[HN Gopher] Dual use of artificial-intelligence-powered drug dis...
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       Dual use of artificial-intelligence-powered drug discovery
        
       Author : heliostatic
       Score  : 133 points
       Date   : 2022-03-16 12:49 UTC (10 hours ago)
        
 (HTM) web link (www.nature.com)
 (TXT) w3m dump (www.nature.com)
        
       | spupe wrote:
       | Honestly, it sounded too over-dramatic and did not offer
       | meaningful actionable consequences. The actual data is thin and
       | not surprising at all, and it's also unclear how difficult it
       | would be to design such harmful compounds without AI. I thought
       | any capable chemist could easily come up with hundreds of harmful
       | substances, old and new. I guess the AI is removing the chemist
       | from the equation?
        
         | scratcheee wrote:
         | Quantity is a quality all of its own.
         | 
         | Being able to identify many such compounds very quickly implies
         | some new threat models that are a bit disturbing.
         | 
         | Of the 40000 substances identified, perhaps one of them has
         | another interesting characteristic we've never seen in a toxic
         | compound before? Perhaps such characteristics could be
         | idenfified and filtered for, and perhaps someone could pin down
         | something entirely unique and outside of any threat-assessment
         | anyone's produced.
         | 
         | >and not surprising at all it's obvious in retrospect, but they
         | claim that the threat vector had not been seriously concidered
         | before, and I see no reason to doubt their assessment. Many
         | things aren't surprising once they've been pointed out, but
         | were missed for far too long beforehand, and I personally had
         | never concidered this before, despite seeing multiple articles
         | about AI-generated substances for positive purposes.
        
           | wombatpm wrote:
           | For example, is one of the super VX alternatives a good
           | candidate for a binary type delivery? Where two or more
           | compounds react on deployment to create the toxic version.
           | Now you can have people safely (for some value of safe when
           | performing organic chemistry) producing the components in
           | many more laboratories
        
       | [deleted]
        
       | tginart wrote:
       | It is trivial that you can flip a sign on any network optimizing
       | for something good and now it's optimizing for something bad...
       | 
       | But it is still interesting that the network generalized to these
       | toxic nerve agents without having them in the training set
        
       | SamBam wrote:
       | This is also currently being discussed here:
       | https://news.ycombinator.com/item?id=30698803
       | 
       | (Top of the front page, 56 comments.)
        
       | amelius wrote:
       | Use of these drugs would go against the Geneva Protocol.
        
         | csee wrote:
         | The people who would use them don't care about the Geneva
         | Protocol.
        
           | wolverine876 wrote:
           | > The people who would use them don't care about the Geneva
           | Protocol.
           | 
           | Unless you mean that, by definition, anyone who violates the
           | Geneva Conventions doesn't care about them, you are
           | overlooking that most major militaries observe the Geneva
           | Conventions to a great extent. They are cleverly written to
           | make it in everyone's interests.
        
         | 323 wrote:
         | Putin did it in Salisbury and nothing happened to him.
        
           | [deleted]
        
       | krageon wrote:
       | Quite an interesting paper in it's impact study, but the
       | questions it asks all boil down to "the masses are not to be
       | trusted with our vaunted knowledge, because harm can be done. How
       | can we prevent them from moving outside the boundaries of
       | knowledge we like" and then the example used is how GPT-3 is
       | managed. This is without a doubt a terrific example of bad
       | technological stewardship: Any malicious state actor gets to use
       | what you make for evil, while at the same time keeping it away
       | from the folks you're making it for. I wish they had had a more
       | substantial and innovative thing to say about it, but as it
       | stands it reads as regressive.
        
         | wolverine876 wrote:
         | > "the masses are not to be trusted with our vaunted knowledge
         | ..."
         | 
         | The masses will use AI to do bioweapon design? That doesn't
         | sound like something most people could do.
        
         | scratcheee wrote:
         | I disagree with your interpretation.
         | 
         | Would it be better if nobody had access to easier ways to
         | produce new and innovative nerve agents? Yes, of course it
         | would be better.
         | 
         | Do I prefer a world where only state actors can build nerve
         | agents, vs a world that includes state actors plus more? Yes,
         | less sources of nerve agents is more good.
         | 
         | You might as well complain how pointless it is to block
         | proliferation of nuclear weapons when malicious state actors
         | already have them.
         | 
         | The world wont be safer by spreading nuclear weapons to more
         | people, and similarly for nerve agents.
         | 
         | Fortunately, this sounds similar to nuclear weapons in another
         | way, designing the weapon is not the hard part that limits them
         | to state actors, its producing them that's hard.
         | 
         | Still, nuclear powers don't tend to publish their weapon plans
         | publicly, for good reason, and the same logic should apply
         | here.
         | 
         | I'm not using the comparison to imply this is as serious as
         | nuclear proliferation btw, just that it's a useful example of
         | knowledge that really should be kept limited.
        
