The history of animal testing goes back to the writings of the Ancient Greeks in the 4th and 3rd centuries BCE, with Aristotle (384–322 BCE) and Erasistratus (304–258 BCE) one of the first documented to perform experiments on nonhuman animals.Cohen and Loew 1984. Galen, a physician in 2nd-century Rome, dissected pigs and goats, and is known as the "Father of Vivisection.""History of nonhuman animal research" , Laboratory Primate Advocacy Group. Avenzoar, an Arabic physician in 12th-century Moorish Spain who also practiced dissection, introduced animal testing as an experimental method of testing surgical procedures before applying them to human patients. Although the exact purpose of the procedure was unclear, the Neolithic surgeon performed trepanation on a cow in 3400-3000 BCE. This is the earliest known surgery to have been performed on an animal, and it is possible that the procedure was done on a dead cow in order for the surgeon to practice their skills.

History of animal testing

In 1242, Ibn al-Nafis provided accurate descriptions of the circulation of blood in mammals. A complete description of this circulation was later provided in the 17th century by William Harvey.

In his unfinished 1627 utopian novel, New Atlantis, scientist and philosopher Francis Bacon proposed a research center containing "parks and enclosures of all sorts of beasts and birds which we use ... for dissections and trials; that thereby we may take light what may be wrought upon the body of man."

In the 1660s, the physicist Robert Boyle conducted many experiments with a pump to investigate the effects of rarefied air. He listed two experiments on living nonhuman animals: "Experiment 40", which tested the ability of insects to fly under reduced air pressure, and the dramatic "Experiment 41," which demonstrated the reliance of living creatures on the air for their survival. Boyle conducted numerous trials during which he placed a large variety of different nonhuman animals, including birds, mice, eels, snails and flies, in the vessel of the pump and studied their reactions as the air was removed. Here, he describes an injured lark:

In the 18th century, Antoine Lavoisier decided to use a guinea pig in a calorimeter because he wanted to prove that respiration was a form of combustion. He had an impression that combustion and respiration are chemically identical. Lavoisier demonstrated this with the help of Pierre-Simon Laplace. They both carefully measured the amount of "carbon dioxide and heat given off by a guinea pig as (they) breathed". Then they contrasted this to "the amount of heat produced when they burned carbon to produce the same amount of carbon dioxide as had been exhaled by the guinea pig". Their conclusion made Lavoisier confident "that respiration is a form of combustion". Also, the result showed that the heat mammals produce through respiration allowed their bodies to be above room temperature.

In the second volume of his Statical Essays, Haemastaticks (1733), Stephen Hales accounts several different experiments he conducted on animals. One of his most notable experiments is one he conducted on an unanesthetized elderly mare. He devised a contraption using a brass canula, the excised windpipe of a goose, and a tall glass tube to observe the horse's "force of blood." Because of this, Hales is recognized as being the first person to measure blood pressure.

In the 1780s, Luigi Galvani demonstrated that electricity applied to a dead, dissected, frog's leg muscle caused it to twitch, which led to an appreciation for the relationship between electricity and animation. In the 1880s, Louis Pasteur convincingly demonstrated the germ theory of medicine by giving anthrax to sheep. In the 1890s, Ivan Pavlov famously used dogs to describe classical conditioning.

In 1921 Otto Loewi provided the first substantial evidence that neuronal communication with target cells occurred via chemical synapses. He extracted two hearts from frogs and left them beating in an ionic bath. He stimulated the attached Vagus nerve of the first heart and observed its beating slowed. When the second heart was placed in the ionic bath of the first, it also slowed. O. Loewi (1921) "Uber humorale Ubertragbarkeit der Herznervenwirkung. I." Pflügers Archiv, 189, pp. 239-242

In the 1920s, Edgar Adrian formulated the theory of neural communication that the frequency of action potentials, and not the size of the action potentials, was the basis for communicating the magnitude of the signal. His work was performed in an isolated frog nerve-muscle preparation. Adrian was awarded a Nobel Prize for his work. Adrian Nobel Prize

In the 1960s David Hubel and Torsten Wiesel demonstrated the macro columnar organization of visual areas in cats and monkeys, and provided physiological evidence for the critical period for the development of disparity sensitivity in vision (i.e.: the main cue for depth perception), and were awarded a Nobel Prize for their work.

In 1996 Dolly the sheep was born, the first mammal to be cloned from an adult cell., AnimalResearch.Info Dolly the Sheep The process by which Dolly the sheep was cloned utilized a process known as nuclear transfer applied by lead scientist Ian Wilmut. Although other scientists were not immediately able to replicate the experiment, Wilmut argued that the experiment was indeed repeatable, given a timeframe of over a year.

In 1997, innovations in frogs, Xenopus laevis, by developmental biologist Jonathan Slack of the University of Bath, created headless tadpoles, which could allow future applications in donor organ transplantation.

There has been growing concern about both the methodology and the care of animals in laboratories who are used in testing. There is increasing emphasis on more humane and compassionate treatment of other animals. Methodological concerns include factors that make animal study results less reproducible than intended. For example, a 2014 study from McGill University in Montreal, Canada suggests that mice handled by men rather than women showed higher stress levels.

