Barney Gumball: Covid-19, Hydroxychloroquine and the Tragedy of Ignaz Semmelweis

This is an article by Barney Gumball, PhD.

The pandemic has been a tragedy on many levels. Of course there is the tragedy of the deaths, direct and indirect. There is the tragedy of lives ruined by job losses, businesses going to the wall through no fault of the management or owners but by government diktat. There is the tragedy of the stolen futures of children through the shutdown of a functional education system. There is the tragedy of the accumulation of a debt pile of a magnitude more typical of a major war that we will all be paying off for decades either through increased taxes or through the stealth of inflation. This burden will likely fall more heavily on our children and grandchildren, who, through the aforementioned failure of the education system, will be less well equipped to cope with it.

Although much of the burden of this calamity will fall most heavily on the children, they have at least been spared the worst consequences of the virus. Any death is tragic, but the death of a child or young person is especially so because of the lost potential years of productive, good quality life. During this pandemic the perpetually offended online outrage mobs attacked anyone who dared point out this obvious truth, claiming all lives are equal and no cost is too great to save a single life.

However the cost-benefit analysis forms the basis of the method used by the National Institute for Care Excellence (NICE) when assessing the cost effectiveness of new medical treatments in the form of the metric ‘quality-adjusted-life-years’ or QALYs. In QALYs terms at least, by sparing the young this pandemic has been much less severe than it would have been had it affected young and old equally, or worse, the young disproportionately. One of the great triumphs of modern medicine and public health programs has been the reduction of infant and child mortality. In QALYs terms, reducing infant and child mortality provides the greatest ‘bang for the buck’ because of the potential for each child saved to live many decades of good quality life. Much of this progress has been won by advances in vaccination which have for example eradicated the scourges of polio and smallpox among others. But other simpler measures such as improved sanitation have also played a major role in this progress.

Undoubtedly though, all of these improvements have the scientific method to thank for providing the scientific understanding that enabled this progress and set the ‘age of reason’ apart from former times, characterized as they were by superstition and belief in ‘miasmas’, ‘bad airs’ and so forth. Through the application of reason and scientific method by men of science such as Jenner, John Snow of Broad Street cholera outbreak fame, Pasteur, Lister and Semmelweis were these advances made. Many in Britain will likely have at least a vague idea of what most of these men did in the cause of reducing mortality, however the last name Semmelweis, is likely to be obscure for many. This is unfortunate as his story provides a timely and salutary lesson, of which I will have more to say.

Given the unparalleled success of the scientific method at saving lives, writing as a scientist myself I am dismayed by the further tragedy of the apparent loss of reason, the suspension of the scientific method and the proliferation of irrationality and fear. The latter has been amply stoked by a media who palpably salivate at the prospect of running more fear-mongering stories, no matter how anecdotal or tenuous the supporting evidence. In the early days of the escalating crisis in March so many stories and rumours were circulating that it became difficult to know what information to trust. One particularly shameful trend was the media’s ghoulish pursuit of stories about younger people succumbing to the virus with a gleeful implied subtext of ‘see, told you so, it’s not just killing the old’.

Tragic as those cases were, as the pandemic has evolved, it has become inarguable that, save for extremely rare cases often with special circumstances, the virus spares the young. It is said that the first victim of war is the truth and in this respect the early days of the crisis felt like war. At least the commonsense advice on frequent hand-washing was constantly reinforced, and the British government at least, announced publicly that masks were of no use outside of clinical settings. When the abrupt U-turn on the mask guidance occurred, it was notable that the hand-washing message was no longer forcefully reinforced. The narrative shifted and to my mind at least it seemed as though the mask had become the new talisman to ward off the evil Covid miasma at the expense of the commonsense hand-washing and distancing message.

One of the stories that was circulating at that time concerned the efficacy of an old anti-malarial drug chloroquine, perhaps now better known by its derivative hydroxychloroquine. Anecdotal reports out of China and South Korea suggested that positive results in treating symptomatic cases had been observed in those countries. The academic literature from the time of the SARS outbreak in 2005 suggested anti-viral efficacy, in-vitro at least. A mechanism of action as an ionophore had been proposed. In the early stages of the pandemic a French professor of medicine in Marseille, Didier Raoult, reported shortening of the duration of infection and better outcomes in a small cohort of patients by use of hydroxychloroquine (in combination with the antibiotic azithromycin). Raoult’s work was guardedly well received at first. Some commentators critiqued the small numbers involved in the study but Prof. Raoult could hardly be blamed for this in the exponential growth phase of a pandemic. Reports on his work tended to conclude with that stock phrase used to manage expectations in reports about potential medical breakthroughs – ‘more research needed’.

