FREQUENTLY ASKED QUESTIONS
The Care of Use of Animals in Biomedical Research

  8. Why Use Animals?
  9. What are the Most Commonly Used Animal Models?
10. Which Animals are Studied for their Unique Characteristics?
11. Where Would We Be Without Animal Research?
12. Man’s Best Friend ... and Research Partner
13. How Many and What Kinds of Animals are Used in Biomedical Research?
14. How are Animals Used in Biomedical Research Cared For?
15. What Laws, Regulations and Guidelines Govern Animal Research?

FAQ — General Questions (1-7)

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12. MAN'S BEST FRIEND ... AND RESEARCH PARTNER?
(Taken from Unit II, Chapter 3, of the Rx for Science Literacy teacher manual.)

People and Dogs Can Benefit From Each Other in the Search for New Drug Therapies
Did your veterinarian ever instruct you to disinfect a canine wound with Betadine from your medicine cabinet? Have you ever owned an arthritic dog whose painful joints were soothed by the aspirin you opened for your own splitting headache? Did the treatment your veterinarian prescribed for Fido’s last case of diarrhea include dosing your dog with the same Pepto-Bismol that makes you grimace?

It’s enough to make you wonder if your dog should join you on your next shopping trip down the health and beauty aisle. What’s more is that the similarities in human and canine medications go beyond over-the-counter products to include prescription pharmaceuticals as well.

If your dog comes down with a bladder infection, for instance, your vet may prescribe an antibiotic called amoxicillin. It’s the same antibiotic that your physician may prescribe for you if you develop a bladder infection.

Suppose the problem is a gastrointestinal ailment like salmonellosis or giardiasis, tummy troubles caused respectively by bacteria and protozoans. An antibiotic called furazolidone is commonly used to combat both conditions, in people and in dogs.

Antibiotics are far from being the only crossover medications in human and canine health. If your dog should have the misfortune to suffer from uveitis, an inflammatory condition of the eye, your veterinarian may prescribe atropine drops, the same medication your ophthalmologist uses to dilate your pupils for a comprehensive eye exam.

A dog suffering from an acute case of dermatitis may be treated with an injection of hydrocortisone. If you should happen to have a run-in with poison ivy, you’ll probably use the same steroidal anti-inflammatory in its topical form, a lotion or cream; and if you’ve really rolled around in the itchy stuff, you too might receive a shot.

Do you take Lasix (furosemide) for high blood pressure or heart problems? Someday your dog might take it too, if it develops congestive heart failure. Furosemide is regarded as one of the most effective canine diuretics. Diuretics are medications used to reduce the presence of fluids in the body by increasing urination. The history of Lasix provides a good example of the usual route that medications take in their use by humans and pets. Lasix was introduced by Hoechst Pharmaceuticals into human health care in 1966 to control the buildup of fluids associated with heart failure and kidney and liver diseases. It also is used in people for treatment of high blood pressure. Eleven years later, Hoechst-Roussel Agri-Vet, the manufacturer's animal health division, introduced Lasix for veterinary use. Dogs (and cats and horses) with congestive heart failure benefit from adminis-tration of Lasix.

CROSSOVER THERAPIES
Historically, chemical compounds begin their pharmaceutical careers treating human ailments and then migrate into veterinary medicine to treat similar conditions in animals.

One of the most notable examples is the dog/diabetes connection. Dogs have been used to experiment with pancreatic transplants and to study the visual impairment and circulatory problems that diabetics often suffer.

The canine role in diabetes research has paid off for dogs too since diabetes is one of the most common endocrine disorders to occur in the dog. In modem veterinary medicine, diabetes has become a treatable disease in dogs. Management of the condition is achieved through insulin therapy and diet modification, similar to what is prescribed for humans.

THE RESEARCH CYCLE
The process of medications moving full circle from animal experimentation to human therapy and then to animal therapy is common. But can the process work the other way around? Does a drug developed with the intention of treating an animal disease ever find its way into the human pharmacopoeia? Until quite recently, the answer was no, but in the 1980s, the drug ivermectin changed that.

Dog owners know ivermectin as Heartgard-30, a once-a-month canine heartworm preventive. Ivermectin was first introduced by Merck & Co. in 1981 as Ivomec, a medication to treat lung-worms and other nematode parasites of cattle. Ivermectin works against these unpleasant critters by inhibiting chemical reactions in their central nervous systems, resulting in paralysis that allows them to be expelled from the host animal’s system.

