Can a lab leak spark a Global Pandemic?

General view of what a lab leak would actually imply in Nature

To start this discussion I will copy/paste here one of my comments to Kevin McKernan’s substack Quasi-Species Swarms in SARs-CoV-2, (Link to my comment):

Hi Kevin,

I've been reading this again and I would like to share a few perspectives. You said,

"the swarming effect wont dilute this out fast enough to prevent global transmission".

This would imply, it seems to me, that according to your thesis, until a given "novel/leaked" strain dilutes itself into the background of endemic viruses, correct me if I am wrong, it would transmit and proliferate itself globally maintaining its genomic traits (in this case, its virulence). In other words, as you said

"the rate of divergence in the swarm is too slow to fizzle out global spread of pathogenic variants".

You also said the following:

"The sequencing data clearly shows the duration of each variants and how long this clade remained the dominant member of the swarm. I see no reason a more virulent leaked clone couldn’t last just as long and lap the globe.

There is now a $100B incentive for a Biotech company or state actor to create a new virus and profit from the vaccines or testing industries that will quickly reboot for the next leak."

These statements would imply that any such genetic sequences, created in a lab via artificial means, would proliferate and propagate themselves and behave as if they were already dominant stable structures of the ecosystem, which is completely not true. The problem that I see is that you are conflating the general dynamics of such systems when they are already in equilibrium, as you said, "The sequencing data clearly shows the duration of each variants and how long this clade remained the dominant member of the swarm", and applying that knowledge to whatever new lab made variation comes around, as if they could, whenever they want to, find such a dominant structure via cell culture, animal passage, computer simulations and the use of molecular biology tools. In fact, I would argue, it is impossible to do so. We cannot know via any of those means, if the genome that we are studying has the potential to become dominant in any way, once it is in nature.

Problems that I see with this and farther explanation of my perspective:

1) The concept of transmission chain and the conclusions we derive from it are not accurate. We always start to acquire genetic sequencing data when the general dynamics of the system are already in place and most likely the genetic materials that we are trying to measure/track are already ubiquitous.

Waves in this case can very easily be seen as modulatory effects of such dynamical system, or in other words, quasi-stable states of proliferation guided by seasonality and related cycles driven by a myriad of other environmental factors that cannot be properly isolated from one another and are completely heterogeneous. Thus, what is "traveling" are not waves of infection/virions, but rather, waves of information that may produce proliferation of virions with given genomic traits under very particular conditions.

2) There is something extremely important at this stage of our understanding of this phenomena in relation to your point, "Much of the sequencing surveillance is simply mapping to a reference genome and likely only seeing dominant members of the swarm with over 5% allele frequency".

This extremely important point is the fact that the most dominant genomes are not necessarily the most relevant ones for the coherence and behavior of the whole dynamics of the system, as it moves from equilibrium, to quasi-equilibrium, to proliferation phases. This point is quite complex and there is not much in relation to it within the literature, if any, so I will leave it here. However this could very well open a whole new line of research in my opinion. Although we would need to re-evaluate and better characterize the foundational theories and language used to describe viral dynamics for this line of research to occur, which is not very likely because we are extremely bias and quite dogmatic in the field of virology, due to its links with epidemiology, public health and the whole industry.

3) Coming back to point (1), in order to have [waves of information that may produce proliferation of virions] within the ecosystem (in this case the human ecosystem), such virions must be stable, that is, the genomic traits expressed by such signals must conform to all other interactions in the network. This would include modulatory phase transitions within the network of related dominant and subdominant strains (that as I said in point (2), we may not even be able to measure), as well as regulatory processes related to the microbiota and their inherent dynamics, in conjunction with the extremely complex and heterogeneous network of interactions that belongs to the immune system and its web of communications and information transfer in different cohorts of the population, including different species and related signaling pathways that travel throughout the ecosystem in a myriad of different ways. That is, an extremely complex system, which cannot be predicted with our current understanding, and perhaps it never will be.

This whole set of dynamic equilibria would create the potential landscape for the evolutionary dynamics of all genetic variations that are allowed to proliferate, modulate and travel throughout the system, which in this case would be the whole globe, if we are making reference to coronavirus sequences from which we can generate tangible and measurable isolates. That is to say, we cannot predict if a given genome would be able to travel in this network. For sure we cannot make it to be a dominant and permanent feature of the network. Imagining that we can, is, quite frankly, a bit delusional if we think about it more carefully.

THEREFORE, if a lab leak or some other contamination event happens, there will never be a spread of such genomic traits until they have adapted themselves to the general dynamics of the system, which may take years, decades, or even never happen. And that is why I would call it a contamination event, not a lab leak. In the case of a biological agent that is capable of limited spread with some degree of virulence, what moves are waves of non-equilibrium states, and therefore a biological agent would not be able to proliferate as a disease-causing agent beyond the second to third layer of direct exposure to the agent. This of course is an estimate, it will be different for different potential agents, if they are indeed possible in any way other than an extremely high dose directly applied to the given target, like we do in animal experiments. The limited spread will occur due to the lost of the given characteristics that promote such non-equilibrium state (e.g. purity, quantity, concentration, proteomic transient alterations, transient genomic patterns...).

AI generated voice reading the conclusion:

Now Let’s end this introduction with some fearmongering pictures so the reader can be subconsciously induced to believe the exact opposite of everything that I just said:

Maybe this one would be better, just so we do not end up in a state of delusion: