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
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
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
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.proxyum.researchport.umd.edu/nature/journal/v214/n5090/pdf/214764
a0.pdf
Chapter 8: Hunter and Griffith
 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?”
Nature vol 215 September 2, 1967
http://www.nature.com.proxyum.researchport.umd.edu/nature/jou
rnal/v215/n5105/pdf/2151043a0.pdf
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
Patricia Merz
 Graduate student
Nature vol 306 Dec 1, 1983
 Wanted to try to look at
the infectious agent




Electron microscope
“Sticks” were denser in
later stages of the disease
Later called scrapieassociated fibrils (SAF)
Were they causing the
disease or were they a
cause of the disease?
http://www.nature.com.proxyum.researchport.umd.edu/nature/journal/v306/n5942/pdf/306474a0.pdf
Merz, Somerville, Gibbs, Gadjusek- 1984
http://www.jstor.org.proxyum.researchport.umd.edu/stable/1693519
Naming The Infectious Agent
Science-1982
http://www.jstor.org.proxyum.researchport.umd.edu/stable/pdfplus/1687927.pdf?acceptTC=true&acceptTC=true&jpdConfirm=true
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 Prize1997
 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 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