Down on the Ol' Biomedical Farm
Nearly 10,000 years ago, humans began the long process of domesticating species of wild animals. There was a well-defined sequence to these events, with sheep and goats the first to be brought under direct human control and exploitation. Pigs, cattle, horses, camels, and chickens followed. Although varying among species, the general rationale behind domestication was to provide reliable, easily utilized sources of either food, fiber, by-products, or use in religious rituals.
Over the centuries, humans gained extensive experience in consciously and unconsciously manipulating the genetics of these domesticated species. Such efforts produced the thousands of breeds and varieties seen today. This process of artificial selection remained relatively unchanged until the 20th century, when the pace of livestock-based experimentation increased. A major acceleration has occurred in the past few decades at the institutions conducting such investigations.
In the United States, the land-grant university system was established by Congress in the mid-1880's, primarily to promote agricultural research and provide advanced educational opportunities for a broader segment of the population. There is at least one such university in each state. By 1887, the Hatch Act established state agricultural experimental stations to further expand research activities involving domestic farmed species. State agricultural extension services were initiated in 1914, completing the triad of institutionalized support for agriculture-related animal experiments seen today.
These agencies concentrated on developing new means of providing abundant and inexpensive animal protein and fiber, as well as devising means to reduce the human labor involved in such activities. The infamous crate housing of veal calves and pregnant sows and battery cages for laying hens resulted from such research efforts. A majority of this type of research and associated teaching is done in animal, dairy, poultry, and veterinary science departments at the land-grant universities and at many schools of veterinary medicine.
Within the last few decades, a major split occurred with the use of farmed animal species in research activities. The food and fiber efforts continued, but increasing numbers of biomedical scientists began adopting animal ‘models’ based of domestic livestock rather than the customary species used in laboratories. In part, this was done to replace the use of such animals as cats, dogs, and primates, which was no longer widely supported by the general public. A basic assumption behind the switch was the notion that people would be less concerned about animals commonly used for food or fiber.
Our laws and regulations appear to reflect such a bias. Animals utilized in agriculture-related research have no effective protection under the existing animal welfare laws and are often treated according to the cost/benefit considerations associated with production standards. Such activities are frequently inhumane. Practices common in agricultural research would not be allowed in most biomedical laboratories.
In contrast, domestic livestock used as ‘human models’ in biomedical research and testing may live in more supervised and regulated environments, with the exception of chickens or other birds, who are entirely excluded from federal welfare laws. They are, however, routinely subjected to a wide variety of experimental manipulations, including induced diseases, injuries, and behavioral pathologies. All of these are artificially created conditions claimed to be ‘similar’ or ‘relevant’ to human clinical, rather than commercial, concerns. Thus, different housing, care and utilization criteria exist for the same domestic farm species, based solely on the research questions being asked.
Although collectively a minority among all species exploited in biomedical research, millions of cattle, chickens, goats, horses, sheep, and pigs are used each year. An examination of the National Institutes of Health’s (NIH) MEDLINE/PubMed and CRISP (Computer Retrieval of Information on Scientific Projects) databases for the most recent years indicates that the above animals are regularly used, with a major emphasis on pigs and sheep.
The following discussion briefly describes typical examples of how members of these species and the variety of induced ‘animal models’ are currently used to support those research efforts. Of particular note, despite the vast evolutionary distance between all of these animals and humans, none of the former escaped the AIDS-animal model hysteria that assaulted the more traditional laboratory animal species.
CattleAs with most traditionally farmed animals, cattle are used primarily to improve the human food supply and to obtain biochemical, cell, organ, and tissue samples for a wide variety of in vitro applications.
Following public health concerns related to ‘mad cow disease’ or bovine spongiform encephalopathy (BSE), a chronic, degenerative disorder which is caused by a variant of normal protein particles called prions, researchers at Virginia Polytechnic Institute and State University began receiving federal funds to genetically alter cattle to lack or ‘knock-out’ the prion gene. Between 2003 and 2004, the veterinary research team received $134,500 and $164,800 respectively, and it is funded through at least 2005. They are not alone. Like many others worldwide, researchers at Texas A&M are striving to do the same, and they have even applied for a patent on their methods.
Cattle, including calves, are used in projects on narcolepsy, reproductive physiology, and safety testing of recombinant vaccines. They are also used in infectious disease research (Washington State University; 2001-05; $60,900-$84,500/yr.), and experiments related to repair cartilage damage (University of Minnesota; 2004-2007; $223,173/yr.).
