What about HIV? 10 years "incubation" period and 100% mortality. If it was as contagious as the flu it would have killed almost 100% of the human population. Isn't it a scary thought?.
It is not the only virus. Rabies, also has 100% mortality.
From what I've read in the press, if you don't take the drug cocktail regularly, it's 100% mortality.
I remember that first newspaper articles on the mystery disease in the early 80's. They were only 1 inch or 2 inches long and talked about mystery cases of Kaposi's Sarcoma at first, then mysterious pneumonia cases. Then a tidal wave of longer articles as it became an epidemic.
A former roommate of mine was a nurse in Toronto General's AIDS floor (or wing.) One day she said to me about her work, "All that crackling." The advanced patients' lungs crackle as the ventilator forces their lungs to expand and contract.
Part of why SARS-CoV-2 is so hard to handle is the long incubation period, with many people being asymptomatic carriers and other people having initial symptoms that look a lot like much less rare diseases. Is there a reason to think we couldn't have another disease that worked this way but with detection being even harder?
I suspect the “perfect virus” adaptively speaking isn’t deadly at all - burning down a home your future ancestors could live in doesn’t seem like a good strategy.
There are many perfect viruses in this sense. They're all around us and we hardly take notice, and they've been around.
New viruses tend to be more virulent than old ones. And new viruses tend to get less virulent over time -- else they die out. Ebola's incubation, transmission, morbidity, and mortality are such that it burns itself out. The common cold's are such that... it's common. Covid-19's are such that it's causing massive economic damage even if the recoveries are V-shaped. Hopefully covid-19 will get less virulent soon though.
To play devil’s advocate — a not insubstantial amount of the economic damage is self-induced. We could accept some degree of risk and the associated consequences to reduce that, but we have not for various reasons that are subject to debate. I suspect in hindsight we’ll find we have overreacted due to a lack of good information.
I also suspect that some of it is just revealing economic malaise that already existed but was hidden, and this served as a Schelling point for it to reveal itself.
No economy, healthy or otherwise can withstand being intentionally dismantled and the pieces burned to ash.
If you order the world to stop production or trade for an indefinite period, poverty and depression is the only possible result, no matter how healthy the production and trade were before being stopped
> no matter how healthy the production and trade were before being stopped
The economy had at least two noticeable and possibly systemic issues before Covid-19. The several yield curve inversions combined with funding problems in the repo market. We certainly hope for a V-shaped recovery but there is no telling what kind of issues have been attributed to the virus that may still be there when this passes.
The flip side is even 1% of a populace dying is going to impede daily life even if we were all sociopaths. In reality, once hospitals get overloaded, the number is quite a bit higher than 1%. So to do nothing would also be choosing economic and societal turmoil.
Yes, and it's also not as though everyone just goes on their merry way in the midst of a pandemic just because a politician declares the country "re-opened". A large percentage of people will continue trying to isolate themselves and their families until they feel assured the outbreak is over and risk of infection is low. This will severely impact the economy whether or not there are official restrictions in place.
The only way to really get the economy going again is to deal with the virus.
Virulent here means "how bad it is to the host species". A virus with high morbidity and mortality, and high contagiousness, is a pretty virulent virus. Now, if it is too virulent, the virus might die off -- become extinct. If it is very contagious but does not sicken or kill the host, then the host won't even notice, and the virus will flourish. If continuing to exist were the virus' goal -it can't exactly have a goal, now can it?-, then being less virulent would be in its best interests. But viruses don't have goals, and this just amounts to an observation: that highly virulent viruses are rare, and that those that survive tend to be the less virulent strains.
Natural selection is a physical process that is continually exploring the search space for exactly that sweet spot.
The fact that it has been over a hundred years (equivalent to hundreds of millions of “lifetimes” for viruses/bacteriae) since the last pandemic of this proportion that affects humans is a clear indication that humans as hosts must not be all that valuable in terms of natural selection.
No, it's that killing the host isn't a good strategy.
