BY CRAIG MALISOW
The purpose-bred laboratory beagle is a remarkably versatile animal. It can be used to ingest a toxic compound until it dies and to ascertain human safety guidelines for pesticides. Its heart, brain and prostate are easily accessible for cancer studies. It is bred to be docile and obedient, and, if necessary, it can be purchased sans working vocal cords. For around $700, you get a 33-pound specimen that needs no more than 8 square feet of kennel space, per federal law.
For some research, including certain cardiovascular and skeletal studies — and especially testing that involves a treadmill — a beagle may not be appropriate. The preferred model for these studies is a large, mature, outbred, barrel-chested mongrel or hound. Their larger size ensures a higher volume of blood that can be sampled.
In 2013, approximately 74,000 dogs were used in scientific research, according to the Humane Society of the United States' tabulation of data provided by the U.S. Department of Agriculture. The majority of dogs were used by private companies, but in 2012, the National Institutes of Health funded $263.5 million in grants for studies using dogs, with $45.3 million devoted to pharmaceutical testing.
Even though much of the work is taxpayer-funded, these institutions are loath to discuss specific studies, or even the use of dogs in general, with the media.
Most institutions purchase their dogs from just a handful of large dealers, including Marshall BioResources in upstate New York, which has trademarked the phrase "Marshall Beagle." Another supplier, Ridglan Farms in Wisconsin, boasts a "breeding colony which consists of approximately 750 bitches and 70 stud dogs." Covance Research, based in New Jersey, is another major player in purpose-bred beagles and "industry-leading hounds optimal for a variety of studies."
In the private sector, companies like Stillmeadow in Sugar Land, Texas, contract with pesticide manufacturers to conduct toxicity testing on dogs, as well as pharmacokinetic testing — how a drug is absorbed into the body — for pharmaceutical companies. Nanospectra, a start-up that licensed intellectual property from Rice University to eradicate cancerous tumors with lasers, tested its promising device on the healthy prostates of beagles. A veterinary ultrasound company in Arlington, Sound-Eklin, borrows dogs from the municipal pound for training purposes, adopting out the dogs when it can or returning them to the shelter when there aren't enough fosters or adopters available.
Because of public sentiment surrounding the practice, the word "dog" does not appear in the SEC filings of some publicly owned animal providers, such as Charles River Labs, nor does the literature include stock photos of scientists working with beagles — these are limited to mice. Marshall Bio-Resources' online catalog of trademarked beagles and crossbred hounds is password-protected.
The basic outlines of dog-related research conducted by public institutions can be gleaned from published studies and online grant-tracking through the National Institutes of Health, although it helps to have a PhD in order to translate the abstracts into plain English. With private companies, finding out what dogs are being used for is more difficult, and depends in large part on a company's transparency.
In addition to cancer studies, Texas research institutions are using federal money for dog-related studies to improve treatments for hemophilia, for brain protection after cardiac arrest, for MRSA and even for obesity.
In Houston, where globally renowned public institutions such as MD Anderson and the University of Texas Health Science Center at Houston are working to develop treatments and cures to reduce human suffering, dogs are a part of the process that public-relations departments would rather not discuss.
Dogs have been considered valuable lab animals since at least 1657, when Sir Christopher Wren, experimenting on dogs, became the first person to successfully inject substances into an animal's bloodstream. (The substances in this case were wine and opium.)
Wren's experiment led to the development of blood transfusion, and the use of dogs continued from there. The Centers for Disease Control and Prevention credits their use in the discovery of insulin, the vaccination of rabies, the function of neurons, open-heart surgery and the development of pacemakers, among other advances. Less Nobel-worthy uses have included giving beagles tracheotomies and forcing them to inhale cigarette smoke. There's also the sacrifice another group of dogs made for the sake of humanity — and the Burlington Hosiery Company — in a 1976 study titled "Three-Week Vaginal Irritation Study With Treated Panty Hose Fabric (Cotton and Nylon) in Beagle Dogs."
Although the use of dogs has greatly decreased, from 211,000 in 1979 to the most recent estimate of 74,000 in 2013, they remain a preferred research model for certain types of testing.
