Feature Article/From Thebes to Toronto

From Thebes to Toronto and the 21st Century: An Incredible Journey

Lee J. Sanders, DPM

Editor’s note: This article is a tran- nature of the ailment, its origin, and script of the address of the American treatment. It is commonly believed Association President, that the history of began Health Care and Education, given in with the Greeks, and that prior to the June 2001 at the Association’s 61st time of Hippocrates, there was little Annual Meeting and Scientific that could be called an art of medi- Sessions in Philadelphia, Pa. cine. Nevertheless, for more than 2,000 years before the birth of The story of diabetes mellitus—its dis- Hippocrates, Egyptian physicians had covery, description, and treatment—is been striving to diagnose and treat a remarkable chronicle covering 3,500 disease. was the first years of medical history. My civilization known to have an exten- President’s Address, “From Thebes to sive study of medicine and to have left Toronto and the 21st Century” will behind written records of its practices take you on an incredible journey and procedures. through time, highlighting major mile- Across the Nile from Luxor, on the stones in the history of diabetes. West Bank, sits the Necropolis of Regrettably, health care providers Ancient Thebes, a vast land of tombs receive very little instruction in the and temples built to honor the . Most medical pharaohs and other nobles. It was and nursing students today have a here, in the vicinity of Thebes, that rather limited, contemporary knowl- German Egyptologist Georg Ebers edge of diabetes. The history of acquired his famous in 1872. advances in diabetes prior to the dis- Named for him, the is covery of at the University of one of the most famous documents Toronto, in 1921, has been obscured relating to the ancient practice of by the passage of time. Historical medicine. Written about 1550 BCE, concepts of the causes and nature of abundant evidence suggests that it diabetes have either been forgotten or was copied from a series of books never learned. many centuries older. One passage It is my belief that knowledge of dates from the First Dynasty (circa history affords a better understanding 3400 BCE). of contemporary issues and clearer The first reference to diabetes mel- vision as we look to the future. It is litus is attributed to the Ebers my pleasure to share this thrilling Papyrus, which mentions remedies for story with you, and to reveal the ori- the treatment of excessive urination gin of some of the discoveries that () (Figure 1). The Ebers have brought us to our current under- Papyrus contains remedies “to elimi- standing of diabetes at the dawn of nate urine which is too plentiful.” The the 21st century. Looking at this ail- following mixture was prescribed for ment over the ages makes one fact the treatment of polyuria: clear: the incidence of diabetes has A measuring glass filled with Water increased dramatically, from an from the Bird pond, Elderberry, uncommon ailment during the period Fibres of the asit plant, Fresh Milk, of antiquity to a worldwide epidemic Beer-Swill, Flower of the expected to affect 300 million people Cucumber, and Green Dates Address correspondence and reprint by the year 2025. Urinary troubles in the adult were requests to: Dr. Lee J. Sanders The story of diabetes unfolds dur- also corrected with rectal injections of Chief, Podiatry Section (N323) ing the Age of Antiquity, where we olive oil, honey, sweet beer, sea salt, Acute Care/Specialty Services begin to see the earliest descriptions of and seeds of the wonderfruit. VA Medical Center the symptoms of diabetes. Ancient Egyptian medicine influenced the 1700 South Lincoln Avenue physicians recorded their observations medical practices of neighboring cul- Lebanon, PA 17042 in an attempt to better understand the tures, including the culture of ancient 56 Diabetes Spectrum Volume 15, Number 1, 2002 Feature Article/Sanders