There's dozens of viruses that infect us right good and mostly don't kill the infected. They are really hard to get out of circulation, which is 'success' for a virus, it continues to exist.
Once we had the knowledge to do so, we destroyed smallpox in short order.
Adding to this, that's why we see a lot of the really nasty stuff jumping from originally another host species. They evolved to not kill their host, but once they jump over they cause some systemic issue in the new host that they weren't originally 'intended for'.
COVID-19, SARS, Ebola, AIDS, etc. all fit in this paradigm.
Anything that's not in that "sweet spot" is naturally selected away and quickly extinguished (MERS, SARS, Ebola, etc). We're basically breeding a bioweapon.
Not that there is any other choice though. Food for thought.
Honestly, all sorts of things are possible at the moment. The truth is we don't have enough good data to really know much of anything. And in the absence of info everyone is free to arbitrarily prognosticate. For a forum that's generally pro-data it's somewhat disappointing to see it here.
Just giving voice to the idea that there is a sweet spot. We don't have enough data to know if SARS-CoV-2 hits it. Or enough data to know where that sweet spot even is. (This seems like a very hard thing for epidemiological models to predict.)
Wow! I had no idea that triple helix was possible. Or that we know so much about what genes cause what diseases. Deffo reading up more on genetics and learning about the inner details of viruses.
One of Warren Buffett's primary fears is weapons of mass destruction, I think since the 70s (as stated in his semi-autobiography, Snowball). During the cold-war, he put things like this (paraphrasing from memory): if there's a 4% chance of nuclear war per annum, there's a 70% chance of it happening over the next 30 years. If we reduce the annual chance to 2%, we reduce the 30-year chance to 45%.
for some reason those numbers are not adding up to me. do the chances compound year-over-year? how is the 4% any different in year 1 than in year 30? or any year in between? how does this add up to 70% over a 30 year period
If you assume 4% each year independently of each other year, then the chance of not having nuclear war is 96% in any given year. Over 30 years, your chance of no war is (0.96)^30 = 30%.
> If you assume 4% each year independently of each other year, then the chance of not having nuclear war is 96% in any given year. Over 30 years, your chance of no war is (0.96)^30 = 30%.
It's clearly not independent though, but this calculation remains true if you assume only that not having a nuclear war doesn't change the odds for future years, even if having one does.
My apologies, you are right -- I should have said "4% each year independently of each prior year" -- and it's true that only the negation needs to be independent.
A virus that is extremely deadly, extremely contagious, and has an extremely long incubation period is quite unlikely, if not impossible. As far as I know this is a typical "pick two" triangle.
Why? I agree that in the paper that Altman is referring to [0] H5N1 did appear to decrease in lethality after becoming airborne. The paper does not mention its incubation period.
Do you have references for why a combination of these is not possible (or even unlikely)? I feel that it is quite possible to achieve by using only passage between animals (artificial or otherwise).
Infectiousness and incubation period tend to be in tension with each other, many routes for virus shedding are symptoms (runny nose, cough, etc).
An extremely high death rate also does a better job of motivating responses, which while it isn't directly biological, has a significant impact on transmission.
I'm not so sure we really understand the full possibility space of infectious diseases though.
> Infectiousness and incubation period tend to be in tension with each other, many routes for virus shedding are symptoms (runny nose, cough, etc).
Yeah, I agree, but I think this is somewhat orthogonal to my point—gain-of-function[0] studies seem to indicate that artificial passage is potentially selective enough to make this possible, even though these things are usually negatively correlated.
> An extremely high death rate also does a better job of motivating responses, which while it isn't directly biological, has a significant impact on transmission.
Absolutely. This was also likely why we saw such a huge and immediate response to SARS, which seemed roughly as (if not more) contagious than SARS-nCov-2, but had a CFR of around 10%. SK was also much less well-equipped to handle it then than it would be today (likely due to that exact reason).
> I'm not so sure we really understand the full possibility space of infectious diseases though.
