Trick or Treatment?: Alternative Medicine on Trial pot

6 2 The Truth About Acupuncture 39 3 The Truth About Homeopathy 91 4 The Truth About Chiropractic Therapy 145 § The Truth About Herbal Medicine 191 S Does the Truth Matter?. 236 Ap

S i m o n S i n g h & E d z a r d Ernst

LONDON • TORONTO • SYDNEY • AUCKLAND • JOHANNESBURG

61-63 Uxbridge Road, London W5 5SA

A Random House Group Company

Every effort has been made to obtain the necessary permissions with reference to copyright material, both illustrative and quoted We apologize for any omissions in this respect and will

be pleased to make the appropriate acknowledgements in any future edition

Contents

Introduction 1

1 How Do You Determine the Truth? 6

2 The Truth About Acupuncture 39

3 The Truth About Homeopathy 91

4 The Truth About Chiropractic Therapy 145

§ The Truth About Herbal Medicine 191

(S Does the Truth Matter? 236

Appendix: Rapid Guide to Alternative Therapies 290

Further Reading 329

Acknowledgements 333

Picture Credits 334

Index 335

Introduction

T H E CONTENTS OF THIS BOOK ARE GUIDED ENTIRELY BY A SINGLE PITHY

s e n t e n c e , written o v e r 2,000 y e a r s a g o by H i p p o c r a t e s of C o s

R e c o g n i z e d as the father of m e d i c i n e , he stated:

'There are, in fact, two things, science and opinion;

the former begets knowledge, the latter ignorance.'

If s o m e b o d y p r o p o s e d a n e w m e d i c a l t r e a t m e n t , then H i p p o c r a t e s declared that we should use science to d e c i d e w h e t h e r or not it w o r k s ,

r a t h e r t h a n r e l y i n g o n s o m e b o d y ' s o p i n i o n S c i e n c e e m p l o y s

e x p e r i m e n t s , o b s e r v a t i o n s , trials, a r g u m e n t and discussion in order to arrive at an objective c o n s e n s u s on the truth E v e n w h e n a c o n c l u s i o n

h a s been d e c i d e d , science still p r o b e s and p r o d s its o w n p r o c l a m a t i o n s

j u s t in case it h a s m a d e a m i s t a k e In contrast, opinions are subjective and conflicting, and w h o e v e r has the m o s t persuasive PR c a m p a i g n has the best c h a n c e of p r o m o t i n g their o p i n i o n , regardless of w h e t h e r they are right or w r o n g

G u i d e d by Hippocrates' d i c t u m , this b o o k takes a scientific look at the current plethora of alternative treatments that are rapidly g r o w i n g

in popularity T h e s e treatments are piled high in every p h a r m a c y , written about in every m a g a z i n e , discussed on millions of w e b p a g e s and used by billions of p e o p l e , yet they are regarded with scepticism

by m a n y d o c t o r s

Indeed, our definition of an alternative medicine is any therapy that is not accepted by the majority of mainstream doctors, and typically this also m e a n s that these alternative therapies have mechanisms that lie out-side the current understanding of modern medicine In the language of science, alternative therapies are said to be biologically implausible

N o w a d a y s it is c o m m o n to h e a r the u m b r e l l a t e r m ' c o m p l e m e n t a r y and alternative m e d i c i n e ' , w h i c h correctly implies that s o m e t i m e s

t h e s e t h e r a p i e s a r e u s e d a l o n g s i d e a n d s o m e t i m e s i n s t e a d o f

INTRODUCTION 1

conventional m e d i c i n e Unfortunately it is a lengthy and c l u m s y

p h r a s e , so in a bid for simplicity we h a v e decided to use the term 'alternative m e d i c i n e ' t h r o u g h o u t this b o o k

Surveys show that in m a n y countries o v e r half the population use alternative medicine in one form or another Indeed, it is estimated that the annual global spend on all alternative medicines is in the region of

£40 billion, making it the fastest-growing area of medical spending So

w h o is right: the critic w h o thinks alternative medicine is akin to v o o d o o ,

or the mother w h o entrusts her child's health to alternative medicine? There are three possible answers

1 Perhaps alternative m e d i c i n e is entirely useless Perhaps

persua-sive marketing has fooled us into believing that alternative medicine w o r k s Alternative therapists might seem like nice peo-ple, talking as they do about such appealing concepts as ' n a t u r e ' s

w o n d e r s ' and 'ancient w i s d o m ' , but they might be misleading the public - or m a y b e they are even deluding t h e m s e l v e s T h e y also use impressive b u z z w o r d s like holistic, m e r i d i a n s , self-healing and individualized If we could see past the j a r g o n , then w o u l d

we realize that alternative medicine is j u s t a s c a m ?

2 Or m a y b e alternative m e d i c i n e is o v e r w h e l m i n g l y effective

P e r h a p s the sceptics, including m a n y d o c t o r s , h a v e simply failed

to recognize the benefits of a m o r e holistic, natural, traditional and spiritual a p p r o a c h to health M e d i c i n e h a s n e v e r c l a i m e d to

h a v e all the a n s w e r s , a n d o v e r and over again there h a v e been revolutions in our u n d e r s t a n d i n g of the h u m a n body So will the next revolution lead to a discovery of the m e c h a n i s m s underlying alternative m e d i c i n e ? Or could there be darker forces at w o r k ?

C o u l d it be that the m e d i c a l establishment wants to maintain its

p o w e r and authority, and that doctors criticize alternative m e d i cine in order to quash any rivals? Or might these self-same sceptics be p u p p e t s of the big pharmaceutical corporations w h o merely want to hold on to their profits?

-3 Or d o e s the truth lie s o m e w h e r e in the m i d d l e ?

2

W h a t e v e r the answer, we d e c i d e d to write this b o o k in order to get

to the truth A l t h o u g h there are already plenty of b o o k s that claim to tell y o u the truth about alternative m e d i c i n e , we are confident that o u r s offers an unparalleled level of rigour, authority and i n d e p e n d e n c e We are both trained scientists, so we will e x a m i n e the various alternative therapies in a scrupulous m a n n e r M o r e o v e r , neither of us h a s ever been e m p l o y e d by a pharmaceutical c o m p a n y , and nor h a v e we ever personally profited from the 'natural h e a l t h ' sector - we can honestly say that our only m o t i v e is to get to the truth

A n d our partnership brings b a l a n c e t o the b o o k O n e o f u s , E d z a r d Ernst, is an insider w h o practised m e d i c i n e for m a n y y e a r s , including

s o m e alternative therapies He is the w o r l d ' s first professor of native m e d i c i n e , and his research g r o u p h a s spent fifteen y e a r s trying

alter-to w o r k out w h i c h treatments w o r k and w h i c h do not T h e other of u s ,

S i m o n S i n g h , is an outsider w h o has spent almost t w o d e c a d e s as a science j o u r n a l i s t , w o r k i n g in print, television and r a d i o , a l w a y s striving to explain c o m p l i c a t e d ideas in a way that the general public can g r a s p Together we think that we can get closer to the truth than

a n y b o d y else a n d , equally importantly, we will e n d e a v o u r to explain it

to you in a clear, vivid and c o m p r e h e n s i b l e manner

O u r mission is to reveal the truth about the p o t i o n s , lotions, pills,

n e e d l e s , p u m m e l l i n g and energizing that lie b e y o n d the r e a l m s of c o n ventional m e d i c i n e , but which are b e c o m i n g increasingly attractive for

-m a n y patients W h a t w o r k s , and w h a t d o e s n ' t ? W h a t are the secrets and w h a t are the lies? W h o is trustworthy and w h o is ripping you off?

Do t o d a y ' s d o c t o r s k n o w w h a t is best, or do the old w i v e s ' tales indeed tap into s o m e ancient, superior w i s d o m ? All these questions and m o r e will be a n s w e r e d in this b o o k , the w o r l d ' s m o s t honest and accurate

e x a m i n a t i o n of alternative m e d i c i n e

In particular, we will answer the fundamental question: 'Is alternative medicine effective for treating disease?' Although a short and simple question, w h e n unpacked it becomes somewhat complicated and has many answers depending on three key issues First, which alternative therapy are we talking about? Second, which disease are we applying it to? Third, what is meant by effective? In order to address these questions properly, we h a v e divided the b o o k into six c h a p t e r s

C h a p t e r 1 provides an introduction to the scientific m e t h o d It

e x p l a i n s h o w scientists, by e x p e r i m e n t i n g and o b s e r v i n g , can

deter-m i n e w h e t h e r or not a particular therapy is effective Every conclusion

we reach in the rest of this b o o k d e p e n d s on the scientific m e t h o d and

on an unbiased analysis of the best medical research available S o , by

f i r s t explaining h o w science w o r k s , w e h o p e t o increase your

confi-d e n c e in our s u b s e q u e n t c o n c l u s i o n s

C h a p t e r 2 s h o w s h o w the scientific m e t h o d can be applied to

a c u p u n c t u r e , one of the m o s t established, most tested and m o s t widely used alternative t h e r a p i e s As well as e x a m i n i n g the n u m e r o u s scientific trials that h a v e been c o n d u c t e d on a c u p u n c t u r e , this chapter will also look at its ancient origins in the East, h o w it migrated to the West and h o w it is practised today

Chapters 3 , 4 and 5 use a similar approach to examine the three other major alternative therapies, namely homeopathy, chiropractic therapy and herbal medicine T h e remaining alternative therapies will be covered in the appendix, which offers a brief analysis of over thirty treatments In other w o r d s , every alternative therapy that you are ever likely to encounter will be scientifically evaluated within the pages of this book

T h e sixth and final chapter d r a w s s o m e conclusions based on the

e v i d e n c e in the previous c h a p t e r s and looks ahead to the future of healthcare If there is o v e r w h e l m i n g e v i d e n c e that an alternative therapy does not w o r k , then should it be b a n n e d or is patient choice the key driving force? On the other h a n d , if s o m e alternative therapies are genuinely effective, can they be integrated within m a i n s t r e a m

m e d i c i n e or will there a l w a y s be an a n t a g o n i s m b e t w e e n the

establish-m e n t and alternative therapists?

