When Max von Pettenkofer shot himself to death in 1901, he left behind a storied career as a hygienist and bitter opponent of Robert Koch, the German physician and microbiologist who discovered the cholera bacillus, Vibrio cholerae. Von Pettenkofer, the founder of the Institute of Hygiene in Munich, disputed Koch’s germ theory of disease, which held that a germ is both necessary and sufficient to cause illness. Von Pettenkofer asserted that germs could only cause disease in the presence of a “local” or environmental factor.
The battle between the two men exploded into a bitter divide over the question of the infectivity of cholera. Koch and his fellow contagionists maintained that the bacterium was spread through the water. Von Pettenkofer and his localists believed that cholera was inhaled as a miasma, which arose from earth contaminated by sewage. Anxious to prove his theory that germs alone don’t account for disease, and in the midst of one of the deadliest cholera pandemics of the 1800s, Von Pettenkofer, asked Koch to send him live cholera germs. Koch complied with a vial swarming with cholera bacilli. Von Pettenkofer swallowed the vial’s contents before witnesses. Several days later he reported that not only did he not die, he suffered no lasting effects.
Von Pettenkofer would be proven tragically wrong about cholera’s route of transmission when the city of Hamburg decided not to filter the city’s water, leading to nearly 9,000 deaths. Only a handful of residents died in nearby Altona, which filtered its water through sand. But while von Pettenkofer was wrong about how cholera was transmitted, he was right that a germ alone is often insufficient to account for infection, disease and death. As Paul de Kruif wrote in his famous 1926 book Microbe Hunters, “Murderous germs are everywhere, sneaking into all of us, yet they are able to assassinate only some of us.” Over the years, Koch’s postulates regarding infection would undergo several modifications, as it became clear that pathogens need a vulnerable host in order to cause serious harm, as von Pettenkofer predicted. His theories would also influence our understanding of the importance of environmental factors to public health.
All of this history should sound uncomfortably familiar to anyone who has been following the course of COVID-19’s murderous path through different populations and locations and the bitter debates about how to stop it. As in the cholera wars of the 1890s, different theories about the spread of COVID-19 and methods for reducing the death rate have been marked not only by by scientific conflicts, but also by an increasing distrustful public, political upheavals and even riots. The debates over COVID-19 and the arguments of the past, in which different sides have failed to perceive the possibility that they might not have the whole story, may hold vitally important lessons for President-elect Biden’s COVID-19 task force. Hardened positions, which leave little room for uncertainty and nuance, undermine public trust as various assertions prove wrong.
In today’s COVID-19 wars, the global scientific divide leans heavily in favor of active, and sometimes even draconian, public health interventions, including widespread locking down of nonessential business, mandating masks, restricting travel and imposing quarantines. On the other side, some doctors, scientists and public health officials are questioning the wisdom of this approach in the face of massive unknowns about their efficacy and in light of the clear and growing evidence that such measures may not be working in some cases, and may also be causing net harm. As people are thrown out of work as a direct result of lockdowns, and as more and more families find themselves unable to cover their rent or food, there have been sharp increases in domestic violence, homelessness and illegal drug use.
The two sides of the COVID-19 war are illustrated by two documents, the John Snow Memorandum and the Great Barrington Declaration, which were posted online in October. The former represents the majoritarian position, which supports strict measures to limit human contacts and movements across the board. In the U.S., this approach has included shutting down public gatherings, restricting hotels and numerous small businesses such as restaurants and shops, and throwing millions of Americans out of work. The Great Barrington Declaration, the minority view, advocates “focused protection,” allowing younger and healthier individuals to continue life, work and going to school, while aiming more protective measures at the most vulnerable to the virus—the elderly, the institutionalized and other high-risk individuals. This approach has been employed most fully in Sweden.
Advocates on both sides have dug in, hurling dismissive and vitriolic attacks at individuals in the other camp. These attacks have caused serious reputational harm in some cases and led at least a few scientists to self-censor and avoid publishing data that could inform efforts to dampen death rates from both the virus and its remedies.
