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Timeline for Webpage
(Major researcher(s) or author(s) in parentheses following the statement.)
1730: Description of ovine (sheep) TSE, Scrapie, in British and European sheep. It spread
to many animals because of selective breeding directed toward improving the quality of
wool.
1755: A discussion took place in the British Parliament about the economic effects of
scrapie and the need for government to do something about the disease.
1920: The first human form of a TSE (Transmissible Spongiform Encephalopathy) was
described in Germany (Creutzfeld-Jakob Disease). It was called TSE because the key
pathology was holes in brain tissue. (Creutzfeldt/Jakob)
1936: French veterinarians intentionally transmitted scrapie to uninfected sheep. At the
same time there was an accidental outbreak of scrapie in England in several hundred
sheep that had been immunized with a vaccine prepared from the brain tissue of sheep,
some of which were later discovered to have had scrapie. The study of this outbreak was
published by Gordon in 1946.
1936: Gerstmann-Sträussler-Scheinker (GSS) was first described.
1946: Gordon published his observations on the accidental 1936 outbreak of Scrapie in
the UK.
1947: Scrapie was found in the US in sheep that were imported from the UK.
1947: TSE first described in mink, see in the US, known as Transmissible Mink
Encephalopathy (TME).
1950s: Kuru (shaking disease) was first described in humans in Papua, New Guinea
(Gajdusek).
1954-9: The similiarity between CJD & Kuru and between Kuru & Scrapie was
recognized. (Klatzo or Hadlow)
1954-9: TSEs were believed to be the effect of a "slow virus" that acted slowly with a
long latency period; proposed in 1954 and 1959. (Sigurdsson or Hadlow)
1959: Scrapie was proposed to be similar to Kuru by an American veterinarian.
1960: UV radiation that would destroy nucleic acids was found to have no effect on the
infectivity of scrapie. (Alper)
1961 and 1963: Scrapie was successfully transmitted to mice.
1963: Kuru was successfully transmitted to chimpanzees after incubation periods of 1820 months.
1966: Kuru infected brain was shown to be infectious to chimpanzee brain which lead to
the end of canabalism and control of Kuru in New Guinea (Gajdusek, Gibbs, Alpers)
(Gajdusek Won the Nobel Prize for this work in 1976)
1966: Ionizing radiation that would destroy nucleic acids was found to have no effect on
the infectivity of scrapie. (Tikvah Alper, Haig and Clarke)
1967: Griffith suggested 3 modes of disease spreading that are possible without nucleic
acids, including the protein-only hypothesis, which is central to the current knowledge
about prions.
1967: TSEs were found in wild ungulates of the United States, which are known as
Chronic Wasting Disease (CWD) of deer and elk.
1968 and 1969: CJD and GSS were successfully transmitted to experimental animals.
(Gibbs; Gibbs and Gadjusek)
1975: Scrapie incubation time was shown to be 50% shorter in Syrian hamsters than in
mice. (Marsh and Kimberlin)
1976: Nobel prize awarded to Gajdusek for TSE work.
1982: Prusiner names “prions” (Won Nobel Prize in 1997).
1982: purified fragment of the prion protein (PrP 27-30) was shown to have Scrapie
infectivity, which laid the groundwork to prove that a protein (not a bacterium or virus)
was the infectious agent in TSEs (Prusiner or Bolton.)
1982: A protein was found that was present only in scrapie infected brains, not healthy
brains. (Prusiner)
1982: The term “Prion” was first coined. (Pruisner)
1983: Prion accumulation in neuronal tissue of CJD and other TSEs was proven
(McKinley)
1983: Prusiner demonstrated that PrP 27-30 was present in amyloid plaques in the brain
tissue of humans and other animals infected with TSEs.
1985: The gene encoding PrP was found in the human genome.
1985: The amino acid sequence of PrPc was found to be the same as that of PrPsc, but
conformation was shown to be different.
1985: Pitsham Farm syndrome of "mad cows" was discovered on a British farm.
1985: US stopped importing beef from the UK.
1985: Children who had been injected with 'contaminated' hormones eventually
developed CJD in their 20's. The first four cases were not identified until after ~27,000
children are injected worldwide since 1963. Through this a link between CJD and
contaminated growth hormone was realized. Now genetically engineered growth
hormone is used to treat dwarfism.
1986: BSE (“Mad Cow”) was first verified in the UK.
