98 years since first patient received insulin

11 January, 2020

11th of January 1922, 14 year old Leonard Thompson became the first person in the world with autoimmune diabetes (type 1 diabetes) to receive insulin, isolated (“discovered”) by Frederick Banting and Charles Best 27th of July 1921 (the exact date is debated). Leonard was believed to have had the disease ~3 years when his father approved the experimental trial, and had only a few days left when he was drifting in and out of diabetic coma due to his high glucose and ketoacidosis (1). Within the first 24 hours improvement was seen, but they failed. Twelve days later, the 23d of January, the team (now including biochemist James Collip) resumed the administration of the extract and finally they were was successful. Remarkable progresses was seen and Leonard left the clinic in the Spring 1922, and lived 13 more years but passed away at age 27, eventually of pneumonia. Photo courtesy of Eli Lilly:

Leonards patient records, as well as very comprehensive material about this major discovery still seen as one of the major advances within medicine, can be found here 2 and here 3.

Before the isolation of insulin, autoimmune diabetes was an absolute death sentence. In desperation, most common treatment was starvation diet and pioneers in the field was Frederick Allen and later, Elliott Joslin. Joslin described the method;

We literally starved the child and adult with the faint hope that something new in treatment would appear…It was no fun to starve a child to let him live.”

They could only prolong the life a bit sometimes but it was nothing but painful. Everyone died nevertheless, you can´t live without insulin. There are detailed information of some of the cases. Professor Allan Mazur have written the most interesting and comprehensive review that I´ve seen (4), about Frederick Allen’s “The Rockefeller series”. Beyond tragic, even though it was claimed that the series was not randomly selected and “ranged from the ignorant shiftless poor to the pampered willful rich” (5). The libraries at University of Toronto has a lot of interesting articles, they write: “Prior to the discovery of insulin severe diabetics were treated primarily by means of a strict diet which inevitably led to starvation if not out and out death from the disease. Children in particular suffered terribly from these severely restricted diets. For example, Leonard Thompson weighed only 65 pounds at the age of 14 when he was admitted to the Toronto General Hospital in December 1921, and was receiving only 450 calories per day. Jim Havens weighed less than 74 pounds at the age of 22, and when Elizabeth Hughes arrived in Toronto she weighed only 45 pounds and could barely walk on her own. After five weeks of treatment her weight had increased by ten pounds, and she was reveling in a 2500 calorie diet which included a pint of cream daily, having endured calorie intakes as low as 300 calories per day during the worst periods of her illness. In private correspondence, accounts in the popular press, and even in scientific journals the miraculous return to life and health of these patients once they received insulin was likened to a miracle.” (6)

There is a great timeline around the years for the discovery here 7.

After Leonard Thompson the trial expanded in the Spring 1922, below are some of the children before and after treatment with insulin, well documented by Banting:

 

Banting and colleagues sold the patent to The University of Toronto for one dollar, and Banting is believed to have said “insulin does not belong to me, it belongs to the world”. Quick distribution around the world was possible thanks to collaboration with Eli Lilly. In 1923, insulin was available at most places. The team behind the “discovery” received the Nobel Prize in medicine 1923, 8.

The isolation of insulin, “discovery”, has saved million of lives and is still considered to be one of the most important breakthroughs in medicine ever. The number of people in the world that are daily dependent of insulin to survive are unknown, but believed to be ~200 million (9). Unfortunately many people still today lack access to insulin. Some other great articles about the discovery 101112.

Autoimmune diabetes is one of the oldest diseases we know that still exists, and sad enough a cure is not close (13). Partly due to the complexity of the disease of course, it took years of research and huge developments in technology to be able to proceed. Diabetes research has also been lack of funding, and still is. We have moved from mice to humans, and these studies are expensive. Naturally there is a competition ongoing as well, a race to the cure. The winner will get global attention, all possible awards and of course financial compensation beyond what we have seen before. The latter is an obstacle as well I think. Recently more evidence came that link a virus to the onset of autoimmune diabetes (14), at the same time as several projects in the world are working on a solution to replace what we are missing: insulin-producing beta cells (15, 16). I am personally confident some, or many, will succeed with these trials. The issue is that for a viable cure for everyone, not “only” for the high risk patients with multiple complications and those with hypoglycemia unawareness, collaboration is a must. For a functional cure for all, we must understand the immune system and be able stop the destruction of the beta cells. I understand the purposes for researchers in this field are several, I just want to see less prestige and sometimes a bit more focus on the patients suffering.

Frederick Banting and Charles Best.

