It took years for a Hungarian physician's insight, which saved lives, to become common infection control practice. But today, in the anxiety over Covid-19 treatments, we may be rushing into impatient acceptance before they are properly reviewed.
On March 20, as millions of people around the world turned to the homepage of Google, they would have seen the cartoon of a bald-headed mustachioed man in a bow tie; the cheerful doodle belied the real-life tragedy of this Hungarian physician named Ignaz Semmelweis.
Born in 1818, Dr Semmelweis studied and practised obstetrics in the maternity clinic at Vienna General Hospital after graduating from medical school. The turning point in his life came when he was struck by the high death rate in a maternity ward that was staffed by physicians and medical students: 13 per cent to 18 per cent of new mothers were dying of childbed fever, also known as puerperal fever. This was in stark contrast to a ward that was run by midwives where only about 2 per cent of women died of the same condition.
Dr Semmelweis delved into it without making much headway until the death of a senior colleague, Professor Jakob Kolletschka, from an overwhelming infection after he accidentally cut himself with a scalpel used in an autopsy of one of the women.
In an account published many years later, Dr Semmelweis wrote: "Totally shattered, I brooded over the case with intense emotion, until it crosses my mind... that childbed fever and the death of Professor Kolletschka were one and the same... The fact of the matter was that the transmitting source of the cadaver particles was to be found in the hands of the students and attending physicians."
The physicians, Dr Semmelweis realised, were unlike the midwives because they carried out post-mortems on women who died of childhood fever. Dr Semmelweis believed his fellow physicians were carrying invisible "cadaver particles" on their hands from the corpses they had dissected, and these same unwashed hands were delivering babies in the ward. He did an experiment: He made anyone examining a woman in that ward wash their hands in a chlorinated lime solution.
Within months, the dramatic results of this simple change were apparent: The maternal mortality rate dropped to 1 per cent to 2 per cent, matching that of the midwives' ward.
Dr Semmelweis' momentous discovery was an idea before its time. Diseases then were thought to spread by some toxic miasma drifting through the air. Dr Semmelweis was claiming something radical - that some invisible particles on doctors' hands were to blame - which did not go down well with his fellow doctors and many resisted his theory.
Dr Semmelweis, who did not speak German well, largely shied away from speaking about his findings at medical conferences, and as he did not publish the details of his observations and conclusions in medical journals, only those who had seen the results of his hand-washing experiments first-hand had good reasons to accept them.
When he did finally publish his findings some 17 years later, it was in the form of a rambling book that was roundly criticised as unfocused and lacking in rigorous scientific reasoning. Unable to contain his bitterness, Dr Semmelweis inserted salvoes of abuses at his detractors within the pages and accused them of murdering mothers. The response of the medical community was either to attack it or - just as damning - to ignore it.
At the age of 47, he suffered a mental breakdown and was admitted to an asylum. Two weeks later, he was dead. It was thought that he died from sepsis after a wound on his hand became infected.
It was only much later after his death that he was both lionised as "the father of infection control" who revolutionised medicine with that singular act of hand-washing, and mythologised as an archetypal tragic Greek hero overwhelmed and destroyed by forces beyond his control.
But in many ways, this hero had brought it upon himself. Among the various salutary lessons that his life has for us is the importance of being able to effectively communicate scientific findings and their implications - something that, now more than ever in this time of the coronavirus and the existential threat it carries, demands our attention.
BAD AND GOOD SCIENCE
As chance would have it, on the very same day that Google honoured Dr Semmelweis on its homepage, a paper appeared in the International Journal of Antimicrobial Agents that reported the findings of a trial conducted in a research centre in Marseille of the drug hydroxychloroquine (an anti-malarial drug) among patients with Covid-19 infection.
Shortly after, United States President Donald Trump touted hydroxychloroquine as a "game changer" in a press conference. "It can help them, but it's not going to hurt them," he said. "That's the beauty of it."
It prompted an almost immediate caution by Dr Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, that the evidence for its efficacy is "anecdotal" and "not done in a controlled clinical trial". (President Trump had since gone on to say that he has been taking this drug as a preventive measure.)
