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History of animal testing

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One of Pavlov’s dogs with a saliva-catch container and tube surgically implanted in his muzzle. Pavlov Museum, 2005

The history of animal testing goes back to the writings of the Greeks in the third and fourth centuries B.C., with Aristotle (384-322 B.C.) and Erasistratus (304-258 B.C.) among the first to perform experiments on living animals.[1] Galen, a physician in second-century Rome, dissected pigs and goats, and is known as the "father of vivisection." [2]

Early debate

For philosophical issues relating history of ethics in animal rights see Animal Rights.

In 1655, physiologist Edmund O'Meara is recorded as saying that "the miserable torture of vivisection places the body in an unnatural state."[3][4] O'Meara thus expressed one of the chief scientific objections to vivisection: that the pain that the subject endured would interfere with the accuracy of the results. On the other side of the debate, those in favor of animal testing held that experiments on living animals were necessary to advance medical and biological knowledge. Many of the early objections to animal testing came from another angle — many people believed that animals are inferior to humans and thus so different that any results obtained from animals would be inapplicable to humans.[4]

In 1822, in the British parliament, Richard Martin MP piloted the first parliamentary bill in the world to give animals a degree of protection in law. This first bill related to farm animals. The first to regulate animal experimentation in Britain was the Cruelty to Animals Act (1876). One of the people who campaigned to see the bill introduced was Charles Darwin (1809-1882). He said, in a letter of March 22, 1871 to Professor Ray Lankester: "You ask about my opinion on vivisection. I quite agree that it is justifiable for real investigations on physiology; but not for mere damnable and detestable curiosity. It is a subject which makes me sick with horror, so I will not say another word about it, else I shall not sleep to-night." The bill remained on the statute books until the introduction of the Animals (Scientific Procedures) Act (1986).

Both pro- and anti-animal vivisection positions could create substantial popular emotions as early the early 1900s, as the Brown Dog affair showed, in which English medical students repeatedly clashed by the hundreds with opponents of animal vivisections.

Basic science advances

In the 1600s, William Harvey described the movement of blood in mammals. In the 1700s, Antoine Lavoisier, used a guinea pig in a calorimeter to prove that respiration was a form of combustion, and Stephen Hales measured blood pressure in the horse. 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 strong 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. [5]

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. [6]

In the 1960s David Hubel and Torsten Wiesel demonstrated the macrocolumnar organization of visual areas in cats and monkeys, and provided physiological evidence for the critical period for the development of disparity sensitivity in vision (ie: 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.

Medical advances

Insulin was isolated from dogs in 1922, and revolutionized the treatment of diabetes.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.[7] Salk's team created a vaccine against the strains of polio in cell cultures of Rhesus monkey kidney cells. The vaccine was made publically available in 1955, and reduced the incidence of polio 15-fold in the USA over the following five years.[8] 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 USA by 1965.[9] 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 for each monkey.

Also in the 1940s, John Cade tested lithium salts in guinea pigs in a search for pharmaceuticals with anticonvulsant properties. The animals seemed calmer in their mood. He then tested lithium on himself, before using it to treat recurrent mania.[10] The introduction of lithium revolutionized the treatment of manic-depressives by the 1970s. Prior to Cade's animal testing, manic-depressives were treated with lobotomy or electro-convulsive therapy.

In the 1950's the first safer, non-volatile anaesthetic halothane was developed through studies on rodents, rabbits, dogs, cats and monkeys.[11] 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.[12]

In 1960, Albert Starr pioneered heart valve replacement surgery in humans after a series of surgical advances in dogs.[13] 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 gluteraldehyde 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".[14]

In the 1970s, leprosy multi-drug antibiotic treatments were developed first in armadillos, then in humans. In 1996 the anti-viral AIDS drug, Tenofovir, had its anti-retroviral efficacy evaluated in Rhesus monkey studies at the University of Washington Regional Primate Research Center.[15][16]

Throughout the twentieth century, research that used live animals has led to many medical advances and treatments for human diseases, such as: diphtheria vaccine,[17] organ transplant techniques and anti-transplant rejection medications,[18][19][20][21][22] the heart-lung machine,[23] heart replacement valves,[24] insulin for treatment of diabetes,[25][26] antibiotics like penicillin,[27] and whooping cough vaccine.[28]

Presently, animal experimentation continues to be used in research that aims to solve medical problems from Alzheimer's disease,[29] multiple sclerosis[30] spinal cord injury,[31] and many more conditions in which there is no useful in vitro model system available.

Veterinary advances

A veterinary surgeon at work with a black cat.

Animal testing for veterinary studies accounts for around five per cent of research using animals. Treatments to each of the following animal diseases have been derived from animal studies: rabies,[17] anthrax,[17] glanders,[17] Feline immunodeficiency virus (FIV),[32] tuberculosis,[17] Texas cattle fever,[17] Classical swine fever (hog cholera),[17] Heartworm and other parasitic infections.[33]

Basic and applied research in veterinary medicine continues in varied topics, such as searching for improved treatments and vaccines for feline leukemia virus and improving veterinary oncology.

