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- Herausgeber: John Wiley & Sons
- Kategorie: Wissenschaft und neue Technologien
- Serie: Addiction Press
- Sprache: Englisch
In 1922, an unlikely team of researchers in Toronto made one of the most important medical breakthroughs of the century: insulin. Their discovery seemed miraculous. When it was given to diabetic patients on the brink of death, their condition rapidly improved. Those present could barely believe their eyes: they had witnessed resurrection.
However, this was no simple cure. Injections must be taken for life. Without them, symptoms quickly return, often with fatal results. But while a lifetime on insulin poses great challenges, it also offers opportunities. In this revelatory history, Stuart Bradwel looks back on one of medicine’s most celebrated innovations. Setting professional narrative against subjective patient experience, he tells the story of a drug that has challenged many of the basic assumptions upon which medical practice is built, both inside and outside the clinic.
Nevertheless, Bradwel reminds us that the centenary of this apparent “wonder drug” should be no cause for celebration. Insulin often remains inaccessible to those who need it most: elusive prescriptions, uneven availability and sky-high prices result in rationing and desperate do-it-yourself research and development. In the face of bootstraps rhetoric and “Pharma Bro” capitalists, patients across the world are left to fend for themselves. There is a long way to go in the twenty-first century until insulin truly fulfils the extraordinary promises made by its discovery.
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CONTENTS
Cover
Series Page
Title Page
Copyright
Abbreviations
Acknowledgements
Preface
Notes
Introduction: What Is Insulin and Why Does It Matter?
Insulin and Diabetes
A (Very) Short History of Diabetes Before Insulin
Insulin at One Hundred
Notes
1 Toronto, 1921–1923
Banting’s ‘Eureka’ Moment
The Early Experiments
The First Human Trial
The Reaction
The Aftermath
Evaluating Toronto
Notes
2 Insulin in Practice, 1922–1978
The Early Insulin Era
Life on Insulin
Free Diets
The Reassertion of ‘Orthodoxy’
Notes
3 ‘Intensification’, 1976–1993
Deus ex machina?
‘Self-Adjustment’
The Diabetes Control and Complications Trial (DCCT)
Düsseldorf
Proto-Intensification
Notes
4 Subjectivity, Paternalism, Neoliberalism, 1993–2002
Subjectivity
Paternalism
Neoliberalism
Notes
5 The Insulin Crisis, 2002–Present
Moralism and Prejudice
Power and Profit
It’s Not Just The Cost
An International Problem
Notes
Conclusion: Insulin for All?
Clinical Issues
‘Good Care’
Technology from Below
Technology from Above
Completing the Circle
Notes
Selected Bibliography
Index
End User License Agreement
List of Illustrations
Introduction
Figure 1
A young girl before and four months after insulin treatment,
c.
1922
Chapter 1
Figure 2
Frederick Banting and Charles Best with laboratory dog, August 1921
Figure 3
Before insulin treatment,
c.
1925
Figure 4
After insulin treatment,
c.
1925
Chapter 3
Figure 5
The Mill Hill infuser, 1976
Figure 6
A selection of insulin pens, 1985–1993
Conclusion
Figure 7
Patient advocates with T1International deliver insulin vials to Eli Lilly
Guide
Cover
Table of Contents
Series Page
Title Page
Copyright
Abbreviations
Acknowledgements
Preface
Introduction: What Is Insulin and Why Does It Matter?
Begin Reading
Conclusion: Insulin for All?
Selected Bibliography
Index
End User License Agreement
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History of Health and Illness Series
Stuart Bradwel, Insulin: A Hundred-Year History
Jonathan Sadowsky, The Empire of Depression: A New History
Orna Ophir, Schizophrenia: An Unfinished History
Insulin
A Hundred-Year History
Stuart Bradwel
polity
Copyright © Stuart Bradwel 2023
The right of Stuart Bradwel to be identified as Author of this Work has been asserted in accordance with the UK Copyright, Designs and Patents Act 1988.
First published in 2023 by Polity Press
Polity Press65 Bridge StreetCambridge CB2 1UR, UK
Polity Press111 River StreetHoboken, NJ 07030, USA
All rights reserved. Except for the quotation of short passages for the purpose of criticism and review, no part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the publisher.
ISBN-13: 978-1-5095-5073-9
A catalogue record for this book is available from the British Library.
Library of Congress Control Number: 2022949655
The publisher has used its best endeavours to ensure that the URLs for external websites referred to in this book are correct and active at the time of going to press. However, the publisher has no responsibility for the websites and can make no guarantee that a site will remain live or that the content is or will remain appropriate.
Every effort has been made to trace all copyright holders, but if any have been overlooked the publisher will be pleased to include any necessary credits in any subsequent reprint or edition.
For further information on Polity, visit our website:politybooks.com
Abbreviations
AAP
Association of American Physicians
ACA
Affordable Care Act
ADA
American Diabetes Association
BDA
British Diabetic Association (Operating as Diabetes UK from 2000)
BERTIE
Beta Cell Education Resources for Training in Insulin and Eating
BMJ
British Medical Journal
CGM
continuous glucose monitoring
CSII
continuous subcutaneous insulin infusion
DAFNE
Dose Adjustment for Normal Eating
DCCT
Diabetes Control and Complications Trial
DESG
Diabetes Education Study Group
DKA
diabetic ketoacidosis
DTTP
Diabetes Teaching and Training Programme
EASD
European Association for the Study of Diabetes
EPP
Expert Patients Programme
FIT
functional insulin therapy
GRI
glucose responsive insulin
HbA1c
glycated haemoglobin
HHS
hyperosmolar hyperglycaemic state
ICT
insulin coma therapy
IDF
International Diabetes Federation
IQWiG
Institute for Quality and Efficiency in Healthcare (Germany)
JDRF
Juvenile Diabetes Research Foundation
MDI
multiple daily injections
MRC
Medical Research Council (UK)
NDDG
National Diabetes Data Group (USA)
NHS
National Health Service (UK)
NPH
Neutral Protamine Hagedorn [Insulin]
OIF
Open Insulin Foundation
PAP
Patient Assistance Programme
PZI
Protamine Zinc Insulin
SBGM
self blood glucose monitoring
T1DM
Type 1 diabetes mellitus
T2DM
Type 2 diabetes mellitus
TGH
Toronto General Hospital
UKPDS
UK Prospective Diabetes Study
WHO
World Health Organization
Acknowledgements
No book is the product of one person alone. Without the help and generosity of others, I would almost certainly have never finished writing this one. Perhaps most importantly, I would like to express my eternal gratitude to those who agreed to participate in interviews – people with diabetes and healthcare professionals alike – while I was completing my PhD studies at the University of Strathclyde. Many of the testimonies that resulted are discussed throughout this work, and it would be far lesser without them.
