One person’s take on how to write a paper in the life sciences

1. One person’s take onhow to write a paper in the life sciences John Boothroyd, PhD Professor of Microbiology and Immunology (among other things) With edits and comments by John Pringle Professor of Genetics

2. Focus here on papers.But good writing is equally important in grants, reports, and indeed almost every career!!And most of the principles are the same.

3. WHY publish? • Make your work public for the greater good (otherwise, no point!) • Establish your reputation as a scientist • Establish your reputation as a grantee who delivers value for money • It FEELS so good!

4. What really matters • Accuracy of the data presented!! (Without this, nothing else matters much.) • Rigor and clarity with which the data are described and interpreted • Intellectual honesty in relating the work to the published literature • “A reputation takes years to build and seconds to lose…”

5. Why write well? • If the writing is clear and mistake-free, there is a natural tendency to suppose that the research has been done with equal care. (And vice versa!!) • Good writing makes potential readers (1) more likely to read your story, (2) more likely to understand it, and (3) less likely to be annoyed with you. (All of which are good!)

6. Sad (or maybe not) but True • A mediocre scientist who writes very well is likely to have a successful independent career. • A brilliant scientist who writes poorly is unlikely to have a successful independent career (although s/he may do well as a student and postdoc).

7. First steps • Begin way before the work is complete to identify “logic holes” AND so that the job is less daunting later • Decide on a tentative title to help crystallize what the paper is really about • Decide on target journal and look carefully at its format (print out a paper) • Sketch out figures and tables (rough) • Decide on authors (with collaborators)

8. Authors • ALL those who: • contributed data that are presented • served an important, on-going intellectual role • Not those who just funded the work, offered a few helpful suggestions, or provided a reagent or two • Not those who just “need another publication”  (even your best friends!) • Order is the responsibility of the senior author • Joint first and last authors possible • Don’t be petty. (Remember, “A reputation takes years to build and seconds to lose…”)

9. Titles (1) • Succinct statement of conclusions rather than methods (unless it's a methods paper!) • But … must be FOREVER and UNDENIABLY TRUE based on DATA SHOWN (and how many conclusions reach that point??) • OK to temper with “Evidence for…”, “Putative”, “Apparent”, “Role of…”

10. Titles (2) Which would you prefer? • “Mapping effector genes by microarray analysis of human foreskin fibroblast cells infected with F1 progeny of a cross between two strains of the obligate intracellular Apicomplexan parasite Toxoplasmagondii.” OR • “Toxoplasmaco-opts host gene expression by injection of a polymorphic kinase homologue.”

11. J. Rosner (1990) Nature 345: 108

15. Good Titles! • Campbell,…, Boothroyd (1984) Nature “Apparent discontinuous transcription of Trypanosomabrucei variant surface-antigen genes” • Sutton ad Boothroyd (1986) Cell “Evidence for trans-splicing in Trypanosomes”

16. Abstract (must stand alone!) • Short and sweet (often a limit by journal) • 1-2 sentences of background • 1-2 sentences to say what was done • 2-3 sentences of what was observed • 1-2 sentences of conclusions reached • Usually no references (but depends on journal format) • No unexplained abbreviations • No unsubstantiated conclusions • Carefully choose key words for search discovery

17. Example Abstract “The majority of known Toxoplasmagondii isolates from Europe and North America belong to three clonal lines that differ dramatically in their virulence, depending on the host [=intro]. To identify the responsible genes [=goal], we mapped virulence in F1 progeny derived from crosses between type II and type III strains, which we introduced into mice [=materials and methods]. Five virulence (VIR) loci were thus identified, and for two of these, genetic complementation showed that a predicted protein kinase (ROP18 and ROP16, respectively) is the key molecule [=results]. Both are hypervariablerhoptry proteins that are secreted into the host cell upon invasion [=more results]. These results suggest that secreted kinases unique to the Apicomplexa are crucial in the host-pathogen interaction [=conclusion].” Saeij et al., (2006) Science 314:1780-1783

18. Introduction • Big picture first • Describe current state of knowledge • Cite selectively and strategically (but include competitors' (= reviewers?) work! • Don’t discuss or anticipate results • End with just 1-2 sentences summarizing what you did and what you found • Remember, you’re telling a story!

19. Example End of Intro “To determine how different strains of Toxoplasma cause different disease, we mapped genes responsible for virulence in mice. We show that a family of polymorphic protein kinases are injected into a host cell during invasion and that these play a major role in strain-specific differences in virulence.”