Nonetheless, initially the prospect of effective treatment by inexpensive, off-patent drugs with decades long history of safe use in several indications including malaria was enthusiastically received. It was enthusiastically reported by the media that countries were stockpiling them and production was being increased.

In the West at least, this all changed on the day of the White House briefing at which President Trump described chloroquine/hydroxychloroquine as game-changers. Now it was political and overnight the narrative changed. Led by Anthony Fauci the medical establishment in the US were now hell bent on discrediting the drugs, using them as a bizarre proxy for attacks on a president that they despised. From this moment on any rational debate about the merits or otherwise of these drugs was impossible and potential beneficiaries of them were henceforth pawns in a political game. Clinical trials were hurriedly put together and seemingly at least contrived to show no benefit by only treating already very sick, hospitalized patients whereas the purported mode of action of the drugs suggested that they should be used for prophylaxis in newly diagnosed cases. The media seized upon a Lancet paper that purportedly showed that the risk of serious cardiac adverse events outweighed any benefit. Their barely concealed delight at one of the world’s foremost medical journals discrediting the president was palpable. So when a few weeks later, following an investigation into irregularities in the data and its sources and the uncovering of a shady company behind the research, the Lancet withdrew the paper, there was barely a whimper from the media.

Nonetheless, the state Governor of New York, Andrew Cuomo, went so far as to issue an executive order banning the prescription of chloroquine or hydroxychloroquine to Covid-19 patients in New York, effectively denying severely ill patients these treatments. That despite anecdotal evidence from physicians who were reporting good outcomes with the use of these drugs. They were studiously ignored, or worse, attacked for being reckless and irresponsible and ‘putting lives at risk’. But consider for a moment that the anecdotal data were the truth. Consider the deaths that could have been prevented had it turned out that these drugs were the game-changers that President Trump claimed?

Cuomo is of course a politician and so the politicization of these drugs to score points against a despised rival would be second nature to him. But surely, eminent men of science and medicine such as Dr Fauci and others such as the editorial board of the Lancet and other esteemed medical journals would never stoop so low as to allow their clinical and scientific judgment to be corrupted by partisan politics. Would they? After all these people are the elite of the medical profession, they have taken the Hippocratic oath and signed up to a code of ethics. Surely they are beyond reproach and would not allow patients in need to become pawns in a game of political point scoring and harmed by the withholding of a potential life-saving treatment in the pursuit of their own political ideology or egotistical ends?

This brings me back to the salutary tale of Ignaz Semmelweis. Semmelweis was a Hungarian-born obstetrician who by accidents of history in 1846 began working at the Vienna General Hospital as deputy of the obstetrics department. The organization of this department was into two separate clinics, separated only by an ante-room. The first clinic was attended solely by doctors and doctors in training, whereas the second was attended solely by midwives. The infant and maternal mortality rates in the first clinic was three times that of the second. This discrepancy was persistent and well known both within and outside the hospital. The overwhelming cause of deaths in the first clinic was ‘puerperal’ or ‘childbed’ fever. So well known was the difference in mortality rates that expectant mothers would beg to not be admitted to the first clinic. Semmelweis, with impeccable scientific method and logic, and a humanitarian concern to alleviate suffering and prevent infant and maternal mortality, set out to establish the source of the discrepancy, and the puerperal fever itself.

Several theories had previously been promulgated to explain the discrepancy, but little attempt at actual scientific investigation had been made prior to Semmelweis. These included the theory that the first clinic was overcrowded compared to the second; the theory that the first clinic was more prone to ‘miasmas’; the theory that patients succumbed to fear on hearing the regular approach of the priest with his bell to administer the last rites to the latest unfortunate victim.

Semmelweis dispensed with the first theory of overcrowding from the simple observation that the second clinic was often more crowded, not least because expectant mothers, knowing about the higher mortality of the first clinic, begged to be admitted to the second, so overcrowding could not be the cause.

Similarly, Semmelweis dispensed with the second theory of ‘miasmas’ by the observation that the clinics were adjacent and shared the same atmosphere.