T h e key t h e m e running t h r o u g h o u t all six c h a p t e r s is ' t r u t h '

C h a p t e r 1 discusses h o w science determines the truth C h a p t e r s 2 - 5 reveal the truth about various alternative therapies b a s e d on the scientific e v i d e n c e C h a p t e r 6 looks at w h y the truth m a t t e r s , and h o w this should influence our attitude towards alternative therapies in the context of twenty-first-century m e d i c i n e

Truth is certainly a reassuring c o m m o d i t y , but in this b o o k it c o m e s

w i t h t w o w a r n i n g s F i r s t , w e will p r e s e n t t h e t r u t h i n a n unapologetically blunt manner So where we find that a particular therapy

does indeed work for a particular illness (e.g St J o h n ' s wort does have antidepressive properties, if used appropriately - see Chapter 5 ) , we will say so clearly In other cases, however, where we discover that a particu-lar therapy is useless, or even harmful, then we shall state this conclusion equally forcefully You have decided to purchase this book in order to find out the truth, so we think we o w e it to you to be direct and honest

T h e second warning is that all the truths in this book are based

on science, because Hippocrates was absolutely correct when he said that science begets knowledge Everything we k n o w about the universe, from the components of an atom to the n u m b e r of galaxies, is thanks to science, and every medical breakthrough, from the development of antiseptics to the eradication of smallpox, has been built upon scientific foundations

Of course, science is not perfect Scientists will readily admit that they do not know everything, but nevertheless the scientific method is without doubt the best mechanism for getting to the truth

If you are a reader w h o is sceptical about the p o w e r of s c i e n c e , then

we kindly request that you at least read C h a p t e r 1 By the e n d of that first chapter, you should be sufficiently c o n v i n c e d about the value of scientific m e t h o d that you will consider accepting the c o n c l u s i o n s in the rest of the b o o k

It could b e , h o w e v e r , that you refuse to a c k n o w l e d g e that science is the best way to decide w h e t h e r or not an alternative therapy w o r k s It

m i g h t be that you are so c l o s e - m i n d e d that you will stick to y o u r

w o r l d v i e w regardless of w h a t science h a s to say You might have an

u n w a v e r i n g belief that all alternative m e d i c i n e is r u b b i s h , or you might

a d a m a n t l y hold the opposite view, that alternative m e d i c i n e offers a

p a n a c e a for all o u r a c h e s , pains and d i s e a s e s In either c a s e , this is not the b o o k for y o u T h e r e is no point in even reading the first chapter if you are not prepared to c o n s i d e r the possibility that the scientific

m e t h o d can act as the arbiter of truth In fact, if you have already m a d e

up y o u r m i n d about alternative m e d i c i n e , then it w o u l d be sensible for you to return this b o o k to the b o o k s h o p and ask for a refund W h y on Earth w o u l d you w a n t to hear about the c o n c l u s i o n s of t h o u s a n d s of research studies w h e n you already h a v e all the a n s w e r s ?

But our hope is that you will be sufficiently o p e n - m i n d e d to want to read further

How Do You Determine the Truth?

'Truth exists - only lies are invented.''

Georges Braque

THIS BOOK IS ABOUT ESTABLISHING THE TRUTH IN RELATION TO

alternative m e d i c i n e W h i c h therapies w o r k and w h i c h o n e s are u s e less? W h i c h therapies are safe and w h i c h o n e s are d a n g e r o u s ?

-T h e s e are q u e s t i o n s that d o c t o r s h a v e a s k e d t h e m s e l v e s for millennia in relation to all forms of m e d i c i n e , and yet it is only c o m -paratively recently that they h a v e d e v e l o p e d an a p p r o a c h that a l l o w s

t h e m to separate the effective from the ineffective, and the safe from

the d a n g e r o u s T h i s a p p r o a c h , k n o w n as evidence-based medicine, h a s

revolutionized medical practice, transforming it from an industry of charlatans and i n c o m p e t e n t s into a s y s t e m of healthcare that can deliver such miracles as transplanting k i d n e y s , r e m o v i n g c a t a r a c t s ,

c o m b a t i n g c h i l d h o o d d i s e a s e s , e r a d i c a t i n g s m a l l p o x a n d s a v i n g literally millions of lives each year

We will e m p l o y the principles of e v i d e n c e - b a s e d m e d i c i n e to test alternative t h e r a p i e s , so it is crucial that we properly explain what it is and h o w it w o r k s Rather than introducing it in a m o d e r n c o n t e x t , we will go back in time to see h o w it e m e r g e d and e v o l v e d , w h i c h will provide a d e e p e r appreciation of its inherent strengths In particular,

we will look back at h o w this a p p r o a c h w a s used to test bloodletting,

a bizarre and previously c o m m o n treatment that involved cutting skin and severing blood vessels in o r d e r to cure every ailment

T h e b o o m in bloodletting started in A n c i e n t G r e e c e , w h e r e it fitted

in naturally with the w i d e s p r e a d view that diseases w e r e c a u s e d by an

i m b a l a n c e of four bodily fluids, otherwise k n o w n as the four humours:

b l o o d , yellow b i l e , black bile and p h l e g m As well as affecting health,

i m b a l a n c e s in these h u m o u r s resulted in particular t e m p e r a m e n t s

B l o o d w a s a s s o c i a t e d with b e i n g o p t i m i s t i c , y e l l o w b i l e w i t h being irascible, black bile with b e i n g depressed and p h l e g m with b e i n g

u n e m o t i o n a l We can still hear the e c h o of h u m o u r i s m in w o r d s such

as s a n g u i n e , c h o l e r i c , m e l a n c h o l i c and p h l e g m a t i c

7

U n a w a r e of h o w blood circulates around the body, G r e e k physicians believed that it could b e c o m e stagnant and thereby cause ill-health

H e n c e , they a d v o c a t e d the r e m o v a l of this stagnant b l o o d , prescribing specific p r o c e d u r e s for different illnesses For e x a m p l e , liver p r o b l e m s were treated by tapping a vein in the right h a n d , w h e r e a s ailments relating to the spleen required tapping a vein in the left h a n d

T h e G r e e k medical tradition w a s held in such reverence that letting g r e w to be a p o p u l a r m e t h o d for treating patients t h r o u g h o u t

blood-E u r o p e in the centuries that followed T h o s e w h o could afford it w o u l d often receive bloodletting from m o n k s in the early M i d d l e A g e s , but then in 1163 P o p e A l e x a n d e r III b a n n e d t h e m from practising this gory medical p r o c e d u r e Thereafter it b e c a m e c o m m o n for barbers to take

on the responsibility of b e i n g the local bleeder T h e y took their role very seriously, carefully refining their techniques and a d o p t i n g new

t e c h n o l o g i e s A l o n g s i d e the simple b l a d e , there w a s the phleam, a

spring-loaded blade that cut to a particular d e p t h In later years this

w a s followed by the scarificator, w h i c h consisted of a dozen or m o r e

spring-loaded blades that simultaneously lacerated the skin

For those barbers w h o preferred a less technological and m o r e natural a p p r o a c h , there w a s the option of using medicinal l e e c h e s T h e business e n d of these b l o o d s u c k i n g parasitic w o r m s has three separate

j a w s , each one of t h e m carrying about 100 delicate teeth T h e y offered

an ideal m e t h o d for bloodletting from a p a t i e n t ' s g u m s , lips or n o s e

M o r e o v e r , the leech delivers an anaesthetic to reduce p a i n , an coagulant to prevent the blood from clotting, and a vasodilator to

anti-e x p a n d its v i c t i m ' s blood vanti-essanti-els and incranti-easanti-e flow To anti-e n a b l anti-e major

b l o o d s u c k i n g s e s s i o n s , doctors w o u l d perform bdellatomy, which

involved slicing into the leech so that blood entered its sucker end and then leaked out of the cut T h i s prevented the leech from b e c o m i n g full and e n c o u r a g e d it to c o n t i n u e s u c k i n g

It is often said that t o d a y ' s red-and-white b a r b e r s h o p pole is

e m b l e m a t i c of the b a r b e r ' s earlier role as surgeon, but it is really associated with his position as bleeder T h e red represents the b l o o d , the white is the tourniquet, the ball at the end s y m b o l i z e s the brass leech basin and the pole itself represents the stick that w a s s q u e e z e d by the patient to increase blood flow

M e a n w h i l e , bloodletting w a s also practised and studied by the m o s t senior medical figures in E u r o p e , such as A m b r o i s e P a r e , w h o w a s the official royal surgeon to four F r e n c h kings during the sixteenth century He wrote extensively on the subject, offering lots of useful hints and tips:

If the leeches be handled with the bare hand, they are angered, and

b e c o m e so stomachfull as that they will not bite; wherefore you shall hold them in a white and clean linen cloth, and apply them to the skin being first lightly scarified, or besmeared with the blood of s o m e other creature, for thus they will take hold of the flesh, together with the skin more greedily and fully To cause them to fall off, you shall put s o m e powder of A l o e s , salt or ashes upon their heads If any desire to know

h o w much blood they have drawn, let him sprinkle them with salt made into powder, as soon as they are c o m e off, for thus they will vomit up what blood soever they have sucked

W h e n E u r o p e a n s colonized the N e w World, they took the practice

of bloodletting with t h e m A m e r i c a n physicians saw no reason to question the techniques taught by the great E u r o p e a n hospitals and universities, so they also considered bloodletting to be a m a i n s t r e a m medical p r o c e d u r e that could be used in a variety of c i r c u m s t a n c e s

H o w e v e r , w h e n it w a s administered to the n a t i o n ' s m o s t important patient in 1799, its use suddenly b e c a m e a controversial issue Was bloodletting really a life-saving medical intervention, or w a s it drain-ing the life out of patients?