The President's enthusiasm for the drug appeared to be largely based on that French study, which he apparently learnt of from Twitter. This small study, which was led by a maverick researcher, involved just 26 patients who received a combination of hydroxychloroquine and an antibiotic called azithromycin. In the final analysis, six patients were excluded, of whom three were transferred to intensive care and one died subsequently.
Of the remaining 20 with mild symptoms, it was likely that they would almost certainly have survived on their own, with or without taking these drugs. It was a hastily done study riddled with many methodological flaws and much criticised by experts in the field, one of whom wryly commented: "My results always look amazing if I leave out the patients who died."
The gold standard to test the efficacy of hydroxychloroquine is a large well-controlled randomised, double-blind clinical trial that would compare it with a placebo (an inert fake medicine that looks exactly like the test drug).
There must be enough patients who consent to participate in this trial and who would be randomly assigned to take either hydroxychloroquine or the placebo. The patients and the researchers who assess them are "blinded" - that is, they do not know who is getting the actual drug and who is getting the placebo. The results based on clearly defined outcome measures are then compared using the appropriate statistical methods to ascertain whether the effects of hydroxychloroquine are significantly and clinically better than the placebo, and not simply due to chance and the noise of human variability.
The findings would be written up and submitted to a journal, where they would be reviewed by other experts to assess whether the methods, analysis and conclusions are sound. This process, which would invariably include further clarifications by the authors in response to the comments of the reviewers, is known as peer review, and is the main mechanism by which scientific journals serve as the gatekeepers between researchers and the rest of the world.
Journals generally take many months, even up to a year, to review and edit a complicated study. Once published, the paper will come under the scrutiny of the wider scientific community, and other researchers would carry out further experiments to support or disprove the findings - which explains why some say one of science's oldest pastimes is to call out the errors of other scientists.
So, good science takes time with this cycle of well-designed and scrupulously conducted studies, rigorous peer reviews, and replications with further studies. But in this desperate time amid so much suffering and dying, this caution and care can seem more like unnecessary dawdling and impediments than essential scientific imperatives.
The scientific community has responded to this sense of urgency and fast-tracked the scientific process for Covid-19 research so much so that everything has become a race.
Everything is sped up: the approval of protocols by ethics boards, the pace that researchers are driving themselves to finish their studies, and the rate that academic and medical journals are publishing these findings.
This desperate eagerness to embrace anything that promises to soften or take away the terror and suffering has its inevitable risks.
Shortly after President Trump's endorsement of hydroxychloroquine, the Food and Drug Administration (or FDA, the agency in America that is responsible for protecting public health by assuring the safety and efficacy of drugs and other products - the equivalent of our Health Sciences Authority) issued an Emergency Use Authorisation for its use in experimental Covid-19 treatment. This decision by the FDA was out of character, having been made with very scant evidence, and came under fire from scientists and physicians.
There were concerns that the indiscriminate use of hydroxychloroquine could potentially add to the death toll from Covid-19 infection because of its serious possible side effects - such as liver and kidney damage, heart failure and cardiac arrest.
And these fears were not unwarranted: A man in Arizona died (and his wife landed in intensive care) after self-medicating themselves with chloroquine phosphate, which was in a formulation sold to clean fish tanks. Similar poisonings have been reported elsewhere in the world.
It did not stop Brazilian President Jair Bolsonaro (an admirer of President Trump) from pushing his country's Health Ministry to recommend using hydroxychloroquine to treat even mild cases of Covid-19.
There is a term called the Semmelweis reflex, which refers to that very human tendency to cling to pre-existing beliefs and to reject fresh ideas that contradict them despite adequate evidence.
It is less likely that this will be the case at this time; in fact, the danger is quite the opposite. With our intense desire for an antidote that promises to return us back to the life we had before this pandemic, we might be just too impatient, to our own detriment.
• Professor Chong Siow Ann, a psychiatrist, is vice-chairman of the medical board (research) at the Institute of Mental Health.
We have been experiencing some problems with subscriber log-ins and apologise for the inconvenience caused. Until we resolve the issues, subscribers need not log in to access ST Digital articles. But a log-in is still required for our PDFs.