In this series, AMS Healthcare addresses the challenges facing healthcare today – particularly in light of the COVID-19 pandemic. The AMS Community promotes compassionate care, development of the leadership needed to realize the promise of technology and the understanding of how our medical history influences the future of our healthcare. A new piece will be posted every Friday on Healthy Debate.
Amid unregulated zeal for experimentation during the scientific revolution, Alexander Pope cautioned in 1709 that a “little learning” is dangerous. Drink deeply from the spring of knowledge, he cautioned, because “shallow draughts intoxicate the brain.”
Owing to the novelty of COVID-19 and the unprecedented speed of research to defeat it, investigators and policymakers have been flooded with new information. They are under enormous pressure to deliver immediate solutions to end the pandemic. The temptation to ignore Pope’s advice and cut corners on the science is understandable but imbibing a “little science” risks lives and wastes resources.
Already, our academic system for assessing the validity of new scientific knowledge has missed what have been unfounded, even fabricated, conclusions on the novel virus. This has led policymakers and media outlets to sometimes publicize premature or erroneous findings. Shallow draughts indeed.
Both the World Health Organization (WHO) and French health minister, for example, warned against the use of ibuprofen for COVID-19. The advice was based on an anecdotal report of symptom aggravation by a specialist in France and a pre-print that outlined only a hypothesis. Clinicians and scientists fought back, compelling WHO to reverse its position. Intoxication begets confusion.
The question of how to balance scientific rigor against moral and social pressures is not new. Robert Koch, the renowned German experimentalist, struggled with this issue. He was celebrated worldwide when he identified the pathogen for tuberculosis (TB) in 1882, then called the “captain” of all diseases. Koch’s famous experimental postulates still infuse disease research with scientific rigor.
Predictably, the world rejoiced again when Koch announced a few years later that he had developed a cure for TB that he called tuberculin (today known as Old Tuberculin). Faith in Koch’s methodological rigor led many to take its effectiveness and safety for granted. Uncharacteristically, he withheld the components of tuberculin and his data – partly with an eye on a future patent but also because his own tests on patients were inconclusive (at least one died from the injection before the announcement). Koch was hesitant to release his formula because of this risk. He privately shared samples and instructions for administering the injectable therapy with trusted colleagues internationally. The Lancet conceded that early publication without proofs was “forced on him by the extraordinary anxiety” around tuberculosis fatalities.
Koch stated that his motive for publishing inconclusive results was to promote “international competition of the noblest kind” but historians and commentators also point to other external demands: nationalist pressure from the German government, Koch’s rivalry with Louis Pasteur, and his financial strains, deteriorating health and marital troubles.
Historian Bert Hansen has analyzed “the frenzy of enthusiasm” among the press and public after Koch’s announcement. Wealthy tuberculosis sufferers traveled to Berlin to demand the new cure. The euphoria soon gave way to disappointment and criticism as more deaths were attributed to the therapy. Despite his faith in its potential, Koch’s therapy was discredited due to its impurities and toxicity. Medical journals like The Lancet eventually published corrections and warnings against tuberculin. Scottish surgeon Watson Cheyne, for instance, cautioned that tuberculin “exposes the patient to a series of risks which are of grave importance.” Tuberculin, however, did lead researchers such as Clemens von Pirquet and Florence B. Seibert to an accurate diagnostic test for TB still in use today.
The tuberculin fiasco illustrates the potential harm of research exceptionalism and media sensationalism to scientific research. Both help circulate a “little science” during the current COVID-19 crisis.
As fears around COVID-19 increase, so too has the temptation to except some studies from bearing the burden of scientific standards in order to meet urgent demand for a vaccine. Koch’s announcement resembles today’s “pre-print” – a public posting of academic research not yet subjected to rigorous peer review. Pre-printing facilitates more rapid dissemination of findings that might hasten the work of other researchers (Koch’s own professed motive). Nevertheless, pre-prints may be the 21st century’s version of Pope’s “little learning” and we ought to take seriously the risks of reduced oversight.
Is peer-review the antidote to shallow draughts? Not necessarily. Like in Koch’s time, science today is not immune to external pressures that jeopardize rigor and safety. Competition for recognition and funding is fierce and investigators often feel compelled to pre-print inconclusive research.
History has a tendency to repeat itself. Recently, The Lancet retracted a paper on hydroxychloroquine and chloroquine treatment for COVID-19 after data were exposed as fraudulent. The study, which appeared to show that the drug increased deaths in COVID-19 patients, led to global disruption of many legitimate trials. Just as Koch initially kept his cure’s components secret, the faulty data in this study, provided by one of its authors – Surgisphere CEO Sapan Desai – was withheld from other co-authors and third-party auditors. We must continue to drink deeply.
Currently, 11 candidate vaccines are under clinical investigation. Sensationalist media coverage of COVID-19 increases pressure on these research teams as well as public health authorities. The media spotlight around Koch’s tuberculin therapy was so bright that newspaper headlines asked unfair questions with shallow implications: “Will it Cure Cancer, Too?” Recently, officials at Germany’s national disease control agency (the Robert Koch Institute) stated prematurely that life could “fully return to normal” once a vaccine is found. The statement sparked news coverage around the globe that has distorted public expectations. Intoxication begets false promises.
In critical situations, we trust scientific and public authorities to guide us. To publicize or recommend interventions that lack established clinical merits threatens to erode that trust. Rather than broadcasting a “little science”– which has potential to overwhelm policymakers and mislead the public – our scientific community is within its rights to concentrate its limited resources on publishing coordinated, rigorous, and verified research. We should all drink deeply.