The Future of Lab A nimal Pathology

The Future of Lab Animal Pathology

Mouse

2007: We need more mouse pathologists !!!!

Cardiff RD. Pathologists needed to cope with mutant mice. Nature. 2007 May 31;447(7144):528.

Barthold SW, Borowsky AD, Brayton C, Bronson R, Cardiff RD, Griffey SM, Ince TA, Nikitin AY, Sundberg J, Valli VE, Ward JM. From whence will they come? - A perspective on the acute shortage of pathologists in biomedical research. J Vet Diagn Invest. 2007 Jul;19(4):455-6.

Schofield PN, Brown SD, Sundberg JP, Arends M, Warren MV, Dubus P, Ellender M, Fiette L, Rozell B, Quintanilla-Martinez L, Raspa M, Song JY, van der Valk M, McKerlie C.PRIME importance of pathology expertise. Nat Biotechnol. 2009 Jan;27(1):24-5.

Warren MV, Studley ML, Dubus P, Fiette L, Rozell B, Quintanilla-Martinez L, Raspa M, Breuer M, Song JY, Gates H, Brown SD, Schofield PN. An impending crisis in the provision of histopathology expertise for mouse functional genomics. J Pathol. 2009 Jan;217(1):4-13..

“…lack of trained pathologists and a lack of trainees entering the field”

“…a significant proportion of vacant posts across Europe remain unfilled for 6 months or more, due to lack of qualified applicants, lack of funding”

2009: Really, you do need us….

Nature. 2010 May 27;465(7297):410. Mouse project to find each gene's role.Abbott A.

International Mouse Phenotyping Consortium (IMPC)The knockout strains will then be put through rigorous, systematic phenotypic screens, which will check for physical and behavioural differences. The information will be stored in a purpose-built, open-access database

Knockout science: massive mouse project to provide window into human diseases.Hampton T.JAMA. 2011 Nov 9;306(18):1968

2010-2012: The role of pathology in high throughput phenotyping

Dis Model Mech. 2012 Jan;5(1):19-25. doi: 10.1242/dmm.008334. Epub 2011 Oct 25. Exploring the elephant: histopathology in high-throughput phenotyping of mutant mice.Schofield PN, Vogel P, Gkoutos GV, Sundberg JP.

“….not only the authors but also the reviewers and editors often have neglected to consult a comparative pathologist during the evaluation of such manuscripts. “

Ince TA, Ward JM, Valli VE, Sgroi D, Nikitin AY, Loda M, Griffey SM, Crum CP, Crawford JM, Bronson RT, Cardiff RD. Do-it-yourself (DIY) pathology. Nat Biotechnol. 2008 Sep;26(9):978-9;

2008: Ummmm….don’t do this at home….

http://goanimate.com/videos/08QjkLMH-psc

Lamborghini Macaque

Giles J. Animal experiments under fire for poor design. Nature. 2006 Dec 21;444(7122):981

2006: Hmmm…there seems to be a problem of translation…

Unreliable researchTrouble at the labOct 19th 2013http://www.economist.com/news/briefing/21588057-scientists-think-science-self-correcting-alarming-degree-it-not-trouble

December 2, 2011 Scientists’ Elusive Goal: Reproducing Study Resultshttp://www.omsj.org/corruption/scientists-elusive-goal-reproducing-study-results

2011: WALL STREET JOURNAL

2013: THE ECONOMIST

2013 Couzin-Frankel J. When mice mislead. Science. 2013 Nov 22;342(6161):922-3

Baker D, Lidster K, Sottomayor A, Amor S. Reproducibility: Research-reporting standards fall short. Nature. 2012 Dec 6;492(7427):4

Nat Rev Neurosci. 2013 May;14(5):365-76.Power failure: why small sample size undermines the reliability of neuroscience.Button KS, Ioannidis JP, Mokrysz C, Nosek BA, Flint J, Robinson ES, Munafò MR.

Publication bias in reports of animal stroke studies leads to major overstatement of efficacy. Sena ES, van der Worp HB, Bath PM, Howells DW, Macleod MR. PLoS Biol. 2010 Mar 30;8(3)

2005: Ioannidis JP. Why most published research findings are false. PLoS Med. 2005 Aug;2(8):e124.

2010: the CONSORT guidelines.Adopted by many clinical journals: the requirements to report whether and how the studies were blinded and randomized, how sample size was determined, how data were handled, and other important determinants of quality clinical science

Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. Plos Med 2010;7:e1000251

2010: Improved design and reporting for human clinical trials

2010: ARRIVE guidelines. Br J Pharmacol. 2010 Aug;160(7)For animal studies

Howells DW, Sena ES, Macleod MR. Bringing rigour to translational medicine. Nat Rev Neurol. 2013 Nov 19

Landis SC et al. A call for transparent reporting to optimize the predictive value of preclinical research. Nature. 2012 Oct 11;490(7419):187-91

Announcement: Reducing our irreproducibility. Nature 496, 398 (25 April 2013)CHECKLIST FOR REVIEWERS: INCL ARRIVE GUIDELINES

2013: Improved design and reporting for animal trials

Mice are not small humans A mouse is not a mouse is not a mouse

Academic environment favors positive results prolific publicationtight budgets promote small sample sizes

Journals: do not enforce consistent design/interpretation standards

Vet pathologists: need genetics/cell bio/research training