New universe of miniproteins is upending cell biology and genetics • Hacker News Board

Re: New universe of miniproteins is upending cell biology and genetics

#111

Post by saltcured » Fri, Oct 18, 2019, 3:53 PM UTC

jerf wrote: post #73

sedeki wrote: post #40

Earlier quoted context omitted.

Wow. I understand that you are a layperson, but that’s a very strong statement in my view. What do you base it on? Or did you just pull it ”out of a hat”?

First, the goal I'm shooting for is the conquest of aging, effective biological immortality, not just living 150-200 years. When understanding a complicated existing system, like a program, with the intention of making changes to it or fixing it, I find there are characteristic phases to it. There's the part where you have no handle on it at all. At this point you think there maybe isn't that much to the system. Then…

Even if we could separate your mind from your body and run it on an immortal computer (or rather succession of computers), I don't think we have any evidence to suggest that making a mind immortal is easier than making immortal tissues and organs.

It's not just making the machine immortal or serviceable. You also need to make the program robust enough to run continuously without crash/reset conditions or other pathological bugs. But, the techniques we understand to engineer "immortal" programs are at odds with the complexity of a real mind, in much the same way as our techniques for engineering machines are at odds with real biology. I.e. it isn't really preserving a real mind if we have to strip away the stateful learning and memory, the moods and emotions, and the inherent potential for bouts of irrationality or even psychosis.

Finally, to "solve aging" for one organism or one mind just raises more questions which are equally as hard. What is an immortal society or civilization? How do new people ever relate to their immortal forebears or participate on equal footing in an economy where some have literally had forever to gather wealth and power? Or does sexual reproduction cease in a future with backup-restore options? Immortality means solving all these levels, otherwise you just replace illness and senescence with accident and violence as the common cause of death...

Re: New universe of miniproteins is upending cell biology and genetics

#112

Post by jerf » Fri, Oct 18, 2019, 4:13 PM UTC

sasaf5 wrote: post #89

jerf wrote: post #31

Earlier quoted context omitted.

I wouldn't be surprised in the slightest that it is easier to build a brain scanning machine and simulate you in a computer than to "solve aging". And don't think I underestimate the difficulty of that, either.

Making a very crude analysis based on the size of data, I would say solving aging is a piece of cake comparing to scanning someone's brain content. Our proteins that eventually break down with aging are coded by the DNA. The DNA is a few GB across. Sure there are mutations, folding and other complexities, but it is still mostly digital data. The brain has 80B neurons, each with thousands of dendrites. You'd need to s…

It depends on how close the biological cells are to being immortal. What I was referring to in somewhat sarcastically in another post is that modern senescence research is basically operating from the position that the cell just has, you know, maybe one or two or three things wrong with it, and if we can "just" extend the teleomeres (presumably with just ingesting some substance), and maybe supplement our diet with a couple of substances, and maybe fix cancer or something, we'll be there.

There are some reasons to believe this may be true, such as the existence of cells in the wild that seem to be effectively immortal, like certain jellyfish and such. (Nothing terrible close to us taxonomically, but at least they're from planet Earth.)

On the other hand, it may turn out that after a couple of quick wins worth, say, 20 or 30 years, that the whole thing devolves into dozens, then hundreds, then thousands, then tens of thousands of interventions, all complicating each other, a good number of them unique to the individual, as you try to pick up the pieces in your ever-aging organs as they continue to find new and exciting ways to fail. Imagine trying to keep an old car running, but you're not actually allowed to just replace parts, and you have to do all the fixes while the car is on the road, and this is just barely the tip of the iceberg. Senescence research may be one of the worst examples of a light-post problem in human history, as they search for this or that substance that will fix aging but the minimal solution is in fact literally gigabytes worth of information converted into biological machines we can barely even conceive of.

If you can read one neuron, you can read two; those problems are not independent. (That's a simplification to some extent, but at this level we'll take it.) If you can understand one protein's function, that doesn't help anywhere near as much with the next one, and the state of the body is roaming through a very high-dimensional space over time, with the interventions all also affecting the next intervention that will be necessary... it can get pretty ugly in there, potentially. Amusingly, the brain is the problem in both cases; biological immortality probably wouldn't be so hard, we could probably solve everything by transplants of freshly-grown organs based on our genetic code... except transplanting a freshly-grown brain in kinda defeats the whole purpose. In the end, both problems may come back to scanning brains one way or another.

Re: New universe of miniproteins is upending cell biology and genetics

#113

Post by beambot » Fri, Oct 18, 2019, 4:38 PM UTC

ddiq wrote: post #88

danharaj wrote: post #7

Earlier quoted context omitted.

This is why you should be very skeptical of anyone who claims transparency between genetics and complex phenotypes.

That doesn't really follow. We don't need to have a complete map genotype to phenotype in order to have an understanding of the weight of genetic component of certain traits. Just because we don't know exactly which genes cause a certain hair color doesn't mean we can't guess which parents are more likely to have children with that hair color. The same goes for behavior that can be measured and predicted. As long as…

If you drop an apple & observe that it falls, you get some predictive value about the nature of gravity. But that's a far cry from computing the orbital dynamics of a spacecraft. Parent's comment on "transparency" in the mapping from genotype to phenotype was more akin to the latter -- and their point stands.

