Baltimore, 29 November 1944
One afternoon in November 1944 the chief of surgery at Johns Hopkins Hospital in Baltimore, Alfred Blalock, sat in his office deep in thought. As usual he had a cigarette on the go: even after losing two years of his early career to tuberculosis, he had never quite managed to give up his forty-a-day habit. With his neatly combed hair, immaculate chalk-stripe suit and donnish glasses, he might easily have been mistaken for a prosperous lawyer, but at the age of forty-five he was already known as one of America’s foremost clinical researchers. A few years earlier he had revolutionised the treatment of circulatory shock, a life-threatening condition in which blood loss makes it difficult for the heart to pump enough fluid to the body. Shock was one of the biggest killers in wartime, frequently the consequence of injury by shrapnel or explosives. Blalock’s experiments led to the routine use of blood-plasma transfusions to treat those with severe wounds, a measure which saved the lives of thousands of servicemen in the Second World War.1
This achievement alone was enough to ensure Blalock’s place in the medical pantheon, but this afternoon he felt only frustration. When his senior resident surgeon, William Longmire, walked into the room he found his boss sitting disconsolately behind a pile of books. In recent weeks Blalock had attempted a series of ambitious and difficult procedures on patients seriously ill with abdominal disorders: none had been successful, and most of the patients had died. ‘Bill, I am discouraged,’ he said to Longmire. ‘Nothing I do works.’2 Blalock was desperate to make an original contribution to surgical history, and to silence colleagues who complained that he was a competent researcher but a mediocre clinician. Recently he had been concentrating his efforts on developing new methods to treat problems with the pancreas and intestines. But only a few days later he would perform a novel and entirely different kind of operation, one that would catapult him to fame and make Johns Hopkins a place of pilgrimage for patients and surgeons from all over the world.
Shortly after their conversation Longmire was summoned to the third floor of the clinic, where Blalock took him to a cot containing one of the hospital’s youngest patients. Her name was Eileen Saxon, and she had been born at Johns Hopkins the previous year. Now fifteen months old, she was desperately ill and being kept alive in an oxygen tent. Longmire was shocked by her condition. She was unusually small for her age, but the first thing he noticed was her colour. Her skin had a deathly pallor, and her lips and fingernails were a dark, inky blue. Eileen was suffering from a congenital condition called tetralogy of Fallot; children unlucky enough to be born with it were known as ‘Blue Babies’, and there was little that could be done for them. The blue tinge to Eileen’s skin was cyanosis, the result of blood bypassing the lungs and circulating through the body unoxygenated. Half of all children in her position would die before the age of three, and fewer than a quarter would make it to the age of ten.3 Those who survived for any length of time endured a miserable existence. Many physicians believed that the smallest degree of excitement would be fatal, and everyday pursuits – school, outdoor play, the cinema, even travel by motor vehicle – were often prohibited.4 Eileen’s future looked bleak.
When Blalock told his junior that he intended to try a new type of operation on her, Longmire was horrified: given her state, he could not believe that she would survive an anaesthetic, let alone a procedure that had never before been attempted.5 The chief anaesthetist, Austin Lamont, concurred. When he heard of Blalock’s plans he flatly refused to take part in proceedings, and the operation was cancelled.6 But one of Lamont’s colleagues, Merel Harmel, was prepared to take the risk, and it was rescheduled for the following day.
Early on the morning of Wednesday 29 November little Eileen was taken into room 706, an operating theatre on the seventh floor of the building that in later years would be known simply as ‘the heart room’. Two large windows provided most of the light; in the summer these were usually thrown open in a futile attempt to gain some respite from the fierce Maryland heat. There was a small observation gallery overlooking the operating table, and several hospital staff were leaning over its rail, having heard rumours that something unusual was about to take place. As Blalock scanned the faces of the spectators he caught sight of his laboratory assistant, and called out to him: ‘Vivien, you’d better come down here.’
In his early thirties, Vivien Thomas was a talented surgical technician with a sophisticated grasp of anatomy and physiology – and almost entirely self-taught. Thomas had planned to become a doctor, but his chances of going to university evaporated after the bank holding his savings collapsed in the aftermath of the Wall Street crash. Instead he found a job working in Blalock’s laboratory in Nashville, where the authorities paid him a pittance and categorised him as a janitor because he was black.7 He soon became so essential to Blalock’s work that when the surgeon moved to Baltimore he insisted that Johns Hopkins employ Thomas too. Since he had no medical qualifications, Thomas usually had no contact with patients. His role was in the animal laboratory, where he performed physiological experiments and helped to develop new surgical procedures. He had perfected the operation Blalock was about to perform, practising it hundreds of times on dogs and refining every detail.
But the idea to operate on these desperately ill children had come from one of the other people standing expectantly in the operating theatre. Helen Taussig was the paediatric cardiologist looking after Eileen Saxon; like Thomas, she had faced prejudice and personal setbacks in her early career. As a student she had been rejected by Harvard Medical School on the grounds that she was a woman, but had nevertheless managed to become the world’s leading expert on congenital heart conditions. Profoundly deaf since her thirties, she had taught herself to diagnose rare conditions using her hands as a stethoscope.8
Thomas and Taussig would play no active part in proceedings, but Blalock leaned heavily on them for advice. The surgical team assisting him was young and formidable; it included William Longmire and William Muller, two outstanding protégés who would soon be appointed to major professorships. Standing at the foot of the table, ready to administer intravenous fluids to the patient, was a twenty-four-year-old intern whose career would outshine even theirs: his name was Denton Cooley, and he was destined to become one of the most celebrated surgeons in the world, and the first to implant an artificial heart.
