Douglas H. McConnell, M.D., FACS 2017 A Tale of Two Pioneers Douglas H. McConnell, M.D., FACS 2017

Introduction I am not Dr. Khan Scientific Discovery The ART and Science of Diabetes Knowledge Development Journey Stanford Journey - Chemistry

Periodic Table

Steinhart Periodic Table

Diabetes Mellitus “Diabetes” is Greek for syphon or “to flow” Mellitus only added much later - Latin for “sweet” 1600 BC Hesy-Ra Egyptian Physician and Official noted frequent urination and wasting 2600 BC to 1922 is 3522 years of human history! 100 years ago - Diabetic coma wards!

Breakthroughs 1870’s Langerhans defined the beta cells - Islands or “Insula” 1889 Minkowski and von Mering at Strasberg created Diabetes by canine pancreatectomy For 30 years attempts were made to isolate and extract the Pancreatic factor - worldwide search 1910 Sir Edward Albert Sharpey-Schafer defined the endocrine function of the pancreas “Insulin” How to extract Insulin?

Banting Contribution Fredrick Grant Banting 1891-1941 Failed his first year at the university! Rebooted into medical program Graduated as M.D. and into Army age 25 Seriously wounded in 1918 - stayed with his men Awarded the Military Cross in 1919

Banting Post War Began training as a surgeon - orthopaedics Returned to home London Ontario Physician/Surgeon needed part time work Part time teacher in physiology Preparing a talk about diabetes for students

Journal Entry October 1920 Diabetus (sp) Ligate pancreatic ducts of dog Keep dogs alive till acini degenerate leaving Islets Try to isolate the internal secretion of these to relieve glycosurea.

Summer Research Project May 1921 University of Toronto laboratory of John MacLeod (skeptic) Medical Student Charles Best July and August “isletin” extractions effective November 16, 1921 Insulin extracted from porcine and bovine CHILLED pancreas

Human Use December 1921 James Collip - biochemist Enhanced the extraction and stability of the “isletin” substance January 11, 1922 used on Leonard Thompson May 3, 1922 “The Effects Produced on Diabetes by Extracts of Pancreas”

Canadian Team Fredrick Banting - Physician, Surgeon, Educator Charles Best - Medical Student, later physician John Macleod - Physiology Lab Director James Collip - Biochemist Acrimony and controversy

Announced 1923 Nobel Prize for Medicine and Physiology awarded to Banting and McLeod Prize money split 4 ways No license fees - given to the world! University of Toronto supervised the early production of Insulin beginning in 1923 Bovine and Porcine extraction utilized until recombinant DNA technology 1982 - 60 years

Frederick Banting Charles Best 1923

Nexus

Rheumatic Mitral Stenosis Sister-in Law Rheumatic Mitral Stenosis Severe Symptoms

Cardio Pulmonary Bypass Progress 1937 1967

Who is this famous American?

Charles Lindbergh

Combat Training South Pacific

Operative CABG Preferred treatment when multi vessel revascularization required Early intervention to preserve LV function Requires close diabetic management during procedure Challenging

Cardiac Surgery Diabetic patients - both type 1 and 2 have: Elevated risk of death and stroke Increased peri-operative complication rate due to peripheral vascular and aortic disease Will require insulin drip for intra and post operative management Elevated risk of wound complications

Prevention Management Delay the onset or stop CAD progress Careful medical management Patient education Preventing CAD is far better than revascularizing the heart with surgery or stents

Thank You