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Humans and animals have been subjects of medical experimentation since the experimental method of science was first developed in the 17th century. Descartes' arguments that animals are not capable of experiencing pain because pain is felt by the soul and animals have no souls allowed for the rise of vivisection in animals. He argued that if human beings could make a clock that chimes at the hour, God could invent a being that reacts to damage as if it felt pain, yet feels none.

Children, prisoners, the indigent, and the disabled, members of minority groups, and other oppressed groups and subgroups have been considered legitimate subjects for human experimentation in the U.S. and elsewhere. Currently, we believe that some groups of humans should be routinely exempt from participation in clinical trials. Among these we count the handicapped, captive populations (children in a boarding school or institution, adults in prisons), those incapable of giving informed consent, and prisoners of war. There remains a further question whether clinical trials are ever ethical, unless performed on medical professionals who freely give consent. Americans trust doctors to act in their individual best interests, but in a clinical trial, the doctor must act in the interest of the larger group, even at the expense of the individual. Even when explicitly informed that this is the case, most laypeople believe that a doctor in a clinical trial would not have recommended participation unless the treatment is likely to be effective in his or her individual case.

The ethical status of animal experimentation is likewise the subject of heated debate. Is it wrong to cause great pain to an animal for trivial, commercial purposes, such as the testing of new oven cleaners and eyeliners? Peter Singer, whose book In Defense of Animalsis the foundation of People for the Ethical Treatment of Animals, argues that the appropriate test for whether an experiment is morally justifiable is to ask whether it would be acceptable to perform the same test (causing the same amount of pain) on an orphaned, retarded infant. If you would not be willing to perform the experiment on an orphaned, retarded infant, but you are willing to perform it on an animal that has the same intelligence as the retarded infant, then your stance is "speciesist." Speciesism, like racism or sexism, is an irrational preference for the interests of one being on the basis of an irrelevant characteristic of that being, whether that characteristic be race, sex, or species.