Musings of an anonymous, pissed off virologist


by Paul Bieniasz

Dr. Bieniasz is Professor and Investigator of the Howard Hughes Medical Institute at Rockefeller University.

As viruses go, SARS-CoV-2, is quite easy to neutralize with antibodies and, it turns out, straightforward to generate effective vaccines based on the spike protein. Perhaps, even probably, those two properties are causally related. Moreover, it appears that it is quite hard (albeit not impossible) to generate resistant spike variants that evade the polyclonal antibody responses elicited by said vaccines. This is all excellent news.

However, if I had a nefarious nature and wanted to ensure that the new SARS-CoV-2 vaccines were rendered impotent, these are a few things I would try.

First, we’d want to maximize the viral population size and diversity. Because SARS-CoV-2 has a proofreading polymerase, we might have to work hard to do this. The four measures outlined below might help accomplish this, assisting the virus to explore as much genetic diversity as possible, generating every conceivable point mutation as frequently as possible.

  • Delay the rollout of testing, so that the virus could spread undetected, seeding outbreaks in geographically, demographically and culturally diverse host populations, rendering it virtually impossible to quash with test-trace-isolate approaches.
  • Implement partial and patchy restrictions on movement and social interactions, thus maintaining consistently large pools of infected individuals.
  • Keep schools open, claiming that children don’t frequently transmit SARS-CoV-2. Because children have generally mild and perhaps more frequently asymptomatic infections, diversifying viral populations are more likely to spread undetected.
  • Start a rumor-mill, making full use of social media and other outlets, with topics such as masks are unnecessary or don’t work, that PCR tests are too sensitive or unreliable, that infection-induced ‘herd immunity’ is a reasonable strategy, or even that SARS-CoV-2 isn’t real. Undermining already inadequate public health measures helps keep viral population sizes large.

Second, during or after the establishment of large and diverse viral populations, we’d begin to apply selection pressure to enrich antibody resistance mutations. For that, we would elicit the help of the medical establishment to implement measures 5 and 6. They, laudably, want to help as many people as possible as quickly as possible — we could exploit this.

  • Treat tens of thousands of people with uncharacterized convalescent plasma of weak/unknown potency, without proper clinical trials, to get the ball rolling in applying some selection pressure to enrich for antibody resistant variants. (Again, I don’t know how effective this would be since it is mostly done in hospitals, where onward transmission would presumably be rare, but it would certainly be worth a try) Immunocompromised individuals with persistent infection might be especially helpful here.
  • Finally, and here’s the kicker: having developed a remarkable two-dose vaccine, that is extraordinarily effective, ADMINISTER IT TO MILLIONS OF PEOPLE – BUT DELAY THE SECOND DOSE. Generating a pool of hosts with just the right amount of neutralizing antibody to apply selection pressure, but also maintain sufficient levels of partially antibody-resistant virus to allow onward transmission is key here. We might not achieve this shortly after the first dose, but if we let immunity wane for a little while, say 4 to 12 weeks, we just might hit the sweet spot.

Of course, I don’t know if the above would be successful, but that’s what I’d try if I wanted to generate vaccine-resistant SARS-CoV-2 variants.

{ 34 comments… add one }
  • Ax D. WhiteMan 5 January 2021, 6:07 pm

    Other than the first three sentences; this piece makes very little sense – except maybe for the part that the author is “pissed off”. That seems to come through pretty well.

  • Dave 5 January 2021, 6:50 pm

    Lesson learned. Don’t post while drunk

  • Jay Gordon 5 January 2021, 9:05 pm

    This is a superb piece of writing. At every possible decision point, we turned left when we should have turned right.


    Jay Gordon
    Proud recipient of PfizerBioNTech 162b2 vaccine candidate 8/22/20 and 9/12/20 as part of Phase 3 testing

  • Jeff 5 January 2021, 10:07 pm

    Not surprised the first comments are by people who prefer freedom of speech over freedom of thought. Thanks for posting, interesting food for thought.

