Breeding Misery

For more than 30 years, Texas A&M University’s Joe Kornegay has been selectively breeding golden retrievers and other dogs to have a crippling and painful disease that resembles muscular dystrophy (MD) in humans—including a particularly debilitating form of the disease called Duchenne muscular dystrophy (DMD). As the disease ravages the bodies of afflicted puppies and adult dogs, their muscles weaken and they struggle to walk, swallow, and even breathe. Three decades of painful experiments on generations of debilitated and suffering dogs have failed to result in a cure or even a treatment that can reverse the course of muscular dystrophy in humans. After PETA released disturbing footage of dogs used in his experiments, Kornegay attempted to defend his use of dogs.

Kornegay claims: He must breed dogs to have muscular dystrophy because there aren’t enough client-owned dogs with the disease for research.

Kornegay’s statement suggests that his aim is to treat dogs with muscular dystrophy. This is not true. He deliberately breeds dogs to have a condition similar to human muscular dystrophy and then subjects them to invasive and sometimes painful experimental manipulations to attempt to “model” muscular dystrophy in humans.

Kornegay claims: “[S]imilar methods are used for dogs with other diseases like hemophilia or retinal diseases. . . . [D]ogs can better predict the potential success of treatments for humans compared to other animals like mice.”

Stating that other experimenters use dogs for other disease research doesn’t justify using dogs for muscular dystrophy studies, particularly when such experiments don’t help people. After more than 30 years, dog muscular dystrophy experiments have provided almost nothing in the way of human clinical treatment. In fact, neither mice nor dogs have yielded reliable information about human muscular dystrophy. Kornegay himself has acknowledged the shortcomings of animal MD research, including the fact that small differences in animal models lead to substantial differences in human clinical testing and increasing failure rates of clinical trials based on data from preclinical animal studies.(1) Kornegay has acknowledged that human muscular dystrophy in dogs is not analogous to muscular dystrophy in humans. A collaborative review led by Kornegay recently confirmed the following:

[J]ust as with other disease states, data derived from [animal] models do not uniformly translate to DMD patients. This failure of translation likely occurs due to both physiologic differences between animals and humans and the lack of sufficient rigor in preclinical studies. … Differences in histologic changes and disease progression undoubtedly reflect disparate pathogenetic mechanisms among species.(2)

Neuroscientist Dr. Lori Marino states the following:

Breeding dogs, or any animal, to suffer from a debilitating disease such as muscular dystrophy and then killing them when they have served your purpose is not ethically justified under any circumstances. It is one thing to try to help the dogs who spontaneously develop this disease, but it is obscene that there is an entire industry committed to perpetuating this cruelty. Canine muscular dystrophy breeding programs, such as those at Texas A&M, UNC Chapel Hill, and the University of Missouri, should end immediately.

Kornegay claims: “There’s not another way [to study muscular dystrophy].”

There are indeed other ways to study DMD that are animal-free and human-relevant. Muscular dystrophy researchers from the University of Washington recently stated the following:

[I]n vitro models using patient-derived cells that are high throughput, fully defined, and biomimetic … provide investigators with a more comprehensive understanding of human skeletal muscle physiology and development in dystrophic disease states, and enable collection of more predictive data in terms of the effect of new chemical entities on human tissues.(3)

Patient-derived induced pluripotent stem cells (iPSCs) allow scientists to observe the disease in the most relevant way, using naturally diseased human cells. With patient-derived iPSCs, researchers at the University of California–Los Angeles recently used the gene editing machinery CRISPR/Cas9 to restore the functionality of the dystrophin protein in human cells, providing a potential avenue for correction of the gene mutation in 60 percent of DMD patients.(4) Adult human skeletal muscle stem cells, also called satellite cells, are being investigated by scientists at Harvard and Stanford universities for their abilities to produce large amounts of muscle progenitors that could be used for drug screening, cell therapy, or functional engraftment.(5,6)

Kornegay states: “The suggestion that these dogs are being depicted through the video in a way that they’re being abused or the care for them is not appropriate is just untrue, to be kind. It couldn’t be farther from the truth.”

In his own publications, Kornegay notes the 20 to 30 percent mortality rate of puppies born in his laboratory,(7) which shows how devastating this form of muscular dystrophy is to dogs. He describes the clinical progression of muscular dystrophy in these young animals in a 2014 publication:

Dystrophic pups are often ineffectual sucklers and exhibit stunted growth. Some have a particularly fulminant form in which severe dyspnea can lead to death or necessitate euthanasia during the neonatal period. By 6 weeks of age, the pelvic limbs may be simultaneously advanced and trismus is noted. Subsequently, dogs develop stilted gait; atrophy of particularly the truncal, temporalis, and certain extensor muscles; a plantigrade stance due to hyperextension of the carpal joints and flexion at the tibiotarsal (TTJ) joints; excessive drooling, suggesting pharyngeal muscle involvement; and initial lumbar kyphosis that progresses to lordosis (Figure 2). Whereas most muscles atrophy, some, such as the CS and tongue, hypertrophy (Kornegay et al. 2003, 2012b).(2)

Kornegay does not explain why dogs are forced to live in small, barren metal runs without soft bedding or blankets to help relieve the pressure on their thin, bony bodies. In his publications, he describes how he and his colleagues mechanically tear the muscles of these dogs: “Dystrophic muscles are particularly prone to injury subsequent to eccentric (lengthening) contractions.… [T]he muscles of the cranial tibial compartment are repeatedly stretched to induce mechanical damage.”(8)

Kornegay claims: The dogs in Texas A&M laboratories are fine because those depicted in the video “[wag] their tails, [walk] up to the person taking the video and [do] ‘what dogs do.’”

