“Montaigne concludes, like Socrates, that ignorance aware of itself is the only true knowledge” – from “Forbidden Knowledge” by Roger Shattuck A useful review of the history of the anti-vaccination movement: Poland & Jacobson 2011. The Age-Old Struggle against the Antivaccinationists NEJM Science educators and those who aim to explain the implications of scientific or clinical observations to the public have their work cut out for them. In large part, this is because helping others, including the diverse population of health care providers and their clients, depends upon more than just critical thinking skills. Equally important is what might be termed “disciplinary literacy,” the ability to evaluate whether the methods applied are adequate and appropriate and so whether a particular observation is relevant to or able to resolve a specific question. To illustrate this point, I consider an essay from 1926 by Peter Frandsen and a 2021 paper by Ou et al. (2021) on the mechanism of hydroxychloroquine inhibition of SARS-CoV-2 replication in tissue culture cells. In Frandsen’s essay, well before the proliferation of unfettered web-based social pontification and ideologically-motivated distortions, he notes that “pseudo and unscientific cults are springing up and finding it easy to get a hold on the popular mind,” and “are making some headway in establishing themselves on an equally recognized basis with scientific medicine,” in part due to their ability to lobby politicians to exclude them from any semblance of “truth in advertising.” Of particular resonance were the efforts in Minnesota, California, and Montana to oppose mandatory vaccination for smallpox. Given these successful anti-vax efforts, Frandsen asks, “is it any wonder that smallpox is one thousand times more prevalent in Montana than in Massachusetts in proportion to population?” One cannot help but analogize to today’s COVID-19 statistics on the dramatically higher rate of hospitalization for the unvaccinated (e.g. Scobie et al., 2021). The comparison is all the more impactful (and disheartening) given the severity of smallpox as a disease, its elimination, in 1977, together with the near elimination of other dangerous viral human diseases (poliomyelitis and measles) primarily via vaccination efforts (Hopkins, 2013), and the discouraging number of high profile celebrities, some of whom I for one previously considered admirable figures (various forms of influencers in modern parlance) who actively promulgate positions that directly contradict objective and reproducible observation and embrace blatantly scientifically untenable beliefs (the vaccine-autism link serves as a prime example). While much is made of the idea that education-based improvements in critical thinking ability can render its practitioners less susceptible to unwarranted conspiracy theories and beliefs (Lantian et al., 2021), the situation becomes more complex when we consider how it is that presumably highly educated practitioners, e.g. medical doctors, can become conspiracists (ignoring for the moment the more banal, and likely universal, reasons associated with greed and the need to draw attention to themselves). As noted, many is the conspiracist who considers themselves to be a “critical freethinker” (see Lantian et al). The fact that they fail to recognize the flaws in their own thinking leads us to ask, what are they missing? A point rarely considered is what we might term “disciplinary literacy.” That is, do the members of an audience have the background information necessary to question foundational presumptions associated with an observation? Here I draw on personal experience. I have (an increasingly historical) interest in the interactions between intermediate filaments and viral infection (Doedens et al., 1994; Murti et al., 1988). In 2020, I found myself involved quite superficially with studies by colleagues here at the University of Colorado Boulder; they reproduced the ability of hydroxychloroquine to inhibit coronavirus replication in cultured cells. Nevertheless, and in the face of various distortions, it quickly became apparent that hydroxychloroquine was ineffective for treating SARS-CoV-2 infection in humans. So, what disciplinary facts did one need to understand this apparent contradiction (which appears to have fueled unreasonable advocacy of hydroxychloroquine treatment for COVID)? The paper by Ou et al. (2021) provides a plausible mechanistic explanation. The process of in vitro infection of various cells appears to involve endocytosis followed by proteolytic events leading to the subsequent movement of viral nucleic acid into the cytoplasm, a prerequisite for viral replication. Hydroxychloroquine treatment acts by blocking the acidification of the endosome, which inhibits the capsid cleavage reaction and the subsequent cytoplasmic transport of the virus’s nucleic acid genome (see figure 1, Ou et al. 2021). In contrast, in vivo infection involves a surface protease, rather than endocytosis, and is therefore independent of endosomal acidification. Without a (disciplinary) understanding of the various mechanisms involve in viral entry, and their relevance in various experimental contexts, it remains a mystery for why hydroxychloroquine treatment blocks viral replication in one system (in vitro cultured cells) and not another (in vivo). In the context of science education and how it can be made more effective, it appears that helping students understand underlying cellular processes, experimental details, and their often substantial impact on observed outcomes is central. This is in contrast to the common focus (in many courses) on the memorization of largely irrelevant details. Understanding how one can be led astray by the differences between experimental systems (and inadequate sample sizes) is essential. One cannot help but think of how mouse studies on diseases such as sepsis (Kolata, 2013) and Alzheimer’s (Reardon, 2018) have been haunted by the assumption that systems that differ in physiologically significant details are good models for human disease and the development of effective treatments. Helping students understand how we come to evaluate observations and the molecular and physiological mechanisms involved should be the primary focus of a modern education in the biological sciences, since it helps build up the disciplinary literacy needed to distinguish reasoned argument from anti-scientific propaganda. Acknowledgement: Thanks to Qing Yang for bringing the Ou et al paper to my attention. Literature cited: Shattuck, R. (1996). Forbidden knowledge: from Prometheus to pornography. New York: St. Martin’s Press. Doedens, J., Maynell, L. A., Klymkowsky, M. W. and Kirkegaard, K. (1994). Secretory pathway function, but not cytoskeletal integrity, is required in poliovirus infection. Arch Virol. suppl. 9, 159-172. Hopkins, D. R. (2013). Disease eradication. New England Journal of Medicine 368, 54-63. Kolata, G. (2013). Mice fall short as test subjects for some of humans’ deadly ills. New York Times 11, 467-477. Lantian, A., Bagneux, V., Delouvée, S. and Gauvrit, N. (2021). Maybe a free thinker but not a critical one: High conspiracy belief is associated with low critical thinking ability. Applied Cognitive Psychology 35, 674-684. Murti, K. G., Goorha, R. and Klymkowsky, M. W. (1988). A functional role for intermediate filaments in the formation of frog virus 3 assembly sites. Virology 162, 264-269. Ou, T., Mou, H., Zhang, L., Ojha, A., Choe, H. and Farzan, M. (2021). Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2. PLoS pathogens 17, e1009212. Reardon, S. (2018). Frustrated Alzheimer’s researchers seek better lab mice. Nature 563, 611-613. Scobie, H. M., Johnson, A. G., Suthar, A. B., Severson, R., Alden, N. B., Balter, S., Bertolino, D., Blythe, D., Brady, S. and Cadwell, B. (2021). Monitoring incidence of covid-19 cases, hospitalizations, and deaths, by vaccination status—13 US jurisdictions, April 4–July 17, 2021. Morbidity and Mortality Weekly Report 70, 1284. |
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