A short “novel” of hope for those ready to enjoy life long health … MILLIONS ARE STILL DYING WHILE LIFE LONG HEALTH IS WITHIN REACH PART ONE: THE LIGHT SHINES BRIGHTLY The trenches were slimy and bloody muddy. They stank with the mix of old blood, rotting mud, and gunpowder. The air hung clammy, heavy with the stench of death – sudden and agonizing, from bullets, artillery shells, mustard gas. Shouting, cries of anguish and pain, the sharp rat-a-tat-tat and ricocheting bullets pierced the darkness and the daylight, making sleep impossible. And for those still unharmed, always … the threat of dying. Or worse … suffering beyond imagination. Such was the Allied soldier’s life in the hundreds of miles of slimy trenches that wormed across the French countryside as World War I stalled in July 1917. Opposing armies were often just dozens of yards apart, so close that they could hear each other’s agonizing cries. You can imagine most everything described … except for one. You cannot fathom the painful suffering and death that threatened day after day, night after night, from the terrible yellow-brown clouds of acrid- smelling mustard gas randomly fired by the Germans. This most destructive weapon of war attacked every one indiscriminately and there was no defense other than prevention – covering all exposed skin and donning gas masks that might be too late or might be ineffective after repeated uses. And yes, the British even used it against the Germans when they captured a stockpile of aerosol canisters in November 1917, just days before the end of hostilities in the War to End All Wars. Victims might not have felt anything at first, so they could unknowingly receive a massive exposure. Seconds to minutes to hours later, their skin and eyes burned and dissolved, their lungs bled, and they endured this untreatable torture for days to weeks before slipping into the relief of death. Those who lived could suffer disfiguring scars and life-long disabilities. The sticky “liquid” settled onto clothes, equipment, and structures and evaporated into a gas when later becoming 1 Common Law Copyright 2009 John Parks Trowbridge – All Rights Reserved warm, so the blistering chemical could cause suffering days later, even to soldiers who never saw the gas cloud or who weren’t even outside of their confined bunkers. As World War II began, the specter of this monster gas again striking their young soldiers hung like a pall in the halls of the British War Ministry as World War II began. Was their fear unfounded? A Geneva treaty in 1926 had banned the use of toxic gases in warfare. But the Italians used poison gas in Ethiopia in 1935 and the Japanese used gas in China in the late 1930s. Later revelations showed that the Germans had fielded an advanced version of mustard gas to their armies in 1937. So one of the major research efforts in the early 1940s was to find something, anything, that could counteract such a poison and salvage the health and lives of exposed soldiers. In the crowded, dingy laboratories of Oxford University in southeastern England, professors frantically toiled long hours through the 70 months of WW II. Scribbling on blackboards and in bulging notebooks, Dr. R. A. Peters led his group of harried biochemists through the maze of strange chemical reactions. They were scrambling to find an antidote to “Lewisite,” an arsenic-based chemical that closely resembles mustard gas. Despite their intensive efforts, it was only at the end of the conflict that they finally perfected “BAL,” the abbreviation for its longer name, “British Anti-Lewisite.”1 The compound (2,3-dimercapto-propanol) is called “Dimercaprol.” Thus, 1945 is hailed as the year that ended the world war that killed over 70 million people, mostly civilians, and the one in which “chelation therapy” was first proposed as a useful and powerful medical treatment.2,3,4 The Metal in the Middle … Chelation The year was 1890, when a French-German chemist, Alfred Werner, received his doctorate in the stunning city of Zürich, Switzerland. The Eiffel Tower, the breathtaking landmark in Paris, France, was less than one year old when he first gazed on it in amazement, as a postdoctoral student in chemistry. 1 Peters RA, Stocken LA and Thompson RHS: British Anti-Lewisite. Nature 156(10):616-619, 1945. 2 Eagle H: The systemic treatment of arsenic poisoning with BAL (2,3-dimercapto-propanol). American Journal of Syphilis, Gonorrhea, and Venereal Diseases 27:114-21, 1946. 3 Eagle H and Magnuson HJ. The systemic treatment of 227 cases of arsenic poisoning (encephalitis, dermatitis, blood dyscrasias, jaundice, fever) with 2,3-dimercaptopropanol (BAL). American Journal of Syphilis, Gonorrhea, and Venereal Diseases 30(5):420-41, 1946. 4 Supplement to the Journal of Pharmacology and Experimental Therapeutics. Baltimore, Maryland: The William and Wilkins Company 87(4):entire publication, 1946. 