In June 1816, Mary Shelley and her husband were enjoying a dinner party with a group of friends. They talked of books and poetry and swapped German ghost stories. The dinner led Shelley to write a short story that she later turned into her 1818 novel, Frankenstein. The book was a cautionary tale of a research scientist who successfully assembled a living being from corpses, only to have his creation turn on him and wreak havoc on the community. The book asks us to be aware of the Frankensteins of unintended consequences all around us. Let’s consider one.
One day in 1991, researchers working in England for the pharmaceutical giant, Pfizer, were taken by surprise. They had been toiling away to develop a chemical compound to treat heart problems. They had come up with Sildenafil. It looked promising but then, during clinical trials, older men who had been taking the compound reported rock-hard erections lasting more than an hour. Those in the placebo-taking control groups reported no such effects. The Pfizer heart research project took a quick turn. More tests were done, the discovery was deemed sound, and so a method of mass producing the compound as a pill in the proper dosage was quickly established. The research team had inadvertently invented Viagra.
Patents were obtained. Observers wryly noted the unusual lightning speed with which the predominately middle-aged men in charge of so many of the world’s government approval processes allowed the little blue pill to machete its way through red tape. Within six months of its American approval, in March 1998, 7 million prescriptions were written, rendering it the country’s most popular medication.
Pfizer’s future changed and its stock and profits rose dramatically. Commercials changed acceptable public conversations by dragging discussions of impotence, or erectile dysfunction, as it was renamed, from the shadows. The research changed the lives of millions of men and couples for whom impotence had been a problem. All was well.
But then, retirement homes and senior-dominated communities began reporting skyrocketing numbers of cases of sexually transmitted diseases. Arizona’s Pima and Maricopa counties, for instance, have unusually large senior populations. From 2005 to 2009 the number of people older than 55 who contracted syphilis and chlamydia for the first time in their lives rose by 87%. As is the case with most corporate, applied research, Pfizer never released the names of those who created Viagra so we don’t know their reaction to the good and bad changes their work brought about. But Mary Shelley would have smiled.
What other research and inventions bring about Frankenstein change? What small decisions have we made in our lives, that ended up big ones in disguise, put us on roads we had hoped to never travel? How many political decisions made for expedient or partisan reasons have helped some but hurt many? Can we rise up as the torch-bearing villagers did in Shelly’s novel and defeat our Frankensteins? Let’s first identify them in our lives and our communities. Then, let’s light the torches.
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Is every child my child? Does ideology end at the bedside of a sick child? I ponder those questions every day when I watch the bravest person I know – my granddaughter. Consider this:
A healthy, happy little boy was suddenly insatiably thirsty. He began urinating a lot and often and feeling increasingly tired. His skin became thin and dry. No matter how much he ate, he continued to lose weight. A few months later he was weak, gray, and skeletal. His eyesight weakened and then his retinas detached rendering him blind. Within nine months, the now bedridden child gasped for air. Less than a year after falling sick, he slipped into a coma and, mercifully, died.
The sad part to this tragic tale is that it was not rare. Ancient Egyptians, Greeks, Chinese, and Indians saw children and adults die in this horrible, mysterious fashion. A first-century Greek researcher, Arataeus of Cappadocia, described the disease as “the melting down of flesh and limbs into urine.” He used the Greek word for “passing through” or “siphon” to name it: diabetes.
For hundreds of years, researchers were stymied. It was suggested that diabetics eat things that the body would have to fight to turn to urine such as almonds and broken bits of coral. It didn’t work. Seventeenth-century Scottish researchers developed a diet treatment in which patients ate nothing but blood puddings, fat, and rancid meat. It didn’t work. In the 1800s, doctors bled diabetics; every day for a week or so, a vein would be opened and pints of supposedly bad blood was drained. It didn’t work. In the early 1900s, diabetic children were hospitalized and fed only 450 calories a day. They were starved to death. German scientists found that eating carbohydrates was linked to symptoms and so they locked up diabetic children and force fed them oatmeal. Nothing worked.
An import step came when German researchers used autopsy studies to link diabetes to the pancreas. The pancreas is a small seahorse-shaped gland that lies between the stomach and spine. You can locate it by pressing your right thumb and little finger together, keeping your other fingers straight and together, and then placing your thumb at the centre of your stomach, even with your lowest rib. Your three extended fingers now approximate the location and size of your pancreas.
German researcher Paul Langerhans advanced learning by postulating that the pancreas produces two types of cells. One is secreted into the small intestine and aids with digestion. He called them external cells. The other is secreted into the bloodstream to regulate glucose levels. He dubbed them internal (later the islets of Langerhans). It was postulated that without the internal clusters of cells, sugars could not be metabolized from food and so suger entered the blood stream and gathered in increasingly high levels as the body could no longer clean and flush it out. Then the awful symptoms began.
It was a breakthrough but for decades afterward, researchers tried but failed to find a way to utilize the new understanding by artificially doing what a dead pancreas could not – extracting cells from a healthy a pancreas and injecting them into a diabetic patient. People continued to die.
Photo: Queen’s University
Frederick Banting grew up on a small Ontario farm. He undertook medical training at the University of Toronto. After service as part of Canada’s First World War Army Medical Corps, and becoming both wounded and decorated, he became a surgeon in Toronto. He later opened a small practice in London, Ontario. The 29-year-old was barely eking out a living.
In the middle of a sleepless night, he was reading a medical journal about diabetes research when he experienced a eureka moment. It appeared clear to him that when extracting secretions from the pancreas, researchers were missing the possibility that external secretions were damaging the internal secretions. The two had to be separated, he thought, and then a serum could be developed using only the internal secretions.