References:

  1. http://www.diabethics.com/diabetes/ketones/
  2. https://insulin.library.utoronto.ca/islandora/object/insulin%3AM10015
  3. https://insulin.library.utoronto.ca/about
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3062586/
  5. https://www.diapedia.org/introduction-to-diabetes-mellitus/1104519416/frederick-allen
  6. https://insulin.library.utoronto.ca/about/patients
  7. https://heritage.utoronto.ca/exhibits/insulin
  8. https://www.nobelprize.org/prizes/medicine/1923/banting/facts/
  9. https://www.liebertpub.com/doi/full/10.1089/dia.2018.0101
  10. https://www.thecanadianencyclopedia.ca/en/article/the-discovery-of-insulin
  11. http://bantinglegacy.ca/banting-insulin/key-dates/
  12. https://www.thestar.com/yourtoronto/once-upon-a-city-archives/2016/01/14/once-upon-a-city-discovering-insulin-was-banting-at-his-best.html
  13. http://www.diabethics.com/diabetes/#history
  14. http://www.diabethics.com/science/enterovirus-in-the-teddy-study/
  15. http://www.diabethics.com/science/closer-a-cure-for-autoimmune-diabetes/
  16. http://www.diabethics.com/science/mucin-capsule

 

 

Hans Jönsson
Scientific diabetes writer and lecturer
https://www.facebook.com/diabethics
https://www.instagram.com/diabethics


 

Idag är det 98 år sedan den första patienten i världen fick insulin

11 januari 1922 blev 14-årige Leonard Thompson den första människan i världen med autoimmun diabetes (typ 1 diabetes) att få insulin, isolerat (”upptäckt”) av Frederick Banting och Charles Best 27 juli 1921 (det exakta datumen är dock debatterat). Leonard tros ha haft sjukdomen i ~3 år när hans far godkände den experimentella behandlingen. Leonard hade bara dagar kvar och pendlade ut och in i koma av ketoacidos (syraförgiftning, 1) pga sitt höga blodsocker. Första 24 timmarna syntes förbättringar, men försöket misslyckades. Tolv dagar senare, den 23 januari, upprepade teamet (nu inkluderat biokemisten James Collip) administreringen av extraktet och lyckades äntligen. Otroliga förbättringar sågs, Leonard lämnade kliniken våren 1922 och levde 13 år till men gick tyvärr bort vid 27 års ålder, eventuellt pga lunginflammation (som emellanåt tros ha varit en effekt av hans allvarliga tillstånd vid insättandet av insulin). Foto från Eli Lilly på Leonard:

 

Leonards journal samt anteckningar, likväl väldigt omfattande dokumentation om denna stora upptäckt, finns här 2 och här 3.

Före isolerandet av insulin var autoimmun diabetes en absolut dödsdom. I desperation, var den mest vanligt förekommande behandlingen svältdiet och pionjärer var Frederick Allen och senare, Elliott Joslin. Joslin beskrev metoden;

We literally starved the child and adult with the faint hope that something new in treatment would appear…It was no fun to starve a child to let him live.”

De kunde endast förlänga livet en del emellanåt men det var inget annat än plågsamt. Alla dog, ingen kan leva utan insulin. Det finns detaljerad information om ett antal av patienterna, professor Allan Mazur har skrivit den mest intressanta och omfattande jag läst, om Frederick Allens ”The Rockefeller series”. Jag skrev om detta för två år sedan 4. Bortom tragiskt, och detta sagt trots att Allen sägs ha förskönat statistiken (5). Biblioteken vid University of Toronto har en mängd intressant material i ämnet, de skiver bland annat: “Prior to the discovery of insulin severe diabetics were treated primarily by means of a strict diet which inevitably led to starvation if not out and out death from the disease. Children in particular suffered terribly from these severely restricted diets. For example, Leonard Thompson weighed only 65 pounds at the age of 14 when he was admitted to the Toronto General Hospital in December 1921, and was receiving only 450 calories per day. Jim Havens weighed less than 74 pounds at the age of 22, and when Elizabeth Hughes arrived in Toronto she weighed only 45 pounds and could barely walk on her own. After five weeks of treatment her weight had increased by ten pounds, and she was reveling in a 2500 calorie diet which included a pint of cream daily, having endured calorie intakes as low as 300 calories per day during the worst periods of her illness. In private correspondence, accounts in the popular press, and even in scientific journals the miraculous return to life and health of these patients once they received insulin was likened to a miracle.” (6)

Det finns även en enkel men fin tidslinje runt åren för upptäckten, här 7.

