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Editorial
Endocrinology, Evidence and Sherlock Holmes Ambika Gopalakrishnan Unnikrishnan, Sanjay Kalra1 CEO and Endocrinologist, Chellaram Diabetes Institute, Pune, Maharashtra, 1Department of Endocrinology, Bharti Hospital, Karnal, Haryana, India
In a famous Sherlock Holmes mystery story, the detective chases the theft of a racehorse called Silver Blaze. Holmes is, of course, helped by Dr Watson, his famous assistant.[1] The discussion between Holmes and the local policeman goes something like this: Gregory (Scotland Yard detective): “Is there any other point to which you would wish to draw my attention?” Holmes: “To the curious incident of the dog in the night-time.” Gregory: “The dog did nothing in the night-time.” Holmes: “That was the curious incident.” This simple interaction between Sherlock Holmes and the Scotland Yard detective is not as simple as it sounds. For, in this interaction, lies the clue to solving the theft. For, when a racehorse was stolen, why did the dog not bark? This led Holmes to the logical conclusion that the thief was someone the dog recognised- and eventually, this clue leads to the unravelling of the mystery. This fictional interaction, written by Sir Arthur Conan Doyle, of Holmes with Gregory has been the basis of several publications, ranging from medicine to fiction, to suggest how the “absence of an evidence” can provide meaning.[2,3] Traditionally, we feel that some facts are “certain” like the barking of a dog during the time that a crime that is committed or, the lowering of TSH when levothyroxine is given, or even, the lowering of glucose when insulin is given. But are these undisputed facts? For example, in a paper published in the New England Journal of Medicine, the authors chose to study TSH levels when thyroxine is given, and discovered that anti-helicobacter pylori therapy could help bring down the TSH further. The basis of this research was that subjects with subjects with helicobacter pylori infection had decreased absorption of thyroxine, and a Corresponding Author: Dr. Sanjay Kalra, Department of Endocrinology, Bharti Hospital, Karnal, Haryana, India. E‑mail:
[email protected]
slightly higher TSH and that treating this had beneficial effects on TSH.[4] Similarly, insulin resistance- so common today, and indeed a key pathophysiologic factor in the genesis of type 2 diabetes.[5] Such stories abound. For example, after the landmark discovery of leptin deficiency causing obesity, scientists found the common form of obesity and type 2 diabetes to be associated with high or normal leptin levels, and this paradox is being unravelled.[6] As scientists and doctors, whenever we see a patient with phenotype that is unusual, or when we see research data that does not follow our pattern of thinking - we tend to ignore the same, as it seems to us to be inconsequential (just like Gregory ignored the lack of barking by the dog in the Holmesian mystery). In our own words, it is an “outlier”. This probably indicates our preference for the normal, the traditional, and the well-established. There is a reason for that- because what is well established is likely to be true. However, is it wise to wish away an outlier? What if, like in the Holmesian story, understanding that very patient behaviour or data leads to a new line of thought? If all research were carried using well established theories- and designed to support well established facts, do we still keep the doors of medical science open for rapid progress, innovation and path-breaking discoveries? In line with this thought process, some journals have already started to question our absolute faith in the all-pervasive sanctity of the p-value in biostatistics.[7,8] At the beginning of this New Year, we, the editors, have decided to write this small piece, to support the unusual, the outlier, and the “out of the box” thinker. This is not to say that our journal is changing strategy- we continue to only accept well-designed, well researched and the highest quality papers submitted to us. However, this is only to express our hope that some of these highest quality submissions will be based on novel research questions and unusual hypotheses- of course, all designed to improve the lives of people. As India grapples with the increasing burden of obesity and type 2 diabetes, and as the focus shifts towards noncommunicable problems, the endocrine community of the country has an important role to play. Traditionally, the
© 2016 Indian Journal of Endocrinology and Metabolism | Published by Wolters Kluwer - Medknow
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Unnikrishnan and Kalra: Endocrinology, Evidence and Sherlock Holmes
endocrinologists have always given high quality specialty care. But here is a new idea, a different thought- that of the endocrinologist as a leader of medical progress. Today, more than ever before, endocrinologists need to take the lead in grappling with common problems like type 2 diabetes, obesity, and osteoporosis and thyroid disease. The solutions may lie in a strategic mix of both conventional and “different” thinking- and this middle path is important. To help take India into the next level of health, endocrinologists need to become leaders who master the middle path- and use this mastery to focus on improving patient care, research and education in their respective fields. And, as editors, we keenly observe the leadership that the endocrine community must and will provide- so that the millions suffering from endocrine illnesses may find hope, health and happiness. We look forward to this year, as being the year of the endocrinologist as a leader of healthcare progress. This would make the endocrinologist, in some way, an outlier, but in many other ways, a harbinger of positive change in health of people.
References 1.
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Doyle AC. Silver Blaze. Available from: http://etc.usf.edu/lit2go/40/ the-memoirs-of-sherlock-holmes/573/adventure-1-silver-blaze/. [Last accessed on 2015 Nov 10]. Le Fanu J. The case of the missing data. BMJ 2002;325:1490–3. Available from: https://en.wikipedia.org/wiki/The_Curious_Incident_ of_the_Dog_in_the_Night-Time. [Last accessed on 2015 Nov 10].
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Centanni M, Gargano L, Canettieri G, Viceconti N, Franchi A, Delle Fave G, et al. Thyroxine in goiter, Helicobacter pylori infection, and chronic gastritis. N Engl J Med 2006;354:1787-95. McAuley KA, Williams SM, Mann JI, Walker RJ, Lewis-Barned NJ, Temple LA, et al. Diagnosing insulin resistance in the general population. Diabetes Care 2001;24:460-4. Murugesan D, Arunachalam T, Ramamurthy V, Subramanian S. Association of polymorphisms in leptin receptor gene with obesity and type 2 diabetes in the local population of Coimbatore. Indian J Hum Genet 2010;16:72–7. Halsey LG, Curran-Everett D, Vowler SL, Drummond GB. The fickle P value generates irreproducible results. Nat Methods 2015;12:179-85. Leek JT, Peng RD. Statistics: P values are just the tip of the iceberg. Nature 2015;520:612.
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[email protected] Access this article online Quick Response Code: Website: www.ijem.in DOI: 10.4103/2230-8210.172290
Cite this article as: Unnikrishnan AG, Kalra S. Endocrinology, Evidence and Sherlock Holmes. Indian J Endocr Metab 2016;20:1-2.
Indian Journal of Endocrinology and Metabolism / Jan-Feb 2016 / Vol 20 | Issue 1