According to a 2006 article in the journal of the Institute for Laboratory Animal Research, most dogs are raised in a "breeding unit" and transferred to a new facility at five to 12 months of age. The move can be incredibly stressful — the article sites a study showing spikes in cortisol levels of 1-year-old beagles moved to their new home. If a dog doesn't get over the stress of the move, its nervous and immune systems can become compromised. Unchecked stress can actually alter a dog's physiology, causing it to develop affective disorders and even diseases, which "can have significant study implications," according to the article.
It's important for staff to interact with dogs and gain their trust. In order to prepare them for a life in a research setting, the authors suggest activities such as having a puppy sit "quietly on a table," exposing "pups to [the] feel of electronic clippers," exposing "pups to transport containers, carts or trolleys" and incorporating "training for additional devices when studies involve metabolism cages, slings, inhalation equipment, jackets or collars."
Research institutions and private companies get their research dogs from two types of license-holders: Class A dealers, who breed dogs on site and sell directly to the buyer, and Class B dealers, who buy dogs from third parties and resell to research clients. Class B dealers can broker deals without actually taking custody of the dogs, but once they do take custody of a dog — from hobby breeders, local pounds or private donations — the dog is classified as "random source."
Unlike their purpose-bred counterparts, random-source dogs are a mixed bag of breed, age and health. Class B random-source dealers have for years faced accusations of stealing people's pets or otherwise fraudulently obtaining their animals, and, in the past 20 years, they fell out of favor. In 2005, the USDA increased inspections of Class B dealers from annually to four times a year. Today there are only three Class B random-source dealers in business, located in Michigan and Ohio.
Facing mounting public pressure, federal researchers, through the National Research Council, examined whether Class B random-source dogs were necessary for future federal studies. The answer was yes — with an asterisk.
In 2009, the National Research Council issued a wishy-washy report on the subject, blaming much of the growing public concern over the use of laboratory dogs on the extremists who were part of what the council called the "animal protection movement."
It was like extremists had crashed the party, spoiling the future of biomedical research with all their talk about animals being treated inhumanely. But as far as the council was concerned, proactive researchers had implemented humane guidelines even before the 1966 passage of the Animal Welfare Act.
At the same time, the council acknowledged that, historically, the random-source animal industry was rife with bad actors, including dealers who stole people's pets. But that didn't change the fact, the council stated, that genetically diverse dogs were still important for research. Large mixed-breeds have deeper chest cavities and large hearts that make them especially valuable for cardiac research. Large, barrel-chested breeds are especially suited for pulmonary work and thoracic surgery; these types of dogs assisted in the development of lung transplant procedures, according to the 2009 report.
The dogs were also just plain practical. According to the report, they cost about half as much as their purpose-bred brethren.
Ultimately, the National Institutes of Health decided to have the best of both worlds: Since the Class B random-source industry had such a black eye, the NIH announced that it would cease funding research that used dogs from those dealers.
At the same time, it asked Class A dealers to provide dogs "with research characteristics consistent" with random-source dogs. (The Class B defunding went into effect in October 2014. A similar policy for random-source cats was implemented in 2012.)
That request for proposal, issued by the NIH's National Heart, Lung and Blood Institute, called for a Class A dealer to provide 1,000 genetically diverse dogs by 2013. The dogs, of course, had to be well-tempered:
• The dog shall approach, and be approachable by humans, and allow people to touch its head and body.
• The dog shall approach and not show fear of novel objects, both in its housing environment and outside its normal housing environment. Dogs shall not show excessive fear of noise.
• Dogs shall allow handlers to restrain them. The handlers should be able to check the dog's mouth, teeth, eyes, feet and tail, without aggressive reactions. Handlers should be able to restrain the dog for access of veins in neck, front and rear leg.
As for the NIH's concern that extremists would somehow throw a monkey wrench into laboratory animal research, it was premature. As it turned out, a 2014 USDA Office of Inspector General audit showed that inspectors had for years failed to adequately investigate facilities and issue substantive fines to researchers who violated the Animal Welfare Act.
