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The discovery of insulin

Science at its finest

Rebecca Nesbit 14 May 2017

I truly don't know how we will go on if this new medicine does nothing

Editor's note: We are pleased to present our second installment in our new series, The League of Imaginary Cats. Read more about the Series in our accompanying editorial, and use the navigation links at the top right to catch up.

Nobody oover the age of 20 should have to live with their parents.

The set meal times… 'eat all your vegetables'; the strict regulations governing time in the shower; the way your socks come out of the wash in neat pairs and are replaced in your underwear drawer, which, worst of all, has been tidied…

It is this growing list of grievances that occupies my mind as I help my mother prepare for supper, an urgent task even though we haven't yet had lunch. There seems to be a complex technique for chopping vegetables, and she is eyeing my carrots with disapproval. "This is going to be ready at 7, so you'll need to be back by 6.30."

"Look, I'll see, but I'll definitely be here in time to eat some."

Taking a deep breath, she says with exaggerated patience, "Everyone is going to be here. It's a family meal."

"I said I'll do my best."

"We'll all be expecting you, and could you please make sure you drop in on Auntie Jilly, she really wants to show you some family trees."

My aunt Gillian, who still expects me to call her Auntie Jilly as if she's oblivious to the fact I'm a graduate of university and not nursery school, has joined the fad for tracing one's family history. She visits graveyards and records offices, and her living room is lined with tatty box files of who knows what. She even learnt to use (in the loosest sense of the word) a computer so that she could subscribe to an ancestry site designed for people just like her; people who believe that knowledge of an interesting past will somehow let them fit better into the present.

"Remember, Auntie Jilly's a frustrated historian," my mother says. "If you'd been there when she was a student you'd realize that. And she's collected so much that she wants to share, far more than names and dates."

"I get that, but why me?"

"You've got a lot of time at the moment..."

"I don't have endless free hours just for family errands. Applying for hundreds of jobs takes a lot more effort than actually doing one."

"I know, love, but it needn't take you long."

How is it that her favourite phrase, I know, love, sounds decidedly like a pacification from someone who really doesn't know? I continue with my defence undeterred. "Auntie Jilly goes on about this as if she's on her deathbed and precious knowledge will be lost to mankind. She's no more likely to die than I am."

"Somewhat less likely if you don't start looking after yourself properly. You're 21 – I shouldn't have to remind you all the time to take your medication."


I put down my half-peeled carrot, grab my wallet and slam the front door behind me. The door-slamming ritual, well practised through my teenage years, had got old, but now I can slam the front door it has regained some power, and means I am free from the scripted arguments that would otherwise continue. I make my own decisions about my health without the help of people who have never suffered anything worse than chicken pox.

In the car I begin to wonder when I last checked my blood sugar level, and whether I should have slammed my bedroom door rather than thrown myself out onto the street. But that would make my mother think she had reminded me, that she needs to keep up her regular flow of reminders that are always phrased as the trials of a long-suffering carer. In the long run though, it would just have perpetuated this idiotic cycle of behaviour. It's only 7 miles until I reach my girlfriend's flat…

By the time I ring the doorbell, I am calm, and the breeze blowing straight through my t-shirt makes me feel momentarily free. Sasha greets me with a smile and a kiss.

"What's up?" she asks.

"If I have to live with Mum and Dad a week longer I swear I will strangle either them or myself."

Her eyes widen slightly. She has a room the size of an operating table, and two flatmates to share a microscopic kitchen with.

I laugh. "Don't worry. I would sleep in the Tesco bike shed before I moved in with three girls."

"Some men's dream."

"That's just what women like to think…"

Sasha's expression turns serious and she takes a step towards me, taking my hand. "Look, just get a job and maybe in a few months time we can think about finding somewhere…"

We prepare lunch in silence. I don't need her to tell me about the importance of getting a job. The perpetual drowning in CVs and rejections, accompanied by the feeling of treading water just so you can get a gulp of fresh air, is only a few months behind her, but already she has forgotten that IT'S NOT MY FAULT. Like my mother, who seems to believe that I haven't noticed the benefits of earning a living.

We eat leaning over the worktop because there's nowhere to sit, and by the time we have eaten the first few bites of pasta the mood has warmed.

"What's your mum done this time?"

"The usual, and insisting I let Auntie Jilly bore me with her research into our family."

"Why don't you?" She shifts her attention from the bowl of pasta to look up at me, her fork paused in mid-air.

"I'm no good at feigning interest."

"It's a skill you need to master for job interviews."

When did she become quite so patronizing?

