H5N1 (2013)
blog.samaltman.com
blog.samaltman.com
The perfect virus is balanced: just deadly enough.
It's possible SARS-CoV-2 hits the 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.
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.
COVID-19, SARS, Ebola, AIDS, etc. all fit in this paradigm.
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.
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.
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.
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
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 only way to really get the economy going again is to deal with the virus.
It is not the only virus. Rabies, also has 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.
https://en.wikipedia.org/wiki/Kaposi's_sarcoma
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.
https://www.youtube.com/watch?v=RIj0iJXTMug
It's really good.
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.
function calc30(odds) {
for (let i = 0; i < 30; i++) {
if (Math.random() < odds) return true;
}
return false;
}
Array.from(Array(10000)).map(() => calc30(0.04)).filter(Boolean).length //=> 7022 or ~70%
Array.from(Array(10000)).map(() => calc30(0.02)).filter(Boolean).length //=> 4545 or ~45%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).
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[0] Table 1 of https://science.sciencemag.org/content/336/6088/1534/tab-pdf
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.
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.
Deadly, Contagious, or Incubation. Pick 2.
This COVID-19 is contagious, and has a long incubation.
The deadly part might be during secondary reinfection, or where it wears down your body’s defenses, that other diseases begins to ravage you.
So, this virus might actually be the perfect combination of all 3.
> 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.
Someone has read Infinite Jest
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.
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.
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.
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.)
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.
[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.
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.
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.
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.
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.
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.
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.
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.
Good luck France. Stay safe.
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
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.
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.
I am not sure if Sam or anyone would have expected this to happen in the near future?
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.
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.