The mood was far from optimistic. Longmire was convinced the girl would die, and Cooley’s considered opinion was that the operation would be ‘a big disaster’.9 Merel Harmel put a mask over Eileen’s face and dripped ether on to it. This was a primitive way of putting a patient to sleep, used since the dawn of anaesthesia in the 1840s; it was also dangerous, as it was difficult to control how deeply or for how long the patient would remain unconscious. As Eileen succumbed to the ether, Blalock and his colleagues – eight in total – gathered around her tiny body. Vivien Thomas remarked that she was so small that it was difficult to believe that there was a patient underneath the sterile drapes.10
Blalock made the first incision on the left side of her chest, starting at her breastbone and extending it to her armpit. As he cut through her muscle in order to gain access to the heart, blood welled up from a number of small arteries. The surgeons were taken aback by its appearance: rather than the free-flowing, bright red fluid they were used to seeing, this was a glutinous blue-black. Longmire described it as ‘like purple molasses’; had he been in charge, the operation would have been abandoned there and then.11
The alarming colour of Eileen’s blood was the cause of her infirmity. Although people often refer to ‘the circulation’ when talking about the movement of blood, there are really two: the pulmonary circulation and the systemic. When the blood has completed its journey around the body and arrives back at the heart it has given up most of its oxygen to the organs and tissues; in this state, it has a blueish tint. The right side of the heart then pumps it to the lungs, where it passes through tiny vessels that allow freshly inhaled oxygen to pass into the red blood cells. At the same time, carbon dioxide – a waste product of processes inside the body’s cells – moves in the opposite direction and is then exhaled. The freshly oxygenated blood, now bright red, travels back to the left side of the heart, ready to be pumped through the rest of the body. Blood therefore passes through the heart twice: first as part of the pulmonary circulation through the lungs, and then as part of the systemic circulation that nourishes all our major organs.
In tetralogy of Fallot this neat arrangement is hopelessly compromised. Those with the condition have four separate cardiac deformities, of which two are responsible for the characteristic skin pallor. Whereas the left and right sides of a normal heart are separated by a wall of tissue, in tetralogy there is a large aperture between the two, known as a septal defect. As a result, oxygenated blood from the lungs mixes freely with blue, deoxygenated blood from the rest of the body. In addition, the pulmonary artery, the vessel through which blood is pumped to the lungs, is drastically narrowed so that its flow is greatly reduced. When the heart of a tetralogy patient contracts, only a small proportion of the deoxygenated blood in the right ventricle is able to escape through the narrowed pulmonary artery towards the lungs; most of it instead passes through the septal defect and into the systemic circulation. Because so little of their blood has travelled through the lungs, Blue Babies have extremely low blood oxygen levels, causing breathlessness, stunted growth and the unhealthy coloration which typifies the condition.
Blalock could not entirely correct this malformation, but by some ingenious plumbing he hoped to improve Eileen’s condition. Having exposed her heart and its major vessels, his plan was to redirect one of her arteries so that instead of delivering blood to her left arm it would instead send it back towards her lungs, increasing her overall oxygen levels. In surgical parlance this type of procedure, in which blood is redirected to where it is most needed, is called a ‘shunt’; within a few years Blalock’s operation would be universally known as the ‘Blalock– Taussig shunt’.fn1
The first challenge was identifying the correct blood vessels. Unless you have seen the inside of the human body at first hand, it’s difficult to appreciate how little it resembles the neat arrangement of nerves and vessels depicted in a textbook. Every patient is different: arteries vary greatly in size or trace entirely unexpected paths; blood vessels sit so close together that they become almost impossible to differentiate. And they lie snugly embedded in tissue, requiring meticulous dissection in order to lay eyes on them in the first place. It took Blalock some time to be sure he had found the two arteries he was looking for.
The first of these was the left pulmonary artery, which takes blood from the heart to the left lung. The procedure would involve shutting off this vessel for as much as half an hour, with the result that Eileen would be breathing through a single lung. This was a huge risk in an already oxygen-deprived patient, and so Blalock temporarily clamped the vessel to see how she would tolerate it. To everybody’s alarm her skin became an even more icy blue, as if her life was ebbing away before their eyes. Harmel attempted to put a tube into the girl’s windpipe in order to deliver oxygen straight to her one functioning lung, but without success: endotracheal tubes for such small children had not yet been manufactured, and the only implement available – a urinary catheter – was hopelessly unsuited to the job.12
There was an anxious wait as the surgeons decided what to do. To their relief, Eileen’s colour improved slightly without further interference; they could continue. With infinite care, Blalock freed a second artery from its surrounding tissue. This was new territory for him: although he had watched Vivien Thomas carry out the procedure on dogs, he had never attempted it himself. He had installed Thomas – the expert, with 200 trial runs under his belt – on a stool behind him, a vantage point from which he could observe and make suggestions. Periodically Blalock would turn to his assistant and ask for advice: is this artery long enough? Is this the right part of the vessel to clamp?
Eileen’s blood vessels were even smaller than those of the dogs Thomas had operated on: the one Blalock needed was no bigger than a matchstick.13 This was the vessel taking blood to her left arm, the left subclavian artery. After isolating a section of the vessel with clamps to ensure no blood was flowing through it, he cut through the artery with a scalpel. He made a small incision in the side of the pulmonary artery and began the most challenging part of the procedure. A fine needle threaded with silk was used to attach the tiny subclavian artery to the pulmonary artery. Placing the sutures required almost inhuman accuracy, and the instruments at Blalock’s disposal were ill-suited to such delicate work. Nothing of this kind had been attempted before on the miniature vessels of a child: the needle and forceps Blalock was using were designed for adult surgery and felt unpleasantly cumbersome, as if he were trying to repair a Swiss watch using a plumber’s wrench.
After what seemed like an eternity, the two vessels were united.14 In theory, a proportion of the blood leaving the heart would be pumped into the subclavian artery and then be redirected back into Eileen’s left lung, increasing its oxygenation. But the vessel was so small that Blalock was unsure if the operation would have much effect. He released the clamps, allowing blood to pass through the new junction for the first time. After checking carefully for signs of bleeding, he closed the chest and stitched the external wound. The operation had lasted a little over an hour and a half; although there was no obvious improvement in Eileen’s condition, she had survived.fn2 Complications followed, however, and for two weeks the little girl’s life hung in the balance. Thereafter she began to make good progress, and on 25 January, almost two months after the operation, she was well enough to go home. Helen Taussig was pleasantly surprised to find that she had started to gain weight, and her episodes of cyanosis became less pronounced. Her parents were delighted: previously too ill to go outside, she was now learning to walk and could join them on outings to their local park.15 The operation had been a modest but definite success.fn3
This outcome seemed to justify further attempts, and on 3 February Blalock operated on a second patient, this time a nine-year-old girl. On her arrival in hospital she was only able to walk thirty feet, stooping and panting; a month after surgery she could walk upright for twice that distance, without any sign of discomfort.16 This was an encouraging development – but better was to come. On 7 February 1945 a desperately ill six-year-old boy was admitted to Johns Hopkins. He was extremely undernourished and could manage only a few paces without losing his breath. Taussig examined him and noted that he was severely cyanosed, recording in her notes that the insides of his cheeks were a deep mulberry colour.17 His parents were adamant that they would take any chance to save their son, and three days later Blalock operated.
