Five centuries after Aristotle, the physician and philosopher Galen came to the world at Pergamum in AD 129. Galen practiced and mastered extensively the art of dissection on many living animal species, but like Aristotle his dissection excluded human bodies. At that time, religious feelings prevented the dissection of human bodies, a custom that was protected under the Roman legal system. In his treatise on physiology, he kept "faith in God, creator of both the body and soul and governing upon life, its strength and weaknesses, health and diseases." He will give medicine a virtual religious aura that was to conquer the Renaissance period and Western Europe.

Vivisection was not popular during the Middles Ages, but during Renaissance, Galen, Hipprocates, Dioscorides and Celsus were newly translated in Latin and became highly influential.Before William Harvey (1578-1658), many arguments from prestigious anatomists were storming the logic of the Galenic scheme about the circulation of blood, which had remained an enigma for centuries, but they did not prove the blood flow through the lungs. Realdus Colombus (1516-1559) was stating the lack of porosity in the interventricular septum of the heart and proposed in 1560 that the blood flowed from the right heart through a pulmonary circulation to the left heart. Other anatomists thought that the pulmonary artery was filled with blood and not with air and that the mitral valve allowed the blood flow in only one direction. Cracks were looming in the Galenic armor. The rebellion cost the life of Serventus in 1553, who was burnt in Geneva after expressing his ideas about the circulation of blood and for which he was judged as a heretic by the Calvinist Church.

The revolutionary Andreas Vesalius (1514-64) was a Belgian anatomist and physician whose dissections of the human body and descriptions of his findings helped correct misconceptions prevailing since the ancient times. He wrote 'De Humani Corporis Fabrica,' which comprised seven volumes on the structure of the human body and which caused him to flee the University of Padua in 1546, when he knew that the Church was after him. Based on vivisection, William Harvey published his theories in 1628 in his famous "On the Motion." Harvey often performed dissections and vivisection of various animals in order to verify the statements made in the accepted textbooks of his time. He elucidated the circulation of the blood through performing experiments in animals. Since experimenting on human bodies could have led him to the stake, he resorted to the use of animals.

In 1637, René Descartes agreed with Harvey's ideas about the circulation of the blood since there was seemingly a connection between Harvey's ideas and Descartes' theories of man as a machine. René Descartes' opinions led him to argue that animals had no soul and could not have consciousness. This theory was critical at that time and promoted the idea that animals could not possibly suffer; animals were only machines and could experience neither pain nor pleasure. Thus, Descartes seemed to resolve the theological question as why God should allow animals to suffer so irremediably, under man's dominion, since they were not responsible for Adam's original sin. This theory encouraged many people to be brutal to animals.

The practice of vivisection continued until late in the nineteenth century. Humane reaction to vivisection started to be vocal in the 18th century and emerged in Great Britain and spread throughout Europe. In striking contrast to the materialistic view of Descartes, cognitivists such as the French philosopher Pierre Gassendi during the 17th century, believed that humans are no more or no less than beasts but rather that the beasts are more like us because animals have sensory organs. Charles Darwin imagined and explained that animals could be different not in their nature but more in degree. He understood that if there was such an obvious physical continuity between species, there was a also a psychological dimension common to animals. Not content to assimilate men as mere animals, he stormed the world when he championed the theory that men were the descent of other existing primates. As usual, the Church and his opponents went after him.

After the 17th century, vivisection, despite the humane movement, continued in small fraternity of callous scientists and France became the center of vivisection led by François Magendie, Claude Bernard who brought vivisection to an art of a long and painful death. They will give a definite aura to animal experimentation emblematic of the new scientific age that was emerging. During the past centuries, it was accepted that the laws supporting life could not be of the same nature than the ones taking place in inanimate objects. Vitalism was another theory that was used to explain the incredible properties of living organisms; the vital forces. Since antiquity, different forces have come into play in organic and inorganic elements. In the former category, vital forces are the cause of the order and balance, which both allow organs and their function towards their goal; life. In the latter category, the laws of physics are enough to explain the various phenomena related to the inorganic sphere. The laws of vitalism and the laws of physics acted in opposition to each other so that the body could be endowed with extraordinary capacities.

