147Joined Jan 2020


Biosecurity at FHI



Interesting, thank you for sharing! I was aware of this report, but did not consider their methodology in-depth at the time of reading. 

Thank you for your thoughts, I agree that this is tricky - but I believe we should at the very least have some discussions on this. The scenario I think about is based on the following reasoning (and targets not yet known pathogens): a) we are conducting research to identify new potential pandemic pathogens, b) DNA synthesis capabilities + other molecular biology capabilities required to synthesise viruses are becoming more accessible, we cannot count on all orders being properly screened, c) only a small number of labs (~20?) actually work on a given potential pandemic pathogen plus some public health folks, definitely not more than 1000s of people, therefore at least 1 to 2 order of magnitude fewer individuals than all those capable of synthesizing the potential pandemic pathogen (this obviously changes once a potential pandemic pathogen enters humans and becomes a pandemic pathogen, then genome definitely needs to be public), d) can we have those few people apply to access the genomes from established databases similar to how people apply to access patient data?  

This is an interesting question which I have thought about a little before, but stopped given infohazards risks from thinking too hard about ways in which this might be possible outweighed the actionability of such insights. For a variety of reasons, which includes this reason, I am a fan of pushing fast response passive immunoprophylaxis platforms and other countermeasure approaches such as the receptor-competition based ones, it seems that whatever we are worried about, such approaches would be robustly good.  

Short answer (mostly based on undergrad immunology and vaccinology): yes there could be things.

 There are different potential reasons for why active immunisation might not work for a given pathogen, the most obvious one being that we cannot induce antibodies that manage to bind to (neutralising) areas on pathogens. This may be because of us only having a limited set of B/T cell receptor genes (and even less flexible MHC receptor (present pathogen peptides to immune cells) genes which might be relevant for inducing immune responses) which might mean that induction is difficult - but these genes vary across the population potentially exactly for the reason that the population is protected from getting wiped out by one specific pathogen. This is somewhat seen in HIV where some individuals are able to develop neutralising antibodies and most others don't - question is whether sequential immunisation with more and more complex antigens (to achieve antibody evolution to penetrate HIV glycan shields) can get us to neutralising antibodies for everyone or not. 

Another mechanism (discussed by Tessa)  might be that antibody-dependent disease enhancement. If any neutralising antibody induction by active vaccination is accompanied by non-neutralising antibodies which may cause ADE for a given pathogen this might be bad. I think this is somewhat a technical challenge, but there might be pathogens which feature unique mechanisms that make overcoming this very difficult.