Heartfelt thanks must also go to Matt Smith, my former supervisor, whose comments on an early version of this manuscript proved invaluable. Similarly, I am grateful to the two anonymous reviewers who provided feedback on the first draft. While I have not been able to implement every one of their many suggestions, their advice gave me much to think about, and it encouraged me to make several important revisions. I must apologise to the second, however, for being unwilling to moderate my political stance!
The majority of the writing here was completed during the COVID-19 pandemic, and for the duration I have been in a position of relative economic precarity. With that in mind I would like to acknowledge the assistance of The Society of Authors, which awarded me an Author’s Foundation grant in 2021. This financial support was much needed, and it allowed me to dedicate several months to full-time work on the manuscript. I would highly recommend that anyone in a similar situation look into the funding streams this organization runs for struggling writers.
For the duration, I have also worked without access to the resources of a university library. This sometimes made it very challenging to find the books and journal articles that I required. I am therefore grateful to Aileen Lichtenstein, Cynthia Tang, Lauren Young, and Viktor Jörgens, each of whom were able to send me material that I may otherwise not have been able to access. Thanks are also due to Alexandra Elbakyan for all of her assistance.
The staff at Polity made the process of bringing this book to fruition as painless as it could be, and I am grateful to each and every one of them. Thanks in particular should go to my editor Julia Davies for her consistent support, enthusiasm, and patience over the last few years. Lindsey Wimpenny also deserves particular credit for her work researching the images that appear in the following pages.
Writing can be a lonely occupation, and I am forever grateful to the friends who have kept me going through both the highs and the lows. Thanks, then, to Roisin Convery, Patrick Foley, James Turner, Jed Howlett, Catherine Smalley, Michael Gordon, Nicola Cacciatore, Erin Stewart, and those I have almost certainly forgotten to name. I do not get the chance to see all of you as often as I might like, but every one of you has helped me, in one way or another, finish this project – even if only by allowing me to forget about it for a time!
As ever, thanks to my parents, Stephen and Barbara, who have always had my back. I cannot begin to express my gratitude for everything that they have done, and everything that they continue to do.
Most of all, thanks to Alyssa McGrow – without a doubt the best person I have ever known. Her consistent enthusiasm for this project pushed me to keep going on even the most difficult days, and her willingness to constructively challenge my ideas from new perspectives has helped shape the following pages more than she can possibly know. Without her love and support, there is a very good chance that this book might never have existed at all.
Preface
For the first two decades of my life, I gave little thought to diabetes, and much less to insulin – the medication used to treat it. What little I did know about the subject came from the media and occasional comments from friends and family members. I had already left school before I met someone who had been touched by the condition – or, more likely, someone who openly discussed it. As a teenager, I spent some time working in a small charity bookshop in Newcastle upon Tyne. One day, one of my older colleagues arrived for his shift ashen faced. He had, he said, been diagnosed with diabetes, and the news had left him – a man in his forties – visibly shaken.
At the time, I did not know what to say. Watching him struggle to adapt to his new life, wincing as he performed insulin injections in the break-room, seemed only to confirm what I had learned from sensationalist headlines and bleak fictional portrayals. Diabetes seemed terrifying. It scared me, and I could not imagine how I would react were it to happen to me.
As it turned out, I was closer than I would have liked to finding out. As a child, I was asthmatic, and, even though the condition had become much milder by my late teens, I still attended routine review appointments for it. In 2009, my GP surgery mistakenly sent out the wrong form with my clinic invitation letter – it asked that I bring in a urine sample. I was puzzled, but I did as it asked.
When I arrived, the nurse was equally confused, but, seeing as I had the sample with me, she decided there was no reason not to check it out. When she tested it for sugar, it came back as a strong positive. Suddenly concerned, she insisted on taking some blood. When the results came back from the laboratory a few days later, they showed that my blood sugar level was significantly elevated. After some confirmatory tests over the next few months, the diagnosis was clear. I had diabetes too. Lucky me.
At only 19 years old, this came as a shock. I quickly learned why my colleague at the bookshop only a few years before had found the experience so difficult. Insulin therapy involved a great deal more than just doing injections – though they too took some time to acclimatize to. Much more challenging was what it did to my sense of self.
Before my diagnosis, I had enjoyed going on long hikes through the wilderness. Sometimes, I would camp in remote spots, miles from the nearest town. Doing so gave me a feeling of independence that was lacking in the rest of my life. In a naïve way typical of adolescence, I liked to imagine that I could, should the situation demand it, be self-sufficient. The idea that I could ever have lived off the land was, of course, pure fantasy. Nonetheless, the idea that I might was, at that time, an important part of my self-image and identity.
Diabetes, however, seemed to make this laughable. I now had to carry insulin and other equipment, and my doctors had explained how important it was to keep my blood sugar levels as stable as possible. If I did not, I might develop serious complications down the line, and in the short term might pass out or even go into a potentially life-threatening coma. This all seemed challenging enough to deal with at home, let alone on some rainy hillside in the Lake District. More importantly, I was now completely reliant upon a pharmaceutical product – and the healthcare infrastructure that provided it. Even a few days without access to insulin could, I was told, prove fatal. Any notion that I might somehow be capable of surviving in the wild for weeks, months, or longer now seemed absurd.
