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In , the Romanian physiologist Nicolas C. Paulescu — was able to extract a crude extract of bovine pancreas in salted water and removed some impurities with sodium hydroxide and hydrochloric acid. He injected it into a diabetic dog and found that it normalized the blood sugar level.

His work was interrupted during World War I. During , Paulescu published at least two papers on his anti-diabetic pancreatic hormone he called it "pancreine" experiments at the Romanian Section of the Society of Biology in Paris.

This was about the same time that Banting began his experiments. Did Banting read Paulescu's papers before he began his own experiments? Because intravenous injections of his pancreatic extracts caused toxic side effects in his dogs, Paulescu administered his extract rectally to humans via a rubber tube; the results were no different from those produced by control doses of saline alone.

What made Paulescu think that a pancreatic extract of a bovine would be physiologically active in a genetically unrelated animal dog? Foreign tissue transplants often are rejected by the immune system of the recipient. Even within the same species e. Frederick Grant Banting — was a young physician surgeon with a private practice in London, Ontario. How much of the literature on diabetes he read prior to his experiments is not known.

In , however, Banting read a paper by the American pathologist Moses Barron, who reported a rare case of a pancreatic stone lithiasis that had obstructed the main pancreatic duct of a human cadaver; all acinar cells of the pancreas disappeared atrophied , but most islet cells remained, results similar to those produced by ligation of pancreatic ducts, as reported in the literature by others Bliss, : p. This observation may have been the stimulus for Banting to envision ligating pancreatic ducts of normal dogs to protect the external secretions digestive enzymes from digesting the internal secretion s hormone[s] while preparing extracts for administration to diabetic dogs.

In , Banting took his idea to John James Rickard Macleod — , professor of physiology at the University of Toronto, because Macleod was an internationally known expert on carbohydrate metabolism. Macleod was not impressed with Banting's idea. Banting obviously had little knowledge about previous experiments of this kind and had no training in experimental physiological research.

Eventually Banting convinced Macleod to provide him with a small surgical room, dogs, and a helper to perform blood and urine glucose tests. Charles Herbert Best — had just graduated with a B. He volunteered to help Banting obtain glucose readings from blood and urine in his dog experiments. After many early failures, Banting succeeded in extracting a pancreatic solution that contained enough anti-diabetic substance from fetal calf pancreas to lower the blood sugar in a dog made diabetic by pancreatectomy.

This meant no more duct ligations and no more shortages of extract, because fetal calves were readily available from meat- processing plants. However, the crude extracts proved somewhat toxic and would not be suitable for testing on humans.

The extraction procedure was improved when fetal calf extracts were passed through an unglazed porcelain filter Berkefeld filter to remove bacterial contaminants. On 23 November , Banting injected himself subcutaneously with the new extract. He observed no adverse effects, but no blood was taken for testing. Banting introduced one extract into his own digestive system via a stomach tube and also observed no adverse effect.

On 11 December , Banting removed a whole dog pancreas, and Best prepared an extract in alcohol. When he injected the extract back into the donor dog, the animal's blood sugar level dropped. This meant that no more degenerated pancreases and no more fetal pancreases were needed.

On 11 January , a year-old diabetic boy, Leonard Thompson, was injected in the buttocks intramuscular? Macleod had previously invited the biochemist James Bertram Collip — from the University of Alberta to join the Toronto team to help purify the extracts of toxic substances and concentrate the active principle for use in diabetic humans.

He tested an aqueous solution of the precipitate on rabbits, with success in reducing blood sugar. Collip's extract was then given to Thomson on 23 January This time there was no doubt about the effectiveness and safety of the treatment Bliss, : pp. Banting and Best published their first paper in on the successful use of a pancreatic extract for normalizing blood sugar glucose levels glycemia in diabetic dogs.

This paper made direct reference to Paulescu's article but misquoted that article as follows: "He [Paulescu] states that injections into peripheral veins produce no effect and his experiments show that second injections do not produce such marked effect as the first," which is not what Paulescu found out or presented.

Later on, Banting said that. I regret very much that there was an error in our translation of Professor Paulescu's article, I cannot recollect, after this length of time, exactly what happened….

I do not remember whether we relied on our own poor French or whether we had a translation made. In any case I would like to state how sorry I am for this unfortunate error. Where did Banting get the idea that tying off the pancreatic duct might cause the acinar cells to degenerate and the pancreatic enzymes to disappear or become inactive? What made him think that the anti-diabetic substance would accumulate in the ligated pancreas instead of disappearing along with the pancreatic enzymes?

Do liver cells and bile degenerate if the bile duct is ligated? Why did Banting choose to wait 6 weeks instead of some shorter or longer duration before attempting to extract insulin from the source pancreas? His first attempt was unsuccessful because the relatively stiff cat-gut ligature loosened and failed to block the ducts.

Six weeks were wasted. Silk thread gave better results after that. At the time Banting was doing his experiments, the chemical structure of insulin was not known; it could have been protein, lipid, carbohydrate, or another form of matter. Biomacromolecules, such as proteins, are more labile subject to degradation when warm and when contaminated by bacteria than when cold and sterile. Macleod advised Banting to keep his extracts cold, and potentially more physiologically stable, in the heat of the Ontario summer.