T h e controversy began on the m o r n i n g of 13 D e c e m b e r 1799, the day that G e o r g e Washington a w o k e with the s y m p t o m s of a cold

W h e n his personal secretary suggested that he take s o m e m e d i c i n e , Washington replied, 'You k n o w I never take anything for a cold I'll let

it go j u s t as it c a m e '

T h e sixty-seven-year-old former president did not think that a sniffle and a sore throat were anything to w o r r y a b o u t , particularly as

he had previously suffered and survived far m o r e severe s i c k n e s s e s

He had contracted smallpox as a teenager, which was followed by a bout of tuberculosis N e x t , w h e n he w a s a y o u n g surveyor, he caught

malaria while w o r k i n g in the mosquito-infested s w a m p s of Virginia

T h e n , in 1 7 5 5 , he m i r a c u l o u s l y survived the Battle of M o n o n g a h e l a ,

e v e n t h o u g h t w o h o r s e s w e r e killed beneath h i m and four m u s k e t balls pierced his uniform He also suffered from p n e u m o n i a , w a s repeatedly afflicted by further bouts of m a l a r i a , and d e v e l o p e d 'a m a l i g n a n t

c a r b u n c l e ' on his h i p that incapacitated h i m for six w e e k s Perversely,

h a v i n g survived b l o o d y battlefields and d a n g e r o u s d i s e a s e s , this ently m i n o r cold contracted on Friday 13th w o u l d p r o v e to be the greatest threat to W a s h i n g t o n ' s life

appar-His condition deteriorated during Friday night, so m u c h so that he

a w o k e in the early h o u r s g a s p i n g for air W h e n Mr Albin R a w l i n s ,

W a s h i n g t o n ' s estate o v e r s e e r , c o n c o c t e d a m i x t u r e of m o l a s s e s , vinegar and butter, he found that his patient could hardly s w a l l o w it

R a w l i n s , w h o w a s also an a c c o m p l i s h e d bloodletter, d e c i d e d that further a c t i o n w a s r e q u i r e d A n x i o u s t o a l l e v i a t e his m a s t e r ' s

s y m p t o m s , he used a surgical knife k n o w n as a lancet to create a small incision in the G e n e r a l ' s a r m and r e m o v e d one-third of a litre of blood into a porcelain b o w l

By the morning of 14 D e c e m b e r there was still no sign of any improvement, so Martha Washington was relieved when three doctors arrived at the house to take care of her husband Dr James Craik, the General's personal physician, was accompanied by Dr Gustavus Richard

Brown and Dr Elisha Cullen Dick They correctly diagnosed cynanche

trachealis ('dog strangulation'), which we would today interpret as a

swelling and inflammation of the epiglottis This would have obstructed Washington's throat and led to his difficulty in breathing

Dr Craik applied s o m e c a n t h a r i d e s (a preparation of dried beetles)

to his throat W h e n this did not h a v e any effect, he opted to bleed the General and r e m o v e d another half a litre of b l o o d At 11 a.m he

r e m o v e d a similar a m o u n t again T h e average h u m a n b o d y contains only 5 litres of b l o o d , so a significant fraction w a s b e i n g bled from Washington at each session Dr Craik did not s e e m c o n c e r n e d He per-formed venesection again in the afternoon, r e m o v i n g a further w h o l e litre of blood

O v e r the next few h o u r s , it a p p e a r e d that the bloodletting w a s ing Washington s e e m e d to r e c o v e r and for a while he w a s able to sit

help-upright T h i s w a s , h o w e v e r , merely a t e m p o r a r y r e m i s s i o n W h e n his condition deteriorated again later that day, the doctors c o n d u c t e d yet

a n o t h e r session of bloodletting This t i m e the b l o o d a p p e a r e d viscous and flowed slowly F r o m a m o d e r n perspective this reflects d e -hydration and a general loss of bodily fluid caused by e x c e s s i v e b l o o d loss

As the e v e n i n g p a s s e d , the doctors could only w a t c h grimly as their

n u m e r o u s bloodlettings and various poultices failed to deliver any signs of recovery Dr C r a i c k and Dr D i c k w o u l d later write: ' T h e

p o w e r s of life s e e m e d n o w manifestly yielding to the force of the order Blisters w e r e applied to the e x t r e m i t i e s , together with a

dis-c a t a p l a s m of bran and vinegar to the throat.'

G e o r g e Washington C u s t i s , t h e d y i n g m a n ' s s t e p g r a n d s o n , d o c u

-m e n t e d the final -m o -m e n t s of A -m e r i c a ' s first President:

As the night advanced it b e c a m e evident that he w a s sinking, and he

s e e m e d fully aware that 'his hour w a s n i g h ' He inquired the time, and

w a s answered a few minutes to ten He spoke no more - the hand of death w a s upon h i m , and he w a s c o n s c i o u s that 'his hour w a s c o m e ' With surprising self-possession he prepared to die C o m p o s i n g his form

at length and folding his arms on his b o s o m , without a sigh, without a groan, the Father of his Country died No pang or struggle told when the noble spirit took its noiseless flight; while so tranquil appeared the manly features in the repose of death, that s o m e m o m e n t s had passed ere those around could believe that the patriarch was no more

G e o r g e W a s h i n g t o n , a giant m a n of 6 feet 314 i n c h e s , h a d been drained of half his blood in less than a day T h e doctors responsible for treating Washington c l a i m e d that such drastic m e a s u r e s had been necessary as a last-ditch resort to save the patient's life, and most of their colleagues supported the decision H o w e v e r , there w e r e also voices of dissent from within the medical c o m m u n i t y A l t h o u g h blood-letting had been an accepted practice in m e d i c i n e for c e n t u r i e s , a minority of d o c t o r s w e r e n o w b e g i n n i n g to question its v a l u e I n d e e d , they argued that bloodletting w a s a hazard to patients, regardless of

w h e r e on the body it took place and irrespective of w h e t h e r it w a s half

How Do You DETERMINE THE T R U T H ? 1 1

a litre or 2 litres that w a s b e i n g t a k e n A c c o r d i n g to these d o c t o r s , Dr

C r a i k , Dr B r o w n and Dr D i c k had effectively killed the former President by needlessly bleeding h i m to d e a t h

But w h o w a s right - the m o s t e m i n e n t d o c t o r s in the land w h o h a d

d o n e their best to save W a s h i n g t o n , or the m a v e r i c k m e d i c s w h o saw bloodletting as a crazy and d a n g e r o u s legacy of A n c i e n t G r e e c e ? Coincidentally, on the day that Washington d i e d , 14 D e c e m b e r

1799, there w a s effectively a legal j u d g e m e n t on w h e t h e r bloodletting

w a s h a r m i n g or healing patients T h e j u d g e m e n t arose as the result of

an article written by the r e n o w n e d English journalist W i l l i a m C o b b e t t ,

w h o w a s living in Philadelphia and w h o had taken an interest in the activities of a physician by the n a m e of Dr Benjamin R u s h , A m e r i c a ' s

m o s t vociferous a n d f a m o u s a d v o c a t e of bloodletting

Dr R u s h w a s a d m i r e d t h r o u g h o u t A m e r i c a for his brilliant m e d i c a l , scientific and political career He had written eighty-five significant publications, including the first A m e r i c a n chemistry textbook; he had been surgeon general of the Continental A r m y ; a n d , m o s t important of all, he had been a signatory to the Declaration of I n d e p e n d e n c e Perhaps his a c h i e v e m e n t s w e r e to be e x p e c t e d , bearing in m i n d that he graduated at the age of j u s t fourteen from the C o l l e g e of N e w Jersey, which later b e c a m e Princeton University

Rush practised at the P e n n s y l v a n i a Hospital in Philadelphia and taught at its medical s c h o o l , which w a s responsible for training three-quarters of A m e r i c a n d o c t o r s during his t e n u r e He w a s so respected that he w a s k n o w n as ' t h e P e n n s y l v a n i a H i p p o c r a t e s ' and is still the only p h y s i c i a n to h a v e h a d a statue erected in his h o n o u r in Washington DC by the A m e r i c a n Medical Association His prolific career had allowed h i m to p e r s u a d e an entire generation of d o c t o r s of the benefits of bloodletting, including the three d o c t o r s w h o had attended General W a s h i n g t o n For R u s h had served with Dr Craik in the Revolutionary War, he had studied m e d i c i n e with Dr B r o w n

in E d i n b u r g h , and he had taught Dr Dick in P e n n s y l v a n i a

Dr R u s h certainly practised w h a t he p r e a c h e d His b e s t - d o c u m e n t e d bloodletting sprees took place during the Philadelphia yellow fever

e p i d e m i c s of 1794 and 1797 He s o m e t i m e s bled 100 patients in a single day, which m e a n t that his clinic had the stench of stale b l o o d and

attracted s w a r m s of flies H o w e v e r , William C o b b e t t , w h o had a particular interest in reporting on medical s c a n d a l s , w a s c o n v i n c e d that

R u s h w a s inadvertently killing m a n y of his patients C o b b e t t b e g a n

e x a m i n i n g the local bills of mortality a n d , sure e n o u g h , noticed an increase in death rates after R u s h ' s colleagues followed his r e c o m -

m e n d a t i o n s for bloodletting This p r o m p t e d h i m to declare that R u s h ' s

m e t h o d s had 'contributed to the d e p o p u l a t i o n of the E a r t h '

Dr R u s h ' s r e s p o n s e to this allegation of malpractice w a s to sue

C o b b e t t for libel in Philadelphia in 1797 D e l a y s and distractions

m e a n t that the case d r a g g e d on for o v e r t w o y e a r s , but by the e n d of

1799 the j u r y w a s ready to m a k e a decision T h e key issue w a s w h e t h e r

C o b b e t t w a s correct in c l a i m i n g that R u s h w a s killing his patients through bloodletting, or w h e t h e r his accusation w a s u n f o u n d e d and

m a l i c i o u s W h i l e C o b b e t t could point to the bills of mortality to back

up his c a s e , this w a s hardly a rigorous analysis of the impact of letting M o r e o v e r , everything else w a s stacked against h i m

blood-For e x a m p l e , the trial called j u s t three w i t n e s s e s , w h o w e r e all doctors sympathetic to Dr R u s h ' s approach to m e d i c i n e A l s o , the case

w a s a r g u e d b y seven l a w y e r s , w h i c h s u g g e s t s that p o w e r s o f persuasion were m o r e influential than e v i d e n c e R u s h , with his wealth and reputation, had the best lawyers in t o w n arguing his c a s e , so Cobbett w a s a l w a y s fighting an uphill battle On top of all t h i s , the j u r y

w a s probably also swayed by the fact that C o b b e t t was not a doctor,

w h e r e a s R u s h w a s o n e of the fathers of A m e r i c a n m e d i c i n e , so it

w o u l d have s e e m e d natural to back R u s h ' s c l a i m

Not surprisingly, Rush w o n the c a s e C o b b e t t w a s ordered to pay

$5,000 to R u s h in c o m p e n s a t i o n , w h i c h w a s the largest a w a r d e v e r paid out in P e n n s y l v a n i a S o , at exactly the s a m e time that G e o r g e Washington was d y i n g after a series of bloodletting p r o c e d u r e s , a court

w a s deciding that it w a s a perfectly satisfactory medical treatment

We c a n n o t , h o w e v e r , rely on an eighteenth-century court to decide

w h e t h e r or not the medical benefits of bloodletting o u t w e i g h any

d a m a g i n g side-effects After all, the j u d g e m e n t w a s probably heavily biased by all the factors already m e n t i o n e d It is also worth r e m e m -bering that C o b b e t t was a foreigner, w h e r e a s R u s h w a s a national h e r o ,

so a j u d g e m e n t against R u s h was almost u n t h i n k a b l e

In order to decide the true value of bloodletting, the medical p r o fession w o u l d require a m o r e r i g o r o u s p r o c e d u r e , s o m e t h i n g e v e n less biased than the fairest court i m a g i n a b l e In fact, while R u s h and