The third theory of death from fear induced by the approach of the priest was a somewhat circular argument that could probably have been dispensed with through logic alone, but Semmelweis nevertheless deployed his ingenuity to falsify it. He instructed the priest to change his route and to silence his bell. After some time spent observing this new ecclesiastical regime it became clear that no change in the mortality rate occurred and Semmelweis was able to dismiss this theory also.

Having refuted all of the prevailing theories, Semmelweis’s breakthrough came when a physician friend of his succumbed to an illness symptomatically identical to puerperal fever following a finger puncture with a scalpel during performance of an autopsy. As it turned out, the doctors and trainees of the first clinic performed autopsies on cadavers in a mortuary adjacent to the first clinic. Semmelweis reasoned that the source of puerperal or childbed fever was ‘cadaveric matter’ on the hands of doctors and trainees who had recently performed autopsies. The midwives of the second clinic never went to the mortuary or touched cadavers. Semmelweis further noted that the doctors did not wash their hands between performing autopsies and obstetric procedures. In what was a brilliant insight for the time, he ordered that the doctors should henceforth wash their hands in chlorinated water after performing autopsies and prior to attending the first clinic. This intervention gave witness to an immediate and dramatic fall in the mortality rate of the first clinic, even falling below that of the second. In modern terms, it is obvious that the cause of puerperal fever in mothers and infants was infection by a pathogen obtained from the cadavers but Semmelweis did this work many years prior to Pasteur’s germ theory of disease which made it all the more remarkable.

Now one might expect that Semmelweis’s advance would have been heralded and he would have been celebrated for his contribution to scientific progress, medicine and his humanitarian efforts to improve the human condition. Unfortunately this could not be further from the truth. Semmelweis’s superiors, understudies and colleagues resented the notion that they were themselves the source of puerperal fever and responsible for the high mortality rate. Under the cover of political unrest they first conspired to have him removed from his post in 1849. Their conspiracy was apparently driven by mere chagrin and bruised egos. Following this, Semmelweis became vocal in his condemnation of the medical establishment for their failure to acknowledge his findings and implement the simple life-saving expedient of hand-washing with chlorinated water. In his frustration he became a polemicist, writing frequent attacks on the medical profession, denouncing them for costing lives. This made Semmelweis a thorn in the side of the Viennese medical establishment and they secretly conspired to have him committed to an insane asylum. Under a pretext of a physician’s visit, Semmelweis was duped into attending the asylum where he was forcefully detained. He immediately realized what was happening, resisted and received a beating from the guards. He was overpowered, placed in a straitjacket and imprisoned in a cell where he developed sepsis from his wounds and died days later.

By the standards of medical evidence of the day Semmelweis’s data and methods were exemplary and have stood the test of time. His work was all the more remarkable because it preceded Pasteur’s germ theory of disease and the modern development of statistics which is supposed to underpin modern ‘evidence based medicine’. What we find in the tragedy of Semmelweis is a story of scientific method par excellence and impeccable logic on the one hand; and hubris, egotism and plain malevolence by an established elite under threat of exposure of their incompetence on the other. Indeed an establishment only too willing to debase their Hippocratic oath, their code of ethics and their humanity to save face and defeat their critic, irrespective of the truth. The women and infants of the Viennese General Hospital were made into mere pawns. Semmelweis at least seemed to understand the QALYs cost-benefit analysis of saving the lives of infants and their young mothers. The cost was a mere chlorinated water solution. Apparently this was too great a cost to bear for the medical establishment.

Surely such a sordid tale could not be repeated in this enlightened age? Could chloroquine/hydroxychloroquine be the chlorinated water of today? Surely in our present age of reason we wouldn’t, even figuratively, label ‘insane’, or beat, imprison and allow to die those that might have identified and advocated a solution to the present calamity?

There is a certain poetic irony in Semmelweis’s story in that he was the father of manual sanitation and disinfection, something that we were being educated on around the clock at the beginning of the pandemic until the talismanic emergence of the infallible mask. There is also irony in the contrast between the politically motivated, seemingly unscientific efforts to discredit a potentially effective treatment for Covid-19 merely because of collective hatred of the person advocating for it, whilst there is every indication that rigorous standards of evidence will be relaxed and regulatory corners will be cut in the ‘race’ for a vaccine. Meanwhile, the virus just continues doing its thing, implacable to human intervention.

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