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鈥淔ind me a cure,鈥� implored Otto Radnitz in 1920 when his daughter Gerty graduated from medical school in Prague, then part of the Austro-Hungarian Empire.
Radnitz had developed diabetes, quite ironic since he was a chemist who managed a sugar refinery and had developed a method for refining sugar. Gerty did not find a cure for diabetes, but according to family lore her father鈥檚 remark stimulated an interest in the metabolism of sugar that would launch a career culminating in her being the first woman to be awarded the Nobel Prize in Medicine and Physiology. The honour, 鈥渇or their discovery of the catalytic conversion of glycogen,鈥� was especially memorable because it was shared with her husband, Carl Cori, one of the rare times the prize was awarded to a couple.
Gerty and Carl met when they entered medical school, but their relationship was put on hold when Carl was drafted into the Austrian army during the First World War. He would later describe how the experience motivated him for research into disease as he witnessed the influenza epidemic sweep through the troops with doctors unable to offer any help.
After the war, Carl returned to university, the couple were married, and they moved to Vienna where Carl found a research position and Gerty worked in a hospital鈥檚 pediatric ward. Life in Vienna was difficult and with the rise of antisemitism and Gerty鈥檚 Jewish heritage, the couple looked for greener pastures and found it in Buffalo, N.Y., where Carl was hired as a biochemist at the State Institute for Malignant Disease and Gerty as an assistant pathologist.
The director of the Institute frowned on the couple working together and even threatened to fire Gerty if the collaboration continued. However, once the couple started to publish pioneering papers about carbohydrate metabolism, the opposition faded. Offers from universities began to pour in, but only for Carl. One even opined that it was 鈥渦n-American鈥� for couples to work together.
Washington University in St. Louis was smart enough to ignore the institution鈥檚 nepotism policies and hired Gerty as well, but for one-10th the salary her husband was to receive. It would be 13 years before her contributions were recognized and she was finally promoted to a position of full professor with the appropriate salary. The Coris would go on to mentor six eventual Nobel Prize winners, an incredible achievement.
So impactful was their work that in 2004, the American Chemical Society would recognize the Coris鈥� lab as a national historic landmark, designating it as 鈥渢he place where pioneering research was carried out that led to the understanding of the metabolism of sugars and elucidated the 鈥楥ori cycle,鈥� the process by which the body reversibly converts glucose and glycogen, the polymeric storage form of this sugar.鈥�
That sounds complicated, so let鈥檚 try to simplify why this research received numerous accolades, including the ultimate one, the Nobel Prize.
The human body is the most complicated machine on the face of the Earth. Unraveling the details of how it works is perhaps the greatest challenge faced by scientists. It is here that the Coris made their contribution by explaining how glycogen, a molecule that is a chain of glucose units, serves as a source of energy.
Everything we do, whether it is typing on a keyboard or running a marathon, requires energy. That energy is provided by a process that in a simplified way can be described as combustion. Any combustion process requires a fuel that reacts with oxygen to yield water and carbon dioxide with the concomitant release of energy. The body relies on the conversion of glucose and fats into a molecule of adenosine triphosphate, or ATP, that actually provides the energy required. But interestingly, the 鈥渂urning鈥� of fats involves a step that requires glucose, which is why the expression 鈥渇ats burn in the flame of carbohydrates鈥� is familiar to endurance athletes.
The critical glucose is supplied by carbohydrates in the diet, but in order to keep blood levels constant, excess glucose molecules are linked together to form glycogen, a polymer that is then stored in muscles and in the liver to be called upon to supply glucose should blood levels drop.
Marathon runners, for example, know that they have to maximize their glycogen storage by loading up on carbohydrates before the race, and that they have to consume glucose during the race in the form of gels or drinks to ensure they have enough fuel.
Everything is fine as long as they keep a pace that allows enough oxygen to be inhaled to support the combustion process. However, should they at some point end up running at a pace that prevents sufficient oxygen uptake, their body can no longer burn glucose or fats in the normal way and has to switch to a different mechanism whereby energy can be derived from glucose without the use of oxygen, This is referred to as 鈥渁naerobic metabolism.鈥�
In this process, glucose generates ATP by being converted into lactic acid. But the glucose in the blood is quickly used up and has to be replenished by the breakdown of muscle glycogen. Soon, the stores of this run out as well. But there is a backup process, as the Coris discovered. The lactic acid that builds up in the blood can be converted back to glycogen in the liver, from where it can resupply the blood with glucose. But this cannot happen indefinitely and eventually blood glucose drops to a level when the athlete 鈥渉its the wall.鈥� Sudden fatigue appears along with a sensation of the legs turning to jelly. Disorientation can ensue as the brain is robbed of its supply of glucose.
These are the complex processes that were deciphered by the Coris. Their efforts are even commemorated in a U.S. stamp that features the molecular structure of glucose-1-phosphate, the critical intermediate in the conversion of glucose into glycogen according to the Cori cycle. Amazingly, the molecular structure, also known as the 鈥淐ori ester,鈥� depicted on the stamp is wrong. The Coris were spared this annoyance since the stamp was issued in 2008, long after they had both died. Although Carl lived to 88, Gerty discovered she had a fatal disease of the bone marrow the same year she was awarded the Nobel Prize and died at 61.
Any marathoner or cyclist who has made use of the timely consumption of carbohydrates to avoid hitting the wall, or 鈥渂onking鈥� as it is also known, owes gratitude to the remarkable husband-and-wife team.