This time he used the innominate artery, a vessel supplying blood to the arm, head and neck. First he severed it just before the point at which it split into the two branches supplying the head and left arm. After suturing its upper extremity closed, he attached the lower part of the vessel, the end nearer the heart, to the right pulmonary artery. This new circuit would redirect some of the boy’s blueish systemic blood back into the lungs for an additional dose of oxygen. When he released the clamps, a stream of blood gushed out of an undetected hole between the sutures; he quickly reapplied the clamps to cut this off and repaired the opening with an extra stitch. This time the join was perfect, and when the circulation was allowed to flow again it did so without any problems.
As the patient’s right lung received its first blood in over an hour, something extraordinary happened. Merel Harmel, the anaesthetist, suddenly cried, ‘He’s a lovely colour now! Take a look!’ Blalock and Taussig moved to the head of the table, and were astonished to see a pink-faced little boy with healthy red lips. Within a few minutes he was awake and asking to get out of bed.18 Elation filled the room. A young medical student who had been observing the operation, Mary Allen Engle, was so moved that she decided then and there to become a cardiologist; she would go on to be one of the field’s leading authorities.19 For the next few days, nurses accustomed to tending critically ill children found themselves dealing with a patient who was desperate to run around and play. The transformation was miraculous: in her case notes, Helen Taussig recorded that ‘his disposition has changed from that of a miserable whining child to a happy smiling boy.’20
That dramatic colour change – from sickly blue to healthy pink – was a proof of success that both medics and the public could readily understand. Blalock and Taussig wrote a report of their three cases for the Journal of the American Medical Association. Before the article had even been printed a journalist from the Associated Press somehow got hold of a copy, realised its significance, and published a story. Editors leapt upon it: at a time when newspapers were full of harrowing details of American deaths in the war in Europe, this was a rare morsel of good news: a happy story of terminally ill children being magically restored to life.21
The effect was electrifying, and the medical world was utterly unprepared for it. Tetralogy of Fallot is one of the more common congenital heart conditions, affecting one in every 2,400 newborns.22 There were thousands of children in the US alone who might be saved by the new operation, invalids presumed to be beyond medical help. Family doctors who knew nothing about Blalock’s breakthrough suddenly received visits from parents demanding a referral to the hospital in Baltimore. Children began to arrive at Johns Hopkins from across the country and then from abroad, and before long a trickle had become a flood. Not all parents could afford the operation, and some small-town newspapers launched public appeals to fund them. Such patients often turned up with a local journalist in tow, and surgeons found themselves constantly answering questions from uninvited members of the press.23
Within a few months the paediatric beds of Johns Hopkins were full, with tetralogy patients (known to the staff as ‘tets’) spilling out into the adult wards. This was an exhausting period for Blalock’s team, who were constantly operating during the day and often called to the wards at night; they barely took a day off. Regular delegations of surgeons arrived from abroad to observe the operation and find out what equipment they would need in order to do it themselves.24
A still more rapturous reception awaited Blalock in Europe. He was invited to spend a month at Guy’s Hospital in London, and on 22 August 1947 Blalock and his wife Mary sailed for England on the Mauretania. He had spent the day before his departure frantically trying to procure a month’s supply of Viceroy cigarettes, which were unobtainable in Britain.25 During his short residency at Guy’s, Blalock operated successfully on ten Blue Babies. His visit was widely reported: one woman from Sevenoaks in Kent, a Mrs Gallard, read about the celebrated American heart surgeon and promptly jumped on a London train to ask him to operate on her eight-year-old son Roger, who was confined to a wheelchair. Four months later a local newspaper reported that he was now able to run around and play with his friends. His mother explained to the journalist, not entirely accurately, that the surgeon had ‘removed Roger’s heart, and while it lay pulsating in his hands, he remodelled it’.26 Displaying a similarly hazy grasp of surgical minutiae, a Daily Mail article the following month claimed that during the procedure another patient’s heart was ‘removed and massaged’.27
Towards the end of his stay, Blalock shared the stage with Helen Taussig for a joint lecture to a packed hall at the British Medical Association. Their presentation ended in spectacular fashion when a spotlight beam suddenly pierced the darkened hall to pick out a nurse sitting on a chair with an angelic and healthy two-year-old on her lap; Blalock had operated on the little girl a week earlier. The leading British surgeon of the day, Russell Brock, described it as ‘a Madonna-like tableau, a perfect climax to an impressive lecture on an epoch-making contribution’.28
Blalock’s tour (his ‘royal progress’, as one of his juniors described it) continued with visits to hospitals in Sweden and France. He left behind an important legacy in Europe: a ‘Blue Baby clinic’ was set up at Guy’s,29 and within a few months the operation was being successfully performed in many other centres across the continent. As they boarded their plane back to America, Blalock remarked to his wife that they had been treated like gods; now they must come down to earth again.30 This was no exaggeration: a massive backlog of cases awaited him in Baltimore. By 1948 there was a three-year waiting list for the operation,31 and two years later a photographic portrait of Blalock was commissioned to commemorate the 1,000th case.32
Despite the hundreds of lives it saved, the work of Blalock, Taussig and Thomas was also fiercely criticised. Antivivisection campaigners were outraged at the number of animal experiments taking place in the Johns Hopkins laboratories, and fought tirelessly to put a stop to them. Experimental surgery on animals had long been standard practice in developing new operations; dogs, whose hearts and major vessels were similar in size to those of humans, were easily available, since most cities had large numbers of unwanted strays. But some of these experiments were of dubious value and inflicted unnecessary suffering. In 1901 one of the pioneers of cardiac surgery, Benjamin Merrill Ricketts, performed experiments on forty-five dogs at his laboratory in Cincinnati, deliberately injuring their hearts and surrounding tissues. ‘The object was to induce as many complications as possible,’ he explained, and in this he was certainly successful: the vast majority of the animals died shortly afterwards.33
By the 1940s researchers had a more enlightened attitude, and Vivien Thomas’s surgical trials on dogs were all conducted with full anaesthesia; those that developed complications were humanely killed. Nevertheless, there were repeated attempts to shut down his research, with campaigners harassing laboratory staff and the suppliers of animals. A national animal-rights movement had emerged in the 1880s, and later succeeded in presenting to Congress a bill to ban animal experimentation.34 It was defeated, but vigorous local campaigns continued in many states. In February 1946, as Congress considered new antivivisection legislation, Blalock gave evidence before a House committee with three of his young patients, explaining that without animal experimentation none of them would have survived.35 He made a powerful case, and the bill was voted down.
