Canine Muscular Dystrophy Experiments Expert Testimony

Nicholas H. Dodman, B.V.M.S., D.A.C.V.B., D.A.C.V.A.A.; Massachusetts State Representative for the Humane Society Veterinary Medical Association and a Member of Its Leadership Council

The Humane Society Veterinary Medical Association (HSVMA) believes that veterinarians have a responsibility “to use our training to protect, care for, and advocate on [animals’] behalf.”[1] Animals affected with Duchenne muscular dystrophy (DMD)—a genetic disorder which causes inherited progressive degenerative muscular disease—develop serious, potentially fatal health problems. Deliberately breeding dogs with this debilitating, and often fatal, inherited disorder is a direct abrogation of that professional responsibility.

The DMD colony dogs captured on video inside Texas A&M appear to exhibit stereotypic behaviors associated with anxiety and distress. They appear to be housed alone, a situation that can exacerbate anxiety and contribute to the development of additional behavior problems. DMD-afflicted dogs can become extremely emaciated due to muscle wasting, yet these dogs do not seem to have access to comfortable bedding to rest upon. Dogs suffering from muscular dystrophy are unable to run, exercise, or enjoy many other natural behaviors of normal dogs.

Breeding dogs who carry the Duchenne muscular dystrophy genetic mutation intentionally causes them unnecessary pain and suffering, and they receive no therapeutic benefits in return for their deprivation. From an ethical veterinary perspective, the humane choice would be to prevent, not perpetuate, the breeding of such at-risk dogs.

Narda G. Robinson, D.O., D.V.M., M.S., F.A.A.M.A.; President and CEO of CuraCore

With degrees in both human and veterinary medicine, I am aware of the differences between dogs and humans that make dogs poor surrogates for muscular dystrophy research. Indeed, canine muscular dystrophy research has not led to treatments that cure or target the cause of muscular dystrophy in human children.

Further, in terms of animal welfare, breeding animals to have a debilitating disease that restricts their movement and ability to function normally, and that eventually results in severe respiratory and cardiac problems, is inexcusable.

Thankfully, human-relevant, non-animal methods for Duchenne muscular dystrophy research are available. These methods may be superior to studying Duchenne-like conditions in other species, as is being done at Texas A&M and elsewhere.

Josh P. Novic, M.D.; Board-Certified Neurologist

It is my strong belief that the fundamental flaw in almost all animal research is a moral one, based on the twofold error that ends justify means and that the animals experimented on are less morally valuable than humans. In addition, considering that canine muscular dystrophy is not entirely analogous to the human form of Duchenne muscular dystrophy, it seems like a molecular genetic approach using human cells or tissues would have far more promise than physiological experiments on other species.

Stephen R. Kaufman, M.D.; Case Western Reserve University

Animal experimentation is frequently misleading and the practice tends to be self-propagating.

Our tax dollars should not be paying for research that, if actually worthwhile, would be supported by private industry.

James H. Yahr, M.D., F.A.C.S.

The plight of dogs being bred to have golden retriever muscular dystrophy in the Texas A&M facility is difficult to watch. It is disturbing that someone would put these wonderful animals through such gruesome experiments. With such serious doubt that the research carried out on these dogs will be of any use to human well-being, breeding programs such as these should be ended immediately.

John J. Pippin, M.D., F.A.C.C.; Director of Academic Affairs for the Physicians Committee for Responsible Medicine

PETA: Do you find that the manifestations of canine DMD are physiologically similar to the manifestations of human DMD?

John Pippin: I believe from the literature that something that looks like DMD can be found, for example in dystrophin-deficient GRMD [golden retriever muscular dystrophy]. But I believe that this is not the same disease, and that approaches targeting this disease will not be relevant for humans. History supports this.

PETA: Do you feel that the use of dogs for DMD research will contribute to the health and well-being of human children affected with the disease?

J.P.: I do not think this will happen, for reasons above and also the very long historical record for all animal-tested treatments and especially for neuromuscular disorders.

PETA: Do you feel that the causes and manifestations of human DMD can be researched without the use of animals? (If so, can you provide us with any examples?)

J.P.: I do believe this, and CRISPR/Cas9, iPSC approaches to replicate human muscle from DMD patients, and chip technologies are leading candidates.

PETA: Do you consider the experiments to be ethically justifiable?

J.P.: I don’t consider these experiments to be ethical under any circumstances. But given the futility of this approach for DMD, the ethical violation is egregious.

I think it’s useful to emphasize that animals (including dogs) have been used for at least six decades without resulting in any useful DMD treatments. The recently approved drug eteplirsen doesn’t work, of course, and its approval is a reflection of the desperation that has resulted from decades of dead-end animal experiments.

I generally also emphasize why animal experiments like this have only rare and random relevance for human diseases, and thus do not meet the definition of science. It’s well-known now that even small differences in genetics, physiology, and even anatomy (rats don’t have gall bladders, right?) can scuttle animal experiments. I think this is memorably expressed in this piano analogy, which I must have seen somewhere but can’t recall. I wrote this for [genetically modified] mouse research, but it applies universally and applies just as well for dogs:

What a specific gene does in a mouse has no predictive value for what it will do in humans. It does not even have predictive value for what will happen in other mouse strains. Most mammals share more than half of their genes, and up to perhaps 98% for chimpanzees and humans. Just as pianos have the same keys, so humans and animals share the same genes. So what makes us different? The way the genes or keys are expressed. Play the keys in a certain order and you hear Chopin, a different order and you hear Ray Charles, yet a different order and it’s Jerry Lee Lewis; same keys but very different outcomes. The same is true with genes. Mice and humans have mostly the same genes; humans even have the gene that in mice allows them to grow a tail. The difference? In humans that gene is not expressed. The different combinations of genes and different gene expressions separate species and even individual humans. When the same genes in different animals have very different expressions according to race (or strain), gender, age, and environmental factors, how in the world can we expect a gene in a mouse’s biological and environmental milieu to tell us anything relevant for the same gene in a person?

There is no reason to believe that dog experiments will translate to human DMD, given that closer genetic relatives such as nonhuman primates (Google “monkeys Duchenne muscular dystrophy research”) have failed universally to advance approaches to the human disease. The GRMD model itself, as well as other canine models (Rottweiler, German Short-Haired Pointer, and Beagle) have been studied at least as far back as the 1980s without benefit to anyone except researchers ($$$). As noted by Collins and Morgan, “Whilst the GRMD dog is undoubtedly the most closely homologous model of the human disease, its scope is restricted because studies are necessarily expensive, small scaled and slow and currently exclude transgenic approaches. Inter-animal variation also makes standardization difficult.”[2]

Also, using Google you will find many instances of research articles acknowledging the failure of animal research for the disease, including specifically GRMD research.

Regarding CRISPR/Cas9, it seems self-evident that its use to modify human genes makes much more sense than continuing to manipulate the genes in animals that cannot replicate the human disease because of the piano analogy.

One definition of stupidity is continuing to do something that never works, expecting a different result. I think half a century of DMD animal experiments, including 30 years of GRMD research, meets this criterion.