exhilarating revision of medical and scientific concepts. Renaissance physicians and scientists questioned conventional thinking with a renewed spirit of curiosity, objectivi- ty, and experimentation. This period accomplished three things in medi- cine: 1) it shattered authority, 2) it laid the foundation for an accurate knowledge of , and 3) it demonstrated how the body’s func- tions should be studied intelligently. It was ’s observa- tions of diabetes in 1674 and Matthew Dobson’s experiments in 1776 that conclusively established the diagnosis of diabetes in the presence of sugar in the urine and blood. Diabetes was no longer considered a Figure 1. Commemorative stamp issued by Egypt in 1971 for the World Health rare ailment. Willis referred to dia- Organization’s World Health Day. The stamp features a section of the Ebers betes as the “pissing evil” and noted Papyrus and a portrait of the Egyptian physician Hesy Re. (Scott catalog #864) that in patients with diabetes, “the urine is wonderfully sweet, as if it Greece. Although the Greek physician Hindu physicians Charaka, Susruta, were imbued with honey or sugar.” Hippocrates, “the father of medi- and Vaghbata described polyuria and He claimed that diabetes was primari- cine,” did not specifically mention glycosuria. They noted the attraction ly a disease of the blood and not the diabetes in his writings, there are of flies and ants to the urine of those kidneys. Willis proposed that the accounts in the Hippocratic writings affected by this ailment. sweetness first appeared in the blood that are consistent with the signs and The practice of medicine in the and was later found in the urine. symptoms of diabetes. There are refer- (350 CE to about 1450 Dobson provided experimental evi- ences to excessive urinary flow with CE) was fundamentally a restatement dence that people with diabetes elimi- wasting of the body. Hippocrates pro- and acceptance of Greco-Roman nate sugar in their urine. He gently moted the concept of preventive medi- teachings. Arabian physicians trans- heated two quarts of urine to dryness. cine. He stressed the influence of diet, lated the works of Hippocrates and The remaining residue was a whitish exercise, and lifestyle on health. and offered minor modifica- cake, which, Dobson wrote, “was Galen and Aretaeus were disciples tions. of Hippocrates. Galen, the most influ- Two prominent medieval physi- ential medical writer of all time, dis- cians who contributed to the knowl- cussed diabetes in a number of his edge of diabetes in the 11th and 12th works. He described the condition as centuries were and Moses rare, as he had only seen two cases. . Maimonides was a He referred to the ailment as “diar- renowned medieval physician, rabbi, rhea of the urine” and “the thirsty and philosopher. Although Galen disease.” wrote that diabetes was rare and that Aretaeus, a contemporary of he had seen only two cases of this ill- Galen, provided the first accurate ness, Maimonides claimed to have description of the symptoms of dia- seen more than 20 cases. He pro- betes (Figure 2). He was the first to posed that diabetes was caused by use the term “diabetes” in connection the sweet waters of the Nile and the with this ailment. The term diabetes prevailing heat that spreads over the was derived from the Greek word for kidneys. siphon. Aretaeus’ classic description No further progress was made in begins “Diabetes is a wonderful affec- the understanding of diabetes until tion, not very frequent among men, the 16th century, when the being a melting down of the flesh and Renaissance physician limbs into urine…” challenged the medical doctrine of The ancient were the first the time and attempted to reform Figure 2. This stamp issued by to coin the term “honey urine,” a medical thinking. Osler described Transkei in 1990 features the image thousand years before the first Paracelsus as the “Luther of medi- of Aretaeus and a brief section of his Europeans recognized the sweet taste cine,” the embodiment of the spirit description of diabetes. (Scott catalog of urine in patients with diabetes. The of revolt. In medicine, there was an #235) 57 Diabetes Spectrum Volume 15, Number 1, 2002 Feature Article/From Thebes to Toronto

