Dick…in memoriam

Finlay MacraeDept of Colorectal Medicine and Genetics, The Royal Melbourne Hospital, AustraliaChair, InSiGHT

Colleague, mentor, visionary, inspirational leader and friend

Professor Richard Cotton.

Dick interlaced his professional life with his personal life…we all enjoyed his journey, achievements and frustrations…His life was about sharing…

Remarkably indeed, Dick brought the science of agriculture to human health

Professor Richard Cotton…in memoriamBorn November 10th 1940, Wangaratta, Victoria

• 1963 B Agr Science (Uni of Melbourne)• 1967 PhD Phenylalanine and tyrosine biosynthesis• 1967 Research Fellow John Curtin School of Medical Research, ANU, Canberra• 1968-70 Research Fellow, Clinical Research Unit, Royal Childrens’ Hospital; Dept of Genetics, Uni of Melb• 1970-71 Post doctoral Fellow, Scripps Clinic• 1971-73 Post doc Fellow, MRC Laboratory of Molecular Laboratory, Cambridge UK*• 1973-74 Senior Research Fellow, Dept of Genetics, Uni of Melbourne• 1975- continued to develop monoclonal antibodies as tools in analysis of enzyme function• 1979-80 Sabbatical, Oxford, UK• 1983- Deputy Director, Birth Defects Research Institute, Uni of Melb• 1986-87 Sabbatical, Oxford*• 1991-6 NHMRC (Senior) Principal Research Fellow• 1992 Initiated the journal Human Mutation• 1996 Established Genomic Disorders Research Centre, Uni of Melb• 1997- Executive, Human Genome Organization• 2003 Gen mapping monograph editor, NCBI, Washington, • 2005 Awarded Member of the Order of Australia• 2006- Convenor, initiator, Scientific Director, Human Variome Project

Dick…truly international reach….

Indeed, Dick had extraordinary international reach….• Extraordinary number of advisory and their roles with international organizations (18)• Faculty and Research team reviews (6)• Journal Abstract reviewer (13)• Editorial Boards (16)• Editorial advisory boards (2)• Journal Editor (1 – Human Mutation)• Invited lectureships and chairs: (145 international; 47 Australian)• Conference organizations: (International 95; Australian 22)• Postgraduate student supervisors and post docs: (66) • Conferences organized (International 95; Australian 22)• Patents (8)

Dick understood that science happens when minds meet …in meetings, not just over the internet…

Prof Richard Cotton…publish!! Publish!!• Referred original journal articles 35• Refereed journal reviews 9• Chapters of books 21• Other publications and influential citations 109• Editorials 13• Commissioned reports 5 • Abstracts 73

Dick new that the best way to communicate and spread his vision is to publish and engage with editors..

Dick reached out to China…believing China was both in need and had the resources to respond to his vision…

Dick’s work will impact science for ever…the discovery of the power of monoclonal antibodies• Conceived, planned and executed experiments designed to decide if

none, one, or both parental IgGs are produced after two Ig producing cell lines are fused. As the answer was both, these experiments laid the practical and theoretical foundation of monoclonal antibodies by Kohler in Milstein’s lab in Cambridge. This work attracted the Nobel prize and a $15Bpa (2000) industry

Application of monoclonal antibodies…•Detailed examination of a series of antibodies to phenylalanine hydroxylase found one which reacts with tryptophan hydroxylase. This antibody has been used to map serotinergic neurones in the human brain seen for the first time, and to enumerate their decrease in Parkinson’s Syndrome and Alzheimer’s Disease

Mutation Detection meetings spawned an international reputation and community interested in mutation detection

“As the best of these methods only detected 70% of all point mutations, I decided to attempt to develop a better method whilst in Oxford where I was fortunate in my quest.

I developed a chemical method the chemical cleavage method (CCM) which has the potential to detect all mutations”

Professor Richard Cotton…his greatest legacy…Born November 10th 1940, Wangaratta, Victoria• 1963 B Agr Science (Uni of Melbourne)

• 1967 PhD Phenylalanine and tyrosine biosynthesis

• 1967 Research Fellow John Curtin School of Medical Research, ANU, Canberra

• 1968-70 Research Fellow, Clinical Research Unit, Royal Childrens’ Hospital; Dept of Genetics, Uni of Melb

• 1970-71 Post doctoral Fellow, Scripps Clinic

• 1971-73 Post doc Fellow, MRC Laboratory of Molecular Laboratory, Cambridge UK*

• 1973-74 Senior Research Fellow, Dept of Genetics, Uni of Melbourne

• 1975- continued to develop monoclonal antibodies as tools in analysis of enzyme function

• 1979-80 Sabbatical, Oxford, UK

• 1983- Deputy Director, Birth Defects Research Institute, Uni of Melb

• 1986-87 Sabbatical, Oxford*

• 1991-6 NHMRC (Senior) Principal Research Fellow

• 1992 Initiated the journal Human Mutation

• 1996 Established Genomic Disorders Research Centre, Uni of Melb

• 1997- Executive, Human Genome Organization

• 2003 Gen mapping monograph editor, NCBI, Washington,

• 2005 Awarded Member of the Order of Australia

• 2006- Convenor, initiator, Scientific Director, Human Variome Project

If for nothing else, Dick’s legacy to InSiGHT is inestimable…but it could be multiplied 26000 times…

Bryony A. Thompson, Amanda B. Spurdle, Marc Greenblatt, John-Paul Plazzer, Kiwamu Akagi, Fahd Al-Mulla, Bharati Bapat, Inge Bernstein, Gabriel Capella, Johan den Dunnen, Desiree du Sart, Mark Farrel, Susan Farrington, Ian Frayling, Thierry Frebourg, David Goldgar, Chris Heinen, Elke Holinski-Feder, Maija Kohonen-Corish, Suet Yi Leung, Annika Lindblom, Kristina Lagerstedt, Alexandra Martins, Pal Moller, Monika Morak, Minna Nystrom, Aurelie Fabre, Paivi Peltomaki, Marta Pineda, Ming Qi, Rajkumar Ramesar, Lene Rasmussen, Brigitte Royer-Pokora, Rodney Scott, Rolf Sijmons, Sean Tavtigian, Carli Tops, Thomas Weber, Juul Wijnen, Michael Woods, Finlay Macrae, Maurizio Genuardi

How does the InSiGHT Variant Interpretation Committee operate? Established in Yokohama, 2007International

Society for Gastrointestinal Hereditary Tumours

5-tiered Classification Criteria:www.insight-group.org/criteria/

Standardized & normalized variant classification scheme

Thompson, Spurdle et al. Nat Genet 46, 107-15 (2014).

LOVD submission classifications vs InSiGHT VIC variant classifications

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27/07/12

Dick’s greatest challenge was marketing his message about the need for the Human Variome Project

Nevertheless, Dick was an inspiration for humanity..

Professor Finlay MacraeChair, InSiGHTRegional Scientific Director, Human Variome ProjectFOD*

Above all, Dick was a happy family man, who loved his family, and all that life brings…

Vale Dick!