Agreed, and this is mostly my worry.
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[0] For an even more terrifying gain-of-function study on H7N9, with higher virulence and mortality than the H5N1 study, the reference is: https://www.nature.com/articles/nature12392
In this case, the virus was also able to be transmitted from ferret to ferret and appeared to have very high concentration in the lungs of ferrets (much more so than H5N1 which was scary enough), which are the usual model for transmission and replication in humans.
Virulence tends to be associated with a short incubation period. If it goes too long, then the immune system has time to respond. Rabies is a weird case in that it has low virulence but high lethality.
> We worry about terrorist attacks and necrotizing fasciitis, but not much about heart disease or car crashes. But in 2011, 17 US citizens worldwide died as a result of terrorism and approximately 150 from necrotizing fasciitis. There were nearly 600,000 deaths resulting from heart disease and over 32,000 from car crashes.
> Based on current data, you are about 35,000 times more likely to die from heart disease than from a terrorist attack. So everyone smart says that we worry about terrorism way too much, and so far, they’ve been right.
Yes, thanks to our natural preference of exceptions, rarities, and oddities which the media fuels us with.
However this ignores any mitigation (and their costs) being done on these dangers. A proper risk analysis includes these.
> But another possibility is that we engineer the perfect happiness drug, with no bad side effects, and no one wants to do anything but lay in bed and take this drug all day, sapping all ambition from the human race. There are a lot of other possibilities too, and it’s very hard to think of them because we don’t have much experience with what's about to happen.
I'm not at all frightened by that because all drugs in past failed on that one. There is no up without a down.
On top of that, human beings want to be useful, they want to give their life purpose. Even if that involves pain. Laying all day in bed (or in quarantine) feels awful.
“ But another possibility is that we engineer the perfect happiness drug, with no bad side effects, and no one wants to do anything but lay in bed and take this drug all day, sapping all ambition from the human race”
Sam doesn't explain why this is scary. Why is ambition more important than happiness? I think if you were taking the happiness drug you wouldn't care that you weren't ambitious. It sounds like Sam is just afraid of letting go of his current value systems.
At some point, ethics becomes axiomatic. You can't deductively derive what you ought to be doing from how the world works. All you can do is try to make the axioms as few and as (seemingly) obvious as possible.
If you're a hedonist utilitarian, then taking the drug that gives you ultimate happiness for as long as you live may well be the best thing to do. But if you, for instance, intrinsically value life and civilization, then the externality the drug would produce might mean that life would end rather quickly, and that would be a bad thing. In simple terms, it would be too selfish for you to take.
Or you could have a value system that's not consequentialist at all. If you have a duty to yourself to stay clear-minded, and you consider drugs to be in violation of this, then you wouldn't take them no matter how much happiness you could get.
As you say, you might alter your value system once you've taken that drug, but that would lead people with other value systems to be even more reluctant in taking it.
I don't think the perfect happiness drug causes you to sit inside and end your life quickly. That sounds a lot like heroine, which we already have, and is very much not perfect.
When I'm happy, I still go out and do things, and the happier I am, the longer I want to live, so I eat healthfully and exercise. The perfect happiness drug would make me want to extend my own life and spread joy to others, so I'd probably still have kids and try to provide for them. If it meanwhile made me give up hopes of winning the Superbowl or founding a unicorn, meh, I'm ok with that.
If you stretch the meaning of "ambition" to cover all of "life and civilization" then I think it's not possible to achieve happiness while dropping ambition.
Perhaps I'm misinterpreting things, but it sounds like this perfect happiness drug would mean the end of the human race and of possibly the only technological civilization in the universe.
I don't think this is the talk I was looking for, but this covers all the points in the one I was thinking about. It's kind of possible to get the DNA sequence of a lethal bacteria, and then pay some DNA synthesis company to make that DNA for you and package that into a living bacteria.
