Alexis Carrel (1873–1944): Visionary vascular surgeon and pioneer in organ transplantation

Alexis Carrel was born in Sainte-Foy-les Lyon, a village in France. He was the eldest of three children. His father was a textile manufacturer and died of pneumonia when Alexis was aged five. His mother undertook embroidering to support her children when his father passed away. He studied medicine in the Lyon School of Medicine, a leading institute of medical education in Europe. He worked under Mathieu Jaboulay (1860–1913), a prestigious surgeon who pioneered a method of arterial anastomosis. Carrel graduated in 1889.

In 1894 the President of France Sadi Carnot (1837–1894) was stabbed in the abdomen by an Italian assassin resulting in severing of the portal vein leading to death. This assassination deeply moved Carrel as he was convinced that the President’s life could have been saved if there was a way of re-joining severed blood vessel together properly.

Carrel published his landmark paper on blood vessel suturing in French in 1902. ¹ He developed the technique of ‘triangulation’ in approximating blood vessels whereby three stay sutures were placed at equal distances from one another along the circumference of the divided vessels and a fine suture was run along the flat surface between each stay suture (Figure 1). He insisted on extreme gentle handling of tissues. He noted that the main cause of previous failure in suturing vessels together was the formation of clots. To address the issue, he used atraumatic small round needles. While most of his contemporaries used large thick absorbable sutures, he used extremely fine sutures made of silk lubricated with Vaseline to stitch vessels together. Anastomosis was performed by eversion of the edges of the endothelial surfaces of the vessels. He was known to grasp the needle in his fingers instead of using a needle holder. He later attributed his manual dexterity to the lessons he received from Madame Leroidier, one of the finest embroiderers in France. To perfect his skill, he practised stitching on paper until he was able to make stitches that would not show on either side. OPEN IN VIEWER

He also followed far stricter aseptic techniques than other surgeons. He wrote ‘It seems that the degree of asepsis under which general surgical operations may successfully be performed is probably insufficient for good results in vascular operations’. ² Carrel’s operating rooms were ‘necessarily guarded against bacterial contamination, acquired the aura of a sanctuary where masked acolytes clad in black gowns and caps performed the aseptic mysteries of experimental surgery and tissue culture’. ³

Carrel failed twice in the clinical examination for a surgical faculty position in Lyon. In 1903 he accompanied a pilgrimage to Lourdes in Southern France where he encountered a young girl named Marie Bailly on the verge of death with tuberculous peritonitis. He witnessed the girl regain consciousness after being sprinkled with drops of holy water from a curative pool. He described the miraculous recovery upon his return to Lyon. His view was held in contempt by the French medical community and he was told that he had no hope to pass his examinations because of his gullibility. Frustrated by the criticisms received, he left for America in 1904.

In 1904 he presented to the Second Medical Congress of the French Language of North America in Montreal a paper on vascular anastomosis. His presentation impressed Karl Beck (1798–1866), Chairman of Physiology at the University of Chicago, who approached him with an offer to take up a teaching position at the University. Carrel accepted the offer to work at the Hull Laboratory at the University of Chicago where he co-authored 28 papers with physiologist Charles Claude Guthrie (1880–1963). ⁴ Topics of the papers included use of vein grafts in the arterial system, replantation of limbs, ⁵ transplantation of ovaries and tissue preservation techniques. Their work showed that venous autografts placed in the arterial system became ‘arterialised’ and developed intimal hyperplasia whereas arteries grafted to the venous system became thin-walled and venous in nature. ² Carrel also developed the ‘Carrel patch’ used in kidney transplantation, whereby a patch of aortic wall containing the orifice of the renal artery is sutured in place to the recipient artery to avoid thrombosis risk posed by small vessel anastomosis.

As the technique for joining blood vessels improved, transplantation of organs became technically easier. Carrel published his first article on the topic of organ transplantation in 1905. ⁶ The article was based on a study in which he transplanted the kidney of a dog into the cervical region, with vascular anastomoses to the external jugular vein and carotid artery, and the ureter connected to the oesophagus. He also transplanted the heart of a small dog into the neck of a larger dog. ⁷ In the same year Harvey Cushing (1869–1939) invited Carrel to deliver a lecture at Johns Hopkins Hospital. Dr Simon Flexner (1863–1946), the director of the Rockefeller Institute in New York, was in the audience. He was impressed with Carrel and invited him to join the Institute.

Carrel joined the Experimental Surgical Department of Rockefeller Institute in 1906 at the age of 33, where he stayed until 1939. His work with suturing blood vessels led to a successful blood transfusion whereby he anastomosed the right popliteal vein of a four-day-old infant to the left radial artery of the infant’s father for blood transfusion, saving the infant who suffered from malaena neonatorum. The pale infant regained colouration within minutes. ⁸ He also performed experiments using paraffin tubes as shunts to prevent spinal ischaemia.

