2.11: Research Animals

Many studies in biology and medicine use animals (95% are rats and mice). We’re biologically similar to these animals. Our hearts, lungs, kidneys, eyes, and livers, function similarly. Protein, fat, and carbohydrate in our food undergo similar chemical reactions in our bodies. Even the required vitamins and minerals are similar. Using animals to study new vaccines, implants for arthritic joints, etc., gives us an idea of how they might work in humans, though this impression can be incorrect.

Animals mirror even such human tendencies as overeating when given appealing food. Rats overeat when offered a variety of human foods (e.g., cookies) instead of their usual fare of nutritionally adequate, greenish-brown pellets and water. Similarly, studies show that overweight people eat much less on a liquid diet. They’d probably eat even less on greenish-brown pellets and water!

Lab rats and mice are bred to be genetically similar, and their environment is controlled precisely. Animal quarters are kept at a comfortable temperature with heat and air conditioning; even light and dark periods are regulated. The best researchers can do with human subjects is to confine them away from home, but who’s to know if someone slips in a prohibited candy bar hidden under the mattress and eaten at midnight?

People can be undependable in doing what they’re told and inaccurate in reporting what they do—problems you don’t have with animal studies. Objective measurements are much more reliable, e.g., measuring cotinine (a nicotine metabolite) in urine to determine how much a person smokes, rather than relying on what he or she tells you.

There are even bottle caps with electronic chips that record when medicine bottles are uncapped, as a check on when people say they’ve taken their pills. If you compare the caloric value of people’s reported physical activity (overestimated) with the calories in the food they say they eat (underestimated), the U.S. population should be losing—not gaining—weight!

Humans vary a lot in genetic make-up, so genetic effects are hard to separate from environmental effects—the old nature-versus-nurture question. Environment is hard to control in human experiments—especially when diet is involved.

It’s hard to pinpoint causes of diseases like breast cancer because of the many variables. Breast cancer is less common in Asia than in the U.S. Is it genetics? Fat intake is less in Asia. Is this a factor? Women of Japanese ancestry who live in the U.S. have more breast cancer than women in Japan. Is this because their diet has changed, or does it reflect other changes?

Animal studies help answer such questions. The studies may not apply to humans, but can provide supporting evidence. Some animal studies show an increase in breast cancer with a high-fat diet. Had scientists not shown this, the hypothesis relating dietary fat to breast cancer in humans might not have been pursued so vigorously.

Animals can be bred to have specific genetic characteristics. For example, some strains are more susceptible to high blood pressure or obesity. Human populations also include sub-populations that may be comparable to such animal strains. For example, a drug for high blood pressure could be first tested on rats with high blood pressure, not only to test its effectiveness, but also to look for side effects. If the drug causes kidney damage in rats, it isn’t likely to be tested in humans.

The shorter life span of animals is used to study the long-term effects of diet on chronic diseases. It’s virtually impossible to control the variables in human studies of how diet in childhood affects development of chronic diseases later in life. Besides, researchers usually like to complete their studies in their lifetime.

Much of the progress in biology and medicine comes from animal studies. A major step toward conquering many human diseases is finding an animal model. A strain of mice that spontaneously develops breast cancer is used not only to study how breast cancer develops, but also to evaluate drugs for treatment and strategies for prevention. Advances in biotechnology and discoveries of disease-causing genes enable breeding of animal models with the exact same disease‑causing genes. A mouse model developed for multiple sclerosis helps in finding a cure.

The effect of specific genes can be studied by inactivating an individual gene in a mouse, creating a “knockout mouse.”* It’s like not knowing the function of the specific part of your car engine, and finding out its function by taking it out to see how it affects the engine.

The use of animals in research becomes more important as the use of human subjects is more restricted. Human experiments are much harder to get approved these days. During World War II, conscientious objectors participated in starvation studies, providing data that are still useful. The subjects fully recovered from the starvation regimen, but such studies wouldn’t be approved in the U.S. today. Studies on U.S. federal prisoners are no longer allowed. Participation was voluntary, but the fact that the volunteers are prisoners can interject a subtle form of coercion to participate.

Because strict guidelines exist for human studies and lawsuits can result from adverse effects, scientists in the U.S. rely more on animal research. Sometimes, people in other countries are used to follow up animal studies. Polio vaccine was first tested on people in the former Soviet Union, even though the vaccine was developed here. A chicken pox vaccine was tested on people in Japan before being tested in our population.

The experiments mentioned in Chapter 1 that tested the effects of supplemental thiamin on beriberi and that tested the infectivity of pellagra wouldn’t be allowed in the U.S. if such studies were proposed today. In the beriberi study, it would be deemed unethical to withhold thiamin-supplemented rice from the control population when there was ample evidence that thiamin prevents beriberi. In the pellagra study, it would be deemed unethical to “infect” healthy people with what was thought to be an infectious agent.

It goes without saying that research animals should be treated humanely and used only when necessary. Federal, state, local, and institutional guidelines and regulations address this concern. Organizations such as the American Veterinary Medical Assoc. have long‑standing guidelines for the humane care and use of research animals.

Scientists are as appalled as anyone else by abuse of animals. Animal abuse shouldn’t be tolerated, but isolated instances of abuse shouldn’t implicate all animal research. Lab animals often are referred to as a single group although they’re used for purposes other than biomedical research (e.g., testing cosmetics and household products).

The animal rights movement has had a big impact on scientific research and includes a range of opinions. Some people don’t object to animal research as such, but seek laws that ban the use of animals obtained from pounds.** Others aggressively advocate a total ban of animal research to the point of raiding laboratories and threatening scientists and their families.

Many animal rights groups focus on the use of larger animals, such as dogs and monkeys, although most research animals are rats and mice. It’s expensive to use animals in research, especially big ones. Scientists don’t use big ones when they can use small ones, and they don’t use animals at all unless they need to. For example, dogs often are used when human-sized organs are needed. Research using larger animals is used to develop such surgical procedures as organ trans-plants, correction of heart defects in newborns, and coronary bypass operations.

Animal research can benefit animals as well. Animal studies investigating leukemia are useful in understanding both human and feline (cat) leukemia. Animal research has led to immunizations against distemper, rabies, infectious hepatitis, anthrax, and tetanus; orthopedic surgery in dogs and horses; cancer treatment in dogs; prevention of brucellosis and tuberculosis in cattle; and improved nutrition for pets.

Ironically, animal-rights activists burned a lab under construction, causing about $3 million in damages to the School of Veterinary Medicine of the Univ. of Calif, at Davis, one of the leading veterinary schools in the country. Its scientists and its graduates have made major contributions to improving the health and welfare of animals.

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*The first knockout mouse was created in 1989 by Mario Capecchi, Martin Evans, and Oliver Smithies, who were awarded a Nobel Prize in 2007.

**Several states and communities now restrict the use of pound animals for research. (Millions of dogs and cats are killed in the U.S. each year in pounds and shelters.) In Massachusetts, for example, dogs and cats used for research must have been bred specifically for research, at a cost of several hundred dollars each.