In short, diabetes threatened the very core of my being by stripping away part of my identity and replacing it with something that was, somehow, not me. If the things that made me recognize myself were gone, then who was I? That, especially for someone so young, was not an easy question to answer.
When, years later, I read Australian novelist Peter Corris’ memoir of his life using insulin, I immediately recognized the same anxiety.1 Imagining people with diabetes as weak and impotent, Corris rebelled against his diagnosis for much of his early life. The subjective meaning he attributed to his condition made him reject the label as he struggled to reassert his sense of identity in light of his diagnosis.
This process of reconstitution in light of illness has been described as ‘biographical work’ by scholars.2 When someone is diagnosed with a chronic disease, their ‘original self’ is synthesized with the challenges and expectations, both biological and otherwise, implied by their condition. People need not become their diagnosis – as some worry they might – but it will inevitably transform them into something new, one way or another. Corris, for example, took up smoking and drank heavily in an effort to push his condition away, but that rebelliousness was in itself a product of it.
This interpretation made me re-evaluate my experience. Diabetes forced me to engage in ‘biographical work’, certainly, but I came to understand that my early belief – that something had been taken – was flawed. There is little that I absolutely cannot do, only more risk factors to acknowledge. Whenever I choose to do something, I must consider how it might affect my blood sugar, and decide whether or not to proceed based on my own subjective priority. A diagnosis of diabetes does not threaten the self. Rather, it reveals it.
Insulin therapy is (currently) a lifelong treatment. It insists that those undergoing it refine their personal value systems on a daily basis. They cannot stay passive because it is they who must do the business of treatment every day, incorporating it into their lives as a whole. Sometimes they may choose to do so as healthcare professionals recommend, other times in ways that they would not approve of. In either case, insulin illustrates their rich subjective world. If anything, it reifies the humanity of those with diabetes in all of its complexity and messiness.
This is also, however, a distinctly political substance. Today, it has never been more so. Many of those who need it, like me, need it absolutely. Without it they simply die and too often they are allowed to. Insulin can tell us a great deal about the individual, but it reveals as much about the collective subjectivities of our societies and the ideological frameworks that sustain them.
Insulin saved my life. Over the last decade and a half, I have become rather well acquainted with it. This subject is, as a result, very personal to me, as I am sure it is to countless others. That will be reflected in the following pages, and I make no claims to neutrality – quite the opposite, in fact. In any case, its hundred-year story is fascinating in its own right, and should be of interest to all of us, familiar with diabetes or not.
Notes
1.
Peter Corris,
Sweet & Sour: A Diabetic Life
(Lismore, NSW: Southern Cross University, 2000).
2.
Juliet Corbin and Anselm L. Strauss, ‘Accompaniments of chronic illness: change in body, self, biography, and biographical time’, in Julius A. Roth and Peter Conrad (eds),
The Experience and Management of Chronic Illness
(Greenwich: JAI Press, 1987), pp. 249–81.
Introduction: What Is Insulin and Why Does It Matter?
In 1892, the British Medical Journal (BMJ) published a sobering account of diabetes mellitus in a boy of ten. The child, referred to only by his initials ‘J.A.C.’, had been admitted to St Thomas’ Hospital in London after ‘complaining of dryness of the throat and mouth, of being very thirsty, troubled with cough, and of passing more water than natural … [and] also, though eating heartily, growing thin’. When he was examined, the ‘flushed, anxious-looking’ boy’s urine ‘gave immediate evidence of abundance of sugar’. House physician Wilford Watkins-Pitchford considered the situation grave. He immediately placed his patient on a limited diet of milk, water, eggs, green vegetables, and biscuits, and ordered that he be given morphine every three hours. The treatment, however, did little. ‘J.A.C.’ deteriorated rapidly. Over the following twenty-four hours, he produced a full ten pints of urine, ‘passing it with great regularity every hour of the day and night’. Three days later, his condition had worsened significantly. His emaciation had become extreme, and he had begun to hyperventilate and vomit. By the evening, the doctors considered him ‘evidently moribund’. He no longer asked for water and, while still apparently conscious, ‘had not strength enough to speak’. He died the following day.1
Cases like that of ‘J.A.C.’ were particularly traumatic before the twentieth century. Not only did they often involve otherwise healthy children and adolescents, but those affected usually died a miserable death. To make matters worse, no one could explain what was happening to them with any conviction.
‘J.A.C.’ was almost certainly experiencing what we would now call Diabetic Ketoacidosis (DKA). Today, he would almost certainly have been given insulin immediately, and there is a good chance that he might have survived to tell the tale. In 1892, however, this was not an option. He did not stand a chance of recovery.
Insulin and Diabetes
So what exactly is insulin – this incredible substance that might have saved ‘J.A.C.’s life? Today, it is thought of primarily as a pharmaceutical product, but it is not a drug in the same sense as, say, an antibiotic. Instead, it is a hormone – something that we all need to live, and which most of us make for ourselves. Cells found in the islets of Langerhans, within the pancreas, pump it out as necessary throughout our lives, and it plays an important role in ensuring that we are able to use the energy that we get from food.2
When we eat carbohydrates, they are broken down into sugars. When this enters the bloodstream, insulin is the substance responsible for making sure that it gets into our cells, which then burn it as fuel. In simple terms, it acts as a key – prompting our bodies to consume what they need to function.
However, in some, like ‘J.A.C.’, the insulin-producing islet cells stop working. This happens when the body’s immune system mistakenly identifies them as a threat and attacks, impairing their function and eventually stopping it altogether. It is still unclear what exactly triggers this, and, while such cases were historically associated with younger and thinner people, it can happen to anyone.
