Abstract

Alexis Carrel and Charles Lindbergh were among the most famous international figures in the 20^th century, Carrel, the surgeon-scientist who won a Nobel prize as a young surgeon, and Lindbergh, the aviator-engineer who pioneered aviation and promoted commercial flight throughout his life. Surprisingly, these two amazing individuals came together to collaborate on the early development of extracorporeal circulation. Their work was interrupted by the onset of World War II, which destroyed one of them and nearly destroyed the other.

Alexis Carrel

The popular president of France, Sadi Carnot, was assassinated by a knife-wielding anarchist in Lyon, France, in June 1894. He died from a vena cava laceration that the surgeons could not repair because vascular repair was not possible at that time. Alexis Carrel, a surgical resident in Lyon, decided that he would develop techniques for suturing blood vessels [1]. He found laboratory space and, working at odd hours, was able to do his experimental work without interfering with his clinical responsibilities. He attributed his manual dexterity, which was considerable, to instructions he received from an embroidress during his residency. He was able to find fine needles and threads in a local haberdashery. The technique that he used for suturing small blood vessels was triangulation, in which three guide sutures allowed the eversion of the suture line, allowing for an intima to intima closure, avoiding suture line thrombosis. In this laboratory, he was able to successfully suture the cut ends of femoral artery to saphenous pain and from carotid artery to jugular vein [2:25-7]. (Figure 1)

For a variety of reasons, he did not pass the extremely difficult surgical examinations so he was unable to get a position at the University of Lyon. He went to Paris for three months in December 1903, where he reflected on his future. In May 1904, he sailed for Montréal, and in August traveled by train to the West Coast of Canada, then east across the United States to Chicago. He spent the next two years in the Hull laboratory of the University of Chicago, working with Dr. Charles Guthrie. In Chicago, Carrel refined his suture technique further in a series of ground-breaking operations experiments. He and Guthrie replaced a segment of carotid artery with jugular vein, demonstrating that venous walls could withstand arterial pressure; this was the first successful vascular homograft. They were also able to transplant kidneys, hearts, thyroid glands and ovaries. The “Carrel patch” utilizing a piece of aortic wall containing the orifice of the renal artery is still used today for kidney transplantation. Together, Carrel and Guthrie published 21 papers in 22 months [2:24-35].

Carrel was disappointed with the level of financial support in Chicago, so in 1906 he accepted an invitation to work at the Rockefeller Institute for Medical Research in New York and began his work there that lasted over 30 years. He found ways to preserve and transplant arteries and veins, transplanted adrenal glands, spleen, intestine, and heart-lung blocks. He amputated and re-implanted the leg of a dog at the thigh successfully. He did operations inside and on the surface of the heart, including coronary arteries, mitral valve, and ventricular septum. The operations he performed on dogs by 1910 were not repeated clinically for many decades: mitral valvotomy in 1948, kidney transplant in 1954, limb replantation in 1962, heart transplantation in 1967, coronary artery bypass in 1968, and heart-lung transplantation in 1981. His work with vascular suturing and transplantation half a century ahead of clinical application. In 1912 Carrel became the first surgeon to be awarded the Nobel Prize for Medicine and Physiology specifically for surgical techniques. At the age of 39 years he was the youngest Nobelist at that time, and the first scientist working in America to win the prize [2:58-61].

During his time at the Rockefeller Institute he made many major contributions, such as the use of endotracheal anesthesia, treatment of wounds (he and a chemist, Henry D. Dakin, developed the Carrel-Dakin solution for irrigating wounds in WWI, which is still used for treating infected wounds), and tissue culture. (Figure 2)

Charles Augustus Lindbergh

Charles Lindbergh was 20 years old in 1922 when he dropped out of the University of Wisconsin mechanical engineering school in order to pursue his dream of becoming a pilot. After brief training, he earned his living barnstorming across the Plains states as a wing walker and parachutist, as well as working as an airplane mechanic. In 1924, he underwent a year of military flight training with the United States Army Air Service Reserve Corps and was commissioned as a 2nd Lieutenant and later as a 1st Lieutenant. Continuing to serve in the reserves, he became an airmail pilot; he distinguished himself through his dedication to his responsibilities for mail delivery under highly adverse conditions [3:84-9].