Cattle, particularly calves, continue to be used in heart experiments. Calves were used at the University of Pittsburgh to measure the dynamics of blood flow following the implantation of left ventricular assist systems. At the Jewish Hospital Heart and Lung Institute, University of Louisville School of Medicine, calves were implanted with AbioCor® artificial hearts and forced to walk on a treadmill. This study was one of 14 animal experiments conducted to develop this device. In another experiment, 19 male Holsteins (black and white cattle usually associated with veal and dairy production) were implanted with artificial hearts, and within the 30 day trial period, six of them died. The first phase of human clinical trials at this hospital began with the first transplant of an AbioCor® heart into a human in 2001. Since then, 13 additional artificial heart transplants have taken place, with limited success. On the informed consent form, potential artificial heart recipients are warned, “…animal results cannot be directly translated to what may occur in human [sic]….”
SheepKnown throughout history as gentle beings, sheep have been used in laboratory experiments since at least the 19th century. They continue to be widely used not only in food production experiments but also in biomedical experiments related to human health. Sheep, particularly females (ewes), are preferred because they are relatively easy to house, they are docile, and their larger bodies allow for ease in performing multiple experimental procedures on them. They are also used in various stages of their life, from fetal to adult.
Perhaps the world’s best known animal to be born into biomedical research is Dolly the sheep. Dolly and many other sheep were born through cloning technology at the Roslin Institute, a Scottish research center. She was born in 1997 and euthanized in 2003 after suffering from lung cancer and an early onset of arthritis. Roslin researchers also use milk from genetically-altered ewes, including Dolly’s lambs, to produce human therapeutic proteins to treat human deficiencies causing hemophilia or cystic fibrosis—a process touted as much ‘easier’ and less expensive than using more humane methods such as harvesting from yeast, bacteria, and human blood and cell cultures.
Sheep are considered, as stated in 2003 in the journal Nature by University of Florida researcher Ken Gerhardt, “the animal of choice for pregnancy research.” In one study described in the article, Gerhardt and his research team removed fetal lambs from their mothers’ wombs, implanted electrodes into their ears, and transplanted the lambs back into their mothers. A loudspeaker was then put next to the mothers’ bodies and recordings were made through the lambs’ ears in order to test what a human fetus might hear in the womb.
Other examples of experiments involving ewes and fetal lambs include causing alcohol-related birth defects (Texas Agricultural Experiment Station/Texas A&M; 1997-2007; $327,000/yr.); inducing fetal brain injury (Oregon Health & Science University; three grants between 2001-07; totaling nearly $573,000/yr.); and fetal sheep studies of coronary artery and congenital heart diseases (University of Iowa; two grants between 2001-06; totaling nearly $507,600/yr.). Pregnant sheep and their fetuses are also subjected to experiments in gene therapy, respiratory failure, nutritional deficiencies, and investigational surgical techniques, among others. Adult sheep are commonly used for studies of reproductive physiology, transplantation, respiratory disease and injuries, viral origins of multiple sclerosis, and medical device implants such as orthopedic implants, heart valves, blood pumps, and intravenous oxygenators.
Daniel L. Traber, a researcher at the University of Texas Medical Branch and the Shriners Burn Institute/Hospital for Children in Galveston, Texas has a 201 page curriculum vitae that illustrates his decades of performing burn injury and smoke inhalation experiments on sheep and other animals. His work has been funded by millions of dollars from NIH since at least 1973. His most recent grant is for a study on burn and inhalation injury in sheep, and he received nearly $261,000 annually from 2000-2004. In his experiments, sheep are subjected to third degree burns by a Bunsen burner over 40 percent of their bodies, and their lungs are injured after smoke from a ‘bee smoker’ is sent through a hole cut in their tracheas (throats). The sheep are often kept alive for 48 hours after injury.
GoatsAlthough they were one of the first ‘livestock’ species to be domesticated, goats are not widely used in agricultural or biomedical research in the U.S. One exception is their preferred status as producers of polyclonal antibodies. Like sheep, goats are also used in experiments involving genetic modification of animals to produce milk containing proteins to combat human diseases such as cancer and viruses such as HIV-1. One such study on HIV-1 and therapeutic antibody-like molecules in goat milk is being conducted by a private company in New York, Progenics Pharmaceuticals, Inc., yet it is funded by the federal government (2000-05; $300,000-$1,000,000/yr.). Other transgenic experiments on goats are being conducted by private companies with federal dollars to improve transgenic methods through germ cell transplantation (GTC Biotherapeutics, Inc., Massachusetts; 2003; $100,000).