With insufficient insulin, the body’s cells are unable to absorb enough energy and, with nowhere to go, sugar begins to build up in the blood. As less insulin is produced, the energy deficit grows. After a point, this produces physical symptoms. People affected feel the need go to the toilet more often as excess sugar is removed via the urine. This leads to dehydration, and a persistent thirst that cannot be quenched.
Symptoms continue to intensify until the amount of insulin being made is no longer enough to meet even basic requirements. At this point, the body’s cells begin to effectively starve, and exhaustion sets in. Protein and fat tissues are broken down to function as an emergency energy source, and visible wasting begins to occur – sometimes over an alarmingly short period of time.
Breaking down these alternative tissues floods the blood with ketones, increasing its acidity and producing a characteristic smell of acetone on the breath. Before long, this leads to DKA, which can be extremely dangerous. It can cause vomiting, stomach pain, breathing difficulties, and disorientation, and, left unchecked, often ends in coma and death.3
Without insulin treatment, this process is universally fatal. The exact prognosis varies, as the islet cells are destroyed only gradually, but absolute insulin deficiency leads to death within a matter of days. By the time serious symptoms begin to appear, a considerable amount of damage has already been done.4 Before insulin, it was rare for anyone to survive beyond a few years following diagnosis.
Today, we would describe this condition as type 1 diabetes mellitus (T1DM). However, this terminology is not particularly old. Before the twentieth century, and for some time into it, diabetes was often considered a singular condition, and cases were distinguished only by symptomatic intensity. If they made a distinction at all, physicians generally referred to T1DM as ‘severe’, ‘juvenile’, or, later, ‘insulin-dependent’ diabetes.
The language we now use was adopted widely only after 1979, following the publication of an influential paper by the USA’s National Diabetes Data Group (NDDG). This suggested that diabetes be understood not as one condition, but as a ‘genetically and clinically heterogeneous group of disorders that share glucose intolerance in common.’5
While ‘severe’ cases of diabetes seemed uniformly deadly, it had always been obvious that some people seemed to be affected more violently than others. Even as ‘J.A.C.’ died, others – most of them older and/or larger – avoided such a rapid downwards trajectory. Some even survived for years or longer with relatively manageable, intermittent symptoms.
In 1840, for example, English doctor C.R. Bree described the case of one 53-year-old man who had come to him in July 1835 complaining of ‘great weakness’. He was not emaciated, but he was passing twelve to fifteen pints of sweet urine daily, had a great appetite, and could not quench his thirst. Bree recommended a few dietary adjustments, and by the beginning of August the man felt much better. His symptoms had not disappeared completely, but they had become tolerable, and he lived for another three years before dying of dropsy.6
Bree’s account almost certainly describes what we would now call type 2 diabetes mellitus (T2DM). Like T1DM, this is a complex condition with no single cause. Age and obesity are considered well-established risk factors for developing it, but they are far from the whole story, and it too can affect anyone. Olympic gold medal-winning rower Steve Redgrave, for example, was diagnosed with T2DM at only 35, despite being a world-class athlete in active training.
People who develop T2DM continue to make insulin, though their islet cells do sometimes show evidence of deterioration. The destructive autoimmune response present in T1DM is absent. Instead, this condition is characterized by insulin resistance. In those affected, the islet cells continue to function, but the insulin they make is far less effective at doing its job. Enough sugar is usually processed to meet basic needs, but much is wasted, and it begins to accumulate in the blood. Minor insulin resistance is often completely asymptomatic, but once blood sugar becomes sufficiently elevated it does become noticeable. As the body flushes the excess sugar through the urine, thirst and dehydration develop and, as a significant amount of energy finds its way into a toilet bowl before it can be used, this is often accompanied by lethargy, and sometimes weight loss.
Because insulin, albeit not enough of it, is present in people with T2DM, they are not usually as susceptible to DKA – though it can occur.7 However, their condition is not benign. In addition to the uncomfortable, frustrating, and sometimes socially embarrassing symptoms, persistently high blood sugar levels can be devastating to the fabric of the body. People with untreated T2DM are significantly more likely than most to develop both heart and kidney disease, suffer strokes, and lose their sight. They also sometimes experience painful nerve damage and sexual problems such as erectile dysfunction, while miscarriages during pregnancy are more common.
Lifestyle changes can in some cases act to restore sensitivity to the body’s own supply of insulin in cases of T2DM, and pills like Metformin can help further, but this is not always sufficient to keep blood sugar beneath the threshold at which damage might occur. While it is not so immediately essential to life itself, injected insulin can play a vitally important role in maintaining health in such cases.
Insulin has been available as a medication since 1922, but it has not trivialized diabetes. As paediatrician and historian Chris Feudtner puts it, its introduction to medical practice was akin to ‘a Greek myth of rebirth turned ironic and macabre’.8 It does not permanently cure anything. It only replaces, or, in the case of T2DM, supplements, something usually made by the body. As a result, those who need it must take it for life.
Complicating things further, insulin is not ‘fire-and-forget’ medication like, for example, an aspirin. If it is not taken in the right amount and at appropriate times to balance out demand, blood sugar levels can rise or fall to dangerous levels. Too much insulin in the body can lead to hypoglycaemia (low blood sugar) which, in extreme cases, can cause unconsciousness and even death. Too little, and sugar levels become dangerously elevated, damaging the organs, nerves, and blood vessels and, left unchecked, perhaps even leading to DKA.
Insulin has, however, transformed the experience of diabetes. Those who are able to access it are given a reprieve that their predecessors were not. Long-term therapy, however, brings its own challenges – some of them very demanding indeed. But we are getting a little ahead of ourselves. It is impossible to discuss the history of insulin as a pharmaceutical tool without first considering the circumstances that led to its ‘discovery’.