Currnet debate

Those who oppose animal research and testing point out the following facts: harm has been caused to humans when relying on animal testing. Drugs considered "safe" after animal tests have been found to actually harm humans (Vioxx, Thalidomide etc.). The premise is that it's impossible to extrapolate data from studying one species and apply it to another. Simple examples of the differences between species include the following: 1) aspirin kills cats; 2) chocolate, onions, grapes and raisins kill dogs; 3) avocado and fumes from non-stick coatings (when overheated) kill birds; and 4) goats can eat strychnine. Those in favor of animal tests have still not been able to adequately address these basic differences between species and why, in light of these basic differences, the public should trust any animal research data.

See also

Notes

  1. ^ Cohen and Loew 1984.
  2. ^ "History of nonhuman animal research", Laboratory Primate Advocacy Group.
  3. ^ Ryder, Richard D. Animal Revolution: Changing Attitudes Towards Speciesism. Berg Publishers, 2000, p. 54.
  4. ^ a b "Animal Experimentation: A Student Guide to Balancing the Issues", Australian and New Zealand Council for the Care of Animals in Research and Teaching (ANZCCART), retrieved December 12, 2007, cites original reference in Maehle, A-H. and Tr6hler, U. 1987. Animal experimentation from antiquity to the end of the eighteenth century: attitudes and arguments. In N. A. Rupke (ed.) Vivisection in Historical Perspective. Croom Helm, London, p. 22
  5. ^ [1] O. Loewi (1921) "Uber humorale Ubertragbarkeit der Herznervenwirkung. I." Pflugers Archiv, 189, pp. 239-242
  6. ^ [2] Adrian Nobel Prize
  7. ^ [www.post-gazette.com/pg/05093/481117.stm] Virus-typing of polio by Salk
  8. ^ [3] Salk polio virus
  9. ^ [4] History of polio vaccine
  10. ^ [5] John Cade and Lithium
  11. ^ Raventos J (1956) Brit J Pharmacol 11, 394
  12. ^ Whalen FX, Bacon DR & Smith HM (2005) Best Pract Res Clin Anaesthesiol 19, 323
  13. ^ Portland surgeon receives top medical prize - OregonLive.com: Breaking News Updates
  14. ^ The Scientist : Blogs
  15. ^ PMPA blocks SIV in monkeys
  16. ^ PMPA is tenofovir
  17. ^ a b c d e f g A reference handbook of the medical sciences. William Wood and Co., 1904, Edited by Albert H. Buck.
  18. ^ Carpentier A et al. (1969) J. Thoracic Cardiovasc. Surg. 58: p. 467
  19. ^ Carrel A (1912) Surg. Gynec. Obst. 14: p. 246
  20. ^ Williamson C (1926) J. Urol. 16: p. 231
  21. ^ Woodruff H & Burg R (1986) in Discoveries in Pharmacology vol 3, ed Parnham & Bruinvels, Elsevier, Amsterdam
  22. ^ Moore F (1964) Give and Take: the Development of Tissue Transplantation. Saunders, New York
  23. ^ Gibbon JH (1937) Arch. Surg. 34, 1105
  24. ^ Starr A (1961) J. Thoracic Cardiovasc. Surg. 42, 673
  25. ^ Pratt J H (1954) A reappraisal of researches leading to the discovery of insulin. J. Hist. Med. 9, 281
  26. ^ Macleod J (1922) Insulin and diabetes, Brit. Med. J. 2: p. 833
  27. ^ Fleming A (1929) Brit J Exper Path 10, 226
  28. ^ Medical Research Council (1956) Br. Med. J. 2: p. 454
  29. ^ Geula C, Wu C-K, Saroff D, Lorenzo A, Yuan M, Yankner BA (1998) Aging renders the brain vulnerable to amyloid β protein neurotoxicity, Nature Medicine 4: p. 827
  30. ^ Jameson BA, McDonnell JM, Marini JC & Korngold R (1994) A rationally designed CD4 analogue inhibits experimental allergic encephalomyelitis, Nature 368: p. 744
  31. ^ Lyuksyutova AL, Lu C-C, Milanesio N (2003) Anterior-posterior guidance of commissural axons by Wnt-Frizzled signaling. Science 302, 1984.
  32. ^ Pu R, Coleman J, Coisman J, Sato E, Tanabe T, Arai M, Yamamoto JK. btype FIV vaccine (Fel-O-Vax FIV) protection against a heterologous subtype B FIV isolate. J Feline Med Surg. (2005) 7(1):65-70, PMID 15686976
  33. ^ Dryden MW, Payne PA. Preventing parasites in cats. Vet Ther (2005) 6:260-267, PMID 16299672

Further reading