  • Tom Steinberg 5 January 2021, 11:26 pm

    This post is timely and uncomfortably on point. Thanks for voicing my thoughts. I’m trying to prepare a short presentation on the general topic, pissed off about about the science-deniers/pinheads have screwed this up, thinking also about HIV deniers — that pandemic is still rolling — and the havoc wrought by people who deny science-based medicine AND the catastrophic role of credential cranks/contrarians — e.g Peter Duesberg/HIV & any number of (credentialed) tolls & SARS-CoV-2.

  • Ashley 6 January 2021, 6:47 am

    Very coherent and well written. We’re shaping up for a humdinger of resistant virus to any vaccine. The question is, when will the government give up trying and we start the hunger games.

  • David 6 January 2021, 11:06 am

    You seem remarkably sure of your final comment, maybe if you wrote a short paper on the subject including data and referring to previously published work?
    Yes there will be a pool of hosts who have had one dose of vaccine but the primary immune response to one dose does not end with the immune system frozen in time. If such a person is infected with the virus before they get their second dose (possible in any vaccine regimen), not only will there be pre-existing antibodies and T cells (remember T cells?) there will be a further adaptive immune response (T and B cell driven) and arguably a shorter period of time when the individual is infected and thus less replication.
    There are nuanced arguments to make about possible problems with delaying the second dose but to state “… if we let immunity wane for a little while, say 4 to 12 weeks, we just might hit the sweet spot” is amateurish and potentially feeds anti vaxers who don’t understand the issues at hand and may well use this piece as a reason to tell people not to get the vaccine at all.
    I also think that this kind of sounding off is disrespectful to the scientists and clinicians that take these kinds of decision – as if you think they are stupid or have no idea what they are talking about.
    Determining the ideal vaccine strategy is very difficult in the best of times – at the very least you could be more respectful of the difficulties in setting out an ideal vaccination plan.

  • Dave 6 January 2021, 10:56 pm

    On this very site, in an early podcast, all the experts were saying don’t wear a mask. They will increase infection rate because lay people touch it all the time to adjust, thereby contaminating their hands and later their eyes, mouth etc. Hindsight is 20/20

  • Richard Minke 7 January 2021, 1:50 am

    In my view point 5 is clearly correct. There is no use at present for convalescent plasma with downsides such as coagulation factors now that monoclonal antibodies are available. Point 6 is probably fundamentally correct. Dr. Shane Crotty says much the same thing [with more elaboration] on MedCram. Best wishes to all who are interested in reasoned debate. Stay safe.

  • lewis mccane 7 January 2021, 10:59 am

    Segragated isolation of the populations Is the true answer to the question.

    It worked with the first sars polio with vaccine. And 1918 Influenza.

    We are too worried about economic slippage to worry about main economic weapon. ( the people )

  • tianhao 7 January 2021, 10:07 pm

    You forgot to mention you can pass covid to other animals to let it mutante more and give it back to us. I’m sure it will be a surprise.

  • Xandur 8 January 2021, 11:12 am

    Well after culling all Minks in Denmark and The Netherlands, we found out that cat and dogs also can cary the Coronavirus (initial test on this used the wrong methodology, hence the redo). We are not culling those and let them live in our houses without lockdown. Nice experiment.

    For more failings (and possibilities for the virus) have a look at this series:

    It promises to be a good virus year

  • Art 9 January 2021, 10:37 am

    Sometimes seeing things from the other side, what would the virus want if it were sentient, clarifies things. And illuminates just how feckless humans can be, even as we haltingly and unevenly try to do the right thing.

  • Peter G 10 January 2021, 9:12 pm

    I have no scientific training. I find it is absolutely necessary for the science community to discuss these potential problems diligently. Since I do not understand scientific shorthand, articles like this help me to understand the issue. I regret though the slightly melodramatic narrative style used here. It is not necessary. Every time I come across a turn of a phrase that might be intended to entertain, I have to address that impact. Critical reading skills acquired in 9th grade keep sticking around. It also diminishes the overall clarity. So please keep us in the loop. Thank you. Just use simple prose. People like myself will thank you. The rest isn’t listening anyway. Best regards, self-isolated in New England.

  • John Harris 13 January 2021, 3:28 pm

    Great essay. But maybe it would be a quick edit to number these measures instead of using bullets. That way when the reader arrives at “measures 5 and 6” it would be clearer what this means.

  • Miguel Quiñones-Mateu 14 January 2021, 4:05 pm

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