granulated and broke easily between At the close of the 19th century, recruited a young biochemist, James the fingers; it smelled sweet like Oscar Minkowski demonstrated con- Bertram Collip, to assist Banting and brown sugar, neither could it be dis- clusively that removal of the Best in obtaining a pancreatic extract. tinguished from sugar, except that the from a dog results in the production An article written in 1920 by sweetness left a slight sense of cool- of fatal diabetes. This was the turning Moses Barron stimulated Banting’s ness on the palate.” Dobson detailed point in determining the endocrine research interests. Barron described his findings in a paper presented to function of the pancreas. the rare case of a pancreatic stone that the medical society of London in The discovery and isolation of blocked the main pancreatic duct. The 1776. Prior to presentation of his insulin at the in blockage resulted in degeneration of findings, Dobson consulted with 1921–22 was one of the greatest the acinar glandular cells but not the William Cullen, one of Britain’s fore- events in the history of medicine. islet cells. Banting wrote the following most clinicians, consultants, and edu- Insulin therapy would soon commute words in his research notebook cators. the death sentence associated with the (Figure 3): It was Cullen who was the first to diagnosis of . “Diabetus distinguish between diabetes mellitus Despite initial rebuffs by JJR Ligate pancreatic ducts of dog. and . In 1769, Macleod, professor of at Keep dogs alive till acini degenerate Cullen published an elaborate classifi- the University of Toronto, the persis- leaving islets. Try to isolate the cation of human diseases. In this clas- tent was finally internal secretion of these to relieve sification, we see for the first time a allowed to begin his research in glycosurea.” distinction between diabetes (melli- Macleod’s laboratory in May 1921. The spelling errors, “diabetus” and tus), with the urine of “the smell, Macleod doubted that Banting would “glycosurea” are Banting’s. It goes to color and flavor of honey,” and dia- be able to isolate the internal secretion show that brilliance and success are betes (insipidus), with limpid but not of the pancreas because of the not necessarily tied to spelling profi- sweet urine. It was Cullen who added destructive effects of the pancreatic ciency. the descriptive adjective mellitus, juice. Banting was assigned laboratory Banting and Best are the figures from the Latin word for honey. space, research animals, and a 22- that history has most closely associat- Cullen wrote to Dobson, “You have year-old research assistant named ed with the discovery of insulin. Yet done something in putting it beyond Charles Herbert Best. Later, Macleod the 1923 Nobel Prize in Medicine was all doubt by your experiments… I not awarded to Banting and Best, have only to add that I wish you but rather to to Banting and would examine both by taste and Macleod. In an attempt to reme- evaporation what might be called dy this injustice, Banting publicly the Urina Potus or that copius acknowledged Best’s role in the limpid urine which runs in some discovery of insulin and shared people after their drinking largely the monetary prize with him. of water or watery liquors.” Macleod agreed to do the same The Experimental Period in the with Collip. history of diabetes began in the In 1926, John Jacob Abel puri- first half of the 19th century with fied insulin and isolated its crys- the experiments of Claude talline structure. The rhombohe- Bernard. Bernard discovered that dral crystals of insulin fascinated the liver releases a substance that him (Figure 4). His studies of affects blood sugar levels. In 1857, insulin helped to develop modern he isolated a starch-like substance concepts of protein chemistry. In that he called “glycogen,” which 1958, was was the precursor of glucose, “the awarded the Nobel Prize in internal secretion” of the liver. Chemistry “for his work on the This observation established the structure of proteins, especially liver’s role as a vital organ in dia- that of insulin.” It was Sanger betes. who was the first to discover the Paul Langerhan’s most famous exact amino acid sequence of the histological finding, the pancreatic protein insulin. Sanger deter- islets, was presented in his doctor- mined that the insulin molecule al dissertation at the University of was composed of two different Berlin in 1869. Langerhans Figure 3. Frederick G. Banting and Charles H. chains of 51 amino acids held acknowledged that he did not Best are seen on this commemorative stamp together by two bridges of sulfur know the function of these duct- issued by Canada in 1999. In the background atoms. less cells, which were later named is a page from Banting’s research notebook, in In 1977, Rosalyn Sussman “islets of Langerhans,” in his which he plans his experimental approach to Yalow won the Nobel Prize in honor by the French histologist obtaining the internal secretion of the pancreas. Medicine for “the development of Laguesse. (Scott catalog #1822a) radioimmunoassays of peptide 58 Diabetes Spectrum Volume 15, Number 1, 2002 Feature Article/Sanders