Obviously doing that will immediately trigger automated detection systems and the FBI will be scheduling a surprise birthday party for you.... but who knows how secure that system is.
http://resiliencemaps.org is a bunch of pandemic flu resources from the H5N1 days - planning specifically for a highly contagious mutation.
Gets into food security etc. It was intended as a toolkit for scenario planners and public health officials. See also guptaoption.com/6.SPRS.php and mattereum.com/CSR (coronavirus work.)
This is, indeed, scary. Now we have global baseline. During pre-covid times self-isolating/self-sufficient communities were crazy-labelled - maybe that's going to change now. Maybe the world, as we know it (during our livetimes), will actually change in very noticable ways.
Pulling off global social distancing is the only short term, generic tool it seems, ie. next virus may not require ventilators to help at all so securing that is not a solution.
Long incubation period is really scary as it renders social distancing useless (too late to be effective); the only survivors are natural survivors (immune system finding it's way to create antibodies) and isolated communities. Or Mars collonies, maybe.
Another thing it’s got me thinking a lot about is how much of the economy’s straight up useless (results of messed up incentives leading to escalating red queen races, as in advertising, or simple organizational waste) or chasing the last few percent of life-satisfaction or convenience. Between the two it seems to be, IDK, like half, conservatively. Which is kind of alarming.
[edit] alarming that so much of our economy is spending that must be done to keep things working (to keep money circulating) but which provides between negative and marginal improvements in the world or our lives, I mean.
I don't think they are useless. We cannot stop breathing for 10 minutes, but we can not eat or drink for days, but no one would say that eating is useless.
The same is happening with our society. We are sick so we suspended the equivalent of eating, while we keep the equivalent of breathing going on.
> next virus may not require ventilators to help at all so securing that is not a solution.
I would be interested to know if I'm missing something, but I believe that respiratory viruses are the only ones that have a large chance of becoming pandemics - sneezing, coughing, breathing, speaking are the only gestures that can spread with no real way of fully protecting yourself from it (save for wearing gas masks). Now, I suppose in principle you could have a virus that causes respiratory symptoms, but that affects some other organ more than the lungs, but I'm not sure how plausible that is biologically.
So, I think it is by far most likely that the next pandemic will also require ventilators and face masks. Stocking up on both everyhwere in the world would be a good idea.
Also, it should become required practice for all countries (and even most large companies) to have significant pandemic reserves. We know for sure that a new pandemic will arise in the future, and there is a good chance that it will happen again in the next 50 years let's say.
> Now, I suppose in principle you could have a virus that causes respiratory symptoms, but that affects some other organ more than the lungs, but I'm not sure how plausible that is biologically
Chicken pox? It's spread through the respiratory system, but primarily affects the skin and nervous system. And it's enormously contagious: we wouldn't have a chance to contain it in a population that started with zero immunity.
Right, insect-based infection is one vector I forgot.
HIV is kind of special,in that it took years before it was recognized as the cause of AIDS, and, since it was mainly affecting stigmatized groups, government efforts to contain it were non-existent for years. I'm not sure that another sexually-transmitted infection would follow the same epidemiology in the current age, at least in the more tolerant countries.
I don't think these fears of terrorism or flesh-eating bacteria are irrational.
The underlying thread here is about control. You can control your diet and lifestyle, and therefore your chances of dying from heart disease. You can't control whether that guy with the backpack on the subway car is carrying a bomb.
It's the same reason why people are way more afraid of flying than driving despite the statistics saying that driving kills way more people. If you or your spouse is behind the wheel, you feel more in control.
The whole point of fear is it focuses on unexpected enemies, like predators.
I think influential people tend to be scared of these rare events simply because those are the ones that actually can effect them. Based on the assumption that influential people tend to be wealth, they have the money to insulate themselves from small incidents but not big crisis. I do not believe Sam Altman has been poor before to truly understand that this pandemic is no different than most people living day to day because any accident can ruin them.