In 1919 the Raymond Orteig Prize offered $25,000 ($355,000 in 2016 dollars) to anyone who could fly from New York to Paris (or vice versa) nonstop. Over the next few years six highly experienced pilots lost their lives in an attempt to win this prize. Lindbergh was a late comer to this competition, was completely unknown, and was financed only by $1000 from his employer, $2000 of his own savings, and a $15,000 loan from two St. Louis businessmen, who requested only that he name the airplane the Spirit of St. Louis [3:95-6]. The Ryan Aircraft Company agreed to build a monoplane for $10,580. Designed by Lindbergh and Donald Hall, Ryan's chief engineer, the Spirit of St. Louis was a fabric-covered, single-seat, single-engine monoplane. It was built in two months and finished on April 28, 1927. (Figure 3)

Lindbergh flew the Spirit from San Diego to St. Louis, then to Roosevelt Field on Long Island. After much preparation, 10 days later, heavily loaded with 2710 pounds of gasoline, drinking water, and a few sandwiches, Lindbergh took off, barely clearing the telephone lines at the end of the runway by about 20 feet. His grueling flight took 33.5 hours through storms and without sophisticated navigation equipment. He and the Spirit landed at the Le Bourget airport near Paris on May 21. He was confused when trying to find the airport by bright lights over broad area, which he later learned were due to the headlights of tens of thousands of cars, which created “the largest traffic jam in Parisian history.” The crowd of 150,000 onlookers carried him off the field. This previously unknown aviator immediately became one of the most famous men in the world [3:112-31].

Lindbergh made many trips as a goodwill ambassador for the US. In 1928, on a stop in Mexico he met a daughter of the US ambassador Dwight Morrow, Anne, whom he married a few months later in May 1929. They had six children; the first was Charles, Jr., born in 1930. In 1932, Charles, Jr., was kidnapped and killed. In response, the US Congress passed the “Lindbergh Law” that made kidnapping across state lines a federal crime [4]. Two years later, Bruno Richard Hauptmann was captured and tried as the kidnapper in what was popularly labeled “the Trial of the Century.” Hauptmann was convicted and executed, an event that is still steeped in controversy [3:350-1].

Anne's older sister Elisabeth suffered from rheumatic mitral valve disease and her health was deteriorating. After his marriage, Lindbergh observed his sister-in-law's progressive deterioration as Elisabeth suffered relapses of her heart disease. He became curious about a valve that had a mechanical function, the mitral valve: why couldn't it be replaced, as one could replace any mechanical valve in a malfunctioning pump? [5]

Carrel and Lindbergh Collaboration

When Lindbergh asked Elisabeth's doctor why her heart could not be repaired, he was told that the heart could not be stopped so that an operation could be done inside; the patient would die. He wondered whether an artificial pump could circulate the blood long enough for a repair to be made. Anne's obstetrical anesthesiologist suggested that a researcher at the Rockefeller Institute might be able to help, and together they met Alexis Carrel in his laboratory on November 28, 1930 [3:221].

Carrel was a pioneer of tissue culture, having accomplished a great deal from 1910 well into the 1920s, including a culture of embryonic heart cells that was maintained continuously for over 34 years [2:51]. Meanwhile he had developed an interest in perfusing whole organs. His efforts had not been successful, however, because he could not maintain sterility of the apparatus. When he showed Lindbergh the device, Carrel commented, “Infection, always infection.” That night, Lindbergh drew some sketches of a glass perfusion device that was later constructed by the glassblower who supplied Carrel's laboratory. Lindbergh and Carrel were able to perfuse tissues of various kinds without infection, for up to a month. They were unable to perfuse whole organs successfully, however, because the required additional metal tubes compromised sterility and infection always resulted [3:224].

Lindbergh designed and built several models to overcome this problem, but discarded all of them. Carrel displayed a consistent willingness to provide organs for each new design, despite the failure of each. Lindbergh finally succeeded in 1935, building a glass pump that was driven by a rotating valve injecting compressed air, which produced pulsatile flow. Oxygenation was achieved by contact of the perfusion fluid with the oxygen-rich air. The air was sterilized by passing it through cotton wool [2:94]. (Figure 4)

In April 1935 they kept a cat's thyroid gland alive for 18 days. Between 1935 and 1938 the two investigators used the pulsatile pump to keep a heart beating for several days, a Fallopian tube maintaining peristalsis, and a pancreas secreting insulin [2:92]. They successfully perfused ovary, kidney, and spleen. Dozens of pumps were built and distributed to laboratories around the world, and thousands of experiments were carried out. The pumps were complex in structure and difficult to maintain, however, so their use fell into disfavor within a few years. Despite disruptive world events, Carrel and Lindbergh continued to work together on the pump intermittently into the early 1940s.

Because of difficulties with sterility, oxygenation, and hemolysis, they were not able to accomplish Lindbergh's dream of heart-lung bypass. It remained for another American, John Gibbon, to make open-heart surgery possible by persistence in addressing and solving all of those problem (and others, such as blood clotting) over a 20-year period from 1933-1953, when he performed the first successful open-heart operation, repairing an atrial septal defect in an 18-year old patient [6]. In his first paper on artificial circulation in 1937, Gibbon gave credit to the work of Carrel and Lindbergh as pioneers in this extracorporeal circulation [7].