Dr Carrel first conceived the idea of aortic-coronary bypass and in 1910 he stated in his address to the American Surgical Association ‘In certain cases of angina pectoris, when the mouth of the coronary arteries is calcified, it would be useful to establish a complementary circulation for the lower part of the arteries'. ⁹ He attempted to perform an anastomosis between the left coronary artery and the descending thoracic aorta using a carotid artery graft in an animal. Although the animal did not survive, the principle of coronary bypass was demonstrated. He also showed that blood vessels could be preserved and maintain patency in cold storage solutions for prolonged periods before use in transplantation. His experiments were reported in his paper ‘Latent Life of Arteries’. ¹⁰

He was awarded the Nobel Prize in October 1912 in recognition of his work on vascular suturing and transplantation of organs, the youngest person and the first United States scientist ever to be awarded the Nobel Prize for Physiology or Medicine. United States President William Taft (1857–1930) said ‘The names of Harvey Pasteur, Walter Reed, Koch, are great names which share the progress toward a superior knowledge of the human and of medicine, and from now on, Dr Carrel will take his place among them'. Although many of the experiments Carrel performed in vascular and organ transplantation were conducted with Guthrie, the Nobel Prize was awarded solely to Carrel. This was thought to be due to the fact that Guthrie conducted head transplant experiments that were considered controversial at that time. ¹¹ Guthrie has written an article of complaint regarding this matter but his efforts were to no avail. ¹²

Carrel married Anne Marie de la Meyrie, a widowed nurse, in 1913. During World War I, Carrel obtained funding by the Rockefeller Foundation to set up a small hospital in Compiegne known as Hôpital Temporaire no 2 where he collaborated with the English chemist Henry Drysdale Dakin (1880–1952) to develop an antiseptic wound irrigation method known as the Carrel–Dakin method. He insisted on the removal of foreign bodies in deep open war wounds followed by copious irrigation with sodium hypochlorite which aided necrotic debridement of devitalized tissue. As antibiotics were not in use then, this antiseptic solution saved the lives of thousands of infected soldiers. He also advocated the notion that surgeon and bacteriologist must work together. He performed daily cultures of wounds and insisted that the wound be closed only when the bacterial count fell to two organisms, or fewer, visible in five oil immersion microscope fields. ¹³ Carrel was made Knight of the Legion of Honor by the French government in the same year.

In the 1920s after his discharge from wartime duties, Carrel focused his research on tissue culture at the Rockefeller Institute. Carrel placed fragments of heart fibroblast from an 18-day-old chick embryo and cultured them in plasma. He managed to keep the cells beating in culture for 34 years. This experiment was widely publicized and headlines such as ‘Heart Tissues Grow and Beat 120 Days’ appeared in the New York Times. In 1923 he published an article on the cultivation of pure strains of epithelial cells, leucocytes and fibroblasts. ¹⁴ He used flat, round tissue culture flasks with narrow sloping necks as containers for the cells, referred to as Carrel flasks. These flasks allowed tissues and fluids to be easily introduced and removed while avoiding bacterial contamination and tissue disturbance.

Carrel later worked with the famous aviator and engineer Charles Augustus Lindbergh (1902–1974) to develop an extracorporeal perfusion pump that was capable of supporting organs in vitro. Lindbergh’s interest in creating a mechanical heart perfusion pump stemmed from an incident where his wife’s older sister contracted rheumatic fever and her doctor said that operation could not be performed as her heart could not be stopped for long enough for surgeons to work on it. They constructed a Pyrex pump in 1935 which sustained a cat thyroid gland for 18 days. ¹⁵ This technique formed the groundwork for future developments in heart–lung devices. Between 1935 and 1939 a total of 898 experiments was carried out in Carrel’s laboratories using the Lindbergh-Rockefeller Institute perfusion apparatus. ¹⁶ In 1938 Carrel also published The Culture of Organs with Lindbergh who once remarked ‘it is astounding to realize how far Carrel was ahead of his time, both in his thoughts and experiments, and how much of his work still remains equal to, or even in advance of, that which has followed’.

In 1935 Carrel published his book Man, the Unknown. He put forward theories that mankind could achieve perfection through selective reproduction. The book was translated into 19 languages. Carrel promoted the idea of applying a regime of eugenics ruled by intellectual elite. He believed fascism was superior because it encouraged ‘men burning with a passion to create’. He wrote ‘Eugenics is indispensable for the perpetuation of the strong. A great race must propagate its best elements’. He also made sensational statements:

Indeed human beings are equal. But individuals are not. The equality of their rights is an illusion. The feeble minded and the men of genius should not be equal before the law. The stupid, the unintelligent … have no right to a higher education’.

His ideology has met with major criticism and resentment. In 1939 at age 65, he was forced to retire and returned to France. He then became Director of the Foundation for the Study of Human Problems set up by the Vichy Government. In August 1943 he suffered a mild heart attack and he passed away at his home in Paris from heart failure in 1944 following a second more serious heart attack at the age of 71.