Friday, June 18, 2010

science used to be so bad ass.

*Nerd alert* This post is about insulin, and science in the 1920s.

Quick review: I don't know if this graphic is specifically for drug production, but it illustrates my point.

Today, it takes YEARS for a drug to go from the laboratory to your pharmacist. We're talking at least a decade.

Taken from the Wikipedia article on "Insulin" (my notes are in square brackets; some words bolded for emphasis):

"In October 1920 Canadian Frederick Banting ... a surgeon by training ... theorized that a relatively pure extract could be made from the islets [from the pancreas] once most of the rest of pancreas was gone.

In the Spring of 1921 Banting traveled to Toronto to explain his idea to J.J.R. Macleod who was Professor of Physiology at the University of Toronto, and asked Macleod if he could use his lab space to test the idea. Macleod was initially skeptical [Banting had NO research experience!!], but eventually agreed to let Banting use his lab space while he was on vacation for the summer. He also supplied Banting with ten dogs to experiment on, and two medical students, Charles Best and Clark Noble, to use as lab assistants, before leaving for Scotland. Since Banting required only one lab assistant, Best and Noble flipped a coin to see which would assist Banting for the first half of the summer. Best won the coin toss, and took the first shift as Banting's assistant. Loss of the coin toss may have proved unfortunate for Noble, given that Banting decided to keep Best for the entire summer, and eventually shared half his Nobel Prize money and a large part of the credit for the discovery of insulin with the winner of the toss. Had Noble won the toss, his career might have taken a different path.

Banting's method was to tie a ligature (string) around the pancreatic duct, and, when examined several weeks later, the pancreatic digestive cells had died and been absorbed by the immune system, leaving thousands of islets. They then isolated an extract from these islets, producing what they called isletin (what we now know as insulin), and tested this extract on the dogs. Banting and Best were then able to keep a pancreatectomized [they cut out her pancreas... suck it PETA!] dog named Alpha alive for the rest of the summer by injecting her with the crude extract they had prepared. Removal of the pancreas in test animals essentially mimics diabetes, leading to elevated blood glucose levels. Alpha was able to remain alive because the extracts ... were able to lower her blood glucose levels.

Banting and Best presented their results to Macleod on his return to Toronto in the fall of 1921, but Macleod pointed out flaws with the experimental design, and suggested the experiments be repeated with more dogs and better equipment. He then supplied Banting and Best with a better laboratory, and began paying Banting a salary from his research grants [no grant applications, no open competitions or job interviews...]. Several weeks later, it was clear the second round of experiments was also a success; and Macleod helped publish their results privately in Toronto that November [quick publishing timeline!]. However, they needed six weeks to extract the isletin, which forced considerable delays. Banting suggested that they try to use fetal calf pancreas, which had not yet developed digestive glands; he was relieved to find that this method worked well [they used fetal calves!! just like that!! no ethics forms to fill out, nothing!]. With the supply problem solved, the next major effort was to purify the extract. In December 1921, Macleod invited the biochemist James Collip to help with this task, and, within a month, the team felt ready for a clinical test [are you following this timeline?! they went from dogs to humans in under a year!! no clinical trials back then!!].

On January 11, 1922, Leonard Thompson, a 14-year-old diabetic who lay dying at the Toronto General Hospital, was given the first injection of insulin. However, the extract was so impure that Thompson suffered a severe allergic reaction, and further injections were canceled. Over the next 12 days, Collip worked day and night to improve the ox-pancreas extract, and a second dose was injected on January 23 [less than two weeks later... without first testing it on a dog!]. This was completely successful, not only in having no obvious side-effects but also in completely eliminating the glycosuria sign of diabetes.

[In hospitals of the day] Children dying from diabetic keto-acidosis were kept in large wards, often with 50 or more patients in a ward, mostly comatose. Grieving family members were often in attendance, awaiting the ... inevitable death.

In one of medicine's more dramatic moments Banting, Best, and Collip went from bed to bed, injecting an entire ward with the new purified extract. Before they had reached the last dying child, the first few were awakening from their coma, to the joyous exclamations of their families. [SERIOUSLY?!!]

... Over the spring of 1922, Best managed to improve his techniques to the point where large quantities of insulin could be extracted on demand, but the preparation remained impure. The drug firm Eli Lilly and Company had offered assistance not long after the first publications in 1921, and they took Lilly up on the offer in April. In November, Lilly made a major breakthrough and were able to produce large quantities of highly refined, 'pure' insulin. Insulin was offered for sale shortly thereafter [less than two years after the initial experiments on dogs!!!]."

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