-C o b b e t t were debating medical matters in a court of law, they w e r e

u n a w a r e that exactly the right sort of p r o c e d u r e for establishing the truth about medical matters had already been d i s c o v e r e d on the other side of the Atlantic and w a s being used to great effect Initially it w a s used to test a radically n e w treatment for a disease that afflicted only sailors, but it w o u l d soon be used to evaluate bloodletting, and in time this approach w o u l d be brought to bear on a w h o l e range of medical interventions, including alternative therapies

Scurvy, limeys and the blood test

In J u n e 1744 a hero of the British navy n a m e d C o m m a n d e r G e o r g e

A n s o n returned h o m e h a v i n g c o m p l e t e d a c i r c u m n a v i g a t i o n of the world that had taken almost four y e a r s A l o n g the way, A n s o n had

fought and captured the Spanish galleon Covadonga, including its

1,313,843 pieces of eight and 35,682 o u n c e s of virgin silver, the most valuable prize in E n g l a n d ' s d e c a d e of fighting against Spain W h e n

A n s o n and his m e n p a r a d e d through L o n d o n , his booty a c c o m p a n i e d him in thirty-two w a g o n s filled with bullion A n s o n h a d , h o w e v e r , paid

a high price for these spoils of war His crew had been repeatedly

struck by a disease k n o w n as scurvy, which had killed m o r e than t w o

out of three of his sailors To put this into context, while only four m e n had b e e n killed d u r i n g A n s o n ' s n a v a l b a t t l e s , o v e r 1,000 h a d

s u c c u m b e d to scurvy

Scurvy had been a constant curse ever since ships had set sail on

v o y a g e s lasting for m o r e than j u s t a few w e e k s T h e first recorded case

of naval scurvy w a s in 1497 as Vasco da G a m a r o u n d e d the C a p e of

G o o d H o p e , and thereafter the incidences increased as e m b o l d e n e d captains sailed further across the g l o b e T h e English surgeon William

C l o w e s , w h o had served in Q u e e n E l i z a b e t h ' s fleet, gave a detailed description of the h o r r e n d o u s s y m p t o m s that w o u l d eventually kill t w o million sailors:

Their g u m s were rotten e v e n to the very roots of their very teeth, and their cheeks hard and s w o l l e n , the teeth were l o o s e neere ready to fall out their breath a filthy savour The legs were feeble and so w e a k , that they were full of aches and paines, with many blewish and reddish staines or spots, s o m e broad and s o m e small like flea-biting

All this m a k e s sense from a m o d e r n point of view, b e c a u s e we k n o w that scurvy is the result of vitamin C deficiency T h e h u m a n b o d y uses vitamin C to p r o d u c e c o l l a g e n , w h i c h glues together the b o d y ' s

m u s c l e s , blood vessels and other structures, and so helps to repair cuts and bruises H e n c e , a lack of vitamin C results in bleeding and the decay of cartilage, l i g a m e n t s , t e n d o n s , b o n e , skin, g u m s and teeth In short, a scurvy patient disintegrates gradually and dies painfully

T h e term ' v i t a m i n ' describes an organic nutrient that is vital for survival, but w h i c h the b o d y c a n n o t p r o d u c e itself; so it h a s to be supplied through food We typically obtain o u r vitamin C from fruit,

s o m e t h i n g that w a s sadly lacking from the average sailor's diet Instead, sailors ate biscuits, salted m e a t , dried fish, all of which w e r e

d e v o i d of vitamin C and likely to be riddled with w e e v i l s In fact, infestation w a s generally considered to be a g o o d sign, b e c a u s e the weevils w o u l d a b a n d o n the meat only w h e n it b e c a m e d a n g e r o u s l y rotten and truly inedible

T h e simple solution would have been to alter the sailors' diet, but scientists had yet to discover vitamin C and were unaware of the im-portance of fresh fruit in preventing scurvy Instead, physicians proposed

a whole series of other remedies Bloodletting, of course, was always worth a try, and other treatments included the consumption of mercury paste, salt water, vinegar, sulphuric acid, hydrochloric acid or Moselle wine Another treatment required burying the patient up to his neck in sand, which was not even very practical in the middle of the Pacific T h e most twisted remedy was hard labour, because doctors observed that scurvy was generally associated with lazy sailors Of course, the doctors had confused cause and effect, because it was scurvy that caused sailors

to be lazy, rather than laziness that m a d e sailors vulnerable to scurvy

T h i s array of pointless r e m e d i e s m e a n t that maritime ambitions during the seventeenth and eighteenth centuries continued to be

How Do You DETERMINE THE T R U T H ? 15

blighted by d e a t h s from scurvy L e a r n e d m e n around the w o r l d w o u l d fabricate arcane theories about the causes of scurvy and d e b a t e the merits of various c u r e s , but n o b o d y s e e m e d capable of stopping the rot that w a s killing h u n d r e d s of t h o u s a n d s of sailors T h e n , in 1746, there

c a m e a major b r e a k t h r o u g h w h e n a y o u n g Scottish naval surgeon

called J a m e s L i n d b o a r d e d H M S Salisbury His sharp brain and

meticulous m i n d a l l o w e d h i m to discard fashion, prejudice, anecdote and hearsay, and instead he tackled the curse of scurvy with e x t r e m e logic and rationality In short, J a m e s Lind w a s destined to succeed

w h e r e all others had failed b e c a u s e he i m p l e m e n t e d w h a t s e e m s to

have been the w o r l d ' s first controlled clinical trial

L i n d ' s tour of duty took h i m around the English C h a n n e l and

M e d i t e r r a n e a n , and e v e n t h o u g h H M S Salisbury n e v e r strayed far

from land, one in ten sailors s h o w e d signs of scurvy by the spring of

1747 L i n d ' s first instinct w a s probably to offer sailors o n e of the m a n y treatments p o p u l a r at the t i m e , but this w a s overtaken by another thought that crossed his m i n d W h a t w o u l d h a p p e n if he treated differ-ent sailors in different w a y s ? By observing w h o r e c o v e r e d and w h o deteriorated he w o u l d be able to d e t e r m i n e which treatments w e r e

effective and which w e r e u s e l e s s To us this m a y s e e m o b v i o u s , but it w a s

a truly r a d i c a l d e p a r t u r e from previous medical c u s t o m

On 20 M a y Lind identified twelve sailors with similarly serious s y m p t o m s of scurvy,

i n a s m u c h as t h e y all had 'putrid g u m s , the spots and lassitude, with w e a k n e s s of their k n e e s ' He then placed their h a m m o c k s in the s a m e portion of the ship and e n s u r e d that they all received the s a m e

b r e a k f a s t , l u n c h a n d d i n n e r ,

t h e r e b y e s t a b l i s h i n g ' o n e d i e t

James Lind c o m m o n to a l l ' In this way, Lind w a s

helping to g u a r a n t e e a fair test b e c a u s e all the patients w e r e similarly sick, similarly h o u s e d and similarly fed

He then d i v i d e d the sailors into six pairs and g a v e e a c h pair a different t r e a t m e n t T h e first pair received a quart of cider, t h e s e c o n d pair r e c e i v e d twenty-five d r o p s of elixir of vitriol (sulphuric acid) three t i m e s a day, the third pair r e c e i v e d t w o spoonfuls of v i n e g a r three t i m e s a day, the fourth pair r e c e i v e d half a pint of sea w a t e r a

d a y , the fifth pair r e c e i v e d a m e d i c i n a l paste c o n s i s t i n g of g a r l i c ,

m u s t a r d , radish root and g u m m y r r h , and the sixth pair r e c e i v e d t w o

o r a n g e s and a l e m o n each day A n o t h e r g r o u p of sick sailors w h o c o n tinued with the n o r m a l naval diet w e r e also m o n i t o r e d and acted as a control g r o u p

-T h e r e are t w o important points to clarify before m o v i n g o n First, the inclusion of oranges and l e m o n s w a s a shot in the dark A l t h o u g h there had been a few reports of l e m o n s relieving s y m p t o m s of scurvy

as far back as 1 6 0 1 , late-eighteenth-century d o c t o r s w o u l d h a v e

v i e w e d fruit as a bizarre r e m e d y H a d the term 'alternative m e d i c i n e ' existed in L i n d ' s era, then his colleagues might have labelled o r a n g e s and l e m o n s as alternative, as they w e r e natural r e m e d i e s that were not

b a c k e d by a plausible theory, and thus they were unlikely to c o m p a r e well against the m o r e established m e d i c i n e s

T h e second important point is that Lind did not include bloodletting

in his trial A l t h o u g h others m a y h a v e felt that bloodletting w a s a p p r o priate for treating scurvy, Lind w a s u n c o n v i n c e d and instead he suspected that the g e n u i n e cure w o u l d be related to diet We shall return to the question of testing bloodletting shortly

-T h e clinicial trial began and Lind waited to see which sailors, if any,

w o u l d recover A l t h o u g h the trial was supposed to last fourteen d a y s , the s h i p ' s supply of citrus fruits c a m e to an end after j u s t six d a y s , so Lind had to evaluate the results at this early stage Fortunately, the c o n -clusion was already o b v i o u s , for the sailors w h o w e r e c o n s u m i n g

l e m o n s and o r a n g e s had m a d e a r e m a r k a b l e and almost c o m p l e t e recovery All the other patients w e r e still suffering from scurvy, except for the cider drinkers w h o s h o w e d slight signs of i m p r o v e m e n t This is probably b e c a u s e cider can also contain small a m o u n t s of vitamin C,

d e p e n d i n g on h o w it is m a d e

17

By controlling variables such as e n v i r o n m e n t and diet, L i n d h a d

d e m o n s t r a t e d that o r a n g e s and l e m o n s w e r e the key to curing scurvy Whilst the n u m b e r s of patients involved in the trial w e r e e x t r e m e l y small, the results he obtained w e r e so striking that he w a s c o n v i n c e d

by the findings He h a d no idea, of c o u r s e , that o r a n g e s and l e m o n s contain vitamin C, or that vitamin C is a key ingredient in the production of c o l l a g e n , but n o n e of this w a s important - the b o t t o m line w a s that his treatment led to a c u r e D e m o n s t r a t i n g that a treatment

is effective is the n u m b e r - o n e priority in m e d i c i n e ; u n d e r s t a n d i n g the exact details of the u n d e r l y i n g m e c h a n i s m can be left as a p r o b l e m for subsequent research

