Smoking Ears and Screaming Teeth - Trevor Norton (2010)
Something in the Blood
‘Blood is a most peculiar fluid, my friend’ – Goethe
Blood is the body’s lifeline. It transports oxygen and the nutrients from our food to every needy organ and tissue. It also dispatches hormones to their place of action and is the supply line for our main defenders against disease. A pinprick of blood contains 7,000 white blood cells eager to engulf alien invaders.
Even the earliest barber-surgeons bestowed great importance upon blood, but instead of trying to retain it within the body they were determined to facilitate its escape. For this we should perhaps blame Galen, a second-century AD Roman doctor who learned his trade mending gladiators and became the Emperor’s physician. He was also the know-all of medicine and his influence lasted for well over a thousand years. Galen decided that all headaches, fevers and apoplexy were caused by a build-up of blood. Draining was the obvious remedy. From then on the bleeding bowl was always to hand and even into the nineteenth century bloodletting was the prime treatment for everything from syphilis to madness. The other physician’s favourite was purging, both oral and anal, so the poor patient got either a knife into his vein or a funnel up his bum – or both.
The simplest bleeding technique was to tie a bandage around the arm, causing the vein to swell, then to lance it, allowing blood to spurt into a bowl. It was called ‘breathing the vein’. Leeches were also the physician’s little helpers. If placed on the skin they bite in and suck away until swollen to four times their original size. When replete they fall off, but if detached prematurely they leave their teeth behind to fester. Leeches inject an anti-coagulant to aid the flow of blood and it continues to encourage bleeding for hours afterwards. Leeching became so popular that thousands of ponds were stripped of their slimy suckers. In 1837 France imported 33 million leeches to meet demand.
‘Cupping’ also became popular. It involved placing a heated glass jar over a cut made in the skin. As the air inside cooled, it contracted, forming a vacuum that sucked blood from the wound. Cupping was commonly used to treat high blood pressure until the 1950s.
Surprisingly, many patients looked forward to regular bloodlettings. Beneath an eighteenth-century drawing of a fine lady being bled by a surgeon the caption reveals her feelings: ‘Courage, Sir. I’ll be brave … Puncture with confidence. Make a good opening. Ahh, the gush of blood surprises you … Oh Gods, the gentle hand, the agreeable puncture … blood drawn makes me feel much better … I sense my vigour return anew.’
The trouble was that ‘heroic’ bleeding became the norm. An early-eighteenth-century novel by Alaine le Sage describes a surgeon treating a canon with gout. After extracting ‘six good porringers of blood’, he instructs his assistant: ‘You will take as much more three hours hence, and tomorrow you will repeat the operation. It is a mere vulgar error that blood is any use to the system; the faster you draw it off the better …’ This regime ‘reduced the old Canon to death’s door in less than two days’.
It was fiction, but no exaggeration. Benjamin Rush, ‘the founding father of American medicine’, believed that ‘hypertension of the arteries’ was the key to disease and the cure was copious bleeding. The nineteenth-century French surgeon Broussais takes the prize for being the greatest bleeder of all time. For efficient draining he used battalions of fifty leeches attached all over the body. Historians claim that he shed more blood than all the wars during his lifetime. It’s estimated that he might have siphoned off 20–30 million litres (35–50 million pints) during his career. His protégé Jean Bouillard also drained his patients dry, both bloodwise and financially. By repeated bloodletting, taking up to three litres, he ensured that the suffering of patients was greatly enhanced. Over a period of six months Louis XIII of France had forty-seven bleedings, a litre at a time. An average-sized man contains only five to six litres of blood.
Many patients were cured to death. The end of Charles II was hastened by repeated bleedings. George Washington merely caught a cold, but the extraction of three litres of blood by continual bloodletting ensured that he died from it. During the First World War some wounded soldiers were drained of even more blood.
While blood was the physician’s free-flowing friend, for surgeons it was the enemy. If a surgeon was foolish enough to open a patient’s chest or abdomen, every tissue his knife touched seeped or fountained opaque blood, obscuring his view and signalling the premature demise of the patient. Uncontrollable blood loss was one of the greatest impediments to the progress of surgery.
After an amputation the stump was sealed with a hot iron that fused skin, muscle and blood vessels, but by this time much of the patient’s blood had already escaped. Moreover, cauterisation – or, in the case of a large bullet wound, pouring scalding oil into the hole – was often more agony than the patient could bear.
