“The best way to have a good idea is to have lots of ideas.” - PDF Document

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  1. Putting Linus Pauling's dictum into practice: “The best way to have a good idea is to have lots of ideas.” John Kirwan Emeritus Professor of Rheumatic Diseases John.Kirwan@Bristol.ac.uk

  2. Linus Pauling (1901-1994) • American chemist, biochemist, peace activist, author, and educator. • One of the founders of the fields of quantum chemistry and molecular biology. • Awarded the Nobel Prize in Chemistry in 1954 and the Nobel Peace Prize in 1962. • Only two people have been awarded Nobel Prizes in different fields, the other being Marie Skłodowska-Curie (Physics 1903, Chemistry 1911).

  3. Linus Pauling (1901-1994) The Pauling Principle: • The best way to have a good idea is to have a lot of ideas and throw away the bad ones. This implies at least two things: • one must be willing to generate many ideas • one must be willing to generate bad ideas

  4. John’s ideas • Since late 1994 I have made a separate folder in my computer storage for each idea I started on • I found 186!

  5. John’s ideas • I went back through every folder and discovered • The date of the first file entry • How much work I did on that idea/project • What came out of it

  6. How much work? • From the number of files stored, and from memory, I estimated this on a 1 to 10 scale 1 – Just an initial proposal or email exchange, no follow up files 10 – Lots and lots of files, emails, notes of meetings, records of draft grant applications, draft papers, hours of soul searching…

  7. What came out of it? • I invented a classification scale:

  8. Outcomes (as at Dec 2015) Outcomes at Dec 2015 by year project started Maximum Output 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 Year project started

  9. Outcomes (as at Dec 2015) Cumulative proportion of projects (%) 100 Especially good Built on Several publications A publication Produced some data Moved forward Started Thought about 90 80 70 60 50 40 30 20 10 0

  10. Outcomes (as at Dec 2015) 74% of projects produced no publications 35 31.9 Proportion of outcomes (%) 30 25 21.1 20 17.8 15 11.4 9.2 10 4.3 5 2.7 1.6 0 Thought about Started Moved forward Produced some data A publication Several publications Built on Especially good

  11. Outcomes (as at Dec 2015) Outcomes at Dec 2015 by year project started Maximum Output R=0.000 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 Year project started

  12. Work done (as at Dec 2015) 69% of work produced no publications 30 27.9 Proportion of work (%) 25 22.4 20 16.6 15 10.6 10 7.7 6.6 5.8 5 2.4 0 Thought about Started Moved forward Produced some data A publication Several publications Built on Especially good

  13. Work and outcome (as at Dec 2015) Work and outcome Especially good Built on R=0.719 Several publications A publication Produced some data Moved forward Started Thought about 0 1 2 3 4 5 6 7 8 9 10 JK's Work (Estimate 0-10; 0.5 = ongoing)

  14. Work and outcome (as at Dec 2015) Mean (95% CI) work and publication status 7 Average work for 5 ‘Especially good’ 8.70 P=0.002 JK's Work (Estimate 0-10) 6 5 4 T-test P <0.00001 3 5.26 2 2.95 1 0 Average work for all non-published Average work for all published

  15. Time first to publication 1994 1998 2000 2003 2004 Project start (Year) 2006 Started project 1994 2007 2008 2009 2011 First publication 2000 2013 2013 2013 Time to first publication = 6 years 2013 2013 2013 1993 1994 1995 1996 1997 1998 1999 2000 2001 Year of first paper 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

  16. Time first to publication 35 Proportion of projects (%) Mean 3.5 years (95% CI 2.9, 4.0) 30 25 20 15 10 5 0 0 1 2 3 4 5 6 7 8 Time to first publication (years)

  17. Philip Hench (1896 – 1965) • American physician awarded the Nobel Prize for Physiology or Medicine in 1950 • Discovery of cortisone and its application for the treatment of rheumatoid arthritis

  18. Glucocorticoid timeline - 1929 to 2009 From Philip Hench’s idea to a treatment recommendation by NHS in 80 years 1929 Jaundice and pregnancy relieve symptoms (1) 1938 Lecithin from adrenals tried 1984 Specialist Registrars call for proper investigation of glucocorticoid actions 1941 Thought Compound E might help 1985 Widespread condemnation of glucocorticoids but also widespread use (9) 1948 Compound E tried (1,2) 1986 ARC Study proposal published (11) 1959, 1960 MRC /Nufield Glucocorticoid study published (3,5) 1995 ARC Study results published (7) West’s ‘lost’ report (6) 1997 COBRA Study (22) 1983 Harris (8) 1998 ARC Follow up (17) 2007 Cochrane meta analysis published (25) 2009 NICE Guidelines (23) 2007 2009 1938 1983 1985 1995 1929 1948 1960 1984 1941 1959 1967 1986 1997 1996 1995 Schaardenburg (26) 2005 Choy (34) 1955 Empire (4) Additional Studies 1995 van Gestel (27) 2005 Wassenberg (33) 2002 van Everdingen (28) 2005 Goekoop (32) 2005 Svensson (31) 2004 Suponitskaia (29) 2004 Capell (30)

  19. The key message... • Pauling was right! • Thinking of and testing ideas that do not work out is an integral part of successful academic activity. • These are not failures – they are part of the process!

  20. Professor John Kirwan John.Kirwan@Bristol.ac.uk Academic Rheumatology Unit