H a d Lind been researching in the twenty-first century, he w o u l d

h a v e reported his findings at a major conference and subsequently published t h e m in a m e d i c a l j o u r n a l O t h e r scientists w o u l d h a v e read his m e t h o d o l o g y and repeated his trial, and within a year or t w o there

w o u l d h a v e been an international c o n s e n s u s on the ability of o r a n g e s and l e m o n s to cure scurvy Unfortunately, the eighteenth-century m e d -ical c o m m u n i t y w a s c o m p a r a t i v e l y splintered, so n e w b r e a k t h r o u g h s were often o v e r l o o k e d

Lind himself did not h e l p matters b e c a u s e he w a s a diffident m a n ,

w h o failed to publicize and p r o m o t e his research Eventually, six years after the trial, he did write up his w o r k in a b o o k dedicated to

C o m m a n d e r A n s o n , w h o had famously lost o v e r 1,000 m e n to scurvy

just a few years earlier Treatise on the Scurvy w a s an intimidating

t o m e consisting of 4 0 0 pages written in a p l o d d i n g style, so not surprisingly it w o n h i m few s u p p o r t e r s

Worse still, Lind u n d e r m i n e d the credibility of his cure with his

d e v e l o p m e n t of a concentrated version of l e m o n j u i c e that w o u l d be

easier to transport, store, preserve and administer T h i s so-called rob

w a s created by heating and e v a p o r a t i n g lemon j u i c e , but Lind did not realize that this process destroyed vitamin C, the active ingredient that cured scurvy T h e r e f o r e , a n y b o d y w h o followed L i n d ' s r e c o m m e n d -ation soon b e c a m e disillusioned, b e c a u s e the l e m o n r o b w a s almost totally ineffective S o , despite a successful trial, the simple l e m o n cure

w a s i g n o r e d , scurvy c o n t i n u e d u n a b a t e d and m a n y m o r e sailors d i e d

By the time that the S e v e n Years War with F r a n c e had e n d e d in 1 7 6 3 ,

the tallies s h o w e d that 1,512 British sailors had been killed in action and 100,000 had been killed by scurvy

H o w e v e r , in 1780, thirty-three years after the original trial, L i n d ' s

w o r k c a u g h t the eye of the influential physician Gilbert B l a n e

N i c k n a m e d ' C h i l l b l a i n ' b e c a u s e of his frosty d e m e a n o u r , B l a n e had

s t u m b l e d u p o n L i n d ' s treatise on scurvy while he w a s preparing for his first naval posting with the British fleet in the C a r i b b e a n He w a s

i m p r e s s e d by L i n d ' s declaration that he w o u l d ' p r o p o s e nothing dictated merely from theory; but shall confirm all by e x p e r i e n c e and facts, the surest and m o s t unerring g u i d e s ' Inspired by L i n d ' s approach and interested in his c o n c l u s i o n , B l a n e decided that he w o u l d scrupulously m o n i t o r mortality rates t h r o u g h o u t the British fleet in the West Indies in order to see w h a t w o u l d h a p p e n if he introduced l e m o n s

to the diet of all sailors

A l t h o u g h B l a n e ' s study w a s less rigorously controlled than L i n d ' s

r e s e a r c h , it did involve a m u c h larger n u m b e r of sailors and its results were arguably even m o r e striking D u r i n g his first year in the West Indies there were 12,019 sailors in the British fleet, of w h o m only sixty died in c o m b a t and a further 1,518 died of d i s e a s e , with scurvy

a c c o u n t i n g for the o v e r w h e l m i n g majority of these d e a t h s H o w e v e r , after Blane introduced l e m o n s into the diet, the mortality rate w a s cut

in half Later, limes w e r e often used instead of l e m o n s , which led to

limeys as a slang term for British sailors and later for Brits in general

Not only did Blane b e c o m e c o n v i n c e d of the i m p o r t a n c e of fresh fruit, but fifteen y e a r s later he w a s able to i m p l e m e n t scurvy prevention throughout the British fleet w h e n he w a s appointed to the Sick and Hurt B o a r d , w h i c h w a s responsible for determining naval medical p r o c e d u r e s On 5 M a r c h 1795 the B o a r d and the A d m i r a l t y agreed that sailors' lives w o u l d be saved if they w e r e issued a daily ration of just three-quarters of an o u n c e of l e m o n j u i c e Lind had died

j u s t o n e year earlier, but his mission to rid British ships of scurvy had been ably c o m p l e t e d by B l a n e

T h e British had been tardy in adopting lemon therapy, as almost half

a century had passed since L i n d ' s g r o u n d b r e a k i n g trial, but m a n y other nations were even tardier T h i s g a v e Britain a h u g e a d v a n t a g e in terms

of colonizing distant lands and w i n n i n g sea battles with its E u r o p e a n

n e i g h b o u r s F o r e x a m p l e , prior to the Battle of Trafalgar in 1805,

N a p o l e o n had p l a n n e d to i n v a d e Britain, but he w a s p r e v e n t e d from

d o i n g so by a British naval b l o c k a d e that trapped his ships in their

h o m e ports for several m o n t h s Bottling up the F r e n c h fleet w a s possible only b e c a u s e the British ships supplied their c r e w s with fruit,

w h i c h m e a n t that they did not h a v e to interrupt their tour of duty to bring on board n e w healthy sailors to replace those that w o u l d h a v e been d y i n g from scurvy I n d e e e d , it is no exaggeration to say that

L i n d ' s invention of the clinical trial and B l a n e ' s c o n s e q u e n t p r o m o t i o n

of l e m o n s to treat scurvy saved the nation, b e c a u s e N a p o l e o n ' s a r m y

w a s m u c h stronger than its British counterpart, so a failed b l o c k a d e

w o u l d probably h a v e resulted in a successful F r e n c h invasion

T h e fate of a nation is of major historic i m p o r t a n c e , yet the application of the clinical trial w o u l d h a v e e v e n greater significance in the centuries a h e a d M e d i c a l researchers w o u l d go on to use clinical trials routinely to d e c i d e w h i c h treatments w o r k e d and w h i c h w e r e in-effective In turn, this w o u l d allow doctors to save h u n d r e d s of millions of lives around the world b e c a u s e they w o u l d be able to cure diseases by confidently relying on proven m e d i c i n e s , rather than m i s -takenly a d v o c a t i n g q u a c k r e m e d i e s

Bloodletting, b e c a u s e of its central role in m e d i c i n e , w a s o n e of the first treatments to be submitted to testing via the controlled clinical trial In 1809, j u s t a d e c a d e after Washington had u n d e r g o n e blood-letting on his d e a t h b e d , a Scottish military surgeon called A l e x a n d e r

H a m i l t o n set out to d e t e r m i n e w h e t h e r or not it w a s advisable to bleed patients Ideally, his clinical trial w o u l d h a v e e x a m i n e d the impact of bloodletting on a single disease or s y m p t o m , such as g o n o r r h o e a or fever, b e c a u s e the results tend to be clearer if a trial is focused on one treatment for o n e a i l m e n t H o w e v e r , the trial took place while

H a m i l t o n w a s serving in the Peninsular War in P o r t u g a l , w h e r e battlefield conditions did not afford him the luxury of c o n d u c t i n g an ideal trial - instead, he e x a m i n e d the impact of bloodletting on a broad range of c o n d i t i o n s To be fair to H a m i l t o n , this w a s not such an u n r e a s o n a b l e design for his trial, b e c a u s e at the time blood-letting w a s t o u t e d as a p a n a c e a - if p h y s i c i a n s b e l i e v e d that bloodletting could c u r e every d i s e a s e , then it c o u l d be argued

that the trial should include patients with every d i s e a s e

H a m i l t o n b e g a n his trial by dividing a s a m p l e of 3 6 6 soldiers with

a variety of medical p r o b l e m s into three g r o u p s T h e first t w o g r o u p s were treated by himself and a colleague ( M r A n d e r s o n ) without resort-ing to bloodletting, w h e r e a s the third g r o u p w a s treated by an u n n a m e d doctor w h o administered the usual treatment of e m p l o y i n g a lancet to bleed his patients T h e results of the trial w e r e clear:

It had been so arranged, that this number was admitted, alternately, in such a manner that each of us had one third of the whole The sick were indiscriminately received, and were attended as nearly as possible with the same care and accommodated with the same comforts Neither

Mr Anderson nor I ever once employed the lancet He lost two, I four cases; whilst out of the other third thirty-five patients died.'

T h e death rate for patients treated with bloodletting w a s ten times greater than for those patients w h o a v o i d e d bloodletting T h i s w a s a

d a m n i n g indictment on d r a w i n g b l o o d and a vivid d e m o n s t r a t i o n that

it caused death rather than saved lives It w o u l d h a v e been hard to argue with the trial's c o n c l u s i o n , b e c a u s e it scored highly in terms of

t w o of the main factors that d e t e r m i n e the quality of a trial

First, the trial w a s carefully controlled, which m e a n s that the separate groups of patients w e r e treated similarly e x c e p t for o n e par-ticular factor, n a m e l y bloodletting This allowed H a m i l t o n to isolate the impact of bloodletting H a d the bloodletting g r o u p been kept in poorer conditions or given a different diet, then the higher death rate could h a v e been attributed to e n v i r o n m e n t or nutrition, but H a m i l t o n had e n s u r e d that all the g r o u p s received the ' s a m e c a r e ' and ' s a m e

c o m f o r t s ' Therefore bloodletting alone could be identified as b e i n g responsible for the higher death rate in the third g r o u p

S e c o n d , H a m i l t o n had tried to ensure that his trial was fair by guaranteeing that the g r o u p s that w e r e b e i n g studied were on a v e r a g e

as similar as p o s s i b l e He achieved this by avoiding any systematic

a s s i g n m e n t of patients, such as deliberately steering elderly soldiers towards the bloodletting g r o u p , w h i c h w o u l d have biased the trial against bloodletting Instead, H a m i l t o n assigned patients to each g r o u p

21

' a l t e r n a t e l y ' a n d ' i n d i s c r i m i n a t e l y ' , w h i c h t o d a y i s k n o w n a s

randomizing the allocation of treatments in a trial If the patients are

r a n d o m l y assigned to g r o u p s , then it can be a s s u m e d that the groups will be broadly similar in terms of any factor, such as a g e , i n c o m e ,

g e n d e r or the severity of the illness, w h i c h m i g h t affect a p a t i e n t ' s

out-c o m e R a n d o m i z a t i o n e v e n allows for u n k n o w n faout-ctors to be b a l a n out-c e d equally across the g r o u p s Fairness through r a n d o m i z a t i o n is par-ticularly effective if the initial pool of participants is large In this c a s e , the n u m b e r of participants (366 patients) w a s impressively large