If only the blood lost could be replaced, lives could be saved. The obvious thing to do was to link up the patient to a healthy volunteer and let blood flow from one to the other. In 1650 an Englishman called Francis Potter tried direct transfusion via flexible tubes made from animal windpipes tipped with a quill to pierce the patient’s vein. It was a failure. The first effective transfusion between animals was by Richard Lower in 1666. Christopher Wren, the astronomer/architect, also pioneered exchanges of blood between dogs. This led Samuel Pepys to consider: ‘pretty wishes, as of blood of a Quaker to be let into an Archbishop … but, if it takes, [it could] be of mighty use to man’s health, for the amending of bad blood by borrowing from a better body’. Animal transfusions became novelty demonstrations at scientific soirées. At the Royal Society in 1667 Jean-Baptiste Denys transfused the blood of a sheep into Arthur Cogan, ‘a debauched man’. Miraculously, Cogan survived, but became ‘a little cracked in the head’. When one of Denys’s patients died there was a scandal, until it was discovered that the man had been poisoned by his wife.
In 1829 a Doctor Blundell published a description of his ‘Gravitator’ apparatus for human transfusions. In his illustration the stoic donor stands to attention with his punctured arm outstretched and blood squirting into the funnel atop the Gravitator. It then flows down a vertical tube into a cannula stuck in the patient’s arm. The rate of flow is regulated by a small tap and perhaps by the donor crying: ‘Enough, I have but three pints left!’
Blundell claimed (erroneously) that transfusions had not ‘proved fatal in any one instance’ but warned that if the patient’s features are ‘convulsed, the flow of blood should be checked … So long as no spasmodic twitching of the features or other alarming symptoms are observed, we may proceed without fear.’ However, ‘the heart and vascular system being feeble, there is reason to believe … that sudden death might … be produced’.
Wisely, he recommended that physicians should ‘confine transfusions to cases in which there seems to be no hope for the patient, unless blood can be thrown into the veins’. Recently the American Society of Anaesthesiologists has issued similar advice to doctors, following studies indicating that far more infections and higher incidences of stroke, heart attack and kidney failure occur within a month of having transfusions following operations. Patients having the same operations but no transfusion fare far better.
Blundell was aware that there might be ‘possible though unknown risks’ in blood transfusion. How right he was. It would be over seventy years before blood groups were described by Karl Landsteiner. He wondered why so many transfusions killed the patient. When he took blood from his colleagues and mixed it with his own sometimes the red blood cells became sticky and clumped together, which would be fatal if it happened inside the body. The clumping never occurred when mixing two blood samples from the same person. Landsteiner hypothesised that the clumping indicated that the blood was responding to an antigen in the other blood in the mix. Antigens are substances that stimulate the body’s defences to produce antibodies to neutralise them, because they are perceived as being ‘foreign’. Clearly blood would not respond to antigens that it possessed itself, so there must be different types of blood characterised by having different antigens.
Landsteiner identified two antigens, A and B. That gave four possible blood groups i.e. those with one or other of the antigens (A or B), or both (group AB) or neither (group O). Thus he could predict which group would react against others. Providing the donor and recipient had the same blood group all would be well, but not all other combinations were necessarily incompatible. Group O has no antigens for other groups to react against so group O blood can be given safely to anyone, whatever their blood group. It is the universal donor. Group AB already has both antigens and so doesn’t perceive them as alien. AB is therefore the universal recipient. The story is a little more complicated than that as there are other factors that create incompatibility. Nonetheless, blood could now be tested in advance for compatibility before a transfusion, although this did not become routine until blood banks were established in the late 1930s. Nowadays one in three of us will have a blood transfusion at some point in our lifetime.
For transfusions it would be ideal to have large quantities of O group blood, the universal donor, but only just over forty per cent of people in western countries are type O. To solve this problem, in 1981 a biochemist called Jack Goldstein and his team deliberately transfused themselves with blood of a different type from their own.
They had found an enzyme that could snip off the antigen from group B blood cells so that they became group O. Experiments with monkeys indicated that small quantities of ‘converted’ B cells survived inside recipients whose immune systems would not tolerate unconverted cells. But was it safe to give to humans? There was only one way to find out. The scientists must test it on themselves.
Each participant was chosen because he had a different blood group from the others. If all the B group blood had been transformed to O, all would be well. If not, then some of the team, including Goldstein, would be in dire peril.
Fortunately all went well. Goldstein demonstrated that no one had developed antibodies to the converted cells. Further tests on volunteers confirmed that transformed cells could furnish a bank of O group blood for the purpose of transfusion.
If a researcher needs a blood sample he rarely visits the blood bank, he merely pricks his finger or that of a colleague. Many blood disorders are confined to human beings. In such cases animals do not make good guinea pigs. Self-experimentation is alive and well in many laboratories. Nowhere has the tradition been stronger than at the Washington University Medical School in St Louis or, as it is affectionately known, the Kamikaze School of Medicine.
