid to selection amongst projects competing for scarce research funds.
Publisher: Springer Science + Business Media
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