Animals as Chemical Factories | Hacker News Reader

Animals as Chemical Factories

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47 pointsroyalroad62 comments

Cell-free synthesis is the next step. Theres slow progress, but very interesting operational models if it works.

I once visited a lab near Berlin where they told me that cell-free synthesis is basically like cell-based synthesis, just that they kill the cells first and use what's inside. The major benefit, I was told, was that you don't have to keep the cells alive.

It sounds very odd at first glance but seems very fascinating to me (and I know way less about biology than I would like to), this idea of dissecting a system into its pieces because we know how to use the pieces in a superior way to the original system itself.

I don't like that description very much. The cell being "alive" is literally the top reason the cellular machineries work so well. By being "alive" it is keeping the environment optimal and perfect for the enzymes to run and being productive. Taking this away and then seeing problems about efficiency is like taking off the wheels and then asking why the car is not running well.

They are trying to fix it by maintaining the same cytoplasmic conditions using all the machines and sensors in a bioreactor. But that can scale is a different question. The narrow ranges of conditions biological processes require is already hard to maintain while the cells itself is still whole and using more than half of its enzymes to do this.

Think of it more as just getting to the one function that you are using. I think a cell free technique that people might have heard of even in high school biology at this point is the polymerase chain reaction. Rather than have some cell we grow in some growth media under certain conditions optimal for cell growth and harvest cloned DNA from these cells, we have isolated the involved protein directly (DNA Polymerase). We know exactly what temperature is most optimal for each step, and infact depending on what targets of DNA we are looking at certain temperatures may be more optimal for these targets. We know the exact pH that these molecules are most effective at and this might not even be a pH found in the cell but one determined empirically by measuring enzyme activity across a gradient of pH and/or temperature ranges among other potential conditions. We know the inputs and reaction and can supply just enough of these molecules as we need to drive satisfactory yield in order to decrease our costs. We can optimize the timing of this temperature-dependent reaction again to the specifics of the DNA molecule that we are amplifying. We can change how quickly this reaction is heated up or cooled down to optimize for product yield. We can change out components of this reaction such as our enzyme for ones that might operate faster with less accuracy, or ones that operate slower with higher fidelity, or ones found from other species that might have these properties, or engineered proteins that might have these properties.

Many reasons why you'd want to go cell free. You are no longer binned into the cell but are now just throwing things into a tube where you can control all the parameters that matter for your desired function.

Biology really is the ultimate modular system!

I have strong doubt it will work. On paper we are just removing an arbitrary boundary that is the cell membrane/wall and combine trillions of cells together to form a giant cell. So it sounds very reasonable and attractive in engineering terms. But these are biological systems inherently designed/evolved to work in one special condition that is the cytoplasm of the host...

Any engineer would know the kind of troubles that can occur if we remove a critical principle of the original design that was there since the system's inception and is literally hardcoded on an operational/abstract level into the system's functions. Trying to fix that mess is unlikely to yield anything close to the original and requires manipulating techniques and knowledge highly intimate within the system.

And we know barely anything about the intimate and detail operation of the molecular structures inside a cell. We know the broad strokes. But ask any biochemist if they are confident of the entire reaction pathway of any enzymes down to the thermodynamics calculations associated with all conformational changes. Maybe you will find a dozen enzymes that we can describe at this detail.

And to optimize cell free synthesis, we would need to know of tens of thousands more. It is possible, but it isn't something I would expect to see soon unless there are major breakthroughs.

All that matters is that it works and is easier or cheaper than existing cell based techniques. If it does, whats the harm then? This is why people are figuring this out on grant funded work after all, to see if it is in fact cheaper than existing techniques. This is how we have found many optimizations to lab work and other processes through basic research in the past.

TXTL systems already works. And there are antibodies (not many) that can only be produced cell free.

The problem is really scale.

Cell-free synthesis is really nice for R/D (it's fast!) but honestly kinda sucks for producing things. Cells have a really nice property of making more of themselves for the cost of basic chemicals (salt, sugar, nitrogen).

TXTL also can be pretty finicky generally - cold storage is required, have to store chemicals separately, ribosomes tend to fall apart and not get recycled, etc. Cells will heal themselves perfectly (sometimes too perfectly, kicking out your construct)

The idea of using a controlled, cell-free environment to churn out proteins or antibodies is so elegant

> Today, companies such as Twist Bioscience can synthesize DNA for about $0.07 per base.

Marburg (what about Ebola?) has only ~20k bp, so ... about USD 3k to synthesise?

Then you have to insert it into a viable donor cell which might not be easy or cheap.

DNA synthesis companies try to detect if the DNA you want to synthesize is any known virus, so they can call the bio-terrorism police.

It's incredible to see how far we've come in developing synthetic alternatives

Clostridium acetobutylicum, WW1 Acetone production.