Some examples of experiments utilizing goats include: measuring the effects of anesthesia on brain/neurological activity by implanting electrodes into the brains of live goats (University of California at Davis; 1998-2006; $234,400-$240,900/yr.) and a 26-year study of cartilage repair (Case Western University, Ohio; 1986-2005; $359,500-$973,000/yr.). Goats are also used in studies related to gene delivery (or ‘therapy’), bone implants/reconstruction, xeografting, respiratory physiology, and medical diagnostic procedures, among others.
EquinesBecause of their size and associated difficulties in housing, horses, donkeys, and ponies are not extensively used in biomedical experimentation. Much of the research conducted utilizing horses is tied to the horse industry, focusing on areas such as 'improving' breeding techniques and other issues related to horse racing. Such research is being conducted at Southern Illinois University, the University of Florida, and the University of Kentucky (to name a few), all of which are sponsoring horse nutrition and breeding research. In addition, Southern Illinois University is attemptng to clone a horse. Adding insult to injury, many of the foals born as a 'by-product' of university research are sold at auctions, where many horses are purchased by brokers, sent to slaughter, and their flesh sold for over $20 per pound in Europe and Japan.
Biomedical research protocols generally use horses as cell, embryo, or tissue 'donors' related to reproductive physiology, models for human neuromuscular disorders, and infectious diseases. For example, one study funded by NIH is developing a horse model of amyotrophic lateral sclerosis (ALS), a uniquely human malady (Cornell University; 2003-05; $187,000/yr.). Although horses do suffer from equine motor neuron disease (EMND), a neuro-degenerative disorder that causes weakness, muscle wasting, and weight loss, symptoms similar to ALS, equines do not acquire ALS. Interestingly, rats (who also do not naturally acquire ALS) will also be utilized in this project as the experimenters investigate the effects of diet on neuromotor disease. Researchers will apply data achieved by studying rats to horses afflicted with EMND, which they claim will provide "a major breakthrough towards the understanding of the mechanism" of the human disease, ALS.
PigsDuring recent decades, the use of pigs in biomedical research, testing, and education has increased dramatically, involving every major field of experimentation. Due to these animals’ large adult size, a variety of mini- and micro-pigs, who consume fewer resources and require less space, have been ‘created’ by laboratories through genetic manipulation and selective breeding in an effort to meet this increasing demand.
Pigs are common in experiments regarding cardiovascular systems, blood dynamics, nutritional deficiencies, alcoholism, drug abuse, general metabolic functions, gastroenteritis, live toxicity, stomach ulcers, diarrhea, colon diseases, gallstones, dysentery, respiratory diseases, diabetes, kidney and bladder diseases, organ-specific toxicity, dermatology, and neurological studies, to name a few.
Pigs are also subjected to research involving organ transplantation and the federal government funds numerous efforts to develop transgenic pigs whose internal organs may be genetically 'suitable' for implantation in human patients, a process known as xenotransplantation. Much of this research focuses on developing animal organs that will not be rejected by human transplant patients. For example, NIH has given Massachusetts General Hospital nearly $330,000 (2003-06) to "establish a large animal model of chronic lung rejection." Another project also utilizing pigs in xenotransplantation rejection studies is the University of Minnesota (1999-2007; $297,000/yr.).
Other studies utilizing pigs investigate "the risk posed by persistent porcine viruses, which may escape detection by standard screening methods to become pathogenic in humans following xenotransplantation" (University of Minnesota; 2000-04; $143,000/yr.). The possibility of spreading viruses from one species to another is very real in xenotransplantation and is considered a contentious issue in the debate regarding animal to human transplantation. Cloning is also a controversial topic in the biomedical community but, nonetheless, NIH is funding a study at the University of Pittsburgh (2003-06; $256,700/yr.) that aims to clone pigs who are genetically modified so that their organs would be less likely to be rejected in human recipients.