         | verisimi wrote:
         | But ..
         | 
         | "Risk of misuse The thought had never previously struck us. We
         | were vaguely aware of security concerns around work with
         | pathogens or toxic chemicals, but that did not relate to us; we
         | primarily operate in a virtual setting."!!!
         | 
         | Operating in the rarefied air of 'science' they were unaware of
         | the risk of misuse!
         | 
         | I don't think they can even conceive of the idea that the
         | government might misuse this technology.
        
           | [deleted]
        
           | krageon wrote:
           | > Operation in the rarefied air of 'science' they were
           | unaware of the risk of misuse!
           | 
           | The thundering irony of this concept in a timeline where a
           | (group of) scientist(s) discovered fission cannot be
           | overstated.
        
             | jjoonathan wrote:
             | The thundering irony of blaming the group of people who
             | made you aware of a problem for being unaware of the
             | problem is even more difficult to overstate.
        
           | jjoonathan wrote:
           | They wrote a paper on it. They weren't just aware, they were
           | demonstrably aware. Or are you suggesting that we blame
           | people for having a finite mental processing speed?
        
             | verisimi wrote:
             | I'm saying its a funny to say that they were unaware of the
             | risks when they started on the research. I mean, its not
             | beyond imagination that AI could be/is being used for
             | nefarious ends.
             | 
             | I think we agree...??
        
         | 323 wrote:
         | Do you think everybody should have the right to design a Sars-
         | Cov-4 in their kitchen just because it's soon going to be
         | technologically possible and free speech?
        
       | 323 wrote:
       | This particular issue, toxins, doesn't seem like a huge problem
       | in practice.
       | 
       | You can already buy extremely potent toxins that also work
       | against humans at the hardware store (some
       | pesticides/insecticides/rat poisons).
       | 
       | New toxins might be interesting for covert operations, for
       | example killing someone without being detected by a toxicological
       | report, but this seem to have limited usage.
        
       | heliostatic wrote:
       | From the paper:
       | 
       | > In less than 6 hours after starting on our in-house server, our
       | model generated 40,000 molecules that scored within our desired
       | threshold. In the process, the AI designed not only VX, but also
       | many other known chemical warfare agents that we identified
       | through visual confirmation with structures in public chemistry
       | databases. Many new molecules were also designed that looked
       | equally plausible. These new molecules were predicted to be more
       | toxic, based on the predicted LD50 values, than publicly known
       | chemical warfare agents (Fig. 1). This was unexpected because the
       | datasets we used for training the AI did not include these nerve
       | agents. The virtual molecules even occupied a region of molecular
       | property space that was entirely separate from the many thousands
       | of molecules in the organism-specific LD50 model, which comprises
       | mainly pesticides, environmental toxins and drugs (Fig. 1). By
       | inverting the use of our machine learning models, we had
       | transformed our innocuous generative model from a helpful tool of
       | medicine to a generator of likely deadly molecules.
        
         | ReptileMan wrote:
         | That is really in the attack of captain obvious territory. Next
         | we can expect - we turn our algorithm to find energy storage
         | molecules and what we got is explosives.
        
           | spicybright wrote:
           | Researchers seemed surprised by the results.
           | 
           | And, from a lay person like myself, I wouldn't have thought
           | "make medications for specific illnesses, and make sure they
           | don't effect the rest of the body" is the logical opposite of
           | "make chemicals that kill people as effectively as possible".
        
         | bottled_poe wrote:
         | This sounds suspiciously like manufacturing weapons? I'm most
         | interested to understand how this project was permitted in the
         | first place. Even the public disclosure of this research feels
         | negligent.
        
           | [deleted]
        
           | spupe wrote:
           | No one has to apply for a license to use machine learning
           | models. They are merely communicating the fact that it's so
           | trivially easy to do something like this, that pretty much
           | anyone with an interest will be able to do so. The question
           | is whether it was already trivially easy to design such
           | compounds before or not, which I think it was, but I would be
           | glad to hear a counterpoint.
        
