
H5N1 (2013) - reese_john
https://blog.samaltman.com/h5n1
======
_acco
The deadlier a virus is, the earlier it will trip alarm systems/panic. And as
we've all learned in the past few weeks, in outbreaks days matter.

The perfect virus is balanced: just deadly _enough_.

It's possible SARS-CoV-2 hits the sweet spot.

~~~
hatsunearu
It's natural selection all the way up.

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.

~~~
thomasz
No, we're causing strong selection bias towards something like the common
cold.

------
RobertoG
If you want to get really scared and don't sleep tonight I suggest this
presentation by John Sotos in 2019 Def Con:

[https://www.youtube.com/watch?v=RIj0iJXTMug](https://www.youtube.com/watch?v=RIj0iJXTMug)

It's really good.

~~~
nojvek
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.

------
CapriciousCptl
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%.

~~~
VWWHFSfQ
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

~~~
zamfi
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%.

~~~
dragonwriter
> 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.

~~~
zamfi
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.

------
choeger
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.

~~~
LolWolf
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).

——

[0] Table 1 of [https://science.sciencemag.org/content/336/6088/1534/tab-
pdf](https://science.sciencemag.org/content/336/6088/1534/tab-pdf)

~~~
maxerickson
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.

~~~
LolWolf
> 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.

\---

[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](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.

------
Fnoord
> 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.

------
dang
Discussed at the time:
[https://news.ycombinator.com/item?id=6889204](https://news.ycombinator.com/item?id=6889204)

------
ttobbaybbob
“ 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”

Someone has read Infinite Jest

~~~
bagacrap
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.

~~~
someguyorother
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.

~~~
bagacrap
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.

------
hatsunearu
[https://www.youtube.com/watch?v=VoqHJxf8hWQ](https://www.youtube.com/watch?v=VoqHJxf8hWQ)

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.

------
leashless
[http://resiliencemaps.org](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.)

------
mirekrusin
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.

~~~
tsimionescu
> 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.

~~~
mirekrusin
Zika, HIV are not about sneezing.

~~~
tsimionescu
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.

------
artursapek
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.

------
esturk
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.

------
nojvek
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.

------
Softcadbury
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.

~~~
blackrock
Damned if you do. Damned if you don’t.

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.

------
pelasaco
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?

------
jostmey
We need a pandemic detection system, which is what I get out this blog post.

------
bionhoward
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

~~~
bagacrap
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.

~~~
bionhoward
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

------
magicroot75
This article is about bioterrorist threats. It still underplays the idea of a
natural pandemic as being "unlikely to occur in nature."

------
baq
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...?

~~~
hilbertseries
I think creating that virus is probably very challenging.

------
deepaksurti
>> 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?

~~~
mdonahoe
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.

------
cryptonector
> 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.