Make EColi Productive Again

TBF, it's been producing all kinds of chemical effects for longer than human beings have existed ;-)

And, now it's proving its survivor's brutally superior intelligence by going from just procreating within our misery, to now tricking us into propagating it willingly and in likely far more beneficial conditions!

Is that our petri dishes softly chuckling?

Petri dishes? I thought we let those suckers spawn in giant vats when we need to produce sizable amounts of proteins

Humans also consume more meat than required to stay alive ...

(Before anyone starts to make moral statements)

from the viewpoint of TFA, meat is a way to (very lossily!) harvest the solar input that goes (over summer months, anyway) into extensive grasslands (inedible by humans in its unbred state), and gather that over several years into a package which (no external refrigeration needed!) transports itself to market/slaughter.

and doing so so very, very deliciously, at that.

and no more B-12 shots needed.

(I'm not in any way against vegatarianism and eat rather little meat, most of it bird, but I know of the diffulties some people have with strictly vegetarian diets. At some point, I hope genetic engineering will figure out how to produce the requisite proteins, and our animals can roam free, fertilizing our fields with only sheep dogs to bother them.)

That used to be true when a pig would feed an entire family for a year. You're about 100 years out of date if you think this is still the case.

Please feel free to point out which parts of the comment are incorrect.

Not GP, but you present a very one-sided view, almost like a commercial for the meat industry.

The grassland is presented as a given, but often they were created for the cattles.

Long time ago, my country used to be primal forest.

Some centuries ago most of it has been converted to “usable forest” where people grow food and wood.

Today it’s only crops and ~natural~ grassland for cattle.

Producing how much methane?

Yet another instance of how people view the biosphere as a resource to be exploited for their own monetary profit and short-term benefit. That type of logic and thinking is a dead end. I've never had a silk robe and I doubt I would be any better off if I did have one. I'd much prefer clean air, water, and unpoisoned land for growing nutritious food.

we use people as machines to move stuff around and make new stuff. humans are the only creatures that have to pay to live on this planet, if they don't pay, they can't have food/shelter/etc.

And we use people as sex machines, unfortunately.

"People know the part I'm playing." --"Just a Gigalo" lyrics

And people use most anything in that capacity, Rule #42 is not a theorem, after all.

While the callously selfish oppressive monsters don't care how their victims feel, so long as they get their pleasure. Greed for money and sex are really the same kind of selfish vice. And callousness to the misery of others and heartlessly disrespecting a person's human right to choose what we do with whom they will, are two of the primary drivers of unhappiness upon our Earth today.

Compassion is a balm for all such vices, but we must choose to learn the truth of its importance and then choose to manifest it in our ideals, attitudes, and behaviors. It, like all things human, is within our power, both individually and collectively, but, first, we must give a sh_t.

With the context that "payment" is a way to make labor fungible and labor is expenditure of calories, every creature has to pay to live.

Humans probably spend fewer calories on survival (with better results) and more calories on pleasure than any other species. This is partly thanks to society.

So humans probably "pay" the least of any species just to exist.

> more calories on pleasure than any other species

That’s true we aren’t cheap on the pleasure calories, on the other hands most mammals seems to include pleasure in hunting or building their shelter or other activities. Think to dolphins, Wolfe, or rabbits. We humans have created many pleasant activities to forget our workday -which is not a pleasure for most-, while the lion enjoy its nap before an exiting hunt tonight with fellows.

If squirrels could figure out how to make money I'm sure someone would be happy to charge them rent

Well said, friend. That is an important aspect of the Way. We must be gentle with our mother Earth in order to compassionately harmonize with future generations' happiness.

But what I really, really want is hemp clothing. When I was in Atlanta in the 90s, there was a hemp shop, where I bought the best jeans, shorts, and hats I've ever had. They got nothing but more comfortable over time, breathed excellently and never molded (not that I tried). I could imagine that they would've lasted my lifetime, or even more.

Sadly, they shrunk terribly over time, and by that I mean I "grew" out of them :-)

Now, all I've seen on the net are 60%-40% cotton blends, IIRC, not the 100% hemp that was available back then. It doesn't look like the new cannabis acceptance here in America has produced hemp cloth, but I could be wrong. I imagine that growers are more focused on the likely more lucrative drug version of the plant. That said, it's been years since I searched the net for sellers, but my daughter has the skills and the 503a to make me a sweet kilt and jumpsuit and long-sleeve long-hanging shirt, should the funds come through.

"Hemp for victory!" --WWII American poster slogan

Could it be that it is more sustainable to have them as blends?

I doubt it. I'm pretty sure the % cotton would wear out much sooner, but that's just my intuition.

Silk worm industry is the definition of long-term sustainable exploitation of biosphere. It was done for thousand years, with minimal resources, no polution, it captures CO2... It only takes a few worms and some leafs! Chemical alternatives are poluting and poising, land air and waters!

How about we leave the silk worms alone.

Silk worms would starve to death if left alone.

Did they agree on to be later breed, boil then breed their kids and boils them too? This is crazy. We all know the reason we feed them is for our own interest.