             | jjoonathan wrote:
             | Synthesis was, and still is, the hard part. It was already
             | easy to find public information on seriously nasty nerve
             | agents.
             | 
             | For some intuition on the difficulty in synthesis, note
             | that explosive chemistry and synthesis is comparatively
             | trivial, yet there are relatively few terror attacks that
             | go beyond commercial-off-the-shelf compounds and almost
             | none that do it well.
             | 
             | Personally, I think this model would be a boon for public
             | safety because contract synthesis operations could use it
             | to screen incoming requests for "nerve gas but changed up a
             | bit." Basic chemical intuition probably already gets them
             | far in this regard, but a published model could be
             | standardized and mandated.
             | 
             | Someone else in the thread asked about next steps. Those
             | would be good next steps.
        
               | monkeybutton wrote:
               | IIRC Germany experienced some rather horrific accidents
               | in their facilities for manufacturing chemical weapons.
        
               | semi-extrinsic wrote:
               | > there are relatively few terror attacks that go beyond
               | commercial-off-the-shelf compounds and almost none that
               | do it well
               | 
               | The 2011 Norway attacks, 2002 Bali bombings, 2005 London
               | underground bombings, 2008 Mumbai attacks... There is a
               | long list of deadly terrorist attacks using homemade
               | explosives, I don't think this is something to be
               | dismissed.
        
               | civilized wrote:
               | > There is a long list of deadly terrorist attacks using
               | homemade explosives
               | 
               | But they used well-known and readily available compounds.
               | They don't attempt to use novel ones. It would just make
               | the attack way more difficult to execute.
        
           | jwuphysics wrote:
           | They've certainly given this some thought:
           | 
           | > We are but one very small company in a universe of many
           | hundreds of companies using AI software for drug discovery
           | and de novo design. How many of them have even considered
           | repurposing, or misuse, possibilities? Most will work on
           | small molecules, and many of the companies are very well
           | funded and likely using the global chemistry network to make
           | their AI-designed molecules. How many people have the know-
           | how to find the pockets of chemical space that can be filled
           | with molecules predicted to be orders of magnitude more toxic
           | than VX?
        
           | bpodgursky wrote:
           | I would rather than policymakers hear about the destructive
           | potential of this technology before, and not after, an actual
           | bad actor uses it.
        
           | jhgb wrote:
           | There's a major difference between drafting and
           | manufacturing.
        
           | dekhn wrote:
           | What do you mean, "permitted"? It's not illegal to run these
           | sorts of computational jobs or publish the results.
        
           | numpad0 wrote:
           | Freedom of speech. In the free world, you're free to plan
           | almost anything from planning grocery procurement to dreaming
           | global thermonuclear war, given you DON'T PUT BAD STUFF IN
           | ACTION. That's where and how the line is drawn. There are
           | dangerous extensions to the definition of action but that's
           | the theory.
           | 
           | Also if it's not put it in action but rather discussed
           | publicly, that's just helping the society prepare and evolve.
        
             | vmception wrote:
             | Right, just don't take the plea deal, make bail, get a
             | lawyer that can appeal every motion, and stay solvent
             | through the first appeals court, the supreme court, the
             | remand back to trial court, and the subsequent ruling, hope
             | the prosecutor is bored enough to avoid a retrail, and
             | don't get into crime during those 8 years so you get your
             | bail back, and hope you don't get tried at the state level
             | 
             | If you can actually afford your rights, be my guest!
        
             | wolverine876 wrote:
             | It is illegal to conspire to commit crimes, at least many
             | of them.
        
             | randcraw wrote:
             | No, the US has long classified speech on weapons of mass
             | destruction, like how to configure shaped charges to
             | trigger atom bombs. You're not free to circumvent those
             | restraints. It's likely that identifying molecules suited
             | only to become bioweapons or publishing how to synthesize
             | them will also fall under the same strictures, as necessary
             | to ensure public safety.
             | 
             | Free speech is a principle to guide laws, not a law unto
             | itself. Protecting speech that makes people less free is
             | oxymoronic.
        
               | Teever wrote:
               | Yeah but how is this going to be enforced?
               | 
               | Are you going to spell out in the law exactly what people
               | aren't allowed to research? You've just implemented a
               | holding pattern while giving them a road map on what to
               | research. So your holding pattern is going to be set up
               | to buy you x number of years, where you assume it will
               | take your adversary x number of years to fill in the gaps
               | on the map you just gave them.
               | 
               | Is that enough?
        