Today medical researchers call this a randomized controlled trial (or

R C T ) or a randomized clinical trial, and it is c o n s i d e r e d t h e gold

standard for putting therapies to the test

A l t h o u g h H a m i l t o n s u c c e e d e d in c o n d u c t i n g the first r a n d o m i z e d clinical trial on the effects of bloodletting, he failed to publish his results In fact, we k n o w of H a m i l t o n ' s r e s e a r c h only b e c a u s e his d o c u m e n t s w e r e rediscovered in 1987 a m o n g papers hidden in a trunk lodged with the R o y a l C o l l e g e of Physicians in E d i n b u r g h Failure to publish is a serious dereliction of duty for any medical researcher, because publication has t w o important c o n s e q u e n c e s First,

it e n c o u r a g e s others to replicate the r e s e a r c h , which might either reveal errors in the original research or confirm the result S e c o n d , publi-cation is the best w a y to disseminate n e w r e s e a r c h , so that others can apply what has been learned

L a c k of publication m e a n t that H a m i l t o n ' s bloodletting trial had no impact on the w i d e s p r e a d e n t h u s i a s m for the practice Instead, it w o u l d take a few m o r e years before other medical p i o n e e r s , such as the French doctor Pierre L o u i s , w o u l d c o n d u c t their o w n trials and con-

f i r m H a m i l t o n ' s c o n c l u s i o n T h e s e results, w h i c h w e r e properly published and d i s s e m i n a t e d , repeatedly s h o w e d that bloodletting w a s not a lifesaver, but rather it w a s a potential killer In light of these find-

i n g s , it s e e m s highly likely that bloodletting w a s largely responsible for the death of G e o r g e W a s h i n g t o n

Unfortunately, b e c a u s e these anti-bloodletting c o n c l u s i o n s were contrary to the prevailing view, m a n y doctors struggled to accept them and e v e n tried their best to u n d e r m i n e t h e m F o r e x a m p l e , w h e n Pierre Louis published the results of his trials in 1 8 2 8 , m a n y doctors

d i s m i s s e d his negative conclusion about bloodletting precisely b e c a u s e

it w a s based on the data gathered by analysing large n u m b e r s of patients T h e y slated his so-called ' n u m e r i c a l m e t h o d ' b e c a u s e they were m o r e interested in treating the individual patient lying in front of

t h e m than in w h a t might h a p p e n to a large s a m p l e of patients L o u i s

r e s p o n d e d by arguing that it w a s impossible to k n o w w h e t h e r or not a treatment might be safe and effective for the individual patient unless

it had been d e m o n s t r a t e d to be safe and effective for a large n u m b e r of patients: 'A therapeutic agent c a n n o t be e m p l o y e d with any discrimi-nation or probability of success in a given c a s e , unless its general efficacy, in a n a l o g o u s c a s e s , h a s been previously ascertained with-out the aid of statistics nothing like real m e d i c i n e is p o s s i b l e '

And when the Scottish doctor Alexander M a c L e a n advocated the use

of medical trials to test treatments while he was working in India in 1818, critics argued that it was wrong to experiment with the health of patients

in this way He responded by pointing out that avoiding trials would mean that medicine would for ever be nothing more than a collection of untested treatments, which might be wholly ineffective or dangerous He described medicine practised without any evidence as 'a continued series

of experiments upon the lives of our fellow creatures.'

Despite the invention of the clinical trial and regardless of the

e v i d e n c e against bloodletting, m a n y E u r o p e a n doctors c o n t i n u e d to bleed their patients, so m u c h so that France had to import 42 million leeches in 1 8 3 3 But as each d e c a d e p a s s e d , rationality began to take hold a m o n g d o c t o r s , trials b e c a m e m o r e c o m m o n , and d a n g e r o u s and useless therapies such as bloodletting began to d e c l i n e

Prior to the clinical trial, a d o c t o r decided his treatment for a ticular patient by relying on his o w n prejudices, or on what he had been taught by his p e e r s , or on his m i s r e m e m b e r e d experiences of dealing with a handful of patients with a similar condition After the advent of the clinical trial, doctors could c h o o s e their treatment for a single patient by e x a m i n i n g the e v i d e n c e from several trials, perhaps involving t h o u s a n d s of patients T h e r e w a s still no guarantee that a treatment that had s u c c e e d e d during a set of trials w o u l d cure a partic-ular patient, but any doctor w h o adopted this approach w a s giving his patient the best possible c h a n c e of recovery

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L i n d ' s invention of the clinical trial had triggered a gradual r e v o lution that gained m o m e n t u m d u r i n g the course of t h e nineteenth century It transformed m e d i c i n e from a d a n g e r o u s lottery in the eighteenth century into a rational discipline in the twentieth century

-T h e clinical trial h e l p e d give birth to m o d e r n m e d i c i n e , w h i c h h a s

e n a b l e d us to live longer, healthier, h a p p i e r lives

in m a k i n g decisions about the care of individual p a t i e n t s '

E v i d e n c e - b a s e d m e d i c i n e e m p o w e r s d o c t o r s b y p r o v i d i n g t h e m with the m o s t reliable information, and therefore it benefits patients by increasing the likelihood that they will receive the m o s t appropriate treatment F r o m a twenty-first-century p e r s p e c t i v e , it s e e m s o b v i o u s that m e d i c a l d e c i s i o n s should be based on e v i d e n c e , typically from

r a n d o m i z e d clinical trials, but the e m e r g e n c e of e v i d e n c e - b a s e d

m e d i c i n e m a r k s a turning point in the history of m e d i c i n e

Prior to the d e v e l o p m e n t of e v i d e n c e - b a s e d m e d i c i n e , doctors w e r e spectacularly ineffective T h o s e patients w h o r e c o v e r e d from disease

w e r e usually successful despite the treatments they h a d r e c e i v e d , not

b e c a u s e of t h e m B u t o n c e the m e d i c a l establishment had adopted such simple ideas as the clinical trial, then progress b e c a m e swift Today the clinical trial is routine in the d e v e l o p m e n t of n e w treatments and medical experts agree that e v i d e n c e - b a s e d m e d i c i n e is the key to effective h e a l t h c a r e

H o w e v e r , p e o p l e outside the m e d i c a l e s t a b l i s h m e n t s o m e t i m e s find the c o n c e p t of e v i d e n c e - b a s e d m e d i c i n e c o l d , confusing and

intimidating If you h a v e any s y m p a t h y with this point of v i e w , t h e n ,

o n c e a g a i n , it is worth r e m e m b e r i n g w h a t the w o r l d w a s like before the advent of the clinical trial and e v i d e n c e - b a s e d m e d i c i n e : d o c t o r s w e r e oblivious to the h a r m they c a u s e d by b l e e d i n g millions of p e o p l e , indeed killing m a n y o f t h e m , including G e o r g e W a s h i n g t o n T h e s e

d o c t o r s w e r e not stupid or evil; they m e r e l y lacked the k n o w l e d g e that

e m e r g e s w h e n medical trials flourish

Recall Benjamin R u s h , for e x a m p l e , the prolific b l e e d e r w h o sued for libel and w o n his case on the day that W a s h i n g t o n died He w a s a brilliant, well-educated m a n and a c o m p a s s i o n a t e o n e , w h o w a s responsible for recognizing addiction as a m e d i c a l condition and realizing that alcoholics lose the capacity to control their drinking behaviour He w a s also an a d v o c a t e for w o m e n ' s r i g h t s , fought to abolish slavery and c a m p a i g n e d against capital p u n i s h m e n t H o w e v e r , this c o m b i n a t i o n of intelligence and d e c e n c y w a s not e n o u g h to stop

h i m from killing h u n d r e d s of patients by bleeding t h e m to d e a t h , and

e n c o u r a g i n g m a n y of his students to do exactly the s a m e

R u s h w a s fooled by his respect for ancient ideas c o u p l e d with the ad hoc reasons that w e r e invented to justify the use of b l o o d l e t t i n g F o r

e x a m p l e , it w o u l d have been easy for R u s h to m i s t a k e the sedation

c a u s e d by bloodletting for a g e n u i n e i m p r o v e m e n t , u n a w a r e that he

w a s draining the life out of his patients He w a s also probably confused

by his o w n m e m o r y , selectively r e m e m b e r i n g those of his patients w h o

s u r v i v e d b l e e d i n g and c o n v e n i e n t l y forgetting those w h o d i e d

M o r e o v e r , Rush w o u l d h a v e been t e m p t e d to attribute any success to his treatment and to dismiss any failure as the fault of a patient w h o in any case w a s destined to d i e

A l t h o u g h e v i d e n c e - b a s e d m e d i c i n e n o w c o n d e m n s the sort of bloodletting that R u s h indulged in, it is important to point out that

e v i d e n c e - b a s e d m e d i c i n e also m e a n s r e m a i n i n g open to n e w e v i d e n c e and revising c o n c l u s i o n s For e x a m p l e , thanks to the latest e v i d e n c e from n e w trials, bloodletting is o n c e again an acceptable treatment in very specific situations - it has n o w been d e m o n s t r a t e d , for i n s t a n c e , that bloodletting as a last resort can ease the fluid overload c a u s e d by heart failure Similarly, there is n o w a role for leeches in helping patients recover from s o m e forms of surgery F o r e x a m p l e , in 2 0 0 7 a

w o m a n in Yorkshire had leeches placed in her m o u t h four times a day for a w e e k and a half after h a v i n g a c a n c e r o u s t u m o u r r e m o v e d and her tongue reconstructed T h i s w a s b e c a u s e leeches release c h e m i c a l s that increase blood flow and thus accelerate healing