The first reported instance of intimidation occurred in China in December 2019, when Li Wenliang, an ophthalmologist at Wuhan Central Hospital, warned of a new infectious outbreak, and urged his colleagues to take protective measures. According to an accounting of the events, Li was “censured by hospital leaders and summoned to the Public Security Bureau in Wuhan, where he was forced to sign a statement in which he was accused of spreading false rumors and disturbing the public order.” Li would die on February 7, of COVID-19.
In the U.S., John Ioannidis, an epidemiologist and professor of medicine at Stanford University, was subjected to attacks, not at the hands of public officials, but his fellow scientists. Ioannidis has authored some of the most cited journal articles in medical history and was praised in a 2010 article in The Atlanticas possibly “one of the most influential scientists alive.” Yet he was pilloried when he published an opinion essay expressing concerns that we lacked data on the efficacy of draconian responses to the outbreak, such as lockdowns, and that such measures could cause their own harms. We read some of the obscene and defamatory e-mails that were sent to Ioannidis and his administrators and colleagues at Stanford. Numerous misleading claims were advanced in the press, including the charge that he had a financial conflict of interest related to a study of the prevalence of COVID-19 that he co-authored. But a fact-finding review by an external legal firm determined that Ioannidis did not have a financial conflict. Ioannidis would come under more fire when he published an analysis showing that the infection fatality rate of COVID-19 was far lower than initially reported. Later, the Centers for Disease Control and Prevention published similarly low rates (which varied by age group, time and location) and the World Health Organization published updated research by Ioannidis showing a low overall infection fatality rate.
In Sweden, where the minority view of the Great Barrington Declaration has been put into practice, several doctors report being bullied and their jobs threatened for speaking out against their country’s approach. In another case, Lonni Besançon, a French postdoctoral fellow at Linköping University, in Sweden, received multiple death threats after he made comments about Didier Raoult, the French researcher who claimed that hydroxychloroquine was effective for the treatment of COVID-19 Besançon said Raoult violated editorial standards for a peer-reviewed research article that was published one day after submission and that Raoult’s team had editorial conflicts of interest . Raoult’s work would soon be shown to be shoddy and possibly fraudulent.
These attacks and others like them have led at least some scientists to self-censor, for fear their contrarian positions would leave them open to reputational damage that could potentially threaten their careers. One epidemiologist told us the environment was “too toxic” to talk to us, even anonymously. The British journalist Laurie Clarke reported similar difficulties when she tried to interview epidemiologists who questioned the majoritarian views regarding population-based lockdowns. One expert told her via e-mail that “putting your head above the parapet is a dangerous thing to do at the moment”.
Even when experts are willing to raise their heads, publication bias can further reinforce group think. Stefan Baral, an epidemiologist and associate professor at Johns Hopkins Center for Global Health, reports that a letter he wrote about the potential harms of population-wide lockdowns was rejected from more than 10 scientific journals and 6 newspapers in April. Baral, a highly published public health expert, said that the rejections could be, in his words, “because there was nothing useful in there.” But, he adds, “it was the first time in my career that I could not get a piece placed anywhere .”
The effects of public health interventions can be very difficult to assess, so evidence gleaned from the few instances of randomized controlled trials of such interventions become particularly important. Yet the highly anticipated results of the only randomized controlled trial of mask wearing and COVID-19 infection went unpublished for months. Researchers, anxious to learn of the results, contacted Thomas Lars Benfield, a lead investigator on the study of 6,000 community-dwelling residents in Denmark, about the delay in publication. Benfield responded that the results would be published, “As soon as a journal is brave enough to accept the paper.” The paper finally appeared, after a five-month delay, on November 18 in the Annals of Internal Medicine. It showed no clear benefit from mask wearing in the community setting. In an accompanying editorial, the editors recommended mask wearing while noting that any benefit is likely to be “small,” and adding, “With fierce resistance to mask recommendations by leaders and the public in some locales, is it irresponsible for Annals to publish these results, which could easily be misused by those opposed to mask recommendations? We think not. More irresponsible would be to not publish the results of carefully designed research because the findings were not as favorable or definitive as some may have hoped.”