Contesting the prejudices and values of his peers, Magendie also championed the necessity to add evidence to support a theory and rejected the fashion to hold true an opinion without a proof. In this context, Magendie decided to apply a more objective method to experimental physiology in order to link the facts to their interpretation. Unfortunately, living animals would serve as tools to establish his new ideas. Magendie was interested in the mechanical properties of blood vessels, but he never proved their ability to constrict. He was intrigued by the mechanism of coagulation and the potentials of blood transfusion. His pioneer studies of the effects of drugs on various parts of the body led to the scientific introduction into medical practice of compounds such as strychnine and morphine. However, those substances were already known and used a long time ago. In 1822, he confirmed and elaborated the observation made by the Scottish anatomist Sir Charles Bell that the anterior roots of the spinal nerves had a motor function, while the posterior roots served to communicate sensory impulses.

Claude Bernard, Magendie's student, studied induced forms of diabetes in dogs and noticed a connection with the wall of the fourth ventricle in the brain but he never understood the role of the pancreas in diabetes and he thought that it was a disease of the liver instead. Not sooner than the mid 20th century, the liberation of neuropeptides from the nervous cells, transported through the blood stream, up to the liver where they find their targets, would give the final explanation of this induced and transient hyperglycemia. However, he isolated the substance causing the presence of sugar in the liver, glycogen. Claude Bernard, after cutting, burning, and poisoning countless of animals, finally understood the importance of the internal balance of the cells and that the animals possess control systems, which adjust their interactions and exchanges with their surroundings in such a way that the physical state and chemical composition of the internal environment remain essentially constant. These ideas were taken further in 1929 by John Barcroft (England, 1872-1947) in lectures he gave when he visited Harvard, and by W.B. Cannon (America, 1871-1945) who introduced the word 'homeostasis.'

Then, Louis Pasteur championed changes in hospital practices to minimize the spread of disease caused by microbes. That was a time when surgeons and physicians were not familiar with aseptic methods and sterilization, did not even bother washing their hands during their regular pratice. Microorganisms, such as viruses could not be observed and therefore ignored; a simple act like washing one's hands before or after examining a patient was viewed as squeamish mannerism and needless ritual by many. Post-surgical infections leading to septicemia, amputation and deaths were so common that many patients could not survive a simple surgery. The acceptance of aseptic procedures was a revolution in medical practice and saved many more lives than any known treatment at that time.

The birth of modern surgery from now on, possible thanks to anesthetics, aseptic methods and later antibiotics in the mid 20th-century, owe little if not nothing to animal experimentation. Pasteur re-discovered that weakened forms of a microbe could be used as an immunization against more virulent forms of the microbe. However, vaccination (inoculation) was known centuries ago, until Jenner Edward actually tested the first vaccine against smalpoox in 1796. It was a happy success. Then, Pasteur found agents so small that they could not be seen under a microscope, thus suggesting much later the world of viruses that transmitted rabies. Of course, Pasteur could not see viruses under his optic microscope. Anton van Leenwenhoek (1632-1723) discovered the microscope and logically his observations led him to see for the first time microorganisms.

As a result of his intense work, Pasteur developed techniques to vaccinate dogs against rabies and to treat humans bitten by allegedly rabid dogs, although rabies were difficult to diagnose and rarely transmitted to people. It's beyond doubt that the first vaccines were dangerous to administer to patients. Satisfactory tests in rabbits and dogs were no evidence that vaccines would actually be safe and efficacious. Even today, the vaccine is given only if there are strong assumptions that rabies may develop. In fact, it is too dangerous to vaccinate people against this rare infectious disease. Pasteur also developed pasteurization, which is a process by which harmful microbes in perishable food products are destroyed using heat, but without destroying the food. In the treatment and prevention of rabies, Louis Pasteur discovered the method for attenuating virulent microorganisms that is the basis of vaccination. Then, he developed vaccines against chicken pox, anthrax and swine erysipelas by reproducing the works of others, without crediting their contribution.

Under the introduction of new methods of asepsis and the revolutionary cell theory of the German pathologist Rudolf Virchow, expounded one year earlier than Darwin's 'On the Origin of Species,' the disease occurred at the level of the cell and a normal and healthy cell could become diseased. His ideas led to the discoveries of cell division and differentiation. The cell theory was a remarkable perception of the fabrics of nature. Thus, cells from plants or animals had properties in common and from species to species they retain basic features. It followed, in the minds of the experimenters, that animal cells might be mimicking human cells, in the same way as twins look like the same. Virchow's insight also propelled the use of animals in modern medical science, straying away form clinical observation and human-based investigation. Animals would be use on a large scale to "reproduce" what was already known in patients in order to "prove" the original observation. From now, as the old Europe was losing its scientific aura, the emerging scientific and medical elite in North America would set out to build the new foundations of animal-based experimental medicine.