Whether his predecessors did likewise is debatable, especially before the advent of refrigeration. Although Best and Taylor : p. They also give some details of how secretin can be extracted from intestinal tissue:. If the wall of the intestine of any animal is ground up with water and then filtered so as to free it of solid particles, the clear fluid so obtained will be found to contain large amounts of secretin; for when the fluid is injected into the blood of another animal, a very abundant secretion of pancreatic juice results.

Insulin may have been extracted by Banting and Best from pancreatic tissue in essentially the same manner as described here for the extraction of secretin from the intestinal membrane. Another intestinal hormone that stimulates the secretion of pancreatic juice is called pancreozymin.

Secretin mainly induces secretion of the water and salts of the pancreatic juice, whereas pancreozymin mainly stimulates secretion of enzymes. As Bliss : pp. There were eight distinct and essential steps or stages leading to the production of an insulin that was sufficiently pure to be used in the treatment of diabetes and which could be produced in adequate quantity to meet the urgent demand.

The first of the steps was the use of alcohol in extracting the hormone from the minced pancreas. This was announced by Zuelzer in Berlin in It was rediscovered by the Toronto investigators in , who did not know of Zuelzer's work. The second was a method of determining the amount of sugar quickly and accurately in a small quantity of blood.

This was devised by Lewis and Benedict in New York in The third was the discovery of Kleiner and Meltzer in that an aqueous extract of the normal pancreas injected into the veins of a normal dog reduced hyperglycemia as well as glycosuria.

The fourth step was the discovery that the active principle was maximally insoluble in 95 percent alcohol. This was made by Banting, Best and Collip in December The fifth was the preparation by Collip of the first relatively non-toxic insulin to be used in the treatment of diabetes January with success.

The sixth step was the physiological assay based on Collip's observation February [actually December] that insulin in adequate amount usually produced convulsions in normal rabbits when the blood sugar fell to 46 mg per cc. The seventh was the discovery by Doisy, Somogyi and Shaffer of St. Louis, that insulin was precipitated at the iso-electric point…. The eighth and final step was the development of methods of large-scale production by the chemical engineers of the Eli Lilly Co.

A devastating criticism of Banting and Best's work by Dr. He opined that Banting's hypothesis that duct ligation was necessary for trypsin-producing cells to atrophy before making an extract of the internal secretion was false. Trypsin is not active in the pancreas. It is produced as trypsinogen, and becomes acted on by another ferment — enterokinase, secreted by the small intestine. There was no physiological basis for their duct experiments Bliss, : p.

Roberts also pointed out that Banting and Best had misinterpreted their experiment on 18—19 August Their data show that extracts from whole pancreases were more effective and more lasting than those made from degenerated pancreases. However, Banting and Best claimed that whole-gland extract was weaker and, thus, reinforced their hypothesis Bliss, : p.

Roberts concluded that. The production of insulin originated in a wrongly conceived, wrongly conducted, and wrongly interpreted series of experiments…. Banting himself never seems to have read or known about Roberts' criticisms….

For the next thirty years no one else studied Banting and Best's experiments carefully and critically. Bliss, : pp. During the experiments of Banting and Best, it was found that insulin could be extracted from a whole, normal, unligated pancreas and that the pancreases of fetal cattle or pigs are just as effective as those of dogs as a commercial source of insulin.

Fetal cells in the islets of Langerhans develop sooner than the acinar cells, so there would be no digestive enzymes to destroy the insulin during the extraction procedure, and no need to perform duct ligations.

In hindsight, the dog experiments were probably unnecessary for the discovery of insulin. However, those early experiments eventually led to the clinical use of insulin. This would almost certainly have been discovered sooner or later by other workers. But think of how many people might have suffered and died of diabetes before this knowledge would become available without the dog experiments. On what basis do scientists choose the organisms for their experiments?

In the case of diabetes, why were dogs chosen? Chimpanzees are more closely related to humans than dogs are, but their use in experiments has serious ethical and economic considerations. When doing surgery, size matters. Removal of a pancreas is an easier job on a large dog than on a small rabbit or a cat. Imagine surgical ligation of pancreatic ducts in a rat! Also, domestic dogs are more receptive to injections and periodic blood sampling than pigs or calves, and they require less food and space for housing lower costs.

Hundreds of unligated rabbits were used by Collip to test the potency, dosage, and safety of his extracts. Students may want to know what happened to the dog that had its pancreas removed as a source for extraction of insulin.

It must be remembered that in those early days there were fewer animal welfare laws than we have today. Science ethics should always evaluate the need to perform experiments on animals in terms of their potential medical or veterinary benefits. Many dogs that cannot find a home or cannot be housed indefinitely by animal shelters must be euthanized or else die of starvation and neglect.

Is it not more ethical to humanely euthanize an animal in the search for a potential medical treatment than to allow an animal to suffer and die in this way? If the discovery of insulin is defined as the time the first extracts lowered the blood sugar of dogs, then the priority for the discovery belongs to Zuelzer, Scott, Murlin, Paulescu, and others. Search Engine. Great Personality. World Wonders. Tell Me Why. Sports Buzz. Recent Posts. Disclosure This policy is valid from 01 May This blog is a personal blog written and edited by me.

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