In fact, the audit showed that inspectors had wasted an incredible amount of time and money by conducting at least 500 inspections on facilities that no longer even used animals for research.
Perhaps most serious, the OIG audit showed that many researchers were failing their lab animals in the most fundamental way: They were inaccurately reporting how much pain was inflicted upon their dogs.
Animals used in studies are ranked in three "pain/distress" categories. In order to comply with the Animal Welfare Act, researchers need to justify instances where animals are subjected to pain without the aid of pain-relieving drugs. The OIG audit found that many labs had placed animals in the wrong pain category. (The categories include "no pain, no drugs"; "with pain, with drugs"; and "with pain, no drugs.")
The audit stopped short of explicitly saying that researchers were underreporting the number of animals subjected to pain without any relief, but the Humane Society of the U.S. had made this accusation 12 years before the audit.
In a 2002 letter to the National Institutes of Health, an HSUS senior vice president pointed to a host of government-funded studies in which it appeared the animals were subjected to a high level of pain but were placed in a lower pain category.
One such study, at the University of Illinois-Chicago, measured the toxicity of a potential breast cancer drug regimen in 13 female beagles. USDA guidelines call for toxicity tests to be placed in the highest pain category, but the dogs used in this study were placed in a lower level. During the beagles' 90-day dosing, it became evident that, in addition to causing diarrhea, the drug was taking a toxic toll on the dogs' reproductive tracts. Their ovaries atrophied, and they experienced vaginal discharge because of lesions on the intestines, ovaries, fallopian tubes, uterus, vagina and cervix.
Compared with monkeys, hardly any dogs are used at Houston's MD Anderson Cancer Center. Since 2010, the institution has registered the use of only 34 dogs with the USDA. But the National Cancer Institute and the National Institute of Biomedical Imaging and Bioengineering have granted more than $2 million to MD Anderson for studies that include dogs.
Unfortunately, it's difficult to find out the extent of these studies since an MD Anderson spokeswoman told us in an email, "I've not been able to find someone here who is interested in participating in the story."
But generally, scientists consider dogs especially well-suited for cancer research. Like humans, dogs suffer spontaneous lung cancer, and tumors can spread the same way in both species. According to the National Cancer Institute, dogs and humans have similar immune systems, making dogs a good model for cancer immunotherapies. The NCI also states that dogs' size is especially suitable for collecting samples and performing surgery.
According to an NIH database, the dog-involved work being done at MD Anderson includes a study on the use of a drug called bleomycin in the treatment of squamous cell carcinoma — a cancer of the mouth, head and neck that is the fourth-most common type of malignancy in males. Bleomycin is already used in the treatment of Hodgkin's lymphoma.
The study was proposed in 2010, at which time bleomycin had already yielded positive results in mice, and preliminary studies using two dogs look promising, according to the project's leader.
Moreover, since the lab already has an animal cancer treatment unit, researchers could "recruit client-owned dogs."
An article resulting from the study, published in the March 2015 issue of the Journal of Cellular and Molecular Medicine, noted the safety and efficacy of the treatment on 13 dogs and emphasized that "not a single adverse event was noted even in animals receiving the highest doses ... over multiple treatment cycles."
Like MD Anderson, the University of Texas Health Science Center at Houston is tight-lipped about its research with dogs.
"There is no one here interested in participating in that story," spokeswoman Deborah Mann Lake told the Houston Press.
According to USDA records, the institution has conducted studies on 59 dogs since 2010. But the Houston Press was unable to find corresponding data on the National Institutes of Health's online grant database, suggesting that, whatever UT-Health Science Center was doing with its dogs, it wasn't federally funded.
Meanwhile, the Texas Heart Institute has stopped using dogs altogether. This, despite the fact that the NIH says that dogs are great models for heart research because the canine cardiovascular system is similar "in both size and function" to people's. (Larger dogs, with deeper chest cavities and large hearts, have made especially good candidates in the development of both surgical techniques and the implantation of devices like pacemakers, according to the NIH.)