failure, heart disease, stroke, preventable (Figure 5). Hopefulness in and amputations.” the treatment of was possi- Diabetes is the leading cause of ble. He wrote, “Consequently, it has new cases of blindness in adults aged been forced upon me that gangrene is 20 to 74 years. The prevalence of not Heaven-sent but is earth-born.” retinopathy is strongly related to the His remedy was a team approach to duration of diabetes and uncontrolled diabetes care, which included patient high blood glucose levels. After 20 education in foot care, medical nutri- years, nearly all people with type 1 tion therapy, exercise, prompt treat- diabetes and nearly two-thirds of peo- ment of foot infections, and, when ple with have some necessary, specialized surgical care. evidence of . Public awareness of the serious Diabetes is also the leading cause of nature of diabetes and its complica- end-stage renal disease in the United tions remains very limited, despite the States and Europe. The Diabetes fact that diabetes is one of the leading Control and Complications Trial and causes of death and disability in the the United Kingdom Prospective United States. The message to “Know Diabetes Study have shown conclu- More About Diabetes” is important sively that intensive diabetes therapy for all people. However, it is most significantly reduces the risk of devel- critical for those who are at high risk oping retinopathy and kidney disease for diabetes and who have not as yet Figure 4. Insulin crystals are repre- in people with diabetes. been diagnosed. This message is also sented on this commemorative stamp Abundant evidence shows that peo- important for health maintenance issued by Japan in 1994 for the 15th ple with diabetes are at high risk for organizations and hospital adminis- International Diabetes Federation cardiovascular disease: coronary heart trators, government officials, and Congress, held in Kobe. (Scott cata- disease, stroke, peripheral arterial dis- third-party payers. log #2433) ease, and cardiomyopathy. Heart dis- Scientific evidence demonstrates hormones.” Working together with ease is the leading cause of diabetes- that much of the morbidity and mor- Sol Berson, these investigators devel- related deaths and hospitalizations. tality of diabetes can be reduced by oped a tool that would stimulate a Adults with diabetes have heart dis- aggressive treatment with diet, exer- revolution in biological and medical ease death rates about two to four cise, and improved blood glucose research. times as high as those of adults with- control. Diabetes self-management The pig has played an important out diabetes. The risk of stroke is four education with self-monitoring of role in the history of diabetes as a times higher in people with diabetes. blood glucose is the cornerstone of source of insulin and life for people Therefore, having diabetes is itself a care for all people with diabetes with diabetes. For many years, risk factor for developing cardiovas- (Figure 6). Unfortunately, there is still beef/pork were the only cular disease. a significant disparity between cur- source of insulin. Human insulin In 1934, Joslin wrote a paper, “The rent and desired diabetes care and became available in the early 1980s Menace of Diabetic Gangrene,” pub- practices. and was the first commercial product lished in the New developed by recombinant DNA tech- England Journal of nology. The origin of the term Medicine. Joslin noted “insulin” is from the Latin word for that following the island: insula. introduction of The discovery and therapeutic insulin, mortality from application of insulin in the 1920s had was a miraculous development in the fallen significantly treatment of diabetes that enabled from 60 to 5%. Yet, individuals affected by this disease to deaths from diabetic live an almost-normal life. It soon gangrene (of the foot became apparent, however, that and leg) had risen sig- insulin did not cure diabetes. As peo- nificantly. The reason ple began to live longer, they experi- for this complication, enced complications that had not pre- Joslin alleged, was viously been seen. Elliot P. Joslin that physicians were noted that “The era of coma as the not aggressive enough central problem of diabetes has given in their treatment of Figure 5. The Dominican Republic issued a series of way to the era of complications. diabetes. stamps, Lucha Contra La Diabetes (Fight Against People with diabetes are at increased Joslin firmly Diabetes) in 1974 to raise awareness of the serious risk for the development of serious believed that gangrene complications of diabetes. This stamp calls attention complications, including blindness, and amputations were to lower limb amputations. (Scott catalog #725-726) 59 Diabetes Spectrum Volume 15, Number 1, 2002 Feature Article/From Thebes to Toronto

In its 1998 report, written in the history of diabetes. the congressionally There is genuine optimism in our mandated Diabetes search for a cure. Research Working Group recognized Lee J. Sanders, DPM, is chief of the the great urgency Podiatry Section of the Acute Care and extraordinary and Specialty Services Department at opportunities facing the VA Medical Center, in Lebanon, us today in diabetes Pa. research. Mapping of the human Proceeds from Dr. Sanders’ book The genome marks a new Philatelic History of Diabetes: In era in medical Search of a Cure are being donated to research, paving the the American Diabetes Association way for the treat- Research Foundation. The book can Figure 6. The cornerstone of care for people with dia- ment and cure of be ordered in paperback for $14.95 or betes is self-management education. St. Vincent issued many serious dis- in hardback for $24.95 by calling 1- this stamp in 1989, raising awareness of the impor- eases. In the 21st 800-232-6733 or visiting the tance of diabetes education and commemorating the century, we are wit- Association’s online bookstore at 25th Anniversary of the Lions Club of St. Vincent. nessing an exciting store.diabetes.org. (Scott catalog #1305) new chapter being

60 Diabetes Spectrum Volume 15, Number 1, 2002