by Burch, Druin
The European trial was published in 1994. It showed that AZT, a drug with significant side effects and to which HIV could rapidly develop resistance, did nothing to increase the survival of HIV-positive patients in the early stage of the disease, or to slow their progression to AIDS. The American optimism was the result of an earnest desire that a drug should help, not a thorough examination of whether it actually did. It turned out to be wrong.
The push from AIDS activists to shortcut lengthy trials continued. Another drug, dideoxyinosine, was released under what was called a ‘parallel track’. As well as being used for a clinical trial, in comparison with the existing AZT, it was also released to those outside the trial who wanted to take it. The effects were predictable. Many people were happy to take the drug without definite proof that it worked, judging that it was more likely to do them good than harm. And there were so few left who were willing to be uncertain, that the trial almost collapsed for lack of participants. ‘The current turn of events reminds us’, wrote a medical commentator at the time, ‘that we cannot obtain highly reliable evidence about a new treatment without the full co-operation of relatively large numbers of suffering human beings.’ AIDS patients found it difficult to co-operate. Their prejudice that new drugs were likely to work was too strong.
The scepticism that many doctors have so slowly and painfully acquired is not something widely shared outside the profession. Yet the idea that even the most reasonable-sounding theories should be subjected to tests probably has more potential to make the world a better place than all the drugs that doctors possess. Economics, politics, social care and education are full of policies that are based on beliefs held as a matter of principle rather than because they are supported by objective tests. Humility, even more than pills, is the healthiest thing that doctors have to offer.
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1 The germ warfare site at Camp Detrick, which Merck was involved with while developing streptomycin, was converted to attack cancer as a result.
24 Revolutionary Confidence
SOMETIMES, WHEN TWO strong and opinionated men do battle, it is best to be standing well clear. At a distance of a little over two centuries, we are well placed to relish the explosive collision of William Cobbett and Benjamin Rush.
Rush came into the world at Christmas 1745, a little way outside of Philadelphia. Brought up by an evangelistic and hard-working mother, he went into medicine at the age of fifteen. Having already graduated from the College of New Jersey (now Princeton), he studied with leading Philadelphia doctors. The College of Philadelphia, founded in 1749 by Benjamin Franklin, was the first medical school on American shores, but even in the eyes of the most partisan patriots it was not the pinnacle of medical science. Rush studied there and then moved on. For two years from 1766, he was at Edinburgh, the leading medical school in the English-speaking world. He completed his studies with stints in Paris and London before returning to Philadelphia, where he was promptly appointed professor.
Within five years of returning to America Rush was well established, as a politician as well as a doctor. An early abolitionist, he campaigned against slavery in person and print. Thomas Paine’s successful 1776 pamphlet Common Sense, which did so much to promote the American Revolution, was encouraged, edited and named by Rush. The same year, aged thirty, Rush was elected to the Second Congressional Congress, signed the Declaration of Independence (chiefly written by his friend Thomas Jefferson), and married the sixteen-year-old daughter of another signatory.
During the subsequent war, Rush showed his willingness to risk his life and lose his friends over issues of conscience. Attached to the Continental army, he provided medical support at many of the major battles. It was at Trenton that ‘for the first time war appeared to me in its awful plenitude of horrors’. Thereafter he was at Princeton (where he found friends dying on both sides of the conflict), Brandywine and Germantown. He was with the army during its winter rest in Valley Forge. When Rush wrote to Washington, complaining of the manner in which John Shippen – Rush’s old teacher from Philadelphia, now surgeon-general – was organising the army’s medical services, Shippen was sacked and court-martialled. Soon afterwards Rush wrote to Patrick Henry, governor of Virginia, suggesting that Washington too was incompetent and ought to be removed from his command. This time Rush came off worst. He left the army and returned home. His next war began in 1793, when yellow fever invaded Philadelphia.