Of course they agreed. It is like little boys and cutting digs. They just love that shit!

You are so fun man I wonder why you don’t use your real account to gather lol points.

Pretty rich coming from someone sending virtue signals from a device I presume isn’t constructed from twigs and berries.

Must be difficult as a person who doesn’t exploit the biosphere.. you’ll have to let us know how you mastered photosynthesis.

I don't eat meat and don't drive cars. How about you?

As a level 99 druid, I have not moved from this spot in over 300 hundred years. My clothes consist of centuries accumulation of dust. I eat meat, but only beings that choose to end their existence in my perpetually open mouth. I breathe four times a year. I reproduce by sporulation, prodigiously, my offspring is responsible for the ozone layer. I convey this information to you by way of telepathy through an intermediary, Shawn of Ohio, an intern in IT who maintains his WFH infrastructure by peddling a stationary bicycle.

Can’t achieve perfection so goodness is out of question?

It takes a few worms and lots of leafs. Got a friend in that industry and the partnership with Brazil is flourishing.

Counterpoint: being useful to a more successful species is a staggeringly effective evolutionary strategy. Nature is chock full of symbiotic relationships and it's a perfectly valid ecological niche. Symbionts exist whether or not the host is capable of feeling bad about it.

By becoming attached to such a successful species as humans, any symbiont species has an extremely good chance of surviving for as long as the host species. Including long after they'd have gone extinct naturally.

Most species that humans like or find useful will eventually end up colonizing entire star systems along with us. Those species will continue to live on in their evolutionary descendants long after the sun exapnds and earth becomes inhospitable.

Personally I call that a successful species.

Or we could just leave the worms alone and let them be hunted to extinction by predators or die out in natural climate or ecological shifts over time. I guess that's nicer than species continuity into galactic time scales.

Very interesting take. However there’s some important difference between the species that express this behavior in the wild, free world (think pilot fish) and those that are breed, used, breed again then killed -all while in forced captivity.

I doubt the livestock would define itself as a "successful” if it could use language.

Humans as chemical and organ factories.

Humans currently produce industrial poisons on an unimaginable scale so you're not far off.

Note that this is another difference between we human beings and the rest of the animals. Yes, non-human animals can take advantage of other animals' chemical factories (ants' use of aphids' sugar excretions come to my mind), but only we human beings can use our abstract conceptual thinking ability and scientific process to discover the nature of nature's chemistry and then put that knowledge to use.

After my first-glance gist of the article, I've been eagerly awaiting mass-produced spider silk for quite some time. I wonder if it will be suitable for usage as thread? Will it be waterproof? Will it have that wonderful flexibility and strength per mass that has been envisioned?

I first read about industrial use of spider silk literally 25 years ago in Discover Magazine. I'm going to assume it's just never going to make economic sense.

Could you elaborate on why you think so?

It's been 25 years.

To give some humility, we've been around for hundreds of thousands of years as a species and for most of that time we could not have done what you've stated above. Farming, cities, animal husbandry, etc. are very very new for homo sapiens.

You really can't use "thing humans do in modern times" as an indicator of the superiority of humans. For a start no individual human could do something like build an industrial process for exploitation anymore than an individual termite could build a city since no individual has all the knowledge required nor could they build that knowledge from scratch. If all it took was a singular individual and not a collective we would have achieved this much sooner in our history. Your aphid example is much closer to how humanity operates than you give it credit.

That is absolutely cool and amazing that we can do that though. Being able to build on the works of others I think is way more metal than having a single individual or a small group of individuals doing it.

One with no humility has no humility to give.

Anyone who starts a sentence with "You really can't use" is preaching from atop their perch of various sh_ts, horsesh_t and bullsh_t, especially. Get over youself.

The problem with spider silk is that it isn't just a chemical. We can make spider silk. There are plenty of papers where the spider silk proteins are produced by bacteria and spun into a fiber. The problem is that this fiber basically behaves like regular silk.

Spider silk is partially crystallized and partially amorphous in a semi-disordered pattern that maximizes the toughness of the finished product. The way the silk is slowly concentrated out of solution during spinning in the spinneret is crucial to obtaining the desired properties. There have been attempts to replicate this process, e.g.:

https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.2008033...

However, a scalable design is incredibly difficult to achieve. Frankly, I'd be happy if we could just make regular silk cheaper than the worm fiber.

That's an all-time great comment. Thank you very much.

Yeah, it makes sense that, because Nature wastes nothing, the entire system is required to produce that wonder material. Our focusing just on the chemical structure of what is produced in its "glands" (?) is indicative of our having only a shallow grasp of the intricacies of our world, especially of its life.

Nature grows ever more wondrous the more we learn about it.

> but only we human beings can use our abstract conceptual thinking ability and scientific process to discover the nature of nature's chemistry and then put that knowledge to use.

I heavily doubt we needed this to domesticate animals. What is the possible value of projecting 19th century concepts onto prehistory?

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