Local activists in Baltimore were more tenacious, and succeeded in preventing medical researchers from using unclaimed stray dogs for their experiments. Without a ready supply of animals, hospitals took to buying them in from neighbouring states, and when this practice was also deemed unlawful matters came to a head.36 Baltimore City Council announced a public vote – popularly known as the ‘dog referendum’ – to decide whether the use of animals for medical research should be prohibited. The pro-vivisection camp indulged in some emotive tactics in its attempt to win the public over. When Helen Taussig spoke at an open meeting she was accompanied by a brigade of her patients: healthy, smiling children, many of whom had brought their pet dogs.37 The star of the campaign was a playful and photogenic mongrel called Anna, an early survivor of Vivien Thomas’s surgical trials. She appeared in an educational film and was photographed for Life magazine with one of the children who had been saved by the operation.38 The result of the dog referendum was decisive: the anti-vivisection faction was resoundingly defeated by a margin of more than four to one.39 To commemorate the win, Blalock commissioned a portrait of Anna, which remains on display at the hospital today.40
Blalock and his first Blue Baby success of 1944 captured the public attention as no operation had before. Most modern surgeons would agree with Russell Brock’s assessment that it represented the starting point of modern heart surgery, although Blalock had not operated on the organ itself, but on the blood vessels around it. Nor had he cured his patients: the operation was palliative, improving their quality of life rather than correcting the underlying condition. It was not until a decade later that another surgeon, C. Walton Lillehei, succeeded in curing a cyanotic infant.41
Tetralogy of Fallot is only one of a vast array of cardiac malformations, many of which at the time offered a still gloomier outlook for patients, with no hope of cure. The battle against congenital disease was only just beginning, but Blalock had made an effective assault on its ramparts. To give a sense of quite how significant a shift this represented, here is what the Scottish cardiologist James Mackenzie had to say about therapy for congenital conditions in his influential textbook Diseases of the Heart, published in 1908: ‘If the heart maintains the circulation well, no treatment is required. In more serious cases, beyond attending to the child’s comfort and nourishment, special treatment for the heart is of little benefit.’42 In a work of several hundred pages Mackenzie devotes only a couple to congenital heart disease, and two meagre sentences to its treatment. Other experts had little else to offer: parents were advised to keep their children warm and, if possible, move to a balmy climate. In a lecture delivered at Great Ormond Street Hospital in 1906, Frederick Poynton recommended fattening them up like a Christmas turkey: ‘No overcoat fits so well and acts so effectually as an undercoat of adipose tissue.’43
The fact that so little could be done for congenital heart disease at the turn of the twentieth century made it a deeply unfashionable area of research, and knowledge of individual disorders was virtually non-existent. Doctors could generally offer a diagnosis no more specific than ‘malformation of the heart’. This is in some ways strange, since giant strides had already been made in the understanding of other types of heart disease, and congenital conditions had been among the first to be identified. Indeed, a Babylonian tablet once held by the Library at Nineveh, now in the collection of the British Museum, refers to a probable cardiac malformation from more than 2,500 years ago: ‘When a woman gives birth to an infant that has the heart open and has no skin, the country will suffer from calamities.’44 This appears to be a description of ectopia cordis, a rare condition in which the heart is formed outside the ribcage and protrudes through the chest, exposed to the air and beating in plain sight. In ancient civilisations such horrible deformities were often seen as an evil portent, making them worthy of record.
Early modern science also had a fascination with the grotesque. In 1665 the inaugural issue of the first scientific journal, the Royal Society’s Philosophical Transactions, contained an article by Robert Boyle entitled ‘An Account of a very odd monstrous calf’.45 Prodigies and monsters were a common feature of the journal in its early years, and malformations seen in stillborn infants were a particular source of fascination. One such description, entitled ‘A Monstrous Human Foetus, Having Neither Head, Heart, Lungs, Stomach, Spleen, Pancreas, Liver, nor Kidnies’, was reproduced as a pamphlet and widely circulated. It was in an article of this kind that tetralogy of Fallot was first described.
The seventeenth-century Danish scientist Nicolas Steno enjoyed a varied career during which he made important contributions to anatomy and geology, and later became a bishop. His most celebrated achievement was to prove that heart tissue was muscular. In 1673 he published an account of an autopsy he had carried out on a stillborn infant, sensationally entitled ‘Monstrous Embryo Dissected Near Paris’. The child exhibited a number of deformities, including a cleft lip and palate and webbed fingers on one hand; many of the organs had passed through a hole in the abdomen and were visible externally. When questioned by Steno and his colleagues, the mother suggested that these anomalies had been caused by her fondness for rabbit stew.46 This was not what interested them most, however: ‘The unusual form of the arteries arising from the heart attracted the chief attention and called for admiration.’ Steno was struck by the form of the pulmonary artery, which was much narrower than normal. Intrigued, he then dissected the heart and found that there was a septal defect – a hole in the tissue between the left and right ventricles. In addition the aorta, the main artery supplying blood to the rest of the body, did not arise from the left ventricle as it should, but communicated with both the left and right ventricles.47
These cardiac deformities – a narrowed pulmonary artery (known as pulmonary stenosis), a ventricular septal defect and an overriding aorta – are three of the four characteristic defects of tetralogy of Fallot. The fourth, not mentioned by Steno, is a thickening of the wall of the right ventricle: its clinical name is right ventricular hypertrophy, and it is caused by the difficulty the heart encounters in pumping blood through the narrowed pulmonary artery.fn4 Steno was flummoxed by the discovery, concluding with the observation, ‘As to the cause of this phenomenon, I have nothing to say.’48
By the late nineteenth century at least seven investigators had described this combination of cardiac malformations and the symptoms it caused. So it may seem strange that the condition is now named after an obscure French medic whose research took place a full two centuries after Steno’s. In 1888, Étienne-Louis Arthur Fallot published a long article based on his observations of three cyanotic young men he had encountered at his hospital in Marseille. The first two patients died, and at a post-mortem he found the four characteristic deformities in their hearts. When the third patient was admitted with identical symptoms not long afterwards, Fallot diagnosed him with the same congenital disease, and predicted the cardiac malformations that would be found at autopsy. The man died shortly afterwards, and Fallot was shown to be correct. He then made a careful study of all the documented examples he could find of cyanotic disease, which he called ‘la maladie bleue’. Earlier writers had often been confused about what caused the blue colour of their patients, attributing it to a single cardiac deformity or to a secondary feature which was absent in other cases. Fallot asserted that he had identified four separate features of this disease which were always present: pulmonary stenosis; a ventricular septal defect; right ventricular hypertrophy; and an overriding aorta. ‘The constancy with which this group is reproduced is no less remarkable than its coexistence with the clinical syndrome of blue disease,’ he wrote.49 He called this group of four features a ‘tetralogy’, a misnomer that has pained classically educated medics ever since.fn5
The year after Fallot’s paper appeared, a young Canadian called Maude Abbott applied to study medicine at McGill University in Montreal. Despite a vigorous campaign which was endorsed by several of the city’s grandees, the faculty refused to admit her to a department which had hitherto been exclusively male. Rebuffed, Abbott instead went to Bishop’s University, where as part of its first intake of female medical students she won numerous prizes.50 For most of the twentieth century the field of heart surgery would be dominated by men; it was not until the 1960s that the first woman, Nina Starr Braunwald, would make inroads into this very male world.51 It is therefore notable that the two people who added most to our knowledge of congenital heart disease – Abbott and Taussig – were both women who had to fight even to be admitted to the medical profession.