A (Very) Short History of Diabetes Before Insulin
While it has been given a variety of names throughout history, diabetes is likely ancient. The term itself was first used by the classical Greeks, and is derived from their word for ‘siphon’, or ‘to pass through’, reflecting the huge amount of urine produced by those affected. ‘Mellitus’ – Latin for ‘sweet like honey’ – was later appended to indicate the characteristic abundance of sugar that it contained.9
Serious illnesses with symptoms paralleling those experienced by ‘J.A.C.’ in late nineteenth-century Britain have been described across cultural boundaries throughout recorded history. The Ebers Papyrus, an Egyptian document dated to around 1552 BC, contains reference, albeit quite vague, to ‘urine which is too plentiful’.10 Ayurvedic texts from the Indian subcontinent are more precise, identifying madhumeha – ‘honey-urine’ – as a dangerous condition characterized by the passage of great quantities of sweet urine, unquenchable thirst, and bad breath.11 In imperial China, xiāo kě (消渴) – ‘wasting-thirst’ – was associated with frequent urination, extreme thirst and hunger, and rapid weight loss well over two thousand years ago.12
The most complete, and likely most cited, classical account comes from the second century Greek physician Aretaeus of Cappadocia, who practiced in what is now eastern Turkey. Describing the symptoms and progress of those affected in excruciating detail, he wrote that:
The patients never stop making water, but the flow is incessant, as if from the opening of aqueducts … the patient is short-lived, if the constitution of the disease be completely established; for the melting is rapid, the death speedy. Moreover, life is disgusting and painful; thirst, unquenchable.13
These old accounts are often incomplete and fragmentary, but the key elements remain strikingly consistent across vastly disparate societies and time periods. Most early accounts of diabetes appear to describe T1DM. This is not surprising. Such cases were rare enough to be notable – Aretaeus thought the condition ‘not very frequent among men’ – while the intensity of symptoms made them difficult to ignore.
In 1679, however, Thomas Willis, court physician to Charles I, argued in his posthumously published Pharmaceutie Rationalis that diabetes had become considerably more prevalent than it had once been. Apparently something of a trendsetter, Willis blamed this squarely on overindulgence:
The Diabetes was a Disease so rare among the Ancients, that many famous Physicians have not so much as mentioned it, and Galen never knew above two that were troubled with it; but in our Age, that is given so much to drinking and especially to guzzling of strong Wine, we meet with very frequent, not to say daily examples and instances of this Distemper.14
Willis believed that diabetes could effectively be controlled, writing that ‘this disease at first beginning is oftentimes easily cured; but when grown strong in a man, very seldom and with great difficulty’. He gives the example of one ‘noble Earl … in the very vigour of his Age’, whose symptoms were successfully eased following treatment:
[He] became much inclined to excessive urination; and when for several Months he had been used ever now and then to make great quantities of water he at last (it seemed) fell into a diabetes that was obstinate and strong and almost desperate. For besides that in the space of 24 hours he voided almost a Gallon and a half of limpid, clear and wonderfully sweet water, that tasted as if it had been mixed with Honey; he was likewise troubled with an extraordinary thirst, and as it were, an Hecktick Fever, with a mighty languishing of his spirits, weakness in his limbs, and consumption of his whole body.15
After being given several plant-based remedies and placed on a restricted diet, the Earl gradually recovered. Within a month, he was ‘almost quite well’ – his urine no longer tasted of sugar and it ‘did not much exceed the quantity of that liquid matter which he took in’. Eventually, after ‘recovering his usual tenure of spirits and strength he returned to his former diet.’ Tellingly, his symptoms returned intermittently for the remainder of his life:
But yet the disposition to this Distemper did not so totally leave him but that afterwards, oftentimes, through disorders in his Diet and perhaps irregularities in the seasons of the Year, being inclined to a relapse he made water at first in great quantities and then clear and sweet with thirstiness feverishness and languishment of his spirits [sic].16
This certainly does not seem to reflect the terminal condition described by Aretaeus and other early writers. Willis was an extraordinarily successful physician whose wealth and status meant that most of his patients came from the elite ranks of Stuart society. As he explicitly pointed out, this demographic was not known for its temperance, and obesity was not uncommon. Moving in these circles, it is very likely that the majority of Willis’ cases involved T2DM.
Willis’ powerful patients in the mid-1600s were a small minority unrepresentative of the general population of Britain. However, by the nineteenth century most physicians did tend to agree that diabetes had become commonplace. Many echoed his claim that it was a disease of affluence, and most of those seeking treatment in this period certainly did come from the more prosperous sections of society.
At the same time, others were beginning to highlight that it seemed to have become significantly more survivable than most historical accounts suggested it should be. In 1866, Scottish physician George Harley wrote that:
At one time, when a patient was said to have diabetes, it was considered tantamount to saying his days were numbered. As our knowledge has increased, however, we have learned that although it is but seldom possible for us to eradicate the disease, we can, nevertheless, so mitigate its effects as not only to prolong the life of the individual, but to render it a tolerable, if not even an agreeable one.17
Harley – like many of his contemporaries – was eager to credit the effort of the medical profession with any apparent improvement in prognosis, but it is quite likely that he was actually just observing the consequences of broad demographic changes within Victorian society. Thanks to the Industrial Revolution and the global hegemony of Britain’s vast colonial empire, by 1866 there were considerably more people in the UK that would today be considered at high risk of T2DM than there had been a hundred years before.
The medical profession did have some success at ameliorating the symptoms of these new patients. In 1797, John Rollo, then surgeon-general of the Royal Artillery, outlined a low-carbohydrate, high-fat ‘animal food’ diet that appeared to have some positive effect. One 57-year-old general officer under his care, for example, had been diagnosed with diabetes approximately three years prior, and regularly produced ‘ten or twelve pints [of sweet urine] in … twenty-four hours’. When consulted, Rollo advised him to adopt a heavily restricted diet that sounds singularly unappetizing: blood pudding for lunch, ‘game and old meats which have been long kept, and, as far as the stomach may bear, fat and rancid old meats’ for dinner, and bread and butter for both breakfast and supper, washed down with a mixture of milk and lime water.
