Notes

Outline

Reading Scientific Papers Simon Hunt Dunn School of Pathology

Purposes of This Class Learn some guidelines to help you assess: Scientific content of a primary research article Style of presentation Encourage reflection on the way you currently read a paper To change your habits to improve them To read more efficiently and effectively

Levels of Engagement

AVOID CELIBACY!

A Typical Doctoral Thesis ~ 300 references 2.5 years a 10 papers per month Plus all those papers that don’t make it!

Why read in depth? To check basis of your own project Reliability of assumptions Especially those critical to the logic of your design Monitoring and comparing other approaches Sensor for possibly being scooped Assessing own lab’s approach To study important claims in related fields Technical or theoretical developments To enable mature discussion with others Develop your original viewpoint For inspiration to write well And what to avoid

The scientific literature Primary research reports Secondary Literature Summary overviews News&Views, MiniReviews, Cutting Edge Review Metadata analysis (Tertiary) (textbooks)

What to Read? At what Level? Test against purposes of reading See Levels of Engagement See Why Read in Depth Use of Bibliographic tools Citation indexing Treat big-name authors the same as little-name or no-name authors

Careful reading 1 – the question What question is being asked? How clearly stated? Sharply focussed? Is it important? Will it make an advance whichever answer is got? Is it original? What have others suggested as answers?

Careful reading 2 - design How does study design address the Q? Is it a direct or an indirect approach? If methodology were not limiting, what would be the best way? Is it compatible with what really happens biologically in the cell/ the animal/ the bug… (“in vivo” versus “in plastico” versus “in silico”)

The Scientific Method A formal set of rules for forming and testing hypotheses Usually employed loosely and often unconsciously Devise the good Q Observe closely For the unexpected as well as the anticipated Create an explanatory model That can be helpfully predictive

What is a Hypothesis? From Greek – “Foundation, Base” “Hypo” – not yet fully developed “Thesis” – a placing [what is a Hyperthesis??  Perhaps you could write one??] An informed guess about the way a process might work Predictive Needs logic, prior knowledge, insight, creativity

Testing a Hypothesis It can be disproved, never proved (Popper) Read “Pluto’s Republic”, Medawar, PB (1984) “The Logic of Scientific Discovery” – Popper, KR (1977) Must include controls

A Formal Theory A system of statements and ideas that explains a group of related facts or phenomena A set of interconnected hypotheses that Have withstood rigorous exptl testing Consistently resist scientists’ attempts to disprove them Is no longer “half-baked”

Common Study Design Faults/Oversights Seeks to confirm hypothesis by supplying an additional example Non-Popperian Uses absence of evidence as evidence of absence Accepts correlation as causation If mutant lacks a normal function, accepts that wild-type provides that function Deletion approach should be complemented by test of adding-back wild-type

Careful Reading 3 - controls Versions of the expt where everything is the same except for the single variable that is under test “Negative”: omit/inactivate/vary test material “Positive”: ensure assay system is working properly, so that lack of activity of test material is interpretable “Restorative”: reconstitution of diminished/zero activity by re-supplying normal material

Careful Reading 4 - Reproducibility Is it a big effect? “Signal:Noise” ratio Do they quantify the variance associated with the observations? Error bars Number of repetitions May be statistically significant, but is the effect of marginal magnitude? Internally self-consistent? Do different figures in the paper show same effect? Is the data selective? Is M&M detailed enough to permit replication of expt? By others “skilled in the art”?

Careful Reading 5 – Resolution of the Question Is the original Q answered? What assumptions did the authors make? Explicit.  Are these reasonable? Not stated.  Are these reasonable? Would you have made the same interpretation from those data? What remains unanswered? Are there interesting new Qs raised?

Techniques for careful reading 1 Get the gist, from Title and Abstract Carefully read for, and Identify, the Question Q Understand but do not accept what the authors consider the Answer to be Use the Introduction only if necessary It will be strongly biassed Identify the key data Table/Figure that supplies the answer Understand enough methodology to see how the data were obtained Carefully read, for controls and reproducibility

Techniques for careful reading 2 Seek data that support, extend or qualify Scrutinise other Figures or Tables Throughout, make your own annotations Probably on a printout/Xerox copy Distinguish your own “Brain-On” ideas/comments (e.g. put “ME” in front of them) from notes on the authors’ text (“THEY”) Do not merely use highlighter alone Encourages “Brain-Off” technique

Techniques for careful reading 3 Compare your interpretation with the authors’ Read Discussion Carefully read for the Design Carefully read for Conclusion How far does it resolve the Q that was posed? How far do you accept it? Make your own interpretation Minimise assumptions and dependence on other models or hypotheses – try to interpret it stand-alone

The healthy sceptic resists…. Gizmo merchants Spin doctors Temptresses

Take Home Get stuck in! Skim, yes, but also Immerse sometimes Be ready to sweat and fret as you interpret! Then you must be doing the right thing

Reading and online materials Victoria E McMillan, “Writing Papers in the Biological Sciences”. 2nd ed. Bedford Books, 1997. Robert A Day, “How to Write and Publish a Scientific Paper” 5th ed. Oryx Press, 1998 Jan Pechenik and Bernard Lamb, “How to write about Biology”, Longman, 1994 http://research.biology.arizona.edu/mosquito/willott/proj/Survive/paper.html http://online.sfsu.edu/~jareyes/physlab/labreport.html http://www.psb.ox.ac.uk/prclinks.htm http://www.biochem.arizona.edu/classes/bioc568/papers.htm http://www.hbcollege.com/student/scipaper1.html