The Existential Threat of Pandemic Pathogens: Part 2

There's lots of other things to think about when you think about infectious disease. Helminths, ectoparasites, amoeba, non-carbon based, so that's something when you talk about the mission to Mars, and thinking about how you're going to deal with organisms that may or may not come back there.

So there's lots of different things to think about, but really our consensus was that viruses are most likely going to be the GCBR agent, because of their mutability and their rapidity of spread, and their lack of an antiviral.

But when you get into viruses, there's so many viruses. There's lots of different rules and exceptions. Would the virus's genes be RNA, or DNA? Will it copy itself in the cytoplasm of a cell or will it be in the nucleus? Will it have a segmented genome like flu? Flu is one of the most prolific viruses, and the reason why it's so good at infecting people is because it can shuffle its genes, because they're all on a segment, and it can basically be like a deck of cards that switches different genes. So that's something that is really important to think about, whether it's segmented versus non-segmented. Does it have a really big genome like MERS and SARS? Or is it a very small genome?

And then what about these ones that are spread by mosquitoes? They get very high levels of the blood in people, are those the kind of viruses that are gonna be able to cause GCBR? In just a couple of headlines a monkey pox, which is a DNA virus that people are very nervous about in the wake of the smallpox eradication, people aren't vaccinating for smallpox routinely anymore, now monkey pox has resurged and the vaccine was protective against monkey pox.

So when you think about viruses, there's lots of different things to think about. Probably when you think about GCBR-level risks, flu goes to the top of this list, because it's done it so many times before. And we do have this scare right now that's been going on since probably the 1990s, regarding avian influenza. That's a picture from my local county fair in my hometown outside of Pittsburgh.

And when you think of avian flu, one of the scariest versions of this is H7N9. We're right now in the sixth wave, but in the fifth wave we saw some very, very scary things happen. You saw changes showing this virus being more likely to be able to transmit between humans, we've seen antiviral resistance in this strain, we've seen the genetics of the strain change so much that the vaccine that's stockpiled, there was a mismatch. And we've seen it evolve high pathogenicity in chickens.

This is the CDC's ranking of viruses. A and B are both H7N9. So it's at the highest risk for emergency impact. So this is probably one of the scariest viruses that we face. And it meets a lot of those criteria that we talked about.

When you look at the steps in pandemic emergence, there's a bunch of steps that a virus has to do, this is specific for influenza. We're already down to around 3 to 4. The infection is replicating sufficiently to produce infectious virus, but we're seeing very stuttered human transmission. But we're getting down that road with H7N9.

So this isn't something that's very theoretical, what I'm talking about, this is something that we're dealing with today, now, in China, with H7N9.

I think what the CDC does is they actually rank the different properties of the virus, which I think is a very good thing to do. It might not always be accurate, but it does definitely give you some framework for how to evaluate viruses, and that's what we were doing with this framework, was trying to take this type of an assessment tool of viruses, of influenza, and apply it to the whole microbial world. And that's what this new paradigm that we made was going to try to accomplish.

So what do you do when you come up with these ideas, when you come up with these types of lists of things that might cause this? You can do what CEPI did. CEPI is the Coalition for Epidemic Preparedness and Innovation. It's a major funder for vaccine research, and what they did is they came up with a list that they took from the WHO blueprint for research, and picked some to actually go after.

I think that's one way to do this, where you have diseases that meet this criteria, then you invest money to go into it, to develop vaccines.

People did think about space bacteria, but it's unlikely that space bacteria, if they're adapted to Mars, are going to be able to do very well in humans on Earth, because there's totally different conditions that would allow them to flourish on one planet, that wouldn't apply to another planet.

We talked to lots of people that were thinking about salamanders and frogs, which are being decimated by these sapronotic pathogens, but don't necessarily affect humans.

So a couple more conclusions there. Any microbe is capable of causing a GCBR. But we believe that RNA viruses are the most pressing and likely threat, because of their mutability, their zoonotic potential. Bacterial antimicrobial resistance is unlikely to reach GCBR levels, and GCBR level of widespread fungal disease is unlikely due to its temperature restrictions, and there are very select conditions for a prion-caused GCBR.

The last part of the talk, I just want to emphasize a few things. We're always surprised about infectious disease, and I list a bunch of them here. H1N1 coming from Mexico, zika, SARS, MERS, and there's lots of people investing in surveillance and prediction approaches.

I think there's two basic approaches. There is this global virome approach, where people will go out and sequence everything that they want to do, and try to find a list of viruses that are out there. It tells you maybe what's coming, but it's very expensive, and 99 percent of those viruses are probably not going to pose any threat to humans. Also, what if the next GCBR or the next pandemic is not viral?

So that's one way to do it. Or there's another way to do it. I think this is the way I favor. It's looking at people that are getting infected by novel diseases. Looking at people like bush meat hunters, people who work in abattoirs, looking for what's called viral chatter, things that go from the first forays of a pathogen into humans. And then, looking at different hot spots. Instead of trying to sequence things, focus on things that are actually causing infections.

And then you think about unknown diagnoses. 50% of our septic shock cases, even in the United States, don't have a diagnosis, and I think that people just treat for symptoms and not necessarily for fevers. So I think that we're going about this a little bit wrongly. I think going after these unknown etiologies, all over the world, trying to figure out where these infections are occurring and actually running things down to specific diagnoses, instead of just saying, "You've got some viral syndrome." I think that's the way to go about it.

A headline just came out of Nature a couple of days ago that really validates what we're saying, which is that you should spend much more on surveying actual infections, not on trying to predict things by viral cataloging. So, what's out there, is lots of biological dark matter. We've got lots of viruses out there, lots of bacteria out there that nobody knows about. And I think we're at the stage now, that we have this tricorder culture, that Captain Kirk is holding there from Star Trek, where Bones, the doctor, would just scan someone and know exactly what they have.

We've got lots of new technologies, and I think that you can start and figure out what disease X is going to be, and that's the new WHO nomenclature for the unknown unknown. And I do think we're at that point now, but only if we actually harness these diagnostic tests.

When you think about infectious disease risk, you have to also think about human actions and that there are human actions that can enhance pandemic potential. Mistakes, political or scientific, fears of the unknown and also, complex disasters. So, if there's a war, for example, at the same time as an infectious disease, it can raise something to a GCBR-level.

So I'm going to conclude here, people keep asking me for books to read. There are lots of people who are first trying to get into this field. These are some of the ones that I could think of, that I think are interesting. This is an article I wrote for The Atlantic, Why Hasn't Disease Wiped Out the Human Race? If you just Google that, you'll find that under my name in the Atlantic, where I try to summarize some of the stuff that I talked about here. And then, these are some interesting books that I think really give you a flavor for this, and a few other ones that I didn't have pictures of.

A Viral Storm by Nathan Wolf and Level 4: Virus Hunters of the CDC by McCormick, that's the book that really got me interested in all of that. It came out in 1996. And this is the book that really started for me when I was a little child. That was the one that my parents read me over and over and over again, which is the story of the rabies vaccine. So, thank you for your interest and I'm happy to take any questions in the time that's remaining, and I have office hours as well and feel free to follow me on Twitter or read my blog. Thanks again for your attention.


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