It had a tradition of self-experimentation long before William Harrington came to the university. In 1945 he had been a student in Boston, working nights at a local hospital. A seventeen-year-old girl came in with blood emerging from her womb. To the horror of her parents, a doctor chastised her for undergoing an illegal abortion. Harrington was instructed to examine her blood and discovered that she had a dearth of platelets (blood cells essential for clotting). This was not the aftermath of a botched abortion. The girl was seriously ill, but he had no idea what disease this could be.
It was called ITP for short. We often complain that a doctor’s writing is illegible but even the clearest hand wouldn’t make sense out of ‘idiopathic thrombocytopenic purpura’. Thrombocytopenic translates as ‘deficiency of platelets’, and idiopathic means ‘of unknown cause’. One of its symptoms is purple bruises (purpura) arising from the slightest pressure, even the flick of a feather. In adults blood emerges from every orifice and the patient may die from internal bleeding or a bleed in the brain causing a stroke.
The blood sample had saved the girl’s honour, but not her life. She died on the operating table. Harrington decided he would search for a cure for ITP.
That was why he came to train under Carl Moore, the head of the Washington University Medical School. Harrington impressed Moore with his theory that ITP might develop when a body reacts against its own platelets. Blood cells are born in the bone marrow and end up in the spleen where they are broken down and some of their constituents are recycled. There are two obvious ways in which a catastrophic deficiency of platelets might arise: either the bone marrow ceases to produce them or the spleen goes into overdrive and destroys them faster than they can be replaced.
According to Harrington the easiest way to distinguish which of these was responsible was to inject blood from a patient with severe ITP into a healthy volunteer. If production in the marrow was to blame one would expect a gradual decline in the number of platelets in the guinea pig, but if something was destroying them his platelet count would plummet. The guinea pig would, of course, be Harrington.
Before the transfer experiment began his colleagues took marrow samples from Harrington’s breastbone with a stout needle. As Victor Herbert had found it was even more painful than it sounds and potentially hazardous.
At the beginning, Harrington’s blood contained fifty times more platelets than that of the donor with ITP. But that was about to change. After receiving half a litre of blood from the patient, he became ill almost immediately and within hours his platelets had all but vanished. Before the day was out he had blood spots on his skin, the first signs of ITP.
The donor had received half a litre of Harrington’s blood, but her platelet count didn’t improve and she was bleeding profusely. It didn’t augur well for her or for Harrington.
He was so concerned that he might suffer a stroke that he slept upright to lower the blood flow to his brain. His platelets weren’t increasing and his colleagues now realised what danger he was in. He bruised at the slightest touch and was terrified that the doctor’s rough examination might rupture his spleen and he would bleed to death.
It was several days before Harrington’s platelet count began to recover. He was overjoyed, but mostly because he had shown that, although his bone marrow was normal throughout the experiment, he had developed ITP because something in the donated blood was destroying his platelets. Also, his healthy blood had not helped the sick patient because her blood had destroyed the platelets he had donated to her. Against all odds and after fifty-six blood transfusions she too fully recovered.
In the most convincing way possible William Harrington had shown that the body could turn against its own cells. It was the first clear demonstration of what we now call an autoimmune disease.
Harrington, his colleagues and technicians were the guinea pigs for many subsequent experiments to uncover the mysteries of ITP. Indeed his boss, Carl Moore, was in hospital recovering from one of these experiments when he interviewed a young chap for a fellowship. Thomas Brittingham tried to ignore the blood streaming from Moore’s nose as they discussed the question of why some transfusions failed even when the blood groups of the donor and the recipient matched. Could it be that the recipient produced antibodies against alien white blood cells just as it did for red cells? If so, these antibodies might be a useful ally in the fight against leukaemia, a disease characterised by a huge overproduction of white cells.
Brittingham decided that the best test would be to inject himself with blood from someone with leukaemia and see what happened. What might happen was that he would give himself cancer of the blood. Experiments elsewhere had shown that leukaemia could be transmitted to mice and birds and even a single cancerous cell would suffice. J. B. Thiersch in Adelaide attempted to use blood and lymph from patients with chronic leukaemia, hoping that the transferred cells would establish themselves in the bodies of other patients. His hopes were dashed when they failed to contract leukaemia. He experimented on patients who were terminally ill with diabetes, syphilis, pernicious anaemia and cancers other than leukaemia. This was not, he thought, entirely satisfactory because many of them thoughtlessly died of their original illnesses without giving his experiment a chance to work. Moreover, from fighting their respective diseases they might already have had sufficient antibodies to prevent the leukaemia from taking. As they were so unsuitable it is perhaps a pity that they should have been subjected to additional stress during the final months of their lives.