Impressively, the man soon did seem to improve. After some time on Rollo’s diet, he was no longer so thirsty and he was passing between two and four pints of urine daily. He even appeared to be regaining his strength. Following his apparent recovery, the officer in question – who had ‘very great impatience under restriction’ – returned home to Portsmouth. After receiving permission from another physician to ‘eat what he pleased, and to drink wine’ following a bowel complaint, his diabetic symptoms soon returned. Rollo, with some justification, took this as vindication for his approach to treatment.18
Rollo’s restricted diet was highly influential, and while other physicians tinkered somewhat with the formula, most maintained the principle that diabetes was best treated by proportionally reducing carbohydrate in favour of greater quantities of meat and fat. This method of treatment remained common into the twentieth century, probably because it did, on at least some occasions, seem to work – particularly for those we would now recognize as having T2DM.
Nonetheless, no treatment could do anything for ‘severe’ cases, who continued to die quickly. By the middle of the nineteenth century, the stark differences in outcomes between people diagnosed with diabetes prompted some speculation that at least two distinct conditions might be responsible. In 1863, Manchester physician Daniel Noble, for example, asked whether it might be ‘possible to establish pathological distinctions in cases of diabetes, according to their origin, the course of the symptoms, and their curability’.19
In 1866, George Harley had (correctly) surmised that ‘saccharine urine is not itself the disease, but merely the most prominent sign of … a variety of morbid actions’. He distinguished between diabetes he thought was caused by ‘excessive formation’ on one hand, and by ‘defective assimilation’ on the other:
In those resulting from excessive formation the patient is not necessarily emaciated and weak. He may, on the contrary, look both fat and ruddy – appearing, in fact, to be the very bloom of health … In this class of patients it is not until the disease has made considerable inroads on the constitution that there is any marked emaciation.
In the second class of cases, on the other hand, namely, those resulting from defective assimilation, emaciation is one of the earliest and most prominent symptoms, the loss of the flesh being often very marked before the nature of the disease is detected.
Harley’s descriptions quite clearly reflect T2DM and T1DM respectively, but his theory was entirely speculative.20 He was only one voice amongst many, and, throughout the nineteenth century, doctors came to very little agreement as they sought to explain the root cause of diabetic symptoms and draw lines between different ‘types’ of the condition – if they believed any such division could be made at all.
One major barrier to any real consensus about what exactly diabetes was, and why some people seemed to become far sicker than others, was the ambiguity of its origin. Until the late nineteenth century, physicians argued at length about where to locate its ‘seat’ in the body. By the late nineteenth century the pancreas had – correctly – been implicated several times, for example by French physician Étienne Lancereaux, but an undeniable link remained elusive.21
This changed in 1889, when German physicians Oskar Minkowski and Josef von Mering removed the pancreas of one of their experimental dogs for study. Following this procedure, they later reported, the animal had begun to relieve itself uncontrollably all over the laboratory floor and had died soon after. On examination, its urine was found to be full of sugar. It appeared to have spontaneously developed the kind of quickly fatal symptoms seen only in the most ‘severe’ cases of diabetes, though precisely why neither could say for sure.22
The concept of an insulin-like substance, in the very broad sense, can probably be traced to French-Mauritian physiologist Charles-Édouard Brown-Séquard. From the mid-nineteenth century, Brown-Séquard argued that various glands throughout the body produced ‘internal secretions’ that each played an essential role in maintaining health.23 Building on this, he later went on to suggest that, if extracted, they might have therapeutic value.24 His ideas were controversial at first, and his belief that injections of bull semen might rejuvenate old men who had long since lost their strength and virility was predictably mocked by his peers, but in principle he was correct – he had, in fact, identified the group of substances University College London’s Ernest Starling would, in 1905, give the collective name ‘hormones’.25
By the mid-1890s Brown-Séquard’s theory had become widely influential.26 One reason for this was that the work of other researchers seemed to lend it clear support. Minkowski and von Mering’s experience, for example, had after all shown that, without a pancreas, dogs would become sick and die in short order. In 1891 the idea gained even further traction when George Redmayne Murray reported that he had been able to successfully treat a woman with myxoedema – advanced hypothyroidism – by injecting her with extracts from the thyroid glands of a sheep.27
Murray’s success prompted a great deal of optimism amongst the medical community, particularly when it became apparent that the extract could be given orally without issue.28 By 1893 Brown-Séquard clearly considered his ideas thoroughly vindicated, highlighting diabetes as one example of a condition he thought would – like myxoedema – benefit from treatment with organ extracts. ‘There cannot be a doubt now’, he claimed, that the pancreas, ‘like the testicles, the ovaries, [and] the kidneys, has an internal secretion, which is even more important than its external one [i.e., digestive fluids]’.29
He was, of course, correct, and was describing the hormone Belgian Jean de Meyer would christen ‘insuline’ in 1909.30 However, initial attempts to use pancreatic extract were not promising.31 While he defended his ‘internal secretion’ theory, Brown-Séquard was forced to concede that ‘while injections of the pancreatic liquid have been useful … no case of cure, to my knowledge, has been recorded’.32
By the end of the nineteenth century, growing attention to the ‘internal secretion’ of the pancreas discouraged many physicians from believing that multiple varieties of diabetes existed. In 1896, for example, Canadian physician William Osler suggested that while both ‘acute’ and ‘chronic’ forms existed, there was ‘no essential difference between them, except that in the former the patients are younger, the course more rapid, and the emaciation more marked’.33
By 1919, New York’s Frederick Allen – widely acknowledged as one of the foremost global specialists on diabetes – felt comfortable arguing that it was one thing and one thing alone: a condition resulting from ‘a deficiency of the internal secretion of the islands of Langerhans’.34 He had little time for those who continued to suggest otherwise, brusquely dismissing the work of Lancereaux, for example, as ‘generally discredited’.35 The status of the islet cells in the pancreas ‘as the seat of the specific diabetic disturbance’, he declared, ‘is now as firmly established as any fact in physiology or pathology’.36
Allen believed that high blood sugar was more than an indicator that the pancreas was producing insufficient ‘internal secretion’. He also thought that it could make things worse by overworking the islet cells, and in doing so causing them to degenerate further.37 The greater the burden placed on the organ, he argued, the more rapid this process would be. A ‘mild’ case would, left unchecked, always become a ‘severe’ one, and a ‘severe’ one would eventually become terminal.