William Cobbett was there at the same time, having arrived by a very different route. ‘I do not remember the time when I did not earn my living,’ he wrote. ‘My first occupation was driving the birds from the turnip-seeds, and the rooks from the peas.’ At the time he was barely big enough to make it over a country stile. Later, in 1774 at the ripe age of eleven, Cobbett decided that he wished to work at the Royal Botanical Gardens at Kew, on the edge of London. His decision to go to Kew was impulsive. The eleven-year-old Cobbett set off from his father’s farm in Farnham, Surrey, and walked the thirty-five miles to Kew Gardens near Richmond. His unexpected profits from the adventure came when he rashly spent his pennies, not on food, but on a book. ‘The title was so odd that my curiosity was excited. I had the threepence, but then I could have no supper.’ Cobbett chose the book and went hungry. It was A Tale of a Tub, Jonathan Swift’s satire on religion, medicine, politics, and oppression. That first reading of it became, according to Cobbett’s later accounts of himself, ‘what I have always considered a birth of intellect’. When a later impulse took him into the army nine years later, he used his free time to pursue his love of reading. Posted to Canada, he became a self-educated and forcibly angry sergeant major, provoked by the corruption and injustice around him. After collecting evidence of embezzlement, Cobbett discovered that the officers he was trying to bring to justice were manoeuvring to destroy the evidence and have him framed for treason. He fled to Paris in March 1792, taking his new wife with him. For six months there he was happy, but the Revolutionary bloodshed and the prospect of a war with Britain caused him to flee once again. This time he chose America.
He ended up in Philadelphia. In 1793 it was the nation’s capital. Including the suburbs that surrounded it, it was also the largest city, thronged with 40 or even 50,000 souls. Medical opinions were easily gained and, if you wanted someone who held a degree in the subject, you had eighty fully qualified physicians to choose from.
Benjamin Rush, one of them, was the first to suggest that 1793 was seeing a yellow fever epidemic. A feverish illness, characterised by fatal bleeding in many of those affected, it is now known to be a virus spread by certain mosquitoes. From July 1793 it was striking people down on Philadelphia’s squalid waterfront. They tended to be the poorest and the most destitute. Their deaths attracted little attention. In August, Rush began seeing cases amongst his own patients. They prompted him to ask his colleagues about their own recent experiences. On hearing that yellow fever was becoming widespread, Rush began pointing out that things were likely to get worse. His views were unpopular. Rush ‘was immediately ridiculed and attacked from all sides as an alarmist’. That was despite the fact the city had been struck many times before, from 1699 through to 1762. Fortunately, unpopularity did not scare Dr Rush; he was accustomed to it. He gathered infamy as well as admiration in the course of his many missions, as eager to change people and as willing to fight them as Cobbett. Prison reform, free schooling for the poor, women’s rights and kind treatment for the mentally sick – many of Rush’s causes were noble. Their desirability, not their practicality, was what appealed to him. If something was right, it was worth pushing for, even if there was no real prospect of success. You never knew until you tried. ‘As the War Office of the United States was established in the time of peace,’ Rush declared during one of his campaigns, ‘it is equally reasonable that a Peace Office should be established in the time of war.’ It never has been.
Despite Rush’s training at Edinburgh, London and Paris, he felt European doctrines were not suited to America. Old theories
seemed to lack power in the New World. Medicine seemed not as effective, and medical beliefs not so accurate, as he had been taught to believe. Like many before him, Rush leapt from this potentially promising realisation into disaster. Rather than questioning the values of theories, and exploring better ways to test them, he came up with his own.
His favourite concerned fever. Rather than representing different diseases, as he had been taught, Rush felt that fever was disease. Clearly, he decided, it was something to do with the blood, which was hot. ‘I have formerly said there is but one fever in the world. Be not startled, gentlemen, follow me and I will say there is but one disease in the world.’ In itself, Rush’s theory was neither more effective nor more useless than those of the Scots, English and French who had trained him. In some ways it was not that different either. What mattered was the way he put it into practice.
