All of Ponder Stibbons's Comments + Replies

I think this is a very good point.. Evolution has given humans the brain plasticity to create brain connectivity so that a predisposition for morality can be turned into a fully fledged sense of morality. There is, for sure, likely some basic structure in the brain that predisposes us to develop morality but I’d be of the view the crucial basic genes that control this structure are, firstly present in primates, and at least, other mammals, and, secondly, the mutations in these genes required to generate the morally inclined human brain, are far fewer than ... (read more)

A personal anecdote. Many, many moons ago I started my research career at a large multinational organisation in a profitable steady business. I enjoyed the job, the perks were nice, I did the work and did well in the system. Some years later my group were asked to take a training course run by an external organisation. We were set a scenario “Imagine your company has only money for 6 months? What are you going to do about It?” We, cossetted in our big company mindset, thought the question hilarious and ludicrous.

 Fast forward a number of years, the co... (read more)

    I‘m afraid you’ll have to do more to convince me of the argument that Lavoisierian theory held up the development of chemistry for decades by denying the role of energy. Can you provide some evidence?  Until the discovery of the atomic model, chemistry by necessity had to be an empirical science where practitioners discovered phenomena and linked them together and drew parallels, and progressed in that manner. Great progress was made without a deep underlying theory of how chemistry worked. It was well known that some reactions gave out ... (read more)

Interesting example. I think the movie theatre in practice always has value and counts towards wealth, because even if you don’t have time/inclination to use it, you could in principle sell the house to an appropriate movie buff, for more than you could if you didn’t have the theatre, and use the extra money to do more of what you want to do. So the “potential“ argument still works. This argument could also be applied to a heck of a lot of other things we might own but have little use for.  On that basis, EBay is a great wealth generator!

1Bo Chin12d
In the process of trying to understand how the world works, I've learned that it's essentially human capital that defines what society is all about, completely different context and take than my initial interest. I was mistaken because I was taught about the distractions from the wealth model just like everyone else is. That's what I ended up focusing on because I had a stupid encounter with one of those distractions known as racism. I feel lucky that the system is able to show its true colors this way. I'm grateful for the lessons I've learned. The wealth model is very detached from your everyday human experience, which is why racism, innate tribalistic tendencies, is able to facade the wealth model that's much harder to be seen and understood because you actually need to read a lot about different aspects of society. Wealth model is also based on a the very human nature of greed, but that's more of a tendencies of the biological tendencies than tendencies that are strictly human since the conservation of resource is closely tied to survival as a living organism. Tribalism is just a derivative of this fundamental biological need.

I see “wealth” not as a collection of desirable things but as a potential or a power. An individual who has some wealth has the potential or power to undertake certain things they would like to do, over and above basic survival. An individual with greater wealth has greater choice of the things they can choose to do. Such things might include eating Michelin 3 star food, or driving a Ferrari along the coast. They also might include a simple afternoon walk in the woods. In the latter case the  “wealth“ required to undertake this activity comprises havi... (read more)

3Adam Zerner14d
Interesting. I like that point about potential. I think it is similar to what Ericf was saying [] about wealth and value. That wealth is the ability to continuously generate value. If your house has a movie theater but you have no free time to enjoy it, I see how you might not want to count that as wealth because you don't actually have an ability to derive value from it. But I'm hesitant. If you solve the free time problem, now the movie theater does generate value. So it's better to have the movie theater than to not have it. That seems like it should count for something. After talking this through in the comments I'm seeing that ultimately there are a bunch of subtly different concepts out there and we don't really have clear and widely known names for each of the concepts (it's possible that in some subfield of eg. economics they've thought about these things and come up with terminology).

Yes, the lab protocol it actually suggests would likely lead to an explosion and injury to the operator. Mixing sodium metal and a reagent and adding heat does not usually end well unless/even done under an inert atmosphere (nitrogen or argon).. Also there is no mention of a “work-up step,“ which here would usually involves careful quenching with ethanol necessary to remove residual reactive sodium, and then shaking with an aqueous base. 

It is rarely wrong to follow what you are passionate about. Go for it. But do think hard before discarding your placement in industry. Obtaining a diverse set of career relevant experiences early on is valuable. Industrial placements look good on a resumé as well.

I did wonder whether one reason it might be hard to commercialise orexins was because, being peptides, delivery would be difficult.