While he understood diabetes as a singular condition, Allen did recognize that, cruelly, children seemed to develop life-threatening symptoms more rapidly than their older counterparts, insisting that ‘every case … in a child calls for the most careful treatment from the earliest possible moment’.38 As his long-time ally Elliott Joslin wrote in 1916, however, the ‘melancholy fact’ was that ‘where diabetes appears in its most severe type, as in children, coma is its expression’.39
By the 1920s, Allen had become well-known for his radical approach to dietary treatment. If deterioration was caused by undue pressure on the islet cells, he thought, then normalizing blood sugar through nutritional restriction would reduce that stress and stall the progression of diabetes. Dietary regulation was by this point nothing new, but Allen deviated from his predecessors by advocating a particularly aggressive strategy, and claimed that remaining consistently underweight was beneficial. His method involved, to put it mildly, radical under-nutrition. Where those undergoing treatment in the nineteenth century might have complained about being asked to cut bread, wine, and sweet foods from their diets, their prescriptions would have looked positively indulgent to Allen, who not only demanded drastically reduced carbohydrate intake, but substantially less food altogether.
It is not at all surprising that Allen’s strategy was pejoratively referred to as the ‘starvation diet’, or that the name stuck. While his exact prescription was tailored to each individual, patients at New York’s Rockefeller Institute, where Allen worked from 1913, were often subject to extreme nutritional restriction alongside periods of almost total deprivation, particularly if they were young and/or admitted with serious symptoms.
One 13-year-old boy, for example, was hospitalized with shortness of breath and disorientation on 12 February 1917, and was quickly found to have extremely sugary urine. On his first day of admission, he was given only 20 ml of soup, which was increased to 60 ml – plus 40 ml of coffee – for the next four days. Following this period of fasting he was moved onto a ‘standard’ diet, which still amounted to only 240 calories daily for around two weeks.40
Unsurprisingly, Allen was not popular amongst his patients. In addition to his harsh approach to treatment, he was every inch the stereotype of the paternalistic early twentieth century physician – a severe, humourless man who valued hard work, temperance, and discipline above all else. Combined with an absolute faith in his own style of diabetes management, he held a palpable contempt for those who breached his ‘rules’. As far as Allen was concerned, insubordination was one of the primary causes of death in those under his care: he separated fatalities into two groups, those attributed to ‘disobedience of patient’, and those in which ‘failure of treatment’ was responsible.41 He viewed the moral character of those under his care as an integral part of management, and felt that those who ‘failed’ in their duty brought disaster upon themselves:
The patients who died from breaking diet were not driven to desperation by hunger or suffering. They were generally not the ones who had to endure the greatest privations. They were rather the ignorant, the careless, the weak-willed, the neuropathic, and others who would not have been faithful to any restrictions no matter how mild.42
It is difficult to imagine how oppressive this must have made life on the wards, but Allen’s case records give some indication as to the kind of environment his patients endured while accommodated at the Rockefeller, particularly if he decided that they were, for whatever reason, lazy or untrustworthy. In one case, when he could not explain a ‘barely perceptible’ resurgence of sugar in the urine of one visually impaired and bedridden 12-year-old, he interrogated the boy, who eventually admitted to breaking his diet:
It had seemed that a blind boy isolated in a hospital room and so weak that he could scarcely leave his bed would not be able to obtain food surreptitiously when only trustworthy persons were admitted. It turned out that his supposed helplessness was the very thing that gave him opportunities which other persons lacked … the attempt to evade the strict watch kept over him appealed to him as a sort of game or battle of wits, so that he even took things for which he had no real desire.
The boy, who had been given fewer than seven hundred calories daily for almost a week, and on some days considerably less, had been eating ‘tooth-paste and bird-seed, the latter being obtained from the cage of a canary which he had asked for’. Allen did not consider that this behaviour might reflect the desperation of an unbearably hungry child unwilling to openly challenge his doctor’s instruction, and appears instead to have concluded that the whole episode was some kind of infantile game.43
Despite all of this, he did not lack for prospective clients. This speaks to quite how hopeless ‘severe’ cases of diabetes must have seemed. Why else would anyone have subjected themselves or their loved ones to this kind of ordeal? The response amongst the medical community was also enthusiastic. By the First World War Allen had become highly influential on both sides of the Atlantic. In 1917, British physician Otto Leyton eagerly endorsed his method, which he described as ‘the modern treatment of diabetes mellitus’.44 George Graham used a similar approach at London’s St Bartholomew’s Hospital in 1921, making it even more onerous by insisting his patients remain in bed for most of the day. He justified this by suggesting that it might make dietary restriction more bearable, but also admitted that it was first implemented to ensure that his staff could keep close tabs on them.45
It is difficult to accurately assess how effective this harsh treatment was. We do know that of 44 patients under Allen’s care at the Rockefeller in 1915 – not all of whom will have had T1DM – almost half were dead by the end of 1917.46 Some had died of complications related to diabetes. Others simply starved. Even Allen admitted that it could only delay, not prevent, the inevitable.47 When, years later, one physician described early twentieth century treatment as little more than ‘a counsel of desperation’, the assessment seemed little exaggeration.48
One of Allen’s most famous patients was a young girl called Elizabeth Hughes. Hughes had been diagnosed with diabetes in 1918 at the age of eleven, and she came under his care a few months later in early 1919. She was placed on a diet typical of Allen’s practice – 889 calories per day. While she personally did not, with some justification, much enjoy the doctor’s company, Allen considered her a model patient. As her health waned, she continued to abide strictly by her prescribed treatment. Nonetheless, few expected her to live into adulthood. Even Allen must have been pessimistic, and his stated mission to wring as much life out of his patients as possible in the hope that they might live long enough to see a cure must have seemed cold comfort:
Final attention must again be called to the limitations inherent in every dietetic treatment. It affords only rest of a weakened function, when a stimulus is often needed. Essential progress must take the direction of supplementing the negative and passive therapy with a positive and active force. The knowledge of diabetes is advancing rapidly enough that even the patient whose outlook seems darkest should take courage to remain alive in the hope of treatment that can be called curative.49
In the early months of 1922, however, it seemed that just such a ‘positive and active force’ might finally be within reach. Promising news had begun to arrive from Canada. A team of researchers in Toronto, led by Frederick Banting, claimed to have successfully produced an effective pancreatic extract that could stop diabetes in its tracks. The substance – insulin – seemed almost miraculous: it appeared to have brought those children it was tested on back from the very brink of death (see Figure 1).