Abbott was later appointed to what might have been a dreary job as assistant curator of the medical museum of McGill, the university that had rejected her as a student. Browsing its collections she became intrigued by one specimen in a glass jar, a heart with a strange deformity. She sought the advice of Sir William Osler, Canada’s most eminent clinician and one of the founding professors of Johns Hopkins medical school. He encouraged her to make congenital heart conditions the subject of her research, commissioning her to write a chapter on the topic for his textbook The Principles and Practice of Medicine.
Abbott tracked down and examined 412 separate cases of cardiac malformations. She became so immersed in the subject that she continued to amass examples long after the publication of Osler’s book, and by the 1920s had studied over 1,000 hearts with abnormalities.52 This was an undertaking unprecedented in its scope, and by 1936, when she published an illustrated book based on her findings, the Atlas of Congenital Cardiac Disease, she was the world’s acknowledged expert. When Helen Taussig, then a young paediatrician, first became interested in congenital heart conditions she went on a pilgrimage to McGill to tap this vast reservoir of knowledge; Abbott was enormously helpful, showing Taussig specimens from her collection, and comparing them with X-ray images of the same defect.53 Maude Abbott died in 1940, four years before Taussig’s astonishing Blue Baby triumph. But she did live long enough to see a surgeon from Boston, Robert Gross, achieve the first outright cure of a congenital abnormality.
In the first century AD the Roman surgeon Galen made a startlingly accurate observation whose true significance would not be appreciated until a millennium and a half later. In book XV of his study of human anatomy, De Usu Partium, he wrote: ‘The ductus joining the aorta to the pulmonary artery not only ceases to grow after birth, when all the other parts of the animal are growing, but it can be seen to become thinner and thinner, until as time progresses, it dries up completely and wears away.’54
A ‘ductus’ is a duct or channel, and the example Galen describes is an important quirk of human development. When we are adults, our blood passes from the right side of the heart through the pulmonary artery to the lungs; after oxygenation it then returns through the pulmonary veins to the left side of the heart, which pumps it through the aorta to the rest of the body. Although linked, the two circulations are distinct; indeed, the blood pressure is significantly higher in the systemic circulation than that which passes through the lungs.
Before we are born the situation is rather different. A foetus in the womb receives all its oxygen from its mother via the placenta. It cannot yet use its lungs, so there is no need for a large volume of blood to pass through them. Most of the circulation therefore bypasses the lungs through two temporary canals: the foramen ovale, a small window between the left and right sides of the heart; and the ductus arteriosus, a short vessel which joins the aorta and pulmonary artery near their origin at the top of the organ. The ductus arteriosus usually closes in the first week after birth, just as Galen observed, and the circulation to the lungs and to the rest of the body are separated. William Harvey noted in the seventeenth century that a large volume of blood passes through this passage during foetal life, and his friend Nathaniel Highmore, the first to accept Harvey’s findings about the circulation of the blood, noticed that the closure of the ductus and the foramen ovale coincided with the onset of respiration through the lungs.55
In the eighteenth century it emerged that this elegant mechanism did not always work as it should: surgeons examining corpses on the mortuary slab began to find adult hearts in which the foramen ovale had failed to close.56 In other bodies they observed that the ductus arteriosus had remained open – or patent – well into adulthood. In some cases this defect had no obvious effect on the patient; others suffered shortness of breath, an irregular heart rhythm or stunted growth. Strangely, some physicians believed that those with a patent ductus or foramen ovale were able to breathe underwater. The source of this misconception was Harvey, who observed that foetuses were able to survive in the womb without breathing; he speculated that a patent ductus and foramen ovale might be the physiological mechanism that allowed aquatic birds like ducks and geese to spend long periods of time submerged.57 It was a neat suggestion, but well wide of the mark: in fact the muscles of diving birds and mammals contain high levels of myoglobin, a protein which stores oxygen and enables them to hold their breath for several minutes.58
Patent ductus arteriosus was thus one of the first congenital heart defects to be described and understood, and by the beginning of the twentieth century doctors could also diagnose it with reasonable confidence. In 1898 George Alexander Gibson of the Edinburgh Royal Infirmary wrote about a characteristic noise which could be heard through the stethoscope when examining affected patients. This ‘distinct thrill’,59 as he called it, is now known as a Gibson murmurfn6 and is sometimes likened to the sound of a washing machine. Being able to recognise the condition was the essential first step towards treating it, and only a few years later another heart specialist correctly predicted how a patent ductus could be cured.