But, apparently not, nasal spray works just fine …

So the domain I’m most familiar with is early stage drug discovery In industry. This requires multidisciplinary teams of chemists, computational chemists, biochemists, biologists, crystallographers etc. Chemists tend to be associated with one project at a time and I don’t perceive part-time working to be beneficial there. However the other disciplines are often associated with multiple projects.  So there’s a natural way to halve (say) the workload without reducing efficiency.  The part-time scientist should be highly experienced, committed to what they are doing, and have few management responsibilities. If that holds then my experience is they are at least as productive than a full time worker,  hour for hour.

Very interesting points. But some of them are surely specific to the size, workforce make-up and activities of your organisation. I’d  like to put an alternative view on point 14,  at least as it applies to an organisation with longer timelines and a more autonomous working regime (so less opportunity for blocking). My experience is that part-time workers can be more productive hour for hour than full-time workers, in the right work domain. A fully committed part-time worker has a ready-made excuse to avoid those meetings that don’t make them pro... (read more)

What actual domains have you had this experience of part time workers in?

Adding to my first comment, another basic problem that at least applies to organic chemical assemblies, is that easily constructed useful engineering shapes such as straight lines (acetylenes, polyenes), planes (graphene ) or spherical/ellipsoidal curves (buckminsterfullerene like structures) are always replete with free electrons. This makes them somewhat reactive in oxidative atmospheres. Everybody looked at the spherical buckminsterfullerene molecule and said “wow, a super-lubricant!” Nope, it is too darn reactive to have a useful lifetime. This is actu... (read more)

It’s my opinion that Drexler simply underestimated the basic scientific problems that yet needed to be solved. The discrete nature of atoms and the limited range of geometries that can be utilised for structures at the nanoscale alone make complex molecular machine design extraordinarily challenging. Drug design is challenging enough and all we usually need to do there is create the right shaped static block to fit the working part of the target protein and stop it functioning (OK, I over-simplify, but a drug is a very long way from a molecular machine). A... (read more)

I think you make a good point, but I also think fear of being attacked is not a good excuse for failing to be altruistic, at least if the altruism is through financial means. After all it is easy ( and very common) to give anonymously.

That’s not to say anonymous altruistic acts are entirely sacrificial. Usually there is some significant payback in terms of well-being (assuagement of guilt for the good fortune of one’s own relative affluence, for instance).

In Advanced Driving courses a key component was (and may still be -it’s been awhile) commentary driving. You sit next to an instructor and listen to them give a commentary on everything they are tracking, for instance other road users, pedestrians, road signs,  bends, obstacles, occluders of vision etc; and how these observations affect their decision making, as they drive.  Then you practice doing the same, out loud, and, ideally, develop the discipline to continue practising this after the course. I found this was a very effective way of learning from an expert, and I’m sure my driving became the safer because of it.

There is the saying “Genius will out” and it was true for the four individuals you mention. But there are equally, cases where an enlightened teacher in an unpromising school has recognised genius, perhaps emerging from a lowly background, and helped it flourish, when perhaps it otherwise would have withered. Gauss comes to mind as one example. In decent schools today I would be pretty hopeful that genius, even if coupled to unconventionality, would be identified and nurtured. Of course not all schools are decent.

I also disagree strongly with that paragraph, at least as it applies to higher mammals subject to consistent, objective and lengthy study.  If I read it to include that context ( and perhaps I’m mistaken to do so), it appears to be dismissive (trolling even) of the conclusions of,  at the very least, respected animal behaviour researchers such as Lorenz, Goodall and Fossey. 

Instead of appealing to  “empathy with an animal“ as a good guide,  I would rather discuss body language. “Body language“ is called such for good reason. Before... (read more)

I think this hypothesis for some kinds of chronic pain makes sense and is helpful to me. Thanks for posting. The only thing I would comment on is in regard to the physiological mechanism at work. For me, the vicious cycle enabler of my own chronic pain (neck - ascribed to incipient arthritis, wheneverI ask a professional) is, I’m pretty sure, not blood flow restriction but muscle spasming. I wonder if others might say the same? I do find it is frequently self-fulfilling. If I think I’m going to get a seriously stiff neck in the night, then I will get a seriously stiff neck by morning plus accompanying serious headache.  I too have no medical training so disclaimers as to what is really going on.

