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Brain Trust Chapters 8 & 9

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

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Brain Trust Chapters 8 & 9

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  1. Brain Trust Chapters 8 & 9 Taylor Goldbeck

  2. 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 • 1921-1923- Creutzfeldt writes three papers describing 5 patients with CJD • 1934/1935- Jean Cuille and Paul-Louis Chelle inject brain slurry from scrapie sheep into a sheep and observe scrapie symptoms twenty-two months later • 1936- Gordon produces the louping ill vaccine • 1937/1938- Sheep injected with louping ill vaccine show signs of scrapie • 1947- Scrapie appears in the US • TME was identified in Wisconsin by Hartsough • 1955- Zigas arrives in New Guinea and observes Kuru in the Fore tribe • 1957- 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

  3. Timeline of What We Know So Far • 1958- USDA sends Hadlow to Compton to research Scrapie • 1959- Hadlow sees Gajdusek's kuru show at the Wellcome Medical Museum • Hadlow sends a letter to Gajdusek describing the similarities between scrapie and kuru • 1961- 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 mink • 1964- Gajdusek holds a conference at NIH describing kuru, scrapie, CJD and related diseases • 1965- The chimps injected with Kuru begin to show Kuru symptoms • 1967- Alpers had a “eureka” moment about cannibalism and kuru • 1968- Gibbs, Gajdusek and Alpers publish a paper in Science publish their findings • 1976- Gajdusek wins Nobel Prize

  4. Chapter 8: Rivalry and Scrapie Strains • Compton vsMoredun • “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

  5. Chapter 8: Dr. TikvahAlper http://www.nature.com.proxy-um.researchport.umd.edu/nature/journal/v214/n5090/pdf/214764a0.pdf • Dr. TikvahAlper- 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

  6. Chapter 8: Hunter and Griffith Nature vol 215 September 2, 1967 http://www.nature.com.proxy-um.researchport.umd.edu/nature/journal/v215/n5105/pdf/2151043a0.pdf • Gordon 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?”

  7. Dr. Stanley Prusiner • Described 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

  8. Patricia Merz Nature vol 306 Dec 1, 1983 http://www.nature.com.proxy-um.researchport.umd.edu/nature/journal/v306/n5942/pdf/306474a0.pdf • Graduate student • Wanted 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?

  9. Merz, Somerville, Gibbs, Gadjusek- 1984 http://www.jstor.org.proxy-um.researchport.umd.edu/stable/1693519

  10. Naming The Infectious Agent Science-1982 http://www.jstor.org.proxy-um.researchport.umd.edu/stable/pdfplus/1687927.pdf?acceptTC=true&acceptTC=true&jpdConfirm=true

  11. 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?

  12. 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?

  13. How it works! • Domino Effect • Susceptibility • 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

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