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BMJ 2015;351:h6708 doi: 10.1136/bmj.

h6708 (Published 14 December 2015)

Page 1 of 2



Siddharta Mukherjee’s three laws of medicine
How 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.1
It follows the author Siddharta Mukherjee’s The Emperor of All
Maladies,2 an equally arresting title for a very large book. Both
are a delight to read and adopt a similar style. Real clinical
stories are turned into parables and aphorisms that illustrate
various aspects of real clinical medicine. In that way they not
only resonate with clinicians but, more importantly, offer a wide
readership the opportunity to understand and share in the deep
issues of how medicine advances and how medical decisions
are made.
Anyone who tries to lay down laws for medicine is bound to be
accused of hubris. But there is a gentle irony in Mukherjee’s
title, which he immediately subverts with the subtitle “Field
Notes from an Uncertain Science.” At the end of the book he
explicitly throws off the cloak of the lawgiver to reveal the real
oncology teacher offering three challenging assertions for his
new residents to chew over. He happily concedes that lots of
similar “laws” could be devised. The essays on the three laws
included in the book follow the great tradition begun by
Montaigne and Bacon and exemplified in post-war British
medicine by Richard Asher3 and Peter Medawar.4 The laws all
address the central paradox that “medicine asks you to make
perfect decisions with imperfect information.” It’s the sort of
theme that would have made Montaigne purr with delight.

Strong intuition is much more powerful
than a weak test

In Novum Organum (1620),5 Francis Bacon attacked what he
called idols of the tribe. “Idols of the Tribe are rooted in human
nature itself and in the very tribe or race of men. For people
falsely claim that human sense is the measure of things, whereas
in fact all perceptions of sense and mind are built to the scale
of man and not the universe.” In his first law, Mukherjee
challenges the idea that baconian analysis and induction really
work better than trained instinct in clinical practice. It’s a tricky
argument, and his opening example fell flat for me. A man with
very rapid weight loss in late middle age can have only a limited
range of illnesses, and before turning over the page to find out

the diagnosis I had concluded that an initial discussion about
HIV testing was mandatory.

So when Thomas Bayes makes an appearance soon after,
elegantly accompanied by Groucho Marx, arguing that a test
can be interpreted sanely only in the context of prior
probabilities, I would have framed this situation as lying at the
20-30% level rather than “infinitesimally low.” But never mind.
What follows is excellent, and Bayes has rarely been so well
explained and celebrated.

For an audience more familiar with the development of evidence
based medicine, the argument could have been developed
further. Evidence based medicine tries to use baconian methods
to weight the value of various elements of diagnostic strategies
for important conditions. But increasingly the clinical decision
rules which emerge seem overcomplex, weak, and conditional,
and when such rules are tested in clinical practice, their
predictive value is usually found to be no better than clinical
judgment, instinct, or gestalt, depending on which word you
like. But this is not an argument to go back to worshipping the
idol of authority. It is just an acknowledgment that both sides
of the brain—the analytical and the panoptical—are needed to
practise good medicine.

“Normals” teach us rules; “outliers” teach
us laws
Initially, I had difficulty following the wording of this law, but
Mukherjee illustrates it nicely with the history of astronomy.
His account runs through Copernicus, Brahe, and Kepler, but I
was surprised when it stopped in 1605 with Kepler’s deduction
of elliptical orbits based on the “outlier” coming and going
behaviour of Mars. The ultimate example of deduction from an
outlier is Einstein’s 1915 paper, “Explanation of the perihelion
motion of mercury from general relativity theory,”6 which used
a tiny observational discrepancy to overturn our entire
understanding of time and space.
Clinical outliers do indeed teach us new laws, but we still tend
to ignore them. The classic example is the discovery of gluten
For personal use only: See rights and reprints


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

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as the cause of coeliac disease when the Germans blocked the
supply of grain to the occupied Netherlands in 1944-45. Most
children lost weight, but a few who had previously been wasting
away suddenly seemed to improve, until their bread supply was
restored 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 autoimmunity
where further outlier observations may yet uncover new “laws.”

With a logic I don’t really understand, Mukherjee chooses
autism instead as his example, and then arrives at his own
specialty of oncology. Here treatments which are of zero benefit
to most patients can induce complete remission in others. When
people are alive who by all rights should be dead, statistical
meta-analysis can tell us nothing. We do then indeed need to
seek new laws, and oncology is doing that faster than any other
part of medicine. Elsewhere, the pile of valuable clues we throw
away by statistically reducing everything to mean effect sizes
stands as a reproach to the way we use “evidence.” I think this
may be the most valuable insight of this book: cherish the
outlier, who is trying to tell you something you have not thought

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

For personal use only: See rights and reprints

taxonomy of bias, not to eliminate it altogether but to minimise
the harm it might do to patients.

The last page states that “the discipline of medicine concerns
the manipulation of knowledge under uncertainty.” You can
discuss the evidence endlessly in the coffee room, but in the
consultation you have to “plump,” to use a favourite word from
Isaiah Berlin. Berlin was also fond of quoting Kant’s saying
that “From the crooked timber of humanity, no straight thing
was ever made.” 8 This book is true to medicine because it
follows the knots and curves of human experience, rather than
trying to chop them straight and make them into flatpack
furniture. Through its shape and style as well as its contents, it
conveys the reality of clinical decision making, and I cannot
think of another that does it so succinctly and so well.
Competing interests: I have read and understood BMJ policy on
declaration of interests and have no relevant interests to declare.
Provenance and peer review: Commissioned; not externally peer

Mukherjee S. The laws of medicine: field notes from an uncertain science. TED Books,
Mukherjee S. The emperor of all maladies: a biography of cancer. Harper Collins, 2011.
Asher R. Straight and crooked thinking in medicine. BMJ 1954;2:460.
Medawar P. The strange case of the spotted mice; and other classic essays on science.
Oxford University Press, 1996.
Bacon F. Novum organum scientiarum. Aphorism 41, 1620. Elibron Classics, 2005.
Einstein A. Erklärung der Perihelbewgung des Merkur aus der allgemeinen
Relativitätstheorie. Preussische Akademie der Wissenschaften, Sitzungsberichte
Paveley WF. From Aretaeus to Crosby: a history of coeliac disease. BMJ 1988;297:1646.
Kant I. Idea for a general history with a cosmopolitan purpose. Proposition 6. 1784.

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