Medicine learned of type 1 diabetes early with the observation of people who seemed to eat food and make honey out of it (diabetes mellitus means “honey passing through”). It was induced in animals for the first time in 1889 when Oskar Minkowski surgically removed the pancreas of a dog. Thus did the dance of knowledge of diabetes in humans and animals begin.
Using the tools of molecular biology scientists can fish for the gene that instructs cells to make insulin. It is perhaps not surprising that mammals like dogs and pigs make insulin. All mammals have similar internal anatomy and analogous metabolism, and seem to have steady blood sugar in the healthy state. And insulin regulates blood sugar.
On the other hand it is surprising that yeast have DNA that encodes insulin-like protein, and yeast responds to human insulin by altering its metabolism. Given that yeast is a single cell, that seems very surprising. There is no pancreas in yeast and no liver; in effect the yeast cell is a single-cell liver. Why does it need insulin? It seems whatever insulin does, it is rooted deep in the tree of life because our ancestors and yeast ancestors parted over a billion years ago.
At the most basic philosophical level this may not be too surprising. Fuel is always short, and allocation of scarce fuel is a fact of all life. And glucose is liquid fuel; it is the kerosene powering the jets of living organisms.
Pigs made their big contribution to diabetes research back in the 1920s. It had been generally believed that the pancreas made a single hormone called “insulin”, the lack of which caused type 1 diabetes. The Canadians Banting, Best and McCollup found it by purifying it from pancreases of pigs. They chose pig pancreases because they were cheap and abundant (compared with human’s or dog’s). So their process of scaled up and marked the beginning of the commercial insulin business.
When pancreas transplantation was found to produce nearly natural insulin delivery in 1966 scientists began to consider how to transplant only the part of the pancreas needed to cure diabetes, the islets. Thus began the quest for purified islets of Langerhans. Human islets — most famously using the Edmonton Protocol — are proven to normalize blood sugar. But there aren’t enough human islets available to realize a cure.
Pigs may save the day. The only nonhuman islets that have been shown to work in human beings are pig islets. Fortunately, pigs have the promise to provide large quantities of tissue, and at least one pig herd is free of all the viruses considered to have the potential to harm humans.
Pig insulin differs from human insulin. So does dog insulin. But the two are identical! It is only by chance, since they are on different branches of the mammalian tree of life. Thus the two species most useful for human diabetes studies share something neither does with us, the same insulin.
Don’t slight the co-workers in your interesting historical review! Its bad enough that the Scot, Macleod, tried to steal the credit for the work of Banting and Best without giving poor James Collip a Scots-Irish ‘Mc’ to boot. Similarly, the demonstration in 1889 that diabetes could be produced in dogs by the ligature of the pancreas is usually attributed to Minkowski and his partner, von Mehring. I’m inclined to take as much credit away from Minkowski as he gets for his 1889 discovery, since in 1908, after his student, Joseph Zuelzer, successfully isolated insulin from a calf pancreas and had some clinical success injecting it into a dying diabetic, Minkowski misidentified the ensuing hypoglycemic shock in the patient as an ‘allergic’ reaction to the foreign calf protein, and forbad Zuelzer from ever using his ‘dangerous’ extract again for that reason. A little further titration of doses and logical reasoning about how excess insulin might affect the body might have permitted Zuelzer to anticipate the results of Banting and Best by 14 years, thus saving thousands of lives, had Minkowski not over-reacted. When a positive result is temporarily achieved in a patient dying from an incurable disease, the proper thing to do is not to abandon that line of research at the first sign of a negative side-effect, but is instead to refine it to try to eliminate the side-effect.
A similar instance of that kind of illogical reasoning which has plagued diabetes research since the start is the whole waste of effort represented by the Edmonton Protocol. Since it was well known when work on this avenue was begun that the entire American population of three hundred million people could produce only 4500 cadavers for kidney donation per year, what use could even a successful version of the Edmonton Protocol have been to the 1.5 million type 1 diabetics in the U.S. if it required islets harvested from between one and three cadaver pancreas donors per patient to work! The supply of cadaver organs would not have sufficed even to keep pace with the number of new cases of type 1 diabetes emerging every year, so its public health significance could be calculated from day one of the experiment to be zero. And people wonder why there is so little progress in diabetes research after so much money and time have been spent on finding a cure!
To add to my earlier historical commentary, I would like to contribute to your biological speculations by considering why the genes predisposing people to develop type 1 diabetes may have survived as long as they have, given their obvious evolutionary disadvantages. One theory proposed draws on an analogy with evergreens, which decrease their water content and increase the sugar content in their needles at the onset of winter to achieve protection from freezing. The fact that the peak onset for new cases of type 1 diabetes is in the autumn at the first signs of cold suggests that the diabetes genes in humans may be performing a similar cryoprotective function to these water-shedding, sugar-concentrating genes in evergreens. It is especially noteworthy that type 1 diabetes is concentrated in colder countries and everywhere in Europe which was settled by the marauding Vikings in the Middle Ages, such as Sardinia and SIcily. Perhaps during the last Ice Age, only diabetics had the capacity to shed fluid and concentrate sugar in their tissues at the onset of more extreme cold, and with this physiological cryoprotection they had a great survival advantage. As long as human life expectancy remained very short and people did not survive to reproduce much after the age of onset of diabetes around puberty or shortly thereafter, the diabetes genes were a distinct survival advantage. Only with longer lifespans following the Ice Age did those without the cryoprotective diabetes genes begin to reproduce more offspring than diabetics.
See: S. Moalem, et al, “The Sweet Thing about Type 1 Diabetes: A Cryoprotective Evolutionary Adaptation,” Medical Hypotheses, vol. 65, p. 8 (2005).