The perfect deadly virus would have to be some sort of a time bomb virus. Everyone thinks it’s common flu and is spread to 90% of humans. Couple of years later it undergoes metamorphosis and turns into lethal suffocating or heart attacks. It would be almost impossible to control this.
Bio weapons are perhaps the nastiest of any weapon. Someone smart enough could make it in a lab and it could bring the entire globe to its knees.
There's an interesting story about h1n1 in France. At the time it appeared, the French government took it really seriously and spent 2 billions to buy masks and vaccines. Fortunately the virus didn't spread, but the government's reaction was highly criticized.
For the covid19, the reaction was too slow, hospitals now struggle to get masks and I'm convinced that's because they didn't want to reproduce the h1n1 over reaction...
On the opposite, you have the South Korea who was highly prepared with masks and protocols, apparently thanks to their experience with Mers virus.
Let's hope that, thanks to covid19, a lot of countries will take strict measures, like South Korea before and that a virus like h5n1 won't wipe half of the world.
I wonder why France only chose to do a quarantine, after 6,000 people were infected. By the time you confirm someone is infected, then you might have 10 times the actual number infected. Meaning, France might have 60,000 infected, when they finally mandated the quarantine.
In another interview, the Scientist Ron Fouchier, said: "that GOF experiments are the only way to learn crucial information on what makes a flu virus a pandemic candidate.", I would like to know if he was able to predict COVID-19 and how he is really using his gained knowledge on H5N1 to fight COVID-19?
It wouldn’t be surprising for nCoV to evolve now since it has so many opportunities. For example, a strain which breaks the viral proofreading mechanism would dramatically increase the diversity of new strains. That would be bad because a more diverse Coronavirus would become a moving target for therapies, and thus, an endemic disease, exponentially more lethal than flu. Just imagine the economic impact if this became an annual event. We’d have to get much better at treatment and distancing
We designed a gene therapy for Covid19 but have yet to find a great manufacturing partner; if anyone knows someone who can do cGMP manufacturing of AAV, please let me know via email at bion at bitpharma dot com
what does "exponentially more lethal" mean here? The lethality is not yet known, but whatever it is, it's a multiplicative factor compared to flu.
I don't think there would be much economic impact if this were annual. The overarching impact would be a reduced lifespan in developed countries (by a small number!). We wouldn't shut down everything every year.
What I mean is, nCoV is already shown to be exponentially more lethal than flu. If it becomes an annual event, that’s a major uptick in selection pressure
The more complex an organism, the more a proof-reading mechanism is required.
Enveloped Coronaviruses are complex enough that a break of the proof-reading mechanism will almost certainly also be fatal to the virus.
That is why you're much more likely to see mutations in smaller simpler viruses like Rhinovirus - and why vaccination efforts are futile.
...but you are correct that this is a statistics question - at what number of infected humans, does the odds of a meaningful mutation occur? 10^6 humans? 10^9 humans? 10^12 humans? We don't really know.
So with the advent of CRISPR is the only thing stopping a particularly sociopathic entrepreneur from creating a virus+vaccine combo in a Deus Ex scenario... ethics of lab technicians doing gene splicing? What could possibly go wrong...?
>> a virus that spreads extremely easily, has greater than 50% mortality, and has an incubation period of several weeks? ... without the world having time to prepare, could wipe out more than half the population in a matter of months.
I am not sure if Sam or anyone would have expected this to happen in the near future?
Sam seems preoccupied with a weaponized virus rather than a natural mutation.
Gates had a 2015 TED talk about “the next epidemic”
Hopefully we will be more prepared for the next one. Covid-19’s mortality is much lower than 50%, so in some sense this is a warm up for the big one that Sam fears.
> For whatever reason, we seem to be wired to overweight the risk of the dramatic, scary, but very unlikely and underweight the risk of the mundane, familiar, and probable.
Two things. One, we do not sufficiently emphasize pandemics/epidemics -- this is partly because these things have been fairly rare and rarely very bad, and we have a way of focusing on what we're able to be aware of. As a result we get very upset when rare, very noticeable events happen, but we don't take notice of the risk of their happening when... they're not happening.