               | randcraw wrote:
               | No, from what I've observed, such laws most directly
               | constrain those who fund research as well as those who
               | solicit/promote it. Often they accompany other criminal
               | charges rather than motivate prosecution as a primary
               | charge.
               | 
               | Security and espionage laws are often not directly
               | enforceable. Their value is to "pile on", adding severity
               | to related matters, such as charges committing or aiding
               | past terrorist acts or planning therefor. Ideally the
               | threat of direct prosecution for a crime would deter
               | possible perpetrators, but making penalties more severe
               | and extending incarceration are useful roles for laws
               | too.
        
               | wolverine876 wrote:
               | > classified speech
               | 
               | That applies to government employees, who willingly agree
               | to be bound by classification. I think that if someone
               | outside had the information, they could publish it
               | (probably a very bad idea).
               | 
               | Also, the press has a right to publish classified
               | information.
        
               | philipkglass wrote:
               | The United States has had "born secret" laws about
               | nuclear weapons details for decades [1], but it's unclear
               | if they are actually compatible with the Constitution.
               | There was a case in 1979 that could have established
               | whether "born secret" nuclear information is a valid
               | exception to the First Amendment, but the government
               | dropped its case before the courts could rule on it [2].
               | The "born secret" concept does not apply to biological or
               | chemical weapons.
               | 
               | Your nearest research university library probably holds
               | publications about the effects and synthesis of chemical
               | warfare agents, like _Some aspects of the chemistry and
               | toxic action of organic compounds containing phosphorus
               | and fluorine_ by Bernard Charles Saunders:
               | https://catalog.lib.uchicago.edu/vufind/Record/587946
               | 
               | Which is also scanned and available online:
               | https://archive.org/details/B-001-026-884-ALL
               | 
               | [1] https://en.wikipedia.org/wiki/Born_secret
               | 
               | [2] https://en.wikipedia.org/wiki/United_States_v._Progre
               | ssive,_....
        
         | [deleted]
        
         | echelon wrote:
         | This is more evidence for why I think the "Vulnerable World
         | Hypothesis" is not only a real framework, but that it describes
         | the most eminent danger to society. It's far more dangerous
         | than nuclear MAD, in my opinion.
         | 
         | We're entering into a future where average educated people will
         | be able to synthesize biochemical agents, delivery mechanisms,
         | viruses, and more. I've thought up half a dozen low-hanging
         | fruit that I think anyone could build today. You can probably
         | do the same if you think about it.
         | 
         | You don't even have to attack humans. Our society is dependent
         | on a lot of assumptions.
         | 
         | And just as VWH states, I don't think it can be defended
         | against. It's scary.
        
           | muaytimbo wrote:
           | It's not trivial to synthesize VX-like compounds without
           | killing yourself. You would definitely need an "above
           | average" educated/trained person.
        
           | qq66 wrote:
           | I don't even think you need a hostile actor, you could just
           | have an incompetent actor who flips the sign on a value, and
           | instead of designing a biological agent to maximize wheat
           | production, designs one that minimizes wheat production, and
           | ends up exterminating all global wheat.
        
             | spicybright wrote:
             | To be fair, at least for your example, you'd need a really
             | long chain of incompetent actors to kill off wheat.
             | 
             | We should really be scared of the lone and bored grad
             | student making a wheat killer and accidentally dropping the
             | test tube.
        
       | zanethomas wrote:
       | Someone somewhere is now generating new psychoactive drug
       | candidates.
        
         | rocgf wrote:
         | Well, we can definitely hope so.
        
         | ellimilial wrote:
         | Try a nociception, drug design or pharmacy group at your local
         | university. Chances are they've been doing this for years.
        
       | catchclose8919 wrote:
       | ...heh, can't believe it we're not yet at _" Siri, use the
       | TensorFlow 4.6 OmegaFold model to design potentially stable
       | variants of COVID-25 with active BSE prionic inserts. ...DONE.
       | Great, now place an order of the best generated sequence to the
       | cheapest gene synthesis provider in <unregulared country x>. Air-
       | mail delivery."_
        
         | jdrc wrote:
         | Siri, print 10B vaccines
        
         | jostmey wrote:
         | You should read "Oryx and Crake" by Atwood
        
         | [deleted]
        
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