"A management decision was made in early 2012 to permanently eliminate the use of dogs in research," THI spokesman Frank Michel said. At the time the decision was made, one three-year study was already in place.
"The hearts of these animals were used in the study of the molecular and chemical causes of atrial fibrillation (AFIB), which is linked in humans to sudden cardiac arrest and strokes," Michel explained in an email. "The study was aimed at preventing AFIB, an abnormal rhythm of the heart characterized by rapid and irregular heartbeats." (Michel noted that the dogs in that study came from a Class A dealer.)
Michel also explained that the Texas Heart Institute decided to stop using dogs for two reasons: "We understand the societal sentiments about it and wanted to be responsive to [those] sensitivities, and ... the canine physiology is not the best match for the types of research underway now at THI." (USDA records indicate the institute primarily uses sheep and pigs for its studies.)
While some studies may seem benign, others include detailed descriptions of how a dog is actually injured for the purpose of research.
At Texas A&M, for instance, a lot of research is being done on Duchenne muscular dystrophy, which affects approximately one out of every 3,500-7,500 males. In this condition, the absence of a protein called dystrophin causes the deterioration of skeletal and cardiac muscle.
The work is led by nationally renowned researcher Joe Kornegay, who maintains a colony of golden retrievers afflicted with Duchenne. A 2012 journal article discussing these studies states that, unlike mice, golden retrievers afflicted with Duchenne "develop progressive, fatal disease strikingly similar to the human condition."
The article explains that, to measure muscle degeneration, a dog's ankle joint was extended by using a tiny motor called a servomotor, which is attached to a lever. Then the muscles "are repeatedly stretched to induce mechanical damage." Dogs were subjected to "three sets of ten stretches," with a 5-second rest between stretches and a 4-minute rest between sets.
At Houston's Nanospectra Biosciences, founded in 2002, researchers have licensed nanoshell technology developed at Rice University. The idea works like this: Nanoshells, tiny gold-plated particles, are injected intravenously into a cancer patient, with the nanoshells — or AuroShells, as Nanospectra calls them — bonding to the tumor. The target area is then lit up with a "near-infrared laser," according to the company's website. "The AuroShell particles are specifically designed to absorb this wavelength and convert the laser light into heat." This obliterates the tumor, while not harming the surrounding tissue.
The toxicity was tested using 36 beagles, according to a 2012 article in the International Journal of Toxicity that concluded that the nanoshell particles "are not associated with any toxic effects."
The lack of toxicity means the particles can be used to treat cancer in dogs as well as humans. Nanospectra CEO David Jorden told the Houston Press in an email that the company has treated 18 dogs in pilot studies that began in 2014. Two more dogs are scheduled for cancer treatment — one at A&M and the other at Virginia Tech.
When they aren't helping researchers test potential new ways to attack cancer and heart disease, dogs are also being used to tell us at what point ingesting a pesticide is fatal.
The U.S. Environmental Protection Agency has historically required pesticide toxicity tests using both rodent and non-rodent species, with dogs making up most of the latter. The agency used to require both a one-year and a 13-week study, but jettisoned the former in 2007 after determining that the longer study did not provide "additional, essential" information, according to a retrospective study. Standard EPA forms for the "acute oral toxicity and pathogenicity" test advise researchers to "state only the prominent clinical signs" of the animals after they've ingested the substance, and to "not dwell on clinical signs that are most likely due to agonal death."
Theodora Capaldo, president and director of the New England Anti-Vivisection Society, says it wasn't just the time span of the tests that was redundant, but the requirement for a second, non-rodent species in the first place. She says recent studies have shown that adding "50 dogs or 25 dogs at the end of that long line of testing doesn't give us any new information that we didn't already have from just using rodents."
Like other advocates who oppose animal testing, Capaldo likes to point out the statistic that says that as many as 90 percent of pharmaceuticals tested on animals have adverse effects in humans, making animal testing an allegedly poor predictor.
"It's not only cruel, it's inaccurate," she says. "Science is progressing. Policy and attitude of researchers is not necessarily progressing as rapidly as the science is."