4Steven Byrnes8mo
Hmm. Speculating on some possibilities: 1. Vasoconstriction commands from the brain → Nerve doesn’t get enough blood → abnormal nerve firing → muscle spasm 2. Vasoconstriction commands from the brain → Muscle doesn’t get enough blood → muscle has insufficient oxygen, buildup of waste products, ion imbalance [], etc. → muscle spasm 3. Skeletal muscle commands from the brain → “chronic, excessive muscle tone” [] → muscle spasm (I’m speculating that 1 and/or 2 might be real things, on the basis that you can get muscle spasms after a really intense workout.) I know very little about the physiology of muscle spasms. But it’s fun to speculate! And thanks for your comment :)

We may not run out of ideas but we may run out of exploitable physics. For instance what is most needed at the moment is a clean, cheap and large scale energy source that can replace gas,  oil, and coal, without which much of the technological and economic development of the last hundred and fifty years or so would have been impossible. Perhaps fusion can be that thing. Perhaps we can paper over the Sahara with photovoltaics. Perhaps we can design fail-safe fission reactors more acceptable to the general population. Let’s assume we will solve the vari... (read more)

I agree with you on both counts. So, I concede, saving millions in research costs may be small beer. But I don’t see that invalidates the argument in my previous comment, which is about getting good drugs discovered as fast as is feasible. Achieving this will still have significant economic and humanitarian benefit even if they are no cheaper to develop. There are worthwhile drugs we have today that we wouldn’t have without Structure-Based Design. 

The solving of the protein folding problem will also help us to design artificial enzymes and molecular machines. That won‘t be small potatoes either IMO.

Not a bottleneck so much as a numbers game. Difficult diseases require many shots on goal to maximise the chance of a successful program. That means trying to go after as many biological targets as there are rationales for,  and a variety of different approaches (or chemical series) for each target. Success may even require knocking out two targets in a drug combination approach. You don’t absolutely need protein structures of a target to have a successful drug-design program but using them as a template for molecular design  (Structure-Based Dru... (read more)

Most of the money spent in developing drugs is not about finding targets but about running clinical studies to validate targets. The time when structure-based drug design became possible did not coincide with drug development getting cheaper.

OK, the question asked for demonstration of economic value now and I grant you AlphaFold,  which is solely a research enabler, has not demonstrated that to date. Whether AlphaFold will have a significant role in breaking Eroom’s law is a good question but cannot be answered for at least 10 years. I would still argue that the future economic benefits of what has already been done with AlphaFold and made open access, are likely to be substantial. Consider Alzheimer’s. The current global economic  burden is reckoned to be $300 B, p.a. rising in futu... (read more)

It's unclear to me why we should expect protein-structure prediction to be the bottleneck for finding an Alzheimer cure.

I agree with your assessment of the BridgeBase ‘bots. They can appear to play very well a lot of the time but often make plays that look foolish, or sometimes bizarre. Nook played against the best (by competition) bridge ‘bots available. However, against Nook, as I understand, even these ‘bots sometimes made poor plays that quite average human players would know not to make.

DeepMind have delivered AlphaFold thereby solving a really important outstanding scientific problem. They have used it to generate 3D models of almost every human protein (and then some) which have been released to the community. This is, actually, a huge deal. It will save many many millions in research costs and speed up the generation of new therapeutics.

The US GDP is 21 trillion. Saving millions of research dollars is a rounding error and not significant economic value. There's no sign of Eroom's law stopping and being reversed by discoveries like AlphaFold.

I think this idea absolutely hits the spot.  A well worn saying is that good workers are generally promoted beyond their own capability. This is true but often because they get bogged down with meetings, fire-fighting, admin, pleasing the (Wo)Man etc.., lots of reactive stuff. My experience exactly. I changed jobs, gave up management, went down to three days a week (gaining two days of slack), declined as many meetings, as I could getaway with and became more productive than any time previously, largely because of having time to let ideas slowly gestate, play with stuff, notice the subtle things, and thereby make progress in useful directions.  I swear my employer effectively gets 5 days out of me. I should be paid more!

I think there is a danger that the current abilities of ML models in drug design are being overstated. The authors appear to have taken a known toxicity mode ( probably acetylcholinesterase inhibition - the biological target of VX, Novichok and many old pesticides) and trained their model to produce other structures with activity against this enzyme. Their model claims to have produced significantly more active structures but none were synthesised. Current ML models in drug design are good at finding similar examples of known drugs, but are much less good ... (read more)

3Garrett Baker10mo
Good analysis, but I did not upvote because of the potential info-hazard that explaining how to use AI to more effectively create hazardous compounds poses. I'd like others to do the same, and you should consider deleting this comment.