title: A short history of the use of animals in vaccine development and quality control.
abstract: Man has been using animals since early times to gain an insight into health, illness and death. The oldest known medical standard work, the Corpus Hippocraticum (circa 350 BC), contains descriptions of experiments on pigs. Although the first attempt at immunoprophylaxis dates as far back as the 6th century (variolation was practised in China to protect people against smallpox), it was not until the middle of the 19th century that animal experimentation acquired full scientific status in the development and quality control of immunobiological products. It was Louis Pasteur and Robert Koch who, through studies on animals, succeeded in underpinning the causal relationship between infectious diseases and micro-organisms, thus opening the way to the discovery of effective therapeutic and prophylactic agents for a number of these diseases. In several respects, the experimental animal work carried out in the last decade of the 19th century to find an effective and reliable way of treating and preventing diphtheria determined the use of animals. Many common routine animal tests in the quality control of immunobiologicals arose from diphtheria research. Conversely, diphtheria was one of the first diseases where experimental animal research laid the foundation for effectively reducing child mortality. This had a very profound impact on the attitude of society towards animal experiments in those days and almost completely eliminated the growing influence of the antivivisection movement. The interest in the possibilities of replacement, reduction and refinement (the Three-Rs concept) of the use of laboratory animals is increasing for several reasons, including concern about animal welfare. The root of animal welfare can be traced back to the 18th century with the formulation of utilitarian ethics. One characteristic feature of these ethics was that the interests of any creature which is submitted to any procedure should be taken into consideration. This presentation sets out some major historical contributions of animal experiments to the development and quality control of immunobiologicals. Attention is also paid to the changing attitude of society towards animal experiments and its impact on the development of alternative methods. It is concluded that, although animal experiments have played an important part, a new area is now beginning in which increasing emphasis will be placed on in vitro methods.
authors.affiliation: National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
authors.forename: C F
authors.initials: CF
authors.lastname: Hendriksen
mesh_terms: D000826:Animal Testing Alternatives / Q000266:history*; D000827:Animal Welfare / Q000266:history; D000818:Animals; D004165:Diphtheria / Q000266:history / Q000628:therapy; D004168:Diphtheria Toxoid / Q000266:history; D049671:History, 18th Century; D049672:History, 19th Century; D049673:History, 20th Century; D049690:History, Ancient; D006801:Humans; D011054:Poliovirus Vaccine, Inactivated / Q000266:history; D011786:Quality Control; D014612:Vaccines / Q000266:history*
chemical_list: D004168:Diphtheria Toxoid; D011054:Poliovirus Vaccine, Inactivated; D014612:Vaccines