Capaldo points to human-cell-based tissue culture as the future of drug testing, something that's seconded by Kathleen Conlee, vice president of animal research issues at the Humane Society of the U.S.
Conlee is excited about the Tissue Chip for Drug Screening initiative, a collaboration among the National Institutes of Health, the FDA and the Defense Advanced Research Projects Agency. The initiative hopes to develop 3-D "human tissue chips" modeled on human organs, which, according to the NIH's website, could "predict whether a candidate drug, vaccine or biological agent is safe or toxic in humans in a faster and more cost-effective way than current methods."
"Our argument," Conlee says, "is this technology is only going to continue to improve, where the animal models will always have their limitations."
Some lab dogs make it out at the end, and that's where groups like Beagle Freedom Project come in. The southern California-based rescue claims to have found homes for roughly 450 former lab beagles in the past four years. About one-third have had their vocal cords snipped. In many cases, the group must sign confidentiality agreements, promising not to disclose the name or location of the research facility the dogs came from.
In addition to finding homes for retired lab dogs, BFP has developed an effective PR campaign spreading awareness of lab dogs in general, gaining the ire of pro-animal-testing groups such as the Foundation for Biomedical Research and the National Association for Biomedical Research, who claim BFP is affiliated with the extremist Animal Liberation Front. (BFP's founder, Shannon Keith, is a Los Angeles-based attorney who directed a 2006 documentary on the Animal Liberation Front. She also represented a militant group of international anti-animal-testing activists called Stop Huntingdon Animal Cruelty.)
Typically it's a lower-level animal care technician who contacts the group about the possibility of releasing dogs the lab has no use for, says BFP Research Specialist Jeremy Beckham.
"This tech is the person who has been in charge of taking 'care' of the animals, sometimes, for the past several years," Beckham explains in an email. "Cleaning their cages, feeding them, carrying them to and from the room where they are experimented on. When the study ends they are often pained to know these animals will be euthanized even if they are healthy, and they beg the higher-ups to let them find homes. Typically these techs have already taken a beagle or two, asked their friends and family, and are out of options."
BFP covers all the costs of picking up the dogs and getting them checked out by a vet. Sometimes the organization will pick the dogs up at the lab; sometimes it'll be in a nearby public parking lot. In some cases, when there's an issue of lingering medical conditions, a lab will let BFP know what type of experiments the dogs have undergone, but the group is just as often in the dark.
Not surprisingly, it can take a while for the dogs to adjust outside the confines of a lab. Some have never seen grass, Beckham says.
"Being outside can be a little overwhelming and overstimulating — all these new sights and textures and sounds," he explains. "It can cause a little bit of shell shock in them."
In July 2014, the group coordinated the release of seven beagles in Texas, ages 2 to 9, that had spent their lives in what was described only as a "testing laboratory on the Texas/Mexico border." Keith stated in a press release at the time, "They were in pretty bad shape. Some had cuts all over their faces. They were very, very dirty and very, very scared."
The Houston Press sought comment from another beagle rescue organization, the Foundation for Biomedical Research-approved Beagle Rescue League Inc., whose president, Carolyn Sterner, declined. But in an interview with the Foundation for Biomedical Research, Sterner stated that the dogs her group has homed "come to us in wonderful condition ... The dogs are healthy, have excellent veterinary records and generally come to us with a positive association with people."
Meanwhile, BFP sends mailers to every research lab in the country that experiments on dogs and cats, offering to find homes for the animals once they're done being used.
"We get very, very few replies to this, and it's very startling that most laboratories right now are just summarily killing the dogs and the cats, even if they survive to the end of the experiment ... I think it's because they're worried about public relations, you know, because all of these dogs that get adopted, they become little walking ambassadors of the issue."
That's why BFP is pushing for laws in four states that would make research institutions that receive public money attempt to find homes for dogs once they're done with them. The bills have drawn opposition from some facilities, including the University of California system, whose officials claimed in part that the measure would increase costs.
"We're not even interfering with the research — they can still use the dogs and cats in whatever experiments they want to," Beckham says. "We're just saying: If the dog or cat survives, please try to place them in a home."
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