There’s a word for not being able to handle this: misophonia

It seems that for some people (myself included) it generates a primal urge.

Or stepping off an escalator and just stopping right there to get their bearings.

Some rules weaken, and others are created or subtly change - that’s why parents can never get their kids’ slang quite right. It’s not that the parents can’t simply weaken their grammar, it’s that the kids do some things differently with very strict rules.

Thank you for writing ‘a lot’ and not ‘alot’.

I see that alot.

^ ^ ^ ^ that’s my trigger

So do I understand correctly that a certain hox gene is activated in basically all cells which are in the “domain” of a certain vertebrae

Yes

and they all activate some subset of homeobox genes which in combination with the original hox gene cause them to start turning into all the different parts associated with that vertebrae (so organs and other structures)?

Not quite. The hox gene creates a protein that tells the nearby cells that they are in a specific segment. After this specific cells in that segment start signalling so they cooperatively lay out the cardinal directions to make that specific segment. In the shoulder segment, for example, a specific cell becomes the tip of the arm and tells all the cells about it with its signalling protein. All the cells in between it and the root now ‘know’ which part of the arm to grow.

This is a cascade of ever finer positioned ‘location markers’ that guide generic cells to specialise correctly.

Ultimately, as two bones grow into each other, they know to form a joint, and as that joint takes form the joint surfaces fit each other exactly.

Would we then need an entirely new hox gene to produce even a single gill? (I know you basically just laid out most of a response to this question.) Because I would assume although the exact point at which the development of our arms and legs begins is part of the whole hox gene “superstructure”, but couldn’t we ‘basically just’ highjack this same system and duplicate this gene to produce at least a single gill in the region where the current hox gene for our neck is expressed?

Assuming we want to keep our neck, jaw and ear features, we need to keep our existing hox gene and all the genes that turn on in this cascade to produce these structure. If we alter them, our development will change.

The issue is that in a fish or shark, exactly the same location marker is used to lay down their gills. So adding a shark hox gene will result in a human segment at that location. Hox is a marker - not the full set of instructions to build the segment.

We therefore need

1. A new location marker for the gill
2. And we need our developing cells to recognise this new signal
3. And we need a development pathway to create a gill which includes new location markers, and the ability for cells to differentiate in the right place to new tissues
4. New genes for specific proteins to create these new tissues (which may be copyable from other organisms)

Long story short: what is the biggest reason why we can’t just hack into a later part of the sequence and continue on from there with what you said?

Well, we can’t reuse the existing one because it creates human structure. So we need brand new genes for 2 and 3.

I’m not a professional in this area, but I haven’t seen anything that suggests we can fo this yet.

I think part 4 (the bit about creating new tissues) might in fact be the easier part. But to cause them to be developed at the right time in the right place and at the correct size with brand new signals is waaaay out there.

Or would your proposed plan also just end up like this in the final product and you laid it out like this because it’s already the most viable route into this mess? 😅

Speaking as someone whose last practical biology wiped out all the very expensive cell colonies, and that was 30 years ago, I hope my wild suggestions here are even vaguely in the right direction.

In a way, your jaw is a gill arch, just built in a different way with some interesting diversions. After a couple of 100 million years, the changes do add up.

If you really had to add in a gill, i have a plan, but I need to talk about one important evolutionary trick: duplication and divergence.

A fairly common DNA copying error causes a section of a chromosome to be duplicated in the offpring. In most cases this is fatal or prevents children, but some duplications work out just fine.

For instance mammals lost colour vision in the time of the dinosaurs - mammals were probably nocturnal. The loss was caused by losing genes for the yellow colour receptors in the eye. This is why dogs and cats see in something akin to black and white (they do see red and blue and all the yellows and greens are just shades of red and blue).

But apes were lucky. An accident duplicated the existant red receptor and, over time, because there are now two genes, one gene was gradually selected for a higher and higher light frequency. This has become our green receptor and all apes see in red-green-blue colour.

Duplication is not necessarily fatal because it just codes for something we already have. But once there are 2 genes, evolution can select away for different capabilities and we end up with something new.

Ok, with that out the way let’s plan!

1. Add in a few new sections into the human body by adding some new hox genes. This would give us a significantly longer neck - probably fatal without medical support.
2. Duplicate and diverge the genes used to trigger gill arch/neck and jaw development and modify the developmental genes that respond to them. This would preserve the development the upper neck as humans (to keep the jaw and ear) while allowing something else to happen lower down
3. In the lower section work out a way to develop like our basal forms (something eel-like) and trigger this development with the modified genes from step 2.

Step 1 might be possible today. Step 2 might be within current reach (but it would take incredible work to disentangle all the connected system in development and the working body. Step 3 is beyond current tech (as I understand).

If you like this, this goes under the moniker ‘evo/dev’ - evolution of the ‘development’ of the organism. A lot of genes don’t code for proteins that ‘do’ something in the body, like haemoglobin or fingernails - they code proteins that tell the body how to develop from a single cell. Many are active for a short window in development. Some are active in a single location, like at the thumb end of the limb bud, and tell the cells where to become a finger, thumb or palm bone. Some work across vastly different animal classes - the ‘build an eye here’ gene works in humans and flies and everything in-between.

In short, we could, but the cost would be incredible.

All vertebrates are animals that develop from a series of segments, with a vertebra at the core. In our time from eel-like fish, we’ve specialised these segments so, for example, we have ribs on the vertebra corresponding to the rib cage.