On 6 May 1907 an American doctor, John Munro, gave a speech to a meeting of the Philadelphia Academy of Surgery. He explained that some years earlier he had been treating a baby girl who subsequently died; during the post-mortem examination he found a large patent ductus, and it occurred to him that it would not have been difficult to repair it: ‘The simplicity of the remedy was so striking that I at once made further dissections, and satisfied myself that it would be possible to ligate [tie] the duct provided a diagnosis could be made beforehand.’ Munro suggested that artificially closing the ductus would be followed by ‘permanent restoration to a normal function of the lungs and arteries’,60 and pleaded with his colleagues not to dismiss the idea out of hand. He was thinking along the right lines, but given the primitive state of anaesthesia at this date it is probably fortunate that no surgeon dared attempt it until many years later.
Although disregarded, Munro’s suggestion was not entirely forgotten. In the early 1920s Evarts Graham, professor of surgery at Washington University in St Louis, became convinced that it should be possible to cure a patient with patent ductus arteriosus by closing the vessel surgically. He approached the professor of paediatrics at the St Louis Children’s Hospital, explained the problem, and asked his colleague to send him a suitable patient for operation. To his irritation, the patient who duly appeared in his office was a fifty-three-year-old man whose condition was far too advanced to make him a plausible candidate for surgery. It seems the paediatrician was irked by his junior colleague’s effrontery, and had deliberately sent him an unsuitable patient to ensure that he could not take an unacceptable surgical risk. Russell Brock later suggested that this ‘cruel and stupid’ act delayed the advent of heart surgery in children by fifteen years.61
The first surgeon to succeed in closing a patent ductus arteriosus met similar resistance to the idea, and had to resort to subterfuge in order to overcome it. In 1938 Robert Gross was thirty-three and a junior surgeon at Boston Children’s Hospital. Born with severely impaired vision in one eye, Gross struggled with depth perception. His father, who was a piano-maker, helped him develop his hand-eye coordination by employing him in his workshop. Later, when he revealed his ambition to become a surgeon, Gross senior gave him clocks to take apart and reassemble; as his fine-motor skills improved, the clocks got smaller. Remarkably, Gross never revealed this disability during his career: only after his retirement did he approach a colleague for advice, and when a congenital cataract was removed from the affected eye he experienced binocular vision for the first time in his life.62
Gross had seen several small children die of a cardiac infection called acute bacterial endocarditis, a common complication of a patent ductus arteriosus. He was both frustrated by his inability to do anything for them and attracted to the mechanical nature of the problem. He was convinced that tying off the blood vessel was feasible. Two other surgeons had by now attempted the procedure, but one had failed to close the vessel and the other had found when he opened the patient that the condition had been misdiagnosed.63 Gross spent many hours in the laboratory devising a new operation, which he tested on dogs and then on cadavers. When he was satisfied that he had a workable procedure he approached his head of department, William Ladd, and explained the proposition. Ladd was unimpressed, telling him to continue his research and explicitly prohibiting him from trying his method on a patient.
Undaunted, Gross bided his time. Ladd was in the habit of taking his annual holiday every August, and as soon as he was safely on a boat to Europe, Gross acted. He selected two patients he thought suitable for operation, reasoning that even if the first died he would have a second chance to demonstrate that the procedure worked. This may seem a curiously unemotional, even callous, approach, but it was entirely pragmatic. Any candidate for surgery would already be gravely ill and would inevitably die if left untreated. If they failed to survive the operation it would prove nothing, since such a high-risk patient faced long odds however perfect the surgery. A single success, on the other hand, would be proof positive that Gross’s new operation was sound.
Happily, as things turned out he needed only one. The first patient he chose was Lorraine Sweeney, a seven-year-old girl who had been admitted to the Children’s Hospital on 17 August 1938. From early childhood she had been short of breath, and was diagnosed with patent ductus arteriosus. After starting school she began to experience strange episodes in which she became frightened and clutched her breast; when asked what the matter was she would whisper ‘something wrong inside of here’. Her mother was alarmed by a loud buzzing noise she could hear emanating from inside the little girl’s chest. Her symptoms worsened, and it soon became clear that if left untreated her life would be short.
On 26 August 1938, Gross began an operation that would seal his reputation as one of the great pioneers of paediatric medicine. He was assisted by Thomas Lanman, the most senior member of the surgical staff after Ladd,64 and Betty Lank agreed to administer the anaesthetic. His colleagues were well aware that they were defying their boss, but were impressed by Gross’s steely determination: he was a serious-minded and impressive individual.
It is easily overlooked that anaesthetists were as much the heroes of these early operations as the surgeons. Their equipment was basic, and they were being asked to anaesthetise patients more critically ill than any who had previously undergone surgery, many of them tiny babies. In the early days of anaesthesia, when the job involved little more than dripping ether or chloroform on to a mask to put the patient to sleep, it was thought to be an undemanding role, and anaesthetists were typically nurses rather than qualified physicians. Betty Lank belonged to this caste of nurse-anaesthetists; only in the 1940s would board-certified physicians (known in the US as anesthesiologists) take over the job.
With limited equipment to monitor the condition of patients while they were unconscious, the task of keeping them alive was daunting. But theirs were not the only lives at risk. Chloroform and ether are both toxic, and ether highly flammable. For Lorraine Sweeney’s operation Betty Lank used a recently discovered anaesthetic agent, cyclopropane. This was widely regarded as a huge improvement on the older drugs: when mixed with oxygen it was easily inhaled, it gave quick and deep anaesthesia, and patients experienced none of the post-operative nausea associated with chloroform. Unfortunately the oxygen–cyclopropane mixture had one major drawback: it was dangerously explosive, and thus necessitated extraordinary precautions. The temperature and humidity of the operating theatre were carefully controlled; staff were prohibited from wearing silk, wool, leather or wooden shoes; and electrical equipment could not be turned on or off during the operation. Anaesthetists were even advised to switch to another gas if there were thunderstorms in the area.65 Nevertheless, accidents still occurred. During an operation for lung cancer at another Boston hospital a few years earlier a spark had caused a major explosion, killing the patient instantly.66 So when Betty Lank admitted that she was ‘scared to death’ by the prospect of this operation, it’s possible it was not merely the wrath of Dr Ladd that she feared.
