29 Pages Posted: 25 Jun 2020

Date Written: April 27, 2020

Abstract

Variolation is a form of inoculation that relies on an unmodified form of the virus causing the disease to stimulate immunity. As with vaccination, it promises to protect the inoculated individual against both contracting the full-blown form of the disease and passing the disease on to others. Used against smallpox, it was effective and common on all continents by the late 1700s. Vaccination is undoubtedly safer and easier to implement, but only if one has a vaccine.



Here I contemplate the use of variolation against SARS-CoV-2 as there are theoretical grounds for expecting a controlled dose of the virus introduced into the body through an advantageous route to usually lead to a mild form of disease that nonetheless stimulates immunity. The objective is to establish the plausibility of variolation as a policy option for governments, opening up new goals for researchers in immunology and public health.



Reviewing the traditional arguments against variolation, I conclude that the contagiousness of the inoculated can today be managed, probably even on the massive scale required for herd immunity. Compared to herd immunity achieved without a vaccine and assuming R0 = 3, I estimate that variolation can reduce mortality by at least 92 per cent in the UK. Even if a vaccine can be developed quickly, an immediate focus on variolation could reduce mortality if government policy in the meantime emphasizes restarting the economy.



Variolation could be deployed in three modes: as an option for individuals, as a requirement for workers in roles where they have a high risk of transmitting the virus, and as the basis for a program of mass inoculation aimed at rapidly establishing herd immunity. I identify the main barriers to its usage as lying in the regulation of research and medicines and argue that the current crisis has exposed conceptual flaws in both regimes. In research, a recent and arguably undemocratic conception of ethics has made the challenge trials needed to protect the health of the population impractical, a defect that is now biting. In medicines, the distinction between doing and allowing harm on which the regime rests cannot hold when the risk of harm for everybody is largely determined by government policy. I articulate revisions to both that could speed the development of both vaccination and variolation.



I conclude that variolation could be an effective and flexible weapon in combating the pandemic. Used in a campaign of mass inoculation, it promises many countries a quick, certain and relatively low-mortality path to herd immunity, and hence to the restoration of normal daily and economic life. That is, it offers an exit route from the current crisis.



Should it turn out that infection by HCoV-NL63, a less harmful coronavirus that binds to the same ACE 2 receptor, confers immunity to SARS-CoV-2, then it would offer a form of inoculation lying in between vaccination and variolation and the same kind of reasoning could also justify its use. The possibility of variolation should form part of the planning for future pandemics.