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Richard GH Cotton: He may have been a bit before his time - Michael Watson

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A tribute to Dick Cotton from Michael Watson. Part 2 of the inaugural Richard Cotton Memorial lecture.

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Richard GH Cotton: He may have been a bit before his time - Michael Watson

  1. 1. Richard (Dick) GH Cotton He May Have Been a Bit Before His Time Michael S. Watson American College of Medical Genetics and Genomics
  2. 2. Career with Threads to Major Healthcare Innovations • A career that: ▫ focused on the prevention and treatment of genetic disorders. ▫ impacted the development of many of the healthcare programs most valued by the public today such as newborn screening ▫ will impact the integration of genetics and genomics into healthcare well into the future.  mutation detection  mutation databases  world-wide partnerships
  3. 3. 1960s – PKU • Dick began his career studying biochemical genetics in bacteria and synthesis of amino acids • This led to his developing a novel affinity adsorbent to phenylalanine hydroxylase (1968) to aid in the study of structure and function of the enzyme ▫ Doctoral thesis – “Studies on the enzymes concerned with phenylalanine and tyrosine biosynthesis” • He went on to do fundamental postdoc work on monoclonal antibodies that led to a Nobel Prize for Physiology or Medicine award to his mentor in 1984 ▫ Today we have monoclonal antibody treatments such as Rituximab
  4. 4. 1970 – 80s • Returned to research in amino acids ▫ Generated sufficient protein sequence to allow Woo’s initial cloning of phenylalanine hydroxylase (PAH) • Appreciated the role of BH4 in PAH enzyme activity ▫ First DHPR deficient patient was found in Australia (1975)  Developed first DHPR blood assays that became basis for diagnosis at the gene product level  Conceived the use of tetrahydrobiopterin (BH4) loading tests to identify individuals with severe variants in PAH ▫ Led to Kuvan (BH4)as a PKU treatment for some patients
  5. 5. 1990s • Founded journal Human Mutation in 1992 to catalog variation and relationships to disease severity
  6. 6. Late 1990s -2000s Frustrated by Difficulties in Studying PAH and DHPR Genes • Recognized that an underlying structural susceptibility of mismatched DNA strands could be exploited by demonstrating that they could be exposed by enzymatic or chemical cleavage ▫ Opened up the opportunity to detect every single base variant in a gene • Led to a career in mutation detection methods • Led development of HUGO group on mutation detection ▫ Formed HUGO Database Initiative that ultimately became the Human Genome Variation Society (HGVS) • Led development by HGVS (2001) of standards for variant nomenclature
  7. 7. Enzyme Cleavage Method for Mutation Detection
  8. 8. Inspired by “Completion” of Human Genome Project • Recognized need for international effort to systematically: ▫ Collect ▫ Curate ▫ Interpret ▫ Share information on genetic variation • • Led to the formation of HVP in Melbourne in 2006
  9. 9. Late 2000s - • Encouraged and cajoled colleagues to adopt data collection tools (LSDBs) and to share
  10. 10. • A remarkable career that ended before he could see the fruits of his work in projects like Global Globin 2020 and the BRCA Challenge Cheers to Dick

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