In yet another instance, a research article reporting data on the benefits and harms of lockdowns based on epidemiologic data from Sweden and other countries sat for two months at one of the top four medical journals before being rejected . The importance of this article can’t be overstated; it reviews the utility of an empowerment approach relying on recommendations in Sweden as compared to a norm of police-enforced mandates. One might be tempted to think the delay resulted from the article lacking scientific merit. However, it will be published by the Annals of Epidemiology and readers will be able to judge for themselves.In light of episodes like these, a toxic environment, self-censoring and publication bias combine to explain the dearth of skeptical or heterodox findings and views regarding ways to control COVID-19.
The net effect of academic bullying and ad hominem attacks has been the creation and maintenance of “groupthink”—a problem that carries its own deadly consequences. There is little doubt that as the world faces second and third waves of COVID-19, public health measures such as the various forms of lockdown can both save lives and cause deaths. Now, with news of vaccines released by Moderna and by Pfizer and Germany’s BioNTech, President-elect Biden’s COVID task force would do well to avoid making hurried assumptions about either vaccines or other public health measures. The task force should review all the data and address concerns about research rigor and transparency. And no matter how effective a vaccine may be, rolling it out is projected to take many months, a situation that could be exacerbated by the considerable vaccine resistance among members of the public.
That means there will still be a need for reasonable and effective public health measures for many months to come. An exhausted public is now fed up with conflicting messaging from the Trump White House and public health experts, as well as isolation and loss of income. People are becoming increasingly resistant to the prospect of more public health measures that restrict their lives. Silencing any science-based viewpoint that would lift some of the most oppressive aspects of controlling the spread of the virus could leave the public even more resistant to public health measures. The new administration will also need public health messaging that helps people understand the evidence and reasoning behind it.
Fortunately, some doctors and researchers are engaging in respectful dialogue. In October, a group of researchers with divergent views participated in a virtual debate between seemingly warring sides. The debate was the brainchild of Colleen Hanrahan, assistant scientist at Johns Hopkins Bloomberg School of Public Health. Hanrahan laughs as she recalls how she rounded up the participants, saying she told the experts that Johns Hopkins wanted a non-confrontational conversation, and she expected it to be “slightly more civil than the first presidential debate.”
Sponsored by Johns Hopkins University, the debate participants represented viewpoints aligned with both the John Snow Memorandum and the Great Barrington Declaration. It was notable not only for its civility, but also for the areas of agreement that emerged regarding lockdowns. Audience members were thrilled and submitted comments like this one: “If only our current culture encouraged reasonable evidence-based and scholarly discussion like this. The issue is nuanced and requires careful balance of all considerations, and you can’t have that with closed minds, short attention spans, and personal insults being hurled. THANK YOU!”
The experts discussed everything from herd immunity to contact tracing, testing and isolation, as well as risk-based protections versus geographic lockdowns. While differences remained about how to focus lockdowns, all agreed that they should and could be avoided in many cases. Another area of agreement: the measure of successful interventions can’t rest solely on the number of deaths from COVID-19. The downstream harms of lockdowns must be included in the benefit-to-harm calculus.
It is critical that Biden’s task force avoid creating a majoritarian echo chamber and instead continues the approach pursued by the experts who convened for the Johns Hopkins debate. Only by entertaining a broader, scientifically informed view of what might work will the next phase of COVID-19 control be acceptable to a deeply divided public.
Clarification added after publication: the authors have collaborated in the past with both John Ioannidis and Vinay Prasad, who are discussed in this essay and in the accompanying sidebar.