Ivermectin’s effectiveness against larval worms makes it a useful weapon in the prevention of heartworm, a filarial disease, but canine heartworm was not the only filarial disease found to be treatable with ivermectin. In parts of Central and West Africa and in areas of Central and South America, a disease known scientifically as onchocerciasis threatens more than 100 million people with impairment or total loss of their eyesight. The principal transmitting agent for this disease is not the mosquito but Simulium neavei, the African species of black fly.

As many North American campers can attest, black flies breed in areas of rapidly running water and are most apt to thrive in biting swarms near the banks of rivers and streams. The same is true of the African species. Hence the common African and American name for onchocerciasis: river blindness. The greatest risk for contracting river blindness occurs in areas of Nigeria, Zaire, Ethiopia, Cameroon and Venezuela.

The nematode culprit in onchocerciasis is Onchocerca volvulus. When a black fly carrying O. volvulus larvae in their infective stage bites a human, the worms burrow under the skin and mature. With a life span of 10 to 15 years in their human host, the worms can grow as long as two feet. Under the skin, they cause intense itching, disfigurement and loss of skin elasticity. When O. volvulus larvae are ready to reproduce, the female worms release millions of microfilariae into the bloodstream. As the microfilariae migrate through the body, some invade the eye. Those that accumulate in the tissues of the eye cause lesions that lead to a slow deterioration of vision and eventually to blindness.

Treatment with Mectizan, Merck’s trade name for the human form of ivermectin, paralyzes and kills the microfilariae infecting the eye. An annual dose of the drug reverses early lesions in the cornea and arrests further development of other lesions, thus halting worsening of vision. Given twice yearly, ivermectin also reverses disfigurement and restores skin elasticity.

Merck’s research efforts into ivermectin’s efficacy against heartworm and river blindness were conducted virtually concurrently. In fact, a Merck scientist’s report of early research on the use of ivermectin against O. volvulus cites results of studies showing the drug’s effectiveness against D. immitis in dogs.

Ivermectin is the first, but not the only pharmaceutical used to treat dogs that have been adapted to combat a human disease. Another veterinary worming agent, levanusole, moved from the animal to the human health arena in 1990. Levamisole has been marketed for about 25 years and is used occasionally in dog care for elimination of parasitic nematodes such as intestinal roundworms and adult heartworms. Its primary application, though, is as a livestock wormer.

According to a May 20, 1992, article in The Wall Street Journal, exploration of other applications for levamisole began when farmers noticed that livestock they had recently dewormed appeared to have a lower incidence of shipping fever, a respiratory disease that occurs especially in young animals under stress. Lab work began to investigate levamisole’s potential as an antiviral agent or immunity enhancer. The studies, conducted in both animals and people, demonstrated that levamisole is indeed a stimulant to the immune system.

Scientists found that levamisole used in conjunction with 5-FU, a commonly prescribed chemotherapy drug, produced notable therapeutic effects in patients with an advanced form of colon cancer. In the clinical trials, people treated with the levamisole and 5-FU combination suffered 40 fewer recurrences of the disease, and the death rate was reduced by one-third, according to statistics cited in the Journal article.

BIOTECHNOLOGICAL HORIZONS
In addition to exploring potential new therapeutic uses for existing drugs, pharmaceutical companies are turning to biotechnology for new treatments for cancer and viral diseases. Unfortunately, this field promises little likelihood of direct cross-utilization of drugs by canine and human patients, according to Ted Weigel, director of marketing at Synbiotics Corporation, a California firm specializing in veterinary biotechnology. An understanding of the function of one of Synbiotics’ products, Canine Lymphoma Monoclonal Antibody 231 (CL/MAb 231), will help to explain why this is so.

Antibodies combat disease by attacking and neutralizing foreign substances. Biotechnological researchers program monoclonal antibodies to carry out search-and-destroy missions against specific foreign substances. Monoclonal antibodies that target tumor cells are specific to the species in which they will be used, Weigel says. In the case of CL/MAb 231, the targets are canine lymphoma or cells only. Thus, an antibody that neutralizes lymphoma tumor cells in dogs would be ineffective in humans and vice versa.

Nonetheless, the technology behind the manufacture of biotech pharmaceuticals, such as monoclonal antibodies and genetically engineered vaccines, is similar for all species. In fact, Weigel says human pharmaceutical companies are currently at work on monoclonal antibody therapies for human cancers. “If we [in the biotechnology industry] can build a feline leukemia vaccine,” says Weigel, “then someday we ought to be able to build a leukemia vaccine for humans.”

The dog may be human’s best friend, but the history of human and canine pharmacology seems to show that people can be the dog’s best friend, too.

(This article appeared in the October 1993 issue of DOG FANCY magazine and has been reprinted with the permission of the author, Mary Warzecha.)

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