In medicine

In the 1880s and 1890s, Emil von Behring isolated the diphtheria toxin and demonstrated its effects in guinea pigs. He went on to demonstrate immunity against diphtheria in other animals in 1898 by injecting a mix of toxin and antitoxin. This work constituted in part the rationale for awarding von Behring the 1901 Nobel Prize in Physiology or Medicine. Roughly 15 years later, Behring announced such a mix suitable for human immunity which largely banished diphtheria from the scourges of humankind. The antitoxin is famously commemorated each year in the Iditarod race, which is modeled after the Nome in the 1925 serum run to Nome. The success of the animal studies in producing the diphtheria antitoxin are attributed by some as a cause of the decline of the early 20th century antivivisectionist movement in the USA.Walter B. Cannon Papers, American Philosophical Society

In 1921, Frederick Banting tied up the pancreatic ducts of dogs and discovered that the isolates of pancreatic secretion could be used to keep dogs with diabetes alive. He followed up these experiments with the chemical isolation of insulin in 1922 with John Macleod. These experiments used bovine sources instead of dogs to improve the supply. The first person treated was Leonard Thompson, a 14-year-old diabetic who only weighed 65 pounds and was about to slip into a coma and die. After the first dose, the formulation had to be re-worked, a process that took 12 days. The second dose was effective.Discovery of Insulin These two won the Nobel Prize in Physiology or Medicine in 1923 for their discovery of insulin and its treatment of diabetes mellitus. Thompson lived 13 more years taking insulin. Before insulin's clinical use, a diagnosis of diabetes mellitus meant death; Thompson had been diagnosed in 1919.

In 1943, Selman Waksman's laboratory discovered streptomycin using a series of screens to find antibacterial substances from the soil. Waksman coined the term antibiotic with regards to these substances. Waksman would win the Nobel Prize in Physiology or Medicine in 1952 for his discoveries in antibiotics. Corwin Hinshaw and William Feldman took the streptomycin samples and cured tuberculosis in four guinea pigs with it. Hinshaw followed these studies with human trials that provided a dramatic advance in the ability to stop and reverse the progression of tuberculosis. Hinshaw obituary Streptomycin Mortality from tuberculosis in the UK has diminished from the early 20th century due to better hygiene and improved living standards, but from the moment antibiotics were introduced, the fall became steep so that by the 1980s mortality in developed countries was effectively zero.Is Science NecessaryAuthor: Max PerutzPage: 37-41Published 1989Publisher E.P. Dutton/NAL Penguin Inc

In the 1940s, Jonas Salk used rhesus monkey cross-contamination studies to isolate the three forms of the polio virus that affected hundreds of thousands yearly. Virus-typing of polio by Salk Salk's team created a vaccine against the strains of polio in cell cultures of rhesus monkey kidney cells. The vaccine was made publicly available in 1955 and reduced the incidence of polio 15-fold in the USA over the following five years. Salk polio virus Albert Sabin made a superior "live" vaccine by passing the polio virus through animal hosts, including monkeys. The vaccine was produced for mass consumption in 1963 and is still in use today. It had virtually eradicated polio in the US by 1965. History of polio vaccine It has been estimated that 100,000 rhesus monkeys were killed in the course of developing the polio vaccines, and 65 doses of vaccine were produced from each monkey. Writing in the Winston-Salem Journal in 1992, Sabin said, "Without the use of nonhuman animals and human (animals), it would have been impossible to acquire the important knowledge needed to prevent much suffering and premature death not only among humans but (other) animals as well."

Also in the 1940s, John Cade tested lithium salts in guinea pigs in a search for pharmaceuticals with anticonvulsant properties. The nonhuman animals seemed calmer in their mood. He then tested lithium on himself, before using it to treat recurrent mania. The introduction of lithium revolutionized the treatment of manic-depressives by the 1970s. Prior to Cade's animal testing, manic-depressives were treated with a lobotomy or electro-convulsive therapy.

In the 1950s the first safer, volatile anaesthetic halothane was developed through studies on rodents, rabbits, dogs, cats and monkeys.Raventos J (1956) Br J Pharmacol 11, 394 This paved the way for a whole new generation of modern general anaesthetics – also developed by animal studies – without which modern, complex surgical operations would be virtually impossible.Whalen FX, Bacon DR & Smith HM (2005) Best Pract Res Clin Anaesthesiol 19, 323

In 1960, Albert Starr pioneered heart valve replacement surgery in humans after a series of surgical advances in dogs. He received the Lasker Medical Award in 2007 for his efforts, along with Alain Carpentier. In 1968 Carpentier made heart valve replacements from the heart valves of pigs, which are pre-treated with glutaraldehyd to blunt immune response. Over 300,000 people receive heart valve replacements derived from Starr and Carpentier's designs annually. Carpentier said of Starr's initial advances "Before his prosthetic, patients with valvular disease would die."