CHRISTMAS 2015

Siddharta Mukherjee’s three laws of medicineHow medicine always defies lawgivers

Richard Lehman senior advisory fellow

UK Cochrane Centre, Oxford OX2 7LG, UK

The Laws of Medicine is an arresting title for a very small book.1It follows the author SiddhartaMukherjee’s The Emperor of AllMaladies,2 an equally arresting title for a very large book. Bothare a delight to read and adopt a similar style. Real clinicalstories are turned into parables and aphorisms that illustratevarious aspects of real clinical medicine. In that way they notonly resonate with clinicians but, more importantly, offer a widereadership the opportunity to understand and share in the deepissues of how medicine advances and how medical decisionsare made.Anyone who tries to lay down laws for medicine is bound to beaccused of hubris. But there is a gentle irony in Mukherjee’stitle, which he immediately subverts with the subtitle “FieldNotes from an Uncertain Science.” At the end of the book heexplicitly throws off the cloak of the lawgiver to reveal the realoncology teacher offering three challenging assertions for hisnew residents to chew over. He happily concedes that lots ofsimilar “laws” could be devised. The essays on the three lawsincluded in the book follow the great tradition begun byMontaigne and Bacon and exemplified in post-war Britishmedicine by Richard Asher3 and Peter Medawar.4 The laws alladdress the central paradox that “medicine asks you to makeperfect decisions with imperfect information.” It’s the sort oftheme that would have made Montaigne purr with delight.

Strong intuition is much more powerfulthan a weak testIn Novum Organum (1620),5 Francis Bacon attacked what hecalled idols of the tribe. “Idols of the Tribe are rooted in humannature itself and in the very tribe or race of men. For peoplefalsely claim that human sense is the measure of things, whereasin fact all perceptions of sense and mind are built to the scaleof man and not the universe.” In his first law, Mukherjeechallenges the idea that baconian analysis and induction reallywork better than trained instinct in clinical practice. It’s a trickyargument, and his opening example fell flat for me. Aman withvery rapid weight loss in late middle age can have only a limitedrange of illnesses, and before turning over the page to find out

the diagnosis I had concluded that an initial discussion aboutHIV testing was mandatory.So when Thomas Bayes makes an appearance soon after,elegantly accompanied by Groucho Marx, arguing that a testcan be interpreted sanely only in the context of priorprobabilities, I would have framed this situation as lying at the20-30% level rather than “infinitesimally low.” But never mind.What follows is excellent, and Bayes has rarely been so wellexplained and celebrated.For an audiencemore familiar with the development of evidencebased medicine, the argument could have been developedfurther. Evidence basedmedicine tries to use baconianmethodsto weight the value of various elements of diagnostic strategiesfor important conditions. But increasingly the clinical decisionrules which emerge seem overcomplex, weak, and conditional,and when such rules are tested in clinical practice, theirpredictive value is usually found to be no better than clinicaljudgment, instinct, or gestalt, depending on which word youlike. But this is not an argument to go back to worshipping theidol of authority. It is just an acknowledgment that both sidesof the brain—the analytical and the panoptical—are needed topractise good medicine.

“Normals” teach us rules; “outliers” teachus lawsInitially, I had difficulty following the wording of this law, butMukherjee illustrates it nicely with the history of astronomy.His account runs through Copernicus, Brahe, and Kepler, but Iwas surprised when it stopped in 1605 with Kepler’s deductionof elliptical orbits based on the “outlier” coming and goingbehaviour of Mars. The ultimate example of deduction from anoutlier is Einstein’s 1915 paper, “Explanation of the perihelionmotion of mercury from general relativity theory,”6 which useda tiny observational discrepancy to overturn our entireunderstanding of time and space.Clinical outliers do indeed teach us new laws, but we still tendto ignore them. The classic example is the discovery of gluten

edgar.lehman@btopenworld.com

For personal use only: See rights and reprints http://www.bmj.com/permissions Subscribe: http://www.bmj.com/subscribe