2 Common Law Copyright 2009 John Parks Trowbridge – All Rights Reserved The 1890s were the Golden Age of Bicycles, with cycles being a popular way to get around this most prominent metropolitan and cultural center in all of Europe. Armand Peugeot had just begun producing his first (noisy!) automobiles, so Werner likely dodged a few of these novel horseless carriages while walking across the French boulevards. He was fascinated by an unexplained way in which cobalt appeared to “cuddle” into an ammonia/chloride molecule. In 1893, after his return to teach in Zurich, he proposed a theory of “variable valence” (chemical charges and reactivity) and “coordination” or “complexion” (forming complexes) chemistry, explaining the loose bonding of a mineral that “nested” within a surrounding molecule.5 To put 1893 into context, just 10 years earlier the University of Texas at Austin had been founded. Soon, the Lone Star Showdown athletic rivalry began with Texas A&M University, which was founded in 1876. (“Hook ‘em, Horns!” and “Gig ‘em, Aggies!” are famous hand signals and battle-cries in Texas and parts everywhere as alumni gather to perpetuate the passionate competition.) In 1903, two Ohio bicycle designers – Orville and Wilbur Wright – made the earth- shattering controlled powered flight 10 years later, at Kitty Hawk, North Carolina. (Some people still secretly think that the Wright brothers were Aggie engineering graduates.) Professor Werner insisted that the “coordination” concept came to him in a dream. A dream at 2 in the morning! An important dream? Important enough to win the 1913 Nobel Prize, the first awarded for inorganic chemistry. While we think of the 20th century as so advanced, recall that 1913 was only the 50th anniversary of the carnage during the Battle of Gettysburg in the American Civil War. (In 4 days of engagement, some 8,000 Americans died [Union and Confederate], 27,000 were wounded, another 11,000 captured or missing.) Werner’s work was profound in ushering chemistry concepts into the 20th century; the next inorganic chemist to be honored with a Nobel Prize was not until 1973. The Prohibition of alcohol in the United States started in 1920, oddly at the beginning of social and societal upheaval known as “The Roaring Twenties.” Rebellious teens and young adult “flappers,” no longer coming to maturity under the dark clouds of war, partied the nights away dancing the Charleston – and sipping (gulping?) “bootleg” liquor in the speakeasies. Chemists Sir Gilbert T. Morgan and H. D. K. Drew, had more serious issues on their mind as they sat at their laboratory desks. Their attention focused on Werner’s provocative ideas 5 Morgan GT: Alfred Werner. J Chem Soc (London) 117:1639-1648 3 Common Law Copyright 2009 John Parks Trowbridge – All Rights Reserved about minerals in molecular complexes. Seeking to clarify the concept, they coined the word “chelate.” “The adjective chelate, derived from the great claw or chele (Greek) of the lobster or other crustaceans, is suggested for the caliperlike groups which function as two associating units and fasten to the central atom so as to produce heterocyclic rings.”6 Confusing? Sort of. But this visualization of “heterocyclic rings” is critical to development of chelation therapy as a miraculous medical treatment. Benzene, for example, is a molecular ring that consists only of carbon atoms. A heterocyclic ring is made of different atoms – such as carbon, nitrogen, oxygen, sulfur, and so on – which allow a line or string of atoms to bend around corners somewhat, to form the “nest” into which a metal ion can cuddle. BINGO! Chelation! The term “claw” merely means a “pincer” (such as on a crab or lobster or mud-bug), pinching or binding the metal in such a way to form one or more continuous rings by “holding together” with the other (different or “hetero”) atoms in the molecule. It was exactly this understanding of the concept of chelation that motivated Peters and the other British biochemists to start the search for (and finally develop) BAL. EDTA – The Tongue-Twister That Can Save Your Life The idea of “binding” a metal ion found its first application in – of all places – the dyeing of clothing fabrics! As the resentful German nation marched from an unstable peace after WW I toward the dawn of WW II, the ambitious government knew that it would soon be isolated from a number of needed raw materials. One of them was citric acid, which was being imported in great quantities to make more uniformly smooth coloration in fabrics. When calcium is present in “hard water,” it binds to certain dyes, leaving streaks in the finished cloth. Chemist F. Munz was ordered to pursue development of a compound to replace citric acid, considered an essential step for future independence of the textile industry.