Once the gas had been administered and Lorraine was asleep, Gross opened an incision on the left side of her chest. After cutting through the muscle that lay beneath, he severed the cartilage connecting her third rib to the breastbone, and moved the rib out of the way. As air entered her chest through the incision the left lung collapsed, giving Gross a clear view of the heart and its major blood vessels. His fingers were now just millimetres away from the ductus arteriosus, but it would take him more than an hour to find and expose it. In order to do so he needed to dissect the aorta and pulmonary artery free of their surrounding tissue, without causing major bleeding or damaging any of the delicate structures around the heart. In an article written thirteen years later and based on his experience of 412 such operations, Gross emphasised the formidable difficulty of this stage, observing that ‘in so crowded a space a single false step can lead to disaster.’ In later operations he would devote as much as two hours to this painstaking task.67
With the major vessels carefully exposed, Gross could see the ductus joining the pulmonary artery and the aorta. It was only 5 millimetres long, but its 8-millimetre diameter meant that a large volume of blood was passing through it every second. Placing a finger on the heart, he felt an alarming vibration: not just the usual powerful contractions, but an unnatural buzzing that continued even between the heartbeats. He placed the end of a stethoscope on the pulmonary artery and heard a deafening continuous roar that reminded him of steam escaping from some enormous engine. He carefully passed a loop of silk around the ductus and drew it tight. The surgical team waited nervously, watching for any sign that the circulation had been compromised. When three minutes had elapsed without any crisis, Gross decided to tie the loose ends of the silk to close the ductus permanently.
When he did so the worrying vibration disappeared instantly. Relieved, Gross closed Lorraine’s chest and sewed up his incision. The operation had been fraught, but the child had withstood the procedure well, and there had never been any threat to her life. The following day Lorraine was well enough to sit in a chair; within forty-eight hours she was walking around the ward.68
In their clinical reports surgeons sometimes note that a patient had a ‘stormy’ post-operative recovery. This is euphemistic, usually indicating a series of unpleasant and possibly life-threatening complications. In Lorraine Sweeney’s case the word was appropriate in its literal sense: as she convalesced a dramatic hurricane swept into Boston. When Gross visited her bedside he was pleased to discover that she was in excellent health: her greatest worry was that the wind would knock down the sandcastle she had just built.69 A little girl on the brink of death had been transformed into a perfectly happy child able to live a normal life.
Not everybody was delighted by this success. Dr Ladd – still on holiday in Europe – read about the operation in a newspaper and was furious at Gross’s insubordination. When he first saw Gross after his return to work he asked him if there was anything new he ought to know about. ‘Nope, not much, nothing new,’ was his junior’s reply.70 Relations between the two men would remain permanently frosty.71 What perhaps most irritated Ladd was that Gross had been right. All four of his first patients thrived after their operation,72 and Ladd reluctantly allowed him to undertake more. But things did not go smoothly for long. When the twelfth patient returned from hospital her parents threw a party to welcome her home. In the midst of the celebrations the guest of honour suddenly collapsed and died. A post-mortem revealed that the ligature had cut through the ductus, resulting in massive haemorrhage. After this incident Gross modified the procedure, and instead of closing the ductus by tying it, he began to divide it with a scalpel before suturing the ends. This was a trickier operation, but provided a safer long-term solution.
By 1944, when Alfred Blalock gave a talk to the Massachusetts Medical Society about recent advances in surgery, he could report that Gross had successfully operated on over 60 patients, observing that there were an estimated 20,000 people in the US alone who stood to gain from the procedure.73 By 1951 the number of patients had risen to over 400, with more than 97 per cent of them cured.74 Other surgeons reported excellent results with the new operation. In 1943 a boy aged thirteen was treated in Edinburgh, and five years later was accepted for army service with the top A1 rating for physical condition. He became regimental boxing champion and claimed to be able to run 100 yards in 10 seconds.75 A short length of silk thread, placed and tied with superlative skill, had turned an invalid into an athlete.
The success of Gross’s 1938 operation was one of the developments that emboldened Blalock to develop his Blue Baby procedure. But in the six-year period between these two landmarks another important blow was struck against congenital heart disease. Although both Gross and Blalock were involved in the research behind this development, it was a Swede, Clarence Crafoord, who made the breakthrough.
The aorta is the largest blood vessel in the human body: it’s the artery through which freshly oxygenated blood is pumped to all the major organs. About the diameter of a garden hose, it originates at the top of the left ventricle of the heart, ascends for a few centimetres and then curves downwards in a loop known as the aortic arch. It then continues into the abdomen for around thirteen centimetres before splitting into two. Three branches off the top of the aortic arch provide blood to the head and upper limbs; the abdominal aorta supplies the lower half of the body. An unimpeded flow through this crucial vessel is absolutely essential.
In a relatively common congenital abnormality called coarctation of the aorta, a section of the vessel is constricted to a fraction of its normal diameter. Because blood has to be forced through this narrowing, pressure is increased above the constriction and decreased below it. This leads to a striking symptom in which patients have much higher blood pressure in their arms than in their legs. Blood vessels in the thorax often become enlarged as the body struggles to improve circulation to the abdomen, sometimes becoming so swollen that they cause erosion to the ribs. This is a natural compensation mechanism, akin to what happens on a road network when a major route between two towns is closed: vehicles soon start to bypass the blockage by using smaller side roads, with traffic reaching its destination via a more circuitous route. Similarly, the major arteries are not the only routes to the major organs: blood can also reach them via a labyrinthine network of smaller vessels known as collaterals. The human body has another trick: new collaterals can form between large vessels, and smaller vessels can enlarge to allow more blood to pass through them.
Even with these coping mechanisms, coarctation is a debilitating and life-threatening condition. Sufferers can develop complications including high blood pressure and heart failure, and without treatment have a life expectancy of just thirty-four.76 The abnormality was not regularly diagnosed until enough was known about different congenital heart conditions to distinguish between them. One cardiologist noted in the 1930s that doctors had recently begun to encounter more cases, though this is probably because they were getting better at spotting the warning signs.77 There was no known treatment, and as late as 1944 one of the most widely used textbooks ventured only that patients should be protected from infections or undue exertion.78 Unknown to its author, a radical cure was just around the corner – thanks to a discovery made by accident.
By the mid-1930s surgeons in America and Europe were conducting hundreds of animal experiments in order to establish the likely difficulties of surgery on the heart and its major vessels. One thing they worried about was the effect of interrupting the blood supply to the rest of the body. They realised that if they needed to cut into the aorta they would first have to stop blood flowing through it in order to avoid excessive bleeding. Doing so even for a few minutes would deprive the major organs of their oxygen supply, which most experts believed would rapidly prove fatal.
