Best for his part couldn’t stand Collip or Macleod and eventually ended up disliking Banting, too. In short, they more or less all ended up loathing one another. But at least the world got insulin.
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Diabetes comes in two varieties. Indeed, it is really two diseases, with similar complications and management issues but generally different pathologies. In type 1 diabetes, the body stops producing insulin altogether. In type 2 diabetes, insulin is less effective, usually because of a combination of decreased production and because the cells on which it acts don’t respond as they normally would. This is referred to as insulin resistance. Type 1 tends to be inherited; type 2 is usually a consequence of lifestyle. But it’s not quite as simple as that. Although type 2 is unequivocally associated with unhealthy living, it also tends to run in families, suggesting a genetic component. Similarly, although type 1 diabetes is associated with a fault in a person’s HLA (human leukocyte antigen) genes, only some people with the fault get diabetes, indicating that there is some additional, unrecognized trigger. Many researchers suspect a link to levels of exposure to a range of pathogens in early life. Others have suggested an imbalance in the victim’s gut microbes or possibly even a connection to how comfortable and well nourished one was in the womb.
What can be said is that rates everywhere are soaring. Between 1980 and 2014, the number of adults in the world with diabetes of one type or another went from just over 100 million to well over 400 million. Ninety percent of them had type 2 diabetes. Type 2 is growing especially fast in developing countries that have been adopting our bad Western habits of poor diet and inactive lifestyle. Yet type 1 is also growing swiftly. In Finland, it has gone up by 550 percent since 1950. It continues to rise almost everywhere at a rate of about 3 to 5 percent a year, for reasons no one understands.
Although insulin has transformed the lives of millions of diabetics, it is not a perfect solution. For one thing, it cannot be given orally, because it is broken down in the gut before it can be absorbed and put to use, so it must be injected, which is both a tedious process and a crude one. In a healthy body, insulin levels are monitored and adjusted second by second. In a diabetic, they are adjusted only periodically, when the patient self-medicates. That means that insulin levels are still not quite right much of the time, and that has a cumulative negative effect.
Insulin is a hormone. Hormones are the bicycle couriers of the body, delivering chemical messages all around the teeming metropolis that is you. They are defined as any substance that is produced in one part of the body and causes an action somewhere else, but beyond that they are not easy to characterize. They come in different sizes, have different chemistries, go to different places, have different effects when they get there. Some are proteins, some are steroids, some are from a group called amines. They are linked by their purpose, not their chemistry. Our understanding of them is far from complete, and much of what we do know is surprisingly recent.
John Wass, professor of endocrinology at Oxford University, is smitten with hormones. “I love hormones,” he likes to say. When we met, in a café in Oxford at the end of a long working day, he was clutching an armful of disorderly papers but looking surprisingly fresh for someone who had flown in that morning from ENDO 2018, the annual conference of the Endocrine Society in the United States.
“It’s madness,” he tells me in a delighted tone. “You have eight or ten thousand endocrinologists from all over the planet. The meetings start at five thirty in the morning and can go on until nine o’clock at night, so there’s a lot to take in and you end up with”—he shakes the papers for me—“a lot of reading. It’s very useful but a bit mad.”
Wass is a tireless campaigner for a better appreciation of hormones and what they do for us. “They were the last major system in the body to be discovered,” he says. “And we are still discovering more all the time. I know I am biased, but it is really a terribly exciting field.”
As late as 1958, only about twenty hormones were known. No one seems to know quite how many there are now. “Oh, I think it must be at least eighty,” says Wass, “but perhaps as many as a hundred now. We really do keep discovering more all the time.”
Until very recently, it was thought that hormones are produced exclusively in the body’s endocrine glands (hence the name endocrinology for this branch of medicine). An endocrine gland is one that secretes its products directly into the bloodstream, as opposed to exocrine glands, which secrete onto a surface (like sweat glands onto skin or salivary glands into the mouth). The principal endocrine glands—the thyroid, parathyroid, pituitary, pineal, hypothalamus, thymus, testes (in men), ovaries (in women), pancreas—are scattered all around the body but work together closely. They are mostly tiny and altogether weigh no more than a few ounces but have an importance to your happiness and well-being that is entirely disproportionate to their modest dimensions.
The pituitary gland, for instance, which is buried deep within your brain directly behind your eyes, is only about the size of a baked bean, yet its effects can be—literally—enormous. Robert Wadlow of Alton, Illinois, the tallest human who ever lived to that point, had a pituitary condition that caused him to grow ceaselessly because of continuous overproduction of growth hormone. A shy and cheerful soul, he was taller than his (normal-sized) father by the age of eight, was 6 feet 11 inches tall at the age of twelve, and over 8 feet tall when he graduated from high school in 1936—all because of a little chemical overexertion by this baked bean in the middle of his skull. He never stopped growing and was just a fraction under 9 feet tall at his greatest eminence. Though not fat, he weighed about five hundred pounds. His shoes were a size 40. By his early twenties, he could walk only with great difficulty. To support himself, he wore leg braces, which caused chafing, and that led to a serious infection that grew septic and killed him as he slept on July 15, 1940. He was just twenty-two. His height at death was 8 feet 11.1 inches. He was much loved and is still celebrated in his hometown.
It is clearly ironic that such a large body resulted from a malfunction in a minuscule gland. The pituitary is often called the master gland because it controls so much. It produces (or regulates the production of) growth hormone, cortisol, estrogen and testosterone, oxytocin, adrenaline, and much else. When you exercise vigorously, the pituitary squirts endorphins into your bloodstream. Endorphins are the same chemicals released when you eat or have sex. They are closely related to opiates. That’s why it is called the runner’s high. There is barely a corner of your life that the pituitary doesn’t touch, yet its functions weren’t even broadly understood until well into the twentieth century.
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The field of modern endocrinology got off to a somewhat bumpy start, in good measure because of the enthusiastic but misguided endeavors of an otherwise brilliant man named Charles-Édouard Brown-Séquard (1817–94). Brown-Séquard was a man literally of many nations. He was born on the Indian Ocean island of Mauritius, which made him Mauritian and British because Mauritius was then a British colony, but his mother was French and his father was American, so he had claims to four nationalities from the moment of his first breath. He never met his father, a ship’s captain who was lost at sea before his son’s birth. Brown-Séquard grew up in France and trained as a physician there but then rotated between Europe and America, seldom staying in either long. In one twenty-five-year period, he made sixty Atlantic crossings—this when one trip in a lifetime was exceptional—taking up a variety of posts, many of considerable eminence, in Britain, France, Switzerland, and the United States. During the same period, he wrote nine books and more than five hundred papers; edited three journals; taught at Harvard, the University of Geneva, and the Faculté de Médecine in Paris; lectured widely; and became a leading authority on epilepsy, neurology, rigor mortis, and the secretions of glands. But it was an experiment he conducted in Paris in 1889, at the stately age of seventy-two, that secured his permanent, and somewhat risible, fame.