Even dogs kept in the most abysmal settings, and often especially those dogs, will wag their tail at an approaching human, hoping for some comfort. Dr. James Serpell of the University of Pennsylvania’s School of Veterinary Medicine writes, “Tail movements are used [by dogs] in a variety of contexts related to a variety of moods,” including “general friendliness,” “as an appeasement signal,” or as indicative of a threat or aggression. (9) The dogs in the video exhibit stereotypic behaviors, such as repetitive pacing and biting at the bars of their cage. Stereotypies are thought to be “reflective of the thwarting of highly motivated behaviors. Although most captive animals’ needs for food, water, and shelter are met (consummatory needs), the speciestypical behaviors normally associated with the acquisition of those needs (appetitive needs) are not, in most cases. This situation may leave these animals in a highly motivated state to perform particular motor behaviors for which hundreds or thousands of years of evolution have prepared them.”(10,11)

Kornegay claims: Dogs are protected because the facility is regulated by the U.S. Department of Agriculture (USDA).

The USDA is the agency responsible for enforcing the federal Animal Welfare Act (AWA), but the AWA does not prohibit or review any experiment, no matter how painful, pointless, or cruel. The law mandates only minimal housing and care standards for dogs in laboratories.

Kornegay claims: He has written more than 30 publications about his research on muscular dystrophy in dogs, including a 2013 article titled “Comparative Genomics of X-linked Muscular Dystrophies: The Golden Retriever Model.”

Thirty papers and more than 30 years of experiments on dogs have failed to produce an effective treatment or cure for human muscular dystrophy. The length of one’s publication record is a measure of quantity, not quality or effectiveness of research. Rewarding investigators for the quantity of their research has been cited as a major factor contributing to the current reproducibility crisis in biomedical research. According to one estimate, $28 billion a year is spent on animal research that cannot be replicated.(12) As Begley and Ioannidis stated in their 2015 review of the issue, “In judging the merit of people, it is important to identify rigorous metrics that reward quality and reproducibility rather than volume and quantity.”(13)

Kornegay states: “I’ve had to come to terms with what I’ve spent over 30 years doing and the value of that. I’m convinced the research is valuable, it’s important and that progress is being made.”

Kornegay offers no real evidence that these experiments are valuable, because there is none. Dr. Stephen Kaufman of Case Western Reserve University stated, “Animal experimentation is frequently misleading and the practice tends to be self-propagating.”

References

1) Kornegay, Joe N. “One Man’s View of One Health: Translational Lessons Learned from a Canine Model of Duchenne Muscular Dystrophy.” AAVMC, 2014 Recognition Lecture, Association of American Veterinary Medical Colleges, Alexandria, Va., 15 Mar. 2014,

2) Kornegay, Joe N., et al. “Pharmacologic Management of Duchenne Muscular Dystrophy: Target Identification and Preclinical Trials.” ILAR Journal 55.1 (2014): 119-149.

3) Smith, A.S.T., et al. “Muscular Dystrophy in a Dish: Engineered Human Skeletal Muscle Mimetics for Disease Modeling and Drug Discovery.” Drug Discovery Today 21.9 (2016): 1387-1398.

4) Young, C. S., et al. “A Single CRISPR-Cas9 Deletion Strategy That Targets the Majority of DMD Patients Restores Dystrophin Function in hiPSC-Derived Muscle Cells.” Cell Stem Cell 18.4 (2016): 533-540.

5) Chal, J., et al. “Generation of Human Muscle Fibers and Satellite-Like Cells From Human Pluripotent Stem Cells in Vitro.” Nature Protocols 11.10 (2016): 1833-1850.

6) Charville, G.W., et al. “Ex Vivo Expansion and In Vivo Self-Renewal of Human Muscle Stem Cells.” Stem Cell Reports 5.4 (2015): 621-632.

7) Kornegay, Joe N., et al. “Golden Retriever Muscular Dystrophy (GRMD): Developing and Maintaining a Colony and Physiological Functional Measurements.” Methods in Molecular Biology 709 (2011): 105-123.

8) Kornegay, Joe N., et al. “Canine Models of Duchenne Muscular Dystrophy and Their Use in Therapeutic Strategies.” Mammalian Genome 23.0 (2012): 85-108.

9) Bradshaw, J.W.S. and H.M.R. Nott. “Social and Communication Behavior of Companion Dogs,” in The Domestic Dog: Its Evolution, Behaviour, and Interactions With People by James Serpell, 115-130. (Cambridge: Cambridge University Press, 1995).

10) Rushen, J. and G. Mason. “A Decade-or-More’s Progress in Understanding Stereotypic Behaviour” in Stereotypic Animal Behavior: Fundamentals and Applications to Welfare, 2 nd ed., eds. Mason G and J Rushen, 1-18. (Wallingford, Wash.: CABI, 2006).

11) Tynes, V., and L. Sinn. “Abnormal Repetitive Behaviors in Dogs and Cats: A Guide for Practitioners.” Veterinary Clinics of North America: Small Animal Practice 44.3 (2014): 543-564.

12) Freedman, Leonard P., Iain M. Cockburn, and Timothy S. Simcoe. “The Economics of Reproducibility in Preclinical Research.” PLoS Biology 13.6 (2015): e1002165.

13) Begley, C.G., and P.A. Ioannidis. “Reproducibility in Science: Improving the Standard for Basic and Preclinical Research” Circulation Research 116 (2015) 116-126.