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, and 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 one-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 whenever 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. NIH 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.