My word

How to ask questions(in 10 easy steps)Mark M. Davis

In learning to navigate a particularfield of science, students arecontinually fed large chunks ofinformation and asked to solveproblems, but little or no time isspent learning how to ask questions,at least in any formal way. This mayjust be a pedagogical oversight, butI suspect it reflects the fact thatquestioning is an inherentlysubversive activity and deeplyresented in most societies, especiallyby the elites as they have the most tolose if things get out of hand. In anyevent, I have compiled my ownidiosyncratic list of rules to live byand hope others may join in.

1. “Don’t follow leaders (watch theparking meters)” — Bob Dylan

The ‘leaders’ in any givenfield have their own agendasand blindspots. There are alsoinvariably crowds of peoplefollowing them and the competitionis fierce. At the same time you don’thave all day to get going ondeveloping alternatives.

2. Don’t follow the crowd.While most people and sheep

are more comfortable in herds,in science it is very difficult todo anything interesting whenyou’re trampling over the sameground as everyone else. Best toformulate an unique questionand/or approach.

3. Don’t ask ‘What’s the next step?’,ask ‘What’s missing from this picture?’

The next step is already beingdone by the leaders and theirfollowers, so unless things haveground to a halt over sometechnicality (as they frequently do)you’re better off working onsomething completely different.

4. “To make importantdiscoveries, ask importantquestions” — Peter Medawar

This means doing yourhomework and really finding holesin dogma or in The Big Picture thatneed attention.

5. “Leave your stepping stonesbehind, you’d better use your sense.

Forget what you have gathered fromcoincidence.” — Bob Dylan

Generals fight the last war,scientists recycle the last ‘big’experiment. When I was a student,the cloning of antibody genesanswered many of the outstandingquestions in that field, leading someto think that cloning any gene wouldanswer all the questions associatedwith that protein.

Questioning is an inherentlysubversive activity and deeplyresented in most societies

When the first MHC proteinwas crystallized and revealed ata glance what ‘antigenpresentation’ and ‘MHC restrictedrecognition’ was all about, therearose a similar belief that X-raycrystal structures would reveal all.Neither of these conclusions heldup under scrutiny at the timeand they are patently ludicrousin retrospect.

6. Expect opposition to any reallyimportant question if it falls outside of‘conventional wisdom’.

“Are we lost, Dad, I arsked sweetly. Shut up he explained.” — Ring

Lardner JrIt seems to be human nature to

resent the questioning offundamental assumptions. Thus youmust expect trouble, even in science,if you’re on to something reallyimportant. The good news is that areally convincing experiment orthree can turn the tide, whereas ahalf-baked one will have the

opposite effect. Again careful studyand experimental design are key.

7. Know your tools, know yourself.Especially now in the era of ‘kits’

for all occasions, it is tempting to notreally know the basis of manyprocedures or technical areas. Whileno one should try to mastereverything, it is very important toknow the technical nuts and bolts(and the ancient literature) of a fewtechniques that are central to yourinterests. Thus when the kit fails oryou want to go beyond it, you can atleast try some things. (The later partof the title is self-explanatory).

8. Failure is educational.Getting acquainted with an area

of experimental science can belikened to beating your head againstthe wall in a darkened room — oneemerges bruised but reasonablyknowledgeable about the roughfeatures of the wall. In science ouronly sensory tool is experimentationand ‘failed’ experiments, ifexecuted properly, provide insightinto what is productive for aparticular ‘wall’. Eventually one getsan ‘intuition’ as to which approachesare likely to be productive andwhich are not.

9. Don’t subscribe to ‘the technique-of-the-month club’.

Use what is appropriate to solve aproblem that you care about,whether high or low tech, bruteforce, or whatever.

10. ‘The art of the possible’Science, as well as many other

things, makes progress based onwhat is possible versus what mighthappen in a dream world. If availableor long-term approaches cannotanswer at least one questiondefinitively in the area of interest,don’t waste your time.

Address: Howard Hughes Medical Instituteand, Department of Microbiology andImmunology, Stanford University School ofMedicine, Stanford, California 94305, USA,but presently visiting the John RadcliffeHospital Institute for Molecular Medicine inOxford, UK.

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