NIH is also funding a "Swine in Biomedical Research" conference which is meant to "stimulate interactions between researchers working within swine and human genomics and identify needs and opportunities to fully exploit this animal model. [emphasis added]" The grantee, in requesting the funding, made a telling statement regarding the use of pigs in research, claiming, "As porcine-specific genomic information becomes increasingly available, characterization and adoption of pigs as human models in many disease categories will accelerate." The scope of biomedical research funded by NIH reflects this statement, since it is extremely broad and seemingly without purposeful limits. Other examples include a dermatology study where pigs are intentionally burned to develop a technique to evaluate superficial lesions (Texas Engineering Experiment Station; 2003-07; $323,700/yr.); a cardiovascular study in which pigs are administered cocaine to investigate the drug's effect on their hearts (Allegheny-Singer Research Institute; 1996-2007; $262,500/yr.); a project investigating swallowing mechanics in infants, despite the obvious anatomical differences between pigs and humans (University of Cincinnati; 1998-2006; $289,000/yr.); research on newborn and juvenile pigs who are subjected to intentional brain injury (University of Pennsylvania; 2000-05; $277,000/yr.); a pig model of cystic fibrosis, a uniquely human genetic disease (University of Iowa; 2004-09; $1,633,000/yr.); utilization of a pig model to investigate bone regeneration of the mandible (University of Washington; 2002-06; $279,700/yr.).
BirdsAlthough all species of poultry and a few exotic birds are used in biomedical research and testing, chickens and pigeons are those most commonly utilized. The latter are particularly popular with experimental psychologists. Exact numbers of birds killed each year in laboratories are unknown because they are not covered by the Animal Welfare Act, but the figure is well into the millions. These animals are inexpensive, easily acquired, and they need minimal expertise in care, characteristics that explain their variety and longevity of use in research protocols.
Large numbers of chickens are used as cell, tissue, organ, and biomedical 'donors,' especially for studies of muscle physiology. They are also utilized in antibody production and, according to The Laboratory Chicken (2002), "within the last five years, the chicken has found increased uses in biomedical research, principally for production of polyclonal antibodies to be used in a wide variety of research efforts." Additionally, the University of Connecticut is one of several locations that maintain federally supported "core chicken facilities" to produce different breeds of poultry and fertile eggs from mutant types. And pharmaceutical companies like Merck, Bayer, and Pfizer maintain chicken flocks to test their drug products.
Researchers' claims of relevance for induced animal models of human disease often verge on the ridiculous. This tendency is particularly apparent in the use of chickens. These birds are promoted as surrogates for such human clinical conditions as arteriosclerosis, autoimmune disease, cystic fibrosis, dietary and nutritional deficiencies, multiple sclerosis, muscular dystrophies, near-sightedness, narcolepsy, neurofibromatosis, scleroderma, systemic sclerosis, and thyroiditis. Not surprisingly, none of these afflictions occurs naturally in birds.
Chickens are often utilized in studies investigating various aspects of sight, and the NIH funds several such projects. One project at the Mayo Clinic College of Medicine, Rochester is using chickens as animal models to determine why cataracts form (1987-2004; $354,000/yr.), while a project at Boston University was given $323,000 (2002-06) to develop sutureless ophthalmic surgeries. Another study investigates the application of stem cell transplantation to treat a variety of eye diseases (University of Washington; 2002-06; $375,000/yr.). This project is funded despite the fact that practical application of stem cell transplantation is not yet possible.
Although the anatomy and physiology of birds is very different from that of humans, chickens are also used in investigating auditory functions (Children’s Hospital, Boston; 1992-2006; $355,000/yr.); the development of a new human flu vaccine (Aventis Pasteur, Inc.; 2000-04; $1,400,000/yr.); polyclonal antibodies for biodefense (Origen Therapeutics; 2004-05; $/yr.); tissue regeneration (University of Southern California; 1995-2008; $/yr.); while other studies include obesity research (University of Wisconsin); a musculosketal study at Princeton University where turkeys are forced to run on treadmills; and cloning research (AviGenics; $2,000,000 from the Department of Commerce).
Chickens are also forced to endure experimentation sponsored by the agriculture industry. Companies such as AviGenics are genetically modifying chickens in an attempt to ‘create’ lines of meat with economically ‘favorable’ traits such as large muscle mass and quick growth. Other research aimed at minimizing production costs and resources includes stress reduction studies, specifically regarding pecking aggression (Department of Animal Science at Iowa State University) and forced molting and food deprivation (University of Georgia). The goal of such studies is strictly to streamline production to maximize profit, not to minimize animal suffering and cruelty.