A tribute to Dick Cotton from Finlay Macrae. Part 1 of the inaugural Richard Cotton Memorial lecture.

1. Dick…in memoriam
Finlay Macrae
Dept of Colorectal Medicine
and Genetics,
The Royal Melbourne Hospital,
Australia
Chair, InSiGHT
Colleague, mentor, visionary,
inspirational leader and friend
Professor
Richard
Cotton.

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

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

4. Professor Richard Cotton…in memoriam
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

5. Dick…truly international reach….

6. 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)

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

8. 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

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

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

11. 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

12. 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

13. 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”

14. 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

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

17. 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

18. 5-tiered Classification Criteria:
www.insight-group.org/criteria/
Standardized & normalized variant
classification scheme
Thompson, Spurdle et al. Nat Genet 46, 107-15 (2014).

19. LOVD submission classifications vs
InSiGHT VIC variant classifications
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
No known
pathogenicity
Probably no
pathogenicity
Unknown Probably
pathogenic
Pathogenic
Class 5b
Class 5a
Class 4
Class 3
Class 2
Class 1
24%
15%
Submitter classification
Finalclassification

20. InSiGHT Mismatch Repair Database
Number of monthly database views
0
5000
10000
15000
20000
25000
30000
35000
40000
45000
50000
2008Jul
2008Sep
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2013Sep
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Date

21. InSiGHT Mismatch Repair Database
Number of unique database visitors
0
500
1000
1500
2000
2500
2008Jul
2008Sep
2008Nov
2009Jan
2009Mar
2009May
2009Jul
2009Sep
2009Nov
2010Jan
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2014Mar
2014May
2014Jul
2014Sep
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2015Jan
DAte

22. 27/07/12

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

24. Nevertheless, Dick was an inspiration for
humanity..
Professor Finlay Macrae
Chair, InSiGHT
Regional Scientific Director,
Human Variome Project
FOD*

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