Both Suffer Public Vilification

The two men were deeply impressed with each other's brilliance, and gradually became very close friends, despite Lindbergh's innate shyness and Carrel's remoteness. Lindbergh was especially influenced by Carrel's philosophical views, which he summarized in his 1935 best-selling bookMan the Unknown. Many of his views were illiberal, even Nietzchean in outlook — for example:

The democratic principle has contributed to the collapse of civilization in opposing the development of an elite. Indeed human beings are equal. But individuals are not. The equality of their of their rights is an illusion. The feeble minded and the man of genius should not be equal before the law. The stupid, the unintelligent, those who are dispersed, incapable of attention, of effort…[should not have] the same electoral power as the fully developed individuals. Sexes are not equal.” [8:97]

Carrel reached the Rockefeller Institute's mandatory retirement age and was refused special exception. In his anger he denounced the Institute, closed his laboratory and sailed for France in July 1939. Two months later Germany invaded Poland, starting World War II. A few months after Poland fell, Germany invaded and conquered France, and installed a puppet government in the town of Vichy. In1941 Marshal Pétain, head of Vichy France, offered Carrel realization of his long-held dream of creating an organization, the Institute of Man, in which he could bring together a collection of scientists and humanists to study the nature of human life. Because of his acceptance of this support, other interactions with Vichy and the German government, and his own writings that reflected his authoritarian attitudes and mysticism, Carrel was widely believed to be a Nazi collaborator. After the liberation of France in 1944 he was removed from his responsibilities at the Institute and placed under guard while evidence of his collaboration was sought by prosecutors. He was widely vilified under charges of being a Nazi apologist, racist, and eugenicist, became sullen and depressed, had a series of heart attacks, and died of a myocardial infarction in November 1944, a broken man [2:121]. No hard evidence of collaboration has ever been found and it seems likely that the charges against him were grossly exaggerated.

The 1935 murder trial of B.R. Hauptmann, the killer of Charles, Jr., produced an enormous amount of publicity and stresses on Charles and Anne Lindbergh. Lindbergh was able to evade public attention by immersing himself in his work in Carrel's laboratory, but invasion of the privacy of themselves and their children by the press eventually became unbearable. After the trial, the publicity-shy Lindberghs escaped unwelcome attention by sailing to England [3:340]. While in Europe they visited Germany where Lindbergh accepted a medal from Hitler's second in command Hermann Goering. Together with his earlier favorable comments on the German National Socialist Party (the Nazi Party), his acceptance of this medal tarnished his reputation at home.

The Lindberghs returned to the US in April 1939, just before the outbreak of WW II. Lindbergh became a leading spokesman for the America First Committee, which advocated strongly against the US entering the war against Nazi Germany, a position that earned him the further enmity of the majority of Americans who favored entering the war. He resigned his commission as colonel in the Army Air Corps (the predecessor of the US Air Force). When the Pacific war broke out with the bombing of Pearl Harbor on December 7, 1941, he requested reinstatement of his commission, which the administration refused. He continued to work on aviation, however, helping the Ford Motor Company in the design and construction of the B-24 bomber and working with the Mayo Clinic on the physiologic effects of high altitudes [3:438-47].

In 1944 Lindbergh traveled to the South Pacific as a civilian technical representative, and despite that role, flew 50 combat missions against the Japanese. After the war ended in 1945 he served as consultant and advisor to many aviation groups, including the newly formed US Air Force, and he was awarded the Wright Brothers Memorial Trophy and the Guggenheim Medal for his lifetime of work in aviation. He won the 1954 Pulitzer Prize for his bookThe Spirit of St. Louis and a 1957 movie with the same name, starring Jimmy Stewart, was based on the book. He helped in the design of the Boeing 747 jumbo jet and was deeply involved with environmental issues from the mid-1950s until his death 20 years later. Although Lindbergh's request for reinstatement of his army commission had been denied by two presidents, Franklin D. Roosevelt and Harry S. Truman, in 1954 President Dwight D. Eisenhower restored his commission and appointed him Brigadier General in the US Air Force [3:487-8].

Charles Lindbergh's favorite place on earth was his home near the remote town of Hana on the island of Maui, Hawaii, where he died quietly of cancer in 1974. At the time of his death, his rehabilitation as a popular public figure was largely complete, a very different outcome from the fate of his close friend and colleague, the other giant of the 20^th century, Alexis Carrel.

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