The unanswered questions on the Covid-19 variant created in the laboratory in Boston

One of the questions that was answered very early on concerns the role of mutations that, as the pandemic progressed, accumulated on the Spike protein of the Sars-CoV-2 virus: it has long been known that these mutations contribute both to the ability of the virus to recognize the human ACE-2 receptor, and therefore to enter the cell, and above all to withdraw the virus from antibody recognition.

The protein, in fact, and particularly some of its portions, is what the immune system is able to “see” better than the virus, given that it protrudes outside the viral particle, well exposed to the recognition of suitable antibodies; it is not surprising, therefore, if the mutations that define strains with immunoevasive capacity occur precisely at Spike’s charge, that is to say what is the immunodominant antigen of Sars-CoV-2. After all, when Spike was chosen to make the first vaccines, one of the reasons was precisely her high immunogenicity, that is, the robust recognition made by the immune system for that protein. Now, a new preprint released by a large research group, led primarily by Boston University, has shown that, indeed, the mutations observed in the Spike protein of the Omicron strain determine precisely the ability of the virus to spread rapidly and to evade the immune response, while they are not linked to the decreased pathogenicity of the strain; the determinants of pathogenicity, therefore, must be outside of Spike, in other proteins of the virus. So far, it would seem a job like many others, useful to increase our knowledge on the pathogen it deals with; problems arise, however, when analyzing the method used by the researchers to obtain the aforementioned result. In short, the “original” virus was taken, the one with which the pandemic began, and on that the Omicron Spike protein was “grafted”. Thus, a chimeric virus was obtained which in mice maintains roughly the lethality of the original strain, but acquires immunoevasiveness and invasive capacity typical of Omicron, with which demonstrating that the Omicron Spike protein does not influence or has little influence on the pathogenicity, but modulates antibody recognition and cell invasion capacity.

Obviously, such a way of proceeding immediately caused newspapers to shout about the scandal, such as the Daily Mail, which headlines the creation of a virus with a lethality of 80 percent. Articles of this nature were promptly stigmatized by the University of Boston, which essentially notes first of all how, in the particular mice used by the researchers, the original virus has a lethality of 100 percent, and secondly, how the research in question cannot be considered gain-of-function, a type of controversial research that requires special permissions (apparently not obtained from Boston), because no viruses with new functions have been obtained, and instead of the original virus, a slightly variant has been obtained less lethal. For once, I believe that the tabloids that have shouted outrage from the scientific community are right, considering the very defense of Boston. It is true that the chimeric virus obtained is less lethal than the original one; but it is far more lethal than Omicron, and of this strain it maintains the immunoevasion and high propagation capabilities, as the authors themselves have demonstrated. Since, in the end, what matters is the mortality of a virus, and not just its lethality – the number of deaths it is capable of doing in a population, and not just how many of the sick die – and it being clear that a ‘infectivity and immunoevasiveness equal to that of Omicron at the present time would lead, if combined with a lethality like that of the Wuhan virus, to a catastrophe, it is true that the experiment conducted in Boston raises more than a doubt about the relationship between costs and benefits and about the permissions such research should obtain. As I have written in the past, I believe that, particularly in a phase like the present one, certain types of experimental activity should be severely limited; and, apparently, even the NIAID, the regulatory body should have evaluated the research in question in advance and in detail, was not informed correctly, despite being present in the thanks section of the preprint.

Maybe, formally, what has been done is not gain-of-function research; as a molecular biologist I believe it is, but in any case the point here is not formal, but substantial, and linked to the danger itself of what has been done. Of course, the safety standards and the laboratories used are such as to reduce the risk to the minimum possible when working with dangerous pathogens; but for what reason must this risk be taken? What have we obtained, from experiments in mice, that we already did not really know or did not understand, and above all with what clear benefits as regards the therapy or containment of the virus? How much can we allow ourselves the luxury of playing with mutants more lethal than Omicron, but with the same diffusive and evasive capacity towards population immunity?