When yellow fever had last gripped Philadelphia, in 1762, Rush was in his first year at medical school, too inexperienced to form much of an impression. Things were different now. Of the first five patients that Rush saw with yellow fever, four died. Their treatment had been, by contemporary standards, fairly benign. They were given a little mercury to encourage urination and diarrhoea (both of which made them less likely to survive). Then another laxative, to encourage a bit more diarrhoea (worsening their dehydration). Finally, as though to compensate for their medical treatment a little, they were given some food and drink.
Four of the five dying struck Rush as unconscionable. God, he felt, was always willing to provide a cure if only there was someone pious and energetic enough to seek it out. Aflame to do so, Rush read everything he could on yellow fever. He found an account from a doctor working in Virginia, fifty years before. Cutting open his patients after they died, their physician reported that their guts had been full of blood.
Rush had an epiphany. A fever was caused by blood, too much of it. Yellow fever was characterised by people’s blood spilling out of them – from their noses and gums, from small wounds and internally into bruises and into their guts. They were obviously dying from an excess of blood! The way forward was clear and he had the pioneering spirit to blaze it.
I preferred frequent and small, to large bleedings in the beginnings of September, but toward the height and close of the epidemic, I saw no inconvenience from the loss of a pint and even 20 ounces of blood at a time. I drew from many persons 70 and 80 ounces in five days, and from a few a much larger quantity.
Eighty ounces works out at about 2.5 litres, roughly half of the amount of blood within a man’s body, and more of a woman’s. Rush said that he never once lost a patient that he was able to bleed on seven different occasions. A commentator has pointed out that this was not surprising, given that blood was generally taken on a daily basis and yellow fever worked itself out within seven to ten days. One might also have reasonably observed that anyone able to survive seven encounters with Dr Rush was not going to be snuffed out by anything so mild as a major infective illness.
People fled Philadelphia. Up to half of them left the city while the epidemic was under way. One was Thomas Jefferson, who reckoned that a third of those who picked up the infection quickly died of it. A painstaking modern attempt to find out what happened to Rush’s patients suggested that their chances were significantly worse. Only around half survived.
Never anything other than courageous, and committed to trying to make the world a better place in the ways he saw open to him, Rush refused to quit his post. That put him in a minority, and a dangerous one. Of the doctors who stayed, ten died. At one point there were only two others, besides Rush, left living in the city. The worse the disease got, the more Rush’s conviction grew that he held in his hands the power to save people. ‘Americans are tougher than Europeans,’ taught Rush. ‘American diseases are, correspondingly, tougher than mild European diseases; to cure Americans will require uniquely powerful doses administered by heroic American physicians.’ He increased tenfold the doses of mercury and of laxatives that he gave to his patients. He recommended that the majority of their blood be removed, up to 80 per cent of what they contained. When he felt ill himself, one day in September, he swallowed some laxatives and had a colleague remove over a pint of blood. The next day he felt better and returned to tending the sick. Their blood covered the front yard of Rush’s house, and the flies swarmed to it. ‘Never before’, said Rush, ‘did I experience such a sublime joy as I now felt in contemplating the success of my remedies.’ In the hundred days that yellow fever besieged the depopulated city, over 4,000 of those who remained died.
When the epidemic finished, Rush’s joy continued. His theories were proven and his powers demonstrated. ‘Depletion therapy’, as it was called, became something that Rush evangelised. It worked for pretty much everything, he explained, but it was especially good for yellow fever. Since Philadelphia went on to have annual epidemics over the next few years, he had reason to do everything he could to persuade people of the value of his discovery.
Rush burnt with a sense of mission. Part of it came from his sense of religious duty, the rest from his conviction that the New World offered an opportunity – practically required a duty – for forward-thinking men to conquer the limitations of the natural world. Other doctors placed ‘undue reliance upon the powers of nature in curing disease’. Action, felt Rush, was what was needed, a willingness to practise in medicine what the new Americans were doing in politics, a willingness to be ‘heroic, bold, courageous, manly, and patriotic’.
Oliver Wendell Holmes later described Rush’s position with damning sympathy:
His mind was in a perpetual state of exaltation produced by the stirring scenes in which he had taken part . . . But he could not help feeling that Nature had been a good deal shaken by the Declaration of Independence, and that American [medical] art was getting to be rather too much for her – especially as illustrated in his own practice.
