brain trust chapters 8 & 9
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Brain Trust Chapters 8 & 9. Taylor Goldbeck. Timeline of What We Know So Far. 1700s - Farmers report sheep with scrapie -like symptoms 1913 - Creutzfeldt observes a patient with CJD 1918 - McFadyean publishes a landmark paper on scrapie - PowerPoint PPT PresentationTRANSCRIPT
TAYLOR GOLDBECK
Brain Trust Chapters 8 & 9
1700s- Farmers report sheep with scrapie-like symptoms1913- Creutzfeldt observes a patient with CJD1918- McFadyean publishes a landmark paper on scrapie1921-1923- Creutzfeldt writes three papers describing 5 patients with CJD1934/1935- Jean Cuille and Paul-Louis Chelle inject brain slurry from scrapie sheep
into a sheep and observe scrapie symptoms twenty-two months later1936- Gordon produces the louping ill vaccine1937/1938- Sheep injected with louping ill vaccine show signs of scrapie1947- Scrapie appears in the US
• TME was identified in Wisconsin by Hartsough1955- Zigas arrives in New Guinea and observes Kuru in the Fore tribe1957- Gajdusek arrives in New Guinea and observes Kuru
• Gajdusek sees the similarities between CJD and Kuru• Gajdusek and Zigas write two articles about Kuru• The possibility of cannibalism as the causes is considered but dismissed
Timeline of What We Know So Far
1958- USDA sends Hadlow to Compton to research Scrapie1959- Hadlow sees Gajdusek's kuru show at the Wellcome Medical Museum
• Hadlow sends a letter to Gajdusek describing the similarities between scrapie and kuru1961- Lindenbaum and Glasse arrive in New Guinea
• Ann and John Lyle publish a paper on the possible relationship between cannibalism and kuru
1963- Gibbs and Gajdusek inject a chimp with Kuru as well as other animals. They begin working at Patuxent.
• A veterinarian in Idaho reports signs of a neurological disease in Mink. It became clear that rendered cows were used as feed for the mink.
1963- Hadlow shows TME is transmissible by injecting mink brain slurry into another mink1964- Gajdusek holds a conference at NIH describing kuru, scrapie, CJD and related diseases1965- The chimps injected with Kuru begin to show Kuru symptoms1967- Alpers had a “eureka” moment about cannibalism and kuru1968- Gibbs, Gajdusek and Alpers publish a paper in Science publish their findings1976- Gajdusek wins Nobel Prize
Timeline of What We Know So Far
Chapter 8: Rivalry and Scrapie Strains
Compton vs Moredun“The Battle of Washington”Alan Dickinson with Richard Chandler at
Compton Identified more than twenty scrapie “strains” Strain 22C and 22A
Results and conclusions Strain 22A outcompeted strain 22C Showed scrapie strains competed with each other in
the same host animal
Chapter 8: Dr. Tikvah Alper
Dr. Tikvah Alper- 1967 Radiobiologist Tried to kill scrapie
with ultraviolet and gamma radiation
Major idea: Said scrapie was too small to be a virus and proposed scrapie could be replicated without DNA
http://www.nature.com.proxy-um.researchport.umd.edu/nature/journal/v214/n5090/pdf/214764a0.pdf
Chapter 8: Hunter and GriffithGordon Hunter
Institute for Research on Animal Diseases at Compton
Tried to isolate infectious agent using enzymes so it could be purified
Had more success than Dr. Alper with enzymes that break down proteins over radiation
Conclusion: Proteins are essential to scrapie
Mathematician J.S Griffith “Is a self-replicating protein
completely out of the question?” http://www.nature.com.proxy-
um.researchport.umd.edu/nature/journal/v215/n5105/pdf/2151043a0.pdf
Nature vol 215 September 2, 1967
Dr. Stanley PrusinerDescribed as very
competitive and eager (“publish or perish”)
Had a patient with CJD “I began to think that defining
the molecular structure of this elusive agent might be a wonderful research project”
Worked with Hadlow on scrapie
1968- Traveled to New Guinea and worked with Kuru patients with Gadjusek
Research led him to believe infectious agent was a protein and not a virus
Patricia Merz
Graduate studentWanted to try to look
at the infectious agent Electron microscope “Sticks” were denser in
later stages of the disease
Later called scrapie-associated fibrils (SAF)
Were they causing the disease or were they a cause of the disease?
Nature vol 306 Dec 1, 1983
http://www.nature.com.proxy-um.researchport.umd.edu/nature/journal/v306/n5942/pdf/306474a0.pdf
Merz, Somerville, Gibbs, Gadjusek- 1984
http://www.jstor.org.proxy-um.researchport.umd.edu/stable/1693519
Naming The Infectious Agent
http://www.jstor.org.proxy-um.researchport.umd.edu/stable/pdfplus/1687927.pdf?acceptTC=true&acceptTC=true&jpdConfirm=true
Science-1982
Backlash
Gajdusek: “I pointed out to [Prusiner] that I would give the disease agents a proper name when we were sure what the molecular structure was… It was a clever political move on his part to jump the gun”
Do you think it is fair that Prusiner named the infectious agent?
Prion Protein (PrP) Prusiner and Leroy Hood
Determined sequence and structure of the prion protein
PrP was found in normal cells, but with different properties. Normal: easily digested with
certain enzymes Scrapie Protein: Resistant to
these enzymes, different shape Prusiner receives the Nobel
Prize-1997 After all Prusiner has done
with Hood, has your decision changed on whether you think he had the right to name the infectious agent?
How it works!Domino EffectSusceptibility
There are different mutations in the prion protein that make individuals more or less susceptible to CJD or Kuru
Mutations at position 129 Met/Met 129 lethal mutation
(40% European and US population)
Val/Val 129 lethal mutation (13% European and US population)
Different shapes of prion protein have been found that affect susceptibility