As the daughter of veteran American politician Charles Evans Hughes – a former Governor of New York who had only narrowly lost to Woodrow Wilson as the Republican nominee in the 1916 presidential election – Elizabeth was as well cared-for as any child of her era could have hoped to have been. She was able to rest in comfortable surroundings and was attended to daily by a private nurse. By the summer of 1922, however, she was in increasingly poor health. Horrendously emaciated, she weighed only 40 lbs (18 kg) and was so exhausted that she struggled to walk. However, she was fortunate to be born into such a high-status family. After repeated requests by her parents, Banting agreed to take her on as a private patient.
Figure 1. A young girl before and four months after insulin treatment, c.1922
Source: Wellcome Collection
Hughes travelled to Toronto and received her first injections of insulin in August, and afterwards recovered quickly. The sugar in her urine disappeared, and within a fortnight Banting was allowing her a diet of around 2500 calories per day, leaving the starved girl overwhelmed with relief. At the end of September, she wrote elatedly to her parents:
As you know I am simply bursting to see you and can hardly wait for you to actually see with your own eyes what I’m eating nowadays, for if you didn’t I declare you’d think it was a fairy tale. I know you will hardly know me as your weak, thin daughter, for I look entirely different everybody says, and I can even see it myself.50
Hughes soon left the hospital, and ended up living into her seventies. Within a matter of weeks, she appeared to have recovered almost completely with little to show for her ordeal. Insulin seemed an almost unbelievable achievement, and a hundred years later this still seems a fair assessment. To date, it has saved countless lives, and, should we let it, it will save countless more.
Insulin at One Hundred
Hughes is a good place to finish the introduction of a book celebrating a century of insulin. She was one of its most high-profile early recipients and her story has become well known, but she also highlights its darker implications. Every human body requires insulin, but most make their own. For those who no longer do, injections are as vital as food, water, or oxygen. If treatment is stopped, symptoms return quickly and death looms not far beyond. While it is often described as a chronic condition, T1DM in particular is better understood as a persistently treated acute one – each injection only delays deterioration for a few more hours. There is no ‘cure’. Insulin only maintains life for as long as the people who need it can get it.
In the 1920s, those who required insulin usually had to buy it. In these early years, when supplies remained stretched, this could be costly. In Canada in 1923, for example, it could cost up to a dollar per day in a country where the average annual income was only around C$500.51 Hughes’ life was saved as much by her class context as it was by any pharmaceutical product, and while it is difficult not to be moved by her tale of triumph over adversity, it is important to remember that it occurred alongside countless tragedies.
Many people continued to die needlessly of untreated (or insufficiently treated) diabetes after the introduction of insulin to medical practice. Unsurprisingly, most of Banting’s private clients came from the upper echelons of North American society. Hughes was the daughter of a statesman. James Havens – who went on to become an accomplished artist – was the son of a congressman. Teddy Ryder must have felt in comparatively privileged company as the child of a humble engineer!
Had she been born poor to an insignificant family, Hughes would almost certainly not have survived. When we take the time to celebrate the ‘discovery’ of insulin, it is vitally important that we acknowledge the countless working-class Elizabeths who died and were forgotten even as she received her first life-saving injections. This is particularly relevant today. In 2023, over a full century later, many continue to meet this fate for no other reason than simple economic misfortune. Insulin accessibility remains a major issue across the world despite well-established manufacturing operations that produce enough to meet the needs of all who require it. This is a particular issue in low- and middle-income states where poverty is rife, average wages are low, and healthcare infrastructures are both underdeveloped and underfunded, if they meaningfully exist at all.
However, ideology as well as deprivation remains the source of much suffering. The United States is probably the most egregious example of this. Despite being the richest, most powerful, and most culturally influential country on the planet, its political leadership has consistently shown itself to be remarkably unwilling to enact legislation that would provide full access to medical care for all of its citizens. Most working-age Americans rely upon private insurance policies often tied to employment – either their own or that of a family member.52 Private insurance is often very expensive, and even the more comprehensive schemes demand significant contributions from the individual in the form of deductibles and ‘co-pays’. Worse, those in poorly paid (and usually under-appreciated) jobs often do not receive insurance at all. In these cases, they are responsible for purchasing their own coverage, and, given the oppressive cost, some end up going without. The most vulnerable in American society are asked to pay the most, despite being the least capable of doing so. Many simply do not even attempt to access the care they need when they become sick or get injured in the knowledge that doing so might land them in significant debt, even where they acknowledge that the decision puts their health at serious risk.