"People seem to look to family trees to work out who they are, but they forget that they only have 42 chromosomes, and by the time you go back five generations you have 64 ancestors."

"Every one of your chromosomes is shared by people Auntie Jilly has been researching."

"Not necessarily. Plenty of people are wrong about who their father is."

"True, but some of the information she's researched is about your grandparents, and unless you are accusing your mother or grandmothers…"

"I don't need Auntie Jilly's box files to tell me about my grandparents, and anyway I share 96% of my DNA with a chimp." I look down at the dark hairs covering my arms, and wonder if in my case it's even more.

"But you only need the genes you share to give you one thing in common, and it doesn't matter about the differences. Anyway, it could be fun, particularly if the scandal has been recorded."

We eat the rest of the meal as if we have forgotten the technical hitch of getting a job. We dream about a house with ivy growing up the front, and a dining room table, and the holidays we will instantly be available to afford. When we are done she washes up the bowls while I reach behind the tins and vegetables crammed into her cupboard to find some chocolate.

"Do you think you should?"

"Why the hell does nobody trust me?!" I toss the chocolate back into the cupboard, but this starts a chain reaction of collapse that ends with both of us catching satsumas and carrots as they bounce towards the floor.

"Sorry," I say when she has re-balanced her food supply with an unnecessary show of difficulty. I see there's no way back for this visit so I find myself once again in my car, but this time heading towards Auntie Jilly's.

As Auntie Jilly ushers me into her house I'm met with a familiar musty smell. Even the hallway has a shelf of books gathering dust.

"This is a surprise. Did your mother finally persuade you to humour your aging aunt?"

"You're not aging Auntie Jilly, and actually my mum and Sasha forced me here with more pestering: take your medication, find yourself a job, there's a good boy." My imitations elicit a laugh. "You're a last resort…”

Auntie Jilly takes this in good spirit, and puts the kettle on. In the living room, fortified by cups of tea, she reverently lays out the family tree on the floor, then starts on the history she has compiled. The box files, sandwiched between some hefty reference books, are immaculately labelled. Auntie Jilly hands me a Xerox of a hand-written page, the spidery sprawl barely intelligible in the hazy black dots of the photocopy. "This is a journal extract from my great grandmother, talking about her son Leonard."

11 January 1922, Toronto General Hospital

Leonard had the strength to walk to his ward, but not much more. The doctors questioned him and I worried that it would be more than he could manage, he has already endured so much.

I was instructed to leave while the doctors performed the procedure, and to my relief a kindly nurse found me in the corridor, and sat me down whilst I waited.

I truly don't know how we will go on if this new medicine does nothing to ease his suffering.

My image of these Canadian ancestors is surprisingly vivid, with dingy hospital corridors and pragmatic nurses who are entirely subordinate to the male doctors. "What procedure did he have?"

"Quite simple actually – it's just that he was the first. They injected a brown muck into his buttocks, which was a pancreatic extract from a cow. Doesn't sound major, but this boy, your great uncle, was 14 and only weighed 65 lbs – that's what you weighed when you were 9."

"And what happened?"

"An abscess developed at one injection site, and he didn't gain any weight."

"So he died of diabetes?"

"On the contrary, he later went on to get a job and even play baseball." Auntie Jilly says this with a smile, as if by researching these events she can share the credit for their success. "Read this." She pulls out another printed sheet and hands it over with a flourish. This one is dated 23 January 1922.

We have returned to the hospital to try a lower dose. Though I have little hope of success and my friends ask me what's the point of trying again, I feel the implications of not being able to help him are so severe that I am willing to take this chance. These doctors, I feel, have staked their career on it.

"She's absolutely right," Auntie Jilly says. "The doctors had staked their career on it. The ringleader was Fred Banting, who started his experiments without a wage because he was so convinced they could work. The whole project, and fear of being overshadowed, proved incredibly stressful, and I have the proof."

Auntie Jilly reverently removes some yellowing paper from a document wallet. This time it's a pen and ink drawing depicting two scientists, one sitting on top of the other while trying to strangle him.

"This was given to me by my great aunt from a different branch of the family, only to be united with Leonard's side in the following generation. She was a close friend of Clark Noble, who was the artist of the cartoon and a colleague of its subjects. He got almost no recognition for his input, and I like to see this drawing as his contribution to the story of insulin."

The caricature of two men, ridiculous not glorious in the discovery that allows me to lead a normal life, makes me smile. "Science at its finest. What are they doing?"

"The strangler is Fred Banting, the strangled is Bert Collip. The discovery of insulin only happened because of Banting, but he wasn't allowed to be there when they injected Leonard because he didn't have treatment rights at the hospital. He is arguing with Collip because Collip wouldn't tell him how he made the extract that worked on Leonard."

