Great post! This matches closely with the lessons I've learned and advice I've given after working with virologists and biosafety professionals. I'd also give a plug for the book Biosecurity Dilemmas for anyone who wants to do a deeper dive in the trade offs in this space.
Yeah, you bring up a really good point: most of the "bugs" circulating aren't harmful, so if we have a surveillance system that's completely pathogen agnostic we'll be chasing beneficial gut bacteria or harmless phage. In my previous job in a wastewater testing lab, one of the positive controls we used was a virus that infects peppers- we'd find tons of it.
With regards to viruses, the virus needs to be able to enter human cells, take over the cellular machinery to replicate, and evade the human immune response. We know broadly what kinds of virus families can do this and what kinds can't, so if we see a virus in a family that can infect humans that is increasing exponentially in our surveillance system, we know there is an outbreak/epidemic. We can then do some bench science to figure out what human cells it's infecting, how it's evading the immune system, etc. The viruses that we coexist with relatively well, such as human cytomegalovirus, have coevolved with humans over millennia. A novel virus that was increasing rapidly in a human population would be cause for concern even if there is no symptoms yet. Also, many times there are symptoms, but they are not connected to the novel pathogen because they look so much like other diseases- flu and COVID-19, for example.
With regards to bacteria, I'll admit I'm not as knowledgeable there, but I'm also not as worried in the near term about GCBRs from bacteria.
You write:
...spreading but causes no ill effects (like the majority of microbes in our body).
The second part of your statement makes sense to me- the vast majority of microbes in our body cause no ill effects in people with a healthy immune system. However, I'm not so sure about the first statement: if it's spreading, that means it's either taking over human cells and turning them into virus factories, or it's colonizing more and more human tissue. That means the balance between the immune system and this microbe is out of whack. "Harmless" bacteria or viruses that start spreading out of control kill immunocompromised people all the time- a big part of the "no ill effects" is actually that it's not spreading, but that it's in a stable equilibria with your body and immune system.
Glad to find another Plague Inc fan. I think in the vast majority of cases, that winning strategy only works in the game, because symptoms are directly related to viral replication and the immune system's response to viral replication.
You're right that when we're talking about engineered pandemics this is something to keep an eye out for, but luckily our immune systems are very good at keeping their eyes out
The infectious period and the symptomatic period, and how they interact, is generally more important than how long a pathogen can lay "dormant". However, HIV is an example of when a case can be infectious even during the dormant period- that is very concerning, it's like asymptomatic transmission for COVID-19 but on a much larger scale. People are certainly concerned about a pathogen that has an infectious period that starts before the symptomatic period- it's even bolded on the slidedeck from the presentation you linked to: "I have bolded this because in multiple modeling studies, and in experience...if a disease is contagious during the incubation period, when you're not sick, then it's very, very hard to control".
There will certainly be some patients who die in the next few decades from some damage the SARS-CoV-2 infection did to an organ system or from immune system dysregulation from a SARS-CoV-2 infection. Novel pathogens that infect large swathes of the population often have longer term effects. Following the 1889 "Russian flu" pandemic there was even a noticeable increase in suicides among flu victims (https://macsphere.mcmaster.ca/handle/11375/14366; it was likely not a flu but in fact a novel coronavirus!). However, the magnitude is nowhere near the level needed to bring SARS-CoV-2 into GCBR status. While it is true that people can die of measles, EBV, or herpes after recovering from an acute infection, this is by no means likely. HIV is the outlier here, but it has meaningful differences from SARS-CoV-2: it has a much, much higher mutation rate, it uses reverse transcriptase to integrate its genome into the host cell's genome, and it preferentially attacks immune cells (measles also attacks the immune system in a different way, by attacking memory cells). So yes, in my opinion, we are out of the woods with COVID-19 with regards to GCBRs.
The main countermeasure to pathogens that take a while to cause symptoms is good epidemiologic surveillance systems. This "starts the clock" faster on countermeasures. Ideally, you would want a pathogen agnostic system, like what is being worked on at the Nucleic Acid Observatory. There's a game called Plague Inc that models this one aspect well- the sooner humanity realizes something is spreading, the sooner they slow the spread and create cures.
This is a really great summary and reference document, thanks for writing this! I have two comments:
1. There is a difference between detectable levels of RNA/DNA/Antigen and an active, transmissible infection. While most of the time this is not important when thinking about a global surveillance system, it is good to keep in mind especially in PoP testing.
Edit: You address my point 1 in your Part 2
2. You write:
However, while we can use animal surveillance systems to regularly monitor animals’ health and collect samples, we lack the capability of characterizing the pathogens effectively so as to predict their virulence and transmissibility to humans. This is a serious problem as it is infeasible to analyze and monitor every single pathogen strain found in animals. Microbiologists are working on this problem, but until then, zoonotic surveillance may not be suitable as an early-warning system
Kevin Esvelt has convincingly argued that we should not do this, because this would publish what and where viruses or pathogens are that could cause a pandemic to bad actors. It seems related to your point on "Potential for Dual-Use by Bad Actors". While the technology itself may not be used by bad actors, the information gathered would immediately be an information hazard which could be used by bad actors.
Again, thanks a lot for this overview of the topic!
