Britton Chance: Olympian and Developer of Stop-Flow Methods

Britton Chance was born in Wilkes-Barre, Pennsylvania in 1913. He spent many summers during his youth sailing, and his love of the sea was the catalyst for his first significant contribution to science and technology. When he was just a teenager, Chance invented an autosteering device that detected deviations in a ship’s course and generated a feedback signal to redirect the ship’s steering mechanisms. Later in life, his love of sailing and intense competitive spirit landed him a spot on the U.S. yacht Olympic team where he won a gold medal in the 1952 Olympics. Chance received his Bachelor’s of Science degree from the University of Pennsylvania in 1935 and remained there for graduate school. Around this time, Glenn Millikan, at Cambridge University, had developed a novel stop-flow apparatus to measure the formation of oxymyoglobin resulting from the combination of oxygen with myoglobin (1). During his thesis research, Chance observed that “adding H2O2 to a crude preparation of peroxidase gave a colored compound that could go on to oxidize a variety of phenols” (2). He believed it might be possible to study the intermediates in the peroxide interaction if he could make a “micro” version of Millikan’s apparatus. So, in 1937, under the supervision of Martin Kilpatrick, he started construction of a rapid-flow apparatus. In 1938, while still a graduate student at the University of Pennsylvania, Chance was offered a contract by the British General Electric Company to test his autosteering device on a ship going from London to New Zealand and Australia. Shortly after his arrival in London, Chance visited with Millikan hoping to study under him. Millikan accepted him as his research student, and after Chance returned from his voyage he started constructing a second microflow apparatus. He completed the apparatus by 1939 and did some initial studies on luciferase O2 reactions. In 1940, Chance returned to Pennsylvania to visit his parents but was unable to return to Cambridge due to the onset of World War II. Fortunately, he was accepted back at the University of Pennsylvania and began construction of a third version of his rapid-flow instrument. Once it was completed, Chance used this new instrument to elucidate the peroxidase enzyme-substrate reactions, which is the subject of the Journal of Biological Chemistry (JBC) Classic reprinted here. At this time, there were many theories about how enzymes worked. Leonor Michaelis, the subject of a previous JBC Classic (3), and Maud Menten had proposed their theory which stated that the relationship between enzymatic activity and enzyme and substrate concentration could be explained by the existence of an intermediate enzyme-substrate compound (4). Their theory was modified by Thaddeus Briggs and J. B. S. Haldane who pointed out that the rate of formation of the intermediate could be limited by the number of collisions between the enzyme and substrate (5). However, at the time, there were no experimental observations of the intermediates, and the reaction velocity constants were lumped into one term, the Michaelis-Menten constant, rather than determined separately. In his paper, Chance used the reaction between horseradish peroxidase and hydrogen peroxide to prove the existence of the intermediate compound and to determine the rates of THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 279, No. 50, Issue of December 10, p. e10, 2004 © 2004 by The American Society for Biochemistry and Molecular Biology, Inc. Printed in U.S.A.