Efter Leonard Thompson utvidgades behandlingen våren 1922, här är ett antal av de barn Banting dokumenterade väl, före och efter insättande av insulin:

Banting med kollegor sålde patentet till University of Toronto för en dollar, och Banting sägs ha sagt ”insulin does not belong to me, it belongs to the world”. Snabb distribution runt världen möjliggjordes tack vare ett samarbete med Eli Lilly. 1923, året efter det lyckosamma försöker på Leonard, fanns det på de flesta platser. Teamet belönades med 1923 års Nobelpris i medicin 8.

Isolerandet av insulin, ”upptäckten”, har räddat livet på oräkneligt många miljoner människor och räknas än idag som en av de största upptäckterna inom medicin någonsin. Antalet idag dagligen beroende av insulin är okänt, men tros vara ~200 miljoner (9). Tyvärr har än idag inte alla idag tillgång till insulin. Ytterligare ett par mycket fina artiklar i ämnet finns här för den intresserade 101112.

Diabetes är en av de äldsta sjukdomar vi känner till, men ett botemedel är tyvärr inte nära förestående (13). Delvis på grund av komplexiteten för sjukdomen naturligtvis, det tog åratal av forskning och krävdes stora tekniska framsteg för att över huvudtaget komma framåt. Diabetesforskningen har också lidit av brist på medel, och gör det fortfarande. Vi har förflyttat oss från forskning på möss allena, till människor, och de studierna är kostsamma. Naturligtvis pågår även en kapplöpning mot botemedlet. Den som lyckas får enorm global uppmärksamhet, ära och berömmelse och alla möjliga utmärkelser, men även ekonomisk kompensation sannolikt bortom vad som hittills setts. Det senare är tyvärr även ett hinder tror jag. Nyligen visade jag att hypotesen för att virus är inblandat i utvecklingen av autoimmun diabetes stärkts (13), samtidigt som det pågår flera projekt i världen som syftar till att ersätta det vi saknar: insulinproducerande betaceller (1516). Jag är helt övertygad om att någon, eller flera, av dessa kommer lyckas. Problemet är att vi för ett botemedel för alla och inte “bara” högriskpatienter med komplikationer eller som inte känner av sina hypoglykemier, hypoglykemisk omedvetenhet, så måste forskarna samarbeta. För ett funktionellt botemedel måste vi förstå vad som felar i immunförsvaret, och kunna stoppa det från att angripa våra betaceller. Jag om någon vet att många av dessa forskares syften är flera, jag när dock en önskan om att se lite mindre prestige och emellanåt ett större fokus på de patienter som lider. Med det sistnämnda inte sagt att det idag är ovidkommande för åtminstone majoriteten av forskarna.

Frederick Banting och Charles Best.

 

Avslutningsvis tackar jag en följare och diabetespappa som heter Martin som skickade en QR-kod han tagit fram för mig, helt på eget bevåg, som support. Om du vill stödja mitt arbete så tar du en bild på den i din swish-app. Tack.

 

Referenser:

  1. http://www.diabethics.com/diabetes/ketones/
  2. https://insulin.library.utoronto.ca/islandora/object/insulin%3AM10015
  3. https://insulin.library.utoronto.ca/about
  4. http://www.diabethics.com/science/insulinproduktion
  5. https://www.diapedia.org/introduction-to-diabetes-mellitus/1104519416/frederick-allen
  6. https://insulin.library.utoronto.ca/about/patients
  7. https://heritage.utoronto.ca/exhibits/insulin
  8. https://www.nobelprize.org/prizes/medicine/1923/banting/facts/
  9. https://www.liebertpub.com/doi/full/10.1089/dia.2018.0101
  10. https://www.thecanadianencyclopedia.ca/en/article/the-discovery-of-insulin
  11. http://bantinglegacy.ca/banting-insulin/key-dates/
  12. https://www.thestar.com/yourtoronto/once-upon-a-city-archives/2016/01/14/once-upon-a-city-discovering-insulin-was-banting-at-his-best.html
  13. http://www.diabethics.com/diabetes/#history
  14. http://www.diabethics.com/science/enterovirus-in-the-teddy-study/
  15. http://www.diabethics.com/science/closer-a-cure-for-autoimmune-diabetes
  16. http://www.diabethics.com/science/mucin-capsule/

 

 

Hans Jönsson
Vetenskaplig diabetesskribent och föreläsare
https://www.facebook.com/diabethics
https://www.instagram.com/diabethics

 

 

Autoimmune diabetes Cure Insulin Typ 1 diabetes Type 1 diabetes