Second, we do very much care about intent. Nobody doubts that if Al-Qaeda had been able to steal and use nuclear weapons, they would have -- their intent was evil, and that meant they needed to be taken care of. As long terrorists can only kill a few, we can ignore them, but given their intent is to kill many, we can't ignore them entirely. Regarding car crashes and other accidents, the rates of fatalities per-mile traveled and such have been going down, and can be expected to go down further as technology progresses -- and we do invest in improving technology to make our roads and cars safer.
Fatalities from terrorism and fatalities from traffic accidents are simply not comparable -- they're apples and oranges. Accident fatalities won't spike, but terrorism fatalities are liable to spike intolerably at any moment. The difference is intent: no one intends to make traffic accidents occur, but there are people who intend to kill many other people. Perhaps in the long run both obey statistical distributions, just different ones, but for the human psyche, intent counts.
Perhaps we shouldn't care about intent. Or perhaps we should focus on limiting the capabilities of those with evil intent -- but this is not much different than saying we must continue to put effort into hunting terrorists.
Anyone making the traffic accident vs. terrorism comparison needs to acknowledge the intent distinction if they are to be taken seriously. They almost never do though.
> Also in 2011, some researchers figured out how to reengineer H5N1—avian influenza virus—to make it much scarier by causing five mutations at the same time that all together made the virus both easy to spread and quite lethal. These five mutations could all occur in nature, but it’d be unlikely in the same copy of the virus. I have no doubt that the media overstated the danger, but it’s still worth thinking about.
Is it possible to overstate the danger of engineered pathogens? All that's needed for that to lead to catastrophe, besides engineering, is intent, or accidental release. Naturally occurring pathogens are acts of god. Engineered pathogens are not -- their use against populations certainly isn't, even if resulting from lab accidents.
If an engineered pathogen could kill millions, and all that's missing is intent, then engineered pathogens are as problematic as nuclear weapons. More problematic than nuclear weapons, in fact, because the technology needed to engineer pathogens is harder to control, easier to come by / develop, etc. The only mitigation is the -admittedly massive- risk to the user of having the pathogen hit them too.
Pathogen engineering comes with a number of advantages to developing and using them, and just one disadvantage:
- adv.: cheap, difficult to control against proliferation
- adv.: plausible deniability, allowing anonymous use
- disadv.: can boomerang on the user
The disadvantage is the strongest reason to believe that covid-19 wasn't both, engineered and released with intent. And if it was, it has boomeranged.
That one disadvantage can be negated with time by also developing vaccines and treatments ahead of use. But that wouldn't work for a state actor, as that would erase plausible deniability and thus invite counter-attacks if used. Fortunately, developing vaccines and treatments gets costly enough to put it beyond a terrorist group's means, but then, a suicidal terrorist might use it anyways.
But even if bioweapons are unlikely to be used with intent, doesn't mean that they aren't worth worrying about. Lab accidents are a possibility, thus something to worry about.
Going back to the first point above, there really are many threats to worry about, and we can't all worry equally about all of them. This is why we have a national security apparatus: so we can focus sufficient resources on each threat. Even if the national security apparatus here, in the U.S., had done everything right as to pandemics, they would have to have been doing it for many years.
One thing we can count on is the national security apparatus taking pandemics much more seriously going forwards, though that will be at the risk of preparing to fight yesterday's war, ignoring the risk that tomorrow's threat may look much different. If that happens, it will be because humans have a hard time planning against the unknown or the unlikely.
Before 9/11 there were people who thought that passenger airplane attacks were a threat, but those were not taken seriously. We see this over and over. I wouldn't bet on anyone being particularly readier for the next big problem than we were in this case, in the case of Katrina, in the case of 9/11, in 1918, in 1941, etc.
The perfect virus is balanced: just deadly enough.
It's possible SARS-CoV-2 hits the sweet spot.