I take it from her and hold it up to the light. The portrayal of Banting, who appears simultaneously geeky and furious, is perfect. His glasses are large and round; his hair, brushed sideways over his head, is sticking up in anger. I strain to read the title, in beautiful looping handwriting:

The discovery of insulin.

In 1923 the Nobel Prize for Physiology or Medicine was awarded to Fred Banting and JJR (Jack) Macleod for the discovery of insulin. Diabetes is one of the biggest health challenges in the UK today, and the discovery of insulin has had a huge effect on millions of lives.

As early as the 1860s it was known there were two types of diabetics: those who suffered emaciation and died quickly, and those who were 'fat and ruddy' and died more slowly. We now know these as Type 1 diabetes, which begins in infancy and is caused by the body's inability to produce insulin, and Type 2, which is most commonly seen in overweight adults and is caused by the body's inability to detect insulin. The effect in both cases is that the body is unable to regulate its blood sugar level.

The first clue that Type 1 diabetes was caused by the absence of a secretion from the pancreas came in 1889 when a scientist in Strasbourg noticed that removing a dog's pancreas caused severe wasting diabetes.

In 1892 it was shown that giving sheep thyroid extract to humans cured myxoedema (thinning of the skin caused by an underactive thyroid). It stood to reason that the same would be true of pancreatic extracts and diabetes. Between 1900 and 1921 this was tried by various physicians, but with no clear method to their studies and no way of testing whether it worked, other than asking the patient whether they felt better. The result was that at least five people came close to discovering insulin, but all their attempts turned out to be failures.

One of the scientists who came close to discovering insulin was Ernest Scott. This was when Macleod first became involved, being approached by Scott in 1912. Macleod was, apparently, 'not interested, just shrugged it off'.

In 1919, American scientist Israel Kleiner published results showing that injecting pancreatic extracts into dogs that had their pancreas removed caused their blood sugar levels to fall. His contract was terminated because this sort of research was seen as futile.

Fred Banting did his medical studies at the University of Toronto and, after a spell in the army, set up his own practice. To earn extra money he worked part-time teaching students at the University of Western Ontario. It was through this that he gained an interest in diabetes, and in 1920 he approached Jack Macleod, a Professor at the University of Toronto. Again, the meeting wasn't positive; Macleod still shared the prevailing pessimism about finding the pancreatic secretion.

The following year Macleod provided Banting with an ill-equipped lab and the assistance of his student Charles Best. Crucially, Best was able to measure blood sugar levels in very small blood samples. They quickly had success in dogs, so Banting was able to persuade Macleod that he was worthy of better facilities and a salary. Biochemist Bert Collip joined the team.

On 11 January 1922 a pancreatic extract from cows was injected into the buttocks of 14-year-old Leonard Thompson. Following the injection his blood sugar fell, but no clinical effect was seen and he developed a sterile abscess at one injection site. This was deemed a failure, but on 23 January they tried again with a lower dose of extract made by Collip, with more delivered over the next 24 hours.

Banting was excluded from the trial because he did not have treatment rights at Toronto General Hospital. Collip refused to tell Banting how he had made the extract, which led to a confrontation where Banting grabbed Collip by the collar. Another of Macleod's students, Clark Noble, drew a cartoon showing Banting sitting on Collip and trying to choke him.

Noble’s story is interesting in itself, given his involvement in both the discovery of insulin and of his brother’s chemotherapy research, which led to very little recognition for him. His story could have been very different (and who knows, perhaps the story of insulin’s discovery too) if he hadn’t lost a coin toss between him and Best to determine who would become Banting’s assistant.

By the end of 1922, 50 diabetic patients, many with very severe symptoms, had received insulin. The importance of the discovery was so instantly clear that Banting and Macleod were awarded the Nobel Prize very shortly after their initial discovery. Banting was so cross at having to share the prize with Macleod, who he believed had not done enough, that he almost refused it. When he was persuaded to accept he shared his money with Best, and Macleod later shared his with Collip.

Insulin from different vertebrates is very similar, which allowed the use of cow or pig insulin in humans. Even insulin from some species of fish is similar enough to be effective in humans. But since 1982, synthetic 'human' insulin has been manufactured using genetic engineering.

The various scientists who came close to discovering insulin between 1900 and 1920 contributed to our understanding of the disease, but admitted defeat when experiments failed. The discovery of insulin is a prime example of a scientific discovery that involved the efforts of many people, of whom only a minority – Banting, Best and colleagues – are now widely recognized.