In a series of experiments in 1935 Clarence Crafoord, a surgeon at the Sabbatsberg Hospital in Stockholm, put this assumption to the test. Using dogs as his test subjects, he placed a clamp over the aorta to prevent any blood flowing to the rest of the body. He found to his surprise that it was safe to interrupt the circulation for as much as twenty-five minutes, as long as the brain continued to receive an adequate supply.fn7 This he achieved by attaching the cerebral blood vessels to the circulation of a second dog, using glass and rubber tubes.
This result was not at first thought to have any relevance to surgery in human patients, but it turned out to have unexpected significance. Some years later Crafoord was operating on a child with a patent ductus. He used a silk ligature to tie the ductus closed, but when he tightened the thread it cut straight through the walls of the vessel. The bleeding was copious, and Crafoord failed to bring it under control. In desperation he placed a clamp across the aorta to stop all blood flow. This allowed him to close both severed ends of the ductus with sutures, an undertaking which took almost half an hour.79 Remembering his earlier animal experiments, he was confident that most of the child’s organs would not be harmed by such a long interruption to their circulation, but worried that the brain or spinal cord would be irreversibly damaged, causing paralysis or even death.
When the child awoke from the anaesthetic, Crafoord and his team were delighted to find that these fears were unfounded: there was no neurological damage. This set him thinking about coarctation of the aorta, a problem he had discussed with Robert Gross on one of his regular visits to the US. Both men agreed that if the obstructed area was short enough, it should be feasible to cut out the affected section of blood vessel and suture together the two ends. But doing so would involve placing a clamp over the aorta for the duration of the procedure. This would take considerable time, an hour or more, and they believed that cutting off the body’s blood supply for so long would inevitably have disastrous results; indeed, Gross had tried the procedure in dogs, and found that many of them suffered partial paralysis.80
The fact that his ductus patient had survived for half an hour with the circulation interrupted suggested to Crafoord that this was not the insuperable obstacle it had first appeared, particularly since coarctation patients tended to have well-developed collaterals which sent blood to the organs via a secondary network of vessels. He asked his colleagues to look out for suitable patients for operation, and in October 1944 was presented with the perfect candidate, a twelve-year-old boy.
On 19 October Crafoord operated. When he opened the boy’s chest and exposed the major blood vessels he had a clear view of the curve of the aorta, a tight arch that rose from the top of the heart and then turned downwards. At that point it suddenly narrowed into a constriction which drastically reduced the amount of blood that could pass through the vessel. Crafoord placed forceps on the aorta on either side of this obstruction, clamping it shut. This stopped any blood from flowing through the lower part of the aorta; crucially, the circulation to the brain via the two carotid arteries (which arise from the top of the aortic arch) was not interrupted. A segment of the aorta was now bloodless, and he could cut out the affected section and join the two severed ends. With the heart still beating a few centimetres from his instruments, this was a task requiring immense dexterity and concentration. First he inserted three stitches at equal distances around the diameter of the vessel; with these holding the two cut ends of the aorta together he could then insert fine silk sutures in between them. By the time he had finished, the aorta had been clamped shut for over two hours. This was long enough to be a concern, but Crafoord knew that the brain would not be harmed, and was optimistic that the collateral circulation had been sufficient to sustain the other major organs. When he released the forceps to let blood through the repaired vessel he was relieved to find that there were no leaks: the most dangerous part of the procedure was over.
After an operation lasting six hours, an exhausted Crafoord put the final stitch in the little boy’s chest. His patient developed a fever and a chest infection, but soon improved. Two weeks later Crafoord performed the same procedure on a twenty-seven-year-old farmer who had become too ill to work. This too was a success, and when he examined both patients the following March they were in excellent health; the farmer had even returned to work.81
Meanwhile in Boston, Robert Gross and his colleague Charles Hufnagel had independently come to the conclusion that it might be possible to repair coarctation by temporarily clamping the aorta. Unaware that Crafoord had already done exactly this, Gross operated on two patients. The first died needlessly after the aortic clamps were removed too quickly, resulting in a sudden change in blood pressure which overwhelmed the patient’s circulation. When the operation was next performed, Gross was careful to remove the clamps slowly and the patient made a good recovery. Thinking he had achieved something entirely new, Gross added a postscript about his ‘breakthrough’ to a paper he had already submitted for publication.82 When he learned that Crafoord had beaten him to it by a couple of weeks Gross was furious, believing that the Swede had exploited his own research; five years later he banished a visiting surgeon from his operating theatre after finding out that he had been Crafoord’s assistant.83 Such competitions to become the first to perform an operation – to ‘establish priority’, as it is known – would become a common feature of the next few decades: like the race to put a man on the Moon in the 1960s, these contests would drive progress, but they would also lead to rivalries and bitter disputes.
Being the first matters little, of course, unless the procedure works. Happily, the early operations for congenital heart conditions really did work. One of Blalock’s earliest Blue Babies, a boy called Samuel Sanders, went on to become a great pianist, the recital partner of Itzhak Perlman and Mstislav Rostropovich, and lived until 1999.84 Crafoord was still in touch with his first coarctation patient in 1974, thirty years after his operation.85 Most spectacularly Lorraine Sweeney Nicoli, whose life Robert Gross saved in 1938, became a great-grandmother, gave an address at Gross’s funeral, and was still alive and well in the summer of 2015.
That is not to say that these techniques represented the last word in surgical sophistication. Only a couple of years after the first Blalock –Taussig shunt, Willis Potts in Chicago unveiled a modified version of the procedure which gave still better results.86 Later, Denton Cooley – who had been in theatre for Blalock’s historic first operation – would refine it further. Despite these improvements, surgeons still yearned to find a cure for tetralogy of Fallot, rather than simply alleviate its symptoms. To achieve this, though, would involve finding a way to operate inside the heart; and if such a thing could be done it would also open the way to treating myriad other types of heart disease.
When Albert Blalock died in 1965, Lord Brock, President of the Royal College of Surgeons, wrote that his work had ‘inspired and stimulated the advances in cardiac surgery that followed with almost breathless rapidity’.87 Indeed, within a few years of the first Blue Baby operation the field had been transformed. The era of open-heart surgery was about to begin; and after the brilliant successes of Gross, Crafoord and Blalock, surgeons on both sides of the Atlantic sensed that still greater discoveries lay in store.