1986: FFI first described.
1988: The UK mandated the destruction of BSE stricken cows, and BSE cases must now
be reported.
1988: A ruminant to ruminant feed ban was introduced to prohibit feeding to cattle the
rendered remains of other animals that might include BSE infected cattle and Scrapie
infected sheep.
1989: US banned the import of ruminants and ruminant products from BSE infected
countries, and all cattle that were imported from the UK between 1981 to 1989 were
being watched (only 4 were alive at the end of 2000).
1989: The hereditary linkage of human prion diseases to PrP mutations described
(HSIAO)
1989: The mutation that causes GSS was discovered in the PrP gene. (Prusiner)
1989-1992: An undetected virus was proposed as the source of TSE’s. (Manuelidis and
Pocchiari)
1990: A surveillance team was setup in Britain to ascertain possible links between BSE
and CJD.
1990: TSE was found in cats. The transmission was likely caused by feeding meat and
bone meal containing BSE or prion-contaminated bovine tissues.
1992: The BSE epidemic began to decline in UK.
1992: A TSE was found in a zoo monkey (marmoset). Transmission was likely caused
by feeding BSE containing foods.
1993: PrP knockout mice were found to not get TSEs when infected with PrPsc. (Aguzzi)
1994: The first case of vCJD was reported. (Disease established in 1995.) There are
currently at least 101 reported, confirmed deaths, and some people with the disease are
still alive. Evidence suggests that this disease is “mad cow” in humans, contracted by
consuming infected beef.
1994: The in vitro addition of PrPsc to isolated radiolabeled *PrPC was shown to recruit
radiolabled PrPc to the PrPSC precipitate. (Caughey)
1994: Transgenic mice with PrP gene containing the mutation that causes GSS were
shown to develop spontaneous TSE. (Prusiner)
1995: Several cases of CJD were described in unusually young patients, and extensive
amyloid plaques found in the brain tissue. Because of this vCJD was established as a
unique form of CJD.
1996: A cause and effect link was proposed between BSE and vCJD. (Will)
1997: A second Nobel Prize was awarded for TSE work (Prusiner).
1997: The US banned all import of rendered products of all species that came from
Europe.
1997: A ruminant to ruminant feed ban was introduced in the US to prevent the chance of
an epidemic of BSE in US cattle.
1997: When brain grafts of PrPC neurons were put into PrP knockout mice and the brains
were subsequently infected with Scrapie the results were that TSE developed only in
grafted tissue. (Aguzzi)
2000: A total of 87 cases of vCJD were described in Britain with 3 other cases outside the
UK (France & Ireland).
2001: As of April 2001 all cattle that were slaughtered in the US must be certified that
they have not been fed ruminant MBM. Almost 200,000 diseased cattle dead and
4,500,000 asymptomatic cattle had been destroyed in the UK.
2003: BSE was reported in Canada, although there is still none in US. The outbreak in
Canada has apparently been eliminated.
Bibliography:
CJD Insight. A short history of transmissible spongiform encephalopathy. URL
http://www.cjdinsight.org/Deana/history.html. (07 December 2003).
The College of St. Scholastica. Prions Proteinaceous Infectious
Particles TSE Transmissible Spongiform Encephalopathy PrPC vs. PrPSC. URL
http://216.239.41.104/search?q=cache:HyS2b5cHo8J:www.css.edu/USERS/pstein/CHM3430/Prions.ppt+%22prion+history%22&hl=e
n&ie=UTF-8. (7 December 2003).
New Scientist.com. Timeline: The rise and rise of BSE. URL
http://www.newscientist.com/hottopics/bse/bsetimeline.jsp. (07 December 2003).
University of Illinois at Champaign-Urbana Department of Animal Sciences. 20 July
2001. An Historic Timeline of Important Events Related to the Discovery, Development
and Understanding of TSEs. URL
http://w3.aces.uiuc.edu/AnSci/BSE/Index_Timeline.htm. (07 December 2003).
.
University of Illinois at Champaign-Urbana Department of Animal Sciences.
July 20, 2001. Human Spongiform Encephalopathies. URL
http://w3.aces.uiuc.edu/AnSci/BSE/Human_TSEs.htm. (07 December 2003).
V.S.E.F. Library of Medicine. Prion Diseases. URL
http://www.vlomnepal.com/downloads/PrionDiseases.pdf. (07 December 2003).