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Putting '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

[email protected] Linus Pauling (1901-1994)

• American , biochemist, activist, author, and educator. • One of the founders of the fields of quantum and . • Awarded the in Chemistry in 1954 and the in 1962. • Only two people have been awarded Nobel Prizes in different fields, the other being Marie Skłodowska-Curie ( 1903, Chemistry 1911). 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 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! 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 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… What came out of it?

• I invented a classification scale: Maximum Output O utcomes

1993

1994 started project yearby 2015 Dec at Outcomes 1995 1996

1997 2015) Dec at (as 1998 1999 Year started project 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 Outcomes (as at Dec 2015)

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

74% of projects produced no publications 35 31.9 30

25 21.1 20 17.8 15 11.4 10 9.2 4.3 5 1.6 2.7 Proportion of outcomes (%) of outcomes Proportion 0 Thought Started Moved Produced A publication Several Built on Especially about forward some data publications good Maximum Output O utcomes

1993 R=0.000

1994 started project yearby 2015 Dec at Outcomes 1995 1996

1997 2015) Dec at (as 1998 1999 Year started project 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 Work done (as at Dec 2015) 69% of work produced no publications 30 27.9

25 22.4 20 16.6 15 10.6 10 7.7 5.8 6.6

Proportion of workProportion (%) 5 2.4 0 Thought Started Moved Produced A publication Several Built on Especially about forward some data publications good Work and outcome (as at Dec 2015)

Work and outcome

Especially good Built on Several publications R=0.719 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) Work and outcome (as at Dec 2015)

Mean (95% CI) work and publication status

7 Average work for 5 ‘Especially good’

- 10) 6 8.70 P=0.002 5 4 T-test 3 5.26 P <0.00001 2 2.95 1

JK's Work (EstimateJK's Work 0 0 Average work for all Average work for all non-published published Time first to publication

1994 1998 2000 2003 2004 2006 Started project 2007 2008 1994 2009 2011 First publication 2013 2000 2013 2013 Project start (Year) 2013 Time to first publication = 6 years 2013 2013 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 of first paper Time first to publication

35 Mean 3.5 years 30 (95% CI 2.9, 4.0) 25 20 15 10 5

Proportion of projects (%) of projects Proportion 0 0 1 2 3 4 5 6 7 8 Time to first publication (years) Philip Hench (1896 – 1965)

• American physician awarded the Nobel Prize for or in 1950 • Discovery of cortisone and its application for the treatment of rheumatoid arthritis 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

1941 Thought Compound E might help 1984 Specialist Registrars call for proper investigation of glucocorticoid actions

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)

West’s ‘lost’ report (6) 1995 ARC Study results published (7)

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 1985 1983 1995 1929 1948 1960 1984 1941 1959 1967 1996 1986 1997

1995 Schaardenburg (26) 2005 Choy (34) 1955 Empire (4) Additional 1995 van Gestel (27) 2005 Wassenberg (33) Studies 2002 van Everdingen (28) 2005 Goekoop (32)

2004 Suponitskaia (29) 2004 Capell (30) 2005 Svensson (31) 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! Professor John Kirwan [email protected]

Academic Rheumatology Unit