BMJ 2015;351:h6708 doi: 10.1136/bmj.h6708 (Published 14 December 2015) Page 1 of 2

Editorials

EDITORIALS

as the cause of coeliac disease when the Germans blocked thesupply of grain to the occupied Netherlands in 1944-45. Mostchildren lost weight, but a fewwho had previously been wastingaway suddenly seemed to improve, until their bread supply wasrestored by the Allies.7 Thanks to decades of detective work,we now have a fairly good understanding of this condition,though it still falls in an area between allergy and autoimmunitywhere further outlier observations may yet uncover new “laws.”With a logic I don’t really understand, Mukherjee choosesautism instead as his example, and then arrives at his ownspecialty of oncology. Here treatments which are of zero benefitto most patients can induce complete remission in others.Whenpeople are alive who by all rights should be dead, statisticalmeta-analysis can tell us nothing. We do then indeed need toseek new laws, and oncology is doing that faster than any otherpart of medicine. Elsewhere, the pile of valuable clues we throwaway by statistically reducing everything to mean effect sizesstands as a reproach to the way we use “evidence.” I think thismay be the most valuable insight of this book: cherish theoutlier, who is trying to tell you something you have not thoughtof.

For every perfect medical experiment,there is a perfect human biasLike Bacon, Montaigne delighted in describing how peopledeceive themselves, but unlike him, he was entirely happy tolet them. Mukherjee’s closing essay on bias has Montaigne’sdigressive charm, and although he comes close to describingthe same idols as Bacon, he is not confident that they can beunseated. “Perhaps the simplest way to tackle the bias problemis to confront it head-on and incorporate [it] into the verydefinition of medicine.” I agree. In fact I think we need a whole

taxonomy of bias, not to eliminate it altogether but to minimisethe harm it might do to patients.The last page states that “the discipline of medicine concernsthe manipulation of knowledge under uncertainty.” You candiscuss the evidence endlessly in the coffee room, but in theconsultation you have to “plump,” to use a favourite word fromIsaiah Berlin. Berlin was also fond of quoting Kant’s sayingthat “From the crooked timber of humanity, no straight thingwas ever made.” 8 This book is true to medicine because itfollows the knots and curves of human experience, rather thantrying to chop them straight and make them into flatpackfurniture. Through its shape and style as well as its contents, itconveys the reality of clinical decision making, and I cannotthink of another that does it so succinctly and so well.

Competing interests: I have read and understood BMJ policy ondeclaration of interests and have no relevant interests to declare.Provenance and peer review: Commissioned; not externally peerreviewed.

1 Mukherjee S. The laws of medicine: field notes from an uncertain science. TED Books,2015.

2 Mukherjee S. The emperor of all maladies: a biography of cancer. Harper Collins, 2011.3 Asher R. Straight and crooked thinking in medicine. BMJ 1954;2:460.4 Medawar P. The strange case of the spotted mice; and other classic essays on science.

Oxford University Press, 1996.5 Bacon F. Novum organum scientiarum. Aphorism 41, 1620. Elibron Classics, 2005.6 Einstein A. Erklärung der Perihelbewgung des Merkur aus der allgemeinen

Relativitätstheorie. Preussische Akademie der Wissenschaften, Sitzungsberichte1915;2:831-9.

7 Paveley WF. From Aretaeus to Crosby: a history of coeliac disease. BMJ 1988;297:1646.8 Kant I. Idea for a general history with a cosmopolitan purpose. Proposition 6. 1784.

Cite this as: BMJ 2015;351:h6708© BMJ Publishing Group Ltd 2015

For personal use only: See rights and reprints http://www.bmj.com/permissions Subscribe: http://www.bmj.com/subscribe

BMJ 2015;351:h6708 doi: 10.1136/bmj.h6708 (Published 14 December 2015) Page 2 of 2

EDITORIALS