William Cobbett, writing about the yellow fever epidemics from 1793 onwards, was not so charitable. ‘Bleeding a man to death, no matter what the disease,’ he suggested, ‘could not be the proper method of saving his life.’ The actions of Rush appalled him, and wielding his satirical newspaper, the Porcupine’s Gazette, he rode into battle. There is no doubt that part of Cobbett’s anger was due to Rush’s political beliefs, and the doctor’s tendency, like Jefferson, to overlook the worst parts of the French Revolution in order to praise its ideals. Having watched the slaughter in Paris at first hand, Cobbett was in no mood to keep quiet while another needless massacre took place. And if Rush was skilled at drawing blood with a lancet, so was Cobbett with his pen.
In this case the truth, as well as the louder voice, belonged to Cobbett. The Porcupine’s Gazette ‘was the most widely read newspaper in the United States’. That was quite an achievement for a publication whose editor was patriotically English, and whose stingingly satiric views were English to match. Even George Washington read it, and sent copies to friends. ‘Making allowances for the asperity of an Englishman,’ he said to one, ‘for some of his strong and coarse expressions; and a want of official information of many facts; it is not a bad thing.’
Cobbett mocked Rush’s use of mercury and accused him of ensuring that tens of thousands of American lives were lost through poisoning and blood loss. ‘The mode of treatment advised by Doctor Rush cannot, in the yellow fever, fail of being certain death,’ he wrote. A libel suit followed. It was brought by Rush in the autumn of 1797. The court hearing, however, was extensively delayed – possibly due to other enemies of Rush, keen to prolong and publicise his ordeal.
Cobbett’s attacks successfully destroyed Rush as a doctor; they failed to accomplish the better alternative of improving him. Jefferson had written to Rush on the importance of tolerance between those who disagreed. ‘With a man possessing so many other estimable qualities, why should we be dissocialized by mere difference of opinion in politics, in religion, in philosophy, or anything else?’ Despite their mutual zeal for refor
ming others, this was not a view that appealed much to Cobbett or Rush.
Thursday 12 December was a cold day in Virginia. Washington rode around his farm in rain, hail and snow, then had his evening meal without changing his wet clothes. The next day he felt unwell and spent it quietly, staying mostly indoors. In the evening he read aloud to his wife before going to bed. Between two and three in the morning, Washington woke her to tell her that he felt worse. In the morning, the Saturday, Washington asked his plantation supervisor to bleed him. The man took away around a third of a litre of Washington’s blood. Before lunchtime the first doctor arrived. He bled Washington twice more, removing another litre and a quarter litres (over two pints) of blood. When the next doctor arrived in the middle of the afternoon, Washington was bled another full litre. Mercury was given in order to induce diarrhoea. Repeated doses of drugs were used to make Washington vomit. Hot cups were applied to his flesh to raise up large blood-filled blisters.
Washington probably contained about five litres of blood, of which over half was directly removed by bleeding. The vomiting, diarrhoea and blistering helped dehydrate him further, as did the fever and inflammation that came from being unwell in the first place. Towards the end of the Saturday, the physicians now crowding around Washington’s bed noticed that his blood seemed different. Rather than flowing with brisk freedom when a vein or an artery was opened, it was thick and sticky and only oozed away slowly.
‘Pray take no more trouble about me,’ Washington told his doctors. ‘Let me go quietly.’ He died a little after ten o’clock on the Saturday evening.
Writing the following February, William Cobbett reckoned the total amount of blood removed came to ‘108 ounces, which is nine pounds, and which makes in measure, nine pints, or one gallon and a pint!!!’ He thought it deserved a few exclamation marks. There is every reason to distrust his higher total, but to respect the feelings that led him to inflate it. Washington had successfully brought America into peaceful relations with Britain, fighting off the efforts of the more pro-French republicans like Jefferson. To Cobbett he was something of a hero. And Washington’s death was hastened, if not entirely caused, by the attentions of his doctors.