To support arms and legs, specific vertebra have become highly specialised in the form of hips and shoulders.

Gills are composed of a series of gill arches, one on each vertebra in the neck area. These structures have (in eels) a lot of blood vessels to carry the blood that needs reoxygenation.

An interesting thing happened as the eel-like creatures differentiated, evolved jaws and ultimately ended up as mammals and humans: nature co-opted the specific vertebra that had these gill features and turned them into jaws and ears and a variety of other features in the head and neck. For example the tiny bones in your ear were once fish jawbones which were previously one (or more) gill arches.

The stupendously complex anatomy in this area comes from all the short-term ‘decisions’ evolution took to make all the magnificent creatures that inhabit the earth.

For example the nerve that connects the brain to the larynx (the recurrent laryngeal nerve) emerges from a vertebra high up in the neck, decends down under the aorta in the chest and then back up into the neck to the larynx. In the giraffe, the nerve is many meters long, even as it’s direct path could be a few centimeters. The reason is that the heart used to be close to the gills in fish and sharks. As the heart moved in land animals, the nerve was caught in a loop around the critical aorta and it was ‘pulled’ along for the evolutionary ride.

So, in order to turn your gills back on, you need to unprogram 450m years of evolution of the structures you call your head, face and neck.

I’d recommend ‘Your inner fish’ by Shubin - it’s a wonderful read and explains this in far more detail that I can manage.

This is true for only red and green loght detecting proteins (opsins) - the blue opsin gene is on chromosome 7.

The red and green detecting proteins have an interesting history in humans.

Fish, amphibians, lizards and birds have 4 different opsins: for red, green, yellow and blue colours. And the blue opsin sees up into the ultra-violet. Most animals can see waaaay more colours in the world than we (or any mammal) can. So what happened that makes mammal vision so poor?

It’s thought that all mammals descend from one or a few species of nocturnal mammal that survived the catastrophe that wiped out the dinosaurs at the end of the Cretaceous. The colour detecting cells (the cones) need a lot of light compared to ones that see in black-and-white (the rods) and therefore nocturnal animals frequently lose cones in favour of the more sensitive rods for better night vision. The mammals that survived the Cretaceous extinction had also lost the green and yellow opsins while keeping red and blue - basically the two different ends of the light spectrum.

Consequently today most mammals still have only 2 opsins so your cat or dog is red-green colourblind.

Why do humans see green? Probably because our monkey forebears, who lived in trees and ate leaves, needed to distinguish red leaves and red fruit (visible to birds) from the green background.

But how did we bring back the green opsin? A whole section of the X chromosome (where the red opsin is coded) got duplicated in a dna copying mistake and then there were two genes for red opsins. As there are different alleles (versions), they could be selected for independently and so one red opsin drifted up the spectrum to be specific for green. So our green opsin is a completely different gene to the green opsin in fish, birds, etc. This kind of evolution happens a lot which is why, for example, there are many families of similar hormones like testosterone and estrogen. And steroids too.

It is terribly sad - they must live in a world of hurt.

However so many of these people actively try to hurt LGBTQ+ and trans people by inciting hate and changing laws to harm the non-straight. In particular they have been preaching that being gay/trans equates to being a child molester. This is horrific and needs to stop. Exposing the hypocrisy is essential to reducing the harm they are inflicting to real people right now

Typically you need about 1GB graphics RAM for each billion parameters (i.e. one byte per parameter). This is a 405B parameter model. Ouch.

Edit: you can try quantizing it. This reduces the amount of memory required per parameter to 4 bits, 2 bits or even 1 bit. As you reduce the size, the performance of the model can suffer. So in the extreme case you might be able to run this in under 64GB of graphics RAM.

I think that’s a better plan than physically printing keys. I’d also want to save the keys in another format somewhere - perhaps using a small script to export them into a safe store in the cloud or a box I control somewhere

You need at least two copies in two different places - places that will not burn down/explode/flood/collapse/be locked down by the police at the same time.

An enterprise is going to be commissioning new computers or reformatting existing ones at least once per day. This means the bitlocker key list would need printouts at least every day in two places.

Given the above, it’s easy to see that this process will fail from time to time, in ways like accicentally leaking a document with all these keys.

I agree, so much legislation is broken, the legislators aren’t doing shit, so we citizens need to fix it!

But we could start with the right to repair.

I had a Sinclair QL which pioneered the keyboard. It wasn’t great - it was far behind the Acorn BBCs and the Commodores) but it was quite usable.

There was significant vertical travel, and there was variation in the push the key gave back - increasing to a point of no return, then a quick downward movement to the thunk of the end of key travel.

I could type moderately fast on it.

If you’re pushing everyone’s buttons it’ll end badly.

I’m going to suggest food items that we still take from nature and eat with minimal preparation:

• Honey
• Fish like salmon, trout, grouper
• Shellfish (eg oysters)

We have evidence of shellfish and fish being eaten for a very long time - at least the middle stone age at 140kya - in middens which are 10s of thousands of years old.

Honey is likely to have been a food source - a treat even - even before humans left Africa (so before 100kya) but sadly this would be invisible in the archeological record

There is non-zero risk in every surgery, and this is a major surgery. There is non-zero risk of very very severe consequences: brain infection, stroke being just some. While these risks are low, they are non-zero. The volunteers have the possibility of losing everything.

Java programmers are also functionally illiterate