Re: New universe of miniproteins is upending cell biology and genetics

#114

Post by danharaj » Fri, Oct 18, 2019, 5:29 PM UTC

beambot wrote: post #113

ddiq wrote: post #88

Earlier quoted context omitted.

That doesn't really follow. We don't need to have a complete map genotype to phenotype in order to have an understanding of the weight of genetic component of certain traits. Just because we don't know exactly which genes cause a certain hair color doesn't mean we can't guess which parents are more likely to have children with that hair color. The same goes for behavior that can be measured and predicted. As long as…

If you drop an apple & observe that it falls, you get some predictive value about the nature of gravity. But that's a far cry from computing the orbital dynamics of a spacecraft. Parent's comment on "transparency" in the mapping from genotype to phenotype was more akin to the latter -- and their point stands.

You can read their comment history to contextualize their angle.

Re: New universe of miniproteins is upending cell biology and genetics

#115

Post by rosybox » Fri, Oct 18, 2019, 5:41 PM UTC

JohnBerea wrote: post #101

andreygrehov wrote: post #92

Earlier quoted context omitted.

I never read the book, but during the last couple years I became more attentive to things in life. Nothing special, but just the general flow of life so to speak. I started noticing an interesting pattern. There is pretty much always exists a single solution to any problem. A core solution. A polymorphism in programming could be an example of what I mean. Say you have a program with a bunch of similar entities and a…

The human genome is full of harmful mutations. While many are widespread and some are shared by everyone, we each still have our own unique collection of them. I often wonder how much longer we'd live with every obviously harmful mutation reverted.

It's probably not black and white, some of those harmful mutation may have necessary benefits in some other function. It's like drinking a poison that will kill in the long term but you need to live in the short term.

Re: New universe of miniproteins is upending cell biology and genetics

#116

Post by rdlecler1 » Fri, Oct 18, 2019, 5:44 PM UTC

beambot wrote: post #113

ddiq wrote: post #88

Earlier quoted context omitted.

That doesn't really follow. We don't need to have a complete map genotype to phenotype in order to have an understanding of the weight of genetic component of certain traits. Just because we don't know exactly which genes cause a certain hair color doesn't mean we can't guess which parents are more likely to have children with that hair color. The same goes for behavior that can be measured and predicted. As long as…

If you drop an apple & observe that it falls, you get some predictive value about the nature of gravity. But that's a far cry from computing the orbital dynamics of a spacecraft. Parent's comment on "transparency" in the mapping from genotype to phenotype was more akin to the latter -- and their point stands.

We sent astronauts to the moon with Newtonian physics. No need for relativity. This is more akin to relativity in that it expands our domain knowledge and explanatory power but the old model already does most of the work.

Re: New universe of miniproteins is upending cell biology and genetics

#117

Post by gateKeeper » Fri, Oct 18, 2019, 6:31 PM UTC

That was the most interesting article I have read in a while. Thank you for sharing.

Re: New universe of miniproteins is upending cell biology and genetics

#118

Post by innomatics » Fri, Oct 18, 2019, 7:16 PM UTC

sasaf5 wrote: post #89

jerf wrote: post #31

Earlier quoted context omitted.

I wouldn't be surprised in the slightest that it is easier to build a brain scanning machine and simulate you in a computer than to "solve aging". And don't think I underestimate the difficulty of that, either.

Making a very crude analysis based on the size of data, I would say solving aging is a piece of cake comparing to scanning someone's brain content. Our proteins that eventually break down with aging are coded by the DNA. The DNA is a few GB across. Sure there are mutations, folding and other complexities, but it is still mostly digital data. The brain has 80B neurons, each with thousands of dendrites. You'd need to s…

Both are hard problems. However the folding properties of both nucleic acid and proteins is where the complexity lies.

It's the 3D structure, not the sequences so much of these molecules that determine intra- extra- and inter-cellular behaviour.

So we'll never fully understand the brain until we understand the genome and proteome.

Re: New universe of miniproteins is upending cell biology and genetics

#119

Post by Eugeleo » Fri, Oct 18, 2019, 7:51 PM UTC

hprotagonist wrote: post #42

jdironman wrote: post #39

Earlier quoted context omitted.

We are just in the debugging phase.

i've been doing biological/biomedical research for about 20 years now (god, that's a scary thought...) I don't think that biology is well modeled by "being a meat computer", in general, but as far as the analogy goes ... : What we are debugging is 4.5 billion years of grad student code in at least a few dozen languages, with no documentation, method names that are outright lies, no separation of concerns at all, the…

OT, if I may ask, in what field eare you working exactly? I study bioinformatics and I always love to hear stories from someone with experience in the field (it is really hard to come by those people).

I have an email address on my profile, if you’d like to contact me more directly.

Re: New universe of miniproteins is upending cell biology and genetics

#120

Post by JohnBerea » Sat, Oct 19, 2019, 5:27 AM UTC

rosybox wrote: post #115

JohnBerea wrote: post #101

Earlier quoted context omitted.

The human genome is full of harmful mutations. While many are widespread and some are shared by everyone, we each still have our own unique collection of them. I often wonder how much longer we'd live with every obviously harmful mutation reverted.

It's probably not black and white, some of those harmful mutation may have necessary benefits in some other function. It's like drinking a poison that will kill in the long term but you need to live in the short term.

Such mutations are highly popularized and simultaneously very rare.