Brittingham was very gung-ho about his self-experiment. He thought it would be great if he could prove that leukaemia was a transmissible disease. Great for science perhaps, but not for Thomas Brittingham, who was a thirty-year-old father of three.
A leukaemia patient supplied him with blood containing forty times more white cells than was normal. Brittingham strove to provide the best possible circumstances to favour infection. He repeatedly injected himself – ten times – with two large syringes of cancerous blood over a period of twenty weeks. After each injection his head pounded, he felt nauseous and was fluctuating between fever and chills for twelve hours or more. But his white-cell count did not increase appreciably as it would have had he contracted leukaemia. By his ninth injection he had developed many antibodies against the sick patient’s white blood cells. He had proved his point. In the publication of his results he cautiously stated that he had no signs of leukaemia so far.
Brittingham expanded his study to include injecting himself with blood from patients with a variety of blood conditions, including cancers. One of these conditions was aplastic anaemia, in which both the red and white cells are depleted. Within moments of injecting the ‘tainted’ blood he felt weak and breathless. This was followed by vomiting and diarrhoea. His blood pressure dropped dramatically and his lungs were filling with fluid. He was given oxygen to help him to breathe, but nothing seemed to alleviate the crisis.
He took a long time to recover and on the way he developed hepatitis B, got a clot in his jugular vein and, most distressing of all, he became allergic to alcohol.
It could have been worse – a nurse was spotted about to put into his drip a type of cortisone that was for intramuscular use only. It might have killed him. It could have been worse still. At the very beginning of the experiment a friend persuaded Brittingham to inject only fifty millilitres of blood into himself – he had planned to use a dose five times greater.
Not all the self-experiments at the Kamikaze Clinic were life-threatening; some just verged on the bizarre. In 1920 Samuel Grant and Alfred Goldman studied a condition called tetany in which the body develops uncontrollable twitches that get more serious if it persists. The spasms can spread to the larynx and the spinal muscles and become far more painful.
The causes were unknown, but there was the suggestion that people having a panic attack and breathing rapidly could induce it. It called for a bout of self-experimentation. So Grant and Goldman took a deep breath – indeed, they took fourteen deep breaths a minute, in time with a metronome. Soon their fingers tingled and their facial muscles became so rigid that they couldn’t speak. During one trial Goldman suddenly shrieked and his entire body went into spasm, his back arched like a bow. After twenty or so rounds of this, they concluded that hyperventilation could indeed cause tetany.
Meanwhile, 4,000 kilometres away in Cambridge University, young Jack Haldane, a super-talented Jack of all trades, was also energetically hyperventilating. He was trying to change the body’s chemistry and confirm that carbon dioxide stimulates breathing. He found that over-breathing for an hour or more flushed out all the carbon dioxide from his lungs and then he felt no urgency to breathe at all. He turned blue and developed severe pins and needles in his hands. His nerve endings were still spiking two weeks later. His most striking symptom enabled him to claim the world record for one and a half hours of continual spasm of the hands and face.
Getting rid of too much carbon dioxide removes carbonic acid from the blood, making it more alkaline. Always up for a challenge, Jack decided to investigate the effects of making the blood more acid. He tried the direct method of drinking hydrochloric acid, but noted that this had a tendency to dissolve his teeth. Even a one per cent solution corroded his throat so he never cared to drink more than half a litre at a time. His calculations indicated that it would take seven litres to achieve a significant change in the acidity of his blood. He turned instead to smuggling the acid into his body ‘under false pretences’ by drinking ammonium chloride, which breaks down internally, liberating hydrochloric acid. The acid combines with other chemicals in the body, giving off carbon dioxide. Soon he was generating seven litres of carbon dioxide an hour. After several days of taking ammonium chloride he could hardly walk. A colleague found him ‘drunk’ on the stairs and rushed to his aid. ‘It’s nothing,’ Haldane assured him. ‘It’s just that I’m only eighty per cent sodium haldanate at the present moment.’
To neutralise the acid and make his blood more alkaline again he hyperventilated and swallowed eighty-five grams of bicarbonate of soda. This made his liver fizz like a ‘Seidlitz’ powder and led to a preoccupation with trying to breathe.
Pregnant women and their babies sometimes suffer from tetany because their blood becomes too alkaline. They are given diluted ammonium chloride and rapidly recover, thanks to Haldane’s appetite for self-experimentation which, as we shall see, was far from satisfied.
Blood transfusion, 1828. Hopefully the donor’s blood group was compatible with the recipient’s.