I think seeing the attacks that he's captured by crypto interests was useful, in that future EA political forays will know that attack is coming and be able to fend it off better. Worth $11 mil in itself, probably not, but the expected value was already pretty high (a decent probability of having someone in congress who can champion bills no one disagrees with but doesn't want to spend time and effort on) so this information gained is helpful and might make either future campaigns more successful or alternatively dissuade future spending in this area. Definitely good to try once, we'll see how it plays out in the long run. We didn't know he'd lose until he lost!
This article from Seth Stephens-Davidowitz describes a paper (here) that examines who are the people in the top 0.1% of earners in the US, making at least $1.58 million per year. It was interesting to me in that many of those people were not high-status jobs, but rather owning unsexy businesses such as a car dealership or a beverage distribution operation. Obviously, this has implications for how we structure society, but it could also be a good thing to keep in mind for those interested in earning to give- owning a plumbing company might be a better route for some than trying to make it big on wall street.
I've found a benefit of learning by writing is figuring out what's actually not important at all. I wrote some COVID updates, and often things I was mad about- public communication, policies, etc were just not important when it came to writing down stuff in a way that helped other people navigate the risk environment.
Procrastination was definitely a motivator for me too. Better than my procrastination strategy yesterday of watching 30 minutes of boating failures!
Here's an update video on the Maternal Center of Excellence
Great post! This matches closely with the lessons I've learned and advice I've given after working with virologists and biosafety professionals. I'd also give a plug for the book Biosecurity Dilemmas for anyone who wants to do a deeper dive in the trade offs in this space.
Yeah, you bring up a really good point: most of the "bugs" circulating aren't harmful, so if we have a surveillance system that's completely pathogen agnostic we'll be chasing beneficial gut bacteria or harmless phage. In my previous job in a wastewater testing lab, one of the positive controls we used was a virus that infects peppers- we'd find tons of it.
With regards to viruses, the virus needs to be able to enter human cells, take over the cellular machinery to replicate, and evade the human immune response. We know broadly what kinds of virus families can do this and what kinds can't, so if we see a virus in a family that can infect humans that is increasing exponentially in our surveillance system, we know there is an outbreak/epidemic. We can then do some bench science to figure out what human cells it's infecting, how it's evading the immune system, etc. The viruses that we coexist with relatively well, such as human cytomegalovirus, have coevolved with humans over millennia. A novel virus that was increasing rapidly in a human population would be cause for concern even if there is no symptoms yet. Also, many times there are symptoms, but they are not connected to the novel pathogen because they look so much like other diseases- flu and COVID-19, for example.
With regards to bacteria, I'll admit I'm not as knowledgeable there, but I'm also not as worried in the near term about GCBRs from bacteria.
You write:
The second part of your statement makes sense to me- the vast majority of microbes in our body cause no ill effects in people with a healthy immune system. However, I'm not so sure about the first statement: if it's spreading, that means it's either taking over human cells and turning them into virus factories, or it's colonizing more and more human tissue. That means the balance between the immune system and this microbe is out of whack. "Harmless" bacteria or viruses that start spreading out of control kill immunocompromised people all the time- a big part of the "no ill effects" is actually that it's not spreading, but that it's in a stable equilibria with your body and immune system.
Glad to find another Plague Inc fan. I think in the vast majority of cases, that winning strategy only works in the game, because symptoms are directly related to viral replication and the immune system's response to viral replication.
You're right that when we're talking about engineered pandemics this is something to keep an eye out for, but luckily our immune systems are very good at keeping their eyes out
"I have bolded this because in multiple modeling studies, and in experience...if a disease is contagious during the incubation period, when you're not sick, then it's very, very hard to control".
This is a really great summary and reference document, thanks for writing this! I have two comments:
1. There is a difference between detectable levels of RNA/DNA/Antigen and an active, transmissible infection. While most of the time this is not important when thinking about a global surveillance system, it is good to keep in mind especially in PoP testing.
Edit: You address my point 1 in your Part 2
2. You write:
Kevin Esvelt has convincingly argued that we should not do this, because this would publish what and where viruses or pathogens are that could cause a pandemic to bad actors. It seems related to your point on "Potential for Dual-Use by Bad Actors". While the technology itself may not be used by bad actors, the information gathered would immediately be an information hazard which could be used by bad actors.
Again, thanks a lot for this overview of the topic!
I think seeing the attacks that he's captured by crypto interests was useful, in that future EA political forays will know that attack is coming and be able to fend it off better. Worth $11 mil in itself, probably not, but the expected value was already pretty high (a decent probability of having someone in congress who can champion bills no one disagrees with but doesn't want to spend time and effort on) so this information gained is helpful and might make either future campaigns more successful or alternatively dissuade future spending in this area. Definitely good to try once, we'll see how it plays out in the long run. We didn't know he'd lose until he lost!
https://www.nytimes.com/2022/05/14/opinion/sunday/rich-happiness-big-data.html
This article from Seth Stephens-Davidowitz describes a paper (here) that examines who are the people in the top 0.1% of earners in the US, making at least $1.58 million per year. It was interesting to me in that many of those people were not high-status jobs, but rather owning unsexy businesses such as a car dealership or a beverage distribution operation. Obviously, this has implications for how we structure society, but it could also be a good thing to keep in mind for those interested in earning to give- owning a plumbing company might be a better route for some than trying to make it big on wall street.
I've found a benefit of learning by writing is figuring out what's actually not important at all. I wrote some COVID updates, and often things I was mad about- public communication, policies, etc were just not important when it came to writing down stuff in a way that helped other people navigate the risk environment.