D e s p i t e b e i n g a n u n d o u b t e d force for g o o d , e v i d e n c e - b a s e d

m e d i c i n e is occasionally treated with suspicion S o m e people perceive

it as b e i n g a strategy for a l l o w i n g the medical e s t a b l i s h m e n t to defend its o w n m e m b e r s and their t r e a t m e n t s , while e x c l u d i n g outsiders w h o offer alternative t r e a t m e n t s In fact, as we h a v e seen already, the o p p o -site is often true, b e c a u s e e v i d e n c e - b a s e d m e d i c i n e actually allows outsiders to be heard - it e n d o r s e s any treatment that turns out to be effective, regardless of w h o is behind it, and regardless of h o w strange

it might appear to b e L e m o n j u i c e as a treatment for scurvy w a s an implausible r e m e d y , but the establishment had to accept it b e c a u s e it

w a s b a c k e d up by e v i d e n c e from trials Bloodletting, on the other

h a n d , w a s very m u c h a standard treatment, but the establishment eventually had to reject its o w n practice b e c a u s e it w a s u n d e r m i n e d by

e v i d e n c e from trials

T h e r e is one episode from the history of m e d i c i n e that illustrates particularly well h o w an e v i d e n c e - b a s e d approach forces the medical establishment to accept the c o n c l u s i o n s that e m e r g e w h e n m e d i c i n e is put to the test Florence N i g h t i n g a l e , the Lady with the L a m p , was a

w o m a n with very little reputation, but she still m a n a g e d to win a bitter

a r g u m e n t against the m a l e - d o m i n a t e d m e d i c a l e s t a b l i s h m e n t by

a r m i n g herself with solid, irrefutable data Indeed, she can be seen as

o n e of the earliest a d v o c a t e s of e v i d e n c e - b a s e d m e d i c i n e , and she cessfully used it to transform Victorian healthcare

suc-Florence and her sister were born during an e x t e n d e d and very ductive two-year-long Italian h o n e y m o o n taken by their parents William and Frances N i g h t i n g a l e F l o r e n c e ' s older sister w a s born in

pro-1819 and n a m e d P a r t h e n o p e after the city of her birth - P a r t h e n o p e being the G r e e k n a m e for N a p l e s T h e n Florence w a s born in the spring of 1820, and she t o o w a s n a m e d after the city of her birth It w a s

e x p e c t e d that F l o r e n c e Nightingale w o u l d g r o w up to live the life of a privileged English Victorian lady, but as a teenager she regularly

c l a i m e d to hear G o d ' s voice guiding her H e n c e , it s e e m s that her

desire to b e c o m e a nurse w a s the result of a ' d i v i n e c a l l i n g ' T h i s distressed her p a r e n t s , b e c a u s e nurses w e r e generally v i e w e d as being poorly e d u c a t e d , p r o m i s c u o u s and often d r u n k , but these w e r e exactly the prejudices that Florence w a s d e t e r m i n e d to crush

T h e prospect of Florence nursing in Britain w a s already s h o c k i n g

e n o u g h , so her parents w o u l d h a v e been d o u b l y terrified by her s u b sequent decision to w o r k in the hospitals of the C r i m e a n War F l o r e n c e

-had read scandalous reports in n e w s p a p e r s such as The Times, w h i c h

highlighted the large n u m b e r of soldiers w h o w e r e s u c c u m b i n g to cholera and malaria She volunteered her services, and by N o v e m b e r

1854 Florence w a s running the Scutari Hospital in Turkey, w h i c h w a s notorious for its filthy w a r d s , dirty b e d s , b l o c k e d sewers and rotten food It soon b e c a m e clear to her that the m a i n c a u s e of death w a s not the w o u n d s suffered by the soldiers, but rather the diseases that ran rife

u n d e r such squalid c o n d i t i o n s As one official report a d m i t t e d , ' T h e

w i n d blew s e w e r air up the pipes of n u m e r o u s o p e n privies into the corridors and w a r d s w h e r e the sick w e r e l y i n g '

Nightingale set about transforming the hospital by providing decent food, clean linen, clearing out the drains and o p e n i n g the w i n d o w s to let in fresh air In j u s t o n e w e e k she r e m o v e d 215 handcarts of filth, flushed the sewers nineteen times and buried the carcasses of t w o

h o r s e s , a c o w and four d o g s w h i c h had been found in the hospital

g r o u n d s T h e officers and d o c t o r s w h o had previously run the institution felt that these changes were an insult to their professionalism and fought her every step of the way, but she p u s h e d ahead regardless

T h e results s e e m e d to vindicate her m e t h o d s : in February 1855 the death rate for all admitted soldiers w a s 43 per cent, but after her reforms it fell dramatically to j u s t 2 per cent in J u n e 1855 W h e n she returned to Britain in the s u m m e r of 1856, Nightingale w a s greeted as

a h e r o , in large part due to The Times'?, support:

Wherever there is disease in its most dangerous form, and the hand of the spoiler distressingly nigh, there is that incomparable w o m a n sure to

be seen; her benignant presence is an influence for g o o d comfort e v e n amid the struggles of expiring nature She is a 'ministering angel' with- out any exaggeration in these hospitals, and, as her slender form glides

27

quietly along each corridor, every f e l l o w ' s face softens with gratitude at the sight of her

H o w e v e r , there w e r e still m a n y sceptics T h e principal medical officer of the army argued that N i g h t i n g a l e ' s higher survival rates w e r e not necessarily d u e to her i m p r o v e d h y g i e n e He pointed out that her apparent success m i g h t h a v e been due to treating soldiers with less serious w o u n d s , or m a y b e they were treated during a period of milder weather, or m a y b e there w a s s o m e other factor that had not b e e n taken into a c c o u n t

Fortunately, as well as being an exceptionally dedicated military

n u r s e , Nightingale w a s also a brilliant statistician H e r father, William

N i g h t i n g a l e , had been b r o a d m i n d e d e n o u g h to believe that w o m e n should be properly e d u c a t e d , so F l o r e n c e had studied Italian, L a t i n ,

G r e e k , history, and particularly m a t h e m a t i c s In fact, she had received tutoring from s o m e of B r i t a i n ' s finest m a t h e m a t i c i a n s , such as J a m e s Sylvester and A r t h u r Cayley

S o , w h e n she w a s c h a l l e n g e d by the British e s t a b l i s h m e n t , she d r e w upon this m a t h e m a t i c a l training and used statistical a r g u m e n t s to back

h e r c l a i m that i m p r o v e d h y g i e n e led t o h i g h e r s u r v i v a l r a t e s Nightingale had scrupulously c o m p i l e d detailed records of her patients throughout her time in the C r i m e a , so she w a s able to trawl through

t h e m and find all sorts of e v i d e n c e that proved that she w a s right about the importance of h y g i e n e in healthcare

For e x a m p l e , to s h o w that the filth at Scutari Hospital had been killing soldiers, she used her records to c o m p a r e a g r o u p of soldiers treated at Scutari in the early u n h y g i e n i c days with a control g r o u p of injured soldiers w h o at the s a m e time were being kept at their o w n

a r m y c a m p If the c a m p - b a s e d control g r o u p fared better than the Scutari g r o u p , then this w o u l d indicate that the conditions that Nightingale e n c o u n t e r e d w h e n she arrived at Scutari w e r e indeed

d o i n g m o r e h a r m than g o o d Sure e n o u g h , the c a m p - b a s e d soldiers had

a mortality rate of 27 d e a t h s per 1,000 c o m p a r e d with 4 2 7 per 1,000 at Scutari T h i s was only o n e set of statistics, but w h e n put alongside other c o m p a r i s o n s it helped Nightingale to win her a r g u m e n t about the importance of h y g i e n e

N i g h t i n g a l e w a s c o n v i n c e d that all other major m e d i c a l decisions

o u g h t to be b a s e d on similar sorts of e v i d e n c e , so she fought for the

e s t a b l i s h m e n t of a R o y a l C o m m i s s i o n on the Health of the A r m y , to

w h i c h she herself s u b m i t t e d several h u n d r e d p a g e s of detailed statistics At a time w h e n it w a s c o n s i d e r e d radical merely to include data tables, she also drew m u l t i c o l o u r e d d i a g r a m s that w o u l d not look out of place in a m o d e r n b o a r d r o o m presentation She e v e n invented

an elaborate version of the pie chart, k n o w n as the polar area chart,

w h i c h h e l p e d to illustrate her data She realized that illustrating her statistics w o u l d be e n o r m o u s l y helpful in selling her a r g u m e n t to politicians, w h o w e r e usually not well versed in m a t h e m a t i c s

In d u e c o u r s e , N i g h t i n g a l e ' s statistical studies s p e a r h e a d e d a r e v o lution in a r m y hospitals, b e c a u s e the R o y a l C o m m i s s i o n ' s report led to the e s t a b l i s h m e n t of an A r m y M e d i c a l S c h o o l and a system of collect-ing m e d i c a l r e c o r d s In turn, this resulted in a careful monitoring of which c o n d i t i o n s and treatments did and did not benefit patients Today, Florence Nightingale is best k n o w n as the founder of m o d e r n

-n u r s i -n g , h a v i -n g established a c u r r i c u l u m a-nd trai-ni-ng college for

n u r s e s H o w e v e r , it can be argued that her lifelong c a m p a i g n i n g for health reforms based on statistical e v i d e n c e had an even m o r e signifi-cant impact on healthcare She was elected the first female m e m b e r of the Royal Statistical Society in 1858, and w e n t on to b e c o m e an hon-orary m e m b e r of the A m e r i c a n Statistical A s s o c i a t i o n

N i g h t i n g a l e ' s passion for statistics e n a b l e d her to persuade the

g o v e r n m e n t of the i m p o r t a n c e of a w h o l e series of health r e f o r m s F o r

e x a m p l e , m a n y people had argued that training nurses w a s a waste of

t i m e , b e c a u s e patients cared for by trained nurses actually had a higher mortality rate than those treated by untrained staff N i g h t i n g a l e , h o w -ever, pointed out that this w a s only b e c a u s e m o r e serious cases w e r e being sent to those w a r d s with trained n u r s e s If the intention is to

c o m p a r e the results from t w o g r o u p s , then it is essential (as discussed earlier) to assign patients r a n d o m l y to the t w o g r o u p s Sure e n o u g h ,

w h e n N i g h t i n g a l e set up trials in which patients w e r e r a n d o m l y assigned to trained and untrained n u r s e s , it b e c a m e clear that the cohort

of patients treated by trained nurses fared much better than their parts in wards with untrained nurses Furthermore, Nightingale used

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April 1854-March 1855

statistics to show that h o m e births were safer than hospital births, sumably because British h o m e s were cleaner than Victorian hospitals Her interests also ranged overseas, because she also used mathematics to study the influence of sanitation on healthcare in rural India

pre-A n d throughout her long career, N i g h t i n g a l e ' s c o m m i t m e n t to

w o r k i n g with soldiers n e v e r w a n e d In o n e of her later studies, she

o b s e r v e d that soldiers based in Britain in p e a c e t i m e had an annual mortality rate of 20 per 1,000, nearly twice that of civilians, which she suspected w a s d u e to poor conditions in their b a r r a c k s She calculated the death toll across the w h o l e British a r m y d u e to poor

a c c o m m o d a t i o n and then m a d e a c o m m e n t that highlighted h o w this

w a s such a needless w a s t e of y o u n g lives: 'You m i g h t as well take 1,100 m e n every year out upon Salisbury Plain and shoot t h e m '

T h e lesson to be learned from Florence N i g h t i n g a l e ' s medical

t r i u m p h s is that scientific testing is not j u s t the best w a y to establish truth in m e d i c i n e , but it is also the best m e c h a n i s m for having that truth

r e c o g n i z e d T h e results f r o m scientific tests are so powerful that they even enable a relative u n k n o w n such as N i g h t i n g a l e - a y o u n g w o m a n , not part of the e s t a b l i s h m e n t , w i t h o u t a great reputation - to p r o v e that she is right and that those in p o w e r are w r o n g Without m e d i c a l test-ing, lone visionaries s u c h as N i g h t i n g a l e w o u l d be ignored, while doctors w o u l d continue to operate a c c o r d i n g to a corrupt b o d y of

m e d i c a l k n o w l e d g e b a s e d m e r e l y o n t r a d i t i o n , d o g m a , f a s h i o n , politics, marketing and a n e c d o t e

A stroke of genius

Before applying an e v i d e n c e - b a s e d a p p r o a c h to evaluating alternative

m e d i c i n e , it is worth r e - e m p h a s i z i n g that it p r o v i d e s extraordinarily powerful and persuasive c o n c l u s i o n s I n d e e d , it is not j u s t the m e d i c a l establishment that has to t u g its forelock in the face of e v i d e n c e - b a s e d

m e d i c i n e , b e c a u s e g o v e r n m e n t s can also be forced to c h a n g e their policies and corporations m a y h a v e to alter their products a c c o r d i n g to what the scientific e v i d e n c e s h o w s O n e final story illustrates exactly

h o w scientific e v i d e n c e c a n m a k e the w o r l d sit u p , listen and act regarding health issues - it c o n c e r n s the research that dramatically revealed the previously u n k n o w n d a n g e r s of s m o k i n g

T h i s research w a s c o n d u c t e d by Sir Austin Bradford Hill and Sir Richard Doll, w h o had c u r i o u s l y mirrored each other in their back-

g r o u n d s Hill had w a n t e d to follow in his father's footsteps and

b e c o m e a doctor, but a b o u t of tuberculosis m a d e this i m p o s s i b l e , so instead he pursued a m o r e m a t h e m a t i c a l career D o l l ' s ambition w a s to study m a t h e m a t i c s at C a m b r i d g e , but he got drunk on three pints of Trinity Audit A l e (8 per c e n t alcohol) the night before his entrance

e x a m and underperformed, so instead he p u r s u e d a career in m e d i c i n e

T h e result w a s a pair of m e n with strong interests in both healthcare and statistics

Hill's career had involved research into a wide variety of health issues In the 1940s, for instance, he demonstrated a link b e t w e e n arsenic and cancer in c h e m i c a l workers by e x a m i n i n g death certificates, and he went on to p r o v e that rubella during p r e g n a n c y could lead

to deformities in b a b i e s He also c o n d u c t e d important research

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into the effectiveness of antibiotics against t u b e r c u l o s i s , the disease that had e n d e d his h o p e s of b e c o m i n g a doctor T h e n , in 1 9 4 8 , H i l l ' s interest turned t o w a r d s lung cancer, b e c a u s e there h a d been a sixfold increase in cases of the disease in j u s t t w o d e c a d e s E x p e r t s w e r e divided as to w h a t w a s b e h i n d this health crisis, with s o m e of t h e m dis-missing it as a c o n s e q u e n c e of better d i a g n o s i s , while others suggested that lung c a n c e r w a s b e i n g triggered by industrial pollution, car fumes

o r perhaps s m o k i n g

With no c o n s e n s u s in sight, Hill t e a m e d up with Doll and decided to investigate o n e of the p r o p o s e d causes of lung cancer, n a m e l y s m o k -ing H o w e v e r , they faced an o b v i o u s p r o b l e m - they could not c o n d u c t

a r a n d o m i z e d clinical trial in this particular context F o r i n s t a n c e , it

w o u l d h a v e been u n e t h i c a l , impractical and pointless to take 100

t e e n a g e r s , p e r s u a d e half of t h e m to s m o k e for a w e e k , and then look for signs of lung cancer

Instead, Hill and Doll d e c i d e d that it w o u l d be necessary to devise

a prospective cohort study or an observational study, w h i c h m e a n s that

a g r o u p of healthy individuals is initially identified and then their s u b sequent health is m o n i t o r e d while they carry on their day-to-day lives

-T h i s is a m u c h less interventionist approach than a r a n d o m i z e d cal trial, w h i c h is w h y a prospective cohort study is preferable for exploring long-term health issues

clini-To spot any link b e t w e e n s m o k i n g and lung c a n c e r in their prospective cohort study, Hill and Doll w o r k e d out that they w o u l d need to recruit volunteers w h o fulfilled three important criteria First, the participants had to be established s m o k e r s or v e h e m e n t n o n -

s m o k e r s , b e c a u s e this increased the likelihood that the pattern of

b e h a v i o u r of any individual w o u l d continue t h r o u g h o u t the study, which w o u l d last several y e a r s S e c o n d , the participants had to be reli-able and d e d i c a t e d , i n a s m u c h as they w o u l d h a v e to c o m m i t to the project and submit regular updates on their health and s m o k i n g habits during the course of the prospective cohort study T h i r d , in o r d e r to control for other factors, it w o u l d h e l p if all the participants w e r e sim-ilar in terms of their b a c k g r o u n d s , i n c o m e and w o r k i n g c o n d i t i o n s

A l s o , the n u m b e r of participants h a d to be large, possibly several

t h o u s a n d , b e c a u s e this w o u l d lead to m o r e accurate c o n c l u s i o n s

F i n d i n g a g r o u p of participants that m e t these d e m a n d i n g

require-m e n t s w a s not a trivial task, but Hill eventually t h o u g h t of a solution while playing golf This p r o m p t e d his friend Dr W y n n e Griffith to

c o m m e n t , T d o n ' t k n o w w h a t kind of golfer he [is], but that w a s a stroke of g e n i u s ' Hill's brilliant idea w a s to use d o c t o r s as his g u i n e a

p i g s D o c t o r s fitted the bill perfectly: there w e r e lots of t h e m , m a n y

w e r e h e a v y s m o k e r s , they w e r e perfectly able to m o n i t o r their health and report b a c k , and they w e r e a relatively h o m o g e n o u s subset of the population

W h e n the s m o k i n g study c o m m e n c e d i n 1 9 5 1 , t h e plan w a s t o

m o n i t o r m o r e than 30,000 British d o c t o r s o v e r t h e c o u r s e of five

d e c a d e s , but a clear pattern w a s already e m e r g i n g by 1954 T h e r e h a d been thirty-seven d e a t h s from lung c a n c e r and e v e r y single o n e of

t h e m w a s a smoker As the data a c c u m u l a t e d , the study implied that

s m o k i n g increased the risk of lung c a n c e r by a factor of twenty, and

m o r e o v e r it w a s linked to a range of other health p r o b l e m s , including heart attacks

T h e British D o c t o r s Study, as it w a s k n o w n , w a s g i v i n g rise to such

s h o c k i n g results that s o m e medical researchers w e r e initially reluctant

to accept the findings Similarly, the cigarette industry q u e s t i o n e d the research m e t h o d o l o g y , arguing that there must be a flaw in the w a y that the information w a s being gathered or a n a l y s e d Fortunately, British d o c t o r s w e r e less sceptical about Hill and D o l l ' s e m e r g i n g

c o n c l u s i o n s , because they t h e m s e l v e s had been so involved in the study H e n c e , they w e r e not slow in advising the public against

s m o k i n g

B e c a u s e a link b e t w e e n cigarettes and lung c a n c e r w o u l d affect

s m o k e r s around the w o r l d , it w a s important that the w o r k of Hill and Doll w a s replicated and c h e c k e d T h e results of a n o t h e r study, this time involving 190,000 A m e r i c a n s , w e r e also a n n o u n c e d in 1954, and the conclusion painted a similarly stark picture M e a n w h i l e , r e s e a r c h with mice s h o w e d that half of t h e m d e v e l o p e d c a n c e r o u s lesions w h e n their skin w a s coated in the tarry liquid extracted from t o b a c c o s m o k e ,

s h o w i n g that cigarettes definitely c o n t a i n e d c a r c i n o g e n s T h e picture was c o m p l e t e d with m o r e data from Hill and D o l l ' s o n g o i n g fifty-year study - it reinforced in explicit detail the deadly effects of t o b a c c o F o r

e x a m p l e , the analysis of British doctors s h o w e d that those born in the 1920s w h o s m o k e d w e r e three times m o r e likely to die in their m i d d l e age than their n o n - s m o k i n g c o l l e a g u e s M o r e specifically, 4 3 per cent

of s m o k e r s c o m p a r e d to 15 p e r cent of n o n - s m o k e r s died b e t w e e n the ages of 35 and 69 y e a r s

Doll w a s as s h o c k e d as a n y o n e by the d a m n i n g e v i d e n c e against

s m o k i n g : T myself did not e x p e c t to find s m o k i n g w a s a major p r o b

-l e m If I ' d had to bet m o n e y at that t i m e , I w o u -l d h a v e put it on

s o m e t h i n g to do with the r o a d s and m o t o r c a r s ' Doll and Hill did not start their research in order to achieve a specific result, but instead they

w e r e merely curious and c o n c e r n e d about getting to the truth M o r e generally, well-designed scientific studies and trials are not e n g i n e e r e d

to achieve an e x p e c t e d o u t c o m e , but rather they should be transparent and fair, and those c o n d u c t i n g the research should be o p e n to w h a t e v e r results e m e r g e

T h e British D o c t o r s Survey and similar studies were attacked by the

t o b a c c o industry, but D o l l , Hill and their colleagues fought b a c k and

d e m o n s t r a t e d that rigorous scientific research can establish the truth with such a level of authority that e v e n the m o s t powerful organiz-ations cannot deny the facts for long T h e link b e t w e e n s m o k i n g and lung cancer was proved beyond all reasonable doubt because of evidence emerging from several independent sources, each one confirming the results of the other It is worth reiterating that progress in m e d i c i n e requires independent replication - i.e similar studies by m o r e than o n e research g r o u p s h o w i n g similar findings A n y conclusion that e m e r g e s from such a body of e v i d e n c e is likely to be robust

Hill and Doll's research ultimately led to a raft of measures designed

to persuade us not to s m o k e , which in turn has resulted in a 50 per cent

d e c r e a s e in s m o k i n g in m a n y parts of t h e d e v e l o p e d w o r l d Unfortunately, s m o k i n g still remains the single biggest cause of preventable deaths worldwide, because significant new markets are open-ing up in the developing world Also, for many smokers the addiction is

so great that they ignore or deny the scientific evidence W h e n Hill and

Doll first published their research in the British Medical Journal, an

a c c o m p a n y i n g editorial recounted a very telling anecdote: 'It is said that the reader of an A m e r i c a n magazine was so disturbed by an article