The next weekend, he arrived without an appointment at the office of the University of Toronto’s professor of physiology, J. J. R. Macleod, who was famous for his work on the metabolism of carbohydrates. McLeod listened patiently but was unimpressed by the young man with little knowledge of current diabetes research, without a Ph.D., and with no clinical research experience. After several more visits, Banting was about to give up when he saw the professor lean back and close his eyes. But then, McLeod leaned forward, smiled, and said the idea just might work.
In April 1921, Banting arrived at McLeod’s small lab. He met fourth-year student Charles Best who would assist. They used dogs. Banting removed the pancreas of some to induce diabetes. He removed part of the panaceas from others and then, with blood vessels still in place, sewed the severed portion just below the skin of the abdomen. He then tied off, ligated, the grafted portion and waited for the external cells to die. Internal cell clusters were then extracted, purified and processed using water at first and, as they learned more, alcohol. They then injected the extraction into depancreatized dogs. Some showed slightly positive reactions but most didn’t. Many died. The determined Banting and Best slaved away in the smelly, sweltering lab, painstakingly honing the process of removing impurities from the extracts.
In July, after a number of revisions and failed experiments, they injected a depancreatized white terrier with duct-ligated extract. Blood sugar levels dropped from dangerous highs to near normal levels. With their extract in its body, the dog was metabolizing sugar as if its pancreas was still there. Unable to estimate the amount of extract necessary, the dog died. They learned. They injected another dog that had fallen into a diabetic coma with new extract and marveled as the dog awoke, wobbled to its feet, and then walked about the room. Banting and Best were ecstatic. They called their extract Isletin.
A month later, shortly after MacLeod’s return from an extended absence overseas, Banting stormed into the professor’s office with a list of demands including a salary, more assistance, and changes to the lab. A young man was hired to tend to the dogs, biochemistry professor James Bertram Collip joined the research team, a bigger lab was found, back pay for Banting and Best was paid, and a university lecturing job was found for Banting who at that point was just a few dollars from destitution.
Research moved more quickly when Banting began using the pancreas of unborn calves that he procured from local abattoirs. The diabetic dogs began responding better and living longer. Finally, it was time
His name was Leonard Thompson. He was 14 years old. He was from a poor family and so was a public ward patient at the Toronto General Hospital. His diabetes had been diagnosed nearly two years before. He was emaciated and near death. He weighed only 65 pounds. His skin was gray, he could no longer walk, and had trouble focussing and even staying conscious. Banting explained the extract trial to Thompson’s father who quickly consented.
On January 11, 1922, two doses of isletin extract were injected into young Thompson’s backside. Thompson was too ill to even flinch. The sugar in his blood and urine dropped by 25%. It was good but not great. The disappointing results were deemed the result of impurities in the extract and so they went back to work with Collip whipping up batches like a chef trying new recipes.
Two weeks later they walked back across the street to Toronto General Hospital’s H Ward. Leonard’s condition had worsened. He was now fading in and out of a coma. The boy was given two injections that afternoon and one the next morning. It worked. Miraculously, he sat up. He smiled. The fog that had haunted his eyes for so long suddenly cleared. He asked for food. Leonard was Lazareth.
Banting opposed patenting what they were now calling insulin. He insisted that medical advances belonged to all and were for the good of mankind. A patent was eventually applied for in the names of Best and Collip and with the direction that it would be assigned to the University of Toronto. It was written so anyone could use their process to manufacture insulin but that no one else could patent the process. It thereby deprived anyone from stopping anyone else from manufacturing insulin. American legalities later led to Banting’s name being added to the patent.
True to Banting’s principles, the Indiana-based Eli Lilly and Company was afforded an exclusive deal to manufacture insulin in the United States but for the first year it had to be distributed free of charge. Toronto’s Connaught Laboratories manufactured and distributed free insulin in Canada. It was also agreed that the university would happily send the formula to any researcher in the world for free, in return for a promise that insulin would not be produced for sale.
By the end of 1923, diabetes patients in Canada, the United States, and parts of Europe were receiving insulin injections. Each represented an inspiring and heartrending story of recovery as they stepped back from death’s door. The 1923 Nobel Prize for Physiology or Medicine was awarded to Banting and McLeod. McLeod shared his prize money with Collip and Banting shared his with Best.
Among the millions of lives that have been saved by the work of Banting and his Toronto colleagues, and those upon whose shoulders they stood, is my granddaughter. She’s eight years old. For three years now she has pricked her thumb to draw then test blood six to ten times a day. It hurts every time. Trust me, I’ve done it, and it hurts. She now injects herself with insulin six or more times a day. She watches what she eats and her Mom counts every carbohydrate consumed to adjust insulin dosages. It’s an awful disease but it doesn’t define her. Before the work of Banting, Best, and the others, though, it would have killed her.
We know now that type two diabetes is mostly contracted by adults and mostly due to lifestyle choices. But type one attacks children. No one knows why. For some reason, a virus that gives some kids a cold kills the pancreas of others. Today, over 420 million people around the world and about 10% of Canadians have diabetes. Most have type two. About 26,000 Canadian children have type one.
And so we are back to our initial question. God bless the determined researchers who are working in labs every day, uncelebrated, and often underfunded and underpaid. And God bless those who support the idea that our circle of community involves devoting charitable giving and a sliver of our tax money for research. We are helping people we’ll never meet. We are making all children ours. We are saying where ideological arguments should die so that fewer children will; at the bedside of a sick child.
Someday the cure for type one diabetes will be found. Banting and Best will be remembered. And on that day, I will stand with my granddaughter, and we will cheer.
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