20. Grammar • Don’t use long strings of nouns as modifiers • [“Toxoplasma-infected human foreskin fibroblast monolayers were incubated with…”] • Hyphenate nouns used to modify • [“Toxoplasma-infected cells”; “cell-cycle genes”; etc.] [But NOT “well-established” or "genes that control the cell-cycle.”] • Learn to use punctuation well (it MATTERS!) • For example, commas go at natural pauses (as you would in speaking), including before conjunctions

21. The genes, that control this response, were identified, without resorting to genetics. The genes that control this response were identified without resorting to genetics. The genes? that control this response? were identified? without resorting to genetics? Penguin press

22. The genes, that control this response, were identified, without resorting to genetics. The genes that control this response were identified without resorting to genetics. The genes? that control this response? were identified? without resorting to genetics? Penguin press

23. Materials and Methods • Goals: • enable others to understand and repeat your experiments (focus on KEY details) • Do NOT describe standard techniques that could be done many ways and wouldn’t alter the results • how you introduced a transgene probably isn’t important; exactly what you introduced is • DO describe crucial details of: • all strain details • cloned genes (via primers is often easiest) • antibodies used (how raised or catalogue number and supplier) • database versions, etc.

24. Results Every paragraph is a mini-paper: • Introduction – background and context (why you’re doing it) • Materials and methods – what was done • Results – what was seen • Interpretation/conclusion – what it means (first-order conclusion) • First person OK but use sparingly (e.g., when it is a personal thought or action, such as "We conclude…")

25. Tips for Results • Begin the first or second sentence of most or even every paragraph with “To…” • Middle is, “The results (Fig. 3) show…[literal description of what is seen]” • End with, “These results suggest that…” • Use past tense in describing what was done or observed, “To …., the parasites were transfected with…” • Use present tense in stating what we learn, “These results indicate that a mutation in xxx is responsible for …” OR conclusions that have been well vetted previously and are generally accepted in the field.

26. “To…” examples Anderson, et al. (2009) Eukaryotic Cell 8:398-409

27. More Tips for Results • Phrases to avoid: • “In order to…” Use “To…” • “Whether or not…” Just use “Whether…” • “Since…” [“Since the parasites were transfected with a Cre-expressing plasmid…” – Use “As” or “Because” to avoid confusion about whether “since” refers to time or causality] • “The data waswere used to…” • Hierarchy of strength for last sentences…: “The results prove/show/demonstrate > indicate > strongly suggest > argue for > suggest > support the notion > are consistent with > are not inconsistent with …

28. Some General Tips • Make it flow – tell a STORY: it is YOUR job to make it comprehensible to the reader • Say what you mean with the simplest words • Avoid jargon: e.g., “the gel was run”, “the oligonucleotide was kinased”, “the sequence was blasted against” • Avoid needless words (but don’t be shy about using the ones you need!)

29. More Tips • Don’t use comparative adjectives in a vacuum: • The mutants were relatively virulent… • The mutants were more virulent (LD50 20-fold less) than wild type… • Avoid emotive adjectives: • Incredibly, amazingly, astonishingly … • But do key in reader to whether result is expected or not: • Surprisingly, Interestingly, Importantly, Similarly, As expected, Consistent with the results described above [But NOT "Consistently,…"!!]

30. Figure Legends • Title (or first sentence) should state the experiment being presented OR (when possible) the point being made. • Then describe what was done (but don't duplicate M & M!) and what is shown. • Don’t discuss the results or give any interpretation (beyond what is in the title; i.e., NO “these results show…”)

31. More on Figure Legends • EVERY detail of figure must be explained: • Arrows, boxing, hatching, triangles, … • Use “Details as in Fig. 2” wherever truly identical

32. Figures • Use big fonts so legible when reduced • When possible, label so reader can understand without having to read the figure legend • But still label each part “A”, “B”, etc. (for ease of reference in the text), and still write a careful and complete legend! • Label gel lanes by description at top and by number at bottom (for easy reference)

33. More on Figures • Use arrows to highlight key aspects • Think about whether color really helps (often it doesn’t or indeed actually hurts) + at some journals it is expensive! • Scale to journal column size, if possible

34. Discussion (1) • Start with one or two sentence (NO MORE) of overall recap, “The results presented here show that…” • Use to discuss second-order and big-picture conclusions of the work (what it all means, implications, etc.) • Do not go back over all the results, only discuss those that truly need further discussion

35. Discussion (2) • Share your wisdom with the reader but don’t abandon rigor or feed the dogma mill: • “The results strongly suggest… However, we cannot exclude the possibility that …” • Let the data speak for themselves – avoid hyperbole and claims of “This is the first…” [save that for the cover letter!]

36. Acknowledgements • Be inclusive (think hard about this) • Be generous (“cast your bread upon the waters,…”!) (there's no cost!) • Be careful about acknowledging grant/fellowship support • Can acknowledge grant support of an investigator who is not an author (e.g., if one of her/his students or postdocs IS an author)

37. Concluding Comments • Write at peak times and in solid chunks (remember just how important this is!). • Proof-read (and spell-check) before you pass it to anyone else. Twice, at least! • Have a lab-mate read and micro-edit it. • Have someone outside your field read it. • Enjoy telling a story and communicating the fruits of your labor. • "Hard writing makes easy reading!"

38. And lastly… • Write assuming that 10 years from now the most aggressive, obnoxious trial lawyer will wave your paper in your face and challenge you on every word of every sentence!

41. Thanks to my group, who happily put up with my obsessive-compulsive editing!